Id |
Subject |
Object |
Predicate |
Lexical cue |
T137 |
11-22 |
NN |
denotes |
Amyloidosis |
T138 |
0-104 |
sentence |
denotes |
Persistent Amyloidosis following Suppression of Aβ Production in a Transgenic Model of Alzheimer Disease |
T139 |
23-32 |
VBG |
denotes |
following |
T140 |
33-44 |
NN |
denotes |
Suppression |
T141 |
45-47 |
IN |
denotes |
of |
T142 |
48-50 |
NN |
denotes |
Aβ |
T143 |
51-61 |
NN |
denotes |
Production |
T144 |
62-64 |
IN |
denotes |
in |
T145 |
65-66 |
DT |
denotes |
a |
T146 |
78-83 |
NN |
denotes |
Model |
T147 |
67-77 |
JJ |
denotes |
Transgenic |
T148 |
84-86 |
IN |
denotes |
of |
T149 |
87-96 |
NNP |
denotes |
Alzheimer |
T150 |
97-104 |
NN |
denotes |
Disease |
T151 |
104-105 |
sentence |
denotes |
|
T152 |
154-164 |
sentence |
denotes |
Background |
T153 |
154-164 |
NN |
denotes |
Background |
T154 |
164-373 |
sentence |
denotes |
The proteases (secretases) that cleave amyloid-β (Aβ) peptide from the amyloid precursor protein (APP) have been the focus of considerable investigation in the development of treatments for Alzheimer disease. |
T155 |
165-168 |
DT |
denotes |
The |
T156 |
180-190 |
NNS |
denotes |
secretases |
T157 |
169-178 |
NNS |
denotes |
proteases |
T158 |
179-180 |
-LRB- |
denotes |
( |
T159 |
273-277 |
VBN |
denotes |
been |
T160 |
190-191 |
-RRB- |
denotes |
) |
T161 |
192-196 |
WDT |
denotes |
that |
T162 |
197-203 |
VBP |
denotes |
cleave |
T163 |
204-211 |
NN |
denotes |
amyloid |
T164 |
212-213 |
NN |
denotes |
β |
T165 |
211-212 |
HYPH |
denotes |
- |
T166 |
219-226 |
NN |
denotes |
peptide |
T167 |
214-215 |
-LRB- |
denotes |
( |
T168 |
215-217 |
NN |
denotes |
Aβ |
T169 |
217-218 |
-RRB- |
denotes |
) |
T170 |
227-231 |
IN |
denotes |
from |
T171 |
232-235 |
DT |
denotes |
the |
T172 |
254-261 |
NN |
denotes |
protein |
T173 |
236-243 |
NN |
denotes |
amyloid |
T174 |
244-253 |
NN |
denotes |
precursor |
T175 |
262-263 |
-LRB- |
denotes |
( |
T176 |
263-266 |
NN |
denotes |
APP |
T177 |
266-267 |
-RRB- |
denotes |
) |
T178 |
268-272 |
VBP |
denotes |
have |
T179 |
278-281 |
DT |
denotes |
the |
T180 |
282-287 |
NN |
denotes |
focus |
T181 |
288-290 |
IN |
denotes |
of |
T182 |
291-303 |
JJ |
denotes |
considerable |
T183 |
304-317 |
NN |
denotes |
investigation |
T184 |
318-320 |
IN |
denotes |
in |
T185 |
321-324 |
DT |
denotes |
the |
T186 |
325-336 |
NN |
denotes |
development |
T187 |
337-339 |
IN |
denotes |
of |
T188 |
340-350 |
NNS |
denotes |
treatments |
T189 |
351-354 |
IN |
denotes |
for |
T190 |
355-364 |
NNP |
denotes |
Alzheimer |
T191 |
365-372 |
NN |
denotes |
disease |
T192 |
372-373 |
. |
denotes |
. |
T193 |
373-603 |
sentence |
denotes |
The prediction has been that reducing Aβ production in the brain, even after the onset of clinical symptoms and the development of associated pathology, will facilitate the repair of damaged tissue and removal of amyloid lesions. |
T194 |
374-377 |
DT |
denotes |
The |
T195 |
378-388 |
NN |
denotes |
prediction |
T196 |
393-397 |
VBN |
denotes |
been |
T197 |
389-392 |
VBZ |
denotes |
has |
T198 |
398-402 |
IN |
denotes |
that |
T199 |
532-542 |
VB |
denotes |
facilitate |
T200 |
403-411 |
VBG |
denotes |
reducing |
T201 |
412-414 |
NN |
denotes |
Aβ |
T202 |
415-425 |
NN |
denotes |
production |
T203 |
426-428 |
IN |
denotes |
in |
T204 |
429-432 |
DT |
denotes |
the |
T205 |
433-438 |
NN |
denotes |
brain |
T206 |
438-440 |
, |
denotes |
, |
T207 |
440-444 |
RB |
denotes |
even |
T208 |
445-450 |
IN |
denotes |
after |
T209 |
451-454 |
DT |
denotes |
the |
T210 |
455-460 |
NN |
denotes |
onset |
T211 |
461-463 |
IN |
denotes |
of |
T212 |
464-472 |
JJ |
denotes |
clinical |
T213 |
473-481 |
NNS |
denotes |
symptoms |
T214 |
482-485 |
CC |
denotes |
and |
T215 |
486-489 |
DT |
denotes |
the |
T216 |
490-501 |
NN |
denotes |
development |
T217 |
502-504 |
IN |
denotes |
of |
T218 |
505-515 |
VBN |
denotes |
associated |
T219 |
516-525 |
NN |
denotes |
pathology |
T220 |
525-527 |
, |
denotes |
, |
T221 |
527-531 |
MD |
denotes |
will |
T222 |
543-546 |
DT |
denotes |
the |
T223 |
547-553 |
NN |
denotes |
repair |
T224 |
554-556 |
IN |
denotes |
of |
T225 |
557-564 |
VBN |
denotes |
damaged |
T226 |
565-571 |
NN |
denotes |
tissue |
T227 |
572-575 |
CC |
denotes |
and |
T228 |
576-583 |
NN |
denotes |
removal |
T229 |
584-586 |
IN |
denotes |
of |
T230 |
587-594 |
NN |
denotes |
amyloid |
T231 |
595-602 |
NNS |
denotes |
lesions |
T232 |
602-603 |
. |
denotes |
. |
T233 |
603-723 |
sentence |
denotes |
However, no long-term studies using animal models of amyloid pathology have yet been performed to test this hypothesis. |
T234 |
604-611 |
RB |
denotes |
However |
T235 |
689-698 |
VBN |
denotes |
performed |
T236 |
611-613 |
, |
denotes |
, |
T237 |
613-615 |
DT |
denotes |
no |
T238 |
626-633 |
NNS |
denotes |
studies |
T239 |
616-620 |
JJ |
denotes |
long |
T240 |
621-625 |
NN |
denotes |
term |
T241 |
620-621 |
HYPH |
denotes |
- |
T242 |
634-639 |
VBG |
denotes |
using |
T243 |
640-646 |
NN |
denotes |
animal |
T244 |
647-653 |
NNS |
denotes |
models |
T245 |
654-656 |
IN |
denotes |
of |
T246 |
657-664 |
NN |
denotes |
amyloid |
T247 |
665-674 |
NN |
denotes |
pathology |
T248 |
675-679 |
VBP |
denotes |
have |
T249 |
680-683 |
RB |
denotes |
yet |
T250 |
684-688 |
VBN |
denotes |
been |
T251 |
699-701 |
TO |
denotes |
to |
T252 |
702-706 |
VB |
denotes |
test |
T253 |
707-711 |
DT |
denotes |
this |
T254 |
712-722 |
NN |
denotes |
hypothesis |
T255 |
722-723 |
. |
denotes |
. |
T256 |
723-745 |
sentence |
denotes |
Methods and Findings |
T257 |
725-732 |
NNS |
denotes |
Methods |
T258 |
733-736 |
CC |
denotes |
and |
T259 |
737-745 |
NNS |
denotes |
Findings |
T260 |
745-891 |
sentence |
denotes |
We have generated a transgenic mouse model that genetically mimics the arrest of Aβ production expected from treatment with secretase inhibitors. |
T261 |
746-748 |
PRP |
denotes |
We |
T262 |
754-763 |
VBN |
denotes |
generated |
T263 |
749-753 |
VBP |
denotes |
have |
T264 |
764-765 |
DT |
denotes |
a |
T265 |
783-788 |
NN |
denotes |
model |
T266 |
766-776 |
JJ |
denotes |
transgenic |
T267 |
777-782 |
NN |
denotes |
mouse |
T268 |
789-793 |
WDT |
denotes |
that |
T269 |
806-812 |
VBZ |
denotes |
mimics |
T270 |
794-805 |
RB |
denotes |
genetically |
T271 |
813-816 |
DT |
denotes |
the |
T272 |
817-823 |
NN |
denotes |
arrest |
T273 |
824-826 |
IN |
denotes |
of |
T274 |
827-829 |
NN |
denotes |
Aβ |
T275 |
830-840 |
NN |
denotes |
production |
T276 |
841-849 |
VBN |
denotes |
expected |
T277 |
850-854 |
IN |
denotes |
from |
T278 |
855-864 |
NN |
denotes |
treatment |
T279 |
865-869 |
IN |
denotes |
with |
T280 |
870-879 |
NN |
denotes |
secretase |
T281 |
880-890 |
NNS |
denotes |
inhibitors |
T282 |
890-891 |
. |
denotes |
. |
T283 |
891-977 |
sentence |
denotes |
These mice overexpress mutant APP from a vector that can be regulated by doxycycline. |
T284 |
892-897 |
DT |
denotes |
These |
T285 |
898-902 |
NNS |
denotes |
mice |
T286 |
903-914 |
VBP |
denotes |
overexpress |
T287 |
915-921 |
NN |
denotes |
mutant |
T288 |
922-925 |
NN |
denotes |
APP |
T289 |
926-930 |
IN |
denotes |
from |
T290 |
931-932 |
DT |
denotes |
a |
T291 |
933-939 |
NN |
denotes |
vector |
T292 |
940-944 |
WDT |
denotes |
that |
T293 |
952-961 |
VBN |
denotes |
regulated |
T294 |
945-948 |
MD |
denotes |
can |
T295 |
949-951 |
VB |
denotes |
be |
T296 |
962-964 |
IN |
denotes |
by |
T297 |
965-976 |
NN |
denotes |
doxycycline |
T298 |
976-977 |
. |
denotes |
. |
T299 |
977-1076 |
sentence |
denotes |
Under normal conditions, high-level expression of APP quickly induces fulminant amyloid pathology. |
T300 |
978-983 |
IN |
denotes |
Under |
T301 |
1040-1047 |
VBZ |
denotes |
induces |
T302 |
984-990 |
JJ |
denotes |
normal |
T303 |
991-1001 |
NNS |
denotes |
conditions |
T304 |
1001-1003 |
, |
denotes |
, |
T305 |
1003-1007 |
JJ |
denotes |
high |
T306 |
1008-1013 |
NN |
denotes |
level |
T307 |
1007-1008 |
HYPH |
denotes |
- |
T308 |
1014-1024 |
NN |
denotes |
expression |
T309 |
1025-1027 |
IN |
denotes |
of |
T310 |
1028-1031 |
NN |
denotes |
APP |
T311 |
1032-1039 |
RB |
denotes |
quickly |
T312 |
1048-1057 |
JJ |
denotes |
fulminant |
T313 |
1066-1075 |
NN |
denotes |
pathology |
T314 |
1058-1065 |
NN |
denotes |
amyloid |
T315 |
1075-1076 |
. |
denotes |
. |
T316 |
1076-1236 |
sentence |
denotes |
We show that doxycycline administration inhibits transgenic APP expression by greater than 95% and reduces Aβ production to levels found in nontransgenic mice. |
T317 |
1077-1079 |
PRP |
denotes |
We |
T318 |
1080-1084 |
VBP |
denotes |
show |
T319 |
1085-1089 |
IN |
denotes |
that |
T320 |
1117-1125 |
VBZ |
denotes |
inhibits |
T321 |
1090-1101 |
NN |
denotes |
doxycycline |
T322 |
1102-1116 |
NN |
denotes |
administration |
T323 |
1126-1136 |
JJ |
denotes |
transgenic |
T324 |
1141-1151 |
NN |
denotes |
expression |
T325 |
1137-1140 |
NN |
denotes |
APP |
T326 |
1152-1154 |
IN |
denotes |
by |
T327 |
1155-1162 |
JJR |
denotes |
greater |
T328 |
1168-1170 |
CD |
denotes |
95 |
T329 |
1163-1167 |
IN |
denotes |
than |
T330 |
1170-1171 |
NN |
denotes |
% |
T331 |
1172-1175 |
CC |
denotes |
and |
T332 |
1176-1183 |
VBZ |
denotes |
reduces |
T333 |
1184-1186 |
NN |
denotes |
Aβ |
T334 |
1187-1197 |
NN |
denotes |
production |
T335 |
1198-1200 |
IN |
denotes |
to |
T336 |
1201-1207 |
NNS |
denotes |
levels |
T337 |
1208-1213 |
VBN |
denotes |
found |
T338 |
1214-1216 |
IN |
denotes |
in |
T339 |
1217-1230 |
JJ |
denotes |
nontransgenic |
T340 |
1231-1235 |
NNS |
denotes |
mice |
T341 |
1235-1236 |
. |
denotes |
. |
T342 |
1236-1342 |
sentence |
denotes |
Suppression of transgenic Aβ synthesis in this model abruptly halts the progression of amyloid pathology. |
T343 |
1237-1248 |
NN |
denotes |
Suppression |
T344 |
1299-1304 |
VBZ |
denotes |
halts |
T345 |
1249-1251 |
IN |
denotes |
of |
T346 |
1252-1262 |
JJ |
denotes |
transgenic |
T347 |
1266-1275 |
NN |
denotes |
synthesis |
T348 |
1263-1265 |
NN |
denotes |
Aβ |
T349 |
1276-1278 |
IN |
denotes |
in |
T350 |
1279-1283 |
DT |
denotes |
this |
T351 |
1284-1289 |
NN |
denotes |
model |
T352 |
1290-1298 |
RB |
denotes |
abruptly |
T353 |
1305-1308 |
DT |
denotes |
the |
T354 |
1309-1320 |
NN |
denotes |
progression |
T355 |
1321-1323 |
IN |
denotes |
of |
T356 |
1324-1331 |
NN |
denotes |
amyloid |
T357 |
1332-1341 |
NN |
denotes |
pathology |
T358 |
1341-1342 |
. |
denotes |
. |
T359 |
1342-1495 |
sentence |
denotes |
However, formation and disaggregation of amyloid deposits appear to be in disequilibrium as the plaques require far longer to disperse than to assemble. |
T360 |
1343-1350 |
RB |
denotes |
However |
T361 |
1401-1407 |
VBP |
denotes |
appear |
T362 |
1350-1352 |
, |
denotes |
, |
T363 |
1352-1361 |
NN |
denotes |
formation |
T364 |
1362-1365 |
CC |
denotes |
and |
T365 |
1366-1380 |
NN |
denotes |
disaggregation |
T366 |
1381-1383 |
IN |
denotes |
of |
T367 |
1384-1391 |
NN |
denotes |
amyloid |
T368 |
1392-1400 |
NNS |
denotes |
deposits |
T369 |
1408-1410 |
TO |
denotes |
to |
T370 |
1411-1413 |
VB |
denotes |
be |
T371 |
1414-1416 |
IN |
denotes |
in |
T372 |
1417-1431 |
NN |
denotes |
disequilibrium |
T373 |
1432-1434 |
IN |
denotes |
as |
T374 |
1447-1454 |
VBP |
denotes |
require |
T375 |
1435-1438 |
DT |
denotes |
the |
T376 |
1439-1446 |
NNS |
denotes |
plaques |
T377 |
1455-1458 |
RB |
denotes |
far |
T378 |
1459-1465 |
RBR |
denotes |
longer |
T379 |
1466-1468 |
TO |
denotes |
to |
T380 |
1469-1477 |
VB |
denotes |
disperse |
T381 |
1478-1482 |
IN |
denotes |
than |
T382 |
1486-1494 |
VB |
denotes |
assemble |
T383 |
1483-1485 |
TO |
denotes |
to |
T384 |
1494-1495 |
. |
denotes |
. |
T385 |
1495-1667 |
sentence |
denotes |
Mice in which APP synthesis was suppressed for as long as 6 mo after the formation of Aβ deposits retain a considerable amyloid load, with little sign of active clearance. |
T386 |
1496-1500 |
NNS |
denotes |
Mice |
T387 |
1594-1600 |
VBP |
denotes |
retain |
T388 |
1501-1503 |
IN |
denotes |
in |
T389 |
1528-1538 |
VBN |
denotes |
suppressed |
T390 |
1504-1509 |
WDT |
denotes |
which |
T391 |
1510-1513 |
NN |
denotes |
APP |
T392 |
1514-1523 |
NN |
denotes |
synthesis |
T393 |
1524-1527 |
VBD |
denotes |
was |
T394 |
1539-1542 |
IN |
denotes |
for |
T395 |
1543-1545 |
RB |
denotes |
as |
T396 |
1554-1555 |
CD |
denotes |
6 |
T397 |
1546-1550 |
JJ |
denotes |
long |
T398 |
1551-1553 |
IN |
denotes |
as |
T399 |
1556-1558 |
NN |
denotes |
mo |
T400 |
1559-1564 |
IN |
denotes |
after |
T401 |
1565-1568 |
DT |
denotes |
the |
T402 |
1569-1578 |
NN |
denotes |
formation |
T403 |
1579-1581 |
IN |
denotes |
of |
T404 |
1582-1584 |
NN |
denotes |
Aβ |
T405 |
1585-1593 |
NNS |
denotes |
deposits |
T406 |
1601-1602 |
DT |
denotes |
a |
T407 |
1624-1628 |
NN |
denotes |
load |
T408 |
1603-1615 |
JJ |
denotes |
considerable |
T409 |
1616-1623 |
NN |
denotes |
amyloid |
T410 |
1628-1630 |
, |
denotes |
, |
T411 |
1630-1634 |
IN |
denotes |
with |
T412 |
1635-1641 |
JJ |
denotes |
little |
T413 |
1642-1646 |
NN |
denotes |
sign |
T414 |
1647-1649 |
IN |
denotes |
of |
T415 |
1650-1656 |
JJ |
denotes |
active |
T416 |
1657-1666 |
NN |
denotes |
clearance |
T417 |
1666-1667 |
. |
denotes |
. |
T418 |
1667-1679 |
sentence |
denotes |
Conclusion |
T419 |
1669-1679 |
NN |
denotes |
Conclusion |
T420 |
1679-1811 |
sentence |
denotes |
This study demonstrates that amyloid lesions in transgenic mice are highly stable structures in vivo that are slow to disaggregate. |
T421 |
1680-1684 |
DT |
denotes |
This |
T422 |
1685-1690 |
NN |
denotes |
study |
T423 |
1691-1703 |
VBZ |
denotes |
demonstrates |
T424 |
1704-1708 |
IN |
denotes |
that |
T425 |
1744-1747 |
VBP |
denotes |
are |
T426 |
1709-1716 |
NN |
denotes |
amyloid |
T427 |
1717-1724 |
NNS |
denotes |
lesions |
T428 |
1725-1727 |
IN |
denotes |
in |
T429 |
1728-1738 |
JJ |
denotes |
transgenic |
T430 |
1739-1743 |
NNS |
denotes |
mice |
T431 |
1748-1754 |
RB |
denotes |
highly |
T432 |
1755-1761 |
JJ |
denotes |
stable |
T433 |
1762-1772 |
NNS |
denotes |
structures |
T434 |
1773-1775 |
FW |
denotes |
in |
T435 |
1776-1780 |
FW |
denotes |
vivo |
T436 |
1781-1785 |
WDT |
denotes |
that |
T437 |
1786-1789 |
VBP |
denotes |
are |
T438 |
1790-1794 |
JJ |
denotes |
slow |
T439 |
1795-1797 |
TO |
denotes |
to |
T440 |
1798-1810 |
VB |
denotes |
disaggregate |
T441 |
1810-1811 |
. |
denotes |
. |
T442 |
1811-2079 |
sentence |
denotes |
Our findings suggest that arresting Aβ production in patients with Alzheimer disease should halt the progression of pathology, but that early treatment may be imperative, as it appears that amyloid deposits, once formed, will require additional intervention to clear. |
T443 |
1812-1815 |
PRP$ |
denotes |
Our |
T444 |
1816-1824 |
NNS |
denotes |
findings |
T445 |
1825-1832 |
VBP |
denotes |
suggest |
T446 |
1833-1837 |
IN |
denotes |
that |
T447 |
1904-1908 |
VB |
denotes |
halt |
T448 |
1838-1847 |
VBG |
denotes |
arresting |
T449 |
1848-1850 |
NN |
denotes |
Aβ |
T450 |
1851-1861 |
NN |
denotes |
production |
T451 |
1862-1864 |
IN |
denotes |
in |
T452 |
1865-1873 |
NNS |
denotes |
patients |
T453 |
1874-1878 |
IN |
denotes |
with |
T454 |
1879-1888 |
NNP |
denotes |
Alzheimer |
T455 |
1889-1896 |
NN |
denotes |
disease |
T456 |
1897-1903 |
MD |
denotes |
should |
T457 |
1909-1912 |
DT |
denotes |
the |
T458 |
1913-1924 |
NN |
denotes |
progression |
T459 |
1925-1927 |
IN |
denotes |
of |
T460 |
1928-1937 |
NN |
denotes |
pathology |
T461 |
1937-1939 |
, |
denotes |
, |
T462 |
1939-1942 |
CC |
denotes |
but |
T463 |
1943-1947 |
IN |
denotes |
that |
T464 |
1968-1970 |
VB |
denotes |
be |
T465 |
1948-1953 |
JJ |
denotes |
early |
T466 |
1954-1963 |
NN |
denotes |
treatment |
T467 |
1964-1967 |
MD |
denotes |
may |
T468 |
1971-1981 |
JJ |
denotes |
imperative |
T469 |
1981-1983 |
, |
denotes |
, |
T470 |
1983-1985 |
IN |
denotes |
as |
T471 |
1989-1996 |
VBZ |
denotes |
appears |
T472 |
1986-1988 |
PRP |
denotes |
it |
T473 |
1997-2001 |
IN |
denotes |
that |
T474 |
2038-2045 |
VB |
denotes |
require |
T475 |
2002-2009 |
NN |
denotes |
amyloid |
T476 |
2010-2018 |
NNS |
denotes |
deposits |
T477 |
2018-2020 |
, |
denotes |
, |
T478 |
2020-2024 |
IN |
denotes |
once |
T479 |
2025-2031 |
VBN |
denotes |
formed |
T480 |
2031-2033 |
, |
denotes |
, |
T481 |
2033-2037 |
MD |
denotes |
will |
T482 |
2046-2056 |
JJ |
denotes |
additional |
T483 |
2057-2069 |
NN |
denotes |
intervention |
T484 |
2070-2072 |
TO |
denotes |
to |
T485 |
2073-2078 |
VB |
denotes |
clear |
T486 |
2078-2079 |
. |
denotes |
. |
T706 |
2264-2268 |
IN |
denotes |
Over |
T707 |
2269-2270 |
DT |
denotes |
a |
T708 |
2271-2277 |
NN |
denotes |
decade |
T709 |
2278-2281 |
RB |
denotes |
ago |
T710 |
2313-2322 |
VBD |
denotes |
predicted |
T711 |
2282-2285 |
DT |
denotes |
the |
T712 |
2302-2312 |
NN |
denotes |
hypothesis |
T713 |
2286-2293 |
NN |
denotes |
amyloid |
T714 |
2294-2301 |
NN |
denotes |
cascade |
T715 |
2323-2327 |
IN |
denotes |
that |
T716 |
2371-2375 |
VBP |
denotes |
lead |
T717 |
2328-2337 |
VBN |
denotes |
increased |
T718 |
2338-2344 |
NNS |
denotes |
levels |
T719 |
2345-2347 |
IN |
denotes |
of |
T720 |
2348-2355 |
NN |
denotes |
amyloid |
T721 |
2356-2357 |
NN |
denotes |
β |
T722 |
2355-2356 |
HYPH |
denotes |
- |
T723 |
2363-2370 |
NN |
denotes |
peptide |
T724 |
2358-2359 |
-LRB- |
denotes |
( |
T725 |
2359-2361 |
NN |
denotes |
Aβ |
T726 |
2361-2362 |
-RRB- |
denotes |
) |
T727 |
2376-2378 |
IN |
denotes |
to |
T728 |
2379-2388 |
JJ |
denotes |
secondary |
T729 |
2389-2400 |
NNS |
denotes |
pathologies |
T730 |
2401-2405 |
WDT |
denotes |
that |
T731 |
2417-2426 |
VBP |
denotes |
culminate |
T732 |
2406-2416 |
RB |
denotes |
ultimately |
T733 |
2427-2429 |
IN |
denotes |
in |
T734 |
2430-2433 |
DT |
denotes |
the |
T735 |
2434-2439 |
NN |
denotes |
onset |
T736 |
2440-2442 |
IN |
denotes |
of |
T737 |
2443-2452 |
NNP |
denotes |
Alzheimer |
T738 |
2453-2460 |
NN |
denotes |
disease |
T739 |
2461-2462 |
-LRB- |
denotes |
( |
T740 |
2462-2464 |
NN |
denotes |
AD |
T741 |
2464-2465 |
-RRB- |
denotes |
) |
T742 |
2466-2467 |
-LRB- |
denotes |
[ |
T743 |
2467-2468 |
CD |
denotes |
1 |
T744 |
2468-2469 |
-RRB- |
denotes |
] |
T745 |
2469-2470 |
. |
denotes |
. |
T746 |
2470-2770 |
sentence |
denotes |
Early support for this hypothesis came from genetic studies linking early-onset AD to mutations in the amyloid precursor protein (APP), from which Aβ is derived, and presenilins 1 and 2, which are interchangeable components of a endoprotease complex that releases Aβ from APP (for review see [2,3]). |
T747 |
2471-2476 |
JJ |
denotes |
Early |
T748 |
2477-2484 |
NN |
denotes |
support |
T749 |
2505-2509 |
VBD |
denotes |
came |
T750 |
2485-2488 |
IN |
denotes |
for |
T751 |
2489-2493 |
DT |
denotes |
this |
T752 |
2494-2504 |
NN |
denotes |
hypothesis |
T753 |
2510-2514 |
IN |
denotes |
from |
T754 |
2515-2522 |
JJ |
denotes |
genetic |
T755 |
2523-2530 |
NNS |
denotes |
studies |
T756 |
2531-2538 |
VBG |
denotes |
linking |
T757 |
2539-2544 |
JJ |
denotes |
early |
T758 |
2545-2550 |
NN |
denotes |
onset |
T759 |
2544-2545 |
HYPH |
denotes |
- |
T760 |
2551-2553 |
NN |
denotes |
AD |
T761 |
2554-2556 |
IN |
denotes |
to |
T762 |
2557-2566 |
NNS |
denotes |
mutations |
T763 |
2567-2569 |
IN |
denotes |
in |
T764 |
2570-2573 |
DT |
denotes |
the |
T765 |
2592-2599 |
NN |
denotes |
protein |
T766 |
2574-2581 |
NN |
denotes |
amyloid |
T767 |
2582-2591 |
NN |
denotes |
precursor |
T768 |
2600-2601 |
-LRB- |
denotes |
( |
T769 |
2601-2604 |
NN |
denotes |
APP |
T770 |
2604-2605 |
-RRB- |
denotes |
) |
T771 |
2605-2607 |
, |
denotes |
, |
T772 |
2607-2611 |
IN |
denotes |
from |
T773 |
2624-2631 |
VBN |
denotes |
derived |
T774 |
2612-2617 |
WDT |
denotes |
which |
T775 |
2618-2620 |
NN |
denotes |
Aβ |
T776 |
2621-2623 |
VBZ |
denotes |
is |
T777 |
2631-2633 |
, |
denotes |
, |
T778 |
2633-2636 |
CC |
denotes |
and |
T779 |
2637-2648 |
NNS |
denotes |
presenilins |
T780 |
2649-2650 |
CD |
denotes |
1 |
T781 |
2651-2654 |
CC |
denotes |
and |
T782 |
2655-2656 |
CD |
denotes |
2 |
T783 |
2656-2658 |
, |
denotes |
, |
T784 |
2658-2663 |
WDT |
denotes |
which |
T785 |
2664-2667 |
VBP |
denotes |
are |
T786 |
2668-2683 |
JJ |
denotes |
interchangeable |
T787 |
2684-2694 |
NNS |
denotes |
components |
T788 |
2695-2697 |
IN |
denotes |
of |
T789 |
2698-2699 |
DT |
denotes |
a |
T790 |
2713-2720 |
NN |
denotes |
complex |
T791 |
2700-2712 |
NN |
denotes |
endoprotease |
T792 |
2721-2725 |
WDT |
denotes |
that |
T793 |
2726-2734 |
VBZ |
denotes |
releases |
T794 |
2735-2737 |
NN |
denotes |
Aβ |
T795 |
2738-2742 |
IN |
denotes |
from |
T796 |
2743-2746 |
NN |
denotes |
APP |
T797 |
2747-2748 |
-LRB- |
denotes |
( |
T798 |
2759-2762 |
VBP |
denotes |
see |
T799 |
2748-2751 |
IN |
denotes |
for |
T800 |
2752-2758 |
NN |
denotes |
review |
T801 |
2763-2764 |
-LRB- |
denotes |
[ |
T802 |
2764-2765 |
CD |
denotes |
2 |
T803 |
2766-2767 |
CD |
denotes |
3 |
T804 |
2765-2766 |
, |
denotes |
, |
T805 |
2767-2768 |
-RRB- |
denotes |
] |
T806 |
2768-2769 |
-RRB- |
denotes |
) |
T807 |
2769-2770 |
. |
denotes |
. |
T808 |
2770-2984 |
sentence |
denotes |
If, as predicted, overproduction of Aβ initiates the cascade of events leading to disease, then therapeutic strategies that lower Aβ levels should either arrest or reverse the progression from peptide to dementia. |
T809 |
2771-2773 |
IN |
denotes |
If |
T810 |
2810-2819 |
VBZ |
denotes |
initiates |
T811 |
2773-2775 |
, |
denotes |
, |
T812 |
2775-2777 |
IN |
denotes |
as |
T813 |
2778-2787 |
VBN |
denotes |
predicted |
T814 |
2787-2789 |
, |
denotes |
, |
T815 |
2789-2803 |
NN |
denotes |
overproduction |
T816 |
2804-2806 |
IN |
denotes |
of |
T817 |
2807-2809 |
NN |
denotes |
Aβ |
T818 |
2925-2931 |
VB |
denotes |
arrest |
T819 |
2820-2823 |
DT |
denotes |
the |
T820 |
2824-2831 |
NN |
denotes |
cascade |
T821 |
2832-2834 |
IN |
denotes |
of |
T822 |
2835-2841 |
NNS |
denotes |
events |
T823 |
2842-2849 |
VBG |
denotes |
leading |
T824 |
2850-2852 |
IN |
denotes |
to |
T825 |
2853-2860 |
NN |
denotes |
disease |
T826 |
2860-2862 |
, |
denotes |
, |
T827 |
2862-2866 |
RB |
denotes |
then |
T828 |
2867-2878 |
JJ |
denotes |
therapeutic |
T829 |
2879-2889 |
NNS |
denotes |
strategies |
T830 |
2890-2894 |
WDT |
denotes |
that |
T831 |
2895-2900 |
VBP |
denotes |
lower |
T832 |
2901-2903 |
NN |
denotes |
Aβ |
T833 |
2904-2910 |
NNS |
denotes |
levels |
T834 |
2911-2917 |
MD |
denotes |
should |
T835 |
2918-2924 |
CC |
denotes |
either |
T836 |
2932-2934 |
CC |
denotes |
or |
T837 |
2935-2942 |
VB |
denotes |
reverse |
T838 |
2943-2946 |
DT |
denotes |
the |
T839 |
2947-2958 |
NN |
denotes |
progression |
T840 |
2959-2963 |
IN |
denotes |
from |
T841 |
2964-2971 |
NN |
denotes |
peptide |
T842 |
2972-2974 |
IN |
denotes |
to |
T843 |
2975-2983 |
NN |
denotes |
dementia |
T844 |
2983-2984 |
. |
denotes |
. |
T845 |
2984-3196 |
sentence |
denotes |
Early evidence from clinical trials of antibody-mediated clearance, one of the first Aβ-lowering approaches tested in humans, suggested that treatments designed to reduce amyloid burden may indeed be beneficial. |
T846 |
2985-2990 |
JJ |
denotes |
Early |
T847 |
2991-2999 |
NN |
denotes |
evidence |
T848 |
3111-3120 |
VBD |
denotes |
suggested |
T849 |
3000-3004 |
IN |
denotes |
from |
T850 |
3005-3013 |
JJ |
denotes |
clinical |
T851 |
3014-3020 |
NNS |
denotes |
trials |
T852 |
3021-3023 |
IN |
denotes |
of |
T853 |
3024-3032 |
NN |
denotes |
antibody |
T854 |
3033-3041 |
VBN |
denotes |
mediated |
T855 |
3032-3033 |
HYPH |
denotes |
- |
T856 |
3042-3051 |
NN |
denotes |
clearance |
T857 |
3051-3053 |
, |
denotes |
, |
T858 |
3053-3056 |
CD |
denotes |
one |
T859 |
3057-3059 |
IN |
denotes |
of |
T860 |
3060-3063 |
DT |
denotes |
the |
T861 |
3082-3092 |
NNS |
denotes |
approaches |
T862 |
3064-3069 |
JJ |
denotes |
first |
T863 |
3070-3072 |
NN |
denotes |
Aβ |
T864 |
3073-3081 |
VBG |
denotes |
lowering |
T865 |
3072-3073 |
HYPH |
denotes |
- |
T866 |
3093-3099 |
VBN |
denotes |
tested |
T867 |
3100-3102 |
IN |
denotes |
in |
T868 |
3103-3109 |
NNS |
denotes |
humans |
T869 |
3109-3111 |
, |
denotes |
, |
T870 |
3121-3125 |
IN |
denotes |
that |
T871 |
3182-3184 |
VB |
denotes |
be |
T872 |
3126-3136 |
NNS |
denotes |
treatments |
T873 |
3137-3145 |
VBN |
denotes |
designed |
T874 |
3146-3148 |
TO |
denotes |
to |
T875 |
3149-3155 |
VB |
denotes |
reduce |
T876 |
3156-3163 |
NN |
denotes |
amyloid |
T877 |
3164-3170 |
NN |
denotes |
burden |
T878 |
3171-3174 |
MD |
denotes |
may |
T879 |
3175-3181 |
RB |
denotes |
indeed |
T880 |
3185-3195 |
JJ |
denotes |
beneficial |
T881 |
3195-3196 |
. |
denotes |
. |
T882 |
3196-3488 |
sentence |
denotes |
Although the trials were halted because of adverse effects in a subset of volunteers [4,5], further analysis of several patients found evidence that amyloid pathology, and to a lesser degree cognitive function, was improved in proportion to the patient's titer of Aβ-specific antibody [6,7]. |
T883 |
3197-3205 |
IN |
denotes |
Although |
T884 |
3222-3228 |
VBN |
denotes |
halted |
T885 |
3206-3209 |
DT |
denotes |
the |
T886 |
3210-3216 |
NNS |
denotes |
trials |
T887 |
3217-3221 |
VBD |
denotes |
were |
T888 |
3326-3331 |
VBD |
denotes |
found |
T889 |
3229-3236 |
IN |
denotes |
because |
T890 |
3237-3239 |
IN |
denotes |
of |
T891 |
3240-3247 |
JJ |
denotes |
adverse |
T892 |
3248-3255 |
NNS |
denotes |
effects |
T893 |
3256-3258 |
IN |
denotes |
in |
T894 |
3259-3260 |
DT |
denotes |
a |
T895 |
3261-3267 |
NN |
denotes |
subset |
T896 |
3268-3270 |
IN |
denotes |
of |
T897 |
3271-3281 |
NNS |
denotes |
volunteers |
T898 |
3282-3283 |
-LRB- |
denotes |
[ |
T899 |
3285-3286 |
CD |
denotes |
5 |
T900 |
3283-3284 |
CD |
denotes |
4 |
T901 |
3284-3285 |
, |
denotes |
, |
T902 |
3286-3287 |
-RRB- |
denotes |
] |
T903 |
3287-3289 |
, |
denotes |
, |
T904 |
3289-3296 |
JJ |
denotes |
further |
T905 |
3297-3305 |
NN |
denotes |
analysis |
T906 |
3306-3308 |
IN |
denotes |
of |
T907 |
3309-3316 |
JJ |
denotes |
several |
T908 |
3317-3325 |
NNS |
denotes |
patients |
T909 |
3332-3340 |
NN |
denotes |
evidence |
T910 |
3341-3345 |
IN |
denotes |
that |
T911 |
3412-3420 |
VBN |
denotes |
improved |
T912 |
3346-3353 |
NN |
denotes |
amyloid |
T913 |
3354-3363 |
NN |
denotes |
pathology |
T914 |
3363-3365 |
, |
denotes |
, |
T915 |
3365-3368 |
CC |
denotes |
and |
T916 |
3369-3371 |
IN |
denotes |
to |
T917 |
3398-3406 |
NN |
denotes |
function |
T918 |
3372-3373 |
DT |
denotes |
a |
T919 |
3381-3387 |
NN |
denotes |
degree |
T920 |
3374-3380 |
JJR |
denotes |
lesser |
T921 |
3388-3397 |
JJ |
denotes |
cognitive |
T922 |
3406-3408 |
, |
denotes |
, |
T923 |
3408-3411 |
VBD |
denotes |
was |
T924 |
3421-3423 |
IN |
denotes |
in |
T925 |
3424-3434 |
NN |
denotes |
proportion |
T926 |
3435-3437 |
IN |
denotes |
to |
T927 |
3438-3441 |
DT |
denotes |
the |
T928 |
3442-3449 |
NN |
denotes |
patient |
T929 |
3452-3457 |
NN |
denotes |
titer |
T930 |
3449-3451 |
POS |
denotes |
's |
T931 |
3458-3460 |
IN |
denotes |
of |
T932 |
3461-3463 |
NN |
denotes |
Aβ |
T933 |
3464-3472 |
JJ |
denotes |
specific |
T934 |
3463-3464 |
HYPH |
denotes |
- |
T935 |
3473-3481 |
NN |
denotes |
antibody |
T936 |
3482-3483 |
-LRB- |
denotes |
[ |
T937 |
3485-3486 |
CD |
denotes |
7 |
T938 |
3483-3484 |
CD |
denotes |
6 |
T939 |
3484-3485 |
, |
denotes |
, |
T940 |
3486-3487 |
-RRB- |
denotes |
] |
T941 |
3487-3488 |
. |
denotes |
. |
T942 |
3488-3677 |
sentence |
denotes |
While this approach is promising, constant exposure to antibodies that recognize an epitope highly enriched in the brain may have unexpected side effects that will limit its long-term use. |
T943 |
3489-3494 |
IN |
denotes |
While |
T944 |
3509-3511 |
VBZ |
denotes |
is |
T945 |
3495-3499 |
DT |
denotes |
this |
T946 |
3500-3508 |
NN |
denotes |
approach |
T947 |
3614-3618 |
VB |
denotes |
have |
T948 |
3512-3521 |
JJ |
denotes |
promising |
T949 |
3521-3523 |
, |
denotes |
, |
T950 |
3523-3531 |
JJ |
denotes |
constant |
T951 |
3532-3540 |
NN |
denotes |
exposure |
T952 |
3541-3543 |
IN |
denotes |
to |
T953 |
3544-3554 |
NNS |
denotes |
antibodies |
T954 |
3555-3559 |
WDT |
denotes |
that |
T955 |
3560-3569 |
VBP |
denotes |
recognize |
T956 |
3570-3572 |
DT |
denotes |
an |
T957 |
3573-3580 |
NN |
denotes |
epitope |
T958 |
3581-3587 |
RB |
denotes |
highly |
T959 |
3588-3596 |
VBN |
denotes |
enriched |
T960 |
3597-3599 |
IN |
denotes |
in |
T961 |
3600-3603 |
DT |
denotes |
the |
T962 |
3604-3609 |
NN |
denotes |
brain |
T963 |
3610-3613 |
MD |
denotes |
may |
T964 |
3619-3629 |
JJ |
denotes |
unexpected |
T965 |
3635-3642 |
NNS |
denotes |
effects |
T966 |
3630-3634 |
NN |
denotes |
side |
T967 |
3643-3647 |
WDT |
denotes |
that |
T968 |
3653-3658 |
VB |
denotes |
limit |
T969 |
3648-3652 |
MD |
denotes |
will |
T970 |
3659-3662 |
PRP$ |
denotes |
its |
T971 |
3673-3676 |
NN |
denotes |
use |
T972 |
3663-3667 |
JJ |
denotes |
long |
T973 |
3668-3672 |
NN |
denotes |
term |
T974 |
3667-3668 |
HYPH |
denotes |
- |
T975 |
3676-3677 |
. |
denotes |
. |
T976 |
3677-3843 |
sentence |
denotes |
An alternative approach that is being actively pursued for future treatment of AD seeks to lower Aβ levels by limiting its production from the precursor protein APP. |
T977 |
3678-3680 |
DT |
denotes |
An |
T978 |
3693-3701 |
NN |
denotes |
approach |
T979 |
3681-3692 |
JJ |
denotes |
alternative |
T980 |
3760-3765 |
VBZ |
denotes |
seeks |
T981 |
3702-3706 |
WDT |
denotes |
that |
T982 |
3725-3732 |
VBN |
denotes |
pursued |
T983 |
3707-3709 |
VBZ |
denotes |
is |
T984 |
3710-3715 |
VBG |
denotes |
being |
T985 |
3716-3724 |
RB |
denotes |
actively |
T986 |
3733-3736 |
IN |
denotes |
for |
T987 |
3737-3743 |
JJ |
denotes |
future |
T988 |
3744-3753 |
NN |
denotes |
treatment |
T989 |
3754-3756 |
IN |
denotes |
of |
T990 |
3757-3759 |
NN |
denotes |
AD |
T991 |
3766-3768 |
TO |
denotes |
to |
T992 |
3769-3774 |
VB |
denotes |
lower |
T993 |
3775-3777 |
NN |
denotes |
Aβ |
T994 |
3778-3784 |
NNS |
denotes |
levels |
T995 |
3785-3787 |
IN |
denotes |
by |
T996 |
3788-3796 |
VBG |
denotes |
limiting |
T997 |
3797-3800 |
PRP$ |
denotes |
its |
T998 |
3801-3811 |
NN |
denotes |
production |
T999 |
3812-3816 |
IN |
denotes |
from |
T1000 |
3817-3820 |
DT |
denotes |
the |
T1001 |
3831-3838 |
NN |
denotes |
protein |
T1002 |
3821-3830 |
NN |
denotes |
precursor |
T1003 |
3839-3842 |
NN |
denotes |
APP |
T1004 |
3842-3843 |
. |
denotes |
. |
T1005 |
3843-4032 |
sentence |
denotes |
Peptide Aβ is released from APP by the action of two enzymes, the β-APP cleaving enzyme 1 (BACE1) and γ-secretase, which cleave the holoprotein at the N- and C-termini of Aβ, respectively. |
T1006 |
3844-3851 |
NN |
denotes |
Peptide |
T1007 |
3852-3854 |
NN |
denotes |
Aβ |
T1008 |
3858-3866 |
VBN |
denotes |
released |
T1009 |
3855-3857 |
VBZ |
denotes |
is |
T1010 |
3867-3871 |
IN |
denotes |
from |
T1011 |
3872-3875 |
NN |
denotes |
APP |
T1012 |
3876-3878 |
IN |
denotes |
by |
T1013 |
3879-3882 |
DT |
denotes |
the |
T1014 |
3883-3889 |
NN |
denotes |
action |
T1015 |
3890-3892 |
IN |
denotes |
of |
T1016 |
3893-3896 |
CD |
denotes |
two |
T1017 |
3897-3904 |
NNS |
denotes |
enzymes |
T1018 |
3904-3906 |
, |
denotes |
, |
T1019 |
3906-3909 |
DT |
denotes |
the |
T1020 |
3925-3931 |
NN |
denotes |
enzyme |
T1021 |
3910-3911 |
NN |
denotes |
β |
T1022 |
3912-3915 |
NN |
denotes |
APP |
T1023 |
3911-3912 |
HYPH |
denotes |
- |
T1024 |
3916-3924 |
VBG |
denotes |
cleaving |
T1025 |
3932-3933 |
CD |
denotes |
1 |
T1026 |
3934-3935 |
-LRB- |
denotes |
( |
T1027 |
3935-3940 |
NN |
denotes |
BACE1 |
T1028 |
3940-3941 |
-RRB- |
denotes |
) |
T1029 |
3942-3945 |
CC |
denotes |
and |
T1030 |
3946-3947 |
SYM |
denotes |
γ |
T1031 |
3948-3957 |
NN |
denotes |
secretase |
T1032 |
3947-3948 |
HYPH |
denotes |
- |
T1033 |
3957-3959 |
, |
denotes |
, |
T1034 |
3959-3964 |
WDT |
denotes |
which |
T1035 |
3965-3971 |
VBP |
denotes |
cleave |
T1036 |
3972-3975 |
DT |
denotes |
the |
T1037 |
3976-3987 |
NN |
denotes |
holoprotein |
T1038 |
3988-3990 |
IN |
denotes |
at |
T1039 |
3991-3994 |
DT |
denotes |
the |
T1040 |
4004-4011 |
NNS |
denotes |
termini |
T1041 |
3995-3996 |
NN |
denotes |
N |
T1042 |
3996-3997 |
HYPH |
denotes |
- |
T1043 |
3998-4001 |
CC |
denotes |
and |
T1044 |
4002-4003 |
NN |
denotes |
C |
T1045 |
4003-4004 |
HYPH |
denotes |
- |
T1046 |
4012-4014 |
IN |
denotes |
of |
T1047 |
4015-4017 |
NN |
denotes |
Aβ |
T1048 |
4017-4019 |
, |
denotes |
, |
T1049 |
4019-4031 |
RB |
denotes |
respectively |
T1050 |
4031-4032 |
. |
denotes |
. |
T1051 |
4032-4196 |
sentence |
denotes |
Several inhibitors of γ-secretase have already been produced [8,9], and small molecule inhibitors of β-APP cleaving enzyme 1 are currently being developed [10,11]. |
T1052 |
4033-4040 |
JJ |
denotes |
Several |
T1053 |
4041-4051 |
NNS |
denotes |
inhibitors |
T1054 |
4085-4093 |
VBN |
denotes |
produced |
T1055 |
4052-4054 |
IN |
denotes |
of |
T1056 |
4055-4056 |
SYM |
denotes |
γ |
T1057 |
4057-4066 |
NN |
denotes |
secretase |
T1058 |
4056-4057 |
HYPH |
denotes |
- |
T1059 |
4067-4071 |
VBP |
denotes |
have |
T1060 |
4072-4079 |
RB |
denotes |
already |
T1061 |
4080-4084 |
VBN |
denotes |
been |
T1062 |
4094-4095 |
-LRB- |
denotes |
[ |
T1063 |
4097-4098 |
CD |
denotes |
9 |
T1064 |
4095-4096 |
CD |
denotes |
8 |
T1065 |
4096-4097 |
, |
denotes |
, |
T1066 |
4098-4099 |
-RRB- |
denotes |
] |
T1067 |
4099-4101 |
, |
denotes |
, |
T1068 |
4101-4104 |
CC |
denotes |
and |
T1069 |
4105-4110 |
JJ |
denotes |
small |
T1070 |
4120-4130 |
NNS |
denotes |
inhibitors |
T1071 |
4111-4119 |
NN |
denotes |
molecule |
T1072 |
4178-4187 |
VBN |
denotes |
developed |
T1073 |
4131-4133 |
IN |
denotes |
of |
T1074 |
4134-4135 |
NN |
denotes |
β |
T1075 |
4136-4139 |
NN |
denotes |
APP |
T1076 |
4135-4136 |
HYPH |
denotes |
- |
T1077 |
4140-4148 |
VBG |
denotes |
cleaving |
T1078 |
4149-4155 |
NN |
denotes |
enzyme |
T1079 |
4156-4157 |
CD |
denotes |
1 |
T1080 |
4158-4161 |
VBP |
denotes |
are |
T1081 |
4162-4171 |
RB |
denotes |
currently |
T1082 |
4172-4177 |
VBG |
denotes |
being |
T1083 |
4188-4189 |
-LRB- |
denotes |
[ |
T1084 |
4192-4194 |
CD |
denotes |
11 |
T1085 |
4189-4191 |
CD |
denotes |
10 |
T1086 |
4191-4192 |
, |
denotes |
, |
T1087 |
4194-4195 |
-RRB- |
denotes |
] |
T1088 |
4195-4196 |
. |
denotes |
. |
T1089 |
4196-4308 |
sentence |
denotes |
The long-term effectiveness of this approach in either humans or model systems, however, has not been reported. |
T1090 |
4197-4200 |
DT |
denotes |
The |
T1091 |
4211-4224 |
NN |
denotes |
effectiveness |
T1092 |
4201-4205 |
JJ |
denotes |
long |
T1093 |
4206-4210 |
NN |
denotes |
term |
T1094 |
4205-4206 |
HYPH |
denotes |
- |
T1095 |
4299-4307 |
VBN |
denotes |
reported |
T1096 |
4225-4227 |
IN |
denotes |
of |
T1097 |
4228-4232 |
DT |
denotes |
this |
T1098 |
4233-4241 |
NN |
denotes |
approach |
T1099 |
4242-4244 |
IN |
denotes |
in |
T1100 |
4245-4251 |
CC |
denotes |
either |
T1101 |
4252-4258 |
NNS |
denotes |
humans |
T1102 |
4259-4261 |
CC |
denotes |
or |
T1103 |
4262-4267 |
NN |
denotes |
model |
T1104 |
4268-4275 |
NNS |
denotes |
systems |
T1105 |
4275-4277 |
, |
denotes |
, |
T1106 |
4277-4284 |
RB |
denotes |
however |
T1107 |
4284-4286 |
, |
denotes |
, |
T1108 |
4286-4289 |
VBZ |
denotes |
has |
T1109 |
4290-4293 |
RB |
denotes |
not |
T1110 |
4294-4298 |
VBN |
denotes |
been |
T1111 |
4307-4308 |
. |
denotes |
. |
T1112 |
4308-4604 |
sentence |
denotes |
Although loss of β-APP cleaving enzyme 1 function can prevent the development of plaques in transgenic mouse models for AD (F. Laird, H. Cai, P. C. Wong, personal communication), it is not known whether the brain can clear pre-existing amyloid deposits once production of Aβ has been suppressed. |
T1113 |
4309-4317 |
IN |
denotes |
Although |
T1114 |
4363-4370 |
VB |
denotes |
prevent |
T1115 |
4318-4322 |
NN |
denotes |
loss |
T1116 |
4323-4325 |
IN |
denotes |
of |
T1117 |
4326-4327 |
NN |
denotes |
β |
T1118 |
4328-4331 |
NN |
denotes |
APP |
T1119 |
4327-4328 |
HYPH |
denotes |
- |
T1120 |
4332-4340 |
VBG |
denotes |
cleaving |
T1121 |
4350-4358 |
NN |
denotes |
function |
T1122 |
4341-4347 |
NN |
denotes |
enzyme |
T1123 |
4348-4349 |
CD |
denotes |
1 |
T1124 |
4359-4362 |
MD |
denotes |
can |
T1125 |
4498-4503 |
VBN |
denotes |
known |
T1126 |
4371-4374 |
DT |
denotes |
the |
T1127 |
4375-4386 |
NN |
denotes |
development |
T1128 |
4387-4389 |
IN |
denotes |
of |
T1129 |
4390-4397 |
NNS |
denotes |
plaques |
T1130 |
4398-4400 |
IN |
denotes |
in |
T1131 |
4401-4411 |
JJ |
denotes |
transgenic |
T1132 |
4418-4424 |
NNS |
denotes |
models |
T1133 |
4412-4417 |
NN |
denotes |
mouse |
T1134 |
4425-4428 |
IN |
denotes |
for |
T1135 |
4429-4431 |
NN |
denotes |
AD |
T1136 |
4432-4433 |
-LRB- |
denotes |
( |
T1137 |
4433-4435 |
NNP |
denotes |
F. |
T1138 |
4436-4441 |
NNP |
denotes |
Laird |
T1139 |
4441-4443 |
, |
denotes |
, |
T1140 |
4443-4445 |
NNP |
denotes |
H. |
T1141 |
4446-4449 |
NNP |
denotes |
Cai |
T1142 |
4449-4451 |
, |
denotes |
, |
T1143 |
4451-4453 |
NNP |
denotes |
P. |
T1144 |
4454-4456 |
NNP |
denotes |
C. |
T1145 |
4457-4461 |
NNP |
denotes |
Wong |
T1146 |
4461-4463 |
, |
denotes |
, |
T1147 |
4463-4471 |
JJ |
denotes |
personal |
T1148 |
4472-4485 |
NN |
denotes |
communication |
T1149 |
4485-4486 |
-RRB- |
denotes |
) |
T1150 |
4486-4488 |
, |
denotes |
, |
T1151 |
4488-4490 |
PRP |
denotes |
it |
T1152 |
4491-4493 |
VBZ |
denotes |
is |
T1153 |
4494-4497 |
RB |
denotes |
not |
T1154 |
4504-4511 |
IN |
denotes |
whether |
T1155 |
4526-4531 |
VB |
denotes |
clear |
T1156 |
4512-4515 |
DT |
denotes |
the |
T1157 |
4516-4521 |
NN |
denotes |
brain |
T1158 |
4522-4525 |
MD |
denotes |
can |
T1159 |
4532-4544 |
JJ |
denotes |
pre-existing |
T1160 |
4553-4561 |
NNS |
denotes |
deposits |
T1161 |
4545-4552 |
NN |
denotes |
amyloid |
T1162 |
4562-4566 |
IN |
denotes |
once |
T1163 |
4593-4603 |
VBN |
denotes |
suppressed |
T1164 |
4567-4577 |
NN |
denotes |
production |
T1165 |
4578-4580 |
IN |
denotes |
of |
T1166 |
4581-4583 |
NN |
denotes |
Aβ |
T1167 |
4584-4587 |
VBZ |
denotes |
has |
T1168 |
4588-4592 |
VBN |
denotes |
been |
T1169 |
4603-4604 |
. |
denotes |
. |
T1170 |
4604-4736 |
sentence |
denotes |
Clearly, the amyloid-lowering approach should be rigorously examined in animal models before these reagents are tested in patients. |
T1171 |
4605-4612 |
RB |
denotes |
Clearly |
T1172 |
4665-4673 |
VBN |
denotes |
examined |
T1173 |
4612-4614 |
, |
denotes |
, |
T1174 |
4614-4617 |
DT |
denotes |
the |
T1175 |
4635-4643 |
NN |
denotes |
approach |
T1176 |
4618-4625 |
NN |
denotes |
amyloid |
T1177 |
4626-4634 |
VBG |
denotes |
lowering |
T1178 |
4625-4626 |
HYPH |
denotes |
- |
T1179 |
4644-4650 |
MD |
denotes |
should |
T1180 |
4651-4653 |
VB |
denotes |
be |
T1181 |
4654-4664 |
RB |
denotes |
rigorously |
T1182 |
4674-4676 |
IN |
denotes |
in |
T1183 |
4677-4683 |
NN |
denotes |
animal |
T1184 |
4684-4690 |
NNS |
denotes |
models |
T1185 |
4691-4697 |
IN |
denotes |
before |
T1186 |
4717-4723 |
VBN |
denotes |
tested |
T1187 |
4698-4703 |
DT |
denotes |
these |
T1188 |
4704-4712 |
NNS |
denotes |
reagents |
T1189 |
4713-4716 |
VBP |
denotes |
are |
T1190 |
4724-4726 |
IN |
denotes |
in |
T1191 |
4727-4735 |
NNS |
denotes |
patients |
T1192 |
4735-4736 |
. |
denotes |
. |
T1193 |
4736-4839 |
sentence |
denotes |
However, the chemical secretase inhibitors most likely to reach human trials are still in development. |
T1194 |
4737-4744 |
RB |
denotes |
However |
T1195 |
4814-4817 |
VBP |
denotes |
are |
T1196 |
4744-4746 |
, |
denotes |
, |
T1197 |
4746-4749 |
DT |
denotes |
the |
T1198 |
4769-4779 |
NNS |
denotes |
inhibitors |
T1199 |
4750-4758 |
JJ |
denotes |
chemical |
T1200 |
4759-4768 |
NN |
denotes |
secretase |
T1201 |
4780-4784 |
RBS |
denotes |
most |
T1202 |
4785-4791 |
JJ |
denotes |
likely |
T1203 |
4792-4794 |
TO |
denotes |
to |
T1204 |
4795-4800 |
VB |
denotes |
reach |
T1205 |
4801-4806 |
JJ |
denotes |
human |
T1206 |
4807-4813 |
NNS |
denotes |
trials |
T1207 |
4818-4823 |
RB |
denotes |
still |
T1208 |
4824-4826 |
IN |
denotes |
in |
T1209 |
4827-4838 |
NN |
denotes |
development |
T1210 |
4838-4839 |
. |
denotes |
. |
T1211 |
4839-4948 |
sentence |
denotes |
Therefore, we developed a mouse model of Alzheimer-type amyloid that expresses a controllable APP transgene. |
T1212 |
4840-4849 |
RB |
denotes |
Therefore |
T1213 |
4854-4863 |
VBD |
denotes |
developed |
T1214 |
4849-4851 |
, |
denotes |
, |
T1215 |
4851-4853 |
PRP |
denotes |
we |
T1216 |
4864-4865 |
DT |
denotes |
a |
T1217 |
4872-4877 |
NN |
denotes |
model |
T1218 |
4866-4871 |
NN |
denotes |
mouse |
T1219 |
4878-4880 |
IN |
denotes |
of |
T1220 |
4881-4890 |
NNP |
denotes |
Alzheimer |
T1221 |
4891-4895 |
NN |
denotes |
type |
T1222 |
4890-4891 |
HYPH |
denotes |
- |
T1223 |
4896-4903 |
NN |
denotes |
amyloid |
T1224 |
4904-4908 |
WDT |
denotes |
that |
T1225 |
4909-4918 |
VBZ |
denotes |
expresses |
T1226 |
4919-4920 |
DT |
denotes |
a |
T1227 |
4938-4947 |
NN |
denotes |
transgene |
T1228 |
4921-4933 |
JJ |
denotes |
controllable |
T1229 |
4934-4937 |
NN |
denotes |
APP |
T1230 |
4947-4948 |
. |
denotes |
. |
T1231 |
4948-5082 |
sentence |
denotes |
This system, commonly known as the tet-off system, can be regulated by analogs of tetracycline administered in food or water [12,13]. |
T1232 |
4949-4953 |
DT |
denotes |
This |
T1233 |
4954-4960 |
NN |
denotes |
system |
T1234 |
5007-5016 |
VBN |
denotes |
regulated |
T1235 |
4960-4962 |
, |
denotes |
, |
T1236 |
4962-4970 |
RB |
denotes |
commonly |
T1237 |
4971-4976 |
VBN |
denotes |
known |
T1238 |
4977-4979 |
IN |
denotes |
as |
T1239 |
4980-4983 |
DT |
denotes |
the |
T1240 |
4992-4998 |
NN |
denotes |
system |
T1241 |
4984-4987 |
NN |
denotes |
tet |
T1242 |
4988-4991 |
NN |
denotes |
off |
T1243 |
4987-4988 |
HYPH |
denotes |
- |
T1244 |
4998-5000 |
, |
denotes |
, |
T1245 |
5000-5003 |
MD |
denotes |
can |
T1246 |
5004-5006 |
VB |
denotes |
be |
T1247 |
5017-5019 |
IN |
denotes |
by |
T1248 |
5020-5027 |
NNS |
denotes |
analogs |
T1249 |
5028-5030 |
IN |
denotes |
of |
T1250 |
5031-5043 |
NN |
denotes |
tetracycline |
T1251 |
5044-5056 |
VBN |
denotes |
administered |
T1252 |
5057-5059 |
IN |
denotes |
in |
T1253 |
5060-5064 |
NN |
denotes |
food |
T1254 |
5065-5067 |
CC |
denotes |
or |
T1255 |
5068-5073 |
NN |
denotes |
water |
T1256 |
5074-5075 |
-LRB- |
denotes |
[ |
T1257 |
5078-5080 |
CD |
denotes |
13 |
T1258 |
5075-5077 |
CD |
denotes |
12 |
T1259 |
5077-5078 |
, |
denotes |
, |
T1260 |
5080-5081 |
-RRB- |
denotes |
] |
T1261 |
5081-5082 |
. |
denotes |
. |
T1262 |
5082-5482 |
sentence |
denotes |
The strong expression levels produced with the tet-off vectors, combined with the ability to reduce this expression by several orders of magnitude with tetracycline [14], allowed for a stringent test of how a highly effective pharmaceutical inhibitor of Aβ production would impact the progression of amyloid pathology and whether reversal of these lesions might be possible following such treatment. |
T1263 |
5083-5086 |
DT |
denotes |
The |
T1264 |
5105-5111 |
NNS |
denotes |
levels |
T1265 |
5087-5093 |
JJ |
denotes |
strong |
T1266 |
5094-5104 |
NN |
denotes |
expression |
T1267 |
5254-5261 |
VBD |
denotes |
allowed |
T1268 |
5112-5120 |
VBN |
denotes |
produced |
T1269 |
5121-5125 |
IN |
denotes |
with |
T1270 |
5126-5129 |
DT |
denotes |
the |
T1271 |
5138-5145 |
NNS |
denotes |
vectors |
T1272 |
5130-5133 |
NN |
denotes |
tet |
T1273 |
5134-5137 |
NN |
denotes |
off |
T1274 |
5133-5134 |
HYPH |
denotes |
- |
T1275 |
5145-5147 |
, |
denotes |
, |
T1276 |
5147-5155 |
VBN |
denotes |
combined |
T1277 |
5156-5160 |
IN |
denotes |
with |
T1278 |
5161-5164 |
DT |
denotes |
the |
T1279 |
5165-5172 |
NN |
denotes |
ability |
T1280 |
5173-5175 |
TO |
denotes |
to |
T1281 |
5176-5182 |
VB |
denotes |
reduce |
T1282 |
5183-5187 |
DT |
denotes |
this |
T1283 |
5188-5198 |
NN |
denotes |
expression |
T1284 |
5199-5201 |
IN |
denotes |
by |
T1285 |
5202-5209 |
JJ |
denotes |
several |
T1286 |
5210-5216 |
NNS |
denotes |
orders |
T1287 |
5217-5219 |
IN |
denotes |
of |
T1288 |
5220-5229 |
NN |
denotes |
magnitude |
T1289 |
5230-5234 |
IN |
denotes |
with |
T1290 |
5235-5247 |
NN |
denotes |
tetracycline |
T1291 |
5248-5249 |
-LRB- |
denotes |
[ |
T1292 |
5249-5251 |
CD |
denotes |
14 |
T1293 |
5251-5252 |
-RRB- |
denotes |
] |
T1294 |
5252-5254 |
, |
denotes |
, |
T1295 |
5262-5265 |
IN |
denotes |
for |
T1296 |
5266-5267 |
DT |
denotes |
a |
T1297 |
5278-5282 |
NN |
denotes |
test |
T1298 |
5268-5277 |
JJ |
denotes |
stringent |
T1299 |
5283-5285 |
IN |
denotes |
of |
T1300 |
5286-5289 |
WRB |
denotes |
how |
T1301 |
5357-5363 |
VB |
denotes |
impact |
T1302 |
5290-5291 |
DT |
denotes |
a |
T1303 |
5324-5333 |
NN |
denotes |
inhibitor |
T1304 |
5292-5298 |
RB |
denotes |
highly |
T1305 |
5299-5308 |
JJ |
denotes |
effective |
T1306 |
5309-5323 |
JJ |
denotes |
pharmaceutical |
T1307 |
5334-5336 |
IN |
denotes |
of |
T1308 |
5337-5339 |
NN |
denotes |
Aβ |
T1309 |
5340-5350 |
NN |
denotes |
production |
T1310 |
5351-5356 |
MD |
denotes |
would |
T1311 |
5364-5367 |
DT |
denotes |
the |
T1312 |
5368-5379 |
NN |
denotes |
progression |
T1313 |
5380-5382 |
IN |
denotes |
of |
T1314 |
5383-5390 |
NN |
denotes |
amyloid |
T1315 |
5391-5400 |
NN |
denotes |
pathology |
T1316 |
5401-5404 |
CC |
denotes |
and |
T1317 |
5405-5412 |
IN |
denotes |
whether |
T1318 |
5445-5447 |
VB |
denotes |
be |
T1319 |
5413-5421 |
NN |
denotes |
reversal |
T1320 |
5422-5424 |
IN |
denotes |
of |
T1321 |
5425-5430 |
DT |
denotes |
these |
T1322 |
5431-5438 |
NNS |
denotes |
lesions |
T1323 |
5439-5444 |
MD |
denotes |
might |
T1324 |
5448-5456 |
JJ |
denotes |
possible |
T1325 |
5457-5466 |
VBG |
denotes |
following |
T1326 |
5467-5471 |
JJ |
denotes |
such |
T1327 |
5472-5481 |
NN |
denotes |
treatment |
T1328 |
5481-5482 |
. |
denotes |
. |
T1535 |
5493-5502 |
NN |
denotes |
Transgene |
T1536 |
5503-5515 |
NN |
denotes |
Construction |
T1537 |
5515-5915 |
sentence |
denotes |
We created a tetracycline-responsive chimeric mouse/human APP695Swedish/Indiana (swe/ind) vector by replacing the promoter region of the moPrP.XhoI vector (also known as pPrPpE1/E2,3sal [15]) with the tetracycline-responsive promoter of pTetSplice (Life Technologies, Rockville, Maryland, United States), and then ligating mouse APP with a humanized Aβ domain (mo/huAPP695) cDNA into the new vector. |
T1538 |
5516-5518 |
PRP |
denotes |
We |
T1539 |
5519-5526 |
VBD |
denotes |
created |
T1540 |
5527-5528 |
DT |
denotes |
a |
T1541 |
5606-5612 |
NN |
denotes |
vector |
T1542 |
5529-5541 |
NN |
denotes |
tetracycline |
T1543 |
5542-5552 |
JJ |
denotes |
responsive |
T1544 |
5541-5542 |
HYPH |
denotes |
- |
T1545 |
5553-5561 |
JJ |
denotes |
chimeric |
T1546 |
5562-5567 |
NN |
denotes |
mouse |
T1547 |
5567-5568 |
HYPH |
denotes |
/ |
T1548 |
5568-5573 |
JJ |
denotes |
human |
T1549 |
5574-5587 |
NN |
denotes |
APP695Swedish |
T1550 |
5588-5595 |
NNP |
denotes |
Indiana |
T1551 |
5587-5588 |
HYPH |
denotes |
/ |
T1552 |
5596-5597 |
-LRB- |
denotes |
( |
T1553 |
5597-5600 |
NN |
denotes |
swe |
T1554 |
5601-5604 |
NN |
denotes |
ind |
T1555 |
5600-5601 |
HYPH |
denotes |
/ |
T1556 |
5604-5605 |
-RRB- |
denotes |
) |
T1557 |
5613-5615 |
IN |
denotes |
by |
T1558 |
5616-5625 |
VBG |
denotes |
replacing |
T1559 |
5626-5629 |
DT |
denotes |
the |
T1560 |
5639-5645 |
NN |
denotes |
region |
T1561 |
5630-5638 |
NN |
denotes |
promoter |
T1562 |
5646-5648 |
IN |
denotes |
of |
T1563 |
5649-5652 |
DT |
denotes |
the |
T1564 |
5664-5670 |
NN |
denotes |
vector |
T1565 |
5653-5663 |
NN |
denotes |
moPrP.XhoI |
T1566 |
5671-5672 |
-LRB- |
denotes |
( |
T1567 |
5677-5682 |
VBN |
denotes |
known |
T1568 |
5672-5676 |
RB |
denotes |
also |
T1569 |
5683-5685 |
IN |
denotes |
as |
T1570 |
5686-5693 |
NN |
denotes |
pPrPpE1 |
T1571 |
5697-5701 |
NN |
denotes |
3sal |
T1572 |
5693-5694 |
HYPH |
denotes |
/ |
T1573 |
5694-5696 |
NN |
denotes |
E2 |
T1574 |
5696-5697 |
, |
denotes |
, |
T1575 |
5702-5703 |
-LRB- |
denotes |
[ |
T1576 |
5703-5705 |
CD |
denotes |
15 |
T1577 |
5705-5706 |
-RRB- |
denotes |
] |
T1578 |
5706-5707 |
-RRB- |
denotes |
) |
T1579 |
5708-5712 |
IN |
denotes |
with |
T1580 |
5713-5716 |
DT |
denotes |
the |
T1581 |
5741-5749 |
NN |
denotes |
promoter |
T1582 |
5717-5729 |
NN |
denotes |
tetracycline |
T1583 |
5730-5740 |
JJ |
denotes |
responsive |
T1584 |
5729-5730 |
HYPH |
denotes |
- |
T1585 |
5750-5752 |
IN |
denotes |
of |
T1586 |
5753-5763 |
NN |
denotes |
pTetSplice |
T1587 |
5764-5765 |
-LRB- |
denotes |
( |
T1588 |
5770-5782 |
NNP |
denotes |
Technologies |
T1589 |
5765-5769 |
NNP |
denotes |
Life |
T1590 |
5782-5784 |
, |
denotes |
, |
T1591 |
5784-5793 |
NNP |
denotes |
Rockville |
T1592 |
5793-5795 |
, |
denotes |
, |
T1593 |
5795-5803 |
NNP |
denotes |
Maryland |
T1594 |
5803-5805 |
, |
denotes |
, |
T1595 |
5805-5811 |
NNP |
denotes |
United |
T1596 |
5812-5818 |
NNP |
denotes |
States |
T1597 |
5818-5819 |
-RRB- |
denotes |
) |
T1598 |
5819-5821 |
, |
denotes |
, |
T1599 |
5821-5824 |
CC |
denotes |
and |
T1600 |
5825-5829 |
RB |
denotes |
then |
T1601 |
5830-5838 |
VBG |
denotes |
ligating |
T1602 |
5839-5844 |
NN |
denotes |
mouse |
T1603 |
5845-5848 |
NN |
denotes |
APP |
T1604 |
5849-5853 |
IN |
denotes |
with |
T1605 |
5854-5855 |
DT |
denotes |
a |
T1606 |
5869-5875 |
NN |
denotes |
domain |
T1607 |
5856-5865 |
JJ |
denotes |
humanized |
T1608 |
5866-5868 |
NN |
denotes |
Aβ |
T1609 |
5890-5894 |
NN |
denotes |
cDNA |
T1610 |
5876-5877 |
-LRB- |
denotes |
( |
T1611 |
5877-5879 |
NN |
denotes |
mo |
T1612 |
5880-5888 |
NN |
denotes |
huAPP695 |
T1613 |
5879-5880 |
HYPH |
denotes |
/ |
T1614 |
5888-5889 |
-RRB- |
denotes |
) |
T1615 |
5895-5899 |
IN |
denotes |
into |
T1616 |
5900-5903 |
DT |
denotes |
the |
T1617 |
5908-5914 |
NN |
denotes |
vector |
T1618 |
5904-5907 |
JJ |
denotes |
new |
T1619 |
5914-5915 |
. |
denotes |
. |
T1620 |
5915-6285 |
sentence |
denotes |
We began by cloning the tetracycline-responsive promoter (bp 6–481) from pTetSplice by PCR using primers that added external BamHI and NotI sites to the 5′ end and a BamHI site to the 3′ end, while destroying XhoI and BamHI sites within the promoter (forward: GCC GGA TCC GCG GCC GCC GTC GAG TTT ACC ACT CCC TAT C; reverse: GCC GGA TCC ACT CTA GAA GAT CCC CGG GTA CCG). |
T1621 |
5916-5918 |
PRP |
denotes |
We |
T1622 |
5919-5924 |
VBD |
denotes |
began |
T1623 |
5925-5927 |
IN |
denotes |
by |
T1624 |
5928-5935 |
VBG |
denotes |
cloning |
T1625 |
5936-5939 |
DT |
denotes |
the |
T1626 |
5964-5972 |
NN |
denotes |
promoter |
T1627 |
5940-5952 |
NN |
denotes |
tetracycline |
T1628 |
5953-5963 |
JJ |
denotes |
responsive |
T1629 |
5952-5953 |
HYPH |
denotes |
- |
T1630 |
5973-5974 |
-LRB- |
denotes |
( |
T1631 |
5977-5978 |
CD |
denotes |
6 |
T1632 |
5974-5976 |
NN |
denotes |
bp |
T1633 |
5978-5979 |
SYM |
denotes |
– |
T1634 |
5979-5982 |
CD |
denotes |
481 |
T1635 |
5982-5983 |
-RRB- |
denotes |
) |
T1636 |
5984-5988 |
IN |
denotes |
from |
T1637 |
5989-5999 |
NN |
denotes |
pTetSplice |
T1638 |
6000-6002 |
IN |
denotes |
by |
T1639 |
6003-6006 |
NN |
denotes |
PCR |
T1640 |
6007-6012 |
VBG |
denotes |
using |
T1641 |
6013-6020 |
NNS |
denotes |
primers |
T1642 |
6021-6025 |
WDT |
denotes |
that |
T1643 |
6026-6031 |
VBD |
denotes |
added |
T1644 |
6032-6040 |
JJ |
denotes |
external |
T1645 |
6056-6061 |
NNS |
denotes |
sites |
T1646 |
6041-6046 |
NN |
denotes |
BamHI |
T1647 |
6047-6050 |
CC |
denotes |
and |
T1648 |
6051-6055 |
NN |
denotes |
NotI |
T1649 |
6062-6064 |
IN |
denotes |
to |
T1650 |
6065-6068 |
DT |
denotes |
the |
T1651 |
6072-6075 |
NN |
denotes |
end |
T1652 |
6069-6070 |
CD |
denotes |
5 |
T1653 |
6070-6071 |
SYM |
denotes |
′ |
T1654 |
6076-6079 |
CC |
denotes |
and |
T1655 |
6080-6081 |
DT |
denotes |
a |
T1656 |
6088-6092 |
NN |
denotes |
site |
T1657 |
6082-6087 |
NN |
denotes |
BamHI |
T1658 |
6093-6095 |
IN |
denotes |
to |
T1659 |
6096-6099 |
DT |
denotes |
the |
T1660 |
6103-6106 |
NN |
denotes |
end |
T1661 |
6100-6101 |
CD |
denotes |
3 |
T1662 |
6101-6102 |
SYM |
denotes |
′ |
T1663 |
6106-6108 |
, |
denotes |
, |
T1664 |
6108-6113 |
IN |
denotes |
while |
T1665 |
6114-6124 |
VBG |
denotes |
destroying |
T1666 |
6125-6129 |
NN |
denotes |
XhoI |
T1667 |
6140-6145 |
NNS |
denotes |
sites |
T1668 |
6130-6133 |
CC |
denotes |
and |
T1669 |
6134-6139 |
NN |
denotes |
BamHI |
T1670 |
6146-6152 |
IN |
denotes |
within |
T1671 |
6153-6156 |
DT |
denotes |
the |
T1672 |
6157-6165 |
NN |
denotes |
promoter |
T1673 |
6166-6167 |
-LRB- |
denotes |
( |
T1674 |
6280-6283 |
NN |
denotes |
CCG |
T1675 |
6167-6174 |
NN |
denotes |
forward |
T1676 |
6228-6229 |
NN |
denotes |
C |
T1677 |
6174-6176 |
: |
denotes |
: |
T1678 |
6176-6179 |
NN |
denotes |
GCC |
T1679 |
6180-6183 |
NN |
denotes |
GGA |
T1680 |
6184-6187 |
NN |
denotes |
TCC |
T1681 |
6188-6191 |
NN |
denotes |
GCG |
T1682 |
6192-6195 |
NN |
denotes |
GCC |
T1683 |
6196-6199 |
NN |
denotes |
GCC |
T1684 |
6200-6203 |
NN |
denotes |
GTC |
T1685 |
6204-6207 |
NN |
denotes |
GAG |
T1686 |
6208-6211 |
NN |
denotes |
TTT |
T1687 |
6212-6215 |
NN |
denotes |
ACC |
T1688 |
6216-6219 |
NN |
denotes |
ACT |
T1689 |
6220-6223 |
NN |
denotes |
CCC |
T1690 |
6224-6227 |
NN |
denotes |
TAT |
T1691 |
6229-6230 |
: |
denotes |
; |
T1692 |
6231-6238 |
NN |
denotes |
reverse |
T1693 |
6238-6240 |
: |
denotes |
: |
T1694 |
6240-6243 |
NN |
denotes |
GCC |
T1695 |
6244-6247 |
NN |
denotes |
GGA |
T1696 |
6248-6251 |
NN |
denotes |
TCC |
T1697 |
6252-6255 |
NN |
denotes |
ACT |
T1698 |
6256-6259 |
NN |
denotes |
CTA |
T1699 |
6260-6263 |
NN |
denotes |
GAA |
T1700 |
6264-6267 |
NN |
denotes |
GAT |
T1701 |
6268-6271 |
NN |
denotes |
CCC |
T1702 |
6272-6275 |
NN |
denotes |
CGG |
T1703 |
6276-6279 |
NN |
denotes |
GTA |
T1704 |
6283-6284 |
-RRB- |
denotes |
) |
T1705 |
6284-6285 |
. |
denotes |
. |
T1706 |
6285-6551 |
sentence |
denotes |
We then isolated the moPrP.XhoI intron by amplification with primers that added an external BamHI site to the 5′ end of exon 1 and ran through the Asp718 site of exon 2 (forward: GCC GGA TCC GAT CAG CAG ACC GAT TCT GG; reverse: GCC GGT ACC ACT AGG AAG GCA GAA TGC). |
T1707 |
6286-6288 |
PRP |
denotes |
We |
T1708 |
6294-6302 |
VBD |
denotes |
isolated |
T1709 |
6289-6293 |
RB |
denotes |
then |
T1710 |
6303-6306 |
DT |
denotes |
the |
T1711 |
6318-6324 |
NN |
denotes |
intron |
T1712 |
6307-6317 |
NN |
denotes |
moPrP.XhoI |
T1713 |
6325-6327 |
IN |
denotes |
by |
T1714 |
6328-6341 |
NN |
denotes |
amplification |
T1715 |
6342-6346 |
IN |
denotes |
with |
T1716 |
6347-6354 |
NNS |
denotes |
primers |
T1717 |
6355-6359 |
WDT |
denotes |
that |
T1718 |
6360-6365 |
VBD |
denotes |
added |
T1719 |
6366-6368 |
DT |
denotes |
an |
T1720 |
6384-6388 |
NN |
denotes |
site |
T1721 |
6369-6377 |
JJ |
denotes |
external |
T1722 |
6378-6383 |
NN |
denotes |
BamHI |
T1723 |
6389-6391 |
IN |
denotes |
to |
T1724 |
6392-6395 |
DT |
denotes |
the |
T1725 |
6399-6402 |
NN |
denotes |
end |
T1726 |
6396-6397 |
CD |
denotes |
5 |
T1727 |
6397-6398 |
SYM |
denotes |
′ |
T1728 |
6403-6405 |
IN |
denotes |
of |
T1729 |
6406-6410 |
NN |
denotes |
exon |
T1730 |
6411-6412 |
CD |
denotes |
1 |
T1731 |
6413-6416 |
CC |
denotes |
and |
T1732 |
6417-6420 |
VBD |
denotes |
ran |
T1733 |
6421-6428 |
IN |
denotes |
through |
T1734 |
6429-6432 |
DT |
denotes |
the |
T1735 |
6440-6444 |
NN |
denotes |
site |
T1736 |
6433-6439 |
NN |
denotes |
Asp718 |
T1737 |
6445-6447 |
IN |
denotes |
of |
T1738 |
6448-6452 |
NN |
denotes |
exon |
T1739 |
6453-6454 |
CD |
denotes |
2 |
T1740 |
6455-6456 |
-LRB- |
denotes |
( |
T1741 |
6546-6549 |
NN |
denotes |
TGC |
T1742 |
6456-6463 |
NN |
denotes |
forward |
T1743 |
6501-6503 |
NN |
denotes |
GG |
T1744 |
6463-6465 |
: |
denotes |
: |
T1745 |
6465-6468 |
NN |
denotes |
GCC |
T1746 |
6469-6472 |
NN |
denotes |
GGA |
T1747 |
6473-6476 |
NN |
denotes |
TCC |
T1748 |
6477-6480 |
NN |
denotes |
GAT |
T1749 |
6481-6484 |
NN |
denotes |
CAG |
T1750 |
6485-6488 |
NN |
denotes |
CAG |
T1751 |
6489-6492 |
NN |
denotes |
ACC |
T1752 |
6493-6496 |
NN |
denotes |
GAT |
T1753 |
6497-6500 |
NN |
denotes |
TCT |
T1754 |
6503-6504 |
: |
denotes |
; |
T1755 |
6505-6512 |
NN |
denotes |
reverse |
T1756 |
6512-6514 |
: |
denotes |
: |
T1757 |
6514-6517 |
NN |
denotes |
GCC |
T1758 |
6518-6521 |
NN |
denotes |
GGT |
T1759 |
6522-6525 |
NN |
denotes |
ACC |
T1760 |
6526-6529 |
NN |
denotes |
ACT |
T1761 |
6530-6533 |
NN |
denotes |
AGG |
T1762 |
6534-6537 |
NN |
denotes |
AAG |
T1763 |
6538-6541 |
NN |
denotes |
GCA |
T1764 |
6542-6545 |
NN |
denotes |
GAA |
T1765 |
6549-6550 |
-RRB- |
denotes |
) |
T1766 |
6550-6551 |
. |
denotes |
. |
T1767 |
6551-6902 |
sentence |
denotes |
This 2-kb intron fragment was cloned into a TA cloning vector (Invitrogen, Carlsbad, California, United States), then excised by Asp718 digestion and ligated to the 6.8-kb Asp718 fragment of moPrP.XhoI containing exon 2, exon 3, the 3′ UTR, and pBluescript to generate an intermediate vector with all three exons and a central intron but no promoter. |
T1768 |
6552-6556 |
DT |
denotes |
This |
T1769 |
6569-6577 |
NN |
denotes |
fragment |
T1770 |
6557-6558 |
CD |
denotes |
2 |
T1771 |
6559-6561 |
NN |
denotes |
kb |
T1772 |
6558-6559 |
HYPH |
denotes |
- |
T1773 |
6562-6568 |
NN |
denotes |
intron |
T1774 |
6582-6588 |
VBN |
denotes |
cloned |
T1775 |
6578-6581 |
VBD |
denotes |
was |
T1776 |
6589-6593 |
IN |
denotes |
into |
T1777 |
6594-6595 |
DT |
denotes |
a |
T1778 |
6607-6613 |
NN |
denotes |
vector |
T1779 |
6596-6598 |
NN |
denotes |
TA |
T1780 |
6599-6606 |
NN |
denotes |
cloning |
T1781 |
6614-6615 |
-LRB- |
denotes |
( |
T1782 |
6615-6625 |
NNP |
denotes |
Invitrogen |
T1783 |
6625-6627 |
, |
denotes |
, |
T1784 |
6627-6635 |
NNP |
denotes |
Carlsbad |
T1785 |
6635-6637 |
, |
denotes |
, |
T1786 |
6637-6647 |
NNP |
denotes |
California |
T1787 |
6647-6649 |
, |
denotes |
, |
T1788 |
6649-6655 |
NNP |
denotes |
United |
T1789 |
6656-6662 |
NNP |
denotes |
States |
T1790 |
6662-6663 |
-RRB- |
denotes |
) |
T1791 |
6663-6665 |
, |
denotes |
, |
T1792 |
6665-6669 |
RB |
denotes |
then |
T1793 |
6670-6677 |
VBN |
denotes |
excised |
T1794 |
6678-6680 |
IN |
denotes |
by |
T1795 |
6681-6687 |
NN |
denotes |
Asp718 |
T1796 |
6688-6697 |
NN |
denotes |
digestion |
T1797 |
6698-6701 |
CC |
denotes |
and |
T1798 |
6702-6709 |
VBN |
denotes |
ligated |
T1799 |
6710-6712 |
IN |
denotes |
to |
T1800 |
6713-6716 |
DT |
denotes |
the |
T1801 |
6731-6739 |
NN |
denotes |
fragment |
T1802 |
6717-6720 |
CD |
denotes |
6.8 |
T1803 |
6721-6723 |
NN |
denotes |
kb |
T1804 |
6720-6721 |
HYPH |
denotes |
- |
T1805 |
6724-6730 |
NN |
denotes |
Asp718 |
T1806 |
6740-6742 |
IN |
denotes |
of |
T1807 |
6743-6753 |
NN |
denotes |
moPrP.XhoI |
T1808 |
6754-6764 |
VBG |
denotes |
containing |
T1809 |
6765-6769 |
NN |
denotes |
exon |
T1810 |
6770-6771 |
CD |
denotes |
2 |
T1811 |
6771-6773 |
, |
denotes |
, |
T1812 |
6773-6777 |
NN |
denotes |
exon |
T1813 |
6778-6779 |
CD |
denotes |
3 |
T1814 |
6779-6781 |
, |
denotes |
, |
T1815 |
6781-6784 |
DT |
denotes |
the |
T1816 |
6788-6791 |
NN |
denotes |
UTR |
T1817 |
6785-6786 |
CD |
denotes |
3 |
T1818 |
6786-6787 |
SYM |
denotes |
′ |
T1819 |
6791-6793 |
, |
denotes |
, |
T1820 |
6793-6796 |
CC |
denotes |
and |
T1821 |
6797-6808 |
NN |
denotes |
pBluescript |
T1822 |
6809-6811 |
TO |
denotes |
to |
T1823 |
6812-6820 |
VB |
denotes |
generate |
T1824 |
6821-6823 |
DT |
denotes |
an |
T1825 |
6837-6843 |
NN |
denotes |
vector |
T1826 |
6824-6836 |
JJ |
denotes |
intermediate |
T1827 |
6844-6848 |
IN |
denotes |
with |
T1828 |
6849-6852 |
DT |
denotes |
all |
T1829 |
6859-6864 |
NNS |
denotes |
exons |
T1830 |
6853-6858 |
CD |
denotes |
three |
T1831 |
6865-6868 |
CC |
denotes |
and |
T1832 |
6869-6870 |
DT |
denotes |
a |
T1833 |
6879-6885 |
NN |
denotes |
intron |
T1834 |
6871-6878 |
JJ |
denotes |
central |
T1835 |
6886-6889 |
CC |
denotes |
but |
T1836 |
6890-6892 |
DT |
denotes |
no |
T1837 |
6893-6901 |
NN |
denotes |
promoter |
T1838 |
6901-6902 |
. |
denotes |
. |
T1839 |
6902-7057 |
sentence |
denotes |
This vector was then opened at the BamHI site introduced by the intron cloning primer, and ligated to the 0.5-kb BamHI-cut tetracycline promoter fragment. |
T1840 |
6903-6907 |
DT |
denotes |
This |
T1841 |
6908-6914 |
NN |
denotes |
vector |
T1842 |
6924-6930 |
VBN |
denotes |
opened |
T1843 |
6915-6918 |
VBD |
denotes |
was |
T1844 |
6919-6923 |
RB |
denotes |
then |
T1845 |
6931-6933 |
IN |
denotes |
at |
T1846 |
6934-6937 |
DT |
denotes |
the |
T1847 |
6944-6948 |
NN |
denotes |
site |
T1848 |
6938-6943 |
NN |
denotes |
BamHI |
T1849 |
6949-6959 |
VBN |
denotes |
introduced |
T1850 |
6960-6962 |
IN |
denotes |
by |
T1851 |
6963-6966 |
DT |
denotes |
the |
T1852 |
6982-6988 |
NN |
denotes |
primer |
T1853 |
6967-6973 |
NN |
denotes |
intron |
T1854 |
6974-6981 |
NN |
denotes |
cloning |
T1855 |
6988-6990 |
, |
denotes |
, |
T1856 |
6990-6993 |
CC |
denotes |
and |
T1857 |
6994-7001 |
VBN |
denotes |
ligated |
T1858 |
7002-7004 |
IN |
denotes |
to |
T1859 |
7005-7008 |
DT |
denotes |
the |
T1860 |
7048-7056 |
NN |
denotes |
fragment |
T1861 |
7009-7012 |
CD |
denotes |
0.5 |
T1862 |
7013-7015 |
NN |
denotes |
kb |
T1863 |
7012-7013 |
HYPH |
denotes |
- |
T1864 |
7016-7021 |
NN |
denotes |
BamHI |
T1865 |
7022-7025 |
NN |
denotes |
cut |
T1866 |
7021-7022 |
HYPH |
denotes |
- |
T1867 |
7026-7038 |
NN |
denotes |
tetracycline |
T1868 |
7039-7047 |
NN |
denotes |
promoter |
T1869 |
7056-7057 |
. |
denotes |
. |
T1870 |
7057-7273 |
sentence |
denotes |
This ligation generated a 9.3-kb vector encoding the tetracycline promoter from pTetSplice with two exons, one intron, and the original 3′ UTR of the moPrP.XhoI vector, all carried in the pBluescript cloning vector. |
T1871 |
7058-7062 |
DT |
denotes |
This |
T1872 |
7063-7071 |
NN |
denotes |
ligation |
T1873 |
7072-7081 |
VBD |
denotes |
generated |
T1874 |
7082-7083 |
DT |
denotes |
a |
T1875 |
7091-7097 |
NN |
denotes |
vector |
T1876 |
7084-7087 |
CD |
denotes |
9.3 |
T1877 |
7088-7090 |
NN |
denotes |
kb |
T1878 |
7087-7088 |
HYPH |
denotes |
- |
T1879 |
7098-7106 |
VBG |
denotes |
encoding |
T1880 |
7107-7110 |
DT |
denotes |
the |
T1881 |
7124-7132 |
NN |
denotes |
promoter |
T1882 |
7111-7123 |
NN |
denotes |
tetracycline |
T1883 |
7133-7137 |
IN |
denotes |
from |
T1884 |
7138-7148 |
NN |
denotes |
pTetSplice |
T1885 |
7149-7153 |
IN |
denotes |
with |
T1886 |
7154-7157 |
CD |
denotes |
two |
T1887 |
7158-7163 |
NNS |
denotes |
exons |
T1888 |
7163-7165 |
, |
denotes |
, |
T1889 |
7165-7168 |
CD |
denotes |
one |
T1890 |
7169-7175 |
NN |
denotes |
intron |
T1891 |
7175-7177 |
, |
denotes |
, |
T1892 |
7177-7180 |
CC |
denotes |
and |
T1893 |
7181-7184 |
DT |
denotes |
the |
T1894 |
7197-7200 |
NN |
denotes |
UTR |
T1895 |
7185-7193 |
JJ |
denotes |
original |
T1896 |
7194-7195 |
CD |
denotes |
3 |
T1897 |
7195-7196 |
SYM |
denotes |
′ |
T1898 |
7201-7203 |
IN |
denotes |
of |
T1899 |
7204-7207 |
DT |
denotes |
the |
T1900 |
7219-7225 |
NN |
denotes |
vector |
T1901 |
7208-7218 |
NN |
denotes |
moPrP.XhoI |
T1902 |
7225-7227 |
, |
denotes |
, |
T1903 |
7227-7230 |
RB |
denotes |
all |
T1904 |
7231-7238 |
VBN |
denotes |
carried |
T1905 |
7239-7241 |
IN |
denotes |
in |
T1906 |
7242-7245 |
DT |
denotes |
the |
T1907 |
7266-7272 |
NN |
denotes |
vector |
T1908 |
7246-7257 |
NNP |
denotes |
pBluescript |
T1909 |
7258-7265 |
NN |
denotes |
cloning |
T1910 |
7272-7273 |
. |
denotes |
. |
T1911 |
7273-7723 |
sentence |
denotes |
We incorporated the Swedish (KM570/571NL) and Indiana (V617F) mutations into the mo/huAPP695 cDNA (in BS-KS) by PCR using a four-primer strategy: first, two partially overlapping products were generated in separate reactions using primers that encode the desired mutations (Swedish forward: GGA GAT CTC TGA AGT GAA TCT GGA TGC AGA ATT CCG/Indiana reverse: GGG TGA TGA AAA TCA CGG TTG C; Indiana forward: CAA CCG TGA TTT TCA TCA CCC TGG/M13 reverse). |
T1912 |
7274-7276 |
PRP |
denotes |
We |
T1913 |
7277-7289 |
VBD |
denotes |
incorporated |
T1914 |
7467-7476 |
VBN |
denotes |
generated |
T1915 |
7290-7293 |
DT |
denotes |
the |
T1916 |
7336-7345 |
NNS |
denotes |
mutations |
T1917 |
7294-7301 |
NNP |
denotes |
Swedish |
T1918 |
7302-7303 |
-LRB- |
denotes |
( |
T1919 |
7309-7314 |
NN |
denotes |
571NL |
T1920 |
7303-7308 |
NN |
denotes |
KM570 |
T1921 |
7308-7309 |
HYPH |
denotes |
/ |
T1922 |
7314-7315 |
-RRB- |
denotes |
) |
T1923 |
7316-7319 |
CC |
denotes |
and |
T1924 |
7320-7327 |
NNP |
denotes |
Indiana |
T1925 |
7328-7329 |
-LRB- |
denotes |
( |
T1926 |
7329-7334 |
NN |
denotes |
V617F |
T1927 |
7334-7335 |
-RRB- |
denotes |
) |
T1928 |
7346-7350 |
IN |
denotes |
into |
T1929 |
7351-7354 |
DT |
denotes |
the |
T1930 |
7367-7371 |
NN |
denotes |
cDNA |
T1931 |
7355-7357 |
NN |
denotes |
mo |
T1932 |
7358-7366 |
NN |
denotes |
huAPP695 |
T1933 |
7357-7358 |
HYPH |
denotes |
/ |
T1934 |
7372-7373 |
-LRB- |
denotes |
( |
T1935 |
7373-7375 |
IN |
denotes |
in |
T1936 |
7376-7378 |
NN |
denotes |
BS |
T1937 |
7379-7381 |
NN |
denotes |
KS |
T1938 |
7378-7379 |
HYPH |
denotes |
- |
T1939 |
7381-7382 |
-RRB- |
denotes |
) |
T1940 |
7383-7385 |
IN |
denotes |
by |
T1941 |
7386-7389 |
NN |
denotes |
PCR |
T1942 |
7390-7395 |
VBG |
denotes |
using |
T1943 |
7396-7397 |
DT |
denotes |
a |
T1944 |
7410-7418 |
NN |
denotes |
strategy |
T1945 |
7398-7402 |
CD |
denotes |
four |
T1946 |
7403-7409 |
NN |
denotes |
primer |
T1947 |
7402-7403 |
HYPH |
denotes |
- |
T1948 |
7418-7420 |
: |
denotes |
: |
T1949 |
7420-7425 |
RB |
denotes |
first |
T1950 |
7425-7427 |
, |
denotes |
, |
T1951 |
7427-7430 |
CD |
denotes |
two |
T1952 |
7453-7461 |
NNS |
denotes |
products |
T1953 |
7431-7440 |
RB |
denotes |
partially |
T1954 |
7441-7452 |
VBG |
denotes |
overlapping |
T1955 |
7462-7466 |
VBD |
denotes |
were |
T1956 |
7477-7479 |
IN |
denotes |
in |
T1957 |
7480-7488 |
JJ |
denotes |
separate |
T1958 |
7489-7498 |
NNS |
denotes |
reactions |
T1959 |
7499-7504 |
VBG |
denotes |
using |
T1960 |
7505-7512 |
NNS |
denotes |
primers |
T1961 |
7513-7517 |
WDT |
denotes |
that |
T1962 |
7518-7524 |
VBP |
denotes |
encode |
T1963 |
7525-7528 |
DT |
denotes |
the |
T1964 |
7537-7546 |
NNS |
denotes |
mutations |
T1965 |
7529-7536 |
VBN |
denotes |
desired |
T1966 |
7547-7548 |
-LRB- |
denotes |
( |
T1967 |
7710-7713 |
NN |
denotes |
M13 |
T1968 |
7548-7555 |
NNP |
denotes |
Swedish |
T1969 |
7556-7563 |
NN |
denotes |
forward |
T1970 |
7609-7612 |
NN |
denotes |
CCG |
T1971 |
7563-7565 |
: |
denotes |
: |
T1972 |
7565-7568 |
NN |
denotes |
GGA |
T1973 |
7569-7572 |
NN |
denotes |
GAT |
T1974 |
7573-7576 |
NN |
denotes |
CTC |
T1975 |
7577-7580 |
NN |
denotes |
TGA |
T1976 |
7581-7584 |
NN |
denotes |
AGT |
T1977 |
7585-7588 |
NN |
denotes |
GAA |
T1978 |
7589-7592 |
NN |
denotes |
TCT |
T1979 |
7593-7596 |
NNP |
denotes |
GGA |
T1980 |
7597-7600 |
NNP |
denotes |
TGC |
T1981 |
7601-7604 |
NNP |
denotes |
AGA |
T1982 |
7605-7608 |
NNP |
denotes |
ATT |
T1983 |
7658-7659 |
NN |
denotes |
C |
T1984 |
7612-7613 |
HYPH |
denotes |
/ |
T1985 |
7613-7620 |
NNP |
denotes |
Indiana |
T1986 |
7621-7628 |
NN |
denotes |
reverse |
T1987 |
7628-7630 |
: |
denotes |
: |
T1988 |
7630-7633 |
NN |
denotes |
GGG |
T1989 |
7634-7637 |
NN |
denotes |
TGA |
T1990 |
7638-7641 |
NN |
denotes |
TGA |
T1991 |
7642-7645 |
NN |
denotes |
AAA |
T1992 |
7646-7649 |
NN |
denotes |
TCA |
T1993 |
7650-7653 |
NN |
denotes |
CGG |
T1994 |
7654-7657 |
NN |
denotes |
TTG |
T1995 |
7659-7660 |
: |
denotes |
; |
T1996 |
7661-7668 |
NNP |
denotes |
Indiana |
T1997 |
7669-7676 |
NN |
denotes |
forward |
T1998 |
7676-7678 |
: |
denotes |
: |
T1999 |
7678-7681 |
NN |
denotes |
CAA |
T2000 |
7682-7685 |
NN |
denotes |
CCG |
T2001 |
7686-7689 |
NN |
denotes |
TGA |
T2002 |
7690-7693 |
NN |
denotes |
TTT |
T2003 |
7694-7697 |
NN |
denotes |
TCA |
T2004 |
7698-7701 |
NN |
denotes |
TCA |
T2005 |
7702-7705 |
NN |
denotes |
CCC |
T2006 |
7706-7709 |
NN |
denotes |
TGG |
T2007 |
7709-7710 |
HYPH |
denotes |
/ |
T2008 |
7714-7721 |
RB |
denotes |
reverse |
T2009 |
7721-7722 |
-RRB- |
denotes |
) |
T2010 |
7722-7723 |
. |
denotes |
. |
T2011 |
7723-7847 |
sentence |
denotes |
The two PCR products were ligated, digested with BglII and ApaI and cloned back into the original mo/huAPP695-BS-KS vector. |
T2012 |
7724-7727 |
DT |
denotes |
The |
T2013 |
7736-7744 |
NNS |
denotes |
products |
T2014 |
7728-7731 |
CD |
denotes |
two |
T2015 |
7732-7735 |
NN |
denotes |
PCR |
T2016 |
7750-7757 |
VBN |
denotes |
ligated |
T2017 |
7745-7749 |
VBD |
denotes |
were |
T2018 |
7757-7759 |
, |
denotes |
, |
T2019 |
7759-7767 |
VBN |
denotes |
digested |
T2020 |
7768-7772 |
IN |
denotes |
with |
T2021 |
7773-7778 |
NN |
denotes |
BglII |
T2022 |
7779-7782 |
CC |
denotes |
and |
T2023 |
7783-7787 |
NN |
denotes |
ApaI |
T2024 |
7788-7791 |
CC |
denotes |
and |
T2025 |
7792-7798 |
VBN |
denotes |
cloned |
T2026 |
7799-7803 |
RB |
denotes |
back |
T2027 |
7804-7808 |
IN |
denotes |
into |
T2028 |
7809-7812 |
DT |
denotes |
the |
T2029 |
7840-7846 |
NN |
denotes |
vector |
T2030 |
7813-7821 |
JJ |
denotes |
original |
T2031 |
7822-7824 |
NN |
denotes |
mo |
T2032 |
7837-7839 |
NN |
denotes |
KS |
T2033 |
7824-7825 |
HYPH |
denotes |
/ |
T2034 |
7825-7833 |
NN |
denotes |
huAPP695 |
T2035 |
7833-7834 |
HYPH |
denotes |
- |
T2036 |
7834-7836 |
NN |
denotes |
BS |
T2037 |
7836-7837 |
HYPH |
denotes |
- |
T2038 |
7846-7847 |
. |
denotes |
. |
T2039 |
7847-7974 |
sentence |
denotes |
Finally, the new APP695swe/ind was subcloned into the XhoI site of the moPrP-tetP vector from above to complete the construct. |
T2040 |
7848-7855 |
RB |
denotes |
Finally |
T2041 |
7883-7892 |
VBN |
denotes |
subcloned |
T2042 |
7855-7857 |
, |
denotes |
, |
T2043 |
7857-7860 |
DT |
denotes |
the |
T2044 |
7875-7878 |
NN |
denotes |
ind |
T2045 |
7861-7864 |
JJ |
denotes |
new |
T2046 |
7865-7874 |
NN |
denotes |
APP695swe |
T2047 |
7874-7875 |
HYPH |
denotes |
/ |
T2048 |
7879-7882 |
VBD |
denotes |
was |
T2049 |
7893-7897 |
IN |
denotes |
into |
T2050 |
7898-7901 |
DT |
denotes |
the |
T2051 |
7907-7911 |
NN |
denotes |
site |
T2052 |
7902-7906 |
NN |
denotes |
XhoI |
T2053 |
7912-7914 |
IN |
denotes |
of |
T2054 |
7915-7918 |
DT |
denotes |
the |
T2055 |
7930-7936 |
NN |
denotes |
vector |
T2056 |
7919-7924 |
NN |
denotes |
moPrP |
T2057 |
7925-7929 |
NN |
denotes |
tetP |
T2058 |
7924-7925 |
HYPH |
denotes |
- |
T2059 |
7937-7941 |
IN |
denotes |
from |
T2060 |
7942-7947 |
RB |
denotes |
above |
T2061 |
7948-7950 |
TO |
denotes |
to |
T2062 |
7951-7959 |
VB |
denotes |
complete |
T2063 |
7960-7963 |
DT |
denotes |
the |
T2064 |
7964-7973 |
NN |
denotes |
construct |
T2065 |
7973-7974 |
. |
denotes |
. |
T2158 |
7976-7986 |
JJ |
denotes |
Pronuclear |
T2159 |
7987-7996 |
NN |
denotes |
Injection |
T2160 |
7996-7998 |
, |
denotes |
, |
T2161 |
7998-8007 |
NN |
denotes |
Screening |
T2162 |
8008-8010 |
IN |
denotes |
of |
T2163 |
8011-8019 |
NNS |
denotes |
Founders |
T2164 |
8019-8021 |
, |
denotes |
, |
T2165 |
8021-8024 |
CC |
denotes |
and |
T2166 |
8025-8036 |
NN |
denotes |
Maintenance |
T2167 |
8037-8039 |
IN |
denotes |
of |
T2168 |
8040-8043 |
DT |
denotes |
the |
T2169 |
8044-8049 |
NNS |
denotes |
Lines |
T2170 |
8049-8164 |
sentence |
denotes |
The moPrP-tetP-mo/huAPP695swe/ind vector was linearized and the pBluescript domain excised by digestion with NotI. |
T2171 |
8050-8053 |
DT |
denotes |
The |
T2172 |
8084-8090 |
NN |
denotes |
vector |
T2173 |
8054-8059 |
NN |
denotes |
moPrP |
T2174 |
8080-8083 |
NN |
denotes |
ind |
T2175 |
8059-8060 |
HYPH |
denotes |
- |
T2176 |
8060-8064 |
NN |
denotes |
tetP |
T2177 |
8064-8065 |
HYPH |
denotes |
- |
T2178 |
8065-8067 |
NN |
denotes |
mo |
T2179 |
8067-8068 |
HYPH |
denotes |
/ |
T2180 |
8068-8079 |
NN |
denotes |
huAPP695swe |
T2181 |
8079-8080 |
HYPH |
denotes |
/ |
T2182 |
8095-8105 |
VBN |
denotes |
linearized |
T2183 |
8091-8094 |
VBD |
denotes |
was |
T2184 |
8106-8109 |
CC |
denotes |
and |
T2185 |
8110-8113 |
DT |
denotes |
the |
T2186 |
8126-8132 |
NN |
denotes |
domain |
T2187 |
8114-8125 |
NNP |
denotes |
pBluescript |
T2188 |
8133-8140 |
VBN |
denotes |
excised |
T2189 |
8141-8143 |
IN |
denotes |
by |
T2190 |
8144-8153 |
NN |
denotes |
digestion |
T2191 |
8154-8158 |
IN |
denotes |
with |
T2192 |
8159-8163 |
NN |
denotes |
NotI |
T2193 |
8163-8164 |
. |
denotes |
. |
T2194 |
8164-8270 |
sentence |
denotes |
The purified vector was injected into the pronucleus of fertilized eggs from C57BL/6J × C3HeJ F1 matings. |
T2195 |
8165-8168 |
DT |
denotes |
The |
T2196 |
8178-8184 |
NN |
denotes |
vector |
T2197 |
8169-8177 |
VBN |
denotes |
purified |
T2198 |
8189-8197 |
VBN |
denotes |
injected |
T2199 |
8185-8188 |
VBD |
denotes |
was |
T2200 |
8198-8202 |
IN |
denotes |
into |
T2201 |
8203-8206 |
DT |
denotes |
the |
T2202 |
8207-8217 |
NN |
denotes |
pronucleus |
T2203 |
8218-8220 |
IN |
denotes |
of |
T2204 |
8221-8231 |
VBN |
denotes |
fertilized |
T2205 |
8232-8236 |
NNS |
denotes |
eggs |
T2206 |
8237-8241 |
IN |
denotes |
from |
T2207 |
8242-8247 |
NN |
denotes |
C57BL |
T2208 |
8253-8258 |
NN |
denotes |
C3HeJ |
T2209 |
8247-8248 |
HYPH |
denotes |
/ |
T2210 |
8248-8250 |
NN |
denotes |
6J |
T2211 |
8251-8252 |
SYM |
denotes |
× |
T2212 |
8262-8269 |
NNS |
denotes |
matings |
T2213 |
8259-8261 |
NN |
denotes |
F1 |
T2214 |
8269-8270 |
. |
denotes |
. |
T2215 |
8270-8407 |
sentence |
denotes |
Founder animals were screened for the presence of the transgene by three-way PCR using the S36 and PrP-S/PrP-AS primers described below. |
T2216 |
8271-8278 |
NN |
denotes |
Founder |
T2217 |
8279-8286 |
NNS |
denotes |
animals |
T2218 |
8292-8300 |
VBN |
denotes |
screened |
T2219 |
8287-8291 |
VBD |
denotes |
were |
T2220 |
8301-8304 |
IN |
denotes |
for |
T2221 |
8305-8308 |
DT |
denotes |
the |
T2222 |
8309-8317 |
NN |
denotes |
presence |
T2223 |
8318-8320 |
IN |
denotes |
of |
T2224 |
8321-8324 |
DT |
denotes |
the |
T2225 |
8325-8334 |
NN |
denotes |
transgene |
T2226 |
8335-8337 |
IN |
denotes |
by |
T2227 |
8338-8343 |
CD |
denotes |
three |
T2228 |
8344-8347 |
NN |
denotes |
way |
T2229 |
8343-8344 |
HYPH |
denotes |
- |
T2230 |
8348-8351 |
NN |
denotes |
PCR |
T2231 |
8352-8357 |
VBG |
denotes |
using |
T2232 |
8358-8361 |
DT |
denotes |
the |
T2233 |
8383-8390 |
NNS |
denotes |
primers |
T2234 |
8362-8365 |
NN |
denotes |
S36 |
T2235 |
8366-8369 |
CC |
denotes |
and |
T2236 |
8370-8373 |
NN |
denotes |
PrP |
T2237 |
8380-8382 |
NN |
denotes |
AS |
T2238 |
8373-8374 |
HYPH |
denotes |
- |
T2239 |
8374-8375 |
NN |
denotes |
S |
T2240 |
8375-8376 |
HYPH |
denotes |
/ |
T2241 |
8376-8379 |
NN |
denotes |
PrP |
T2242 |
8379-8380 |
HYPH |
denotes |
- |
T2243 |
8391-8400 |
VBN |
denotes |
described |
T2244 |
8401-8406 |
RB |
denotes |
below |
T2245 |
8406-8407 |
. |
denotes |
. |
T2246 |
8407-8692 |
sentence |
denotes |
Transgene-positive founders were bred to animals expressing the tetracycline transactivator (tTA) under control of the calcium-calmodulin kinase IIα (CaMKIIα) promoter obtained from Jackson Laboratory [16] (Bar Harbor, Maine, United States; stock # 3010; B6;CBA-TgN[Camk2a-tTA]1Mmay). |
T2247 |
8408-8417 |
NN |
denotes |
Transgene |
T2248 |
8418-8426 |
JJ |
denotes |
positive |
T2249 |
8417-8418 |
HYPH |
denotes |
- |
T2250 |
8427-8435 |
NNS |
denotes |
founders |
T2251 |
8441-8445 |
VBN |
denotes |
bred |
T2252 |
8436-8440 |
VBD |
denotes |
were |
T2253 |
8446-8448 |
IN |
denotes |
to |
T2254 |
8449-8456 |
NNS |
denotes |
animals |
T2255 |
8457-8467 |
VBG |
denotes |
expressing |
T2256 |
8468-8471 |
DT |
denotes |
the |
T2257 |
8485-8499 |
NN |
denotes |
transactivator |
T2258 |
8472-8484 |
NN |
denotes |
tetracycline |
T2259 |
8500-8501 |
-LRB- |
denotes |
( |
T2260 |
8501-8504 |
NN |
denotes |
tTA |
T2261 |
8504-8505 |
-RRB- |
denotes |
) |
T2262 |
8506-8511 |
IN |
denotes |
under |
T2263 |
8512-8519 |
NN |
denotes |
control |
T2264 |
8520-8522 |
IN |
denotes |
of |
T2265 |
8523-8526 |
DT |
denotes |
the |
T2266 |
8567-8575 |
NN |
denotes |
promoter |
T2267 |
8527-8534 |
NN |
denotes |
calcium |
T2268 |
8535-8545 |
NN |
denotes |
calmodulin |
T2269 |
8534-8535 |
HYPH |
denotes |
- |
T2270 |
8553-8556 |
NN |
denotes |
IIα |
T2271 |
8546-8552 |
NN |
denotes |
kinase |
T2272 |
8557-8558 |
-LRB- |
denotes |
( |
T2273 |
8558-8565 |
NN |
denotes |
CaMKIIα |
T2274 |
8565-8566 |
-RRB- |
denotes |
) |
T2275 |
8576-8584 |
VBN |
denotes |
obtained |
T2276 |
8585-8589 |
IN |
denotes |
from |
T2277 |
8590-8597 |
NNP |
denotes |
Jackson |
T2278 |
8598-8608 |
NNP |
denotes |
Laboratory |
T2279 |
8609-8610 |
-LRB- |
denotes |
[ |
T2280 |
8610-8612 |
CD |
denotes |
16 |
T2281 |
8612-8613 |
-RRB- |
denotes |
] |
T2282 |
8614-8615 |
-LRB- |
denotes |
( |
T2283 |
8619-8625 |
NNP |
denotes |
Harbor |
T2284 |
8615-8618 |
NNP |
denotes |
Bar |
T2285 |
8625-8627 |
, |
denotes |
, |
T2286 |
8627-8632 |
NNP |
denotes |
Maine |
T2287 |
8632-8634 |
, |
denotes |
, |
T2288 |
8634-8640 |
NNP |
denotes |
United |
T2289 |
8641-8647 |
NNP |
denotes |
States |
T2290 |
8647-8648 |
: |
denotes |
; |
T2291 |
8649-8654 |
NN |
denotes |
stock |
T2292 |
8685-8690 |
NN |
denotes |
1Mmay |
T2293 |
8655-8656 |
SYM |
denotes |
# |
T2294 |
8657-8661 |
CD |
denotes |
3010 |
T2295 |
8661-8662 |
: |
denotes |
; |
T2296 |
8663-8665 |
NN |
denotes |
B6 |
T2297 |
8665-8666 |
: |
denotes |
; |
T2298 |
8666-8669 |
NN |
denotes |
CBA |
T2299 |
8669-8670 |
HYPH |
denotes |
- |
T2300 |
8670-8673 |
NN |
denotes |
TgN |
T2301 |
8673-8674 |
-LRB- |
denotes |
[ |
T2302 |
8674-8680 |
NN |
denotes |
Camk2a |
T2303 |
8680-8681 |
HYPH |
denotes |
- |
T2304 |
8681-8684 |
NN |
denotes |
tTA |
T2305 |
8684-8685 |
-RRB- |
denotes |
] |
T2306 |
8690-8691 |
-RRB- |
denotes |
) |
T2307 |
8691-8692 |
. |
denotes |
. |
T2308 |
8692-8813 |
sentence |
denotes |
The colony was thereafter maintained by crossing single transgenic tTA and APP offspring for each of the four APP lines. |
T2309 |
8693-8696 |
DT |
denotes |
The |
T2310 |
8697-8703 |
NN |
denotes |
colony |
T2311 |
8719-8729 |
VBN |
denotes |
maintained |
T2312 |
8704-8707 |
VBD |
denotes |
was |
T2313 |
8708-8718 |
RB |
denotes |
thereafter |
T2314 |
8730-8732 |
IN |
denotes |
by |
T2315 |
8733-8741 |
VBG |
denotes |
crossing |
T2316 |
8742-8748 |
JJ |
denotes |
single |
T2317 |
8772-8781 |
NN |
denotes |
offspring |
T2318 |
8749-8759 |
JJ |
denotes |
transgenic |
T2319 |
8760-8763 |
NN |
denotes |
tTA |
T2320 |
8764-8767 |
CC |
denotes |
and |
T2321 |
8768-8771 |
NN |
denotes |
APP |
T2322 |
8782-8785 |
IN |
denotes |
for |
T2323 |
8786-8790 |
DT |
denotes |
each |
T2324 |
8791-8793 |
IN |
denotes |
of |
T2325 |
8794-8797 |
DT |
denotes |
the |
T2326 |
8807-8812 |
NNS |
denotes |
lines |
T2327 |
8798-8802 |
CD |
denotes |
four |
T2328 |
8803-8806 |
NN |
denotes |
APP |
T2329 |
8812-8813 |
. |
denotes |
. |
T2330 |
8813-8869 |
sentence |
denotes |
All mice were provided fresh food and water ad libitum. |
T2331 |
8814-8817 |
DT |
denotes |
All |
T2332 |
8818-8822 |
NNS |
denotes |
mice |
T2333 |
8828-8836 |
VBN |
denotes |
provided |
T2334 |
8823-8827 |
VBD |
denotes |
were |
T2335 |
8837-8842 |
JJ |
denotes |
fresh |
T2336 |
8843-8847 |
NN |
denotes |
food |
T2337 |
8848-8851 |
CC |
denotes |
and |
T2338 |
8852-8857 |
NN |
denotes |
water |
T2339 |
8858-8860 |
FW |
denotes |
ad |
T2340 |
8861-8868 |
FW |
denotes |
libitum |
T2341 |
8868-8869 |
. |
denotes |
. |
T2342 |
8869-9026 |
sentence |
denotes |
Animal protocols were approved by both the Johns Hopkins University and the California Institute of Technology Institutional Animal Care and Use Committees. |
T2343 |
8870-8876 |
NN |
denotes |
Animal |
T2344 |
8877-8886 |
NNS |
denotes |
protocols |
T2345 |
8892-8900 |
VBN |
denotes |
approved |
T2346 |
8887-8891 |
VBD |
denotes |
were |
T2347 |
8901-8903 |
IN |
denotes |
by |
T2348 |
8904-8908 |
DT |
denotes |
both |
T2349 |
8927-8937 |
NNP |
denotes |
University |
T2350 |
8909-8912 |
DT |
denotes |
the |
T2351 |
8913-8918 |
NNP |
denotes |
Johns |
T2352 |
8919-8926 |
NNP |
denotes |
Hopkins |
T2353 |
9015-9025 |
NNPS |
denotes |
Committees |
T2354 |
8938-8941 |
CC |
denotes |
and |
T2355 |
8942-8945 |
DT |
denotes |
the |
T2356 |
8957-8966 |
NNP |
denotes |
Institute |
T2357 |
8946-8956 |
NNP |
denotes |
California |
T2358 |
8967-8969 |
IN |
denotes |
of |
T2359 |
8970-8980 |
NNP |
denotes |
Technology |
T2360 |
8981-8994 |
NNP |
denotes |
Institutional |
T2361 |
8995-9001 |
NNP |
denotes |
Animal |
T2362 |
9002-9006 |
NNP |
denotes |
Care |
T2363 |
9007-9010 |
CC |
denotes |
and |
T2364 |
9011-9014 |
NNP |
denotes |
Use |
T2365 |
9025-9026 |
. |
denotes |
. |
T2408 |
9028-9039 |
NN |
denotes |
Doxycycline |
T2409 |
9040-9054 |
NN |
denotes |
Administration |
T2410 |
9054-9190 |
sentence |
denotes |
Doxycycline (dox) was administered through commercially available dox-containing chow (BioServ, Frenchtown, New Jersey, United States). |
T2411 |
9055-9066 |
NN |
denotes |
Doxycycline |
T2412 |
9077-9089 |
VBN |
denotes |
administered |
T2413 |
9067-9068 |
-LRB- |
denotes |
( |
T2414 |
9068-9071 |
NN |
denotes |
dox |
T2415 |
9071-9072 |
-RRB- |
denotes |
) |
T2416 |
9073-9076 |
VBD |
denotes |
was |
T2417 |
9090-9097 |
IN |
denotes |
through |
T2418 |
9098-9110 |
RB |
denotes |
commercially |
T2419 |
9111-9120 |
JJ |
denotes |
available |
T2420 |
9136-9140 |
NN |
denotes |
chow |
T2421 |
9121-9124 |
NN |
denotes |
dox |
T2422 |
9125-9135 |
VBG |
denotes |
containing |
T2423 |
9124-9125 |
HYPH |
denotes |
- |
T2424 |
9141-9142 |
-LRB- |
denotes |
( |
T2425 |
9142-9149 |
NNP |
denotes |
BioServ |
T2426 |
9149-9151 |
, |
denotes |
, |
T2427 |
9151-9161 |
NNP |
denotes |
Frenchtown |
T2428 |
9161-9163 |
, |
denotes |
, |
T2429 |
9163-9166 |
NNP |
denotes |
New |
T2430 |
9167-9173 |
NNP |
denotes |
Jersey |
T2431 |
9173-9175 |
, |
denotes |
, |
T2432 |
9175-9181 |
NNP |
denotes |
United |
T2433 |
9182-9188 |
NNP |
denotes |
States |
T2434 |
9188-9189 |
-RRB- |
denotes |
) |
T2435 |
9189-9190 |
. |
denotes |
. |
T2436 |
9190-9346 |
sentence |
denotes |
The chow contained 200 mg/kg of antibiotic; based on estimated consumption of 5 g per mouse per day, the expected dose to each animal was 1 mg dox per day. |
T2437 |
9191-9194 |
DT |
denotes |
The |
T2438 |
9195-9199 |
NN |
denotes |
chow |
T2439 |
9200-9209 |
VBD |
denotes |
contained |
T2440 |
9325-9328 |
VBD |
denotes |
was |
T2441 |
9210-9213 |
CD |
denotes |
200 |
T2442 |
9214-9216 |
NN |
denotes |
mg |
T2443 |
9216-9217 |
SYM |
denotes |
/ |
T2444 |
9217-9219 |
NN |
denotes |
kg |
T2445 |
9220-9222 |
IN |
denotes |
of |
T2446 |
9223-9233 |
JJ |
denotes |
antibiotic |
T2447 |
9233-9234 |
: |
denotes |
; |
T2448 |
9235-9240 |
VBN |
denotes |
based |
T2449 |
9241-9243 |
IN |
denotes |
on |
T2450 |
9244-9253 |
VBN |
denotes |
estimated |
T2451 |
9254-9265 |
NN |
denotes |
consumption |
T2452 |
9266-9268 |
IN |
denotes |
of |
T2453 |
9269-9270 |
CD |
denotes |
5 |
T2454 |
9271-9272 |
NN |
denotes |
g |
T2455 |
9273-9276 |
IN |
denotes |
per |
T2456 |
9277-9282 |
NN |
denotes |
mouse |
T2457 |
9283-9286 |
IN |
denotes |
per |
T2458 |
9287-9290 |
NN |
denotes |
day |
T2459 |
9290-9292 |
, |
denotes |
, |
T2460 |
9292-9295 |
DT |
denotes |
the |
T2461 |
9305-9309 |
NN |
denotes |
dose |
T2462 |
9296-9304 |
VBN |
denotes |
expected |
T2463 |
9310-9312 |
IN |
denotes |
to |
T2464 |
9313-9317 |
DT |
denotes |
each |
T2465 |
9318-9324 |
NN |
denotes |
animal |
T2466 |
9329-9330 |
CD |
denotes |
1 |
T2467 |
9331-9333 |
NN |
denotes |
mg |
T2468 |
9334-9337 |
NN |
denotes |
dox |
T2469 |
9338-9341 |
IN |
denotes |
per |
T2470 |
9342-9345 |
NN |
denotes |
day |
T2471 |
9345-9346 |
. |
denotes |
. |
T2472 |
9346-9432 |
sentence |
denotes |
The average 25-g animal therefore received 40 μg of dox per gram body weight per day. |
T2473 |
9347-9350 |
DT |
denotes |
The |
T2474 |
9364-9370 |
NN |
denotes |
animal |
T2475 |
9351-9358 |
JJ |
denotes |
average |
T2476 |
9359-9361 |
CD |
denotes |
25 |
T2477 |
9362-9363 |
NN |
denotes |
g |
T2478 |
9361-9362 |
HYPH |
denotes |
- |
T2479 |
9381-9389 |
VBD |
denotes |
received |
T2480 |
9371-9380 |
RB |
denotes |
therefore |
T2481 |
9390-9392 |
CD |
denotes |
40 |
T2482 |
9393-9395 |
NN |
denotes |
μg |
T2483 |
9396-9398 |
IN |
denotes |
of |
T2484 |
9399-9402 |
NN |
denotes |
dox |
T2485 |
9403-9406 |
IN |
denotes |
per |
T2486 |
9407-9411 |
NN |
denotes |
gram |
T2487 |
9417-9423 |
NN |
denotes |
weight |
T2488 |
9412-9416 |
NN |
denotes |
body |
T2489 |
9424-9427 |
IN |
denotes |
per |
T2490 |
9428-9431 |
NN |
denotes |
day |
T2491 |
9431-9432 |
. |
denotes |
. |
T2492 |
9432-9508 |
sentence |
denotes |
Chow was changed 1–2 times per week to prevent breakdown of the antibiotic. |
T2493 |
9433-9437 |
NN |
denotes |
Chow |
T2494 |
9442-9449 |
VBN |
denotes |
changed |
T2495 |
9438-9441 |
VBD |
denotes |
was |
T2496 |
9450-9451 |
CD |
denotes |
1 |
T2497 |
9452-9453 |
CD |
denotes |
2 |
T2498 |
9451-9452 |
SYM |
denotes |
– |
T2499 |
9454-9459 |
NNS |
denotes |
times |
T2500 |
9460-9463 |
IN |
denotes |
per |
T2501 |
9464-9468 |
NN |
denotes |
week |
T2502 |
9469-9471 |
TO |
denotes |
to |
T2503 |
9472-9479 |
VB |
denotes |
prevent |
T2504 |
9480-9489 |
NN |
denotes |
breakdown |
T2505 |
9490-9492 |
IN |
denotes |
of |
T2506 |
9493-9496 |
DT |
denotes |
the |
T2507 |
9497-9507 |
NN |
denotes |
antibiotic |
T2508 |
9507-9508 |
. |
denotes |
. |
T2635 |
9510-9520 |
NN |
denotes |
Genotyping |
T2636 |
9520-9651 |
sentence |
denotes |
Offspring were genotyped for the presence of each transgene by PCR amplification of genomic DNA extracted from a 5-mm tail biopsy. |
T2637 |
9521-9530 |
NN |
denotes |
Offspring |
T2638 |
9536-9545 |
VBN |
denotes |
genotyped |
T2639 |
9531-9535 |
VBD |
denotes |
were |
T2640 |
9546-9549 |
IN |
denotes |
for |
T2641 |
9550-9553 |
DT |
denotes |
the |
T2642 |
9554-9562 |
NN |
denotes |
presence |
T2643 |
9563-9565 |
IN |
denotes |
of |
T2644 |
9566-9570 |
DT |
denotes |
each |
T2645 |
9571-9580 |
NN |
denotes |
transgene |
T2646 |
9581-9583 |
IN |
denotes |
by |
T2647 |
9584-9587 |
NN |
denotes |
PCR |
T2648 |
9588-9601 |
NN |
denotes |
amplification |
T2649 |
9602-9604 |
IN |
denotes |
of |
T2650 |
9605-9612 |
JJ |
denotes |
genomic |
T2651 |
9613-9616 |
NN |
denotes |
DNA |
T2652 |
9617-9626 |
VBN |
denotes |
extracted |
T2653 |
9627-9631 |
IN |
denotes |
from |
T2654 |
9632-9633 |
DT |
denotes |
a |
T2655 |
9644-9650 |
NN |
denotes |
biopsy |
T2656 |
9634-9635 |
CD |
denotes |
5 |
T2657 |
9636-9638 |
NN |
denotes |
mm |
T2658 |
9635-9636 |
HYPH |
denotes |
- |
T2659 |
9639-9643 |
NN |
denotes |
tail |
T2660 |
9650-9651 |
. |
denotes |
. |
T2661 |
9651-9790 |
sentence |
denotes |
Tails were heated to 95 °C for 45 min in 250 μl of 50 mM NaOH, vortexed, then neutralized with an equal volume of 0.5 M Tris-HCl (pH 5.5). |
T2662 |
9652-9657 |
NNS |
denotes |
Tails |
T2663 |
9663-9669 |
VBN |
denotes |
heated |
T2664 |
9658-9662 |
VBD |
denotes |
were |
T2665 |
9670-9672 |
IN |
denotes |
to |
T2666 |
9673-9675 |
CD |
denotes |
95 |
T2667 |
9676-9678 |
NN |
denotes |
°C |
T2668 |
9679-9682 |
IN |
denotes |
for |
T2669 |
9683-9685 |
CD |
denotes |
45 |
T2670 |
9686-9689 |
NN |
denotes |
min |
T2671 |
9690-9692 |
IN |
denotes |
in |
T2672 |
9693-9696 |
CD |
denotes |
250 |
T2673 |
9697-9699 |
NN |
denotes |
μl |
T2674 |
9700-9702 |
IN |
denotes |
of |
T2675 |
9703-9705 |
CD |
denotes |
50 |
T2676 |
9706-9708 |
NN |
denotes |
mM |
T2677 |
9709-9713 |
NN |
denotes |
NaOH |
T2678 |
9713-9715 |
, |
denotes |
, |
T2679 |
9715-9723 |
VBN |
denotes |
vortexed |
T2680 |
9723-9725 |
, |
denotes |
, |
T2681 |
9725-9729 |
RB |
denotes |
then |
T2682 |
9730-9741 |
VBN |
denotes |
neutralized |
T2683 |
9742-9746 |
IN |
denotes |
with |
T2684 |
9747-9749 |
DT |
denotes |
an |
T2685 |
9756-9762 |
NN |
denotes |
volume |
T2686 |
9750-9755 |
JJ |
denotes |
equal |
T2687 |
9763-9765 |
IN |
denotes |
of |
T2688 |
9766-9769 |
CD |
denotes |
0.5 |
T2689 |
9770-9771 |
NN |
denotes |
M |
T2690 |
9777-9780 |
NN |
denotes |
HCl |
T2691 |
9772-9776 |
NN |
denotes |
Tris |
T2692 |
9776-9777 |
HYPH |
denotes |
- |
T2693 |
9781-9782 |
-LRB- |
denotes |
( |
T2694 |
9782-9784 |
NN |
denotes |
pH |
T2695 |
9785-9788 |
CD |
denotes |
5.5 |
T2696 |
9788-9789 |
-RRB- |
denotes |
) |
T2697 |
9789-9790 |
. |
denotes |
. |
T2698 |
9790-9883 |
sentence |
denotes |
Debris was sedimented by centrifugation, and 3 μl of supernatant was used for amplification. |
T2699 |
9791-9797 |
NN |
denotes |
Debris |
T2700 |
9802-9812 |
VBN |
denotes |
sedimented |
T2701 |
9798-9801 |
VBD |
denotes |
was |
T2702 |
9813-9815 |
IN |
denotes |
by |
T2703 |
9816-9830 |
NN |
denotes |
centrifugation |
T2704 |
9830-9832 |
, |
denotes |
, |
T2705 |
9832-9835 |
CC |
denotes |
and |
T2706 |
9836-9837 |
CD |
denotes |
3 |
T2707 |
9838-9840 |
NN |
denotes |
μl |
T2708 |
9860-9864 |
VBN |
denotes |
used |
T2709 |
9841-9843 |
IN |
denotes |
of |
T2710 |
9844-9855 |
NN |
denotes |
supernatant |
T2711 |
9856-9859 |
VBD |
denotes |
was |
T2712 |
9865-9868 |
IN |
denotes |
for |
T2713 |
9869-9882 |
NN |
denotes |
amplification |
T2714 |
9882-9883 |
. |
denotes |
. |
T2715 |
9883-9990 |
sentence |
denotes |
Genotyping for APP and tTA transgenes was performed in the same PCR reaction, using five separate primers. |
T2716 |
9884-9894 |
VBG |
denotes |
Genotyping |
T2717 |
9926-9935 |
VBN |
denotes |
performed |
T2718 |
9895-9898 |
IN |
denotes |
for |
T2719 |
9899-9902 |
NN |
denotes |
APP |
T2720 |
9911-9921 |
NNS |
denotes |
transgenes |
T2721 |
9903-9906 |
CC |
denotes |
and |
T2722 |
9907-9910 |
NN |
denotes |
tTA |
T2723 |
9922-9925 |
VBD |
denotes |
was |
T2724 |
9936-9938 |
IN |
denotes |
in |
T2725 |
9939-9942 |
DT |
denotes |
the |
T2726 |
9952-9960 |
NN |
denotes |
reaction |
T2727 |
9943-9947 |
JJ |
denotes |
same |
T2728 |
9948-9951 |
NN |
denotes |
PCR |
T2729 |
9960-9962 |
, |
denotes |
, |
T2730 |
9962-9967 |
VBG |
denotes |
using |
T2731 |
9968-9972 |
CD |
denotes |
five |
T2732 |
9982-9989 |
NNS |
denotes |
primers |
T2733 |
9973-9981 |
JJ |
denotes |
separate |
T2734 |
9989-9990 |
. |
denotes |
. |
T2735 |
9990-10207 |
sentence |
denotes |
APP was amplified using forward primer S36 located in the 3′ end of the APP cDNA (CCG AGA TCT CTG AAG TGA AGA TGG ATG) and reverse primer PrP-AS-J located in the 3′ UTR of the vector (CCA AGC CTA GAC CAC GAG AAT GC). |
T2736 |
9991-9994 |
NN |
denotes |
APP |
T2737 |
9999-10008 |
VBN |
denotes |
amplified |
T2738 |
9995-9998 |
VBD |
denotes |
was |
T2739 |
10009-10014 |
VBG |
denotes |
using |
T2740 |
10015-10022 |
RB |
denotes |
forward |
T2741 |
10030-10033 |
NN |
denotes |
S36 |
T2742 |
10023-10029 |
NN |
denotes |
primer |
T2743 |
10034-10041 |
VBN |
denotes |
located |
T2744 |
10042-10044 |
IN |
denotes |
in |
T2745 |
10045-10048 |
DT |
denotes |
the |
T2746 |
10052-10055 |
NN |
denotes |
end |
T2747 |
10049-10050 |
CD |
denotes |
3 |
T2748 |
10050-10051 |
SYM |
denotes |
′ |
T2749 |
10056-10058 |
IN |
denotes |
of |
T2750 |
10059-10062 |
DT |
denotes |
the |
T2751 |
10067-10071 |
NN |
denotes |
cDNA |
T2752 |
10063-10066 |
NN |
denotes |
APP |
T2753 |
10072-10073 |
-LRB- |
denotes |
( |
T2754 |
10105-10108 |
NN |
denotes |
ATG |
T2755 |
10073-10076 |
NN |
denotes |
CCG |
T2756 |
10077-10080 |
NN |
denotes |
AGA |
T2757 |
10081-10084 |
NN |
denotes |
TCT |
T2758 |
10085-10088 |
NN |
denotes |
CTG |
T2759 |
10089-10092 |
NN |
denotes |
AAG |
T2760 |
10093-10096 |
NN |
denotes |
TGA |
T2761 |
10097-10100 |
NN |
denotes |
AGA |
T2762 |
10101-10104 |
NN |
denotes |
TGG |
T2763 |
10108-10109 |
-RRB- |
denotes |
) |
T2764 |
10110-10113 |
CC |
denotes |
and |
T2765 |
10114-10121 |
JJ |
denotes |
reverse |
T2766 |
10136-10137 |
NN |
denotes |
J |
T2767 |
10122-10128 |
NN |
denotes |
primer |
T2768 |
10129-10132 |
NN |
denotes |
PrP |
T2769 |
10132-10133 |
HYPH |
denotes |
- |
T2770 |
10133-10135 |
NN |
denotes |
AS |
T2771 |
10135-10136 |
HYPH |
denotes |
- |
T2772 |
10138-10145 |
VBN |
denotes |
located |
T2773 |
10146-10148 |
IN |
denotes |
in |
T2774 |
10149-10152 |
DT |
denotes |
the |
T2775 |
10156-10159 |
NN |
denotes |
UTR |
T2776 |
10153-10154 |
CD |
denotes |
3 |
T2777 |
10154-10155 |
SYM |
denotes |
′ |
T2778 |
10160-10162 |
IN |
denotes |
of |
T2779 |
10163-10166 |
DT |
denotes |
the |
T2780 |
10167-10173 |
NN |
denotes |
vector |
T2781 |
10174-10175 |
-LRB- |
denotes |
( |
T2782 |
10203-10205 |
NN |
denotes |
GC |
T2783 |
10175-10178 |
NN |
denotes |
CCA |
T2784 |
10179-10182 |
NN |
denotes |
AGC |
T2785 |
10183-10186 |
NN |
denotes |
CTA |
T2786 |
10187-10190 |
NN |
denotes |
GAC |
T2787 |
10191-10194 |
NN |
denotes |
CAC |
T2788 |
10195-10198 |
NN |
denotes |
GAG |
T2789 |
10199-10202 |
NN |
denotes |
AAT |
T2790 |
10205-10206 |
-RRB- |
denotes |
) |
T2791 |
10206-10207 |
. |
denotes |
. |
T2792 |
10207-10463 |
sentence |
denotes |
The tTA transgene was detected using a primer set that amplified across its two subdomains with tet forward located within the Tn10 tetracycline repressor (CGC TGT GGG GCA TTT TAC TTT AG) and tet reverse within the HSV1 VP16 (CAT GTC CAG ATC GAA ATC GTC). |
T2793 |
10208-10211 |
DT |
denotes |
The |
T2794 |
10216-10225 |
NN |
denotes |
transgene |
T2795 |
10212-10215 |
NN |
denotes |
tTA |
T2796 |
10230-10238 |
VBN |
denotes |
detected |
T2797 |
10226-10229 |
VBD |
denotes |
was |
T2798 |
10239-10244 |
VBG |
denotes |
using |
T2799 |
10245-10246 |
DT |
denotes |
a |
T2800 |
10254-10257 |
NN |
denotes |
set |
T2801 |
10247-10253 |
NN |
denotes |
primer |
T2802 |
10258-10262 |
WDT |
denotes |
that |
T2803 |
10263-10272 |
VBD |
denotes |
amplified |
T2804 |
10273-10279 |
IN |
denotes |
across |
T2805 |
10280-10283 |
PRP$ |
denotes |
its |
T2806 |
10288-10298 |
NNS |
denotes |
subdomains |
T2807 |
10284-10287 |
CD |
denotes |
two |
T2808 |
10299-10303 |
IN |
denotes |
with |
T2809 |
10304-10307 |
NN |
denotes |
tet |
T2810 |
10308-10315 |
RB |
denotes |
forward |
T2811 |
10316-10323 |
VBN |
denotes |
located |
T2812 |
10324-10330 |
IN |
denotes |
within |
T2813 |
10331-10334 |
DT |
denotes |
the |
T2814 |
10353-10362 |
NN |
denotes |
repressor |
T2815 |
10335-10339 |
NN |
denotes |
Tn10 |
T2816 |
10340-10352 |
NN |
denotes |
tetracycline |
T2817 |
10363-10364 |
-LRB- |
denotes |
( |
T2818 |
10392-10394 |
NN |
denotes |
AG |
T2819 |
10364-10367 |
NN |
denotes |
CGC |
T2820 |
10368-10371 |
NN |
denotes |
TGT |
T2821 |
10372-10375 |
NN |
denotes |
GGG |
T2822 |
10376-10379 |
NN |
denotes |
GCA |
T2823 |
10380-10383 |
NN |
denotes |
TTT |
T2824 |
10384-10387 |
NN |
denotes |
TAC |
T2825 |
10388-10391 |
NN |
denotes |
TTT |
T2826 |
10394-10395 |
-RRB- |
denotes |
) |
T2827 |
10396-10399 |
CC |
denotes |
and |
T2828 |
10400-10403 |
NN |
denotes |
tet |
T2829 |
10404-10411 |
JJ |
denotes |
reverse |
T2830 |
10412-10418 |
IN |
denotes |
within |
T2831 |
10419-10422 |
DT |
denotes |
the |
T2832 |
10428-10432 |
NN |
denotes |
VP16 |
T2833 |
10423-10427 |
NN |
denotes |
HSV1 |
T2834 |
10433-10434 |
-LRB- |
denotes |
( |
T2835 |
10458-10461 |
NN |
denotes |
GTC |
T2836 |
10434-10437 |
NN |
denotes |
CAT |
T2837 |
10438-10441 |
NN |
denotes |
GTC |
T2838 |
10442-10445 |
NN |
denotes |
CAG |
T2839 |
10446-10449 |
NN |
denotes |
ATC |
T2840 |
10450-10453 |
NN |
denotes |
GAA |
T2841 |
10454-10457 |
NN |
denotes |
ATC |
T2842 |
10461-10462 |
-RRB- |
denotes |
) |
T2843 |
10462-10463 |
. |
denotes |
. |
T2844 |
10463-10816 |
sentence |
denotes |
All reactions, whether transgene-positive or not, amplified a segment of the endogenous prion protein gene as a control for DNA quality using a forward primer, PrP-S-J, specific to the mouse PrP open reading frame (GGG ACT ATG TGG ACT GAT GTC GG) and a reverse primer, PrP-AS-J, shared by the 3′ UTR of the endogenous PrP gene and the transgene vector. |
T2845 |
10464-10467 |
DT |
denotes |
All |
T2846 |
10468-10477 |
NNS |
denotes |
reactions |
T2847 |
10514-10523 |
VBD |
denotes |
amplified |
T2848 |
10477-10479 |
, |
denotes |
, |
T2849 |
10479-10486 |
IN |
denotes |
whether |
T2850 |
10497-10505 |
JJ |
denotes |
positive |
T2851 |
10487-10496 |
NN |
denotes |
transgene |
T2852 |
10496-10497 |
HYPH |
denotes |
- |
T2853 |
10506-10508 |
CC |
denotes |
or |
T2854 |
10509-10512 |
RB |
denotes |
not |
T2855 |
10512-10514 |
, |
denotes |
, |
T2856 |
10524-10525 |
DT |
denotes |
a |
T2857 |
10526-10533 |
NN |
denotes |
segment |
T2858 |
10534-10536 |
IN |
denotes |
of |
T2859 |
10537-10540 |
DT |
denotes |
the |
T2860 |
10566-10570 |
NN |
denotes |
gene |
T2861 |
10541-10551 |
JJ |
denotes |
endogenous |
T2862 |
10552-10557 |
NN |
denotes |
prion |
T2863 |
10558-10565 |
NN |
denotes |
protein |
T2864 |
10571-10573 |
IN |
denotes |
as |
T2865 |
10574-10575 |
DT |
denotes |
a |
T2866 |
10576-10583 |
NN |
denotes |
control |
T2867 |
10584-10587 |
IN |
denotes |
for |
T2868 |
10588-10591 |
NN |
denotes |
DNA |
T2869 |
10592-10599 |
NN |
denotes |
quality |
T2870 |
10600-10605 |
VBG |
denotes |
using |
T2871 |
10606-10607 |
DT |
denotes |
a |
T2872 |
10616-10622 |
NN |
denotes |
primer |
T2873 |
10608-10615 |
JJ |
denotes |
forward |
T2874 |
10622-10624 |
, |
denotes |
, |
T2875 |
10624-10627 |
NN |
denotes |
PrP |
T2876 |
10630-10631 |
NN |
denotes |
J |
T2877 |
10627-10628 |
HYPH |
denotes |
- |
T2878 |
10628-10629 |
NN |
denotes |
S |
T2879 |
10629-10630 |
HYPH |
denotes |
- |
T2880 |
10631-10633 |
, |
denotes |
, |
T2881 |
10633-10641 |
JJ |
denotes |
specific |
T2882 |
10642-10644 |
IN |
denotes |
to |
T2883 |
10645-10648 |
DT |
denotes |
the |
T2884 |
10672-10677 |
NN |
denotes |
frame |
T2885 |
10649-10654 |
NN |
denotes |
mouse |
T2886 |
10655-10658 |
NN |
denotes |
PrP |
T2887 |
10659-10663 |
JJ |
denotes |
open |
T2888 |
10664-10671 |
NN |
denotes |
reading |
T2889 |
10678-10679 |
-LRB- |
denotes |
( |
T2890 |
10707-10709 |
NN |
denotes |
GG |
T2891 |
10679-10682 |
NN |
denotes |
GGG |
T2892 |
10683-10686 |
NN |
denotes |
ACT |
T2893 |
10687-10690 |
NN |
denotes |
ATG |
T2894 |
10691-10694 |
NN |
denotes |
TGG |
T2895 |
10695-10698 |
NN |
denotes |
ACT |
T2896 |
10699-10702 |
NN |
denotes |
GAT |
T2897 |
10703-10706 |
NN |
denotes |
GTC |
T2898 |
10709-10710 |
-RRB- |
denotes |
) |
T2899 |
10711-10714 |
CC |
denotes |
and |
T2900 |
10715-10716 |
DT |
denotes |
a |
T2901 |
10725-10731 |
NN |
denotes |
primer |
T2902 |
10717-10724 |
JJ |
denotes |
reverse |
T2903 |
10731-10733 |
, |
denotes |
, |
T2904 |
10733-10736 |
NN |
denotes |
PrP |
T2905 |
10740-10741 |
NN |
denotes |
J |
T2906 |
10736-10737 |
HYPH |
denotes |
- |
T2907 |
10737-10739 |
NN |
denotes |
AS |
T2908 |
10739-10740 |
HYPH |
denotes |
- |
T2909 |
10741-10743 |
, |
denotes |
, |
T2910 |
10743-10749 |
VBN |
denotes |
shared |
T2911 |
10750-10752 |
IN |
denotes |
by |
T2912 |
10753-10756 |
DT |
denotes |
the |
T2913 |
10760-10763 |
NN |
denotes |
UTR |
T2914 |
10757-10758 |
CD |
denotes |
3 |
T2915 |
10758-10759 |
SYM |
denotes |
′ |
T2916 |
10764-10766 |
IN |
denotes |
of |
T2917 |
10767-10770 |
DT |
denotes |
the |
T2918 |
10786-10790 |
NN |
denotes |
gene |
T2919 |
10771-10781 |
JJ |
denotes |
endogenous |
T2920 |
10782-10785 |
NN |
denotes |
PrP |
T2921 |
10791-10794 |
CC |
denotes |
and |
T2922 |
10795-10798 |
DT |
denotes |
the |
T2923 |
10809-10815 |
NN |
denotes |
vector |
T2924 |
10799-10808 |
NN |
denotes |
transgene |
T2925 |
10815-10816 |
. |
denotes |
. |
T2926 |
10816-10920 |
sentence |
denotes |
Amplification reactions were run for 37 cycles at 94 °C for 30 s, 64 °C for 1 min, and 72 °C for 1 min. |
T2927 |
10817-10830 |
NN |
denotes |
Amplification |
T2928 |
10831-10840 |
NNS |
denotes |
reactions |
T2929 |
10846-10849 |
VBN |
denotes |
run |
T2930 |
10841-10845 |
VBD |
denotes |
were |
T2931 |
10850-10853 |
IN |
denotes |
for |
T2932 |
10854-10856 |
CD |
denotes |
37 |
T2933 |
10857-10863 |
NNS |
denotes |
cycles |
T2934 |
10864-10866 |
IN |
denotes |
at |
T2935 |
10867-10869 |
CD |
denotes |
94 |
T2936 |
10870-10872 |
NN |
denotes |
°C |
T2937 |
10873-10876 |
IN |
denotes |
for |
T2938 |
10877-10879 |
CD |
denotes |
30 |
T2939 |
10880-10881 |
NN |
denotes |
s |
T2940 |
10881-10883 |
, |
denotes |
, |
T2941 |
10883-10885 |
CD |
denotes |
64 |
T2942 |
10886-10888 |
NN |
denotes |
°C |
T2943 |
10889-10892 |
IN |
denotes |
for |
T2944 |
10893-10894 |
CD |
denotes |
1 |
T2945 |
10895-10898 |
NN |
denotes |
min |
T2946 |
10898-10900 |
, |
denotes |
, |
T2947 |
10900-10903 |
CC |
denotes |
and |
T2948 |
10904-10906 |
CD |
denotes |
72 |
T2949 |
10907-10909 |
NN |
denotes |
°C |
T2950 |
10910-10913 |
IN |
denotes |
for |
T2951 |
10914-10915 |
CD |
denotes |
1 |
T2952 |
10916-10919 |
NN |
denotes |
min |
T2953 |
10919-10920 |
. |
denotes |
. |
T2954 |
10920-11011 |
sentence |
denotes |
All samples, transgenic and wild-type, gave a 750-bp product from the endogenous PrP gene. |
T2955 |
10921-10924 |
DT |
denotes |
All |
T2956 |
10925-10932 |
NNS |
denotes |
samples |
T2957 |
10960-10964 |
VBD |
denotes |
gave |
T2958 |
10932-10934 |
, |
denotes |
, |
T2959 |
10934-10944 |
JJ |
denotes |
transgenic |
T2960 |
10945-10948 |
CC |
denotes |
and |
T2961 |
10949-10953 |
JJ |
denotes |
wild |
T2962 |
10954-10958 |
NN |
denotes |
type |
T2963 |
10953-10954 |
HYPH |
denotes |
- |
T2964 |
10958-10960 |
, |
denotes |
, |
T2965 |
10965-10966 |
DT |
denotes |
a |
T2966 |
10974-10981 |
NN |
denotes |
product |
T2967 |
10967-10970 |
CD |
denotes |
750 |
T2968 |
10971-10973 |
NN |
denotes |
bp |
T2969 |
10970-10971 |
HYPH |
denotes |
- |
T2970 |
10982-10986 |
IN |
denotes |
from |
T2971 |
10987-10990 |
DT |
denotes |
the |
T2972 |
11006-11010 |
NN |
denotes |
gene |
T2973 |
10991-11001 |
JJ |
denotes |
endogenous |
T2974 |
11002-11005 |
NN |
denotes |
PrP |
T2975 |
11010-11011 |
. |
denotes |
. |
T2976 |
11011-11110 |
sentence |
denotes |
The APP transgene yielded an additional band at 400 bp; the tTA product fell in between at 480 bp. |
T2977 |
11012-11015 |
DT |
denotes |
The |
T2978 |
11020-11029 |
NN |
denotes |
transgene |
T2979 |
11016-11019 |
NN |
denotes |
APP |
T2980 |
11030-11037 |
VBD |
denotes |
yielded |
T2981 |
11084-11088 |
VBD |
denotes |
fell |
T2982 |
11038-11040 |
DT |
denotes |
an |
T2983 |
11052-11056 |
NN |
denotes |
band |
T2984 |
11041-11051 |
JJ |
denotes |
additional |
T2985 |
11057-11059 |
IN |
denotes |
at |
T2986 |
11060-11063 |
CD |
denotes |
400 |
T2987 |
11064-11066 |
NN |
denotes |
bp |
T2988 |
11066-11067 |
: |
denotes |
; |
T2989 |
11068-11071 |
DT |
denotes |
the |
T2990 |
11076-11083 |
NN |
denotes |
product |
T2991 |
11072-11075 |
NN |
denotes |
tTA |
T2992 |
11089-11091 |
RB |
denotes |
in |
T2993 |
11092-11099 |
RB |
denotes |
between |
T2994 |
11100-11102 |
IN |
denotes |
at |
T2995 |
11103-11106 |
CD |
denotes |
480 |
T2996 |
11107-11109 |
NN |
denotes |
bp |
T2997 |
11109-11110 |
. |
denotes |
. |
T3141 |
11112-11126 |
NN |
denotes |
Immunoblotting |
T3142 |
11127-11139 |
NN |
denotes |
Quantitation |
T3143 |
11126-11127 |
HYPH |
denotes |
/ |
T3144 |
11139-11456 |
sentence |
denotes |
Frozen cortical or whole forebrain tissue was homogenized by sonication in five volumes of phosphate-buffered saline (PBS) with 5 mM EDTA and protease inhibitors (Mammalian cell cocktail, Sigma, St. Louis, Missouri, United States), using a probe sonicator set to 50% output (TEKMAR, Cincinnati, Ohio, United States). |
T3145 |
11140-11146 |
VBN |
denotes |
Frozen |
T3146 |
11175-11181 |
NN |
denotes |
tissue |
T3147 |
11147-11155 |
JJ |
denotes |
cortical |
T3148 |
11156-11158 |
CC |
denotes |
or |
T3149 |
11159-11164 |
JJ |
denotes |
whole |
T3150 |
11165-11174 |
NN |
denotes |
forebrain |
T3151 |
11186-11197 |
VBN |
denotes |
homogenized |
T3152 |
11182-11185 |
VBD |
denotes |
was |
T3153 |
11198-11200 |
IN |
denotes |
by |
T3154 |
11201-11211 |
NN |
denotes |
sonication |
T3155 |
11212-11214 |
IN |
denotes |
in |
T3156 |
11215-11219 |
CD |
denotes |
five |
T3157 |
11220-11227 |
NNS |
denotes |
volumes |
T3158 |
11228-11230 |
IN |
denotes |
of |
T3159 |
11231-11240 |
NN |
denotes |
phosphate |
T3160 |
11241-11249 |
VBN |
denotes |
buffered |
T3161 |
11240-11241 |
HYPH |
denotes |
- |
T3162 |
11250-11256 |
NN |
denotes |
saline |
T3163 |
11257-11258 |
-LRB- |
denotes |
( |
T3164 |
11258-11261 |
NN |
denotes |
PBS |
T3165 |
11261-11262 |
-RRB- |
denotes |
) |
T3166 |
11263-11267 |
IN |
denotes |
with |
T3167 |
11268-11269 |
CD |
denotes |
5 |
T3168 |
11270-11272 |
NN |
denotes |
mM |
T3169 |
11291-11301 |
NNS |
denotes |
inhibitors |
T3170 |
11273-11277 |
NN |
denotes |
EDTA |
T3171 |
11278-11281 |
CC |
denotes |
and |
T3172 |
11282-11290 |
NN |
denotes |
protease |
T3173 |
11302-11303 |
-LRB- |
denotes |
( |
T3174 |
11318-11326 |
NN |
denotes |
cocktail |
T3175 |
11303-11312 |
JJ |
denotes |
Mammalian |
T3176 |
11313-11317 |
NN |
denotes |
cell |
T3177 |
11326-11328 |
, |
denotes |
, |
T3178 |
11328-11333 |
NNP |
denotes |
Sigma |
T3179 |
11333-11335 |
, |
denotes |
, |
T3180 |
11335-11338 |
NNP |
denotes |
St. |
T3181 |
11339-11344 |
NNP |
denotes |
Louis |
T3182 |
11344-11346 |
, |
denotes |
, |
T3183 |
11346-11354 |
NNP |
denotes |
Missouri |
T3184 |
11354-11356 |
, |
denotes |
, |
T3185 |
11356-11362 |
NNP |
denotes |
United |
T3186 |
11363-11369 |
NNP |
denotes |
States |
T3187 |
11369-11370 |
-RRB- |
denotes |
) |
T3188 |
11370-11372 |
, |
denotes |
, |
T3189 |
11372-11377 |
VBG |
denotes |
using |
T3190 |
11378-11379 |
DT |
denotes |
a |
T3191 |
11386-11395 |
NN |
denotes |
sonicator |
T3192 |
11380-11385 |
NN |
denotes |
probe |
T3193 |
11396-11399 |
VBN |
denotes |
set |
T3194 |
11400-11402 |
IN |
denotes |
to |
T3195 |
11403-11405 |
CD |
denotes |
50 |
T3196 |
11405-11406 |
NN |
denotes |
% |
T3197 |
11407-11413 |
NN |
denotes |
output |
T3198 |
11414-11415 |
-LRB- |
denotes |
( |
T3199 |
11415-11421 |
NNP |
denotes |
TEKMAR |
T3200 |
11421-11423 |
, |
denotes |
, |
T3201 |
11423-11433 |
NNP |
denotes |
Cincinnati |
T3202 |
11433-11435 |
, |
denotes |
, |
T3203 |
11435-11439 |
NNP |
denotes |
Ohio |
T3204 |
11439-11441 |
, |
denotes |
, |
T3205 |
11441-11447 |
NNP |
denotes |
United |
T3206 |
11448-11454 |
NNP |
denotes |
States |
T3207 |
11454-11455 |
-RRB- |
denotes |
) |
T3208 |
11455-11456 |
. |
denotes |
. |
T3209 |
11456-11600 |
sentence |
denotes |
After dilution with an equal volume of PBS/EDTA/protease inhibitor, the samples were centrifuged briefly and the supernatant used for analysis. |
T3210 |
11457-11462 |
IN |
denotes |
After |
T3211 |
11542-11553 |
VBN |
denotes |
centrifuged |
T3212 |
11463-11471 |
NN |
denotes |
dilution |
T3213 |
11472-11476 |
IN |
denotes |
with |
T3214 |
11477-11479 |
DT |
denotes |
an |
T3215 |
11486-11492 |
NN |
denotes |
volume |
T3216 |
11480-11485 |
JJ |
denotes |
equal |
T3217 |
11493-11495 |
IN |
denotes |
of |
T3218 |
11496-11499 |
NN |
denotes |
PBS |
T3219 |
11505-11513 |
NN |
denotes |
protease |
T3220 |
11499-11500 |
HYPH |
denotes |
/ |
T3221 |
11500-11504 |
NN |
denotes |
EDTA |
T3222 |
11504-11505 |
HYPH |
denotes |
/ |
T3223 |
11514-11523 |
NN |
denotes |
inhibitor |
T3224 |
11523-11525 |
, |
denotes |
, |
T3225 |
11525-11528 |
DT |
denotes |
the |
T3226 |
11529-11536 |
NNS |
denotes |
samples |
T3227 |
11537-11541 |
VBD |
denotes |
were |
T3228 |
11554-11561 |
RB |
denotes |
briefly |
T3229 |
11562-11565 |
CC |
denotes |
and |
T3230 |
11566-11569 |
DT |
denotes |
the |
T3231 |
11570-11581 |
NN |
denotes |
supernatant |
T3232 |
11582-11586 |
VBN |
denotes |
used |
T3233 |
11587-11590 |
IN |
denotes |
for |
T3234 |
11591-11599 |
NN |
denotes |
analysis |
T3235 |
11599-11600 |
. |
denotes |
. |
T3236 |
11600-12037 |
sentence |
denotes |
Fifty micrograms (6E10 and CT15) or 5 μg (22C11) of brain homogenate was loaded per lane onto 7.5%, 10%–20%, or 4%–20% Tris-HCl PAGE gels (Bio-Rad Laboratories, Hercules, California, United States) and electrophoresed for several hours in 1× Tris-glycine–sodium dodecyl sulfate (1×TG-SDS) buffer (6E10 and 22C11; Amresco, Solon, Ohio, United States) or 1× Tris-tricine-SDS buffer (CT15; Invitrogen, Carlsbad, California, United States). |
T3237 |
11601-11606 |
CD |
denotes |
Fifty |
T3238 |
11607-11617 |
NNS |
denotes |
micrograms |
T3239 |
11619-11623 |
NN |
denotes |
6E10 |
T3240 |
11618-11619 |
-LRB- |
denotes |
( |
T3241 |
11674-11680 |
VBN |
denotes |
loaded |
T3242 |
11624-11627 |
CC |
denotes |
and |
T3243 |
11628-11632 |
NN |
denotes |
CT15 |
T3244 |
11632-11633 |
-RRB- |
denotes |
) |
T3245 |
11634-11636 |
CC |
denotes |
or |
T3246 |
11637-11638 |
CD |
denotes |
5 |
T3247 |
11639-11641 |
NN |
denotes |
μg |
T3248 |
11643-11648 |
NN |
denotes |
22C11 |
T3249 |
11642-11643 |
-LRB- |
denotes |
( |
T3250 |
11648-11649 |
-RRB- |
denotes |
) |
T3251 |
11650-11652 |
IN |
denotes |
of |
T3252 |
11653-11658 |
NN |
denotes |
brain |
T3253 |
11659-11669 |
NN |
denotes |
homogenate |
T3254 |
11670-11673 |
VBD |
denotes |
was |
T3255 |
11681-11684 |
IN |
denotes |
per |
T3256 |
11685-11689 |
NN |
denotes |
lane |
T3257 |
11690-11694 |
IN |
denotes |
onto |
T3258 |
11695-11698 |
CD |
denotes |
7.5 |
T3259 |
11698-11699 |
NN |
denotes |
% |
T3260 |
11729-11733 |
NN |
denotes |
PAGE |
T3261 |
11699-11701 |
, |
denotes |
, |
T3262 |
11701-11703 |
CD |
denotes |
10 |
T3263 |
11703-11704 |
NN |
denotes |
% |
T3264 |
11704-11705 |
SYM |
denotes |
– |
T3265 |
11707-11708 |
NN |
denotes |
% |
T3266 |
11705-11707 |
CD |
denotes |
20 |
T3267 |
11708-11710 |
, |
denotes |
, |
T3268 |
11710-11712 |
CC |
denotes |
or |
T3269 |
11713-11714 |
CD |
denotes |
4 |
T3270 |
11714-11715 |
NN |
denotes |
% |
T3271 |
11715-11716 |
SYM |
denotes |
– |
T3272 |
11718-11719 |
NN |
denotes |
% |
T3273 |
11716-11718 |
CD |
denotes |
20 |
T3274 |
11720-11724 |
NN |
denotes |
Tris |
T3275 |
11724-11725 |
HYPH |
denotes |
- |
T3276 |
11725-11728 |
NN |
denotes |
HCl |
T3277 |
11734-11738 |
NNS |
denotes |
gels |
T3278 |
11739-11740 |
-LRB- |
denotes |
( |
T3279 |
11748-11760 |
NNP |
denotes |
Laboratories |
T3280 |
11740-11743 |
NNP |
denotes |
Bio |
T3281 |
11744-11747 |
NNP |
denotes |
Rad |
T3282 |
11743-11744 |
HYPH |
denotes |
- |
T3283 |
11760-11762 |
, |
denotes |
, |
T3284 |
11762-11770 |
NNP |
denotes |
Hercules |
T3285 |
11770-11772 |
, |
denotes |
, |
T3286 |
11772-11782 |
NNP |
denotes |
California |
T3287 |
11782-11784 |
, |
denotes |
, |
T3288 |
11784-11790 |
NNP |
denotes |
United |
T3289 |
11791-11797 |
NNP |
denotes |
States |
T3290 |
11797-11798 |
-RRB- |
denotes |
) |
T3291 |
11799-11802 |
CC |
denotes |
and |
T3292 |
11803-11818 |
VBN |
denotes |
electrophoresed |
T3293 |
11819-11822 |
IN |
denotes |
for |
T3294 |
11823-11830 |
JJ |
denotes |
several |
T3295 |
11831-11836 |
NNS |
denotes |
hours |
T3296 |
11837-11839 |
IN |
denotes |
in |
T3297 |
11840-11841 |
CD |
denotes |
1 |
T3298 |
11871-11878 |
NN |
denotes |
sulfate |
T3299 |
11841-11842 |
SYM |
denotes |
× |
T3300 |
11843-11847 |
NN |
denotes |
Tris |
T3301 |
11847-11848 |
HYPH |
denotes |
- |
T3302 |
11848-11855 |
NN |
denotes |
glycine |
T3303 |
11855-11856 |
HYPH |
denotes |
– |
T3304 |
11856-11862 |
NN |
denotes |
sodium |
T3305 |
11863-11870 |
NN |
denotes |
dodecyl |
T3306 |
11890-11896 |
NN |
denotes |
buffer |
T3307 |
11879-11880 |
-LRB- |
denotes |
( |
T3308 |
11880-11881 |
CD |
denotes |
1 |
T3309 |
11885-11888 |
NN |
denotes |
SDS |
T3310 |
11881-11882 |
SYM |
denotes |
× |
T3311 |
11882-11884 |
NN |
denotes |
TG |
T3312 |
11884-11885 |
HYPH |
denotes |
- |
T3313 |
11888-11889 |
-RRB- |
denotes |
) |
T3314 |
11897-11898 |
-LRB- |
denotes |
( |
T3315 |
11914-11921 |
NNP |
denotes |
Amresco |
T3316 |
11898-11902 |
NN |
denotes |
6E10 |
T3317 |
11903-11906 |
CC |
denotes |
and |
T3318 |
11907-11912 |
NN |
denotes |
22C11 |
T3319 |
11912-11913 |
: |
denotes |
; |
T3320 |
11921-11923 |
, |
denotes |
, |
T3321 |
11923-11928 |
NNP |
denotes |
Solon |
T3322 |
11928-11930 |
, |
denotes |
, |
T3323 |
11930-11934 |
NNP |
denotes |
Ohio |
T3324 |
11934-11936 |
, |
denotes |
, |
T3325 |
11936-11942 |
NNP |
denotes |
United |
T3326 |
11943-11949 |
NNP |
denotes |
States |
T3327 |
11949-11950 |
-RRB- |
denotes |
) |
T3328 |
11951-11953 |
CC |
denotes |
or |
T3329 |
11954-11955 |
CD |
denotes |
1 |
T3330 |
11974-11980 |
NN |
denotes |
buffer |
T3331 |
11955-11956 |
SYM |
denotes |
× |
T3332 |
11957-11961 |
NN |
denotes |
Tris |
T3333 |
11970-11973 |
NN |
denotes |
SDS |
T3334 |
11961-11962 |
HYPH |
denotes |
- |
T3335 |
11962-11969 |
NN |
denotes |
tricine |
T3336 |
11969-11970 |
HYPH |
denotes |
- |
T3337 |
11981-11982 |
-LRB- |
denotes |
( |
T3338 |
11988-11998 |
NNP |
denotes |
Invitrogen |
T3339 |
11982-11986 |
NN |
denotes |
CT15 |
T3340 |
11986-11987 |
: |
denotes |
; |
T3341 |
11998-12000 |
, |
denotes |
, |
T3342 |
12000-12008 |
NNP |
denotes |
Carlsbad |
T3343 |
12008-12010 |
, |
denotes |
, |
T3344 |
12010-12020 |
NNP |
denotes |
California |
T3345 |
12020-12022 |
, |
denotes |
, |
T3346 |
12022-12028 |
NNP |
denotes |
United |
T3347 |
12029-12035 |
NNP |
denotes |
States |
T3348 |
12035-12036 |
-RRB- |
denotes |
) |
T3349 |
12036-12037 |
. |
denotes |
. |
T3350 |
12037-12197 |
sentence |
denotes |
Proteins were transferred overnight to 0.45-μm Optitran nitrocellulose (Schleicher and Schuell, Keene, New Hampshire, United States) in 1× TG buffer (Amresco). |
T3351 |
12038-12046 |
NNS |
denotes |
Proteins |
T3352 |
12052-12063 |
VBN |
denotes |
transferred |
T3353 |
12047-12051 |
VBD |
denotes |
were |
T3354 |
12064-12073 |
RB |
denotes |
overnight |
T3355 |
12074-12076 |
IN |
denotes |
to |
T3356 |
12077-12081 |
CD |
denotes |
0.45 |
T3357 |
12082-12084 |
NN |
denotes |
μm |
T3358 |
12081-12082 |
HYPH |
denotes |
- |
T3359 |
12094-12108 |
NN |
denotes |
nitrocellulose |
T3360 |
12085-12093 |
NNP |
denotes |
Optitran |
T3361 |
12109-12110 |
-LRB- |
denotes |
( |
T3362 |
12110-12120 |
NNP |
denotes |
Schleicher |
T3363 |
12121-12124 |
CC |
denotes |
and |
T3364 |
12125-12132 |
NNP |
denotes |
Schuell |
T3365 |
12132-12134 |
, |
denotes |
, |
T3366 |
12134-12139 |
NNP |
denotes |
Keene |
T3367 |
12139-12141 |
, |
denotes |
, |
T3368 |
12141-12144 |
NNP |
denotes |
New |
T3369 |
12145-12154 |
NNP |
denotes |
Hampshire |
T3370 |
12154-12156 |
, |
denotes |
, |
T3371 |
12156-12162 |
NNP |
denotes |
United |
T3372 |
12163-12169 |
NNP |
denotes |
States |
T3373 |
12169-12170 |
-RRB- |
denotes |
) |
T3374 |
12171-12173 |
IN |
denotes |
in |
T3375 |
12174-12175 |
CD |
denotes |
1 |
T3376 |
12180-12186 |
NN |
denotes |
buffer |
T3377 |
12175-12176 |
SYM |
denotes |
× |
T3378 |
12177-12179 |
NN |
denotes |
TG |
T3379 |
12187-12188 |
-LRB- |
denotes |
( |
T3380 |
12188-12195 |
NNP |
denotes |
Amresco |
T3381 |
12195-12196 |
-RRB- |
denotes |
) |
T3382 |
12196-12197 |
. |
denotes |
. |
T3383 |
12197-12722 |
sentence |
denotes |
Blots were blocked in PBS containing 5% nonfat dry milk powder, and incubated for 3 h at room temperature in blocking solution with one of the following antibodies: mouse monoclonal 22C11 (kind gift of Konrad Beyreuther and Andreas Weidemann; [17]) diluted 1:1,000, mouse monoclonal 6E10 (Signet Laboratories, Dedham, Massachusetts, United States) diluted 1:2,500, rabbit polyclonal anti-superoxide dismutase 1 (m/hSOD1) [18] diluted 1:2,500 to 1:4,000, or rabbit polyclonal CT15 (kind gift of Ed Koo; [19]) diluted 1:1,000. |
T3384 |
12198-12203 |
NNS |
denotes |
Blots |
T3385 |
12209-12216 |
VBN |
denotes |
blocked |
T3386 |
12204-12208 |
VBD |
denotes |
were |
T3387 |
12217-12219 |
IN |
denotes |
in |
T3388 |
12220-12223 |
NN |
denotes |
PBS |
T3389 |
12224-12234 |
VBG |
denotes |
containing |
T3390 |
12235-12236 |
CD |
denotes |
5 |
T3391 |
12236-12237 |
NN |
denotes |
% |
T3392 |
12254-12260 |
NN |
denotes |
powder |
T3393 |
12238-12244 |
JJ |
denotes |
nonfat |
T3394 |
12249-12253 |
NN |
denotes |
milk |
T3395 |
12245-12248 |
JJ |
denotes |
dry |
T3396 |
12260-12262 |
, |
denotes |
, |
T3397 |
12262-12265 |
CC |
denotes |
and |
T3398 |
12266-12275 |
VBN |
denotes |
incubated |
T3399 |
12276-12279 |
IN |
denotes |
for |
T3400 |
12280-12281 |
CD |
denotes |
3 |
T3401 |
12282-12283 |
NN |
denotes |
h |
T3402 |
12284-12286 |
IN |
denotes |
at |
T3403 |
12287-12291 |
NN |
denotes |
room |
T3404 |
12292-12303 |
NN |
denotes |
temperature |
T3405 |
12304-12306 |
IN |
denotes |
in |
T3406 |
12307-12315 |
NN |
denotes |
blocking |
T3407 |
12316-12324 |
NN |
denotes |
solution |
T3408 |
12325-12329 |
IN |
denotes |
with |
T3409 |
12330-12333 |
CD |
denotes |
one |
T3410 |
12334-12336 |
IN |
denotes |
of |
T3411 |
12337-12340 |
DT |
denotes |
the |
T3412 |
12351-12361 |
NNS |
denotes |
antibodies |
T3413 |
12341-12350 |
VBG |
denotes |
following |
T3414 |
12361-12363 |
: |
denotes |
: |
T3415 |
12363-12368 |
NN |
denotes |
mouse |
T3416 |
12380-12385 |
NN |
denotes |
22C11 |
T3417 |
12369-12379 |
JJ |
denotes |
monoclonal |
T3418 |
12386-12387 |
-LRB- |
denotes |
( |
T3419 |
12442-12444 |
CD |
denotes |
17 |
T3420 |
12387-12391 |
JJ |
denotes |
kind |
T3421 |
12392-12396 |
NN |
denotes |
gift |
T3422 |
12397-12399 |
IN |
denotes |
of |
T3423 |
12400-12406 |
NNP |
denotes |
Konrad |
T3424 |
12407-12417 |
NNP |
denotes |
Beyreuther |
T3425 |
12418-12421 |
CC |
denotes |
and |
T3426 |
12422-12429 |
NNP |
denotes |
Andreas |
T3427 |
12430-12439 |
NNP |
denotes |
Weidemann |
T3428 |
12439-12440 |
: |
denotes |
; |
T3429 |
12441-12442 |
-LRB- |
denotes |
[ |
T3430 |
12444-12445 |
-RRB- |
denotes |
] |
T3431 |
12445-12446 |
-RRB- |
denotes |
) |
T3432 |
12447-12454 |
VBN |
denotes |
diluted |
T3433 |
12455-12456 |
CD |
denotes |
1 |
T3434 |
12456-12457 |
SYM |
denotes |
: |
T3435 |
12457-12462 |
CD |
denotes |
1,000 |
T3436 |
12462-12464 |
, |
denotes |
, |
T3437 |
12464-12469 |
NN |
denotes |
mouse |
T3438 |
12481-12485 |
NN |
denotes |
6E10 |
T3439 |
12470-12480 |
JJ |
denotes |
monoclonal |
T3440 |
12486-12487 |
-LRB- |
denotes |
( |
T3441 |
12494-12506 |
NNP |
denotes |
Laboratories |
T3442 |
12487-12493 |
NNP |
denotes |
Signet |
T3443 |
12506-12508 |
, |
denotes |
, |
T3444 |
12508-12514 |
NNP |
denotes |
Dedham |
T3445 |
12514-12516 |
, |
denotes |
, |
T3446 |
12516-12529 |
NNP |
denotes |
Massachusetts |
T3447 |
12529-12531 |
, |
denotes |
, |
T3448 |
12531-12537 |
NNP |
denotes |
United |
T3449 |
12538-12544 |
NNP |
denotes |
States |
T3450 |
12544-12545 |
-RRB- |
denotes |
) |
T3451 |
12546-12553 |
VBN |
denotes |
diluted |
T3452 |
12554-12555 |
CD |
denotes |
1 |
T3453 |
12555-12556 |
SYM |
denotes |
: |
T3454 |
12556-12561 |
CD |
denotes |
2,500 |
T3455 |
12561-12563 |
, |
denotes |
, |
T3456 |
12563-12569 |
NN |
denotes |
rabbit |
T3457 |
12612-12617 |
NN |
denotes |
hSOD1 |
T3458 |
12570-12580 |
JJ |
denotes |
polyclonal |
T3459 |
12581-12596 |
JJ |
denotes |
anti-superoxide |
T3460 |
12597-12606 |
NN |
denotes |
dismutase |
T3461 |
12607-12608 |
CD |
denotes |
1 |
T3462 |
12609-12610 |
-LRB- |
denotes |
( |
T3463 |
12610-12611 |
NN |
denotes |
m |
T3464 |
12611-12612 |
HYPH |
denotes |
/ |
T3465 |
12617-12618 |
-RRB- |
denotes |
) |
T3466 |
12619-12620 |
-LRB- |
denotes |
[ |
T3467 |
12620-12622 |
CD |
denotes |
18 |
T3468 |
12622-12623 |
-RRB- |
denotes |
] |
T3469 |
12624-12631 |
VBN |
denotes |
diluted |
T3470 |
12632-12633 |
CD |
denotes |
1 |
T3471 |
12633-12634 |
SYM |
denotes |
: |
T3472 |
12634-12639 |
CD |
denotes |
2,500 |
T3473 |
12640-12642 |
IN |
denotes |
to |
T3474 |
12643-12644 |
CD |
denotes |
1 |
T3475 |
12644-12645 |
SYM |
denotes |
: |
T3476 |
12645-12650 |
CD |
denotes |
4,000 |
T3477 |
12650-12652 |
, |
denotes |
, |
T3478 |
12652-12654 |
CC |
denotes |
or |
T3479 |
12655-12661 |
NN |
denotes |
rabbit |
T3480 |
12673-12677 |
NN |
denotes |
CT15 |
T3481 |
12662-12672 |
JJ |
denotes |
polyclonal |
T3482 |
12678-12679 |
-LRB- |
denotes |
( |
T3483 |
12684-12688 |
NN |
denotes |
gift |
T3484 |
12679-12683 |
JJ |
denotes |
kind |
T3485 |
12689-12691 |
IN |
denotes |
of |
T3486 |
12692-12694 |
NNP |
denotes |
Ed |
T3487 |
12695-12698 |
NNP |
denotes |
Koo |
T3488 |
12698-12699 |
: |
denotes |
; |
T3489 |
12700-12701 |
-LRB- |
denotes |
[ |
T3490 |
12701-12703 |
CD |
denotes |
19 |
T3491 |
12703-12704 |
-RRB- |
denotes |
] |
T3492 |
12704-12705 |
-RRB- |
denotes |
) |
T3493 |
12706-12713 |
VBN |
denotes |
diluted |
T3494 |
12714-12715 |
CD |
denotes |
1 |
T3495 |
12715-12716 |
SYM |
denotes |
: |
T3496 |
12716-12721 |
CD |
denotes |
1,000 |
T3497 |
12721-12722 |
. |
denotes |
. |
T3498 |
12722-12933 |
sentence |
denotes |
Subsequently, the blots were washed with PBS containing 0.1% Tween-20, and then incubated with either goat anti-mouse– or goat anti-rabbit–HRP conjugated secondary antibody diluted 1:1,000 in blocking solution. |
T3499 |
12723-12735 |
RB |
denotes |
Subsequently |
T3500 |
12752-12758 |
VBN |
denotes |
washed |
T3501 |
12735-12737 |
, |
denotes |
, |
T3502 |
12737-12740 |
DT |
denotes |
the |
T3503 |
12741-12746 |
NNS |
denotes |
blots |
T3504 |
12747-12751 |
VBD |
denotes |
were |
T3505 |
12759-12763 |
IN |
denotes |
with |
T3506 |
12764-12767 |
NN |
denotes |
PBS |
T3507 |
12768-12778 |
VBG |
denotes |
containing |
T3508 |
12779-12782 |
CD |
denotes |
0.1 |
T3509 |
12782-12783 |
NN |
denotes |
% |
T3510 |
12784-12789 |
NN |
denotes |
Tween |
T3511 |
12789-12790 |
HYPH |
denotes |
- |
T3512 |
12790-12792 |
CD |
denotes |
20 |
T3513 |
12792-12794 |
, |
denotes |
, |
T3514 |
12794-12797 |
CC |
denotes |
and |
T3515 |
12798-12802 |
RB |
denotes |
then |
T3516 |
12803-12812 |
VBN |
denotes |
incubated |
T3517 |
12813-12817 |
IN |
denotes |
with |
T3518 |
12818-12824 |
CC |
denotes |
either |
T3519 |
12825-12829 |
NN |
denotes |
goat |
T3520 |
12887-12895 |
NN |
denotes |
antibody |
T3521 |
12830-12840 |
JJ |
denotes |
anti-mouse |
T3522 |
12840-12841 |
HYPH |
denotes |
– |
T3523 |
12842-12844 |
CC |
denotes |
or |
T3524 |
12845-12849 |
NN |
denotes |
goat |
T3525 |
12850-12861 |
JJ |
denotes |
anti-rabbit |
T3526 |
12861-12862 |
HYPH |
denotes |
– |
T3527 |
12862-12865 |
NN |
denotes |
HRP |
T3528 |
12866-12876 |
VBN |
denotes |
conjugated |
T3529 |
12877-12886 |
JJ |
denotes |
secondary |
T3530 |
12896-12903 |
VBN |
denotes |
diluted |
T3531 |
12904-12905 |
CD |
denotes |
1 |
T3532 |
12905-12906 |
SYM |
denotes |
: |
T3533 |
12906-12911 |
CD |
denotes |
1,000 |
T3534 |
12912-12914 |
IN |
denotes |
in |
T3535 |
12915-12923 |
NN |
denotes |
blocking |
T3536 |
12924-12932 |
NN |
denotes |
solution |
T3537 |
12932-12933 |
. |
denotes |
. |
T3538 |
12933-13109 |
sentence |
denotes |
After several additional rinses in PBS with 0.1% Tween-20, blots were developed with enhanced chemiluminescence reagent and imaged with the Bio-Rad Molecular Imager FX system. |
T3539 |
12934-12939 |
IN |
denotes |
After |
T3540 |
13004-13013 |
VBN |
denotes |
developed |
T3541 |
12940-12947 |
JJ |
denotes |
several |
T3542 |
12959-12965 |
NNS |
denotes |
rinses |
T3543 |
12948-12958 |
JJ |
denotes |
additional |
T3544 |
12966-12968 |
IN |
denotes |
in |
T3545 |
12969-12972 |
NN |
denotes |
PBS |
T3546 |
12973-12977 |
IN |
denotes |
with |
T3547 |
12978-12981 |
CD |
denotes |
0.1 |
T3548 |
12983-12988 |
NN |
denotes |
Tween |
T3549 |
12981-12982 |
NN |
denotes |
% |
T3550 |
12988-12989 |
HYPH |
denotes |
- |
T3551 |
12989-12991 |
CD |
denotes |
20 |
T3552 |
12991-12993 |
, |
denotes |
, |
T3553 |
12993-12998 |
NNS |
denotes |
blots |
T3554 |
12999-13003 |
VBD |
denotes |
were |
T3555 |
13014-13018 |
IN |
denotes |
with |
T3556 |
13019-13027 |
VBN |
denotes |
enhanced |
T3557 |
13046-13053 |
NN |
denotes |
reagent |
T3558 |
13028-13045 |
NN |
denotes |
chemiluminescence |
T3559 |
13054-13057 |
CC |
denotes |
and |
T3560 |
13058-13064 |
VBN |
denotes |
imaged |
T3561 |
13065-13069 |
IN |
denotes |
with |
T3562 |
13070-13073 |
DT |
denotes |
the |
T3563 |
13102-13108 |
NN |
denotes |
system |
T3564 |
13074-13077 |
NNP |
denotes |
Bio |
T3565 |
13078-13081 |
NNP |
denotes |
Rad |
T3566 |
13077-13078 |
HYPH |
denotes |
- |
T3567 |
13099-13101 |
NNP |
denotes |
FX |
T3568 |
13082-13091 |
NNP |
denotes |
Molecular |
T3569 |
13092-13098 |
NNP |
denotes |
Imager |
T3570 |
13108-13109 |
. |
denotes |
. |
T3571 |
13109-13252 |
sentence |
denotes |
Staining intensity within each lane was quantified using the Quantity One image analysis software (Molecular Imager FX, Bio-Rad Laboratories). |
T3572 |
13110-13118 |
NN |
denotes |
Staining |
T3573 |
13119-13128 |
NN |
denotes |
intensity |
T3574 |
13150-13160 |
VBN |
denotes |
quantified |
T3575 |
13129-13135 |
IN |
denotes |
within |
T3576 |
13136-13140 |
DT |
denotes |
each |
T3577 |
13141-13145 |
NN |
denotes |
lane |
T3578 |
13146-13149 |
VBD |
denotes |
was |
T3579 |
13161-13166 |
VBG |
denotes |
using |
T3580 |
13167-13170 |
DT |
denotes |
the |
T3581 |
13199-13207 |
NN |
denotes |
software |
T3582 |
13171-13179 |
NNP |
denotes |
Quantity |
T3583 |
13180-13183 |
CD |
denotes |
One |
T3584 |
13184-13189 |
NN |
denotes |
image |
T3585 |
13190-13198 |
NN |
denotes |
analysis |
T3586 |
13208-13209 |
-LRB- |
denotes |
( |
T3587 |
13226-13228 |
NNP |
denotes |
FX |
T3588 |
13209-13218 |
NNP |
denotes |
Molecular |
T3589 |
13219-13225 |
NNP |
denotes |
Imager |
T3590 |
13228-13230 |
, |
denotes |
, |
T3591 |
13230-13233 |
NNP |
denotes |
Bio |
T3592 |
13234-13237 |
NNP |
denotes |
Rad |
T3593 |
13233-13234 |
HYPH |
denotes |
- |
T3594 |
13238-13250 |
NNP |
denotes |
Laboratories |
T3595 |
13250-13251 |
-RRB- |
denotes |
) |
T3596 |
13251-13252 |
. |
denotes |
. |
T3597 |
13252-13337 |
sentence |
denotes |
Background was calculated from across the image and subtracted from the entire file. |
T3598 |
13253-13263 |
NN |
denotes |
Background |
T3599 |
13268-13278 |
VBN |
denotes |
calculated |
T3600 |
13264-13267 |
VBD |
denotes |
was |
T3601 |
13279-13283 |
IN |
denotes |
from |
T3602 |
13284-13290 |
IN |
denotes |
across |
T3603 |
13291-13294 |
DT |
denotes |
the |
T3604 |
13295-13300 |
NN |
denotes |
image |
T3605 |
13301-13304 |
CC |
denotes |
and |
T3606 |
13305-13315 |
VBN |
denotes |
subtracted |
T3607 |
13316-13320 |
IN |
denotes |
from |
T3608 |
13321-13324 |
DT |
denotes |
the |
T3609 |
13332-13336 |
NN |
denotes |
file |
T3610 |
13325-13331 |
JJ |
denotes |
entire |
T3611 |
13336-13337 |
. |
denotes |
. |
T3612 |
13337-13466 |
sentence |
denotes |
The signal intensity for each band (corrected signal intensity × pixel number) was then calculated using the Volume report tool. |
T3613 |
13338-13341 |
DT |
denotes |
The |
T3614 |
13349-13358 |
NN |
denotes |
intensity |
T3615 |
13342-13348 |
NN |
denotes |
signal |
T3616 |
13426-13436 |
VBN |
denotes |
calculated |
T3617 |
13359-13362 |
IN |
denotes |
for |
T3618 |
13363-13367 |
DT |
denotes |
each |
T3619 |
13368-13372 |
NN |
denotes |
band |
T3620 |
13373-13374 |
-LRB- |
denotes |
( |
T3621 |
13391-13400 |
NN |
denotes |
intensity |
T3622 |
13374-13383 |
VBN |
denotes |
corrected |
T3623 |
13384-13390 |
NN |
denotes |
signal |
T3624 |
13401-13402 |
SYM |
denotes |
× |
T3625 |
13403-13408 |
NN |
denotes |
pixel |
T3626 |
13409-13415 |
NN |
denotes |
number |
T3627 |
13415-13416 |
-RRB- |
denotes |
) |
T3628 |
13417-13420 |
VBD |
denotes |
was |
T3629 |
13421-13425 |
RB |
denotes |
then |
T3630 |
13437-13442 |
VBG |
denotes |
using |
T3631 |
13443-13446 |
DT |
denotes |
the |
T3632 |
13461-13465 |
NN |
denotes |
tool |
T3633 |
13447-13453 |
NN |
denotes |
Volume |
T3634 |
13454-13460 |
NN |
denotes |
report |
T3635 |
13465-13466 |
. |
denotes |
. |
T3710 |
13468-13472 |
NN |
denotes |
Slot |
T3711 |
13473-13477 |
NN |
denotes |
Blot |
T3712 |
13483-13491 |
NN |
denotes |
Analysis |
T3713 |
13478-13482 |
NN |
denotes |
mRNA |
T3714 |
13491-13683 |
sentence |
denotes |
Five micrograms per sample of total RNA extracted from fresh-frozen brain, liver, kidney, heart, lung, spleen, and skeletal muscle was vacuum-filtered through 0.45-μm Optitran nitrocellulose. |
T3715 |
13492-13496 |
CD |
denotes |
Five |
T3716 |
13497-13507 |
NNS |
denotes |
micrograms |
T3717 |
13634-13642 |
VBN |
denotes |
filtered |
T3718 |
13508-13511 |
IN |
denotes |
per |
T3719 |
13512-13518 |
NN |
denotes |
sample |
T3720 |
13519-13521 |
IN |
denotes |
of |
T3721 |
13522-13527 |
JJ |
denotes |
total |
T3722 |
13528-13531 |
NN |
denotes |
RNA |
T3723 |
13532-13541 |
VBN |
denotes |
extracted |
T3724 |
13542-13546 |
IN |
denotes |
from |
T3725 |
13547-13552 |
JJ |
denotes |
fresh |
T3726 |
13553-13559 |
VBN |
denotes |
frozen |
T3727 |
13552-13553 |
HYPH |
denotes |
- |
T3728 |
13560-13565 |
NN |
denotes |
brain |
T3729 |
13565-13567 |
, |
denotes |
, |
T3730 |
13567-13572 |
NN |
denotes |
liver |
T3731 |
13572-13574 |
, |
denotes |
, |
T3732 |
13574-13580 |
NN |
denotes |
kidney |
T3733 |
13580-13582 |
, |
denotes |
, |
T3734 |
13582-13587 |
NN |
denotes |
heart |
T3735 |
13587-13589 |
, |
denotes |
, |
T3736 |
13589-13593 |
NN |
denotes |
lung |
T3737 |
13593-13595 |
, |
denotes |
, |
T3738 |
13595-13601 |
NN |
denotes |
spleen |
T3739 |
13601-13603 |
, |
denotes |
, |
T3740 |
13603-13606 |
CC |
denotes |
and |
T3741 |
13607-13615 |
JJ |
denotes |
skeletal |
T3742 |
13616-13622 |
NN |
denotes |
muscle |
T3743 |
13623-13626 |
VBD |
denotes |
was |
T3744 |
13627-13633 |
NN |
denotes |
vacuum |
T3745 |
13633-13634 |
HYPH |
denotes |
- |
T3746 |
13643-13650 |
IN |
denotes |
through |
T3747 |
13651-13655 |
CD |
denotes |
0.45 |
T3748 |
13656-13658 |
NN |
denotes |
μm |
T3749 |
13655-13656 |
HYPH |
denotes |
- |
T3750 |
13668-13682 |
NN |
denotes |
nitrocellulose |
T3751 |
13659-13667 |
NNP |
denotes |
Optitran |
T3752 |
13682-13683 |
. |
denotes |
. |
T3753 |
13683-13851 |
sentence |
denotes |
After several washes through the manifold with 10× SSC, blots were UV-cross-linked and probed with a radiolabeled ∼350-bp BglII–XhoI cDNA fragment of mo/huAPP695 cDNA. |
T3754 |
13684-13689 |
IN |
denotes |
After |
T3755 |
13754-13766 |
VBN |
denotes |
cross-linked |
T3756 |
13690-13697 |
JJ |
denotes |
several |
T3757 |
13698-13704 |
NNS |
denotes |
washes |
T3758 |
13705-13712 |
IN |
denotes |
through |
T3759 |
13713-13716 |
DT |
denotes |
the |
T3760 |
13717-13725 |
NN |
denotes |
manifold |
T3761 |
13726-13730 |
IN |
denotes |
with |
T3762 |
13731-13733 |
CD |
denotes |
10 |
T3763 |
13735-13738 |
NN |
denotes |
SSC |
T3764 |
13733-13734 |
SYM |
denotes |
× |
T3765 |
13738-13740 |
, |
denotes |
, |
T3766 |
13740-13745 |
NNS |
denotes |
blots |
T3767 |
13746-13750 |
VBD |
denotes |
were |
T3768 |
13751-13753 |
NN |
denotes |
UV |
T3769 |
13753-13754 |
HYPH |
denotes |
- |
T3770 |
13767-13770 |
CC |
denotes |
and |
T3771 |
13771-13777 |
VBN |
denotes |
probed |
T3772 |
13778-13782 |
IN |
denotes |
with |
T3773 |
13783-13784 |
DT |
denotes |
a |
T3774 |
13822-13830 |
NN |
denotes |
fragment |
T3775 |
13785-13797 |
VBN |
denotes |
radiolabeled |
T3776 |
13798-13799 |
SYM |
denotes |
∼ |
T3777 |
13799-13802 |
CD |
denotes |
350 |
T3778 |
13803-13805 |
NN |
denotes |
bp |
T3779 |
13802-13803 |
HYPH |
denotes |
- |
T3780 |
13806-13811 |
NN |
denotes |
BglII |
T3781 |
13812-13816 |
NN |
denotes |
XhoI |
T3782 |
13811-13812 |
HYPH |
denotes |
– |
T3783 |
13817-13821 |
NN |
denotes |
cDNA |
T3784 |
13831-13833 |
IN |
denotes |
of |
T3785 |
13834-13836 |
NN |
denotes |
mo |
T3786 |
13837-13845 |
NN |
denotes |
huAPP695 |
T3787 |
13836-13837 |
HYPH |
denotes |
/ |
T3788 |
13846-13850 |
NN |
denotes |
cDNA |
T3789 |
13850-13851 |
. |
denotes |
. |
T3790 |
13851-14183 |
sentence |
denotes |
After hybridizing overnight at 65 °C in 1% BSA/1 mM EDTA/0.5 M sodium phosphate buffer (pH 7.2)/7% SDS [20], the blots were washed twice at 65 °C for 30 min each in 0.1% BSA/1 mM EDTA/40 mM sodium phosphate buffer (pH 7.2)/5% SDS before two final 30-min washes at 65 °C with 1 mM EDTA/40 mM sodium phosphate buffer (pH 7.2)/1% SDS. |
T3791 |
13852-13857 |
IN |
denotes |
After |
T3792 |
13976-13982 |
VBN |
denotes |
washed |
T3793 |
13858-13869 |
VBG |
denotes |
hybridizing |
T3794 |
13870-13879 |
RB |
denotes |
overnight |
T3795 |
13880-13882 |
IN |
denotes |
at |
T3796 |
13883-13885 |
CD |
denotes |
65 |
T3797 |
13886-13888 |
NN |
denotes |
°C |
T3798 |
13889-13891 |
IN |
denotes |
in |
T3799 |
13892-13893 |
CD |
denotes |
1 |
T3800 |
13893-13894 |
NN |
denotes |
% |
T3801 |
13895-13898 |
NN |
denotes |
BSA |
T3802 |
13898-13899 |
HYPH |
denotes |
/ |
T3803 |
13899-13900 |
CD |
denotes |
1 |
T3804 |
13901-13903 |
NN |
denotes |
mM |
T3805 |
13904-13908 |
NN |
denotes |
EDTA |
T3806 |
13908-13909 |
HYPH |
denotes |
/ |
T3807 |
13909-13912 |
CD |
denotes |
0.5 |
T3808 |
13913-13914 |
NN |
denotes |
M |
T3809 |
13932-13938 |
NN |
denotes |
buffer |
T3810 |
13915-13921 |
NN |
denotes |
sodium |
T3811 |
13922-13931 |
NN |
denotes |
phosphate |
T3812 |
13939-13940 |
-LRB- |
denotes |
( |
T3813 |
13940-13942 |
NN |
denotes |
pH |
T3814 |
13943-13946 |
CD |
denotes |
7.2 |
T3815 |
13946-13947 |
-RRB- |
denotes |
) |
T3816 |
13947-13948 |
HYPH |
denotes |
/ |
T3817 |
13948-13949 |
CD |
denotes |
7 |
T3818 |
13949-13950 |
NN |
denotes |
% |
T3819 |
13951-13954 |
NN |
denotes |
SDS |
T3820 |
13955-13956 |
-LRB- |
denotes |
[ |
T3821 |
13956-13958 |
CD |
denotes |
20 |
T3822 |
13958-13959 |
-RRB- |
denotes |
] |
T3823 |
13959-13961 |
, |
denotes |
, |
T3824 |
13961-13964 |
DT |
denotes |
the |
T3825 |
13965-13970 |
NNS |
denotes |
blots |
T3826 |
13971-13975 |
VBD |
denotes |
were |
T3827 |
13983-13988 |
RB |
denotes |
twice |
T3828 |
13989-13991 |
IN |
denotes |
at |
T3829 |
13992-13994 |
CD |
denotes |
65 |
T3830 |
13995-13997 |
NN |
denotes |
°C |
T3831 |
13998-14001 |
IN |
denotes |
for |
T3832 |
14002-14004 |
CD |
denotes |
30 |
T3833 |
14005-14008 |
NN |
denotes |
min |
T3834 |
14009-14013 |
DT |
denotes |
each |
T3835 |
14014-14016 |
IN |
denotes |
in |
T3836 |
14017-14020 |
CD |
denotes |
0.1 |
T3837 |
14020-14021 |
NN |
denotes |
% |
T3838 |
14022-14025 |
NN |
denotes |
BSA |
T3839 |
14025-14026 |
HYPH |
denotes |
/ |
T3840 |
14026-14027 |
CD |
denotes |
1 |
T3841 |
14028-14030 |
NN |
denotes |
mM |
T3842 |
14031-14035 |
NN |
denotes |
EDTA |
T3843 |
14035-14036 |
HYPH |
denotes |
/ |
T3844 |
14036-14038 |
CD |
denotes |
40 |
T3845 |
14039-14041 |
NN |
denotes |
mM |
T3846 |
14059-14065 |
NN |
denotes |
buffer |
T3847 |
14042-14048 |
NN |
denotes |
sodium |
T3848 |
14049-14058 |
NN |
denotes |
phosphate |
T3849 |
14066-14067 |
-LRB- |
denotes |
( |
T3850 |
14067-14069 |
NN |
denotes |
pH |
T3851 |
14070-14073 |
CD |
denotes |
7.2 |
T3852 |
14073-14074 |
-RRB- |
denotes |
) |
T3853 |
14074-14075 |
HYPH |
denotes |
/ |
T3854 |
14075-14076 |
CD |
denotes |
5 |
T3855 |
14076-14077 |
NN |
denotes |
% |
T3856 |
14078-14081 |
NN |
denotes |
SDS |
T3857 |
14082-14088 |
IN |
denotes |
before |
T3858 |
14089-14092 |
CD |
denotes |
two |
T3859 |
14106-14112 |
NNS |
denotes |
washes |
T3860 |
14093-14098 |
JJ |
denotes |
final |
T3861 |
14099-14101 |
CD |
denotes |
30 |
T3862 |
14102-14105 |
NN |
denotes |
min |
T3863 |
14101-14102 |
HYPH |
denotes |
- |
T3864 |
14113-14115 |
IN |
denotes |
at |
T3865 |
14116-14118 |
CD |
denotes |
65 |
T3866 |
14119-14121 |
NN |
denotes |
°C |
T3867 |
14122-14126 |
IN |
denotes |
with |
T3868 |
14127-14128 |
CD |
denotes |
1 |
T3869 |
14129-14131 |
NN |
denotes |
mM |
T3870 |
14132-14136 |
NN |
denotes |
EDTA |
T3871 |
14136-14137 |
HYPH |
denotes |
/ |
T3872 |
14137-14139 |
CD |
denotes |
40 |
T3873 |
14140-14142 |
NN |
denotes |
mM |
T3874 |
14160-14166 |
NN |
denotes |
buffer |
T3875 |
14143-14149 |
NN |
denotes |
sodium |
T3876 |
14150-14159 |
NN |
denotes |
phosphate |
T3877 |
14167-14168 |
-LRB- |
denotes |
( |
T3878 |
14168-14170 |
NN |
denotes |
pH |
T3879 |
14171-14174 |
CD |
denotes |
7.2 |
T3880 |
14174-14175 |
-RRB- |
denotes |
) |
T3881 |
14175-14176 |
HYPH |
denotes |
/ |
T3882 |
14176-14177 |
CD |
denotes |
1 |
T3883 |
14177-14178 |
NN |
denotes |
% |
T3884 |
14179-14182 |
NN |
denotes |
SDS |
T3885 |
14182-14183 |
. |
denotes |
. |
T3886 |
14183-14268 |
sentence |
denotes |
Blots were wrapped wet and exposed to phosphorscreens overnight at room temperature. |
T3887 |
14184-14189 |
NNS |
denotes |
Blots |
T3888 |
14195-14202 |
VBN |
denotes |
wrapped |
T3889 |
14190-14194 |
VBD |
denotes |
were |
T3890 |
14203-14206 |
JJ |
denotes |
wet |
T3891 |
14207-14210 |
CC |
denotes |
and |
T3892 |
14211-14218 |
VBN |
denotes |
exposed |
T3893 |
14219-14221 |
IN |
denotes |
to |
T3894 |
14222-14237 |
NNS |
denotes |
phosphorscreens |
T3895 |
14238-14247 |
RB |
denotes |
overnight |
T3896 |
14248-14250 |
IN |
denotes |
at |
T3897 |
14251-14255 |
NN |
denotes |
room |
T3898 |
14256-14267 |
NN |
denotes |
temperature |
T3899 |
14267-14268 |
. |
denotes |
. |
T4137 |
14270-14277 |
NN |
denotes |
Amyloid |
T4138 |
14278-14287 |
NN |
denotes |
Histology |
T4139 |
14287-14401 |
sentence |
denotes |
Mice were euthanized by ether inhalation and brains removed for immersion fixation in 4% paraformaldehyde/1× PBS. |
T4140 |
14288-14292 |
NNS |
denotes |
Mice |
T4141 |
14298-14308 |
VBN |
denotes |
euthanized |
T4142 |
14293-14297 |
VBD |
denotes |
were |
T4143 |
14309-14311 |
IN |
denotes |
by |
T4144 |
14312-14317 |
NN |
denotes |
ether |
T4145 |
14318-14328 |
NN |
denotes |
inhalation |
T4146 |
14329-14332 |
CC |
denotes |
and |
T4147 |
14333-14339 |
NNS |
denotes |
brains |
T4148 |
14340-14347 |
VBN |
denotes |
removed |
T4149 |
14348-14351 |
IN |
denotes |
for |
T4150 |
14352-14361 |
NN |
denotes |
immersion |
T4151 |
14362-14370 |
NN |
denotes |
fixation |
T4152 |
14371-14373 |
IN |
denotes |
in |
T4153 |
14374-14375 |
CD |
denotes |
4 |
T4154 |
14375-14376 |
NN |
denotes |
% |
T4155 |
14377-14393 |
NN |
denotes |
paraformaldehyde |
T4156 |
14393-14394 |
HYPH |
denotes |
/ |
T4157 |
14394-14395 |
CD |
denotes |
1 |
T4158 |
14397-14400 |
NN |
denotes |
PBS |
T4159 |
14395-14396 |
SYM |
denotes |
× |
T4160 |
14400-14401 |
. |
denotes |
. |
T4161 |
14401-14579 |
sentence |
denotes |
After 48 h in fixative at 4 °C, brains were transferred to PBS, dehydrated in alcohols, treated with cedarwood oil and methylsalicylate, and embedded in paraffin for sectioning. |
T4162 |
14402-14407 |
IN |
denotes |
After |
T4163 |
14446-14457 |
VBN |
denotes |
transferred |
T4164 |
14408-14410 |
CD |
denotes |
48 |
T4165 |
14411-14412 |
NN |
denotes |
h |
T4166 |
14413-14415 |
IN |
denotes |
in |
T4167 |
14416-14424 |
JJ |
denotes |
fixative |
T4168 |
14425-14427 |
IN |
denotes |
at |
T4169 |
14428-14429 |
CD |
denotes |
4 |
T4170 |
14430-14432 |
NN |
denotes |
°C |
T4171 |
14432-14434 |
, |
denotes |
, |
T4172 |
14434-14440 |
NNS |
denotes |
brains |
T4173 |
14441-14445 |
VBD |
denotes |
were |
T4174 |
14458-14460 |
IN |
denotes |
to |
T4175 |
14461-14464 |
NN |
denotes |
PBS |
T4176 |
14464-14466 |
, |
denotes |
, |
T4177 |
14466-14476 |
VBN |
denotes |
dehydrated |
T4178 |
14477-14479 |
IN |
denotes |
in |
T4179 |
14480-14488 |
NNS |
denotes |
alcohols |
T4180 |
14488-14490 |
, |
denotes |
, |
T4181 |
14490-14497 |
VBN |
denotes |
treated |
T4182 |
14498-14502 |
IN |
denotes |
with |
T4183 |
14503-14512 |
NN |
denotes |
cedarwood |
T4184 |
14513-14516 |
NN |
denotes |
oil |
T4185 |
14517-14520 |
CC |
denotes |
and |
T4186 |
14521-14537 |
NN |
denotes |
methylsalicylate |
T4187 |
14537-14539 |
, |
denotes |
, |
T4188 |
14539-14542 |
CC |
denotes |
and |
T4189 |
14543-14551 |
VBN |
denotes |
embedded |
T4190 |
14552-14554 |
IN |
denotes |
in |
T4191 |
14555-14563 |
NN |
denotes |
paraffin |
T4192 |
14564-14567 |
IN |
denotes |
for |
T4193 |
14568-14578 |
VBG |
denotes |
sectioning |
T4194 |
14578-14579 |
. |
denotes |
. |
T4195 |
14579-14600 |
sentence |
denotes |
Hirano silver stain |
T4196 |
14581-14587 |
NN |
denotes |
Hirano |
T4197 |
14595-14600 |
NN |
denotes |
stain |
T4198 |
14588-14594 |
NN |
denotes |
silver |
T4199 |
14600-14738 |
sentence |
denotes |
Silver impregnation histology was performed on 10-μm paraffin-embedded sections by Hirano's modification of the Bielschowsky method [21]. |
T4200 |
14601-14607 |
NN |
denotes |
Silver |
T4201 |
14621-14630 |
NN |
denotes |
histology |
T4202 |
14608-14620 |
NN |
denotes |
impregnation |
T4203 |
14635-14644 |
VBN |
denotes |
performed |
T4204 |
14631-14634 |
VBD |
denotes |
was |
T4205 |
14645-14647 |
IN |
denotes |
on |
T4206 |
14648-14650 |
CD |
denotes |
10 |
T4207 |
14651-14653 |
NN |
denotes |
μm |
T4208 |
14650-14651 |
HYPH |
denotes |
- |
T4209 |
14672-14680 |
NNS |
denotes |
sections |
T4210 |
14654-14662 |
NN |
denotes |
paraffin |
T4211 |
14663-14671 |
VBN |
denotes |
embedded |
T4212 |
14662-14663 |
HYPH |
denotes |
- |
T4213 |
14681-14683 |
IN |
denotes |
by |
T4214 |
14684-14690 |
NNP |
denotes |
Hirano |
T4215 |
14693-14705 |
NN |
denotes |
modification |
T4216 |
14690-14692 |
POS |
denotes |
's |
T4217 |
14706-14708 |
IN |
denotes |
of |
T4218 |
14709-14712 |
DT |
denotes |
the |
T4219 |
14726-14732 |
NN |
denotes |
method |
T4220 |
14713-14725 |
NNP |
denotes |
Bielschowsky |
T4221 |
14733-14734 |
-LRB- |
denotes |
[ |
T4222 |
14734-14736 |
CD |
denotes |
21 |
T4223 |
14736-14737 |
-RRB- |
denotes |
] |
T4224 |
14737-14738 |
. |
denotes |
. |
T4225 |
14738-14890 |
sentence |
denotes |
Briefly, sections were deparaffinized through xylene and alcohols into tap water before being placed into fresh 20% silver nitrate solution for 20 min. |
T4226 |
14739-14746 |
RB |
denotes |
Briefly |
T4227 |
14762-14776 |
VBN |
denotes |
deparaffinized |
T4228 |
14746-14748 |
, |
denotes |
, |
T4229 |
14748-14756 |
NNS |
denotes |
sections |
T4230 |
14757-14761 |
VBD |
denotes |
were |
T4231 |
14777-14784 |
IN |
denotes |
through |
T4232 |
14785-14791 |
NN |
denotes |
xylene |
T4233 |
14792-14795 |
CC |
denotes |
and |
T4234 |
14796-14804 |
NNS |
denotes |
alcohols |
T4235 |
14805-14809 |
IN |
denotes |
into |
T4236 |
14810-14813 |
NN |
denotes |
tap |
T4237 |
14814-14819 |
NN |
denotes |
water |
T4238 |
14820-14826 |
IN |
denotes |
before |
T4239 |
14827-14832 |
VBG |
denotes |
being |
T4240 |
14833-14839 |
VBN |
denotes |
placed |
T4241 |
14840-14844 |
IN |
denotes |
into |
T4242 |
14845-14850 |
JJ |
denotes |
fresh |
T4243 |
14870-14878 |
NN |
denotes |
solution |
T4244 |
14851-14853 |
CD |
denotes |
20 |
T4245 |
14853-14854 |
NN |
denotes |
% |
T4246 |
14855-14861 |
NN |
denotes |
silver |
T4247 |
14862-14869 |
NN |
denotes |
nitrate |
T4248 |
14879-14882 |
IN |
denotes |
for |
T4249 |
14883-14885 |
CD |
denotes |
20 |
T4250 |
14886-14889 |
NN |
denotes |
min |
T4251 |
14889-14890 |
. |
denotes |
. |
T4252 |
14890-15034 |
sentence |
denotes |
After being washed thoroughly with distilled water, slides were immersed in 20% silver nitrate solution titrated with fresh ammonium hydroxide. |
T4253 |
14891-14896 |
IN |
denotes |
After |
T4254 |
14955-14963 |
VBN |
denotes |
immersed |
T4255 |
14897-14902 |
VBG |
denotes |
being |
T4256 |
14903-14909 |
VBN |
denotes |
washed |
T4257 |
14910-14920 |
RB |
denotes |
thoroughly |
T4258 |
14921-14925 |
IN |
denotes |
with |
T4259 |
14926-14935 |
JJ |
denotes |
distilled |
T4260 |
14936-14941 |
NN |
denotes |
water |
T4261 |
14941-14943 |
, |
denotes |
, |
T4262 |
14943-14949 |
NNS |
denotes |
slides |
T4263 |
14950-14954 |
VBD |
denotes |
were |
T4264 |
14964-14966 |
IN |
denotes |
in |
T4265 |
14967-14969 |
CD |
denotes |
20 |
T4266 |
14969-14970 |
NN |
denotes |
% |
T4267 |
14986-14994 |
NN |
denotes |
solution |
T4268 |
14971-14977 |
NN |
denotes |
silver |
T4269 |
14978-14985 |
NN |
denotes |
nitrate |
T4270 |
14995-15003 |
VBN |
denotes |
titrated |
T4271 |
15004-15008 |
IN |
denotes |
with |
T4272 |
15009-15014 |
JJ |
denotes |
fresh |
T4273 |
15024-15033 |
NN |
denotes |
hydroxide |
T4274 |
15015-15023 |
NN |
denotes |
ammonium |
T4275 |
15033-15034 |
. |
denotes |
. |
T4276 |
15034-15315 |
sentence |
denotes |
After 20 min, slides were washed with ammonia water before being individually developed with 100 μl of developer (20 ml of 37% formaldehyde, 100 ml of distilled water, 50 μl of concentrated nitric acid, and 0.5 g of citric acid) added to 50 ml of titrated silver nitrate solution. |
T4277 |
15035-15040 |
IN |
denotes |
After |
T4278 |
15061-15067 |
VBN |
denotes |
washed |
T4279 |
15041-15043 |
CD |
denotes |
20 |
T4280 |
15044-15047 |
NN |
denotes |
min |
T4281 |
15047-15049 |
, |
denotes |
, |
T4282 |
15049-15055 |
NNS |
denotes |
slides |
T4283 |
15056-15060 |
VBD |
denotes |
were |
T4284 |
15068-15072 |
IN |
denotes |
with |
T4285 |
15073-15080 |
NN |
denotes |
ammonia |
T4286 |
15081-15086 |
NN |
denotes |
water |
T4287 |
15087-15093 |
IN |
denotes |
before |
T4288 |
15094-15099 |
VBG |
denotes |
being |
T4289 |
15113-15122 |
VBN |
denotes |
developed |
T4290 |
15100-15112 |
RB |
denotes |
individually |
T4291 |
15123-15127 |
IN |
denotes |
with |
T4292 |
15128-15131 |
CD |
denotes |
100 |
T4293 |
15132-15134 |
NN |
denotes |
μl |
T4294 |
15135-15137 |
IN |
denotes |
of |
T4295 |
15138-15147 |
NN |
denotes |
developer |
T4296 |
15148-15149 |
-LRB- |
denotes |
( |
T4297 |
15152-15154 |
NN |
denotes |
ml |
T4298 |
15149-15151 |
CD |
denotes |
20 |
T4299 |
15155-15157 |
IN |
denotes |
of |
T4300 |
15158-15160 |
CD |
denotes |
37 |
T4301 |
15160-15161 |
NN |
denotes |
% |
T4302 |
15162-15174 |
NN |
denotes |
formaldehyde |
T4303 |
15174-15176 |
, |
denotes |
, |
T4304 |
15176-15179 |
CD |
denotes |
100 |
T4305 |
15180-15182 |
NN |
denotes |
ml |
T4306 |
15183-15185 |
IN |
denotes |
of |
T4307 |
15186-15195 |
JJ |
denotes |
distilled |
T4308 |
15196-15201 |
NN |
denotes |
water |
T4309 |
15201-15203 |
, |
denotes |
, |
T4310 |
15203-15205 |
CD |
denotes |
50 |
T4311 |
15206-15208 |
NN |
denotes |
μl |
T4312 |
15209-15211 |
IN |
denotes |
of |
T4313 |
15212-15224 |
VBN |
denotes |
concentrated |
T4314 |
15232-15236 |
NN |
denotes |
acid |
T4315 |
15225-15231 |
JJ |
denotes |
nitric |
T4316 |
15236-15238 |
, |
denotes |
, |
T4317 |
15238-15241 |
CC |
denotes |
and |
T4318 |
15242-15245 |
CD |
denotes |
0.5 |
T4319 |
15246-15247 |
NN |
denotes |
g |
T4320 |
15248-15250 |
IN |
denotes |
of |
T4321 |
15251-15257 |
JJ |
denotes |
citric |
T4322 |
15258-15262 |
NN |
denotes |
acid |
T4323 |
15262-15263 |
-RRB- |
denotes |
) |
T4324 |
15264-15269 |
VBN |
denotes |
added |
T4325 |
15270-15272 |
IN |
denotes |
to |
T4326 |
15273-15275 |
CD |
denotes |
50 |
T4327 |
15276-15278 |
NN |
denotes |
ml |
T4328 |
15279-15281 |
IN |
denotes |
of |
T4329 |
15282-15290 |
VBN |
denotes |
titrated |
T4330 |
15306-15314 |
NN |
denotes |
solution |
T4331 |
15291-15297 |
NN |
denotes |
silver |
T4332 |
15298-15305 |
NN |
denotes |
nitrate |
T4333 |
15314-15315 |
. |
denotes |
. |
T4334 |
15315-15429 |
sentence |
denotes |
Slides were then rinsed in tap water, fixed in 5% sodium thiosulfate, and dehydrated through alcohols and xylene. |
T4335 |
15316-15322 |
NNS |
denotes |
Slides |
T4336 |
15333-15339 |
VBN |
denotes |
rinsed |
T4337 |
15323-15327 |
VBD |
denotes |
were |
T4338 |
15328-15332 |
RB |
denotes |
then |
T4339 |
15340-15342 |
IN |
denotes |
in |
T4340 |
15343-15346 |
NN |
denotes |
tap |
T4341 |
15347-15352 |
NN |
denotes |
water |
T4342 |
15352-15354 |
, |
denotes |
, |
T4343 |
15354-15359 |
VBN |
denotes |
fixed |
T4344 |
15360-15362 |
IN |
denotes |
in |
T4345 |
15363-15364 |
CD |
denotes |
5 |
T4346 |
15364-15365 |
NN |
denotes |
% |
T4347 |
15373-15384 |
NN |
denotes |
thiosulfate |
T4348 |
15366-15372 |
NN |
denotes |
sodium |
T4349 |
15384-15386 |
, |
denotes |
, |
T4350 |
15386-15389 |
CC |
denotes |
and |
T4351 |
15390-15400 |
VBN |
denotes |
dehydrated |
T4352 |
15401-15408 |
IN |
denotes |
through |
T4353 |
15409-15417 |
NNS |
denotes |
alcohols |
T4354 |
15418-15421 |
CC |
denotes |
and |
T4355 |
15422-15428 |
NN |
denotes |
xylene |
T4356 |
15428-15429 |
. |
denotes |
. |
T4357 |
15429-15452 |
sentence |
denotes |
Thioflavin-S staining |
T4358 |
15431-15441 |
NN |
denotes |
Thioflavin |
T4359 |
15442-15443 |
NN |
denotes |
S |
T4360 |
15441-15442 |
HYPH |
denotes |
- |
T4361 |
15444-15452 |
NN |
denotes |
staining |
T4362 |
15452-15638 |
sentence |
denotes |
Following deparaffinization of sections through xylene and alcohols, amyloid impregnation with thioflavin-S was performed according to the Guntern modification of the standard protocol. |
T4363 |
15453-15462 |
VBG |
denotes |
Following |
T4364 |
15565-15574 |
VBN |
denotes |
performed |
T4365 |
15463-15480 |
NN |
denotes |
deparaffinization |
T4366 |
15481-15483 |
IN |
denotes |
of |
T4367 |
15484-15492 |
NNS |
denotes |
sections |
T4368 |
15493-15500 |
IN |
denotes |
through |
T4369 |
15501-15507 |
NN |
denotes |
xylene |
T4370 |
15508-15511 |
CC |
denotes |
and |
T4371 |
15512-15520 |
NNS |
denotes |
alcohols |
T4372 |
15520-15522 |
, |
denotes |
, |
T4373 |
15522-15529 |
NN |
denotes |
amyloid |
T4374 |
15530-15542 |
NN |
denotes |
impregnation |
T4375 |
15543-15547 |
IN |
denotes |
with |
T4376 |
15548-15558 |
NN |
denotes |
thioflavin |
T4377 |
15559-15560 |
NN |
denotes |
S |
T4378 |
15558-15559 |
HYPH |
denotes |
- |
T4379 |
15561-15564 |
VBD |
denotes |
was |
T4380 |
15575-15584 |
VBG |
denotes |
according |
T4381 |
15585-15587 |
IN |
denotes |
to |
T4382 |
15588-15591 |
DT |
denotes |
the |
T4383 |
15600-15612 |
NN |
denotes |
modification |
T4384 |
15592-15599 |
NN |
denotes |
Guntern |
T4385 |
15613-15615 |
IN |
denotes |
of |
T4386 |
15616-15619 |
DT |
denotes |
the |
T4387 |
15629-15637 |
NN |
denotes |
protocol |
T4388 |
15620-15628 |
JJ |
denotes |
standard |
T4389 |
15637-15638 |
. |
denotes |
. |
T4390 |
15638-15858 |
sentence |
denotes |
Slides holding 10-μm paraffin sections were washed twice in distilled water, then immersed for 5 min in a 0.25% potassium permanganate solution, followed by 5 min in a 1% potassium metabisulfate/1% oxalic acid solution. |
T4391 |
15639-15645 |
NNS |
denotes |
Slides |
T4392 |
15683-15689 |
VBN |
denotes |
washed |
T4393 |
15646-15653 |
VBG |
denotes |
holding |
T4394 |
15654-15656 |
CD |
denotes |
10 |
T4395 |
15657-15659 |
NN |
denotes |
μm |
T4396 |
15656-15657 |
HYPH |
denotes |
- |
T4397 |
15669-15677 |
NNS |
denotes |
sections |
T4398 |
15660-15668 |
NN |
denotes |
paraffin |
T4399 |
15678-15682 |
VBD |
denotes |
were |
T4400 |
15690-15695 |
RB |
denotes |
twice |
T4401 |
15696-15698 |
IN |
denotes |
in |
T4402 |
15699-15708 |
JJ |
denotes |
distilled |
T4403 |
15709-15714 |
NN |
denotes |
water |
T4404 |
15714-15716 |
, |
denotes |
, |
T4405 |
15716-15720 |
RB |
denotes |
then |
T4406 |
15721-15729 |
VBN |
denotes |
immersed |
T4407 |
15730-15733 |
IN |
denotes |
for |
T4408 |
15734-15735 |
CD |
denotes |
5 |
T4409 |
15736-15739 |
NN |
denotes |
min |
T4410 |
15740-15742 |
IN |
denotes |
in |
T4411 |
15743-15744 |
DT |
denotes |
a |
T4412 |
15774-15782 |
NN |
denotes |
solution |
T4413 |
15745-15749 |
CD |
denotes |
0.25 |
T4414 |
15749-15750 |
NN |
denotes |
% |
T4415 |
15751-15760 |
NN |
denotes |
potassium |
T4416 |
15761-15773 |
NN |
denotes |
permanganate |
T4417 |
15782-15784 |
, |
denotes |
, |
T4418 |
15784-15792 |
VBN |
denotes |
followed |
T4419 |
15793-15795 |
IN |
denotes |
by |
T4420 |
15796-15797 |
CD |
denotes |
5 |
T4421 |
15798-15801 |
NN |
denotes |
min |
T4422 |
15802-15804 |
IN |
denotes |
in |
T4423 |
15805-15806 |
DT |
denotes |
a |
T4424 |
15849-15857 |
NN |
denotes |
solution |
T4425 |
15807-15808 |
CD |
denotes |
1 |
T4426 |
15808-15809 |
NN |
denotes |
% |
T4427 |
15820-15833 |
NN |
denotes |
metabisulfate |
T4428 |
15810-15819 |
NN |
denotes |
potassium |
T4429 |
15833-15834 |
HYPH |
denotes |
/ |
T4430 |
15834-15835 |
CD |
denotes |
1 |
T4431 |
15835-15836 |
NN |
denotes |
% |
T4432 |
15844-15848 |
NN |
denotes |
acid |
T4433 |
15837-15843 |
JJ |
denotes |
oxalic |
T4434 |
15857-15858 |
. |
denotes |
. |
T4435 |
15858-16010 |
sentence |
denotes |
After this preparation, slides were placed into a filtered aqueous 0.02% thioflavin-S solution (Chroma-Gesellschaft Schmid, Kongen, Germany) for 8 min. |
T4436 |
15859-15864 |
IN |
denotes |
After |
T4437 |
15895-15901 |
VBN |
denotes |
placed |
T4438 |
15865-15869 |
DT |
denotes |
this |
T4439 |
15870-15881 |
NN |
denotes |
preparation |
T4440 |
15881-15883 |
, |
denotes |
, |
T4441 |
15883-15889 |
NNS |
denotes |
slides |
T4442 |
15890-15894 |
VBD |
denotes |
were |
T4443 |
15902-15906 |
IN |
denotes |
into |
T4444 |
15907-15908 |
DT |
denotes |
a |
T4445 |
15945-15953 |
NN |
denotes |
solution |
T4446 |
15909-15917 |
VBN |
denotes |
filtered |
T4447 |
15918-15925 |
JJ |
denotes |
aqueous |
T4448 |
15926-15930 |
CD |
denotes |
0.02 |
T4449 |
15930-15931 |
NN |
denotes |
% |
T4450 |
15932-15942 |
NN |
denotes |
thioflavin |
T4451 |
15943-15944 |
NN |
denotes |
S |
T4452 |
15942-15943 |
HYPH |
denotes |
- |
T4453 |
15954-15955 |
-LRB- |
denotes |
( |
T4454 |
15975-15981 |
NNP |
denotes |
Schmid |
T4455 |
15955-15961 |
NNP |
denotes |
Chroma |
T4456 |
15962-15974 |
NNP |
denotes |
Gesellschaft |
T4457 |
15961-15962 |
HYPH |
denotes |
- |
T4458 |
15981-15983 |
, |
denotes |
, |
T4459 |
15983-15989 |
NNP |
denotes |
Kongen |
T4460 |
15989-15991 |
, |
denotes |
, |
T4461 |
15991-15998 |
NNP |
denotes |
Germany |
T4462 |
15998-15999 |
-RRB- |
denotes |
) |
T4463 |
16000-16003 |
IN |
denotes |
for |
T4464 |
16004-16005 |
CD |
denotes |
8 |
T4465 |
16006-16009 |
NN |
denotes |
min |
T4466 |
16009-16010 |
. |
denotes |
. |
T4467 |
16010-16194 |
sentence |
denotes |
Excess stain was removed by two brief rinses in 80% ethanol, then two in distilled water, after which slides were finished in aqueous mounting medium for florescence photomicrography. |
T4468 |
16011-16017 |
JJ |
denotes |
Excess |
T4469 |
16018-16023 |
NN |
denotes |
stain |
T4470 |
16028-16035 |
VBN |
denotes |
removed |
T4471 |
16024-16027 |
VBD |
denotes |
was |
T4472 |
16036-16038 |
IN |
denotes |
by |
T4473 |
16039-16042 |
CD |
denotes |
two |
T4474 |
16049-16055 |
NNS |
denotes |
rinses |
T4475 |
16043-16048 |
JJ |
denotes |
brief |
T4476 |
16056-16058 |
IN |
denotes |
in |
T4477 |
16059-16061 |
CD |
denotes |
80 |
T4478 |
16061-16062 |
NN |
denotes |
% |
T4479 |
16063-16070 |
NN |
denotes |
ethanol |
T4480 |
16070-16072 |
, |
denotes |
, |
T4481 |
16072-16076 |
RB |
denotes |
then |
T4482 |
16077-16080 |
CD |
denotes |
two |
T4483 |
16081-16083 |
IN |
denotes |
in |
T4484 |
16084-16093 |
JJ |
denotes |
distilled |
T4485 |
16094-16099 |
NN |
denotes |
water |
T4486 |
16099-16101 |
, |
denotes |
, |
T4487 |
16101-16106 |
IN |
denotes |
after |
T4488 |
16125-16133 |
VBN |
denotes |
finished |
T4489 |
16107-16112 |
WDT |
denotes |
which |
T4490 |
16113-16119 |
NNS |
denotes |
slides |
T4491 |
16120-16124 |
VBD |
denotes |
were |
T4492 |
16134-16136 |
IN |
denotes |
in |
T4493 |
16137-16144 |
JJ |
denotes |
aqueous |
T4494 |
16154-16160 |
NN |
denotes |
medium |
T4495 |
16145-16153 |
NN |
denotes |
mounting |
T4496 |
16161-16164 |
IN |
denotes |
for |
T4497 |
16165-16176 |
NN |
denotes |
florescence |
T4498 |
16177-16193 |
NN |
denotes |
photomicrography |
T4499 |
16193-16194 |
. |
denotes |
. |
T4500 |
16194-16267 |
sentence |
denotes |
Ubiquitin, glial fibrillary acidic protein, and Aβ immunohistochemistry |
T4501 |
16196-16205 |
NN |
denotes |
Ubiquitin |
T4502 |
16205-16207 |
, |
denotes |
, |
T4503 |
16207-16212 |
JJ |
denotes |
glial |
T4504 |
16231-16238 |
NN |
denotes |
protein |
T4505 |
16213-16223 |
JJ |
denotes |
fibrillary |
T4506 |
16224-16230 |
JJ |
denotes |
acidic |
T4507 |
16238-16240 |
, |
denotes |
, |
T4508 |
16240-16243 |
CC |
denotes |
and |
T4509 |
16244-16246 |
NN |
denotes |
Aβ |
T4510 |
16247-16267 |
NN |
denotes |
immunohistochemistry |
T4511 |
16267-16368 |
sentence |
denotes |
Prior to immunostaining, slides were deparaffinized by oven heating followed by immersion in xylene. |
T4512 |
16268-16273 |
JJ |
denotes |
Prior |
T4513 |
16274-16276 |
IN |
denotes |
to |
T4514 |
16305-16319 |
VBN |
denotes |
deparaffinized |
T4515 |
16277-16291 |
NN |
denotes |
immunostaining |
T4516 |
16291-16293 |
, |
denotes |
, |
T4517 |
16293-16299 |
NNS |
denotes |
slides |
T4518 |
16300-16304 |
VBD |
denotes |
were |
T4519 |
16320-16322 |
IN |
denotes |
by |
T4520 |
16323-16327 |
NN |
denotes |
oven |
T4521 |
16328-16335 |
NN |
denotes |
heating |
T4522 |
16336-16344 |
VBN |
denotes |
followed |
T4523 |
16345-16347 |
IN |
denotes |
by |
T4524 |
16348-16357 |
NN |
denotes |
immersion |
T4525 |
16358-16360 |
IN |
denotes |
in |
T4526 |
16361-16367 |
NN |
denotes |
xylene |
T4527 |
16367-16368 |
. |
denotes |
. |
T4528 |
16368-16523 |
sentence |
denotes |
After rehydration through graded alcohols into tap water, endogenous peroxidase activity was quenched by incubation with 3% hydrogen peroxide in methanol. |
T4529 |
16369-16374 |
IN |
denotes |
After |
T4530 |
16462-16470 |
VBN |
denotes |
quenched |
T4531 |
16375-16386 |
NN |
denotes |
rehydration |
T4532 |
16387-16394 |
IN |
denotes |
through |
T4533 |
16395-16401 |
VBN |
denotes |
graded |
T4534 |
16402-16410 |
NNS |
denotes |
alcohols |
T4535 |
16411-16415 |
IN |
denotes |
into |
T4536 |
16416-16419 |
NN |
denotes |
tap |
T4537 |
16420-16425 |
NN |
denotes |
water |
T4538 |
16425-16427 |
, |
denotes |
, |
T4539 |
16427-16437 |
JJ |
denotes |
endogenous |
T4540 |
16449-16457 |
NN |
denotes |
activity |
T4541 |
16438-16448 |
NN |
denotes |
peroxidase |
T4542 |
16458-16461 |
VBD |
denotes |
was |
T4543 |
16471-16473 |
IN |
denotes |
by |
T4544 |
16474-16484 |
NN |
denotes |
incubation |
T4545 |
16485-16489 |
IN |
denotes |
with |
T4546 |
16490-16491 |
CD |
denotes |
3 |
T4547 |
16491-16492 |
NN |
denotes |
% |
T4548 |
16502-16510 |
NN |
denotes |
peroxide |
T4549 |
16493-16501 |
NN |
denotes |
hydrogen |
T4550 |
16511-16513 |
IN |
denotes |
in |
T4551 |
16514-16522 |
NN |
denotes |
methanol |
T4552 |
16522-16523 |
. |
denotes |
. |
T4553 |
16523-16606 |
sentence |
denotes |
Slides were microwaved for 5–7 min in water, cooled for 5 min, then washed in TBS. |
T4554 |
16524-16530 |
NNS |
denotes |
Slides |
T4555 |
16536-16546 |
VBN |
denotes |
microwaved |
T4556 |
16531-16535 |
VBD |
denotes |
were |
T4557 |
16547-16550 |
IN |
denotes |
for |
T4558 |
16551-16552 |
CD |
denotes |
5 |
T4559 |
16553-16554 |
CD |
denotes |
7 |
T4560 |
16552-16553 |
SYM |
denotes |
– |
T4561 |
16555-16558 |
NN |
denotes |
min |
T4562 |
16559-16561 |
IN |
denotes |
in |
T4563 |
16562-16567 |
NN |
denotes |
water |
T4564 |
16567-16569 |
, |
denotes |
, |
T4565 |
16569-16575 |
VBN |
denotes |
cooled |
T4566 |
16576-16579 |
IN |
denotes |
for |
T4567 |
16580-16581 |
CD |
denotes |
5 |
T4568 |
16582-16585 |
NN |
denotes |
min |
T4569 |
16585-16587 |
, |
denotes |
, |
T4570 |
16587-16591 |
RB |
denotes |
then |
T4571 |
16592-16598 |
VBN |
denotes |
washed |
T4572 |
16599-16601 |
IN |
denotes |
in |
T4573 |
16602-16605 |
NN |
denotes |
TBS |
T4574 |
16605-16606 |
. |
denotes |
. |
T4575 |
16606-16703 |
sentence |
denotes |
Nonspecific staining was blocked for 1 h with 3% normal goat serum and 0.1% Triton-X 100 in TBS. |
T4576 |
16607-16618 |
JJ |
denotes |
Nonspecific |
T4577 |
16619-16627 |
NN |
denotes |
staining |
T4578 |
16632-16639 |
VBN |
denotes |
blocked |
T4579 |
16628-16631 |
VBD |
denotes |
was |
T4580 |
16640-16643 |
IN |
denotes |
for |
T4581 |
16644-16645 |
CD |
denotes |
1 |
T4582 |
16646-16647 |
NN |
denotes |
h |
T4583 |
16648-16652 |
IN |
denotes |
with |
T4584 |
16653-16654 |
CD |
denotes |
3 |
T4585 |
16654-16655 |
NN |
denotes |
% |
T4586 |
16668-16673 |
NN |
denotes |
serum |
T4587 |
16656-16662 |
JJ |
denotes |
normal |
T4588 |
16663-16667 |
NN |
denotes |
goat |
T4589 |
16674-16677 |
CC |
denotes |
and |
T4590 |
16678-16681 |
CD |
denotes |
0.1 |
T4591 |
16681-16682 |
NN |
denotes |
% |
T4592 |
16690-16691 |
NN |
denotes |
X |
T4593 |
16683-16689 |
NN |
denotes |
Triton |
T4594 |
16689-16690 |
HYPH |
denotes |
- |
T4595 |
16692-16695 |
CD |
denotes |
100 |
T4596 |
16696-16698 |
IN |
denotes |
in |
T4597 |
16699-16702 |
NN |
denotes |
TBS |
T4598 |
16702-16703 |
. |
denotes |
. |
T4599 |
16703-17100 |
sentence |
denotes |
Slides were then placed into primary antibody (rabbit anti-Aβ peptide polyclonal antibody, Zymed Laboratories, South San Francisco, California, United States; rabbit anti-ubiquitin and rabbit anti–glial fibrillary acidic protein (GFAP) polyclonal antibodies, Dako, Carpinteria, California, United States) diluted 1:500 in TBS with 2% normal goat serum and incubated overnight at room temperature. |
T4600 |
16704-16710 |
NNS |
denotes |
Slides |
T4601 |
16721-16727 |
VBN |
denotes |
placed |
T4602 |
16711-16715 |
VBD |
denotes |
were |
T4603 |
16716-16720 |
RB |
denotes |
then |
T4604 |
16728-16732 |
IN |
denotes |
into |
T4605 |
16733-16740 |
JJ |
denotes |
primary |
T4606 |
16741-16749 |
NN |
denotes |
antibody |
T4607 |
16750-16751 |
-LRB- |
denotes |
( |
T4608 |
16951-16961 |
NNS |
denotes |
antibodies |
T4609 |
16751-16757 |
NN |
denotes |
rabbit |
T4610 |
16785-16793 |
NN |
denotes |
antibody |
T4611 |
16758-16765 |
JJ |
denotes |
anti-Aβ |
T4612 |
16766-16773 |
NN |
denotes |
peptide |
T4613 |
16774-16784 |
JJ |
denotes |
polyclonal |
T4614 |
16793-16795 |
, |
denotes |
, |
T4615 |
16795-16800 |
NNP |
denotes |
Zymed |
T4616 |
16801-16813 |
NNP |
denotes |
Laboratories |
T4617 |
16813-16815 |
, |
denotes |
, |
T4618 |
16815-16820 |
NNP |
denotes |
South |
T4619 |
16825-16834 |
NNP |
denotes |
Francisco |
T4620 |
16821-16824 |
NNP |
denotes |
San |
T4621 |
16834-16836 |
, |
denotes |
, |
T4622 |
16836-16846 |
NNP |
denotes |
California |
T4623 |
16846-16848 |
, |
denotes |
, |
T4624 |
16848-16854 |
NNP |
denotes |
United |
T4625 |
16855-16861 |
NNP |
denotes |
States |
T4626 |
16861-16862 |
: |
denotes |
; |
T4627 |
16863-16869 |
NN |
denotes |
rabbit |
T4628 |
16870-16884 |
JJ |
denotes |
anti-ubiquitin |
T4629 |
16885-16888 |
CC |
denotes |
and |
T4630 |
16889-16895 |
NN |
denotes |
rabbit |
T4631 |
16896-16906 |
JJ |
denotes |
anti–glial |
T4632 |
16907-16917 |
JJ |
denotes |
fibrillary |
T4633 |
16925-16932 |
NN |
denotes |
protein |
T4634 |
16918-16924 |
JJ |
denotes |
acidic |
T4635 |
16933-16934 |
-LRB- |
denotes |
( |
T4636 |
16934-16938 |
NN |
denotes |
GFAP |
T4637 |
16938-16939 |
-RRB- |
denotes |
) |
T4638 |
16940-16950 |
JJ |
denotes |
polyclonal |
T4639 |
16961-16963 |
, |
denotes |
, |
T4640 |
16963-16967 |
NNP |
denotes |
Dako |
T4641 |
16967-16969 |
, |
denotes |
, |
T4642 |
16969-16980 |
NNP |
denotes |
Carpinteria |
T4643 |
16980-16982 |
, |
denotes |
, |
T4644 |
16982-16992 |
NNP |
denotes |
California |
T4645 |
16992-16994 |
, |
denotes |
, |
T4646 |
16994-17000 |
NNP |
denotes |
United |
T4647 |
17001-17007 |
NNP |
denotes |
States |
T4648 |
17007-17008 |
-RRB- |
denotes |
) |
T4649 |
17009-17016 |
VBN |
denotes |
diluted |
T4650 |
17017-17018 |
CD |
denotes |
1 |
T4651 |
17018-17019 |
SYM |
denotes |
: |
T4652 |
17019-17022 |
CD |
denotes |
500 |
T4653 |
17023-17025 |
IN |
denotes |
in |
T4654 |
17026-17029 |
NN |
denotes |
TBS |
T4655 |
17030-17034 |
IN |
denotes |
with |
T4656 |
17035-17036 |
CD |
denotes |
2 |
T4657 |
17036-17037 |
NN |
denotes |
% |
T4658 |
17050-17055 |
NN |
denotes |
serum |
T4659 |
17038-17044 |
JJ |
denotes |
normal |
T4660 |
17045-17049 |
NN |
denotes |
goat |
T4661 |
17056-17059 |
CC |
denotes |
and |
T4662 |
17060-17069 |
VBN |
denotes |
incubated |
T4663 |
17070-17079 |
RB |
denotes |
overnight |
T4664 |
17080-17082 |
IN |
denotes |
at |
T4665 |
17083-17087 |
NN |
denotes |
room |
T4666 |
17088-17099 |
NN |
denotes |
temperature |
T4667 |
17099-17100 |
. |
denotes |
. |
T4668 |
17100-17507 |
sentence |
denotes |
After being washed of excess primary antibody with several changes of TBS, slides were incubated with either the Vectastain Elite anti-rabbit secondary system (anti-Aβ; Vector Laboratories, Burlingame, California, United States) or peroxidase/anti-peroxidase reagents (anti-ubitquitin and anti-GFAP; Sternberger Monoclonals, Lutherville, Maryland, United States) according to the manufacturers' directions. |
T4669 |
17101-17106 |
IN |
denotes |
After |
T4670 |
17188-17197 |
VBN |
denotes |
incubated |
T4671 |
17107-17112 |
VBG |
denotes |
being |
T4672 |
17113-17119 |
VBN |
denotes |
washed |
T4673 |
17120-17122 |
IN |
denotes |
of |
T4674 |
17123-17129 |
JJ |
denotes |
excess |
T4675 |
17138-17146 |
NN |
denotes |
antibody |
T4676 |
17130-17137 |
JJ |
denotes |
primary |
T4677 |
17147-17151 |
IN |
denotes |
with |
T4678 |
17152-17159 |
JJ |
denotes |
several |
T4679 |
17160-17167 |
NNS |
denotes |
changes |
T4680 |
17168-17170 |
IN |
denotes |
of |
T4681 |
17171-17174 |
NN |
denotes |
TBS |
T4682 |
17174-17176 |
, |
denotes |
, |
T4683 |
17176-17182 |
NNS |
denotes |
slides |
T4684 |
17183-17187 |
VBD |
denotes |
were |
T4685 |
17198-17202 |
IN |
denotes |
with |
T4686 |
17203-17209 |
CC |
denotes |
either |
T4687 |
17253-17259 |
NN |
denotes |
system |
T4688 |
17210-17213 |
DT |
denotes |
the |
T4689 |
17214-17224 |
NNP |
denotes |
Vectastain |
T4690 |
17225-17230 |
NNP |
denotes |
Elite |
T4691 |
17231-17242 |
JJ |
denotes |
anti-rabbit |
T4692 |
17243-17252 |
JJ |
denotes |
secondary |
T4693 |
17260-17261 |
-LRB- |
denotes |
( |
T4694 |
17277-17289 |
NNP |
denotes |
Laboratories |
T4695 |
17261-17268 |
JJ |
denotes |
anti-Aβ |
T4696 |
17268-17269 |
: |
denotes |
; |
T4697 |
17270-17276 |
NNP |
denotes |
Vector |
T4698 |
17289-17291 |
, |
denotes |
, |
T4699 |
17291-17301 |
NNP |
denotes |
Burlingame |
T4700 |
17301-17303 |
, |
denotes |
, |
T4701 |
17303-17313 |
NNP |
denotes |
California |
T4702 |
17313-17315 |
, |
denotes |
, |
T4703 |
17315-17321 |
NNP |
denotes |
United |
T4704 |
17322-17328 |
NNP |
denotes |
States |
T4705 |
17328-17329 |
-RRB- |
denotes |
) |
T4706 |
17330-17332 |
CC |
denotes |
or |
T4707 |
17333-17343 |
NN |
denotes |
peroxidase |
T4708 |
17360-17368 |
NNS |
denotes |
reagents |
T4709 |
17343-17344 |
HYPH |
denotes |
/ |
T4710 |
17344-17359 |
JJ |
denotes |
anti-peroxidase |
T4711 |
17369-17370 |
-LRB- |
denotes |
( |
T4712 |
17413-17424 |
NNPS |
denotes |
Monoclonals |
T4713 |
17370-17385 |
JJ |
denotes |
anti-ubitquitin |
T4714 |
17386-17389 |
CC |
denotes |
and |
T4715 |
17390-17399 |
JJ |
denotes |
anti-GFAP |
T4716 |
17399-17400 |
: |
denotes |
; |
T4717 |
17401-17412 |
NNP |
denotes |
Sternberger |
T4718 |
17424-17426 |
, |
denotes |
, |
T4719 |
17426-17437 |
NNP |
denotes |
Lutherville |
T4720 |
17437-17439 |
, |
denotes |
, |
T4721 |
17439-17447 |
NNP |
denotes |
Maryland |
T4722 |
17447-17449 |
, |
denotes |
, |
T4723 |
17449-17455 |
NNP |
denotes |
United |
T4724 |
17456-17462 |
NNP |
denotes |
States |
T4725 |
17462-17463 |
-RRB- |
denotes |
) |
T4726 |
17464-17473 |
VBG |
denotes |
according |
T4727 |
17474-17476 |
IN |
denotes |
to |
T4728 |
17477-17480 |
DT |
denotes |
the |
T4729 |
17481-17494 |
NNS |
denotes |
manufacturers |
T4730 |
17496-17506 |
NNS |
denotes |
directions |
T4731 |
17494-17495 |
POS |
denotes |
' |
T4732 |
17506-17507 |
. |
denotes |
. |
T4733 |
17507-17613 |
sentence |
denotes |
Antibody binding was visualized with diaminobenzidene, and sections were counterstained with hematoxylin. |
T4734 |
17508-17516 |
NN |
denotes |
Antibody |
T4735 |
17517-17524 |
NN |
denotes |
binding |
T4736 |
17529-17539 |
VBN |
denotes |
visualized |
T4737 |
17525-17528 |
VBD |
denotes |
was |
T4738 |
17540-17544 |
IN |
denotes |
with |
T4739 |
17545-17561 |
NN |
denotes |
diaminobenzidene |
T4740 |
17561-17563 |
, |
denotes |
, |
T4741 |
17563-17566 |
CC |
denotes |
and |
T4742 |
17567-17575 |
NNS |
denotes |
sections |
T4743 |
17581-17595 |
VBN |
denotes |
counterstained |
T4744 |
17576-17580 |
VBD |
denotes |
were |
T4745 |
17596-17600 |
IN |
denotes |
with |
T4746 |
17601-17612 |
NN |
denotes |
hematoxylin |
T4747 |
17612-17613 |
. |
denotes |
. |
T4787 |
17615-17621 |
NN |
denotes |
Filter |
T4788 |
17627-17632 |
NN |
denotes |
Assay |
T4789 |
17622-17626 |
NN |
denotes |
Trap |
T4790 |
17632-17784 |
sentence |
denotes |
An aliquot of each cortical homogenate used for Western blotting above was partially solubilized by the addition of SDS to a final concentration of 1%. |
T4791 |
17633-17635 |
DT |
denotes |
An |
T4792 |
17636-17643 |
NN |
denotes |
aliquot |
T4793 |
17718-17729 |
VBN |
denotes |
solubilized |
T4794 |
17644-17646 |
IN |
denotes |
of |
T4795 |
17647-17651 |
DT |
denotes |
each |
T4796 |
17661-17671 |
NN |
denotes |
homogenate |
T4797 |
17652-17660 |
JJ |
denotes |
cortical |
T4798 |
17672-17676 |
VBN |
denotes |
used |
T4799 |
17677-17680 |
IN |
denotes |
for |
T4800 |
17681-17688 |
NNP |
denotes |
Western |
T4801 |
17689-17697 |
NN |
denotes |
blotting |
T4802 |
17698-17703 |
RB |
denotes |
above |
T4803 |
17704-17707 |
VBD |
denotes |
was |
T4804 |
17708-17717 |
RB |
denotes |
partially |
T4805 |
17730-17732 |
IN |
denotes |
by |
T4806 |
17733-17736 |
DT |
denotes |
the |
T4807 |
17737-17745 |
NN |
denotes |
addition |
T4808 |
17746-17748 |
IN |
denotes |
of |
T4809 |
17749-17752 |
NN |
denotes |
SDS |
T4810 |
17753-17755 |
IN |
denotes |
to |
T4811 |
17756-17757 |
DT |
denotes |
a |
T4812 |
17764-17777 |
NN |
denotes |
concentration |
T4813 |
17758-17763 |
JJ |
denotes |
final |
T4814 |
17778-17780 |
IN |
denotes |
of |
T4815 |
17781-17782 |
CD |
denotes |
1 |
T4816 |
17782-17783 |
NN |
denotes |
% |
T4817 |
17783-17784 |
. |
denotes |
. |
T4818 |
17784-17972 |
sentence |
denotes |
Serial 1:2 dilutions were made with 1× PBS/1% SDS, and 100 μl of each dilution was then vacuum-filtered through a pre-wet 0.22-μm cellulose acetate membrane (Schleicher and Schuell) [22]. |
T4819 |
17785-17791 |
JJ |
denotes |
Serial |
T4820 |
17796-17805 |
NNS |
denotes |
dilutions |
T4821 |
17792-17793 |
CD |
denotes |
1 |
T4822 |
17793-17794 |
SYM |
denotes |
: |
T4823 |
17794-17795 |
CD |
denotes |
2 |
T4824 |
17811-17815 |
VBN |
denotes |
made |
T4825 |
17806-17810 |
VBD |
denotes |
were |
T4826 |
17816-17820 |
IN |
denotes |
with |
T4827 |
17821-17822 |
CD |
denotes |
1 |
T4828 |
17824-17827 |
NN |
denotes |
PBS |
T4829 |
17822-17823 |
SYM |
denotes |
× |
T4830 |
17827-17828 |
HYPH |
denotes |
/ |
T4831 |
17828-17829 |
CD |
denotes |
1 |
T4832 |
17829-17830 |
NN |
denotes |
% |
T4833 |
17831-17834 |
NN |
denotes |
SDS |
T4834 |
17834-17836 |
, |
denotes |
, |
T4835 |
17836-17839 |
CC |
denotes |
and |
T4836 |
17840-17843 |
CD |
denotes |
100 |
T4837 |
17844-17846 |
NN |
denotes |
μl |
T4838 |
17880-17888 |
VBN |
denotes |
filtered |
T4839 |
17847-17849 |
IN |
denotes |
of |
T4840 |
17850-17854 |
DT |
denotes |
each |
T4841 |
17855-17863 |
NN |
denotes |
dilution |
T4842 |
17864-17867 |
VBD |
denotes |
was |
T4843 |
17868-17872 |
RB |
denotes |
then |
T4844 |
17873-17879 |
NN |
denotes |
vacuum |
T4845 |
17879-17880 |
HYPH |
denotes |
- |
T4846 |
17889-17896 |
IN |
denotes |
through |
T4847 |
17897-17898 |
DT |
denotes |
a |
T4848 |
17933-17941 |
NN |
denotes |
membrane |
T4849 |
17899-17906 |
JJ |
denotes |
pre-wet |
T4850 |
17907-17911 |
CD |
denotes |
0.22 |
T4851 |
17912-17914 |
NN |
denotes |
μm |
T4852 |
17911-17912 |
HYPH |
denotes |
- |
T4853 |
17915-17924 |
NN |
denotes |
cellulose |
T4854 |
17925-17932 |
NN |
denotes |
acetate |
T4855 |
17942-17943 |
-LRB- |
denotes |
( |
T4856 |
17943-17953 |
NNP |
denotes |
Schleicher |
T4857 |
17954-17957 |
CC |
denotes |
and |
T4858 |
17958-17965 |
NNP |
denotes |
Schuell |
T4859 |
17965-17966 |
-RRB- |
denotes |
) |
T4860 |
17967-17968 |
-LRB- |
denotes |
[ |
T4861 |
17968-17970 |
CD |
denotes |
22 |
T4862 |
17970-17971 |
-RRB- |
denotes |
] |
T4863 |
17971-17972 |
. |
denotes |
. |
T4864 |
17972-18188 |
sentence |
denotes |
Each well was washed several times with PBS, after which blots were incubated overnight with polyclonal anti-Aβ antibody (Zymed Laboratories) diluted 1:600 in a blocking solution of 1× TBS/5% nonfat dry milk powder. |
T4865 |
17973-17977 |
DT |
denotes |
Each |
T4866 |
17978-17982 |
NN |
denotes |
well |
T4867 |
17987-17993 |
VBN |
denotes |
washed |
T4868 |
17983-17986 |
VBD |
denotes |
was |
T4869 |
17994-18001 |
JJ |
denotes |
several |
T4870 |
18002-18007 |
NNS |
denotes |
times |
T4871 |
18008-18012 |
IN |
denotes |
with |
T4872 |
18013-18016 |
NN |
denotes |
PBS |
T4873 |
18016-18018 |
, |
denotes |
, |
T4874 |
18018-18023 |
IN |
denotes |
after |
T4875 |
18041-18050 |
VBN |
denotes |
incubated |
T4876 |
18024-18029 |
WDT |
denotes |
which |
T4877 |
18030-18035 |
NNS |
denotes |
blots |
T4878 |
18036-18040 |
VBD |
denotes |
were |
T4879 |
18051-18060 |
RB |
denotes |
overnight |
T4880 |
18061-18065 |
IN |
denotes |
with |
T4881 |
18066-18076 |
JJ |
denotes |
polyclonal |
T4882 |
18085-18093 |
NN |
denotes |
antibody |
T4883 |
18077-18084 |
JJ |
denotes |
anti-Aβ |
T4884 |
18094-18095 |
-LRB- |
denotes |
( |
T4885 |
18101-18113 |
NNP |
denotes |
Laboratories |
T4886 |
18095-18100 |
NNP |
denotes |
Zymed |
T4887 |
18113-18114 |
-RRB- |
denotes |
) |
T4888 |
18115-18122 |
VBN |
denotes |
diluted |
T4889 |
18123-18124 |
CD |
denotes |
1 |
T4890 |
18124-18125 |
SYM |
denotes |
: |
T4891 |
18125-18128 |
CD |
denotes |
600 |
T4892 |
18129-18131 |
IN |
denotes |
in |
T4893 |
18132-18133 |
DT |
denotes |
a |
T4894 |
18143-18151 |
NN |
denotes |
solution |
T4895 |
18134-18142 |
NN |
denotes |
blocking |
T4896 |
18152-18154 |
IN |
denotes |
of |
T4897 |
18155-18156 |
CD |
denotes |
1 |
T4898 |
18158-18161 |
NN |
denotes |
TBS |
T4899 |
18156-18157 |
SYM |
denotes |
× |
T4900 |
18181-18187 |
NN |
denotes |
powder |
T4901 |
18161-18162 |
HYPH |
denotes |
/ |
T4902 |
18162-18163 |
CD |
denotes |
5 |
T4903 |
18163-18164 |
NN |
denotes |
% |
T4904 |
18176-18180 |
NN |
denotes |
milk |
T4905 |
18165-18171 |
JJ |
denotes |
nonfat |
T4906 |
18172-18175 |
JJ |
denotes |
dry |
T4907 |
18187-18188 |
. |
denotes |
. |
T4908 |
18188-18376 |
sentence |
denotes |
After washing the blots three times for 10 min each in 1× TBS/0.1% Tween-20, the membrane was incubated for 1 h with HRP-conjugated protein A (Sigma) diluted 1:5,000 in blocking solution. |
T4909 |
18189-18194 |
IN |
denotes |
After |
T4910 |
18283-18292 |
VBN |
denotes |
incubated |
T4911 |
18195-18202 |
VBG |
denotes |
washing |
T4912 |
18203-18206 |
DT |
denotes |
the |
T4913 |
18207-18212 |
NNS |
denotes |
blots |
T4914 |
18213-18218 |
CD |
denotes |
three |
T4915 |
18219-18224 |
NNS |
denotes |
times |
T4916 |
18225-18228 |
IN |
denotes |
for |
T4917 |
18229-18231 |
CD |
denotes |
10 |
T4918 |
18232-18235 |
NN |
denotes |
min |
T4919 |
18236-18240 |
DT |
denotes |
each |
T4920 |
18241-18243 |
IN |
denotes |
in |
T4921 |
18244-18245 |
CD |
denotes |
1 |
T4922 |
18247-18250 |
NN |
denotes |
TBS |
T4923 |
18245-18246 |
SYM |
denotes |
× |
T4924 |
18250-18251 |
HYPH |
denotes |
/ |
T4925 |
18251-18254 |
CD |
denotes |
0.1 |
T4926 |
18254-18255 |
NN |
denotes |
% |
T4927 |
18256-18261 |
NN |
denotes |
Tween |
T4928 |
18261-18262 |
HYPH |
denotes |
- |
T4929 |
18262-18264 |
CD |
denotes |
20 |
T4930 |
18264-18266 |
, |
denotes |
, |
T4931 |
18266-18269 |
DT |
denotes |
the |
T4932 |
18270-18278 |
NN |
denotes |
membrane |
T4933 |
18279-18282 |
VBD |
denotes |
was |
T4934 |
18293-18296 |
IN |
denotes |
for |
T4935 |
18297-18298 |
CD |
denotes |
1 |
T4936 |
18299-18300 |
NN |
denotes |
h |
T4937 |
18301-18305 |
IN |
denotes |
with |
T4938 |
18306-18309 |
NN |
denotes |
HRP |
T4939 |
18310-18320 |
VBN |
denotes |
conjugated |
T4940 |
18309-18310 |
HYPH |
denotes |
- |
T4941 |
18329-18330 |
NN |
denotes |
A |
T4942 |
18321-18328 |
NN |
denotes |
protein |
T4943 |
18331-18332 |
-LRB- |
denotes |
( |
T4944 |
18332-18337 |
NNP |
denotes |
Sigma |
T4945 |
18337-18338 |
-RRB- |
denotes |
) |
T4946 |
18339-18346 |
VBN |
denotes |
diluted |
T4947 |
18347-18348 |
CD |
denotes |
1 |
T4948 |
18348-18349 |
SYM |
denotes |
: |
T4949 |
18349-18354 |
CD |
denotes |
5,000 |
T4950 |
18355-18357 |
IN |
denotes |
in |
T4951 |
18358-18366 |
NN |
denotes |
blocking |
T4952 |
18367-18375 |
NN |
denotes |
solution |
T4953 |
18375-18376 |
. |
denotes |
. |
T4954 |
18376-18569 |
sentence |
denotes |
The membranes were again washed three times with 1× TBS/0.1% Tween-20, before antibody binding was detected with enhanced chemiluminescence (PerkinElmer, Boston, Massachusetts, United States). |
T4955 |
18377-18380 |
DT |
denotes |
The |
T4956 |
18381-18390 |
NNS |
denotes |
membranes |
T4957 |
18402-18408 |
VBN |
denotes |
washed |
T4958 |
18391-18395 |
VBD |
denotes |
were |
T4959 |
18396-18401 |
RB |
denotes |
again |
T4960 |
18409-18414 |
CD |
denotes |
three |
T4961 |
18415-18420 |
NNS |
denotes |
times |
T4962 |
18421-18425 |
IN |
denotes |
with |
T4963 |
18426-18427 |
CD |
denotes |
1 |
T4964 |
18429-18432 |
NN |
denotes |
TBS |
T4965 |
18427-18428 |
SYM |
denotes |
× |
T4966 |
18432-18433 |
HYPH |
denotes |
/ |
T4967 |
18433-18436 |
CD |
denotes |
0.1 |
T4968 |
18436-18437 |
NN |
denotes |
% |
T4969 |
18438-18443 |
NN |
denotes |
Tween |
T4970 |
18443-18444 |
HYPH |
denotes |
- |
T4971 |
18444-18446 |
CD |
denotes |
20 |
T4972 |
18446-18448 |
, |
denotes |
, |
T4973 |
18448-18454 |
IN |
denotes |
before |
T4974 |
18476-18484 |
VBN |
denotes |
detected |
T4975 |
18455-18463 |
NN |
denotes |
antibody |
T4976 |
18464-18471 |
NN |
denotes |
binding |
T4977 |
18472-18475 |
VBD |
denotes |
was |
T4978 |
18485-18489 |
IN |
denotes |
with |
T4979 |
18490-18498 |
VBN |
denotes |
enhanced |
T4980 |
18499-18516 |
NN |
denotes |
chemiluminescence |
T4981 |
18517-18518 |
-LRB- |
denotes |
( |
T4982 |
18518-18529 |
NNP |
denotes |
PerkinElmer |
T4983 |
18529-18531 |
, |
denotes |
, |
T4984 |
18531-18537 |
NNP |
denotes |
Boston |
T4985 |
18537-18539 |
, |
denotes |
, |
T4986 |
18539-18552 |
NNP |
denotes |
Massachusetts |
T4987 |
18552-18554 |
, |
denotes |
, |
T4988 |
18554-18560 |
NNP |
denotes |
United |
T4989 |
18561-18567 |
NNP |
denotes |
States |
T4990 |
18567-18568 |
-RRB- |
denotes |
) |
T4991 |
18568-18569 |
. |
denotes |
. |
T4992 |
18569-18756 |
sentence |
denotes |
Digital images of each blot were captured with a Molecular Imager FX gel documentation system, and the intensity of Aβ staining was quantified using Quantity One image analysis software. |
T4993 |
18570-18577 |
JJ |
denotes |
Digital |
T4994 |
18578-18584 |
NNS |
denotes |
images |
T4995 |
18603-18611 |
VBN |
denotes |
captured |
T4996 |
18585-18587 |
IN |
denotes |
of |
T4997 |
18588-18592 |
DT |
denotes |
each |
T4998 |
18593-18597 |
NN |
denotes |
blot |
T4999 |
18598-18602 |
VBD |
denotes |
were |
T5000 |
18612-18616 |
IN |
denotes |
with |
T5001 |
18617-18618 |
DT |
denotes |
a |
T5002 |
18657-18663 |
NN |
denotes |
system |
T5003 |
18619-18628 |
JJ |
denotes |
Molecular |
T5004 |
18629-18635 |
NNP |
denotes |
Imager |
T5005 |
18636-18638 |
NNP |
denotes |
FX |
T5006 |
18639-18642 |
NN |
denotes |
gel |
T5007 |
18643-18656 |
NN |
denotes |
documentation |
T5008 |
18663-18665 |
, |
denotes |
, |
T5009 |
18665-18668 |
CC |
denotes |
and |
T5010 |
18669-18672 |
DT |
denotes |
the |
T5011 |
18673-18682 |
NN |
denotes |
intensity |
T5012 |
18702-18712 |
VBN |
denotes |
quantified |
T5013 |
18683-18685 |
IN |
denotes |
of |
T5014 |
18686-18688 |
NN |
denotes |
Aβ |
T5015 |
18689-18697 |
NN |
denotes |
staining |
T5016 |
18698-18701 |
VBD |
denotes |
was |
T5017 |
18713-18718 |
VBG |
denotes |
using |
T5018 |
18719-18727 |
NNP |
denotes |
Quantity |
T5019 |
18747-18755 |
NN |
denotes |
software |
T5020 |
18728-18731 |
CD |
denotes |
One |
T5021 |
18732-18737 |
NN |
denotes |
image |
T5022 |
18738-18746 |
NN |
denotes |
analysis |
T5023 |
18755-18756 |
. |
denotes |
. |
T5075 |
18758-18760 |
NN |
denotes |
Aβ |
T5076 |
18761-18766 |
NN |
denotes |
ELISA |
T5077 |
18766-18944 |
sentence |
denotes |
An aliquot of cortical homogenate generated for Western analysis described above was subjected to a three-step sequential extraction using PBS, 2% SDS, and 70% formic acid (FA). |
T5078 |
18767-18769 |
DT |
denotes |
An |
T5079 |
18770-18777 |
NN |
denotes |
aliquot |
T5080 |
18852-18861 |
VBN |
denotes |
subjected |
T5081 |
18778-18780 |
IN |
denotes |
of |
T5082 |
18781-18789 |
JJ |
denotes |
cortical |
T5083 |
18790-18800 |
NN |
denotes |
homogenate |
T5084 |
18801-18810 |
VBN |
denotes |
generated |
T5085 |
18811-18814 |
IN |
denotes |
for |
T5086 |
18815-18822 |
NNP |
denotes |
Western |
T5087 |
18823-18831 |
NN |
denotes |
analysis |
T5088 |
18832-18841 |
VBN |
denotes |
described |
T5089 |
18842-18847 |
RB |
denotes |
above |
T5090 |
18848-18851 |
VBD |
denotes |
was |
T5091 |
18862-18864 |
IN |
denotes |
to |
T5092 |
18865-18866 |
DT |
denotes |
a |
T5093 |
18889-18899 |
NN |
denotes |
extraction |
T5094 |
18867-18872 |
CD |
denotes |
three |
T5095 |
18873-18877 |
NN |
denotes |
step |
T5096 |
18872-18873 |
HYPH |
denotes |
- |
T5097 |
18878-18888 |
JJ |
denotes |
sequential |
T5098 |
18900-18905 |
VBG |
denotes |
using |
T5099 |
18906-18909 |
NN |
denotes |
PBS |
T5100 |
18909-18911 |
, |
denotes |
, |
T5101 |
18911-18912 |
CD |
denotes |
2 |
T5102 |
18912-18913 |
NN |
denotes |
% |
T5103 |
18914-18917 |
NN |
denotes |
SDS |
T5104 |
18917-18919 |
, |
denotes |
, |
T5105 |
18919-18922 |
CC |
denotes |
and |
T5106 |
18923-18925 |
CD |
denotes |
70 |
T5107 |
18925-18926 |
NN |
denotes |
% |
T5108 |
18927-18933 |
JJ |
denotes |
formic |
T5109 |
18934-18938 |
NN |
denotes |
acid |
T5110 |
18939-18940 |
-LRB- |
denotes |
( |
T5111 |
18940-18942 |
NN |
denotes |
FA |
T5112 |
18942-18943 |
-RRB- |
denotes |
) |
T5113 |
18943-18944 |
. |
denotes |
. |
T5114 |
18944-19140 |
sentence |
denotes |
At each step, the sample was sonicated in appropriate buffer and centrifuged at 100,000g for 30 min (1- to 1.5-mo samples) or 60 min (6- to 12-mo samples) at 4 °C as previously described [23–25]. |
T5115 |
18945-18947 |
IN |
denotes |
At |
T5116 |
18974-18983 |
VBN |
denotes |
sonicated |
T5117 |
18948-18952 |
DT |
denotes |
each |
T5118 |
18953-18957 |
NN |
denotes |
step |
T5119 |
18957-18959 |
, |
denotes |
, |
T5120 |
18959-18962 |
DT |
denotes |
the |
T5121 |
18963-18969 |
NN |
denotes |
sample |
T5122 |
18970-18973 |
VBD |
denotes |
was |
T5123 |
18984-18986 |
IN |
denotes |
in |
T5124 |
18987-18998 |
JJ |
denotes |
appropriate |
T5125 |
18999-19005 |
NN |
denotes |
buffer |
T5126 |
19006-19009 |
CC |
denotes |
and |
T5127 |
19010-19021 |
VBN |
denotes |
centrifuged |
T5128 |
19022-19024 |
IN |
denotes |
at |
T5129 |
19025-19033 |
CD |
denotes |
100,000g |
T5130 |
19034-19037 |
IN |
denotes |
for |
T5131 |
19038-19040 |
CD |
denotes |
30 |
T5132 |
19041-19044 |
NN |
denotes |
min |
T5133 |
19045-19046 |
-LRB- |
denotes |
( |
T5134 |
19059-19066 |
NNS |
denotes |
samples |
T5135 |
19046-19047 |
CD |
denotes |
1 |
T5136 |
19052-19055 |
CD |
denotes |
1.5 |
T5137 |
19047-19048 |
HYPH |
denotes |
- |
T5138 |
19049-19051 |
IN |
denotes |
to |
T5139 |
19056-19058 |
NN |
denotes |
mo |
T5140 |
19055-19056 |
HYPH |
denotes |
- |
T5141 |
19066-19067 |
-RRB- |
denotes |
) |
T5142 |
19068-19070 |
CC |
denotes |
or |
T5143 |
19071-19073 |
CD |
denotes |
60 |
T5144 |
19074-19077 |
NN |
denotes |
min |
T5145 |
19078-19079 |
-LRB- |
denotes |
( |
T5146 |
19091-19098 |
NNS |
denotes |
samples |
T5147 |
19079-19080 |
CD |
denotes |
6 |
T5148 |
19085-19087 |
CD |
denotes |
12 |
T5149 |
19080-19081 |
HYPH |
denotes |
- |
T5150 |
19082-19084 |
IN |
denotes |
to |
T5151 |
19088-19090 |
NN |
denotes |
mo |
T5152 |
19087-19088 |
HYPH |
denotes |
- |
T5153 |
19098-19099 |
-RRB- |
denotes |
) |
T5154 |
19100-19102 |
IN |
denotes |
at |
T5155 |
19103-19104 |
CD |
denotes |
4 |
T5156 |
19105-19107 |
NN |
denotes |
°C |
T5157 |
19108-19110 |
IN |
denotes |
as |
T5158 |
19122-19131 |
VBN |
denotes |
described |
T5159 |
19111-19121 |
RB |
denotes |
previously |
T5160 |
19132-19133 |
-LRB- |
denotes |
[ |
T5161 |
19133-19135 |
CD |
denotes |
23 |
T5162 |
19135-19136 |
SYM |
denotes |
– |
T5163 |
19136-19138 |
CD |
denotes |
25 |
T5164 |
19138-19139 |
-RRB- |
denotes |
] |
T5165 |
19139-19140 |
. |
denotes |
. |
T5166 |
19140-19245 |
sentence |
denotes |
The supernatant was removed for analysis, and the pellet was sonicated in the next solution in sequence. |
T5167 |
19141-19144 |
DT |
denotes |
The |
T5168 |
19145-19156 |
NN |
denotes |
supernatant |
T5169 |
19161-19168 |
VBN |
denotes |
removed |
T5170 |
19157-19160 |
VBD |
denotes |
was |
T5171 |
19169-19172 |
IN |
denotes |
for |
T5172 |
19173-19181 |
NN |
denotes |
analysis |
T5173 |
19181-19183 |
, |
denotes |
, |
T5174 |
19183-19186 |
CC |
denotes |
and |
T5175 |
19187-19190 |
DT |
denotes |
the |
T5176 |
19191-19197 |
NN |
denotes |
pellet |
T5177 |
19202-19211 |
VBN |
denotes |
sonicated |
T5178 |
19198-19201 |
VBD |
denotes |
was |
T5179 |
19212-19214 |
IN |
denotes |
in |
T5180 |
19215-19218 |
DT |
denotes |
the |
T5181 |
19224-19232 |
NN |
denotes |
solution |
T5182 |
19219-19223 |
JJ |
denotes |
next |
T5183 |
19233-19235 |
IN |
denotes |
in |
T5184 |
19236-19244 |
NN |
denotes |
sequence |
T5185 |
19244-19245 |
. |
denotes |
. |
T5186 |
19245-19408 |
sentence |
denotes |
The 2% SDS extracts were diluted in EC buffer, and the FA extracts neutralized with 1M Tris-phosphate buffer (pH 11) then diluted with EC buffer prior to testing. |
T5187 |
19246-19249 |
DT |
denotes |
The |
T5188 |
19257-19265 |
NNS |
denotes |
extracts |
T5189 |
19250-19251 |
CD |
denotes |
2 |
T5190 |
19251-19252 |
NN |
denotes |
% |
T5191 |
19253-19256 |
NN |
denotes |
SDS |
T5192 |
19271-19278 |
VBN |
denotes |
diluted |
T5193 |
19266-19270 |
VBD |
denotes |
were |
T5194 |
19279-19281 |
IN |
denotes |
in |
T5195 |
19282-19284 |
NN |
denotes |
EC |
T5196 |
19285-19291 |
NN |
denotes |
buffer |
T5197 |
19291-19293 |
, |
denotes |
, |
T5198 |
19293-19296 |
CC |
denotes |
and |
T5199 |
19297-19300 |
DT |
denotes |
the |
T5200 |
19304-19312 |
NNS |
denotes |
extracts |
T5201 |
19301-19303 |
NN |
denotes |
FA |
T5202 |
19313-19324 |
VBN |
denotes |
neutralized |
T5203 |
19325-19329 |
IN |
denotes |
with |
T5204 |
19330-19332 |
NN |
denotes |
1M |
T5205 |
19348-19354 |
NN |
denotes |
buffer |
T5206 |
19333-19337 |
NN |
denotes |
Tris |
T5207 |
19337-19338 |
HYPH |
denotes |
- |
T5208 |
19338-19347 |
NN |
denotes |
phosphate |
T5209 |
19355-19356 |
-LRB- |
denotes |
( |
T5210 |
19356-19358 |
NN |
denotes |
pH |
T5211 |
19359-19361 |
CD |
denotes |
11 |
T5212 |
19361-19362 |
-RRB- |
denotes |
) |
T5213 |
19363-19367 |
RB |
denotes |
then |
T5214 |
19368-19375 |
VBD |
denotes |
diluted |
T5215 |
19376-19380 |
IN |
denotes |
with |
T5216 |
19381-19383 |
NN |
denotes |
EC |
T5217 |
19384-19390 |
NN |
denotes |
buffer |
T5218 |
19391-19396 |
JJ |
denotes |
prior |
T5219 |
19397-19399 |
IN |
denotes |
to |
T5220 |
19400-19407 |
NN |
denotes |
testing |
T5221 |
19407-19408 |
. |
denotes |
. |
T5222 |
19408-19594 |
sentence |
denotes |
Human Aβ was measured in each fraction using BAN50 for capture (epitope Aβ1–16) and BA27 and BC05 for detection (Aβ40 and Aβ42, respectively) (Takeda Chemical Industries, Osaka, Japan). |
T5223 |
19409-19414 |
JJ |
denotes |
Human |
T5224 |
19415-19417 |
NN |
denotes |
Aβ |
T5225 |
19422-19430 |
VBN |
denotes |
measured |
T5226 |
19418-19421 |
VBD |
denotes |
was |
T5227 |
19431-19433 |
IN |
denotes |
in |
T5228 |
19434-19438 |
DT |
denotes |
each |
T5229 |
19439-19447 |
NN |
denotes |
fraction |
T5230 |
19448-19453 |
VBG |
denotes |
using |
T5231 |
19454-19459 |
NN |
denotes |
BAN50 |
T5232 |
19460-19463 |
IN |
denotes |
for |
T5233 |
19464-19471 |
NN |
denotes |
capture |
T5234 |
19472-19473 |
-LRB- |
denotes |
( |
T5235 |
19485-19487 |
NN |
denotes |
16 |
T5236 |
19473-19480 |
NN |
denotes |
epitope |
T5237 |
19481-19484 |
NN |
denotes |
Aβ1 |
T5238 |
19484-19485 |
HYPH |
denotes |
– |
T5239 |
19487-19488 |
-RRB- |
denotes |
) |
T5240 |
19489-19492 |
CC |
denotes |
and |
T5241 |
19493-19497 |
NN |
denotes |
BA27 |
T5242 |
19498-19501 |
CC |
denotes |
and |
T5243 |
19502-19506 |
NN |
denotes |
BC05 |
T5244 |
19507-19510 |
IN |
denotes |
for |
T5245 |
19511-19520 |
NN |
denotes |
detection |
T5246 |
19521-19522 |
-LRB- |
denotes |
( |
T5247 |
19522-19526 |
NN |
denotes |
Aβ40 |
T5248 |
19527-19530 |
CC |
denotes |
and |
T5249 |
19531-19535 |
NN |
denotes |
Aβ42 |
T5250 |
19535-19537 |
, |
denotes |
, |
T5251 |
19537-19549 |
RB |
denotes |
respectively |
T5252 |
19549-19550 |
-RRB- |
denotes |
) |
T5253 |
19551-19552 |
-LRB- |
denotes |
( |
T5254 |
19568-19578 |
NNPS |
denotes |
Industries |
T5255 |
19552-19558 |
NNP |
denotes |
Takeda |
T5256 |
19559-19567 |
NNP |
denotes |
Chemical |
T5257 |
19578-19580 |
, |
denotes |
, |
T5258 |
19580-19585 |
NNP |
denotes |
Osaka |
T5259 |
19585-19587 |
, |
denotes |
, |
T5260 |
19587-19592 |
NNP |
denotes |
Japan |
T5261 |
19592-19593 |
-RRB- |
denotes |
) |
T5262 |
19593-19594 |
. |
denotes |
. |
T5263 |
19594-19751 |
sentence |
denotes |
Total Aβ (mouse + human; 1- to 1.5-mo samples only) was measured in each fraction using BNT77 for capture (epitope Aβ11–28) and BA27 and BC05 for detection. |
T5264 |
19595-19600 |
JJ |
denotes |
Total |
T5265 |
19601-19603 |
NN |
denotes |
Aβ |
T5266 |
19651-19659 |
VBN |
denotes |
measured |
T5267 |
19604-19605 |
-LRB- |
denotes |
( |
T5268 |
19633-19640 |
NNS |
denotes |
samples |
T5269 |
19605-19610 |
NN |
denotes |
mouse |
T5270 |
19611-19612 |
SYM |
denotes |
+ |
T5271 |
19613-19618 |
JJ |
denotes |
human |
T5272 |
19618-19619 |
: |
denotes |
; |
T5273 |
19620-19621 |
CD |
denotes |
1 |
T5274 |
19626-19629 |
CD |
denotes |
1.5 |
T5275 |
19621-19622 |
HYPH |
denotes |
- |
T5276 |
19623-19625 |
IN |
denotes |
to |
T5277 |
19630-19632 |
NN |
denotes |
mo |
T5278 |
19629-19630 |
HYPH |
denotes |
- |
T5279 |
19641-19645 |
RB |
denotes |
only |
T5280 |
19645-19646 |
-RRB- |
denotes |
) |
T5281 |
19647-19650 |
VBD |
denotes |
was |
T5282 |
19660-19662 |
IN |
denotes |
in |
T5283 |
19663-19667 |
DT |
denotes |
each |
T5284 |
19668-19676 |
NN |
denotes |
fraction |
T5285 |
19677-19682 |
VBG |
denotes |
using |
T5286 |
19683-19688 |
NN |
denotes |
BNT77 |
T5287 |
19689-19692 |
IN |
denotes |
for |
T5288 |
19693-19700 |
NN |
denotes |
capture |
T5289 |
19701-19702 |
-LRB- |
denotes |
( |
T5290 |
19710-19714 |
NN |
denotes |
Aβ11 |
T5291 |
19702-19709 |
NN |
denotes |
epitope |
T5292 |
19714-19715 |
HYPH |
denotes |
– |
T5293 |
19715-19717 |
CD |
denotes |
28 |
T5294 |
19717-19718 |
-RRB- |
denotes |
) |
T5295 |
19719-19722 |
CC |
denotes |
and |
T5296 |
19723-19727 |
NN |
denotes |
BA27 |
T5297 |
19728-19731 |
CC |
denotes |
and |
T5298 |
19732-19736 |
NN |
denotes |
BC05 |
T5299 |
19737-19740 |
IN |
denotes |
for |
T5300 |
19741-19750 |
NN |
denotes |
detection |
T5301 |
19750-19751 |
. |
denotes |
. |
T5302 |
19751-19848 |
sentence |
denotes |
All values were calculated as picomoles per gram based on the initial weight of cortical tissue. |
T5303 |
19752-19755 |
DT |
denotes |
All |
T5304 |
19756-19762 |
NNS |
denotes |
values |
T5305 |
19768-19778 |
VBN |
denotes |
calculated |
T5306 |
19763-19767 |
VBD |
denotes |
were |
T5307 |
19779-19781 |
IN |
denotes |
as |
T5308 |
19782-19791 |
NNS |
denotes |
picomoles |
T5309 |
19792-19795 |
IN |
denotes |
per |
T5310 |
19796-19800 |
NN |
denotes |
gram |
T5311 |
19801-19806 |
VBN |
denotes |
based |
T5312 |
19807-19809 |
IN |
denotes |
on |
T5313 |
19810-19813 |
DT |
denotes |
the |
T5314 |
19822-19828 |
NN |
denotes |
weight |
T5315 |
19814-19821 |
JJ |
denotes |
initial |
T5316 |
19829-19831 |
IN |
denotes |
of |
T5317 |
19832-19840 |
JJ |
denotes |
cortical |
T5318 |
19841-19847 |
NN |
denotes |
tissue |
T5319 |
19847-19848 |
. |
denotes |
. |
T5339 |
19850-19858 |
NN |
denotes |
Activity |
T5340 |
19859-19869 |
NN |
denotes |
Monitoring |
T5341 |
19869-19978 |
sentence |
denotes |
Daily basal activity was studied in 28 CaMKIIα-tTA × tet-APPswe/ind line 107 mice between 4 and 5 mo of age. |
T5342 |
19870-19875 |
JJ |
denotes |
Daily |
T5343 |
19882-19890 |
NN |
denotes |
activity |
T5344 |
19876-19881 |
JJ |
denotes |
basal |
T5345 |
19895-19902 |
VBN |
denotes |
studied |
T5346 |
19891-19894 |
VBD |
denotes |
was |
T5347 |
19903-19905 |
IN |
denotes |
in |
T5348 |
19906-19908 |
CD |
denotes |
28 |
T5349 |
19947-19951 |
NNS |
denotes |
mice |
T5350 |
19909-19916 |
NN |
denotes |
CaMKIIα |
T5351 |
19934-19937 |
NN |
denotes |
ind |
T5352 |
19916-19917 |
HYPH |
denotes |
- |
T5353 |
19917-19920 |
NN |
denotes |
tTA |
T5354 |
19921-19922 |
SYM |
denotes |
× |
T5355 |
19923-19926 |
NN |
denotes |
tet |
T5356 |
19926-19927 |
HYPH |
denotes |
- |
T5357 |
19927-19933 |
NN |
denotes |
APPswe |
T5358 |
19933-19934 |
HYPH |
denotes |
/ |
T5359 |
19938-19942 |
NN |
denotes |
line |
T5360 |
19943-19946 |
CD |
denotes |
107 |
T5361 |
19952-19959 |
IN |
denotes |
between |
T5362 |
19960-19961 |
CD |
denotes |
4 |
T5363 |
19968-19970 |
NN |
denotes |
mo |
T5364 |
19962-19965 |
CC |
denotes |
and |
T5365 |
19966-19967 |
CD |
denotes |
5 |
T5366 |
19971-19973 |
IN |
denotes |
of |
T5367 |
19974-19977 |
NN |
denotes |
age |
T5368 |
19977-19978 |
. |
denotes |
. |
T5369 |
19978-20134 |
sentence |
denotes |
Animals were separated into individual cages immediately before the start of each experiment (n = 3–6 per genotype untreated, 2–5 per genotype dox-reared). |
T5370 |
19979-19986 |
NNS |
denotes |
Animals |
T5371 |
19992-20001 |
VBN |
denotes |
separated |
T5372 |
19987-19991 |
VBD |
denotes |
were |
T5373 |
20002-20006 |
IN |
denotes |
into |
T5374 |
20007-20017 |
JJ |
denotes |
individual |
T5375 |
20018-20023 |
NNS |
denotes |
cages |
T5376 |
20024-20035 |
RB |
denotes |
immediately |
T5377 |
20036-20042 |
IN |
denotes |
before |
T5378 |
20043-20046 |
DT |
denotes |
the |
T5379 |
20047-20052 |
NN |
denotes |
start |
T5380 |
20053-20055 |
IN |
denotes |
of |
T5381 |
20056-20060 |
DT |
denotes |
each |
T5382 |
20061-20071 |
NN |
denotes |
experiment |
T5383 |
20072-20073 |
-LRB- |
denotes |
( |
T5384 |
20079-20080 |
CD |
denotes |
6 |
T5385 |
20073-20074 |
NN |
denotes |
n |
T5386 |
20075-20076 |
SYM |
denotes |
= |
T5387 |
20077-20078 |
CD |
denotes |
3 |
T5388 |
20078-20079 |
SYM |
denotes |
– |
T5389 |
20081-20084 |
IN |
denotes |
per |
T5390 |
20085-20093 |
NN |
denotes |
genotype |
T5391 |
20094-20103 |
JJ |
denotes |
untreated |
T5392 |
20103-20105 |
, |
denotes |
, |
T5393 |
20105-20106 |
CD |
denotes |
2 |
T5394 |
20107-20108 |
CD |
denotes |
5 |
T5395 |
20106-20107 |
SYM |
denotes |
– |
T5396 |
20109-20112 |
IN |
denotes |
per |
T5397 |
20113-20121 |
NN |
denotes |
genotype |
T5398 |
20122-20125 |
NN |
denotes |
dox |
T5399 |
20126-20132 |
VBN |
denotes |
reared |
T5400 |
20125-20126 |
HYPH |
denotes |
- |
T5401 |
20132-20133 |
-RRB- |
denotes |
) |
T5402 |
20133-20134 |
. |
denotes |
. |
T5403 |
20134-20363 |
sentence |
denotes |
The cages were placed inside activity-monitoring frames designed to count every time the animal passed through one of three photobeams spanning the width of the cage (San Diego Instruments, San Diego, California, United States). |
T5404 |
20135-20138 |
DT |
denotes |
The |
T5405 |
20139-20144 |
NNS |
denotes |
cages |
T5406 |
20150-20156 |
VBN |
denotes |
placed |
T5407 |
20145-20149 |
VBD |
denotes |
were |
T5408 |
20157-20163 |
IN |
denotes |
inside |
T5409 |
20164-20172 |
NN |
denotes |
activity |
T5410 |
20173-20183 |
VBG |
denotes |
monitoring |
T5411 |
20172-20173 |
HYPH |
denotes |
- |
T5412 |
20184-20190 |
NNS |
denotes |
frames |
T5413 |
20191-20199 |
VBN |
denotes |
designed |
T5414 |
20200-20202 |
TO |
denotes |
to |
T5415 |
20203-20208 |
VB |
denotes |
count |
T5416 |
20209-20214 |
DT |
denotes |
every |
T5417 |
20215-20219 |
NN |
denotes |
time |
T5418 |
20220-20223 |
DT |
denotes |
the |
T5419 |
20224-20230 |
NN |
denotes |
animal |
T5420 |
20231-20237 |
VBN |
denotes |
passed |
T5421 |
20238-20245 |
IN |
denotes |
through |
T5422 |
20246-20249 |
CD |
denotes |
one |
T5423 |
20250-20252 |
IN |
denotes |
of |
T5424 |
20253-20258 |
CD |
denotes |
three |
T5425 |
20259-20269 |
NNS |
denotes |
photobeams |
T5426 |
20270-20278 |
VBG |
denotes |
spanning |
T5427 |
20279-20282 |
DT |
denotes |
the |
T5428 |
20283-20288 |
NN |
denotes |
width |
T5429 |
20289-20291 |
IN |
denotes |
of |
T5430 |
20292-20295 |
DT |
denotes |
the |
T5431 |
20296-20300 |
NN |
denotes |
cage |
T5432 |
20301-20302 |
-LRB- |
denotes |
( |
T5433 |
20312-20323 |
NNP |
denotes |
Instruments |
T5434 |
20302-20305 |
NNP |
denotes |
San |
T5435 |
20306-20311 |
NNP |
denotes |
Diego |
T5436 |
20323-20325 |
, |
denotes |
, |
T5437 |
20325-20328 |
NNP |
denotes |
San |
T5438 |
20329-20334 |
NNP |
denotes |
Diego |
T5439 |
20334-20336 |
, |
denotes |
, |
T5440 |
20336-20346 |
NNP |
denotes |
California |
T5441 |
20346-20348 |
, |
denotes |
, |
T5442 |
20348-20354 |
NNP |
denotes |
United |
T5443 |
20355-20361 |
NNP |
denotes |
States |
T5444 |
20361-20362 |
-RRB- |
denotes |
) |
T5445 |
20362-20363 |
. |
denotes |
. |
T5446 |
20363-20491 |
sentence |
denotes |
Experiments were started midway through the light phase of the day, and data were collected in 1-h bins for the following 48 h. |
T5447 |
20364-20375 |
NNS |
denotes |
Experiments |
T5448 |
20381-20388 |
VBN |
denotes |
started |
T5449 |
20376-20380 |
VBD |
denotes |
were |
T5450 |
20389-20395 |
RB |
denotes |
midway |
T5451 |
20396-20403 |
IN |
denotes |
through |
T5452 |
20404-20407 |
DT |
denotes |
the |
T5453 |
20414-20419 |
NN |
denotes |
phase |
T5454 |
20408-20413 |
NN |
denotes |
light |
T5455 |
20420-20422 |
IN |
denotes |
of |
T5456 |
20423-20426 |
DT |
denotes |
the |
T5457 |
20427-20430 |
NN |
denotes |
day |
T5458 |
20430-20432 |
, |
denotes |
, |
T5459 |
20432-20435 |
CC |
denotes |
and |
T5460 |
20436-20440 |
NNS |
denotes |
data |
T5461 |
20446-20455 |
VBN |
denotes |
collected |
T5462 |
20441-20445 |
VBD |
denotes |
were |
T5463 |
20456-20458 |
IN |
denotes |
in |
T5464 |
20459-20460 |
CD |
denotes |
1 |
T5465 |
20461-20462 |
NN |
denotes |
h |
T5466 |
20460-20461 |
HYPH |
denotes |
- |
T5467 |
20463-20467 |
NNS |
denotes |
bins |
T5468 |
20468-20471 |
IN |
denotes |
for |
T5469 |
20472-20475 |
DT |
denotes |
the |
T5470 |
20489-20490 |
NN |
denotes |
h |
T5471 |
20476-20485 |
JJ |
denotes |
following |
T5472 |
20486-20488 |
CD |
denotes |
48 |
T5473 |
20490-20491 |
. |
denotes |
. |
T5474 |
20491-20638 |
sentence |
denotes |
Testing rooms were maintained on the same 13:11 h day:night cycle as the main animal housing areas and were closed to entry during the experiment. |
T5475 |
20492-20499 |
NN |
denotes |
Testing |
T5476 |
20500-20505 |
NNS |
denotes |
rooms |
T5477 |
20511-20521 |
VBN |
denotes |
maintained |
T5478 |
20506-20510 |
VBD |
denotes |
were |
T5479 |
20522-20524 |
IN |
denotes |
on |
T5480 |
20525-20528 |
DT |
denotes |
the |
T5481 |
20552-20557 |
NN |
denotes |
cycle |
T5482 |
20529-20533 |
JJ |
denotes |
same |
T5483 |
20534-20536 |
CD |
denotes |
13 |
T5484 |
20540-20541 |
NN |
denotes |
h |
T5485 |
20536-20537 |
SYM |
denotes |
: |
T5486 |
20537-20539 |
CD |
denotes |
11 |
T5487 |
20542-20545 |
NN |
denotes |
day |
T5488 |
20545-20546 |
SYM |
denotes |
: |
T5489 |
20546-20551 |
NN |
denotes |
night |
T5490 |
20558-20560 |
IN |
denotes |
as |
T5491 |
20561-20564 |
DT |
denotes |
the |
T5492 |
20585-20590 |
NNS |
denotes |
areas |
T5493 |
20565-20569 |
JJ |
denotes |
main |
T5494 |
20570-20576 |
NN |
denotes |
animal |
T5495 |
20577-20584 |
NN |
denotes |
housing |
T5496 |
20591-20594 |
CC |
denotes |
and |
T5497 |
20595-20599 |
VBD |
denotes |
were |
T5498 |
20600-20606 |
VBN |
denotes |
closed |
T5499 |
20607-20609 |
IN |
denotes |
to |
T5500 |
20610-20615 |
NN |
denotes |
entry |
T5501 |
20616-20622 |
IN |
denotes |
during |
T5502 |
20623-20626 |
DT |
denotes |
the |
T5503 |
20627-20637 |
NN |
denotes |
experiment |
T5504 |
20637-20638 |
. |
denotes |
. |
T5510 |
20640-20651 |
JJ |
denotes |
Statistical |
T5511 |
20652-20660 |
NNS |
denotes |
Analyses |
T5512 |
20660-20932 |
sentence |
denotes |
Statistical analyses of protein expression, ELISA data, and filter trap assays were performed by ANOVA with Tukey's honest significant difference post-hoc test applied to significant main effects or interactions (Statistica 6.0, StatSoft, Tulsa, Oklahoma, United States). |
T5513 |
20661-20672 |
JJ |
denotes |
Statistical |
T5514 |
20673-20681 |
NNS |
denotes |
analyses |
T5515 |
20745-20754 |
VBN |
denotes |
performed |
T5516 |
20682-20684 |
IN |
denotes |
of |
T5517 |
20685-20692 |
NN |
denotes |
protein |
T5518 |
20693-20703 |
NN |
denotes |
expression |
T5519 |
20703-20705 |
, |
denotes |
, |
T5520 |
20705-20710 |
NN |
denotes |
ELISA |
T5521 |
20711-20715 |
NNS |
denotes |
data |
T5522 |
20715-20717 |
, |
denotes |
, |
T5523 |
20717-20720 |
CC |
denotes |
and |
T5524 |
20721-20727 |
NN |
denotes |
filter |
T5525 |
20728-20732 |
NN |
denotes |
trap |
T5526 |
20733-20739 |
NNS |
denotes |
assays |
T5527 |
20740-20744 |
VBD |
denotes |
were |
T5528 |
20755-20757 |
IN |
denotes |
by |
T5529 |
20758-20763 |
NN |
denotes |
ANOVA |
T5530 |
20764-20768 |
IN |
denotes |
with |
T5531 |
20769-20774 |
NNP |
denotes |
Tukey |
T5532 |
20816-20820 |
NN |
denotes |
test |
T5533 |
20774-20776 |
POS |
denotes |
's |
T5534 |
20777-20783 |
JJ |
denotes |
honest |
T5535 |
20784-20795 |
JJ |
denotes |
significant |
T5536 |
20796-20806 |
NN |
denotes |
difference |
T5537 |
20807-20811 |
FW |
denotes |
post |
T5538 |
20812-20815 |
FW |
denotes |
hoc |
T5539 |
20811-20812 |
HYPH |
denotes |
- |
T5540 |
20821-20828 |
VBN |
denotes |
applied |
T5541 |
20829-20831 |
IN |
denotes |
to |
T5542 |
20832-20843 |
JJ |
denotes |
significant |
T5543 |
20849-20856 |
NNS |
denotes |
effects |
T5544 |
20844-20848 |
JJ |
denotes |
main |
T5545 |
20857-20859 |
CC |
denotes |
or |
T5546 |
20860-20872 |
NNS |
denotes |
interactions |
T5547 |
20873-20874 |
-LRB- |
denotes |
( |
T5548 |
20874-20884 |
NNP |
denotes |
Statistica |
T5549 |
20885-20888 |
CD |
denotes |
6.0 |
T5550 |
20888-20890 |
, |
denotes |
, |
T5551 |
20890-20898 |
NNP |
denotes |
StatSoft |
T5552 |
20898-20900 |
, |
denotes |
, |
T5553 |
20900-20905 |
NNP |
denotes |
Tulsa |
T5554 |
20905-20907 |
, |
denotes |
, |
T5555 |
20907-20915 |
NNP |
denotes |
Oklahoma |
T5556 |
20915-20917 |
, |
denotes |
, |
T5557 |
20917-20923 |
NNP |
denotes |
United |
T5558 |
20924-20930 |
NNP |
denotes |
States |
T5559 |
20930-20931 |
-RRB- |
denotes |
) |
T5560 |
20931-20932 |
. |
denotes |
. |
T5561 |
20932-21072 |
sentence |
denotes |
In cases of positively skewed data distribution, log10(x + 0.5) transformation was applied to the raw data before submitting them to ANOVA. |
T5562 |
20933-20935 |
IN |
denotes |
In |
T5563 |
21016-21023 |
VBN |
denotes |
applied |
T5564 |
20936-20941 |
NNS |
denotes |
cases |
T5565 |
20942-20944 |
IN |
denotes |
of |
T5566 |
20945-20955 |
RB |
denotes |
positively |
T5567 |
20956-20962 |
VBN |
denotes |
skewed |
T5568 |
20968-20980 |
NN |
denotes |
distribution |
T5569 |
20963-20967 |
NNS |
denotes |
data |
T5570 |
20980-20982 |
, |
denotes |
, |
T5571 |
20982-20987 |
NN |
denotes |
log10 |
T5572 |
20988-20989 |
NN |
denotes |
x |
T5573 |
20987-20988 |
-LRB- |
denotes |
( |
T5574 |
20997-21011 |
NN |
denotes |
transformation |
T5575 |
20990-20991 |
SYM |
denotes |
+ |
T5576 |
20992-20995 |
CD |
denotes |
0.5 |
T5577 |
20995-20996 |
-RRB- |
denotes |
) |
T5578 |
21012-21015 |
VBD |
denotes |
was |
T5579 |
21024-21026 |
IN |
denotes |
to |
T5580 |
21027-21030 |
DT |
denotes |
the |
T5581 |
21035-21039 |
NNS |
denotes |
data |
T5582 |
21031-21034 |
JJ |
denotes |
raw |
T5583 |
21040-21046 |
IN |
denotes |
before |
T5584 |
21047-21057 |
VBG |
denotes |
submitting |
T5585 |
21058-21062 |
PRP |
denotes |
them |
T5586 |
21063-21065 |
IN |
denotes |
to |
T5587 |
21066-21071 |
NN |
denotes |
ANOVA |
T5588 |
21071-21072 |
. |
denotes |
. |
T6511 |
21082-21084 |
PRP |
denotes |
We |
T6512 |
21085-21089 |
VBD |
denotes |
used |
T6513 |
21090-21093 |
DT |
denotes |
the |
T6514 |
21112-21118 |
NN |
denotes |
system |
T6515 |
21094-21097 |
NN |
denotes |
tet |
T6516 |
21098-21101 |
NN |
denotes |
off |
T6517 |
21097-21098 |
HYPH |
denotes |
- |
T6518 |
21102-21111 |
NN |
denotes |
transgene |
T6519 |
21119-21121 |
TO |
denotes |
to |
T6520 |
21122-21129 |
VB |
denotes |
express |
T6521 |
21130-21131 |
DT |
denotes |
a |
T6522 |
21146-21153 |
NN |
denotes |
version |
T6523 |
21132-21138 |
JJ |
denotes |
double |
T6524 |
21139-21145 |
NN |
denotes |
mutant |
T6525 |
21154-21156 |
IN |
denotes |
of |
T6526 |
21157-21165 |
JJ |
denotes |
chimeric |
T6527 |
21169-21177 |
NN |
denotes |
huAPP695 |
T6528 |
21166-21168 |
NN |
denotes |
mo |
T6529 |
21168-21169 |
HYPH |
denotes |
/ |
T6530 |
21178-21179 |
-LRB- |
denotes |
( |
T6531 |
21179-21182 |
NN |
denotes |
swe |
T6532 |
21187-21192 |
NN |
denotes |
KM570 |
T6533 |
21182-21183 |
HYPH |
denotes |
/ |
T6534 |
21183-21186 |
NN |
denotes |
ind |
T6535 |
21192-21194 |
, |
denotes |
, |
T6536 |
21194-21199 |
NN |
denotes |
571NL |
T6537 |
21199-21201 |
, |
denotes |
, |
T6538 |
21201-21204 |
CC |
denotes |
and |
T6539 |
21205-21210 |
NN |
denotes |
V617F |
T6540 |
21210-21211 |
-RRB- |
denotes |
) |
T6541 |
21212-21216 |
IN |
denotes |
from |
T6542 |
21217-21218 |
DT |
denotes |
a |
T6543 |
21243-21251 |
NN |
denotes |
promoter |
T6544 |
21219-21231 |
NN |
denotes |
tetracycline |
T6545 |
21232-21242 |
JJ |
denotes |
responsive |
T6546 |
21231-21232 |
HYPH |
denotes |
- |
T6547 |
21252-21253 |
-LRB- |
denotes |
[ |
T6548 |
21256-21258 |
CD |
denotes |
13 |
T6549 |
21253-21255 |
CD |
denotes |
12 |
T6550 |
21255-21256 |
, |
denotes |
, |
T6551 |
21258-21259 |
-RRB- |
denotes |
] |
T6552 |
21259-21260 |
. |
denotes |
. |
T6553 |
21260-21401 |
sentence |
denotes |
Transgenic APP expression was activated by crossing the APPswe/ind mice to animals producing tTA under control of the CaMKIIα promoter [16]. |
T6554 |
21261-21271 |
JJ |
denotes |
Transgenic |
T6555 |
21272-21275 |
NN |
denotes |
APP |
T6556 |
21276-21286 |
NN |
denotes |
expression |
T6557 |
21291-21300 |
VBN |
denotes |
activated |
T6558 |
21287-21290 |
VBD |
denotes |
was |
T6559 |
21301-21303 |
IN |
denotes |
by |
T6560 |
21304-21312 |
VBG |
denotes |
crossing |
T6561 |
21313-21316 |
DT |
denotes |
the |
T6562 |
21328-21332 |
NNS |
denotes |
mice |
T6563 |
21317-21323 |
NN |
denotes |
APPswe |
T6564 |
21324-21327 |
NN |
denotes |
ind |
T6565 |
21323-21324 |
HYPH |
denotes |
/ |
T6566 |
21333-21335 |
IN |
denotes |
to |
T6567 |
21336-21343 |
NNS |
denotes |
animals |
T6568 |
21344-21353 |
VBG |
denotes |
producing |
T6569 |
21354-21357 |
NN |
denotes |
tTA |
T6570 |
21358-21363 |
IN |
denotes |
under |
T6571 |
21364-21371 |
NN |
denotes |
control |
T6572 |
21372-21374 |
IN |
denotes |
of |
T6573 |
21375-21378 |
DT |
denotes |
the |
T6574 |
21387-21395 |
NN |
denotes |
promoter |
T6575 |
21379-21386 |
NN |
denotes |
CaMKIIα |
T6576 |
21396-21397 |
-LRB- |
denotes |
[ |
T6577 |
21397-21399 |
CD |
denotes |
16 |
T6578 |
21399-21400 |
-RRB- |
denotes |
] |
T6579 |
21400-21401 |
. |
denotes |
. |
T6580 |
21401-21595 |
sentence |
denotes |
After initial screening of founders, we identified four lines of tet-APPswe/ind mice that produced very high levels of transgene product in offspring coexpressing tTA (Figures 1 and Figure S1). |
T6581 |
21402-21407 |
IN |
denotes |
After |
T6582 |
21442-21452 |
VBD |
denotes |
identified |
T6583 |
21408-21415 |
JJ |
denotes |
initial |
T6584 |
21416-21425 |
NN |
denotes |
screening |
T6585 |
21426-21428 |
IN |
denotes |
of |
T6586 |
21429-21437 |
NNS |
denotes |
founders |
T6587 |
21437-21439 |
, |
denotes |
, |
T6588 |
21439-21441 |
PRP |
denotes |
we |
T6589 |
21453-21457 |
CD |
denotes |
four |
T6590 |
21458-21463 |
NNS |
denotes |
lines |
T6591 |
21464-21466 |
IN |
denotes |
of |
T6592 |
21467-21470 |
NN |
denotes |
tet |
T6593 |
21478-21481 |
NN |
denotes |
ind |
T6594 |
21470-21471 |
HYPH |
denotes |
- |
T6595 |
21471-21477 |
NN |
denotes |
APPswe |
T6596 |
21477-21478 |
HYPH |
denotes |
/ |
T6597 |
21482-21486 |
NNS |
denotes |
mice |
T6598 |
21487-21491 |
WDT |
denotes |
that |
T6599 |
21492-21500 |
VBD |
denotes |
produced |
T6600 |
21501-21505 |
RB |
denotes |
very |
T6601 |
21506-21510 |
JJ |
denotes |
high |
T6602 |
21511-21517 |
NNS |
denotes |
levels |
T6603 |
21518-21520 |
IN |
denotes |
of |
T6604 |
21521-21530 |
NN |
denotes |
transgene |
T6605 |
21531-21538 |
NN |
denotes |
product |
T6606 |
21539-21541 |
IN |
denotes |
in |
T6607 |
21542-21551 |
NN |
denotes |
offspring |
T6608 |
21552-21564 |
VBG |
denotes |
coexpressing |
T6609 |
21565-21568 |
NN |
denotes |
tTA |
T6610 |
21569-21570 |
-LRB- |
denotes |
( |
T6611 |
21570-21577 |
NNS |
denotes |
Figures |
T6612 |
21578-21579 |
CD |
denotes |
1 |
T6613 |
21580-21583 |
CC |
denotes |
and |
T6614 |
21584-21590 |
NN |
denotes |
Figure |
T6615 |
21591-21593 |
NN |
denotes |
S1 |
T6616 |
21593-21594 |
-RRB- |
denotes |
) |
T6617 |
21594-21595 |
. |
denotes |
. |
T6618 |
21595-21846 |
sentence |
denotes |
Compared to a standard APP transgenic line used for previous amyloid studies by our laboratory (line C3–3; [15,26,27]), we estimated that the four controllable lines produce transgenic APP protein at 10- to 30-fold over endogenous levels (Figure S1). |
T6619 |
21596-21604 |
VBN |
denotes |
Compared |
T6620 |
21719-21728 |
VBD |
denotes |
estimated |
T6621 |
21605-21607 |
IN |
denotes |
to |
T6622 |
21608-21609 |
DT |
denotes |
a |
T6623 |
21634-21638 |
NN |
denotes |
line |
T6624 |
21610-21618 |
JJ |
denotes |
standard |
T6625 |
21619-21622 |
NN |
denotes |
APP |
T6626 |
21623-21633 |
JJ |
denotes |
transgenic |
T6627 |
21639-21643 |
VBN |
denotes |
used |
T6628 |
21644-21647 |
IN |
denotes |
for |
T6629 |
21648-21656 |
JJ |
denotes |
previous |
T6630 |
21665-21672 |
NNS |
denotes |
studies |
T6631 |
21657-21664 |
NN |
denotes |
amyloid |
T6632 |
21673-21675 |
IN |
denotes |
by |
T6633 |
21676-21679 |
PRP$ |
denotes |
our |
T6634 |
21680-21690 |
NN |
denotes |
laboratory |
T6635 |
21691-21692 |
-LRB- |
denotes |
( |
T6636 |
21710-21712 |
CD |
denotes |
27 |
T6637 |
21692-21696 |
NN |
denotes |
line |
T6638 |
21697-21699 |
NN |
denotes |
C3 |
T6639 |
21699-21700 |
HYPH |
denotes |
– |
T6640 |
21700-21701 |
CD |
denotes |
3 |
T6641 |
21701-21702 |
: |
denotes |
; |
T6642 |
21703-21704 |
-LRB- |
denotes |
[ |
T6643 |
21704-21706 |
CD |
denotes |
15 |
T6644 |
21706-21707 |
, |
denotes |
, |
T6645 |
21707-21709 |
CD |
denotes |
26 |
T6646 |
21709-21710 |
, |
denotes |
, |
T6647 |
21712-21713 |
-RRB- |
denotes |
] |
T6648 |
21713-21714 |
-RRB- |
denotes |
) |
T6649 |
21714-21716 |
, |
denotes |
, |
T6650 |
21716-21718 |
PRP |
denotes |
we |
T6651 |
21729-21733 |
IN |
denotes |
that |
T6652 |
21762-21769 |
VBP |
denotes |
produce |
T6653 |
21734-21737 |
DT |
denotes |
the |
T6654 |
21756-21761 |
NNS |
denotes |
lines |
T6655 |
21738-21742 |
CD |
denotes |
four |
T6656 |
21743-21755 |
JJ |
denotes |
controllable |
T6657 |
21770-21780 |
JJ |
denotes |
transgenic |
T6658 |
21785-21792 |
NN |
denotes |
protein |
T6659 |
21781-21784 |
NN |
denotes |
APP |
T6660 |
21793-21795 |
IN |
denotes |
at |
T6661 |
21796-21798 |
CD |
denotes |
10 |
T6662 |
21798-21799 |
HYPH |
denotes |
- |
T6663 |
21800-21802 |
IN |
denotes |
to |
T6664 |
21803-21810 |
RB |
denotes |
30-fold |
T6665 |
21811-21815 |
IN |
denotes |
over |
T6666 |
21816-21826 |
JJ |
denotes |
endogenous |
T6667 |
21827-21833 |
NNS |
denotes |
levels |
T6668 |
21834-21835 |
-LRB- |
denotes |
( |
T6669 |
21842-21844 |
NN |
denotes |
S1 |
T6670 |
21835-21841 |
NN |
denotes |
Figure |
T6671 |
21844-21845 |
-RRB- |
denotes |
) |
T6672 |
21845-21846 |
. |
denotes |
. |
T6673 |
21846-22107 |
sentence |
denotes |
This estimate was confirmed by direct comparison of APP levels in nontransgenic and tet-off APP mice using an antibody that recognizes both endogenous APP (and amyloid precursor-like protein 2) and the transgenic protein (monoclonal antibody 22C11; Figure 1D). |
T6674 |
21847-21851 |
DT |
denotes |
This |
T6675 |
21852-21860 |
NN |
denotes |
estimate |
T6676 |
21865-21874 |
VBN |
denotes |
confirmed |
T6677 |
21861-21864 |
VBD |
denotes |
was |
T6678 |
21875-21877 |
IN |
denotes |
by |
T6679 |
21878-21884 |
JJ |
denotes |
direct |
T6680 |
21885-21895 |
NN |
denotes |
comparison |
T6681 |
21896-21898 |
IN |
denotes |
of |
T6682 |
21899-21902 |
NN |
denotes |
APP |
T6683 |
21903-21909 |
NNS |
denotes |
levels |
T6684 |
21910-21912 |
IN |
denotes |
in |
T6685 |
21913-21926 |
JJ |
denotes |
nontransgenic |
T6686 |
21943-21947 |
NNS |
denotes |
mice |
T6687 |
21927-21930 |
CC |
denotes |
and |
T6688 |
21931-21934 |
NN |
denotes |
tet |
T6689 |
21935-21938 |
NN |
denotes |
off |
T6690 |
21934-21935 |
HYPH |
denotes |
- |
T6691 |
21939-21942 |
NN |
denotes |
APP |
T6692 |
21948-21953 |
VBG |
denotes |
using |
T6693 |
21954-21956 |
DT |
denotes |
an |
T6694 |
21957-21965 |
NN |
denotes |
antibody |
T6695 |
21966-21970 |
WDT |
denotes |
that |
T6696 |
21971-21981 |
VBZ |
denotes |
recognizes |
T6697 |
21982-21986 |
CC |
denotes |
both |
T6698 |
21998-22001 |
NN |
denotes |
APP |
T6699 |
21987-21997 |
JJ |
denotes |
endogenous |
T6700 |
22002-22003 |
-LRB- |
denotes |
( |
T6701 |
22003-22006 |
CC |
denotes |
and |
T6702 |
22007-22014 |
NN |
denotes |
amyloid |
T6703 |
22030-22037 |
NN |
denotes |
protein |
T6704 |
22015-22024 |
NN |
denotes |
precursor |
T6705 |
22025-22029 |
JJ |
denotes |
like |
T6706 |
22024-22025 |
HYPH |
denotes |
- |
T6707 |
22038-22039 |
CD |
denotes |
2 |
T6708 |
22039-22040 |
-RRB- |
denotes |
) |
T6709 |
22041-22044 |
CC |
denotes |
and |
T6710 |
22045-22048 |
DT |
denotes |
the |
T6711 |
22060-22067 |
NN |
denotes |
protein |
T6712 |
22049-22059 |
JJ |
denotes |
transgenic |
T6713 |
22068-22069 |
-LRB- |
denotes |
( |
T6714 |
22103-22105 |
NN |
denotes |
1D |
T6715 |
22069-22079 |
JJ |
denotes |
monoclonal |
T6716 |
22089-22094 |
NN |
denotes |
22C11 |
T6717 |
22080-22088 |
NN |
denotes |
antibody |
T6718 |
22094-22095 |
: |
denotes |
; |
T6719 |
22096-22102 |
NN |
denotes |
Figure |
T6720 |
22105-22106 |
-RRB- |
denotes |
) |
T6721 |
22106-22107 |
. |
denotes |
. |
T6722 |
22107-23908 |
sentence |
denotes |
Figure 1 Control of Transgenic APP Expression by Dox
(A) Western blotting for transgenic APP using the human-specific 6E10 antibody shows expression of full-length protein in forebrain tissue from young predeposit double transgenic animals (line 107) and its suppression following dox treatment. Untreated animals show high levels of transgene expression; protein levels drop dramatically in animals acutely treated with dox for 2 wk. A faint, but detectable band of full-length protein remains in acutely treated animals that can be eliminated in mice born and raised on dox.
(B) Immunoblotting with the N-terminal antibody 22C11 to detect both transgenic and endogenous protein shows that dox treatment reduces APP/APLP to levels found in nontransgenic mice.
(C) Measurement of signal intensity from the Western blot in (A) shows transgenic APP levels are decreased more than 95% by dox in both acutely and chronically treated animals (97.2% for 4 wk + 2 wk dox, 98.0% for reared on dox versus 4 wk untreated; ANOVA effect of treatment group F 4,15 = 85.55, p < 0.001). APP levels in 4 wk + 2 wk dox, reared on dox, and nontransgenic (NTg) were not significantly different (p > 0.9, Tukey post-hoc test).
(D) Measurement of signal intensity from the Western blot in (B) shows total APP/APLP levels in dox-treated tTA/APP mice are significantly lower than in 4-wk-old untreated mice (ANOVA effect of treatment group F 4,15 = 84.41, p < 0.001) and indistinguishable from those of nontransgenic animals (p > 0.9, Tukey post-hoc test). *, p < 0.001 versus untreated 4-wk-old mice, Tukey post-hoc test applied to significant effect of group ANOVA. Importantly, all four new lines of tet-off APP mice showed nearly complete suppression of the transgene following dox treatment (Figures 1 and Figure S1). |
T6723 |
23754-23765 |
RB |
denotes |
Importantly |
T6724 |
23806-23812 |
VBD |
denotes |
showed |
T6725 |
23765-23767 |
, |
denotes |
, |
T6726 |
23767-23770 |
DT |
denotes |
all |
T6727 |
23780-23785 |
NNS |
denotes |
lines |
T6728 |
23771-23775 |
CD |
denotes |
four |
T6729 |
23776-23779 |
JJ |
denotes |
new |
T6730 |
23786-23788 |
IN |
denotes |
of |
T6731 |
23789-23792 |
NN |
denotes |
tet |
T6732 |
23793-23796 |
NN |
denotes |
off |
T6733 |
23792-23793 |
HYPH |
denotes |
- |
T6734 |
23801-23805 |
NNS |
denotes |
mice |
T6735 |
23797-23800 |
NN |
denotes |
APP |
T6736 |
23813-23819 |
RB |
denotes |
nearly |
T6737 |
23820-23828 |
JJ |
denotes |
complete |
T6738 |
23829-23840 |
NN |
denotes |
suppression |
T6739 |
23841-23843 |
IN |
denotes |
of |
T6740 |
23844-23847 |
DT |
denotes |
the |
T6741 |
23848-23857 |
NN |
denotes |
transgene |
T6742 |
23858-23867 |
VBG |
denotes |
following |
T6743 |
23868-23871 |
NN |
denotes |
dox |
T6744 |
23872-23881 |
NN |
denotes |
treatment |
T6745 |
23882-23883 |
-LRB- |
denotes |
( |
T6746 |
23883-23890 |
NNS |
denotes |
Figures |
T6747 |
23891-23892 |
CD |
denotes |
1 |
T6748 |
23893-23896 |
CC |
denotes |
and |
T6749 |
23897-23903 |
NN |
denotes |
Figure |
T6750 |
23904-23906 |
NN |
denotes |
S1 |
T6751 |
23906-23907 |
-RRB- |
denotes |
) |
T6752 |
23907-23908 |
. |
denotes |
. |
T6753 |
23908-24091 |
sentence |
denotes |
We focused on one of the four lines, line 107, to examine in more detail the time dependence and extent of transgene suppression following either acute or chronic treatment with dox. |
T6754 |
23909-23911 |
PRP |
denotes |
We |
T6755 |
23912-23919 |
VBD |
denotes |
focused |
T6756 |
23920-23922 |
IN |
denotes |
on |
T6757 |
23923-23926 |
CD |
denotes |
one |
T6758 |
23927-23929 |
IN |
denotes |
of |
T6759 |
23930-23933 |
DT |
denotes |
the |
T6760 |
23939-23944 |
NNS |
denotes |
lines |
T6761 |
23934-23938 |
CD |
denotes |
four |
T6762 |
23944-23946 |
, |
denotes |
, |
T6763 |
23946-23950 |
NN |
denotes |
line |
T6764 |
23951-23954 |
CD |
denotes |
107 |
T6765 |
23954-23956 |
, |
denotes |
, |
T6766 |
23956-23958 |
TO |
denotes |
to |
T6767 |
23959-23966 |
VB |
denotes |
examine |
T6768 |
23967-23969 |
IN |
denotes |
in |
T6769 |
23970-23974 |
JJR |
denotes |
more |
T6770 |
23975-23981 |
NN |
denotes |
detail |
T6771 |
23982-23985 |
DT |
denotes |
the |
T6772 |
23991-24001 |
NN |
denotes |
dependence |
T6773 |
23986-23990 |
NN |
denotes |
time |
T6774 |
24002-24005 |
CC |
denotes |
and |
T6775 |
24006-24012 |
NN |
denotes |
extent |
T6776 |
24013-24015 |
IN |
denotes |
of |
T6777 |
24016-24025 |
NN |
denotes |
transgene |
T6778 |
24026-24037 |
NN |
denotes |
suppression |
T6779 |
24038-24047 |
VBG |
denotes |
following |
T6780 |
24048-24054 |
CC |
denotes |
either |
T6781 |
24072-24081 |
NN |
denotes |
treatment |
T6782 |
24055-24060 |
JJ |
denotes |
acute |
T6783 |
24061-24063 |
CC |
denotes |
or |
T6784 |
24064-24071 |
JJ |
denotes |
chronic |
T6785 |
24082-24086 |
IN |
denotes |
with |
T6786 |
24087-24090 |
NN |
denotes |
dox |
T6787 |
24090-24091 |
. |
denotes |
. |
T6788 |
24091-24371 |
sentence |
denotes |
Two dox-treated groups were compared to two untreated groups: one group of mice was born and raised on dox, a second group was treated with dox for 2 wk starting at 1 mo of age (4 wk + 2 wk dox); two untreated groups kept on normal chow were harvested at either 4 or 6 wk of age. |
T6789 |
24092-24095 |
CD |
denotes |
Two |
T6790 |
24108-24114 |
NNS |
denotes |
groups |
T6791 |
24096-24099 |
NN |
denotes |
dox |
T6792 |
24100-24107 |
VBN |
denotes |
treated |
T6793 |
24099-24100 |
HYPH |
denotes |
- |
T6794 |
24120-24128 |
VBN |
denotes |
compared |
T6795 |
24115-24119 |
VBD |
denotes |
were |
T6796 |
24334-24343 |
VBN |
denotes |
harvested |
T6797 |
24129-24131 |
IN |
denotes |
to |
T6798 |
24132-24135 |
CD |
denotes |
two |
T6799 |
24146-24152 |
NNS |
denotes |
groups |
T6800 |
24136-24145 |
JJ |
denotes |
untreated |
T6801 |
24152-24154 |
: |
denotes |
: |
T6802 |
24154-24157 |
CD |
denotes |
one |
T6803 |
24158-24163 |
NN |
denotes |
group |
T6804 |
24176-24180 |
VBN |
denotes |
born |
T6805 |
24164-24166 |
IN |
denotes |
of |
T6806 |
24167-24171 |
NNS |
denotes |
mice |
T6807 |
24172-24175 |
VBD |
denotes |
was |
T6808 |
24181-24184 |
CC |
denotes |
and |
T6809 |
24185-24191 |
VBN |
denotes |
raised |
T6810 |
24192-24194 |
IN |
denotes |
on |
T6811 |
24195-24198 |
NN |
denotes |
dox |
T6812 |
24198-24200 |
, |
denotes |
, |
T6813 |
24200-24201 |
DT |
denotes |
a |
T6814 |
24209-24214 |
NN |
denotes |
group |
T6815 |
24202-24208 |
JJ |
denotes |
second |
T6816 |
24219-24226 |
VBN |
denotes |
treated |
T6817 |
24215-24218 |
VBD |
denotes |
was |
T6818 |
24227-24231 |
IN |
denotes |
with |
T6819 |
24232-24235 |
NN |
denotes |
dox |
T6820 |
24236-24239 |
IN |
denotes |
for |
T6821 |
24240-24241 |
CD |
denotes |
2 |
T6822 |
24242-24244 |
NN |
denotes |
wk |
T6823 |
24245-24253 |
VBG |
denotes |
starting |
T6824 |
24254-24256 |
IN |
denotes |
at |
T6825 |
24257-24258 |
CD |
denotes |
1 |
T6826 |
24259-24261 |
NN |
denotes |
mo |
T6827 |
24262-24264 |
IN |
denotes |
of |
T6828 |
24265-24268 |
NN |
denotes |
age |
T6829 |
24269-24270 |
-LRB- |
denotes |
( |
T6830 |
24272-24274 |
NN |
denotes |
wk |
T6831 |
24270-24271 |
CD |
denotes |
4 |
T6832 |
24275-24276 |
SYM |
denotes |
+ |
T6833 |
24277-24278 |
CD |
denotes |
2 |
T6834 |
24279-24281 |
NN |
denotes |
wk |
T6835 |
24282-24285 |
NN |
denotes |
dox |
T6836 |
24285-24286 |
-RRB- |
denotes |
) |
T6837 |
24286-24287 |
: |
denotes |
; |
T6838 |
24288-24291 |
CD |
denotes |
two |
T6839 |
24302-24308 |
NNS |
denotes |
groups |
T6840 |
24292-24301 |
JJ |
denotes |
untreated |
T6841 |
24309-24313 |
VBN |
denotes |
kept |
T6842 |
24314-24316 |
IN |
denotes |
on |
T6843 |
24317-24323 |
JJ |
denotes |
normal |
T6844 |
24324-24328 |
NN |
denotes |
chow |
T6845 |
24329-24333 |
VBD |
denotes |
were |
T6846 |
24344-24346 |
IN |
denotes |
at |
T6847 |
24347-24353 |
CC |
denotes |
either |
T6848 |
24354-24355 |
CD |
denotes |
4 |
T6849 |
24361-24363 |
NN |
denotes |
wk |
T6850 |
24356-24358 |
CC |
denotes |
or |
T6851 |
24359-24360 |
CD |
denotes |
6 |
T6852 |
24364-24366 |
IN |
denotes |
of |
T6853 |
24367-24370 |
NN |
denotes |
age |
T6854 |
24370-24371 |
. |
denotes |
. |
T6855 |
24371-24442 |
sentence |
denotes |
Animals born and raised on dox harbored no transgenic APP (Figure 1A). |
T6856 |
24372-24379 |
NNS |
denotes |
Animals |
T6857 |
24403-24411 |
VBD |
denotes |
harbored |
T6858 |
24380-24384 |
VBN |
denotes |
born |
T6859 |
24385-24388 |
CC |
denotes |
and |
T6860 |
24389-24395 |
VBN |
denotes |
raised |
T6861 |
24396-24398 |
IN |
denotes |
on |
T6862 |
24399-24402 |
NN |
denotes |
dox |
T6863 |
24412-24414 |
DT |
denotes |
no |
T6864 |
24426-24429 |
NN |
denotes |
APP |
T6865 |
24415-24425 |
JJ |
denotes |
transgenic |
T6866 |
24430-24431 |
-LRB- |
denotes |
( |
T6867 |
24438-24440 |
NN |
denotes |
1A |
T6868 |
24431-24437 |
NN |
denotes |
Figure |
T6869 |
24440-24441 |
-RRB- |
denotes |
) |
T6870 |
24441-24442 |
. |
denotes |
. |
T6871 |
24442-24571 |
sentence |
denotes |
Following as little as 2 wk of dox treatment, transgenic APP expression was reduced by more than 95% compared to pre-dox levels. |
T6872 |
24443-24452 |
VBG |
denotes |
Following |
T6873 |
24519-24526 |
VBN |
denotes |
reduced |
T6874 |
24453-24455 |
RB |
denotes |
as |
T6875 |
24466-24467 |
CD |
denotes |
2 |
T6876 |
24456-24462 |
JJ |
denotes |
little |
T6877 |
24463-24465 |
IN |
denotes |
as |
T6878 |
24468-24470 |
NN |
denotes |
wk |
T6879 |
24471-24473 |
IN |
denotes |
of |
T6880 |
24474-24477 |
NN |
denotes |
dox |
T6881 |
24478-24487 |
NN |
denotes |
treatment |
T6882 |
24487-24489 |
, |
denotes |
, |
T6883 |
24489-24499 |
JJ |
denotes |
transgenic |
T6884 |
24504-24514 |
NN |
denotes |
expression |
T6885 |
24500-24503 |
NN |
denotes |
APP |
T6886 |
24515-24518 |
VBD |
denotes |
was |
T6887 |
24527-24529 |
IN |
denotes |
by |
T6888 |
24530-24534 |
JJR |
denotes |
more |
T6889 |
24540-24542 |
CD |
denotes |
95 |
T6890 |
24535-24539 |
IN |
denotes |
than |
T6891 |
24542-24543 |
NN |
denotes |
% |
T6892 |
24544-24552 |
VBN |
denotes |
compared |
T6893 |
24553-24555 |
IN |
denotes |
to |
T6894 |
24556-24563 |
JJ |
denotes |
pre-dox |
T6895 |
24564-24570 |
NNS |
denotes |
levels |
T6896 |
24570-24571 |
. |
denotes |
. |
T6897 |
24571-24810 |
sentence |
denotes |
The residual expression remaining in acutely treated mice represents less than 4% of the transgenic protein produced in the absence of dox (Figure 1C), and likely results from slight leakage at the level of transcription (data not shown). |
T6898 |
24572-24575 |
DT |
denotes |
The |
T6899 |
24585-24595 |
NN |
denotes |
expression |
T6900 |
24576-24584 |
JJ |
denotes |
residual |
T6901 |
24630-24640 |
VBZ |
denotes |
represents |
T6902 |
24596-24605 |
VBG |
denotes |
remaining |
T6903 |
24606-24608 |
IN |
denotes |
in |
T6904 |
24609-24616 |
RB |
denotes |
acutely |
T6905 |
24617-24624 |
VBN |
denotes |
treated |
T6906 |
24625-24629 |
NNS |
denotes |
mice |
T6907 |
24641-24645 |
JJR |
denotes |
less |
T6908 |
24651-24652 |
CD |
denotes |
4 |
T6909 |
24646-24650 |
IN |
denotes |
than |
T6910 |
24652-24653 |
NN |
denotes |
% |
T6911 |
24654-24656 |
IN |
denotes |
of |
T6912 |
24657-24660 |
DT |
denotes |
the |
T6913 |
24672-24679 |
NN |
denotes |
protein |
T6914 |
24661-24671 |
JJ |
denotes |
transgenic |
T6915 |
24680-24688 |
VBN |
denotes |
produced |
T6916 |
24689-24691 |
IN |
denotes |
in |
T6917 |
24692-24695 |
DT |
denotes |
the |
T6918 |
24696-24703 |
NN |
denotes |
absence |
T6919 |
24704-24706 |
IN |
denotes |
of |
T6920 |
24707-24710 |
NN |
denotes |
dox |
T6921 |
24711-24712 |
-LRB- |
denotes |
( |
T6922 |
24719-24721 |
NN |
denotes |
1C |
T6923 |
24712-24718 |
NN |
denotes |
Figure |
T6924 |
24721-24722 |
-RRB- |
denotes |
) |
T6925 |
24722-24724 |
, |
denotes |
, |
T6926 |
24724-24727 |
CC |
denotes |
and |
T6927 |
24728-24734 |
RB |
denotes |
likely |
T6928 |
24735-24742 |
VBZ |
denotes |
results |
T6929 |
24743-24747 |
IN |
denotes |
from |
T6930 |
24748-24754 |
JJ |
denotes |
slight |
T6931 |
24755-24762 |
NN |
denotes |
leakage |
T6932 |
24763-24765 |
IN |
denotes |
at |
T6933 |
24766-24769 |
DT |
denotes |
the |
T6934 |
24770-24775 |
NN |
denotes |
level |
T6935 |
24776-24778 |
IN |
denotes |
of |
T6936 |
24779-24792 |
NN |
denotes |
transcription |
T6937 |
24793-24794 |
-LRB- |
denotes |
( |
T6938 |
24803-24808 |
VBN |
denotes |
shown |
T6939 |
24794-24798 |
NNS |
denotes |
data |
T6940 |
24799-24802 |
RB |
denotes |
not |
T6941 |
24808-24809 |
-RRB- |
denotes |
) |
T6942 |
24809-24810 |
. |
denotes |
. |
T6943 |
24810-25129 |
sentence |
denotes |
Importantly, the total amount of APP (endogenous plus transgenic) and related APLPs in both acute and chronically treated animals was statistically indistinguishable from that in nontransgenic mice (Figure 1D; statistical analyses for experiments throughout the study are presented in the accompanying figure legends). |
T6944 |
24811-24822 |
RB |
denotes |
Importantly |
T6945 |
24941-24944 |
VBD |
denotes |
was |
T6946 |
24822-24824 |
, |
denotes |
, |
T6947 |
24824-24827 |
DT |
denotes |
the |
T6948 |
24834-24840 |
NN |
denotes |
amount |
T6949 |
24828-24833 |
JJ |
denotes |
total |
T6950 |
24841-24843 |
IN |
denotes |
of |
T6951 |
24844-24847 |
NN |
denotes |
APP |
T6952 |
24848-24849 |
-LRB- |
denotes |
( |
T6953 |
24849-24859 |
JJ |
denotes |
endogenous |
T6954 |
24860-24864 |
CC |
denotes |
plus |
T6955 |
24865-24875 |
JJ |
denotes |
transgenic |
T6956 |
24875-24876 |
-RRB- |
denotes |
) |
T6957 |
24877-24880 |
CC |
denotes |
and |
T6958 |
24881-24888 |
JJ |
denotes |
related |
T6959 |
24889-24894 |
NNS |
denotes |
APLPs |
T6960 |
24895-24897 |
IN |
denotes |
in |
T6961 |
24898-24902 |
CC |
denotes |
both |
T6962 |
24903-24908 |
JJ |
denotes |
acute |
T6963 |
24933-24940 |
NNS |
denotes |
animals |
T6964 |
24909-24912 |
CC |
denotes |
and |
T6965 |
24913-24924 |
RB |
denotes |
chronically |
T6966 |
24925-24932 |
VBN |
denotes |
treated |
T6967 |
24945-24958 |
RB |
denotes |
statistically |
T6968 |
24959-24976 |
JJ |
denotes |
indistinguishable |
T6969 |
24977-24981 |
IN |
denotes |
from |
T6970 |
24982-24986 |
DT |
denotes |
that |
T6971 |
24987-24989 |
IN |
denotes |
in |
T6972 |
24990-25003 |
JJ |
denotes |
nontransgenic |
T6973 |
25004-25008 |
NNS |
denotes |
mice |
T6974 |
25009-25010 |
-LRB- |
denotes |
( |
T6975 |
25017-25019 |
NN |
denotes |
1D |
T6976 |
25010-25016 |
NN |
denotes |
Figure |
T6977 |
25019-25020 |
: |
denotes |
; |
T6978 |
25021-25032 |
JJ |
denotes |
statistical |
T6979 |
25033-25041 |
NNS |
denotes |
analyses |
T6980 |
25083-25092 |
VBN |
denotes |
presented |
T6981 |
25042-25045 |
IN |
denotes |
for |
T6982 |
25046-25057 |
NNS |
denotes |
experiments |
T6983 |
25058-25068 |
IN |
denotes |
throughout |
T6984 |
25069-25072 |
DT |
denotes |
the |
T6985 |
25073-25078 |
NN |
denotes |
study |
T6986 |
25079-25082 |
VBP |
denotes |
are |
T6987 |
25093-25095 |
IN |
denotes |
in |
T6988 |
25096-25099 |
DT |
denotes |
the |
T6989 |
25120-25127 |
NNS |
denotes |
legends |
T6990 |
25100-25112 |
VBG |
denotes |
accompanying |
T6991 |
25113-25119 |
NN |
denotes |
figure |
T6992 |
25127-25128 |
-RRB- |
denotes |
) |
T6993 |
25128-25129 |
. |
denotes |
. |
T6994 |
25129-25341 |
sentence |
denotes |
To ensure that Aβ production was suppressed in concert with the dox-mediated inhibition of its precursor APPswe/ind, we measured Aβ40 and Aβ42 levels by ELISA in forebrain homogenates from young tet-off animals. |
T6995 |
25130-25132 |
TO |
denotes |
To |
T6996 |
25133-25139 |
VB |
denotes |
ensure |
T6997 |
25250-25258 |
VBD |
denotes |
measured |
T6998 |
25140-25144 |
IN |
denotes |
that |
T6999 |
25163-25173 |
VBN |
denotes |
suppressed |
T7000 |
25145-25147 |
NN |
denotes |
Aβ |
T7001 |
25148-25158 |
NN |
denotes |
production |
T7002 |
25159-25162 |
VBD |
denotes |
was |
T7003 |
25174-25176 |
IN |
denotes |
in |
T7004 |
25177-25184 |
NN |
denotes |
concert |
T7005 |
25185-25189 |
IN |
denotes |
with |
T7006 |
25190-25193 |
DT |
denotes |
the |
T7007 |
25207-25217 |
NN |
denotes |
inhibition |
T7008 |
25194-25197 |
NN |
denotes |
dox |
T7009 |
25198-25206 |
VBN |
denotes |
mediated |
T7010 |
25197-25198 |
HYPH |
denotes |
- |
T7011 |
25218-25220 |
IN |
denotes |
of |
T7012 |
25221-25224 |
PRP$ |
denotes |
its |
T7013 |
25225-25234 |
NN |
denotes |
precursor |
T7014 |
25235-25241 |
NN |
denotes |
APPswe |
T7015 |
25242-25245 |
NN |
denotes |
ind |
T7016 |
25241-25242 |
HYPH |
denotes |
/ |
T7017 |
25245-25247 |
, |
denotes |
, |
T7018 |
25247-25249 |
PRP |
denotes |
we |
T7019 |
25259-25263 |
NN |
denotes |
Aβ40 |
T7020 |
25273-25279 |
NNS |
denotes |
levels |
T7021 |
25264-25267 |
CC |
denotes |
and |
T7022 |
25268-25272 |
NN |
denotes |
Aβ42 |
T7023 |
25280-25282 |
IN |
denotes |
by |
T7024 |
25283-25288 |
NN |
denotes |
ELISA |
T7025 |
25289-25291 |
IN |
denotes |
in |
T7026 |
25292-25301 |
NN |
denotes |
forebrain |
T7027 |
25302-25313 |
NNS |
denotes |
homogenates |
T7028 |
25314-25318 |
IN |
denotes |
from |
T7029 |
25319-25324 |
JJ |
denotes |
young |
T7030 |
25333-25340 |
NNS |
denotes |
animals |
T7031 |
25325-25328 |
NN |
denotes |
tet |
T7032 |
25329-25332 |
NN |
denotes |
off |
T7033 |
25328-25329 |
HYPH |
denotes |
- |
T7034 |
25340-25341 |
. |
denotes |
. |
T7035 |
25341-25518 |
sentence |
denotes |
At 1 mo of age, the mice lacked visible amyloid aggregates that might act as an intractable reservoir of peptide remaining in the brain after the transgene had been suppressed. |
T7036 |
25342-25344 |
IN |
denotes |
At |
T7037 |
25367-25373 |
VBD |
denotes |
lacked |
T7038 |
25345-25346 |
CD |
denotes |
1 |
T7039 |
25347-25349 |
NN |
denotes |
mo |
T7040 |
25350-25352 |
IN |
denotes |
of |
T7041 |
25353-25356 |
NN |
denotes |
age |
T7042 |
25356-25358 |
, |
denotes |
, |
T7043 |
25358-25361 |
DT |
denotes |
the |
T7044 |
25362-25366 |
NNS |
denotes |
mice |
T7045 |
25374-25381 |
JJ |
denotes |
visible |
T7046 |
25390-25400 |
NNS |
denotes |
aggregates |
T7047 |
25382-25389 |
NN |
denotes |
amyloid |
T7048 |
25401-25405 |
WDT |
denotes |
that |
T7049 |
25412-25415 |
VB |
denotes |
act |
T7050 |
25406-25411 |
MD |
denotes |
might |
T7051 |
25416-25418 |
IN |
denotes |
as |
T7052 |
25419-25421 |
DT |
denotes |
an |
T7053 |
25434-25443 |
NN |
denotes |
reservoir |
T7054 |
25422-25433 |
JJ |
denotes |
intractable |
T7055 |
25444-25446 |
IN |
denotes |
of |
T7056 |
25447-25454 |
NN |
denotes |
peptide |
T7057 |
25455-25464 |
VBG |
denotes |
remaining |
T7058 |
25465-25467 |
IN |
denotes |
in |
T7059 |
25468-25471 |
DT |
denotes |
the |
T7060 |
25472-25477 |
NN |
denotes |
brain |
T7061 |
25478-25483 |
IN |
denotes |
after |
T7062 |
25507-25517 |
VBN |
denotes |
suppressed |
T7063 |
25484-25487 |
DT |
denotes |
the |
T7064 |
25488-25497 |
NN |
denotes |
transgene |
T7065 |
25498-25501 |
VBD |
denotes |
had |
T7066 |
25502-25506 |
VBN |
denotes |
been |
T7067 |
25517-25518 |
. |
denotes |
. |
T7068 |
25518-25764 |
sentence |
denotes |
To further ensure we could detect any such insoluble aggregates that might bias our measure of changes in peptide synthesis, we performed a sequential three-step extraction with PBS, 2% SDS, and 70% FA that would separate peptides by solubility. |
T7069 |
25519-25521 |
TO |
denotes |
To |
T7070 |
25530-25536 |
VB |
denotes |
ensure |
T7071 |
25522-25529 |
RB |
denotes |
further |
T7072 |
25647-25656 |
VBD |
denotes |
performed |
T7073 |
25537-25539 |
PRP |
denotes |
we |
T7074 |
25546-25552 |
VB |
denotes |
detect |
T7075 |
25540-25545 |
MD |
denotes |
could |
T7076 |
25553-25556 |
DT |
denotes |
any |
T7077 |
25572-25582 |
NNS |
denotes |
aggregates |
T7078 |
25557-25561 |
JJ |
denotes |
such |
T7079 |
25562-25571 |
JJ |
denotes |
insoluble |
T7080 |
25583-25587 |
WDT |
denotes |
that |
T7081 |
25594-25598 |
VB |
denotes |
bias |
T7082 |
25588-25593 |
MD |
denotes |
might |
T7083 |
25599-25602 |
PRP$ |
denotes |
our |
T7084 |
25603-25610 |
NN |
denotes |
measure |
T7085 |
25611-25613 |
IN |
denotes |
of |
T7086 |
25614-25621 |
NNS |
denotes |
changes |
T7087 |
25622-25624 |
IN |
denotes |
in |
T7088 |
25625-25632 |
NN |
denotes |
peptide |
T7089 |
25633-25642 |
NN |
denotes |
synthesis |
T7090 |
25642-25644 |
, |
denotes |
, |
T7091 |
25644-25646 |
PRP |
denotes |
we |
T7092 |
25657-25658 |
DT |
denotes |
a |
T7093 |
25681-25691 |
NN |
denotes |
extraction |
T7094 |
25659-25669 |
JJ |
denotes |
sequential |
T7095 |
25670-25675 |
CD |
denotes |
three |
T7096 |
25676-25680 |
NN |
denotes |
step |
T7097 |
25675-25676 |
HYPH |
denotes |
- |
T7098 |
25692-25696 |
IN |
denotes |
with |
T7099 |
25697-25700 |
NN |
denotes |
PBS |
T7100 |
25700-25702 |
, |
denotes |
, |
T7101 |
25702-25703 |
CD |
denotes |
2 |
T7102 |
25703-25704 |
NN |
denotes |
% |
T7103 |
25705-25708 |
NN |
denotes |
SDS |
T7104 |
25708-25710 |
, |
denotes |
, |
T7105 |
25710-25713 |
CC |
denotes |
and |
T7106 |
25714-25716 |
CD |
denotes |
70 |
T7107 |
25716-25717 |
NN |
denotes |
% |
T7108 |
25718-25720 |
NN |
denotes |
FA |
T7109 |
25721-25725 |
WDT |
denotes |
that |
T7110 |
25732-25740 |
VB |
denotes |
separate |
T7111 |
25726-25731 |
MD |
denotes |
would |
T7112 |
25741-25749 |
NNS |
denotes |
peptides |
T7113 |
25750-25752 |
IN |
denotes |
by |
T7114 |
25753-25763 |
NN |
denotes |
solubility |
T7115 |
25763-25764 |
. |
denotes |
. |
T7116 |
25764-26107 |
sentence |
denotes |
We compared the levels of human transgene-derived Aβ40 and Aβ42 in untreated mice at 4 and 6 wk of age to animals that had either been born and raised on dox or that had been left untreated for 4 wk and then placed on dox chow for 2 wk prior to harvest (the same groups described above for immunoblot analysis of APPswe/ind levels, line 107). |
T7117 |
25765-25767 |
PRP |
denotes |
We |
T7118 |
25768-25776 |
VBD |
denotes |
compared |
T7119 |
25777-25780 |
DT |
denotes |
the |
T7120 |
25781-25787 |
NNS |
denotes |
levels |
T7121 |
25788-25790 |
IN |
denotes |
of |
T7122 |
25791-25796 |
JJ |
denotes |
human |
T7123 |
25797-25806 |
NN |
denotes |
transgene |
T7124 |
25807-25814 |
VBN |
denotes |
derived |
T7125 |
25806-25807 |
HYPH |
denotes |
- |
T7126 |
25815-25819 |
NN |
denotes |
Aβ40 |
T7127 |
25820-25823 |
CC |
denotes |
and |
T7128 |
25824-25828 |
NN |
denotes |
Aβ42 |
T7129 |
25829-25831 |
IN |
denotes |
in |
T7130 |
25832-25841 |
JJ |
denotes |
untreated |
T7131 |
25842-25846 |
NNS |
denotes |
mice |
T7132 |
25847-25849 |
IN |
denotes |
at |
T7133 |
25850-25851 |
CD |
denotes |
4 |
T7134 |
25858-25860 |
NN |
denotes |
wk |
T7135 |
25852-25855 |
CC |
denotes |
and |
T7136 |
25856-25857 |
CD |
denotes |
6 |
T7137 |
25861-25863 |
IN |
denotes |
of |
T7138 |
25864-25867 |
NN |
denotes |
age |
T7139 |
25868-25870 |
IN |
denotes |
to |
T7140 |
25871-25878 |
NNS |
denotes |
animals |
T7141 |
25879-25883 |
WDT |
denotes |
that |
T7142 |
25900-25904 |
VBN |
denotes |
born |
T7143 |
25884-25887 |
VBD |
denotes |
had |
T7144 |
25888-25894 |
CC |
denotes |
either |
T7145 |
25895-25899 |
VBN |
denotes |
been |
T7146 |
25905-25908 |
CC |
denotes |
and |
T7147 |
25909-25915 |
VBN |
denotes |
raised |
T7148 |
25916-25918 |
IN |
denotes |
on |
T7149 |
25919-25922 |
NN |
denotes |
dox |
T7150 |
25923-25925 |
CC |
denotes |
or |
T7151 |
25926-25930 |
WDT |
denotes |
that |
T7152 |
25940-25944 |
VBN |
denotes |
left |
T7153 |
25931-25934 |
VBD |
denotes |
had |
T7154 |
25935-25939 |
VBN |
denotes |
been |
T7155 |
25945-25954 |
JJ |
denotes |
untreated |
T7156 |
25955-25958 |
IN |
denotes |
for |
T7157 |
25959-25960 |
CD |
denotes |
4 |
T7158 |
25961-25963 |
NN |
denotes |
wk |
T7159 |
25964-25967 |
CC |
denotes |
and |
T7160 |
25968-25972 |
RB |
denotes |
then |
T7161 |
25973-25979 |
VBN |
denotes |
placed |
T7162 |
25980-25982 |
IN |
denotes |
on |
T7163 |
25983-25986 |
NN |
denotes |
dox |
T7164 |
25987-25991 |
NN |
denotes |
chow |
T7165 |
25992-25995 |
IN |
denotes |
for |
T7166 |
25996-25997 |
CD |
denotes |
2 |
T7167 |
25998-26000 |
NN |
denotes |
wk |
T7168 |
26001-26006 |
JJ |
denotes |
prior |
T7169 |
26007-26009 |
IN |
denotes |
to |
T7170 |
26010-26017 |
NN |
denotes |
harvest |
T7171 |
26018-26019 |
-LRB- |
denotes |
( |
T7172 |
26097-26101 |
NN |
denotes |
line |
T7173 |
26019-26022 |
DT |
denotes |
the |
T7174 |
26028-26034 |
NNS |
denotes |
groups |
T7175 |
26023-26027 |
JJ |
denotes |
same |
T7176 |
26035-26044 |
VBN |
denotes |
described |
T7177 |
26045-26050 |
RB |
denotes |
above |
T7178 |
26051-26054 |
IN |
denotes |
for |
T7179 |
26055-26065 |
NN |
denotes |
immunoblot |
T7180 |
26066-26074 |
NN |
denotes |
analysis |
T7181 |
26075-26077 |
IN |
denotes |
of |
T7182 |
26078-26084 |
NN |
denotes |
APPswe |
T7183 |
26085-26088 |
NN |
denotes |
ind |
T7184 |
26084-26085 |
HYPH |
denotes |
/ |
T7185 |
26089-26095 |
NNS |
denotes |
levels |
T7186 |
26095-26097 |
, |
denotes |
, |
T7187 |
26102-26105 |
CD |
denotes |
107 |
T7188 |
26105-26106 |
-RRB- |
denotes |
) |
T7189 |
26106-26107 |
. |
denotes |
. |
T7190 |
26107-26383 |
sentence |
denotes |
Consistent with the reduction in full-length APPswe/ind synthesis shown by immunoblot (see Figure 1), we found that transgene-derived Aβ levels were completely suppressed in animals born and raised on dox, and were sharply reduced following acute (2 wk) antibiotic treatment. |
T7191 |
26108-26118 |
JJ |
denotes |
Consistent |
T7192 |
26213-26218 |
VBD |
denotes |
found |
T7193 |
26119-26123 |
IN |
denotes |
with |
T7194 |
26124-26127 |
DT |
denotes |
the |
T7195 |
26128-26137 |
NN |
denotes |
reduction |
T7196 |
26138-26140 |
IN |
denotes |
in |
T7197 |
26141-26145 |
JJ |
denotes |
full |
T7198 |
26146-26152 |
NN |
denotes |
length |
T7199 |
26145-26146 |
HYPH |
denotes |
- |
T7200 |
26164-26173 |
NN |
denotes |
synthesis |
T7201 |
26153-26159 |
NN |
denotes |
APPswe |
T7202 |
26160-26163 |
NN |
denotes |
ind |
T7203 |
26159-26160 |
HYPH |
denotes |
/ |
T7204 |
26174-26179 |
VBN |
denotes |
shown |
T7205 |
26180-26182 |
IN |
denotes |
by |
T7206 |
26183-26193 |
NN |
denotes |
immunoblot |
T7207 |
26194-26195 |
-LRB- |
denotes |
( |
T7208 |
26195-26198 |
VB |
denotes |
see |
T7209 |
26199-26205 |
NN |
denotes |
Figure |
T7210 |
26206-26207 |
CD |
denotes |
1 |
T7211 |
26207-26208 |
-RRB- |
denotes |
) |
T7212 |
26208-26210 |
, |
denotes |
, |
T7213 |
26210-26212 |
PRP |
denotes |
we |
T7214 |
26219-26223 |
IN |
denotes |
that |
T7215 |
26268-26278 |
VBN |
denotes |
suppressed |
T7216 |
26224-26233 |
NN |
denotes |
transgene |
T7217 |
26234-26241 |
VBN |
denotes |
derived |
T7218 |
26233-26234 |
HYPH |
denotes |
- |
T7219 |
26245-26251 |
NNS |
denotes |
levels |
T7220 |
26242-26244 |
NN |
denotes |
Aβ |
T7221 |
26252-26256 |
VBD |
denotes |
were |
T7222 |
26257-26267 |
RB |
denotes |
completely |
T7223 |
26279-26281 |
IN |
denotes |
in |
T7224 |
26282-26289 |
NNS |
denotes |
animals |
T7225 |
26290-26294 |
VBN |
denotes |
born |
T7226 |
26295-26298 |
CC |
denotes |
and |
T7227 |
26299-26305 |
VBN |
denotes |
raised |
T7228 |
26306-26308 |
IN |
denotes |
on |
T7229 |
26309-26312 |
NN |
denotes |
dox |
T7230 |
26312-26314 |
, |
denotes |
, |
T7231 |
26314-26317 |
CC |
denotes |
and |
T7232 |
26318-26322 |
VBD |
denotes |
were |
T7233 |
26331-26338 |
VBN |
denotes |
reduced |
T7234 |
26323-26330 |
RB |
denotes |
sharply |
T7235 |
26339-26348 |
VBG |
denotes |
following |
T7236 |
26349-26354 |
JJ |
denotes |
acute |
T7237 |
26373-26382 |
NN |
denotes |
treatment |
T7238 |
26355-26356 |
-LRB- |
denotes |
( |
T7239 |
26358-26360 |
NN |
denotes |
wk |
T7240 |
26356-26357 |
CD |
denotes |
2 |
T7241 |
26360-26361 |
-RRB- |
denotes |
) |
T7242 |
26362-26372 |
JJ |
denotes |
antibiotic |
T7243 |
26382-26383 |
. |
denotes |
. |
T7244 |
26383-26549 |
sentence |
denotes |
Compared to the levels in untreated 4-wk-old mice, PBS-soluble Aβ42 dropped by 95.2% following 2 wk of dox treatment and by 99.2% with chronic treatment (Figure 2A). |
T7245 |
26384-26392 |
VBN |
denotes |
Compared |
T7246 |
26452-26459 |
VBD |
denotes |
dropped |
T7247 |
26393-26395 |
IN |
denotes |
to |
T7248 |
26396-26399 |
DT |
denotes |
the |
T7249 |
26400-26406 |
NNS |
denotes |
levels |
T7250 |
26407-26409 |
IN |
denotes |
in |
T7251 |
26410-26419 |
JJ |
denotes |
untreated |
T7252 |
26429-26433 |
NNS |
denotes |
mice |
T7253 |
26420-26421 |
CD |
denotes |
4 |
T7254 |
26422-26424 |
NN |
denotes |
wk |
T7255 |
26421-26422 |
HYPH |
denotes |
- |
T7256 |
26425-26428 |
JJ |
denotes |
old |
T7257 |
26424-26425 |
HYPH |
denotes |
- |
T7258 |
26433-26435 |
, |
denotes |
, |
T7259 |
26435-26438 |
NN |
denotes |
PBS |
T7260 |
26439-26446 |
JJ |
denotes |
soluble |
T7261 |
26438-26439 |
HYPH |
denotes |
- |
T7262 |
26447-26451 |
NN |
denotes |
Aβ42 |
T7263 |
26460-26462 |
IN |
denotes |
by |
T7264 |
26463-26467 |
CD |
denotes |
95.2 |
T7265 |
26467-26468 |
NN |
denotes |
% |
T7266 |
26469-26478 |
VBG |
denotes |
following |
T7267 |
26479-26480 |
CD |
denotes |
2 |
T7268 |
26481-26483 |
NN |
denotes |
wk |
T7269 |
26484-26486 |
IN |
denotes |
of |
T7270 |
26487-26490 |
NN |
denotes |
dox |
T7271 |
26491-26500 |
NN |
denotes |
treatment |
T7272 |
26501-26504 |
CC |
denotes |
and |
T7273 |
26505-26507 |
IN |
denotes |
by |
T7274 |
26514-26518 |
IN |
denotes |
with |
T7275 |
26508-26512 |
CD |
denotes |
99.2 |
T7276 |
26512-26513 |
NN |
denotes |
% |
T7277 |
26519-26526 |
JJ |
denotes |
chronic |
T7278 |
26527-26536 |
NN |
denotes |
treatment |
T7279 |
26537-26538 |
-LRB- |
denotes |
( |
T7280 |
26545-26547 |
NN |
denotes |
2A |
T7281 |
26538-26544 |
NN |
denotes |
Figure |
T7282 |
26547-26548 |
-RRB- |
denotes |
) |
T7283 |
26548-26549 |
. |
denotes |
. |
T7284 |
26549-26660 |
sentence |
denotes |
Similarly, SDS-soluble Aβ42 decreased by 75.2% and 94.8% following 2-wk or lifelong dox treatment (Figure 2B). |
T7285 |
26550-26559 |
RB |
denotes |
Similarly |
T7286 |
26578-26587 |
VBD |
denotes |
decreased |
T7287 |
26559-26561 |
, |
denotes |
, |
T7288 |
26561-26564 |
NN |
denotes |
SDS |
T7289 |
26565-26572 |
JJ |
denotes |
soluble |
T7290 |
26564-26565 |
HYPH |
denotes |
- |
T7291 |
26573-26577 |
NN |
denotes |
Aβ42 |
T7292 |
26588-26590 |
IN |
denotes |
by |
T7293 |
26591-26595 |
CD |
denotes |
75.2 |
T7294 |
26595-26596 |
NN |
denotes |
% |
T7295 |
26597-26600 |
CC |
denotes |
and |
T7296 |
26601-26605 |
CD |
denotes |
94.8 |
T7297 |
26605-26606 |
NN |
denotes |
% |
T7298 |
26607-26616 |
VBG |
denotes |
following |
T7299 |
26617-26618 |
CD |
denotes |
2 |
T7300 |
26619-26621 |
NN |
denotes |
wk |
T7301 |
26618-26619 |
HYPH |
denotes |
- |
T7302 |
26638-26647 |
NN |
denotes |
treatment |
T7303 |
26622-26624 |
CC |
denotes |
or |
T7304 |
26625-26633 |
JJ |
denotes |
lifelong |
T7305 |
26634-26637 |
NN |
denotes |
dox |
T7306 |
26648-26649 |
-LRB- |
denotes |
( |
T7307 |
26656-26658 |
NN |
denotes |
2B |
T7308 |
26649-26655 |
NN |
denotes |
Figure |
T7309 |
26658-26659 |
-RRB- |
denotes |
) |
T7310 |
26659-26660 |
. |
denotes |
. |
T7311 |
26660-26894 |
sentence |
denotes |
Only the FA fraction revealed a small dox-resistant pool of peptide in acutely treated animals that we believe represents stable predeposit aggregates that have already accumulated by 4 wk of age when treatment was begun (Figure 2C). |
T7312 |
26661-26665 |
RB |
denotes |
Only |
T7313 |
26673-26681 |
NN |
denotes |
fraction |
T7314 |
26666-26669 |
DT |
denotes |
the |
T7315 |
26670-26672 |
NN |
denotes |
FA |
T7316 |
26682-26690 |
VBD |
denotes |
revealed |
T7317 |
26691-26692 |
DT |
denotes |
a |
T7318 |
26713-26717 |
NN |
denotes |
pool |
T7319 |
26693-26698 |
JJ |
denotes |
small |
T7320 |
26699-26702 |
NN |
denotes |
dox |
T7321 |
26703-26712 |
JJ |
denotes |
resistant |
T7322 |
26702-26703 |
HYPH |
denotes |
- |
T7323 |
26718-26720 |
IN |
denotes |
of |
T7324 |
26721-26728 |
NN |
denotes |
peptide |
T7325 |
26729-26731 |
IN |
denotes |
in |
T7326 |
26732-26739 |
RB |
denotes |
acutely |
T7327 |
26740-26747 |
VBN |
denotes |
treated |
T7328 |
26748-26755 |
NNS |
denotes |
animals |
T7329 |
26756-26760 |
WDT |
denotes |
that |
T7330 |
26764-26771 |
VBP |
denotes |
believe |
T7331 |
26761-26763 |
PRP |
denotes |
we |
T7332 |
26772-26782 |
VBZ |
denotes |
represents |
T7333 |
26783-26789 |
JJ |
denotes |
stable |
T7334 |
26801-26811 |
NNS |
denotes |
aggregates |
T7335 |
26790-26800 |
JJ |
denotes |
predeposit |
T7336 |
26812-26816 |
WDT |
denotes |
that |
T7337 |
26830-26841 |
VBN |
denotes |
accumulated |
T7338 |
26817-26821 |
VBP |
denotes |
have |
T7339 |
26822-26829 |
RB |
denotes |
already |
T7340 |
26842-26844 |
IN |
denotes |
by |
T7341 |
26845-26846 |
CD |
denotes |
4 |
T7342 |
26847-26849 |
NN |
denotes |
wk |
T7343 |
26850-26852 |
IN |
denotes |
of |
T7344 |
26853-26856 |
NN |
denotes |
age |
T7345 |
26857-26861 |
WRB |
denotes |
when |
T7346 |
26876-26881 |
VBN |
denotes |
begun |
T7347 |
26862-26871 |
NN |
denotes |
treatment |
T7348 |
26872-26875 |
VBD |
denotes |
was |
T7349 |
26882-26883 |
-LRB- |
denotes |
( |
T7350 |
26890-26892 |
NN |
denotes |
2C |
T7351 |
26883-26889 |
NN |
denotes |
Figure |
T7352 |
26892-26893 |
-RRB- |
denotes |
) |
T7353 |
26893-26894 |
. |
denotes |
. |
T7354 |
26894-27056 |
sentence |
denotes |
Indeed, animals that were born and raised on dox did not harbor this reservoir of treatment-resistant peptide, with 96.3% less Aβ42 than untreated 4-wk-old mice. |
T7355 |
26895-26901 |
RB |
denotes |
Indeed |
T7356 |
26952-26958 |
VB |
denotes |
harbor |
T7357 |
26901-26903 |
, |
denotes |
, |
T7358 |
26903-26910 |
NNS |
denotes |
animals |
T7359 |
26911-26915 |
WDT |
denotes |
that |
T7360 |
26921-26925 |
VBN |
denotes |
born |
T7361 |
26916-26920 |
VBD |
denotes |
were |
T7362 |
26926-26929 |
CC |
denotes |
and |
T7363 |
26930-26936 |
VBN |
denotes |
raised |
T7364 |
26937-26939 |
IN |
denotes |
on |
T7365 |
26940-26943 |
NN |
denotes |
dox |
T7366 |
26944-26947 |
VBD |
denotes |
did |
T7367 |
26948-26951 |
RB |
denotes |
not |
T7368 |
26959-26963 |
DT |
denotes |
this |
T7369 |
26964-26973 |
NN |
denotes |
reservoir |
T7370 |
26974-26976 |
IN |
denotes |
of |
T7371 |
26977-26986 |
NN |
denotes |
treatment |
T7372 |
26987-26996 |
JJ |
denotes |
resistant |
T7373 |
26986-26987 |
HYPH |
denotes |
- |
T7374 |
26997-27004 |
NN |
denotes |
peptide |
T7375 |
27004-27006 |
, |
denotes |
, |
T7376 |
27006-27010 |
IN |
denotes |
with |
T7377 |
27011-27015 |
CD |
denotes |
96.3 |
T7378 |
27015-27016 |
NN |
denotes |
% |
T7379 |
27017-27021 |
JJR |
denotes |
less |
T7380 |
27022-27026 |
NN |
denotes |
Aβ42 |
T7381 |
27027-27031 |
IN |
denotes |
than |
T7382 |
27032-27041 |
JJ |
denotes |
untreated |
T7383 |
27051-27055 |
NNS |
denotes |
mice |
T7384 |
27042-27043 |
CD |
denotes |
4 |
T7385 |
27044-27046 |
NN |
denotes |
wk |
T7386 |
27043-27044 |
HYPH |
denotes |
- |
T7387 |
27047-27050 |
JJ |
denotes |
old |
T7388 |
27046-27047 |
HYPH |
denotes |
- |
T7389 |
27055-27056 |
. |
denotes |
. |
T7390 |
27056-27301 |
sentence |
denotes |
Measurement of total Aβ in chronically treated mice, including endogenous and transgene-derived peptide, demonstrated that Aβ levels in tet-off APP mice were reduced to the level of endogenous peptide found in nontransgenic animals (Figure 2D). |
T7391 |
27057-27068 |
NN |
denotes |
Measurement |
T7392 |
27162-27174 |
VBD |
denotes |
demonstrated |
T7393 |
27069-27071 |
IN |
denotes |
of |
T7394 |
27072-27077 |
JJ |
denotes |
total |
T7395 |
27078-27080 |
NN |
denotes |
Aβ |
T7396 |
27081-27083 |
IN |
denotes |
in |
T7397 |
27084-27095 |
RB |
denotes |
chronically |
T7398 |
27096-27103 |
VBN |
denotes |
treated |
T7399 |
27104-27108 |
NNS |
denotes |
mice |
T7400 |
27108-27110 |
, |
denotes |
, |
T7401 |
27110-27119 |
VBG |
denotes |
including |
T7402 |
27120-27130 |
JJ |
denotes |
endogenous |
T7403 |
27153-27160 |
NN |
denotes |
peptide |
T7404 |
27131-27134 |
CC |
denotes |
and |
T7405 |
27135-27144 |
NN |
denotes |
transgene |
T7406 |
27145-27152 |
VBN |
denotes |
derived |
T7407 |
27144-27145 |
HYPH |
denotes |
- |
T7408 |
27160-27162 |
, |
denotes |
, |
T7409 |
27175-27179 |
IN |
denotes |
that |
T7410 |
27215-27222 |
VBN |
denotes |
reduced |
T7411 |
27180-27182 |
NN |
denotes |
Aβ |
T7412 |
27183-27189 |
NNS |
denotes |
levels |
T7413 |
27190-27192 |
IN |
denotes |
in |
T7414 |
27193-27196 |
NN |
denotes |
tet |
T7415 |
27197-27200 |
NN |
denotes |
off |
T7416 |
27196-27197 |
HYPH |
denotes |
- |
T7417 |
27205-27209 |
NNS |
denotes |
mice |
T7418 |
27201-27204 |
NN |
denotes |
APP |
T7419 |
27210-27214 |
VBD |
denotes |
were |
T7420 |
27223-27225 |
IN |
denotes |
to |
T7421 |
27226-27229 |
DT |
denotes |
the |
T7422 |
27230-27235 |
NN |
denotes |
level |
T7423 |
27236-27238 |
IN |
denotes |
of |
T7424 |
27239-27249 |
JJ |
denotes |
endogenous |
T7425 |
27250-27257 |
NN |
denotes |
peptide |
T7426 |
27258-27263 |
VBN |
denotes |
found |
T7427 |
27264-27266 |
IN |
denotes |
in |
T7428 |
27267-27280 |
JJ |
denotes |
nontransgenic |
T7429 |
27281-27288 |
NNS |
denotes |
animals |
T7430 |
27289-27290 |
-LRB- |
denotes |
( |
T7431 |
27297-27299 |
NN |
denotes |
2D |
T7432 |
27290-27296 |
NN |
denotes |
Figure |
T7433 |
27299-27300 |
-RRB- |
denotes |
) |
T7434 |
27300-27301 |
. |
denotes |
. |
T7435 |
27301-27512 |
sentence |
denotes |
Taken together with the immunoblotting data for full-length APPswe/ind, the ELISA measurements indicate that dox-mediated suppression of transgenic APPswe/ind synthesis leads to parallel reduction of Aβ levels. |
T7436 |
27302-27307 |
VBN |
denotes |
Taken |
T7437 |
27397-27405 |
VBP |
denotes |
indicate |
T7438 |
27308-27316 |
RB |
denotes |
together |
T7439 |
27317-27321 |
IN |
denotes |
with |
T7440 |
27322-27325 |
DT |
denotes |
the |
T7441 |
27341-27345 |
NNS |
denotes |
data |
T7442 |
27326-27340 |
NN |
denotes |
immunoblotting |
T7443 |
27346-27349 |
IN |
denotes |
for |
T7444 |
27350-27354 |
JJ |
denotes |
full |
T7445 |
27355-27361 |
NN |
denotes |
length |
T7446 |
27354-27355 |
HYPH |
denotes |
- |
T7447 |
27369-27372 |
NN |
denotes |
ind |
T7448 |
27362-27368 |
NN |
denotes |
APPswe |
T7449 |
27368-27369 |
HYPH |
denotes |
/ |
T7450 |
27372-27374 |
, |
denotes |
, |
T7451 |
27374-27377 |
DT |
denotes |
the |
T7452 |
27384-27396 |
NNS |
denotes |
measurements |
T7453 |
27378-27383 |
NN |
denotes |
ELISA |
T7454 |
27406-27410 |
IN |
denotes |
that |
T7455 |
27471-27476 |
VBZ |
denotes |
leads |
T7456 |
27411-27414 |
NN |
denotes |
dox |
T7457 |
27415-27423 |
VBN |
denotes |
mediated |
T7458 |
27414-27415 |
HYPH |
denotes |
- |
T7459 |
27424-27435 |
NN |
denotes |
suppression |
T7460 |
27436-27438 |
IN |
denotes |
of |
T7461 |
27439-27449 |
JJ |
denotes |
transgenic |
T7462 |
27461-27470 |
NN |
denotes |
synthesis |
T7463 |
27450-27456 |
NN |
denotes |
APPswe |
T7464 |
27457-27460 |
NN |
denotes |
ind |
T7465 |
27456-27457 |
HYPH |
denotes |
/ |
T7466 |
27477-27479 |
IN |
denotes |
to |
T7467 |
27480-27488 |
JJ |
denotes |
parallel |
T7468 |
27489-27498 |
NN |
denotes |
reduction |
T7469 |
27499-27501 |
IN |
denotes |
of |
T7470 |
27502-27504 |
NN |
denotes |
Aβ |
T7471 |
27505-27511 |
NNS |
denotes |
levels |
T7472 |
27511-27512 |
. |
denotes |
. |
T7473 |
27512-30499 |
sentence |
denotes |
Figure 2 Aβ Levels Are Dramatically Reduced by Transgene Suppression
Cortical homogenates from young, predeposit tTA/APP mice used for Western blot in Figure 1 (line 107) were fractionated by sequential multi-step extraction with PBS, 2% SDS, and 70% FA followed by human-specific Aβ ELISA to measure transgene-derived peptide in each fraction. Aβ40 is shown in white, Aβ42 in black.
(A) PBS-soluble Aβ levels are substantially reduced by both acute and chronic dox treatment (ANOVA, effect of treatment group F 4,24 = 137.10 and 386.01, p < 0.001, for Aβ40 and Aβ42, respectively). Aβ levels in treated animals are indistinguishable from nontransgenic (NTg) animals (p > 0.3, Tukey post-hoc test).
(B) In the young animals tested here prior to the formation of visible amyloid deposits, most Aβ is extracted into the SDS fraction (84% and 76% of all transgene-derived Aβ40 and Aβ42, respectively). As in the PBS-soluble fraction, Aβ levels in the SDS fraction are significantly lowered by dox treatment compared to untreated animals (ANOVA effect of group F 4,24 = 197.57 and 163.48, p < 0.001, for Aβ40 and Aβ42, respectively). Acutely treated animals retained a small (although significant) amount of residual peptide (p < 0.001 compared to nontransgeinc, Tukey post-hoc test), whereas Aβ levels in mice born and raised on dox were reduced to levels indistinguishable from nontransgenic (p > 0.8, Tukey post-hoc test).
(C) The FA-soluble fraction already contains a small but significant pool of aggregated Aβ42 in untreated animals by 4 wk of age (p < 0.05 versus nontransgenic; Tukey post-hoc test applied to significant effect of group ANOVA F 4,24 = 17.11, p < 0.001). By 6 wk of age, the amount of Aβ in the FA fraction is increased significantly preceding the appearance of visible deposits 2 wk later. The FA pool is the only peptide fraction not lowered by acute dox treatment (4 wk untreated = 4 wk + 2 wk dox, p > 0.9, Tukey post-hoc test), consistent with poor turnover of aggregated Aβ species.
(D) Measurements of total Aβ, including both endogenous and transgene-derived peptides, show that animals born and raised on dox harbor Aβ levels identical to nontransgenic animals (p > 0.9, Tukey post-hoc test, effect of group ANOVA F 4,24 = 39.13 and 35.29, p < 0.001, for Aβ40 and Aβ42, respectively). Whereas chronic transgene suppression fully prevents synthesis of both peptides, acute dox treatment fully suppresses Aβ40 levels (p > 0.8, Tukey post-hoc test), but leaves a small amount of nonsuppressed Aβ42. The residual Aβ42 observed in acutely treated young animals derives from uncleared aggregates extracted in the SDS and FA fractions. *, p < 0.05; **, p < 0.005; ***, p < 0.001 versus 4-wk-old untreated mice, Tukey post-hoc applied to significant effect of group ANOVA. The ELISA data also confirmed that incorporation of the Swedish and Indiana mutations led to high levels of Aβ42, which we predicted would induce rapid plaque formation in untreated animals. |
T7474 |
30309-30312 |
DT |
denotes |
The |
T7475 |
30319-30323 |
NNS |
denotes |
data |
T7476 |
30313-30318 |
NN |
denotes |
ELISA |
T7477 |
30329-30338 |
VBD |
denotes |
confirmed |
T7478 |
30324-30328 |
RB |
denotes |
also |
T7479 |
30339-30343 |
IN |
denotes |
that |
T7480 |
30395-30398 |
VBD |
denotes |
led |
T7481 |
30344-30357 |
NN |
denotes |
incorporation |
T7482 |
30358-30360 |
IN |
denotes |
of |
T7483 |
30361-30364 |
DT |
denotes |
the |
T7484 |
30385-30394 |
NNS |
denotes |
mutations |
T7485 |
30365-30372 |
JJ |
denotes |
Swedish |
T7486 |
30373-30376 |
CC |
denotes |
and |
T7487 |
30377-30384 |
NNP |
denotes |
Indiana |
T7488 |
30399-30401 |
IN |
denotes |
to |
T7489 |
30402-30406 |
JJ |
denotes |
high |
T7490 |
30407-30413 |
NNS |
denotes |
levels |
T7491 |
30414-30416 |
IN |
denotes |
of |
T7492 |
30417-30421 |
NN |
denotes |
Aβ42 |
T7493 |
30421-30423 |
, |
denotes |
, |
T7494 |
30423-30428 |
WDT |
denotes |
which |
T7495 |
30432-30441 |
VBD |
denotes |
predicted |
T7496 |
30429-30431 |
PRP |
denotes |
we |
T7497 |
30442-30447 |
MD |
denotes |
would |
T7498 |
30448-30454 |
VB |
denotes |
induce |
T7499 |
30455-30460 |
JJ |
denotes |
rapid |
T7500 |
30468-30477 |
NN |
denotes |
formation |
T7501 |
30461-30467 |
NN |
denotes |
plaque |
T7502 |
30478-30480 |
IN |
denotes |
in |
T7503 |
30481-30490 |
JJ |
denotes |
untreated |
T7504 |
30491-30498 |
NNS |
denotes |
animals |
T7505 |
30498-30499 |
. |
denotes |
. |
T7506 |
30499-30648 |
sentence |
denotes |
Histological characterization of double transgenic (CaMKIIα-tTA × tet-APPswe/ind) mice revealed early-onset amyloid formation in all four new lines. |
T7507 |
30500-30512 |
JJ |
denotes |
Histological |
T7508 |
30513-30529 |
NN |
denotes |
characterization |
T7509 |
30587-30595 |
VBD |
denotes |
revealed |
T7510 |
30530-30532 |
IN |
denotes |
of |
T7511 |
30533-30539 |
JJ |
denotes |
double |
T7512 |
30582-30586 |
NNS |
denotes |
mice |
T7513 |
30540-30550 |
JJ |
denotes |
transgenic |
T7514 |
30551-30552 |
-LRB- |
denotes |
( |
T7515 |
30570-30576 |
NN |
denotes |
APPswe |
T7516 |
30552-30559 |
NN |
denotes |
CaMKIIα |
T7517 |
30559-30560 |
HYPH |
denotes |
- |
T7518 |
30560-30563 |
NN |
denotes |
tTA |
T7519 |
30564-30565 |
SYM |
denotes |
× |
T7520 |
30566-30569 |
NN |
denotes |
tet |
T7521 |
30569-30570 |
HYPH |
denotes |
- |
T7522 |
30576-30577 |
HYPH |
denotes |
/ |
T7523 |
30577-30580 |
JJ |
denotes |
ind |
T7524 |
30580-30581 |
-RRB- |
denotes |
) |
T7525 |
30596-30601 |
JJ |
denotes |
early |
T7526 |
30602-30607 |
NN |
denotes |
onset |
T7527 |
30601-30602 |
HYPH |
denotes |
- |
T7528 |
30616-30625 |
NN |
denotes |
formation |
T7529 |
30608-30615 |
NN |
denotes |
amyloid |
T7530 |
30626-30628 |
IN |
denotes |
in |
T7531 |
30629-30632 |
DT |
denotes |
all |
T7532 |
30642-30647 |
NNS |
denotes |
lines |
T7533 |
30633-30637 |
CD |
denotes |
four |
T7534 |
30638-30641 |
JJ |
denotes |
new |
T7535 |
30647-30648 |
. |
denotes |
. |
T7536 |
30648-30724 |
sentence |
denotes |
Amyloid plaques were seen in mice as young as 8 wk of age (data not shown). |
T7537 |
30649-30656 |
NN |
denotes |
Amyloid |
T7538 |
30657-30664 |
NNS |
denotes |
plaques |
T7539 |
30670-30674 |
VBN |
denotes |
seen |
T7540 |
30665-30669 |
VBD |
denotes |
were |
T7541 |
30675-30677 |
IN |
denotes |
in |
T7542 |
30678-30682 |
NNS |
denotes |
mice |
T7543 |
30683-30685 |
RB |
denotes |
as |
T7544 |
30686-30691 |
JJ |
denotes |
young |
T7545 |
30692-30694 |
IN |
denotes |
as |
T7546 |
30695-30696 |
CD |
denotes |
8 |
T7547 |
30697-30699 |
NN |
denotes |
wk |
T7548 |
30700-30702 |
IN |
denotes |
of |
T7549 |
30703-30706 |
NN |
denotes |
age |
T7550 |
30707-30708 |
-LRB- |
denotes |
( |
T7551 |
30717-30722 |
VBN |
denotes |
shown |
T7552 |
30708-30712 |
NNS |
denotes |
data |
T7553 |
30713-30716 |
RB |
denotes |
not |
T7554 |
30722-30723 |
-RRB- |
denotes |
) |
T7555 |
30723-30724 |
. |
denotes |
. |
T7556 |
30724-30903 |
sentence |
denotes |
Plaques were limited to the forebrain, including the cortex, hippocampus, olfactory bulb, and striatum, where the CaMKIIα promoter is known to be most active [16,28] (Figure S2). |
T7557 |
30725-30732 |
NNS |
denotes |
Plaques |
T7558 |
30738-30745 |
VBN |
denotes |
limited |
T7559 |
30733-30737 |
VBD |
denotes |
were |
T7560 |
30746-30748 |
IN |
denotes |
to |
T7561 |
30749-30752 |
DT |
denotes |
the |
T7562 |
30753-30762 |
NN |
denotes |
forebrain |
T7563 |
30762-30764 |
, |
denotes |
, |
T7564 |
30764-30773 |
VBG |
denotes |
including |
T7565 |
30774-30777 |
DT |
denotes |
the |
T7566 |
30778-30784 |
NN |
denotes |
cortex |
T7567 |
30784-30786 |
, |
denotes |
, |
T7568 |
30786-30797 |
NN |
denotes |
hippocampus |
T7569 |
30797-30799 |
, |
denotes |
, |
T7570 |
30799-30808 |
JJ |
denotes |
olfactory |
T7571 |
30809-30813 |
NN |
denotes |
bulb |
T7572 |
30813-30815 |
, |
denotes |
, |
T7573 |
30815-30818 |
CC |
denotes |
and |
T7574 |
30819-30827 |
NN |
denotes |
striatum |
T7575 |
30827-30829 |
, |
denotes |
, |
T7576 |
30829-30834 |
WRB |
denotes |
where |
T7577 |
30859-30864 |
VBN |
denotes |
known |
T7578 |
30835-30838 |
DT |
denotes |
the |
T7579 |
30847-30855 |
NN |
denotes |
promoter |
T7580 |
30839-30846 |
NN |
denotes |
CaMKIIα |
T7581 |
30856-30858 |
VBZ |
denotes |
is |
T7582 |
30865-30867 |
TO |
denotes |
to |
T7583 |
30868-30870 |
VB |
denotes |
be |
T7584 |
30871-30875 |
RBS |
denotes |
most |
T7585 |
30876-30882 |
JJ |
denotes |
active |
T7586 |
30883-30884 |
-LRB- |
denotes |
[ |
T7587 |
30887-30889 |
CD |
denotes |
28 |
T7588 |
30884-30886 |
CD |
denotes |
16 |
T7589 |
30886-30887 |
, |
denotes |
, |
T7590 |
30889-30890 |
-RRB- |
denotes |
] |
T7591 |
30891-30892 |
-LRB- |
denotes |
( |
T7592 |
30899-30901 |
NN |
denotes |
S2 |
T7593 |
30892-30898 |
NN |
denotes |
Figure |
T7594 |
30901-30902 |
-RRB- |
denotes |
) |
T7595 |
30902-30903 |
. |
denotes |
. |
T7596 |
30903-31013 |
sentence |
denotes |
By 6 mo of age, amyloid burden became severe, covering large areas of the cortex and hippocampus (Figure S3). |
T7597 |
30904-30906 |
IN |
denotes |
By |
T7598 |
30935-30941 |
VBD |
denotes |
became |
T7599 |
30907-30908 |
CD |
denotes |
6 |
T7600 |
30909-30911 |
NN |
denotes |
mo |
T7601 |
30912-30914 |
IN |
denotes |
of |
T7602 |
30915-30918 |
NN |
denotes |
age |
T7603 |
30918-30920 |
, |
denotes |
, |
T7604 |
30920-30927 |
NN |
denotes |
amyloid |
T7605 |
30928-30934 |
NN |
denotes |
burden |
T7606 |
30942-30948 |
JJ |
denotes |
severe |
T7607 |
30948-30950 |
, |
denotes |
, |
T7608 |
30950-30958 |
VBG |
denotes |
covering |
T7609 |
30959-30964 |
JJ |
denotes |
large |
T7610 |
30965-30970 |
NNS |
denotes |
areas |
T7611 |
30971-30973 |
IN |
denotes |
of |
T7612 |
30974-30977 |
DT |
denotes |
the |
T7613 |
30978-30984 |
NN |
denotes |
cortex |
T7614 |
30985-30988 |
CC |
denotes |
and |
T7615 |
30989-31000 |
NN |
denotes |
hippocampus |
T7616 |
31001-31002 |
-LRB- |
denotes |
( |
T7617 |
31009-31011 |
NN |
denotes |
S3 |
T7618 |
31002-31008 |
NN |
denotes |
Figure |
T7619 |
31011-31012 |
-RRB- |
denotes |
) |
T7620 |
31012-31013 |
. |
denotes |
. |
T7621 |
31013-31142 |
sentence |
denotes |
No lesions were seen in the cerebellum or brain stem even at late ages, consistent with CaMKIIα-controlled transgene expression. |
T7622 |
31014-31016 |
DT |
denotes |
No |
T7623 |
31017-31024 |
NNS |
denotes |
lesions |
T7624 |
31030-31034 |
VBN |
denotes |
seen |
T7625 |
31025-31029 |
VBD |
denotes |
were |
T7626 |
31035-31037 |
IN |
denotes |
in |
T7627 |
31038-31041 |
DT |
denotes |
the |
T7628 |
31042-31052 |
NN |
denotes |
cerebellum |
T7629 |
31053-31055 |
CC |
denotes |
or |
T7630 |
31056-31061 |
NN |
denotes |
brain |
T7631 |
31062-31066 |
NN |
denotes |
stem |
T7632 |
31067-31071 |
RB |
denotes |
even |
T7633 |
31072-31074 |
IN |
denotes |
at |
T7634 |
31075-31079 |
JJ |
denotes |
late |
T7635 |
31080-31084 |
NNS |
denotes |
ages |
T7636 |
31084-31086 |
, |
denotes |
, |
T7637 |
31086-31096 |
JJ |
denotes |
consistent |
T7638 |
31097-31101 |
IN |
denotes |
with |
T7639 |
31102-31109 |
NN |
denotes |
CaMKIIα |
T7640 |
31110-31120 |
VBN |
denotes |
controlled |
T7641 |
31109-31110 |
HYPH |
denotes |
- |
T7642 |
31131-31141 |
NN |
denotes |
expression |
T7643 |
31121-31130 |
NN |
denotes |
transgene |
T7644 |
31141-31142 |
. |
denotes |
. |
T7645 |
31142-31276 |
sentence |
denotes |
Unlike what is thought to occur in the human disease, the first visible plaques in the tet-off APP mice are fibrillar-cored deposits. |
T7646 |
31143-31149 |
IN |
denotes |
Unlike |
T7647 |
31247-31250 |
VBP |
denotes |
are |
T7648 |
31150-31154 |
WP |
denotes |
what |
T7649 |
31158-31165 |
VBN |
denotes |
thought |
T7650 |
31155-31157 |
VBZ |
denotes |
is |
T7651 |
31166-31168 |
TO |
denotes |
to |
T7652 |
31169-31174 |
VB |
denotes |
occur |
T7653 |
31175-31177 |
IN |
denotes |
in |
T7654 |
31178-31181 |
DT |
denotes |
the |
T7655 |
31188-31195 |
NN |
denotes |
disease |
T7656 |
31182-31187 |
JJ |
denotes |
human |
T7657 |
31195-31197 |
, |
denotes |
, |
T7658 |
31197-31200 |
DT |
denotes |
the |
T7659 |
31215-31222 |
NNS |
denotes |
plaques |
T7660 |
31201-31206 |
JJ |
denotes |
first |
T7661 |
31207-31214 |
JJ |
denotes |
visible |
T7662 |
31223-31225 |
IN |
denotes |
in |
T7663 |
31226-31229 |
DT |
denotes |
the |
T7664 |
31242-31246 |
NNS |
denotes |
mice |
T7665 |
31230-31233 |
NN |
denotes |
tet |
T7666 |
31234-31237 |
NN |
denotes |
off |
T7667 |
31233-31234 |
HYPH |
denotes |
- |
T7668 |
31238-31241 |
NN |
denotes |
APP |
T7669 |
31251-31260 |
JJ |
denotes |
fibrillar |
T7670 |
31261-31266 |
VBN |
denotes |
cored |
T7671 |
31260-31261 |
HYPH |
denotes |
- |
T7672 |
31267-31275 |
NNS |
denotes |
deposits |
T7673 |
31275-31276 |
. |
denotes |
. |
T7674 |
31276-31411 |
sentence |
denotes |
We have noted the same early appearance of cored deposits in other lines of APP transgenic mice that harbor the Swedish mutation [27]. |
T7675 |
31277-31279 |
PRP |
denotes |
We |
T7676 |
31285-31290 |
VBN |
denotes |
noted |
T7677 |
31280-31284 |
VBP |
denotes |
have |
T7678 |
31291-31294 |
DT |
denotes |
the |
T7679 |
31306-31316 |
NN |
denotes |
appearance |
T7680 |
31295-31299 |
JJ |
denotes |
same |
T7681 |
31300-31305 |
JJ |
denotes |
early |
T7682 |
31317-31319 |
IN |
denotes |
of |
T7683 |
31320-31325 |
VBN |
denotes |
cored |
T7684 |
31326-31334 |
NNS |
denotes |
deposits |
T7685 |
31335-31337 |
IN |
denotes |
in |
T7686 |
31338-31343 |
JJ |
denotes |
other |
T7687 |
31344-31349 |
NNS |
denotes |
lines |
T7688 |
31350-31352 |
IN |
denotes |
of |
T7689 |
31353-31356 |
NN |
denotes |
APP |
T7690 |
31368-31372 |
NNS |
denotes |
mice |
T7691 |
31357-31367 |
JJ |
denotes |
transgenic |
T7692 |
31373-31377 |
WDT |
denotes |
that |
T7693 |
31378-31384 |
VBP |
denotes |
harbor |
T7694 |
31385-31388 |
DT |
denotes |
the |
T7695 |
31397-31405 |
NN |
denotes |
mutation |
T7696 |
31389-31396 |
JJ |
denotes |
Swedish |
T7697 |
31406-31407 |
-LRB- |
denotes |
[ |
T7698 |
31407-31409 |
CD |
denotes |
27 |
T7699 |
31409-31410 |
-RRB- |
denotes |
] |
T7700 |
31410-31411 |
. |
denotes |
. |
T7701 |
31411-31514 |
sentence |
denotes |
Diffuse plaques were apparent in 6-mo-old tTA/APP mice, and became relatively abundant by 9 mo of age. |
T7702 |
31412-31419 |
NN |
denotes |
Diffuse |
T7703 |
31420-31427 |
NNS |
denotes |
plaques |
T7704 |
31428-31432 |
VBD |
denotes |
were |
T7705 |
31433-31441 |
JJ |
denotes |
apparent |
T7706 |
31442-31444 |
IN |
denotes |
in |
T7707 |
31445-31446 |
CD |
denotes |
6 |
T7708 |
31447-31449 |
NN |
denotes |
mo |
T7709 |
31446-31447 |
HYPH |
denotes |
- |
T7710 |
31450-31453 |
JJ |
denotes |
old |
T7711 |
31449-31450 |
HYPH |
denotes |
- |
T7712 |
31462-31466 |
NNS |
denotes |
mice |
T7713 |
31454-31457 |
NN |
denotes |
tTA |
T7714 |
31458-31461 |
NN |
denotes |
APP |
T7715 |
31457-31458 |
HYPH |
denotes |
/ |
T7716 |
31466-31468 |
, |
denotes |
, |
T7717 |
31468-31471 |
CC |
denotes |
and |
T7718 |
31472-31478 |
VBD |
denotes |
became |
T7719 |
31479-31489 |
RB |
denotes |
relatively |
T7720 |
31490-31498 |
JJ |
denotes |
abundant |
T7721 |
31499-31501 |
IN |
denotes |
by |
T7722 |
31502-31503 |
CD |
denotes |
9 |
T7723 |
31504-31506 |
NN |
denotes |
mo |
T7724 |
31507-31509 |
IN |
denotes |
of |
T7725 |
31510-31513 |
NN |
denotes |
age |
T7726 |
31513-31514 |
. |
denotes |
. |
T7727 |
31514-31668 |
sentence |
denotes |
At older ages (9–12 mo) amyloid deposits were visible in the thalamus, which has also been observed in mice expressing mutant APP via the Thy-1 promoter. |
T7728 |
31515-31517 |
IN |
denotes |
At |
T7729 |
31556-31560 |
VBD |
denotes |
were |
T7730 |
31518-31523 |
JJR |
denotes |
older |
T7731 |
31524-31528 |
NNS |
denotes |
ages |
T7732 |
31529-31530 |
-LRB- |
denotes |
( |
T7733 |
31530-31531 |
CD |
denotes |
9 |
T7734 |
31532-31534 |
CD |
denotes |
12 |
T7735 |
31531-31532 |
SYM |
denotes |
– |
T7736 |
31535-31537 |
NN |
denotes |
mo |
T7737 |
31537-31538 |
-RRB- |
denotes |
) |
T7738 |
31539-31546 |
NN |
denotes |
amyloid |
T7739 |
31547-31555 |
NNS |
denotes |
deposits |
T7740 |
31561-31568 |
JJ |
denotes |
visible |
T7741 |
31569-31571 |
IN |
denotes |
in |
T7742 |
31572-31575 |
DT |
denotes |
the |
T7743 |
31576-31584 |
NN |
denotes |
thalamus |
T7744 |
31584-31586 |
, |
denotes |
, |
T7745 |
31586-31591 |
WDT |
denotes |
which |
T7746 |
31606-31614 |
VBN |
denotes |
observed |
T7747 |
31592-31595 |
VBZ |
denotes |
has |
T7748 |
31596-31600 |
RB |
denotes |
also |
T7749 |
31601-31605 |
VBN |
denotes |
been |
T7750 |
31615-31617 |
IN |
denotes |
in |
T7751 |
31618-31622 |
NNS |
denotes |
mice |
T7752 |
31623-31633 |
VBG |
denotes |
expressing |
T7753 |
31634-31640 |
NN |
denotes |
mutant |
T7754 |
31641-31644 |
NN |
denotes |
APP |
T7755 |
31645-31648 |
IN |
denotes |
via |
T7756 |
31649-31652 |
DT |
denotes |
the |
T7757 |
31659-31667 |
NN |
denotes |
promoter |
T7758 |
31653-31656 |
NN |
denotes |
Thy |
T7759 |
31656-31657 |
HYPH |
denotes |
- |
T7760 |
31657-31658 |
CD |
denotes |
1 |
T7761 |
31667-31668 |
. |
denotes |
. |
T7762 |
31668-31826 |
sentence |
denotes |
The presence of amyloid pathology in this region has been attributed to axonal transport of APP/Aβ to the terminals of cortical neurons in the thalamus [29]. |
T7763 |
31669-31672 |
DT |
denotes |
The |
T7764 |
31673-31681 |
NN |
denotes |
presence |
T7765 |
31727-31737 |
VBN |
denotes |
attributed |
T7766 |
31682-31684 |
IN |
denotes |
of |
T7767 |
31685-31692 |
NN |
denotes |
amyloid |
T7768 |
31693-31702 |
NN |
denotes |
pathology |
T7769 |
31703-31705 |
IN |
denotes |
in |
T7770 |
31706-31710 |
DT |
denotes |
this |
T7771 |
31711-31717 |
NN |
denotes |
region |
T7772 |
31718-31721 |
VBZ |
denotes |
has |
T7773 |
31722-31726 |
VBN |
denotes |
been |
T7774 |
31738-31740 |
IN |
denotes |
to |
T7775 |
31741-31747 |
JJ |
denotes |
axonal |
T7776 |
31748-31757 |
NN |
denotes |
transport |
T7777 |
31758-31760 |
IN |
denotes |
of |
T7778 |
31761-31764 |
NN |
denotes |
APP |
T7779 |
31765-31767 |
NN |
denotes |
Aβ |
T7780 |
31764-31765 |
HYPH |
denotes |
/ |
T7781 |
31768-31770 |
IN |
denotes |
to |
T7782 |
31771-31774 |
DT |
denotes |
the |
T7783 |
31775-31784 |
NNS |
denotes |
terminals |
T7784 |
31785-31787 |
IN |
denotes |
of |
T7785 |
31788-31796 |
JJ |
denotes |
cortical |
T7786 |
31797-31804 |
NNS |
denotes |
neurons |
T7787 |
31805-31807 |
IN |
denotes |
in |
T7788 |
31808-31811 |
DT |
denotes |
the |
T7789 |
31812-31820 |
NN |
denotes |
thalamus |
T7790 |
31821-31822 |
-LRB- |
denotes |
[ |
T7791 |
31822-31824 |
CD |
denotes |
29 |
T7792 |
31824-31825 |
-RRB- |
denotes |
] |
T7793 |
31825-31826 |
. |
denotes |
. |
T7794 |
31826-31944 |
sentence |
denotes |
Most importantly, only double transgenic mice, expressing both the tTA and APP transgenes, developed amyloid lesions. |
T7795 |
31827-31831 |
RBS |
denotes |
Most |
T7796 |
31832-31843 |
RB |
denotes |
importantly |
T7797 |
31918-31927 |
VBD |
denotes |
developed |
T7798 |
31843-31845 |
, |
denotes |
, |
T7799 |
31845-31849 |
RB |
denotes |
only |
T7800 |
31868-31872 |
NNS |
denotes |
mice |
T7801 |
31850-31856 |
JJ |
denotes |
double |
T7802 |
31857-31867 |
JJ |
denotes |
transgenic |
T7803 |
31872-31874 |
, |
denotes |
, |
T7804 |
31874-31884 |
VBG |
denotes |
expressing |
T7805 |
31885-31889 |
CC |
denotes |
both |
T7806 |
31906-31916 |
NNS |
denotes |
transgenes |
T7807 |
31890-31893 |
DT |
denotes |
the |
T7808 |
31894-31897 |
NN |
denotes |
tTA |
T7809 |
31898-31901 |
CC |
denotes |
and |
T7810 |
31902-31905 |
NN |
denotes |
APP |
T7811 |
31916-31918 |
, |
denotes |
, |
T7812 |
31928-31935 |
NN |
denotes |
amyloid |
T7813 |
31936-31943 |
NNS |
denotes |
lesions |
T7814 |
31943-31944 |
. |
denotes |
. |
T7815 |
31944-32027 |
sentence |
denotes |
Single transgenic mice up to 15 mo of age showed no sign of pathology (Figure S3). |
T7816 |
31945-31951 |
JJ |
denotes |
Single |
T7817 |
31952-31962 |
JJ |
denotes |
transgenic |
T7818 |
31963-31967 |
NNS |
denotes |
mice |
T7819 |
31987-31993 |
VBD |
denotes |
showed |
T7820 |
31968-31970 |
IN |
denotes |
up |
T7821 |
31974-31976 |
CD |
denotes |
15 |
T7822 |
31971-31973 |
IN |
denotes |
to |
T7823 |
31977-31979 |
NN |
denotes |
mo |
T7824 |
31980-31982 |
IN |
denotes |
of |
T7825 |
31983-31986 |
NN |
denotes |
age |
T7826 |
31994-31996 |
DT |
denotes |
no |
T7827 |
31997-32001 |
NN |
denotes |
sign |
T7828 |
32002-32004 |
IN |
denotes |
of |
T7829 |
32005-32014 |
NN |
denotes |
pathology |
T7830 |
32015-32016 |
-LRB- |
denotes |
( |
T7831 |
32023-32025 |
NN |
denotes |
S3 |
T7832 |
32016-32022 |
NN |
denotes |
Figure |
T7833 |
32025-32026 |
-RRB- |
denotes |
) |
T7834 |
32026-32027 |
. |
denotes |
. |
T7835 |
32027-32137 |
sentence |
denotes |
Similarly, amyloid pathology can be completely prevented in double transgenic animals born and raised on dox. |
T7836 |
32028-32037 |
RB |
denotes |
Similarly |
T7837 |
32075-32084 |
VBN |
denotes |
prevented |
T7838 |
32037-32039 |
, |
denotes |
, |
T7839 |
32039-32046 |
NN |
denotes |
amyloid |
T7840 |
32047-32056 |
NN |
denotes |
pathology |
T7841 |
32057-32060 |
MD |
denotes |
can |
T7842 |
32061-32063 |
VB |
denotes |
be |
T7843 |
32064-32074 |
RB |
denotes |
completely |
T7844 |
32085-32087 |
IN |
denotes |
in |
T7845 |
32088-32094 |
JJ |
denotes |
double |
T7846 |
32095-32105 |
JJ |
denotes |
transgenic |
T7847 |
32106-32113 |
NNS |
denotes |
animals |
T7848 |
32114-32118 |
VBN |
denotes |
born |
T7849 |
32119-32122 |
CC |
denotes |
and |
T7850 |
32123-32129 |
VBN |
denotes |
raised |
T7851 |
32130-32132 |
IN |
denotes |
on |
T7852 |
32133-32136 |
NN |
denotes |
dox |
T7853 |
32136-32137 |
. |
denotes |
. |
T7854 |
32137-32440 |
sentence |
denotes |
Animals from our highest expressing line (line 885) maintained on dox for up to 1 y harbored no amyloid pathology (data not shown), indicating that residual leakage of transgene expression in the presence of dox does not provide sufficient Aβ peptide to induce amyloid formation even over long periods. |
T7855 |
32138-32145 |
NNS |
denotes |
Animals |
T7856 |
32222-32230 |
VBD |
denotes |
harbored |
T7857 |
32146-32150 |
IN |
denotes |
from |
T7858 |
32151-32154 |
PRP$ |
denotes |
our |
T7859 |
32174-32178 |
NN |
denotes |
line |
T7860 |
32155-32162 |
JJS |
denotes |
highest |
T7861 |
32163-32173 |
VBG |
denotes |
expressing |
T7862 |
32179-32180 |
-LRB- |
denotes |
( |
T7863 |
32180-32184 |
NN |
denotes |
line |
T7864 |
32185-32188 |
CD |
denotes |
885 |
T7865 |
32188-32189 |
-RRB- |
denotes |
) |
T7866 |
32190-32200 |
VBN |
denotes |
maintained |
T7867 |
32201-32203 |
IN |
denotes |
on |
T7868 |
32204-32207 |
NN |
denotes |
dox |
T7869 |
32208-32211 |
IN |
denotes |
for |
T7870 |
32212-32214 |
IN |
denotes |
up |
T7871 |
32215-32217 |
IN |
denotes |
to |
T7872 |
32218-32219 |
CD |
denotes |
1 |
T7873 |
32220-32221 |
NN |
denotes |
y |
T7874 |
32231-32233 |
DT |
denotes |
no |
T7875 |
32242-32251 |
NN |
denotes |
pathology |
T7876 |
32234-32241 |
NN |
denotes |
amyloid |
T7877 |
32252-32253 |
-LRB- |
denotes |
( |
T7878 |
32262-32267 |
VBN |
denotes |
shown |
T7879 |
32253-32257 |
NNS |
denotes |
data |
T7880 |
32258-32261 |
RB |
denotes |
not |
T7881 |
32267-32268 |
-RRB- |
denotes |
) |
T7882 |
32268-32270 |
, |
denotes |
, |
T7883 |
32270-32280 |
VBG |
denotes |
indicating |
T7884 |
32281-32285 |
IN |
denotes |
that |
T7885 |
32359-32366 |
VB |
denotes |
provide |
T7886 |
32286-32294 |
JJ |
denotes |
residual |
T7887 |
32295-32302 |
NN |
denotes |
leakage |
T7888 |
32303-32305 |
IN |
denotes |
of |
T7889 |
32306-32315 |
NN |
denotes |
transgene |
T7890 |
32316-32326 |
NN |
denotes |
expression |
T7891 |
32327-32329 |
IN |
denotes |
in |
T7892 |
32330-32333 |
DT |
denotes |
the |
T7893 |
32334-32342 |
NN |
denotes |
presence |
T7894 |
32343-32345 |
IN |
denotes |
of |
T7895 |
32346-32349 |
NN |
denotes |
dox |
T7896 |
32350-32354 |
VBZ |
denotes |
does |
T7897 |
32355-32358 |
RB |
denotes |
not |
T7898 |
32367-32377 |
JJ |
denotes |
sufficient |
T7899 |
32381-32388 |
NN |
denotes |
peptide |
T7900 |
32378-32380 |
NN |
denotes |
Aβ |
T7901 |
32389-32391 |
TO |
denotes |
to |
T7902 |
32392-32398 |
VB |
denotes |
induce |
T7903 |
32399-32406 |
NN |
denotes |
amyloid |
T7904 |
32407-32416 |
NN |
denotes |
formation |
T7905 |
32417-32421 |
RB |
denotes |
even |
T7906 |
32422-32426 |
IN |
denotes |
over |
T7907 |
32427-32431 |
JJ |
denotes |
long |
T7908 |
32432-32439 |
NNS |
denotes |
periods |
T7909 |
32439-32440 |
. |
denotes |
. |
T7910 |
32440-32689 |
sentence |
denotes |
To mimic therapeutic intervention with inhibitors of Aβ production, we raised a group of 25 double transgenic mice (CaMKIIα-tTA × APP line 107) on normal food until 6 mo of age, when we knew amyloid formation was already well underway in the brain. |
T7911 |
32441-32443 |
TO |
denotes |
To |
T7912 |
32444-32449 |
VB |
denotes |
mimic |
T7913 |
32512-32518 |
VBD |
denotes |
raised |
T7914 |
32450-32461 |
JJ |
denotes |
therapeutic |
T7915 |
32462-32474 |
NN |
denotes |
intervention |
T7916 |
32475-32479 |
IN |
denotes |
with |
T7917 |
32480-32490 |
NNS |
denotes |
inhibitors |
T7918 |
32491-32493 |
IN |
denotes |
of |
T7919 |
32494-32496 |
NN |
denotes |
Aβ |
T7920 |
32497-32507 |
NN |
denotes |
production |
T7921 |
32507-32509 |
, |
denotes |
, |
T7922 |
32509-32511 |
PRP |
denotes |
we |
T7923 |
32519-32520 |
DT |
denotes |
a |
T7924 |
32521-32526 |
NN |
denotes |
group |
T7925 |
32527-32529 |
IN |
denotes |
of |
T7926 |
32530-32532 |
CD |
denotes |
25 |
T7927 |
32551-32555 |
NNS |
denotes |
mice |
T7928 |
32533-32539 |
JJ |
denotes |
double |
T7929 |
32540-32550 |
JJ |
denotes |
transgenic |
T7930 |
32556-32557 |
-LRB- |
denotes |
( |
T7931 |
32571-32574 |
NN |
denotes |
APP |
T7932 |
32557-32564 |
NN |
denotes |
CaMKIIα |
T7933 |
32564-32565 |
HYPH |
denotes |
- |
T7934 |
32565-32568 |
NN |
denotes |
tTA |
T7935 |
32569-32570 |
SYM |
denotes |
× |
T7936 |
32575-32579 |
NN |
denotes |
line |
T7937 |
32580-32583 |
CD |
denotes |
107 |
T7938 |
32583-32584 |
-RRB- |
denotes |
) |
T7939 |
32585-32587 |
IN |
denotes |
on |
T7940 |
32588-32594 |
JJ |
denotes |
normal |
T7941 |
32595-32599 |
NN |
denotes |
food |
T7942 |
32600-32605 |
IN |
denotes |
until |
T7943 |
32606-32607 |
CD |
denotes |
6 |
T7944 |
32608-32610 |
NN |
denotes |
mo |
T7945 |
32611-32613 |
IN |
denotes |
of |
T7946 |
32614-32617 |
NN |
denotes |
age |
T7947 |
32617-32619 |
, |
denotes |
, |
T7948 |
32619-32623 |
WRB |
denotes |
when |
T7949 |
32627-32631 |
VBD |
denotes |
knew |
T7950 |
32624-32626 |
PRP |
denotes |
we |
T7951 |
32632-32639 |
NN |
denotes |
amyloid |
T7952 |
32640-32649 |
NN |
denotes |
formation |
T7953 |
32650-32653 |
VBD |
denotes |
was |
T7954 |
32654-32661 |
RB |
denotes |
already |
T7955 |
32662-32666 |
RB |
denotes |
well |
T7956 |
32667-32675 |
JJ |
denotes |
underway |
T7957 |
32676-32678 |
IN |
denotes |
in |
T7958 |
32679-32682 |
DT |
denotes |
the |
T7959 |
32683-32688 |
NN |
denotes |
brain |
T7960 |
32688-32689 |
. |
denotes |
. |
T7961 |
32689-32834 |
sentence |
denotes |
At 6 mo, half of the animals were switched from normal chow to food containing dox at 200 mg/kg until they were sacrificed at 9 or 12 mo of age. |
T7962 |
32690-32692 |
IN |
denotes |
At |
T7963 |
32724-32732 |
VBN |
denotes |
switched |
T7964 |
32693-32694 |
CD |
denotes |
6 |
T7965 |
32695-32697 |
NN |
denotes |
mo |
T7966 |
32697-32699 |
, |
denotes |
, |
T7967 |
32699-32703 |
NN |
denotes |
half |
T7968 |
32704-32706 |
IN |
denotes |
of |
T7969 |
32707-32710 |
DT |
denotes |
the |
T7970 |
32711-32718 |
NNS |
denotes |
animals |
T7971 |
32719-32723 |
VBD |
denotes |
were |
T7972 |
32733-32737 |
IN |
denotes |
from |
T7973 |
32738-32744 |
JJ |
denotes |
normal |
T7974 |
32745-32749 |
NN |
denotes |
chow |
T7975 |
32750-32752 |
IN |
denotes |
to |
T7976 |
32753-32757 |
NN |
denotes |
food |
T7977 |
32758-32768 |
VBG |
denotes |
containing |
T7978 |
32769-32772 |
NN |
denotes |
dox |
T7979 |
32773-32775 |
IN |
denotes |
at |
T7980 |
32776-32779 |
CD |
denotes |
200 |
T7981 |
32780-32782 |
NN |
denotes |
mg |
T7982 |
32782-32783 |
SYM |
denotes |
/ |
T7983 |
32783-32785 |
NN |
denotes |
kg |
T7984 |
32786-32791 |
IN |
denotes |
until |
T7985 |
32802-32812 |
VBN |
denotes |
sacrificed |
T7986 |
32792-32796 |
PRP |
denotes |
they |
T7987 |
32797-32801 |
VBD |
denotes |
were |
T7988 |
32813-32815 |
IN |
denotes |
at |
T7989 |
32816-32817 |
CD |
denotes |
9 |
T7990 |
32824-32826 |
NN |
denotes |
mo |
T7991 |
32818-32820 |
CC |
denotes |
or |
T7992 |
32821-32823 |
CD |
denotes |
12 |
T7993 |
32827-32829 |
IN |
denotes |
of |
T7994 |
32830-32833 |
NN |
denotes |
age |
T7995 |
32833-32834 |
. |
denotes |
. |
T7996 |
32834-32904 |
sentence |
denotes |
The remaining control animals were kept on standard chow (untreated). |
T7997 |
32835-32838 |
DT |
denotes |
The |
T7998 |
32857-32864 |
NNS |
denotes |
animals |
T7999 |
32839-32848 |
VBG |
denotes |
remaining |
T8000 |
32849-32856 |
NN |
denotes |
control |
T8001 |
32870-32874 |
VBN |
denotes |
kept |
T8002 |
32865-32869 |
VBD |
denotes |
were |
T8003 |
32875-32877 |
IN |
denotes |
on |
T8004 |
32878-32886 |
JJ |
denotes |
standard |
T8005 |
32887-32891 |
NN |
denotes |
chow |
T8006 |
32892-32893 |
-LRB- |
denotes |
( |
T8007 |
32893-32902 |
JJ |
denotes |
untreated |
T8008 |
32902-32903 |
-RRB- |
denotes |
) |
T8009 |
32903-32904 |
. |
denotes |
. |
T8010 |
32904-33049 |
sentence |
denotes |
In all, four cohorts were created: 6 mo untreated (n = 7), 9 mo untreated (n = 5), 6 mo + 3 mo treated (n = 8), and 6 mo + 6 mo treated (n = 5). |
T8011 |
32905-32907 |
IN |
denotes |
In |
T8012 |
32931-32938 |
VBN |
denotes |
created |
T8013 |
32908-32911 |
DT |
denotes |
all |
T8014 |
32911-32913 |
, |
denotes |
, |
T8015 |
32913-32917 |
CD |
denotes |
four |
T8016 |
32918-32925 |
NNS |
denotes |
cohorts |
T8017 |
32926-32930 |
VBD |
denotes |
were |
T8018 |
32938-32940 |
: |
denotes |
: |
T8019 |
32940-32941 |
CD |
denotes |
6 |
T8020 |
32942-32944 |
NN |
denotes |
mo |
T8021 |
32945-32954 |
JJ |
denotes |
untreated |
T8022 |
32955-32956 |
-LRB- |
denotes |
( |
T8023 |
32960-32961 |
CD |
denotes |
7 |
T8024 |
32956-32957 |
NN |
denotes |
n |
T8025 |
32958-32959 |
SYM |
denotes |
= |
T8026 |
32961-32962 |
-RRB- |
denotes |
) |
T8027 |
32962-32964 |
, |
denotes |
, |
T8028 |
32964-32965 |
CD |
denotes |
9 |
T8029 |
32966-32968 |
NN |
denotes |
mo |
T8030 |
32969-32978 |
JJ |
denotes |
untreated |
T8031 |
32979-32980 |
-LRB- |
denotes |
( |
T8032 |
32984-32985 |
CD |
denotes |
5 |
T8033 |
32980-32981 |
NN |
denotes |
n |
T8034 |
32982-32983 |
SYM |
denotes |
= |
T8035 |
32985-32986 |
-RRB- |
denotes |
) |
T8036 |
32986-32988 |
, |
denotes |
, |
T8037 |
32988-32989 |
CD |
denotes |
6 |
T8038 |
32990-32992 |
NN |
denotes |
mo |
T8039 |
32993-32994 |
SYM |
denotes |
+ |
T8040 |
32995-32996 |
CD |
denotes |
3 |
T8041 |
32997-32999 |
NN |
denotes |
mo |
T8042 |
33000-33007 |
VBN |
denotes |
treated |
T8043 |
33008-33009 |
-LRB- |
denotes |
( |
T8044 |
33013-33014 |
CD |
denotes |
8 |
T8045 |
33009-33010 |
NN |
denotes |
n |
T8046 |
33011-33012 |
SYM |
denotes |
= |
T8047 |
33014-33015 |
-RRB- |
denotes |
) |
T8048 |
33015-33017 |
, |
denotes |
, |
T8049 |
33017-33020 |
CC |
denotes |
and |
T8050 |
33021-33022 |
CD |
denotes |
6 |
T8051 |
33023-33025 |
NN |
denotes |
mo |
T8052 |
33026-33027 |
SYM |
denotes |
+ |
T8053 |
33028-33029 |
CD |
denotes |
6 |
T8054 |
33030-33032 |
NN |
denotes |
mo |
T8055 |
33033-33040 |
VBN |
denotes |
treated |
T8056 |
33041-33042 |
-LRB- |
denotes |
( |
T8057 |
33046-33047 |
CD |
denotes |
5 |
T8058 |
33042-33043 |
NN |
denotes |
n |
T8059 |
33044-33045 |
SYM |
denotes |
= |
T8060 |
33047-33048 |
-RRB- |
denotes |
) |
T8061 |
33048-33049 |
. |
denotes |
. |
T8062 |
33049-33172 |
sentence |
denotes |
Full suppression (>95%) of transgenic APPswe/ind levels in the dox-treated animals was confirmed by immunoblot (Figure 3). |
T8063 |
33050-33054 |
JJ |
denotes |
Full |
T8064 |
33055-33066 |
NN |
denotes |
suppression |
T8065 |
33137-33146 |
VBN |
denotes |
confirmed |
T8066 |
33067-33068 |
-LRB- |
denotes |
( |
T8067 |
33071-33072 |
NN |
denotes |
% |
T8068 |
33068-33069 |
SYM |
denotes |
> |
T8069 |
33069-33071 |
CD |
denotes |
95 |
T8070 |
33072-33073 |
-RRB- |
denotes |
) |
T8071 |
33074-33076 |
IN |
denotes |
of |
T8072 |
33077-33087 |
JJ |
denotes |
transgenic |
T8073 |
33099-33105 |
NNS |
denotes |
levels |
T8074 |
33088-33094 |
NN |
denotes |
APPswe |
T8075 |
33095-33098 |
NN |
denotes |
ind |
T8076 |
33094-33095 |
HYPH |
denotes |
/ |
T8077 |
33106-33108 |
IN |
denotes |
in |
T8078 |
33109-33112 |
DT |
denotes |
the |
T8079 |
33125-33132 |
NNS |
denotes |
animals |
T8080 |
33113-33116 |
NN |
denotes |
dox |
T8081 |
33117-33124 |
VBN |
denotes |
treated |
T8082 |
33116-33117 |
HYPH |
denotes |
- |
T8083 |
33133-33136 |
VBD |
denotes |
was |
T8084 |
33147-33149 |
IN |
denotes |
by |
T8085 |
33150-33160 |
NN |
denotes |
immunoblot |
T8086 |
33161-33162 |
-LRB- |
denotes |
( |
T8087 |
33162-33168 |
NN |
denotes |
Figure |
T8088 |
33169-33170 |
CD |
denotes |
3 |
T8089 |
33170-33171 |
-RRB- |
denotes |
) |
T8090 |
33171-33172 |
. |
denotes |
. |
T8091 |
33172-33399 |
sentence |
denotes |
To ensure that the transgene could be suppressed as rapidly in 6-mo-old mice with fulminant pathology as it can in young, predeposit animals, we treated an additional set of 6-mo-old animals with dox for 1 wk prior to harvest. |
T8092 |
33173-33175 |
TO |
denotes |
To |
T8093 |
33176-33182 |
VB |
denotes |
ensure |
T8094 |
33318-33325 |
VBD |
denotes |
treated |
T8095 |
33183-33187 |
IN |
denotes |
that |
T8096 |
33211-33221 |
VBN |
denotes |
suppressed |
T8097 |
33188-33191 |
DT |
denotes |
the |
T8098 |
33192-33201 |
NN |
denotes |
transgene |
T8099 |
33202-33207 |
MD |
denotes |
could |
T8100 |
33208-33210 |
VB |
denotes |
be |
T8101 |
33222-33224 |
RB |
denotes |
as |
T8102 |
33225-33232 |
RB |
denotes |
rapidly |
T8103 |
33233-33235 |
IN |
denotes |
in |
T8104 |
33236-33237 |
CD |
denotes |
6 |
T8105 |
33238-33240 |
NN |
denotes |
mo |
T8106 |
33237-33238 |
HYPH |
denotes |
- |
T8107 |
33241-33244 |
JJ |
denotes |
old |
T8108 |
33240-33241 |
HYPH |
denotes |
- |
T8109 |
33245-33249 |
NNS |
denotes |
mice |
T8110 |
33250-33254 |
IN |
denotes |
with |
T8111 |
33255-33264 |
JJ |
denotes |
fulminant |
T8112 |
33265-33274 |
NN |
denotes |
pathology |
T8113 |
33275-33277 |
IN |
denotes |
as |
T8114 |
33281-33284 |
MD |
denotes |
can |
T8115 |
33278-33280 |
PRP |
denotes |
it |
T8116 |
33285-33287 |
IN |
denotes |
in |
T8117 |
33288-33293 |
JJ |
denotes |
young |
T8118 |
33306-33313 |
NNS |
denotes |
animals |
T8119 |
33293-33295 |
, |
denotes |
, |
T8120 |
33295-33305 |
JJ |
denotes |
predeposit |
T8121 |
33313-33315 |
, |
denotes |
, |
T8122 |
33315-33317 |
PRP |
denotes |
we |
T8123 |
33326-33328 |
DT |
denotes |
an |
T8124 |
33340-33343 |
NN |
denotes |
set |
T8125 |
33329-33339 |
JJ |
denotes |
additional |
T8126 |
33344-33346 |
IN |
denotes |
of |
T8127 |
33347-33348 |
CD |
denotes |
6 |
T8128 |
33349-33351 |
NN |
denotes |
mo |
T8129 |
33348-33349 |
HYPH |
denotes |
- |
T8130 |
33352-33355 |
JJ |
denotes |
old |
T8131 |
33351-33352 |
HYPH |
denotes |
- |
T8132 |
33356-33363 |
NNS |
denotes |
animals |
T8133 |
33364-33368 |
IN |
denotes |
with |
T8134 |
33369-33372 |
NN |
denotes |
dox |
T8135 |
33373-33376 |
IN |
denotes |
for |
T8136 |
33377-33378 |
CD |
denotes |
1 |
T8137 |
33379-33381 |
NN |
denotes |
wk |
T8138 |
33382-33387 |
JJ |
denotes |
prior |
T8139 |
33388-33390 |
IN |
denotes |
to |
T8140 |
33391-33398 |
NN |
denotes |
harvest |
T8141 |
33398-33399 |
. |
denotes |
. |
T8142 |
33399-33640 |
sentence |
denotes |
Importantly, both APPswe/ind and APP–C-terminal fragment levels were fully suppressed after only 1 wk of treatment, indicating that the in vivo half-life of APPswe/ind and its processed C-terminal fragments are relatively short (Figure 3D). |
T8143 |
33400-33411 |
RB |
denotes |
Importantly |
T8144 |
33475-33485 |
VBN |
denotes |
suppressed |
T8145 |
33411-33413 |
, |
denotes |
, |
T8146 |
33413-33417 |
CC |
denotes |
both |
T8147 |
33425-33428 |
NN |
denotes |
ind |
T8148 |
33418-33424 |
NN |
denotes |
APPswe |
T8149 |
33424-33425 |
HYPH |
denotes |
/ |
T8150 |
33439-33447 |
JJ |
denotes |
terminal |
T8151 |
33429-33432 |
CC |
denotes |
and |
T8152 |
33433-33436 |
NN |
denotes |
APP |
T8153 |
33437-33438 |
NN |
denotes |
C |
T8154 |
33436-33437 |
HYPH |
denotes |
– |
T8155 |
33438-33439 |
HYPH |
denotes |
- |
T8156 |
33457-33463 |
NNS |
denotes |
levels |
T8157 |
33448-33456 |
NN |
denotes |
fragment |
T8158 |
33464-33468 |
VBD |
denotes |
were |
T8159 |
33469-33474 |
RB |
denotes |
fully |
T8160 |
33486-33491 |
IN |
denotes |
after |
T8161 |
33492-33496 |
RB |
denotes |
only |
T8162 |
33499-33501 |
NN |
denotes |
wk |
T8163 |
33497-33498 |
CD |
denotes |
1 |
T8164 |
33502-33504 |
IN |
denotes |
of |
T8165 |
33505-33514 |
NN |
denotes |
treatment |
T8166 |
33514-33516 |
, |
denotes |
, |
T8167 |
33516-33526 |
VBG |
denotes |
indicating |
T8168 |
33527-33531 |
IN |
denotes |
that |
T8169 |
33607-33610 |
VBP |
denotes |
are |
T8170 |
33532-33535 |
DT |
denotes |
the |
T8171 |
33549-33553 |
NN |
denotes |
life |
T8172 |
33536-33538 |
FW |
denotes |
in |
T8173 |
33539-33543 |
FW |
denotes |
vivo |
T8174 |
33544-33548 |
NN |
denotes |
half |
T8175 |
33548-33549 |
HYPH |
denotes |
- |
T8176 |
33554-33556 |
IN |
denotes |
of |
T8177 |
33557-33563 |
NN |
denotes |
APPswe |
T8178 |
33564-33567 |
NN |
denotes |
ind |
T8179 |
33563-33564 |
HYPH |
denotes |
/ |
T8180 |
33568-33571 |
CC |
denotes |
and |
T8181 |
33572-33575 |
PRP$ |
denotes |
its |
T8182 |
33597-33606 |
NNS |
denotes |
fragments |
T8183 |
33576-33585 |
VBN |
denotes |
processed |
T8184 |
33586-33587 |
NN |
denotes |
C |
T8185 |
33588-33596 |
JJ |
denotes |
terminal |
T8186 |
33587-33588 |
HYPH |
denotes |
- |
T8187 |
33611-33621 |
RB |
denotes |
relatively |
T8188 |
33622-33627 |
JJ |
denotes |
short |
T8189 |
33628-33629 |
-LRB- |
denotes |
( |
T8190 |
33636-33638 |
NN |
denotes |
3D |
T8191 |
33629-33635 |
NN |
denotes |
Figure |
T8192 |
33638-33639 |
-RRB- |
denotes |
) |
T8193 |
33639-33640 |
. |
denotes |
. |
T8194 |
33640-35569 |
sentence |
denotes |
Figure 3 Robust Transgene Suppression in Older Mice with Preexisting Amyloid Pathology
(A) Cortical homogenates from 6- to 12-mo-old animals used for pathology studies described below (line 107) were immunoblotted with human-specific antibody 6E10 to examine transgene suppression following 3 or 6 mo of dox treatment. The blot was co-immunostained for endogenous superoxide dismutase 1 (SOD1) as a control for loading.
(B) Quantitation of signal intensity from the Western blot shown in (A). Transgenic APP levels are significantly suppressed following 3 or 6 mo of dox treatment (96.9% and 97.6%, respectively). *, p < 0.001 compared to 6-mo-old untreated animals, Tukey post-hoc test applied to significant effect of group ANOVA F 3,12 = 107.22, p < 0.001. These data demonstrate that strong transgene suppression is attained both before and after the onset of amyloid pathology (see Figure 1 for predeposit experiments).
(C) Experimental design. To examine the effects of chronic Aβ suppression on amyloid pathology after the onset of deposition, we compared untreated controls harvested at 6 and 9 mo of age to animals placed on dox at 6 mo of age and harvested after 3 or 6 mo of treatment.
(D) Dox treatment leads to rapid transgene suppression even in 6-mo-old tTA/APP mice. Immunostaining with 6E10 shows APPswe/ind levels are dramatically reduced in 6-mo-old mice treated for 1 wk with dox (upper panel). A separate blot was immunostained for APP C-terminal fragments with CT15 antibody to show that the precursors to Aβ cleavage are decreased in parallel with the full-length protein (middle panel). Costaining for superoxide dismutase 1 was used as an internal control for loading (lower panel, taken from bottom half of 6E10 blot). Tissue sections from each animal in the four treatment groups were stained for amyloid pathology by Hirano silver, Campbell-Switzer silver, thioflavin-S, and Aβ immunohistochemistry. |
T8195 |
35387-35393 |
NN |
denotes |
Tissue |
T8196 |
35394-35402 |
NNS |
denotes |
sections |
T8197 |
35454-35461 |
VBN |
denotes |
stained |
T8198 |
35403-35407 |
IN |
denotes |
from |
T8199 |
35408-35412 |
DT |
denotes |
each |
T8200 |
35413-35419 |
NN |
denotes |
animal |
T8201 |
35420-35422 |
IN |
denotes |
in |
T8202 |
35423-35426 |
DT |
denotes |
the |
T8203 |
35442-35448 |
NNS |
denotes |
groups |
T8204 |
35427-35431 |
CD |
denotes |
four |
T8205 |
35432-35441 |
NN |
denotes |
treatment |
T8206 |
35449-35453 |
VBD |
denotes |
were |
T8207 |
35462-35465 |
IN |
denotes |
for |
T8208 |
35466-35473 |
NN |
denotes |
amyloid |
T8209 |
35474-35483 |
NN |
denotes |
pathology |
T8210 |
35484-35486 |
IN |
denotes |
by |
T8211 |
35487-35493 |
NNP |
denotes |
Hirano |
T8212 |
35494-35500 |
NN |
denotes |
silver |
T8213 |
35500-35502 |
, |
denotes |
, |
T8214 |
35502-35510 |
NNP |
denotes |
Campbell |
T8215 |
35511-35518 |
NNP |
denotes |
Switzer |
T8216 |
35510-35511 |
HYPH |
denotes |
- |
T8217 |
35519-35525 |
NN |
denotes |
silver |
T8218 |
35525-35527 |
, |
denotes |
, |
T8219 |
35527-35537 |
NN |
denotes |
thioflavin |
T8220 |
35538-35539 |
NN |
denotes |
S |
T8221 |
35537-35538 |
HYPH |
denotes |
- |
T8222 |
35539-35541 |
, |
denotes |
, |
T8223 |
35541-35544 |
CC |
denotes |
and |
T8224 |
35545-35547 |
NN |
denotes |
Aβ |
T8225 |
35548-35568 |
NN |
denotes |
immunohistochemistry |
T8226 |
35568-35569 |
. |
denotes |
. |
T8227 |
35569-35715 |
sentence |
denotes |
As expected, the 6 mo untreated cohort displayed moderate amyloid pathology, and the 9 mo untreated cohort progressed to a severe amyloid burden. |
T8228 |
35570-35572 |
IN |
denotes |
As |
T8229 |
35573-35581 |
VBN |
denotes |
expected |
T8230 |
35609-35618 |
VBD |
denotes |
displayed |
T8231 |
35581-35583 |
, |
denotes |
, |
T8232 |
35583-35586 |
DT |
denotes |
the |
T8233 |
35602-35608 |
NN |
denotes |
cohort |
T8234 |
35587-35588 |
CD |
denotes |
6 |
T8235 |
35589-35591 |
NN |
denotes |
mo |
T8236 |
35592-35601 |
JJ |
denotes |
untreated |
T8237 |
35619-35627 |
JJ |
denotes |
moderate |
T8238 |
35636-35645 |
NN |
denotes |
pathology |
T8239 |
35628-35635 |
NN |
denotes |
amyloid |
T8240 |
35645-35647 |
, |
denotes |
, |
T8241 |
35647-35650 |
CC |
denotes |
and |
T8242 |
35651-35654 |
DT |
denotes |
the |
T8243 |
35670-35676 |
NN |
denotes |
cohort |
T8244 |
35655-35656 |
CD |
denotes |
9 |
T8245 |
35657-35659 |
NN |
denotes |
mo |
T8246 |
35660-35669 |
JJ |
denotes |
untreated |
T8247 |
35677-35687 |
VBD |
denotes |
progressed |
T8248 |
35688-35690 |
IN |
denotes |
to |
T8249 |
35691-35692 |
DT |
denotes |
a |
T8250 |
35708-35714 |
NN |
denotes |
burden |
T8251 |
35693-35699 |
JJ |
denotes |
severe |
T8252 |
35700-35707 |
NN |
denotes |
amyloid |
T8253 |
35714-35715 |
. |
denotes |
. |
T8254 |
35715-35988 |
sentence |
denotes |
In contrast, the extent of amyloid pathology in mice from the 6 mo + 3 mo treated or 6 mo + 6 mo treated cohorts closely resembled that of the 6 mo untreated cohort, despite the significant age difference between the treated and untreated groups (Figures 4 and Figure S3). |
T8255 |
35716-35718 |
IN |
denotes |
In |
T8256 |
35837-35846 |
VBD |
denotes |
resembled |
T8257 |
35719-35727 |
NN |
denotes |
contrast |
T8258 |
35727-35729 |
, |
denotes |
, |
T8259 |
35729-35732 |
DT |
denotes |
the |
T8260 |
35733-35739 |
NN |
denotes |
extent |
T8261 |
35740-35742 |
IN |
denotes |
of |
T8262 |
35743-35750 |
NN |
denotes |
amyloid |
T8263 |
35751-35760 |
NN |
denotes |
pathology |
T8264 |
35761-35763 |
IN |
denotes |
in |
T8265 |
35764-35768 |
NNS |
denotes |
mice |
T8266 |
35769-35773 |
IN |
denotes |
from |
T8267 |
35774-35777 |
DT |
denotes |
the |
T8268 |
35821-35828 |
NNS |
denotes |
cohorts |
T8269 |
35778-35779 |
CD |
denotes |
6 |
T8270 |
35780-35782 |
NN |
denotes |
mo |
T8271 |
35790-35797 |
VBN |
denotes |
treated |
T8272 |
35783-35784 |
SYM |
denotes |
+ |
T8273 |
35785-35786 |
CD |
denotes |
3 |
T8274 |
35787-35789 |
NN |
denotes |
mo |
T8275 |
35798-35800 |
CC |
denotes |
or |
T8276 |
35801-35802 |
CD |
denotes |
6 |
T8277 |
35803-35805 |
NN |
denotes |
mo |
T8278 |
35813-35820 |
VBN |
denotes |
treated |
T8279 |
35806-35807 |
SYM |
denotes |
+ |
T8280 |
35808-35809 |
CD |
denotes |
6 |
T8281 |
35810-35812 |
NN |
denotes |
mo |
T8282 |
35829-35836 |
RB |
denotes |
closely |
T8283 |
35847-35851 |
DT |
denotes |
that |
T8284 |
35852-35854 |
IN |
denotes |
of |
T8285 |
35855-35858 |
DT |
denotes |
the |
T8286 |
35874-35880 |
NN |
denotes |
cohort |
T8287 |
35859-35860 |
CD |
denotes |
6 |
T8288 |
35861-35863 |
NN |
denotes |
mo |
T8289 |
35864-35873 |
JJ |
denotes |
untreated |
T8290 |
35880-35882 |
, |
denotes |
, |
T8291 |
35882-35889 |
IN |
denotes |
despite |
T8292 |
35890-35893 |
DT |
denotes |
the |
T8293 |
35910-35920 |
NN |
denotes |
difference |
T8294 |
35894-35905 |
JJ |
denotes |
significant |
T8295 |
35906-35909 |
NN |
denotes |
age |
T8296 |
35921-35928 |
IN |
denotes |
between |
T8297 |
35929-35932 |
DT |
denotes |
the |
T8298 |
35955-35961 |
NNS |
denotes |
groups |
T8299 |
35933-35940 |
VBN |
denotes |
treated |
T8300 |
35941-35944 |
CC |
denotes |
and |
T8301 |
35945-35954 |
JJ |
denotes |
untreated |
T8302 |
35962-35963 |
-LRB- |
denotes |
( |
T8303 |
35963-35970 |
NNS |
denotes |
Figures |
T8304 |
35971-35972 |
CD |
denotes |
4 |
T8305 |
35973-35976 |
CC |
denotes |
and |
T8306 |
35977-35983 |
NN |
denotes |
Figure |
T8307 |
35984-35986 |
NN |
denotes |
S3 |
T8308 |
35986-35987 |
-RRB- |
denotes |
) |
T8309 |
35987-35988 |
. |
denotes |
. |
T8310 |
35988-36160 |
sentence |
denotes |
Well-formed plaques remained in the treated animals after 6 mo of transgene suppression, even though as much time was given to clear the lesions as they had taken to form. |
T8311 |
35989-35993 |
RB |
denotes |
Well |
T8312 |
35994-36000 |
VBN |
denotes |
formed |
T8313 |
35993-35994 |
HYPH |
denotes |
- |
T8314 |
36001-36008 |
NNS |
denotes |
plaques |
T8315 |
36009-36017 |
VBD |
denotes |
remained |
T8316 |
36018-36020 |
IN |
denotes |
in |
T8317 |
36021-36024 |
DT |
denotes |
the |
T8318 |
36033-36040 |
NNS |
denotes |
animals |
T8319 |
36025-36032 |
VBN |
denotes |
treated |
T8320 |
36041-36046 |
IN |
denotes |
after |
T8321 |
36047-36048 |
CD |
denotes |
6 |
T8322 |
36049-36051 |
NN |
denotes |
mo |
T8323 |
36052-36054 |
IN |
denotes |
of |
T8324 |
36055-36064 |
NN |
denotes |
transgene |
T8325 |
36065-36076 |
NN |
denotes |
suppression |
T8326 |
36076-36078 |
, |
denotes |
, |
T8327 |
36078-36082 |
RB |
denotes |
even |
T8328 |
36107-36112 |
VBN |
denotes |
given |
T8329 |
36083-36089 |
IN |
denotes |
though |
T8330 |
36090-36092 |
RB |
denotes |
as |
T8331 |
36093-36097 |
JJ |
denotes |
much |
T8332 |
36098-36102 |
NN |
denotes |
time |
T8333 |
36103-36106 |
VBD |
denotes |
was |
T8334 |
36113-36115 |
TO |
denotes |
to |
T8335 |
36116-36121 |
VB |
denotes |
clear |
T8336 |
36122-36125 |
DT |
denotes |
the |
T8337 |
36126-36133 |
NNS |
denotes |
lesions |
T8338 |
36134-36136 |
IN |
denotes |
as |
T8339 |
36146-36151 |
VBN |
denotes |
taken |
T8340 |
36137-36141 |
PRP |
denotes |
they |
T8341 |
36142-36145 |
VBD |
denotes |
had |
T8342 |
36152-36154 |
TO |
denotes |
to |
T8343 |
36155-36159 |
VB |
denotes |
form |
T8344 |
36159-36160 |
. |
denotes |
. |
T8345 |
36160-36254 |
sentence |
denotes |
Moreover, both types of amyloid, diffuse and fibrillar, remained intact throughout treatment. |
T8346 |
36161-36169 |
RB |
denotes |
Moreover |
T8347 |
36217-36225 |
VBD |
denotes |
remained |
T8348 |
36169-36171 |
, |
denotes |
, |
T8349 |
36171-36175 |
DT |
denotes |
both |
T8350 |
36176-36181 |
NNS |
denotes |
types |
T8351 |
36182-36184 |
IN |
denotes |
of |
T8352 |
36185-36192 |
NN |
denotes |
amyloid |
T8353 |
36192-36194 |
, |
denotes |
, |
T8354 |
36194-36201 |
JJ |
denotes |
diffuse |
T8355 |
36202-36205 |
CC |
denotes |
and |
T8356 |
36206-36215 |
JJ |
denotes |
fibrillar |
T8357 |
36215-36217 |
, |
denotes |
, |
T8358 |
36226-36232 |
JJ |
denotes |
intact |
T8359 |
36233-36243 |
IN |
denotes |
throughout |
T8360 |
36244-36253 |
NN |
denotes |
treatment |
T8361 |
36253-36254 |
. |
denotes |
. |
T8362 |
36254-36412 |
sentence |
denotes |
Using the Campbell-Switzer silver stain to distinguish different forms of amyloid, we found diffuse plaques were as persistent as cored deposits (Figure S4). |
T8363 |
36255-36260 |
VBG |
denotes |
Using |
T8364 |
36341-36346 |
VBD |
denotes |
found |
T8365 |
36261-36264 |
DT |
denotes |
the |
T8366 |
36289-36294 |
NN |
denotes |
stain |
T8367 |
36265-36273 |
NNP |
denotes |
Campbell |
T8368 |
36274-36281 |
NNP |
denotes |
Switzer |
T8369 |
36273-36274 |
HYPH |
denotes |
- |
T8370 |
36282-36288 |
NN |
denotes |
silver |
T8371 |
36295-36297 |
TO |
denotes |
to |
T8372 |
36298-36309 |
VB |
denotes |
distinguish |
T8373 |
36310-36319 |
JJ |
denotes |
different |
T8374 |
36320-36325 |
NNS |
denotes |
forms |
T8375 |
36326-36328 |
IN |
denotes |
of |
T8376 |
36329-36336 |
NN |
denotes |
amyloid |
T8377 |
36336-36338 |
, |
denotes |
, |
T8378 |
36338-36340 |
PRP |
denotes |
we |
T8379 |
36347-36354 |
JJ |
denotes |
diffuse |
T8380 |
36355-36362 |
NNS |
denotes |
plaques |
T8381 |
36363-36367 |
VBD |
denotes |
were |
T8382 |
36368-36370 |
RB |
denotes |
as |
T8383 |
36371-36381 |
JJ |
denotes |
persistent |
T8384 |
36382-36384 |
IN |
denotes |
as |
T8385 |
36385-36390 |
VBN |
denotes |
cored |
T8386 |
36391-36399 |
NNS |
denotes |
deposits |
T8387 |
36400-36401 |
-LRB- |
denotes |
( |
T8388 |
36408-36410 |
NN |
denotes |
S4 |
T8389 |
36401-36407 |
NN |
denotes |
Figure |
T8390 |
36410-36411 |
-RRB- |
denotes |
) |
T8391 |
36411-36412 |
. |
denotes |
. |
T8392 |
36412-36537 |
sentence |
denotes |
It was nevertheless clear that dox-induced suppression of transgenic APP had completely halted the progression of pathology. |
T8393 |
36413-36415 |
PRP |
denotes |
It |
T8394 |
36416-36419 |
VBD |
denotes |
was |
T8395 |
36420-36432 |
RB |
denotes |
nevertheless |
T8396 |
36433-36438 |
JJ |
denotes |
clear |
T8397 |
36439-36443 |
IN |
denotes |
that |
T8398 |
36501-36507 |
VBN |
denotes |
halted |
T8399 |
36444-36447 |
NN |
denotes |
dox |
T8400 |
36448-36455 |
VBN |
denotes |
induced |
T8401 |
36447-36448 |
HYPH |
denotes |
- |
T8402 |
36456-36467 |
NN |
denotes |
suppression |
T8403 |
36468-36470 |
IN |
denotes |
of |
T8404 |
36471-36481 |
JJ |
denotes |
transgenic |
T8405 |
36482-36485 |
NN |
denotes |
APP |
T8406 |
36486-36489 |
VBD |
denotes |
had |
T8407 |
36490-36500 |
RB |
denotes |
completely |
T8408 |
36508-36511 |
DT |
denotes |
the |
T8409 |
36512-36523 |
NN |
denotes |
progression |
T8410 |
36524-36526 |
IN |
denotes |
of |
T8411 |
36527-36536 |
NN |
denotes |
pathology |
T8412 |
36536-36537 |
. |
denotes |
. |
T8413 |
36537-38441 |
sentence |
denotes |
Figure 4 Suppression of Transgenic APP Arrests Progression of Amyloid Pathology
(A) Aggregated Aβ was quantified in cortical tissue from dox-treated and control tTA/APP mice (line 107) using a filter trap assay. Serial dilutions of protein homogenate were passed through a cellulose acetate filter; protein aggregates larger than the pore size were trapped and immunostained for Aβ.
(B) Quantitation of signal intensity in the linear range of each filter trap dilution series (arrow in [A]) was used to compare aggregate load across treatment groups. Aggregated Aβ increased significantly between 6 and 9 mo of age in untreated mice (significant effect of group ANOVA F 3,18 = 7.85, p < 0.002). This progression of pathology was completely prevented by transgene suppression. The amount of aggregated Aβ was identical in untreated mice at 6 mo of age to that in 9- or 12-mo-old animals treated with dox (p > 0.9, Tukey post-hoc test). Single transgenic tTA samples were included as negative controls and showed no signal above background. *, p < 0.01; **, p < 0.005 versus 9-mo-old untreated mice, Tukey post-hoc test; ***, p < 0.001 versus 9-mo-old untreated mice, Student's t-test.
(C) Amyloid pathology in the hippocampus of representative mice from each treatment group: Hirano silver stain (top row), thioflavin-S (middle row), and Aβ immunohistochemistry (bottom row). Amyloid burden increases dramatically between 6 and 9 mo of age in untreated animals, but remains stable in transgene-suppressed mice over the same period (6 mo + 3 mo dox and 6 mo + 6 mo dox). Single transgenic animals (tTA only shown here) show no sign of amyloid pathology at any age tested. To confirm that the arrest of plaques without any sign of clearance was not unique to the line 107 mice, we repeated the dox-suppression experiment in a second line of tet-off APP mice (CaMKIIα-tTA × tet-APPswe/ind line 18; n = 22). |
T8414 |
38209-38211 |
TO |
denotes |
To |
T8415 |
38212-38219 |
VB |
denotes |
confirm |
T8416 |
38317-38325 |
VBD |
denotes |
repeated |
T8417 |
38220-38224 |
IN |
denotes |
that |
T8418 |
38277-38280 |
VBD |
denotes |
was |
T8419 |
38225-38228 |
DT |
denotes |
the |
T8420 |
38229-38235 |
NN |
denotes |
arrest |
T8421 |
38236-38238 |
IN |
denotes |
of |
T8422 |
38239-38246 |
NNS |
denotes |
plaques |
T8423 |
38247-38254 |
IN |
denotes |
without |
T8424 |
38255-38258 |
DT |
denotes |
any |
T8425 |
38259-38263 |
NN |
denotes |
sign |
T8426 |
38264-38266 |
IN |
denotes |
of |
T8427 |
38267-38276 |
NN |
denotes |
clearance |
T8428 |
38281-38284 |
RB |
denotes |
not |
T8429 |
38285-38291 |
JJ |
denotes |
unique |
T8430 |
38292-38294 |
IN |
denotes |
to |
T8431 |
38295-38298 |
DT |
denotes |
the |
T8432 |
38308-38312 |
NNS |
denotes |
mice |
T8433 |
38299-38303 |
NN |
denotes |
line |
T8434 |
38304-38307 |
CD |
denotes |
107 |
T8435 |
38312-38314 |
, |
denotes |
, |
T8436 |
38314-38316 |
PRP |
denotes |
we |
T8437 |
38326-38329 |
DT |
denotes |
the |
T8438 |
38346-38356 |
NN |
denotes |
experiment |
T8439 |
38330-38333 |
NN |
denotes |
dox |
T8440 |
38334-38345 |
NN |
denotes |
suppression |
T8441 |
38333-38334 |
HYPH |
denotes |
- |
T8442 |
38357-38359 |
IN |
denotes |
in |
T8443 |
38360-38361 |
DT |
denotes |
a |
T8444 |
38369-38373 |
NN |
denotes |
line |
T8445 |
38362-38368 |
JJ |
denotes |
second |
T8446 |
38374-38376 |
IN |
denotes |
of |
T8447 |
38377-38380 |
NN |
denotes |
tet |
T8448 |
38381-38384 |
NN |
denotes |
off |
T8449 |
38380-38381 |
HYPH |
denotes |
- |
T8450 |
38389-38393 |
NNS |
denotes |
mice |
T8451 |
38385-38388 |
NN |
denotes |
APP |
T8452 |
38394-38395 |
-LRB- |
denotes |
( |
T8453 |
38424-38428 |
NN |
denotes |
line |
T8454 |
38395-38402 |
NN |
denotes |
CaMKIIα |
T8455 |
38420-38423 |
NN |
denotes |
ind |
T8456 |
38402-38403 |
HYPH |
denotes |
- |
T8457 |
38403-38406 |
NN |
denotes |
tTA |
T8458 |
38407-38408 |
SYM |
denotes |
× |
T8459 |
38409-38412 |
NN |
denotes |
tet |
T8460 |
38412-38413 |
HYPH |
denotes |
- |
T8461 |
38413-38419 |
NN |
denotes |
APPswe |
T8462 |
38419-38420 |
HYPH |
denotes |
/ |
T8463 |
38429-38431 |
CD |
denotes |
18 |
T8464 |
38431-38432 |
: |
denotes |
; |
T8465 |
38433-38434 |
NN |
denotes |
n |
T8466 |
38437-38439 |
CD |
denotes |
22 |
T8467 |
38435-38436 |
SYM |
denotes |
= |
T8468 |
38439-38440 |
-RRB- |
denotes |
) |
T8469 |
38440-38441 |
. |
denotes |
. |
T8470 |
38441-38634 |
sentence |
denotes |
Again, long-term dox treatment was begun at 6 mo of age, and mice were harvested after 3 mo of transgene suppression (6 mo untreated, n = 8; 9 mo untreated, n = 6; 6 mo + 3 mo treated, n = 8). |
T8471 |
38442-38447 |
RB |
denotes |
Again |
T8472 |
38477-38482 |
VBN |
denotes |
begun |
T8473 |
38447-38449 |
, |
denotes |
, |
T8474 |
38449-38453 |
JJ |
denotes |
long |
T8475 |
38454-38458 |
NN |
denotes |
term |
T8476 |
38453-38454 |
HYPH |
denotes |
- |
T8477 |
38463-38472 |
NN |
denotes |
treatment |
T8478 |
38459-38462 |
NN |
denotes |
dox |
T8479 |
38473-38476 |
VBD |
denotes |
was |
T8480 |
38483-38485 |
IN |
denotes |
at |
T8481 |
38486-38487 |
CD |
denotes |
6 |
T8482 |
38488-38490 |
NN |
denotes |
mo |
T8483 |
38491-38493 |
IN |
denotes |
of |
T8484 |
38494-38497 |
NN |
denotes |
age |
T8485 |
38497-38499 |
, |
denotes |
, |
T8486 |
38499-38502 |
CC |
denotes |
and |
T8487 |
38503-38507 |
NNS |
denotes |
mice |
T8488 |
38513-38522 |
VBN |
denotes |
harvested |
T8489 |
38508-38512 |
VBD |
denotes |
were |
T8490 |
38523-38528 |
IN |
denotes |
after |
T8491 |
38529-38530 |
CD |
denotes |
3 |
T8492 |
38531-38533 |
NN |
denotes |
mo |
T8493 |
38534-38536 |
IN |
denotes |
of |
T8494 |
38537-38546 |
NN |
denotes |
transgene |
T8495 |
38547-38558 |
NN |
denotes |
suppression |
T8496 |
38559-38560 |
-LRB- |
denotes |
( |
T8497 |
38631-38632 |
CD |
denotes |
8 |
T8498 |
38560-38561 |
CD |
denotes |
6 |
T8499 |
38562-38564 |
NN |
denotes |
mo |
T8500 |
38565-38574 |
JJ |
denotes |
untreated |
T8501 |
38580-38581 |
CD |
denotes |
8 |
T8502 |
38574-38576 |
, |
denotes |
, |
T8503 |
38576-38577 |
NN |
denotes |
n |
T8504 |
38578-38579 |
SYM |
denotes |
= |
T8505 |
38581-38582 |
: |
denotes |
; |
T8506 |
38583-38584 |
CD |
denotes |
9 |
T8507 |
38585-38587 |
NN |
denotes |
mo |
T8508 |
38588-38597 |
JJ |
denotes |
untreated |
T8509 |
38603-38604 |
CD |
denotes |
6 |
T8510 |
38597-38599 |
, |
denotes |
, |
T8511 |
38599-38600 |
NN |
denotes |
n |
T8512 |
38601-38602 |
SYM |
denotes |
= |
T8513 |
38604-38605 |
: |
denotes |
; |
T8514 |
38606-38607 |
CD |
denotes |
6 |
T8515 |
38615-38617 |
NN |
denotes |
mo |
T8516 |
38608-38610 |
NN |
denotes |
mo |
T8517 |
38611-38612 |
SYM |
denotes |
+ |
T8518 |
38613-38614 |
CD |
denotes |
3 |
T8519 |
38618-38625 |
VBN |
denotes |
treated |
T8520 |
38625-38627 |
, |
denotes |
, |
T8521 |
38627-38628 |
NN |
denotes |
n |
T8522 |
38629-38630 |
SYM |
denotes |
= |
T8523 |
38632-38633 |
-RRB- |
denotes |
) |
T8524 |
38633-38634 |
. |
denotes |
. |
T8525 |
38634-38730 |
sentence |
denotes |
Immunoblotting for APP confirmed full transgene suppression in the treated animals (Figure S5). |
T8526 |
38635-38649 |
NN |
denotes |
Immunoblotting |
T8527 |
38658-38667 |
VBD |
denotes |
confirmed |
T8528 |
38650-38653 |
IN |
denotes |
for |
T8529 |
38654-38657 |
NN |
denotes |
APP |
T8530 |
38668-38672 |
JJ |
denotes |
full |
T8531 |
38683-38694 |
NN |
denotes |
suppression |
T8532 |
38673-38682 |
NN |
denotes |
transgene |
T8533 |
38695-38697 |
IN |
denotes |
in |
T8534 |
38698-38701 |
DT |
denotes |
the |
T8535 |
38710-38717 |
NNS |
denotes |
animals |
T8536 |
38702-38709 |
VBN |
denotes |
treated |
T8537 |
38718-38719 |
-LRB- |
denotes |
( |
T8538 |
38726-38728 |
NN |
denotes |
S5 |
T8539 |
38719-38725 |
NN |
denotes |
Figure |
T8540 |
38728-38729 |
-RRB- |
denotes |
) |
T8541 |
38729-38730 |
. |
denotes |
. |
T8542 |
38730-38858 |
sentence |
denotes |
As in the line 107 mice described above, amyloid burden worsened substantially in the untreated mice between 6 and 9 mo of age. |
T8543 |
38731-38733 |
IN |
denotes |
As |
T8544 |
38787-38795 |
VBD |
denotes |
worsened |
T8545 |
38734-38736 |
IN |
denotes |
in |
T8546 |
38737-38740 |
DT |
denotes |
the |
T8547 |
38750-38754 |
NNS |
denotes |
mice |
T8548 |
38741-38745 |
NN |
denotes |
line |
T8549 |
38746-38749 |
CD |
denotes |
107 |
T8550 |
38755-38764 |
VBN |
denotes |
described |
T8551 |
38765-38770 |
RB |
denotes |
above |
T8552 |
38770-38772 |
, |
denotes |
, |
T8553 |
38772-38779 |
NN |
denotes |
amyloid |
T8554 |
38780-38786 |
NN |
denotes |
burden |
T8555 |
38796-38809 |
RB |
denotes |
substantially |
T8556 |
38810-38812 |
IN |
denotes |
in |
T8557 |
38813-38816 |
DT |
denotes |
the |
T8558 |
38827-38831 |
NNS |
denotes |
mice |
T8559 |
38817-38826 |
JJ |
denotes |
untreated |
T8560 |
38832-38839 |
IN |
denotes |
between |
T8561 |
38840-38841 |
CD |
denotes |
6 |
T8562 |
38848-38850 |
NN |
denotes |
mo |
T8563 |
38842-38845 |
CC |
denotes |
and |
T8564 |
38846-38847 |
CD |
denotes |
9 |
T8565 |
38851-38853 |
IN |
denotes |
of |
T8566 |
38854-38857 |
NN |
denotes |
age |
T8567 |
38857-38858 |
. |
denotes |
. |
T8568 |
38858-38991 |
sentence |
denotes |
Suppression of transgene expression abruptly arrested progression of pathology (Figure S6), but again without any sign of reduction. |
T8569 |
38859-38870 |
NN |
denotes |
Suppression |
T8570 |
38904-38912 |
VBD |
denotes |
arrested |
T8571 |
38871-38873 |
IN |
denotes |
of |
T8572 |
38874-38883 |
NN |
denotes |
transgene |
T8573 |
38884-38894 |
NN |
denotes |
expression |
T8574 |
38895-38903 |
RB |
denotes |
abruptly |
T8575 |
38913-38924 |
NN |
denotes |
progression |
T8576 |
38925-38927 |
IN |
denotes |
of |
T8577 |
38928-38937 |
NN |
denotes |
pathology |
T8578 |
38938-38939 |
-LRB- |
denotes |
( |
T8579 |
38946-38948 |
NN |
denotes |
S6 |
T8580 |
38939-38945 |
NN |
denotes |
Figure |
T8581 |
38948-38949 |
-RRB- |
denotes |
) |
T8582 |
38949-38951 |
, |
denotes |
, |
T8583 |
38951-38954 |
CC |
denotes |
but |
T8584 |
38961-38968 |
IN |
denotes |
without |
T8585 |
38955-38960 |
RB |
denotes |
again |
T8586 |
38969-38972 |
DT |
denotes |
any |
T8587 |
38973-38977 |
NN |
denotes |
sign |
T8588 |
38978-38980 |
IN |
denotes |
of |
T8589 |
38981-38990 |
NN |
denotes |
reduction |
T8590 |
38990-38991 |
. |
denotes |
. |
T8591 |
38991-39095 |
sentence |
denotes |
Both silver- and thioflavin-S-positive plaques could still be found in each of the dox-treated animals. |
T8592 |
38992-38996 |
CC |
denotes |
Both |
T8593 |
38997-39003 |
NN |
denotes |
silver |
T8594 |
39022-39030 |
JJ |
denotes |
positive |
T8595 |
39003-39004 |
HYPH |
denotes |
- |
T8596 |
39005-39008 |
CC |
denotes |
and |
T8597 |
39009-39019 |
NN |
denotes |
thioflavin |
T8598 |
39020-39021 |
NN |
denotes |
S |
T8599 |
39019-39020 |
HYPH |
denotes |
- |
T8600 |
39021-39022 |
HYPH |
denotes |
- |
T8601 |
39031-39038 |
NNS |
denotes |
plaques |
T8602 |
39054-39059 |
VBN |
denotes |
found |
T8603 |
39039-39044 |
MD |
denotes |
could |
T8604 |
39045-39050 |
RB |
denotes |
still |
T8605 |
39051-39053 |
VB |
denotes |
be |
T8606 |
39060-39062 |
IN |
denotes |
in |
T8607 |
39063-39067 |
DT |
denotes |
each |
T8608 |
39068-39070 |
IN |
denotes |
of |
T8609 |
39071-39074 |
DT |
denotes |
the |
T8610 |
39087-39094 |
NNS |
denotes |
animals |
T8611 |
39075-39078 |
NN |
denotes |
dox |
T8612 |
39079-39086 |
VBN |
denotes |
treated |
T8613 |
39078-39079 |
HYPH |
denotes |
- |
T8614 |
39094-39095 |
. |
denotes |
. |
T8615 |
39095-39278 |
sentence |
denotes |
We biochemically measured the amount of aggregated Aβ in the brains of our mice before and after transgene suppression using filter trap analysis of cortical tissue from each animal. |
T8616 |
39096-39098 |
PRP |
denotes |
We |
T8617 |
39113-39121 |
VBD |
denotes |
measured |
T8618 |
39099-39112 |
RB |
denotes |
biochemically |
T8619 |
39122-39125 |
DT |
denotes |
the |
T8620 |
39126-39132 |
NN |
denotes |
amount |
T8621 |
39133-39135 |
IN |
denotes |
of |
T8622 |
39136-39146 |
VBN |
denotes |
aggregated |
T8623 |
39147-39149 |
NN |
denotes |
Aβ |
T8624 |
39150-39152 |
IN |
denotes |
in |
T8625 |
39153-39156 |
DT |
denotes |
the |
T8626 |
39157-39163 |
NNS |
denotes |
brains |
T8627 |
39164-39166 |
IN |
denotes |
of |
T8628 |
39167-39170 |
PRP$ |
denotes |
our |
T8629 |
39171-39175 |
NNS |
denotes |
mice |
T8630 |
39176-39182 |
IN |
denotes |
before |
T8631 |
39183-39186 |
CC |
denotes |
and |
T8632 |
39187-39192 |
IN |
denotes |
after |
T8633 |
39193-39202 |
NN |
denotes |
transgene |
T8634 |
39203-39214 |
NN |
denotes |
suppression |
T8635 |
39215-39220 |
VBG |
denotes |
using |
T8636 |
39221-39227 |
NN |
denotes |
filter |
T8637 |
39228-39232 |
NN |
denotes |
trap |
T8638 |
39233-39241 |
NN |
denotes |
analysis |
T8639 |
39242-39244 |
IN |
denotes |
of |
T8640 |
39245-39253 |
JJ |
denotes |
cortical |
T8641 |
39254-39260 |
NN |
denotes |
tissue |
T8642 |
39261-39265 |
IN |
denotes |
from |
T8643 |
39266-39270 |
DT |
denotes |
each |
T8644 |
39271-39277 |
NN |
denotes |
animal |
T8645 |
39277-39278 |
. |
denotes |
. |
T8646 |
39278-39501 |
sentence |
denotes |
In this assay, serial dilutions of protein homogenate are passed through a cellulose acetate filter; particles larger than the pore size of the filter become trapped in the membrane and are revealed by immunoblotting [22]. |
T8647 |
39279-39281 |
IN |
denotes |
In |
T8648 |
39337-39343 |
VBN |
denotes |
passed |
T8649 |
39282-39286 |
DT |
denotes |
this |
T8650 |
39287-39292 |
NN |
denotes |
assay |
T8651 |
39292-39294 |
, |
denotes |
, |
T8652 |
39294-39300 |
JJ |
denotes |
serial |
T8653 |
39301-39310 |
NNS |
denotes |
dilutions |
T8654 |
39311-39313 |
IN |
denotes |
of |
T8655 |
39314-39321 |
NN |
denotes |
protein |
T8656 |
39322-39332 |
NN |
denotes |
homogenate |
T8657 |
39333-39336 |
VBP |
denotes |
are |
T8658 |
39430-39436 |
VBP |
denotes |
become |
T8659 |
39344-39351 |
IN |
denotes |
through |
T8660 |
39352-39353 |
DT |
denotes |
a |
T8661 |
39372-39378 |
NN |
denotes |
filter |
T8662 |
39354-39363 |
NN |
denotes |
cellulose |
T8663 |
39364-39371 |
NN |
denotes |
acetate |
T8664 |
39378-39379 |
: |
denotes |
; |
T8665 |
39380-39389 |
NNS |
denotes |
particles |
T8666 |
39390-39396 |
JJR |
denotes |
larger |
T8667 |
39397-39401 |
IN |
denotes |
than |
T8668 |
39402-39405 |
DT |
denotes |
the |
T8669 |
39411-39415 |
NN |
denotes |
size |
T8670 |
39406-39410 |
NN |
denotes |
pore |
T8671 |
39416-39418 |
IN |
denotes |
of |
T8672 |
39419-39422 |
DT |
denotes |
the |
T8673 |
39423-39429 |
NN |
denotes |
filter |
T8674 |
39437-39444 |
JJ |
denotes |
trapped |
T8675 |
39445-39447 |
IN |
denotes |
in |
T8676 |
39448-39451 |
DT |
denotes |
the |
T8677 |
39452-39460 |
NN |
denotes |
membrane |
T8678 |
39461-39464 |
CC |
denotes |
and |
T8679 |
39465-39468 |
VBP |
denotes |
are |
T8680 |
39469-39477 |
VBN |
denotes |
revealed |
T8681 |
39478-39480 |
IN |
denotes |
by |
T8682 |
39481-39495 |
NN |
denotes |
immunoblotting |
T8683 |
39496-39497 |
-LRB- |
denotes |
[ |
T8684 |
39497-39499 |
CD |
denotes |
22 |
T8685 |
39499-39500 |
-RRB- |
denotes |
] |
T8686 |
39500-39501 |
. |
denotes |
. |
T8687 |
39501-39723 |
sentence |
denotes |
Consistent with our visual analysis of the histological sections, line 107 tTA/APP mice treated with dox for 3 or 6 mo had the same amount of aggregated Aβ as when they started treatment at 6 mo of age (Figure 4A and 4B). |
T8688 |
39502-39512 |
JJ |
denotes |
Consistent |
T8689 |
39621-39624 |
VBD |
denotes |
had |
T8690 |
39513-39517 |
IN |
denotes |
with |
T8691 |
39518-39521 |
PRP$ |
denotes |
our |
T8692 |
39529-39537 |
NN |
denotes |
analysis |
T8693 |
39522-39528 |
JJ |
denotes |
visual |
T8694 |
39538-39540 |
IN |
denotes |
of |
T8695 |
39541-39544 |
DT |
denotes |
the |
T8696 |
39558-39566 |
NNS |
denotes |
sections |
T8697 |
39545-39557 |
JJ |
denotes |
histological |
T8698 |
39566-39568 |
, |
denotes |
, |
T8699 |
39568-39572 |
NN |
denotes |
line |
T8700 |
39585-39589 |
NNS |
denotes |
mice |
T8701 |
39573-39576 |
CD |
denotes |
107 |
T8702 |
39577-39580 |
NN |
denotes |
tTA |
T8703 |
39581-39584 |
NN |
denotes |
APP |
T8704 |
39580-39581 |
HYPH |
denotes |
/ |
T8705 |
39590-39597 |
VBN |
denotes |
treated |
T8706 |
39598-39602 |
IN |
denotes |
with |
T8707 |
39603-39606 |
NN |
denotes |
dox |
T8708 |
39607-39610 |
IN |
denotes |
for |
T8709 |
39611-39612 |
CD |
denotes |
3 |
T8710 |
39618-39620 |
NN |
denotes |
mo |
T8711 |
39613-39615 |
CC |
denotes |
or |
T8712 |
39616-39617 |
CD |
denotes |
6 |
T8713 |
39625-39628 |
DT |
denotes |
the |
T8714 |
39634-39640 |
NN |
denotes |
amount |
T8715 |
39629-39633 |
JJ |
denotes |
same |
T8716 |
39641-39643 |
IN |
denotes |
of |
T8717 |
39644-39654 |
VBN |
denotes |
aggregated |
T8718 |
39655-39657 |
NN |
denotes |
Aβ |
T8719 |
39658-39660 |
IN |
denotes |
as |
T8720 |
39661-39665 |
WRB |
denotes |
when |
T8721 |
39671-39678 |
VBD |
denotes |
started |
T8722 |
39666-39670 |
PRP |
denotes |
they |
T8723 |
39679-39688 |
NN |
denotes |
treatment |
T8724 |
39689-39691 |
IN |
denotes |
at |
T8725 |
39692-39693 |
CD |
denotes |
6 |
T8726 |
39694-39696 |
NN |
denotes |
mo |
T8727 |
39697-39699 |
IN |
denotes |
of |
T8728 |
39700-39703 |
NN |
denotes |
age |
T8729 |
39704-39705 |
-LRB- |
denotes |
( |
T8730 |
39712-39714 |
NN |
denotes |
4A |
T8731 |
39705-39711 |
NN |
denotes |
Figure |
T8732 |
39715-39718 |
CC |
denotes |
and |
T8733 |
39719-39721 |
NN |
denotes |
4B |
T8734 |
39721-39722 |
-RRB- |
denotes |
) |
T8735 |
39722-39723 |
. |
denotes |
. |
T8736 |
39723-39832 |
sentence |
denotes |
In contrast, untreated 9-mo-old mice had almost twice as much aggregated Aβ as either of the treated groups. |
T8737 |
39724-39726 |
IN |
denotes |
In |
T8738 |
39761-39764 |
VBD |
denotes |
had |
T8739 |
39727-39735 |
NN |
denotes |
contrast |
T8740 |
39735-39737 |
, |
denotes |
, |
T8741 |
39737-39746 |
JJ |
denotes |
untreated |
T8742 |
39756-39760 |
NNS |
denotes |
mice |
T8743 |
39747-39748 |
CD |
denotes |
9 |
T8744 |
39749-39751 |
NN |
denotes |
mo |
T8745 |
39748-39749 |
HYPH |
denotes |
- |
T8746 |
39752-39755 |
JJ |
denotes |
old |
T8747 |
39751-39752 |
HYPH |
denotes |
- |
T8748 |
39765-39771 |
RB |
denotes |
almost |
T8749 |
39772-39777 |
RB |
denotes |
twice |
T8750 |
39781-39785 |
JJ |
denotes |
much |
T8751 |
39778-39780 |
RB |
denotes |
as |
T8752 |
39797-39799 |
NN |
denotes |
Aβ |
T8753 |
39786-39796 |
VBN |
denotes |
aggregated |
T8754 |
39800-39802 |
IN |
denotes |
as |
T8755 |
39803-39809 |
DT |
denotes |
either |
T8756 |
39810-39812 |
IN |
denotes |
of |
T8757 |
39813-39816 |
DT |
denotes |
the |
T8758 |
39825-39831 |
NNS |
denotes |
groups |
T8759 |
39817-39824 |
VBN |
denotes |
treated |
T8760 |
39831-39832 |
. |
denotes |
. |
T8761 |
39832-40059 |
sentence |
denotes |
Filter trap analysis of line 18 tTA/APP mice yielded similar results: the increase in aggregated Aβ observed in untreated animals between 6 and 9 mo of age was completely arrested by transgene suppression (Figure S5C and S5D). |
T8762 |
39833-39839 |
NN |
denotes |
Filter |
T8763 |
39845-39853 |
NN |
denotes |
analysis |
T8764 |
39840-39844 |
NN |
denotes |
trap |
T8765 |
39878-39885 |
VBD |
denotes |
yielded |
T8766 |
39854-39856 |
IN |
denotes |
of |
T8767 |
39857-39861 |
NN |
denotes |
line |
T8768 |
39873-39877 |
NNS |
denotes |
mice |
T8769 |
39862-39864 |
CD |
denotes |
18 |
T8770 |
39865-39868 |
NN |
denotes |
tTA |
T8771 |
39869-39872 |
NN |
denotes |
APP |
T8772 |
39868-39869 |
HYPH |
denotes |
/ |
T8773 |
40004-40012 |
VBN |
denotes |
arrested |
T8774 |
39886-39893 |
JJ |
denotes |
similar |
T8775 |
39894-39901 |
NNS |
denotes |
results |
T8776 |
39901-39903 |
: |
denotes |
: |
T8777 |
39903-39906 |
DT |
denotes |
the |
T8778 |
39907-39915 |
NN |
denotes |
increase |
T8779 |
39916-39918 |
IN |
denotes |
in |
T8780 |
39919-39929 |
VBN |
denotes |
aggregated |
T8781 |
39930-39932 |
NN |
denotes |
Aβ |
T8782 |
39933-39941 |
VBN |
denotes |
observed |
T8783 |
39942-39944 |
IN |
denotes |
in |
T8784 |
39945-39954 |
JJ |
denotes |
untreated |
T8785 |
39955-39962 |
NNS |
denotes |
animals |
T8786 |
39963-39970 |
IN |
denotes |
between |
T8787 |
39971-39972 |
CD |
denotes |
6 |
T8788 |
39979-39981 |
NN |
denotes |
mo |
T8789 |
39973-39976 |
CC |
denotes |
and |
T8790 |
39977-39978 |
CD |
denotes |
9 |
T8791 |
39982-39984 |
IN |
denotes |
of |
T8792 |
39985-39988 |
NN |
denotes |
age |
T8793 |
39989-39992 |
VBD |
denotes |
was |
T8794 |
39993-40003 |
RB |
denotes |
completely |
T8795 |
40013-40015 |
IN |
denotes |
by |
T8796 |
40016-40025 |
NN |
denotes |
transgene |
T8797 |
40026-40037 |
NN |
denotes |
suppression |
T8798 |
40038-40039 |
-LRB- |
denotes |
( |
T8799 |
40046-40049 |
NN |
denotes |
S5C |
T8800 |
40039-40045 |
NN |
denotes |
Figure |
T8801 |
40050-40053 |
CC |
denotes |
and |
T8802 |
40054-40057 |
NN |
denotes |
S5D |
T8803 |
40057-40058 |
-RRB- |
denotes |
) |
T8804 |
40058-40059 |
. |
denotes |
. |
T8805 |
40059-40250 |
sentence |
denotes |
We next used ELISA to measure total Aβ in the brains of each group to determine whether any change in the amount or solubility of peptide occurred while APPswe/ind expression was suppressed. |
T8806 |
40060-40062 |
PRP |
denotes |
We |
T8807 |
40068-40072 |
VBD |
denotes |
used |
T8808 |
40063-40067 |
RB |
denotes |
next |
T8809 |
40073-40078 |
NN |
denotes |
ELISA |
T8810 |
40079-40081 |
TO |
denotes |
to |
T8811 |
40082-40089 |
VB |
denotes |
measure |
T8812 |
40090-40095 |
JJ |
denotes |
total |
T8813 |
40096-40098 |
NN |
denotes |
Aβ |
T8814 |
40099-40101 |
IN |
denotes |
in |
T8815 |
40102-40105 |
DT |
denotes |
the |
T8816 |
40106-40112 |
NNS |
denotes |
brains |
T8817 |
40113-40115 |
IN |
denotes |
of |
T8818 |
40116-40120 |
DT |
denotes |
each |
T8819 |
40121-40126 |
NN |
denotes |
group |
T8820 |
40127-40129 |
TO |
denotes |
to |
T8821 |
40130-40139 |
VB |
denotes |
determine |
T8822 |
40140-40147 |
IN |
denotes |
whether |
T8823 |
40198-40206 |
VBD |
denotes |
occurred |
T8824 |
40148-40151 |
DT |
denotes |
any |
T8825 |
40152-40158 |
NN |
denotes |
change |
T8826 |
40159-40161 |
IN |
denotes |
in |
T8827 |
40162-40165 |
DT |
denotes |
the |
T8828 |
40166-40172 |
NN |
denotes |
amount |
T8829 |
40173-40175 |
CC |
denotes |
or |
T8830 |
40176-40186 |
NN |
denotes |
solubility |
T8831 |
40187-40189 |
IN |
denotes |
of |
T8832 |
40190-40197 |
NN |
denotes |
peptide |
T8833 |
40207-40212 |
IN |
denotes |
while |
T8834 |
40239-40249 |
VBN |
denotes |
suppressed |
T8835 |
40213-40219 |
NN |
denotes |
APPswe |
T8836 |
40220-40223 |
NN |
denotes |
ind |
T8837 |
40219-40220 |
HYPH |
denotes |
/ |
T8838 |
40224-40234 |
NN |
denotes |
expression |
T8839 |
40235-40238 |
VBD |
denotes |
was |
T8840 |
40249-40250 |
. |
denotes |
. |
T8841 |
40250-40443 |
sentence |
denotes |
Cortical homogenates were sequentially extracted to separate peptide into PBS-, SDS-, and FA-soluble fractions, then transgene-derived Aβ40 and Aβ42 were measured by human-specific ELISA [23]. |
T8842 |
40251-40259 |
JJ |
denotes |
Cortical |
T8843 |
40260-40271 |
NNS |
denotes |
homogenates |
T8844 |
40290-40299 |
VBN |
denotes |
extracted |
T8845 |
40272-40276 |
VBD |
denotes |
were |
T8846 |
40277-40289 |
RB |
denotes |
sequentially |
T8847 |
40405-40413 |
VBN |
denotes |
measured |
T8848 |
40300-40302 |
TO |
denotes |
to |
T8849 |
40303-40311 |
VB |
denotes |
separate |
T8850 |
40312-40319 |
NN |
denotes |
peptide |
T8851 |
40320-40324 |
IN |
denotes |
into |
T8852 |
40325-40328 |
NN |
denotes |
PBS |
T8853 |
40344-40351 |
JJ |
denotes |
soluble |
T8854 |
40328-40329 |
HYPH |
denotes |
- |
T8855 |
40329-40331 |
, |
denotes |
, |
T8856 |
40331-40334 |
NN |
denotes |
SDS |
T8857 |
40334-40335 |
HYPH |
denotes |
- |
T8858 |
40335-40337 |
, |
denotes |
, |
T8859 |
40337-40340 |
CC |
denotes |
and |
T8860 |
40341-40343 |
NN |
denotes |
FA |
T8861 |
40343-40344 |
HYPH |
denotes |
- |
T8862 |
40352-40361 |
NNS |
denotes |
fractions |
T8863 |
40361-40363 |
, |
denotes |
, |
T8864 |
40363-40367 |
RB |
denotes |
then |
T8865 |
40368-40377 |
NN |
denotes |
transgene |
T8866 |
40378-40385 |
VBN |
denotes |
derived |
T8867 |
40377-40378 |
HYPH |
denotes |
- |
T8868 |
40386-40390 |
NN |
denotes |
Aβ40 |
T8869 |
40391-40394 |
CC |
denotes |
and |
T8870 |
40395-40399 |
NN |
denotes |
Aβ42 |
T8871 |
40400-40404 |
VBD |
denotes |
were |
T8872 |
40414-40416 |
IN |
denotes |
by |
T8873 |
40417-40422 |
JJ |
denotes |
human |
T8874 |
40423-40431 |
JJ |
denotes |
specific |
T8875 |
40422-40423 |
HYPH |
denotes |
- |
T8876 |
40432-40437 |
NN |
denotes |
ELISA |
T8877 |
40438-40439 |
-LRB- |
denotes |
[ |
T8878 |
40439-40441 |
CD |
denotes |
23 |
T8879 |
40441-40442 |
-RRB- |
denotes |
] |
T8880 |
40442-40443 |
. |
denotes |
. |
T8881 |
40443-40595 |
sentence |
denotes |
In all animals harboring amyloid deposits, we found that the vast majority of Aβ (>99%) was extracted into the SDS and FA fractions (Figure 5A and 5B). |
T8882 |
40444-40446 |
IN |
denotes |
In |
T8883 |
40490-40495 |
VBD |
denotes |
found |
T8884 |
40447-40450 |
DT |
denotes |
all |
T8885 |
40451-40458 |
NNS |
denotes |
animals |
T8886 |
40459-40468 |
VBG |
denotes |
harboring |
T8887 |
40469-40476 |
NN |
denotes |
amyloid |
T8888 |
40477-40485 |
NNS |
denotes |
deposits |
T8889 |
40485-40487 |
, |
denotes |
, |
T8890 |
40487-40489 |
PRP |
denotes |
we |
T8891 |
40496-40500 |
IN |
denotes |
that |
T8892 |
40536-40545 |
VBN |
denotes |
extracted |
T8893 |
40501-40504 |
DT |
denotes |
the |
T8894 |
40510-40518 |
NN |
denotes |
majority |
T8895 |
40505-40509 |
JJ |
denotes |
vast |
T8896 |
40519-40521 |
IN |
denotes |
of |
T8897 |
40522-40524 |
NN |
denotes |
Aβ |
T8898 |
40525-40526 |
-LRB- |
denotes |
( |
T8899 |
40529-40530 |
NN |
denotes |
% |
T8900 |
40526-40527 |
SYM |
denotes |
> |
T8901 |
40527-40529 |
CD |
denotes |
99 |
T8902 |
40530-40531 |
-RRB- |
denotes |
) |
T8903 |
40532-40535 |
VBD |
denotes |
was |
T8904 |
40546-40550 |
IN |
denotes |
into |
T8905 |
40551-40554 |
DT |
denotes |
the |
T8906 |
40566-40575 |
NNS |
denotes |
fractions |
T8907 |
40555-40558 |
NN |
denotes |
SDS |
T8908 |
40559-40562 |
CC |
denotes |
and |
T8909 |
40563-40565 |
NN |
denotes |
FA |
T8910 |
40576-40577 |
-LRB- |
denotes |
( |
T8911 |
40584-40586 |
NN |
denotes |
5A |
T8912 |
40577-40583 |
NN |
denotes |
Figure |
T8913 |
40587-40590 |
CC |
denotes |
and |
T8914 |
40591-40593 |
NN |
denotes |
5B |
T8915 |
40593-40594 |
-RRB- |
denotes |
) |
T8916 |
40594-40595 |
. |
denotes |
. |
T8917 |
40595-40816 |
sentence |
denotes |
Consistent with the filter trap results presented above, there were no significant differences in SDS- or FA-soluble Aβ between the 6 mo untreated cohort and either the 6 mo + 3 mo treated or 6 mo + 6 mo treated cohorts. |
T8918 |
40596-40606 |
JJ |
denotes |
Consistent |
T8919 |
40659-40663 |
VBD |
denotes |
were |
T8920 |
40607-40611 |
IN |
denotes |
with |
T8921 |
40612-40615 |
DT |
denotes |
the |
T8922 |
40628-40635 |
NNS |
denotes |
results |
T8923 |
40616-40622 |
NN |
denotes |
filter |
T8924 |
40623-40627 |
NN |
denotes |
trap |
T8925 |
40636-40645 |
VBN |
denotes |
presented |
T8926 |
40646-40651 |
RB |
denotes |
above |
T8927 |
40651-40653 |
, |
denotes |
, |
T8928 |
40653-40658 |
EX |
denotes |
there |
T8929 |
40664-40666 |
DT |
denotes |
no |
T8930 |
40679-40690 |
NNS |
denotes |
differences |
T8931 |
40667-40678 |
JJ |
denotes |
significant |
T8932 |
40691-40693 |
IN |
denotes |
in |
T8933 |
40694-40697 |
NN |
denotes |
SDS |
T8934 |
40705-40712 |
JJ |
denotes |
soluble |
T8935 |
40697-40698 |
HYPH |
denotes |
- |
T8936 |
40699-40701 |
CC |
denotes |
or |
T8937 |
40702-40704 |
NN |
denotes |
FA |
T8938 |
40704-40705 |
HYPH |
denotes |
- |
T8939 |
40713-40715 |
NN |
denotes |
Aβ |
T8940 |
40716-40723 |
IN |
denotes |
between |
T8941 |
40724-40727 |
DT |
denotes |
the |
T8942 |
40743-40749 |
NN |
denotes |
cohort |
T8943 |
40728-40729 |
CD |
denotes |
6 |
T8944 |
40730-40732 |
NN |
denotes |
mo |
T8945 |
40733-40742 |
JJ |
denotes |
untreated |
T8946 |
40750-40753 |
CC |
denotes |
and |
T8947 |
40754-40760 |
CC |
denotes |
either |
T8948 |
40808-40815 |
NNS |
denotes |
cohorts |
T8949 |
40761-40764 |
DT |
denotes |
the |
T8950 |
40765-40766 |
CD |
denotes |
6 |
T8951 |
40767-40769 |
NN |
denotes |
mo |
T8952 |
40770-40771 |
SYM |
denotes |
+ |
T8953 |
40772-40773 |
CD |
denotes |
3 |
T8954 |
40774-40776 |
NN |
denotes |
mo |
T8955 |
40777-40784 |
VBN |
denotes |
treated |
T8956 |
40785-40787 |
CC |
denotes |
or |
T8957 |
40788-40789 |
CD |
denotes |
6 |
T8958 |
40790-40792 |
NN |
denotes |
mo |
T8959 |
40793-40794 |
SYM |
denotes |
+ |
T8960 |
40795-40796 |
CD |
denotes |
6 |
T8961 |
40797-40799 |
NN |
denotes |
mo |
T8962 |
40800-40807 |
VBN |
denotes |
treated |
T8963 |
40815-40816 |
. |
denotes |
. |
T8964 |
40816-40973 |
sentence |
denotes |
However, brains of both 6 mo + 3 mo and 6 mo + 6 mo treated cohorts contained roughly twice as much PBS-soluble Aβ40 as untreated 6-mo-old mice (Figure 5C). |
T8965 |
40817-40824 |
RB |
denotes |
However |
T8966 |
40885-40894 |
VBD |
denotes |
contained |
T8967 |
40824-40826 |
, |
denotes |
, |
T8968 |
40826-40832 |
NNS |
denotes |
brains |
T8969 |
40833-40835 |
IN |
denotes |
of |
T8970 |
40836-40840 |
CC |
denotes |
both |
T8971 |
40843-40845 |
NN |
denotes |
mo |
T8972 |
40841-40842 |
CD |
denotes |
6 |
T8973 |
40869-40876 |
VBN |
denotes |
treated |
T8974 |
40846-40847 |
SYM |
denotes |
+ |
T8975 |
40848-40849 |
CD |
denotes |
3 |
T8976 |
40850-40852 |
NN |
denotes |
mo |
T8977 |
40853-40856 |
CC |
denotes |
and |
T8978 |
40857-40858 |
CD |
denotes |
6 |
T8979 |
40859-40861 |
NN |
denotes |
mo |
T8980 |
40862-40863 |
SYM |
denotes |
+ |
T8981 |
40864-40865 |
CD |
denotes |
6 |
T8982 |
40866-40868 |
NN |
denotes |
mo |
T8983 |
40877-40884 |
NNS |
denotes |
cohorts |
T8984 |
40895-40902 |
RB |
denotes |
roughly |
T8985 |
40903-40908 |
RB |
denotes |
twice |
T8986 |
40912-40916 |
JJ |
denotes |
much |
T8987 |
40909-40911 |
RB |
denotes |
as |
T8988 |
40929-40933 |
NN |
denotes |
Aβ40 |
T8989 |
40917-40920 |
NN |
denotes |
PBS |
T8990 |
40920-40921 |
HYPH |
denotes |
- |
T8991 |
40921-40928 |
JJ |
denotes |
soluble |
T8992 |
40934-40936 |
IN |
denotes |
as |
T8993 |
40937-40946 |
JJ |
denotes |
untreated |
T8994 |
40956-40960 |
NNS |
denotes |
mice |
T8995 |
40947-40948 |
CD |
denotes |
6 |
T8996 |
40949-40951 |
NN |
denotes |
mo |
T8997 |
40948-40949 |
HYPH |
denotes |
- |
T8998 |
40952-40955 |
JJ |
denotes |
old |
T8999 |
40951-40952 |
HYPH |
denotes |
- |
T9000 |
40961-40962 |
-LRB- |
denotes |
( |
T9001 |
40969-40971 |
NN |
denotes |
5C |
T9002 |
40962-40968 |
NN |
denotes |
Figure |
T9003 |
40971-40972 |
-RRB- |
denotes |
) |
T9004 |
40972-40973 |
. |
denotes |
. |
T9005 |
40973-41056 |
sentence |
denotes |
Levels of Aβ42 showed a similar trend, but did not reach statistical significance. |
T9006 |
40974-40980 |
NNS |
denotes |
Levels |
T9007 |
40989-40995 |
VBD |
denotes |
showed |
T9008 |
40981-40983 |
IN |
denotes |
of |
T9009 |
40984-40988 |
NN |
denotes |
Aβ42 |
T9010 |
40996-40997 |
DT |
denotes |
a |
T9011 |
41006-41011 |
NN |
denotes |
trend |
T9012 |
40998-41005 |
JJ |
denotes |
similar |
T9013 |
41011-41013 |
, |
denotes |
, |
T9014 |
41013-41016 |
CC |
denotes |
but |
T9015 |
41017-41020 |
VBD |
denotes |
did |
T9016 |
41025-41030 |
VB |
denotes |
reach |
T9017 |
41021-41024 |
RB |
denotes |
not |
T9018 |
41031-41042 |
JJ |
denotes |
statistical |
T9019 |
41043-41055 |
NN |
denotes |
significance |
T9020 |
41055-41056 |
. |
denotes |
. |
T9021 |
41056-41373 |
sentence |
denotes |
In fact, levels of PBS-soluble Aβ40 and Aβ42 in the 6 mo + 3 mo and 6 mo + 6 mo treated cohorts were most similar to that of the 9 mo untreated cohort, suggesting that age, as opposed to synthetic rate (which would be negligible in the treated animals), may determine the fraction of PBS-soluble Aβ in these animals. |
T9022 |
41057-41059 |
IN |
denotes |
In |
T9023 |
41153-41157 |
VBD |
denotes |
were |
T9024 |
41060-41064 |
NN |
denotes |
fact |
T9025 |
41064-41066 |
, |
denotes |
, |
T9026 |
41066-41072 |
NNS |
denotes |
levels |
T9027 |
41073-41075 |
IN |
denotes |
of |
T9028 |
41076-41079 |
NN |
denotes |
PBS |
T9029 |
41080-41087 |
JJ |
denotes |
soluble |
T9030 |
41079-41080 |
HYPH |
denotes |
- |
T9031 |
41088-41092 |
NN |
denotes |
Aβ40 |
T9032 |
41093-41096 |
CC |
denotes |
and |
T9033 |
41097-41101 |
NN |
denotes |
Aβ42 |
T9034 |
41102-41104 |
IN |
denotes |
in |
T9035 |
41105-41108 |
DT |
denotes |
the |
T9036 |
41145-41152 |
NNS |
denotes |
cohorts |
T9037 |
41109-41110 |
CD |
denotes |
6 |
T9038 |
41111-41113 |
NN |
denotes |
mo |
T9039 |
41114-41115 |
SYM |
denotes |
+ |
T9040 |
41116-41117 |
CD |
denotes |
3 |
T9041 |
41118-41120 |
NN |
denotes |
mo |
T9042 |
41121-41124 |
CC |
denotes |
and |
T9043 |
41125-41126 |
CD |
denotes |
6 |
T9044 |
41127-41129 |
NN |
denotes |
mo |
T9045 |
41130-41131 |
SYM |
denotes |
+ |
T9046 |
41132-41133 |
CD |
denotes |
6 |
T9047 |
41134-41136 |
NN |
denotes |
mo |
T9048 |
41137-41144 |
VBN |
denotes |
treated |
T9049 |
41158-41162 |
RBS |
denotes |
most |
T9050 |
41163-41170 |
JJ |
denotes |
similar |
T9051 |
41171-41173 |
IN |
denotes |
to |
T9052 |
41174-41178 |
DT |
denotes |
that |
T9053 |
41179-41181 |
IN |
denotes |
of |
T9054 |
41182-41185 |
DT |
denotes |
the |
T9055 |
41201-41207 |
NN |
denotes |
cohort |
T9056 |
41186-41187 |
CD |
denotes |
9 |
T9057 |
41188-41190 |
NN |
denotes |
mo |
T9058 |
41191-41200 |
JJ |
denotes |
untreated |
T9059 |
41207-41209 |
, |
denotes |
, |
T9060 |
41209-41219 |
VBG |
denotes |
suggesting |
T9061 |
41220-41224 |
IN |
denotes |
that |
T9062 |
41315-41324 |
VB |
denotes |
determine |
T9063 |
41225-41228 |
NN |
denotes |
age |
T9064 |
41228-41230 |
, |
denotes |
, |
T9065 |
41230-41232 |
IN |
denotes |
as |
T9066 |
41233-41240 |
VBN |
denotes |
opposed |
T9067 |
41241-41243 |
IN |
denotes |
to |
T9068 |
41244-41253 |
JJ |
denotes |
synthetic |
T9069 |
41254-41258 |
NN |
denotes |
rate |
T9070 |
41259-41260 |
-LRB- |
denotes |
( |
T9071 |
41260-41265 |
WDT |
denotes |
which |
T9072 |
41272-41274 |
VB |
denotes |
be |
T9073 |
41266-41271 |
MD |
denotes |
would |
T9074 |
41275-41285 |
JJ |
denotes |
negligible |
T9075 |
41286-41288 |
IN |
denotes |
in |
T9076 |
41289-41292 |
DT |
denotes |
the |
T9077 |
41301-41308 |
NNS |
denotes |
animals |
T9078 |
41293-41300 |
VBN |
denotes |
treated |
T9079 |
41308-41309 |
-RRB- |
denotes |
) |
T9080 |
41309-41311 |
, |
denotes |
, |
T9081 |
41311-41314 |
MD |
denotes |
may |
T9082 |
41325-41328 |
DT |
denotes |
the |
T9083 |
41329-41337 |
NN |
denotes |
fraction |
T9084 |
41338-41340 |
IN |
denotes |
of |
T9085 |
41341-41344 |
NN |
denotes |
PBS |
T9086 |
41345-41352 |
JJ |
denotes |
soluble |
T9087 |
41344-41345 |
HYPH |
denotes |
- |
T9088 |
41353-41355 |
NN |
denotes |
Aβ |
T9089 |
41356-41358 |
IN |
denotes |
in |
T9090 |
41359-41364 |
DT |
denotes |
these |
T9091 |
41365-41372 |
NNS |
denotes |
animals |
T9092 |
41372-41373 |
. |
denotes |
. |
T9093 |
41373-43701 |
sentence |
denotes |
Figure 5 Aβ ELISA Confirms Arrest of Progression without Clearance of Peptide in Mice with Preexisting Aggregates
Aβ levels in untreated 6- and 9-mo-old tTA/APP line 107 mice (shown in Figure 4) were compared to those in 9- and 12-mo-old animals treated with dox from the age of 6 mo. Single transgenic APP samples were included as negative controls. Cortical homogenates were fractionated by sequential multi-step extraction with PBS, 2% SDS, and 70% FA followed by human-specific Aβ ELISA to measure transgene-derived peptide in each fraction. Aβ40 is shown in white, Aβ42 in black.
(A and B) Most Aβ in the brains of plaque-bearing mice is extracted into the FA and SDS fractions. Consistent with amyloid burden (Figures 4 and Figure S3), SDS- and FA-extracted Aβ levels in untreated 9-mo-old mice were significantly higher than in untreated 6-mo-old mice (Tukey post-hoc test applied to significant effect of group ANOVA for SDS and FA fractions F 3,18 = 4.72–12.92, p < 0.02). In contrast, 3 or 6 mo of transgene suppression held Aβ at levels equivalent to those harbored when treatment was started (p > 0.2 compared to 6 mo untreated mice, Tukey post-hoc test). *, p < 0.05; **, p < 0.005; ***, p < 0.001 versus 9-mo-old untreated mice, Tukey post-hoc test. Significance for APP versus 9-mo-old untreated mice is based on Student's t-test.
(C) The PBS fraction represents less than 0.1% of total Aβ (note the change in y-axis from [A] and [B]), but only here do Aβ levels in the dox-treated mice differ from those in younger untreated mice. Although both peptides appear elevated in the treated groups compared to the untreated 6-mo-old mice, only Aβ40 reaches statistical significance (p < 0.05, Tukey post-hoc test applied to significant effect of group ANOVA for Aβ40 F 3,18 = 4.60, p < 0.02). A similar trend was seen for Aβ42, where ANOVA yielded a significant effect of group for PBS-soluble Aβ42 (F 3,18 = 3.75, p < 0.03), however this was due only to differences between the untreated 6- and 9-mo-old groups. •, p < 0.05 versus 6-mo-old untreated mice, Tukey post-hoc test; •••, p < 0.001 versus 6-mo-old untreated mice, Student's t-test. We also assessed neuritic and glial pathology surrounding the plaques to determine whether there were any changes in nearby tissue following long-term transgene suppression. |
T9094 |
43528-43530 |
PRP |
denotes |
We |
T9095 |
43536-43544 |
VBD |
denotes |
assessed |
T9096 |
43531-43535 |
RB |
denotes |
also |
T9097 |
43545-43553 |
JJ |
denotes |
neuritic |
T9098 |
43564-43573 |
NN |
denotes |
pathology |
T9099 |
43554-43557 |
CC |
denotes |
and |
T9100 |
43558-43563 |
JJ |
denotes |
glial |
T9101 |
43574-43585 |
VBG |
denotes |
surrounding |
T9102 |
43586-43589 |
DT |
denotes |
the |
T9103 |
43590-43597 |
NNS |
denotes |
plaques |
T9104 |
43598-43600 |
TO |
denotes |
to |
T9105 |
43601-43610 |
VB |
denotes |
determine |
T9106 |
43611-43618 |
IN |
denotes |
whether |
T9107 |
43625-43629 |
VBD |
denotes |
were |
T9108 |
43619-43624 |
EX |
denotes |
there |
T9109 |
43630-43633 |
DT |
denotes |
any |
T9110 |
43634-43641 |
NNS |
denotes |
changes |
T9111 |
43642-43644 |
IN |
denotes |
in |
T9112 |
43645-43651 |
JJ |
denotes |
nearby |
T9113 |
43652-43658 |
NN |
denotes |
tissue |
T9114 |
43659-43668 |
VBG |
denotes |
following |
T9115 |
43669-43673 |
JJ |
denotes |
long |
T9116 |
43674-43678 |
NN |
denotes |
term |
T9117 |
43673-43674 |
HYPH |
denotes |
- |
T9118 |
43689-43700 |
NN |
denotes |
suppression |
T9119 |
43679-43688 |
NN |
denotes |
transgene |
T9120 |
43700-43701 |
. |
denotes |
. |
T9121 |
43701-43817 |
sentence |
denotes |
Both Hirano silver stain and ubiquitin immunostaining showed neuritic pathology in all treatment groups (Figure 6). |
T9122 |
43702-43706 |
CC |
denotes |
Both |
T9123 |
43721-43726 |
NN |
denotes |
stain |
T9124 |
43707-43713 |
NNP |
denotes |
Hirano |
T9125 |
43714-43720 |
NN |
denotes |
silver |
T9126 |
43756-43762 |
VBD |
denotes |
showed |
T9127 |
43727-43730 |
CC |
denotes |
and |
T9128 |
43731-43740 |
NN |
denotes |
ubiquitin |
T9129 |
43741-43755 |
NN |
denotes |
immunostaining |
T9130 |
43763-43771 |
JJ |
denotes |
neuritic |
T9131 |
43772-43781 |
NN |
denotes |
pathology |
T9132 |
43782-43784 |
IN |
denotes |
in |
T9133 |
43785-43788 |
DT |
denotes |
all |
T9134 |
43799-43805 |
NNS |
denotes |
groups |
T9135 |
43789-43798 |
NN |
denotes |
treatment |
T9136 |
43806-43807 |
-LRB- |
denotes |
( |
T9137 |
43807-43813 |
NN |
denotes |
Figure |
T9138 |
43814-43815 |
CD |
denotes |
6 |
T9139 |
43815-43816 |
-RRB- |
denotes |
) |
T9140 |
43816-43817 |
. |
denotes |
. |
T9141 |
43817-43923 |
sentence |
denotes |
Similarly, activated astrocytes immunostained for GFAP were found near plaques in all animals (Figure 6). |
T9142 |
43818-43827 |
RB |
denotes |
Similarly |
T9143 |
43878-43883 |
VBN |
denotes |
found |
T9144 |
43827-43829 |
, |
denotes |
, |
T9145 |
43829-43838 |
VBN |
denotes |
activated |
T9146 |
43839-43849 |
NNS |
denotes |
astrocytes |
T9147 |
43850-43863 |
VBN |
denotes |
immunostained |
T9148 |
43864-43867 |
IN |
denotes |
for |
T9149 |
43868-43872 |
NN |
denotes |
GFAP |
T9150 |
43873-43877 |
VBD |
denotes |
were |
T9151 |
43884-43888 |
IN |
denotes |
near |
T9152 |
43889-43896 |
NNS |
denotes |
plaques |
T9153 |
43897-43899 |
IN |
denotes |
in |
T9154 |
43900-43903 |
DT |
denotes |
all |
T9155 |
43904-43911 |
NNS |
denotes |
animals |
T9156 |
43912-43913 |
-LRB- |
denotes |
( |
T9157 |
43913-43919 |
NN |
denotes |
Figure |
T9158 |
43920-43921 |
CD |
denotes |
6 |
T9159 |
43921-43922 |
-RRB- |
denotes |
) |
T9160 |
43922-43923 |
. |
denotes |
. |
T9161 |
43923-43998 |
sentence |
denotes |
Neuritic and glial pathology were more severe in the older untreated mice. |
T9162 |
43924-43932 |
JJ |
denotes |
Neuritic |
T9163 |
43943-43952 |
NN |
denotes |
pathology |
T9164 |
43933-43936 |
CC |
denotes |
and |
T9165 |
43937-43942 |
JJ |
denotes |
glial |
T9166 |
43953-43957 |
VBD |
denotes |
were |
T9167 |
43958-43962 |
RBR |
denotes |
more |
T9168 |
43963-43969 |
JJ |
denotes |
severe |
T9169 |
43970-43972 |
IN |
denotes |
in |
T9170 |
43973-43976 |
DT |
denotes |
the |
T9171 |
43993-43997 |
NNS |
denotes |
mice |
T9172 |
43977-43982 |
JJR |
denotes |
older |
T9173 |
43983-43992 |
JJ |
denotes |
untreated |
T9174 |
43997-43998 |
. |
denotes |
. |
T9175 |
43998-44193 |
sentence |
denotes |
In contrast, transgene suppression prevented the growth of individual deposits apparent in untreated mice, and limited the surrounding pathology to what was already present when treatment began. |
T9176 |
43999-44001 |
IN |
denotes |
In |
T9177 |
44034-44043 |
VBD |
denotes |
prevented |
T9178 |
44002-44010 |
NN |
denotes |
contrast |
T9179 |
44010-44012 |
, |
denotes |
, |
T9180 |
44012-44021 |
NN |
denotes |
transgene |
T9181 |
44022-44033 |
NN |
denotes |
suppression |
T9182 |
44044-44047 |
DT |
denotes |
the |
T9183 |
44048-44054 |
NN |
denotes |
growth |
T9184 |
44055-44057 |
IN |
denotes |
of |
T9185 |
44058-44068 |
JJ |
denotes |
individual |
T9186 |
44069-44077 |
NNS |
denotes |
deposits |
T9187 |
44078-44086 |
JJ |
denotes |
apparent |
T9188 |
44087-44089 |
IN |
denotes |
in |
T9189 |
44090-44099 |
JJ |
denotes |
untreated |
T9190 |
44100-44104 |
NNS |
denotes |
mice |
T9191 |
44104-44106 |
, |
denotes |
, |
T9192 |
44106-44109 |
CC |
denotes |
and |
T9193 |
44110-44117 |
VBD |
denotes |
limited |
T9194 |
44118-44121 |
DT |
denotes |
the |
T9195 |
44134-44143 |
NN |
denotes |
pathology |
T9196 |
44122-44133 |
VBG |
denotes |
surrounding |
T9197 |
44144-44146 |
IN |
denotes |
to |
T9198 |
44147-44151 |
WP |
denotes |
what |
T9199 |
44152-44155 |
VBD |
denotes |
was |
T9200 |
44156-44163 |
RB |
denotes |
already |
T9201 |
44164-44171 |
JJ |
denotes |
present |
T9202 |
44172-44176 |
WRB |
denotes |
when |
T9203 |
44187-44192 |
VBD |
denotes |
began |
T9204 |
44177-44186 |
NN |
denotes |
treatment |
T9205 |
44192-44193 |
. |
denotes |
. |
T9206 |
44193-44956 |
sentence |
denotes |
Figure 6 Neuritic and Glial Pathology Are Unchanged following Transgene Suppression
Dystrophic neurites and activated astrocytes surround most compact plaques in tet-off APP mice (line 107). Dark-stained, ubiquitin-filled neurites and reactive astrocytes form a halo around cored, fibrillar deposits by 6 mo of age that worsens with time in untreated mice. Both plaque-associated pathologies are arrested, although not reversed, by transgene suppression. Hirano silver stain (top row); GFAP immunohistochemistry (middle row); ubiquitin immunohistochemistry (bottom row). An obvious question we sought to address was whether the deposition of Aβ diminished cognitive ability in untreated mice, and what might happen to cognition when the process was interrupted. |
T9207 |
44766-44768 |
DT |
denotes |
An |
T9208 |
44777-44785 |
NN |
denotes |
question |
T9209 |
44769-44776 |
JJ |
denotes |
obvious |
T9210 |
44807-44810 |
VBD |
denotes |
was |
T9211 |
44786-44788 |
PRP |
denotes |
we |
T9212 |
44789-44795 |
VBD |
denotes |
sought |
T9213 |
44796-44798 |
TO |
denotes |
to |
T9214 |
44799-44806 |
VB |
denotes |
address |
T9215 |
44811-44818 |
IN |
denotes |
whether |
T9216 |
44840-44850 |
VBD |
denotes |
diminished |
T9217 |
44819-44822 |
DT |
denotes |
the |
T9218 |
44823-44833 |
NN |
denotes |
deposition |
T9219 |
44834-44836 |
IN |
denotes |
of |
T9220 |
44837-44839 |
NN |
denotes |
Aβ |
T9221 |
44851-44860 |
JJ |
denotes |
cognitive |
T9222 |
44861-44868 |
NN |
denotes |
ability |
T9223 |
44869-44871 |
IN |
denotes |
in |
T9224 |
44872-44881 |
JJ |
denotes |
untreated |
T9225 |
44882-44886 |
NNS |
denotes |
mice |
T9226 |
44886-44888 |
, |
denotes |
, |
T9227 |
44888-44891 |
CC |
denotes |
and |
T9228 |
44892-44896 |
WP |
denotes |
what |
T9229 |
44903-44909 |
VB |
denotes |
happen |
T9230 |
44897-44902 |
MD |
denotes |
might |
T9231 |
44910-44912 |
IN |
denotes |
to |
T9232 |
44913-44922 |
NN |
denotes |
cognition |
T9233 |
44923-44927 |
WRB |
denotes |
when |
T9234 |
44944-44955 |
VBN |
denotes |
interrupted |
T9235 |
44928-44931 |
DT |
denotes |
the |
T9236 |
44932-44939 |
NN |
denotes |
process |
T9237 |
44940-44943 |
VBD |
denotes |
was |
T9238 |
44955-44956 |
. |
denotes |
. |
T9239 |
44956-45092 |
sentence |
denotes |
Unfortunately, efforts to characterize cognitive behavior were compromised by severe hyperactivity in untreated double transgenic mice. |
T9240 |
44957-44970 |
RB |
denotes |
Unfortunately |
T9241 |
45020-45031 |
VBN |
denotes |
compromised |
T9242 |
44970-44972 |
, |
denotes |
, |
T9243 |
44972-44979 |
NNS |
denotes |
efforts |
T9244 |
44980-44982 |
TO |
denotes |
to |
T9245 |
44983-44995 |
VB |
denotes |
characterize |
T9246 |
44996-45005 |
JJ |
denotes |
cognitive |
T9247 |
45006-45014 |
NN |
denotes |
behavior |
T9248 |
45015-45019 |
VBD |
denotes |
were |
T9249 |
45032-45034 |
IN |
denotes |
by |
T9250 |
45035-45041 |
JJ |
denotes |
severe |
T9251 |
45042-45055 |
NN |
denotes |
hyperactivity |
T9252 |
45056-45058 |
IN |
denotes |
in |
T9253 |
45059-45068 |
JJ |
denotes |
untreated |
T9254 |
45087-45091 |
NNS |
denotes |
mice |
T9255 |
45069-45075 |
JJ |
denotes |
double |
T9256 |
45076-45086 |
JJ |
denotes |
transgenic |
T9257 |
45091-45092 |
. |
denotes |
. |
T9258 |
45092-45277 |
sentence |
denotes |
The tTA/APP animals were often seen running in circles around the perimeter of their cages, and a similar swimming pattern was noted when the mice were tested in the Morris water maze. |
T9259 |
45093-45096 |
DT |
denotes |
The |
T9260 |
45105-45112 |
NNS |
denotes |
animals |
T9261 |
45097-45100 |
NN |
denotes |
tTA |
T9262 |
45101-45104 |
NN |
denotes |
APP |
T9263 |
45100-45101 |
HYPH |
denotes |
/ |
T9264 |
45124-45128 |
VBN |
denotes |
seen |
T9265 |
45113-45117 |
VBD |
denotes |
were |
T9266 |
45118-45123 |
RB |
denotes |
often |
T9267 |
45129-45136 |
VBG |
denotes |
running |
T9268 |
45137-45139 |
IN |
denotes |
in |
T9269 |
45140-45147 |
NNS |
denotes |
circles |
T9270 |
45148-45154 |
IN |
denotes |
around |
T9271 |
45155-45158 |
DT |
denotes |
the |
T9272 |
45159-45168 |
NN |
denotes |
perimeter |
T9273 |
45169-45171 |
IN |
denotes |
of |
T9274 |
45172-45177 |
PRP$ |
denotes |
their |
T9275 |
45178-45183 |
NNS |
denotes |
cages |
T9276 |
45183-45185 |
, |
denotes |
, |
T9277 |
45185-45188 |
CC |
denotes |
and |
T9278 |
45189-45190 |
DT |
denotes |
a |
T9279 |
45208-45215 |
NN |
denotes |
pattern |
T9280 |
45191-45198 |
JJ |
denotes |
similar |
T9281 |
45199-45207 |
NN |
denotes |
swimming |
T9282 |
45220-45225 |
VBN |
denotes |
noted |
T9283 |
45216-45219 |
VBD |
denotes |
was |
T9284 |
45226-45230 |
WRB |
denotes |
when |
T9285 |
45245-45251 |
VBN |
denotes |
tested |
T9286 |
45231-45234 |
DT |
denotes |
the |
T9287 |
45235-45239 |
NNS |
denotes |
mice |
T9288 |
45240-45244 |
VBD |
denotes |
were |
T9289 |
45252-45254 |
IN |
denotes |
in |
T9290 |
45255-45258 |
DT |
denotes |
the |
T9291 |
45272-45276 |
NN |
denotes |
maze |
T9292 |
45259-45265 |
NNP |
denotes |
Morris |
T9293 |
45266-45271 |
NN |
denotes |
water |
T9294 |
45276-45277 |
. |
denotes |
. |
T9295 |
45277-45385 |
sentence |
denotes |
In the radial water maze, repetitive swim patterns were noted with no evidence of choice-motivated actions. |
T9296 |
45278-45280 |
IN |
denotes |
In |
T9297 |
45334-45339 |
VBN |
denotes |
noted |
T9298 |
45281-45284 |
DT |
denotes |
the |
T9299 |
45298-45302 |
NN |
denotes |
maze |
T9300 |
45285-45291 |
JJ |
denotes |
radial |
T9301 |
45292-45297 |
NN |
denotes |
water |
T9302 |
45302-45304 |
, |
denotes |
, |
T9303 |
45304-45314 |
JJ |
denotes |
repetitive |
T9304 |
45320-45328 |
NNS |
denotes |
patterns |
T9305 |
45315-45319 |
NN |
denotes |
swim |
T9306 |
45329-45333 |
VBD |
denotes |
were |
T9307 |
45340-45344 |
IN |
denotes |
with |
T9308 |
45345-45347 |
DT |
denotes |
no |
T9309 |
45348-45356 |
NN |
denotes |
evidence |
T9310 |
45357-45359 |
IN |
denotes |
of |
T9311 |
45360-45366 |
NN |
denotes |
choice |
T9312 |
45367-45376 |
VBN |
denotes |
motivated |
T9313 |
45366-45367 |
HYPH |
denotes |
- |
T9314 |
45377-45384 |
NNS |
denotes |
actions |
T9315 |
45384-45385 |
. |
denotes |
. |
T9316 |
45385-45573 |
sentence |
denotes |
Other studies have dealt with similar problems by excluding animals that do not show adequate attention to the task, retaining only those mice that meet certain performance criteria [30]. |
T9317 |
45386-45391 |
JJ |
denotes |
Other |
T9318 |
45392-45399 |
NNS |
denotes |
studies |
T9319 |
45405-45410 |
VBN |
denotes |
dealt |
T9320 |
45400-45404 |
VBP |
denotes |
have |
T9321 |
45411-45415 |
IN |
denotes |
with |
T9322 |
45416-45423 |
JJ |
denotes |
similar |
T9323 |
45424-45432 |
NNS |
denotes |
problems |
T9324 |
45433-45435 |
IN |
denotes |
by |
T9325 |
45436-45445 |
VBG |
denotes |
excluding |
T9326 |
45446-45453 |
NNS |
denotes |
animals |
T9327 |
45454-45458 |
WDT |
denotes |
that |
T9328 |
45466-45470 |
VB |
denotes |
show |
T9329 |
45459-45461 |
VBP |
denotes |
do |
T9330 |
45462-45465 |
RB |
denotes |
not |
T9331 |
45471-45479 |
JJ |
denotes |
adequate |
T9332 |
45480-45489 |
NN |
denotes |
attention |
T9333 |
45490-45492 |
IN |
denotes |
to |
T9334 |
45493-45496 |
DT |
denotes |
the |
T9335 |
45497-45501 |
NN |
denotes |
task |
T9336 |
45501-45503 |
, |
denotes |
, |
T9337 |
45503-45512 |
VBG |
denotes |
retaining |
T9338 |
45513-45517 |
RB |
denotes |
only |
T9339 |
45524-45528 |
NNS |
denotes |
mice |
T9340 |
45518-45523 |
DT |
denotes |
those |
T9341 |
45529-45533 |
WDT |
denotes |
that |
T9342 |
45534-45538 |
VBP |
denotes |
meet |
T9343 |
45539-45546 |
JJ |
denotes |
certain |
T9344 |
45559-45567 |
NNS |
denotes |
criteria |
T9345 |
45547-45558 |
NN |
denotes |
performance |
T9346 |
45568-45569 |
-LRB- |
denotes |
[ |
T9347 |
45569-45571 |
CD |
denotes |
30 |
T9348 |
45571-45572 |
-RRB- |
denotes |
] |
T9349 |
45572-45573 |
. |
denotes |
. |
T9350 |
45573-45674 |
sentence |
denotes |
In our case, the penetrance of hyperactivity was close to 100%, leaving us with no testable animals. |
T9351 |
45574-45576 |
IN |
denotes |
In |
T9352 |
45619-45622 |
VBD |
denotes |
was |
T9353 |
45577-45580 |
PRP$ |
denotes |
our |
T9354 |
45581-45585 |
NN |
denotes |
case |
T9355 |
45585-45587 |
, |
denotes |
, |
T9356 |
45587-45590 |
DT |
denotes |
the |
T9357 |
45591-45601 |
NN |
denotes |
penetrance |
T9358 |
45602-45604 |
IN |
denotes |
of |
T9359 |
45605-45618 |
NN |
denotes |
hyperactivity |
T9360 |
45623-45628 |
JJ |
denotes |
close |
T9361 |
45632-45635 |
CD |
denotes |
100 |
T9362 |
45629-45631 |
IN |
denotes |
to |
T9363 |
45635-45636 |
NN |
denotes |
% |
T9364 |
45636-45638 |
, |
denotes |
, |
T9365 |
45638-45645 |
VBG |
denotes |
leaving |
T9366 |
45646-45648 |
PRP |
denotes |
us |
T9367 |
45649-45653 |
IN |
denotes |
with |
T9368 |
45654-45656 |
DT |
denotes |
no |
T9369 |
45666-45673 |
NNS |
denotes |
animals |
T9370 |
45657-45665 |
JJ |
denotes |
testable |
T9371 |
45673-45674 |
. |
denotes |
. |
T9372 |
45674-45831 |
sentence |
denotes |
This phenotype has not affected previous lines of APPswe mice we have produced, such as lines E1–2 or C3–3, that express lower levels of transgenic protein. |
T9373 |
45675-45679 |
DT |
denotes |
This |
T9374 |
45680-45689 |
NN |
denotes |
phenotype |
T9375 |
45698-45706 |
VBN |
denotes |
affected |
T9376 |
45690-45693 |
VBZ |
denotes |
has |
T9377 |
45694-45697 |
RB |
denotes |
not |
T9378 |
45707-45715 |
JJ |
denotes |
previous |
T9379 |
45716-45721 |
NNS |
denotes |
lines |
T9380 |
45722-45724 |
IN |
denotes |
of |
T9381 |
45725-45731 |
NN |
denotes |
APPswe |
T9382 |
45732-45736 |
NNS |
denotes |
mice |
T9383 |
45737-45739 |
PRP |
denotes |
we |
T9384 |
45745-45753 |
VBN |
denotes |
produced |
T9385 |
45740-45744 |
VBP |
denotes |
have |
T9386 |
45753-45755 |
, |
denotes |
, |
T9387 |
45755-45759 |
JJ |
denotes |
such |
T9388 |
45760-45762 |
IN |
denotes |
as |
T9389 |
45763-45768 |
NNS |
denotes |
lines |
T9390 |
45769-45771 |
NN |
denotes |
E1 |
T9391 |
45771-45772 |
HYPH |
denotes |
– |
T9392 |
45772-45773 |
CD |
denotes |
2 |
T9393 |
45774-45776 |
CC |
denotes |
or |
T9394 |
45777-45779 |
NN |
denotes |
C3 |
T9395 |
45779-45780 |
HYPH |
denotes |
– |
T9396 |
45780-45781 |
CD |
denotes |
3 |
T9397 |
45781-45783 |
, |
denotes |
, |
T9398 |
45783-45787 |
WDT |
denotes |
that |
T9399 |
45788-45795 |
VBP |
denotes |
express |
T9400 |
45796-45801 |
JJR |
denotes |
lower |
T9401 |
45802-45808 |
NNS |
denotes |
levels |
T9402 |
45809-45811 |
IN |
denotes |
of |
T9403 |
45812-45822 |
JJ |
denotes |
transgenic |
T9404 |
45823-45830 |
NN |
denotes |
protein |
T9405 |
45830-45831 |
. |
denotes |
. |
T9406 |
45831-45978 |
sentence |
denotes |
Indeed, in past studies where hyperactivity was not a factor, we established a clear relationship between amyloid load and cognitive ability [31]. |
T9407 |
45832-45838 |
RB |
denotes |
Indeed |
T9408 |
45897-45908 |
VBD |
denotes |
established |
T9409 |
45838-45840 |
, |
denotes |
, |
T9410 |
45840-45842 |
IN |
denotes |
in |
T9411 |
45843-45847 |
JJ |
denotes |
past |
T9412 |
45848-45855 |
NNS |
denotes |
studies |
T9413 |
45856-45861 |
WRB |
denotes |
where |
T9414 |
45876-45879 |
VBD |
denotes |
was |
T9415 |
45862-45875 |
NN |
denotes |
hyperactivity |
T9416 |
45880-45883 |
RB |
denotes |
not |
T9417 |
45884-45885 |
DT |
denotes |
a |
T9418 |
45886-45892 |
NN |
denotes |
factor |
T9419 |
45892-45894 |
, |
denotes |
, |
T9420 |
45894-45896 |
PRP |
denotes |
we |
T9421 |
45909-45910 |
DT |
denotes |
a |
T9422 |
45917-45929 |
NN |
denotes |
relationship |
T9423 |
45911-45916 |
JJ |
denotes |
clear |
T9424 |
45930-45937 |
IN |
denotes |
between |
T9425 |
45938-45945 |
NN |
denotes |
amyloid |
T9426 |
45946-45950 |
NN |
denotes |
load |
T9427 |
45951-45954 |
CC |
denotes |
and |
T9428 |
45955-45964 |
JJ |
denotes |
cognitive |
T9429 |
45965-45972 |
NN |
denotes |
ability |
T9430 |
45973-45974 |
-LRB- |
denotes |
[ |
T9431 |
45974-45976 |
CD |
denotes |
31 |
T9432 |
45976-45977 |
-RRB- |
denotes |
] |
T9433 |
45977-45978 |
. |
denotes |
. |
T9434 |
45978-46232 |
sentence |
denotes |
However, in the current study, we feel that although the poor performance of the tTA/APP mice in the maze tests could technically be scored as cognitive impairment, the animals' severe hyperactivity made interpretation of the cognitive tasks impossible. |
T9435 |
45979-45986 |
RB |
denotes |
However |
T9436 |
46013-46017 |
VBP |
denotes |
feel |
T9437 |
45986-45988 |
, |
denotes |
, |
T9438 |
45988-45990 |
IN |
denotes |
in |
T9439 |
45991-45994 |
DT |
denotes |
the |
T9440 |
46003-46008 |
NN |
denotes |
study |
T9441 |
45995-46002 |
JJ |
denotes |
current |
T9442 |
46008-46010 |
, |
denotes |
, |
T9443 |
46010-46012 |
PRP |
denotes |
we |
T9444 |
46018-46022 |
IN |
denotes |
that |
T9445 |
46178-46182 |
VBD |
denotes |
made |
T9446 |
46023-46031 |
IN |
denotes |
although |
T9447 |
46112-46118 |
VBN |
denotes |
scored |
T9448 |
46032-46035 |
DT |
denotes |
the |
T9449 |
46041-46052 |
NN |
denotes |
performance |
T9450 |
46036-46040 |
JJ |
denotes |
poor |
T9451 |
46053-46055 |
IN |
denotes |
of |
T9452 |
46056-46059 |
DT |
denotes |
the |
T9453 |
46068-46072 |
NNS |
denotes |
mice |
T9454 |
46060-46063 |
NN |
denotes |
tTA |
T9455 |
46064-46067 |
NN |
denotes |
APP |
T9456 |
46063-46064 |
HYPH |
denotes |
/ |
T9457 |
46073-46075 |
IN |
denotes |
in |
T9458 |
46076-46079 |
DT |
denotes |
the |
T9459 |
46085-46090 |
NNS |
denotes |
tests |
T9460 |
46080-46084 |
NN |
denotes |
maze |
T9461 |
46091-46096 |
MD |
denotes |
could |
T9462 |
46097-46108 |
RB |
denotes |
technically |
T9463 |
46109-46111 |
VB |
denotes |
be |
T9464 |
46119-46121 |
IN |
denotes |
as |
T9465 |
46122-46131 |
JJ |
denotes |
cognitive |
T9466 |
46132-46142 |
NN |
denotes |
impairment |
T9467 |
46142-46144 |
, |
denotes |
, |
T9468 |
46144-46147 |
DT |
denotes |
the |
T9469 |
46148-46155 |
NNS |
denotes |
animals |
T9470 |
46164-46177 |
NN |
denotes |
hyperactivity |
T9471 |
46155-46156 |
POS |
denotes |
' |
T9472 |
46157-46163 |
JJ |
denotes |
severe |
T9473 |
46183-46197 |
NN |
denotes |
interpretation |
T9474 |
46221-46231 |
JJ |
denotes |
impossible |
T9475 |
46198-46200 |
IN |
denotes |
of |
T9476 |
46201-46204 |
DT |
denotes |
the |
T9477 |
46215-46220 |
NNS |
denotes |
tasks |
T9478 |
46205-46214 |
JJ |
denotes |
cognitive |
T9479 |
46231-46232 |
. |
denotes |
. |
T9480 |
46232-46521 |
sentence |
denotes |
In order to understand the nature and extent of hyperactivity in the tTA/APP mice, we quantified daily activity levels in double transgenic animals along with their single transgenic and nontransgenic siblings using four-beam frames designed to monitor ambulation within an enclosed cage. |
T9481 |
46233-46235 |
IN |
denotes |
In |
T9482 |
46319-46329 |
VBD |
denotes |
quantified |
T9483 |
46236-46241 |
NN |
denotes |
order |
T9484 |
46242-46244 |
TO |
denotes |
to |
T9485 |
46245-46255 |
VB |
denotes |
understand |
T9486 |
46256-46259 |
DT |
denotes |
the |
T9487 |
46260-46266 |
NN |
denotes |
nature |
T9488 |
46267-46270 |
CC |
denotes |
and |
T9489 |
46271-46277 |
NN |
denotes |
extent |
T9490 |
46278-46280 |
IN |
denotes |
of |
T9491 |
46281-46294 |
NN |
denotes |
hyperactivity |
T9492 |
46295-46297 |
IN |
denotes |
in |
T9493 |
46298-46301 |
DT |
denotes |
the |
T9494 |
46310-46314 |
NNS |
denotes |
mice |
T9495 |
46302-46305 |
NN |
denotes |
tTA |
T9496 |
46306-46309 |
NN |
denotes |
APP |
T9497 |
46305-46306 |
HYPH |
denotes |
/ |
T9498 |
46314-46316 |
, |
denotes |
, |
T9499 |
46316-46318 |
PRP |
denotes |
we |
T9500 |
46330-46335 |
JJ |
denotes |
daily |
T9501 |
46345-46351 |
NNS |
denotes |
levels |
T9502 |
46336-46344 |
NN |
denotes |
activity |
T9503 |
46352-46354 |
IN |
denotes |
in |
T9504 |
46355-46361 |
JJ |
denotes |
double |
T9505 |
46362-46372 |
JJ |
denotes |
transgenic |
T9506 |
46373-46380 |
NNS |
denotes |
animals |
T9507 |
46381-46386 |
IN |
denotes |
along |
T9508 |
46387-46391 |
IN |
denotes |
with |
T9509 |
46392-46397 |
PRP$ |
denotes |
their |
T9510 |
46434-46442 |
NNS |
denotes |
siblings |
T9511 |
46398-46404 |
JJ |
denotes |
single |
T9512 |
46405-46415 |
JJ |
denotes |
transgenic |
T9513 |
46416-46419 |
CC |
denotes |
and |
T9514 |
46420-46433 |
JJ |
denotes |
nontransgenic |
T9515 |
46443-46448 |
VBG |
denotes |
using |
T9516 |
46449-46453 |
CD |
denotes |
four |
T9517 |
46454-46458 |
NN |
denotes |
beam |
T9518 |
46453-46454 |
HYPH |
denotes |
- |
T9519 |
46459-46465 |
NNS |
denotes |
frames |
T9520 |
46466-46474 |
VBN |
denotes |
designed |
T9521 |
46475-46477 |
TO |
denotes |
to |
T9522 |
46478-46485 |
VB |
denotes |
monitor |
T9523 |
46486-46496 |
NN |
denotes |
ambulation |
T9524 |
46497-46503 |
IN |
denotes |
within |
T9525 |
46504-46506 |
DT |
denotes |
an |
T9526 |
46516-46520 |
NN |
denotes |
cage |
T9527 |
46507-46515 |
VBN |
denotes |
enclosed |
T9528 |
46520-46521 |
. |
denotes |
. |
T9529 |
46521-46678 |
sentence |
denotes |
As shown in Figure 7, the double transgenic mice were up to 10-fold more active during the dark phase of the day–night cycle than any of the control groups. |
T9530 |
46522-46524 |
IN |
denotes |
As |
T9531 |
46525-46530 |
VBN |
denotes |
shown |
T9532 |
46571-46575 |
VBD |
denotes |
were |
T9533 |
46531-46533 |
IN |
denotes |
in |
T9534 |
46534-46540 |
NN |
denotes |
Figure |
T9535 |
46541-46542 |
CD |
denotes |
7 |
T9536 |
46542-46544 |
, |
denotes |
, |
T9537 |
46544-46547 |
DT |
denotes |
the |
T9538 |
46566-46570 |
NNS |
denotes |
mice |
T9539 |
46548-46554 |
JJ |
denotes |
double |
T9540 |
46555-46565 |
JJ |
denotes |
transgenic |
T9541 |
46576-46578 |
IN |
denotes |
up |
T9542 |
46582-46589 |
RB |
denotes |
10-fold |
T9543 |
46579-46581 |
IN |
denotes |
to |
T9544 |
46595-46601 |
JJ |
denotes |
active |
T9545 |
46590-46594 |
RBR |
denotes |
more |
T9546 |
46602-46608 |
IN |
denotes |
during |
T9547 |
46609-46612 |
DT |
denotes |
the |
T9548 |
46618-46623 |
NN |
denotes |
phase |
T9549 |
46613-46617 |
NN |
denotes |
dark |
T9550 |
46624-46626 |
IN |
denotes |
of |
T9551 |
46627-46630 |
DT |
denotes |
the |
T9552 |
46641-46646 |
NN |
denotes |
cycle |
T9553 |
46631-46634 |
NN |
denotes |
day |
T9554 |
46635-46640 |
NN |
denotes |
night |
T9555 |
46634-46635 |
HYPH |
denotes |
– |
T9556 |
46647-46651 |
IN |
denotes |
than |
T9557 |
46652-46655 |
DT |
denotes |
any |
T9558 |
46656-46658 |
IN |
denotes |
of |
T9559 |
46659-46662 |
DT |
denotes |
the |
T9560 |
46671-46677 |
NNS |
denotes |
groups |
T9561 |
46663-46670 |
NN |
denotes |
control |
T9562 |
46677-46678 |
. |
denotes |
. |
T9563 |
46678-46800 |
sentence |
denotes |
Activity levels appeared to follow a relatively normal diurnal cycle, decreasing substantially during the daylight hours. |
T9564 |
46679-46687 |
NN |
denotes |
Activity |
T9565 |
46688-46694 |
NNS |
denotes |
levels |
T9566 |
46695-46703 |
VBD |
denotes |
appeared |
T9567 |
46704-46706 |
TO |
denotes |
to |
T9568 |
46707-46713 |
VB |
denotes |
follow |
T9569 |
46714-46715 |
DT |
denotes |
a |
T9570 |
46742-46747 |
NN |
denotes |
cycle |
T9571 |
46716-46726 |
RB |
denotes |
relatively |
T9572 |
46727-46733 |
JJ |
denotes |
normal |
T9573 |
46734-46741 |
JJ |
denotes |
diurnal |
T9574 |
46747-46749 |
, |
denotes |
, |
T9575 |
46749-46759 |
VBG |
denotes |
decreasing |
T9576 |
46760-46773 |
RB |
denotes |
substantially |
T9577 |
46774-46780 |
IN |
denotes |
during |
T9578 |
46781-46784 |
DT |
denotes |
the |
T9579 |
46794-46799 |
NNS |
denotes |
hours |
T9580 |
46785-46793 |
NN |
denotes |
daylight |
T9581 |
46799-46800 |
. |
denotes |
. |
T9582 |
46800-46908 |
sentence |
denotes |
However, even during the light phase, the tTA/APP mice remained many-fold more active than normal controls. |
T9583 |
46801-46808 |
RB |
denotes |
However |
T9584 |
46856-46864 |
VBD |
denotes |
remained |
T9585 |
46808-46810 |
, |
denotes |
, |
T9586 |
46810-46814 |
RB |
denotes |
even |
T9587 |
46815-46821 |
IN |
denotes |
during |
T9588 |
46822-46825 |
DT |
denotes |
the |
T9589 |
46832-46837 |
NN |
denotes |
phase |
T9590 |
46826-46831 |
NN |
denotes |
light |
T9591 |
46837-46839 |
, |
denotes |
, |
T9592 |
46839-46842 |
DT |
denotes |
the |
T9593 |
46851-46855 |
NNS |
denotes |
mice |
T9594 |
46843-46846 |
NN |
denotes |
tTA |
T9595 |
46847-46850 |
NN |
denotes |
APP |
T9596 |
46846-46847 |
HYPH |
denotes |
/ |
T9597 |
46865-46874 |
RB |
denotes |
many-fold |
T9598 |
46875-46879 |
RBR |
denotes |
more |
T9599 |
46880-46886 |
JJ |
denotes |
active |
T9600 |
46887-46891 |
IN |
denotes |
than |
T9601 |
46892-46898 |
JJ |
denotes |
normal |
T9602 |
46899-46907 |
NNS |
denotes |
controls |
T9603 |
46907-46908 |
. |
denotes |
. |
T9604 |
46908-47046 |
sentence |
denotes |
This behavior was partially, but not consistently, reversed by 1 mo of transgene suppression beginning at 4–5 mo of age (data not shown). |
T9605 |
46909-46913 |
DT |
denotes |
This |
T9606 |
46914-46922 |
NN |
denotes |
behavior |
T9607 |
46960-46968 |
VBN |
denotes |
reversed |
T9608 |
46923-46926 |
VBD |
denotes |
was |
T9609 |
46927-46936 |
RB |
denotes |
partially |
T9610 |
46936-46938 |
, |
denotes |
, |
T9611 |
46938-46941 |
CC |
denotes |
but |
T9612 |
46942-46945 |
RB |
denotes |
not |
T9613 |
46946-46958 |
RB |
denotes |
consistently |
T9614 |
46958-46960 |
, |
denotes |
, |
T9615 |
46969-46971 |
IN |
denotes |
by |
T9616 |
46972-46973 |
CD |
denotes |
1 |
T9617 |
46974-46976 |
NN |
denotes |
mo |
T9618 |
46977-46979 |
IN |
denotes |
of |
T9619 |
46980-46989 |
NN |
denotes |
transgene |
T9620 |
46990-47001 |
NN |
denotes |
suppression |
T9621 |
47002-47011 |
VBG |
denotes |
beginning |
T9622 |
47012-47014 |
IN |
denotes |
at |
T9623 |
47015-47016 |
CD |
denotes |
4 |
T9624 |
47017-47018 |
CD |
denotes |
5 |
T9625 |
47016-47017 |
SYM |
denotes |
– |
T9626 |
47019-47021 |
NN |
denotes |
mo |
T9627 |
47022-47024 |
IN |
denotes |
of |
T9628 |
47025-47028 |
NN |
denotes |
age |
T9629 |
47029-47030 |
-LRB- |
denotes |
( |
T9630 |
47039-47044 |
VBN |
denotes |
shown |
T9631 |
47030-47034 |
NNS |
denotes |
data |
T9632 |
47035-47038 |
RB |
denotes |
not |
T9633 |
47044-47045 |
-RRB- |
denotes |
) |
T9634 |
47045-47046 |
. |
denotes |
. |
T9635 |
47046-47130 |
sentence |
denotes |
In contrast, hyperactivity was completely abolished by rearing tTA/APP mice on dox. |
T9636 |
47047-47049 |
IN |
denotes |
In |
T9637 |
47089-47098 |
VBN |
denotes |
abolished |
T9638 |
47050-47058 |
NN |
denotes |
contrast |
T9639 |
47058-47060 |
, |
denotes |
, |
T9640 |
47060-47073 |
NN |
denotes |
hyperactivity |
T9641 |
47074-47077 |
VBD |
denotes |
was |
T9642 |
47078-47088 |
RB |
denotes |
completely |
T9643 |
47099-47101 |
IN |
denotes |
by |
T9644 |
47102-47109 |
VBG |
denotes |
rearing |
T9645 |
47110-47113 |
NN |
denotes |
tTA |
T9646 |
47114-47117 |
NN |
denotes |
APP |
T9647 |
47113-47114 |
HYPH |
denotes |
/ |
T9648 |
47118-47122 |
NNS |
denotes |
mice |
T9649 |
47123-47125 |
IN |
denotes |
on |
T9650 |
47126-47129 |
NN |
denotes |
dox |
T9651 |
47129-47130 |
. |
denotes |
. |
T9652 |
47130-47231 |
sentence |
denotes |
Animals born and raised on dox showed activity levels similar to the untreated controls (Figure 7C). |
T9653 |
47131-47138 |
NNS |
denotes |
Animals |
T9654 |
47162-47168 |
VBD |
denotes |
showed |
T9655 |
47139-47143 |
VBN |
denotes |
born |
T9656 |
47144-47147 |
CC |
denotes |
and |
T9657 |
47148-47154 |
VBN |
denotes |
raised |
T9658 |
47155-47157 |
IN |
denotes |
on |
T9659 |
47158-47161 |
NN |
denotes |
dox |
T9660 |
47169-47177 |
NN |
denotes |
activity |
T9687 |
47297-47301 |
JJ |
denotes |
wild |
T9688 |
47302-47306 |
NN |
denotes |
type |
T9689 |
47301-47302 |
HYPH |
denotes |
- |
T9690 |
47306-47308 |
, |
denotes |
, |
T9691 |
47315-47322 |
VBN |
denotes |
altered |
T9692 |
47333-47340 |
NNS |
denotes |
rhythms |
T9693 |
47323-47332 |
JJ |
denotes |
circadian |
T9694 |
47341-47345 |
IN |
denotes |
with |
T9695 |
47346-47349 |
RB |
denotes |
far |
T9696 |
47350-47354 |
JJR |
denotes |
less |
T9697 |
47355-47366 |
NN |
denotes |
distinction |
T9698 |
47367-47374 |
IN |
denotes |
between |
T9699 |
47375-47380 |
PRP$ |
denotes |
their |
T9700 |
47409-47415 |
NNS |
denotes |
levels |
T9701 |
47381-47384 |
NN |
denotes |
day |
T9702 |
47384-47385 |
HYPH |
denotes |
- |
T9703 |
47386-47389 |
CC |
denotes |
and |
T9704 |
47390-47399 |
NN |
denotes |
nighttime |
T9705 |
47400-47408 |
NN |
denotes |
activity |
T9706 |
47415-47416 |
. |
denotes |
. |
T10541 |
48164-48166 |
PRP |
denotes |
We |
T10542 |
48167-48174 |
VBP |
denotes |
present |
T10543 |
48175-48176 |
DT |
denotes |
a |
T10544 |
48187-48192 |
NN |
denotes |
model |
T10545 |
48177-48180 |
JJ |
denotes |
new |
T10546 |
48181-48186 |
NN |
denotes |
mouse |
T10547 |
48193-48196 |
IN |
denotes |
for |
T10548 |
48197-48199 |
NN |
denotes |
AD |
T10549 |
48200-48204 |
WDT |
denotes |
that |
T10550 |
48209-48217 |
VBN |
denotes |
designed |
T10551 |
48205-48208 |
VBD |
denotes |
was |
T10552 |
48218-48220 |
TO |
denotes |
to |
T10553 |
48221-48225 |
VB |
denotes |
test |
T10554 |
48226-48229 |
DT |
denotes |
the |
T10555 |
48230-48242 |
NNS |
denotes |
consequences |
T10556 |
48243-48245 |
IN |
denotes |
of |
T10557 |
48246-48256 |
VBG |
denotes |
inhibiting |
T10558 |
48257-48259 |
NN |
denotes |
Aβ |
T10559 |
48260-48270 |
NN |
denotes |
production |
T10560 |
48271-48276 |
IN |
denotes |
after |
T10561 |
48277-48280 |
DT |
denotes |
the |
T10562 |
48281-48286 |
NN |
denotes |
onset |
T10563 |
48287-48289 |
IN |
denotes |
of |
T10564 |
48290-48297 |
NN |
denotes |
amyloid |
T10565 |
48298-48307 |
NN |
denotes |
pathology |
T10566 |
48307-48308 |
. |
denotes |
. |
T10567 |
48308-48463 |
sentence |
denotes |
New lines of transgenic mice were developed for this study that express high levels of APPswe/ind under the control of a tetracycline-responsive promoter. |
T10568 |
48309-48312 |
JJ |
denotes |
New |
T10569 |
48313-48318 |
NNS |
denotes |
lines |
T10570 |
48343-48352 |
VBN |
denotes |
developed |
T10571 |
48319-48321 |
IN |
denotes |
of |
T10572 |
48322-48332 |
JJ |
denotes |
transgenic |
T10573 |
48333-48337 |
NNS |
denotes |
mice |
T10574 |
48338-48342 |
VBD |
denotes |
were |
T10575 |
48353-48356 |
IN |
denotes |
for |
T10576 |
48357-48361 |
DT |
denotes |
this |
T10577 |
48362-48367 |
NN |
denotes |
study |
T10578 |
48368-48372 |
WDT |
denotes |
that |
T10579 |
48373-48380 |
VBP |
denotes |
express |
T10580 |
48381-48385 |
JJ |
denotes |
high |
T10581 |
48386-48392 |
NNS |
denotes |
levels |
T10582 |
48393-48395 |
IN |
denotes |
of |
T10583 |
48396-48402 |
NN |
denotes |
APPswe |
T10584 |
48403-48406 |
NN |
denotes |
ind |
T10585 |
48402-48403 |
HYPH |
denotes |
/ |
T10586 |
48407-48412 |
IN |
denotes |
under |
T10587 |
48413-48416 |
DT |
denotes |
the |
T10588 |
48417-48424 |
NN |
denotes |
control |
T10589 |
48425-48427 |
IN |
denotes |
of |
T10590 |
48428-48429 |
DT |
denotes |
a |
T10591 |
48454-48462 |
NN |
denotes |
promoter |
T10592 |
48430-48442 |
NN |
denotes |
tetracycline |
T10593 |
48443-48453 |
JJ |
denotes |
responsive |
T10594 |
48442-48443 |
HYPH |
denotes |
- |
T10595 |
48462-48463 |
. |
denotes |
. |
T10596 |
48463-48661 |
sentence |
denotes |
We demonstrate that treatment with dox suppresses steady-state levels of both APPswe/ind and its C-terminal fragments, indicating that the mutant proteins have a relatively short half-life in vivo. |
T10597 |
48464-48466 |
PRP |
denotes |
We |
T10598 |
48467-48478 |
VBP |
denotes |
demonstrate |
T10599 |
48479-48483 |
IN |
denotes |
that |
T10600 |
48503-48513 |
VBZ |
denotes |
suppresses |
T10601 |
48484-48493 |
NN |
denotes |
treatment |
T10602 |
48494-48498 |
IN |
denotes |
with |
T10603 |
48499-48502 |
NN |
denotes |
dox |
T10604 |
48514-48520 |
JJ |
denotes |
steady |
T10605 |
48521-48526 |
NN |
denotes |
state |
T10606 |
48520-48521 |
HYPH |
denotes |
- |
T10607 |
48527-48533 |
NNS |
denotes |
levels |
T10608 |
48534-48536 |
IN |
denotes |
of |
T10609 |
48537-48541 |
CC |
denotes |
both |
T10610 |
48549-48552 |
NN |
denotes |
ind |
T10611 |
48542-48548 |
NN |
denotes |
APPswe |
T10612 |
48548-48549 |
HYPH |
denotes |
/ |
T10613 |
48553-48556 |
CC |
denotes |
and |
T10614 |
48557-48560 |
PRP$ |
denotes |
its |
T10615 |
48572-48581 |
NNS |
denotes |
fragments |
T10616 |
48561-48562 |
NN |
denotes |
C |
T10617 |
48562-48563 |
HYPH |
denotes |
- |
T10618 |
48563-48571 |
JJ |
denotes |
terminal |
T10619 |
48581-48583 |
, |
denotes |
, |
T10620 |
48583-48593 |
VBG |
denotes |
indicating |
T10621 |
48594-48598 |
IN |
denotes |
that |
T10622 |
48619-48623 |
VBP |
denotes |
have |
T10623 |
48599-48602 |
DT |
denotes |
the |
T10624 |
48610-48618 |
NN |
denotes |
proteins |
T10625 |
48603-48609 |
NN |
denotes |
mutant |
T10626 |
48624-48625 |
DT |
denotes |
a |
T10627 |
48648-48652 |
NN |
denotes |
life |
T10628 |
48626-48636 |
RB |
denotes |
relatively |
T10629 |
48637-48642 |
JJ |
denotes |
short |
T10630 |
48643-48647 |
NN |
denotes |
half |
T10631 |
48647-48648 |
HYPH |
denotes |
- |
T10632 |
48653-48655 |
FW |
denotes |
in |
T10633 |
48656-48660 |
FW |
denotes |
vivo |
T10634 |
48660-48661 |
. |
denotes |
. |
T10635 |
48661-48841 |
sentence |
denotes |
Transgenic expression of APPswe/ind and consequent overproduction of Aβ42 cause early-onset amyloid deposition in untreated mice, in which deposits appear as early as 2 mo of age. |
T10636 |
48662-48672 |
JJ |
denotes |
Transgenic |
T10637 |
48673-48683 |
NN |
denotes |
expression |
T10638 |
48736-48741 |
VBP |
denotes |
cause |
T10639 |
48684-48686 |
IN |
denotes |
of |
T10640 |
48687-48693 |
NN |
denotes |
APPswe |
T10641 |
48694-48697 |
NN |
denotes |
ind |
T10642 |
48693-48694 |
HYPH |
denotes |
/ |
T10643 |
48698-48701 |
CC |
denotes |
and |
T10644 |
48702-48712 |
JJ |
denotes |
consequent |
T10645 |
48713-48727 |
NN |
denotes |
overproduction |
T10646 |
48728-48730 |
IN |
denotes |
of |
T10647 |
48731-48735 |
NN |
denotes |
Aβ42 |
T10648 |
48742-48747 |
JJ |
denotes |
early |
T10649 |
48748-48753 |
NN |
denotes |
onset |
T10650 |
48747-48748 |
HYPH |
denotes |
- |
T10651 |
48762-48772 |
NN |
denotes |
deposition |
T10652 |
48754-48761 |
NN |
denotes |
amyloid |
T10653 |
48773-48775 |
IN |
denotes |
in |
T10654 |
48776-48785 |
JJ |
denotes |
untreated |
T10655 |
48786-48790 |
NNS |
denotes |
mice |
T10656 |
48790-48792 |
, |
denotes |
, |
T10657 |
48792-48794 |
IN |
denotes |
in |
T10658 |
48810-48816 |
VBP |
denotes |
appear |
T10659 |
48795-48800 |
WDT |
denotes |
which |
T10660 |
48801-48809 |
NNS |
denotes |
deposits |
T10661 |
48817-48819 |
RB |
denotes |
as |
T10662 |
48820-48825 |
RB |
denotes |
early |
T10663 |
48826-48828 |
IN |
denotes |
as |
T10664 |
48829-48830 |
CD |
denotes |
2 |
T10665 |
48831-48833 |
NN |
denotes |
mo |
T10666 |
48834-48836 |
IN |
denotes |
of |
T10667 |
48837-48840 |
NN |
denotes |
age |
T10668 |
48840-48841 |
. |
denotes |
. |
T10669 |
48841-48990 |
sentence |
denotes |
Amyloid burden worsens significantly with age, and by 9 mo, the hippocampus and cortex of untreated mice are largely filled with aggregated peptide. |
T10670 |
48842-48849 |
NN |
denotes |
Amyloid |
T10671 |
48850-48856 |
NN |
denotes |
burden |
T10672 |
48857-48864 |
VBZ |
denotes |
worsens |
T10673 |
48865-48878 |
RB |
denotes |
significantly |
T10674 |
48879-48883 |
IN |
denotes |
with |
T10675 |
48884-48887 |
NN |
denotes |
age |
T10676 |
48887-48889 |
, |
denotes |
, |
T10677 |
48889-48892 |
CC |
denotes |
and |
T10678 |
48893-48895 |
IN |
denotes |
by |
T10679 |
48959-48965 |
VBN |
denotes |
filled |
T10680 |
48896-48897 |
CD |
denotes |
9 |
T10681 |
48898-48900 |
NN |
denotes |
mo |
T10682 |
48900-48902 |
, |
denotes |
, |
T10683 |
48902-48905 |
DT |
denotes |
the |
T10684 |
48906-48917 |
NN |
denotes |
hippocampus |
T10685 |
48918-48921 |
CC |
denotes |
and |
T10686 |
48922-48928 |
NN |
denotes |
cortex |
T10687 |
48929-48931 |
IN |
denotes |
of |
T10688 |
48932-48941 |
JJ |
denotes |
untreated |
T10689 |
48942-48946 |
NNS |
denotes |
mice |
T10690 |
48947-48950 |
VBP |
denotes |
are |
T10691 |
48951-48958 |
RB |
denotes |
largely |
T10692 |
48966-48970 |
IN |
denotes |
with |
T10693 |
48971-48981 |
VBN |
denotes |
aggregated |
T10694 |
48982-48989 |
NN |
denotes |
peptide |
T10695 |
48989-48990 |
. |
denotes |
. |
T10696 |
48990-49103 |
sentence |
denotes |
We find that suppression of transgenic APP by more than 95% abruptly halts the progression of amyloid pathology. |
T10697 |
48991-48993 |
PRP |
denotes |
We |
T10698 |
48994-48998 |
VBP |
denotes |
find |
T10699 |
48999-49003 |
IN |
denotes |
that |
T10700 |
49060-49065 |
VBZ |
denotes |
halts |
T10701 |
49004-49015 |
NN |
denotes |
suppression |
T10702 |
49016-49018 |
IN |
denotes |
of |
T10703 |
49019-49029 |
JJ |
denotes |
transgenic |
T10704 |
49030-49033 |
NN |
denotes |
APP |
T10705 |
49034-49036 |
IN |
denotes |
by |
T10706 |
49037-49041 |
JJR |
denotes |
more |
T10707 |
49047-49049 |
CD |
denotes |
95 |
T10708 |
49042-49046 |
IN |
denotes |
than |
T10709 |
49049-49050 |
NN |
denotes |
% |
T10710 |
49051-49059 |
RB |
denotes |
abruptly |
T10711 |
49066-49069 |
DT |
denotes |
the |
T10712 |
49070-49081 |
NN |
denotes |
progression |
T10713 |
49082-49084 |
IN |
denotes |
of |
T10714 |
49085-49092 |
NN |
denotes |
amyloid |
T10715 |
49093-49102 |
NN |
denotes |
pathology |
T10716 |
49102-49103 |
. |
denotes |
. |
T10717 |
49103-49296 |
sentence |
denotes |
Importantly, this outcome occurs in animals already harboring considerable amyloid pathology, a situation similar to what might be expected in patients to be treated with secretase inhibitors. |
T10718 |
49104-49115 |
RB |
denotes |
Importantly |
T10719 |
49130-49136 |
VBZ |
denotes |
occurs |
T10720 |
49115-49117 |
, |
denotes |
, |
T10721 |
49117-49121 |
DT |
denotes |
this |
T10722 |
49122-49129 |
NN |
denotes |
outcome |
T10723 |
49137-49139 |
IN |
denotes |
in |
T10724 |
49140-49147 |
NNS |
denotes |
animals |
T10725 |
49148-49155 |
RB |
denotes |
already |
T10726 |
49156-49165 |
VBG |
denotes |
harboring |
T10727 |
49166-49178 |
JJ |
denotes |
considerable |
T10728 |
49187-49196 |
NN |
denotes |
pathology |
T10729 |
49179-49186 |
NN |
denotes |
amyloid |
T10730 |
49196-49198 |
, |
denotes |
, |
T10731 |
49198-49199 |
DT |
denotes |
a |
T10732 |
49200-49209 |
NN |
denotes |
situation |
T10733 |
49210-49217 |
JJ |
denotes |
similar |
T10734 |
49218-49220 |
IN |
denotes |
to |
T10735 |
49221-49225 |
WP |
denotes |
what |
T10736 |
49235-49243 |
VBN |
denotes |
expected |
T10737 |
49226-49231 |
MD |
denotes |
might |
T10738 |
49232-49234 |
VB |
denotes |
be |
T10739 |
49244-49246 |
IN |
denotes |
in |
T10740 |
49247-49255 |
NNS |
denotes |
patients |
T10741 |
49256-49258 |
TO |
denotes |
to |
T10742 |
49262-49269 |
VBN |
denotes |
treated |
T10743 |
49259-49261 |
VB |
denotes |
be |
T10744 |
49270-49274 |
IN |
denotes |
with |
T10745 |
49275-49284 |
NN |
denotes |
secretase |
T10746 |
49285-49295 |
NNS |
denotes |
inhibitors |
T10747 |
49295-49296 |
. |
denotes |
. |
T10748 |
49296-49469 |
sentence |
denotes |
Somewhat unexpectedly, we observe no appreciable clearance of deposited amyloid even following periods of transgene suppression equal to the time taken for plaques to form. |
T10749 |
49297-49305 |
RB |
denotes |
Somewhat |
T10750 |
49306-49318 |
RB |
denotes |
unexpectedly |
T10751 |
49323-49330 |
VBP |
denotes |
observe |
T10752 |
49318-49320 |
, |
denotes |
, |
T10753 |
49320-49322 |
PRP |
denotes |
we |
T10754 |
49331-49333 |
DT |
denotes |
no |
T10755 |
49346-49355 |
NN |
denotes |
clearance |
T10756 |
49334-49345 |
JJ |
denotes |
appreciable |
T10757 |
49356-49358 |
IN |
denotes |
of |
T10758 |
49359-49368 |
VBN |
denotes |
deposited |
T10759 |
49369-49376 |
NN |
denotes |
amyloid |
T10760 |
49377-49381 |
RB |
denotes |
even |
T10761 |
49382-49391 |
VBG |
denotes |
following |
T10762 |
49392-49399 |
NNS |
denotes |
periods |
T10763 |
49400-49402 |
IN |
denotes |
of |
T10764 |
49403-49412 |
NN |
denotes |
transgene |
T10765 |
49413-49424 |
NN |
denotes |
suppression |
T10766 |
49425-49430 |
JJ |
denotes |
equal |
T10767 |
49431-49433 |
IN |
denotes |
to |
T10768 |
49434-49437 |
DT |
denotes |
the |
T10769 |
49438-49442 |
NN |
denotes |
time |
T10770 |
49443-49448 |
VBN |
denotes |
taken |
T10771 |
49449-49452 |
IN |
denotes |
for |
T10772 |
49464-49468 |
VB |
denotes |
form |
T10773 |
49453-49460 |
NNS |
denotes |
plaques |
T10774 |
49461-49463 |
TO |
denotes |
to |
T10775 |
49468-49469 |
. |
denotes |
. |
T10776 |
49469-49687 |
sentence |
denotes |
This latter finding indicates that compared to other disease-associated protein aggregates such as mutant huntingtin, which clear in less than 3 mo [32], the disaggregation of extracellular amyloid is relatively slow. |
T10777 |
49470-49474 |
DT |
denotes |
This |
T10778 |
49482-49489 |
NN |
denotes |
finding |
T10779 |
49475-49481 |
JJ |
denotes |
latter |
T10780 |
49490-49499 |
VBZ |
denotes |
indicates |
T10781 |
49500-49504 |
IN |
denotes |
that |
T10782 |
49668-49670 |
VBZ |
denotes |
is |
T10783 |
49505-49513 |
VBN |
denotes |
compared |
T10784 |
49514-49516 |
IN |
denotes |
to |
T10785 |
49517-49522 |
JJ |
denotes |
other |
T10786 |
49550-49560 |
NNS |
denotes |
aggregates |
T10787 |
49523-49530 |
NN |
denotes |
disease |
T10788 |
49531-49541 |
VBN |
denotes |
associated |
T10789 |
49530-49531 |
HYPH |
denotes |
- |
T10790 |
49542-49549 |
NN |
denotes |
protein |
T10791 |
49561-49565 |
JJ |
denotes |
such |
T10792 |
49566-49568 |
IN |
denotes |
as |
T10793 |
49569-49575 |
NN |
denotes |
mutant |
T10794 |
49576-49586 |
NN |
denotes |
huntingtin |
T10795 |
49586-49588 |
, |
denotes |
, |
T10796 |
49588-49593 |
WDT |
denotes |
which |
T10797 |
49594-49599 |
VBP |
denotes |
clear |
T10798 |
49600-49602 |
IN |
denotes |
in |
T10799 |
49603-49607 |
JJR |
denotes |
less |
T10800 |
49613-49614 |
CD |
denotes |
3 |
T10801 |
49608-49612 |
IN |
denotes |
than |
T10802 |
49615-49617 |
NN |
denotes |
mo |
T10803 |
49618-49619 |
-LRB- |
denotes |
[ |
T10804 |
49619-49621 |
CD |
denotes |
32 |
T10805 |
49621-49622 |
-RRB- |
denotes |
] |
T10806 |
49622-49624 |
, |
denotes |
, |
T10807 |
49624-49627 |
DT |
denotes |
the |
T10808 |
49628-49642 |
NN |
denotes |
disaggregation |
T10809 |
49643-49645 |
IN |
denotes |
of |
T10810 |
49646-49659 |
JJ |
denotes |
extracellular |
T10811 |
49660-49667 |
NN |
denotes |
amyloid |
T10812 |
49671-49681 |
RB |
denotes |
relatively |
T10813 |
49682-49686 |
JJ |
denotes |
slow |
T10814 |
49686-49687 |
. |
denotes |
. |
T10815 |
49687-49858 |
sentence |
denotes |
Notably, pharmaceutical γ-secretase inhibitors published to date show less strict regulation of Aβ production following chronic administration than we have attained here. |
T10816 |
49688-49695 |
RB |
denotes |
Notably |
T10817 |
49753-49757 |
VBP |
denotes |
show |
T10818 |
49695-49697 |
, |
denotes |
, |
T10819 |
49697-49711 |
JJ |
denotes |
pharmaceutical |
T10820 |
49724-49734 |
NNS |
denotes |
inhibitors |
T10821 |
49712-49713 |
SYM |
denotes |
γ |
T10822 |
49714-49723 |
NN |
denotes |
secretase |
T10823 |
49713-49714 |
HYPH |
denotes |
- |
T10824 |
49735-49744 |
VBN |
denotes |
published |
T10825 |
49745-49747 |
IN |
denotes |
to |
T10826 |
49748-49752 |
NN |
denotes |
date |
T10827 |
49758-49762 |
RBR |
denotes |
less |
T10828 |
49763-49769 |
JJ |
denotes |
strict |
T10829 |
49770-49780 |
NN |
denotes |
regulation |
T10830 |
49781-49783 |
IN |
denotes |
of |
T10831 |
49784-49786 |
NN |
denotes |
Aβ |
T10832 |
49787-49797 |
NN |
denotes |
production |
T10833 |
49798-49807 |
VBG |
denotes |
following |
T10834 |
49808-49815 |
JJ |
denotes |
chronic |
T10835 |
49816-49830 |
NN |
denotes |
administration |
T10836 |
49831-49835 |
IN |
denotes |
than |
T10837 |
49844-49852 |
VBN |
denotes |
attained |
T10838 |
49836-49838 |
PRP |
denotes |
we |
T10839 |
49839-49843 |
VBP |
denotes |
have |
T10840 |
49853-49857 |
RB |
denotes |
here |
T10841 |
49857-49858 |
. |
denotes |
. |
T10842 |
49858-50068 |
sentence |
denotes |
Two independent compounds tested in Tg2576 [33] and TgCRND8 [34] transgenic mice show no more than 85% suppression of Aβ40 levels, and where measured, even less suppression of Aβ42 (approximately 60%) [35,36]. |
T10843 |
49859-49862 |
CD |
denotes |
Two |
T10844 |
49875-49884 |
NNS |
denotes |
compounds |
T10845 |
49863-49874 |
JJ |
denotes |
independent |
T10846 |
49940-49944 |
VBP |
denotes |
show |
T10847 |
49885-49891 |
VBN |
denotes |
tested |
T10848 |
49892-49894 |
IN |
denotes |
in |
T10849 |
49895-49901 |
NN |
denotes |
Tg2576 |
T10850 |
49924-49934 |
JJ |
denotes |
transgenic |
T10851 |
49902-49903 |
-LRB- |
denotes |
[ |
T10852 |
49903-49905 |
CD |
denotes |
33 |
T10853 |
49905-49906 |
-RRB- |
denotes |
] |
T10854 |
49907-49910 |
CC |
denotes |
and |
T10855 |
49911-49918 |
NN |
denotes |
TgCRND8 |
T10856 |
49919-49920 |
-LRB- |
denotes |
[ |
T10857 |
49920-49922 |
CD |
denotes |
34 |
T10858 |
49922-49923 |
-RRB- |
denotes |
] |
T10859 |
49935-49939 |
NNS |
denotes |
mice |
T10860 |
49945-49947 |
RB |
denotes |
no |
T10861 |
49958-49960 |
CD |
denotes |
85 |
T10862 |
49948-49952 |
JJR |
denotes |
more |
T10863 |
49953-49957 |
IN |
denotes |
than |
T10864 |
49960-49961 |
NN |
denotes |
% |
T10865 |
49962-49973 |
NN |
denotes |
suppression |
T10866 |
49974-49976 |
IN |
denotes |
of |
T10867 |
49977-49981 |
NN |
denotes |
Aβ40 |
T10868 |
49982-49988 |
NNS |
denotes |
levels |
T10869 |
49988-49990 |
, |
denotes |
, |
T10870 |
49990-49993 |
CC |
denotes |
and |
T10871 |
49994-49999 |
WRB |
denotes |
where |
T10872 |
50000-50008 |
VBN |
denotes |
measured |
T10873 |
50020-50031 |
NN |
denotes |
suppression |
T10874 |
50008-50010 |
, |
denotes |
, |
T10875 |
50010-50014 |
RB |
denotes |
even |
T10876 |
50015-50019 |
JJR |
denotes |
less |
T10877 |
50032-50034 |
IN |
denotes |
of |
T10878 |
50035-50039 |
NN |
denotes |
Aβ42 |
T10879 |
50040-50041 |
-LRB- |
denotes |
( |
T10880 |
50057-50058 |
NN |
denotes |
% |
T10881 |
50041-50054 |
RB |
denotes |
approximately |
T10882 |
50055-50057 |
CD |
denotes |
60 |
T10883 |
50058-50059 |
-RRB- |
denotes |
) |
T10884 |
50060-50061 |
-LRB- |
denotes |
[ |
T10885 |
50064-50066 |
CD |
denotes |
36 |
T10886 |
50061-50063 |
CD |
denotes |
35 |
T10887 |
50063-50064 |
, |
denotes |
, |
T10888 |
50066-50067 |
-RRB- |
denotes |
] |
T10889 |
50067-50068 |
. |
denotes |
. |
T10890 |
50068-50340 |
sentence |
denotes |
Thus, even after accounting for the much higher APP expression levels in our mice than in the Tg2576 and TgCRND8 lines, we have achieved better absolute suppression of Aβ production with the tet-off system than is currently possible with published γ-secretase inhibitors. |
T10891 |
50069-50073 |
RB |
denotes |
Thus |
T10892 |
50197-50205 |
VBN |
denotes |
achieved |
T10893 |
50073-50075 |
, |
denotes |
, |
T10894 |
50075-50079 |
RB |
denotes |
even |
T10895 |
50080-50085 |
IN |
denotes |
after |
T10896 |
50086-50096 |
VBG |
denotes |
accounting |
T10897 |
50097-50100 |
IN |
denotes |
for |
T10898 |
50101-50104 |
DT |
denotes |
the |
T10899 |
50132-50138 |
NNS |
denotes |
levels |
T10900 |
50105-50109 |
RB |
denotes |
much |
T10901 |
50110-50116 |
JJR |
denotes |
higher |
T10902 |
50117-50120 |
NN |
denotes |
APP |
T10903 |
50121-50131 |
NN |
denotes |
expression |
T10904 |
50139-50141 |
IN |
denotes |
in |
T10905 |
50142-50145 |
PRP$ |
denotes |
our |
T10906 |
50146-50150 |
NNS |
denotes |
mice |
T10907 |
50151-50155 |
IN |
denotes |
than |
T10908 |
50156-50158 |
IN |
denotes |
in |
T10909 |
50159-50162 |
DT |
denotes |
the |
T10910 |
50182-50187 |
NNS |
denotes |
lines |
T10911 |
50163-50169 |
NN |
denotes |
Tg2576 |
T10912 |
50170-50173 |
CC |
denotes |
and |
T10913 |
50174-50181 |
NN |
denotes |
TgCRND8 |
T10914 |
50187-50189 |
, |
denotes |
, |
T10915 |
50189-50191 |
PRP |
denotes |
we |
T10916 |
50192-50196 |
VBP |
denotes |
have |
T10917 |
50206-50212 |
RBR |
denotes |
better |
T10918 |
50222-50233 |
NN |
denotes |
suppression |
T10919 |
50213-50221 |
JJ |
denotes |
absolute |
T10920 |
50234-50236 |
IN |
denotes |
of |
T10921 |
50237-50239 |
NN |
denotes |
Aβ |
T10922 |
50240-50250 |
NN |
denotes |
production |
T10923 |
50251-50255 |
IN |
denotes |
with |
T10924 |
50256-50259 |
DT |
denotes |
the |
T10925 |
50268-50274 |
NN |
denotes |
system |
T10926 |
50260-50263 |
NN |
denotes |
tet |
T10927 |
50264-50267 |
NN |
denotes |
off |
T10928 |
50263-50264 |
HYPH |
denotes |
- |
T10929 |
50275-50279 |
IN |
denotes |
than |
T10930 |
50280-50282 |
VBZ |
denotes |
is |
T10931 |
50283-50292 |
RB |
denotes |
currently |
T10932 |
50293-50301 |
JJ |
denotes |
possible |
T10933 |
50302-50306 |
IN |
denotes |
with |
T10934 |
50307-50316 |
VBN |
denotes |
published |
T10935 |
50329-50339 |
NNS |
denotes |
inhibitors |
T10936 |
50317-50318 |
SYM |
denotes |
γ |
T10937 |
50319-50328 |
NN |
denotes |
secretase |
T10938 |
50318-50319 |
HYPH |
denotes |
- |
T10939 |
50339-50340 |
. |
denotes |
. |
T10940 |
50340-50572 |
sentence |
denotes |
Since even the most advanced future pharmaceutical agents are unlikely to attain more complete control of Aβ production than achieved here, this system provides a salient test of therapeutic intervention with Aβ-lowering compounds. |
T10941 |
50341-50346 |
IN |
denotes |
Since |
T10942 |
50399-50402 |
VBP |
denotes |
are |
T10943 |
50347-50351 |
RB |
denotes |
even |
T10944 |
50392-50398 |
NNS |
denotes |
agents |
T10945 |
50352-50355 |
DT |
denotes |
the |
T10946 |
50356-50360 |
RBS |
denotes |
most |
T10947 |
50361-50369 |
JJ |
denotes |
advanced |
T10948 |
50370-50376 |
JJ |
denotes |
future |
T10949 |
50377-50391 |
JJ |
denotes |
pharmaceutical |
T10950 |
50493-50501 |
VBZ |
denotes |
provides |
T10951 |
50403-50411 |
JJ |
denotes |
unlikely |
T10952 |
50412-50414 |
TO |
denotes |
to |
T10953 |
50415-50421 |
VB |
denotes |
attain |
T10954 |
50422-50426 |
RBR |
denotes |
more |
T10955 |
50427-50435 |
JJ |
denotes |
complete |
T10956 |
50436-50443 |
NN |
denotes |
control |
T10957 |
50444-50446 |
IN |
denotes |
of |
T10958 |
50447-50449 |
NN |
denotes |
Aβ |
T10959 |
50450-50460 |
NN |
denotes |
production |
T10960 |
50461-50465 |
IN |
denotes |
than |
T10961 |
50466-50474 |
VBN |
denotes |
achieved |
T10962 |
50475-50479 |
RB |
denotes |
here |
T10963 |
50479-50481 |
, |
denotes |
, |
T10964 |
50481-50485 |
DT |
denotes |
this |
T10965 |
50486-50492 |
NN |
denotes |
system |
T10966 |
50502-50503 |
DT |
denotes |
a |
T10967 |
50512-50516 |
NN |
denotes |
test |
T10968 |
50504-50511 |
JJ |
denotes |
salient |
T10969 |
50517-50519 |
IN |
denotes |
of |
T10970 |
50520-50531 |
JJ |
denotes |
therapeutic |
T10971 |
50532-50544 |
NN |
denotes |
intervention |
T10972 |
50545-50549 |
IN |
denotes |
with |
T10973 |
50550-50552 |
NN |
denotes |
Aβ |
T10974 |
50553-50561 |
VBG |
denotes |
lowering |
T10975 |
50552-50553 |
HYPH |
denotes |
- |
T10976 |
50562-50571 |
NNS |
denotes |
compounds |
T10977 |
50571-50572 |
. |
denotes |
. |
T10978 |
50572-50760 |
sentence |
denotes |
Although the progression of amyloid deposition was sharply arrested by this approach, we found that a substantial amyloid burden remained even after long periods of transgene suppression. |
T10979 |
50573-50581 |
IN |
denotes |
Although |
T10980 |
50632-50640 |
VBN |
denotes |
arrested |
T10981 |
50582-50585 |
DT |
denotes |
the |
T10982 |
50586-50597 |
NN |
denotes |
progression |
T10983 |
50598-50600 |
IN |
denotes |
of |
T10984 |
50601-50608 |
NN |
denotes |
amyloid |
T10985 |
50609-50619 |
NN |
denotes |
deposition |
T10986 |
50620-50623 |
VBD |
denotes |
was |
T10987 |
50624-50631 |
RB |
denotes |
sharply |
T10988 |
50662-50667 |
VBD |
denotes |
found |
T10989 |
50641-50643 |
IN |
denotes |
by |
T10990 |
50644-50648 |
DT |
denotes |
this |
T10991 |
50649-50657 |
NN |
denotes |
approach |
T10992 |
50657-50659 |
, |
denotes |
, |
T10993 |
50659-50661 |
PRP |
denotes |
we |
T10994 |
50668-50672 |
IN |
denotes |
that |
T10995 |
50702-50710 |
VBD |
denotes |
remained |
T10996 |
50673-50674 |
DT |
denotes |
a |
T10997 |
50695-50701 |
NN |
denotes |
burden |
T10998 |
50675-50686 |
JJ |
denotes |
substantial |
T10999 |
50687-50694 |
NN |
denotes |
amyloid |
T11000 |
50711-50715 |
RB |
denotes |
even |
T11001 |
50716-50721 |
IN |
denotes |
after |
T11002 |
50722-50726 |
JJ |
denotes |
long |
T11003 |
50727-50734 |
NNS |
denotes |
periods |
T11004 |
50735-50737 |
IN |
denotes |
of |
T11005 |
50738-50747 |
NN |
denotes |
transgene |
T11006 |
50748-50759 |
NN |
denotes |
suppression |
T11007 |
50759-50760 |
. |
denotes |
. |
T11008 |
50760-50919 |
sentence |
denotes |
We examined a small number of animals after 12 mo of dox treatment (beginning at 6 mo of age), and found that amyloid deposits were still relatively abundant. |
T11009 |
50761-50763 |
PRP |
denotes |
We |
T11010 |
50764-50772 |
VBD |
denotes |
examined |
T11011 |
50773-50774 |
DT |
denotes |
a |
T11012 |
50781-50787 |
NN |
denotes |
number |
T11013 |
50775-50780 |
JJ |
denotes |
small |
T11014 |
50788-50790 |
IN |
denotes |
of |
T11015 |
50791-50798 |
NNS |
denotes |
animals |
T11016 |
50799-50804 |
IN |
denotes |
after |
T11017 |
50805-50807 |
CD |
denotes |
12 |
T11018 |
50808-50810 |
NN |
denotes |
mo |
T11019 |
50811-50813 |
IN |
denotes |
of |
T11020 |
50814-50817 |
NN |
denotes |
dox |
T11021 |
50818-50827 |
NN |
denotes |
treatment |
T11022 |
50828-50829 |
-LRB- |
denotes |
( |
T11023 |
50829-50838 |
VBG |
denotes |
beginning |
T11024 |
50839-50841 |
IN |
denotes |
at |
T11025 |
50842-50843 |
CD |
denotes |
6 |
T11026 |
50844-50846 |
NN |
denotes |
mo |
T11027 |
50847-50849 |
IN |
denotes |
of |
T11028 |
50850-50853 |
NN |
denotes |
age |
T11029 |
50853-50854 |
-RRB- |
denotes |
) |
T11030 |
50854-50856 |
, |
denotes |
, |
T11031 |
50856-50859 |
CC |
denotes |
and |
T11032 |
50860-50865 |
VBD |
denotes |
found |
T11033 |
50866-50870 |
IN |
denotes |
that |
T11034 |
50888-50892 |
VBD |
denotes |
were |
T11035 |
50871-50878 |
NN |
denotes |
amyloid |
T11036 |
50879-50887 |
NNS |
denotes |
deposits |
T11037 |
50893-50898 |
RB |
denotes |
still |
T11038 |
50899-50909 |
RB |
denotes |
relatively |
T11039 |
50910-50918 |
JJ |
denotes |
abundant |
T11040 |
50918-50919 |
. |
denotes |
. |
T11041 |
50919-50963 |
sentence |
denotes |
Longer-term treatments are now in progress. |
T11042 |
50920-50926 |
JJ |
denotes |
Longer |
T11043 |
50927-50931 |
NN |
denotes |
term |
T11044 |
50926-50927 |
HYPH |
denotes |
- |
T11045 |
50932-50942 |
NNS |
denotes |
treatments |
T11046 |
50943-50946 |
VBP |
denotes |
are |
T11047 |
50947-50950 |
RB |
denotes |
now |
T11048 |
50951-50953 |
IN |
denotes |
in |
T11049 |
50954-50962 |
NN |
denotes |
progress |
T11050 |
50962-50963 |
. |
denotes |
. |
T11051 |
50963-51266 |
sentence |
denotes |
At the latest treatment interval analyzed by ELISA, animals administered dox for 6 mo showed elevated levels of PBS-soluble Aβ (see Figure 5) that could be interpreted as an indication that the plaques are slowly releasing peptide (or oligomeric Aβ) into the soluble pool and might eventually dissolve. |
T11052 |
50964-50966 |
IN |
denotes |
At |
T11053 |
51050-51056 |
VBD |
denotes |
showed |
T11054 |
50967-50970 |
DT |
denotes |
the |
T11055 |
50988-50996 |
NN |
denotes |
interval |
T11056 |
50971-50977 |
JJS |
denotes |
latest |
T11057 |
50978-50987 |
NN |
denotes |
treatment |
T11058 |
50997-51005 |
VBN |
denotes |
analyzed |
T11059 |
51006-51008 |
IN |
denotes |
by |
T11060 |
51009-51014 |
NN |
denotes |
ELISA |
T11061 |
51014-51016 |
, |
denotes |
, |
T11062 |
51016-51023 |
NNS |
denotes |
animals |
T11063 |
51024-51036 |
VBN |
denotes |
administered |
T11064 |
51037-51040 |
NN |
denotes |
dox |
T11065 |
51041-51044 |
IN |
denotes |
for |
T11066 |
51045-51046 |
CD |
denotes |
6 |
T11067 |
51047-51049 |
NN |
denotes |
mo |
T11068 |
51057-51065 |
VBN |
denotes |
elevated |
T11069 |
51066-51072 |
NNS |
denotes |
levels |
T11070 |
51073-51075 |
IN |
denotes |
of |
T11071 |
51076-51079 |
NN |
denotes |
PBS |
T11072 |
51080-51087 |
JJ |
denotes |
soluble |
T11073 |
51079-51080 |
HYPH |
denotes |
- |
T11074 |
51088-51090 |
NN |
denotes |
Aβ |
T11075 |
51091-51092 |
-LRB- |
denotes |
( |
T11076 |
51092-51095 |
VB |
denotes |
see |
T11077 |
51096-51102 |
NN |
denotes |
Figure |
T11078 |
51103-51104 |
CD |
denotes |
5 |
T11079 |
51104-51105 |
-RRB- |
denotes |
) |
T11080 |
51106-51110 |
WDT |
denotes |
that |
T11081 |
51120-51131 |
VBN |
denotes |
interpreted |
T11082 |
51111-51116 |
MD |
denotes |
could |
T11083 |
51117-51119 |
VB |
denotes |
be |
T11084 |
51132-51134 |
IN |
denotes |
as |
T11085 |
51135-51137 |
DT |
denotes |
an |
T11086 |
51138-51148 |
NN |
denotes |
indication |
T11087 |
51149-51153 |
IN |
denotes |
that |
T11088 |
51177-51186 |
VBG |
denotes |
releasing |
T11089 |
51154-51157 |
DT |
denotes |
the |
T11090 |
51158-51165 |
NNS |
denotes |
plaques |
T11091 |
51166-51169 |
VBP |
denotes |
are |
T11092 |
51170-51176 |
RB |
denotes |
slowly |
T11093 |
51187-51194 |
NN |
denotes |
peptide |
T11094 |
51195-51196 |
-LRB- |
denotes |
( |
T11095 |
51196-51198 |
CC |
denotes |
or |
T11096 |
51199-51209 |
JJ |
denotes |
oligomeric |
T11097 |
51210-51212 |
NN |
denotes |
Aβ |
T11098 |
51212-51213 |
-RRB- |
denotes |
) |
T11099 |
51214-51218 |
IN |
denotes |
into |
T11100 |
51219-51222 |
DT |
denotes |
the |
T11101 |
51231-51235 |
NN |
denotes |
pool |
T11102 |
51223-51230 |
JJ |
denotes |
soluble |
T11103 |
51236-51239 |
CC |
denotes |
and |
T11104 |
51240-51245 |
MD |
denotes |
might |
T11105 |
51257-51265 |
VB |
denotes |
dissolve |
T11106 |
51246-51256 |
RB |
denotes |
eventually |
T11107 |
51265-51266 |
. |
denotes |
. |
T11108 |
51266-51471 |
sentence |
denotes |
Whether inhibiting Aβ production longer than 6 (or 12) mo may ultimately result in clearance of amyloid is under investigation; unfortunately, the life span of the model eventually limits this experiment. |
T11109 |
51267-51274 |
IN |
denotes |
Whether |
T11110 |
51340-51346 |
VB |
denotes |
result |
T11111 |
51275-51285 |
VBG |
denotes |
inhibiting |
T11112 |
51286-51288 |
NN |
denotes |
Aβ |
T11113 |
51289-51299 |
NN |
denotes |
production |
T11114 |
51300-51306 |
RBR |
denotes |
longer |
T11115 |
51307-51311 |
IN |
denotes |
than |
T11116 |
51312-51313 |
CD |
denotes |
6 |
T11117 |
51322-51324 |
NN |
denotes |
mo |
T11118 |
51314-51315 |
-LRB- |
denotes |
( |
T11119 |
51315-51317 |
CC |
denotes |
or |
T11120 |
51318-51320 |
CD |
denotes |
12 |
T11121 |
51320-51321 |
-RRB- |
denotes |
) |
T11122 |
51325-51328 |
MD |
denotes |
may |
T11123 |
51329-51339 |
RB |
denotes |
ultimately |
T11124 |
51371-51373 |
VBZ |
denotes |
is |
T11125 |
51347-51349 |
IN |
denotes |
in |
T11126 |
51350-51359 |
NN |
denotes |
clearance |
T11127 |
51360-51362 |
IN |
denotes |
of |
T11128 |
51363-51370 |
NN |
denotes |
amyloid |
T11129 |
51448-51454 |
VBZ |
denotes |
limits |
T11130 |
51374-51379 |
IN |
denotes |
under |
T11131 |
51380-51393 |
NN |
denotes |
investigation |
T11132 |
51393-51394 |
: |
denotes |
; |
T11133 |
51395-51408 |
RB |
denotes |
unfortunately |
T11134 |
51408-51410 |
, |
denotes |
, |
T11135 |
51410-51413 |
DT |
denotes |
the |
T11136 |
51419-51423 |
NN |
denotes |
span |
T11137 |
51414-51418 |
NN |
denotes |
life |
T11138 |
51424-51426 |
IN |
denotes |
of |
T11139 |
51427-51430 |
DT |
denotes |
the |
T11140 |
51431-51436 |
NN |
denotes |
model |
T11141 |
51437-51447 |
RB |
denotes |
eventually |
T11142 |
51455-51459 |
DT |
denotes |
this |
T11143 |
51460-51470 |
NN |
denotes |
experiment |
T11144 |
51470-51471 |
. |
denotes |
. |
T11145 |
51471-51595 |
sentence |
denotes |
Therapeutics used in humans will have considerably more time to act than is possible within the life span of rodent models. |
T11146 |
51472-51484 |
NNS |
denotes |
Therapeutics |
T11147 |
51505-51509 |
VB |
denotes |
have |
T11148 |
51485-51489 |
VBN |
denotes |
used |
T11149 |
51490-51492 |
IN |
denotes |
in |
T11150 |
51493-51499 |
NNS |
denotes |
humans |
T11151 |
51500-51504 |
MD |
denotes |
will |
T11152 |
51510-51522 |
RB |
denotes |
considerably |
T11153 |
51523-51527 |
JJR |
denotes |
more |
T11154 |
51528-51532 |
NN |
denotes |
time |
T11155 |
51533-51535 |
TO |
denotes |
to |
T11156 |
51536-51539 |
VB |
denotes |
act |
T11157 |
51540-51544 |
IN |
denotes |
than |
T11158 |
51545-51547 |
VBZ |
denotes |
is |
T11159 |
51548-51556 |
JJ |
denotes |
possible |
T11160 |
51557-51563 |
IN |
denotes |
within |
T11161 |
51564-51567 |
DT |
denotes |
the |
T11162 |
51573-51577 |
NN |
denotes |
span |
T11163 |
51568-51572 |
NN |
denotes |
life |
T11164 |
51578-51580 |
IN |
denotes |
of |
T11165 |
51581-51587 |
NN |
denotes |
rodent |
T11166 |
51588-51594 |
NNS |
denotes |
models |
T11167 |
51594-51595 |
. |
denotes |
. |
T11168 |
51595-51685 |
sentence |
denotes |
Long-term treatments would certainly be possible and could be a key to effective therapy. |
T11169 |
51596-51600 |
JJ |
denotes |
Long |
T11170 |
51601-51605 |
NN |
denotes |
term |
T11171 |
51600-51601 |
HYPH |
denotes |
- |
T11172 |
51606-51616 |
NNS |
denotes |
treatments |
T11173 |
51633-51635 |
VB |
denotes |
be |
T11174 |
51617-51622 |
MD |
denotes |
would |
T11175 |
51623-51632 |
RB |
denotes |
certainly |
T11176 |
51636-51644 |
JJ |
denotes |
possible |
T11177 |
51645-51648 |
CC |
denotes |
and |
T11178 |
51649-51654 |
MD |
denotes |
could |
T11179 |
51655-51657 |
VB |
denotes |
be |
T11180 |
51658-51659 |
DT |
denotes |
a |
T11181 |
51660-51663 |
NN |
denotes |
key |
T11182 |
51664-51666 |
IN |
denotes |
to |
T11183 |
51667-51676 |
JJ |
denotes |
effective |
T11184 |
51677-51684 |
NN |
denotes |
therapy |
T11185 |
51684-51685 |
. |
denotes |
. |
T11186 |
51685-51982 |
sentence |
denotes |
Overall, however, we interpret our findings as evidence that AD therapies that significantly lower the production of Aβ (by either inhibiting secretase activity or inhibiting APP expression) may not quickly reverse preexisting pathology, but should effectively halt further deposition of amyloid. |
T11187 |
51686-51693 |
RB |
denotes |
Overall |
T11188 |
51707-51716 |
VBP |
denotes |
interpret |
T11189 |
51693-51695 |
, |
denotes |
, |
T11190 |
51695-51702 |
RB |
denotes |
however |
T11191 |
51702-51704 |
, |
denotes |
, |
T11192 |
51704-51706 |
PRP |
denotes |
we |
T11193 |
51717-51720 |
PRP$ |
denotes |
our |
T11194 |
51721-51729 |
NNS |
denotes |
findings |
T11195 |
51730-51732 |
IN |
denotes |
as |
T11196 |
51733-51741 |
NN |
denotes |
evidence |
T11197 |
51742-51746 |
IN |
denotes |
that |
T11198 |
51893-51900 |
VB |
denotes |
reverse |
T11199 |
51747-51749 |
NN |
denotes |
AD |
T11200 |
51750-51759 |
NNS |
denotes |
therapies |
T11201 |
51760-51764 |
WDT |
denotes |
that |
T11202 |
51779-51784 |
VBP |
denotes |
lower |
T11203 |
51765-51778 |
RB |
denotes |
significantly |
T11204 |
51785-51788 |
DT |
denotes |
the |
T11205 |
51789-51799 |
NN |
denotes |
production |
T11206 |
51800-51802 |
IN |
denotes |
of |
T11207 |
51803-51805 |
NN |
denotes |
Aβ |
T11208 |
51806-51807 |
-LRB- |
denotes |
( |
T11209 |
51807-51809 |
IN |
denotes |
by |
T11210 |
51810-51816 |
CC |
denotes |
either |
T11211 |
51817-51827 |
VBG |
denotes |
inhibiting |
T11212 |
51828-51837 |
NN |
denotes |
secretase |
T11213 |
51838-51846 |
NN |
denotes |
activity |
T11214 |
51847-51849 |
CC |
denotes |
or |
T11215 |
51850-51860 |
VBG |
denotes |
inhibiting |
T11216 |
51861-51864 |
NN |
denotes |
APP |
T11217 |
51865-51875 |
NN |
denotes |
expression |
T11218 |
51875-51876 |
-RRB- |
denotes |
) |
T11219 |
51877-51880 |
MD |
denotes |
may |
T11220 |
51881-51884 |
RB |
denotes |
not |
T11221 |
51885-51892 |
RB |
denotes |
quickly |
T11222 |
51901-51912 |
JJ |
denotes |
preexisting |
T11223 |
51913-51922 |
NN |
denotes |
pathology |
T11224 |
51922-51924 |
, |
denotes |
, |
T11225 |
51924-51927 |
CC |
denotes |
but |
T11226 |
51928-51934 |
MD |
denotes |
should |
T11227 |
51947-51951 |
VB |
denotes |
halt |
T11228 |
51935-51946 |
RB |
denotes |
effectively |
T11229 |
51952-51959 |
JJ |
denotes |
further |
T11230 |
51960-51970 |
NN |
denotes |
deposition |
T11231 |
51971-51973 |
IN |
denotes |
of |
T11232 |
51974-51981 |
NN |
denotes |
amyloid |
T11233 |
51981-51982 |
. |
denotes |
. |
T11234 |
51982-52300 |
sentence |
denotes |
In interpreting our study, it should be remembered that the earliest plaques to appear in these mice, like other APP transgenics harboring the Swedish mutation [27], are predominantly fibrillar deposits, which may be less tractable than the diffuse aggregates thought to come first in the course of the human disease. |
T11235 |
51983-51985 |
IN |
denotes |
In |
T11236 |
52023-52033 |
VBN |
denotes |
remembered |
T11237 |
51986-51998 |
VBG |
denotes |
interpreting |
T11238 |
51999-52002 |
PRP$ |
denotes |
our |
T11239 |
52003-52008 |
NN |
denotes |
study |
T11240 |
52008-52010 |
, |
denotes |
, |
T11241 |
52010-52012 |
PRP |
denotes |
it |
T11242 |
52013-52019 |
MD |
denotes |
should |
T11243 |
52020-52022 |
VB |
denotes |
be |
T11244 |
52034-52038 |
IN |
denotes |
that |
T11245 |
52149-52152 |
VBP |
denotes |
are |
T11246 |
52039-52042 |
DT |
denotes |
the |
T11247 |
52052-52059 |
NNS |
denotes |
plaques |
T11248 |
52043-52051 |
JJS |
denotes |
earliest |
T11249 |
52060-52062 |
TO |
denotes |
to |
T11250 |
52063-52069 |
VB |
denotes |
appear |
T11251 |
52070-52072 |
IN |
denotes |
in |
T11252 |
52073-52078 |
DT |
denotes |
these |
T11253 |
52079-52083 |
NNS |
denotes |
mice |
T11254 |
52083-52085 |
, |
denotes |
, |
T11255 |
52085-52089 |
IN |
denotes |
like |
T11256 |
52090-52095 |
JJ |
denotes |
other |
T11257 |
52100-52111 |
NNS |
denotes |
transgenics |
T11258 |
52096-52099 |
NN |
denotes |
APP |
T11259 |
52112-52121 |
VBG |
denotes |
harboring |
T11260 |
52122-52125 |
DT |
denotes |
the |
T11261 |
52134-52142 |
NN |
denotes |
mutation |
T11262 |
52126-52133 |
JJ |
denotes |
Swedish |
T11263 |
52143-52144 |
-LRB- |
denotes |
[ |
T11264 |
52144-52146 |
CD |
denotes |
27 |
T11265 |
52146-52147 |
-RRB- |
denotes |
] |
T11266 |
52147-52149 |
, |
denotes |
, |
T11267 |
52153-52166 |
RB |
denotes |
predominantly |
T11268 |
52167-52176 |
JJ |
denotes |
fibrillar |
T11269 |
52177-52185 |
NNS |
denotes |
deposits |
T11270 |
52185-52187 |
, |
denotes |
, |
T11271 |
52187-52192 |
WDT |
denotes |
which |
T11272 |
52197-52199 |
VB |
denotes |
be |
T11273 |
52193-52196 |
MD |
denotes |
may |
T11274 |
52200-52204 |
RBR |
denotes |
less |
T11275 |
52205-52214 |
JJ |
denotes |
tractable |
T11276 |
52215-52219 |
IN |
denotes |
than |
T11277 |
52220-52223 |
DT |
denotes |
the |
T11278 |
52232-52242 |
NNS |
denotes |
aggregates |
T11279 |
52224-52231 |
JJ |
denotes |
diffuse |
T11280 |
52243-52250 |
VBN |
denotes |
thought |
T11281 |
52251-52253 |
TO |
denotes |
to |
T11282 |
52254-52258 |
VB |
denotes |
come |
T11283 |
52259-52264 |
RB |
denotes |
first |
T11284 |
52265-52267 |
IN |
denotes |
in |
T11285 |
52268-52271 |
DT |
denotes |
the |
T11286 |
52272-52278 |
NN |
denotes |
course |
T11287 |
52279-52281 |
IN |
denotes |
of |
T11288 |
52282-52285 |
DT |
denotes |
the |
T11289 |
52292-52299 |
NN |
denotes |
disease |
T11290 |
52286-52291 |
JJ |
denotes |
human |
T11291 |
52299-52300 |
. |
denotes |
. |
T11292 |
52300-52461 |
sentence |
denotes |
However, our data suggest that once diffuse deposits are formed in these mice, they are no more easily cleared in our system than cored plaques (see Figure S4). |
T11293 |
52301-52308 |
RB |
denotes |
However |
T11294 |
52319-52326 |
VBP |
denotes |
suggest |
T11295 |
52308-52310 |
, |
denotes |
, |
T11296 |
52310-52313 |
PRP$ |
denotes |
our |
T11297 |
52314-52318 |
NNS |
denotes |
data |
T11298 |
52327-52331 |
IN |
denotes |
that |
T11299 |
52404-52411 |
VBN |
denotes |
cleared |
T11300 |
52332-52336 |
IN |
denotes |
once |
T11301 |
52358-52364 |
VBN |
denotes |
formed |
T11302 |
52337-52344 |
JJ |
denotes |
diffuse |
T11303 |
52345-52353 |
NNS |
denotes |
deposits |
T11304 |
52354-52357 |
VBP |
denotes |
are |
T11305 |
52365-52367 |
IN |
denotes |
in |
T11306 |
52368-52373 |
DT |
denotes |
these |
T11307 |
52374-52378 |
NNS |
denotes |
mice |
T11308 |
52378-52380 |
, |
denotes |
, |
T11309 |
52380-52384 |
PRP |
denotes |
they |
T11310 |
52385-52388 |
VBP |
denotes |
are |
T11311 |
52389-52391 |
RB |
denotes |
no |
T11312 |
52392-52396 |
RBR |
denotes |
more |
T11313 |
52397-52403 |
RB |
denotes |
easily |
T11314 |
52412-52414 |
IN |
denotes |
in |
T11315 |
52415-52418 |
PRP$ |
denotes |
our |
T11316 |
52419-52425 |
NN |
denotes |
system |
T11317 |
52426-52430 |
IN |
denotes |
than |
T11318 |
52431-52436 |
VBN |
denotes |
cored |
T11319 |
52437-52444 |
NNS |
denotes |
plaques |
T11320 |
52445-52446 |
-LRB- |
denotes |
( |
T11321 |
52446-52449 |
VB |
denotes |
see |
T11322 |
52450-52456 |
NN |
denotes |
Figure |
T11323 |
52457-52459 |
NN |
denotes |
S4 |
T11324 |
52459-52460 |
-RRB- |
denotes |
) |
T11325 |
52460-52461 |
. |
denotes |
. |
T11326 |
52461-52637 |
sentence |
denotes |
An additional consideration we recognize is that a small amount of transgene expression continues in the presence of dox and that endogenous mouse Aβ continues to be produced. |
T11327 |
52462-52464 |
DT |
denotes |
An |
T11328 |
52476-52489 |
NN |
denotes |
consideration |
T11329 |
52465-52475 |
JJ |
denotes |
additional |
T11330 |
52503-52505 |
VBZ |
denotes |
is |
T11331 |
52490-52492 |
PRP |
denotes |
we |
T11332 |
52493-52502 |
VBP |
denotes |
recognize |
T11333 |
52506-52510 |
IN |
denotes |
that |
T11334 |
52550-52559 |
VBZ |
denotes |
continues |
T11335 |
52511-52512 |
DT |
denotes |
a |
T11336 |
52519-52525 |
NN |
denotes |
amount |
T11337 |
52513-52518 |
JJ |
denotes |
small |
T11338 |
52526-52528 |
IN |
denotes |
of |
T11339 |
52529-52538 |
NN |
denotes |
transgene |
T11340 |
52539-52549 |
NN |
denotes |
expression |
T11341 |
52560-52562 |
IN |
denotes |
in |
T11342 |
52563-52566 |
DT |
denotes |
the |
T11343 |
52567-52575 |
NN |
denotes |
presence |
T11344 |
52576-52578 |
IN |
denotes |
of |
T11345 |
52579-52582 |
NN |
denotes |
dox |
T11346 |
52583-52586 |
CC |
denotes |
and |
T11347 |
52587-52591 |
IN |
denotes |
that |
T11348 |
52612-52621 |
VBZ |
denotes |
continues |
T11349 |
52592-52602 |
JJ |
denotes |
endogenous |
T11350 |
52609-52611 |
NN |
denotes |
Aβ |
T11351 |
52603-52608 |
NN |
denotes |
mouse |
T11352 |
52622-52624 |
TO |
denotes |
to |
T11353 |
52628-52636 |
VBN |
denotes |
produced |
T11354 |
52625-52627 |
VB |
denotes |
be |
T11355 |
52636-52637 |
. |
denotes |
. |
T11356 |
52637-52782 |
sentence |
denotes |
It is possible that the combined low levels of endogenous mouse Aβ and nonsuppressed human peptide are sufficient to maintain existing deposits. |
T11357 |
52638-52640 |
PRP |
denotes |
It |
T11358 |
52641-52643 |
VBZ |
denotes |
is |
T11359 |
52644-52652 |
JJ |
denotes |
possible |
T11360 |
52653-52657 |
IN |
denotes |
that |
T11361 |
52737-52740 |
VBP |
denotes |
are |
T11362 |
52658-52661 |
DT |
denotes |
the |
T11363 |
52675-52681 |
NNS |
denotes |
levels |
T11364 |
52662-52670 |
VBN |
denotes |
combined |
T11365 |
52671-52674 |
JJ |
denotes |
low |
T11366 |
52682-52684 |
IN |
denotes |
of |
T11367 |
52685-52695 |
JJ |
denotes |
endogenous |
T11368 |
52702-52704 |
NN |
denotes |
Aβ |
T11369 |
52696-52701 |
NN |
denotes |
mouse |
T11370 |
52729-52736 |
NN |
denotes |
peptide |
T11371 |
52705-52708 |
CC |
denotes |
and |
T11372 |
52709-52722 |
JJ |
denotes |
nonsuppressed |
T11373 |
52723-52728 |
JJ |
denotes |
human |
T11374 |
52741-52751 |
JJ |
denotes |
sufficient |
T11375 |
52752-52754 |
TO |
denotes |
to |
T11376 |
52755-52763 |
VB |
denotes |
maintain |
T11377 |
52764-52772 |
VBG |
denotes |
existing |
T11378 |
52773-52781 |
NNS |
denotes |
deposits |
T11379 |
52781-52782 |
. |
denotes |
. |
T11380 |
52782-52987 |
sentence |
denotes |
However, these low levels of peptide are not sufficient to induce new amyloid formation, as CaMKIIα-tTA × tetAPPswe/ind mice raised on dox for up to a year do not develop amyloid lesions (data not shown). |
T11381 |
52783-52790 |
RB |
denotes |
However |
T11382 |
52820-52823 |
VBP |
denotes |
are |
T11383 |
52790-52792 |
, |
denotes |
, |
T11384 |
52792-52797 |
DT |
denotes |
these |
T11385 |
52802-52808 |
NNS |
denotes |
levels |
T11386 |
52798-52801 |
JJ |
denotes |
low |
T11387 |
52809-52811 |
IN |
denotes |
of |
T11388 |
52812-52819 |
NN |
denotes |
peptide |
T11389 |
52824-52827 |
RB |
denotes |
not |
T11390 |
52828-52838 |
JJ |
denotes |
sufficient |
T11391 |
52839-52841 |
TO |
denotes |
to |
T11392 |
52842-52848 |
VB |
denotes |
induce |
T11393 |
52849-52852 |
JJ |
denotes |
new |
T11394 |
52861-52870 |
NN |
denotes |
formation |
T11395 |
52853-52860 |
NN |
denotes |
amyloid |
T11396 |
52870-52872 |
, |
denotes |
, |
T11397 |
52872-52874 |
IN |
denotes |
as |
T11398 |
52946-52953 |
VB |
denotes |
develop |
T11399 |
52875-52882 |
NN |
denotes |
CaMKIIα |
T11400 |
52899-52902 |
NN |
denotes |
ind |
T11401 |
52882-52883 |
HYPH |
denotes |
- |
T11402 |
52883-52886 |
NN |
denotes |
tTA |
T11403 |
52887-52888 |
SYM |
denotes |
× |
T11404 |
52889-52898 |
NN |
denotes |
tetAPPswe |
T11405 |
52898-52899 |
HYPH |
denotes |
/ |
T11406 |
52903-52907 |
NNS |
denotes |
mice |
T11407 |
52908-52914 |
VBN |
denotes |
raised |
T11408 |
52915-52917 |
IN |
denotes |
on |
T11409 |
52918-52921 |
NN |
denotes |
dox |
T11410 |
52922-52925 |
IN |
denotes |
for |
T11411 |
52926-52928 |
IN |
denotes |
up |
T11412 |
52932-52933 |
DT |
denotes |
a |
T11413 |
52929-52931 |
IN |
denotes |
to |
T11414 |
52934-52938 |
NN |
denotes |
year |
T11415 |
52939-52941 |
VBP |
denotes |
do |
T11416 |
52942-52945 |
RB |
denotes |
not |
T11417 |
52954-52961 |
NN |
denotes |
amyloid |
T11418 |
52962-52969 |
NNS |
denotes |
lesions |
T11419 |
52970-52971 |
-LRB- |
denotes |
( |
T11420 |
52980-52985 |
VBN |
denotes |
shown |
T11421 |
52971-52975 |
NNS |
denotes |
data |
T11422 |
52976-52979 |
RB |
denotes |
not |
T11423 |
52985-52986 |
-RRB- |
denotes |
) |
T11424 |
52986-52987 |
. |
denotes |
. |
T11425 |
52987-53167 |
sentence |
denotes |
It is also clear that in this genetic system, we have raised the production of Aβ to levels not found in humans to accelerate pathology into an experimentally feasible time frame. |
T11426 |
52988-52990 |
PRP |
denotes |
It |
T11427 |
52991-52993 |
VBZ |
denotes |
is |
T11428 |
52994-52998 |
RB |
denotes |
also |
T11429 |
52999-53004 |
JJ |
denotes |
clear |
T11430 |
53005-53009 |
IN |
denotes |
that |
T11431 |
53042-53048 |
VBN |
denotes |
raised |
T11432 |
53010-53012 |
IN |
denotes |
in |
T11433 |
53013-53017 |
DT |
denotes |
this |
T11434 |
53026-53032 |
NN |
denotes |
system |
T11435 |
53018-53025 |
JJ |
denotes |
genetic |
T11436 |
53032-53034 |
, |
denotes |
, |
T11437 |
53034-53036 |
PRP |
denotes |
we |
T11438 |
53037-53041 |
VBP |
denotes |
have |
T11439 |
53049-53052 |
DT |
denotes |
the |
T11440 |
53053-53063 |
NN |
denotes |
production |
T11441 |
53064-53066 |
IN |
denotes |
of |
T11442 |
53067-53069 |
NN |
denotes |
Aβ |
T11443 |
53070-53072 |
IN |
denotes |
to |
T11444 |
53073-53079 |
NNS |
denotes |
levels |
T11445 |
53080-53083 |
RB |
denotes |
not |
T11446 |
53084-53089 |
VBN |
denotes |
found |
T11447 |
53090-53092 |
IN |
denotes |
in |
T11448 |
53093-53099 |
NNS |
denotes |
humans |
T11449 |
53100-53102 |
TO |
denotes |
to |
T11450 |
53103-53113 |
VB |
denotes |
accelerate |
T11451 |
53114-53123 |
NN |
denotes |
pathology |
T11452 |
53124-53128 |
IN |
denotes |
into |
T11453 |
53129-53131 |
DT |
denotes |
an |
T11454 |
53161-53166 |
NN |
denotes |
frame |
T11455 |
53132-53146 |
RB |
denotes |
experimentally |
T11456 |
53147-53155 |
JJ |
denotes |
feasible |
T11457 |
53156-53160 |
NN |
denotes |
time |
T11458 |
53166-53167 |
. |
denotes |
. |
T11459 |
53167-53426 |
sentence |
denotes |
This system allowed us to create an approximately 20-fold differential between APP/Aβ synthetic rates before and after treatment, yet the in vivo equilibrium between aggregated and disaggregated states of Aβ still favored the maintenance of amyloid deposits. |
T11460 |
53168-53172 |
DT |
denotes |
This |
T11461 |
53173-53179 |
NN |
denotes |
system |
T11462 |
53180-53187 |
VBD |
denotes |
allowed |
T11463 |
53382-53389 |
VBD |
denotes |
favored |
T11464 |
53188-53190 |
PRP |
denotes |
us |
T11465 |
53194-53200 |
VB |
denotes |
create |
T11466 |
53191-53193 |
TO |
denotes |
to |
T11467 |
53201-53203 |
DT |
denotes |
an |
T11468 |
53226-53238 |
NN |
denotes |
differential |
T11469 |
53204-53217 |
RB |
denotes |
approximately |
T11470 |
53218-53225 |
JJ |
denotes |
20-fold |
T11471 |
53239-53246 |
IN |
denotes |
between |
T11472 |
53247-53250 |
NN |
denotes |
APP |
T11473 |
53251-53253 |
NN |
denotes |
Aβ |
T11474 |
53250-53251 |
HYPH |
denotes |
/ |
T11475 |
53264-53269 |
NNS |
denotes |
rates |
T11476 |
53254-53263 |
JJ |
denotes |
synthetic |
T11477 |
53270-53276 |
IN |
denotes |
before |
T11478 |
53277-53280 |
CC |
denotes |
and |
T11479 |
53281-53286 |
IN |
denotes |
after |
T11480 |
53287-53296 |
NN |
denotes |
treatment |
T11481 |
53296-53298 |
, |
denotes |
, |
T11482 |
53298-53301 |
RB |
denotes |
yet |
T11483 |
53302-53305 |
DT |
denotes |
the |
T11484 |
53314-53325 |
NN |
denotes |
equilibrium |
T11485 |
53306-53308 |
FW |
denotes |
in |
T11486 |
53309-53313 |
FW |
denotes |
vivo |
T11487 |
53326-53333 |
IN |
denotes |
between |
T11488 |
53334-53344 |
VBN |
denotes |
aggregated |
T11489 |
53363-53369 |
NNS |
denotes |
states |
T11490 |
53345-53348 |
CC |
denotes |
and |
T11491 |
53349-53362 |
VBN |
denotes |
disaggregated |
T11492 |
53370-53372 |
IN |
denotes |
of |
T11493 |
53373-53375 |
NN |
denotes |
Aβ |
T11494 |
53376-53381 |
RB |
denotes |
still |
T11495 |
53390-53393 |
DT |
denotes |
the |
T11496 |
53394-53405 |
NN |
denotes |
maintenance |
T11497 |
53406-53408 |
IN |
denotes |
of |
T11498 |
53409-53416 |
NN |
denotes |
amyloid |
T11499 |
53417-53425 |
NNS |
denotes |
deposits |
T11500 |
53425-53426 |
. |
denotes |
. |
T11501 |
53426-53567 |
sentence |
denotes |
In our opinion, it seems unlikely that amyloid deposits in human brain would be inherently any less stable than those formed in mouse brain. |
T11502 |
53427-53429 |
IN |
denotes |
In |
T11503 |
53446-53451 |
VBZ |
denotes |
seems |
T11504 |
53430-53433 |
PRP$ |
denotes |
our |
T11505 |
53434-53441 |
NN |
denotes |
opinion |
T11506 |
53441-53443 |
, |
denotes |
, |
T11507 |
53443-53445 |
PRP |
denotes |
it |
T11508 |
53452-53460 |
JJ |
denotes |
unlikely |
T11509 |
53461-53465 |
IN |
denotes |
that |
T11510 |
53504-53506 |
VB |
denotes |
be |
T11511 |
53466-53473 |
NN |
denotes |
amyloid |
T11512 |
53474-53482 |
NNS |
denotes |
deposits |
T11513 |
53483-53485 |
IN |
denotes |
in |
T11514 |
53486-53491 |
JJ |
denotes |
human |
T11515 |
53492-53497 |
NN |
denotes |
brain |
T11516 |
53498-53503 |
MD |
denotes |
would |
T11517 |
53507-53517 |
RB |
denotes |
inherently |
T11518 |
53518-53521 |
DT |
denotes |
any |
T11519 |
53527-53533 |
JJ |
denotes |
stable |
T11520 |
53522-53526 |
RBR |
denotes |
less |
T11521 |
53534-53538 |
IN |
denotes |
than |
T11522 |
53539-53544 |
DT |
denotes |
those |
T11523 |
53545-53551 |
VBN |
denotes |
formed |
T11524 |
53552-53554 |
IN |
denotes |
in |
T11525 |
53555-53560 |
NN |
denotes |
mouse |
T11526 |
53561-53566 |
NN |
denotes |
brain |
T11527 |
53566-53567 |
. |
denotes |
. |
T11528 |
53567-53707 |
sentence |
denotes |
However, the human brain may harbor clearance mechanisms not shared by mice that would allow more efficient removal of preexisting amyloid. |
T11529 |
53568-53575 |
RB |
denotes |
However |
T11530 |
53597-53603 |
VB |
denotes |
harbor |
T11531 |
53575-53577 |
, |
denotes |
, |
T11532 |
53577-53580 |
DT |
denotes |
the |
T11533 |
53587-53592 |
NN |
denotes |
brain |
T11534 |
53581-53586 |
JJ |
denotes |
human |
T11535 |
53593-53596 |
MD |
denotes |
may |
T11536 |
53604-53613 |
NN |
denotes |
clearance |
T11537 |
53614-53624 |
NNS |
denotes |
mechanisms |
T11538 |
53625-53628 |
RB |
denotes |
not |
T11539 |
53629-53635 |
VBN |
denotes |
shared |
T11540 |
53636-53638 |
IN |
denotes |
by |
T11541 |
53639-53643 |
NNS |
denotes |
mice |
T11542 |
53644-53648 |
WDT |
denotes |
that |
T11543 |
53655-53660 |
VB |
denotes |
allow |
T11544 |
53649-53654 |
MD |
denotes |
would |
T11545 |
53661-53665 |
RBR |
denotes |
more |
T11546 |
53666-53675 |
JJ |
denotes |
efficient |
T11547 |
53676-53683 |
NN |
denotes |
removal |
T11548 |
53684-53686 |
IN |
denotes |
of |
T11549 |
53687-53698 |
VBG |
denotes |
preexisting |
T11550 |
53699-53706 |
NN |
denotes |
amyloid |
T11551 |
53706-53707 |
. |
denotes |
. |
T11552 |
53707-53862 |
sentence |
denotes |
One potential mechanism by which amyloid may be more efficiently removed in the human disease than in the mouse models is through microglial phagocytosis. |
T11553 |
53708-53711 |
CD |
denotes |
One |
T11554 |
53722-53731 |
NN |
denotes |
mechanism |
T11555 |
53712-53721 |
JJ |
denotes |
potential |
T11556 |
53827-53829 |
VBZ |
denotes |
is |
T11557 |
53732-53734 |
IN |
denotes |
by |
T11558 |
53773-53780 |
VBN |
denotes |
removed |
T11559 |
53735-53740 |
WDT |
denotes |
which |
T11560 |
53741-53748 |
NN |
denotes |
amyloid |
T11561 |
53749-53752 |
MD |
denotes |
may |
T11562 |
53753-53755 |
VB |
denotes |
be |
T11563 |
53756-53760 |
RBR |
denotes |
more |
T11564 |
53761-53772 |
RB |
denotes |
efficiently |
T11565 |
53781-53783 |
IN |
denotes |
in |
T11566 |
53784-53787 |
DT |
denotes |
the |
T11567 |
53794-53801 |
NN |
denotes |
disease |
T11568 |
53788-53793 |
JJ |
denotes |
human |
T11569 |
53802-53806 |
IN |
denotes |
than |
T11570 |
53807-53809 |
IN |
denotes |
in |
T11571 |
53810-53813 |
DT |
denotes |
the |
T11572 |
53820-53826 |
NNS |
denotes |
models |
T11573 |
53814-53819 |
NN |
denotes |
mouse |
T11574 |
53830-53837 |
IN |
denotes |
through |
T11575 |
53838-53848 |
JJ |
denotes |
microglial |
T11576 |
53849-53861 |
NN |
denotes |
phagocytosis |
T11577 |
53861-53862 |
. |
denotes |
. |
T11578 |
53862-54003 |
sentence |
denotes |
Resident microglia in transgenic mouse models localize to tissue surrounding plaques but show little evidence of amyloid engulfment [37–40]. |
T11579 |
53863-53871 |
JJ |
denotes |
Resident |
T11580 |
53872-53881 |
NNS |
denotes |
microglia |
T11581 |
53909-53917 |
VBP |
denotes |
localize |
T11582 |
53882-53884 |
IN |
denotes |
in |
T11583 |
53885-53895 |
JJ |
denotes |
transgenic |
T11584 |
53902-53908 |
NNS |
denotes |
models |
T11585 |
53896-53901 |
NN |
denotes |
mouse |
T11586 |
53918-53920 |
IN |
denotes |
to |
T11587 |
53921-53927 |
NN |
denotes |
tissue |
T11588 |
53928-53939 |
VBG |
denotes |
surrounding |
T11589 |
53940-53947 |
NNS |
denotes |
plaques |
T11590 |
53948-53951 |
CC |
denotes |
but |
T11591 |
53952-53956 |
VBP |
denotes |
show |
T11592 |
53957-53963 |
JJ |
denotes |
little |
T11593 |
53964-53972 |
NN |
denotes |
evidence |
T11594 |
53973-53975 |
IN |
denotes |
of |
T11595 |
53976-53983 |
NN |
denotes |
amyloid |
T11596 |
53984-53994 |
NN |
denotes |
engulfment |
T11597 |
53995-53996 |
-LRB- |
denotes |
[ |
T11598 |
53996-53998 |
CD |
denotes |
37 |
T11599 |
53998-53999 |
SYM |
denotes |
– |
T11600 |
53999-54001 |
CD |
denotes |
40 |
T11601 |
54001-54002 |
-RRB- |
denotes |
] |
T11602 |
54002-54003 |
. |
denotes |
. |
T11603 |
54003-54161 |
sentence |
denotes |
In contrast, microglia surrounding amyloid plaques in human brain show a much higher state of activation with greater expression of complement receptor [40]. |
T11604 |
54004-54006 |
IN |
denotes |
In |
T11605 |
54070-54074 |
VBP |
denotes |
show |
T11606 |
54007-54015 |
NN |
denotes |
contrast |
T11607 |
54015-54017 |
, |
denotes |
, |
T11608 |
54017-54026 |
NNS |
denotes |
microglia |
T11609 |
54027-54038 |
VBG |
denotes |
surrounding |
T11610 |
54039-54046 |
NN |
denotes |
amyloid |
T11611 |
54047-54054 |
NNS |
denotes |
plaques |
T11612 |
54055-54057 |
IN |
denotes |
in |
T11613 |
54058-54063 |
JJ |
denotes |
human |
T11614 |
54064-54069 |
NN |
denotes |
brain |
T11615 |
54075-54076 |
DT |
denotes |
a |
T11616 |
54089-54094 |
NN |
denotes |
state |
T11617 |
54077-54081 |
RB |
denotes |
much |
T11618 |
54082-54088 |
JJR |
denotes |
higher |
T11619 |
54095-54097 |
IN |
denotes |
of |
T11620 |
54098-54108 |
NN |
denotes |
activation |
T11621 |
54109-54113 |
IN |
denotes |
with |
T11622 |
54114-54121 |
JJR |
denotes |
greater |
T11623 |
54122-54132 |
NN |
denotes |
expression |
T11624 |
54133-54135 |
IN |
denotes |
of |
T11625 |
54136-54146 |
NN |
denotes |
complement |
T11626 |
54147-54155 |
NN |
denotes |
receptor |
T11627 |
54156-54157 |
-LRB- |
denotes |
[ |
T11628 |
54157-54159 |
CD |
denotes |
40 |
T11629 |
54159-54160 |
-RRB- |
denotes |
] |
T11630 |
54160-54161 |
. |
denotes |
. |
T11631 |
54161-54274 |
sentence |
denotes |
Thus, the role of microglia in amyloid metabolism is minor in transgenic models compared to the human condition. |
T11632 |
54162-54166 |
RB |
denotes |
Thus |
T11633 |
54212-54214 |
VBZ |
denotes |
is |
T11634 |
54166-54168 |
, |
denotes |
, |
T11635 |
54168-54171 |
DT |
denotes |
the |
T11636 |
54172-54176 |
NN |
denotes |
role |
T11637 |
54177-54179 |
IN |
denotes |
of |
T11638 |
54180-54189 |
NNS |
denotes |
microglia |
T11639 |
54190-54192 |
IN |
denotes |
in |
T11640 |
54193-54200 |
NN |
denotes |
amyloid |
T11641 |
54201-54211 |
NN |
denotes |
metabolism |
T11642 |
54215-54220 |
JJ |
denotes |
minor |
T11643 |
54221-54223 |
IN |
denotes |
in |
T11644 |
54224-54234 |
JJ |
denotes |
transgenic |
T11645 |
54235-54241 |
NNS |
denotes |
models |
T11646 |
54242-54250 |
VBN |
denotes |
compared |
T11647 |
54251-54253 |
IN |
denotes |
to |
T11648 |
54254-54257 |
DT |
denotes |
the |
T11649 |
54264-54273 |
NN |
denotes |
condition |
T11650 |
54258-54263 |
JJ |
denotes |
human |
T11651 |
54273-54274 |
. |
denotes |
. |
T11652 |
54274-54565 |
sentence |
denotes |
Somewhat paradoxically, several studies further demonstrate that treatment with anti-inflammatory drugs to reduce microglial activation actually lowers amyloid load in APP transgenic mice, suggesting a role for mouse microglia in the formation and maintenance of amyloid aggregates [41–43]. |
T11653 |
54275-54283 |
RB |
denotes |
Somewhat |
T11654 |
54284-54297 |
RB |
denotes |
paradoxically |
T11655 |
54323-54334 |
VBP |
denotes |
demonstrate |
T11656 |
54297-54299 |
, |
denotes |
, |
T11657 |
54299-54306 |
JJ |
denotes |
several |
T11658 |
54307-54314 |
NNS |
denotes |
studies |
T11659 |
54315-54322 |
RB |
denotes |
further |
T11660 |
54335-54339 |
IN |
denotes |
that |
T11661 |
54420-54426 |
VBZ |
denotes |
lowers |
T11662 |
54340-54349 |
NN |
denotes |
treatment |
T11663 |
54350-54354 |
IN |
denotes |
with |
T11664 |
54355-54372 |
JJ |
denotes |
anti-inflammatory |
T11665 |
54373-54378 |
NNS |
denotes |
drugs |
T11666 |
54379-54381 |
TO |
denotes |
to |
T11667 |
54382-54388 |
VB |
denotes |
reduce |
T11668 |
54389-54399 |
JJ |
denotes |
microglial |
T11669 |
54400-54410 |
NN |
denotes |
activation |
T11670 |
54411-54419 |
RB |
denotes |
actually |
T11671 |
54427-54434 |
NN |
denotes |
amyloid |
T11672 |
54435-54439 |
NN |
denotes |
load |
T11673 |
54440-54442 |
IN |
denotes |
in |
T11674 |
54443-54446 |
NN |
denotes |
APP |
T11675 |
54447-54457 |
JJ |
denotes |
transgenic |
T11676 |
54458-54462 |
NNS |
denotes |
mice |
T11677 |
54462-54464 |
, |
denotes |
, |
T11678 |
54464-54474 |
VBG |
denotes |
suggesting |
T11679 |
54475-54476 |
DT |
denotes |
a |
T11680 |
54477-54481 |
NN |
denotes |
role |
T11681 |
54482-54485 |
IN |
denotes |
for |
T11682 |
54486-54491 |
NN |
denotes |
mouse |
T11683 |
54492-54501 |
NNS |
denotes |
microglia |
T11684 |
54502-54504 |
IN |
denotes |
in |
T11685 |
54505-54508 |
DT |
denotes |
the |
T11686 |
54509-54518 |
NN |
denotes |
formation |
T11687 |
54519-54522 |
CC |
denotes |
and |
T11688 |
54523-54534 |
NN |
denotes |
maintenance |
T11689 |
54535-54537 |
IN |
denotes |
of |
T11690 |
54538-54545 |
NN |
denotes |
amyloid |
T11691 |
54546-54556 |
NNS |
denotes |
aggregates |
T11692 |
54557-54558 |
-LRB- |
denotes |
[ |
T11693 |
54558-54560 |
CD |
denotes |
41 |
T11694 |
54560-54561 |
SYM |
denotes |
– |
T11695 |
54561-54563 |
CD |
denotes |
43 |
T11696 |
54563-54564 |
-RRB- |
denotes |
] |
T11697 |
54564-54565 |
. |
denotes |
. |
T11698 |
54565-54701 |
sentence |
denotes |
However, this outcome may be alternatively explained by direct effects of many anti-inflammatory drugs on γ-secretase cleavage [44–47]. |
T11699 |
54566-54573 |
RB |
denotes |
However |
T11700 |
54609-54618 |
VBN |
denotes |
explained |
T11701 |
54573-54575 |
, |
denotes |
, |
T11702 |
54575-54579 |
DT |
denotes |
this |
T11703 |
54580-54587 |
NN |
denotes |
outcome |
T11704 |
54588-54591 |
MD |
denotes |
may |
T11705 |
54592-54594 |
VB |
denotes |
be |
T11706 |
54595-54608 |
RB |
denotes |
alternatively |
T11707 |
54619-54621 |
IN |
denotes |
by |
T11708 |
54622-54628 |
JJ |
denotes |
direct |
T11709 |
54629-54636 |
NNS |
denotes |
effects |
T11710 |
54637-54639 |
IN |
denotes |
of |
T11711 |
54640-54644 |
JJ |
denotes |
many |
T11712 |
54663-54668 |
NNS |
denotes |
drugs |
T11713 |
54645-54662 |
JJ |
denotes |
anti-inflammatory |
T11714 |
54669-54671 |
IN |
denotes |
on |
T11715 |
54672-54673 |
SYM |
denotes |
γ |
T11716 |
54674-54683 |
NN |
denotes |
secretase |
T11717 |
54673-54674 |
HYPH |
denotes |
- |
T11718 |
54684-54692 |
NN |
denotes |
cleavage |
T11719 |
54693-54694 |
-LRB- |
denotes |
[ |
T11720 |
54694-54696 |
CD |
denotes |
44 |
T11721 |
54696-54697 |
SYM |
denotes |
– |
T11722 |
54697-54699 |
CD |
denotes |
47 |
T11723 |
54699-54700 |
-RRB- |
denotes |
] |
T11724 |
54700-54701 |
. |
denotes |
. |
T11725 |
54701-54992 |
sentence |
denotes |
Nonetheless, the role of microglia in both the human condition and the mouse models is poorly understood, and differences in microglial reactivity between the two could lead to significantly faster amyloid clearance in the brains of patients with AD than we observe in the tet-off APP mice. |
T11726 |
54702-54713 |
RB |
denotes |
Nonetheless |
T11727 |
54786-54788 |
VBZ |
denotes |
is |
T11728 |
54713-54715 |
, |
denotes |
, |
T11729 |
54715-54718 |
DT |
denotes |
the |
T11730 |
54719-54723 |
NN |
denotes |
role |
T11731 |
54724-54726 |
IN |
denotes |
of |
T11732 |
54727-54736 |
NNS |
denotes |
microglia |
T11733 |
54737-54739 |
IN |
denotes |
in |
T11734 |
54740-54744 |
CC |
denotes |
both |
T11735 |
54755-54764 |
NN |
denotes |
condition |
T11736 |
54745-54748 |
DT |
denotes |
the |
T11737 |
54749-54754 |
JJ |
denotes |
human |
T11738 |
54765-54768 |
CC |
denotes |
and |
T11739 |
54769-54772 |
DT |
denotes |
the |
T11740 |
54779-54785 |
NNS |
denotes |
models |
T11741 |
54773-54778 |
NN |
denotes |
mouse |
T11742 |
54789-54795 |
RB |
denotes |
poorly |
T11743 |
54796-54806 |
VBN |
denotes |
understood |
T11744 |
54806-54808 |
, |
denotes |
, |
T11745 |
54808-54811 |
CC |
denotes |
and |
T11746 |
54812-54823 |
NNS |
denotes |
differences |
T11747 |
54871-54875 |
VB |
denotes |
lead |
T11748 |
54824-54826 |
IN |
denotes |
in |
T11749 |
54827-54837 |
JJ |
denotes |
microglial |
T11750 |
54838-54848 |
NN |
denotes |
reactivity |
T11751 |
54849-54856 |
IN |
denotes |
between |
T11752 |
54857-54860 |
DT |
denotes |
the |
T11753 |
54861-54864 |
CD |
denotes |
two |
T11754 |
54865-54870 |
MD |
denotes |
could |
T11755 |
54876-54878 |
IN |
denotes |
to |
T11756 |
54879-54892 |
RB |
denotes |
significantly |
T11757 |
54893-54899 |
JJR |
denotes |
faster |
T11758 |
54908-54917 |
NN |
denotes |
clearance |
T11759 |
54900-54907 |
NN |
denotes |
amyloid |
T11760 |
54918-54920 |
IN |
denotes |
in |
T11761 |
54921-54924 |
DT |
denotes |
the |
T11762 |
54925-54931 |
NNS |
denotes |
brains |
T11763 |
54932-54934 |
IN |
denotes |
of |
T11764 |
54935-54943 |
NNS |
denotes |
patients |
T11765 |
54944-54948 |
IN |
denotes |
with |
T11766 |
54949-54951 |
NN |
denotes |
AD |
T11767 |
54952-54956 |
IN |
denotes |
than |
T11768 |
54960-54967 |
VBP |
denotes |
observe |
T11769 |
54957-54959 |
PRP |
denotes |
we |
T11770 |
54968-54970 |
IN |
denotes |
in |
T11771 |
54971-54974 |
DT |
denotes |
the |
T11772 |
54987-54991 |
NNS |
denotes |
mice |
T11773 |
54975-54978 |
NN |
denotes |
tet |
T11774 |
54979-54982 |
NN |
denotes |
off |
T11775 |
54978-54979 |
HYPH |
denotes |
- |
T11776 |
54983-54986 |
NN |
denotes |
APP |
T11777 |
54991-54992 |
. |
denotes |
. |
T11778 |
54992-55191 |
sentence |
denotes |
Given the relatively minor role played by microglia in other mouse models of amyloidosis, we think it unlikely that these cells have influenced the rate of amyloid clearance in the tet-off APP mice. |
T11779 |
54993-54998 |
VBN |
denotes |
Given |
T11780 |
55086-55091 |
VBP |
denotes |
think |
T11781 |
54999-55002 |
DT |
denotes |
the |
T11782 |
55020-55024 |
NN |
denotes |
role |
T11783 |
55003-55013 |
RB |
denotes |
relatively |
T11784 |
55014-55019 |
JJ |
denotes |
minor |
T11785 |
55025-55031 |
VBN |
denotes |
played |
T11786 |
55032-55034 |
IN |
denotes |
by |
T11787 |
55035-55044 |
NNS |
denotes |
microglia |
T11788 |
55045-55047 |
IN |
denotes |
in |
T11789 |
55048-55053 |
JJ |
denotes |
other |
T11790 |
55060-55066 |
NNS |
denotes |
models |
T11791 |
55054-55059 |
NN |
denotes |
mouse |
T11792 |
55067-55069 |
IN |
denotes |
of |
T11793 |
55070-55081 |
NN |
denotes |
amyloidosis |
T11794 |
55081-55083 |
, |
denotes |
, |
T11795 |
55083-55085 |
PRP |
denotes |
we |
T11796 |
55092-55094 |
PRP |
denotes |
it |
T11797 |
55095-55103 |
JJ |
denotes |
unlikely |
T11798 |
55104-55108 |
IN |
denotes |
that |
T11799 |
55126-55136 |
VBN |
denotes |
influenced |
T11800 |
55109-55114 |
DT |
denotes |
these |
T11801 |
55115-55120 |
NNS |
denotes |
cells |
T11802 |
55121-55125 |
VBP |
denotes |
have |
T11803 |
55137-55140 |
DT |
denotes |
the |
T11804 |
55141-55145 |
NN |
denotes |
rate |
T11805 |
55146-55148 |
IN |
denotes |
of |
T11806 |
55149-55156 |
NN |
denotes |
amyloid |
T11807 |
55157-55166 |
NN |
denotes |
clearance |
T11808 |
55167-55169 |
IN |
denotes |
in |
T11809 |
55170-55173 |
DT |
denotes |
the |
T11810 |
55186-55190 |
NNS |
denotes |
mice |
T11811 |
55174-55177 |
NN |
denotes |
tet |
T11812 |
55178-55181 |
NN |
denotes |
off |
T11813 |
55177-55178 |
HYPH |
denotes |
- |
T11814 |
55182-55185 |
NN |
denotes |
APP |
T11815 |
55190-55191 |
. |
denotes |
. |
T11816 |
55191-55329 |
sentence |
denotes |
Even so, we considered the possibility that chronic dox treatment may have altered the activation state of microglia in our treated mice. |
T11817 |
55192-55196 |
RB |
denotes |
Even |
T11818 |
55197-55199 |
RB |
denotes |
so |
T11819 |
55204-55214 |
VBD |
denotes |
considered |
T11820 |
55199-55201 |
, |
denotes |
, |
T11821 |
55201-55203 |
PRP |
denotes |
we |
T11822 |
55215-55218 |
DT |
denotes |
the |
T11823 |
55219-55230 |
NN |
denotes |
possibility |
T11824 |
55231-55235 |
IN |
denotes |
that |
T11825 |
55267-55274 |
VBN |
denotes |
altered |
T11826 |
55236-55243 |
JJ |
denotes |
chronic |
T11827 |
55248-55257 |
NN |
denotes |
treatment |
T11828 |
55244-55247 |
NN |
denotes |
dox |
T11829 |
55258-55261 |
MD |
denotes |
may |
T11830 |
55262-55266 |
VB |
denotes |
have |
T11831 |
55275-55278 |
DT |
denotes |
the |
T11832 |
55290-55295 |
NN |
denotes |
state |
T11833 |
55279-55289 |
NN |
denotes |
activation |
T11834 |
55296-55298 |
IN |
denotes |
of |
T11835 |
55299-55308 |
NNS |
denotes |
microglia |
T11836 |
55309-55311 |
IN |
denotes |
in |
T11837 |
55312-55315 |
PRP$ |
denotes |
our |
T11838 |
55324-55328 |
NNS |
denotes |
mice |
T11839 |
55316-55323 |
VBN |
denotes |
treated |
T11840 |
55328-55329 |
. |
denotes |
. |
T11841 |
55329-55452 |
sentence |
denotes |
Dox is structurally similar to minocycline, a reported anti-inflammatory drug and inhibitor of microglial activation [48]. |
T11842 |
55330-55333 |
NN |
denotes |
Dox |
T11843 |
55334-55336 |
VBZ |
denotes |
is |
T11844 |
55337-55349 |
RB |
denotes |
structurally |
T11845 |
55350-55357 |
JJ |
denotes |
similar |
T11846 |
55358-55360 |
IN |
denotes |
to |
T11847 |
55361-55372 |
NN |
denotes |
minocycline |
T11848 |
55372-55374 |
, |
denotes |
, |
T11849 |
55374-55375 |
DT |
denotes |
a |
T11850 |
55403-55407 |
NN |
denotes |
drug |
T11851 |
55376-55384 |
VBN |
denotes |
reported |
T11852 |
55385-55402 |
JJ |
denotes |
anti-inflammatory |
T11853 |
55408-55411 |
CC |
denotes |
and |
T11854 |
55412-55421 |
NN |
denotes |
inhibitor |
T11855 |
55422-55424 |
IN |
denotes |
of |
T11856 |
55425-55435 |
JJ |
denotes |
microglial |
T11857 |
55436-55446 |
NN |
denotes |
activation |
T11858 |
55447-55448 |
-LRB- |
denotes |
[ |
T11859 |
55448-55450 |
CD |
denotes |
48 |
T11860 |
55450-55451 |
-RRB- |
denotes |
] |
T11861 |
55451-55452 |
. |
denotes |
. |
T11862 |
55452-55642 |
sentence |
denotes |
However, if dox does have anti-inflammatory activity, then, based on previous studies with other anti-inflammatories, we would have expected to find less amyloid in the dox-treated animals. |
T11863 |
55453-55460 |
RB |
denotes |
However |
T11864 |
55585-55593 |
VBN |
denotes |
expected |
T11865 |
55460-55462 |
, |
denotes |
, |
T11866 |
55462-55464 |
IN |
denotes |
if |
T11867 |
55474-55478 |
VB |
denotes |
have |
T11868 |
55465-55468 |
NN |
denotes |
dox |
T11869 |
55469-55473 |
VBZ |
denotes |
does |
T11870 |
55479-55496 |
JJ |
denotes |
anti-inflammatory |
T11871 |
55497-55505 |
NN |
denotes |
activity |
T11872 |
55505-55507 |
, |
denotes |
, |
T11873 |
55507-55511 |
RB |
denotes |
then |
T11874 |
55511-55513 |
, |
denotes |
, |
T11875 |
55513-55518 |
VBN |
denotes |
based |
T11876 |
55519-55521 |
IN |
denotes |
on |
T11877 |
55522-55530 |
JJ |
denotes |
previous |
T11878 |
55531-55538 |
NNS |
denotes |
studies |
T11879 |
55539-55543 |
IN |
denotes |
with |
T11880 |
55544-55549 |
JJ |
denotes |
other |
T11881 |
55550-55569 |
NNS |
denotes |
anti-inflammatories |
T11882 |
55569-55571 |
, |
denotes |
, |
T11883 |
55571-55573 |
PRP |
denotes |
we |
T11884 |
55574-55579 |
MD |
denotes |
would |
T11885 |
55580-55584 |
VB |
denotes |
have |
T11886 |
55594-55596 |
TO |
denotes |
to |
T11887 |
55597-55601 |
VB |
denotes |
find |
T11888 |
55602-55606 |
RBR |
denotes |
less |
T11889 |
55607-55614 |
NN |
denotes |
amyloid |
T11890 |
55615-55617 |
IN |
denotes |
in |
T11891 |
55618-55621 |
DT |
denotes |
the |
T11892 |
55634-55641 |
NNS |
denotes |
animals |
T11893 |
55622-55625 |
NN |
denotes |
dox |
T11894 |
55626-55633 |
VBN |
denotes |
treated |
T11895 |
55625-55626 |
HYPH |
denotes |
- |
T11896 |
55641-55642 |
. |
denotes |
. |
T11897 |
55642-55674 |
sentence |
denotes |
Clearly, that was not the case. |
T11898 |
55643-55650 |
RB |
denotes |
Clearly |
T11899 |
55657-55660 |
VBD |
denotes |
was |
T11900 |
55650-55652 |
, |
denotes |
, |
T11901 |
55652-55656 |
DT |
denotes |
that |
T11902 |
55661-55664 |
RB |
denotes |
not |
T11903 |
55665-55668 |
DT |
denotes |
the |
T11904 |
55669-55673 |
NN |
denotes |
case |
T11905 |
55673-55674 |
. |
denotes |
. |
T11906 |
55674-55968 |
sentence |
denotes |
While it is possible that dox acts in some other way to slow amyloid clearance, data from multiple studies demonstrate that microglial responses are normally weak in the mouse AD models [37–40], and thus it is doubtful that dox-mediated microglial inhibition affected the outcome of our study. |
T11907 |
55675-55680 |
IN |
denotes |
While |
T11908 |
55684-55686 |
VBZ |
denotes |
is |
T11909 |
55681-55683 |
PRP |
denotes |
it |
T11910 |
55782-55793 |
VBP |
denotes |
demonstrate |
T11911 |
55687-55695 |
JJ |
denotes |
possible |
T11912 |
55696-55700 |
IN |
denotes |
that |
T11913 |
55705-55709 |
VBZ |
denotes |
acts |
T11914 |
55701-55704 |
NN |
denotes |
dox |
T11915 |
55710-55712 |
IN |
denotes |
in |
T11916 |
55713-55717 |
DT |
denotes |
some |
T11917 |
55724-55727 |
NN |
denotes |
way |
T11918 |
55718-55723 |
JJ |
denotes |
other |
T11919 |
55728-55730 |
TO |
denotes |
to |
T11920 |
55731-55735 |
VB |
denotes |
slow |
T11921 |
55736-55743 |
NN |
denotes |
amyloid |
T11922 |
55744-55753 |
NN |
denotes |
clearance |
T11923 |
55753-55755 |
, |
denotes |
, |
T11924 |
55755-55759 |
NNS |
denotes |
data |
T11925 |
55760-55764 |
IN |
denotes |
from |
T11926 |
55765-55773 |
JJ |
denotes |
multiple |
T11927 |
55774-55781 |
NNS |
denotes |
studies |
T11928 |
55794-55798 |
IN |
denotes |
that |
T11929 |
55820-55823 |
VBP |
denotes |
are |
T11930 |
55799-55809 |
JJ |
denotes |
microglial |
T11931 |
55810-55819 |
NNS |
denotes |
responses |
T11932 |
55824-55832 |
RB |
denotes |
normally |
T11933 |
55833-55837 |
JJ |
denotes |
weak |
T11934 |
55838-55840 |
IN |
denotes |
in |
T11935 |
55841-55844 |
DT |
denotes |
the |
T11936 |
55854-55860 |
NNS |
denotes |
models |
T11937 |
55845-55850 |
NN |
denotes |
mouse |
T11938 |
55851-55853 |
NN |
denotes |
AD |
T11939 |
55861-55862 |
-LRB- |
denotes |
[ |
T11940 |
55862-55864 |
CD |
denotes |
37 |
T11941 |
55864-55865 |
SYM |
denotes |
– |
T11942 |
55865-55867 |
CD |
denotes |
40 |
T11943 |
55867-55868 |
-RRB- |
denotes |
] |
T11944 |
55868-55870 |
, |
denotes |
, |
T11945 |
55870-55873 |
CC |
denotes |
and |
T11946 |
55874-55878 |
RB |
denotes |
thus |
T11947 |
55882-55884 |
VBZ |
denotes |
is |
T11948 |
55879-55881 |
PRP |
denotes |
it |
T11949 |
55885-55893 |
JJ |
denotes |
doubtful |
T11950 |
55894-55898 |
IN |
denotes |
that |
T11951 |
55934-55942 |
VBD |
denotes |
affected |
T11952 |
55899-55902 |
NN |
denotes |
dox |
T11953 |
55903-55911 |
VBN |
denotes |
mediated |
T11954 |
55902-55903 |
HYPH |
denotes |
- |
T11955 |
55923-55933 |
NN |
denotes |
inhibition |
T11956 |
55912-55922 |
JJ |
denotes |
microglial |
T11957 |
55943-55946 |
DT |
denotes |
the |
T11958 |
55947-55954 |
NN |
denotes |
outcome |
T11959 |
55955-55957 |
IN |
denotes |
of |
T11960 |
55958-55961 |
PRP$ |
denotes |
our |
T11961 |
55962-55967 |
NN |
denotes |
study |
T11962 |
55967-55968 |
. |
denotes |
. |
T11963 |
55968-56150 |
sentence |
denotes |
The persistence and stability of amyloid deposits in our system is unexpected given the speed with which Aβ aggregates are cleared in other mouse models of therapeutic intervention. |
T11964 |
55969-55972 |
DT |
denotes |
The |
T11965 |
55973-55984 |
NN |
denotes |
persistence |
T11966 |
56033-56035 |
VBZ |
denotes |
is |
T11967 |
55985-55988 |
CC |
denotes |
and |
T11968 |
55989-55998 |
NN |
denotes |
stability |
T11969 |
55999-56001 |
IN |
denotes |
of |
T11970 |
56002-56009 |
NN |
denotes |
amyloid |
T11971 |
56010-56018 |
NNS |
denotes |
deposits |
T11972 |
56019-56021 |
IN |
denotes |
in |
T11973 |
56022-56025 |
PRP$ |
denotes |
our |
T11974 |
56026-56032 |
NN |
denotes |
system |
T11975 |
56036-56046 |
JJ |
denotes |
unexpected |
T11976 |
56047-56052 |
VBN |
denotes |
given |
T11977 |
56053-56056 |
DT |
denotes |
the |
T11978 |
56057-56062 |
NN |
denotes |
speed |
T11979 |
56063-56067 |
IN |
denotes |
with |
T11980 |
56092-56099 |
VBN |
denotes |
cleared |
T11981 |
56068-56073 |
WDT |
denotes |
which |
T11982 |
56074-56076 |
NN |
denotes |
Aβ |
T11983 |
56077-56087 |
NNS |
denotes |
aggregates |
T11984 |
56088-56091 |
VBP |
denotes |
are |
T11985 |
56100-56102 |
IN |
denotes |
in |
T11986 |
56103-56108 |
JJ |
denotes |
other |
T11987 |
56115-56121 |
NNS |
denotes |
models |
T11988 |
56109-56114 |
NN |
denotes |
mouse |
T11989 |
56122-56124 |
IN |
denotes |
of |
T11990 |
56125-56136 |
JJ |
denotes |
therapeutic |
T11991 |
56137-56149 |
NN |
denotes |
intervention |
T11992 |
56149-56150 |
. |
denotes |
. |
T11993 |
56150-56294 |
sentence |
denotes |
Anti-Aβ antibodies injected directly into the brain have been shown to eliminate amyloid deposits in as little as 1 wk after treatment [49–51]. |
T11994 |
56151-56158 |
JJ |
denotes |
Anti-Aβ |
T11995 |
56159-56169 |
NNS |
denotes |
antibodies |
T11996 |
56213-56218 |
VBN |
denotes |
shown |
T11997 |
56170-56178 |
VBN |
denotes |
injected |
T11998 |
56179-56187 |
RB |
denotes |
directly |
T11999 |
56188-56192 |
IN |
denotes |
into |
T12000 |
56193-56196 |
DT |
denotes |
the |
T12001 |
56197-56202 |
NN |
denotes |
brain |
T12002 |
56203-56207 |
VBP |
denotes |
have |
T12003 |
56208-56212 |
VBN |
denotes |
been |
T12004 |
56219-56221 |
TO |
denotes |
to |
T12005 |
56222-56231 |
VB |
denotes |
eliminate |
T12006 |
56232-56239 |
NN |
denotes |
amyloid |
T12007 |
56240-56248 |
NNS |
denotes |
deposits |
T12008 |
56249-56251 |
IN |
denotes |
in |
T12009 |
56252-56254 |
RB |
denotes |
as |
T12010 |
56265-56266 |
CD |
denotes |
1 |
T12011 |
56255-56261 |
JJ |
denotes |
little |
T12012 |
56262-56264 |
IN |
denotes |
as |
T12013 |
56267-56269 |
NN |
denotes |
wk |
T12014 |
56270-56275 |
IN |
denotes |
after |
T12015 |
56276-56285 |
NN |
denotes |
treatment |
T12016 |
56286-56287 |
-LRB- |
denotes |
[ |
T12017 |
56287-56289 |
CD |
denotes |
49 |
T12018 |
56289-56290 |
SYM |
denotes |
– |
T12019 |
56290-56292 |
CD |
denotes |
51 |
T12020 |
56292-56293 |
-RRB- |
denotes |
] |
T12021 |
56293-56294 |
. |
denotes |
. |
T12022 |
56294-56511 |
sentence |
denotes |
Peripheral antibody injection decreases amyloid load more broadly, and although it does not appear to act as quickly as local injection, can significantly reduce amyloid load within 2 mo of initial treatment [52,53]. |
T12023 |
56295-56305 |
JJ |
denotes |
Peripheral |
T12024 |
56315-56324 |
NN |
denotes |
injection |
T12025 |
56306-56314 |
NN |
denotes |
antibody |
T12026 |
56325-56334 |
VBZ |
denotes |
decreases |
T12027 |
56335-56342 |
NN |
denotes |
amyloid |
T12028 |
56343-56347 |
NN |
denotes |
load |
T12029 |
56348-56352 |
RBR |
denotes |
more |
T12030 |
56353-56360 |
RB |
denotes |
broadly |
T12031 |
56360-56362 |
, |
denotes |
, |
T12032 |
56362-56365 |
CC |
denotes |
and |
T12033 |
56366-56374 |
IN |
denotes |
although |
T12034 |
56387-56393 |
VB |
denotes |
appear |
T12035 |
56375-56377 |
PRP |
denotes |
it |
T12036 |
56378-56382 |
VBZ |
denotes |
does |
T12037 |
56383-56386 |
RB |
denotes |
not |
T12038 |
56450-56456 |
VB |
denotes |
reduce |
T12039 |
56394-56396 |
TO |
denotes |
to |
T12040 |
56397-56400 |
VB |
denotes |
act |
T12041 |
56401-56403 |
RB |
denotes |
as |
T12042 |
56404-56411 |
RB |
denotes |
quickly |
T12043 |
56412-56414 |
IN |
denotes |
as |
T12044 |
56415-56420 |
JJ |
denotes |
local |
T12045 |
56421-56430 |
NN |
denotes |
injection |
T12046 |
56430-56432 |
, |
denotes |
, |
T12047 |
56432-56435 |
MD |
denotes |
can |
T12048 |
56436-56449 |
RB |
denotes |
significantly |
T12049 |
56457-56464 |
NN |
denotes |
amyloid |
T12050 |
56465-56469 |
NN |
denotes |
load |
T12051 |
56470-56476 |
IN |
denotes |
within |
T12052 |
56477-56478 |
CD |
denotes |
2 |
T12053 |
56479-56481 |
NN |
denotes |
mo |
T12054 |
56482-56484 |
IN |
denotes |
of |
T12055 |
56485-56492 |
JJ |
denotes |
initial |
T12056 |
56493-56502 |
NN |
denotes |
treatment |
T12057 |
56503-56504 |
-LRB- |
denotes |
[ |
T12058 |
56507-56509 |
CD |
denotes |
53 |
T12059 |
56504-56506 |
CD |
denotes |
52 |
T12060 |
56506-56507 |
, |
denotes |
, |
T12061 |
56509-56510 |
-RRB- |
denotes |
] |
T12062 |
56510-56511 |
. |
denotes |
. |
T12063 |
56511-56680 |
sentence |
denotes |
More recently, an alternative approach has shown that lentiviral transfer of neprilysin can also reduce the number of aggregates in the area of the injection site [54]. |
T12064 |
56512-56516 |
RBR |
denotes |
More |
T12065 |
56517-56525 |
RB |
denotes |
recently |
T12066 |
56555-56560 |
VBN |
denotes |
shown |
T12067 |
56525-56527 |
, |
denotes |
, |
T12068 |
56527-56529 |
DT |
denotes |
an |
T12069 |
56542-56550 |
NN |
denotes |
approach |
T12070 |
56530-56541 |
JJ |
denotes |
alternative |
T12071 |
56551-56554 |
VBZ |
denotes |
has |
T12072 |
56561-56565 |
IN |
denotes |
that |
T12073 |
56609-56615 |
VB |
denotes |
reduce |
T12074 |
56566-56576 |
JJ |
denotes |
lentiviral |
T12075 |
56577-56585 |
NN |
denotes |
transfer |
T12076 |
56586-56588 |
IN |
denotes |
of |
T12077 |
56589-56599 |
NN |
denotes |
neprilysin |
T12078 |
56600-56603 |
MD |
denotes |
can |
T12079 |
56604-56608 |
RB |
denotes |
also |
T12080 |
56616-56619 |
DT |
denotes |
the |
T12081 |
56620-56626 |
NN |
denotes |
number |
T12082 |
56627-56629 |
IN |
denotes |
of |
T12083 |
56630-56640 |
NNS |
denotes |
aggregates |
T12084 |
56641-56643 |
IN |
denotes |
in |
T12085 |
56644-56647 |
DT |
denotes |
the |
T12086 |
56648-56652 |
NN |
denotes |
area |
T12087 |
56653-56655 |
IN |
denotes |
of |
T12088 |
56656-56659 |
DT |
denotes |
the |
T12089 |
56670-56674 |
NN |
denotes |
site |
T12090 |
56660-56669 |
NN |
denotes |
injection |
T12091 |
56675-56676 |
-LRB- |
denotes |
[ |
T12092 |
56676-56678 |
CD |
denotes |
54 |
T12093 |
56678-56679 |
-RRB- |
denotes |
] |
T12094 |
56679-56680 |
. |
denotes |
. |
T12095 |
56680-56890 |
sentence |
denotes |
Careful study of the mechanism behind several of the antibody-mediated therapies has suggested that activated microglia play an important role in the removal of fibrillar plaques after immunization [50,52,55]. |
T12096 |
56681-56688 |
JJ |
denotes |
Careful |
T12097 |
56689-56694 |
NN |
denotes |
study |
T12098 |
56766-56775 |
VBN |
denotes |
suggested |
T12099 |
56695-56697 |
IN |
denotes |
of |
T12100 |
56698-56701 |
DT |
denotes |
the |
T12101 |
56702-56711 |
NN |
denotes |
mechanism |
T12102 |
56712-56718 |
IN |
denotes |
behind |
T12103 |
56719-56726 |
JJ |
denotes |
several |
T12104 |
56727-56729 |
IN |
denotes |
of |
T12105 |
56730-56733 |
DT |
denotes |
the |
T12106 |
56752-56761 |
NNS |
denotes |
therapies |
T12107 |
56734-56742 |
NN |
denotes |
antibody |
T12108 |
56743-56751 |
VBN |
denotes |
mediated |
T12109 |
56742-56743 |
HYPH |
denotes |
- |
T12110 |
56762-56765 |
VBZ |
denotes |
has |
T12111 |
56776-56780 |
IN |
denotes |
that |
T12112 |
56801-56805 |
VBP |
denotes |
play |
T12113 |
56781-56790 |
VBN |
denotes |
activated |
T12114 |
56791-56800 |
NNS |
denotes |
microglia |
T12115 |
56806-56808 |
DT |
denotes |
an |
T12116 |
56819-56823 |
NN |
denotes |
role |
T12117 |
56809-56818 |
JJ |
denotes |
important |
T12118 |
56824-56826 |
IN |
denotes |
in |
T12119 |
56827-56830 |
DT |
denotes |
the |
T12120 |
56831-56838 |
NN |
denotes |
removal |
T12121 |
56839-56841 |
IN |
denotes |
of |
T12122 |
56842-56851 |
JJ |
denotes |
fibrillar |
T12123 |
56852-56859 |
NNS |
denotes |
plaques |
T12124 |
56860-56865 |
IN |
denotes |
after |
T12125 |
56866-56878 |
NN |
denotes |
immunization |
T12126 |
56879-56880 |
-LRB- |
denotes |
[ |
T12127 |
56886-56888 |
CD |
denotes |
55 |
T12128 |
56880-56882 |
CD |
denotes |
50 |
T12129 |
56882-56883 |
, |
denotes |
, |
T12130 |
56883-56885 |
CD |
denotes |
52 |
T12131 |
56885-56886 |
, |
denotes |
, |
T12132 |
56888-56889 |
-RRB- |
denotes |
] |
T12133 |
56889-56890 |
. |
denotes |
. |
T12134 |
56890-57135 |
sentence |
denotes |
However, it has been noted that deletion of the Fc receptor (the primary receptor for microglial opsinization of antibody–antigen complexes) in APP transgenic mouse models has no impact on the effectiveness of antibody-mediated therapy [56,57]. |
T12135 |
56891-56898 |
RB |
denotes |
However |
T12136 |
56912-56917 |
VBN |
denotes |
noted |
T12137 |
56898-56900 |
, |
denotes |
, |
T12138 |
56900-56902 |
PRP |
denotes |
it |
T12139 |
56903-56906 |
VBZ |
denotes |
has |
T12140 |
56907-56911 |
VBN |
denotes |
been |
T12141 |
56918-56922 |
IN |
denotes |
that |
T12142 |
57063-57066 |
VBZ |
denotes |
has |
T12143 |
56923-56931 |
NN |
denotes |
deletion |
T12144 |
56932-56934 |
IN |
denotes |
of |
T12145 |
56935-56938 |
DT |
denotes |
the |
T12146 |
56942-56950 |
NN |
denotes |
receptor |
T12147 |
56939-56941 |
NN |
denotes |
Fc |
T12148 |
56951-56952 |
-LRB- |
denotes |
( |
T12149 |
56952-56955 |
DT |
denotes |
the |
T12150 |
56964-56972 |
NN |
denotes |
receptor |
T12151 |
56956-56963 |
JJ |
denotes |
primary |
T12152 |
56973-56976 |
IN |
denotes |
for |
T12153 |
56977-56987 |
JJ |
denotes |
microglial |
T12154 |
56988-57000 |
NN |
denotes |
opsinization |
T12155 |
57001-57003 |
IN |
denotes |
of |
T12156 |
57004-57012 |
NN |
denotes |
antibody |
T12157 |
57013-57020 |
NN |
denotes |
antigen |
T12158 |
57012-57013 |
HYPH |
denotes |
– |
T12159 |
57021-57030 |
NNS |
denotes |
complexes |
T12160 |
57030-57031 |
-RRB- |
denotes |
) |
T12161 |
57032-57034 |
IN |
denotes |
in |
T12162 |
57035-57038 |
NN |
denotes |
APP |
T12163 |
57039-57049 |
JJ |
denotes |
transgenic |
T12164 |
57056-57062 |
NNS |
denotes |
models |
T12165 |
57050-57055 |
NN |
denotes |
mouse |
T12166 |
57067-57069 |
DT |
denotes |
no |
T12167 |
57070-57076 |
NN |
denotes |
impact |
T12168 |
57077-57079 |
IN |
denotes |
on |
T12169 |
57080-57083 |
DT |
denotes |
the |
T12170 |
57084-57097 |
NN |
denotes |
effectiveness |
T12171 |
57098-57100 |
IN |
denotes |
of |
T12172 |
57101-57109 |
NN |
denotes |
antibody |
T12173 |
57110-57118 |
VBN |
denotes |
mediated |
T12174 |
57109-57110 |
HYPH |
denotes |
- |
T12175 |
57119-57126 |
NN |
denotes |
therapy |
T12176 |
57127-57128 |
-LRB- |
denotes |
[ |
T12177 |
57131-57133 |
CD |
denotes |
57 |
T12178 |
57128-57130 |
CD |
denotes |
56 |
T12179 |
57130-57131 |
, |
denotes |
, |
T12180 |
57133-57134 |
-RRB- |
denotes |
] |
T12181 |
57134-57135 |
. |
denotes |
. |
T12182 |
57135-57406 |
sentence |
denotes |
It is, nevertheless, possible that lack of microglia activation is the major difference between the slow clearance described here, where no perturbation of the immune system is expected, and the rapid clearance described in studies involving antibody or viral injection. |
T12183 |
57136-57138 |
PRP |
denotes |
It |
T12184 |
57139-57141 |
VBZ |
denotes |
is |
T12185 |
57141-57143 |
, |
denotes |
, |
T12186 |
57143-57155 |
RB |
denotes |
nevertheless |
T12187 |
57155-57157 |
, |
denotes |
, |
T12188 |
57157-57165 |
JJ |
denotes |
possible |
T12189 |
57166-57170 |
IN |
denotes |
that |
T12190 |
57200-57202 |
VBZ |
denotes |
is |
T12191 |
57171-57175 |
NN |
denotes |
lack |
T12192 |
57176-57178 |
IN |
denotes |
of |
T12193 |
57179-57188 |
NNS |
denotes |
microglia |
T12194 |
57189-57199 |
NN |
denotes |
activation |
T12195 |
57203-57206 |
DT |
denotes |
the |
T12196 |
57213-57223 |
NN |
denotes |
difference |
T12197 |
57207-57212 |
JJ |
denotes |
major |
T12198 |
57224-57231 |
IN |
denotes |
between |
T12199 |
57232-57235 |
DT |
denotes |
the |
T12200 |
57241-57250 |
NN |
denotes |
clearance |
T12201 |
57236-57240 |
JJ |
denotes |
slow |
T12202 |
57251-57260 |
VBN |
denotes |
described |
T12203 |
57261-57265 |
RB |
denotes |
here |
T12204 |
57265-57267 |
, |
denotes |
, |
T12205 |
57267-57272 |
WRB |
denotes |
where |
T12206 |
57313-57321 |
VBN |
denotes |
expected |
T12207 |
57273-57275 |
DT |
denotes |
no |
T12208 |
57276-57288 |
NN |
denotes |
perturbation |
T12209 |
57289-57291 |
IN |
denotes |
of |
T12210 |
57292-57295 |
DT |
denotes |
the |
T12211 |
57303-57309 |
NN |
denotes |
system |
T12212 |
57296-57302 |
JJ |
denotes |
immune |
T12213 |
57310-57312 |
VBZ |
denotes |
is |
T12214 |
57321-57323 |
, |
denotes |
, |
T12215 |
57323-57326 |
CC |
denotes |
and |
T12216 |
57327-57330 |
DT |
denotes |
the |
T12217 |
57337-57346 |
NN |
denotes |
clearance |
T12218 |
57331-57336 |
JJ |
denotes |
rapid |
T12219 |
57347-57356 |
VBN |
denotes |
described |
T12220 |
57357-57359 |
IN |
denotes |
in |
T12221 |
57360-57367 |
NNS |
denotes |
studies |
T12222 |
57368-57377 |
VBG |
denotes |
involving |
T12223 |
57378-57386 |
NN |
denotes |
antibody |
T12224 |
57396-57405 |
NN |
denotes |
injection |
T12225 |
57387-57389 |
CC |
denotes |
or |
T12226 |
57390-57395 |
JJ |
denotes |
viral |
T12227 |
57405-57406 |
. |
denotes |
. |
T12228 |
57406-57687 |
sentence |
denotes |
In isolation, mild activation of microglia by injection damage or opsinization may not be adequate to induce substantial phagocytosis, but when combined with an Aβ-lowering agent, such as neprilysin or Aβ-targeted antibodies, the two may work in concert to clear peptide deposits. |
T12229 |
57407-57409 |
IN |
denotes |
In |
T12230 |
57494-57496 |
VB |
denotes |
be |
T12231 |
57410-57419 |
NN |
denotes |
isolation |
T12232 |
57419-57421 |
, |
denotes |
, |
T12233 |
57421-57425 |
JJ |
denotes |
mild |
T12234 |
57426-57436 |
NN |
denotes |
activation |
T12235 |
57437-57439 |
IN |
denotes |
of |
T12236 |
57440-57449 |
NNS |
denotes |
microglia |
T12237 |
57450-57452 |
IN |
denotes |
by |
T12238 |
57453-57462 |
NN |
denotes |
injection |
T12239 |
57463-57469 |
NN |
denotes |
damage |
T12240 |
57470-57472 |
CC |
denotes |
or |
T12241 |
57473-57485 |
NN |
denotes |
opsinization |
T12242 |
57486-57489 |
MD |
denotes |
may |
T12243 |
57490-57493 |
RB |
denotes |
not |
T12244 |
57497-57505 |
JJ |
denotes |
adequate |
T12245 |
57506-57508 |
TO |
denotes |
to |
T12246 |
57509-57515 |
VB |
denotes |
induce |
T12247 |
57516-57527 |
JJ |
denotes |
substantial |
T12248 |
57528-57540 |
NN |
denotes |
phagocytosis |
T12249 |
57540-57542 |
, |
denotes |
, |
T12250 |
57542-57545 |
CC |
denotes |
but |
T12251 |
57546-57550 |
WRB |
denotes |
when |
T12252 |
57551-57559 |
VBN |
denotes |
combined |
T12253 |
57645-57649 |
VB |
denotes |
work |
T12254 |
57560-57564 |
IN |
denotes |
with |
T12255 |
57565-57567 |
DT |
denotes |
an |
T12256 |
57580-57585 |
NN |
denotes |
agent |
T12257 |
57568-57570 |
NN |
denotes |
Aβ |
T12258 |
57571-57579 |
VBG |
denotes |
lowering |
T12259 |
57570-57571 |
HYPH |
denotes |
- |
T12260 |
57585-57587 |
, |
denotes |
, |
T12261 |
57587-57591 |
JJ |
denotes |
such |
T12262 |
57592-57594 |
IN |
denotes |
as |
T12263 |
57595-57605 |
NN |
denotes |
neprilysin |
T12264 |
57612-57620 |
VBN |
denotes |
targeted |
T12265 |
57606-57608 |
CC |
denotes |
or |
T12266 |
57609-57611 |
NN |
denotes |
Aβ |
T12267 |
57611-57612 |
HYPH |
denotes |
- |
T12268 |
57621-57631 |
NNS |
denotes |
antibodies |
T12269 |
57631-57633 |
, |
denotes |
, |
T12270 |
57633-57636 |
DT |
denotes |
the |
T12271 |
57637-57640 |
CD |
denotes |
two |
T12272 |
57641-57644 |
MD |
denotes |
may |
T12273 |
57650-57652 |
IN |
denotes |
in |
T12274 |
57653-57660 |
NN |
denotes |
concert |
T12275 |
57661-57663 |
TO |
denotes |
to |
T12276 |
57664-57669 |
VB |
denotes |
clear |
T12277 |
57670-57677 |
NN |
denotes |
peptide |
T12278 |
57678-57686 |
NNS |
denotes |
deposits |
T12279 |
57686-57687 |
. |
denotes |
. |
T12280 |
57687-57918 |
sentence |
denotes |
Consistent with this hypothesis, strong activation of microglia through transgenic expression of TGFβ [58] or central injection of lipopolysaccharide [59,60] can by itself substantially reduce plaque burden in APP transgenic mice. |
T12281 |
57688-57698 |
JJ |
denotes |
Consistent |
T12282 |
57874-57880 |
VB |
denotes |
reduce |
T12283 |
57699-57703 |
IN |
denotes |
with |
T12284 |
57704-57708 |
DT |
denotes |
this |
T12285 |
57709-57719 |
NN |
denotes |
hypothesis |
T12286 |
57719-57721 |
, |
denotes |
, |
T12287 |
57721-57727 |
JJ |
denotes |
strong |
T12288 |
57728-57738 |
NN |
denotes |
activation |
T12289 |
57739-57741 |
IN |
denotes |
of |
T12290 |
57742-57751 |
NNS |
denotes |
microglia |
T12291 |
57752-57759 |
IN |
denotes |
through |
T12292 |
57760-57770 |
JJ |
denotes |
transgenic |
T12293 |
57771-57781 |
NN |
denotes |
expression |
T12294 |
57782-57784 |
IN |
denotes |
of |
T12295 |
57785-57789 |
NN |
denotes |
TGFβ |
T12296 |
57790-57791 |
-LRB- |
denotes |
[ |
T12297 |
57791-57793 |
CD |
denotes |
58 |
T12298 |
57793-57794 |
-RRB- |
denotes |
] |
T12299 |
57795-57797 |
CC |
denotes |
or |
T12300 |
57798-57805 |
JJ |
denotes |
central |
T12301 |
57806-57815 |
NN |
denotes |
injection |
T12302 |
57816-57818 |
IN |
denotes |
of |
T12303 |
57819-57837 |
NN |
denotes |
lipopolysaccharide |
T12304 |
57838-57839 |
-LRB- |
denotes |
[ |
T12305 |
57842-57844 |
CD |
denotes |
60 |
T12306 |
57839-57841 |
CD |
denotes |
59 |
T12307 |
57841-57842 |
, |
denotes |
, |
T12308 |
57844-57845 |
-RRB- |
denotes |
] |
T12309 |
57846-57849 |
MD |
denotes |
can |
T12310 |
57850-57852 |
IN |
denotes |
by |
T12311 |
57853-57859 |
PRP |
denotes |
itself |
T12312 |
57860-57873 |
RB |
denotes |
substantially |
T12313 |
57881-57887 |
NN |
denotes |
plaque |
T12314 |
57888-57894 |
NN |
denotes |
burden |
T12315 |
57895-57897 |
IN |
denotes |
in |
T12316 |
57898-57901 |
NN |
denotes |
APP |
T12317 |
57902-57912 |
JJ |
denotes |
transgenic |
T12318 |
57913-57917 |
NNS |
denotes |
mice |
T12319 |
57917-57918 |
. |
denotes |
. |
T12320 |
57918-58172 |
sentence |
denotes |
But in the case of acute antibody- and/or injury-mediated activation, once the inflammation has passed, and the antibody and bound peptide have been cleared and degraded, the remaining Aβ quickly reaggregates and amyloid pathology is reestablished [49]. |
T12321 |
57919-57922 |
CC |
denotes |
But |
T12322 |
58115-58127 |
VBZ |
denotes |
reaggregates |
T12323 |
57923-57925 |
IN |
denotes |
in |
T12324 |
57926-57929 |
DT |
denotes |
the |
T12325 |
57930-57934 |
NN |
denotes |
case |
T12326 |
57935-57937 |
IN |
denotes |
of |
T12327 |
57938-57943 |
JJ |
denotes |
acute |
T12328 |
57977-57987 |
NN |
denotes |
activation |
T12329 |
57944-57952 |
NN |
denotes |
antibody |
T12330 |
57968-57976 |
VBN |
denotes |
mediated |
T12331 |
57952-57953 |
HYPH |
denotes |
- |
T12332 |
57954-57957 |
CC |
denotes |
and |
T12333 |
57957-57958 |
HYPH |
denotes |
/ |
T12334 |
57958-57960 |
CC |
denotes |
or |
T12335 |
57961-57967 |
NN |
denotes |
injury |
T12336 |
57967-57968 |
HYPH |
denotes |
- |
T12337 |
57987-57989 |
, |
denotes |
, |
T12338 |
57989-57993 |
IN |
denotes |
once |
T12339 |
58015-58021 |
VBN |
denotes |
passed |
T12340 |
57994-57997 |
DT |
denotes |
the |
T12341 |
57998-58010 |
NN |
denotes |
inflammation |
T12342 |
58011-58014 |
VBZ |
denotes |
has |
T12343 |
58021-58023 |
, |
denotes |
, |
T12344 |
58023-58026 |
CC |
denotes |
and |
T12345 |
58027-58030 |
DT |
denotes |
the |
T12346 |
58031-58039 |
NN |
denotes |
antibody |
T12347 |
58068-58075 |
VBN |
denotes |
cleared |
T12348 |
58040-58043 |
CC |
denotes |
and |
T12349 |
58044-58049 |
VBN |
denotes |
bound |
T12350 |
58050-58057 |
NN |
denotes |
peptide |
T12351 |
58058-58062 |
VBP |
denotes |
have |
T12352 |
58063-58067 |
VBN |
denotes |
been |
T12353 |
58076-58079 |
CC |
denotes |
and |
T12354 |
58080-58088 |
VBN |
denotes |
degraded |
T12355 |
58088-58090 |
, |
denotes |
, |
T12356 |
58090-58093 |
DT |
denotes |
the |
T12357 |
58104-58106 |
NN |
denotes |
Aβ |
T12358 |
58094-58103 |
VBG |
denotes |
remaining |
T12359 |
58107-58114 |
RB |
denotes |
quickly |
T12360 |
58128-58131 |
CC |
denotes |
and |
T12361 |
58132-58139 |
NN |
denotes |
amyloid |
T12362 |
58140-58149 |
NN |
denotes |
pathology |
T12363 |
58153-58166 |
VBN |
denotes |
reestablished |
T12364 |
58150-58152 |
VBZ |
denotes |
is |
T12365 |
58167-58168 |
-LRB- |
denotes |
[ |
T12366 |
58168-58170 |
CD |
denotes |
49 |
T12367 |
58170-58171 |
-RRB- |
denotes |
] |
T12368 |
58171-58172 |
. |
denotes |
. |
T12369 |
58172-58350 |
sentence |
denotes |
This finding reinforces the notion that without continued stimulation, microglia in mouse models do not maintain the same level of sustained activation that may occur in humans. |
T12370 |
58173-58177 |
DT |
denotes |
This |
T12371 |
58178-58185 |
NN |
denotes |
finding |
T12372 |
58186-58196 |
VBZ |
denotes |
reinforces |
T12373 |
58197-58200 |
DT |
denotes |
the |
T12374 |
58201-58207 |
NN |
denotes |
notion |
T12375 |
58208-58212 |
IN |
denotes |
that |
T12376 |
58277-58285 |
VB |
denotes |
maintain |
T12377 |
58213-58220 |
IN |
denotes |
without |
T12378 |
58221-58230 |
VBN |
denotes |
continued |
T12379 |
58231-58242 |
NN |
denotes |
stimulation |
T12380 |
58242-58244 |
, |
denotes |
, |
T12381 |
58244-58253 |
NNS |
denotes |
microglia |
T12382 |
58254-58256 |
IN |
denotes |
in |
T12383 |
58257-58262 |
NN |
denotes |
mouse |
T12384 |
58263-58269 |
NNS |
denotes |
models |
T12385 |
58270-58272 |
VBP |
denotes |
do |
T12386 |
58273-58276 |
RB |
denotes |
not |
T12387 |
58286-58289 |
DT |
denotes |
the |
T12388 |
58295-58300 |
NN |
denotes |
level |
T12389 |
58290-58294 |
JJ |
denotes |
same |
T12390 |
58301-58303 |
IN |
denotes |
of |
T12391 |
58304-58313 |
VBN |
denotes |
sustained |
T12392 |
58314-58324 |
NN |
denotes |
activation |
T12393 |
58325-58329 |
WDT |
denotes |
that |
T12394 |
58334-58339 |
VB |
denotes |
occur |
T12395 |
58330-58333 |
MD |
denotes |
may |
T12396 |
58340-58342 |
IN |
denotes |
in |
T12397 |
58343-58349 |
NNS |
denotes |
humans |
T12398 |
58349-58350 |
. |
denotes |
. |
T12399 |
58350-58465 |
sentence |
denotes |
SantaCruz et al. recently published a study of mice that express P301L human tau via a similar vector system [61]. |
T12400 |
58351-58360 |
NNP |
denotes |
SantaCruz |
T12401 |
58377-58386 |
VBD |
denotes |
published |
T12402 |
58361-58363 |
FW |
denotes |
et |
T12403 |
58364-58367 |
FW |
denotes |
al. |
T12404 |
58368-58376 |
RB |
denotes |
recently |
T12405 |
58387-58388 |
DT |
denotes |
a |
T12406 |
58389-58394 |
NN |
denotes |
study |
T12407 |
58395-58397 |
IN |
denotes |
of |
T12408 |
58398-58402 |
NNS |
denotes |
mice |
T12409 |
58403-58407 |
WDT |
denotes |
that |
T12410 |
58408-58415 |
VBP |
denotes |
express |
T12411 |
58416-58421 |
NN |
denotes |
P301L |
T12412 |
58428-58431 |
NN |
denotes |
tau |
T12413 |
58422-58427 |
JJ |
denotes |
human |
T12414 |
58432-58435 |
IN |
denotes |
via |
T12415 |
58436-58437 |
DT |
denotes |
a |
T12416 |
58453-58459 |
NN |
denotes |
system |
T12417 |
58438-58445 |
JJ |
denotes |
similar |
T12418 |
58446-58452 |
NN |
denotes |
vector |
T12419 |
58460-58461 |
-LRB- |
denotes |
[ |
T12420 |
58461-58463 |
CD |
denotes |
61 |
T12421 |
58463-58464 |
-RRB- |
denotes |
] |
T12422 |
58464-58465 |
. |
denotes |
. |
T12423 |
58465-58633 |
sentence |
denotes |
As in our tet-off APP mice, SantaCruz et al. found that tau neurofibrillary tangles, like amyloid plaques, are not cleared efficiently following transgene suppression. |
T12424 |
58466-58468 |
IN |
denotes |
As |
T12425 |
58511-58516 |
VBD |
denotes |
found |
T12426 |
58469-58471 |
IN |
denotes |
in |
T12427 |
58472-58475 |
PRP$ |
denotes |
our |
T12428 |
58488-58492 |
NNS |
denotes |
mice |
T12429 |
58476-58479 |
NN |
denotes |
tet |
T12430 |
58480-58483 |
NN |
denotes |
off |
T12431 |
58479-58480 |
HYPH |
denotes |
- |
T12432 |
58484-58487 |
NN |
denotes |
APP |
T12433 |
58492-58494 |
, |
denotes |
, |
T12434 |
58494-58503 |
NNP |
denotes |
SantaCruz |
T12435 |
58504-58506 |
FW |
denotes |
et |
T12436 |
58507-58510 |
FW |
denotes |
al. |
T12437 |
58517-58521 |
IN |
denotes |
that |
T12438 |
58581-58588 |
VBN |
denotes |
cleared |
T12439 |
58522-58525 |
NN |
denotes |
tau |
T12440 |
58542-58549 |
NNS |
denotes |
tangles |
T12441 |
58526-58541 |
JJ |
denotes |
neurofibrillary |
T12442 |
58549-58551 |
, |
denotes |
, |
T12443 |
58551-58555 |
IN |
denotes |
like |
T12444 |
58556-58563 |
NN |
denotes |
amyloid |
T12445 |
58564-58571 |
NNS |
denotes |
plaques |
T12446 |
58571-58573 |
, |
denotes |
, |
T12447 |
58573-58576 |
VBP |
denotes |
are |
T12448 |
58577-58580 |
RB |
denotes |
not |
T12449 |
58589-58600 |
RB |
denotes |
efficiently |
T12450 |
58601-58610 |
VBG |
denotes |
following |
T12451 |
58611-58620 |
NN |
denotes |
transgene |
T12452 |
58621-58632 |
NN |
denotes |
suppression |
T12453 |
58632-58633 |
. |
denotes |
. |
T12454 |
58633-58836 |
sentence |
denotes |
The lack of clearance in both models of AD pathology comes as a stark contrast to the rapid removal of protein aggregates found in similar tet-off mouse models of Huntington [32] and prion disease [62]. |
T12455 |
58634-58637 |
DT |
denotes |
The |
T12456 |
58638-58642 |
NN |
denotes |
lack |
T12457 |
58687-58692 |
VBZ |
denotes |
comes |
T12458 |
58643-58645 |
IN |
denotes |
of |
T12459 |
58646-58655 |
NN |
denotes |
clearance |
T12460 |
58656-58658 |
IN |
denotes |
in |
T12461 |
58659-58663 |
DT |
denotes |
both |
T12462 |
58664-58670 |
NNS |
denotes |
models |
T12463 |
58671-58673 |
IN |
denotes |
of |
T12464 |
58674-58676 |
NN |
denotes |
AD |
T12465 |
58677-58686 |
NN |
denotes |
pathology |
T12466 |
58693-58695 |
IN |
denotes |
as |
T12467 |
58696-58697 |
DT |
denotes |
a |
T12468 |
58704-58712 |
NN |
denotes |
contrast |
T12469 |
58698-58703 |
JJ |
denotes |
stark |
T12470 |
58713-58715 |
IN |
denotes |
to |
T12471 |
58716-58719 |
DT |
denotes |
the |
T12472 |
58726-58733 |
NN |
denotes |
removal |
T12473 |
58720-58725 |
JJ |
denotes |
rapid |
T12474 |
58734-58736 |
IN |
denotes |
of |
T12475 |
58737-58744 |
NN |
denotes |
protein |
T12476 |
58745-58755 |
NNS |
denotes |
aggregates |
T12477 |
58756-58761 |
VBN |
denotes |
found |
T12478 |
58762-58764 |
IN |
denotes |
in |
T12479 |
58765-58772 |
JJ |
denotes |
similar |
T12480 |
58787-58793 |
NNS |
denotes |
models |
T12481 |
58773-58776 |
NN |
denotes |
tet |
T12482 |
58777-58780 |
NN |
denotes |
off |
T12483 |
58776-58777 |
HYPH |
denotes |
- |
T12484 |
58781-58786 |
NN |
denotes |
mouse |
T12485 |
58794-58796 |
IN |
denotes |
of |
T12486 |
58797-58807 |
NNP |
denotes |
Huntington |
T12487 |
58823-58830 |
NN |
denotes |
disease |
T12488 |
58808-58809 |
-LRB- |
denotes |
[ |
T12489 |
58809-58811 |
CD |
denotes |
32 |
T12490 |
58811-58812 |
-RRB- |
denotes |
] |
T12491 |
58813-58816 |
CC |
denotes |
and |
T12492 |
58817-58822 |
NN |
denotes |
prion |
T12493 |
58831-58832 |
-LRB- |
denotes |
[ |
T12494 |
58832-58834 |
CD |
denotes |
62 |
T12495 |
58834-58835 |
-RRB- |
denotes |
] |
T12496 |
58835-58836 |
. |
denotes |
. |
T12497 |
58836-58998 |
sentence |
denotes |
In these cases, disrupting the input of new monomer to the system via dox-mediated transgene suppression led to relatively rapid clearance of protein aggregates. |
T12498 |
58837-58839 |
IN |
denotes |
In |
T12499 |
58942-58945 |
VBD |
denotes |
led |
T12500 |
58840-58845 |
DT |
denotes |
these |
T12501 |
58846-58851 |
NNS |
denotes |
cases |
T12502 |
58851-58853 |
, |
denotes |
, |
T12503 |
58853-58863 |
VBG |
denotes |
disrupting |
T12504 |
58864-58867 |
DT |
denotes |
the |
T12505 |
58868-58873 |
NN |
denotes |
input |
T12506 |
58874-58876 |
IN |
denotes |
of |
T12507 |
58877-58880 |
JJ |
denotes |
new |
T12508 |
58881-58888 |
NN |
denotes |
monomer |
T12509 |
58889-58891 |
IN |
denotes |
to |
T12510 |
58892-58895 |
DT |
denotes |
the |
T12511 |
58896-58902 |
NN |
denotes |
system |
T12512 |
58903-58906 |
IN |
denotes |
via |
T12513 |
58907-58910 |
NN |
denotes |
dox |
T12514 |
58911-58919 |
VBN |
denotes |
mediated |
T12515 |
58910-58911 |
HYPH |
denotes |
- |
T12516 |
58930-58941 |
NN |
denotes |
suppression |
T12517 |
58920-58929 |
NN |
denotes |
transgene |
T12518 |
58946-58948 |
IN |
denotes |
to |
T12519 |
58949-58959 |
RB |
denotes |
relatively |
T12520 |
58960-58965 |
JJ |
denotes |
rapid |
T12521 |
58966-58975 |
NN |
denotes |
clearance |
T12522 |
58976-58978 |
IN |
denotes |
of |
T12523 |
58979-58986 |
NN |
denotes |
protein |
T12524 |
58987-58997 |
NNS |
denotes |
aggregates |
T12525 |
58997-58998 |
. |
denotes |
. |
T12526 |
58998-59153 |
sentence |
denotes |
By contrast, our study and that of SantaCruz et al. suggest that protein aggregates in AD may be more tenacious than in other neurodegenerative disorders. |
T12527 |
58999-59001 |
IN |
denotes |
By |
T12528 |
59051-59058 |
VBP |
denotes |
suggest |
T12529 |
59002-59010 |
NN |
denotes |
contrast |
T12530 |
59010-59012 |
, |
denotes |
, |
T12531 |
59012-59015 |
PRP$ |
denotes |
our |
T12532 |
59016-59021 |
NN |
denotes |
study |
T12533 |
59022-59025 |
CC |
denotes |
and |
T12534 |
59026-59030 |
DT |
denotes |
that |
T12535 |
59031-59033 |
IN |
denotes |
of |
T12536 |
59034-59043 |
NNP |
denotes |
SantaCruz |
T12537 |
59044-59046 |
FW |
denotes |
et |
T12538 |
59047-59050 |
FW |
denotes |
al. |
T12539 |
59059-59063 |
IN |
denotes |
that |
T12540 |
59093-59095 |
VB |
denotes |
be |
T12541 |
59064-59071 |
NN |
denotes |
protein |
T12542 |
59072-59082 |
NNS |
denotes |
aggregates |
T12543 |
59083-59085 |
IN |
denotes |
in |
T12544 |
59086-59088 |
NN |
denotes |
AD |
T12545 |
59089-59092 |
MD |
denotes |
may |
T12546 |
59096-59100 |
RBR |
denotes |
more |
T12547 |
59101-59110 |
JJ |
denotes |
tenacious |
T12548 |
59111-59115 |
IN |
denotes |
than |
T12549 |
59116-59118 |
IN |
denotes |
in |
T12550 |
59119-59124 |
JJ |
denotes |
other |
T12551 |
59143-59152 |
NNS |
denotes |
disorders |
T12552 |
59125-59142 |
JJ |
denotes |
neurodegenerative |
T12553 |
59152-59153 |
. |
denotes |
. |
T12554 |
59153-59321 |
sentence |
denotes |
Perhaps once aggregated, Aβ and tau are either inherently more stable than other protein aggregates or more resistant to intra- and extracellular clearance mechanisms. |
T12555 |
59154-59161 |
RB |
denotes |
Perhaps |
T12556 |
59190-59193 |
VBP |
denotes |
are |
T12557 |
59162-59166 |
IN |
denotes |
once |
T12558 |
59167-59177 |
VBN |
denotes |
aggregated |
T12559 |
59177-59179 |
, |
denotes |
, |
T12560 |
59179-59181 |
NN |
denotes |
Aβ |
T12561 |
59182-59185 |
CC |
denotes |
and |
T12562 |
59186-59189 |
NN |
denotes |
tau |
T12563 |
59194-59200 |
RB |
denotes |
either |
T12564 |
59217-59223 |
JJ |
denotes |
stable |
T12565 |
59201-59211 |
RB |
denotes |
inherently |
T12566 |
59212-59216 |
RBR |
denotes |
more |
T12567 |
59224-59228 |
IN |
denotes |
than |
T12568 |
59229-59234 |
JJ |
denotes |
other |
T12569 |
59243-59253 |
NNS |
denotes |
aggregates |
T12570 |
59235-59242 |
NN |
denotes |
protein |
T12571 |
59254-59256 |
CC |
denotes |
or |
T12572 |
59257-59261 |
RBR |
denotes |
more |
T12573 |
59262-59271 |
JJ |
denotes |
resistant |
T12574 |
59272-59274 |
IN |
denotes |
to |
T12575 |
59275-59280 |
AFX |
denotes |
intra |
T12576 |
59286-59299 |
JJ |
denotes |
extracellular |
T12577 |
59280-59281 |
HYPH |
denotes |
- |
T12578 |
59282-59285 |
CC |
denotes |
and |
T12579 |
59310-59320 |
NNS |
denotes |
mechanisms |
T12580 |
59300-59309 |
NN |
denotes |
clearance |
T12581 |
59320-59321 |
. |
denotes |
. |
T12582 |
59321-59462 |
sentence |
denotes |
One question we were not able to address in this study is whether abrogating synthesis of new Aβ halts the progression of cognitive decline. |
T12583 |
59322-59325 |
CD |
denotes |
One |
T12584 |
59326-59334 |
NN |
denotes |
question |
T12585 |
59377-59379 |
VBZ |
denotes |
is |
T12586 |
59335-59337 |
PRP |
denotes |
we |
T12587 |
59338-59342 |
VBD |
denotes |
were |
T12588 |
59343-59346 |
RB |
denotes |
not |
T12589 |
59347-59351 |
JJ |
denotes |
able |
T12590 |
59352-59354 |
TO |
denotes |
to |
T12591 |
59355-59362 |
VB |
denotes |
address |
T12592 |
59363-59365 |
IN |
denotes |
in |
T12593 |
59366-59370 |
DT |
denotes |
this |
T12594 |
59371-59376 |
NN |
denotes |
study |
T12595 |
59380-59387 |
IN |
denotes |
whether |
T12596 |
59419-59424 |
VBZ |
denotes |
halts |
T12597 |
59388-59398 |
VBG |
denotes |
abrogating |
T12598 |
59399-59408 |
NN |
denotes |
synthesis |
T12599 |
59409-59411 |
IN |
denotes |
of |
T12600 |
59412-59415 |
JJ |
denotes |
new |
T12601 |
59416-59418 |
NN |
denotes |
Aβ |
T12602 |
59425-59428 |
DT |
denotes |
the |
T12603 |
59429-59440 |
NN |
denotes |
progression |
T12604 |
59441-59443 |
IN |
denotes |
of |
T12605 |
59444-59453 |
JJ |
denotes |
cognitive |
T12606 |
59454-59461 |
NN |
denotes |
decline |
T12607 |
59461-59462 |
. |
denotes |
. |
T12608 |
59462-59619 |
sentence |
denotes |
Studies from the tet-off tau mice suggest that protein clearance may in fact not be required for cognitive improvement following transgene suppression [61]. |
T12609 |
59463-59470 |
NNS |
denotes |
Studies |
T12610 |
59497-59504 |
VBP |
denotes |
suggest |
T12611 |
59471-59475 |
IN |
denotes |
from |
T12612 |
59476-59479 |
DT |
denotes |
the |
T12613 |
59492-59496 |
NNS |
denotes |
mice |
T12614 |
59480-59483 |
NN |
denotes |
tet |
T12615 |
59484-59487 |
NN |
denotes |
off |
T12616 |
59483-59484 |
HYPH |
denotes |
- |
T12617 |
59488-59491 |
NN |
denotes |
tau |
T12618 |
59505-59509 |
IN |
denotes |
that |
T12619 |
59547-59555 |
VBN |
denotes |
required |
T12620 |
59510-59517 |
NN |
denotes |
protein |
T12621 |
59518-59527 |
NN |
denotes |
clearance |
T12622 |
59528-59531 |
MD |
denotes |
may |
T12623 |
59532-59534 |
IN |
denotes |
in |
T12624 |
59535-59539 |
NN |
denotes |
fact |
T12625 |
59540-59543 |
RB |
denotes |
not |
T12626 |
59544-59546 |
VB |
denotes |
be |
T12627 |
59556-59559 |
IN |
denotes |
for |
T12628 |
59560-59569 |
JJ |
denotes |
cognitive |
T12629 |
59570-59581 |
NN |
denotes |
improvement |
T12630 |
59582-59591 |
VBG |
denotes |
following |
T12631 |
59592-59601 |
NN |
denotes |
transgene |
T12632 |
59602-59613 |
NN |
denotes |
suppression |
T12633 |
59614-59615 |
-LRB- |
denotes |
[ |
T12634 |
59615-59617 |
CD |
denotes |
61 |
T12635 |
59617-59618 |
-RRB- |
denotes |
] |
T12636 |
59618-59619 |
. |
denotes |
. |
T12637 |
59619-59815 |
sentence |
denotes |
At present, because of unexpected noncognitive behavioral abnormalities, it is not clear whether the tet-off APP mice can be used to address the same question in the context of amyloid pathology. |
T12638 |
59620-59622 |
IN |
denotes |
At |
T12639 |
59696-59698 |
VBZ |
denotes |
is |
T12640 |
59623-59630 |
JJ |
denotes |
present |
T12641 |
59630-59632 |
, |
denotes |
, |
T12642 |
59632-59639 |
IN |
denotes |
because |
T12643 |
59640-59642 |
IN |
denotes |
of |
T12644 |
59643-59653 |
JJ |
denotes |
unexpected |
T12645 |
59678-59691 |
NNS |
denotes |
abnormalities |
T12646 |
59654-59666 |
JJ |
denotes |
noncognitive |
T12647 |
59667-59677 |
JJ |
denotes |
behavioral |
T12648 |
59691-59693 |
, |
denotes |
, |
T12649 |
59693-59695 |
PRP |
denotes |
it |
T12650 |
59699-59702 |
RB |
denotes |
not |
T12651 |
59703-59708 |
JJ |
denotes |
clear |
T12652 |
59709-59716 |
IN |
denotes |
whether |
T12653 |
59745-59749 |
VBN |
denotes |
used |
T12654 |
59717-59720 |
DT |
denotes |
the |
T12655 |
59733-59737 |
NNS |
denotes |
mice |
T12656 |
59721-59724 |
NN |
denotes |
tet |
T12657 |
59725-59728 |
NN |
denotes |
off |
T12658 |
59724-59725 |
HYPH |
denotes |
- |
T12659 |
59729-59732 |
NN |
denotes |
APP |
T12660 |
59738-59741 |
MD |
denotes |
can |
T12661 |
59742-59744 |
VB |
denotes |
be |
T12662 |
59750-59752 |
TO |
denotes |
to |
T12663 |
59753-59760 |
VB |
denotes |
address |
T12664 |
59761-59764 |
DT |
denotes |
the |
T12665 |
59770-59778 |
NN |
denotes |
question |
T12666 |
59765-59769 |
JJ |
denotes |
same |
T12667 |
59779-59781 |
IN |
denotes |
in |
T12668 |
59782-59785 |
DT |
denotes |
the |
T12669 |
59786-59793 |
NN |
denotes |
context |
T12670 |
59794-59796 |
IN |
denotes |
of |
T12671 |
59797-59804 |
NN |
denotes |
amyloid |
T12672 |
59805-59814 |
NN |
denotes |
pathology |
T12673 |
59814-59815 |
. |
denotes |
. |
T12674 |
59815-59967 |
sentence |
denotes |
Both lines of tTA/APP mice we studied here display extreme hyperactivity visible as cage circling and quantified by activity monitoring (see Figure 7). |
T12675 |
59816-59820 |
DT |
denotes |
Both |
T12676 |
59821-59826 |
NNS |
denotes |
lines |
T12677 |
59859-59866 |
VBP |
denotes |
display |
T12678 |
59827-59829 |
IN |
denotes |
of |
T12679 |
59830-59833 |
NN |
denotes |
tTA |
T12680 |
59834-59837 |
NN |
denotes |
APP |
T12681 |
59833-59834 |
HYPH |
denotes |
/ |
T12682 |
59838-59842 |
NNS |
denotes |
mice |
T12683 |
59843-59845 |
PRP |
denotes |
we |
T12684 |
59846-59853 |
VBN |
denotes |
studied |
T12685 |
59854-59858 |
RB |
denotes |
here |
T12686 |
59867-59874 |
JJ |
denotes |
extreme |
T12687 |
59875-59888 |
NN |
denotes |
hyperactivity |
T12688 |
59889-59896 |
JJ |
denotes |
visible |
T12689 |
59897-59899 |
IN |
denotes |
as |
T12690 |
59900-59904 |
NN |
denotes |
cage |
T12691 |
59905-59913 |
NN |
denotes |
circling |
T12692 |
59914-59917 |
CC |
denotes |
and |
T12693 |
59918-59928 |
VBN |
denotes |
quantified |
T12694 |
59929-59931 |
IN |
denotes |
by |
T12695 |
59932-59940 |
NN |
denotes |
activity |
T12696 |
59941-59951 |
NN |
denotes |
monitoring |
T12697 |
59952-59953 |
-LRB- |
denotes |
( |
T12698 |
59953-59956 |
VB |
denotes |
see |
T12699 |
59957-59963 |
NN |
denotes |
Figure |
T12700 |
59964-59965 |
CD |
denotes |
7 |
T12701 |
59965-59966 |
-RRB- |
denotes |
) |
T12702 |
59966-59967 |
. |
denotes |
. |
T12703 |
59967-60111 |
sentence |
denotes |
Many of the double transgenic mice showed similar circular patterns of swimming near the edge of the tank when tested in the Morris water maze. |
T12704 |
59968-59972 |
JJ |
denotes |
Many |
T12705 |
60003-60009 |
VBD |
denotes |
showed |
T12706 |
59973-59975 |
IN |
denotes |
of |
T12707 |
59976-59979 |
DT |
denotes |
the |
T12708 |
59998-60002 |
NNS |
denotes |
mice |
T12709 |
59980-59986 |
JJ |
denotes |
double |
T12710 |
59987-59997 |
JJ |
denotes |
transgenic |
T12711 |
60010-60017 |
JJ |
denotes |
similar |
T12712 |
60027-60035 |
NNS |
denotes |
patterns |
T12713 |
60018-60026 |
JJ |
denotes |
circular |
T12714 |
60036-60038 |
IN |
denotes |
of |
T12715 |
60039-60047 |
NN |
denotes |
swimming |
T12716 |
60048-60052 |
IN |
denotes |
near |
T12717 |
60053-60056 |
DT |
denotes |
the |
T12718 |
60057-60061 |
NN |
denotes |
edge |
T12719 |
60062-60064 |
IN |
denotes |
of |
T12720 |
60065-60068 |
DT |
denotes |
the |
T12721 |
60069-60073 |
NN |
denotes |
tank |
T12722 |
60074-60078 |
WRB |
denotes |
when |
T12723 |
60079-60085 |
VBN |
denotes |
tested |
T12724 |
60086-60088 |
IN |
denotes |
in |
T12725 |
60089-60092 |
DT |
denotes |
the |
T12726 |
60106-60110 |
NN |
denotes |
maze |
T12727 |
60093-60099 |
NNP |
denotes |
Morris |
T12728 |
60100-60105 |
NN |
denotes |
water |
T12729 |
60110-60111 |
. |
denotes |
. |
T12730 |
60111-60201 |
sentence |
denotes |
Expression of this phenotype makes standard tests of learning and memory uninterpretable. |
T12731 |
60112-60122 |
NN |
denotes |
Expression |
T12732 |
60141-60146 |
VBZ |
denotes |
makes |
T12733 |
60123-60125 |
IN |
denotes |
of |
T12734 |
60126-60130 |
DT |
denotes |
this |
T12735 |
60131-60140 |
NN |
denotes |
phenotype |
T12736 |
60147-60155 |
JJ |
denotes |
standard |
T12737 |
60156-60161 |
NNS |
denotes |
tests |
T12738 |
60185-60200 |
JJ |
denotes |
uninterpretable |
T12739 |
60162-60164 |
IN |
denotes |
of |
T12740 |
60165-60173 |
NN |
denotes |
learning |
T12741 |
60174-60177 |
CC |
denotes |
and |
T12742 |
60178-60184 |
NN |
denotes |
memory |
T12743 |
60200-60201 |
. |
denotes |
. |
T12744 |
60201-60334 |
sentence |
denotes |
Hyperactivity nonspecifically inhibits choice-driven changes in movement, the key element behind all cognitive behavioral paradigms. |
T12745 |
60202-60215 |
NN |
denotes |
Hyperactivity |
T12746 |
60232-60240 |
VBZ |
denotes |
inhibits |
T12747 |
60216-60231 |
RB |
denotes |
nonspecifically |
T12748 |
60241-60247 |
NN |
denotes |
choice |
T12749 |
60248-60254 |
VBN |
denotes |
driven |
T12750 |
60247-60248 |
HYPH |
denotes |
- |
T12751 |
60255-60262 |
NNS |
denotes |
changes |
T12752 |
60263-60265 |
IN |
denotes |
in |
T12753 |
60266-60274 |
NN |
denotes |
movement |
T12754 |
60274-60276 |
, |
denotes |
, |
T12755 |
60276-60279 |
DT |
denotes |
the |
T12756 |
60284-60291 |
NN |
denotes |
element |
T12757 |
60280-60283 |
JJ |
denotes |
key |
T12758 |
60292-60298 |
IN |
denotes |
behind |
T12759 |
60299-60302 |
DT |
denotes |
all |
T12760 |
60324-60333 |
NNS |
denotes |
paradigms |
T12761 |
60303-60312 |
JJ |
denotes |
cognitive |
T12762 |
60313-60323 |
JJ |
denotes |
behavioral |
T12763 |
60333-60334 |
. |
denotes |
. |
T12764 |
60334-60483 |
sentence |
denotes |
We are currently working to determine whether hyperactivity correlates with expression of the APPswe/ind holoprotein or its proteolytic derivatives. |
T12765 |
60335-60337 |
PRP |
denotes |
We |
T12766 |
60352-60359 |
VBG |
denotes |
working |
T12767 |
60338-60341 |
VBP |
denotes |
are |
T12768 |
60342-60351 |
RB |
denotes |
currently |
T12769 |
60360-60362 |
TO |
denotes |
to |
T12770 |
60363-60372 |
VB |
denotes |
determine |
T12771 |
60373-60380 |
IN |
denotes |
whether |
T12772 |
60395-60405 |
VBZ |
denotes |
correlates |
T12773 |
60381-60394 |
NN |
denotes |
hyperactivity |
T12774 |
60406-60410 |
IN |
denotes |
with |
T12775 |
60411-60421 |
NN |
denotes |
expression |
T12776 |
60422-60424 |
IN |
denotes |
of |
T12777 |
60425-60428 |
DT |
denotes |
the |
T12778 |
60440-60451 |
NN |
denotes |
holoprotein |
T12779 |
60429-60435 |
NN |
denotes |
APPswe |
T12780 |
60436-60439 |
NN |
denotes |
ind |
T12781 |
60435-60436 |
HYPH |
denotes |
/ |
T12782 |
60452-60454 |
CC |
denotes |
or |
T12783 |
60455-60458 |
PRP$ |
denotes |
its |
T12784 |
60471-60482 |
NNS |
denotes |
derivatives |
T12785 |
60459-60470 |
JJ |
denotes |
proteolytic |
T12786 |
60482-60483 |
. |
denotes |
. |
T12787 |
60483-60639 |
sentence |
denotes |
Preliminary studies suggest that hyperactivity does not appear quickly when dox-reared mice are shifted to nonmedicated diets (J. L. J., unpublished data). |
T12788 |
60484-60495 |
JJ |
denotes |
Preliminary |
T12789 |
60496-60503 |
NNS |
denotes |
studies |
T12790 |
60504-60511 |
VBP |
denotes |
suggest |
T12791 |
60512-60516 |
IN |
denotes |
that |
T12792 |
60540-60546 |
VB |
denotes |
appear |
T12793 |
60517-60530 |
NN |
denotes |
hyperactivity |
T12794 |
60531-60535 |
VBZ |
denotes |
does |
T12795 |
60536-60539 |
RB |
denotes |
not |
T12796 |
60547-60554 |
RB |
denotes |
quickly |
T12797 |
60555-60559 |
WRB |
denotes |
when |
T12798 |
60580-60587 |
VBN |
denotes |
shifted |
T12799 |
60560-60563 |
NN |
denotes |
dox |
T12800 |
60564-60570 |
VBN |
denotes |
reared |
T12801 |
60563-60564 |
HYPH |
denotes |
- |
T12802 |
60571-60575 |
NNS |
denotes |
mice |
T12803 |
60576-60579 |
VBP |
denotes |
are |
T12804 |
60588-60590 |
IN |
denotes |
to |
T12805 |
60591-60603 |
JJ |
denotes |
nonmedicated |
T12806 |
60604-60609 |
NNS |
denotes |
diets |
T12807 |
60610-60611 |
-LRB- |
denotes |
( |
T12808 |
60633-60637 |
NNS |
denotes |
data |
T12809 |
60611-60613 |
NNP |
denotes |
J. |
T12810 |
60617-60619 |
NNP |
denotes |
J. |
T12811 |
60614-60616 |
NNP |
denotes |
L. |
T12812 |
60619-60621 |
, |
denotes |
, |
T12813 |
60621-60632 |
JJ |
denotes |
unpublished |
T12814 |
60637-60638 |
-RRB- |
denotes |
) |
T12815 |
60638-60639 |
. |
denotes |
. |
T12816 |
60639-60805 |
sentence |
denotes |
These data may indicate that the neuroactive culprit is not immediately present after transgenic APP synthesis is initiated, but requires additional time to develop. |
T12817 |
60640-60645 |
DT |
denotes |
These |
T12818 |
60646-60650 |
NNS |
denotes |
data |
T12819 |
60655-60663 |
VB |
denotes |
indicate |
T12820 |
60651-60654 |
MD |
denotes |
may |
T12821 |
60664-60668 |
IN |
denotes |
that |
T12822 |
60693-60695 |
VBZ |
denotes |
is |
T12823 |
60669-60672 |
DT |
denotes |
the |
T12824 |
60685-60692 |
NN |
denotes |
culprit |
T12825 |
60673-60684 |
JJ |
denotes |
neuroactive |
T12826 |
60696-60699 |
RB |
denotes |
not |
T12827 |
60700-60711 |
RB |
denotes |
immediately |
T12828 |
60712-60719 |
JJ |
denotes |
present |
T12829 |
60720-60725 |
IN |
denotes |
after |
T12830 |
60754-60763 |
VBN |
denotes |
initiated |
T12831 |
60726-60736 |
JJ |
denotes |
transgenic |
T12832 |
60741-60750 |
NN |
denotes |
synthesis |
T12833 |
60737-60740 |
NN |
denotes |
APP |
T12834 |
60751-60753 |
VBZ |
denotes |
is |
T12835 |
60763-60765 |
, |
denotes |
, |
T12836 |
60765-60768 |
CC |
denotes |
but |
T12837 |
60769-60777 |
VBZ |
denotes |
requires |
T12838 |
60778-60788 |
JJ |
denotes |
additional |
T12839 |
60789-60793 |
NN |
denotes |
time |
T12840 |
60794-60796 |
TO |
denotes |
to |
T12841 |
60797-60804 |
VB |
denotes |
develop |
T12842 |
60804-60805 |
. |
denotes |
. |
T12843 |
60805-60936 |
sentence |
denotes |
Alternatively, hyperactivity may be caused by neuronal alterations due to transgene expression during early postnatal development. |
T12844 |
60806-60819 |
RB |
denotes |
Alternatively |
T12845 |
60842-60848 |
VBN |
denotes |
caused |
T12846 |
60819-60821 |
, |
denotes |
, |
T12847 |
60821-60834 |
NN |
denotes |
hyperactivity |
T12848 |
60835-60838 |
MD |
denotes |
may |
T12849 |
60839-60841 |
VB |
denotes |
be |
T12850 |
60849-60851 |
IN |
denotes |
by |
T12851 |
60852-60860 |
JJ |
denotes |
neuronal |
T12852 |
60861-60872 |
NNS |
denotes |
alterations |
T12853 |
60873-60876 |
IN |
denotes |
due |
T12854 |
60877-60879 |
IN |
denotes |
to |
T12855 |
60880-60889 |
NN |
denotes |
transgene |
T12856 |
60890-60900 |
NN |
denotes |
expression |
T12857 |
60901-60907 |
IN |
denotes |
during |
T12858 |
60908-60913 |
JJ |
denotes |
early |
T12859 |
60914-60923 |
JJ |
denotes |
postnatal |
T12860 |
60924-60935 |
NN |
denotes |
development |
T12861 |
60935-60936 |
. |
denotes |
. |
T12862 |
60936-61011 |
sentence |
denotes |
Further experiments are needed to distinguish between these possibilities. |
T12863 |
60937-60944 |
JJ |
denotes |
Further |
T12864 |
60945-60956 |
NNS |
denotes |
experiments |
T12865 |
60961-60967 |
VBN |
denotes |
needed |
T12866 |
60957-60960 |
VBP |
denotes |
are |
T12867 |
60968-60970 |
TO |
denotes |
to |
T12868 |
60971-60982 |
VB |
denotes |
distinguish |
T12869 |
60983-60990 |
IN |
denotes |
between |
T12870 |
60991-60996 |
DT |
denotes |
these |
T12871 |
60997-61010 |
NNS |
denotes |
possibilities |
T12872 |
61010-61011 |
. |
denotes |
. |
T12873 |
61011-61171 |
sentence |
denotes |
In summary, we demonstrate that abrogating Aβ production halts the progression of pathologic changes in a transgenic mouse model of Alzheimer-type amyloidosis. |
T12874 |
61012-61014 |
IN |
denotes |
In |
T12875 |
61027-61038 |
VBP |
denotes |
demonstrate |
T12876 |
61015-61022 |
NN |
denotes |
summary |
T12877 |
61022-61024 |
, |
denotes |
, |
T12878 |
61024-61026 |
PRP |
denotes |
we |
T12879 |
61039-61043 |
IN |
denotes |
that |
T12880 |
61069-61074 |
VBZ |
denotes |
halts |
T12881 |
61044-61054 |
VBG |
denotes |
abrogating |
T12882 |
61055-61057 |
NN |
denotes |
Aβ |
T12883 |
61058-61068 |
NN |
denotes |
production |
T12884 |
61075-61078 |
DT |
denotes |
the |
T12885 |
61079-61090 |
NN |
denotes |
progression |
T12886 |
61091-61093 |
IN |
denotes |
of |
T12887 |
61094-61104 |
JJ |
denotes |
pathologic |
T12888 |
61105-61112 |
NNS |
denotes |
changes |
T12889 |
61113-61115 |
IN |
denotes |
in |
T12890 |
61116-61117 |
DT |
denotes |
a |
T12891 |
61135-61140 |
NN |
denotes |
model |
T12892 |
61118-61128 |
JJ |
denotes |
transgenic |
T12893 |
61129-61134 |
NN |
denotes |
mouse |
T12894 |
61141-61143 |
IN |
denotes |
of |
T12895 |
61144-61153 |
NNP |
denotes |
Alzheimer |
T12896 |
61154-61158 |
NN |
denotes |
type |
T12897 |
61153-61154 |
HYPH |
denotes |
- |
T12898 |
61159-61170 |
NN |
denotes |
amyloidosis |
T12899 |
61170-61171 |
. |
denotes |
. |
T12900 |
61171-61306 |
sentence |
denotes |
However, despite dramatic reductions in Aβ synthesis, neuritic plaques are stable structures in vivo that do not quickly disaggregate. |
T12901 |
61172-61179 |
RB |
denotes |
However |
T12902 |
61243-61246 |
VBP |
denotes |
are |
T12903 |
61179-61181 |
, |
denotes |
, |
T12904 |
61181-61188 |
IN |
denotes |
despite |
T12905 |
61189-61197 |
JJ |
denotes |
dramatic |
T12906 |
61198-61208 |
NNS |
denotes |
reductions |
T12907 |
61209-61211 |
IN |
denotes |
in |
T12908 |
61212-61214 |
NN |
denotes |
Aβ |
T12909 |
61215-61224 |
NN |
denotes |
synthesis |
T12910 |
61224-61226 |
, |
denotes |
, |
T12911 |
61226-61234 |
JJ |
denotes |
neuritic |
T12912 |
61235-61242 |
NNS |
denotes |
plaques |
T12913 |
61247-61253 |
JJ |
denotes |
stable |
T12914 |
61254-61264 |
NNS |
denotes |
structures |
T12915 |
61265-61267 |
FW |
denotes |
in |
T12916 |
61268-61272 |
FW |
denotes |
vivo |
T12917 |
61273-61277 |
WDT |
denotes |
that |
T12918 |
61293-61305 |
VB |
denotes |
disaggregate |
T12919 |
61278-61280 |
VBP |
denotes |
do |
T12920 |
61281-61284 |
RB |
denotes |
not |
T12921 |
61285-61292 |
RB |
denotes |
quickly |
T12922 |
61305-61306 |
. |
denotes |
. |
T12923 |
61306-61502 |
sentence |
denotes |
It is possible that a combination of therapies to limit Aβ production, increase Aβ degradation, and enhance phagocytosis of deposited amyloid may be required to reverse damage associated with AD. |
T12924 |
61307-61309 |
PRP |
denotes |
It |
T12925 |
61310-61312 |
VBZ |
denotes |
is |
T12926 |
61313-61321 |
JJ |
denotes |
possible |
T12927 |
61322-61326 |
IN |
denotes |
that |
T12928 |
61456-61464 |
VBN |
denotes |
required |
T12929 |
61327-61328 |
DT |
denotes |
a |
T12930 |
61329-61340 |
NN |
denotes |
combination |
T12931 |
61341-61343 |
IN |
denotes |
of |
T12932 |
61344-61353 |
NNS |
denotes |
therapies |
T12933 |
61354-61356 |
TO |
denotes |
to |
T12934 |
61357-61362 |
VB |
denotes |
limit |
T12935 |
61363-61365 |
NN |
denotes |
Aβ |
T12936 |
61366-61376 |
NN |
denotes |
production |
T12937 |
61376-61378 |
, |
denotes |
, |
T12938 |
61378-61386 |
VB |
denotes |
increase |
T12939 |
61387-61389 |
NN |
denotes |
Aβ |
T12940 |
61390-61401 |
NN |
denotes |
degradation |
T12941 |
61401-61403 |
, |
denotes |
, |
T12942 |
61403-61406 |
CC |
denotes |
and |
T12943 |
61407-61414 |
VBP |
denotes |
enhance |
T12944 |
61415-61427 |
NN |
denotes |
phagocytosis |
T12945 |
61428-61430 |
IN |
denotes |
of |
T12946 |
61431-61440 |
VBN |
denotes |
deposited |
T12947 |
61441-61448 |
NN |
denotes |
amyloid |
T12948 |
61449-61452 |
MD |
denotes |
may |
T12949 |
61453-61455 |
VB |
denotes |
be |
T12950 |
61465-61467 |
TO |
denotes |
to |
T12951 |
61468-61475 |
VB |
denotes |
reverse |
T12952 |
61476-61482 |
NN |
denotes |
damage |
T12953 |
61483-61493 |
VBN |
denotes |
associated |
T12954 |
61494-61498 |
IN |
denotes |
with |
T12955 |
61499-61501 |
NN |
denotes |
AD |
T12956 |
61501-61502 |
. |
denotes |
. |
T12957 |
61502-61684 |
sentence |
denotes |
However, if started early enough in the course of disease, secretase inhibitors alone could provide substantial benefit in slowing pathogenic processes linked to amyloid deposition. |
T12958 |
61503-61510 |
RB |
denotes |
However |
T12959 |
61595-61602 |
VB |
denotes |
provide |
T12960 |
61510-61512 |
, |
denotes |
, |
T12961 |
61512-61514 |
IN |
denotes |
if |
T12962 |
61515-61522 |
VBN |
denotes |
started |
T12963 |
61523-61528 |
RB |
denotes |
early |
T12964 |
61529-61535 |
RB |
denotes |
enough |
T12965 |
61536-61538 |
IN |
denotes |
in |
T12966 |
61539-61542 |
DT |
denotes |
the |
T12967 |
61543-61549 |
NN |
denotes |
course |
T12968 |
61550-61552 |
IN |
denotes |
of |
T12969 |
61553-61560 |
NN |
denotes |
disease |
T12970 |
61560-61562 |
, |
denotes |
, |
T12971 |
61562-61571 |
NN |
denotes |
secretase |
T12972 |
61572-61582 |
NNS |
denotes |
inhibitors |
T12973 |
61583-61588 |
RB |
denotes |
alone |
T12974 |
61589-61594 |
MD |
denotes |
could |
T12975 |
61603-61614 |
JJ |
denotes |
substantial |
T12976 |
61615-61622 |
NN |
denotes |
benefit |
T12977 |
61623-61625 |
IN |
denotes |
in |
T12978 |
61626-61633 |
VBG |
denotes |
slowing |
T12979 |
61634-61644 |
JJ |
denotes |
pathogenic |
T12980 |
61645-61654 |
NNS |
denotes |
processes |
T12981 |
61655-61661 |
VBN |
denotes |
linked |
T12982 |
61662-61664 |
IN |
denotes |
to |
T12983 |
61665-61672 |
NN |
denotes |
amyloid |
T12984 |
61673-61683 |
NN |
denotes |
deposition |
T12985 |
61683-61684 |
. |
denotes |
. |
T12986 |
61684-61919 |
sentence |
denotes |
Even at later stages in the disease, the presence of substantial microglial activation in human AD [40] suggests that simply slowing the formation of new amyloid deposits may allow ongoing phagocytosis to diminish preexisting lesions. |
T12987 |
61685-61689 |
RB |
denotes |
Even |
T12988 |
61690-61692 |
IN |
denotes |
at |
T12989 |
61789-61797 |
VBZ |
denotes |
suggests |
T12990 |
61693-61698 |
JJR |
denotes |
later |
T12991 |
61699-61705 |
NNS |
denotes |
stages |
T12992 |
61706-61708 |
IN |
denotes |
in |
T12993 |
61709-61712 |
DT |
denotes |
the |
T12994 |
61713-61720 |
NN |
denotes |
disease |
T12995 |
61720-61722 |
, |
denotes |
, |
T12996 |
61722-61725 |
DT |
denotes |
the |
T12997 |
61726-61734 |
NN |
denotes |
presence |
T12998 |
61735-61737 |
IN |
denotes |
of |
T12999 |
61738-61749 |
JJ |
denotes |
substantial |
T13000 |
61761-61771 |
NN |
denotes |
activation |
T13001 |
61750-61760 |
JJ |
denotes |
microglial |
T13002 |
61772-61774 |
IN |
denotes |
in |
T13003 |
61775-61780 |
JJ |
denotes |
human |
T13004 |
61781-61783 |
NN |
denotes |
AD |
T13005 |
61784-61785 |
-LRB- |
denotes |
[ |
T13006 |
61785-61787 |
CD |
denotes |
40 |
T13007 |
61787-61788 |
-RRB- |
denotes |
] |
T13008 |
61798-61802 |
IN |
denotes |
that |
T13009 |
61860-61865 |
VB |
denotes |
allow |
T13010 |
61803-61809 |
RB |
denotes |
simply |
T13011 |
61810-61817 |
VBG |
denotes |
slowing |
T13012 |
61818-61821 |
DT |
denotes |
the |
T13013 |
61822-61831 |
NN |
denotes |
formation |
T13014 |
61832-61834 |
IN |
denotes |
of |
T13015 |
61835-61838 |
JJ |
denotes |
new |
T13016 |
61847-61855 |
NNS |
denotes |
deposits |
T13017 |
61839-61846 |
NN |
denotes |
amyloid |
T13018 |
61856-61859 |
MD |
denotes |
may |
T13019 |
61866-61873 |
JJ |
denotes |
ongoing |
T13020 |
61874-61886 |
NN |
denotes |
phagocytosis |
T13021 |
61890-61898 |
VB |
denotes |
diminish |
T13022 |
61887-61889 |
TO |
denotes |
to |
T13023 |
61899-61910 |
JJ |
denotes |
preexisting |
T13024 |
61911-61918 |
NNS |
denotes |
lesions |
T13025 |
61918-61919 |
. |
denotes |
. |
T13026 |
61919-62158 |
sentence |
denotes |
However, the development of safe and effective secretase inhibitors will ultimately be required to determine whether the human brain has the capacity to repair amyloid-associated damage of AD once the progression of pathology is arrested. |
T13027 |
61920-61927 |
RB |
denotes |
However |
T13028 |
62007-62015 |
VBN |
denotes |
required |
T13029 |
61927-61929 |
, |
denotes |
, |
T13030 |
61929-61932 |
DT |
denotes |
the |
T13031 |
61933-61944 |
NN |
denotes |
development |
T13032 |
61945-61947 |
IN |
denotes |
of |
T13033 |
61948-61952 |
JJ |
denotes |
safe |
T13034 |
61977-61987 |
NNS |
denotes |
inhibitors |
T13035 |
61953-61956 |
CC |
denotes |
and |
T13036 |
61957-61966 |
JJ |
denotes |
effective |
T13037 |
61967-61976 |
NN |
denotes |
secretase |
T13038 |
61988-61992 |
MD |
denotes |
will |
T13039 |
61993-62003 |
RB |
denotes |
ultimately |
T13040 |
62004-62006 |
VB |
denotes |
be |
T13041 |
62016-62018 |
TO |
denotes |
to |
T13042 |
62019-62028 |
VB |
denotes |
determine |
T13043 |
62029-62036 |
IN |
denotes |
whether |
T13044 |
62053-62056 |
VBZ |
denotes |
has |
T13045 |
62037-62040 |
DT |
denotes |
the |
T13046 |
62047-62052 |
NN |
denotes |
brain |
T13047 |
62041-62046 |
JJ |
denotes |
human |
T13048 |
62057-62060 |
DT |
denotes |
the |
T13049 |
62061-62069 |
NN |
denotes |
capacity |
T13050 |
62070-62072 |
TO |
denotes |
to |
T13051 |
62073-62079 |
VB |
denotes |
repair |
T13052 |
62080-62087 |
NN |
denotes |
amyloid |
T13053 |
62088-62098 |
VBN |
denotes |
associated |
T13054 |
62087-62088 |
HYPH |
denotes |
- |
T13055 |
62099-62105 |
NN |
denotes |
damage |
T13056 |
62106-62108 |
IN |
denotes |
of |
T13057 |
62109-62111 |
NN |
denotes |
AD |
T13058 |
62112-62116 |
IN |
denotes |
once |
T13059 |
62149-62157 |
VBN |
denotes |
arrested |
T13060 |
62117-62120 |
DT |
denotes |
the |
T13061 |
62121-62132 |
NN |
denotes |
progression |
T13062 |
62133-62135 |
IN |
denotes |
of |
T13063 |
62136-62145 |
NN |
denotes |
pathology |
T13064 |
62146-62148 |
VBZ |
denotes |
is |
T13065 |
62157-62158 |
. |
denotes |
. |
T9668 |
47227-47229 |
NN |
denotes |
7C |
T9669 |
47220-47226 |
NN |
denotes |
Figure |
T9670 |
47229-47230 |
-RRB- |
denotes |
) |
T9671 |
47230-47231 |
. |
denotes |
. |
T9672 |
47231-47416 |
sentence |
denotes |
Intriguingly, all of the dox-reared animals, both transgenic and wild-type, showed altered circadian rhythms with far less distinction between their day- and nighttime activity levels. |
T9673 |
47232-47244 |
RB |
denotes |
Intriguingly |
T9674 |
47308-47314 |
VBD |
denotes |
showed |
T9675 |
47244-47246 |
, |
denotes |
, |
T9676 |
47246-47249 |
DT |
denotes |
all |
T9677 |
47250-47252 |
IN |
denotes |
of |
T9678 |
47253-47256 |
DT |
denotes |
the |
T9679 |
47268-47275 |
NNS |
denotes |
animals |
T9680 |
47257-47260 |
NN |
denotes |
dox |
T9681 |
47261-47267 |
VBN |
denotes |
reared |
T9682 |
47260-47261 |
HYPH |
denotes |
- |
T9683 |
47275-47277 |
, |
denotes |
, |
T9684 |
47277-47281 |
CC |
denotes |
both |
T9685 |
47282-47292 |
JJ |
denotes |
transgenic |
T9686 |
47293-47296 |
CC |
denotes |
and |
T136 |
0-10 |
JJ |
denotes |
Persistent |
T9661 |
47178-47184 |
NNS |
denotes |
levels |
T9662 |
47185-47192 |
JJ |
denotes |
similar |
T9663 |
47193-47195 |
IN |
denotes |
to |
T9664 |
47196-47199 |
DT |
denotes |
the |
T9665 |
47210-47218 |
NNS |
denotes |
controls |
T9666 |
47200-47209 |
JJ |
denotes |
untreated |
T9667 |
47219-47220 |
-LRB- |
denotes |
( |
R1427 |
T2158 |
T2159 |
amod |
Pronuclear,Injection |
R1428 |
T2160 |
T2159 |
punct |
", ",Injection |
R1429 |
T2161 |
T2159 |
conj |
Screening,Injection |
R1430 |
T2162 |
T2161 |
prep |
of,Screening |
R1431 |
T2163 |
T2162 |
pobj |
Founders,of |
R1432 |
T2164 |
T2161 |
punct |
", ",Screening |
R1433 |
T2165 |
T2161 |
cc |
and,Screening |
R1434 |
T2166 |
T2161 |
conj |
Maintenance,Screening |
R1435 |
T2167 |
T2166 |
prep |
of,Maintenance |
R1436 |
T2168 |
T2169 |
det |
the,Lines |
R1437 |
T2169 |
T2167 |
pobj |
Lines,of |
R1438 |
T2171 |
T2172 |
det |
The,vector |
R1439 |
T2172 |
T2182 |
nsubjpass |
vector,linearized |
R1440 |
T2173 |
T2174 |
compound |
moPrP,ind |
R1441 |
T2174 |
T2172 |
compound |
ind,vector |
R1442 |
T2175 |
T2174 |
punct |
-,ind |
R1443 |
T2176 |
T2174 |
compound |
tetP,ind |
R1444 |
T2177 |
T2174 |
punct |
-,ind |
R1445 |
T2178 |
T2174 |
compound |
mo,ind |
R1446 |
T2179 |
T2174 |
punct |
/,ind |
R1447 |
T2180 |
T2174 |
compound |
huAPP695swe,ind |
R1448 |
T2181 |
T2174 |
punct |
/,ind |
R1449 |
T2183 |
T2182 |
auxpass |
was,linearized |
R1450 |
T2184 |
T2182 |
cc |
and,linearized |
R1451 |
T2185 |
T2186 |
det |
the,domain |
R1452 |
T2186 |
T2188 |
nsubj |
domain,excised |
R1453 |
T2187 |
T2186 |
compound |
pBluescript,domain |
R1454 |
T2188 |
T2182 |
conj |
excised,linearized |
R1455 |
T2189 |
T2188 |
prep |
by,excised |
R1456 |
T2190 |
T2189 |
pobj |
digestion,by |
R1457 |
T2191 |
T2190 |
prep |
with,digestion |
R1458 |
T2192 |
T2191 |
pobj |
NotI,with |
R1459 |
T2193 |
T2188 |
punct |
.,excised |
R1460 |
T2195 |
T2196 |
det |
The,vector |
R1461 |
T2196 |
T2198 |
nsubjpass |
vector,injected |
R1462 |
T2197 |
T2196 |
amod |
purified,vector |
R1463 |
T2199 |
T2198 |
auxpass |
was,injected |
R1464 |
T2200 |
T2198 |
prep |
into,injected |
R1465 |
T2201 |
T2202 |
det |
the,pronucleus |
R1466 |
T2202 |
T2200 |
pobj |
pronucleus,into |
R1467 |
T2203 |
T2202 |
prep |
of,pronucleus |
R1468 |
T2204 |
T2205 |
amod |
fertilized,eggs |
R1469 |
T2205 |
T2203 |
pobj |
eggs,of |
R1470 |
T2206 |
T2205 |
prep |
from,eggs |
R1471 |
T2207 |
T2208 |
nmod |
C57BL,C3HeJ |
R1472 |
T2208 |
T2212 |
compound |
C3HeJ,matings |
R1473 |
T2209 |
T2208 |
punct |
/,C3HeJ |
R1474 |
T2210 |
T2208 |
nmod |
6J,C3HeJ |
R1475 |
T2211 |
T2208 |
punct |
×,C3HeJ |
R1476 |
T2212 |
T2206 |
pobj |
matings,from |
R1477 |
T2213 |
T2212 |
compound |
F1,matings |
R1478 |
T2214 |
T2198 |
punct |
.,injected |
R1479 |
T2216 |
T2217 |
compound |
Founder,animals |
R1480 |
T2217 |
T2218 |
nsubjpass |
animals,screened |
R1481 |
T2219 |
T2218 |
auxpass |
were,screened |
R1482 |
T2220 |
T2218 |
prep |
for,screened |
R1483 |
T2221 |
T2222 |
det |
the,presence |
R1484 |
T2222 |
T2220 |
pobj |
presence,for |
R1485 |
T2223 |
T2222 |
prep |
of,presence |
R1486 |
T2224 |
T2225 |
det |
the,transgene |
R1487 |
T2225 |
T2223 |
pobj |
transgene,of |
R1488 |
T2226 |
T2218 |
prep |
by,screened |
R1489 |
T2227 |
T2228 |
nummod |
three,way |
R1490 |
T2228 |
T2230 |
compound |
way,PCR |
R1491 |
T2229 |
T2228 |
punct |
-,way |
R1492 |
T2230 |
T2226 |
pobj |
PCR,by |
R1493 |
T2231 |
T2218 |
advcl |
using,screened |
R1494 |
T2232 |
T2233 |
det |
the,primers |
R1495 |
T2233 |
T2231 |
dobj |
primers,using |
R1496 |
T2234 |
T2233 |
nmod |
S36,primers |
R1497 |
T2235 |
T2234 |
cc |
and,S36 |
R1498 |
T2236 |
T2237 |
compound |
PrP,AS |
R1500 |
T2238 |
T2237 |
punct |
-,AS |
R1501 |
T2239 |
T2237 |
compound |
S,AS |
R1502 |
T2240 |
T2237 |
punct |
/,AS |
R1503 |
T2241 |
T2237 |
compound |
PrP,AS |
R1504 |
T2242 |
T2237 |
punct |
-,AS |
R1505 |
T2243 |
T2233 |
acl |
described,primers |
R1506 |
T2244 |
T2243 |
advmod |
below,described |
R1507 |
T2245 |
T2218 |
punct |
.,screened |
R1508 |
T2247 |
T2248 |
npadvmod |
Transgene,positive |
R1509 |
T2248 |
T2250 |
amod |
positive,founders |
R1510 |
T2249 |
T2248 |
punct |
-,positive |
R1511 |
T2250 |
T2251 |
nsubjpass |
founders,bred |
R1512 |
T2252 |
T2251 |
auxpass |
were,bred |
R1513 |
T2253 |
T2251 |
prep |
to,bred |
R1514 |
T2254 |
T2253 |
pobj |
animals,to |
R1515 |
T2255 |
T2254 |
acl |
expressing,animals |
R1516 |
T2256 |
T2257 |
det |
the,transactivator |
R1517 |
T2257 |
T2255 |
dobj |
transactivator,expressing |
R1518 |
T2258 |
T2257 |
compound |
tetracycline,transactivator |
R1519 |
T2259 |
T2257 |
punct |
(,transactivator |
R1520 |
T2260 |
T2257 |
appos |
tTA,transactivator |
R1521 |
T2261 |
T2251 |
punct |
),bred |
R1522 |
T2262 |
T2251 |
prep |
under,bred |
R1523 |
T2263 |
T2262 |
pobj |
control,under |
R1524 |
T2264 |
T2263 |
prep |
of,control |
R1525 |
T2265 |
T2266 |
det |
the,promoter |
R1526 |
T2266 |
T2264 |
pobj |
promoter,of |
R1527 |
T2267 |
T2268 |
nmod |
calcium,calmodulin |
R1528 |
T2268 |
T2270 |
nmod |
calmodulin,IIα |
R1529 |
T2269 |
T2268 |
punct |
-,calmodulin |
R1530 |
T2270 |
T2266 |
nmod |
IIα,promoter |
R1531 |
T2271 |
T2270 |
nmod |
kinase,IIα |
R1532 |
T2272 |
T2266 |
punct |
(,promoter |
R1533 |
T2273 |
T2266 |
nmod |
CaMKIIα,promoter |
R1534 |
T2274 |
T2266 |
punct |
),promoter |
R1535 |
T2275 |
T2266 |
acl |
obtained,promoter |
R1536 |
T2276 |
T2275 |
prep |
from,obtained |
R1537 |
T2277 |
T2278 |
compound |
Jackson,Laboratory |
R1538 |
T2278 |
T2276 |
pobj |
Laboratory,from |
R1539 |
T2279 |
T2280 |
punct |
[,16 |
R1540 |
T2280 |
T2278 |
parataxis |
16,Laboratory |
R1541 |
T2281 |
T2280 |
punct |
],16 |
R1542 |
T2282 |
T2283 |
punct |
(,Harbor |
R1543 |
T2283 |
T2275 |
parataxis |
Harbor,obtained |
R1544 |
T2284 |
T2283 |
compound |
Bar,Harbor |
R1545 |
T2285 |
T2283 |
punct |
", ",Harbor |
R1546 |
T2286 |
T2283 |
npadvmod |
Maine,Harbor |
R1547 |
T2287 |
T2283 |
punct |
", ",Harbor |
R1548 |
T2288 |
T2289 |
compound |
United,States |
R1549 |
T2289 |
T2283 |
npadvmod |
States,Harbor |
R1550 |
T2290 |
T2283 |
punct |
;,Harbor |
R1551 |
T2291 |
T2292 |
dep |
stock,1Mmay |
R1552 |
T2292 |
T2283 |
dep |
1Mmay,Harbor |
R1553 |
T2293 |
T2291 |
punct |
#,stock |
R1554 |
T2294 |
T2291 |
nummod |
3010,stock |
R1555 |
T2295 |
T2292 |
punct |
;,1Mmay |
R1556 |
T2296 |
T2292 |
dep |
B6,1Mmay |
R1557 |
T2297 |
T2292 |
punct |
;,1Mmay |
R1558 |
T2298 |
T2292 |
nmod |
CBA,1Mmay |
R1559 |
T2299 |
T2292 |
punct |
-,1Mmay |
R1560 |
T2300 |
T2292 |
nmod |
TgN,1Mmay |
R1561 |
T2301 |
T2292 |
punct |
[,1Mmay |
R1562 |
T2302 |
T2292 |
nmod |
Camk2a,1Mmay |
R1563 |
T2303 |
T2292 |
punct |
-,1Mmay |
R1564 |
T2304 |
T2292 |
nmod |
tTA,1Mmay |
R1565 |
T2305 |
T2292 |
punct |
],1Mmay |
R1566 |
T2306 |
T2283 |
punct |
),Harbor |
R1567 |
T2307 |
T2251 |
punct |
.,bred |
R1568 |
T2309 |
T2310 |
det |
The,colony |
R1569 |
T2310 |
T2311 |
nsubjpass |
colony,maintained |
R1570 |
T2312 |
T2311 |
auxpass |
was,maintained |
R1571 |
T2313 |
T2311 |
advmod |
thereafter,maintained |
R1572 |
T2314 |
T2311 |
prep |
by,maintained |
R1573 |
T2315 |
T2314 |
pcomp |
crossing,by |
R1574 |
T2316 |
T2317 |
amod |
single,offspring |
R1576 |
T2318 |
T2317 |
amod |
transgenic,offspring |
R1577 |
T2319 |
T2317 |
nmod |
tTA,offspring |
R1578 |
T2320 |
T2319 |
cc |
and,tTA |
R1579 |
T2321 |
T2319 |
conj |
APP,tTA |
R1580 |
T2322 |
T2315 |
prep |
for,crossing |
R1581 |
T2323 |
T2322 |
pobj |
each,for |
R1582 |
T2324 |
T2323 |
prep |
of,each |
R1583 |
T2325 |
T2326 |
det |
the,lines |
R1584 |
T2326 |
T2324 |
pobj |
lines,of |
R1585 |
T2327 |
T2326 |
nummod |
four,lines |
R1586 |
T2328 |
T2326 |
compound |
APP,lines |
R1587 |
T2329 |
T2311 |
punct |
.,maintained |
R1588 |
T2331 |
T2332 |
det |
All,mice |
R1589 |
T2332 |
T2333 |
nsubjpass |
mice,provided |
R1590 |
T2334 |
T2333 |
auxpass |
were,provided |
R1591 |
T2335 |
T2336 |
amod |
fresh,food |
R1592 |
T2336 |
T2333 |
dobj |
food,provided |
R1593 |
T2337 |
T2336 |
cc |
and,food |
R1594 |
T2338 |
T2336 |
conj |
water,food |
R1595 |
T2339 |
T2340 |
advmod |
ad,libitum |
R1596 |
T2340 |
T2333 |
advmod |
libitum,provided |
R1597 |
T2341 |
T2333 |
punct |
.,provided |
R1598 |
T2343 |
T2344 |
compound |
Animal,protocols |
R1599 |
T2344 |
T2345 |
nsubjpass |
protocols,approved |
R1600 |
T2346 |
T2345 |
auxpass |
were,approved |
R1601 |
T2347 |
T2345 |
agent |
by,approved |
R1602 |
T2348 |
T2349 |
det |
both,University |
R1603 |
T2349 |
T2353 |
nmod |
University,Committees |
R1604 |
T2350 |
T2349 |
det |
the,University |
R1605 |
T2351 |
T2349 |
nmod |
Johns,University |
R1606 |
T2352 |
T2349 |
nmod |
Hopkins,University |
R1607 |
T2353 |
T2347 |
pobj |
Committees,by |
R1608 |
T2354 |
T2349 |
cc |
and,University |
R1609 |
T2355 |
T2356 |
det |
the,Institute |
R1610 |
T2356 |
T2349 |
conj |
Institute,University |
R1611 |
T2357 |
T2356 |
compound |
California,Institute |
R1612 |
T2358 |
T2356 |
prep |
of,Institute |
R1613 |
T2359 |
T2358 |
pobj |
Technology,of |
R1614 |
T2360 |
T2361 |
nmod |
Institutional,Animal |
R1615 |
T2361 |
T2353 |
nmod |
Animal,Committees |
R1616 |
T2362 |
T2361 |
appos |
Care,Animal |
R1617 |
T2363 |
T2362 |
cc |
and,Care |
R1618 |
T2364 |
T2362 |
conj |
Use,Care |
R1619 |
T2365 |
T2345 |
punct |
.,approved |
R1622 |
T2408 |
T2409 |
compound |
Doxycycline,Administration |
R1623 |
T2411 |
T2412 |
nsubjpass |
Doxycycline,administered |
R1624 |
T2413 |
T2411 |
punct |
(,Doxycycline |
R1625 |
T2414 |
T2411 |
appos |
dox,Doxycycline |
R1626 |
T2415 |
T2411 |
punct |
),Doxycycline |
R1627 |
T2416 |
T2412 |
auxpass |
was,administered |
R1628 |
T2417 |
T2412 |
prep |
through,administered |
R1629 |
T2418 |
T2419 |
advmod |
commercially,available |
R1630 |
T2419 |
T2420 |
amod |
available,chow |
R1631 |
T2420 |
T2417 |
pobj |
chow,through |
R1632 |
T2421 |
T2422 |
npadvmod |
dox,containing |
R1633 |
T2422 |
T2420 |
amod |
containing,chow |
R1634 |
T2423 |
T2422 |
punct |
-,containing |
R1635 |
T2424 |
T2425 |
punct |
(,BioServ |
R1636 |
T2425 |
T2412 |
parataxis |
BioServ,administered |
R1637 |
T2426 |
T2425 |
punct |
", ",BioServ |
R1638 |
T2427 |
T2425 |
npadvmod |
Frenchtown,BioServ |
R1639 |
T2428 |
T2425 |
punct |
", ",BioServ |
R1640 |
T2429 |
T2430 |
compound |
New,Jersey |
R1641 |
T2430 |
T2425 |
npadvmod |
Jersey,BioServ |
R1642 |
T2431 |
T2425 |
punct |
", ",BioServ |
R1643 |
T2432 |
T2433 |
compound |
United,States |
R1644 |
T2433 |
T2425 |
npadvmod |
States,BioServ |
R1645 |
T2434 |
T2425 |
punct |
),BioServ |
R1646 |
T2435 |
T2412 |
punct |
.,administered |
R1647 |
T2437 |
T2438 |
det |
The,chow |
R1648 |
T2438 |
T2439 |
nsubj |
chow,contained |
R1649 |
T2439 |
T2440 |
ccomp |
contained,was |
R1650 |
T2441 |
T2442 |
nummod |
200,mg |
R1651 |
T2442 |
T2439 |
dobj |
mg,contained |
R1652 |
T2443 |
T2444 |
punct |
/,kg |
R1653 |
T2444 |
T2442 |
prep |
kg,mg |
R1654 |
T2445 |
T2442 |
prep |
of,mg |
R1655 |
T2446 |
T2445 |
pobj |
antibiotic,of |
R1656 |
T2447 |
T2440 |
punct |
;,was |
R1657 |
T2448 |
T2440 |
prep |
based,was |
R1658 |
T2449 |
T2448 |
prep |
on,based |
R1659 |
T2450 |
T2451 |
amod |
estimated,consumption |
R1660 |
T2451 |
T2449 |
pobj |
consumption,on |
R1661 |
T2452 |
T2451 |
prep |
of,consumption |
R1662 |
T2453 |
T2454 |
nummod |
5,g |
R1663 |
T2454 |
T2452 |
pobj |
g,of |
R1664 |
T2455 |
T2454 |
prep |
per,g |
R1665 |
T2456 |
T2455 |
pobj |
mouse,per |
R1666 |
T2457 |
T2454 |
prep |
per,g |
R1667 |
T2458 |
T2457 |
pobj |
day,per |
R1668 |
T2459 |
T2440 |
punct |
", ",was |
R1669 |
T2460 |
T2461 |
det |
the,dose |
R1670 |
T2461 |
T2440 |
nsubj |
dose,was |
R1671 |
T2462 |
T2461 |
amod |
expected,dose |
R1672 |
T2463 |
T2461 |
prep |
to,dose |
R1673 |
T2464 |
T2465 |
det |
each,animal |
R1674 |
T2465 |
T2463 |
pobj |
animal,to |
R1675 |
T2466 |
T2467 |
nummod |
1,mg |
R1676 |
T2467 |
T2468 |
compound |
mg,dox |
R1677 |
T2468 |
T2440 |
attr |
dox,was |
R1678 |
T2469 |
T2468 |
prep |
per,dox |
R1679 |
T2470 |
T2469 |
pobj |
day,per |
R1680 |
T2471 |
T2440 |
punct |
.,was |
R1681 |
T2473 |
T2474 |
det |
The,animal |
R1682 |
T2474 |
T2479 |
nsubj |
animal,received |
R1683 |
T2475 |
T2474 |
amod |
average,animal |
R1684 |
T2476 |
T2477 |
nummod |
25,g |
R1685 |
T2477 |
T2474 |
compound |
g,animal |
R1686 |
T2478 |
T2477 |
punct |
-,g |
R1687 |
T2480 |
T2479 |
advmod |
therefore,received |
R1688 |
T2481 |
T2482 |
nummod |
40,μg |
R1689 |
T2482 |
T2479 |
dobj |
μg,received |
R1690 |
T2483 |
T2482 |
prep |
of,μg |
R1691 |
T2484 |
T2483 |
pobj |
dox,of |
R1692 |
T2485 |
T2482 |
prep |
per,μg |
R1693 |
T2486 |
T2487 |
compound |
gram,weight |
R1694 |
T2487 |
T2485 |
pobj |
weight,per |
R1695 |
T2488 |
T2487 |
compound |
body,weight |
R1696 |
T2489 |
T2482 |
prep |
per,μg |
R1697 |
T2490 |
T2489 |
pobj |
day,per |
R1698 |
T2491 |
T2479 |
punct |
.,received |
R1699 |
T2493 |
T2494 |
nsubjpass |
Chow,changed |
R1700 |
T2495 |
T2494 |
auxpass |
was,changed |
R1701 |
T2496 |
T2497 |
quantmod |
1,2 |
R1702 |
T2497 |
T2499 |
nummod |
2,times |
R1703 |
T2498 |
T2497 |
punct |
–,2 |
R1704 |
T2499 |
T2494 |
npadvmod |
times,changed |
R1705 |
T2500 |
T2499 |
prep |
per,times |
R1706 |
T2501 |
T2500 |
pobj |
week,per |
R1707 |
T2502 |
T2503 |
aux |
to,prevent |
R1708 |
T2503 |
T2494 |
advcl |
prevent,changed |
R1709 |
T2504 |
T2503 |
dobj |
breakdown,prevent |
R1710 |
T2505 |
T2504 |
prep |
of,breakdown |
R1711 |
T2506 |
T2507 |
det |
the,antibiotic |
R1712 |
T2507 |
T2505 |
pobj |
antibiotic,of |
R1713 |
T2508 |
T2494 |
punct |
.,changed |
R1718 |
T2637 |
T2638 |
nsubjpass |
Offspring,genotyped |
R1719 |
T2639 |
T2638 |
auxpass |
were,genotyped |
R1720 |
T2640 |
T2638 |
prep |
for,genotyped |
R1721 |
T2641 |
T2642 |
det |
the,presence |
R1722 |
T2642 |
T2640 |
pobj |
presence,for |
R1723 |
T2643 |
T2642 |
prep |
of,presence |
R1724 |
T2644 |
T2645 |
det |
each,transgene |
R1725 |
T2645 |
T2643 |
pobj |
transgene,of |
R1726 |
T2646 |
T2638 |
prep |
by,genotyped |
R1727 |
T2647 |
T2648 |
compound |
PCR,amplification |
R1728 |
T2648 |
T2646 |
pobj |
amplification,by |
R1729 |
T2649 |
T2648 |
prep |
of,amplification |
R1730 |
T2650 |
T2651 |
amod |
genomic,DNA |
R1731 |
T2651 |
T2649 |
pobj |
DNA,of |
R1732 |
T2652 |
T2651 |
acl |
extracted,DNA |
R1733 |
T2653 |
T2652 |
prep |
from,extracted |
R1734 |
T2654 |
T2655 |
det |
a,biopsy |
R1735 |
T2655 |
T2653 |
pobj |
biopsy,from |
R1736 |
T2656 |
T2657 |
nummod |
5,mm |
R1737 |
T2657 |
T2655 |
compound |
mm,biopsy |
R1738 |
T2658 |
T2657 |
punct |
-,mm |
R1739 |
T2659 |
T2655 |
compound |
tail,biopsy |
R1740 |
T2660 |
T2638 |
punct |
.,genotyped |
R1741 |
T2662 |
T2663 |
nsubjpass |
Tails,heated |
R1742 |
T2664 |
T2663 |
auxpass |
were,heated |
R1743 |
T2665 |
T2663 |
prep |
to,heated |
R1744 |
T2666 |
T2667 |
nummod |
95,°C |
R1745 |
T2667 |
T2665 |
pobj |
°C,to |
R1746 |
T2668 |
T2663 |
prep |
for,heated |
R1747 |
T2669 |
T2670 |
nummod |
45,min |
R1748 |
T2670 |
T2668 |
pobj |
min,for |
R1749 |
T2671 |
T2663 |
prep |
in,heated |
R1750 |
T2672 |
T2673 |
nummod |
250,μl |
R1751 |
T2673 |
T2671 |
pobj |
μl,in |
R1752 |
T2674 |
T2673 |
prep |
of,μl |
R1753 |
T2675 |
T2676 |
nummod |
50,mM |
R1754 |
T2676 |
T2677 |
compound |
mM,NaOH |
R1755 |
T2677 |
T2674 |
pobj |
NaOH,of |
R1756 |
T2678 |
T2663 |
punct |
", ",heated |
R1757 |
T2679 |
T2663 |
dep |
vortexed,heated |
R1758 |
T2680 |
T2663 |
punct |
", ",heated |
R1759 |
T2681 |
T2682 |
advmod |
then,neutralized |
R1760 |
T2682 |
T2663 |
dep |
neutralized,heated |
R1761 |
T2683 |
T2682 |
prep |
with,neutralized |
R1762 |
T2684 |
T2685 |
det |
an,volume |
R1763 |
T2685 |
T2683 |
pobj |
volume,with |
R1764 |
T2686 |
T2685 |
amod |
equal,volume |
R1765 |
T2687 |
T2685 |
prep |
of,volume |
R1766 |
T2688 |
T2689 |
nummod |
0.5,M |
R1767 |
T2689 |
T2690 |
compound |
M,HCl |
R1768 |
T2690 |
T2687 |
pobj |
HCl,of |
R1769 |
T2691 |
T2690 |
compound |
Tris,HCl |
R1770 |
T2692 |
T2690 |
punct |
-,HCl |
R1771 |
T2693 |
T2694 |
punct |
(,pH |
R1772 |
T2694 |
T2690 |
parataxis |
pH,HCl |
R1773 |
T2695 |
T2694 |
nummod |
5.5,pH |
R1774 |
T2696 |
T2694 |
punct |
),pH |
R1775 |
T2697 |
T2663 |
punct |
.,heated |
R1776 |
T2699 |
T2700 |
nsubjpass |
Debris,sedimented |
R1777 |
T2701 |
T2700 |
auxpass |
was,sedimented |
R1778 |
T2702 |
T2700 |
prep |
by,sedimented |
R1779 |
T2703 |
T2702 |
pobj |
centrifugation,by |
R1780 |
T2704 |
T2700 |
punct |
", ",sedimented |
R1781 |
T2705 |
T2700 |
cc |
and,sedimented |
R1782 |
T2706 |
T2707 |
nummod |
3,μl |
R1783 |
T2707 |
T2708 |
nsubjpass |
μl,used |
R1784 |
T2708 |
T2700 |
conj |
used,sedimented |
R1785 |
T2709 |
T2707 |
prep |
of,μl |
R1786 |
T2710 |
T2709 |
pobj |
supernatant,of |
R1787 |
T2711 |
T2708 |
auxpass |
was,used |
R1788 |
T2712 |
T2708 |
prep |
for,used |
R1789 |
T2713 |
T2712 |
pobj |
amplification,for |
R1790 |
T2714 |
T2708 |
punct |
.,used |
R1791 |
T2716 |
T2717 |
nsubjpass |
Genotyping,performed |
R1792 |
T2718 |
T2716 |
prep |
for,Genotyping |
R1793 |
T2719 |
T2720 |
nmod |
APP,transgenes |
R1794 |
T2720 |
T2718 |
pobj |
transgenes,for |
R1795 |
T2721 |
T2719 |
cc |
and,APP |
R1796 |
T2722 |
T2719 |
conj |
tTA,APP |
R1797 |
T2723 |
T2717 |
auxpass |
was,performed |
R1798 |
T2724 |
T2717 |
prep |
in,performed |
R1799 |
T2725 |
T2726 |
det |
the,reaction |
R1800 |
T2726 |
T2724 |
pobj |
reaction,in |
R1801 |
T2727 |
T2726 |
amod |
same,reaction |
R1802 |
T2728 |
T2726 |
compound |
PCR,reaction |
R1803 |
T2729 |
T2717 |
punct |
", ",performed |
R1804 |
T2730 |
T2717 |
advcl |
using,performed |
R1805 |
T2731 |
T2732 |
nummod |
five,primers |
R1806 |
T2732 |
T2730 |
dobj |
primers,using |
R1807 |
T2733 |
T2732 |
amod |
separate,primers |
R1808 |
T2734 |
T2717 |
punct |
.,performed |
R1809 |
T2736 |
T2737 |
nsubjpass |
APP,amplified |
R1810 |
T2738 |
T2737 |
auxpass |
was,amplified |
R1811 |
T2739 |
T2737 |
advcl |
using,amplified |
R1812 |
T2740 |
T2741 |
advmod |
forward,S36 |
R1813 |
T2741 |
T2739 |
dobj |
S36,using |
R1814 |
T2742 |
T2741 |
compound |
primer,S36 |
R1815 |
T2743 |
T2741 |
acl |
located,S36 |
R1816 |
T2744 |
T2743 |
prep |
in,located |
R1817 |
T2745 |
T2746 |
det |
the,end |
R1818 |
T2746 |
T2744 |
pobj |
end,in |
R1819 |
T2747 |
T2746 |
nummod |
3,end |
R1820 |
T2748 |
T2747 |
punct |
′,3 |
R1821 |
T2749 |
T2746 |
prep |
of,end |
R1822 |
T2750 |
T2751 |
det |
the,cDNA |
R1823 |
T2751 |
T2749 |
pobj |
cDNA,of |
R1824 |
T2752 |
T2751 |
compound |
APP,cDNA |
R1825 |
T2753 |
T2754 |
punct |
(,ATG |
R1826 |
T2754 |
T2751 |
parataxis |
ATG,cDNA |
R1827 |
T2755 |
T2754 |
compound |
CCG,ATG |
R1828 |
T2756 |
T2754 |
compound |
AGA,ATG |
R1829 |
T2757 |
T2754 |
compound |
TCT,ATG |
R1830 |
T2758 |
T2754 |
compound |
CTG,ATG |
R1831 |
T2759 |
T2754 |
compound |
AAG,ATG |
R1832 |
T2760 |
T2754 |
compound |
TGA,ATG |
R1833 |
T2761 |
T2754 |
compound |
AGA,ATG |
R1834 |
T2762 |
T2754 |
compound |
TGG,ATG |
R1835 |
T2763 |
T2754 |
punct |
),ATG |
R1836 |
T2764 |
T2741 |
cc |
and,S36 |
R1837 |
T2765 |
T2766 |
amod |
reverse,J |
R1838 |
T2766 |
T2741 |
conj |
J,S36 |
R1839 |
T2767 |
T2766 |
compound |
primer,J |
R1840 |
T2768 |
T2766 |
compound |
PrP,J |
R1841 |
T2769 |
T2766 |
punct |
-,J |
R1842 |
T2770 |
T2766 |
compound |
AS,J |
R1843 |
T2771 |
T2766 |
punct |
-,J |
R1844 |
T2772 |
T2766 |
acl |
located,J |
R1845 |
T2773 |
T2772 |
prep |
in,located |
R1846 |
T2774 |
T2775 |
det |
the,UTR |
R1847 |
T2775 |
T2773 |
pobj |
UTR,in |
R1848 |
T2776 |
T2775 |
nummod |
3,UTR |
R1849 |
T2777 |
T2776 |
punct |
′,3 |
R1850 |
T2778 |
T2775 |
prep |
of,UTR |
R1851 |
T2779 |
T2780 |
det |
the,vector |
R1852 |
T2780 |
T2778 |
pobj |
vector,of |
R1853 |
T2781 |
T2782 |
punct |
(,GC |
R1854 |
T2782 |
T2775 |
parataxis |
GC,UTR |
R1855 |
T2783 |
T2782 |
compound |
CCA,GC |
R1856 |
T2784 |
T2782 |
compound |
AGC,GC |
R1857 |
T2785 |
T2782 |
compound |
CTA,GC |
R1858 |
T2786 |
T2782 |
compound |
GAC,GC |
R1859 |
T2787 |
T2782 |
compound |
CAC,GC |
R1860 |
T2788 |
T2782 |
compound |
GAG,GC |
R1861 |
T2789 |
T2782 |
compound |
AAT,GC |
R1862 |
T2790 |
T2782 |
punct |
),GC |
R1863 |
T2791 |
T2737 |
punct |
.,amplified |
R1864 |
T2793 |
T2794 |
det |
The,transgene |
R1865 |
T2794 |
T2796 |
nsubjpass |
transgene,detected |
R1866 |
T2795 |
T2794 |
compound |
tTA,transgene |
R1867 |
T2797 |
T2796 |
auxpass |
was,detected |
R1868 |
T2798 |
T2796 |
advcl |
using,detected |
R1869 |
T2799 |
T2800 |
det |
a,set |
R1870 |
T2800 |
T2798 |
dobj |
set,using |
R1871 |
T2801 |
T2800 |
compound |
primer,set |
R1872 |
T2802 |
T2803 |
dep |
that,amplified |
R1873 |
T2803 |
T2800 |
relcl |
amplified,set |
R1874 |
T2804 |
T2803 |
prep |
across,amplified |
R1875 |
T2805 |
T2806 |
poss |
its,subdomains |
R1876 |
T2806 |
T2804 |
pobj |
subdomains,across |
R1877 |
T2807 |
T2806 |
nummod |
two,subdomains |
R1878 |
T2808 |
T2803 |
prep |
with,amplified |
R1879 |
T2809 |
T2808 |
pobj |
tet,with |
R1880 |
T2810 |
T2809 |
advmod |
forward,tet |
R1881 |
T2811 |
T2809 |
acl |
located,tet |
R1882 |
T2812 |
T2811 |
prep |
within,located |
R1883 |
T2813 |
T2814 |
det |
the,repressor |
R1884 |
T2814 |
T2812 |
pobj |
repressor,within |
R1885 |
T2815 |
T2816 |
compound |
Tn10,tetracycline |
R1886 |
T2816 |
T2814 |
compound |
tetracycline,repressor |
R1887 |
T2817 |
T2818 |
punct |
(,AG |
R1888 |
T2818 |
T2814 |
parataxis |
AG,repressor |
R1889 |
T2819 |
T2818 |
compound |
CGC,AG |
R1890 |
T2820 |
T2818 |
compound |
TGT,AG |
R1891 |
T2821 |
T2818 |
compound |
GGG,AG |
R1892 |
T2822 |
T2818 |
compound |
GCA,AG |
R1893 |
T2823 |
T2818 |
compound |
TTT,AG |
R1894 |
T2824 |
T2818 |
compound |
TAC,AG |
R1895 |
T2825 |
T2818 |
compound |
TTT,AG |
R1896 |
T2826 |
T2818 |
punct |
),AG |
R1897 |
T2827 |
T2809 |
cc |
and,tet |
R1898 |
T2828 |
T2809 |
conj |
tet,tet |
R1899 |
T2829 |
T2828 |
amod |
reverse,tet |
R1900 |
T2830 |
T2828 |
prep |
within,tet |
R1901 |
T2831 |
T2832 |
det |
the,VP16 |
R1902 |
T2832 |
T2830 |
pobj |
VP16,within |
R1903 |
T2833 |
T2832 |
compound |
HSV1,VP16 |
R1904 |
T2834 |
T2835 |
punct |
(,GTC |
R1905 |
T2835 |
T2832 |
parataxis |
GTC,VP16 |
R1906 |
T2836 |
T2835 |
compound |
CAT,GTC |
R1907 |
T2837 |
T2835 |
compound |
GTC,GTC |
R1908 |
T2838 |
T2835 |
compound |
CAG,GTC |
R1909 |
T2839 |
T2835 |
compound |
ATC,GTC |
R1910 |
T2840 |
T2835 |
compound |
GAA,GTC |
R1911 |
T2841 |
T2835 |
compound |
ATC,GTC |
R1912 |
T2842 |
T2835 |
punct |
),GTC |
R1913 |
T2843 |
T2796 |
punct |
.,detected |
R1914 |
T2845 |
T2846 |
det |
All,reactions |
R1915 |
T2846 |
T2847 |
nsubj |
reactions,amplified |
R1916 |
T2848 |
T2847 |
punct |
", ",amplified |
R1917 |
T2849 |
T2850 |
mark |
whether,positive |
R1918 |
T2850 |
T2847 |
advcl |
positive,amplified |
R1919 |
T2851 |
T2850 |
npadvmod |
transgene,positive |
R1920 |
T2852 |
T2850 |
punct |
-,positive |
R1921 |
T2853 |
T2850 |
cc |
or,positive |
R1922 |
T2854 |
T2850 |
conj |
not,positive |
R1923 |
T2855 |
T2847 |
punct |
", ",amplified |
R1924 |
T2856 |
T2857 |
det |
a,segment |
R1925 |
T2857 |
T2847 |
dobj |
segment,amplified |
R1926 |
T2858 |
T2857 |
prep |
of,segment |
R1927 |
T2859 |
T2860 |
det |
the,gene |
R1928 |
T2860 |
T2858 |
pobj |
gene,of |
R1929 |
T2861 |
T2860 |
amod |
endogenous,gene |
R1930 |
T2862 |
T2860 |
compound |
prion,gene |
R1931 |
T2863 |
T2860 |
compound |
protein,gene |
R1932 |
T2864 |
T2847 |
prep |
as,amplified |
R1933 |
T2865 |
T2866 |
det |
a,control |
R1934 |
T2866 |
T2864 |
pobj |
control,as |
R1935 |
T2867 |
T2866 |
prep |
for,control |
R1936 |
T2868 |
T2869 |
compound |
DNA,quality |
R1937 |
T2869 |
T2867 |
pobj |
quality,for |
R1938 |
T2870 |
T2847 |
advcl |
using,amplified |
R1939 |
T2871 |
T2872 |
det |
a,primer |
R1940 |
T2872 |
T2870 |
dobj |
primer,using |
R1941 |
T2873 |
T2872 |
amod |
forward,primer |
R1942 |
T2874 |
T2872 |
punct |
", ",primer |
R1943 |
T2875 |
T2876 |
compound |
PrP,J |
R1944 |
T2876 |
T2872 |
appos |
J,primer |
R1945 |
T2877 |
T2876 |
punct |
-,J |
R1946 |
T2878 |
T2876 |
compound |
S,J |
R1947 |
T2879 |
T2876 |
punct |
-,J |
R1948 |
T2880 |
T2872 |
punct |
", ",primer |
R1949 |
T2881 |
T2872 |
amod |
specific,primer |
R1950 |
T2882 |
T2881 |
prep |
to,specific |
R1951 |
T2883 |
T2884 |
det |
the,frame |
R1952 |
T2884 |
T2882 |
pobj |
frame,to |
R1953 |
T2885 |
T2884 |
nmod |
mouse,frame |
R1954 |
T2886 |
T2884 |
nmod |
PrP,frame |
R1955 |
T2887 |
T2888 |
amod |
open,reading |
R1956 |
T2888 |
T2884 |
compound |
reading,frame |
R1957 |
T2889 |
T2890 |
punct |
(,GG |
R1958 |
T2890 |
T2884 |
parataxis |
GG,frame |
R1959 |
T2891 |
T2890 |
compound |
GGG,GG |
R1960 |
T2892 |
T2890 |
compound |
ACT,GG |
R1961 |
T2893 |
T2890 |
compound |
ATG,GG |
R1962 |
T2894 |
T2890 |
compound |
TGG,GG |
R1963 |
T2895 |
T2890 |
compound |
ACT,GG |
R1964 |
T2896 |
T2890 |
compound |
GAT,GG |
R1965 |
T2897 |
T2890 |
compound |
GTC,GG |
R1966 |
T2898 |
T2890 |
punct |
),GG |
R1967 |
T2899 |
T2872 |
cc |
and,primer |
R1968 |
T2900 |
T2901 |
det |
a,primer |
R1969 |
T2901 |
T2872 |
conj |
primer,primer |
R1970 |
T2902 |
T2901 |
amod |
reverse,primer |
R1971 |
T2903 |
T2901 |
punct |
", ",primer |
R1972 |
T2904 |
T2905 |
compound |
PrP,J |
R1973 |
T2905 |
T2901 |
appos |
J,primer |
R1974 |
T2906 |
T2905 |
punct |
-,J |
R1975 |
T2907 |
T2905 |
compound |
AS,J |
R1976 |
T2908 |
T2905 |
punct |
-,J |
R1977 |
T2909 |
T2901 |
punct |
", ",primer |
R1978 |
T2910 |
T2901 |
acl |
shared,primer |
R1979 |
T2911 |
T2910 |
agent |
by,shared |
R1980 |
T2912 |
T2913 |
det |
the,UTR |
R1981 |
T2913 |
T2911 |
pobj |
UTR,by |
R1982 |
T2914 |
T2913 |
nummod |
3,UTR |
R1983 |
T2915 |
T2914 |
punct |
′,3 |
R1984 |
T2916 |
T2913 |
prep |
of,UTR |
R1985 |
T2917 |
T2918 |
det |
the,gene |
R1986 |
T2918 |
T2916 |
pobj |
gene,of |
R1987 |
T2919 |
T2918 |
amod |
endogenous,gene |
R1988 |
T2920 |
T2918 |
compound |
PrP,gene |
R1989 |
T2921 |
T2918 |
cc |
and,gene |
R1990 |
T2922 |
T2923 |
det |
the,vector |
R1991 |
T2923 |
T2918 |
conj |
vector,gene |
R1992 |
T2924 |
T2923 |
compound |
transgene,vector |
R1993 |
T2925 |
T2847 |
punct |
.,amplified |
R1994 |
T2927 |
T2928 |
compound |
Amplification,reactions |
R1995 |
T2928 |
T2929 |
nsubjpass |
reactions,run |
R1996 |
T2930 |
T2929 |
auxpass |
were,run |
R1997 |
T2931 |
T2929 |
prep |
for,run |
R1998 |
T2932 |
T2933 |
nummod |
37,cycles |
R1999 |
T2933 |
T2931 |
pobj |
cycles,for |
R2000 |
T2934 |
T2929 |
prep |
at,run |
R2001 |
T2935 |
T2936 |
nummod |
94,°C |
R2002 |
T2936 |
T2934 |
pobj |
°C,at |
R2003 |
T2937 |
T2929 |
prep |
for,run |
R2004 |
T2938 |
T2939 |
nummod |
30,s |
R2005 |
T2939 |
T2937 |
pobj |
s,for |
R2006 |
T2940 |
T2929 |
punct |
", ",run |
R2007 |
T2941 |
T2942 |
nummod |
64,°C |
R2008 |
T2942 |
T2929 |
conj |
°C,run |
R2009 |
T2943 |
T2942 |
prep |
for,°C |
R2010 |
T2944 |
T2945 |
nummod |
1,min |
R2011 |
T2945 |
T2943 |
pobj |
min,for |
R2012 |
T2946 |
T2942 |
punct |
", ",°C |
R2013 |
T2947 |
T2942 |
cc |
and,°C |
R2014 |
T2948 |
T2949 |
nummod |
72,°C |
R2015 |
T2949 |
T2942 |
conj |
°C,°C |
R2016 |
T2950 |
T2949 |
prep |
for,°C |
R2017 |
T2951 |
T2952 |
nummod |
1,min |
R2018 |
T2952 |
T2950 |
pobj |
min,for |
R2019 |
T2953 |
T2929 |
punct |
.,run |
R2020 |
T2955 |
T2956 |
det |
All,samples |
R2021 |
T2956 |
T2957 |
nsubj |
samples,gave |
R2022 |
T2958 |
T2956 |
punct |
", ",samples |
R2023 |
T2959 |
T2956 |
amod |
transgenic,samples |
R2024 |
T2960 |
T2959 |
cc |
and,transgenic |
R2025 |
T2961 |
T2962 |
amod |
wild,type |
R2026 |
T2962 |
T2959 |
conj |
type,transgenic |
R2027 |
T2963 |
T2962 |
punct |
-,type |
R2028 |
T2964 |
T2957 |
punct |
", ",gave |
R2029 |
T2965 |
T2966 |
det |
a,product |
R2030 |
T2966 |
T2957 |
dobj |
product,gave |
R2031 |
T2967 |
T2968 |
nummod |
750,bp |
R2032 |
T2968 |
T2966 |
compound |
bp,product |
R2033 |
T2969 |
T2968 |
punct |
-,bp |
R2034 |
T2970 |
T2966 |
prep |
from,product |
R2035 |
T2971 |
T2972 |
det |
the,gene |
R2036 |
T2972 |
T2970 |
pobj |
gene,from |
R2037 |
T2973 |
T2972 |
amod |
endogenous,gene |
R2038 |
T2974 |
T2972 |
compound |
PrP,gene |
R2039 |
T2975 |
T2957 |
punct |
.,gave |
R2040 |
T2977 |
T2978 |
det |
The,transgene |
R2041 |
T2978 |
T2980 |
nsubj |
transgene,yielded |
R2042 |
T2979 |
T2978 |
compound |
APP,transgene |
R2043 |
T2980 |
T2981 |
ccomp |
yielded,fell |
R2044 |
T2982 |
T2983 |
det |
an,band |
R2045 |
T2983 |
T2980 |
dobj |
band,yielded |
R2046 |
T2984 |
T2983 |
amod |
additional,band |
R2047 |
T2985 |
T2983 |
prep |
at,band |
R2048 |
T2986 |
T2987 |
nummod |
400,bp |
R2049 |
T2987 |
T2985 |
pobj |
bp,at |
R2050 |
T2988 |
T2981 |
punct |
;,fell |
R2051 |
T2989 |
T2990 |
det |
the,product |
R2052 |
T2990 |
T2981 |
nsubj |
product,fell |
R2053 |
T2991 |
T2990 |
compound |
tTA,product |
R2054 |
T2992 |
T2993 |
advmod |
in,between |
R2055 |
T2993 |
T2981 |
advmod |
between,fell |
R2056 |
T2994 |
T2981 |
prep |
at,fell |
R2057 |
T2995 |
T2996 |
nummod |
480,bp |
R2058 |
T2996 |
T2994 |
pobj |
bp,at |
R2059 |
T2997 |
T2981 |
punct |
.,fell |
R2060 |
T3141 |
T3142 |
compound |
Immunoblotting,Quantitation |
R2061 |
T3143 |
T3142 |
punct |
/,Quantitation |
R2062 |
T3145 |
T3146 |
amod |
Frozen,tissue |
R2063 |
T3146 |
T3151 |
nsubjpass |
tissue,homogenized |
R2064 |
T3147 |
T3146 |
amod |
cortical,tissue |
R2065 |
T3148 |
T3147 |
cc |
or,cortical |
R2066 |
T3149 |
T3150 |
amod |
whole,forebrain |
R2067 |
T3150 |
T3147 |
conj |
forebrain,cortical |
R2068 |
T3152 |
T3151 |
auxpass |
was,homogenized |
R2069 |
T3153 |
T3151 |
prep |
by,homogenized |
R2070 |
T3154 |
T3153 |
pobj |
sonication,by |
R2071 |
T3155 |
T3151 |
prep |
in,homogenized |
R2072 |
T3156 |
T3157 |
nummod |
five,volumes |
R2073 |
T3157 |
T3155 |
pobj |
volumes,in |
R2074 |
T3158 |
T3157 |
prep |
of,volumes |
R2075 |
T3159 |
T3160 |
npadvmod |
phosphate,buffered |
R2076 |
T3160 |
T3162 |
amod |
buffered,saline |
R2077 |
T3161 |
T3160 |
punct |
-,buffered |
R2078 |
T3162 |
T3158 |
pobj |
saline,of |
R2079 |
T3163 |
T3162 |
punct |
(,saline |
R2080 |
T3164 |
T3162 |
appos |
PBS,saline |
R2081 |
T3165 |
T3151 |
punct |
),homogenized |
R2082 |
T3166 |
T3151 |
prep |
with,homogenized |
R2083 |
T3167 |
T3168 |
nummod |
5,mM |
R2084 |
T3168 |
T3169 |
nmod |
mM,inhibitors |
R2085 |
T3169 |
T3166 |
pobj |
inhibitors,with |
R2086 |
T3170 |
T3169 |
nmod |
EDTA,inhibitors |
R2087 |
T3171 |
T3170 |
cc |
and,EDTA |
R2088 |
T3172 |
T3170 |
conj |
protease,EDTA |
R2089 |
T3173 |
T3174 |
punct |
(,cocktail |
R2090 |
T3174 |
T3169 |
parataxis |
cocktail,inhibitors |
R2091 |
T3175 |
T3174 |
amod |
Mammalian,cocktail |
R2092 |
T3176 |
T3174 |
compound |
cell,cocktail |
R2093 |
T3177 |
T3174 |
punct |
", ",cocktail |
R2094 |
T3178 |
T3174 |
npadvmod |
Sigma,cocktail |
R2095 |
T3179 |
T3174 |
punct |
", ",cocktail |
R2096 |
T3180 |
T3181 |
compound |
St.,Louis |
R2097 |
T3181 |
T3174 |
npadvmod |
Louis,cocktail |
R2098 |
T3182 |
T3174 |
punct |
", ",cocktail |
R2099 |
T3183 |
T3174 |
npadvmod |
Missouri,cocktail |
R2100 |
T3184 |
T3174 |
punct |
", ",cocktail |
R2101 |
T3185 |
T3186 |
compound |
United,States |
R2102 |
T3186 |
T3174 |
npadvmod |
States,cocktail |
R2103 |
T3187 |
T3174 |
punct |
),cocktail |
R2104 |
T3188 |
T3151 |
punct |
", ",homogenized |
R2105 |
T3189 |
T3151 |
advcl |
using,homogenized |
R2106 |
T3190 |
T3191 |
det |
a,sonicator |
R2107 |
T3191 |
T3189 |
dobj |
sonicator,using |
R2108 |
T3192 |
T3191 |
compound |
probe,sonicator |
R2109 |
T3193 |
T3191 |
acl |
set,sonicator |
R2110 |
T3194 |
T3193 |
prep |
to,set |
R2111 |
T3195 |
T3196 |
nummod |
50,% |
R2112 |
T3196 |
T3197 |
compound |
%,output |
R2113 |
T3197 |
T3194 |
pobj |
output,to |
R2114 |
T3198 |
T3199 |
punct |
(,TEKMAR |
R2115 |
T3199 |
T3191 |
parataxis |
TEKMAR,sonicator |
R2116 |
T3200 |
T3199 |
punct |
", ",TEKMAR |
R2117 |
T3201 |
T3199 |
npadvmod |
Cincinnati,TEKMAR |
R2118 |
T3202 |
T3199 |
punct |
", ",TEKMAR |
R2119 |
T3203 |
T3199 |
npadvmod |
Ohio,TEKMAR |
R2120 |
T3204 |
T3199 |
punct |
", ",TEKMAR |
R2121 |
T3205 |
T3206 |
compound |
United,States |
R2122 |
T3206 |
T3199 |
npadvmod |
States,TEKMAR |
R2123 |
T3207 |
T3199 |
punct |
),TEKMAR |
R2124 |
T3208 |
T3151 |
punct |
.,homogenized |
R2125 |
T3210 |
T3211 |
prep |
After,centrifuged |
R2126 |
T3212 |
T3210 |
pobj |
dilution,After |
R2127 |
T3213 |
T3212 |
prep |
with,dilution |
R2128 |
T3214 |
T3215 |
det |
an,volume |
R2129 |
T3215 |
T3213 |
pobj |
volume,with |
R2130 |
T3216 |
T3215 |
amod |
equal,volume |
R2131 |
T3217 |
T3215 |
prep |
of,volume |
R2132 |
T3218 |
T3219 |
compound |
PBS,protease |
R2133 |
T3219 |
T3223 |
compound |
protease,inhibitor |
R2134 |
T3220 |
T3219 |
punct |
/,protease |
R2135 |
T3221 |
T3219 |
compound |
EDTA,protease |
R2136 |
T3222 |
T3219 |
punct |
/,protease |
R2137 |
T3223 |
T3217 |
pobj |
inhibitor,of |
R2138 |
T3224 |
T3211 |
punct |
", ",centrifuged |
R2139 |
T3225 |
T3226 |
det |
the,samples |
R2140 |
T3226 |
T3211 |
nsubjpass |
samples,centrifuged |
R2141 |
T3227 |
T3211 |
auxpass |
were,centrifuged |
R2142 |
T3228 |
T3211 |
advmod |
briefly,centrifuged |
R2143 |
T3229 |
T3211 |
cc |
and,centrifuged |
R2144 |
T3230 |
T3231 |
det |
the,supernatant |
R2145 |
T3231 |
T3232 |
nsubj |
supernatant,used |
R2146 |
T3232 |
T3211 |
conj |
used,centrifuged |
R2147 |
T3233 |
T3232 |
prep |
for,used |
R2148 |
T3234 |
T3233 |
pobj |
analysis,for |
R2149 |
T3235 |
T3211 |
punct |
.,centrifuged |
R2150 |
T3237 |
T3238 |
nummod |
Fifty,micrograms |
R2151 |
T3238 |
T3239 |
nmod |
micrograms,6E10 |
R2152 |
T3239 |
T3241 |
nsubjpass |
6E10,loaded |
R2153 |
T3240 |
T3239 |
punct |
(,6E10 |
R2154 |
T3242 |
T3239 |
cc |
and,6E10 |
R2155 |
T3243 |
T3239 |
conj |
CT15,6E10 |
R2156 |
T3244 |
T3243 |
punct |
),CT15 |
R2157 |
T3245 |
T3239 |
cc |
or,6E10 |
R2158 |
T3246 |
T3247 |
nummod |
5,μg |
R2159 |
T3247 |
T3248 |
nmod |
μg,22C11 |
R2160 |
T3248 |
T3239 |
conj |
22C11,6E10 |
R2161 |
T3249 |
T3248 |
punct |
(,22C11 |
R2162 |
T3250 |
T3248 |
punct |
),22C11 |
R2163 |
T3251 |
T3239 |
prep |
of,6E10 |
R2164 |
T3252 |
T3253 |
compound |
brain,homogenate |
R2165 |
T3253 |
T3251 |
pobj |
homogenate,of |
R2166 |
T3254 |
T3241 |
auxpass |
was,loaded |
R2167 |
T3255 |
T3241 |
prep |
per,loaded |
R2168 |
T3256 |
T3255 |
pobj |
lane,per |
R2169 |
T3257 |
T3241 |
prep |
onto,loaded |
R2170 |
T3258 |
T3259 |
nummod |
7.5,% |
R2171 |
T3259 |
T3260 |
nmod |
%,PAGE |
R2172 |
T3260 |
T3277 |
compound |
PAGE,gels |
R2173 |
T3261 |
T3259 |
punct |
", ",% |
R2174 |
T3262 |
T3263 |
nummod |
10,% |
R2175 |
T3263 |
T3259 |
conj |
%,% |
R2176 |
T3264 |
T3265 |
punct |
–,% |
R2177 |
T3265 |
T3263 |
prep |
%,% |
R2178 |
T3266 |
T3265 |
nummod |
20,% |
R2179 |
T3267 |
T3263 |
punct |
", ",% |
R2180 |
T3268 |
T3263 |
cc |
or,% |
R2181 |
T3269 |
T3270 |
nummod |
4,% |
R2182 |
T3270 |
T3263 |
conj |
%,% |
R2183 |
T3271 |
T3272 |
punct |
–,% |
R2184 |
T3272 |
T3270 |
prep |
%,% |
R2185 |
T3273 |
T3272 |
nummod |
20,% |
R2186 |
T3274 |
T3260 |
compound |
Tris,PAGE |
R2187 |
T3275 |
T3260 |
punct |
-,PAGE |
R2188 |
T3276 |
T3260 |
compound |
HCl,PAGE |
R2189 |
T3277 |
T3257 |
pobj |
gels,onto |
R2190 |
T3278 |
T3279 |
punct |
(,Laboratories |
R2191 |
T3279 |
T3277 |
parataxis |
Laboratories,gels |
R2192 |
T3280 |
T3281 |
compound |
Bio,Rad |
R2193 |
T3281 |
T3279 |
compound |
Rad,Laboratories |
R2194 |
T3282 |
T3281 |
punct |
-,Rad |
R2195 |
T3283 |
T3279 |
punct |
", ",Laboratories |
R2196 |
T3284 |
T3279 |
npadvmod |
Hercules,Laboratories |
R2197 |
T3285 |
T3279 |
punct |
", ",Laboratories |
R2198 |
T3286 |
T3279 |
npadvmod |
California,Laboratories |
R2199 |
T3287 |
T3279 |
punct |
", ",Laboratories |
R2200 |
T3288 |
T3289 |
compound |
United,States |
R2201 |
T3289 |
T3279 |
npadvmod |
States,Laboratories |
R2202 |
T3290 |
T3279 |
punct |
),Laboratories |
R2203 |
T3291 |
T3241 |
cc |
and,loaded |
R2204 |
T3292 |
T3241 |
conj |
electrophoresed,loaded |
R2205 |
T3293 |
T3292 |
prep |
for,electrophoresed |
R2206 |
T3294 |
T3295 |
amod |
several,hours |
R2207 |
T3295 |
T3293 |
pobj |
hours,for |
R2208 |
T3296 |
T3292 |
prep |
in,electrophoresed |
R2209 |
T3297 |
T3298 |
nummod |
1,sulfate |
R2210 |
T3298 |
T3306 |
nmod |
sulfate,buffer |
R2211 |
T3299 |
T3297 |
punct |
×,1 |
R2212 |
T3300 |
T3298 |
nmod |
Tris,sulfate |
R2213 |
T3301 |
T3298 |
punct |
-,sulfate |
R2214 |
T3302 |
T3298 |
nmod |
glycine,sulfate |
R2215 |
T3303 |
T3298 |
punct |
–,sulfate |
R2216 |
T3304 |
T3298 |
nmod |
sodium,sulfate |
R2217 |
T3305 |
T3298 |
nmod |
dodecyl,sulfate |
R2218 |
T3306 |
T3296 |
pobj |
buffer,in |
R2219 |
T3307 |
T3298 |
punct |
(,sulfate |
R2220 |
T3308 |
T3309 |
nummod |
1,SDS |
R2221 |
T3309 |
T3298 |
appos |
SDS,sulfate |
R2222 |
T3310 |
T3308 |
punct |
×,1 |
R2223 |
T3311 |
T3309 |
compound |
TG,SDS |
R2224 |
T3312 |
T3309 |
punct |
-,SDS |
R2225 |
T3313 |
T3306 |
punct |
),buffer |
R2226 |
T3314 |
T3315 |
punct |
(,Amresco |
R2227 |
T3315 |
T3306 |
parataxis |
Amresco,buffer |
R2228 |
T3316 |
T3315 |
dep |
6E10,Amresco |
R2229 |
T3317 |
T3316 |
cc |
and,6E10 |
R2230 |
T3318 |
T3316 |
conj |
22C11,6E10 |
R2231 |
T3319 |
T3315 |
punct |
;,Amresco |
R2232 |
T3320 |
T3315 |
punct |
", ",Amresco |
R2233 |
T3321 |
T3315 |
npadvmod |
Solon,Amresco |
R2234 |
T3322 |
T3315 |
punct |
", ",Amresco |
R2235 |
T3323 |
T3315 |
npadvmod |
Ohio,Amresco |
R2236 |
T3324 |
T3315 |
punct |
", ",Amresco |
R2237 |
T3325 |
T3326 |
compound |
United,States |
R2238 |
T3326 |
T3315 |
npadvmod |
States,Amresco |
R2239 |
T3327 |
T3315 |
punct |
),Amresco |
R2240 |
T3328 |
T3306 |
cc |
or,buffer |
R2241 |
T3329 |
T3330 |
nummod |
1,buffer |
R2242 |
T3330 |
T3306 |
conj |
buffer,buffer |
R2243 |
T3331 |
T3329 |
punct |
×,1 |
R2244 |
T3332 |
T3333 |
compound |
Tris,SDS |
R2245 |
T3333 |
T3330 |
compound |
SDS,buffer |
R2246 |
T3334 |
T3333 |
punct |
-,SDS |
R2247 |
T3335 |
T3333 |
compound |
tricine,SDS |
R2248 |
T3336 |
T3333 |
punct |
-,SDS |
R2249 |
T3337 |
T3338 |
punct |
(,Invitrogen |
R2250 |
T3338 |
T3330 |
parataxis |
Invitrogen,buffer |
R2251 |
T3339 |
T3338 |
dep |
CT15,Invitrogen |
R2252 |
T3340 |
T3338 |
punct |
;,Invitrogen |
R2253 |
T3341 |
T3338 |
punct |
", ",Invitrogen |
R2254 |
T3342 |
T3338 |
npadvmod |
Carlsbad,Invitrogen |
R2255 |
T3343 |
T3338 |
punct |
", ",Invitrogen |
R2256 |
T3344 |
T3338 |
npadvmod |
California,Invitrogen |
R2257 |
T3345 |
T3338 |
punct |
", ",Invitrogen |
R2258 |
T3346 |
T3347 |
compound |
United,States |
R2259 |
T3347 |
T3338 |
npadvmod |
States,Invitrogen |
R2260 |
T3348 |
T3338 |
punct |
),Invitrogen |
R2261 |
T3349 |
T3241 |
punct |
.,loaded |
R2262 |
T3351 |
T3352 |
nsubjpass |
Proteins,transferred |
R2263 |
T3353 |
T3352 |
auxpass |
were,transferred |
R2264 |
T3354 |
T3352 |
advmod |
overnight,transferred |
R2265 |
T3355 |
T3352 |
prep |
to,transferred |
R2266 |
T3356 |
T3357 |
nummod |
0.45,μm |
R2267 |
T3357 |
T3359 |
compound |
μm,nitrocellulose |
R2268 |
T3358 |
T3357 |
punct |
-,μm |
R2269 |
T3359 |
T3355 |
pobj |
nitrocellulose,to |
R2270 |
T3360 |
T3359 |
compound |
Optitran,nitrocellulose |
R2271 |
T3361 |
T3362 |
punct |
(,Schleicher |
R2272 |
T3362 |
T3359 |
parataxis |
Schleicher,nitrocellulose |
R2273 |
T3363 |
T3362 |
cc |
and,Schleicher |
R2274 |
T3364 |
T3362 |
conj |
Schuell,Schleicher |
R2275 |
T3365 |
T3362 |
punct |
", ",Schleicher |
R2276 |
T3366 |
T3362 |
npadvmod |
Keene,Schleicher |
R2277 |
T3367 |
T3362 |
punct |
", ",Schleicher |
R2278 |
T3368 |
T3369 |
compound |
New,Hampshire |
R2279 |
T3369 |
T3362 |
npadvmod |
Hampshire,Schleicher |
R2280 |
T3370 |
T3362 |
punct |
", ",Schleicher |
R2281 |
T3371 |
T3372 |
compound |
United,States |
R2282 |
T3372 |
T3362 |
npadvmod |
States,Schleicher |
R2283 |
T3373 |
T3362 |
punct |
),Schleicher |
R2284 |
T3374 |
T3352 |
prep |
in,transferred |
R2285 |
T3375 |
T3376 |
nummod |
1,buffer |
R2286 |
T3376 |
T3374 |
pobj |
buffer,in |
R2287 |
T3377 |
T3375 |
punct |
×,1 |
R2288 |
T3378 |
T3376 |
compound |
TG,buffer |
R2289 |
T3379 |
T3380 |
punct |
(,Amresco |
R2290 |
T3380 |
T3376 |
parataxis |
Amresco,buffer |
R2291 |
T3381 |
T3380 |
punct |
),Amresco |
R2292 |
T3382 |
T3352 |
punct |
.,transferred |
R2293 |
T3384 |
T3385 |
nsubjpass |
Blots,blocked |
R2294 |
T3386 |
T3385 |
auxpass |
were,blocked |
R2295 |
T3387 |
T3385 |
prep |
in,blocked |
R2296 |
T3388 |
T3387 |
pobj |
PBS,in |
R2297 |
T3389 |
T3388 |
acl |
containing,PBS |
R2298 |
T3390 |
T3391 |
nummod |
5,% |
R2299 |
T3391 |
T3392 |
nmod |
%,powder |
R2300 |
T3392 |
T3389 |
dobj |
powder,containing |
R2301 |
T3393 |
T3394 |
amod |
nonfat,milk |
R2302 |
T3394 |
T3392 |
compound |
milk,powder |
R2303 |
T3395 |
T3394 |
amod |
dry,milk |
R2304 |
T3396 |
T3385 |
punct |
", ",blocked |
R2305 |
T3397 |
T3385 |
cc |
and,blocked |
R2306 |
T3398 |
T3385 |
conj |
incubated,blocked |
R2307 |
T3399 |
T3398 |
prep |
for,incubated |
R2308 |
T3400 |
T3401 |
nummod |
3,h |
R2309 |
T3401 |
T3399 |
pobj |
h,for |
R2310 |
T3402 |
T3398 |
prep |
at,incubated |
R2311 |
T3403 |
T3404 |
compound |
room,temperature |
R2312 |
T3404 |
T3402 |
pobj |
temperature,at |
R2313 |
T3405 |
T3398 |
prep |
in,incubated |
R2314 |
T3406 |
T3407 |
compound |
blocking,solution |
R2315 |
T3407 |
T3405 |
pobj |
solution,in |
R2316 |
T3408 |
T3407 |
prep |
with,solution |
R2317 |
T3409 |
T3408 |
pobj |
one,with |
R2318 |
T3410 |
T3409 |
prep |
of,one |
R2319 |
T3411 |
T3412 |
det |
the,antibodies |
R2320 |
T3412 |
T3410 |
pobj |
antibodies,of |
R2321 |
T3413 |
T3412 |
amod |
following,antibodies |
R2322 |
T3414 |
T3412 |
punct |
: ,antibodies |
R2323 |
T3415 |
T3416 |
nmod |
mouse,22C11 |
R2324 |
T3416 |
T3412 |
appos |
22C11,antibodies |
R2325 |
T3417 |
T3416 |
amod |
monoclonal,22C11 |
R2326 |
T3418 |
T3419 |
punct |
(,17 |
R2328 |
T3420 |
T3421 |
amod |
kind,gift |
R2329 |
T3421 |
T3419 |
dep |
gift,17 |
R2330 |
T3422 |
T3421 |
prep |
of,gift |
R2331 |
T3423 |
T3424 |
compound |
Konrad,Beyreuther |
R2332 |
T3424 |
T3422 |
pobj |
Beyreuther,of |
R2333 |
T3425 |
T3424 |
cc |
and,Beyreuther |
R2334 |
T3426 |
T3427 |
compound |
Andreas,Weidemann |
R2335 |
T3427 |
T3424 |
conj |
Weidemann,Beyreuther |
R2336 |
T3428 |
T3419 |
punct |
;,17 |
R2337 |
T3429 |
T3419 |
punct |
[,17 |
R2338 |
T3430 |
T3419 |
punct |
],17 |
R2339 |
T3431 |
T3419 |
punct |
),17 |
R2340 |
T3432 |
T3416 |
acl |
diluted,22C11 |
R2341 |
T3433 |
T3432 |
npadvmod |
1,diluted |
R2342 |
T3434 |
T3435 |
punct |
:,"1,000" |
R2343 |
T3435 |
T3433 |
prep |
"1,000",1 |
R2344 |
T3436 |
T3416 |
punct |
", ",22C11 |
R2345 |
T3437 |
T3438 |
nmod |
mouse,6E10 |
R2346 |
T3438 |
T3416 |
conj |
6E10,22C11 |
R2347 |
T3439 |
T3438 |
amod |
monoclonal,6E10 |
R2348 |
T3440 |
T3441 |
punct |
(,Laboratories |
R2349 |
T3441 |
T3438 |
parataxis |
Laboratories,6E10 |
R2350 |
T3442 |
T3441 |
compound |
Signet,Laboratories |
R2351 |
T3443 |
T3441 |
punct |
", ",Laboratories |
R2352 |
T3444 |
T3441 |
npadvmod |
Dedham,Laboratories |
R2353 |
T3445 |
T3441 |
punct |
", ",Laboratories |
R2354 |
T3446 |
T3441 |
npadvmod |
Massachusetts,Laboratories |
R2355 |
T3447 |
T3441 |
punct |
", ",Laboratories |
R2356 |
T3448 |
T3449 |
compound |
United,States |
R2357 |
T3449 |
T3441 |
npadvmod |
States,Laboratories |
R2358 |
T3450 |
T3441 |
punct |
),Laboratories |
R2359 |
T3451 |
T3438 |
acl |
diluted,6E10 |
R2360 |
T3452 |
T3451 |
npadvmod |
1,diluted |
R2361 |
T3453 |
T3454 |
punct |
:,"2,500" |
R2362 |
T3454 |
T3452 |
prep |
"2,500",1 |
R2363 |
T3455 |
T3438 |
punct |
", ",6E10 |
R2364 |
T3456 |
T3457 |
nmod |
rabbit,hSOD1 |
R2365 |
T3457 |
T3438 |
conj |
hSOD1,6E10 |
R2366 |
T3458 |
T3457 |
amod |
polyclonal,hSOD1 |
R2367 |
T3459 |
T3457 |
amod |
anti-superoxide,hSOD1 |
R2368 |
T3460 |
T3457 |
nmod |
dismutase,hSOD1 |
R2369 |
T3461 |
T3457 |
nummod |
1,hSOD1 |
R2370 |
T3462 |
T3457 |
punct |
(,hSOD1 |
R2371 |
T3463 |
T3457 |
compound |
m,hSOD1 |
R2372 |
T3464 |
T3457 |
punct |
/,hSOD1 |
R2373 |
T3465 |
T3457 |
punct |
),hSOD1 |
R2374 |
T3466 |
T3467 |
punct |
[,18 |
R2375 |
T3467 |
T3457 |
parataxis |
18,hSOD1 |
R2376 |
T3468 |
T3467 |
punct |
],18 |
R2377 |
T3469 |
T3457 |
acl |
diluted,hSOD1 |
R2378 |
T3470 |
T3469 |
npadvmod |
1,diluted |
R2379 |
T3471 |
T3472 |
punct |
:,"2,500" |
R2380 |
T3472 |
T3470 |
prep |
"2,500",1 |
R2381 |
T3473 |
T3470 |
prep |
to,1 |
R2382 |
T3474 |
T3473 |
pobj |
1,to |
R2383 |
T3475 |
T3476 |
punct |
:,"4,000" |
R2384 |
T3476 |
T3474 |
prep |
"4,000",1 |
R2385 |
T3477 |
T3457 |
punct |
", ",hSOD1 |
R2386 |
T3478 |
T3457 |
cc |
or,hSOD1 |
R2387 |
T3479 |
T3480 |
nmod |
rabbit,CT15 |
R2388 |
T3480 |
T3457 |
conj |
CT15,hSOD1 |
R2389 |
T3481 |
T3480 |
amod |
polyclonal,CT15 |
R2390 |
T3482 |
T3483 |
punct |
(,gift |
R2391 |
T3483 |
T3480 |
parataxis |
gift,CT15 |
R2392 |
T3484 |
T3483 |
amod |
kind,gift |
R2393 |
T3485 |
T3483 |
prep |
of,gift |
R2394 |
T3486 |
T3487 |
compound |
Ed,Koo |
R2395 |
T3487 |
T3485 |
pobj |
Koo,of |
R2396 |
T3488 |
T3483 |
punct |
;,gift |
R2397 |
T3489 |
T3490 |
punct |
[,19 |
R2398 |
T3490 |
T3483 |
parataxis |
19,gift |
R2399 |
T3491 |
T3490 |
punct |
],19 |
R2400 |
T3492 |
T3483 |
punct |
),gift |
R2401 |
T3493 |
T3480 |
acl |
diluted,CT15 |
R2402 |
T3494 |
T3493 |
npadvmod |
1,diluted |
R2403 |
T3495 |
T3496 |
punct |
:,"1,000" |
R2404 |
T3496 |
T3494 |
prep |
"1,000",1 |
R2405 |
T3497 |
T3385 |
punct |
.,blocked |
R2406 |
T3499 |
T3500 |
advmod |
Subsequently,washed |
R2407 |
T3501 |
T3500 |
punct |
", ",washed |
R2408 |
T3502 |
T3503 |
det |
the,blots |
R2409 |
T3503 |
T3500 |
nsubjpass |
blots,washed |
R2410 |
T3504 |
T3500 |
auxpass |
were,washed |
R2411 |
T3505 |
T3500 |
prep |
with,washed |
R2412 |
T3506 |
T3505 |
pobj |
PBS,with |
R2413 |
T3507 |
T3506 |
acl |
containing,PBS |
R2414 |
T3508 |
T3509 |
nummod |
0.1,% |
R2415 |
T3509 |
T3510 |
compound |
%,Tween |
R2416 |
T3510 |
T3507 |
dobj |
Tween,containing |
R2417 |
T3511 |
T3510 |
punct |
-,Tween |
R2418 |
T3512 |
T3510 |
nummod |
20,Tween |
R2419 |
T3513 |
T3500 |
punct |
", ",washed |
R2420 |
T3514 |
T3500 |
cc |
and,washed |
R2421 |
T3515 |
T3516 |
advmod |
then,incubated |
R2422 |
T3516 |
T3500 |
conj |
incubated,washed |
R2423 |
T3517 |
T3516 |
prep |
with,incubated |
R2424 |
T3518 |
T3519 |
preconj |
either,goat |
R2425 |
T3519 |
T3520 |
nmod |
goat,antibody |
R2426 |
T3520 |
T3517 |
pobj |
antibody,with |
R2427 |
T3521 |
T3519 |
amod |
anti-mouse,goat |
R2428 |
T3522 |
T3519 |
punct |
–,goat |
R2429 |
T3523 |
T3519 |
cc |
or,goat |
R2430 |
T3524 |
T3519 |
conj |
goat,goat |
R2431 |
T3525 |
T3524 |
amod |
anti-rabbit,goat |
R2432 |
T3526 |
T3520 |
punct |
–,antibody |
R2433 |
T3527 |
T3528 |
npadvmod |
HRP,conjugated |
R2434 |
T3528 |
T3520 |
amod |
conjugated,antibody |
R2435 |
T3529 |
T3520 |
amod |
secondary,antibody |
R2436 |
T3530 |
T3520 |
acl |
diluted,antibody |
R2437 |
T3531 |
T3530 |
npadvmod |
1,diluted |
R2438 |
T3532 |
T3533 |
punct |
:,"1,000" |
R2439 |
T3533 |
T3531 |
prep |
"1,000",1 |
R2440 |
T3534 |
T3530 |
prep |
in,diluted |
R2441 |
T3535 |
T3536 |
compound |
blocking,solution |
R2442 |
T3536 |
T3534 |
pobj |
solution,in |
R2443 |
T3537 |
T3500 |
punct |
.,washed |
R2444 |
T3539 |
T3540 |
prep |
After,developed |
R2445 |
T3541 |
T3542 |
amod |
several,rinses |
R2446 |
T3542 |
T3539 |
pobj |
rinses,After |
R2447 |
T3543 |
T3542 |
amod |
additional,rinses |
R2448 |
T3544 |
T3542 |
prep |
in,rinses |
R2449 |
T3545 |
T3544 |
pobj |
PBS,in |
R2450 |
T3546 |
T3542 |
prep |
with,rinses |
R2451 |
T3547 |
T3548 |
nummod |
0.1,Tween |
R2452 |
T3548 |
T3546 |
pobj |
Tween,with |
R2453 |
T3549 |
T3547 |
quantmod |
%,0.1 |
R2454 |
T3550 |
T3548 |
punct |
-,Tween |
R2455 |
T3551 |
T3548 |
nummod |
20,Tween |
R2456 |
T3552 |
T3540 |
punct |
", ",developed |
R2457 |
T3553 |
T3540 |
nsubjpass |
blots,developed |
R2458 |
T3554 |
T3540 |
auxpass |
were,developed |
R2459 |
T3555 |
T3540 |
prep |
with,developed |
R2460 |
T3556 |
T3557 |
amod |
enhanced,reagent |
R2461 |
T3557 |
T3555 |
pobj |
reagent,with |
R2462 |
T3558 |
T3557 |
compound |
chemiluminescence,reagent |
R2463 |
T3559 |
T3540 |
cc |
and,developed |
R2464 |
T3560 |
T3540 |
conj |
imaged,developed |
R2465 |
T3561 |
T3560 |
prep |
with,imaged |
R2466 |
T3562 |
T3563 |
det |
the,system |
R2467 |
T3563 |
T3561 |
pobj |
system,with |
R2468 |
T3564 |
T3565 |
compound |
Bio,Rad |
R2469 |
T3565 |
T3567 |
compound |
Rad,FX |
R2470 |
T3566 |
T3565 |
punct |
-,Rad |
R2471 |
T3567 |
T3563 |
compound |
FX,system |
R2472 |
T3568 |
T3567 |
compound |
Molecular,FX |
R2473 |
T3569 |
T3567 |
compound |
Imager,FX |
R2474 |
T3570 |
T3540 |
punct |
.,developed |
R2475 |
T3572 |
T3573 |
compound |
Staining,intensity |
R2476 |
T3573 |
T3574 |
nsubjpass |
intensity,quantified |
R2477 |
T3575 |
T3573 |
prep |
within,intensity |
R2478 |
T3576 |
T3577 |
det |
each,lane |
R2479 |
T3577 |
T3575 |
pobj |
lane,within |
R2480 |
T3578 |
T3574 |
auxpass |
was,quantified |
R2481 |
T3579 |
T3574 |
advcl |
using,quantified |
R2482 |
T3580 |
T3581 |
det |
the,software |
R2483 |
T3581 |
T3579 |
dobj |
software,using |
R2484 |
T3582 |
T3581 |
nmod |
Quantity,software |
R2485 |
T3583 |
T3582 |
nummod |
One,Quantity |
R2486 |
T3584 |
T3585 |
compound |
image,analysis |
R2487 |
T3585 |
T3581 |
compound |
analysis,software |
R2488 |
T3586 |
T3587 |
punct |
(,FX |
R2489 |
T3587 |
T3581 |
parataxis |
FX,software |
R2490 |
T3588 |
T3589 |
compound |
Molecular,Imager |
R2491 |
T3589 |
T3587 |
compound |
Imager,FX |
R2492 |
T3590 |
T3587 |
punct |
", ",FX |
R2493 |
T3591 |
T3592 |
compound |
Bio,Rad |
R2494 |
T3592 |
T3594 |
compound |
Rad,Laboratories |
R2495 |
T3593 |
T3592 |
punct |
-,Rad |
R2496 |
T3594 |
T3587 |
npadvmod |
Laboratories,FX |
R2497 |
T3595 |
T3587 |
punct |
),FX |
R2498 |
T3596 |
T3574 |
punct |
.,quantified |
R2499 |
T3598 |
T3599 |
nsubjpass |
Background,calculated |
R2500 |
T3600 |
T3599 |
auxpass |
was,calculated |
R2501 |
T3601 |
T3599 |
prep |
from,calculated |
R2502 |
T3602 |
T3601 |
prep |
across,from |
R2503 |
T3603 |
T3604 |
det |
the,image |
R2504 |
T3604 |
T3602 |
pobj |
image,across |
R2505 |
T3605 |
T3599 |
cc |
and,calculated |
R2506 |
T3606 |
T3599 |
conj |
subtracted,calculated |
R2507 |
T3607 |
T3606 |
prep |
from,subtracted |
R2508 |
T3608 |
T3609 |
det |
the,file |
R2509 |
T3609 |
T3607 |
pobj |
file,from |
R2510 |
T3610 |
T3609 |
amod |
entire,file |
R2511 |
T3611 |
T3599 |
punct |
.,calculated |
R2512 |
T3613 |
T3614 |
det |
The,intensity |
R2513 |
T3614 |
T3616 |
nsubjpass |
intensity,calculated |
R2514 |
T3615 |
T3614 |
compound |
signal,intensity |
R2515 |
T3617 |
T3614 |
prep |
for,intensity |
R2516 |
T3618 |
T3619 |
det |
each,band |
R2517 |
T3619 |
T3617 |
pobj |
band,for |
R2518 |
T3620 |
T3621 |
punct |
(,intensity |
R2519 |
T3621 |
T3614 |
parataxis |
intensity,intensity |
R2520 |
T3622 |
T3621 |
amod |
corrected,intensity |
R2521 |
T3623 |
T3621 |
compound |
signal,intensity |
R2522 |
T3624 |
T3621 |
punct |
×,intensity |
R2523 |
T3625 |
T3626 |
compound |
pixel,number |
R2524 |
T3626 |
T3621 |
appos |
number,intensity |
R2525 |
T3627 |
T3621 |
punct |
),intensity |
R2526 |
T3628 |
T3616 |
auxpass |
was,calculated |
R2527 |
T3629 |
T3616 |
advmod |
then,calculated |
R2528 |
T3630 |
T3616 |
advcl |
using,calculated |
R2529 |
T3631 |
T3632 |
det |
the,tool |
R2530 |
T3632 |
T3630 |
dobj |
tool,using |
R2531 |
T3633 |
T3634 |
compound |
Volume,report |
R2532 |
T3634 |
T3632 |
compound |
report,tool |
R2533 |
T3635 |
T3616 |
punct |
.,calculated |
R2534 |
T3710 |
T3711 |
compound |
Slot,Blot |
R2535 |
T3711 |
T3712 |
compound |
Blot,Analysis |
R2536 |
T3713 |
T3712 |
compound |
mRNA,Analysis |
R2537 |
T3715 |
T3716 |
nummod |
Five,micrograms |
R2538 |
T3716 |
T3717 |
nsubjpass |
micrograms,filtered |
R2539 |
T3718 |
T3716 |
prep |
per,micrograms |
R2540 |
T3719 |
T3718 |
pobj |
sample,per |
R2541 |
T3720 |
T3719 |
prep |
of,sample |
R2542 |
T3721 |
T3722 |
amod |
total,RNA |
R2543 |
T3722 |
T3720 |
pobj |
RNA,of |
R2544 |
T3723 |
T3722 |
acl |
extracted,RNA |
R2545 |
T3724 |
T3723 |
prep |
from,extracted |
R2546 |
T3725 |
T3726 |
amod |
fresh,frozen |
R2547 |
T3726 |
T3728 |
amod |
frozen,brain |
R2548 |
T3727 |
T3726 |
punct |
-,frozen |
R2549 |
T3728 |
T3724 |
pobj |
brain,from |
R2550 |
T3729 |
T3728 |
punct |
", ",brain |
R2551 |
T3730 |
T3728 |
conj |
liver,brain |
R2552 |
T3731 |
T3730 |
punct |
", ",liver |
R2553 |
T3732 |
T3730 |
conj |
kidney,liver |
R2554 |
T3733 |
T3732 |
punct |
", ",kidney |
R2555 |
T3734 |
T3732 |
conj |
heart,kidney |
R2556 |
T3735 |
T3734 |
punct |
", ",heart |
R2557 |
T3736 |
T3734 |
conj |
lung,heart |
R2558 |
T3737 |
T3736 |
punct |
", ",lung |
R2559 |
T3738 |
T3736 |
conj |
spleen,lung |
R2560 |
T3739 |
T3738 |
punct |
", ",spleen |
R2561 |
T3740 |
T3738 |
cc |
and,spleen |
R2562 |
T3741 |
T3742 |
amod |
skeletal,muscle |
R2563 |
T3742 |
T3738 |
conj |
muscle,spleen |
R2564 |
T3743 |
T3717 |
auxpass |
was,filtered |
R2565 |
T3744 |
T3717 |
dep |
vacuum,filtered |
R2566 |
T3745 |
T3717 |
punct |
-,filtered |
R2567 |
T3746 |
T3717 |
prep |
through,filtered |
R2568 |
T3747 |
T3748 |
nummod |
0.45,μm |
R2569 |
T3748 |
T3750 |
compound |
μm,nitrocellulose |
R2570 |
T3749 |
T3748 |
punct |
-,μm |
R2571 |
T3750 |
T3746 |
pobj |
nitrocellulose,through |
R2572 |
T3751 |
T3750 |
compound |
Optitran,nitrocellulose |
R2573 |
T3752 |
T3717 |
punct |
.,filtered |
R2574 |
T3754 |
T3755 |
prep |
After,cross-linked |
R2575 |
T3756 |
T3757 |
amod |
several,washes |
R2576 |
T3757 |
T3754 |
pobj |
washes,After |
R2577 |
T3758 |
T3757 |
prep |
through,washes |
R2578 |
T3759 |
T3760 |
det |
the,manifold |
R2579 |
T3760 |
T3758 |
pobj |
manifold,through |
R2580 |
T3761 |
T3757 |
prep |
with,washes |
R2581 |
T3762 |
T3763 |
nummod |
10,SSC |
R2582 |
T3763 |
T3761 |
pobj |
SSC,with |
R2583 |
T3764 |
T3762 |
punct |
×,10 |
R2584 |
T3765 |
T3755 |
punct |
", ",cross-linked |
R2585 |
T3766 |
T3755 |
nsubjpass |
blots,cross-linked |
R2586 |
T3767 |
T3755 |
auxpass |
were,cross-linked |
R2587 |
T3768 |
T3755 |
dep |
UV,cross-linked |
R2588 |
T3769 |
T3755 |
punct |
-,cross-linked |
R2589 |
T3770 |
T3755 |
cc |
and,cross-linked |
R2590 |
T3771 |
T3755 |
conj |
probed,cross-linked |
R2591 |
T3772 |
T3771 |
prep |
with,probed |
R2592 |
T3773 |
T3774 |
det |
a,fragment |
R2593 |
T3774 |
T3772 |
pobj |
fragment,with |
R2594 |
T3775 |
T3774 |
amod |
radiolabeled,fragment |
R2595 |
T3776 |
T3777 |
punct |
∼,350 |
R2596 |
T3777 |
T3778 |
nummod |
350,bp |
R2597 |
T3778 |
T3774 |
compound |
bp,fragment |
R2598 |
T3779 |
T3778 |
punct |
-,bp |
R2599 |
T3780 |
T3781 |
compound |
BglII,XhoI |
R2600 |
T3781 |
T3774 |
compound |
XhoI,fragment |
R2601 |
T3782 |
T3781 |
punct |
–,XhoI |
R2602 |
T3783 |
T3774 |
compound |
cDNA,fragment |
R2603 |
T3784 |
T3774 |
prep |
of,fragment |
R2604 |
T3785 |
T3786 |
compound |
mo,huAPP695 |
R2605 |
T3786 |
T3788 |
compound |
huAPP695,cDNA |
R2606 |
T3787 |
T3786 |
punct |
/,huAPP695 |
R2607 |
T3788 |
T3784 |
pobj |
cDNA,of |
R2608 |
T3789 |
T3755 |
punct |
.,cross-linked |
R2609 |
T3791 |
T3792 |
prep |
After,washed |
R2610 |
T3793 |
T3791 |
pcomp |
hybridizing,After |
R2611 |
T3794 |
T3793 |
advmod |
overnight,hybridizing |
R2612 |
T3795 |
T3793 |
prep |
at,hybridizing |
R2613 |
T3796 |
T3797 |
nummod |
65,°C |
R2614 |
T3797 |
T3795 |
pobj |
°C,at |
R2615 |
T3798 |
T3793 |
prep |
in,hybridizing |
R2616 |
T3799 |
T3800 |
nummod |
1,% |
R2617 |
T3800 |
T3801 |
compound |
%,BSA |
R2618 |
T3801 |
T3798 |
pobj |
BSA,in |
R2619 |
T3802 |
T3801 |
punct |
/,BSA |
R2620 |
T3803 |
T3804 |
nummod |
1,mM |
R2621 |
T3804 |
T3805 |
compound |
mM,EDTA |
R2622 |
T3805 |
T3801 |
appos |
EDTA,BSA |
R2623 |
T3806 |
T3801 |
punct |
/,BSA |
R2624 |
T3807 |
T3808 |
nummod |
0.5,M |
R2625 |
T3808 |
T3809 |
compound |
M,buffer |
R2626 |
T3809 |
T3801 |
appos |
buffer,BSA |
R2627 |
T3810 |
T3809 |
compound |
sodium,buffer |
R2628 |
T3811 |
T3809 |
compound |
phosphate,buffer |
R2629 |
T3812 |
T3813 |
punct |
(,pH |
R2630 |
T3813 |
T3809 |
parataxis |
pH,buffer |
R2631 |
T3814 |
T3813 |
nummod |
7.2,pH |
R2632 |
T3815 |
T3813 |
punct |
),pH |
R2633 |
T3816 |
T3801 |
punct |
/,BSA |
R2634 |
T3817 |
T3818 |
nummod |
7,% |
R2635 |
T3818 |
T3819 |
compound |
%,SDS |
R2636 |
T3819 |
T3801 |
appos |
SDS,BSA |
R2637 |
T3820 |
T3821 |
punct |
[,20 |
R2638 |
T3821 |
T3819 |
parataxis |
20,SDS |
R2639 |
T3822 |
T3821 |
punct |
],20 |
R2640 |
T3823 |
T3792 |
punct |
", ",washed |
R2641 |
T3824 |
T3825 |
det |
the,blots |
R2642 |
T3825 |
T3792 |
nsubjpass |
blots,washed |
R2643 |
T3826 |
T3792 |
auxpass |
were,washed |
R2644 |
T3827 |
T3792 |
advmod |
twice,washed |
R2645 |
T3828 |
T3792 |
prep |
at,washed |
R2646 |
T3829 |
T3830 |
nummod |
65,°C |
R2647 |
T3830 |
T3828 |
pobj |
°C,at |
R2648 |
T3831 |
T3792 |
prep |
for,washed |
R2649 |
T3832 |
T3833 |
nummod |
30,min |
R2650 |
T3833 |
T3831 |
pobj |
min,for |
R2651 |
T3834 |
T3833 |
appos |
each,min |
R2652 |
T3835 |
T3792 |
prep |
in,washed |
R2653 |
T3836 |
T3837 |
nummod |
0.1,% |
R2654 |
T3837 |
T3838 |
compound |
%,BSA |
R2655 |
T3838 |
T3835 |
pobj |
BSA,in |
R2656 |
T3839 |
T3838 |
punct |
/,BSA |
R2657 |
T3840 |
T3841 |
nummod |
1,mM |
R2658 |
T3841 |
T3842 |
compound |
mM,EDTA |
R2659 |
T3842 |
T3838 |
appos |
EDTA,BSA |
R2660 |
T3843 |
T3838 |
punct |
/,BSA |
R2661 |
T3844 |
T3845 |
nummod |
40,mM |
R2662 |
T3845 |
T3846 |
compound |
mM,buffer |
R2663 |
T3846 |
T3838 |
appos |
buffer,BSA |
R2664 |
T3847 |
T3846 |
compound |
sodium,buffer |
R2665 |
T3848 |
T3846 |
compound |
phosphate,buffer |
R2666 |
T3849 |
T3850 |
punct |
(,pH |
R2667 |
T3850 |
T3846 |
parataxis |
pH,buffer |
R2668 |
T3851 |
T3850 |
nummod |
7.2,pH |
R2669 |
T3852 |
T3850 |
punct |
),pH |
R2670 |
T3853 |
T3838 |
punct |
/,BSA |
R2671 |
T3854 |
T3855 |
nummod |
5,% |
R2672 |
T3855 |
T3856 |
compound |
%,SDS |
R2673 |
T3856 |
T3838 |
appos |
SDS,BSA |
R2674 |
T3857 |
T3792 |
prep |
before,washed |
R2675 |
T3858 |
T3859 |
nummod |
two,washes |
R2676 |
T3859 |
T3857 |
pobj |
washes,before |
R2677 |
T3860 |
T3859 |
amod |
final,washes |
R2678 |
T3861 |
T3862 |
nummod |
30,min |
R2679 |
T3862 |
T3859 |
compound |
min,washes |
R2680 |
T3863 |
T3862 |
punct |
-,min |
R2681 |
T3864 |
T3859 |
prep |
at,washes |
R2682 |
T3865 |
T3866 |
nummod |
65,°C |
R2683 |
T3866 |
T3864 |
pobj |
°C,at |
R2684 |
T3867 |
T3859 |
prep |
with,washes |
R2685 |
T3868 |
T3869 |
nummod |
1,mM |
R2686 |
T3869 |
T3870 |
compound |
mM,EDTA |
R2687 |
T3870 |
T3867 |
pobj |
EDTA,with |
R2688 |
T3871 |
T3870 |
punct |
/,EDTA |
R2689 |
T3872 |
T3873 |
nummod |
40,mM |
R2690 |
T3873 |
T3874 |
compound |
mM,buffer |
R2691 |
T3874 |
T3870 |
appos |
buffer,EDTA |
R2692 |
T3875 |
T3874 |
compound |
sodium,buffer |
R2693 |
T3876 |
T3874 |
compound |
phosphate,buffer |
R2694 |
T3877 |
T3878 |
punct |
(,pH |
R2695 |
T3878 |
T3874 |
parataxis |
pH,buffer |
R2696 |
T3879 |
T3878 |
nummod |
7.2,pH |
R2697 |
T3880 |
T3878 |
punct |
),pH |
R2698 |
T3881 |
T3870 |
punct |
/,EDTA |
R2699 |
T3882 |
T3883 |
nummod |
1,% |
R2700 |
T3883 |
T3884 |
compound |
%,SDS |
R2701 |
T3884 |
T3870 |
appos |
SDS,EDTA |
R2702 |
T3885 |
T3792 |
punct |
.,washed |
R2703 |
T3887 |
T3888 |
nsubjpass |
Blots,wrapped |
R2704 |
T3889 |
T3888 |
auxpass |
were,wrapped |
R2705 |
T3890 |
T3888 |
advcl |
wet,wrapped |
R2706 |
T3891 |
T3888 |
cc |
and,wrapped |
R2707 |
T3892 |
T3888 |
conj |
exposed,wrapped |
R2708 |
T3893 |
T3892 |
prep |
to,exposed |
R2709 |
T3894 |
T3893 |
pobj |
phosphorscreens,to |
R2710 |
T3895 |
T3892 |
advmod |
overnight,exposed |
R2711 |
T3896 |
T3892 |
prep |
at,exposed |
R2712 |
T3897 |
T3898 |
compound |
room,temperature |
R2713 |
T3898 |
T3896 |
pobj |
temperature,at |
R2714 |
T3899 |
T3888 |
punct |
.,wrapped |
R2715 |
T4137 |
T4138 |
compound |
Amyloid,Histology |
R2716 |
T4140 |
T4141 |
nsubjpass |
Mice,euthanized |
R2717 |
T4142 |
T4141 |
auxpass |
were,euthanized |
R2718 |
T4143 |
T4141 |
prep |
by,euthanized |
R2719 |
T4144 |
T4145 |
compound |
ether,inhalation |
R2720 |
T4145 |
T4143 |
pobj |
inhalation,by |
R2721 |
T4146 |
T4141 |
cc |
and,euthanized |
R2722 |
T4147 |
T4148 |
nsubj |
brains,removed |
R2723 |
T4148 |
T4141 |
conj |
removed,euthanized |
R2724 |
T4149 |
T4148 |
prep |
for,removed |
R2725 |
T4150 |
T4151 |
compound |
immersion,fixation |
R2726 |
T4151 |
T4149 |
pobj |
fixation,for |
R2727 |
T4152 |
T4151 |
prep |
in,fixation |
R2728 |
T4153 |
T4154 |
nummod |
4,% |
R2729 |
T4154 |
T4155 |
compound |
%,paraformaldehyde |
R2730 |
T4155 |
T4152 |
pobj |
paraformaldehyde,in |
R2731 |
T4156 |
T4155 |
punct |
/,paraformaldehyde |
R2732 |
T4157 |
T4158 |
nummod |
1,PBS |
R2733 |
T4158 |
T4155 |
appos |
PBS,paraformaldehyde |
R2734 |
T4159 |
T4157 |
punct |
×,1 |
R2735 |
T4160 |
T4148 |
punct |
.,removed |
R2736 |
T4162 |
T4163 |
prep |
After,transferred |
R2737 |
T4164 |
T4165 |
nummod |
48,h |
R2738 |
T4165 |
T4162 |
pobj |
h,After |
R2739 |
T4166 |
T4165 |
prep |
in,h |
R2740 |
T4167 |
T4166 |
pobj |
fixative,in |
R2741 |
T4168 |
T4165 |
prep |
at,h |
R2742 |
T4169 |
T4170 |
nummod |
4,°C |
R2743 |
T4170 |
T4168 |
pobj |
°C,at |
R2744 |
T4171 |
T4163 |
punct |
", ",transferred |
R2745 |
T4172 |
T4163 |
nsubjpass |
brains,transferred |
R2746 |
T4173 |
T4163 |
auxpass |
were,transferred |
R2747 |
T4174 |
T4163 |
prep |
to,transferred |
R2748 |
T4175 |
T4174 |
pobj |
PBS,to |
R2749 |
T4176 |
T4163 |
punct |
", ",transferred |
R2750 |
T4177 |
T4163 |
conj |
dehydrated,transferred |
R2751 |
T4178 |
T4177 |
prep |
in,dehydrated |
R2752 |
T4179 |
T4178 |
pobj |
alcohols,in |
R2753 |
T4180 |
T4177 |
punct |
", ",dehydrated |
R2754 |
T4181 |
T4177 |
conj |
treated,dehydrated |
R2755 |
T4182 |
T4181 |
prep |
with,treated |
R2756 |
T4183 |
T4184 |
compound |
cedarwood,oil |
R2757 |
T4184 |
T4182 |
pobj |
oil,with |
R2758 |
T4185 |
T4184 |
cc |
and,oil |
R2759 |
T4186 |
T4184 |
conj |
methylsalicylate,oil |
R2760 |
T4187 |
T4181 |
punct |
", ",treated |
R2761 |
T4188 |
T4181 |
cc |
and,treated |
R2762 |
T4189 |
T4181 |
conj |
embedded,treated |
R2763 |
T4190 |
T4189 |
prep |
in,embedded |
R2764 |
T4191 |
T4190 |
pobj |
paraffin,in |
R2765 |
T4192 |
T4189 |
prep |
for,embedded |
R2766 |
T4193 |
T4192 |
pobj |
sectioning,for |
R2767 |
T4194 |
T4163 |
punct |
.,transferred |
R2768 |
T4196 |
T4197 |
compound |
Hirano,stain |
R2769 |
T4198 |
T4197 |
compound |
silver,stain |
R2770 |
T4200 |
T4201 |
compound |
Silver,histology |
R2771 |
T4201 |
T4203 |
nsubjpass |
histology,performed |
R2772 |
T4202 |
T4201 |
compound |
impregnation,histology |
R2773 |
T4204 |
T4203 |
auxpass |
was,performed |
R2774 |
T4205 |
T4203 |
prep |
on,performed |
R2775 |
T4206 |
T4207 |
nummod |
10,μm |
R2776 |
T4207 |
T4209 |
nmod |
μm,sections |
R2777 |
T4208 |
T4207 |
punct |
-,μm |
R2778 |
T4209 |
T4205 |
pobj |
sections,on |
R2779 |
T4210 |
T4211 |
npadvmod |
paraffin,embedded |
R2780 |
T4211 |
T4209 |
amod |
embedded,sections |
R2781 |
T4212 |
T4211 |
punct |
-,embedded |
R2782 |
T4213 |
T4203 |
prep |
by,performed |
R2783 |
T4214 |
T4215 |
poss |
Hirano,modification |
R2784 |
T4215 |
T4213 |
pobj |
modification,by |
R2785 |
T4216 |
T4214 |
case |
's,Hirano |
R2786 |
T4217 |
T4215 |
prep |
of,modification |
R2787 |
T4218 |
T4219 |
det |
the,method |
R2788 |
T4219 |
T4217 |
pobj |
method,of |
R2789 |
T4220 |
T4219 |
compound |
Bielschowsky,method |
R2790 |
T4221 |
T4222 |
punct |
[,21 |
R2791 |
T4222 |
T4203 |
parataxis |
21,performed |
R2792 |
T4223 |
T4222 |
punct |
],21 |
R2793 |
T4224 |
T4203 |
punct |
.,performed |
R2794 |
T4226 |
T4227 |
advmod |
Briefly,deparaffinized |
R2795 |
T4228 |
T4227 |
punct |
", ",deparaffinized |
R2796 |
T4229 |
T4227 |
nsubjpass |
sections,deparaffinized |
R2797 |
T4230 |
T4227 |
auxpass |
were,deparaffinized |
R2798 |
T4231 |
T4227 |
prep |
through,deparaffinized |
R2799 |
T4232 |
T4231 |
pobj |
xylene,through |
R2800 |
T4233 |
T4232 |
cc |
and,xylene |
R2801 |
T4234 |
T4232 |
conj |
alcohols,xylene |
R2802 |
T4235 |
T4227 |
prep |
into,deparaffinized |
R2803 |
T4236 |
T4237 |
compound |
tap,water |
R2804 |
T4237 |
T4235 |
pobj |
water,into |
R2805 |
T4238 |
T4227 |
prep |
before,deparaffinized |
R2806 |
T4239 |
T4240 |
auxpass |
being,placed |
R2807 |
T4240 |
T4238 |
pcomp |
placed,before |
R2808 |
T4241 |
T4240 |
prep |
into,placed |
R2809 |
T4242 |
T4243 |
amod |
fresh,solution |
R2810 |
T4243 |
T4241 |
pobj |
solution,into |
R2811 |
T4244 |
T4245 |
nummod |
20,% |
R2812 |
T4245 |
T4243 |
compound |
%,solution |
R2813 |
T4246 |
T4243 |
compound |
silver,solution |
R2814 |
T4247 |
T4243 |
compound |
nitrate,solution |
R2815 |
T4248 |
T4240 |
prep |
for,placed |
R2816 |
T4249 |
T4250 |
nummod |
20,min |
R2817 |
T4250 |
T4248 |
pobj |
min,for |
R2818 |
T4251 |
T4227 |
punct |
.,deparaffinized |
R2819 |
T4253 |
T4254 |
prep |
After,immersed |
R2820 |
T4255 |
T4256 |
auxpass |
being,washed |
R2821 |
T4256 |
T4253 |
pcomp |
washed,After |
R2822 |
T4257 |
T4256 |
advmod |
thoroughly,washed |
R2823 |
T4258 |
T4256 |
prep |
with,washed |
R2824 |
T4259 |
T4260 |
amod |
distilled,water |
R2825 |
T4260 |
T4258 |
pobj |
water,with |
R2826 |
T4261 |
T4254 |
punct |
", ",immersed |
R2827 |
T4262 |
T4254 |
nsubjpass |
slides,immersed |
R2828 |
T4263 |
T4254 |
auxpass |
were,immersed |
R2829 |
T4264 |
T4254 |
prep |
in,immersed |
R2830 |
T4265 |
T4266 |
nummod |
20,% |
R2831 |
T4266 |
T4267 |
compound |
%,solution |
R2832 |
T4267 |
T4264 |
pobj |
solution,in |
R2833 |
T4268 |
T4269 |
compound |
silver,nitrate |
R2834 |
T4269 |
T4267 |
compound |
nitrate,solution |
R2835 |
T4270 |
T4267 |
acl |
titrated,solution |
R2836 |
T4271 |
T4270 |
prep |
with,titrated |
R2837 |
T4272 |
T4273 |
amod |
fresh,hydroxide |
R2838 |
T4273 |
T4271 |
pobj |
hydroxide,with |
R2839 |
T4274 |
T4273 |
compound |
ammonium,hydroxide |
R2840 |
T4275 |
T4254 |
punct |
.,immersed |
R2841 |
T4277 |
T4278 |
prep |
After,washed |
R2842 |
T4279 |
T4280 |
nummod |
20,min |
R2843 |
T4280 |
T4277 |
pobj |
min,After |
R2844 |
T4281 |
T4278 |
punct |
", ",washed |
R2845 |
T4282 |
T4278 |
nsubjpass |
slides,washed |
R2846 |
T4283 |
T4278 |
auxpass |
were,washed |
R2847 |
T4284 |
T4278 |
prep |
with,washed |
R2848 |
T4285 |
T4286 |
compound |
ammonia,water |
R2849 |
T4286 |
T4284 |
pobj |
water,with |
R2850 |
T4287 |
T4278 |
prep |
before,washed |
R2851 |
T4288 |
T4289 |
auxpass |
being,developed |
R2852 |
T4289 |
T4287 |
pcomp |
developed,before |
R2853 |
T4290 |
T4289 |
advmod |
individually,developed |
R2854 |
T4291 |
T4289 |
prep |
with,developed |
R2855 |
T4292 |
T4293 |
nummod |
100,μl |
R2856 |
T4293 |
T4291 |
pobj |
μl,with |
R2857 |
T4294 |
T4293 |
prep |
of,μl |
R2858 |
T4295 |
T4294 |
pobj |
developer,of |
R2859 |
T4296 |
T4297 |
punct |
(,ml |
R2860 |
T4297 |
T4295 |
parataxis |
ml,developer |
R2861 |
T4298 |
T4297 |
nummod |
20,ml |
R2862 |
T4299 |
T4297 |
prep |
of,ml |
R2863 |
T4300 |
T4301 |
nummod |
37,% |
R2864 |
T4301 |
T4302 |
compound |
%,formaldehyde |
R2865 |
T4302 |
T4299 |
pobj |
formaldehyde,of |
R2866 |
T4303 |
T4297 |
punct |
", ",ml |
R2867 |
T4304 |
T4305 |
nummod |
100,ml |
R2868 |
T4305 |
T4297 |
conj |
ml,ml |
R2869 |
T4306 |
T4305 |
prep |
of,ml |
R2870 |
T4307 |
T4308 |
amod |
distilled,water |
R2871 |
T4308 |
T4306 |
pobj |
water,of |
R2872 |
T4309 |
T4305 |
punct |
", ",ml |
R2873 |
T4310 |
T4311 |
nummod |
50,μl |
R2874 |
T4311 |
T4305 |
conj |
μl,ml |
R2875 |
T4312 |
T4311 |
prep |
of,μl |
R2876 |
T4313 |
T4314 |
amod |
concentrated,acid |
R2877 |
T4314 |
T4312 |
pobj |
acid,of |
R2878 |
T4315 |
T4314 |
amod |
nitric,acid |
R2879 |
T4316 |
T4311 |
punct |
", ",μl |
R2880 |
T4317 |
T4311 |
cc |
and,μl |
R2881 |
T4318 |
T4319 |
nummod |
0.5,g |
R2882 |
T4319 |
T4311 |
conj |
g,μl |
R2883 |
T4320 |
T4319 |
prep |
of,g |
R2884 |
T4321 |
T4322 |
amod |
citric,acid |
R2885 |
T4322 |
T4320 |
pobj |
acid,of |
R2886 |
T4323 |
T4297 |
punct |
),ml |
R2887 |
T4324 |
T4293 |
acl |
added,μl |
R2888 |
T4325 |
T4324 |
prep |
to,added |
R2889 |
T4326 |
T4327 |
nummod |
50,ml |
R2890 |
T4327 |
T4325 |
pobj |
ml,to |
R2891 |
T4328 |
T4327 |
prep |
of,ml |
R2892 |
T4329 |
T4330 |
amod |
titrated,solution |
R2893 |
T4330 |
T4328 |
pobj |
solution,of |
R2894 |
T4331 |
T4332 |
compound |
silver,nitrate |
R2895 |
T4332 |
T4330 |
compound |
nitrate,solution |
R2896 |
T4333 |
T4278 |
punct |
.,washed |
R2897 |
T4335 |
T4336 |
nsubjpass |
Slides,rinsed |
R2898 |
T4337 |
T4336 |
auxpass |
were,rinsed |
R2899 |
T4338 |
T4336 |
advmod |
then,rinsed |
R2900 |
T4339 |
T4336 |
prep |
in,rinsed |
R2901 |
T4340 |
T4341 |
compound |
tap,water |
R2902 |
T4341 |
T4339 |
pobj |
water,in |
R2903 |
T4342 |
T4336 |
punct |
", ",rinsed |
R2904 |
T4343 |
T4336 |
conj |
fixed,rinsed |
R2905 |
T4344 |
T4343 |
prep |
in,fixed |
R2906 |
T4345 |
T4346 |
nummod |
5,% |
R2907 |
T4346 |
T4347 |
compound |
%,thiosulfate |
R2908 |
T4347 |
T4344 |
pobj |
thiosulfate,in |
R2909 |
T4348 |
T4347 |
compound |
sodium,thiosulfate |
R2910 |
T4349 |
T4343 |
punct |
", ",fixed |
R2911 |
T4350 |
T4343 |
cc |
and,fixed |
R2912 |
T4351 |
T4343 |
conj |
dehydrated,fixed |
R2913 |
T4352 |
T4351 |
prep |
through,dehydrated |
R2914 |
T4353 |
T4352 |
pobj |
alcohols,through |
R2915 |
T4354 |
T4353 |
cc |
and,alcohols |
R2916 |
T4355 |
T4353 |
conj |
xylene,alcohols |
R2917 |
T4356 |
T4336 |
punct |
.,rinsed |
R2918 |
T4358 |
T4359 |
compound |
Thioflavin,S |
R2919 |
T4359 |
T4361 |
compound |
S,staining |
R2920 |
T4360 |
T4359 |
punct |
-,S |
R2921 |
T4363 |
T4364 |
prep |
Following,performed |
R2922 |
T4365 |
T4363 |
pobj |
deparaffinization,Following |
R2923 |
T4366 |
T4365 |
prep |
of,deparaffinization |
R2924 |
T4367 |
T4366 |
pobj |
sections,of |
R2925 |
T4368 |
T4365 |
prep |
through,deparaffinization |
R2926 |
T4369 |
T4368 |
pobj |
xylene,through |
R2927 |
T4370 |
T4369 |
cc |
and,xylene |
R2928 |
T4371 |
T4369 |
conj |
alcohols,xylene |
R2929 |
T4372 |
T4364 |
punct |
", ",performed |
R2930 |
T4373 |
T4374 |
compound |
amyloid,impregnation |
R2931 |
T4374 |
T4364 |
nsubjpass |
impregnation,performed |
R2932 |
T4375 |
T4374 |
prep |
with,impregnation |
R2933 |
T4376 |
T4377 |
compound |
thioflavin,S |
R2934 |
T4377 |
T4375 |
pobj |
S,with |
R2935 |
T4378 |
T4377 |
punct |
-,S |
R2936 |
T4379 |
T4364 |
auxpass |
was,performed |
R2937 |
T4380 |
T4364 |
prep |
according,performed |
R2938 |
T4381 |
T4380 |
prep |
to,according |
R2939 |
T4382 |
T4383 |
det |
the,modification |
R2940 |
T4383 |
T4381 |
pobj |
modification,to |
R2941 |
T4384 |
T4383 |
compound |
Guntern,modification |
R2942 |
T4385 |
T4383 |
prep |
of,modification |
R2943 |
T4386 |
T4387 |
det |
the,protocol |
R2944 |
T4387 |
T4385 |
pobj |
protocol,of |
R2945 |
T4388 |
T4387 |
amod |
standard,protocol |
R2946 |
T4389 |
T4364 |
punct |
.,performed |
R2947 |
T4391 |
T4392 |
nsubjpass |
Slides,washed |
R2948 |
T4393 |
T4391 |
acl |
holding,Slides |
R2949 |
T4394 |
T4395 |
nummod |
10,μm |
R2950 |
T4395 |
T4397 |
compound |
μm,sections |
R2951 |
T4396 |
T4395 |
punct |
-,μm |
R2952 |
T4397 |
T4393 |
dobj |
sections,holding |
R2953 |
T4398 |
T4397 |
compound |
paraffin,sections |
R2954 |
T4399 |
T4392 |
auxpass |
were,washed |
R2955 |
T4400 |
T4392 |
advmod |
twice,washed |
R2956 |
T4401 |
T4392 |
prep |
in,washed |
R2957 |
T4402 |
T4403 |
amod |
distilled,water |
R2958 |
T4403 |
T4401 |
pobj |
water,in |
R2959 |
T4404 |
T4392 |
punct |
", ",washed |
R2960 |
T4405 |
T4406 |
advmod |
then,immersed |
R2961 |
T4406 |
T4392 |
dep |
immersed,washed |
R2962 |
T4407 |
T4406 |
prep |
for,immersed |
R2963 |
T4408 |
T4409 |
nummod |
5,min |
R2964 |
T4409 |
T4407 |
pobj |
min,for |
R2965 |
T4410 |
T4406 |
prep |
in,immersed |
R2966 |
T4411 |
T4412 |
det |
a,solution |
R2967 |
T4412 |
T4410 |
pobj |
solution,in |
R2968 |
T4413 |
T4414 |
nummod |
0.25,% |
R2969 |
T4414 |
T4412 |
compound |
%,solution |
R2970 |
T4415 |
T4412 |
compound |
potassium,solution |
R2971 |
T4416 |
T4412 |
compound |
permanganate,solution |
R2972 |
T4417 |
T4406 |
punct |
", ",immersed |
R2973 |
T4418 |
T4406 |
advcl |
followed,immersed |
R2974 |
T4419 |
T4418 |
agent |
by,followed |
R2975 |
T4420 |
T4421 |
nummod |
5,min |
R2976 |
T4421 |
T4419 |
pobj |
min,by |
R2977 |
T4422 |
T4421 |
prep |
in,min |
R2978 |
T4423 |
T4424 |
det |
a,solution |
R2979 |
T4424 |
T4422 |
pobj |
solution,in |
R2980 |
T4425 |
T4426 |
nummod |
1,% |
R2981 |
T4426 |
T4427 |
nmod |
%,metabisulfate |
R2982 |
T4427 |
T4424 |
nmod |
metabisulfate,solution |
R2983 |
T4428 |
T4427 |
nmod |
potassium,metabisulfate |
R2984 |
T4429 |
T4427 |
punct |
/,metabisulfate |
R2985 |
T4430 |
T4431 |
nummod |
1,% |
R2986 |
T4431 |
T4432 |
nmod |
%,acid |
R2987 |
T4432 |
T4427 |
appos |
acid,metabisulfate |
R2988 |
T4433 |
T4432 |
amod |
oxalic,acid |
R2989 |
T4434 |
T4392 |
punct |
.,washed |
R2990 |
T4436 |
T4437 |
prep |
After,placed |
R2991 |
T4438 |
T4439 |
det |
this,preparation |
R2992 |
T4439 |
T4436 |
pobj |
preparation,After |
R2993 |
T4440 |
T4437 |
punct |
", ",placed |
R2994 |
T4441 |
T4437 |
nsubjpass |
slides,placed |
R2995 |
T4442 |
T4437 |
auxpass |
were,placed |
R2996 |
T4443 |
T4437 |
prep |
into,placed |
R2997 |
T4444 |
T4445 |
det |
a,solution |
R2998 |
T4445 |
T4443 |
pobj |
solution,into |
R2999 |
T4446 |
T4445 |
amod |
filtered,solution |
R3000 |
T4447 |
T4445 |
amod |
aqueous,solution |
R3001 |
T4448 |
T4449 |
nummod |
0.02,% |
R3002 |
T4449 |
T4445 |
compound |
%,solution |
R3003 |
T4450 |
T4451 |
compound |
thioflavin,S |
R3004 |
T4451 |
T4445 |
compound |
S,solution |
R3005 |
T4452 |
T4451 |
punct |
-,S |
R3006 |
T4453 |
T4454 |
punct |
(,Schmid |
R3007 |
T4454 |
T4445 |
parataxis |
Schmid,solution |
R3008 |
T4455 |
T4456 |
compound |
Chroma,Gesellschaft |
R3009 |
T4456 |
T4454 |
compound |
Gesellschaft,Schmid |
R3010 |
T4457 |
T4456 |
punct |
-,Gesellschaft |
R3011 |
T4458 |
T4454 |
punct |
", ",Schmid |
R3012 |
T4459 |
T4454 |
npadvmod |
Kongen,Schmid |
R3013 |
T4460 |
T4454 |
punct |
", ",Schmid |
R3014 |
T4461 |
T4454 |
npadvmod |
Germany,Schmid |
R3015 |
T4462 |
T4454 |
punct |
),Schmid |
R3016 |
T4463 |
T4437 |
prep |
for,placed |
R3017 |
T4464 |
T4465 |
nummod |
8,min |
R3018 |
T4465 |
T4463 |
pobj |
min,for |
R3019 |
T4466 |
T4437 |
punct |
.,placed |
R3020 |
T4468 |
T4469 |
amod |
Excess,stain |
R3021 |
T4469 |
T4470 |
nsubjpass |
stain,removed |
R3022 |
T4471 |
T4470 |
auxpass |
was,removed |
R3023 |
T4472 |
T4470 |
agent |
by,removed |
R3024 |
T4473 |
T4474 |
nummod |
two,rinses |
R3025 |
T4474 |
T4472 |
pobj |
rinses,by |
R3026 |
T4475 |
T4474 |
amod |
brief,rinses |
R3027 |
T4476 |
T4474 |
prep |
in,rinses |
R3028 |
T4477 |
T4478 |
nummod |
80,% |
R3029 |
T4478 |
T4479 |
compound |
%,ethanol |
R3030 |
T4479 |
T4476 |
pobj |
ethanol,in |
R3031 |
T4480 |
T4474 |
punct |
", ",rinses |
R3032 |
T4481 |
T4482 |
advmod |
then,two |
R3033 |
T4482 |
T4474 |
appos |
two,rinses |
R3034 |
T4483 |
T4482 |
prep |
in,two |
R3035 |
T4484 |
T4485 |
amod |
distilled,water |
R3036 |
T4485 |
T4483 |
pobj |
water,in |
R3037 |
T4486 |
T4474 |
punct |
", ",rinses |
R3038 |
T4487 |
T4488 |
prep |
after,finished |
R3039 |
T4488 |
T4474 |
relcl |
finished,rinses |
R3040 |
T4489 |
T4487 |
pobj |
which,after |
R3041 |
T4490 |
T4488 |
nsubjpass |
slides,finished |
R3042 |
T4491 |
T4488 |
auxpass |
were,finished |
R3043 |
T4492 |
T4488 |
prep |
in,finished |
R3044 |
T4493 |
T4494 |
amod |
aqueous,medium |
R3045 |
T4494 |
T4492 |
pobj |
medium,in |
R3046 |
T4495 |
T4494 |
compound |
mounting,medium |
R3047 |
T4496 |
T4488 |
prep |
for,finished |
R3048 |
T4497 |
T4498 |
compound |
florescence,photomicrography |
R3049 |
T4498 |
T4496 |
pobj |
photomicrography,for |
R3050 |
T4499 |
T4470 |
punct |
.,removed |
R3051 |
T4502 |
T4501 |
punct |
", ",Ubiquitin |
R3052 |
T4503 |
T4504 |
amod |
glial,protein |
R3053 |
T4504 |
T4501 |
conj |
protein,Ubiquitin |
R3054 |
T4505 |
T4504 |
amod |
fibrillary,protein |
R3055 |
T4506 |
T4504 |
amod |
acidic,protein |
R3056 |
T4507 |
T4504 |
punct |
", ",protein |
R3057 |
T4508 |
T4504 |
cc |
and,protein |
R3058 |
T4509 |
T4510 |
compound |
Aβ,immunohistochemistry |
R3059 |
T4510 |
T4504 |
conj |
immunohistochemistry,protein |
R3060 |
T4512 |
T4513 |
amod |
Prior,to |
R3061 |
T4513 |
T4514 |
prep |
to,deparaffinized |
R3062 |
T4515 |
T4513 |
pobj |
immunostaining,to |
R3063 |
T4516 |
T4514 |
punct |
", ",deparaffinized |
R3064 |
T4517 |
T4514 |
nsubjpass |
slides,deparaffinized |
R3065 |
T4518 |
T4514 |
auxpass |
were,deparaffinized |
R3066 |
T4519 |
T4514 |
prep |
by,deparaffinized |
R3067 |
T4520 |
T4521 |
compound |
oven,heating |
R3068 |
T4521 |
T4519 |
pobj |
heating,by |
R3069 |
T4522 |
T4514 |
advcl |
followed,deparaffinized |
R3070 |
T4523 |
T4522 |
agent |
by,followed |
R3071 |
T4524 |
T4523 |
pobj |
immersion,by |
R3072 |
T4525 |
T4524 |
prep |
in,immersion |
R3073 |
T4526 |
T4525 |
pobj |
xylene,in |
R3074 |
T4527 |
T4514 |
punct |
.,deparaffinized |
R3075 |
T4529 |
T4530 |
prep |
After,quenched |
R3076 |
T4531 |
T4529 |
pobj |
rehydration,After |
R3077 |
T4532 |
T4531 |
prep |
through,rehydration |
R3078 |
T4533 |
T4534 |
amod |
graded,alcohols |
R3079 |
T4534 |
T4532 |
pobj |
alcohols,through |
R3080 |
T4535 |
T4531 |
prep |
into,rehydration |
R3081 |
T4536 |
T4537 |
compound |
tap,water |
R3082 |
T4537 |
T4535 |
pobj |
water,into |
R3083 |
T4538 |
T4530 |
punct |
", ",quenched |
R3084 |
T4539 |
T4540 |
amod |
endogenous,activity |
R3085 |
T4540 |
T4530 |
nsubjpass |
activity,quenched |
R3086 |
T4541 |
T4540 |
compound |
peroxidase,activity |
R3087 |
T4542 |
T4530 |
auxpass |
was,quenched |
R3088 |
T4543 |
T4530 |
agent |
by,quenched |
R3089 |
T4544 |
T4543 |
pobj |
incubation,by |
R3090 |
T4545 |
T4544 |
prep |
with,incubation |
R3091 |
T4546 |
T4547 |
nummod |
3,% |
R3092 |
T4547 |
T4548 |
compound |
%,peroxide |
R3093 |
T4548 |
T4545 |
pobj |
peroxide,with |
R3094 |
T4549 |
T4548 |
compound |
hydrogen,peroxide |
R3095 |
T4550 |
T4544 |
prep |
in,incubation |
R3096 |
T4551 |
T4550 |
pobj |
methanol,in |
R3097 |
T4552 |
T4530 |
punct |
.,quenched |
R3098 |
T4554 |
T4555 |
nsubjpass |
Slides,microwaved |
R3099 |
T4556 |
T4555 |
auxpass |
were,microwaved |
R3100 |
T4557 |
T4555 |
prep |
for,microwaved |
R3101 |
T4558 |
T4559 |
quantmod |
5,7 |
R3102 |
T4559 |
T4561 |
nummod |
7,min |
R3103 |
T4560 |
T4559 |
punct |
–,7 |
R3104 |
T4561 |
T4557 |
pobj |
min,for |
R3105 |
T4562 |
T4555 |
prep |
in,microwaved |
R3106 |
T4563 |
T4562 |
pobj |
water,in |
R3107 |
T4564 |
T4555 |
punct |
", ",microwaved |
R3108 |
T4565 |
T4555 |
dep |
cooled,microwaved |
R3109 |
T4566 |
T4565 |
prep |
for,cooled |
R3110 |
T4567 |
T4568 |
nummod |
5,min |
R3111 |
T4568 |
T4566 |
pobj |
min,for |
R3112 |
T4569 |
T4555 |
punct |
", ",microwaved |
R3113 |
T4570 |
T4571 |
advmod |
then,washed |
R3114 |
T4571 |
T4555 |
dep |
washed,microwaved |
R3115 |
T4572 |
T4571 |
prep |
in,washed |
R3116 |
T4573 |
T4572 |
pobj |
TBS,in |
R3117 |
T4574 |
T4555 |
punct |
.,microwaved |
R3118 |
T4576 |
T4577 |
amod |
Nonspecific,staining |
R3119 |
T4577 |
T4578 |
nsubjpass |
staining,blocked |
R3120 |
T4579 |
T4578 |
auxpass |
was,blocked |
R3121 |
T4580 |
T4578 |
prep |
for,blocked |
R3122 |
T4581 |
T4582 |
nummod |
1,h |
R3123 |
T4582 |
T4580 |
pobj |
h,for |
R3124 |
T4583 |
T4578 |
prep |
with,blocked |
R3125 |
T4584 |
T4585 |
nummod |
3,% |
R3126 |
T4585 |
T4586 |
nmod |
%,serum |
R3127 |
T4586 |
T4583 |
pobj |
serum,with |
R3128 |
T4587 |
T4586 |
amod |
normal,serum |
R3129 |
T4588 |
T4586 |
compound |
goat,serum |
R3130 |
T4589 |
T4586 |
cc |
and,serum |
R3131 |
T4590 |
T4591 |
nummod |
0.1,% |
R3132 |
T4591 |
T4592 |
compound |
%,X |
R3133 |
T4592 |
T4586 |
conj |
X,serum |
R3134 |
T4593 |
T4592 |
compound |
Triton,X |
R3135 |
T4594 |
T4592 |
punct |
-,X |
R3136 |
T4595 |
T4592 |
nummod |
100,X |
R3137 |
T4596 |
T4586 |
prep |
in,serum |
R3138 |
T4597 |
T4596 |
pobj |
TBS,in |
R3139 |
T4598 |
T4578 |
punct |
.,blocked |
R3140 |
T4600 |
T4601 |
nsubjpass |
Slides,placed |
R3141 |
T4602 |
T4601 |
auxpass |
were,placed |
R3142 |
T4603 |
T4601 |
advmod |
then,placed |
R3143 |
T4604 |
T4601 |
prep |
into,placed |
R3144 |
T4605 |
T4606 |
amod |
primary,antibody |
R3145 |
T4606 |
T4604 |
pobj |
antibody,into |
R3146 |
T4607 |
T4608 |
punct |
(,antibodies |
R3147 |
T4608 |
T4606 |
parataxis |
antibodies,antibody |
R3148 |
T4609 |
T4610 |
nmod |
rabbit,antibody |
R3149 |
T4610 |
T4608 |
dep |
antibody,antibodies |
R3150 |
T4611 |
T4610 |
amod |
anti-Aβ,antibody |
R3151 |
T4612 |
T4610 |
nmod |
peptide,antibody |
R3152 |
T4613 |
T4610 |
amod |
polyclonal,antibody |
R3153 |
T4614 |
T4610 |
punct |
", ",antibody |
R3154 |
T4615 |
T4616 |
compound |
Zymed,Laboratories |
R3155 |
T4616 |
T4610 |
npadvmod |
Laboratories,antibody |
R3156 |
T4617 |
T4610 |
punct |
", ",antibody |
R3157 |
T4618 |
T4619 |
compound |
South,Francisco |
R3158 |
T4619 |
T4610 |
npadvmod |
Francisco,antibody |
R3159 |
T4620 |
T4619 |
compound |
San,Francisco |
R3160 |
T4621 |
T4610 |
punct |
", ",antibody |
R3161 |
T4622 |
T4610 |
npadvmod |
California,antibody |
R3162 |
T4623 |
T4610 |
punct |
", ",antibody |
R3163 |
T4624 |
T4625 |
compound |
United,States |
R3164 |
T4625 |
T4610 |
npadvmod |
States,antibody |
R3165 |
T4626 |
T4608 |
punct |
;,antibodies |
R3166 |
T4627 |
T4608 |
nmod |
rabbit,antibodies |
R3167 |
T4628 |
T4627 |
amod |
anti-ubiquitin,rabbit |
R3168 |
T4629 |
T4627 |
cc |
and,rabbit |
R3169 |
T4630 |
T4627 |
conj |
rabbit,rabbit |
R3170 |
T4631 |
T4630 |
amod |
anti–glial,rabbit |
R3171 |
T4632 |
T4633 |
amod |
fibrillary,protein |
R3172 |
T4633 |
T4608 |
nmod |
protein,antibodies |
R3173 |
T4634 |
T4633 |
amod |
acidic,protein |
R3174 |
T4635 |
T4633 |
punct |
(,protein |
R3175 |
T4636 |
T4633 |
appos |
GFAP,protein |
R3176 |
T4637 |
T4608 |
punct |
),antibodies |
R3177 |
T4638 |
T4608 |
amod |
polyclonal,antibodies |
R3178 |
T4639 |
T4608 |
punct |
", ",antibodies |
R3179 |
T4640 |
T4608 |
npadvmod |
Dako,antibodies |
R3180 |
T4641 |
T4608 |
punct |
", ",antibodies |
R3181 |
T4642 |
T4608 |
npadvmod |
Carpinteria,antibodies |
R3182 |
T4643 |
T4608 |
punct |
", ",antibodies |
R3183 |
T4644 |
T4608 |
npadvmod |
California,antibodies |
R3184 |
T4645 |
T4608 |
punct |
", ",antibodies |
R3185 |
T4646 |
T4647 |
compound |
United,States |
R3186 |
T4647 |
T4608 |
npadvmod |
States,antibodies |
R3187 |
T4648 |
T4608 |
punct |
),antibodies |
R3188 |
T4649 |
T4606 |
acl |
diluted,antibody |
R3189 |
T4650 |
T4649 |
npadvmod |
1,diluted |
R3190 |
T4651 |
T4652 |
punct |
:,500 |
R3191 |
T4652 |
T4650 |
prep |
500,1 |
R3192 |
T4653 |
T4649 |
prep |
in,diluted |
R3193 |
T4654 |
T4653 |
pobj |
TBS,in |
R3194 |
T4655 |
T4649 |
prep |
with,diluted |
R3195 |
T4656 |
T4657 |
nummod |
2,% |
R3196 |
T4657 |
T4658 |
nmod |
%,serum |
R3197 |
T4658 |
T4655 |
pobj |
serum,with |
R3198 |
T4659 |
T4658 |
amod |
normal,serum |
R3199 |
T4660 |
T4658 |
compound |
goat,serum |
R3200 |
T4661 |
T4601 |
cc |
and,placed |
R3201 |
T4662 |
T4601 |
conj |
incubated,placed |
R3202 |
T4663 |
T4662 |
advmod |
overnight,incubated |
R3203 |
T4664 |
T4662 |
prep |
at,incubated |
R3204 |
T4665 |
T4666 |
compound |
room,temperature |
R3205 |
T4666 |
T4664 |
pobj |
temperature,at |
R3206 |
T4667 |
T4601 |
punct |
.,placed |
R3207 |
T4669 |
T4670 |
prep |
After,incubated |
R3208 |
T4671 |
T4672 |
auxpass |
being,washed |
R3209 |
T4672 |
T4669 |
pcomp |
washed,After |
R3210 |
T4673 |
T4672 |
prep |
of,washed |
R3211 |
T4674 |
T4675 |
amod |
excess,antibody |
R3212 |
T4675 |
T4673 |
pobj |
antibody,of |
R3213 |
T4676 |
T4675 |
amod |
primary,antibody |
R3214 |
T4677 |
T4672 |
prep |
with,washed |
R3215 |
T4678 |
T4679 |
amod |
several,changes |
R3216 |
T4679 |
T4677 |
pobj |
changes,with |
R3217 |
T4680 |
T4679 |
prep |
of,changes |
R3218 |
T4681 |
T4680 |
pobj |
TBS,of |
R3219 |
T4682 |
T4670 |
punct |
", ",incubated |
R3220 |
T4683 |
T4670 |
nsubjpass |
slides,incubated |
R3221 |
T4684 |
T4670 |
auxpass |
were,incubated |
R3222 |
T4685 |
T4670 |
prep |
with,incubated |
R3223 |
T4686 |
T4687 |
preconj |
either,system |
R3224 |
T4687 |
T4685 |
pobj |
system,with |
R3225 |
T4688 |
T4687 |
det |
the,system |
R3226 |
T4689 |
T4690 |
nmod |
Vectastain,Elite |
R3227 |
T4690 |
T4687 |
nmod |
Elite,system |
R3228 |
T4691 |
T4687 |
amod |
anti-rabbit,system |
R3229 |
T4692 |
T4687 |
amod |
secondary,system |
R3230 |
T4693 |
T4694 |
punct |
(,Laboratories |
R3231 |
T4694 |
T4687 |
parataxis |
Laboratories,system |
R3232 |
T4695 |
T4694 |
amod |
anti-Aβ,Laboratories |
R3233 |
T4696 |
T4694 |
punct |
;,Laboratories |
R3234 |
T4697 |
T4694 |
compound |
Vector,Laboratories |
R3235 |
T4698 |
T4694 |
punct |
", ",Laboratories |
R3236 |
T4699 |
T4694 |
npadvmod |
Burlingame,Laboratories |
R3237 |
T4700 |
T4694 |
punct |
", ",Laboratories |
R3238 |
T4701 |
T4694 |
npadvmod |
California,Laboratories |
R3239 |
T4702 |
T4694 |
punct |
", ",Laboratories |
R3240 |
T4703 |
T4704 |
compound |
United,States |
R3241 |
T4704 |
T4694 |
npadvmod |
States,Laboratories |
R3242 |
T4705 |
T4694 |
punct |
),Laboratories |
R3243 |
T4706 |
T4687 |
cc |
or,system |
R3244 |
T4707 |
T4708 |
nmod |
peroxidase,reagents |
R3245 |
T4708 |
T4687 |
conj |
reagents,system |
R3246 |
T4709 |
T4707 |
punct |
/,peroxidase |
R3247 |
T4710 |
T4707 |
amod |
anti-peroxidase,peroxidase |
R3248 |
T4711 |
T4712 |
punct |
(,Monoclonals |
R3249 |
T4712 |
T4708 |
parataxis |
Monoclonals,reagents |
R3250 |
T4713 |
T4712 |
amod |
anti-ubitquitin,Monoclonals |
R3251 |
T4714 |
T4713 |
cc |
and,anti-ubitquitin |
R3252 |
T4715 |
T4713 |
conj |
anti-GFAP,anti-ubitquitin |
R3253 |
T4716 |
T4712 |
punct |
;,Monoclonals |
R3254 |
T4717 |
T4712 |
compound |
Sternberger,Monoclonals |
R3255 |
T4718 |
T4712 |
punct |
", ",Monoclonals |
R3256 |
T4719 |
T4712 |
npadvmod |
Lutherville,Monoclonals |
R3257 |
T4720 |
T4712 |
punct |
", ",Monoclonals |
R3258 |
T4721 |
T4712 |
npadvmod |
Maryland,Monoclonals |
R3259 |
T4722 |
T4712 |
punct |
", ",Monoclonals |
R3260 |
T4723 |
T4724 |
compound |
United,States |
R3261 |
T4724 |
T4712 |
npadvmod |
States,Monoclonals |
R3262 |
T4725 |
T4712 |
punct |
),Monoclonals |
R3263 |
T4726 |
T4670 |
prep |
according,incubated |
R3264 |
T4727 |
T4726 |
prep |
to,according |
R3265 |
T4728 |
T4729 |
det |
the,manufacturers |
R3266 |
T4729 |
T4730 |
poss |
manufacturers,directions |
R3267 |
T4730 |
T4727 |
pobj |
directions,to |
R3268 |
T4731 |
T4729 |
case |
',manufacturers |
R3269 |
T4732 |
T4670 |
punct |
.,incubated |
R3270 |
T4734 |
T4735 |
compound |
Antibody,binding |
R3271 |
T4735 |
T4736 |
nsubjpass |
binding,visualized |
R3272 |
T4737 |
T4736 |
auxpass |
was,visualized |
R3273 |
T4738 |
T4736 |
prep |
with,visualized |
R3274 |
T4739 |
T4738 |
pobj |
diaminobenzidene,with |
R3275 |
T4740 |
T4736 |
punct |
", ",visualized |
R3276 |
T4741 |
T4736 |
cc |
and,visualized |
R3277 |
T4742 |
T4743 |
nsubjpass |
sections,counterstained |
R3278 |
T4743 |
T4736 |
conj |
counterstained,visualized |
R3279 |
T4744 |
T4743 |
auxpass |
were,counterstained |
R3280 |
T4745 |
T4743 |
prep |
with,counterstained |
R3281 |
T4746 |
T4745 |
pobj |
hematoxylin,with |
R3282 |
T4747 |
T4743 |
punct |
.,counterstained |
R3283 |
T4787 |
T4788 |
compound |
Filter,Assay |
R3284 |
T4789 |
T4788 |
compound |
Trap,Assay |
R3285 |
T4791 |
T4792 |
det |
An,aliquot |
R3286 |
T4792 |
T4793 |
nsubjpass |
aliquot,solubilized |
R3287 |
T4794 |
T4792 |
prep |
of,aliquot |
R3288 |
T4795 |
T4796 |
det |
each,homogenate |
R3289 |
T4796 |
T4794 |
pobj |
homogenate,of |
R3290 |
T4797 |
T4796 |
amod |
cortical,homogenate |
R3291 |
T4798 |
T4796 |
acl |
used,homogenate |
R3292 |
T4799 |
T4798 |
prep |
for,used |
R3293 |
T4800 |
T4801 |
compound |
Western,blotting |
R3294 |
T4801 |
T4799 |
pobj |
blotting,for |
R3295 |
T4802 |
T4798 |
advmod |
above,used |
R3296 |
T4803 |
T4793 |
auxpass |
was,solubilized |
R3297 |
T4804 |
T4793 |
advmod |
partially,solubilized |
R3298 |
T4805 |
T4793 |
prep |
by,solubilized |
R3299 |
T4806 |
T4807 |
det |
the,addition |
R3300 |
T4807 |
T4805 |
pobj |
addition,by |
R3301 |
T4808 |
T4807 |
prep |
of,addition |
R3302 |
T4809 |
T4808 |
pobj |
SDS,of |
R3303 |
T4810 |
T4793 |
prep |
to,solubilized |
R3304 |
T4811 |
T4812 |
det |
a,concentration |
R3305 |
T4812 |
T4810 |
pobj |
concentration,to |
R3306 |
T4813 |
T4812 |
amod |
final,concentration |
R3307 |
T4814 |
T4812 |
prep |
of,concentration |
R3308 |
T4815 |
T4816 |
nummod |
1,% |
R3309 |
T4816 |
T4814 |
pobj |
%,of |
R3310 |
T4817 |
T4793 |
punct |
.,solubilized |
R3311 |
T4819 |
T4820 |
amod |
Serial,dilutions |
R3312 |
T4820 |
T4824 |
nsubjpass |
dilutions,made |
R3313 |
T4821 |
T4820 |
nummod |
1,dilutions |
R3314 |
T4822 |
T4823 |
punct |
:,2 |
R3315 |
T4823 |
T4821 |
prep |
2,1 |
R3316 |
T4825 |
T4824 |
auxpass |
were,made |
R3317 |
T4826 |
T4824 |
prep |
with,made |
R3318 |
T4827 |
T4828 |
nummod |
1,PBS |
R3319 |
T4828 |
T4826 |
pobj |
PBS,with |
R3320 |
T4829 |
T4827 |
punct |
×,1 |
R3321 |
T4830 |
T4828 |
punct |
/,PBS |
R3322 |
T4831 |
T4832 |
nummod |
1,% |
R3323 |
T4832 |
T4833 |
compound |
%,SDS |
R3324 |
T4833 |
T4828 |
appos |
SDS,PBS |
R3325 |
T4834 |
T4824 |
punct |
", ",made |
R3326 |
T4835 |
T4824 |
cc |
and,made |
R3327 |
T4836 |
T4837 |
nummod |
100,μl |
R3328 |
T4837 |
T4838 |
nsubjpass |
μl,filtered |
R3329 |
T4838 |
T4824 |
conj |
filtered,made |
R3330 |
T4839 |
T4837 |
prep |
of,μl |
R3331 |
T4840 |
T4841 |
det |
each,dilution |
R3332 |
T4841 |
T4839 |
pobj |
dilution,of |
R3333 |
T4842 |
T4838 |
auxpass |
was,filtered |
R3334 |
T4843 |
T4838 |
advmod |
then,filtered |
R3335 |
T4844 |
T4838 |
dep |
vacuum,filtered |
R3336 |
T4845 |
T4838 |
punct |
-,filtered |
R3337 |
T4846 |
T4838 |
prep |
through,filtered |
R3338 |
T4847 |
T4848 |
det |
a,membrane |
R3339 |
T4848 |
T4846 |
pobj |
membrane,through |
R3340 |
T4849 |
T4848 |
amod |
pre-wet,membrane |
R3341 |
T4850 |
T4851 |
nummod |
0.22,μm |
R3342 |
T4851 |
T4848 |
compound |
μm,membrane |
R3343 |
T4852 |
T4851 |
punct |
-,μm |
R3344 |
T4853 |
T4848 |
compound |
cellulose,membrane |
R3345 |
T4854 |
T4848 |
compound |
acetate,membrane |
R3346 |
T4855 |
T4856 |
punct |
(,Schleicher |
R3347 |
T4856 |
T4848 |
parataxis |
Schleicher,membrane |
R3348 |
T4857 |
T4856 |
cc |
and,Schleicher |
R3349 |
T4858 |
T4856 |
conj |
Schuell,Schleicher |
R3350 |
T4859 |
T4856 |
punct |
),Schleicher |
R3351 |
T4860 |
T4861 |
punct |
[,22 |
R3352 |
T4861 |
T4838 |
parataxis |
22,filtered |
R3353 |
T4862 |
T4861 |
punct |
],22 |
R3354 |
T4863 |
T4838 |
punct |
.,filtered |
R3355 |
T4865 |
T4866 |
det |
Each,well |
R3356 |
T4866 |
T4867 |
nsubjpass |
well,washed |
R3357 |
T4868 |
T4867 |
auxpass |
was,washed |
R3358 |
T4869 |
T4870 |
amod |
several,times |
R3359 |
T4870 |
T4867 |
dobj |
times,washed |
R3360 |
T4871 |
T4867 |
prep |
with,washed |
R3361 |
T4872 |
T4871 |
pobj |
PBS,with |
R3362 |
T4873 |
T4867 |
punct |
", ",washed |
R3363 |
T4874 |
T4875 |
prep |
after,incubated |
R3364 |
T4875 |
T4867 |
advcl |
incubated,washed |
R3365 |
T4876 |
T4874 |
pobj |
which,after |
R3366 |
T4877 |
T4875 |
nsubjpass |
blots,incubated |
R3367 |
T4878 |
T4875 |
auxpass |
were,incubated |
R3368 |
T4879 |
T4875 |
advmod |
overnight,incubated |
R3369 |
T4880 |
T4875 |
prep |
with,incubated |
R3370 |
T4881 |
T4882 |
amod |
polyclonal,antibody |
R3371 |
T4882 |
T4880 |
pobj |
antibody,with |
R3372 |
T4883 |
T4882 |
amod |
anti-Aβ,antibody |
R3373 |
T4884 |
T4885 |
punct |
(,Laboratories |
R3374 |
T4885 |
T4882 |
parataxis |
Laboratories,antibody |
R3375 |
T4886 |
T4885 |
compound |
Zymed,Laboratories |
R3376 |
T4887 |
T4885 |
punct |
),Laboratories |
R3377 |
T4888 |
T4882 |
acl |
diluted,antibody |
R3378 |
T4889 |
T4888 |
npadvmod |
1,diluted |
R3379 |
T4890 |
T4891 |
punct |
:,600 |
R3380 |
T4891 |
T4889 |
prep |
600,1 |
R3381 |
T4892 |
T4888 |
prep |
in,diluted |
R3382 |
T4893 |
T4894 |
det |
a,solution |
R3383 |
T4894 |
T4892 |
pobj |
solution,in |
R3384 |
T4895 |
T4894 |
compound |
blocking,solution |
R3385 |
T4896 |
T4894 |
prep |
of,solution |
R3386 |
T4897 |
T4898 |
nummod |
1,TBS |
R3387 |
T4898 |
T4900 |
nmod |
TBS,powder |
R3388 |
T4899 |
T4897 |
punct |
×,1 |
R3389 |
T4900 |
T4896 |
pobj |
powder,of |
R3390 |
T4901 |
T4898 |
punct |
/,TBS |
R3391 |
T4902 |
T4903 |
nummod |
5,% |
R3392 |
T4903 |
T4904 |
nmod |
%,milk |
R3393 |
T4904 |
T4898 |
appos |
milk,TBS |
R3394 |
T4905 |
T4904 |
amod |
nonfat,milk |
R3395 |
T4906 |
T4904 |
amod |
dry,milk |
R3396 |
T4907 |
T4867 |
punct |
.,washed |
R3397 |
T4909 |
T4910 |
prep |
After,incubated |
R3398 |
T4911 |
T4909 |
pcomp |
washing,After |
R3399 |
T4912 |
T4913 |
det |
the,blots |
R3400 |
T4913 |
T4911 |
dobj |
blots,washing |
R3401 |
T4914 |
T4915 |
nummod |
three,times |
R3402 |
T4915 |
T4911 |
npadvmod |
times,washing |
R3403 |
T4916 |
T4911 |
prep |
for,washing |
R3404 |
T4917 |
T4918 |
nummod |
10,min |
R3405 |
T4918 |
T4916 |
pobj |
min,for |
R3406 |
T4919 |
T4918 |
appos |
each,min |
R3407 |
T4920 |
T4911 |
prep |
in,washing |
R3408 |
T4921 |
T4922 |
nummod |
1,TBS |
R3409 |
T4922 |
T4920 |
pobj |
TBS,in |
R3410 |
T4923 |
T4921 |
punct |
×,1 |
R3411 |
T4924 |
T4922 |
punct |
/,TBS |
R3412 |
T4925 |
T4926 |
nummod |
0.1,% |
R3413 |
T4926 |
T4927 |
compound |
%,Tween |
R3414 |
T4927 |
T4922 |
appos |
Tween,TBS |
R3415 |
T4928 |
T4927 |
punct |
-,Tween |
R3416 |
T4929 |
T4927 |
nummod |
20,Tween |
R3417 |
T4930 |
T4910 |
punct |
", ",incubated |
R3418 |
T4931 |
T4932 |
det |
the,membrane |
R3419 |
T4932 |
T4910 |
nsubjpass |
membrane,incubated |
R3420 |
T4933 |
T4910 |
auxpass |
was,incubated |
R3421 |
T4934 |
T4910 |
prep |
for,incubated |
R3422 |
T4935 |
T4936 |
nummod |
1,h |
R3423 |
T4936 |
T4934 |
pobj |
h,for |
R3424 |
T4937 |
T4910 |
prep |
with,incubated |
R3425 |
T4938 |
T4939 |
npadvmod |
HRP,conjugated |
R3426 |
T4939 |
T4941 |
amod |
conjugated,A |
R3427 |
T4940 |
T4939 |
punct |
-,conjugated |
R3428 |
T4941 |
T4937 |
pobj |
A,with |
R3429 |
T4942 |
T4941 |
compound |
protein,A |
R3430 |
T4943 |
T4944 |
punct |
(,Sigma |
R3431 |
T4944 |
T4941 |
parataxis |
Sigma,A |
R3432 |
T4945 |
T4944 |
punct |
),Sigma |
R3433 |
T4946 |
T4941 |
acl |
diluted,A |
R3434 |
T4947 |
T4946 |
dobj |
1,diluted |
R3435 |
T4948 |
T4949 |
punct |
:,"5,000" |
R3436 |
T4949 |
T4947 |
prep |
"5,000",1 |
R3437 |
T4950 |
T4946 |
prep |
in,diluted |
R3438 |
T4951 |
T4952 |
compound |
blocking,solution |
R3439 |
T4952 |
T4950 |
pobj |
solution,in |
R3440 |
T4953 |
T4910 |
punct |
.,incubated |
R3441 |
T4955 |
T4956 |
det |
The,membranes |
R3442 |
T4956 |
T4957 |
nsubjpass |
membranes,washed |
R3443 |
T4958 |
T4957 |
auxpass |
were,washed |
R3444 |
T4959 |
T4957 |
advmod |
again,washed |
R3445 |
T4960 |
T4961 |
nummod |
three,times |
R3446 |
T4961 |
T4957 |
npadvmod |
times,washed |
R3447 |
T4962 |
T4957 |
prep |
with,washed |
R3448 |
T4963 |
T4964 |
nummod |
1,TBS |
R3449 |
T4964 |
T4962 |
pobj |
TBS,with |
R3450 |
T4965 |
T4963 |
punct |
×,1 |
R3451 |
T4966 |
T4964 |
punct |
/,TBS |
R3452 |
T4967 |
T4968 |
nummod |
0.1,% |
R3453 |
T4968 |
T4969 |
compound |
%,Tween |
R3454 |
T4969 |
T4964 |
appos |
Tween,TBS |
R3455 |
T4970 |
T4969 |
punct |
-,Tween |
R3456 |
T4971 |
T4969 |
nummod |
20,Tween |
R3457 |
T4972 |
T4957 |
punct |
", ",washed |
R3458 |
T4973 |
T4974 |
mark |
before,detected |
R3459 |
T4974 |
T4957 |
advcl |
detected,washed |
R3460 |
T4975 |
T4976 |
compound |
antibody,binding |
R3461 |
T4976 |
T4974 |
nsubjpass |
binding,detected |
R3462 |
T4977 |
T4974 |
auxpass |
was,detected |
R3463 |
T4978 |
T4974 |
prep |
with,detected |
R3464 |
T4979 |
T4980 |
amod |
enhanced,chemiluminescence |
R3465 |
T4980 |
T4978 |
pobj |
chemiluminescence,with |
R3466 |
T4981 |
T4982 |
punct |
(,PerkinElmer |
R3467 |
T4982 |
T4974 |
parataxis |
PerkinElmer,detected |
R3468 |
T4983 |
T4982 |
punct |
", ",PerkinElmer |
R3469 |
T4984 |
T4982 |
npadvmod |
Boston,PerkinElmer |
R3470 |
T4985 |
T4982 |
punct |
", ",PerkinElmer |
R3471 |
T4986 |
T4982 |
npadvmod |
Massachusetts,PerkinElmer |
R3472 |
T4987 |
T4982 |
punct |
", ",PerkinElmer |
R3473 |
T4988 |
T4989 |
compound |
United,States |
R3474 |
T4989 |
T4982 |
npadvmod |
States,PerkinElmer |
R3475 |
T4990 |
T4982 |
punct |
),PerkinElmer |
R3476 |
T4991 |
T4957 |
punct |
.,washed |
R3477 |
T4993 |
T4994 |
amod |
Digital,images |
R3478 |
T4994 |
T4995 |
nsubjpass |
images,captured |
R3479 |
T4996 |
T4994 |
prep |
of,images |
R3480 |
T4997 |
T4998 |
det |
each,blot |
R3481 |
T4998 |
T4996 |
pobj |
blot,of |
R3482 |
T4999 |
T4995 |
auxpass |
were,captured |
R3483 |
T5000 |
T4995 |
prep |
with,captured |
R3484 |
T5001 |
T5002 |
det |
a,system |
R3485 |
T5002 |
T5000 |
pobj |
system,with |
R3486 |
T5003 |
T5004 |
amod |
Molecular,Imager |
R3487 |
T5004 |
T5005 |
compound |
Imager,FX |
R3488 |
T5005 |
T5002 |
compound |
FX,system |
R3489 |
T5006 |
T5007 |
compound |
gel,documentation |
R3490 |
T5007 |
T5002 |
compound |
documentation,system |
R3491 |
T5008 |
T4995 |
punct |
", ",captured |
R3492 |
T5009 |
T4995 |
cc |
and,captured |
R3493 |
T5010 |
T5011 |
det |
the,intensity |
R3494 |
T5011 |
T5012 |
nsubjpass |
intensity,quantified |
R3495 |
T5012 |
T4995 |
conj |
quantified,captured |
R3496 |
T5013 |
T5011 |
prep |
of,intensity |
R3497 |
T5014 |
T5015 |
compound |
Aβ,staining |
R3498 |
T5015 |
T5013 |
pobj |
staining,of |
R3499 |
T5016 |
T5012 |
auxpass |
was,quantified |
R3500 |
T5017 |
T5012 |
advcl |
using,quantified |
R3501 |
T5018 |
T5019 |
nmod |
Quantity,software |
R3502 |
T5019 |
T5017 |
dobj |
software,using |
R3503 |
T5020 |
T5018 |
nummod |
One,Quantity |
R3504 |
T5021 |
T5022 |
compound |
image,analysis |
R3505 |
T5022 |
T5019 |
compound |
analysis,software |
R3506 |
T5023 |
T5012 |
punct |
.,quantified |
R3507 |
T5075 |
T5076 |
compound |
Aβ,ELISA |
R3508 |
T5078 |
T5079 |
det |
An,aliquot |
R3509 |
T5079 |
T5080 |
nsubjpass |
aliquot,subjected |
R3510 |
T5081 |
T5079 |
prep |
of,aliquot |
R3511 |
T5082 |
T5083 |
amod |
cortical,homogenate |
R3512 |
T5083 |
T5081 |
pobj |
homogenate,of |
R3513 |
T5084 |
T5083 |
acl |
generated,homogenate |
R3514 |
T5085 |
T5084 |
prep |
for,generated |
R3515 |
T5086 |
T5087 |
compound |
Western,analysis |
R3516 |
T5087 |
T5085 |
pobj |
analysis,for |
R3517 |
T5088 |
T5087 |
acl |
described,analysis |
R3518 |
T5089 |
T5088 |
advmod |
above,described |
R3519 |
T5090 |
T5080 |
auxpass |
was,subjected |
R3520 |
T5091 |
T5080 |
prep |
to,subjected |
R3521 |
T5092 |
T5093 |
det |
a,extraction |
R3522 |
T5093 |
T5091 |
pobj |
extraction,to |
R3523 |
T5094 |
T5095 |
nummod |
three,step |
R3524 |
T5095 |
T5093 |
nmod |
step,extraction |
R3525 |
T5096 |
T5095 |
punct |
-,step |
R3526 |
T5097 |
T5093 |
amod |
sequential,extraction |
R3527 |
T5098 |
T5080 |
advcl |
using,subjected |
R3528 |
T5099 |
T5098 |
dobj |
PBS,using |
R3529 |
T5100 |
T5099 |
punct |
", ",PBS |
R3530 |
T5101 |
T5102 |
nummod |
2,% |
R3531 |
T5102 |
T5103 |
compound |
%,SDS |
R3532 |
T5103 |
T5099 |
conj |
SDS,PBS |
R3533 |
T5104 |
T5103 |
punct |
", ",SDS |
R3534 |
T5105 |
T5103 |
cc |
and,SDS |
R3535 |
T5106 |
T5107 |
nummod |
70,% |
R3536 |
T5107 |
T5103 |
conj |
%,SDS |
R3537 |
T5108 |
T5109 |
amod |
formic,acid |
R3538 |
T5109 |
T5107 |
appos |
acid,% |
R3539 |
T5110 |
T5109 |
punct |
(,acid |
R3540 |
T5111 |
T5109 |
appos |
FA,acid |
R3541 |
T5112 |
T5080 |
punct |
),subjected |
R3542 |
T5113 |
T5080 |
punct |
.,subjected |
R3543 |
T5115 |
T5116 |
prep |
At,sonicated |
R3544 |
T5117 |
T5118 |
det |
each,step |
R3545 |
T5118 |
T5115 |
pobj |
step,At |
R3546 |
T5119 |
T5116 |
punct |
", ",sonicated |
R3547 |
T5120 |
T5121 |
det |
the,sample |
R3548 |
T5121 |
T5116 |
nsubjpass |
sample,sonicated |
R3549 |
T5122 |
T5116 |
auxpass |
was,sonicated |
R3550 |
T5123 |
T5116 |
prep |
in,sonicated |
R3551 |
T5124 |
T5125 |
amod |
appropriate,buffer |
R3552 |
T5125 |
T5123 |
pobj |
buffer,in |
R3553 |
T5126 |
T5116 |
cc |
and,sonicated |
R3554 |
T5127 |
T5116 |
conj |
centrifuged,sonicated |
R3555 |
T5128 |
T5127 |
prep |
at,centrifuged |
R3556 |
T5129 |
T5128 |
pobj |
"100,000g",at |
R3557 |
T5130 |
T5127 |
prep |
for,centrifuged |
R3558 |
T5131 |
T5132 |
nummod |
30,min |
R3559 |
T5132 |
T5130 |
pobj |
min,for |
R3560 |
T5133 |
T5134 |
punct |
(,samples |
R3561 |
T5134 |
T5132 |
parataxis |
samples,min |
R3562 |
T5135 |
T5136 |
quantmod |
1,1.5 |
R3563 |
T5136 |
T5139 |
nummod |
1.5,mo |
R3564 |
T5137 |
T5136 |
punct |
-,1.5 |
R3565 |
T5138 |
T5136 |
quantmod |
to,1.5 |
R3566 |
T5139 |
T5134 |
compound |
mo,samples |
R3567 |
T5140 |
T5139 |
punct |
-,mo |
R3568 |
T5141 |
T5134 |
punct |
),samples |
R3569 |
T5142 |
T5132 |
cc |
or,min |
R3570 |
T5143 |
T5144 |
nummod |
60,min |
R3571 |
T5144 |
T5132 |
conj |
min,min |
R3572 |
T5145 |
T5146 |
punct |
(,samples |
R3573 |
T5146 |
T5144 |
parataxis |
samples,min |
R3574 |
T5147 |
T5148 |
quantmod |
6,12 |
R3575 |
T5148 |
T5151 |
nummod |
12,mo |
R3576 |
T5149 |
T5148 |
punct |
-,12 |
R3577 |
T5150 |
T5148 |
quantmod |
to,12 |
R3578 |
T5151 |
T5146 |
compound |
mo,samples |
R3579 |
T5152 |
T5151 |
punct |
-,mo |
R3580 |
T5153 |
T5146 |
punct |
),samples |
R3581 |
T5154 |
T5127 |
prep |
at,centrifuged |
R3582 |
T5155 |
T5156 |
nummod |
4,°C |
R3583 |
T5156 |
T5154 |
pobj |
°C,at |
R3584 |
T5157 |
T5158 |
mark |
as,described |
R3585 |
T5158 |
T5127 |
advcl |
described,centrifuged |
R3586 |
T5159 |
T5158 |
advmod |
previously,described |
R3587 |
T5160 |
T5161 |
punct |
[,23 |
R3588 |
T5161 |
T5127 |
parataxis |
23,centrifuged |
R3589 |
T5162 |
T5163 |
punct |
–,25 |
R3590 |
T5163 |
T5161 |
prep |
25,23 |
R3591 |
T5164 |
T5161 |
punct |
],23 |
R3592 |
T5165 |
T5116 |
punct |
.,sonicated |
R3593 |
T5167 |
T5168 |
det |
The,supernatant |
R3594 |
T5168 |
T5169 |
nsubjpass |
supernatant,removed |
R3595 |
T5170 |
T5169 |
auxpass |
was,removed |
R3596 |
T5171 |
T5169 |
prep |
for,removed |
R3597 |
T5172 |
T5171 |
pobj |
analysis,for |
R3598 |
T5173 |
T5169 |
punct |
", ",removed |
R3599 |
T5174 |
T5169 |
cc |
and,removed |
R3600 |
T5175 |
T5176 |
det |
the,pellet |
R3601 |
T5176 |
T5177 |
nsubjpass |
pellet,sonicated |
R3602 |
T5177 |
T5169 |
conj |
sonicated,removed |
R3603 |
T5178 |
T5177 |
auxpass |
was,sonicated |
R3604 |
T5179 |
T5177 |
prep |
in,sonicated |
R3605 |
T5180 |
T5181 |
det |
the,solution |
R3606 |
T5181 |
T5179 |
pobj |
solution,in |
R3607 |
T5182 |
T5181 |
amod |
next,solution |
R3608 |
T5183 |
T5177 |
prep |
in,sonicated |
R3609 |
T5184 |
T5183 |
pobj |
sequence,in |
R3610 |
T5185 |
T5177 |
punct |
.,sonicated |
R3611 |
T5187 |
T5188 |
det |
The,extracts |
R3612 |
T5188 |
T5192 |
nsubjpass |
extracts,diluted |
R3613 |
T5189 |
T5190 |
nummod |
2,% |
R3614 |
T5190 |
T5188 |
compound |
%,extracts |
R3615 |
T5191 |
T5188 |
compound |
SDS,extracts |
R3616 |
T5193 |
T5192 |
auxpass |
were,diluted |
R3617 |
T5194 |
T5192 |
prep |
in,diluted |
R3618 |
T5195 |
T5196 |
compound |
EC,buffer |
R3619 |
T5196 |
T5194 |
pobj |
buffer,in |
R3620 |
T5197 |
T5192 |
punct |
", ",diluted |
R3621 |
T5198 |
T5192 |
cc |
and,diluted |
R3622 |
T5199 |
T5200 |
det |
the,extracts |
R3623 |
T5200 |
T5202 |
nsubj |
extracts,neutralized |
R3624 |
T5201 |
T5200 |
compound |
FA,extracts |
R3625 |
T5202 |
T5192 |
conj |
neutralized,diluted |
R3626 |
T5203 |
T5202 |
prep |
with,neutralized |
R3627 |
T5204 |
T5205 |
compound |
1M,buffer |
R3628 |
T5205 |
T5203 |
pobj |
buffer,with |
R3629 |
T5206 |
T5205 |
compound |
Tris,buffer |
R3630 |
T5207 |
T5205 |
punct |
-,buffer |
R3631 |
T5208 |
T5205 |
compound |
phosphate,buffer |
R3632 |
T5209 |
T5210 |
punct |
(,pH |
R3633 |
T5210 |
T5205 |
parataxis |
pH,buffer |
R3634 |
T5211 |
T5210 |
nummod |
11,pH |
R3635 |
T5212 |
T5210 |
punct |
),pH |
R3636 |
T5213 |
T5214 |
advmod |
then,diluted |
R3637 |
T5214 |
T5202 |
dep |
diluted,neutralized |
R3638 |
T5215 |
T5214 |
prep |
with,diluted |
R3639 |
T5216 |
T5217 |
compound |
EC,buffer |
R3640 |
T5217 |
T5215 |
pobj |
buffer,with |
R3641 |
T5218 |
T5219 |
amod |
prior,to |
R3642 |
T5219 |
T5214 |
prep |
to,diluted |
R3643 |
T5220 |
T5219 |
pobj |
testing,to |
R3644 |
T5221 |
T5202 |
punct |
.,neutralized |
R3645 |
T5223 |
T5224 |
amod |
Human,Aβ |
R3646 |
T5224 |
T5225 |
nsubjpass |
Aβ,measured |
R3647 |
T5226 |
T5225 |
auxpass |
was,measured |
R3648 |
T5227 |
T5225 |
prep |
in,measured |
R3649 |
T5228 |
T5229 |
det |
each,fraction |
R3650 |
T5229 |
T5227 |
pobj |
fraction,in |
R3651 |
T5230 |
T5225 |
advcl |
using,measured |
R3652 |
T5231 |
T5230 |
dobj |
BAN50,using |
R3653 |
T5232 |
T5230 |
prep |
for,using |
R3654 |
T5233 |
T5232 |
pobj |
capture,for |
R3655 |
T5234 |
T5235 |
punct |
(,16 |
R3656 |
T5235 |
T5233 |
parataxis |
16,capture |
R3657 |
T5236 |
T5235 |
compound |
epitope,16 |
R3658 |
T5237 |
T5235 |
compound |
Aβ1,16 |
R3659 |
T5238 |
T5235 |
punct |
–,16 |
R3660 |
T5239 |
T5235 |
punct |
),16 |
R3661 |
T5240 |
T5230 |
cc |
and,using |
R3662 |
T5241 |
T5230 |
conj |
BA27,using |
R3663 |
T5242 |
T5241 |
cc |
and,BA27 |
R3664 |
T5243 |
T5241 |
conj |
BC05,BA27 |
R3665 |
T5244 |
T5241 |
prep |
for,BA27 |
R3666 |
T5245 |
T5244 |
pobj |
detection,for |
R3667 |
T5246 |
T5247 |
punct |
(,Aβ40 |
R3668 |
T5247 |
T5245 |
parataxis |
Aβ40,detection |
R3669 |
T5248 |
T5247 |
cc |
and,Aβ40 |
R3670 |
T5249 |
T5247 |
conj |
Aβ42,Aβ40 |
R3671 |
T5250 |
T5247 |
punct |
", ",Aβ40 |
R3672 |
T5251 |
T5247 |
advmod |
respectively,Aβ40 |
R3673 |
T5252 |
T5247 |
punct |
),Aβ40 |
R3674 |
T5253 |
T5254 |
punct |
(,Industries |
R3675 |
T5254 |
T5245 |
parataxis |
Industries,detection |
R3676 |
T5255 |
T5254 |
compound |
Takeda,Industries |
R3677 |
T5256 |
T5254 |
compound |
Chemical,Industries |
R3678 |
T5257 |
T5254 |
punct |
", ",Industries |
R3679 |
T5258 |
T5254 |
npadvmod |
Osaka,Industries |
R3680 |
T5259 |
T5254 |
punct |
", ",Industries |
R3681 |
T5260 |
T5254 |
npadvmod |
Japan,Industries |
R3682 |
T5261 |
T5254 |
punct |
),Industries |
R3683 |
T5262 |
T5225 |
punct |
.,measured |
R3684 |
T5264 |
T5265 |
amod |
Total,Aβ |
R3685 |
T5265 |
T5266 |
nsubjpass |
Aβ,measured |
R3686 |
T5267 |
T5268 |
punct |
(,samples |
R3688 |
T5269 |
T5268 |
dep |
mouse,samples |
R3689 |
T5270 |
T5269 |
punct |
+,mouse |
R3690 |
T5271 |
T5269 |
amod |
human,mouse |
R3691 |
T5272 |
T5268 |
punct |
;,samples |
R3692 |
T5273 |
T5274 |
quantmod |
1,1.5 |
R3693 |
T5274 |
T5277 |
nummod |
1.5,mo |
R3694 |
T5275 |
T5274 |
punct |
-,1.5 |
R3695 |
T5276 |
T5274 |
quantmod |
to,1.5 |
R3696 |
T5277 |
T5268 |
compound |
mo,samples |
R3697 |
T5278 |
T5277 |
punct |
-,mo |
R3698 |
T5279 |
T5268 |
advmod |
only,samples |
R3699 |
T5280 |
T5268 |
punct |
),samples |
R3700 |
T5281 |
T5266 |
auxpass |
was,measured |
R3701 |
T5282 |
T5266 |
prep |
in,measured |
R3702 |
T5283 |
T5284 |
det |
each,fraction |
R3703 |
T5284 |
T5282 |
pobj |
fraction,in |
R3704 |
T5285 |
T5266 |
advcl |
using,measured |
R3705 |
T5286 |
T5285 |
dobj |
BNT77,using |
R3706 |
T5287 |
T5285 |
prep |
for,using |
R3707 |
T5288 |
T5287 |
pobj |
capture,for |
R3708 |
T5289 |
T5290 |
punct |
(,Aβ11 |
R3709 |
T5290 |
T5288 |
parataxis |
Aβ11,capture |
R3710 |
T5291 |
T5290 |
compound |
epitope,Aβ11 |
R3711 |
T5292 |
T5290 |
punct |
–,Aβ11 |
R3712 |
T5293 |
T5290 |
nummod |
28,Aβ11 |
R3713 |
T5294 |
T5290 |
punct |
),Aβ11 |
R3714 |
T5295 |
T5285 |
cc |
and,using |
R3715 |
T5296 |
T5285 |
conj |
BA27,using |
R3716 |
T5297 |
T5296 |
cc |
and,BA27 |
R3717 |
T5298 |
T5296 |
conj |
BC05,BA27 |
R3718 |
T5299 |
T5296 |
prep |
for,BA27 |
R3719 |
T5300 |
T5299 |
pobj |
detection,for |
R3720 |
T5301 |
T5266 |
punct |
.,measured |
R3721 |
T5303 |
T5304 |
det |
All,values |
R3722 |
T5304 |
T5305 |
nsubjpass |
values,calculated |
R3723 |
T5306 |
T5305 |
auxpass |
were,calculated |
R3724 |
T5307 |
T5305 |
prep |
as,calculated |
R3725 |
T5308 |
T5307 |
pobj |
picomoles,as |
R3726 |
T5309 |
T5308 |
prep |
per,picomoles |
R3727 |
T5310 |
T5309 |
pobj |
gram,per |
R3728 |
T5311 |
T5305 |
prep |
based,calculated |
R3729 |
T5312 |
T5311 |
prep |
on,based |
R3730 |
T5313 |
T5314 |
det |
the,weight |
R3731 |
T5314 |
T5312 |
pobj |
weight,on |
R3732 |
T5315 |
T5314 |
amod |
initial,weight |
R3733 |
T5316 |
T5314 |
prep |
of,weight |
R3734 |
T5317 |
T5318 |
amod |
cortical,tissue |
R3735 |
T5318 |
T5316 |
pobj |
tissue,of |
R3736 |
T5319 |
T5305 |
punct |
.,calculated |
R3737 |
T5339 |
T5340 |
compound |
Activity,Monitoring |
R3738 |
T5342 |
T5343 |
amod |
Daily,activity |
R3739 |
T5343 |
T5345 |
nsubjpass |
activity,studied |
R3740 |
T5344 |
T5343 |
amod |
basal,activity |
R3741 |
T5346 |
T5345 |
auxpass |
was,studied |
R3742 |
T5347 |
T5345 |
prep |
in,studied |
R3743 |
T5348 |
T5349 |
nummod |
28,mice |
R9 |
T146 |
T144 |
pobj |
Model,in |
R10 |
T147 |
T146 |
amod |
Transgenic,Model |
R15 |
T156 |
T159 |
nsubj |
secretases,been |
R16 |
T157 |
T156 |
nmod |
proteases,secretases |
R17 |
T158 |
T156 |
punct |
(,secretases |
R22 |
T164 |
T166 |
nmod |
β,peptide |
R23 |
T165 |
T164 |
punct |
-,β |
R24 |
T166 |
T162 |
dobj |
peptide,cleave |
R25 |
T167 |
T164 |
punct |
(,β |
R26 |
T168 |
T164 |
appos |
Aβ,β |
R27 |
T169 |
T166 |
punct |
),peptide |
R30 |
T172 |
T170 |
pobj |
protein,from |
R31 |
T173 |
T172 |
compound |
amyloid,protein |
R32 |
T174 |
T172 |
compound |
precursor,protein |
R55 |
T199 |
T196 |
ccomp |
facilitate,been |
R56 |
T200 |
T199 |
csubj |
reducing,facilitate |
R57 |
T201 |
T202 |
compound |
Aβ,production |
R58 |
T202 |
T200 |
dobj |
production,reducing |
R59 |
T203 |
T200 |
prep |
in,reducing |
R60 |
T204 |
T205 |
det |
the,brain |
R61 |
T205 |
T203 |
pobj |
brain,in |
R62 |
T206 |
T199 |
punct |
", ",facilitate |
R63 |
T207 |
T208 |
advmod |
even,after |
R64 |
T208 |
T199 |
prep |
after,facilitate |
R65 |
T209 |
T210 |
det |
the,onset |
R66 |
T210 |
T208 |
pobj |
onset,after |
R67 |
T211 |
T210 |
prep |
of,onset |
R68 |
T212 |
T213 |
amod |
clinical,symptoms |
R69 |
T213 |
T211 |
pobj |
symptoms,of |
R70 |
T214 |
T210 |
cc |
and,onset |
R71 |
T215 |
T216 |
det |
the,development |
R72 |
T216 |
T210 |
conj |
development,onset |
R73 |
T217 |
T216 |
prep |
of,development |
R74 |
T218 |
T219 |
amod |
associated,pathology |
R75 |
T219 |
T217 |
pobj |
pathology,of |
R76 |
T220 |
T199 |
punct |
", ",facilitate |
R77 |
T221 |
T199 |
aux |
will,facilitate |
R92 |
T238 |
T235 |
nsubjpass |
studies,performed |
R93 |
T239 |
T240 |
amod |
long,term |
R95 |
T241 |
T240 |
punct |
-,term |
R115 |
T265 |
T262 |
dobj |
model,generated |
R116 |
T266 |
T265 |
amod |
transgenic,model |
R117 |
T267 |
T265 |
compound |
mouse,model |
R119 |
T269 |
T265 |
relcl |
mimics,model |
R120 |
T270 |
T269 |
advmod |
genetically,mimics |
R141 |
T293 |
T291 |
relcl |
regulated,vector |
R142 |
T294 |
T293 |
aux |
can,regulated |
R143 |
T295 |
T293 |
auxpass |
be,regulated |
R152 |
T306 |
T308 |
compound |
level,expression |
R153 |
T307 |
T306 |
punct |
-,level |
R159 |
T313 |
T301 |
dobj |
pathology,induces |
R160 |
T314 |
T313 |
compound |
amyloid,pathology |
R164 |
T320 |
T318 |
ccomp |
inhibits,show |
R165 |
T321 |
T322 |
compound |
doxycycline,administration |
R166 |
T322 |
T320 |
nsubj |
administration,inhibits |
R168 |
T324 |
T320 |
dobj |
expression,inhibits |
R169 |
T325 |
T324 |
compound |
APP,expression |
R172 |
T328 |
T330 |
nummod |
95,% |
R173 |
T329 |
T328 |
quantmod |
than,95 |
R189 |
T347 |
T345 |
pobj |
synthesis,of |
R190 |
T348 |
T347 |
compound |
Aβ,synthesis |
R214 |
T374 |
T370 |
advcl |
require,be |
R215 |
T375 |
T376 |
det |
the,plaques |
R216 |
T376 |
T374 |
nsubj |
plaques,require |
R222 |
T382 |
T374 |
advcl |
assemble,require |
R223 |
T383 |
T382 |
aux |
to,assemble |
R227 |
T389 |
T386 |
relcl |
suppressed,Mice |
R228 |
T390 |
T388 |
pobj |
which,in |
R229 |
T391 |
T392 |
compound |
APP,synthesis |
R230 |
T392 |
T389 |
nsubjpass |
synthesis,suppressed |
R231 |
T393 |
T389 |
auxpass |
was,suppressed |
R234 |
T396 |
T399 |
nummod |
6,mo |
R235 |
T397 |
T396 |
amod |
long,6 |
R236 |
T398 |
T396 |
quantmod |
as,6 |
R245 |
T407 |
T387 |
dobj |
load,retain |
R246 |
T408 |
T407 |
amod |
considerable,load |
R247 |
T409 |
T407 |
compound |
amyloid,load |
R259 |
T425 |
T423 |
ccomp |
are,demonstrates |
R260 |
T426 |
T427 |
compound |
amyloid,lesions |
R261 |
T427 |
T425 |
nsubj |
lesions,are |
R262 |
T428 |
T427 |
prep |
in,lesions |
R263 |
T429 |
T430 |
amod |
transgenic,mice |
R264 |
T430 |
T428 |
pobj |
mice,in |
R279 |
T447 |
T445 |
advcl |
halt,suggest |
R280 |
T448 |
T447 |
csubj |
arresting,halt |
R281 |
T449 |
T450 |
compound |
Aβ,production |
R282 |
T450 |
T448 |
dobj |
production,arresting |
R283 |
T451 |
T448 |
prep |
in,arresting |
R284 |
T452 |
T451 |
pobj |
patients,in |
R285 |
T453 |
T452 |
prep |
with,patients |
R286 |
T454 |
T455 |
compound |
Alzheimer,disease |
R287 |
T455 |
T453 |
pobj |
disease,with |
R288 |
T456 |
T447 |
aux |
should,halt |
R296 |
T464 |
T447 |
conj |
be,halt |
R297 |
T465 |
T466 |
amod |
early,treatment |
R298 |
T466 |
T464 |
nsubj |
treatment,be |
R299 |
T467 |
T464 |
aux |
may,be |
R303 |
T471 |
T464 |
advcl |
appears,be |
R304 |
T472 |
T471 |
nsubj |
it,appears |
R306 |
T474 |
T471 |
ccomp |
require,appears |
R307 |
T475 |
T476 |
compound |
amyloid,deposits |
R308 |
T476 |
T474 |
nsubj |
deposits,require |
R309 |
T477 |
T474 |
punct |
", ",require |
R310 |
T478 |
T479 |
mark |
once,formed |
R311 |
T479 |
T474 |
advcl |
formed,require |
R312 |
T480 |
T474 |
punct |
", ",require |
R313 |
T481 |
T474 |
aux |
will,require |
R319 |
T136 |
T137 |
amod |
Persistent,Amyloidosis |
R323 |
T706 |
T707 |
quantmod |
Over,a |
R324 |
T707 |
T708 |
nummod |
a,decade |
R325 |
T708 |
T709 |
npadvmod |
decade,ago |
R326 |
T709 |
T710 |
advmod |
ago,predicted |
R327 |
T711 |
T712 |
det |
the,hypothesis |
R328 |
T712 |
T710 |
nsubj |
hypothesis,predicted |
R329 |
T713 |
T714 |
compound |
amyloid,cascade |
R330 |
T714 |
T712 |
compound |
cascade,hypothesis |
R331 |
T715 |
T716 |
mark |
that,lead |
R332 |
T716 |
T710 |
ccomp |
lead,predicted |
R333 |
T717 |
T718 |
amod |
increased,levels |
R334 |
T718 |
T716 |
nsubj |
levels,lead |
R335 |
T719 |
T718 |
prep |
of,levels |
R336 |
T720 |
T721 |
nmod |
amyloid,β |
R337 |
T721 |
T723 |
nmod |
β,peptide |
R338 |
T722 |
T721 |
punct |
-,β |
R339 |
T723 |
T719 |
pobj |
peptide,of |
R340 |
T724 |
T721 |
punct |
(,β |
R341 |
T725 |
T721 |
appos |
Aβ,β |
R342 |
T726 |
T723 |
punct |
),peptide |
R343 |
T727 |
T716 |
prep |
to,lead |
R344 |
T728 |
T729 |
amod |
secondary,pathologies |
R345 |
T729 |
T727 |
pobj |
pathologies,to |
R346 |
T730 |
T731 |
dep |
that,culminate |
R347 |
T731 |
T729 |
relcl |
culminate,pathologies |
R348 |
T732 |
T731 |
advmod |
ultimately,culminate |
R349 |
T733 |
T731 |
prep |
in,culminate |
R350 |
T734 |
T735 |
det |
the,onset |
R351 |
T735 |
T733 |
pobj |
onset,in |
R352 |
T736 |
T735 |
prep |
of,onset |
R353 |
T737 |
T738 |
compound |
Alzheimer,disease |
R354 |
T738 |
T736 |
pobj |
disease,of |
R355 |
T739 |
T738 |
punct |
(,disease |
R356 |
T740 |
T738 |
appos |
AD,disease |
R357 |
T741 |
T716 |
punct |
),lead |
R358 |
T742 |
T743 |
punct |
[,1 |
R359 |
T743 |
T716 |
parataxis |
1,lead |
R360 |
T744 |
T743 |
punct |
],1 |
R361 |
T745 |
T710 |
punct |
.,predicted |
R362 |
T747 |
T748 |
amod |
Early,support |
R363 |
T748 |
T749 |
nsubj |
support,came |
R364 |
T750 |
T748 |
prep |
for,support |
R365 |
T751 |
T752 |
det |
this,hypothesis |
R366 |
T752 |
T750 |
pobj |
hypothesis,for |
R367 |
T753 |
T749 |
prep |
from,came |
R368 |
T754 |
T755 |
amod |
genetic,studies |
R369 |
T755 |
T753 |
pobj |
studies,from |
R370 |
T756 |
T755 |
acl |
linking,studies |
R371 |
T757 |
T758 |
amod |
early,onset |
R372 |
T758 |
T760 |
compound |
onset,AD |
R373 |
T759 |
T758 |
punct |
-,onset |
R374 |
T760 |
T756 |
dobj |
AD,linking |
R375 |
T761 |
T756 |
prep |
to,linking |
R376 |
T762 |
T761 |
pobj |
mutations,to |
R377 |
T763 |
T762 |
prep |
in,mutations |
R378 |
T764 |
T765 |
det |
the,protein |
R379 |
T765 |
T763 |
pobj |
protein,in |
R380 |
T766 |
T765 |
compound |
amyloid,protein |
R381 |
T767 |
T765 |
compound |
precursor,protein |
R382 |
T768 |
T765 |
punct |
(,protein |
R383 |
T769 |
T765 |
appos |
APP,protein |
R384 |
T770 |
T765 |
punct |
),protein |
R385 |
T771 |
T765 |
punct |
", ",protein |
R386 |
T772 |
T773 |
prep |
from,derived |
R387 |
T773 |
T765 |
relcl |
derived,protein |
R388 |
T774 |
T772 |
pobj |
which,from |
R389 |
T775 |
T773 |
nsubjpass |
Aβ,derived |
R390 |
T776 |
T773 |
auxpass |
is,derived |
R391 |
T777 |
T765 |
punct |
", ",protein |
R392 |
T778 |
T765 |
cc |
and,protein |
R393 |
T779 |
T780 |
nmod |
presenilins,1 |
R394 |
T780 |
T765 |
conj |
1,protein |
R395 |
T781 |
T780 |
cc |
and,1 |
R396 |
T782 |
T780 |
conj |
2,1 |
R397 |
T783 |
T780 |
punct |
", ",1 |
R398 |
T784 |
T785 |
dep |
which,are |
R399 |
T785 |
T780 |
relcl |
are,1 |
R400 |
T786 |
T787 |
amod |
interchangeable,components |
R401 |
T787 |
T785 |
attr |
components,are |
R402 |
T788 |
T787 |
prep |
of,components |
R403 |
T789 |
T790 |
det |
a,complex |
R404 |
T790 |
T788 |
pobj |
complex,of |
R405 |
T791 |
T790 |
compound |
endoprotease,complex |
R406 |
T792 |
T793 |
dep |
that,releases |
R407 |
T793 |
T790 |
relcl |
releases,complex |
R408 |
T794 |
T793 |
dobj |
Aβ,releases |
R409 |
T795 |
T793 |
prep |
from,releases |
R410 |
T796 |
T795 |
pobj |
APP,from |
R411 |
T797 |
T798 |
punct |
(,see |
R412 |
T798 |
T793 |
parataxis |
see,releases |
R413 |
T799 |
T798 |
prep |
for,see |
R414 |
T800 |
T799 |
pobj |
review,for |
R415 |
T801 |
T798 |
punct |
[,see |
R416 |
T802 |
T803 |
nummod |
2,3 |
R417 |
T803 |
T798 |
dobj |
3,see |
R418 |
T804 |
T803 |
punct |
",",3 |
R419 |
T805 |
T798 |
punct |
],see |
R420 |
T806 |
T798 |
punct |
),see |
R421 |
T807 |
T749 |
punct |
.,came |
R422 |
T809 |
T810 |
mark |
If,initiates |
R423 |
T810 |
T818 |
advcl |
initiates,arrest |
R424 |
T811 |
T810 |
punct |
", ",initiates |
R425 |
T812 |
T813 |
mark |
as,predicted |
R426 |
T813 |
T810 |
advcl |
predicted,initiates |
R427 |
T814 |
T810 |
punct |
", ",initiates |
R428 |
T815 |
T810 |
nsubj |
overproduction,initiates |
R429 |
T816 |
T815 |
prep |
of,overproduction |
R430 |
T817 |
T816 |
pobj |
Aβ,of |
R431 |
T819 |
T820 |
det |
the,cascade |
R432 |
T820 |
T810 |
dobj |
cascade,initiates |
R433 |
T821 |
T820 |
prep |
of,cascade |
R434 |
T822 |
T821 |
pobj |
events,of |
R435 |
T823 |
T822 |
acl |
leading,events |
R436 |
T824 |
T823 |
prep |
to,leading |
R437 |
T825 |
T824 |
pobj |
disease,to |
R438 |
T826 |
T818 |
punct |
", ",arrest |
R439 |
T827 |
T818 |
advmod |
then,arrest |
R440 |
T828 |
T829 |
amod |
therapeutic,strategies |
R441 |
T829 |
T818 |
nsubj |
strategies,arrest |
R442 |
T830 |
T831 |
dep |
that,lower |
R443 |
T831 |
T829 |
relcl |
lower,strategies |
R444 |
T832 |
T833 |
compound |
Aβ,levels |
R445 |
T833 |
T831 |
dobj |
levels,lower |
R446 |
T834 |
T818 |
aux |
should,arrest |
R447 |
T835 |
T818 |
preconj |
either,arrest |
R448 |
T836 |
T818 |
cc |
or,arrest |
R449 |
T837 |
T818 |
conj |
reverse,arrest |
R450 |
T838 |
T839 |
det |
the,progression |
R451 |
T839 |
T837 |
dobj |
progression,reverse |
R452 |
T840 |
T839 |
prep |
from,progression |
R453 |
T841 |
T840 |
pobj |
peptide,from |
R454 |
T842 |
T840 |
prep |
to,from |
R455 |
T843 |
T842 |
pobj |
dementia,to |
R456 |
T844 |
T818 |
punct |
.,arrest |
R457 |
T846 |
T847 |
amod |
Early,evidence |
R458 |
T847 |
T848 |
nsubj |
evidence,suggested |
R459 |
T849 |
T847 |
prep |
from,evidence |
R460 |
T850 |
T851 |
amod |
clinical,trials |
R461 |
T851 |
T849 |
pobj |
trials,from |
R462 |
T852 |
T851 |
prep |
of,trials |
R463 |
T853 |
T854 |
npadvmod |
antibody,mediated |
R464 |
T854 |
T856 |
amod |
mediated,clearance |
R465 |
T855 |
T854 |
punct |
-,mediated |
R466 |
T856 |
T852 |
pobj |
clearance,of |
R467 |
T857 |
T856 |
punct |
", ",clearance |
R468 |
T858 |
T856 |
appos |
one,clearance |
R469 |
T859 |
T858 |
prep |
of,one |
R470 |
T860 |
T861 |
det |
the,approaches |
R472 |
T862 |
T861 |
amod |
first,approaches |
R473 |
T863 |
T864 |
npadvmod |
Aβ,lowering |
R474 |
T864 |
T861 |
amod |
lowering,approaches |
R475 |
T865 |
T864 |
punct |
-,lowering |
R476 |
T866 |
T861 |
acl |
tested,approaches |
R477 |
T867 |
T866 |
prep |
in,tested |
R478 |
T868 |
T867 |
pobj |
humans,in |
R479 |
T869 |
T848 |
punct |
", ",suggested |
R480 |
T870 |
T871 |
mark |
that,be |
R481 |
T871 |
T848 |
ccomp |
be,suggested |
R482 |
T872 |
T871 |
nsubj |
treatments,be |
R483 |
T873 |
T872 |
acl |
designed,treatments |
R484 |
T874 |
T875 |
aux |
to,reduce |
R485 |
T875 |
T873 |
advcl |
reduce,designed |
R486 |
T876 |
T877 |
compound |
amyloid,burden |
R487 |
T877 |
T875 |
dobj |
burden,reduce |
R488 |
T878 |
T871 |
aux |
may,be |
R489 |
T879 |
T871 |
advmod |
indeed,be |
R490 |
T880 |
T871 |
acomp |
beneficial,be |
R491 |
T881 |
T848 |
punct |
.,suggested |
R492 |
T883 |
T884 |
mark |
Although,halted |
R493 |
T884 |
T888 |
advcl |
halted,found |
R494 |
T885 |
T886 |
det |
the,trials |
R495 |
T886 |
T884 |
nsubjpass |
trials,halted |
R496 |
T887 |
T884 |
auxpass |
were,halted |
R497 |
T889 |
T884 |
prep |
because,halted |
R498 |
T890 |
T889 |
pcomp |
of,because |
R499 |
T891 |
T892 |
amod |
adverse,effects |
R500 |
T892 |
T889 |
pobj |
effects,because |
R501 |
T893 |
T892 |
prep |
in,effects |
R502 |
T894 |
T895 |
det |
a,subset |
R503 |
T895 |
T893 |
pobj |
subset,in |
R504 |
T896 |
T895 |
prep |
of,subset |
R505 |
T897 |
T896 |
pobj |
volunteers,of |
R506 |
T898 |
T899 |
punct |
[,5 |
R507 |
T899 |
T884 |
parataxis |
5,halted |
R508 |
T900 |
T899 |
nummod |
4,5 |
R509 |
T901 |
T899 |
punct |
",",5 |
R510 |
T902 |
T899 |
punct |
],5 |
R511 |
T903 |
T888 |
punct |
", ",found |
R512 |
T904 |
T905 |
amod |
further,analysis |
R513 |
T905 |
T888 |
nsubj |
analysis,found |
R514 |
T906 |
T905 |
prep |
of,analysis |
R515 |
T907 |
T908 |
amod |
several,patients |
R516 |
T908 |
T906 |
pobj |
patients,of |
R517 |
T909 |
T888 |
dobj |
evidence,found |
R518 |
T910 |
T911 |
mark |
that,improved |
R519 |
T911 |
T909 |
acl |
improved,evidence |
R520 |
T912 |
T913 |
compound |
amyloid,pathology |
R521 |
T913 |
T911 |
nsubjpass |
pathology,improved |
R522 |
T914 |
T913 |
punct |
", ",pathology |
R523 |
T915 |
T913 |
cc |
and,pathology |
R524 |
T916 |
T917 |
prep |
to,function |
R525 |
T917 |
T913 |
conj |
function,pathology |
R526 |
T918 |
T919 |
det |
a,degree |
R527 |
T919 |
T916 |
pobj |
degree,to |
R528 |
T920 |
T919 |
amod |
lesser,degree |
R529 |
T921 |
T917 |
amod |
cognitive,function |
R530 |
T922 |
T911 |
punct |
", ",improved |
R531 |
T923 |
T911 |
auxpass |
was,improved |
R532 |
T924 |
T911 |
prep |
in,improved |
R533 |
T925 |
T924 |
pobj |
proportion,in |
R534 |
T926 |
T925 |
prep |
to,proportion |
R535 |
T927 |
T928 |
det |
the,patient |
R536 |
T928 |
T929 |
poss |
patient,titer |
R537 |
T929 |
T926 |
pobj |
titer,to |
R538 |
T930 |
T928 |
case |
's,patient |
R539 |
T931 |
T929 |
prep |
of,titer |
R540 |
T932 |
T933 |
npadvmod |
Aβ,specific |
R541 |
T933 |
T935 |
amod |
specific,antibody |
R542 |
T934 |
T933 |
punct |
-,specific |
R543 |
T935 |
T931 |
pobj |
antibody,of |
R544 |
T936 |
T937 |
punct |
[,7 |
R545 |
T937 |
T911 |
parataxis |
7,improved |
R546 |
T938 |
T937 |
nummod |
6,7 |
R547 |
T939 |
T937 |
punct |
",",7 |
R548 |
T940 |
T937 |
punct |
],7 |
R549 |
T941 |
T888 |
punct |
.,found |
R550 |
T943 |
T944 |
mark |
While,is |
R551 |
T944 |
T947 |
advcl |
is,have |
R552 |
T945 |
T946 |
det |
this,approach |
R553 |
T946 |
T944 |
nsubj |
approach,is |
R554 |
T948 |
T944 |
acomp |
promising,is |
R555 |
T949 |
T947 |
punct |
", ",have |
R556 |
T950 |
T951 |
amod |
constant,exposure |
R557 |
T951 |
T947 |
nsubj |
exposure,have |
R558 |
T952 |
T951 |
prep |
to,exposure |
R559 |
T953 |
T952 |
pobj |
antibodies,to |
R560 |
T954 |
T955 |
dep |
that,recognize |
R561 |
T955 |
T953 |
relcl |
recognize,antibodies |
R562 |
T956 |
T957 |
det |
an,epitope |
R563 |
T957 |
T955 |
dobj |
epitope,recognize |
R564 |
T958 |
T959 |
advmod |
highly,enriched |
R565 |
T959 |
T957 |
amod |
enriched,epitope |
R566 |
T960 |
T959 |
prep |
in,enriched |
R567 |
T961 |
T962 |
det |
the,brain |
R568 |
T962 |
T960 |
pobj |
brain,in |
R569 |
T963 |
T947 |
aux |
may,have |
R570 |
T964 |
T965 |
amod |
unexpected,effects |
R571 |
T965 |
T947 |
dobj |
effects,have |
R572 |
T966 |
T965 |
compound |
side,effects |
R573 |
T967 |
T968 |
dep |
that,limit |
R574 |
T968 |
T965 |
relcl |
limit,effects |
R575 |
T969 |
T968 |
aux |
will,limit |
R576 |
T970 |
T971 |
poss |
its,use |
R577 |
T971 |
T968 |
dobj |
use,limit |
R578 |
T972 |
T973 |
amod |
long,term |
R579 |
T973 |
T971 |
compound |
term,use |
R580 |
T974 |
T973 |
punct |
-,term |
R581 |
T975 |
T947 |
punct |
.,have |
R582 |
T977 |
T978 |
det |
An,approach |
R583 |
T978 |
T980 |
nsubj |
approach,seeks |
R584 |
T979 |
T978 |
amod |
alternative,approach |
R585 |
T981 |
T982 |
dep |
that,pursued |
R586 |
T982 |
T978 |
relcl |
pursued,approach |
R587 |
T983 |
T982 |
aux |
is,pursued |
R588 |
T984 |
T982 |
auxpass |
being,pursued |
R589 |
T985 |
T982 |
advmod |
actively,pursued |
R590 |
T986 |
T982 |
prep |
for,pursued |
R591 |
T987 |
T988 |
amod |
future,treatment |
R592 |
T988 |
T986 |
pobj |
treatment,for |
R593 |
T989 |
T988 |
prep |
of,treatment |
R594 |
T990 |
T989 |
pobj |
AD,of |
R595 |
T991 |
T992 |
aux |
to,lower |
R596 |
T992 |
T980 |
xcomp |
lower,seeks |
R597 |
T993 |
T994 |
compound |
Aβ,levels |
R598 |
T994 |
T992 |
dobj |
levels,lower |
R599 |
T995 |
T992 |
prep |
by,lower |
R600 |
T996 |
T995 |
pcomp |
limiting,by |
R601 |
T997 |
T998 |
poss |
its,production |
R602 |
T998 |
T996 |
dobj |
production,limiting |
R603 |
T999 |
T996 |
prep |
from,limiting |
R604 |
T1000 |
T1001 |
det |
the,protein |
R605 |
T1001 |
T999 |
pobj |
protein,from |
R606 |
T1002 |
T1001 |
compound |
precursor,protein |
R607 |
T1003 |
T1001 |
appos |
APP,protein |
R608 |
T1004 |
T980 |
punct |
.,seeks |
R609 |
T1006 |
T1007 |
compound |
Peptide,Aβ |
R610 |
T1007 |
T1008 |
nsubjpass |
Aβ,released |
R611 |
T1009 |
T1008 |
auxpass |
is,released |
R612 |
T1010 |
T1008 |
prep |
from,released |
R613 |
T1011 |
T1010 |
pobj |
APP,from |
R614 |
T1012 |
T1008 |
agent |
by,released |
R615 |
T1013 |
T1014 |
det |
the,action |
R616 |
T1014 |
T1012 |
pobj |
action,by |
R617 |
T1015 |
T1014 |
prep |
of,action |
R618 |
T1016 |
T1017 |
nummod |
two,enzymes |
R619 |
T1017 |
T1015 |
pobj |
enzymes,of |
R620 |
T1018 |
T1017 |
punct |
", ",enzymes |
R621 |
T1019 |
T1020 |
det |
the,enzyme |
R623 |
T1021 |
T1022 |
compound |
β,APP |
R624 |
T1022 |
T1024 |
npadvmod |
APP,cleaving |
R625 |
T1023 |
T1022 |
punct |
-,APP |
R626 |
T1024 |
T1020 |
amod |
cleaving,enzyme |
R627 |
T1025 |
T1020 |
nummod |
1,enzyme |
R628 |
T1026 |
T1020 |
punct |
(,enzyme |
R629 |
T1027 |
T1020 |
appos |
BACE1,enzyme |
R630 |
T1028 |
T1020 |
punct |
),enzyme |
R631 |
T1029 |
T1020 |
cc |
and,enzyme |
R632 |
T1030 |
T1031 |
punct |
γ,secretase |
R633 |
T1031 |
T1020 |
conj |
secretase,enzyme |
R634 |
T1032 |
T1031 |
punct |
-,secretase |
R635 |
T1033 |
T1017 |
punct |
", ",enzymes |
R636 |
T1034 |
T1035 |
dep |
which,cleave |
R637 |
T1035 |
T1017 |
relcl |
cleave,enzymes |
R638 |
T1036 |
T1037 |
det |
the,holoprotein |
R639 |
T1037 |
T1035 |
dobj |
holoprotein,cleave |
R640 |
T1038 |
T1035 |
prep |
at,cleave |
R641 |
T1039 |
T1040 |
det |
the,termini |
R642 |
T1040 |
T1038 |
pobj |
termini,at |
R643 |
T1041 |
T1040 |
nmod |
N,termini |
R644 |
T1042 |
T1041 |
punct |
-,N |
R645 |
T1043 |
T1041 |
cc |
and,N |
R646 |
T1044 |
T1041 |
conj |
C,N |
R647 |
T1045 |
T1040 |
punct |
-,termini |
R648 |
T1046 |
T1040 |
prep |
of,termini |
R649 |
T1047 |
T1046 |
pobj |
Aβ,of |
R650 |
T1048 |
T1008 |
punct |
", ",released |
R651 |
T1049 |
T1008 |
advmod |
respectively,released |
R652 |
T1050 |
T1008 |
punct |
.,released |
R653 |
T1052 |
T1053 |
amod |
Several,inhibitors |
R654 |
T1053 |
T1054 |
nsubjpass |
inhibitors,produced |
R655 |
T1055 |
T1053 |
prep |
of,inhibitors |
R656 |
T1056 |
T1057 |
punct |
γ,secretase |
R657 |
T1057 |
T1055 |
pobj |
secretase,of |
R658 |
T1058 |
T1057 |
punct |
-,secretase |
R659 |
T1059 |
T1054 |
aux |
have,produced |
R660 |
T1060 |
T1054 |
advmod |
already,produced |
R661 |
T1061 |
T1054 |
auxpass |
been,produced |
R662 |
T1062 |
T1063 |
punct |
[,9 |
R663 |
T1063 |
T1054 |
parataxis |
9,produced |
R664 |
T1064 |
T1063 |
nummod |
8,9 |
R665 |
T1065 |
T1063 |
punct |
",",9 |
R666 |
T1066 |
T1063 |
punct |
],9 |
R667 |
T1067 |
T1054 |
punct |
", ",produced |
R668 |
T1068 |
T1054 |
cc |
and,produced |
R669 |
T1069 |
T1070 |
amod |
small,inhibitors |
R670 |
T1070 |
T1072 |
nsubjpass |
inhibitors,developed |
R671 |
T1071 |
T1070 |
compound |
molecule,inhibitors |
R672 |
T1072 |
T1054 |
conj |
developed,produced |
R673 |
T1073 |
T1070 |
prep |
of,inhibitors |
R674 |
T1074 |
T1075 |
compound |
β,APP |
R675 |
T1075 |
T1077 |
npadvmod |
APP,cleaving |
R676 |
T1076 |
T1075 |
punct |
-,APP |
R677 |
T1077 |
T1078 |
amod |
cleaving,enzyme |
R678 |
T1078 |
T1073 |
pobj |
enzyme,of |
R679 |
T1079 |
T1078 |
nummod |
1,enzyme |
R680 |
T1080 |
T1072 |
aux |
are,developed |
R681 |
T1081 |
T1072 |
advmod |
currently,developed |
R682 |
T1082 |
T1072 |
auxpass |
being,developed |
R683 |
T1083 |
T1084 |
punct |
[,11 |
R684 |
T1084 |
T1072 |
parataxis |
11,developed |
R685 |
T1085 |
T1084 |
nummod |
10,11 |
R686 |
T1086 |
T1084 |
punct |
",",11 |
R687 |
T1087 |
T1084 |
punct |
],11 |
R688 |
T1088 |
T1072 |
punct |
.,developed |
R689 |
T1090 |
T1091 |
det |
The,effectiveness |
R690 |
T1091 |
T1095 |
nsubjpass |
effectiveness,reported |
R691 |
T1092 |
T1093 |
amod |
long,term |
R692 |
T1093 |
T1091 |
compound |
term,effectiveness |
R693 |
T1094 |
T1093 |
punct |
-,term |
R694 |
T1096 |
T1091 |
prep |
of,effectiveness |
R695 |
T1097 |
T1098 |
det |
this,approach |
R696 |
T1098 |
T1096 |
pobj |
approach,of |
R697 |
T1099 |
T1091 |
prep |
in,effectiveness |
R698 |
T1100 |
T1101 |
preconj |
either,humans |
R699 |
T1101 |
T1099 |
pobj |
humans,in |
R700 |
T1102 |
T1101 |
cc |
or,humans |
R701 |
T1103 |
T1104 |
compound |
model,systems |
R702 |
T1104 |
T1101 |
conj |
systems,humans |
R703 |
T1105 |
T1095 |
punct |
", ",reported |
R704 |
T1106 |
T1095 |
advmod |
however,reported |
R705 |
T1107 |
T1095 |
punct |
", ",reported |
R706 |
T1108 |
T1095 |
aux |
has,reported |
R707 |
T1109 |
T1095 |
neg |
not,reported |
R708 |
T1110 |
T1095 |
auxpass |
been,reported |
R709 |
T1111 |
T1095 |
punct |
.,reported |
R710 |
T1113 |
T1114 |
mark |
Although,prevent |
R711 |
T1114 |
T1125 |
advcl |
prevent,known |
R712 |
T1115 |
T1114 |
nsubj |
loss,prevent |
R713 |
T1116 |
T1115 |
prep |
of,loss |
R714 |
T1117 |
T1118 |
compound |
β,APP |
R715 |
T1118 |
T1120 |
npadvmod |
APP,cleaving |
R716 |
T1119 |
T1118 |
punct |
-,APP |
R717 |
T1120 |
T1121 |
amod |
cleaving,function |
R718 |
T1121 |
T1116 |
pobj |
function,of |
R719 |
T1122 |
T1121 |
nmod |
enzyme,function |
R720 |
T1123 |
T1122 |
nummod |
1,enzyme |
R721 |
T1124 |
T1114 |
aux |
can,prevent |
R722 |
T1126 |
T1127 |
det |
the,development |
R723 |
T1127 |
T1114 |
dobj |
development,prevent |
R724 |
T1128 |
T1127 |
prep |
of,development |
R725 |
T1129 |
T1128 |
pobj |
plaques,of |
R726 |
T1130 |
T1114 |
prep |
in,prevent |
R727 |
T1131 |
T1132 |
amod |
transgenic,models |
R728 |
T1132 |
T1130 |
pobj |
models,in |
R729 |
T1133 |
T1132 |
compound |
mouse,models |
R730 |
T1134 |
T1132 |
prep |
for,models |
R731 |
T1135 |
T1134 |
pobj |
AD,for |
R732 |
T1136 |
T1137 |
punct |
(,F. |
R733 |
T1137 |
T1114 |
meta |
F.,prevent |
R734 |
T1138 |
T1137 |
nmod |
Laird,F. |
R735 |
T1139 |
T1137 |
punct |
", ",F. |
R736 |
T1140 |
T1137 |
nmod |
H.,F. |
R737 |
T1141 |
T1137 |
nmod |
Cai,F. |
R738 |
T1142 |
T1137 |
punct |
", ",F. |
R739 |
T1143 |
T1137 |
nmod |
P.,F. |
R740 |
T1144 |
T1137 |
nmod |
C.,F. |
R741 |
T1145 |
T1137 |
nmod |
Wong,F. |
R742 |
T1146 |
T1137 |
punct |
", ",F. |
R743 |
T1147 |
T1137 |
amod |
personal,F. |
R744 |
T1148 |
T1137 |
nmod |
communication,F. |
R745 |
T1149 |
T1137 |
punct |
),F. |
R746 |
T1150 |
T1125 |
punct |
", ",known |
R747 |
T1151 |
T1125 |
nsubjpass |
it,known |
R748 |
T1152 |
T1125 |
auxpass |
is,known |
R749 |
T1153 |
T1125 |
neg |
not,known |
R750 |
T1154 |
T1155 |
mark |
whether,clear |
R751 |
T1155 |
T1125 |
ccomp |
clear,known |
R752 |
T1156 |
T1157 |
det |
the,brain |
R753 |
T1157 |
T1155 |
nsubj |
brain,clear |
R754 |
T1158 |
T1155 |
aux |
can,clear |
R755 |
T1159 |
T1160 |
amod |
pre-existing,deposits |
R756 |
T1160 |
T1155 |
dobj |
deposits,clear |
R757 |
T1161 |
T1160 |
compound |
amyloid,deposits |
R758 |
T1162 |
T1163 |
mark |
once,suppressed |
R759 |
T1163 |
T1155 |
advcl |
suppressed,clear |
R760 |
T1164 |
T1163 |
nsubjpass |
production,suppressed |
R761 |
T1165 |
T1164 |
prep |
of,production |
R762 |
T1166 |
T1165 |
pobj |
Aβ,of |
R763 |
T1167 |
T1163 |
aux |
has,suppressed |
R764 |
T1168 |
T1163 |
auxpass |
been,suppressed |
R765 |
T1169 |
T1125 |
punct |
.,known |
R766 |
T1171 |
T1172 |
advmod |
Clearly,examined |
R767 |
T1173 |
T1172 |
punct |
", ",examined |
R768 |
T1174 |
T1175 |
det |
the,approach |
R769 |
T1175 |
T1172 |
nsubjpass |
approach,examined |
R770 |
T1176 |
T1177 |
npadvmod |
amyloid,lowering |
R771 |
T1177 |
T1175 |
amod |
lowering,approach |
R772 |
T1178 |
T1177 |
punct |
-,lowering |
R773 |
T1179 |
T1172 |
aux |
should,examined |
R774 |
T1180 |
T1172 |
auxpass |
be,examined |
R775 |
T1181 |
T1172 |
advmod |
rigorously,examined |
R776 |
T1182 |
T1172 |
prep |
in,examined |
R777 |
T1183 |
T1184 |
compound |
animal,models |
R778 |
T1184 |
T1182 |
pobj |
models,in |
R779 |
T1185 |
T1186 |
mark |
before,tested |
R780 |
T1186 |
T1172 |
advcl |
tested,examined |
R781 |
T1187 |
T1188 |
det |
these,reagents |
R782 |
T1188 |
T1186 |
nsubjpass |
reagents,tested |
R783 |
T1189 |
T1186 |
auxpass |
are,tested |
R784 |
T1190 |
T1186 |
prep |
in,tested |
R785 |
T1191 |
T1190 |
pobj |
patients,in |
R786 |
T1192 |
T1172 |
punct |
.,examined |
R787 |
T1194 |
T1195 |
advmod |
However,are |
R788 |
T1196 |
T1195 |
punct |
", ",are |
R789 |
T1197 |
T1198 |
det |
the,inhibitors |
R790 |
T1198 |
T1195 |
nsubj |
inhibitors,are |
R791 |
T1199 |
T1198 |
amod |
chemical,inhibitors |
R792 |
T1200 |
T1198 |
compound |
secretase,inhibitors |
R793 |
T1201 |
T1202 |
advmod |
most,likely |
R794 |
T1202 |
T1198 |
amod |
likely,inhibitors |
R795 |
T1203 |
T1204 |
aux |
to,reach |
R796 |
T1204 |
T1202 |
xcomp |
reach,likely |
R797 |
T1205 |
T1206 |
amod |
human,trials |
R798 |
T1206 |
T1204 |
dobj |
trials,reach |
R799 |
T1207 |
T1195 |
advmod |
still,are |
R800 |
T1208 |
T1195 |
prep |
in,are |
R801 |
T1209 |
T1208 |
pobj |
development,in |
R802 |
T1210 |
T1195 |
punct |
.,are |
R803 |
T1212 |
T1213 |
advmod |
Therefore,developed |
R804 |
T1214 |
T1213 |
punct |
", ",developed |
R805 |
T1215 |
T1213 |
nsubj |
we,developed |
R806 |
T1216 |
T1217 |
det |
a,model |
R807 |
T1217 |
T1213 |
dobj |
model,developed |
R808 |
T1218 |
T1217 |
compound |
mouse,model |
R809 |
T1219 |
T1217 |
prep |
of,model |
R810 |
T1220 |
T1221 |
compound |
Alzheimer,type |
R811 |
T1221 |
T1223 |
compound |
type,amyloid |
R812 |
T1222 |
T1221 |
punct |
-,type |
R813 |
T1223 |
T1219 |
pobj |
amyloid,of |
R814 |
T1224 |
T1225 |
dep |
that,expresses |
R815 |
T1225 |
T1223 |
relcl |
expresses,amyloid |
R816 |
T1226 |
T1227 |
det |
a,transgene |
R817 |
T1227 |
T1225 |
dobj |
transgene,expresses |
R818 |
T1228 |
T1227 |
amod |
controllable,transgene |
R819 |
T1229 |
T1227 |
compound |
APP,transgene |
R820 |
T1230 |
T1213 |
punct |
.,developed |
R821 |
T1232 |
T1233 |
det |
This,system |
R822 |
T1233 |
T1234 |
nsubjpass |
system,regulated |
R823 |
T1235 |
T1233 |
punct |
", ",system |
R824 |
T1236 |
T1237 |
advmod |
commonly,known |
R825 |
T1237 |
T1233 |
acl |
known,system |
R826 |
T1238 |
T1237 |
prep |
as,known |
R827 |
T1239 |
T1240 |
det |
the,system |
R828 |
T1240 |
T1238 |
pobj |
system,as |
R829 |
T1241 |
T1242 |
compound |
tet,off |
R830 |
T1242 |
T1240 |
compound |
off,system |
R831 |
T1243 |
T1242 |
punct |
-,off |
R832 |
T1244 |
T1234 |
punct |
", ",regulated |
R833 |
T1245 |
T1234 |
aux |
can,regulated |
R834 |
T1246 |
T1234 |
auxpass |
be,regulated |
R835 |
T1247 |
T1234 |
agent |
by,regulated |
R836 |
T1248 |
T1247 |
pobj |
analogs,by |
R837 |
T1249 |
T1248 |
prep |
of,analogs |
R838 |
T1250 |
T1249 |
pobj |
tetracycline,of |
R839 |
T1251 |
T1250 |
acl |
administered,tetracycline |
R840 |
T1252 |
T1251 |
prep |
in,administered |
R841 |
T1253 |
T1252 |
pobj |
food,in |
R842 |
T1254 |
T1253 |
cc |
or,food |
R843 |
T1255 |
T1253 |
conj |
water,food |
R844 |
T1256 |
T1257 |
punct |
[,13 |
R845 |
T1257 |
T1234 |
parataxis |
13,regulated |
R846 |
T1258 |
T1257 |
nummod |
12,13 |
R847 |
T1259 |
T1257 |
punct |
",",13 |
R848 |
T1260 |
T1257 |
punct |
],13 |
R849 |
T1261 |
T1234 |
punct |
.,regulated |
R850 |
T1263 |
T1264 |
det |
The,levels |
R851 |
T1264 |
T1267 |
nsubj |
levels,allowed |
R852 |
T1265 |
T1264 |
amod |
strong,levels |
R853 |
T1266 |
T1264 |
compound |
expression,levels |
R854 |
T1268 |
T1264 |
acl |
produced,levels |
R855 |
T1269 |
T1268 |
prep |
with,produced |
R856 |
T1270 |
T1271 |
det |
the,vectors |
R857 |
T1271 |
T1269 |
pobj |
vectors,with |
R858 |
T1272 |
T1273 |
compound |
tet,off |
R859 |
T1273 |
T1271 |
compound |
off,vectors |
R860 |
T1274 |
T1273 |
punct |
-,off |
R861 |
T1275 |
T1271 |
punct |
", ",vectors |
R862 |
T1276 |
T1271 |
acl |
combined,vectors |
R863 |
T1277 |
T1276 |
prep |
with,combined |
R864 |
T1278 |
T1279 |
det |
the,ability |
R865 |
T1279 |
T1277 |
pobj |
ability,with |
R866 |
T1280 |
T1281 |
aux |
to,reduce |
R867 |
T1281 |
T1279 |
acl |
reduce,ability |
R868 |
T1282 |
T1283 |
det |
this,expression |
R869 |
T1283 |
T1281 |
dobj |
expression,reduce |
R870 |
T1284 |
T1281 |
prep |
by,reduce |
R871 |
T1285 |
T1286 |
amod |
several,orders |
R872 |
T1286 |
T1284 |
pobj |
orders,by |
R873 |
T1287 |
T1286 |
prep |
of,orders |
R874 |
T1288 |
T1287 |
pobj |
magnitude,of |
R875 |
T1289 |
T1281 |
prep |
with,reduce |
R876 |
T1290 |
T1289 |
pobj |
tetracycline,with |
R877 |
T1291 |
T1292 |
punct |
[,14 |
R878 |
T1292 |
T1281 |
parataxis |
14,reduce |
R879 |
T1293 |
T1292 |
punct |
],14 |
R880 |
T1294 |
T1267 |
punct |
", ",allowed |
R881 |
T1295 |
T1267 |
prep |
for,allowed |
R882 |
T1296 |
T1297 |
det |
a,test |
R883 |
T1297 |
T1295 |
pobj |
test,for |
R884 |
T1298 |
T1297 |
amod |
stringent,test |
R885 |
T1299 |
T1297 |
prep |
of,test |
R886 |
T1300 |
T1301 |
advmod |
how,impact |
R887 |
T1301 |
T1299 |
pobj |
impact,of |
R888 |
T1302 |
T1303 |
det |
a,inhibitor |
R889 |
T1303 |
T1301 |
nsubj |
inhibitor,impact |
R890 |
T1304 |
T1305 |
advmod |
highly,effective |
R891 |
T1305 |
T1303 |
amod |
effective,inhibitor |
R892 |
T1306 |
T1303 |
amod |
pharmaceutical,inhibitor |
R893 |
T1307 |
T1303 |
prep |
of,inhibitor |
R894 |
T1308 |
T1309 |
compound |
Aβ,production |
R895 |
T1309 |
T1307 |
pobj |
production,of |
R896 |
T1310 |
T1301 |
aux |
would,impact |
R897 |
T1311 |
T1312 |
det |
the,progression |
R898 |
T1312 |
T1301 |
dobj |
progression,impact |
R899 |
T1313 |
T1312 |
prep |
of,progression |
R900 |
T1314 |
T1315 |
compound |
amyloid,pathology |
R901 |
T1315 |
T1313 |
pobj |
pathology,of |
R902 |
T1316 |
T1301 |
cc |
and,impact |
R903 |
T1317 |
T1318 |
mark |
whether,be |
R904 |
T1318 |
T1301 |
conj |
be,impact |
R905 |
T1319 |
T1318 |
nsubj |
reversal,be |
R906 |
T1320 |
T1319 |
prep |
of,reversal |
R907 |
T1321 |
T1322 |
det |
these,lesions |
R908 |
T1322 |
T1320 |
pobj |
lesions,of |
R909 |
T1323 |
T1318 |
aux |
might,be |
R910 |
T1324 |
T1318 |
acomp |
possible,be |
R911 |
T1325 |
T1318 |
prep |
following,be |
R912 |
T1326 |
T1325 |
prep |
such,following |
R913 |
T1327 |
T1326 |
pobj |
treatment,such |
R914 |
T1328 |
T1267 |
punct |
.,allowed |
R915 |
T1535 |
T1536 |
compound |
Transgene,Construction |
R916 |
T1538 |
T1539 |
nsubj |
We,created |
R917 |
T1540 |
T1541 |
det |
a,vector |
R918 |
T1541 |
T1539 |
dobj |
vector,created |
R919 |
T1542 |
T1543 |
npadvmod |
tetracycline,responsive |
R920 |
T1543 |
T1541 |
amod |
responsive,vector |
R921 |
T1544 |
T1543 |
punct |
-,responsive |
R922 |
T1545 |
T1541 |
amod |
chimeric,vector |
R923 |
T1546 |
T1541 |
nmod |
mouse,vector |
R924 |
T1547 |
T1546 |
punct |
/,mouse |
R925 |
T1548 |
T1546 |
amod |
human,mouse |
R926 |
T1549 |
T1550 |
nmod |
APP695Swedish,Indiana |
R927 |
T1550 |
T1541 |
nmod |
Indiana,vector |
R928 |
T1551 |
T1550 |
punct |
/,Indiana |
R929 |
T1552 |
T1550 |
punct |
(,Indiana |
R930 |
T1553 |
T1554 |
compound |
swe,ind |
R931 |
T1554 |
T1550 |
appos |
ind,Indiana |
R932 |
T1555 |
T1554 |
punct |
/,ind |
R933 |
T1556 |
T1541 |
punct |
),vector |
R934 |
T1557 |
T1539 |
prep |
by,created |
R935 |
T1558 |
T1557 |
pcomp |
replacing,by |
R936 |
T1559 |
T1560 |
det |
the,region |
R937 |
T1560 |
T1558 |
dobj |
region,replacing |
R938 |
T1561 |
T1560 |
compound |
promoter,region |
R939 |
T1562 |
T1560 |
prep |
of,region |
R940 |
T1563 |
T1564 |
det |
the,vector |
R941 |
T1564 |
T1562 |
pobj |
vector,of |
R942 |
T1565 |
T1564 |
compound |
moPrP.XhoI,vector |
R943 |
T1566 |
T1567 |
punct |
(,known |
R944 |
T1567 |
T1558 |
parataxis |
known,replacing |
R945 |
T1568 |
T1567 |
advmod |
also,known |
R946 |
T1569 |
T1567 |
prep |
as,known |
R947 |
T1570 |
T1571 |
nmod |
pPrPpE1,3sal |
R948 |
T1571 |
T1569 |
pobj |
3sal,as |
R949 |
T1572 |
T1571 |
punct |
/,3sal |
R950 |
T1573 |
T1571 |
nmod |
E2,3sal |
R951 |
T1574 |
T1571 |
punct |
",",3sal |
R952 |
T1575 |
T1576 |
punct |
[,15 |
R953 |
T1576 |
T1567 |
parataxis |
15,known |
R954 |
T1577 |
T1576 |
punct |
],15 |
R955 |
T1578 |
T1567 |
punct |
),known |
R956 |
T1579 |
T1558 |
prep |
with,replacing |
R957 |
T1580 |
T1581 |
det |
the,promoter |
R958 |
T1581 |
T1579 |
pobj |
promoter,with |
R959 |
T1582 |
T1583 |
npadvmod |
tetracycline,responsive |
R960 |
T1583 |
T1581 |
amod |
responsive,promoter |
R961 |
T1584 |
T1583 |
punct |
-,responsive |
R962 |
T1585 |
T1581 |
prep |
of,promoter |
R963 |
T1586 |
T1585 |
pobj |
pTetSplice,of |
R964 |
T1587 |
T1588 |
punct |
(,Technologies |
R965 |
T1588 |
T1586 |
parataxis |
Technologies,pTetSplice |
R966 |
T1589 |
T1588 |
compound |
Life,Technologies |
R967 |
T1590 |
T1588 |
punct |
", ",Technologies |
R968 |
T1591 |
T1588 |
npadvmod |
Rockville,Technologies |
R969 |
T1592 |
T1588 |
punct |
", ",Technologies |
R970 |
T1593 |
T1588 |
npadvmod |
Maryland,Technologies |
R971 |
T1594 |
T1588 |
punct |
", ",Technologies |
R972 |
T1595 |
T1596 |
compound |
United,States |
R973 |
T1596 |
T1588 |
npadvmod |
States,Technologies |
R974 |
T1597 |
T1588 |
punct |
),Technologies |
R975 |
T1598 |
T1558 |
punct |
", ",replacing |
R976 |
T1599 |
T1558 |
cc |
and,replacing |
R977 |
T1600 |
T1601 |
advmod |
then,ligating |
R978 |
T1601 |
T1558 |
conj |
ligating,replacing |
R979 |
T1602 |
T1603 |
compound |
mouse,APP |
R980 |
T1603 |
T1601 |
dobj |
APP,ligating |
R981 |
T1604 |
T1601 |
prep |
with,ligating |
R982 |
T1605 |
T1606 |
det |
a,domain |
R983 |
T1606 |
T1609 |
nmod |
domain,cDNA |
R984 |
T1607 |
T1606 |
amod |
humanized,domain |
R985 |
T1608 |
T1606 |
nmod |
Aβ,domain |
R986 |
T1609 |
T1604 |
pobj |
cDNA,with |
R987 |
T1610 |
T1606 |
punct |
(,domain |
R988 |
T1611 |
T1612 |
compound |
mo,huAPP695 |
R989 |
T1612 |
T1606 |
appos |
huAPP695,domain |
R990 |
T1613 |
T1612 |
punct |
/,huAPP695 |
R991 |
T1614 |
T1609 |
punct |
),cDNA |
R992 |
T1615 |
T1601 |
prep |
into,ligating |
R993 |
T1616 |
T1617 |
det |
the,vector |
R994 |
T1617 |
T1615 |
pobj |
vector,into |
R995 |
T1618 |
T1617 |
amod |
new,vector |
R996 |
T1619 |
T1539 |
punct |
.,created |
R997 |
T1621 |
T1622 |
nsubj |
We,began |
R998 |
T1623 |
T1622 |
prep |
by,began |
R999 |
T1624 |
T1623 |
pcomp |
cloning,by |
R1000 |
T1625 |
T1626 |
det |
the,promoter |
R1001 |
T1626 |
T1624 |
dobj |
promoter,cloning |
R1002 |
T1627 |
T1628 |
npadvmod |
tetracycline,responsive |
R1003 |
T1628 |
T1626 |
amod |
responsive,promoter |
R1004 |
T1629 |
T1628 |
punct |
-,responsive |
R1005 |
T1630 |
T1631 |
punct |
(,6 |
R1006 |
T1631 |
T1626 |
parataxis |
6,promoter |
R1007 |
T1632 |
T1631 |
nmod |
bp,6 |
R1008 |
T1633 |
T1634 |
punct |
–,481 |
R1009 |
T1634 |
T1631 |
prep |
481,6 |
R1010 |
T1635 |
T1631 |
punct |
),6 |
R1011 |
T1636 |
T1624 |
prep |
from,cloning |
R1012 |
T1637 |
T1636 |
pobj |
pTetSplice,from |
R1013 |
T1638 |
T1637 |
prep |
by,pTetSplice |
R1014 |
T1639 |
T1638 |
pobj |
PCR,by |
R1015 |
T1640 |
T1639 |
acl |
using,PCR |
R1016 |
T1641 |
T1640 |
dobj |
primers,using |
R1017 |
T1642 |
T1643 |
dep |
that,added |
R1018 |
T1643 |
T1641 |
relcl |
added,primers |
R1019 |
T1644 |
T1645 |
amod |
external,sites |
R1020 |
T1645 |
T1643 |
dobj |
sites,added |
R1021 |
T1646 |
T1645 |
nmod |
BamHI,sites |
R1022 |
T1647 |
T1646 |
cc |
and,BamHI |
R1023 |
T1648 |
T1646 |
conj |
NotI,BamHI |
R1024 |
T1649 |
T1643 |
prep |
to,added |
R1025 |
T1650 |
T1651 |
det |
the,end |
R1026 |
T1651 |
T1649 |
pobj |
end,to |
R1027 |
T1652 |
T1651 |
nummod |
5,end |
R1028 |
T1653 |
T1652 |
punct |
′,5 |
R1029 |
T1654 |
T1643 |
cc |
and,added |
R1030 |
T1655 |
T1656 |
det |
a,site |
R1031 |
T1656 |
T1643 |
conj |
site,added |
R1032 |
T1657 |
T1656 |
compound |
BamHI,site |
R1033 |
T1658 |
T1656 |
prep |
to,site |
R1034 |
T1659 |
T1660 |
det |
the,end |
R1035 |
T1660 |
T1658 |
pobj |
end,to |
R1036 |
T1661 |
T1660 |
nummod |
3,end |
R1037 |
T1662 |
T1661 |
punct |
′,3 |
R1038 |
T1663 |
T1622 |
punct |
", ",began |
R1039 |
T1664 |
T1665 |
mark |
while,destroying |
R1040 |
T1665 |
T1622 |
advcl |
destroying,began |
R1041 |
T1666 |
T1667 |
nmod |
XhoI,sites |
R1042 |
T1667 |
T1665 |
dobj |
sites,destroying |
R1043 |
T1668 |
T1666 |
cc |
and,XhoI |
R1044 |
T1669 |
T1666 |
conj |
BamHI,XhoI |
R1045 |
T1670 |
T1667 |
prep |
within,sites |
R1046 |
T1671 |
T1672 |
det |
the,promoter |
R1047 |
T1672 |
T1670 |
pobj |
promoter,within |
R1048 |
T1673 |
T1674 |
punct |
(,CCG |
R1049 |
T1674 |
T1665 |
parataxis |
CCG,destroying |
R1050 |
T1675 |
T1676 |
dep |
forward,C |
R1051 |
T1676 |
T1674 |
dep |
C,CCG |
R1052 |
T1677 |
T1676 |
punct |
: ,C |
R1053 |
T1678 |
T1676 |
compound |
GCC,C |
R1054 |
T1679 |
T1676 |
compound |
GGA,C |
R1055 |
T1680 |
T1676 |
compound |
TCC,C |
R1056 |
T1681 |
T1676 |
compound |
GCG,C |
R1057 |
T1682 |
T1676 |
compound |
GCC,C |
R1058 |
T1683 |
T1676 |
compound |
GCC,C |
R1059 |
T1684 |
T1676 |
compound |
GTC,C |
R1060 |
T1685 |
T1676 |
compound |
GAG,C |
R1061 |
T1686 |
T1676 |
compound |
TTT,C |
R1062 |
T1687 |
T1676 |
compound |
ACC,C |
R1063 |
T1688 |
T1676 |
compound |
ACT,C |
R1064 |
T1689 |
T1676 |
compound |
CCC,C |
R1065 |
T1690 |
T1676 |
compound |
TAT,C |
R1066 |
T1691 |
T1674 |
punct |
;,CCG |
R1067 |
T1692 |
T1674 |
dep |
reverse,CCG |
R1068 |
T1693 |
T1674 |
punct |
: ,CCG |
R1069 |
T1694 |
T1674 |
compound |
GCC,CCG |
R1070 |
T1695 |
T1674 |
compound |
GGA,CCG |
R1071 |
T1696 |
T1674 |
compound |
TCC,CCG |
R1072 |
T1697 |
T1674 |
compound |
ACT,CCG |
R1073 |
T1698 |
T1674 |
compound |
CTA,CCG |
R1074 |
T1699 |
T1674 |
compound |
GAA,CCG |
R1075 |
T1700 |
T1674 |
compound |
GAT,CCG |
R1076 |
T1701 |
T1674 |
compound |
CCC,CCG |
R1077 |
T1702 |
T1674 |
compound |
CGG,CCG |
R1078 |
T1703 |
T1674 |
compound |
GTA,CCG |
R1079 |
T1704 |
T1674 |
punct |
),CCG |
R1080 |
T1705 |
T1622 |
punct |
.,began |
R1081 |
T1707 |
T1708 |
nsubj |
We,isolated |
R1082 |
T1709 |
T1708 |
advmod |
then,isolated |
R1083 |
T1710 |
T1711 |
det |
the,intron |
R1084 |
T1711 |
T1708 |
dobj |
intron,isolated |
R1085 |
T1712 |
T1711 |
compound |
moPrP.XhoI,intron |
R1086 |
T1713 |
T1708 |
prep |
by,isolated |
R1087 |
T1714 |
T1713 |
pobj |
amplification,by |
R1088 |
T1715 |
T1714 |
prep |
with,amplification |
R1089 |
T1716 |
T1715 |
pobj |
primers,with |
R1090 |
T1717 |
T1718 |
dep |
that,added |
R1091 |
T1718 |
T1716 |
relcl |
added,primers |
R1092 |
T1719 |
T1720 |
det |
an,site |
R1093 |
T1720 |
T1718 |
dobj |
site,added |
R1094 |
T1721 |
T1720 |
amod |
external,site |
R1095 |
T1722 |
T1720 |
compound |
BamHI,site |
R1096 |
T1723 |
T1718 |
prep |
to,added |
R1097 |
T1724 |
T1725 |
det |
the,end |
R1098 |
T1725 |
T1723 |
pobj |
end,to |
R1099 |
T1726 |
T1725 |
nummod |
5,end |
R1100 |
T1727 |
T1726 |
punct |
′,5 |
R1101 |
T1728 |
T1725 |
prep |
of,end |
R1102 |
T1729 |
T1728 |
pobj |
exon,of |
R1103 |
T1730 |
T1729 |
nummod |
1,exon |
R1104 |
T1731 |
T1718 |
cc |
and,added |
R1105 |
T1732 |
T1718 |
conj |
ran,added |
R1106 |
T1733 |
T1732 |
prep |
through,ran |
R1107 |
T1734 |
T1735 |
det |
the,site |
R1108 |
T1735 |
T1733 |
pobj |
site,through |
R1109 |
T1736 |
T1735 |
compound |
Asp718,site |
R1110 |
T1737 |
T1735 |
prep |
of,site |
R1111 |
T1738 |
T1737 |
pobj |
exon,of |
R1112 |
T1739 |
T1738 |
nummod |
2,exon |
R1113 |
T1740 |
T1741 |
punct |
(,TGC |
R1114 |
T1741 |
T1735 |
parataxis |
TGC,site |
R1115 |
T1742 |
T1743 |
dep |
forward,GG |
R1116 |
T1743 |
T1741 |
dep |
GG,TGC |
R1117 |
T1744 |
T1743 |
punct |
: ,GG |
R1118 |
T1745 |
T1743 |
compound |
GCC,GG |
R1119 |
T1746 |
T1743 |
compound |
GGA,GG |
R1120 |
T1747 |
T1743 |
compound |
TCC,GG |
R1121 |
T1748 |
T1743 |
compound |
GAT,GG |
R1122 |
T1749 |
T1743 |
compound |
CAG,GG |
R1123 |
T1750 |
T1743 |
compound |
CAG,GG |
R1124 |
T1751 |
T1743 |
compound |
ACC,GG |
R1125 |
T1752 |
T1743 |
compound |
GAT,GG |
R1126 |
T1753 |
T1743 |
compound |
TCT,GG |
R1127 |
T1754 |
T1741 |
punct |
;,TGC |
R1128 |
T1755 |
T1741 |
dep |
reverse,TGC |
R1129 |
T1756 |
T1741 |
punct |
: ,TGC |
R1130 |
T1757 |
T1741 |
compound |
GCC,TGC |
R1131 |
T1758 |
T1741 |
compound |
GGT,TGC |
R1132 |
T1759 |
T1741 |
compound |
ACC,TGC |
R1133 |
T1760 |
T1741 |
compound |
ACT,TGC |
R1134 |
T1761 |
T1741 |
compound |
AGG,TGC |
R1135 |
T1762 |
T1741 |
compound |
AAG,TGC |
R1136 |
T1763 |
T1741 |
compound |
GCA,TGC |
R1137 |
T1764 |
T1741 |
compound |
GAA,TGC |
R1138 |
T1765 |
T1741 |
punct |
),TGC |
R1139 |
T1766 |
T1708 |
punct |
.,isolated |
R1140 |
T1768 |
T1769 |
det |
This,fragment |
R1142 |
T1770 |
T1771 |
nummod |
2,kb |
R1143 |
T1771 |
T1769 |
compound |
kb,fragment |
R1144 |
T1772 |
T1771 |
punct |
-,kb |
R1145 |
T1773 |
T1769 |
compound |
intron,fragment |
R1146 |
T1775 |
T1774 |
aux |
was,cloned |
R1147 |
T1776 |
T1774 |
prep |
into,cloned |
R1148 |
T1777 |
T1778 |
det |
a,vector |
R1149 |
T1778 |
T1776 |
pobj |
vector,into |
R1150 |
T1779 |
T1780 |
compound |
TA,cloning |
R1151 |
T1780 |
T1778 |
compound |
cloning,vector |
R1152 |
T1781 |
T1782 |
punct |
(,Invitrogen |
R1153 |
T1782 |
T1778 |
parataxis |
Invitrogen,vector |
R1154 |
T1783 |
T1782 |
punct |
", ",Invitrogen |
R1155 |
T1784 |
T1782 |
npadvmod |
Carlsbad,Invitrogen |
R1156 |
T1785 |
T1782 |
punct |
", ",Invitrogen |
R1157 |
T1786 |
T1782 |
npadvmod |
California,Invitrogen |
R1158 |
T1787 |
T1782 |
punct |
", ",Invitrogen |
R1159 |
T1788 |
T1789 |
compound |
United,States |
R1160 |
T1789 |
T1782 |
npadvmod |
States,Invitrogen |
R1161 |
T1790 |
T1782 |
punct |
),Invitrogen |
R1162 |
T1791 |
T1774 |
punct |
", ",cloned |
R1163 |
T1792 |
T1793 |
advmod |
then,excised |
R1164 |
T1793 |
T1774 |
conj |
excised,cloned |
R1165 |
T1794 |
T1793 |
prep |
by,excised |
R1166 |
T1795 |
T1796 |
compound |
Asp718,digestion |
R1167 |
T1796 |
T1794 |
pobj |
digestion,by |
R1168 |
T1797 |
T1793 |
cc |
and,excised |
R1169 |
T1798 |
T1793 |
conj |
ligated,excised |
R1170 |
T1799 |
T1798 |
prep |
to,ligated |
R1171 |
T1800 |
T1801 |
det |
the,fragment |
R1173 |
T1802 |
T1803 |
nummod |
6.8,kb |
R1174 |
T1803 |
T1801 |
compound |
kb,fragment |
R1175 |
T1804 |
T1803 |
punct |
-,kb |
R1176 |
T1805 |
T1801 |
compound |
Asp718,fragment |
R1177 |
T1806 |
T1801 |
prep |
of,fragment |
R1178 |
T1807 |
T1806 |
pobj |
moPrP.XhoI,of |
R1179 |
T1808 |
T1801 |
acl |
containing,fragment |
R1180 |
T1809 |
T1808 |
dobj |
exon,containing |
R1181 |
T1810 |
T1809 |
nummod |
2,exon |
R1182 |
T1811 |
T1809 |
punct |
", ",exon |
R1183 |
T1812 |
T1809 |
conj |
exon,exon |
R1184 |
T1813 |
T1812 |
nummod |
3,exon |
R1185 |
T1814 |
T1812 |
punct |
", ",exon |
R1186 |
T1815 |
T1816 |
det |
the,UTR |
R1187 |
T1816 |
T1812 |
conj |
UTR,exon |
R1188 |
T1817 |
T1816 |
nummod |
3,UTR |
R1189 |
T1818 |
T1817 |
punct |
′,3 |
R1190 |
T1819 |
T1816 |
punct |
", ",UTR |
R1191 |
T1820 |
T1816 |
cc |
and,UTR |
R1192 |
T1821 |
T1816 |
conj |
pBluescript,UTR |
R1193 |
T1822 |
T1823 |
aux |
to,generate |
R1194 |
T1823 |
T1774 |
advcl |
generate,cloned |
R1195 |
T1824 |
T1825 |
det |
an,vector |
R1196 |
T1825 |
T1823 |
dobj |
vector,generate |
R1197 |
T1826 |
T1825 |
amod |
intermediate,vector |
R1198 |
T1827 |
T1823 |
prep |
with,generate |
R1199 |
T1828 |
T1829 |
det |
all,exons |
R1200 |
T1829 |
T1827 |
pobj |
exons,with |
R1201 |
T1830 |
T1829 |
nummod |
three,exons |
R1202 |
T1831 |
T1829 |
cc |
and,exons |
R1203 |
T1832 |
T1833 |
det |
a,intron |
R1204 |
T1833 |
T1829 |
conj |
intron,exons |
R1205 |
T1834 |
T1833 |
amod |
central,intron |
R1206 |
T1835 |
T1829 |
cc |
but,exons |
R1207 |
T1836 |
T1837 |
det |
no,promoter |
R1208 |
T1837 |
T1829 |
conj |
promoter,exons |
R1209 |
T1838 |
T1774 |
punct |
.,cloned |
R1210 |
T1840 |
T1841 |
det |
This,vector |
R1211 |
T1841 |
T1842 |
nsubjpass |
vector,opened |
R1212 |
T1843 |
T1842 |
auxpass |
was,opened |
R1213 |
T1844 |
T1842 |
advmod |
then,opened |
R1214 |
T1845 |
T1842 |
prep |
at,opened |
R1215 |
T1846 |
T1847 |
det |
the,site |
R1216 |
T1847 |
T1845 |
pobj |
site,at |
R1217 |
T1848 |
T1847 |
compound |
BamHI,site |
R1218 |
T1849 |
T1847 |
acl |
introduced,site |
R1219 |
T1850 |
T1849 |
agent |
by,introduced |
R1220 |
T1851 |
T1852 |
det |
the,primer |
R1221 |
T1852 |
T1850 |
pobj |
primer,by |
R1222 |
T1853 |
T1852 |
compound |
intron,primer |
R1223 |
T1854 |
T1852 |
compound |
cloning,primer |
R1224 |
T1855 |
T1842 |
punct |
", ",opened |
R1225 |
T1856 |
T1842 |
cc |
and,opened |
R1226 |
T1857 |
T1842 |
conj |
ligated,opened |
R1227 |
T1858 |
T1857 |
prep |
to,ligated |
R1228 |
T1859 |
T1860 |
det |
the,fragment |
R1229 |
T1860 |
T1858 |
pobj |
fragment,to |
R1230 |
T1861 |
T1862 |
nummod |
0.5,kb |
R1231 |
T1862 |
T1860 |
compound |
kb,fragment |
R1232 |
T1863 |
T1862 |
punct |
-,kb |
R1233 |
T1864 |
T1865 |
compound |
BamHI,cut |
R1234 |
T1865 |
T1860 |
compound |
cut,fragment |
R1235 |
T1866 |
T1865 |
punct |
-,cut |
R1236 |
T1867 |
T1868 |
compound |
tetracycline,promoter |
R1237 |
T1868 |
T1860 |
compound |
promoter,fragment |
R1238 |
T1869 |
T1842 |
punct |
.,opened |
R1239 |
T1871 |
T1872 |
det |
This,ligation |
R1240 |
T1872 |
T1873 |
nsubj |
ligation,generated |
R1241 |
T1874 |
T1875 |
det |
a,vector |
R1242 |
T1875 |
T1873 |
dobj |
vector,generated |
R1243 |
T1876 |
T1877 |
nummod |
9.3,kb |
R1244 |
T1877 |
T1875 |
compound |
kb,vector |
R1245 |
T1878 |
T1877 |
punct |
-,kb |
R1246 |
T1879 |
T1875 |
acl |
encoding,vector |
R1247 |
T1880 |
T1881 |
det |
the,promoter |
R1248 |
T1881 |
T1879 |
dobj |
promoter,encoding |
R1249 |
T1882 |
T1881 |
compound |
tetracycline,promoter |
R1250 |
T1883 |
T1881 |
prep |
from,promoter |
R1251 |
T1884 |
T1883 |
pobj |
pTetSplice,from |
R1252 |
T1885 |
T1879 |
prep |
with,encoding |
R1253 |
T1886 |
T1887 |
nummod |
two,exons |
R1254 |
T1887 |
T1885 |
pobj |
exons,with |
R1255 |
T1888 |
T1887 |
punct |
", ",exons |
R1256 |
T1889 |
T1890 |
nummod |
one,intron |
R1257 |
T1890 |
T1887 |
conj |
intron,exons |
R1258 |
T1891 |
T1890 |
punct |
", ",intron |
R1259 |
T1892 |
T1890 |
cc |
and,intron |
R1260 |
T1893 |
T1894 |
det |
the,UTR |
R1261 |
T1894 |
T1890 |
conj |
UTR,intron |
R1262 |
T1895 |
T1894 |
amod |
original,UTR |
R1263 |
T1896 |
T1894 |
nummod |
3,UTR |
R1264 |
T1897 |
T1896 |
punct |
′,3 |
R1265 |
T1898 |
T1894 |
prep |
of,UTR |
R1266 |
T1899 |
T1900 |
det |
the,vector |
R1267 |
T1900 |
T1898 |
pobj |
vector,of |
R1268 |
T1901 |
T1900 |
compound |
moPrP.XhoI,vector |
R1269 |
T1902 |
T1887 |
punct |
", ",exons |
R1270 |
T1903 |
T1904 |
advmod |
all,carried |
R1271 |
T1904 |
T1887 |
acl |
carried,exons |
R1272 |
T1905 |
T1904 |
prep |
in,carried |
R1273 |
T1906 |
T1907 |
det |
the,vector |
R1274 |
T1907 |
T1905 |
pobj |
vector,in |
R1275 |
T1908 |
T1909 |
compound |
pBluescript,cloning |
R1276 |
T1909 |
T1907 |
compound |
cloning,vector |
R1277 |
T1910 |
T1873 |
punct |
.,generated |
R1278 |
T1912 |
T1913 |
nsubj |
We,incorporated |
R1279 |
T1913 |
T1914 |
ccomp |
incorporated,generated |
R1280 |
T1915 |
T1916 |
det |
the,mutations |
R1281 |
T1916 |
T1913 |
dobj |
mutations,incorporated |
R1282 |
T1917 |
T1916 |
amod |
Swedish,mutations |
R1283 |
T1918 |
T1919 |
punct |
(,571NL |
R1284 |
T1919 |
T1917 |
parataxis |
571NL,Swedish |
R1285 |
T1920 |
T1919 |
compound |
KM570,571NL |
R1286 |
T1921 |
T1919 |
punct |
/,571NL |
R1287 |
T1922 |
T1919 |
punct |
),571NL |
R1288 |
T1923 |
T1917 |
cc |
and,Swedish |
R1289 |
T1924 |
T1917 |
conj |
Indiana,Swedish |
R1290 |
T1925 |
T1926 |
punct |
(,V617F |
R1291 |
T1926 |
T1924 |
parataxis |
V617F,Indiana |
R1292 |
T1927 |
T1926 |
punct |
),V617F |
R1293 |
T1928 |
T1913 |
prep |
into,incorporated |
R1294 |
T1929 |
T1930 |
det |
the,cDNA |
R1295 |
T1930 |
T1928 |
pobj |
cDNA,into |
R1296 |
T1931 |
T1932 |
compound |
mo,huAPP695 |
R1297 |
T1932 |
T1930 |
compound |
huAPP695,cDNA |
R1298 |
T1933 |
T1932 |
punct |
/,huAPP695 |
R1299 |
T1934 |
T1930 |
punct |
(,cDNA |
R1300 |
T1935 |
T1930 |
prep |
in,cDNA |
R1301 |
T1936 |
T1937 |
compound |
BS,KS |
R1302 |
T1937 |
T1935 |
pobj |
KS,in |
R1303 |
T1938 |
T1937 |
punct |
-,KS |
R1304 |
T1939 |
T1913 |
punct |
),incorporated |
R1305 |
T1940 |
T1913 |
prep |
by,incorporated |
R1306 |
T1941 |
T1940 |
pobj |
PCR,by |
R1307 |
T1942 |
T1913 |
advcl |
using,incorporated |
R1308 |
T1943 |
T1944 |
det |
a,strategy |
R1309 |
T1944 |
T1942 |
dobj |
strategy,using |
R1310 |
T1945 |
T1946 |
nummod |
four,primer |
R1311 |
T1946 |
T1944 |
compound |
primer,strategy |
R1312 |
T1947 |
T1946 |
punct |
-,primer |
R1313 |
T1948 |
T1914 |
punct |
: ,generated |
R1314 |
T1949 |
T1914 |
advmod |
first,generated |
R1315 |
T1950 |
T1914 |
punct |
", ",generated |
R1316 |
T1951 |
T1952 |
nummod |
two,products |
R1317 |
T1952 |
T1914 |
nsubjpass |
products,generated |
R1318 |
T1953 |
T1954 |
advmod |
partially,overlapping |
R1319 |
T1954 |
T1952 |
amod |
overlapping,products |
R1320 |
T1955 |
T1914 |
auxpass |
were,generated |
R1321 |
T1956 |
T1914 |
prep |
in,generated |
R1322 |
T1957 |
T1958 |
amod |
separate,reactions |
R1323 |
T1958 |
T1956 |
pobj |
reactions,in |
R1324 |
T1959 |
T1914 |
advcl |
using,generated |
R1325 |
T1960 |
T1959 |
dobj |
primers,using |
R1326 |
T1961 |
T1962 |
dep |
that,encode |
R1327 |
T1962 |
T1960 |
relcl |
encode,primers |
R1328 |
T1963 |
T1964 |
det |
the,mutations |
R1329 |
T1964 |
T1962 |
dobj |
mutations,encode |
R1330 |
T1965 |
T1964 |
amod |
desired,mutations |
R1331 |
T1966 |
T1967 |
punct |
(,M13 |
R1332 |
T1967 |
T1962 |
parataxis |
M13,encode |
R1333 |
T1968 |
T1969 |
compound |
Swedish,forward |
R1334 |
T1969 |
T1970 |
dep |
forward,CCG |
R1335 |
T1970 |
T1983 |
dep |
CCG,C |
R1336 |
T1971 |
T1970 |
punct |
: ,CCG |
R1337 |
T1972 |
T1970 |
compound |
GGA,CCG |
R1338 |
T1973 |
T1970 |
compound |
GAT,CCG |
R1339 |
T1974 |
T1970 |
compound |
CTC,CCG |
R1340 |
T1975 |
T1970 |
compound |
TGA,CCG |
R1341 |
T1976 |
T1970 |
compound |
AGT,CCG |
R1342 |
T1977 |
T1970 |
compound |
GAA,CCG |
R1343 |
T1978 |
T1970 |
compound |
TCT,CCG |
R1344 |
T1979 |
T1970 |
compound |
GGA,CCG |
R1345 |
T1980 |
T1970 |
compound |
TGC,CCG |
R1346 |
T1981 |
T1970 |
compound |
AGA,CCG |
R1347 |
T1982 |
T1970 |
compound |
ATT,CCG |
R1348 |
T1983 |
T1967 |
dep |
C,M13 |
R1349 |
T1984 |
T1983 |
punct |
/,C |
R1350 |
T1985 |
T1986 |
compound |
Indiana,reverse |
R1351 |
T1986 |
T1983 |
dep |
reverse,C |
R1352 |
T1987 |
T1983 |
punct |
: ,C |
R1353 |
T1988 |
T1983 |
compound |
GGG,C |
R1354 |
T1989 |
T1983 |
compound |
TGA,C |
R1355 |
T1990 |
T1983 |
compound |
TGA,C |
R1356 |
T1991 |
T1983 |
compound |
AAA,C |
R1357 |
T1992 |
T1983 |
compound |
TCA,C |
R1358 |
T1993 |
T1983 |
compound |
CGG,C |
R1359 |
T1994 |
T1983 |
compound |
TTG,C |
R1360 |
T1995 |
T1967 |
punct |
;,M13 |
R1361 |
T1996 |
T1997 |
compound |
Indiana,forward |
R1362 |
T1997 |
T1967 |
dep |
forward,M13 |
R1363 |
T1998 |
T1967 |
punct |
: ,M13 |
R1364 |
T1999 |
T1967 |
compound |
CAA,M13 |
R1365 |
T2000 |
T1967 |
compound |
CCG,M13 |
R1366 |
T2001 |
T1967 |
compound |
TGA,M13 |
R1367 |
T2002 |
T1967 |
compound |
TTT,M13 |
R1368 |
T2003 |
T1967 |
compound |
TCA,M13 |
R1369 |
T2004 |
T1967 |
compound |
TCA,M13 |
R1370 |
T2005 |
T1967 |
compound |
CCC,M13 |
R1371 |
T2006 |
T1967 |
compound |
TGG,M13 |
R1372 |
T2007 |
T1967 |
punct |
/,M13 |
R1373 |
T2008 |
T1967 |
advmod |
reverse,M13 |
R1374 |
T2009 |
T1967 |
punct |
),M13 |
R1375 |
T2010 |
T1914 |
punct |
.,generated |
R1376 |
T2012 |
T2013 |
det |
The,products |
R1377 |
T2013 |
T2016 |
nsubjpass |
products,ligated |
R1378 |
T2014 |
T2013 |
nummod |
two,products |
R1379 |
T2015 |
T2013 |
compound |
PCR,products |
R1380 |
T2017 |
T2016 |
auxpass |
were,ligated |
R1381 |
T2018 |
T2016 |
punct |
", ",ligated |
R1382 |
T2019 |
T2016 |
dep |
digested,ligated |
R1383 |
T2020 |
T2016 |
prep |
with,ligated |
R1384 |
T2021 |
T2020 |
pobj |
BglII,with |
R1385 |
T2022 |
T2021 |
cc |
and,BglII |
R1386 |
T2023 |
T2021 |
conj |
ApaI,BglII |
R1387 |
T2024 |
T2016 |
cc |
and,ligated |
R1388 |
T2025 |
T2016 |
conj |
cloned,ligated |
R1389 |
T2026 |
T2025 |
advmod |
back,cloned |
R1390 |
T2027 |
T2025 |
prep |
into,cloned |
R1391 |
T2028 |
T2029 |
det |
the,vector |
R1392 |
T2029 |
T2027 |
pobj |
vector,into |
R1393 |
T2030 |
T2029 |
amod |
original,vector |
R1394 |
T2031 |
T2032 |
compound |
mo,KS |
R1396 |
T2033 |
T2032 |
punct |
/,KS |
R1397 |
T2034 |
T2032 |
compound |
huAPP695,KS |
R1398 |
T2035 |
T2032 |
punct |
-,KS |
R1399 |
T2036 |
T2032 |
compound |
BS,KS |
R1400 |
T2037 |
T2032 |
punct |
-,KS |
R1401 |
T2038 |
T2016 |
punct |
.,ligated |
R1402 |
T2040 |
T2041 |
advmod |
Finally,subcloned |
R1403 |
T2042 |
T2041 |
punct |
", ",subcloned |
R1404 |
T2043 |
T2044 |
det |
the,ind |
R1405 |
T2044 |
T2041 |
nsubjpass |
ind,subcloned |
R1406 |
T2045 |
T2044 |
amod |
new,ind |
R1407 |
T2046 |
T2044 |
compound |
APP695swe,ind |
R1408 |
T2047 |
T2044 |
punct |
/,ind |
R1409 |
T2048 |
T2041 |
auxpass |
was,subcloned |
R1410 |
T2049 |
T2041 |
prep |
into,subcloned |
R1411 |
T2050 |
T2051 |
det |
the,site |
R1412 |
T2051 |
T2049 |
pobj |
site,into |
R1413 |
T2052 |
T2051 |
compound |
XhoI,site |
R1414 |
T2053 |
T2051 |
prep |
of,site |
R1415 |
T2054 |
T2055 |
det |
the,vector |
R1416 |
T2055 |
T2053 |
pobj |
vector,of |
R1417 |
T2056 |
T2057 |
compound |
moPrP,tetP |
R1418 |
T2057 |
T2055 |
compound |
tetP,vector |
R1419 |
T2058 |
T2057 |
punct |
-,tetP |
R1420 |
T2059 |
T2041 |
prep |
from,subcloned |
R1421 |
T2060 |
T2059 |
pcomp |
above,from |
R1422 |
T2061 |
T2062 |
aux |
to,complete |
R1423 |
T2062 |
T2041 |
advcl |
complete,subcloned |
R1424 |
T2063 |
T2064 |
det |
the,construct |
R1425 |
T2064 |
T2062 |
dobj |
construct,complete |
R1426 |
T2065 |
T2041 |
punct |
.,subcloned |
R3744 |
T5349 |
T5347 |
pobj |
mice,in |
R3745 |
T5350 |
T5351 |
nmod |
CaMKIIα,ind |
R3746 |
T5351 |
T5349 |
nmod |
ind,mice |
R3747 |
T5352 |
T5351 |
punct |
-,ind |
R3748 |
T5353 |
T5351 |
nmod |
tTA,ind |
R3749 |
T5354 |
T5351 |
punct |
×,ind |
R3750 |
T5355 |
T5351 |
nmod |
tet,ind |
R3751 |
T5356 |
T5351 |
punct |
-,ind |
R3752 |
T5357 |
T5351 |
nmod |
APPswe,ind |
R3753 |
T5358 |
T5351 |
punct |
/,ind |
R3754 |
T5359 |
T5349 |
nmod |
line,mice |
R3755 |
T5360 |
T5359 |
nummod |
107,line |
R3756 |
T5361 |
T5362 |
quantmod |
between,4 |
R3757 |
T5362 |
T5363 |
nummod |
4,mo |
R3758 |
T5363 |
T5349 |
npadvmod |
mo,mice |
R3759 |
T5364 |
T5362 |
cc |
and,4 |
R3760 |
T5365 |
T5362 |
conj |
5,4 |
R3761 |
T5366 |
T5363 |
prep |
of,mo |
R3762 |
T5367 |
T5366 |
pobj |
age,of |
R3763 |
T5368 |
T5345 |
punct |
.,studied |
R3764 |
T5370 |
T5371 |
nsubjpass |
Animals,separated |
R3765 |
T5372 |
T5371 |
auxpass |
were,separated |
R3766 |
T5373 |
T5371 |
prep |
into,separated |
R3767 |
T5374 |
T5375 |
amod |
individual,cages |
R3768 |
T5375 |
T5373 |
pobj |
cages,into |
R3769 |
T5376 |
T5377 |
advmod |
immediately,before |
R3770 |
T5377 |
T5371 |
prep |
before,separated |
R3771 |
T5378 |
T5379 |
det |
the,start |
R3772 |
T5379 |
T5377 |
pobj |
start,before |
R3773 |
T5380 |
T5379 |
prep |
of,start |
R3774 |
T5381 |
T5382 |
det |
each,experiment |
R3775 |
T5382 |
T5380 |
pobj |
experiment,of |
R3776 |
T5383 |
T5384 |
punct |
(,6 |
R3777 |
T5384 |
T5371 |
parataxis |
6,separated |
R3778 |
T5385 |
T5384 |
nsubj |
n,6 |
R3779 |
T5386 |
T5384 |
punct |
=,6 |
R3780 |
T5387 |
T5384 |
quantmod |
3,6 |
R3781 |
T5388 |
T5384 |
punct |
–,6 |
R3782 |
T5389 |
T5384 |
prep |
per,6 |
R3783 |
T5390 |
T5389 |
pobj |
genotype,per |
R3784 |
T5391 |
T5390 |
amod |
untreated,genotype |
R3785 |
T5392 |
T5384 |
punct |
", ",6 |
R3786 |
T5393 |
T5394 |
quantmod |
2,5 |
R3787 |
T5394 |
T5384 |
appos |
5,6 |
R3788 |
T5395 |
T5394 |
punct |
–,5 |
R3789 |
T5396 |
T5394 |
prep |
per,5 |
R3790 |
T5397 |
T5396 |
pobj |
genotype,per |
R3791 |
T5398 |
T5399 |
dep |
dox,reared |
R3792 |
T5399 |
T5397 |
acl |
reared,genotype |
R3793 |
T5400 |
T5399 |
punct |
-,reared |
R3794 |
T5401 |
T5384 |
punct |
),6 |
R3795 |
T5402 |
T5371 |
punct |
.,separated |
R3796 |
T5404 |
T5405 |
det |
The,cages |
R3797 |
T5405 |
T5406 |
nsubjpass |
cages,placed |
R3798 |
T5407 |
T5406 |
auxpass |
were,placed |
R3799 |
T5408 |
T5406 |
prep |
inside,placed |
R3800 |
T5409 |
T5410 |
npadvmod |
activity,monitoring |
R3801 |
T5410 |
T5412 |
amod |
monitoring,frames |
R3802 |
T5411 |
T5410 |
punct |
-,monitoring |
R3803 |
T5412 |
T5408 |
pobj |
frames,inside |
R3804 |
T5413 |
T5412 |
acl |
designed,frames |
R3805 |
T5414 |
T5415 |
aux |
to,count |
R3806 |
T5415 |
T5413 |
advcl |
count,designed |
R3807 |
T5416 |
T5417 |
det |
every,time |
R3808 |
T5417 |
T5415 |
dobj |
time,count |
R3809 |
T5418 |
T5419 |
det |
the,animal |
R3810 |
T5419 |
T5420 |
nsubj |
animal,passed |
R3811 |
T5420 |
T5417 |
advcl |
passed,time |
R3812 |
T5421 |
T5420 |
prep |
through,passed |
R3813 |
T5422 |
T5421 |
pobj |
one,through |
R3814 |
T5423 |
T5422 |
prep |
of,one |
R3815 |
T5424 |
T5425 |
nummod |
three,photobeams |
R3816 |
T5425 |
T5423 |
pobj |
photobeams,of |
R3817 |
T5426 |
T5425 |
acl |
spanning,photobeams |
R3818 |
T5427 |
T5428 |
det |
the,width |
R3819 |
T5428 |
T5426 |
dobj |
width,spanning |
R3820 |
T5429 |
T5428 |
prep |
of,width |
R3821 |
T5430 |
T5431 |
det |
the,cage |
R3822 |
T5431 |
T5429 |
pobj |
cage,of |
R3823 |
T5432 |
T5433 |
punct |
(,Instruments |
R3824 |
T5433 |
T5420 |
parataxis |
Instruments,passed |
R3825 |
T5434 |
T5435 |
compound |
San,Diego |
R3826 |
T5435 |
T5433 |
compound |
Diego,Instruments |
R3827 |
T5436 |
T5433 |
punct |
", ",Instruments |
R3828 |
T5437 |
T5438 |
compound |
San,Diego |
R3829 |
T5438 |
T5433 |
npadvmod |
Diego,Instruments |
R3830 |
T5439 |
T5433 |
punct |
", ",Instruments |
R3831 |
T5440 |
T5433 |
npadvmod |
California,Instruments |
R3832 |
T5441 |
T5433 |
punct |
", ",Instruments |
R3833 |
T5442 |
T5443 |
compound |
United,States |
R3834 |
T5443 |
T5433 |
npadvmod |
States,Instruments |
R3835 |
T5444 |
T5433 |
punct |
),Instruments |
R3836 |
T5445 |
T5406 |
punct |
.,placed |
R3837 |
T5447 |
T5448 |
nsubjpass |
Experiments,started |
R3838 |
T5449 |
T5448 |
auxpass |
were,started |
R3839 |
T5450 |
T5451 |
advmod |
midway,through |
R3840 |
T5451 |
T5448 |
prep |
through,started |
R3841 |
T5452 |
T5453 |
det |
the,phase |
R3842 |
T5453 |
T5451 |
pobj |
phase,through |
R3843 |
T5454 |
T5453 |
compound |
light,phase |
R3844 |
T5455 |
T5453 |
prep |
of,phase |
R3845 |
T5456 |
T5457 |
det |
the,day |
R3846 |
T5457 |
T5455 |
pobj |
day,of |
R3847 |
T5458 |
T5448 |
punct |
", ",started |
R3848 |
T5459 |
T5448 |
cc |
and,started |
R3849 |
T5460 |
T5461 |
nsubjpass |
data,collected |
R3850 |
T5461 |
T5448 |
conj |
collected,started |
R3851 |
T5462 |
T5461 |
auxpass |
were,collected |
R3852 |
T5463 |
T5461 |
prep |
in,collected |
R3853 |
T5464 |
T5465 |
nummod |
1,h |
R3854 |
T5465 |
T5467 |
compound |
h,bins |
R3855 |
T5466 |
T5465 |
punct |
-,h |
R3856 |
T5467 |
T5463 |
pobj |
bins,in |
R3857 |
T5468 |
T5461 |
prep |
for,collected |
R3858 |
T5469 |
T5470 |
det |
the,h |
R3859 |
T5470 |
T5468 |
pobj |
h,for |
R3860 |
T5471 |
T5470 |
amod |
following,h |
R3861 |
T5472 |
T5470 |
nummod |
48,h |
R3862 |
T5473 |
T5461 |
punct |
.,collected |
R3863 |
T5475 |
T5476 |
compound |
Testing,rooms |
R3864 |
T5476 |
T5477 |
nsubjpass |
rooms,maintained |
R3865 |
T5478 |
T5477 |
auxpass |
were,maintained |
R3866 |
T5479 |
T5477 |
prep |
on,maintained |
R3867 |
T5480 |
T5481 |
det |
the,cycle |
R3868 |
T5481 |
T5479 |
pobj |
cycle,on |
R3869 |
T5482 |
T5481 |
amod |
same,cycle |
R3870 |
T5483 |
T5484 |
nummod |
13,h |
R3871 |
T5484 |
T5481 |
nmod |
h,cycle |
R3872 |
T5485 |
T5486 |
punct |
:,11 |
R3873 |
T5486 |
T5483 |
prep |
11,13 |
R3874 |
T5487 |
T5481 |
nmod |
day,cycle |
R3875 |
T5488 |
T5489 |
punct |
:,night |
R3876 |
T5489 |
T5487 |
prep |
night,day |
R3877 |
T5490 |
T5481 |
prep |
as,cycle |
R3878 |
T5491 |
T5492 |
det |
the,areas |
R3879 |
T5492 |
T5490 |
pobj |
areas,as |
R3880 |
T5493 |
T5492 |
amod |
main,areas |
R3881 |
T5494 |
T5495 |
compound |
animal,housing |
R3882 |
T5495 |
T5492 |
compound |
housing,areas |
R3883 |
T5496 |
T5477 |
cc |
and,maintained |
R3884 |
T5497 |
T5498 |
auxpass |
were,closed |
R3885 |
T5498 |
T5477 |
conj |
closed,maintained |
R3886 |
T5499 |
T5498 |
prep |
to,closed |
R3887 |
T5500 |
T5499 |
pobj |
entry,to |
R3888 |
T5501 |
T5498 |
prep |
during,closed |
R3889 |
T5502 |
T5503 |
det |
the,experiment |
R3890 |
T5503 |
T5501 |
pobj |
experiment,during |
R3891 |
T5504 |
T5477 |
punct |
.,maintained |
R3892 |
T5510 |
T5511 |
amod |
Statistical,Analyses |
R3893 |
T5513 |
T5514 |
amod |
Statistical,analyses |
R3894 |
T5514 |
T5515 |
nsubjpass |
analyses,performed |
R3895 |
T5516 |
T5514 |
prep |
of,analyses |
R3896 |
T5517 |
T5518 |
compound |
protein,expression |
R3897 |
T5518 |
T5516 |
pobj |
expression,of |
R3898 |
T5519 |
T5518 |
punct |
", ",expression |
R3899 |
T5520 |
T5521 |
compound |
ELISA,data |
R3900 |
T5521 |
T5518 |
conj |
data,expression |
R3901 |
T5522 |
T5521 |
punct |
", ",data |
R3902 |
T5523 |
T5521 |
cc |
and,data |
R3903 |
T5524 |
T5525 |
compound |
filter,trap |
R3904 |
T5525 |
T5526 |
compound |
trap,assays |
R3905 |
T5526 |
T5521 |
conj |
assays,data |
R3906 |
T5527 |
T5515 |
auxpass |
were,performed |
R3907 |
T5528 |
T5515 |
prep |
by,performed |
R3908 |
T5529 |
T5528 |
pobj |
ANOVA,by |
R3909 |
T5530 |
T5515 |
prep |
with,performed |
R3910 |
T5531 |
T5532 |
poss |
Tukey,test |
R3911 |
T5532 |
T5530 |
pobj |
test,with |
R3912 |
T5533 |
T5531 |
case |
's,Tukey |
R3913 |
T5534 |
T5532 |
amod |
honest,test |
R3914 |
T5535 |
T5532 |
amod |
significant,test |
R3915 |
T5536 |
T5532 |
nmod |
difference,test |
R3916 |
T5537 |
T5538 |
nmod |
post,hoc |
R3917 |
T5538 |
T5532 |
nmod |
hoc,test |
R3918 |
T5539 |
T5538 |
punct |
-,hoc |
R3919 |
T5540 |
T5532 |
acl |
applied,test |
R3920 |
T5541 |
T5540 |
prep |
to,applied |
R3921 |
T5542 |
T5543 |
amod |
significant,effects |
R3922 |
T5543 |
T5541 |
pobj |
effects,to |
R3923 |
T5544 |
T5543 |
amod |
main,effects |
R3924 |
T5545 |
T5543 |
cc |
or,effects |
R3925 |
T5546 |
T5543 |
conj |
interactions,effects |
R3926 |
T5547 |
T5548 |
punct |
(,Statistica |
R3927 |
T5548 |
T5515 |
parataxis |
Statistica,performed |
R3928 |
T5549 |
T5548 |
nummod |
6.0,Statistica |
R3929 |
T5550 |
T5548 |
punct |
", ",Statistica |
R3930 |
T5551 |
T5548 |
npadvmod |
StatSoft,Statistica |
R3931 |
T5552 |
T5548 |
punct |
", ",Statistica |
R3932 |
T5553 |
T5548 |
npadvmod |
Tulsa,Statistica |
R3933 |
T5554 |
T5548 |
punct |
", ",Statistica |
R3934 |
T5555 |
T5548 |
npadvmod |
Oklahoma,Statistica |
R3935 |
T5556 |
T5548 |
punct |
", ",Statistica |
R3936 |
T5557 |
T5558 |
compound |
United,States |
R3937 |
T5558 |
T5548 |
npadvmod |
States,Statistica |
R3938 |
T5559 |
T5548 |
punct |
),Statistica |
R3939 |
T5560 |
T5515 |
punct |
.,performed |
R3940 |
T5562 |
T5563 |
prep |
In,applied |
R3941 |
T5564 |
T5562 |
pobj |
cases,In |
R3942 |
T5565 |
T5564 |
prep |
of,cases |
R3943 |
T5566 |
T5567 |
advmod |
positively,skewed |
R3944 |
T5567 |
T5568 |
amod |
skewed,distribution |
R3945 |
T5568 |
T5565 |
pobj |
distribution,of |
R3946 |
T5569 |
T5568 |
compound |
data,distribution |
R3947 |
T5570 |
T5563 |
punct |
", ",applied |
R3948 |
T5571 |
T5572 |
nmod |
log10,x |
R3949 |
T5572 |
T5574 |
nmod |
x,transformation |
R3950 |
T5573 |
T5572 |
punct |
(,x |
R3951 |
T5574 |
T5563 |
nsubjpass |
transformation,applied |
R3952 |
T5575 |
T5572 |
punct |
+,x |
R3953 |
T5576 |
T5572 |
nummod |
0.5,x |
R3954 |
T5577 |
T5572 |
punct |
),x |
R3955 |
T5578 |
T5563 |
auxpass |
was,applied |
R3956 |
T5579 |
T5563 |
prep |
to,applied |
R3957 |
T5580 |
T5581 |
det |
the,data |
R3958 |
T5581 |
T5579 |
pobj |
data,to |
R3959 |
T5582 |
T5581 |
amod |
raw,data |
R3960 |
T5583 |
T5563 |
prep |
before,applied |
R3961 |
T5584 |
T5583 |
pcomp |
submitting,before |
R3962 |
T5585 |
T5584 |
dobj |
them,submitting |
R3963 |
T5586 |
T5584 |
prep |
to,submitting |
R3964 |
T5587 |
T5586 |
pobj |
ANOVA,to |
R3965 |
T5588 |
T5563 |
punct |
.,applied |
R3967 |
T6511 |
T6512 |
nsubj |
We,used |
R3968 |
T6513 |
T6514 |
det |
the,system |
R3969 |
T6514 |
T6512 |
dobj |
system,used |
R3970 |
T6515 |
T6516 |
compound |
tet,off |
R3971 |
T6516 |
T6514 |
compound |
off,system |
R3972 |
T6517 |
T6516 |
punct |
-,off |
R3973 |
T6518 |
T6514 |
compound |
transgene,system |
R3974 |
T6519 |
T6520 |
aux |
to,express |
R3975 |
T6520 |
T6512 |
advcl |
express,used |
R3976 |
T6521 |
T6522 |
det |
a,version |
R3977 |
T6522 |
T6520 |
dobj |
version,express |
R3978 |
T6523 |
T6522 |
amod |
double,version |
R3979 |
T6524 |
T6522 |
compound |
mutant,version |
R3980 |
T6525 |
T6522 |
prep |
of,version |
R3981 |
T6526 |
T6527 |
amod |
chimeric,huAPP695 |
R3982 |
T6527 |
T6525 |
pobj |
huAPP695,of |
R3983 |
T6528 |
T6527 |
compound |
mo,huAPP695 |
R3984 |
T6529 |
T6527 |
punct |
/,huAPP695 |
R3985 |
T6530 |
T6522 |
punct |
(,version |
R3986 |
T6531 |
T6532 |
compound |
swe,KM570 |
R3987 |
T6532 |
T6522 |
appos |
KM570,version |
R3988 |
T6533 |
T6532 |
punct |
/,KM570 |
R3989 |
T6534 |
T6532 |
compound |
ind,KM570 |
R3990 |
T6535 |
T6532 |
punct |
", ",KM570 |
R3991 |
T6536 |
T6532 |
conj |
571NL,KM570 |
R3992 |
T6537 |
T6536 |
punct |
", ",571NL |
R3993 |
T6538 |
T6536 |
cc |
and,571NL |
R3994 |
T6539 |
T6536 |
conj |
V617F,571NL |
R3995 |
T6540 |
T6520 |
punct |
),express |
R3996 |
T6541 |
T6520 |
prep |
from,express |
R3997 |
T6542 |
T6543 |
det |
a,promoter |
R3998 |
T6543 |
T6541 |
pobj |
promoter,from |
R3999 |
T6544 |
T6545 |
npadvmod |
tetracycline,responsive |
R4000 |
T6545 |
T6543 |
amod |
responsive,promoter |
R4001 |
T6546 |
T6545 |
punct |
-,responsive |
R4002 |
T6547 |
T6548 |
punct |
[,13 |
R4003 |
T6548 |
T6520 |
parataxis |
13,express |
R4004 |
T6549 |
T6548 |
nummod |
12,13 |
R4005 |
T6550 |
T6548 |
punct |
",",13 |
R4006 |
T6551 |
T6548 |
punct |
],13 |
R4007 |
T6552 |
T6512 |
punct |
.,used |
R4008 |
T6554 |
T6555 |
amod |
Transgenic,APP |
R4009 |
T6555 |
T6556 |
compound |
APP,expression |
R4010 |
T6556 |
T6557 |
nsubjpass |
expression,activated |
R4011 |
T6558 |
T6557 |
auxpass |
was,activated |
R4012 |
T6559 |
T6557 |
prep |
by,activated |
R4013 |
T6560 |
T6559 |
pcomp |
crossing,by |
R4014 |
T6561 |
T6562 |
det |
the,mice |
R4015 |
T6562 |
T6560 |
dobj |
mice,crossing |
R4016 |
T6563 |
T6564 |
compound |
APPswe,ind |
R4017 |
T6564 |
T6562 |
compound |
ind,mice |
R4018 |
T6565 |
T6564 |
punct |
/,ind |
R4019 |
T6566 |
T6560 |
prep |
to,crossing |
R4020 |
T6567 |
T6566 |
pobj |
animals,to |
R4021 |
T6568 |
T6567 |
acl |
producing,animals |
R4022 |
T6569 |
T6568 |
dobj |
tTA,producing |
R4023 |
T6570 |
T6568 |
prep |
under,producing |
R4024 |
T6571 |
T6570 |
pobj |
control,under |
R4025 |
T6572 |
T6571 |
prep |
of,control |
R4026 |
T6573 |
T6574 |
det |
the,promoter |
R4027 |
T6574 |
T6572 |
pobj |
promoter,of |
R4028 |
T6575 |
T6574 |
compound |
CaMKIIα,promoter |
R4029 |
T6576 |
T6577 |
punct |
[,16 |
R4030 |
T6577 |
T6568 |
parataxis |
16,producing |
R4031 |
T6578 |
T6577 |
punct |
],16 |
R4032 |
T6579 |
T6557 |
punct |
.,activated |
R4033 |
T6581 |
T6582 |
prep |
After,identified |
R4034 |
T6583 |
T6584 |
amod |
initial,screening |
R4035 |
T6584 |
T6581 |
pobj |
screening,After |
R4036 |
T6585 |
T6584 |
prep |
of,screening |
R4037 |
T6586 |
T6585 |
pobj |
founders,of |
R4038 |
T6587 |
T6582 |
punct |
", ",identified |
R4039 |
T6588 |
T6582 |
nsubj |
we,identified |
R4040 |
T6589 |
T6590 |
nummod |
four,lines |
R4041 |
T6590 |
T6582 |
dobj |
lines,identified |
R4042 |
T6591 |
T6590 |
prep |
of,lines |
R4043 |
T6592 |
T6593 |
compound |
tet,ind |
R4044 |
T6593 |
T6597 |
compound |
ind,mice |
R4045 |
T6594 |
T6593 |
punct |
-,ind |
R4046 |
T6595 |
T6593 |
compound |
APPswe,ind |
R4047 |
T6596 |
T6593 |
punct |
/,ind |
R4048 |
T6597 |
T6591 |
pobj |
mice,of |
R4049 |
T6598 |
T6599 |
dep |
that,produced |
R4050 |
T6599 |
T6590 |
relcl |
produced,lines |
R4051 |
T6600 |
T6601 |
advmod |
very,high |
R4052 |
T6601 |
T6602 |
amod |
high,levels |
R4053 |
T6602 |
T6599 |
dobj |
levels,produced |
R4054 |
T6603 |
T6602 |
prep |
of,levels |
R4055 |
T6604 |
T6605 |
compound |
transgene,product |
R4056 |
T6605 |
T6603 |
pobj |
product,of |
R4057 |
T6606 |
T6599 |
prep |
in,produced |
R4058 |
T6607 |
T6606 |
pobj |
offspring,in |
R4059 |
T6608 |
T6607 |
acl |
coexpressing,offspring |
R4060 |
T6609 |
T6608 |
dobj |
tTA,coexpressing |
R4061 |
T6610 |
T6611 |
punct |
(,Figures |
R4062 |
T6611 |
T6599 |
parataxis |
Figures,produced |
R4063 |
T6612 |
T6611 |
nummod |
1,Figures |
R4064 |
T6613 |
T6611 |
cc |
and,Figures |
R4065 |
T6614 |
T6615 |
compound |
Figure,S1 |
R4066 |
T6615 |
T6611 |
conj |
S1,Figures |
R4067 |
T6616 |
T6611 |
punct |
),Figures |
R4068 |
T6617 |
T6582 |
punct |
.,identified |
R4069 |
T6619 |
T6620 |
prep |
Compared,estimated |
R4070 |
T6621 |
T6619 |
prep |
to,Compared |
R4071 |
T6622 |
T6623 |
det |
a,line |
R4072 |
T6623 |
T6621 |
pobj |
line,to |
R4073 |
T6624 |
T6623 |
amod |
standard,line |
R4074 |
T6625 |
T6623 |
nmod |
APP,line |
R4075 |
T6626 |
T6623 |
amod |
transgenic,line |
R4076 |
T6627 |
T6623 |
acl |
used,line |
R4077 |
T6628 |
T6627 |
prep |
for,used |
R4078 |
T6629 |
T6630 |
amod |
previous,studies |
R4079 |
T6630 |
T6628 |
pobj |
studies,for |
R4080 |
T6631 |
T6630 |
compound |
amyloid,studies |
R4081 |
T6632 |
T6630 |
prep |
by,studies |
R4082 |
T6633 |
T6634 |
poss |
our,laboratory |
R4083 |
T6634 |
T6632 |
pobj |
laboratory,by |
R4084 |
T6635 |
T6636 |
punct |
(,27 |
R4085 |
T6636 |
T6627 |
parataxis |
27,used |
R4086 |
T6637 |
T6638 |
compound |
line,C3 |
R4087 |
T6638 |
T6636 |
dep |
C3,27 |
R4088 |
T6639 |
T6638 |
punct |
–,C3 |
R4089 |
T6640 |
T6638 |
nummod |
3,C3 |
R4090 |
T6641 |
T6636 |
punct |
;,27 |
R4091 |
T6642 |
T6636 |
punct |
[,27 |
R4092 |
T6643 |
T6636 |
nummod |
15,27 |
R4093 |
T6644 |
T6636 |
punct |
",",27 |
R4094 |
T6645 |
T6636 |
nummod |
26,27 |
R4095 |
T6646 |
T6636 |
punct |
",",27 |
R4096 |
T6647 |
T6636 |
punct |
],27 |
R4097 |
T6648 |
T6636 |
punct |
),27 |
R4098 |
T6649 |
T6620 |
punct |
", ",estimated |
R4099 |
T6650 |
T6620 |
nsubj |
we,estimated |
R4100 |
T6651 |
T6652 |
mark |
that,produce |
R4101 |
T6652 |
T6620 |
ccomp |
produce,estimated |
R4102 |
T6653 |
T6654 |
det |
the,lines |
R4103 |
T6654 |
T6652 |
nsubj |
lines,produce |
R4104 |
T6655 |
T6654 |
nummod |
four,lines |
R4105 |
T6656 |
T6654 |
amod |
controllable,lines |
R4106 |
T6657 |
T6658 |
amod |
transgenic,protein |
R4107 |
T6658 |
T6652 |
dobj |
protein,produce |
R4108 |
T6659 |
T6658 |
compound |
APP,protein |
R4109 |
T6660 |
T6652 |
prep |
at,produce |
R4110 |
T6661 |
T6660 |
pcomp |
10,at |
R4111 |
T6662 |
T6661 |
punct |
-,10 |
R4112 |
T6663 |
T6661 |
quantmod |
to,10 |
R4113 |
T6664 |
T6661 |
advmod |
30-fold,10 |
R4114 |
T6665 |
T6661 |
prep |
over,10 |
R4115 |
T6666 |
T6667 |
amod |
endogenous,levels |
R4116 |
T6667 |
T6665 |
pobj |
levels,over |
R4117 |
T6668 |
T6669 |
punct |
(,S1 |
R4118 |
T6669 |
T6652 |
parataxis |
S1,produce |
R4119 |
T6670 |
T6669 |
compound |
Figure,S1 |
R4120 |
T6671 |
T6669 |
punct |
),S1 |
R4121 |
T6672 |
T6620 |
punct |
.,estimated |
R4122 |
T6674 |
T6675 |
det |
This,estimate |
R4123 |
T6675 |
T6676 |
nsubjpass |
estimate,confirmed |
R4124 |
T6677 |
T6676 |
auxpass |
was,confirmed |
R4125 |
T6678 |
T6676 |
agent |
by,confirmed |
R4126 |
T6679 |
T6680 |
amod |
direct,comparison |
R4127 |
T6680 |
T6678 |
pobj |
comparison,by |
R4128 |
T6681 |
T6680 |
prep |
of,comparison |
R4129 |
T6682 |
T6683 |
compound |
APP,levels |
R4130 |
T6683 |
T6681 |
pobj |
levels,of |
R4131 |
T6684 |
T6680 |
prep |
in,comparison |
R4132 |
T6685 |
T6686 |
amod |
nontransgenic,mice |
R4133 |
T6686 |
T6684 |
pobj |
mice,in |
R4134 |
T6687 |
T6685 |
cc |
and,nontransgenic |
R4135 |
T6688 |
T6689 |
compound |
tet,off |
R4136 |
T6689 |
T6685 |
conj |
off,nontransgenic |
R4137 |
T6690 |
T6689 |
punct |
-,off |
R4138 |
T6691 |
T6686 |
compound |
APP,mice |
R4139 |
T6692 |
T6676 |
advcl |
using,confirmed |
R4140 |
T6693 |
T6694 |
det |
an,antibody |
R4141 |
T6694 |
T6692 |
dobj |
antibody,using |
R4142 |
T6695 |
T6696 |
dep |
that,recognizes |
R4143 |
T6696 |
T6694 |
relcl |
recognizes,antibody |
R4144 |
T6697 |
T6698 |
preconj |
both,APP |
R4145 |
T6698 |
T6696 |
dobj |
APP,recognizes |
R4146 |
T6699 |
T6698 |
amod |
endogenous,APP |
R4147 |
T6700 |
T6698 |
punct |
(,APP |
R4148 |
T6701 |
T6698 |
cc |
and,APP |
R4149 |
T6702 |
T6703 |
nmod |
amyloid,protein |
R4150 |
T6703 |
T6698 |
conj |
protein,APP |
R4151 |
T6704 |
T6705 |
npadvmod |
precursor,like |
R4152 |
T6705 |
T6703 |
amod |
like,protein |
R4153 |
T6706 |
T6705 |
punct |
-,like |
R4154 |
T6707 |
T6703 |
nummod |
2,protein |
R4155 |
T6708 |
T6703 |
punct |
),protein |
R4156 |
T6709 |
T6698 |
cc |
and,APP |
R4157 |
T6710 |
T6711 |
det |
the,protein |
R4158 |
T6711 |
T6698 |
conj |
protein,APP |
R4159 |
T6712 |
T6711 |
amod |
transgenic,protein |
R4160 |
T6713 |
T6714 |
punct |
(,1D |
R4161 |
T6714 |
T6711 |
parataxis |
1D,protein |
R4162 |
T6715 |
T6716 |
amod |
monoclonal,22C11 |
R4163 |
T6716 |
T6714 |
dep |
22C11,1D |
R4164 |
T6717 |
T6716 |
compound |
antibody,22C11 |
R4165 |
T6718 |
T6714 |
punct |
;,1D |
R4166 |
T6719 |
T6714 |
compound |
Figure,1D |
R4167 |
T6720 |
T6714 |
punct |
),1D |
R4168 |
T6721 |
T6676 |
punct |
.,confirmed |
R4169 |
T6723 |
T6724 |
advmod |
Importantly,showed |
R4170 |
T6725 |
T6724 |
punct |
", ",showed |
R4171 |
T6726 |
T6727 |
det |
all,lines |
R4172 |
T6727 |
T6724 |
nsubj |
lines,showed |
R4173 |
T6728 |
T6727 |
nummod |
four,lines |
R4174 |
T6729 |
T6727 |
amod |
new,lines |
R4175 |
T6730 |
T6727 |
prep |
of,lines |
R4176 |
T6731 |
T6732 |
compound |
tet,off |
R4177 |
T6732 |
T6734 |
compound |
off,mice |
R4178 |
T6733 |
T6732 |
punct |
-,off |
R4179 |
T6734 |
T6730 |
pobj |
mice,of |
R4180 |
T6735 |
T6734 |
compound |
APP,mice |
R4181 |
T6736 |
T6737 |
advmod |
nearly,complete |
R4182 |
T6737 |
T6738 |
amod |
complete,suppression |
R4183 |
T6738 |
T6724 |
dobj |
suppression,showed |
R4184 |
T6739 |
T6738 |
prep |
of,suppression |
R4185 |
T6740 |
T6741 |
det |
the,transgene |
R4186 |
T6741 |
T6739 |
pobj |
transgene,of |
R4187 |
T6742 |
T6724 |
prep |
following,showed |
R4188 |
T6743 |
T6744 |
compound |
dox,treatment |
R4189 |
T6744 |
T6742 |
pobj |
treatment,following |
R4190 |
T6745 |
T6746 |
punct |
(,Figures |
R4191 |
T6746 |
T6724 |
parataxis |
Figures,showed |
R4192 |
T6747 |
T6746 |
nummod |
1,Figures |
R4193 |
T6748 |
T6746 |
cc |
and,Figures |
R4194 |
T6749 |
T6750 |
compound |
Figure,S1 |
R4195 |
T6750 |
T6746 |
conj |
S1,Figures |
R4196 |
T6751 |
T6746 |
punct |
),Figures |
R4197 |
T6752 |
T6724 |
punct |
.,showed |
R4198 |
T6754 |
T6755 |
nsubj |
We,focused |
R4199 |
T6756 |
T6755 |
prep |
on,focused |
R4200 |
T6757 |
T6756 |
pobj |
one,on |
R4201 |
T6758 |
T6757 |
prep |
of,one |
R4202 |
T6759 |
T6760 |
det |
the,lines |
R4203 |
T6760 |
T6758 |
pobj |
lines,of |
R4204 |
T6761 |
T6760 |
nummod |
four,lines |
R4205 |
T6762 |
T6757 |
punct |
", ",one |
R4206 |
T6763 |
T6757 |
appos |
line,one |
R4207 |
T6764 |
T6763 |
nummod |
107,line |
R4208 |
T6765 |
T6755 |
punct |
", ",focused |
R4209 |
T6766 |
T6767 |
aux |
to,examine |
R4210 |
T6767 |
T6755 |
advcl |
examine,focused |
R4211 |
T6768 |
T6767 |
prep |
in,examine |
R4212 |
T6769 |
T6770 |
amod |
more,detail |
R4213 |
T6770 |
T6768 |
pobj |
detail,in |
R4214 |
T6771 |
T6772 |
det |
the,dependence |
R4215 |
T6772 |
T6767 |
dobj |
dependence,examine |
R4216 |
T6773 |
T6772 |
compound |
time,dependence |
R4217 |
T6774 |
T6772 |
cc |
and,dependence |
R4218 |
T6775 |
T6772 |
conj |
extent,dependence |
R4219 |
T6776 |
T6775 |
prep |
of,extent |
R4220 |
T6777 |
T6778 |
compound |
transgene,suppression |
R4221 |
T6778 |
T6776 |
pobj |
suppression,of |
R4222 |
T6779 |
T6772 |
prep |
following,dependence |
R4223 |
T6780 |
T6781 |
preconj |
either,treatment |
R4224 |
T6781 |
T6779 |
pobj |
treatment,following |
R4225 |
T6782 |
T6781 |
amod |
acute,treatment |
R4226 |
T6783 |
T6782 |
cc |
or,acute |
R4227 |
T6784 |
T6782 |
conj |
chronic,acute |
R4228 |
T6785 |
T6781 |
prep |
with,treatment |
R4229 |
T6786 |
T6785 |
pobj |
dox,with |
R4230 |
T6787 |
T6755 |
punct |
.,focused |
R4231 |
T6789 |
T6790 |
nummod |
Two,groups |
R4232 |
T6790 |
T6794 |
nsubjpass |
groups,compared |
R4233 |
T6791 |
T6792 |
npadvmod |
dox,treated |
R4234 |
T6792 |
T6790 |
amod |
treated,groups |
R4235 |
T6793 |
T6792 |
punct |
-,treated |
R4236 |
T6794 |
T6796 |
ccomp |
compared,harvested |
R4237 |
T6795 |
T6794 |
auxpass |
were,compared |
R4238 |
T6797 |
T6794 |
prep |
to,compared |
R4239 |
T6798 |
T6799 |
nummod |
two,groups |
R4240 |
T6799 |
T6797 |
pobj |
groups,to |
R4241 |
T6800 |
T6799 |
amod |
untreated,groups |
R4242 |
T6801 |
T6796 |
punct |
: ,harvested |
R4243 |
T6802 |
T6803 |
nummod |
one,group |
R4244 |
T6803 |
T6804 |
nsubjpass |
group,born |
R4245 |
T6804 |
T6796 |
ccomp |
born,harvested |
R4246 |
T6805 |
T6803 |
prep |
of,group |
R4247 |
T6806 |
T6805 |
pobj |
mice,of |
R4248 |
T6807 |
T6804 |
auxpass |
was,born |
R4249 |
T6808 |
T6804 |
cc |
and,born |
R4250 |
T6809 |
T6804 |
conj |
raised,born |
R4251 |
T6810 |
T6809 |
prep |
on,raised |
R4252 |
T6811 |
T6810 |
pobj |
dox,on |
R4253 |
T6812 |
T6796 |
punct |
", ",harvested |
R4254 |
T6813 |
T6814 |
det |
a,group |
R4255 |
T6814 |
T6816 |
nsubjpass |
group,treated |
R4256 |
T6815 |
T6814 |
amod |
second,group |
R4257 |
T6816 |
T6796 |
ccomp |
treated,harvested |
R4258 |
T6817 |
T6816 |
auxpass |
was,treated |
R4259 |
T6818 |
T6816 |
prep |
with,treated |
R4260 |
T6819 |
T6818 |
pobj |
dox,with |
R4261 |
T6820 |
T6816 |
prep |
for,treated |
R4262 |
T6821 |
T6822 |
nummod |
2,wk |
R4263 |
T6822 |
T6820 |
pobj |
wk,for |
R4264 |
T6823 |
T6816 |
advcl |
starting,treated |
R4265 |
T6824 |
T6823 |
prep |
at,starting |
R4266 |
T6825 |
T6826 |
nummod |
1,mo |
R4267 |
T6826 |
T6824 |
pobj |
mo,at |
R4268 |
T6827 |
T6826 |
prep |
of,mo |
R4269 |
T6828 |
T6827 |
pobj |
age,of |
R4270 |
T6829 |
T6830 |
punct |
(,wk |
R4271 |
T6830 |
T6816 |
parataxis |
wk,treated |
R4272 |
T6831 |
T6830 |
nummod |
4,wk |
R4273 |
T6832 |
T6830 |
punct |
+,wk |
R4274 |
T6833 |
T6834 |
nummod |
2,wk |
R4275 |
T6834 |
T6835 |
compound |
wk,dox |
R4276 |
T6835 |
T6830 |
appos |
dox,wk |
R4277 |
T6836 |
T6830 |
punct |
),wk |
R4278 |
T6837 |
T6796 |
punct |
;,harvested |
R4279 |
T6838 |
T6839 |
nummod |
two,groups |
R4280 |
T6839 |
T6796 |
nsubjpass |
groups,harvested |
R4281 |
T6840 |
T6839 |
amod |
untreated,groups |
R4282 |
T6841 |
T6839 |
acl |
kept,groups |
R4283 |
T6842 |
T6841 |
prep |
on,kept |
R4284 |
T6843 |
T6844 |
amod |
normal,chow |
R4285 |
T6844 |
T6842 |
pobj |
chow,on |
R4286 |
T6845 |
T6796 |
auxpass |
were,harvested |
R4287 |
T6846 |
T6796 |
prep |
at,harvested |
R4288 |
T6847 |
T6848 |
preconj |
either,4 |
R4289 |
T6848 |
T6849 |
nummod |
4,wk |
R4290 |
T6849 |
T6846 |
pobj |
wk,at |
R4291 |
T6850 |
T6848 |
cc |
or,4 |
R4292 |
T6851 |
T6848 |
conj |
6,4 |
R4293 |
T6852 |
T6849 |
prep |
of,wk |
R4294 |
T6853 |
T6852 |
pobj |
age,of |
R4295 |
T6854 |
T6796 |
punct |
.,harvested |
R4296 |
T6856 |
T6857 |
nsubj |
Animals,harbored |
R4297 |
T6858 |
T6856 |
acl |
born,Animals |
R4298 |
T6859 |
T6858 |
cc |
and,born |
R4299 |
T6860 |
T6858 |
conj |
raised,born |
R4300 |
T6861 |
T6860 |
prep |
on,raised |
R4301 |
T6862 |
T6861 |
pobj |
dox,on |
R4302 |
T6863 |
T6864 |
det |
no,APP |
R4303 |
T6864 |
T6857 |
dobj |
APP,harbored |
R4304 |
T6865 |
T6864 |
amod |
transgenic,APP |
R4305 |
T6866 |
T6867 |
punct |
(,1A |
R4306 |
T6867 |
T6857 |
parataxis |
1A,harbored |
R4307 |
T6868 |
T6867 |
compound |
Figure,1A |
R4308 |
T6869 |
T6867 |
punct |
),1A |
R4309 |
T6870 |
T6857 |
punct |
.,harbored |
R4310 |
T6872 |
T6873 |
prep |
Following,reduced |
R4311 |
T6874 |
T6875 |
advmod |
as,2 |
R4312 |
T6875 |
T6878 |
nummod |
2,wk |
R4313 |
T6876 |
T6875 |
amod |
little,2 |
R4314 |
T6877 |
T6875 |
quantmod |
as,2 |
R4315 |
T6878 |
T6872 |
pobj |
wk,Following |
R4316 |
T6879 |
T6878 |
prep |
of,wk |
R4317 |
T6880 |
T6881 |
compound |
dox,treatment |
R4318 |
T6881 |
T6879 |
pobj |
treatment,of |
R4319 |
T6882 |
T6873 |
punct |
", ",reduced |
R4320 |
T6883 |
T6884 |
amod |
transgenic,expression |
R4321 |
T6884 |
T6873 |
nsubjpass |
expression,reduced |
R4322 |
T6885 |
T6884 |
compound |
APP,expression |
R4323 |
T6886 |
T6873 |
auxpass |
was,reduced |
R4324 |
T6887 |
T6873 |
prep |
by,reduced |
R4325 |
T6888 |
T6889 |
amod |
more,95 |
R4326 |
T6889 |
T6891 |
nummod |
95,% |
R4327 |
T6890 |
T6889 |
quantmod |
than,95 |
R4328 |
T6891 |
T6887 |
pobj |
%,by |
R4329 |
T6892 |
T6873 |
prep |
compared,reduced |
R4330 |
T6893 |
T6892 |
prep |
to,compared |
R4331 |
T6894 |
T6895 |
amod |
pre-dox,levels |
R4332 |
T6895 |
T6893 |
pobj |
levels,to |
R4333 |
T6896 |
T6873 |
punct |
.,reduced |
R4334 |
T6898 |
T6899 |
det |
The,expression |
R4335 |
T6899 |
T6901 |
nsubj |
expression,represents |
R4336 |
T6900 |
T6899 |
amod |
residual,expression |
R4337 |
T6902 |
T6899 |
acl |
remaining,expression |
R4338 |
T6903 |
T6902 |
prep |
in,remaining |
R4339 |
T6904 |
T6905 |
advmod |
acutely,treated |
R4340 |
T6905 |
T6906 |
amod |
treated,mice |
R4341 |
T6906 |
T6903 |
pobj |
mice,in |
R4342 |
T6907 |
T6908 |
amod |
less,4 |
R4343 |
T6908 |
T6910 |
nummod |
4,% |
R4344 |
T6909 |
T6908 |
quantmod |
than,4 |
R4345 |
T6910 |
T6901 |
dobj |
%,represents |
R4346 |
T6911 |
T6910 |
prep |
of,% |
R4347 |
T6912 |
T6913 |
det |
the,protein |
R4348 |
T6913 |
T6911 |
pobj |
protein,of |
R4349 |
T6914 |
T6913 |
amod |
transgenic,protein |
R4350 |
T6915 |
T6913 |
acl |
produced,protein |
R4351 |
T6916 |
T6915 |
prep |
in,produced |
R4352 |
T6917 |
T6918 |
det |
the,absence |
R4353 |
T6918 |
T6916 |
pobj |
absence,in |
R4354 |
T6919 |
T6918 |
prep |
of,absence |
R4355 |
T6920 |
T6919 |
pobj |
dox,of |
R4356 |
T6921 |
T6922 |
punct |
(,1C |
R4357 |
T6922 |
T6915 |
parataxis |
1C,produced |
R4358 |
T6923 |
T6922 |
compound |
Figure,1C |
R4359 |
T6924 |
T6922 |
punct |
),1C |
R4360 |
T6925 |
T6901 |
punct |
", ",represents |
R4361 |
T6926 |
T6901 |
cc |
and,represents |
R4362 |
T6927 |
T6928 |
advmod |
likely,results |
R4363 |
T6928 |
T6901 |
conj |
results,represents |
R4364 |
T6929 |
T6928 |
prep |
from,results |
R4365 |
T6930 |
T6931 |
amod |
slight,leakage |
R4366 |
T6931 |
T6929 |
pobj |
leakage,from |
R4367 |
T6932 |
T6931 |
prep |
at,leakage |
R4368 |
T6933 |
T6934 |
det |
the,level |
R4369 |
T6934 |
T6932 |
pobj |
level,at |
R4370 |
T6935 |
T6934 |
prep |
of,level |
R4371 |
T6936 |
T6935 |
pobj |
transcription,of |
R4372 |
T6937 |
T6938 |
punct |
(,shown |
R4373 |
T6938 |
T6928 |
parataxis |
shown,results |
R4374 |
T6939 |
T6938 |
nsubj |
data,shown |
R4375 |
T6940 |
T6938 |
neg |
not,shown |
R4376 |
T6941 |
T6938 |
punct |
),shown |
R4377 |
T6942 |
T6901 |
punct |
.,represents |
R4378 |
T6944 |
T6945 |
advmod |
Importantly,was |
R4379 |
T6946 |
T6945 |
punct |
", ",was |
R4380 |
T6947 |
T6948 |
det |
the,amount |
R4381 |
T6948 |
T6945 |
nsubj |
amount,was |
R4382 |
T6949 |
T6948 |
amod |
total,amount |
R4383 |
T6950 |
T6948 |
prep |
of,amount |
R4384 |
T6951 |
T6950 |
pobj |
APP,of |
R4385 |
T6952 |
T6953 |
punct |
(,endogenous |
R4386 |
T6953 |
T6951 |
parataxis |
endogenous,APP |
R4387 |
T6954 |
T6953 |
cc |
plus,endogenous |
R4388 |
T6955 |
T6953 |
conj |
transgenic,endogenous |
R4389 |
T6956 |
T6953 |
punct |
),endogenous |
R4390 |
T6957 |
T6951 |
cc |
and,APP |
R4391 |
T6958 |
T6959 |
amod |
related,APLPs |
R4392 |
T6959 |
T6951 |
conj |
APLPs,APP |
R4393 |
T6960 |
T6948 |
prep |
in,amount |
R4394 |
T6961 |
T6962 |
preconj |
both,acute |
R4395 |
T6962 |
T6963 |
amod |
acute,animals |
R4396 |
T6963 |
T6960 |
pobj |
animals,in |
R4397 |
T6964 |
T6962 |
cc |
and,acute |
R4398 |
T6965 |
T6966 |
advmod |
chronically,treated |
R4399 |
T6966 |
T6962 |
conj |
treated,acute |
R4400 |
T6967 |
T6968 |
advmod |
statistically,indistinguishable |
R4401 |
T6968 |
T6945 |
acomp |
indistinguishable,was |
R4402 |
T6969 |
T6968 |
prep |
from,indistinguishable |
R4403 |
T6970 |
T6969 |
pobj |
that,from |
R4404 |
T6971 |
T6970 |
prep |
in,that |
R4405 |
T6972 |
T6973 |
amod |
nontransgenic,mice |
R4406 |
T6973 |
T6971 |
pobj |
mice,in |
R4407 |
T6974 |
T6975 |
punct |
(,1D |
R4408 |
T6975 |
T6945 |
parataxis |
1D,was |
R4409 |
T6976 |
T6975 |
compound |
Figure,1D |
R4410 |
T6977 |
T6975 |
punct |
;,1D |
R4411 |
T6978 |
T6979 |
amod |
statistical,analyses |
R4412 |
T6979 |
T6980 |
nsubjpass |
analyses,presented |
R4413 |
T6980 |
T6975 |
ccomp |
presented,1D |
R4414 |
T6981 |
T6979 |
prep |
for,analyses |
R4415 |
T6982 |
T6981 |
pobj |
experiments,for |
R4416 |
T6983 |
T6982 |
prep |
throughout,experiments |
R4417 |
T6984 |
T6985 |
det |
the,study |
R4418 |
T6985 |
T6983 |
pobj |
study,throughout |
R4419 |
T6986 |
T6980 |
auxpass |
are,presented |
R4420 |
T6987 |
T6980 |
prep |
in,presented |
R4421 |
T6988 |
T6989 |
det |
the,legends |
R4422 |
T6989 |
T6987 |
pobj |
legends,in |
R4423 |
T6990 |
T6989 |
amod |
accompanying,legends |
R4424 |
T6991 |
T6989 |
compound |
figure,legends |
R4425 |
T6992 |
T6975 |
punct |
),1D |
R4426 |
T6993 |
T6945 |
punct |
.,was |
R4427 |
T6995 |
T6996 |
aux |
To,ensure |
R4428 |
T6996 |
T6997 |
advcl |
ensure,measured |
R4429 |
T6998 |
T6999 |
mark |
that,suppressed |
R4430 |
T6999 |
T6996 |
ccomp |
suppressed,ensure |
R4431 |
T7000 |
T7001 |
compound |
Aβ,production |
R4432 |
T7001 |
T6999 |
nsubjpass |
production,suppressed |
R4433 |
T7002 |
T6999 |
auxpass |
was,suppressed |
R4434 |
T7003 |
T6999 |
prep |
in,suppressed |
R4435 |
T7004 |
T7003 |
pobj |
concert,in |
R4436 |
T7005 |
T7004 |
prep |
with,concert |
R4437 |
T7006 |
T7007 |
det |
the,inhibition |
R4438 |
T7007 |
T7005 |
pobj |
inhibition,with |
R4439 |
T7008 |
T7009 |
npadvmod |
dox,mediated |
R4440 |
T7009 |
T7007 |
amod |
mediated,inhibition |
R4441 |
T7010 |
T7009 |
punct |
-,mediated |
R4442 |
T7011 |
T7007 |
prep |
of,inhibition |
R4443 |
T7012 |
T7013 |
poss |
its,precursor |
R4444 |
T7013 |
T7011 |
pobj |
precursor,of |
R4445 |
T7014 |
T7015 |
compound |
APPswe,ind |
R4446 |
T7015 |
T7013 |
appos |
ind,precursor |
R4447 |
T7016 |
T7015 |
punct |
/,ind |
R4448 |
T7017 |
T6997 |
punct |
", ",measured |
R4449 |
T7018 |
T6997 |
nsubj |
we,measured |
R4450 |
T7019 |
T7020 |
nmod |
Aβ40,levels |
R4451 |
T7020 |
T6997 |
dobj |
levels,measured |
R4452 |
T7021 |
T7019 |
cc |
and,Aβ40 |
R4453 |
T7022 |
T7019 |
conj |
Aβ42,Aβ40 |
R4454 |
T7023 |
T6997 |
prep |
by,measured |
R4455 |
T7024 |
T7023 |
pobj |
ELISA,by |
R4456 |
T7025 |
T6997 |
prep |
in,measured |
R4457 |
T7026 |
T7027 |
compound |
forebrain,homogenates |
R4458 |
T7027 |
T7025 |
pobj |
homogenates,in |
R4459 |
T7028 |
T7027 |
prep |
from,homogenates |
R4460 |
T7029 |
T7030 |
amod |
young,animals |
R4461 |
T7030 |
T7028 |
pobj |
animals,from |
R4462 |
T7031 |
T7032 |
compound |
tet,off |
R4463 |
T7032 |
T7030 |
compound |
off,animals |
R4464 |
T7033 |
T7032 |
punct |
-,off |
R4465 |
T7034 |
T6997 |
punct |
.,measured |
R4466 |
T7036 |
T7037 |
prep |
At,lacked |
R4467 |
T7038 |
T7039 |
nummod |
1,mo |
R4468 |
T7039 |
T7036 |
pobj |
mo,At |
R4469 |
T7040 |
T7039 |
prep |
of,mo |
R4470 |
T7041 |
T7040 |
pobj |
age,of |
R4471 |
T7042 |
T7037 |
punct |
", ",lacked |
R4472 |
T7043 |
T7044 |
det |
the,mice |
R4473 |
T7044 |
T7037 |
nsubj |
mice,lacked |
R4474 |
T7045 |
T7046 |
amod |
visible,aggregates |
R4475 |
T7046 |
T7037 |
dobj |
aggregates,lacked |
R4476 |
T7047 |
T7046 |
compound |
amyloid,aggregates |
R4477 |
T7048 |
T7049 |
dep |
that,act |
R4478 |
T7049 |
T7046 |
relcl |
act,aggregates |
R4479 |
T7050 |
T7049 |
aux |
might,act |
R4480 |
T7051 |
T7049 |
prep |
as,act |
R4481 |
T7052 |
T7053 |
det |
an,reservoir |
R4482 |
T7053 |
T7051 |
pobj |
reservoir,as |
R4483 |
T7054 |
T7053 |
amod |
intractable,reservoir |
R4484 |
T7055 |
T7053 |
prep |
of,reservoir |
R4485 |
T7056 |
T7055 |
pobj |
peptide,of |
R4486 |
T7057 |
T7053 |
acl |
remaining,reservoir |
R4487 |
T7058 |
T7057 |
prep |
in,remaining |
R4488 |
T7059 |
T7060 |
det |
the,brain |
R4489 |
T7060 |
T7058 |
pobj |
brain,in |
R4490 |
T7061 |
T7062 |
prep |
after,suppressed |
R4491 |
T7062 |
T7057 |
advcl |
suppressed,remaining |
R4492 |
T7063 |
T7064 |
det |
the,transgene |
R4493 |
T7064 |
T7062 |
nsubjpass |
transgene,suppressed |
R4494 |
T7065 |
T7062 |
aux |
had,suppressed |
R4495 |
T7066 |
T7062 |
auxpass |
been,suppressed |
R4496 |
T7067 |
T7037 |
punct |
.,lacked |
R4497 |
T7069 |
T7070 |
aux |
To,ensure |
R4498 |
T7070 |
T7072 |
advcl |
ensure,performed |
R4499 |
T7071 |
T7070 |
advmod |
further,ensure |
R4500 |
T7073 |
T7074 |
nsubj |
we,detect |
R4501 |
T7074 |
T7070 |
advcl |
detect,ensure |
R4502 |
T7075 |
T7074 |
aux |
could,detect |
R4503 |
T7076 |
T7077 |
det |
any,aggregates |
R4504 |
T7077 |
T7074 |
dobj |
aggregates,detect |
R4505 |
T7078 |
T7077 |
amod |
such,aggregates |
R4506 |
T7079 |
T7077 |
amod |
insoluble,aggregates |
R4507 |
T7080 |
T7081 |
dep |
that,bias |
R4508 |
T7081 |
T7077 |
relcl |
bias,aggregates |
R4509 |
T7082 |
T7081 |
aux |
might,bias |
R4510 |
T7083 |
T7084 |
poss |
our,measure |
R4511 |
T7084 |
T7081 |
dobj |
measure,bias |
R4512 |
T7085 |
T7084 |
prep |
of,measure |
R4513 |
T7086 |
T7085 |
pobj |
changes,of |
R4514 |
T7087 |
T7081 |
prep |
in,bias |
R4515 |
T7088 |
T7089 |
compound |
peptide,synthesis |
R4516 |
T7089 |
T7087 |
pobj |
synthesis,in |
R4517 |
T7090 |
T7072 |
punct |
", ",performed |
R4518 |
T7091 |
T7072 |
nsubj |
we,performed |
R4519 |
T7092 |
T7093 |
det |
a,extraction |
R4520 |
T7093 |
T7072 |
dobj |
extraction,performed |
R4521 |
T7094 |
T7093 |
amod |
sequential,extraction |
R4522 |
T7095 |
T7096 |
nummod |
three,step |
R4523 |
T7096 |
T7093 |
compound |
step,extraction |
R4524 |
T7097 |
T7096 |
punct |
-,step |
R4525 |
T7098 |
T7093 |
prep |
with,extraction |
R4526 |
T7099 |
T7098 |
pobj |
PBS,with |
R4527 |
T7100 |
T7099 |
punct |
", ",PBS |
R4528 |
T7101 |
T7102 |
nummod |
2,% |
R4529 |
T7102 |
T7103 |
compound |
%,SDS |
R4530 |
T7103 |
T7099 |
conj |
SDS,PBS |
R4531 |
T7104 |
T7103 |
punct |
", ",SDS |
R4532 |
T7105 |
T7103 |
cc |
and,SDS |
R4533 |
T7106 |
T7107 |
nummod |
70,% |
R4534 |
T7107 |
T7108 |
compound |
%,FA |
R4535 |
T7108 |
T7103 |
conj |
FA,SDS |
R4536 |
T7109 |
T7110 |
dep |
that,separate |
R4537 |
T7110 |
T7093 |
relcl |
separate,extraction |
R4538 |
T7111 |
T7110 |
aux |
would,separate |
R4539 |
T7112 |
T7110 |
dobj |
peptides,separate |
R4540 |
T7113 |
T7110 |
prep |
by,separate |
R4541 |
T7114 |
T7113 |
pobj |
solubility,by |
R4542 |
T7115 |
T7072 |
punct |
.,performed |
R4543 |
T7117 |
T7118 |
nsubj |
We,compared |
R4544 |
T7119 |
T7120 |
det |
the,levels |
R4545 |
T7120 |
T7118 |
dobj |
levels,compared |
R4546 |
T7121 |
T7120 |
prep |
of,levels |
R4547 |
T7122 |
T7123 |
amod |
human,transgene |
R4548 |
T7123 |
T7124 |
npadvmod |
transgene,derived |
R4549 |
T7124 |
T7126 |
amod |
derived,Aβ40 |
R4550 |
T7125 |
T7124 |
punct |
-,derived |
R4551 |
T7126 |
T7121 |
pobj |
Aβ40,of |
R4552 |
T7127 |
T7126 |
cc |
and,Aβ40 |
R4553 |
T7128 |
T7126 |
conj |
Aβ42,Aβ40 |
R4554 |
T7129 |
T7120 |
prep |
in,levels |
R4555 |
T7130 |
T7131 |
amod |
untreated,mice |
R4556 |
T7131 |
T7129 |
pobj |
mice,in |
R4557 |
T7132 |
T7120 |
prep |
at,levels |
R4558 |
T7133 |
T7134 |
nummod |
4,wk |
R4559 |
T7134 |
T7132 |
pobj |
wk,at |
R4560 |
T7135 |
T7133 |
cc |
and,4 |
R4561 |
T7136 |
T7133 |
conj |
6,4 |
R4562 |
T7137 |
T7134 |
prep |
of,wk |
R4563 |
T7138 |
T7137 |
pobj |
age,of |
R4564 |
T7139 |
T7118 |
prep |
to,compared |
R4565 |
T7140 |
T7139 |
pobj |
animals,to |
R4566 |
T7141 |
T7142 |
dep |
that,born |
R4567 |
T7142 |
T7140 |
advcl |
born,animals |
R4568 |
T7143 |
T7142 |
aux |
had,born |
R4569 |
T7144 |
T7142 |
preconj |
either,born |
R4570 |
T7145 |
T7142 |
auxpass |
been,born |
R4571 |
T7146 |
T7142 |
cc |
and,born |
R4572 |
T7147 |
T7142 |
conj |
raised,born |
R4573 |
T7148 |
T7147 |
prep |
on,raised |
R4574 |
T7149 |
T7148 |
pobj |
dox,on |
R4575 |
T7150 |
T7142 |
cc |
or,born |
R4576 |
T7151 |
T7152 |
dep |
that,left |
R4577 |
T7152 |
T7142 |
conj |
left,born |
R4578 |
T7153 |
T7152 |
aux |
had,left |
R4579 |
T7154 |
T7152 |
auxpass |
been,left |
R4580 |
T7155 |
T7152 |
oprd |
untreated,left |
R4581 |
T7156 |
T7152 |
prep |
for,left |
R4582 |
T7157 |
T7158 |
nummod |
4,wk |
R4583 |
T7158 |
T7156 |
pobj |
wk,for |
R4584 |
T7159 |
T7152 |
cc |
and,left |
R4585 |
T7160 |
T7161 |
advmod |
then,placed |
R4586 |
T7161 |
T7152 |
conj |
placed,left |
R4587 |
T7162 |
T7161 |
prep |
on,placed |
R4588 |
T7163 |
T7164 |
compound |
dox,chow |
R4589 |
T7164 |
T7162 |
pobj |
chow,on |
R4590 |
T7165 |
T7161 |
prep |
for,placed |
R4591 |
T7166 |
T7167 |
nummod |
2,wk |
R4592 |
T7167 |
T7165 |
pobj |
wk,for |
R4593 |
T7168 |
T7169 |
amod |
prior,to |
R4594 |
T7169 |
T7167 |
prep |
to,wk |
R4595 |
T7170 |
T7169 |
pobj |
harvest,to |
R4596 |
T7171 |
T7172 |
punct |
(,line |
R4597 |
T7172 |
T7161 |
parataxis |
line,placed |
R4598 |
T7173 |
T7174 |
det |
the,groups |
R4599 |
T7174 |
T7172 |
dep |
groups,line |
R4600 |
T7175 |
T7174 |
amod |
same,groups |
R4601 |
T7176 |
T7174 |
acl |
described,groups |
R4602 |
T7177 |
T7176 |
advmod |
above,described |
R4603 |
T7178 |
T7176 |
prep |
for,described |
R4604 |
T7179 |
T7180 |
compound |
immunoblot,analysis |
R4605 |
T7180 |
T7178 |
pobj |
analysis,for |
R4606 |
T7181 |
T7180 |
prep |
of,analysis |
R4607 |
T7182 |
T7183 |
compound |
APPswe,ind |
R4608 |
T7183 |
T7185 |
compound |
ind,levels |
R4609 |
T7184 |
T7183 |
punct |
/,ind |
R4610 |
T7185 |
T7181 |
pobj |
levels,of |
R4611 |
T7186 |
T7172 |
punct |
", ",line |
R4612 |
T7187 |
T7172 |
nummod |
107,line |
R4613 |
T7188 |
T7172 |
punct |
),line |
R4614 |
T7189 |
T7118 |
punct |
.,compared |
R4615 |
T7191 |
T7192 |
advcl |
Consistent,found |
R4616 |
T7193 |
T7191 |
prep |
with,Consistent |
R4617 |
T7194 |
T7195 |
det |
the,reduction |
R4618 |
T7195 |
T7193 |
pobj |
reduction,with |
R4619 |
T7196 |
T7195 |
prep |
in,reduction |
R4620 |
T7197 |
T7198 |
amod |
full,length |
R4621 |
T7198 |
T7200 |
compound |
length,synthesis |
R4622 |
T7199 |
T7198 |
punct |
-,length |
R4623 |
T7200 |
T7196 |
pobj |
synthesis,in |
R4624 |
T7201 |
T7202 |
compound |
APPswe,ind |
R4625 |
T7202 |
T7200 |
compound |
ind,synthesis |
R4626 |
T7203 |
T7202 |
punct |
/,ind |
R4627 |
T7204 |
T7195 |
acl |
shown,reduction |
R4628 |
T7205 |
T7204 |
agent |
by,shown |
R4629 |
T7206 |
T7205 |
pobj |
immunoblot,by |
R4630 |
T7207 |
T7208 |
punct |
(,see |
R4631 |
T7208 |
T7191 |
parataxis |
see,Consistent |
R4632 |
T7209 |
T7208 |
dobj |
Figure,see |
R4633 |
T7210 |
T7209 |
nummod |
1,Figure |
R4634 |
T7211 |
T7208 |
punct |
),see |
R4635 |
T7212 |
T7192 |
punct |
", ",found |
R4636 |
T7213 |
T7192 |
nsubj |
we,found |
R4637 |
T7214 |
T7215 |
mark |
that,suppressed |
R4638 |
T7215 |
T7192 |
ccomp |
suppressed,found |
R4639 |
T7216 |
T7217 |
npadvmod |
transgene,derived |
R4640 |
T7217 |
T7219 |
amod |
derived,levels |
R4641 |
T7218 |
T7217 |
punct |
-,derived |
R4642 |
T7219 |
T7215 |
nsubjpass |
levels,suppressed |
R4643 |
T7220 |
T7219 |
compound |
Aβ,levels |
R4644 |
T7221 |
T7215 |
auxpass |
were,suppressed |
R4645 |
T7222 |
T7215 |
advmod |
completely,suppressed |
R4646 |
T7223 |
T7215 |
prep |
in,suppressed |
R4647 |
T7224 |
T7223 |
pobj |
animals,in |
R4648 |
T7225 |
T7224 |
acl |
born,animals |
R4649 |
T7226 |
T7225 |
cc |
and,born |
R4650 |
T7227 |
T7225 |
conj |
raised,born |
R4651 |
T7228 |
T7227 |
prep |
on,raised |
R4652 |
T7229 |
T7228 |
pobj |
dox,on |
R4653 |
T7230 |
T7215 |
punct |
", ",suppressed |
R4654 |
T7231 |
T7215 |
cc |
and,suppressed |
R4655 |
T7232 |
T7233 |
auxpass |
were,reduced |
R4656 |
T7233 |
T7215 |
conj |
reduced,suppressed |
R4657 |
T7234 |
T7233 |
advmod |
sharply,reduced |
R4658 |
T7235 |
T7233 |
prep |
following,reduced |
R4659 |
T7236 |
T7237 |
amod |
acute,treatment |
R4660 |
T7237 |
T7235 |
pobj |
treatment,following |
R4661 |
T7238 |
T7239 |
punct |
(,wk |
R4662 |
T7239 |
T7236 |
parataxis |
wk,acute |
R4663 |
T7240 |
T7239 |
nummod |
2,wk |
R4664 |
T7241 |
T7239 |
punct |
),wk |
R4665 |
T7242 |
T7237 |
amod |
antibiotic,treatment |
R4666 |
T7243 |
T7192 |
punct |
.,found |
R4667 |
T7245 |
T7246 |
prep |
Compared,dropped |
R4668 |
T7247 |
T7245 |
prep |
to,Compared |
R4669 |
T7248 |
T7249 |
det |
the,levels |
R4670 |
T7249 |
T7247 |
pobj |
levels,to |
R4671 |
T7250 |
T7249 |
prep |
in,levels |
R4672 |
T7251 |
T7252 |
amod |
untreated,mice |
R4673 |
T7252 |
T7250 |
pobj |
mice,in |
R4674 |
T7253 |
T7254 |
nummod |
4,wk |
R4675 |
T7254 |
T7256 |
npadvmod |
wk,old |
R4676 |
T7255 |
T7254 |
punct |
-,wk |
R4677 |
T7256 |
T7252 |
amod |
old,mice |
R4678 |
T7257 |
T7256 |
punct |
-,old |
R4679 |
T7258 |
T7246 |
punct |
", ",dropped |
R4680 |
T7259 |
T7260 |
npadvmod |
PBS,soluble |
R4681 |
T7260 |
T7262 |
amod |
soluble,Aβ42 |
R4682 |
T7261 |
T7260 |
punct |
-,soluble |
R4683 |
T7262 |
T7246 |
nsubj |
Aβ42,dropped |
R4684 |
T7263 |
T7246 |
prep |
by,dropped |
R4685 |
T7264 |
T7265 |
nummod |
95.2,% |
R4686 |
T7265 |
T7263 |
pobj |
%,by |
R4687 |
T7266 |
T7246 |
prep |
following,dropped |
R4688 |
T7267 |
T7268 |
nummod |
2,wk |
R4689 |
T7268 |
T7266 |
pobj |
wk,following |
R4690 |
T7269 |
T7268 |
prep |
of,wk |
R4691 |
T7270 |
T7271 |
compound |
dox,treatment |
R4692 |
T7271 |
T7269 |
pobj |
treatment,of |
R4693 |
T7272 |
T7246 |
cc |
and,dropped |
R4694 |
T7273 |
T7274 |
prep |
by,with |
R4695 |
T7274 |
T7246 |
conj |
with,dropped |
R4696 |
T7275 |
T7276 |
nummod |
99.2,% |
R4697 |
T7276 |
T7273 |
pobj |
%,by |
R4698 |
T7277 |
T7278 |
amod |
chronic,treatment |
R4699 |
T7278 |
T7274 |
pobj |
treatment,with |
R4700 |
T7279 |
T7280 |
punct |
(,2A |
R4701 |
T7280 |
T7274 |
parataxis |
2A,with |
R4702 |
T7281 |
T7280 |
compound |
Figure,2A |
R4703 |
T7282 |
T7280 |
punct |
),2A |
R4704 |
T7283 |
T7246 |
punct |
.,dropped |
R4705 |
T7285 |
T7286 |
advmod |
Similarly,decreased |
R4706 |
T7287 |
T7286 |
punct |
", ",decreased |
R4707 |
T7288 |
T7289 |
npadvmod |
SDS,soluble |
R4708 |
T7289 |
T7291 |
amod |
soluble,Aβ42 |
R4709 |
T7290 |
T7289 |
punct |
-,soluble |
R4710 |
T7291 |
T7286 |
nsubj |
Aβ42,decreased |
R4711 |
T7292 |
T7286 |
prep |
by,decreased |
R4712 |
T7293 |
T7294 |
nummod |
75.2,% |
R4713 |
T7294 |
T7292 |
pobj |
%,by |
R4714 |
T7295 |
T7294 |
cc |
and,% |
R4715 |
T7296 |
T7297 |
nummod |
94.8,% |
R4716 |
T7297 |
T7294 |
conj |
%,% |
R4717 |
T7298 |
T7286 |
prep |
following,decreased |
R4718 |
T7299 |
T7300 |
nummod |
2,wk |
R4719 |
T7300 |
T7302 |
nmod |
wk,treatment |
R4720 |
T7301 |
T7300 |
punct |
-,wk |
R4721 |
T7302 |
T7298 |
pobj |
treatment,following |
R4722 |
T7303 |
T7300 |
cc |
or,wk |
R4723 |
T7304 |
T7300 |
conj |
lifelong,wk |
R4724 |
T7305 |
T7302 |
compound |
dox,treatment |
R4725 |
T7306 |
T7307 |
punct |
(,2B |
R4726 |
T7307 |
T7286 |
parataxis |
2B,decreased |
R4727 |
T7308 |
T7307 |
compound |
Figure,2B |
R4728 |
T7309 |
T7307 |
punct |
),2B |
R4729 |
T7310 |
T7286 |
punct |
.,decreased |
R4730 |
T7312 |
T7313 |
advmod |
Only,fraction |
R4731 |
T7313 |
T7316 |
nsubj |
fraction,revealed |
R4732 |
T7314 |
T7313 |
det |
the,fraction |
R4733 |
T7315 |
T7313 |
compound |
FA,fraction |
R4734 |
T7317 |
T7318 |
det |
a,pool |
R4735 |
T7318 |
T7316 |
dobj |
pool,revealed |
R4736 |
T7319 |
T7318 |
amod |
small,pool |
R4737 |
T7320 |
T7321 |
npadvmod |
dox,resistant |
R4738 |
T7321 |
T7318 |
amod |
resistant,pool |
R4739 |
T7322 |
T7321 |
punct |
-,resistant |
R4740 |
T7323 |
T7318 |
prep |
of,pool |
R4741 |
T7324 |
T7323 |
pobj |
peptide,of |
R4742 |
T7325 |
T7318 |
prep |
in,pool |
R4743 |
T7326 |
T7327 |
advmod |
acutely,treated |
R4744 |
T7327 |
T7328 |
amod |
treated,animals |
R4745 |
T7328 |
T7325 |
pobj |
animals,in |
R4746 |
T7329 |
T7330 |
dep |
that,believe |
R4747 |
T7330 |
T7318 |
relcl |
believe,pool |
R4748 |
T7331 |
T7330 |
nsubj |
we,believe |
R4749 |
T7332 |
T7330 |
advcl |
represents,believe |
R4750 |
T7333 |
T7334 |
amod |
stable,aggregates |
R4751 |
T7334 |
T7332 |
dobj |
aggregates,represents |
R4752 |
T7335 |
T7334 |
amod |
predeposit,aggregates |
R4753 |
T7336 |
T7337 |
dep |
that,accumulated |
R4754 |
T7337 |
T7334 |
relcl |
accumulated,aggregates |
R4755 |
T7338 |
T7337 |
aux |
have,accumulated |
R4756 |
T7339 |
T7337 |
advmod |
already,accumulated |
R4757 |
T7340 |
T7337 |
prep |
by,accumulated |
R4758 |
T7341 |
T7342 |
nummod |
4,wk |
R4759 |
T7342 |
T7340 |
pobj |
wk,by |
R4760 |
T7343 |
T7342 |
prep |
of,wk |
R4761 |
T7344 |
T7343 |
pobj |
age,of |
R4762 |
T7345 |
T7346 |
advmod |
when,begun |
R4763 |
T7346 |
T7337 |
advcl |
begun,accumulated |
R4764 |
T7347 |
T7346 |
nsubjpass |
treatment,begun |
R4765 |
T7348 |
T7346 |
auxpass |
was,begun |
R4766 |
T7349 |
T7350 |
punct |
(,2C |
R4767 |
T7350 |
T7316 |
parataxis |
2C,revealed |
R4768 |
T7351 |
T7350 |
compound |
Figure,2C |
R4769 |
T7352 |
T7350 |
punct |
),2C |
R4770 |
T7353 |
T7316 |
punct |
.,revealed |
R4771 |
T7355 |
T7356 |
advmod |
Indeed,harbor |
R4772 |
T7357 |
T7356 |
punct |
", ",harbor |
R4773 |
T7358 |
T7356 |
nsubj |
animals,harbor |
R4774 |
T7359 |
T7360 |
dep |
that,born |
R4775 |
T7360 |
T7358 |
relcl |
born,animals |
R4776 |
T7361 |
T7360 |
auxpass |
were,born |
R4777 |
T7362 |
T7360 |
cc |
and,born |
R4778 |
T7363 |
T7360 |
conj |
raised,born |
R4779 |
T7364 |
T7363 |
prep |
on,raised |
R4780 |
T7365 |
T7364 |
pobj |
dox,on |
R4781 |
T7366 |
T7356 |
aux |
did,harbor |
R4782 |
T7367 |
T7356 |
neg |
not,harbor |
R4783 |
T7368 |
T7369 |
det |
this,reservoir |
R4784 |
T7369 |
T7356 |
dobj |
reservoir,harbor |
R4785 |
T7370 |
T7369 |
prep |
of,reservoir |
R4786 |
T7371 |
T7372 |
npadvmod |
treatment,resistant |
R4787 |
T7372 |
T7374 |
amod |
resistant,peptide |
R4788 |
T7373 |
T7372 |
punct |
-,resistant |
R4789 |
T7374 |
T7370 |
pobj |
peptide,of |
R4790 |
T7375 |
T7356 |
punct |
", ",harbor |
R4791 |
T7376 |
T7356 |
prep |
with,harbor |
R4792 |
T7377 |
T7378 |
nummod |
96.3,% |
R4793 |
T7378 |
T7379 |
npadvmod |
%,less |
R4794 |
T7379 |
T7380 |
amod |
less,Aβ42 |
R4795 |
T7380 |
T7376 |
pobj |
Aβ42,with |
R4796 |
T7381 |
T7380 |
prep |
than,Aβ42 |
R4797 |
T7382 |
T7383 |
amod |
untreated,mice |
R4798 |
T7383 |
T7381 |
pobj |
mice,than |
R4799 |
T7384 |
T7385 |
nummod |
4,wk |
R4800 |
T7385 |
T7387 |
npadvmod |
wk,old |
R4801 |
T7386 |
T7385 |
punct |
-,wk |
R4802 |
T7387 |
T7383 |
amod |
old,mice |
R4803 |
T7388 |
T7387 |
punct |
-,old |
R4804 |
T7389 |
T7356 |
punct |
.,harbor |
R4805 |
T7391 |
T7392 |
nsubj |
Measurement,demonstrated |
R4806 |
T7393 |
T7391 |
prep |
of,Measurement |
R4807 |
T7394 |
T7395 |
amod |
total,Aβ |
R4808 |
T7395 |
T7393 |
pobj |
Aβ,of |
R4809 |
T7396 |
T7391 |
prep |
in,Measurement |
R4810 |
T7397 |
T7398 |
advmod |
chronically,treated |
R4811 |
T7398 |
T7399 |
amod |
treated,mice |
R4812 |
T7399 |
T7396 |
pobj |
mice,in |
R4813 |
T7400 |
T7391 |
punct |
", ",Measurement |
R4814 |
T7401 |
T7391 |
prep |
including,Measurement |
R4815 |
T7402 |
T7403 |
amod |
endogenous,peptide |
R4816 |
T7403 |
T7401 |
pobj |
peptide,including |
R4817 |
T7404 |
T7402 |
cc |
and,endogenous |
R4818 |
T7405 |
T7406 |
npadvmod |
transgene,derived |
R4819 |
T7406 |
T7402 |
conj |
derived,endogenous |
R4820 |
T7407 |
T7406 |
punct |
-,derived |
R4821 |
T7408 |
T7392 |
punct |
", ",demonstrated |
R4822 |
T7409 |
T7410 |
mark |
that,reduced |
R4823 |
T7410 |
T7392 |
ccomp |
reduced,demonstrated |
R4824 |
T7411 |
T7412 |
compound |
Aβ,levels |
R4825 |
T7412 |
T7410 |
nsubjpass |
levels,reduced |
R4826 |
T7413 |
T7412 |
prep |
in,levels |
R4827 |
T7414 |
T7415 |
compound |
tet,off |
R4828 |
T7415 |
T7417 |
compound |
off,mice |
R4829 |
T7416 |
T7415 |
punct |
-,off |
R4830 |
T7417 |
T7413 |
pobj |
mice,in |
R4831 |
T7418 |
T7417 |
compound |
APP,mice |
R4832 |
T7419 |
T7410 |
auxpass |
were,reduced |
R4833 |
T7420 |
T7410 |
prep |
to,reduced |
R4834 |
T7421 |
T7422 |
det |
the,level |
R4835 |
T7422 |
T7420 |
pobj |
level,to |
R4836 |
T7423 |
T7422 |
prep |
of,level |
R4837 |
T7424 |
T7425 |
amod |
endogenous,peptide |
R4838 |
T7425 |
T7423 |
pobj |
peptide,of |
R4839 |
T7426 |
T7422 |
acl |
found,level |
R4840 |
T7427 |
T7426 |
prep |
in,found |
R4841 |
T7428 |
T7429 |
amod |
nontransgenic,animals |
R4842 |
T7429 |
T7427 |
pobj |
animals,in |
R4843 |
T7430 |
T7431 |
punct |
(,2D |
R4844 |
T7431 |
T7410 |
parataxis |
2D,reduced |
R4845 |
T7432 |
T7431 |
compound |
Figure,2D |
R4846 |
T7433 |
T7431 |
punct |
),2D |
R4847 |
T7434 |
T7392 |
punct |
.,demonstrated |
R4848 |
T7436 |
T7437 |
advcl |
Taken,indicate |
R4849 |
T7438 |
T7436 |
advmod |
together,Taken |
R4850 |
T7439 |
T7436 |
prep |
with,Taken |
R4851 |
T7440 |
T7441 |
det |
the,data |
R4852 |
T7441 |
T7439 |
pobj |
data,with |
R4853 |
T7442 |
T7441 |
compound |
immunoblotting,data |
R4854 |
T7443 |
T7441 |
prep |
for,data |
R4855 |
T7444 |
T7445 |
amod |
full,length |
R4856 |
T7445 |
T7447 |
compound |
length,ind |
R4857 |
T7446 |
T7445 |
punct |
-,length |
R4858 |
T7447 |
T7443 |
pobj |
ind,for |
R4859 |
T7448 |
T7447 |
compound |
APPswe,ind |
R4860 |
T7449 |
T7447 |
punct |
/,ind |
R4861 |
T7450 |
T7437 |
punct |
", ",indicate |
R4862 |
T7451 |
T7452 |
det |
the,measurements |
R4863 |
T7452 |
T7437 |
nsubj |
measurements,indicate |
R4864 |
T7453 |
T7452 |
compound |
ELISA,measurements |
R4865 |
T7454 |
T7455 |
mark |
that,leads |
R4866 |
T7455 |
T7437 |
ccomp |
leads,indicate |
R4867 |
T7543 |
T7544 |
advmod |
as,young |
R4868 |
T7456 |
T7457 |
npadvmod |
dox,mediated |
R4869 |
T7544 |
T7542 |
amod |
young,mice |
R4870 |
T7545 |
T7544 |
prep |
as,young |
R4871 |
T7457 |
T7459 |
amod |
mediated,suppression |
R4872 |
T7546 |
T7547 |
nummod |
8,wk |
R4873 |
T7547 |
T7545 |
pobj |
wk,as |
R4874 |
T7548 |
T7547 |
prep |
of,wk |
R4875 |
T7458 |
T7457 |
punct |
-,mediated |
R4876 |
T7549 |
T7548 |
pobj |
age,of |
R4877 |
T7550 |
T7551 |
punct |
(,shown |
R4878 |
T7459 |
T7455 |
nsubj |
suppression,leads |
R4879 |
T7551 |
T7539 |
parataxis |
shown,seen |
R4880 |
T7552 |
T7551 |
nsubj |
data,shown |
R4881 |
T7460 |
T7459 |
prep |
of,suppression |
R4882 |
T7553 |
T7551 |
neg |
not,shown |
R4883 |
T7554 |
T7551 |
punct |
),shown |
R4884 |
T7555 |
T7539 |
punct |
.,seen |
R4885 |
T7461 |
T7462 |
amod |
transgenic,synthesis |
R4886 |
T7557 |
T7558 |
nsubjpass |
Plaques,limited |
R4887 |
T7462 |
T7460 |
pobj |
synthesis,of |
R4888 |
T7559 |
T7558 |
auxpass |
were,limited |
R4889 |
T7463 |
T7464 |
compound |
APPswe,ind |
R4890 |
T7560 |
T7558 |
prep |
to,limited |
R4891 |
T7561 |
T7562 |
det |
the,forebrain |
R4892 |
T7562 |
T7560 |
pobj |
forebrain,to |
R4893 |
T7464 |
T7462 |
compound |
ind,synthesis |
R4894 |
T7563 |
T7562 |
punct |
", ",forebrain |
R4895 |
T7564 |
T7562 |
prep |
including,forebrain |
R4896 |
T7565 |
T7566 |
det |
the,cortex |
R4897 |
T7465 |
T7464 |
punct |
/,ind |
R4898 |
T7566 |
T7564 |
pobj |
cortex,including |
R4899 |
T7567 |
T7566 |
punct |
", ",cortex |
R4900 |
T7568 |
T7566 |
conj |
hippocampus,cortex |
R4901 |
T7569 |
T7568 |
punct |
", ",hippocampus |
R4902 |
T7570 |
T7571 |
amod |
olfactory,bulb |
R4903 |
T7466 |
T7455 |
prep |
to,leads |
R4904 |
T7571 |
T7568 |
conj |
bulb,hippocampus |
R4905 |
T7572 |
T7571 |
punct |
", ",bulb |
R4906 |
T7573 |
T7571 |
cc |
and,bulb |
R4907 |
T7467 |
T7468 |
amod |
parallel,reduction |
R4908 |
T7574 |
T7571 |
conj |
striatum,bulb |
R4909 |
T7468 |
T7466 |
pobj |
reduction,to |
R4910 |
T7575 |
T7562 |
punct |
", ",forebrain |
R4911 |
T7576 |
T7577 |
advmod |
where,known |
R4912 |
T7577 |
T7562 |
relcl |
known,forebrain |
R4913 |
T7578 |
T7579 |
det |
the,promoter |
R4914 |
T7469 |
T7468 |
prep |
of,reduction |
R4915 |
T7579 |
T7577 |
nsubjpass |
promoter,known |
R4916 |
T7580 |
T7579 |
compound |
CaMKIIα,promoter |
R4917 |
T7581 |
T7577 |
auxpass |
is,known |
R4918 |
T7470 |
T7471 |
compound |
Aβ,levels |
R4919 |
T7582 |
T7583 |
aux |
to,be |
R4920 |
T7583 |
T7577 |
xcomp |
be,known |
R4921 |
T7584 |
T7585 |
advmod |
most,active |
R4922 |
T7471 |
T7469 |
pobj |
levels,of |
R4923 |
T7585 |
T7583 |
acomp |
active,be |
R4924 |
T7586 |
T7587 |
punct |
[,28 |
R4925 |
T7472 |
T7437 |
punct |
.,indicate |
R4926 |
T7474 |
T7475 |
det |
The,data |
R4927 |
T7587 |
T7577 |
parataxis |
28,known |
R4928 |
T7588 |
T7587 |
nummod |
16,28 |
R4929 |
T7589 |
T7587 |
punct |
",",28 |
R4930 |
T7475 |
T7477 |
nsubj |
data,confirmed |
R4931 |
T7590 |
T7587 |
punct |
],28 |
R4932 |
T7591 |
T7592 |
punct |
(,S2 |
R4933 |
T7476 |
T7475 |
compound |
ELISA,data |
R4934 |
T7592 |
T7558 |
parataxis |
S2,limited |
R4935 |
T7593 |
T7592 |
compound |
Figure,S2 |
R4936 |
T7594 |
T7592 |
punct |
),S2 |
R4937 |
T7478 |
T7477 |
advmod |
also,confirmed |
R4938 |
T7595 |
T7558 |
punct |
.,limited |
R4939 |
T7597 |
T7598 |
prep |
By,became |
R4940 |
T7479 |
T7480 |
mark |
that,led |
R4941 |
T7599 |
T7600 |
nummod |
6,mo |
R4942 |
T7480 |
T7477 |
ccomp |
led,confirmed |
R4943 |
T7600 |
T7597 |
pobj |
mo,By |
R4944 |
T7601 |
T7600 |
prep |
of,mo |
R4945 |
T7602 |
T7601 |
pobj |
age,of |
R4946 |
T7481 |
T7480 |
nsubj |
incorporation,led |
R4947 |
T7603 |
T7598 |
punct |
", ",became |
R4948 |
T7604 |
T7605 |
compound |
amyloid,burden |
R4949 |
T7605 |
T7598 |
nsubj |
burden,became |
R4950 |
T7606 |
T7598 |
acomp |
severe,became |
R4951 |
T7607 |
T7598 |
punct |
", ",became |
R4952 |
T7608 |
T7598 |
advcl |
covering,became |
R4953 |
T7482 |
T7481 |
prep |
of,incorporation |
R4954 |
T7609 |
T7610 |
amod |
large,areas |
R4955 |
T7610 |
T7608 |
dobj |
areas,covering |
R4956 |
T7611 |
T7610 |
prep |
of,areas |
R4957 |
T7483 |
T7484 |
det |
the,mutations |
R4958 |
T7612 |
T7613 |
det |
the,cortex |
R4959 |
T7613 |
T7611 |
pobj |
cortex,of |
R4960 |
T7614 |
T7613 |
cc |
and,cortex |
R4961 |
T7484 |
T7482 |
pobj |
mutations,of |
R4962 |
T7615 |
T7613 |
conj |
hippocampus,cortex |
R4963 |
T7485 |
T7484 |
amod |
Swedish,mutations |
R4964 |
T7616 |
T7617 |
punct |
(,S3 |
R4965 |
T7617 |
T7608 |
parataxis |
S3,covering |
R4966 |
T7618 |
T7617 |
compound |
Figure,S3 |
R4967 |
T7619 |
T7617 |
punct |
),S3 |
R4968 |
T7486 |
T7485 |
cc |
and,Swedish |
R4969 |
T7620 |
T7598 |
punct |
.,became |
R4970 |
T7487 |
T7485 |
conj |
Indiana,Swedish |
R4971 |
T7622 |
T7623 |
det |
No,lesions |
R4972 |
T7623 |
T7624 |
nsubjpass |
lesions,seen |
R4973 |
T7488 |
T7480 |
prep |
to,led |
R4974 |
T7625 |
T7624 |
auxpass |
were,seen |
R4975 |
T7626 |
T7624 |
prep |
in,seen |
R4976 |
T7489 |
T7490 |
amod |
high,levels |
R4977 |
T7627 |
T7628 |
det |
the,cerebellum |
R4978 |
T7628 |
T7626 |
pobj |
cerebellum,in |
R4979 |
T7629 |
T7628 |
cc |
or,cerebellum |
R4980 |
T7490 |
T7488 |
pobj |
levels,to |
R4981 |
T7630 |
T7631 |
compound |
brain,stem |
R4982 |
T7631 |
T7628 |
conj |
stem,cerebellum |
R4983 |
T7632 |
T7633 |
advmod |
even,at |
R4984 |
T7491 |
T7490 |
prep |
of,levels |
R4985 |
T7633 |
T7624 |
prep |
at,seen |
R4986 |
T7634 |
T7635 |
amod |
late,ages |
R4987 |
T7635 |
T7633 |
pobj |
ages,at |
R4988 |
T7492 |
T7491 |
pobj |
Aβ42,of |
R4989 |
T7636 |
T7624 |
punct |
", ",seen |
R4990 |
T7637 |
T7624 |
advcl |
consistent,seen |
R4991 |
T7493 |
T7490 |
punct |
", ",levels |
R4992 |
T7638 |
T7637 |
prep |
with,consistent |
R4993 |
T7639 |
T7640 |
npadvmod |
CaMKIIα,controlled |
R4994 |
T7640 |
T7642 |
amod |
controlled,expression |
R4995 |
T7494 |
T7495 |
dep |
which,predicted |
R4996 |
T7641 |
T7640 |
punct |
-,controlled |
R4997 |
T7642 |
T7638 |
pobj |
expression,with |
R4998 |
T7643 |
T7642 |
compound |
transgene,expression |
R4999 |
T7495 |
T7490 |
relcl |
predicted,levels |
R5000 |
T7644 |
T7624 |
punct |
.,seen |
R5001 |
T7496 |
T7495 |
nsubj |
we,predicted |
R5002 |
T7646 |
T7647 |
prep |
Unlike,are |
R5003 |
T7648 |
T7649 |
dep |
what,thought |
R5004 |
T7497 |
T7498 |
aux |
would,induce |
R5005 |
T7498 |
T7495 |
advcl |
induce,predicted |
R5006 |
T7499 |
T7500 |
amod |
rapid,formation |
R5007 |
T7500 |
T7498 |
dobj |
formation,induce |
R5008 |
T7649 |
T7646 |
pcomp |
thought,Unlike |
R5009 |
T7650 |
T7649 |
auxpass |
is,thought |
R5010 |
T7501 |
T7500 |
compound |
plaque,formation |
R5011 |
T7502 |
T7498 |
prep |
in,induce |
R5012 |
T7651 |
T7652 |
aux |
to,occur |
R5013 |
T7503 |
T7504 |
amod |
untreated,animals |
R5014 |
T7652 |
T7649 |
xcomp |
occur,thought |
R5015 |
T7504 |
T7502 |
pobj |
animals,in |
R5016 |
T7653 |
T7652 |
prep |
in,occur |
R5017 |
T7654 |
T7655 |
det |
the,disease |
R5018 |
T7505 |
T7477 |
punct |
.,confirmed |
R5019 |
T7655 |
T7653 |
pobj |
disease,in |
R5020 |
T7656 |
T7655 |
amod |
human,disease |
R5021 |
T7657 |
T7647 |
punct |
", ",are |
R5022 |
T7507 |
T7508 |
parataxis |
Histological,characterization |
R5023 |
T7658 |
T7659 |
det |
the,plaques |
R5024 |
T7659 |
T7647 |
nsubj |
plaques,are |
R5025 |
T7660 |
T7659 |
amod |
first,plaques |
R5026 |
T7508 |
T7509 |
nsubj |
characterization,revealed |
R5027 |
T7661 |
T7659 |
amod |
visible,plaques |
R5028 |
T7662 |
T7659 |
prep |
in,plaques |
R5029 |
T7663 |
T7664 |
det |
the,mice |
R5030 |
T7510 |
T7508 |
prep |
of,characterization |
R5031 |
T7664 |
T7662 |
pobj |
mice,in |
R5032 |
T7665 |
T7666 |
compound |
tet,off |
R5033 |
T7666 |
T7664 |
compound |
off,mice |
R5034 |
T7511 |
T7512 |
amod |
double,mice |
R5035 |
T7667 |
T7666 |
punct |
-,off |
R5036 |
T7668 |
T7664 |
compound |
APP,mice |
R5037 |
T7669 |
T7670 |
amod |
fibrillar,cored |
R5038 |
T7512 |
T7510 |
pobj |
mice,of |
R5039 |
T7670 |
T7672 |
amod |
cored,deposits |
R5040 |
T7671 |
T7670 |
punct |
-,cored |
R5041 |
T7672 |
T7647 |
attr |
deposits,are |
R5042 |
T7513 |
T7512 |
amod |
transgenic,mice |
R5043 |
T7673 |
T7647 |
punct |
.,are |
R5044 |
T7514 |
T7515 |
punct |
(,APPswe |
R5045 |
T7675 |
T7676 |
nsubj |
We,noted |
R5046 |
T7515 |
T7512 |
parataxis |
APPswe,mice |
R5047 |
T7677 |
T7676 |
aux |
have,noted |
R5048 |
T7516 |
T7515 |
nmod |
CaMKIIα,APPswe |
R5049 |
T7517 |
T7515 |
punct |
-,APPswe |
R5050 |
T7678 |
T7679 |
det |
the,appearance |
R5051 |
T7679 |
T7676 |
dobj |
appearance,noted |
R5052 |
T7518 |
T7515 |
nmod |
tTA,APPswe |
R5053 |
T7680 |
T7679 |
amod |
same,appearance |
R5054 |
T7681 |
T7679 |
amod |
early,appearance |
R5055 |
T7682 |
T7679 |
prep |
of,appearance |
R5056 |
T7683 |
T7684 |
amod |
cored,deposits |
R5057 |
T7684 |
T7682 |
pobj |
deposits,of |
R5058 |
T7519 |
T7515 |
punct |
×,APPswe |
R5059 |
T7685 |
T7679 |
prep |
in,appearance |
R5060 |
T7686 |
T7687 |
amod |
other,lines |
R5061 |
T7520 |
T7515 |
compound |
tet,APPswe |
R5062 |
T7687 |
T7685 |
pobj |
lines,in |
R5063 |
T7688 |
T7687 |
prep |
of,lines |
R5064 |
T7521 |
T7515 |
punct |
-,APPswe |
R5065 |
T7689 |
T7690 |
nmod |
APP,mice |
R5066 |
T7690 |
T7688 |
pobj |
mice,of |
R5067 |
T7691 |
T7690 |
amod |
transgenic,mice |
R5068 |
T7522 |
T7515 |
punct |
/,APPswe |
R5069 |
T7692 |
T7693 |
dep |
that,harbor |
R5070 |
T7693 |
T7687 |
relcl |
harbor,lines |
R5071 |
T7523 |
T7515 |
amod |
ind,APPswe |
R5072 |
T7694 |
T7695 |
det |
the,mutation |
R5073 |
T7695 |
T7693 |
dobj |
mutation,harbor |
R5074 |
T7696 |
T7695 |
amod |
Swedish,mutation |
R5075 |
T7524 |
T7515 |
punct |
),APPswe |
R5076 |
T7697 |
T7698 |
punct |
[,27 |
R5077 |
T7698 |
T7676 |
parataxis |
27,noted |
R5078 |
T7525 |
T7526 |
amod |
early,onset |
R5079 |
T7699 |
T7698 |
punct |
],27 |
R5080 |
T7700 |
T7676 |
punct |
.,noted |
R5081 |
T7526 |
T7528 |
compound |
onset,formation |
R5082 |
T7702 |
T7703 |
compound |
Diffuse,plaques |
R5083 |
T7703 |
T7704 |
nsubj |
plaques,were |
R5084 |
T7527 |
T7526 |
punct |
-,onset |
R5085 |
T7705 |
T7704 |
acomp |
apparent,were |
R5086 |
T7706 |
T7704 |
prep |
in,were |
R5087 |
T7528 |
T7509 |
dobj |
formation,revealed |
R5088 |
T7707 |
T7708 |
nummod |
6,mo |
R5089 |
T7708 |
T7710 |
npadvmod |
mo,old |
R5090 |
T7529 |
T7528 |
compound |
amyloid,formation |
R5091 |
T7709 |
T7708 |
punct |
-,mo |
R5092 |
T7710 |
T7712 |
amod |
old,mice |
R5093 |
T7711 |
T7710 |
punct |
-,old |
R5094 |
T7530 |
T7509 |
prep |
in,revealed |
R5095 |
T7712 |
T7706 |
pobj |
mice,in |
R5096 |
T7713 |
T7714 |
compound |
tTA,APP |
R5097 |
T7714 |
T7712 |
compound |
APP,mice |
R5098 |
T7531 |
T7532 |
det |
all,lines |
R5099 |
T7715 |
T7714 |
punct |
/,APP |
R5100 |
T7716 |
T7704 |
punct |
", ",were |
R5101 |
T7717 |
T7704 |
cc |
and,were |
R5102 |
T7532 |
T7530 |
pobj |
lines,in |
R5103 |
T7718 |
T7704 |
conj |
became,were |
R5104 |
T7719 |
T7720 |
advmod |
relatively,abundant |
R5105 |
T7533 |
T7532 |
nummod |
four,lines |
R5106 |
T7720 |
T7718 |
acomp |
abundant,became |
R5107 |
T7721 |
T7718 |
prep |
by,became |
R5108 |
T7722 |
T7723 |
nummod |
9,mo |
R5109 |
T7723 |
T7721 |
pobj |
mo,by |
R5110 |
T7724 |
T7723 |
prep |
of,mo |
R5111 |
T7725 |
T7724 |
pobj |
age,of |
R5112 |
T7534 |
T7532 |
amod |
new,lines |
R5113 |
T7726 |
T7704 |
punct |
.,were |
R5114 |
T7728 |
T7729 |
prep |
At,were |
R5115 |
T7535 |
T7509 |
punct |
.,revealed |
R5116 |
T7730 |
T7731 |
amod |
older,ages |
R5117 |
T7537 |
T7538 |
compound |
Amyloid,plaques |
R5118 |
T7731 |
T7728 |
pobj |
ages,At |
R5119 |
T7732 |
T7731 |
punct |
(,ages |
R5120 |
T7733 |
T7734 |
quantmod |
9,12 |
R5121 |
T7538 |
T7539 |
nsubjpass |
plaques,seen |
R5122 |
T7734 |
T7736 |
nummod |
12,mo |
R5123 |
T7735 |
T7734 |
punct |
–,12 |
R5124 |
T7736 |
T7731 |
appos |
mo,ages |
R5125 |
T7540 |
T7539 |
auxpass |
were,seen |
R5126 |
T7737 |
T7729 |
punct |
),were |
R5127 |
T7738 |
T7739 |
compound |
amyloid,deposits |
R5128 |
T7739 |
T7729 |
nsubj |
deposits,were |
R5129 |
T7541 |
T7539 |
prep |
in,seen |
R5130 |
T7740 |
T7729 |
acomp |
visible,were |
R5131 |
T7741 |
T7729 |
prep |
in,were |
R5132 |
T7742 |
T7743 |
det |
the,thalamus |
R5133 |
T7542 |
T7541 |
pobj |
mice,in |
R5134 |
T7743 |
T7741 |
pobj |
thalamus,in |
R5136 |
T7744 |
T7743 |
punct |
", ",thalamus |
R5137 |
T7745 |
T7746 |
dep |
which,observed |
R5138 |
T7746 |
T7743 |
relcl |
observed,thalamus |
R5139 |
T7747 |
T7746 |
aux |
has,observed |
R5140 |
T7748 |
T7746 |
advmod |
also,observed |
R5141 |
T7756 |
T7757 |
det |
the,promoter |
R5142 |
T7749 |
T7746 |
auxpass |
been,observed |
R5143 |
T7750 |
T7746 |
prep |
in,observed |
R5144 |
T7751 |
T7750 |
pobj |
mice,in |
R5145 |
T7757 |
T7755 |
pobj |
promoter,via |
R5146 |
T7752 |
T7751 |
acl |
expressing,mice |
R5147 |
T7753 |
T7754 |
compound |
mutant,APP |
R5148 |
T7754 |
T7752 |
dobj |
APP,expressing |
R5149 |
T7758 |
T7757 |
nmod |
Thy,promoter |
R5150 |
T7759 |
T7758 |
punct |
-,Thy |
R5151 |
T7760 |
T7758 |
nummod |
1,Thy |
R5152 |
T7761 |
T7729 |
punct |
.,were |
R5153 |
T7763 |
T7764 |
det |
The,presence |
R5154 |
T7861 |
T7859 |
amod |
expressing,line |
R5155 |
T7862 |
T7859 |
punct |
(,line |
R5156 |
T7863 |
T7859 |
appos |
line,line |
R5157 |
T7764 |
T7765 |
nsubjpass |
presence,attributed |
R5158 |
T7864 |
T7863 |
nummod |
885,line |
R5159 |
T7865 |
T7855 |
punct |
),Animals |
R5160 |
T7866 |
T7855 |
acl |
maintained,Animals |
R5161 |
T7867 |
T7866 |
prep |
on,maintained |
R5162 |
T7868 |
T7867 |
pobj |
dox,on |
R5163 |
T7869 |
T7866 |
prep |
for,maintained |
R5164 |
T7870 |
T7869 |
prep |
up,for |
R5165 |
T7871 |
T7870 |
prep |
to,up |
R5166 |
T7766 |
T7764 |
prep |
of,presence |
R5167 |
T7872 |
T7873 |
nummod |
1,y |
R5168 |
T7873 |
T7871 |
pobj |
y,to |
R5169 |
T7874 |
T7875 |
det |
no,pathology |
R5170 |
T7875 |
T7856 |
dobj |
pathology,harbored |
R5171 |
T7876 |
T7875 |
compound |
amyloid,pathology |
R5172 |
T7767 |
T7768 |
compound |
amyloid,pathology |
R5173 |
T7877 |
T7878 |
punct |
(,shown |
R5174 |
T7878 |
T7875 |
parataxis |
shown,pathology |
R5175 |
T7768 |
T7766 |
pobj |
pathology,of |
R5176 |
T7879 |
T7878 |
nsubj |
data,shown |
R5177 |
T7880 |
T7878 |
neg |
not,shown |
R5178 |
T7881 |
T7875 |
punct |
),pathology |
R5179 |
T7769 |
T7764 |
prep |
in,presence |
R5180 |
T7882 |
T7856 |
punct |
", ",harbored |
R5181 |
T7883 |
T7856 |
advcl |
indicating,harbored |
R5182 |
T7770 |
T7771 |
det |
this,region |
R5183 |
T7884 |
T7885 |
mark |
that,provide |
R5184 |
T7885 |
T7883 |
ccomp |
provide,indicating |
R5185 |
T7886 |
T7887 |
amod |
residual,leakage |
R5186 |
T7771 |
T7769 |
pobj |
region,in |
R5187 |
T7887 |
T7885 |
nsubj |
leakage,provide |
R5188 |
T7888 |
T7887 |
prep |
of,leakage |
R5189 |
T7772 |
T7765 |
aux |
has,attributed |
R5190 |
T7889 |
T7890 |
compound |
transgene,expression |
R5191 |
T7890 |
T7888 |
pobj |
expression,of |
R5192 |
T7891 |
T7887 |
prep |
in,leakage |
R5193 |
T7773 |
T7765 |
auxpass |
been,attributed |
R5194 |
T7892 |
T7893 |
det |
the,presence |
R5195 |
T7893 |
T7891 |
pobj |
presence,in |
R5196 |
T7894 |
T7893 |
prep |
of,presence |
R5197 |
T7774 |
T7765 |
prep |
to,attributed |
R5198 |
T7895 |
T7894 |
pobj |
dox,of |
R5199 |
T7896 |
T7885 |
aux |
does,provide |
R5200 |
T7897 |
T7885 |
neg |
not,provide |
R5201 |
T7775 |
T7776 |
amod |
axonal,transport |
R5202 |
T7898 |
T7899 |
amod |
sufficient,peptide |
R5203 |
T7899 |
T7885 |
dobj |
peptide,provide |
R5204 |
T7900 |
T7899 |
compound |
Aβ,peptide |
R5205 |
T7776 |
T7774 |
pobj |
transport,to |
R5206 |
T7901 |
T7902 |
aux |
to,induce |
R5207 |
T7902 |
T7899 |
acl |
induce,peptide |
R5208 |
T7903 |
T7904 |
compound |
amyloid,formation |
R5209 |
T7777 |
T7776 |
prep |
of,transport |
R5210 |
T7904 |
T7902 |
dobj |
formation,induce |
R5211 |
T7905 |
T7906 |
advmod |
even,over |
R5212 |
T7906 |
T7902 |
prep |
over,induce |
R5213 |
T7907 |
T7908 |
amod |
long,periods |
R5214 |
T7908 |
T7906 |
pobj |
periods,over |
R5215 |
T7778 |
T7779 |
compound |
APP,Aβ |
R5216 |
T7909 |
T7856 |
punct |
.,harbored |
R5217 |
T7911 |
T7912 |
aux |
To,mimic |
R5218 |
T7779 |
T7777 |
pobj |
Aβ,of |
R5219 |
T7912 |
T7913 |
advcl |
mimic,raised |
R5220 |
T7780 |
T7779 |
punct |
/,Aβ |
R5221 |
T7914 |
T7915 |
amod |
therapeutic,intervention |
R5222 |
T7915 |
T7912 |
dobj |
intervention,mimic |
R5223 |
T7916 |
T7912 |
prep |
with,mimic |
R5224 |
T7781 |
T7776 |
prep |
to,transport |
R5225 |
T7917 |
T7916 |
pobj |
inhibitors,with |
R5226 |
T7918 |
T7917 |
prep |
of,inhibitors |
R5227 |
T7782 |
T7783 |
det |
the,terminals |
R5228 |
T7919 |
T7920 |
compound |
Aβ,production |
R5229 |
T7920 |
T7918 |
pobj |
production,of |
R5230 |
T7921 |
T7913 |
punct |
", ",raised |
R5231 |
T7783 |
T7781 |
pobj |
terminals,to |
R5232 |
T7922 |
T7913 |
nsubj |
we,raised |
R5233 |
T7923 |
T7924 |
det |
a,group |
R5234 |
T7784 |
T7783 |
prep |
of,terminals |
R5235 |
T7924 |
T7913 |
dobj |
group,raised |
R5236 |
T7925 |
T7924 |
prep |
of,group |
R5237 |
T7785 |
T7786 |
amod |
cortical,neurons |
R5238 |
T7926 |
T7927 |
nummod |
25,mice |
R5239 |
T7927 |
T7925 |
pobj |
mice,of |
R5240 |
T7928 |
T7929 |
amod |
double,transgenic |
R5241 |
T7786 |
T7784 |
pobj |
neurons,of |
R5242 |
T7929 |
T7927 |
amod |
transgenic,mice |
R5243 |
T7930 |
T7931 |
punct |
(,APP |
R5244 |
T7787 |
T7783 |
prep |
in,terminals |
R5245 |
T7931 |
T7927 |
parataxis |
APP,mice |
R5246 |
T7932 |
T7931 |
nmod |
CaMKIIα,APP |
R5247 |
T7933 |
T7931 |
punct |
-,APP |
R5248 |
T7788 |
T7789 |
det |
the,thalamus |
R5249 |
T7934 |
T7931 |
nmod |
tTA,APP |
R5250 |
T7935 |
T7931 |
punct |
×,APP |
R5251 |
T7789 |
T7787 |
pobj |
thalamus,in |
R5252 |
T7936 |
T7931 |
appos |
line,APP |
R5253 |
T7790 |
T7791 |
punct |
[,29 |
R5254 |
T7791 |
T7765 |
parataxis |
29,attributed |
R5255 |
T7937 |
T7936 |
nummod |
107,line |
R5256 |
T7938 |
T7931 |
punct |
),APP |
R5257 |
T7792 |
T7791 |
punct |
],29 |
R5258 |
T7939 |
T7913 |
prep |
on,raised |
R5259 |
T7940 |
T7941 |
amod |
normal,food |
R5260 |
T7941 |
T7939 |
pobj |
food,on |
R5261 |
T7793 |
T7765 |
punct |
.,attributed |
R5262 |
T7942 |
T7913 |
prep |
until,raised |
R5263 |
T7943 |
T7944 |
nummod |
6,mo |
R5264 |
T7944 |
T7942 |
pobj |
mo,until |
R5265 |
T7945 |
T7944 |
prep |
of,mo |
R5266 |
T7795 |
T7796 |
advmod |
Most,importantly |
R5267 |
T7946 |
T7945 |
pobj |
age,of |
R5268 |
T7947 |
T7913 |
punct |
", ",raised |
R5269 |
T7948 |
T7949 |
advmod |
when,knew |
R5270 |
T7796 |
T7797 |
advmod |
importantly,developed |
R5271 |
T7949 |
T7913 |
advcl |
knew,raised |
R5272 |
T7950 |
T7949 |
nsubj |
we,knew |
R5273 |
T7798 |
T7797 |
punct |
", ",developed |
R5274 |
T7951 |
T7952 |
compound |
amyloid,formation |
R5275 |
T7952 |
T7953 |
nsubj |
formation,was |
R5276 |
T7953 |
T7949 |
advcl |
was,knew |
R5277 |
T7799 |
T7800 |
advmod |
only,mice |
R5278 |
T7954 |
T7953 |
advmod |
already,was |
R5279 |
T7955 |
T7956 |
advmod |
well,underway |
R5280 |
T7956 |
T7953 |
acomp |
underway,was |
R5281 |
T7800 |
T7797 |
nsubj |
mice,developed |
R5282 |
T7957 |
T7953 |
prep |
in,was |
R5283 |
T7958 |
T7959 |
det |
the,brain |
R5284 |
T7801 |
T7802 |
amod |
double,transgenic |
R5285 |
T7959 |
T7957 |
pobj |
brain,in |
R5286 |
T7960 |
T7913 |
punct |
.,raised |
R5287 |
T7802 |
T7800 |
amod |
transgenic,mice |
R5288 |
T7962 |
T7963 |
prep |
At,switched |
R5289 |
T7803 |
T7800 |
punct |
", ",mice |
R5290 |
T7964 |
T7965 |
nummod |
6,mo |
R5291 |
T7965 |
T7962 |
pobj |
mo,At |
R5292 |
T7804 |
T7800 |
acl |
expressing,mice |
R5293 |
T7966 |
T7963 |
punct |
", ",switched |
R5294 |
T7805 |
T7806 |
preconj |
both,transgenes |
R5295 |
T7806 |
T7804 |
dobj |
transgenes,expressing |
R5296 |
T7967 |
T7963 |
nsubjpass |
half,switched |
R5297 |
T7968 |
T7967 |
prep |
of,half |
R5298 |
T7807 |
T7806 |
det |
the,transgenes |
R5299 |
T7969 |
T7970 |
det |
the,animals |
R5300 |
T7970 |
T7968 |
pobj |
animals,of |
R5301 |
T7808 |
T7806 |
nmod |
tTA,transgenes |
R5302 |
T7971 |
T7963 |
auxpass |
were,switched |
R5303 |
T7809 |
T7808 |
cc |
and,tTA |
R5304 |
T7972 |
T7963 |
prep |
from,switched |
R5305 |
T7973 |
T7974 |
amod |
normal,chow |
R5306 |
T7974 |
T7972 |
pobj |
chow,from |
R5307 |
T7810 |
T7808 |
conj |
APP,tTA |
R5308 |
T7975 |
T7963 |
prep |
to,switched |
R5309 |
T7976 |
T7975 |
pobj |
food,to |
R5310 |
T7811 |
T7797 |
punct |
", ",developed |
R5311 |
T7977 |
T7976 |
acl |
containing,food |
R5312 |
T7978 |
T7977 |
dobj |
dox,containing |
R5313 |
T7979 |
T7977 |
prep |
at,containing |
R5314 |
T7980 |
T7981 |
nummod |
200,mg |
R5315 |
T7981 |
T7979 |
pobj |
mg,at |
R5316 |
T7812 |
T7813 |
compound |
amyloid,lesions |
R5317 |
T7982 |
T7983 |
punct |
/,kg |
R5318 |
T7983 |
T7981 |
prep |
kg,mg |
R5319 |
T7984 |
T7985 |
mark |
until,sacrificed |
R5320 |
T7813 |
T7797 |
dobj |
lesions,developed |
R5321 |
T7985 |
T7963 |
advcl |
sacrificed,switched |
R5322 |
T7986 |
T7985 |
nsubjpass |
they,sacrificed |
R5323 |
T7987 |
T7985 |
auxpass |
were,sacrificed |
R5324 |
T7814 |
T7797 |
punct |
.,developed |
R5325 |
T7988 |
T7985 |
prep |
at,sacrificed |
R5326 |
T7989 |
T7990 |
nummod |
9,mo |
R5327 |
T7816 |
T7817 |
amod |
Single,transgenic |
R5328 |
T7990 |
T7988 |
pobj |
mo,at |
R5329 |
T7991 |
T7989 |
cc |
or,9 |
R5330 |
T7992 |
T7989 |
conj |
12,9 |
R5331 |
T7993 |
T7990 |
prep |
of,mo |
R5332 |
T7817 |
T7818 |
amod |
transgenic,mice |
R5333 |
T7994 |
T7993 |
pobj |
age,of |
R5334 |
T7995 |
T7963 |
punct |
.,switched |
R5335 |
T7818 |
T7819 |
nsubj |
mice,showed |
R5336 |
T7997 |
T7998 |
det |
The,animals |
R5337 |
T7998 |
T8001 |
nsubjpass |
animals,kept |
R5338 |
T7820 |
T7821 |
quantmod |
up,15 |
R5339 |
T7999 |
T7998 |
amod |
remaining,animals |
R5340 |
T8000 |
T7998 |
compound |
control,animals |
R5341 |
T7821 |
T7823 |
nummod |
15,mo |
R5342 |
T8002 |
T8001 |
auxpass |
were,kept |
R5343 |
T8003 |
T8001 |
prep |
on,kept |
R5344 |
T8004 |
T8005 |
amod |
standard,chow |
R5345 |
T7822 |
T7821 |
quantmod |
to,15 |
R5346 |
T8005 |
T8003 |
pobj |
chow,on |
R5347 |
T8006 |
T8007 |
punct |
(,untreated |
R5348 |
T7823 |
T7818 |
npadvmod |
mo,mice |
R5349 |
T8007 |
T8001 |
parataxis |
untreated,kept |
R5350 |
T8008 |
T8007 |
punct |
),untreated |
R5351 |
T8009 |
T8001 |
punct |
.,kept |
R5352 |
T7824 |
T7823 |
prep |
of,mo |
R5353 |
T8011 |
T8012 |
prep |
In,created |
R5354 |
T7825 |
T7824 |
pobj |
age,of |
R5355 |
T8013 |
T8011 |
pobj |
all,In |
R5356 |
T8014 |
T8012 |
punct |
", ",created |
R5357 |
T7826 |
T7827 |
det |
no,sign |
R5358 |
T8015 |
T8016 |
nummod |
four,cohorts |
R5359 |
T7827 |
T7819 |
dobj |
sign,showed |
R5360 |
T8016 |
T8012 |
nsubjpass |
cohorts,created |
R5361 |
T7828 |
T7827 |
prep |
of,sign |
R5362 |
T8017 |
T8012 |
auxpass |
were,created |
R5363 |
T8018 |
T8012 |
punct |
: ,created |
R5364 |
T7829 |
T7828 |
pobj |
pathology,of |
R5365 |
T8019 |
T8020 |
nummod |
6,mo |
R5366 |
T8020 |
T8012 |
dobj |
mo,created |
R5367 |
T8021 |
T8020 |
amod |
untreated,mo |
R5368 |
T8022 |
T8023 |
punct |
(,7 |
R5369 |
T7830 |
T7831 |
punct |
(,S3 |
R5370 |
T8023 |
T8020 |
parataxis |
7,mo |
R5371 |
T7831 |
T7819 |
parataxis |
S3,showed |
R5372 |
T8024 |
T8023 |
nsubj |
n,7 |
R5373 |
T8025 |
T8023 |
punct |
=,7 |
R5374 |
T7832 |
T7831 |
compound |
Figure,S3 |
R5375 |
T8026 |
T8023 |
punct |
),7 |
R5376 |
T8027 |
T8020 |
punct |
", ",mo |
R5377 |
T7833 |
T7831 |
punct |
),S3 |
R5378 |
T8028 |
T8029 |
nummod |
9,mo |
R5379 |
T8029 |
T8020 |
conj |
mo,mo |
R5380 |
T8030 |
T8029 |
amod |
untreated,mo |
R5381 |
T7834 |
T7819 |
punct |
.,showed |
R5382 |
T8031 |
T8032 |
punct |
(,5 |
R5383 |
T8032 |
T8029 |
parataxis |
5,mo |
R5384 |
T7836 |
T7837 |
advmod |
Similarly,prevented |
R5385 |
T8033 |
T8032 |
nsubj |
n,5 |
R5386 |
T8034 |
T8032 |
punct |
=,5 |
R5387 |
T8035 |
T8032 |
punct |
),5 |
R5388 |
T7838 |
T7837 |
punct |
", ",prevented |
R5389 |
T8036 |
T8029 |
punct |
", ",mo |
R5390 |
T8037 |
T8038 |
nummod |
6,mo |
R5391 |
T8038 |
T8029 |
conj |
mo,mo |
R5392 |
T8039 |
T8038 |
punct |
+,mo |
R5393 |
T7839 |
T7840 |
compound |
amyloid,pathology |
R5394 |
T8040 |
T8041 |
nummod |
3,mo |
R5395 |
T7840 |
T7837 |
nsubjpass |
pathology,prevented |
R5396 |
T7841 |
T7837 |
aux |
can,prevented |
R5397 |
T8041 |
T8038 |
appos |
mo,mo |
R5398 |
T7842 |
T7837 |
auxpass |
be,prevented |
R5399 |
T8042 |
T8038 |
amod |
treated,mo |
R5400 |
T8043 |
T8044 |
punct |
(,8 |
R5401 |
T7843 |
T7837 |
advmod |
completely,prevented |
R5402 |
T8044 |
T8038 |
parataxis |
8,mo |
R5403 |
T8045 |
T8044 |
nsubj |
n,8 |
R5404 |
T7844 |
T7837 |
prep |
in,prevented |
R5405 |
T8046 |
T8044 |
punct |
=,8 |
R5406 |
T8047 |
T8044 |
punct |
),8 |
R5407 |
T8048 |
T8038 |
punct |
", ",mo |
R5408 |
T7845 |
T7846 |
amod |
double,transgenic |
R5409 |
T8049 |
T8038 |
cc |
and,mo |
R5410 |
T8050 |
T8051 |
nummod |
6,mo |
R5411 |
T8051 |
T8038 |
conj |
mo,mo |
R5412 |
T7846 |
T7847 |
amod |
transgenic,animals |
R5413 |
T8052 |
T8051 |
punct |
+,mo |
R5414 |
T8053 |
T8054 |
nummod |
6,mo |
R5415 |
T7847 |
T7844 |
pobj |
animals,in |
R5419 |
T8057 |
T8051 |
parataxis |
5,mo |
R5420 |
T8058 |
T8057 |
nsubj |
n,5 |
R5421 |
T7848 |
T7847 |
acl |
born,animals |
R5422 |
T8059 |
T8057 |
punct |
=,5 |
R5423 |
T8060 |
T8057 |
punct |
),5 |
R5424 |
T8061 |
T8012 |
punct |
.,created |
R5425 |
T7849 |
T7848 |
cc |
and,born |
R5426 |
T8063 |
T8064 |
amod |
Full,suppression |
R5427 |
T7850 |
T7848 |
conj |
raised,born |
R5428 |
T8064 |
T8065 |
nsubjpass |
suppression,confirmed |
R5429 |
T8066 |
T8067 |
punct |
(,% |
R5430 |
T7851 |
T7850 |
prep |
on,raised |
R5431 |
T8067 |
T8064 |
parataxis |
%,suppression |
R5432 |
T8068 |
T8069 |
punct |
>,95 |
R5433 |
T8069 |
T8067 |
nummod |
95,% |
R5434 |
T7852 |
T7851 |
pobj |
dox,on |
R5435 |
T8070 |
T8067 |
punct |
),% |
R5436 |
T8071 |
T8064 |
prep |
of,suppression |
R5437 |
T7853 |
T7837 |
punct |
.,prevented |
R5438 |
T7855 |
T7856 |
nsubj |
Animals,harbored |
R5439 |
T7857 |
T7855 |
prep |
from,Animals |
R5440 |
T8072 |
T8073 |
amod |
transgenic,levels |
R5441 |
T8073 |
T8071 |
pobj |
levels,of |
R5442 |
T8074 |
T8075 |
compound |
APPswe,ind |
R5443 |
T7858 |
T7859 |
poss |
our,line |
R5444 |
T8075 |
T8073 |
compound |
ind,levels |
R5445 |
T8076 |
T8075 |
punct |
/,ind |
R5446 |
T8077 |
T8073 |
prep |
in,levels |
R5447 |
T7859 |
T7857 |
pobj |
line,from |
R5448 |
T8078 |
T8079 |
det |
the,animals |
R5449 |
T8079 |
T8077 |
pobj |
animals,in |
R5450 |
T7860 |
T7861 |
amod |
highest,expressing |
R5451 |
T8080 |
T8081 |
npadvmod |
dox,treated |
R5452 |
T8081 |
T8079 |
amod |
treated,animals |
R5453 |
T8178 |
T8176 |
pobj |
ind,of |
R5454 |
T8082 |
T8081 |
punct |
-,treated |
R5455 |
T8083 |
T8065 |
auxpass |
was,confirmed |
R5456 |
T8084 |
T8065 |
prep |
by,confirmed |
R5457 |
T8085 |
T8084 |
pobj |
immunoblot,by |
R5458 |
T8086 |
T8087 |
punct |
(,Figure |
R5459 |
T8179 |
T8178 |
punct |
/,ind |
R5460 |
T8087 |
T8065 |
parataxis |
Figure,confirmed |
R5461 |
T8088 |
T8087 |
nummod |
3,Figure |
R5462 |
T8089 |
T8087 |
punct |
),Figure |
R5463 |
T8180 |
T8171 |
cc |
and,life |
R5464 |
T8090 |
T8065 |
punct |
.,confirmed |
R5465 |
T8181 |
T8182 |
poss |
its,fragments |
R5466 |
T8092 |
T8093 |
aux |
To,ensure |
R5467 |
T8093 |
T8094 |
advcl |
ensure,treated |
R5468 |
T8182 |
T8171 |
conj |
fragments,life |
R5469 |
T8095 |
T8096 |
mark |
that,suppressed |
R5470 |
T8096 |
T8093 |
ccomp |
suppressed,ensure |
R5471 |
T8097 |
T8098 |
det |
the,transgene |
R5472 |
T8098 |
T8096 |
nsubjpass |
transgene,suppressed |
R5473 |
T8099 |
T8096 |
aux |
could,suppressed |
R5474 |
T8183 |
T8182 |
amod |
processed,fragments |
R5475 |
T8100 |
T8096 |
auxpass |
be,suppressed |
R5476 |
T8101 |
T8102 |
advmod |
as,rapidly |
R5477 |
T8102 |
T8096 |
advmod |
rapidly,suppressed |
R5478 |
T8184 |
T8185 |
npadvmod |
C,terminal |
R5479 |
T8103 |
T8096 |
prep |
in,suppressed |
R5480 |
T8104 |
T8105 |
nummod |
6,mo |
R5481 |
T8105 |
T8107 |
npadvmod |
mo,old |
R5482 |
T8185 |
T8182 |
amod |
terminal,fragments |
R5483 |
T8106 |
T8105 |
punct |
-,mo |
R5484 |
T8107 |
T8109 |
amod |
old,mice |
R5485 |
T8108 |
T8107 |
punct |
-,old |
R5486 |
T8186 |
T8185 |
punct |
-,terminal |
R5487 |
T8187 |
T8188 |
advmod |
relatively,short |
R5488 |
T8188 |
T8169 |
acomp |
short,are |
R5489 |
T8109 |
T8103 |
pobj |
mice,in |
R5490 |
T8110 |
T8109 |
prep |
with,mice |
R5491 |
T8111 |
T8112 |
amod |
fulminant,pathology |
R5492 |
T8189 |
T8190 |
punct |
(,3D |
R5493 |
T8112 |
T8110 |
pobj |
pathology,with |
R5494 |
T8113 |
T8114 |
mark |
as,can |
R5495 |
T8190 |
T8144 |
parataxis |
3D,suppressed |
R5496 |
T8114 |
T8096 |
advcl |
can,suppressed |
R5497 |
T8115 |
T8114 |
nsubj |
it,can |
R5498 |
T8191 |
T8190 |
compound |
Figure,3D |
R5499 |
T8116 |
T8114 |
prep |
in,can |
R5500 |
T8117 |
T8118 |
amod |
young,animals |
R5501 |
T8192 |
T8190 |
punct |
),3D |
R5502 |
T8118 |
T8116 |
pobj |
animals,in |
R5503 |
T8119 |
T8118 |
punct |
", ",animals |
R5504 |
T8120 |
T8118 |
amod |
predeposit,animals |
R5505 |
T8121 |
T8094 |
punct |
", ",treated |
R5506 |
T8122 |
T8094 |
nsubj |
we,treated |
R5507 |
T8123 |
T8124 |
det |
an,set |
R5508 |
T8193 |
T8144 |
punct |
.,suppressed |
R5509 |
T8124 |
T8094 |
dobj |
set,treated |
R5510 |
T8125 |
T8124 |
amod |
additional,set |
R5511 |
T8126 |
T8124 |
prep |
of,set |
R5512 |
T8195 |
T8196 |
compound |
Tissue,sections |
R5513 |
T8127 |
T8128 |
nummod |
6,mo |
R5514 |
T8128 |
T8130 |
npadvmod |
mo,old |
R5515 |
T8129 |
T8128 |
punct |
-,mo |
R5516 |
T8130 |
T8132 |
amod |
old,animals |
R5517 |
T8196 |
T8197 |
nsubjpass |
sections,stained |
R5518 |
T8131 |
T8130 |
punct |
-,old |
R5519 |
T8132 |
T8126 |
pobj |
animals,of |
R5520 |
T8198 |
T8196 |
prep |
from,sections |
R5521 |
T8133 |
T8132 |
prep |
with,animals |
R5522 |
T8134 |
T8133 |
pobj |
dox,with |
R5523 |
T8135 |
T8124 |
prep |
for,set |
R5524 |
T8136 |
T8137 |
nummod |
1,wk |
R5525 |
T8137 |
T8135 |
pobj |
wk,for |
R5526 |
T8138 |
T8139 |
amod |
prior,to |
R5527 |
T8139 |
T8124 |
prep |
to,set |
R5528 |
T8199 |
T8200 |
det |
each,animal |
R5529 |
T8140 |
T8139 |
pobj |
harvest,to |
R5530 |
T8141 |
T8094 |
punct |
.,treated |
R5531 |
T8200 |
T8198 |
pobj |
animal,from |
R5532 |
T8143 |
T8144 |
advmod |
Importantly,suppressed |
R5533 |
T8201 |
T8200 |
prep |
in,animal |
R5534 |
T8145 |
T8144 |
punct |
", ",suppressed |
R5535 |
T8146 |
T8147 |
preconj |
both,ind |
R5536 |
T8147 |
T8150 |
npadvmod |
ind,terminal |
R5537 |
T8202 |
T8203 |
det |
the,groups |
R5538 |
T8148 |
T8147 |
compound |
APPswe,ind |
R5539 |
T8149 |
T8147 |
punct |
/,ind |
R5540 |
T8150 |
T8156 |
amod |
terminal,levels |
R5541 |
T8203 |
T8201 |
pobj |
groups,in |
R5542 |
T8151 |
T8147 |
cc |
and,ind |
R5543 |
T8152 |
T8153 |
compound |
APP,C |
R5544 |
T8153 |
T8147 |
conj |
C,ind |
R5545 |
T8154 |
T8153 |
punct |
–,C |
R5546 |
T8204 |
T8203 |
nummod |
four,groups |
R5547 |
T8155 |
T8150 |
punct |
-,terminal |
R5548 |
T8156 |
T8144 |
nsubjpass |
levels,suppressed |
R5549 |
T8157 |
T8156 |
compound |
fragment,levels |
R5550 |
T8205 |
T8203 |
compound |
treatment,groups |
R5551 |
T8158 |
T8144 |
auxpass |
were,suppressed |
R5552 |
T8159 |
T8144 |
advmod |
fully,suppressed |
R5553 |
T8206 |
T8197 |
auxpass |
were,stained |
R5554 |
T8160 |
T8144 |
prep |
after,suppressed |
R5555 |
T8161 |
T8162 |
advmod |
only,wk |
R5556 |
T8162 |
T8160 |
pobj |
wk,after |
R5557 |
T8207 |
T8197 |
prep |
for,stained |
R5558 |
T8163 |
T8162 |
nummod |
1,wk |
R5559 |
T8164 |
T8162 |
prep |
of,wk |
R5560 |
T8208 |
T8209 |
compound |
amyloid,pathology |
R5561 |
T8165 |
T8164 |
pobj |
treatment,of |
R5562 |
T8166 |
T8144 |
punct |
", ",suppressed |
R5563 |
T8167 |
T8144 |
advcl |
indicating,suppressed |
R5564 |
T8209 |
T8207 |
pobj |
pathology,for |
R5565 |
T8168 |
T8169 |
mark |
that,are |
R5566 |
T8169 |
T8167 |
ccomp |
are,indicating |
R5567 |
T8170 |
T8171 |
det |
the,life |
R5568 |
T8210 |
T8197 |
agent |
by,stained |
R5569 |
T8171 |
T8169 |
nsubj |
life,are |
R5570 |
T8172 |
T8173 |
advmod |
in,vivo |
R5571 |
T8211 |
T8212 |
compound |
Hirano,silver |
R5572 |
T8173 |
T8171 |
amod |
vivo,life |
R5573 |
T8174 |
T8171 |
compound |
half,life |
R5574 |
T8175 |
T8171 |
punct |
-,life |
R5575 |
T8176 |
T8171 |
prep |
of,life |
R5576 |
T8177 |
T8178 |
compound |
APPswe,ind |
R5577 |
T8212 |
T8210 |
pobj |
silver,by |
R5578 |
T8213 |
T8212 |
punct |
", ",silver |
R5579 |
T8214 |
T8215 |
compound |
Campbell,Switzer |
R5580 |
T8215 |
T8217 |
compound |
Switzer,silver |
R5581 |
T8216 |
T8215 |
punct |
-,Switzer |
R5582 |
T8284 |
T8283 |
prep |
of,that |
R5583 |
T8285 |
T8286 |
det |
the,cohort |
R5584 |
T8217 |
T8212 |
conj |
silver,silver |
R5585 |
T8286 |
T8284 |
pobj |
cohort,of |
R5586 |
T8287 |
T8288 |
nummod |
6,mo |
R5587 |
T8218 |
T8217 |
punct |
", ",silver |
R5588 |
T8288 |
T8289 |
npadvmod |
mo,untreated |
R5589 |
T8289 |
T8286 |
amod |
untreated,cohort |
R5590 |
T8290 |
T8256 |
punct |
", ",resembled |
R5591 |
T8219 |
T8220 |
compound |
thioflavin,S |
R5592 |
T8291 |
T8256 |
prep |
despite,resembled |
R5593 |
T8292 |
T8293 |
det |
the,difference |
R5594 |
T8220 |
T8217 |
conj |
S,silver |
R5595 |
T8293 |
T8291 |
pobj |
difference,despite |
R5596 |
T8294 |
T8293 |
amod |
significant,difference |
R5597 |
T8295 |
T8293 |
compound |
age,difference |
R5598 |
T8221 |
T8220 |
punct |
-,S |
R5599 |
T8296 |
T8293 |
prep |
between,difference |
R5600 |
T8297 |
T8298 |
det |
the,groups |
R5601 |
T8222 |
T8220 |
punct |
", ",S |
R5602 |
T8298 |
T8296 |
pobj |
groups,between |
R5603 |
T8299 |
T8298 |
amod |
treated,groups |
R5604 |
T8300 |
T8299 |
cc |
and,treated |
R5605 |
T8223 |
T8220 |
cc |
and,S |
R5606 |
T8301 |
T8299 |
conj |
untreated,treated |
R5607 |
T8302 |
T8303 |
punct |
(,Figures |
R5608 |
T8303 |
T8256 |
parataxis |
Figures,resembled |
R5609 |
T8224 |
T8225 |
compound |
Aβ,immunohistochemistry |
R5610 |
T8304 |
T8303 |
nummod |
4,Figures |
R5611 |
T8305 |
T8303 |
cc |
and,Figures |
R5612 |
T8306 |
T8307 |
compound |
Figure,S3 |
R5613 |
T8225 |
T8220 |
conj |
immunohistochemistry,S |
R5614 |
T8307 |
T8303 |
conj |
S3,Figures |
R5615 |
T8308 |
T8303 |
punct |
),Figures |
R5616 |
T8226 |
T8197 |
punct |
.,stained |
R5617 |
T8309 |
T8256 |
punct |
.,resembled |
R5618 |
T8311 |
T8312 |
advmod |
Well,formed |
R5619 |
T8228 |
T8229 |
mark |
As,expected |
R5620 |
T8312 |
T8314 |
amod |
formed,plaques |
R5621 |
T8313 |
T8312 |
punct |
-,formed |
R5622 |
T8314 |
T8315 |
nsubj |
plaques,remained |
R5623 |
T8229 |
T8230 |
advcl |
expected,displayed |
R5624 |
T8316 |
T8315 |
prep |
in,remained |
R5625 |
T8317 |
T8318 |
det |
the,animals |
R5626 |
T8318 |
T8316 |
pobj |
animals,in |
R5627 |
T8319 |
T8318 |
amod |
treated,animals |
R5628 |
T8320 |
T8315 |
prep |
after,remained |
R5629 |
T8231 |
T8230 |
punct |
", ",displayed |
R5630 |
T8321 |
T8322 |
nummod |
6,mo |
R5631 |
T8322 |
T8320 |
pobj |
mo,after |
R5632 |
T8323 |
T8322 |
prep |
of,mo |
R5633 |
T8324 |
T8325 |
compound |
transgene,suppression |
R5634 |
T8232 |
T8233 |
det |
the,cohort |
R5635 |
T8325 |
T8323 |
pobj |
suppression,of |
R5636 |
T8326 |
T8315 |
punct |
", ",remained |
R5637 |
T8233 |
T8230 |
nsubj |
cohort,displayed |
R5638 |
T8327 |
T8328 |
advmod |
even,given |
R5639 |
T8328 |
T8315 |
advcl |
given,remained |
R5640 |
T8329 |
T8328 |
mark |
though,given |
R5641 |
T8234 |
T8235 |
nummod |
6,mo |
R5642 |
T8330 |
T8331 |
advmod |
as,much |
R5643 |
T8331 |
T8332 |
amod |
much,time |
R5644 |
T8332 |
T8328 |
nsubjpass |
time,given |
R5645 |
T8235 |
T8233 |
nmod |
mo,cohort |
R5646 |
T8333 |
T8328 |
auxpass |
was,given |
R5647 |
T8334 |
T8335 |
aux |
to,clear |
R5648 |
T8335 |
T8328 |
advcl |
clear,given |
R5649 |
T8236 |
T8233 |
amod |
untreated,cohort |
R5650 |
T8336 |
T8337 |
det |
the,lesions |
R5651 |
T8337 |
T8335 |
dobj |
lesions,clear |
R5652 |
T8338 |
T8339 |
mark |
as,taken |
R5653 |
T8237 |
T8238 |
amod |
moderate,pathology |
R5654 |
T8339 |
T8328 |
advcl |
taken,given |
R5655 |
T8340 |
T8339 |
nsubj |
they,taken |
R5656 |
T8238 |
T8230 |
dobj |
pathology,displayed |
R5657 |
T8341 |
T8339 |
aux |
had,taken |
R5658 |
T8342 |
T8343 |
aux |
to,form |
R5659 |
T8343 |
T8339 |
advcl |
form,taken |
R5660 |
T8239 |
T8238 |
compound |
amyloid,pathology |
R5661 |
T8344 |
T8315 |
punct |
.,remained |
R5662 |
T8346 |
T8347 |
advmod |
Moreover,remained |
R5663 |
T8240 |
T8230 |
punct |
", ",displayed |
R5664 |
T8348 |
T8347 |
punct |
", ",remained |
R5665 |
T8241 |
T8230 |
cc |
and,displayed |
R5666 |
T8349 |
T8350 |
det |
both,types |
R5667 |
T8350 |
T8347 |
nsubj |
types,remained |
R5668 |
T8351 |
T8350 |
prep |
of,types |
R5669 |
T8242 |
T8243 |
det |
the,cohort |
R5670 |
T8352 |
T8351 |
pobj |
amyloid,of |
R5671 |
T8353 |
T8350 |
punct |
", ",types |
R5672 |
T8354 |
T8350 |
amod |
diffuse,types |
R5673 |
T8243 |
T8247 |
nsubj |
cohort,progressed |
R5674 |
T8355 |
T8354 |
cc |
and,diffuse |
R5675 |
T8356 |
T8354 |
conj |
fibrillar,diffuse |
R5676 |
T8244 |
T8245 |
nummod |
9,mo |
R5677 |
T8357 |
T8347 |
punct |
", ",remained |
R5678 |
T8358 |
T8347 |
acomp |
intact,remained |
R5679 |
T8359 |
T8347 |
prep |
throughout,remained |
R5680 |
T8360 |
T8359 |
pobj |
treatment,throughout |
R5681 |
T8361 |
T8347 |
punct |
.,remained |
R5682 |
T8245 |
T8243 |
nmod |
mo,cohort |
R5683 |
T8363 |
T8364 |
advcl |
Using,found |
R5684 |
T8365 |
T8366 |
det |
the,stain |
R5685 |
T8246 |
T8243 |
amod |
untreated,cohort |
R5686 |
T8247 |
T8230 |
conj |
progressed,displayed |
R5687 |
T8248 |
T8247 |
prep |
to,progressed |
R5688 |
T8366 |
T8363 |
dobj |
stain,Using |
R5689 |
T8367 |
T8368 |
compound |
Campbell,Switzer |
R5690 |
T8249 |
T8250 |
det |
a,burden |
R5691 |
T8368 |
T8366 |
compound |
Switzer,stain |
R5692 |
T8369 |
T8368 |
punct |
-,Switzer |
R5693 |
T8370 |
T8366 |
compound |
silver,stain |
R5694 |
T8250 |
T8248 |
pobj |
burden,to |
R5695 |
T8371 |
T8372 |
aux |
to,distinguish |
R5696 |
T8372 |
T8363 |
advcl |
distinguish,Using |
R5697 |
T8251 |
T8250 |
amod |
severe,burden |
R5698 |
T8373 |
T8374 |
amod |
different,forms |
R5699 |
T8374 |
T8372 |
dobj |
forms,distinguish |
R5700 |
T8252 |
T8250 |
compound |
amyloid,burden |
R5701 |
T8375 |
T8374 |
prep |
of,forms |
R5702 |
T8376 |
T8375 |
pobj |
amyloid,of |
R5703 |
T8377 |
T8364 |
punct |
", ",found |
R5704 |
T8253 |
T8247 |
punct |
.,progressed |
R5705 |
T8378 |
T8364 |
nsubj |
we,found |
R5706 |
T8379 |
T8380 |
amod |
diffuse,plaques |
R5707 |
T8255 |
T8256 |
prep |
In,resembled |
R5708 |
T8380 |
T8381 |
nsubj |
plaques,were |
R5709 |
T8381 |
T8364 |
advcl |
were,found |
R5710 |
T8382 |
T8383 |
advmod |
as,persistent |
R5711 |
T8383 |
T8381 |
acomp |
persistent,were |
R5712 |
T8257 |
T8255 |
pobj |
contrast,In |
R5713 |
T8384 |
T8383 |
prep |
as,persistent |
R5714 |
T8385 |
T8386 |
amod |
cored,deposits |
R5715 |
T8386 |
T8384 |
pobj |
deposits,as |
R5716 |
T8258 |
T8256 |
punct |
", ",resembled |
R5717 |
T8387 |
T8388 |
punct |
(,S4 |
R5718 |
T8388 |
T8364 |
parataxis |
S4,found |
R5719 |
T8389 |
T8388 |
compound |
Figure,S4 |
R5720 |
T8259 |
T8260 |
det |
the,extent |
R5721 |
T8260 |
T8256 |
nsubj |
extent,resembled |
R5722 |
T8261 |
T8260 |
prep |
of,extent |
R5723 |
T8390 |
T8388 |
punct |
),S4 |
R5724 |
T8262 |
T8263 |
compound |
amyloid,pathology |
R5725 |
T8391 |
T8364 |
punct |
.,found |
R5726 |
T8263 |
T8261 |
pobj |
pathology,of |
R5727 |
T8393 |
T8394 |
nsubj |
It,was |
R5728 |
T8395 |
T8394 |
advmod |
nevertheless,was |
R5729 |
T8396 |
T8394 |
acomp |
clear,was |
R5730 |
T8397 |
T8398 |
mark |
that,halted |
R5731 |
T8398 |
T8394 |
ccomp |
halted,was |
R5732 |
T8264 |
T8260 |
prep |
in,extent |
R5733 |
T8399 |
T8400 |
npadvmod |
dox,induced |
R5734 |
T8400 |
T8402 |
amod |
induced,suppression |
R5735 |
T8401 |
T8400 |
punct |
-,induced |
R5736 |
T8265 |
T8264 |
pobj |
mice,in |
R5737 |
T8402 |
T8398 |
nsubj |
suppression,halted |
R5738 |
T8403 |
T8402 |
prep |
of,suppression |
R5739 |
T8266 |
T8265 |
prep |
from,mice |
R5740 |
T8404 |
T8405 |
amod |
transgenic,APP |
R5741 |
T8405 |
T8403 |
pobj |
APP,of |
R5742 |
T8406 |
T8398 |
aux |
had,halted |
R5743 |
T8267 |
T8268 |
det |
the,cohorts |
R5744 |
T8407 |
T8398 |
advmod |
completely,halted |
R5745 |
T8408 |
T8409 |
det |
the,progression |
R5746 |
T8268 |
T8266 |
pobj |
cohorts,from |
R5747 |
T8409 |
T8398 |
dobj |
progression,halted |
R5748 |
T8410 |
T8409 |
prep |
of,progression |
R5749 |
T8411 |
T8410 |
pobj |
pathology,of |
R5750 |
T8269 |
T8270 |
nummod |
6,mo |
R5751 |
T8412 |
T8394 |
punct |
.,was |
R5752 |
T8270 |
T8271 |
npadvmod |
mo,treated |
R5753 |
T8414 |
T8415 |
aux |
To,confirm |
R5754 |
T8415 |
T8416 |
advcl |
confirm,repeated |
R5755 |
T8271 |
T8268 |
amod |
treated,cohorts |
R5756 |
T8417 |
T8418 |
mark |
that,was |
R5757 |
T8418 |
T8415 |
ccomp |
was,confirm |
R5758 |
T8272 |
T8270 |
punct |
+,mo |
R5759 |
T8419 |
T8420 |
det |
the,arrest |
R5760 |
T8420 |
T8418 |
nsubj |
arrest,was |
R5761 |
T8421 |
T8420 |
prep |
of,arrest |
R5762 |
T8273 |
T8274 |
nummod |
3,mo |
R5763 |
T8422 |
T8421 |
pobj |
plaques,of |
R5764 |
T8423 |
T8420 |
prep |
without,arrest |
R5765 |
T8274 |
T8270 |
appos |
mo,mo |
R5766 |
T8424 |
T8425 |
det |
any,sign |
R5767 |
T8425 |
T8423 |
pobj |
sign,without |
R5768 |
T8426 |
T8425 |
prep |
of,sign |
R5769 |
T8275 |
T8271 |
cc |
or,treated |
R5770 |
T8427 |
T8426 |
pobj |
clearance,of |
R5771 |
T8428 |
T8418 |
neg |
not,was |
R5772 |
T8276 |
T8277 |
nummod |
6,mo |
R5773 |
T8277 |
T8278 |
npadvmod |
mo,treated |
R5774 |
T8278 |
T8271 |
conj |
treated,treated |
R5775 |
T8429 |
T8418 |
acomp |
unique,was |
R5776 |
T8430 |
T8429 |
prep |
to,unique |
R5777 |
T8279 |
T8277 |
punct |
+,mo |
R5778 |
T8431 |
T8432 |
det |
the,mice |
R5779 |
T8432 |
T8430 |
pobj |
mice,to |
R5780 |
T8280 |
T8281 |
nummod |
6,mo |
R5781 |
T8433 |
T8432 |
nmod |
line,mice |
R5782 |
T8434 |
T8433 |
nummod |
107,line |
R5783 |
T8435 |
T8416 |
punct |
", ",repeated |
R5784 |
T8436 |
T8416 |
nsubj |
we,repeated |
R5785 |
T8437 |
T8438 |
det |
the,experiment |
R5786 |
T8438 |
T8416 |
dobj |
experiment,repeated |
R5787 |
T8281 |
T8277 |
appos |
mo,mo |
R5788 |
T8439 |
T8440 |
compound |
dox,suppression |
R5789 |
T8440 |
T8438 |
compound |
suppression,experiment |
R5790 |
T8282 |
T8256 |
advmod |
closely,resembled |
R5791 |
T8441 |
T8440 |
punct |
-,suppression |
R5792 |
T8442 |
T8416 |
prep |
in,repeated |
R5793 |
T8443 |
T8444 |
det |
a,line |
R5794 |
T8283 |
T8256 |
dobj |
that,resembled |
R5795 |
T8444 |
T8442 |
pobj |
line,in |
R5796 |
T8445 |
T8444 |
amod |
second,line |
R5797 |
T8446 |
T8444 |
prep |
of,line |
R5798 |
T8496 |
T8497 |
punct |
(,8 |
R5799 |
T8447 |
T8448 |
compound |
tet,off |
R5800 |
T8448 |
T8450 |
compound |
off,mice |
R5801 |
T8449 |
T8448 |
punct |
-,off |
R5802 |
T8497 |
T8488 |
parataxis |
8,harvested |
R5803 |
T8498 |
T8499 |
nummod |
6,mo |
R5804 |
T8450 |
T8446 |
pobj |
mice,of |
R5805 |
T8451 |
T8450 |
compound |
APP,mice |
R5806 |
T8499 |
T8500 |
npadvmod |
mo,untreated |
R5807 |
T8452 |
T8453 |
punct |
(,line |
R5808 |
T8453 |
T8416 |
parataxis |
line,repeated |
R5809 |
T8500 |
T8501 |
amod |
untreated,8 |
R5810 |
T8454 |
T8455 |
nmod |
CaMKIIα,ind |
R5811 |
T8455 |
T8453 |
compound |
ind,line |
R5812 |
T8501 |
T8497 |
dep |
8,8 |
R5813 |
T8456 |
T8455 |
punct |
-,ind |
R5814 |
T8457 |
T8455 |
nmod |
tTA,ind |
R5815 |
T8458 |
T8455 |
punct |
×,ind |
R5816 |
T8502 |
T8501 |
punct |
", ",8 |
R5817 |
T8459 |
T8455 |
compound |
tet,ind |
R5818 |
T8460 |
T8455 |
punct |
-,ind |
R5819 |
T8503 |
T8501 |
nsubj |
n,8 |
R5820 |
T8461 |
T8455 |
compound |
APPswe,ind |
R5821 |
T8462 |
T8455 |
punct |
/,ind |
R5822 |
T8463 |
T8453 |
nummod |
18,line |
R5823 |
T8504 |
T8501 |
punct |
=,8 |
R5824 |
T8464 |
T8453 |
punct |
;,line |
R5825 |
T8465 |
T8466 |
nsubj |
n,22 |
R5826 |
T8505 |
T8497 |
punct |
;,8 |
R5827 |
T8466 |
T8453 |
ccomp |
22,line |
R5828 |
T8467 |
T8466 |
punct |
=,22 |
R5829 |
T8468 |
T8453 |
punct |
),line |
R5830 |
T8506 |
T8507 |
nummod |
9,mo |
R5831 |
T8469 |
T8416 |
punct |
.,repeated |
R5832 |
T8471 |
T8472 |
advmod |
Again,begun |
R5833 |
T8473 |
T8472 |
punct |
", ",begun |
R5834 |
T8507 |
T8508 |
npadvmod |
mo,untreated |
R5835 |
T8474 |
T8475 |
amod |
long,term |
R5836 |
T8475 |
T8477 |
compound |
term,treatment |
R5837 |
T8476 |
T8475 |
punct |
-,term |
R5838 |
T8508 |
T8509 |
amod |
untreated,6 |
R5839 |
T8477 |
T8472 |
nsubjpass |
treatment,begun |
R5840 |
T8478 |
T8477 |
compound |
dox,treatment |
R5841 |
T8509 |
T8497 |
dep |
6,8 |
R5842 |
T8479 |
T8472 |
auxpass |
was,begun |
R5843 |
T8480 |
T8472 |
prep |
at,begun |
R5844 |
T8481 |
T8482 |
nummod |
6,mo |
R5845 |
T8510 |
T8509 |
punct |
", ",6 |
R5846 |
T8482 |
T8480 |
pobj |
mo,at |
R5847 |
T8483 |
T8482 |
prep |
of,mo |
R5848 |
T8511 |
T8509 |
nsubj |
n,6 |
R5849 |
T8484 |
T8483 |
pobj |
age,of |
R5850 |
T8485 |
T8472 |
punct |
", ",begun |
R5851 |
T8486 |
T8472 |
cc |
and,begun |
R5852 |
T8512 |
T8509 |
punct |
=,6 |
R5853 |
T8487 |
T8488 |
nsubjpass |
mice,harvested |
R5854 |
T8488 |
T8472 |
conj |
harvested,begun |
R5855 |
T8489 |
T8488 |
auxpass |
were,harvested |
R5856 |
T8513 |
T8497 |
punct |
;,8 |
R5857 |
T8490 |
T8488 |
prep |
after,harvested |
R5858 |
T8491 |
T8492 |
nummod |
3,mo |
R5859 |
T8514 |
T8515 |
nummod |
6,mo |
R5860 |
T8492 |
T8490 |
pobj |
mo,after |
R5861 |
T8493 |
T8492 |
prep |
of,mo |
R5862 |
T8494 |
T8495 |
compound |
transgene,suppression |
R5863 |
T8515 |
T8519 |
npadvmod |
mo,treated |
R5864 |
T8495 |
T8493 |
pobj |
suppression,of |
R5865 |
T8516 |
T8515 |
nmod |
mo,mo |
R5866 |
T8517 |
T8515 |
punct |
+,mo |
R5867 |
T8518 |
T8515 |
nummod |
3,mo |
R5868 |
T8519 |
T8497 |
amod |
treated,8 |
R5869 |
T8603 |
T8602 |
aux |
could,found |
R5870 |
T8520 |
T8497 |
punct |
", ",8 |
R5871 |
T8604 |
T8602 |
advmod |
still,found |
R5872 |
T8605 |
T8602 |
auxpass |
be,found |
R5873 |
T8606 |
T8602 |
prep |
in,found |
R5874 |
T8521 |
T8497 |
nsubj |
n,8 |
R5875 |
T8607 |
T8606 |
pobj |
each,in |
R5876 |
T8608 |
T8607 |
prep |
of,each |
R5877 |
T8522 |
T8497 |
punct |
=,8 |
R5878 |
T8609 |
T8610 |
det |
the,animals |
R5879 |
T8610 |
T8608 |
pobj |
animals,of |
R5880 |
T8611 |
T8612 |
npadvmod |
dox,treated |
R5881 |
T8523 |
T8497 |
punct |
),8 |
R5882 |
T8612 |
T8610 |
amod |
treated,animals |
R5883 |
T8613 |
T8612 |
punct |
-,treated |
R5884 |
T8614 |
T8602 |
punct |
.,found |
R5885 |
T8616 |
T8617 |
nsubj |
We,measured |
R5886 |
T8524 |
T8488 |
punct |
.,harvested |
R5887 |
T8618 |
T8617 |
advmod |
biochemically,measured |
R5888 |
T8619 |
T8620 |
det |
the,amount |
R5889 |
T8526 |
T8527 |
nsubj |
Immunoblotting,confirmed |
R5890 |
T8620 |
T8617 |
dobj |
amount,measured |
R5891 |
T8621 |
T8620 |
prep |
of,amount |
R5892 |
T8622 |
T8623 |
amod |
aggregated,Aβ |
R5893 |
T8623 |
T8621 |
pobj |
Aβ,of |
R5894 |
T8528 |
T8526 |
prep |
for,Immunoblotting |
R5895 |
T8624 |
T8617 |
prep |
in,measured |
R5896 |
T8529 |
T8528 |
pobj |
APP,for |
R5897 |
T8530 |
T8531 |
amod |
full,suppression |
R5898 |
T8625 |
T8626 |
det |
the,brains |
R5899 |
T8626 |
T8624 |
pobj |
brains,in |
R5900 |
T8531 |
T8527 |
dobj |
suppression,confirmed |
R5901 |
T8627 |
T8626 |
prep |
of,brains |
R5902 |
T8628 |
T8629 |
poss |
our,mice |
R5903 |
T8629 |
T8627 |
pobj |
mice,of |
R5904 |
T8532 |
T8531 |
compound |
transgene,suppression |
R5905 |
T8630 |
T8617 |
prep |
before,measured |
R5906 |
T8631 |
T8630 |
cc |
and,before |
R5907 |
T8533 |
T8527 |
prep |
in,confirmed |
R5908 |
T8632 |
T8630 |
conj |
after,before |
R5909 |
T8633 |
T8634 |
compound |
transgene,suppression |
R5910 |
T8534 |
T8535 |
det |
the,animals |
R5911 |
T8634 |
T8632 |
pobj |
suppression,after |
R5912 |
T8635 |
T8617 |
advcl |
using,measured |
R5913 |
T8636 |
T8637 |
compound |
filter,trap |
R5914 |
T8535 |
T8533 |
pobj |
animals,in |
R5915 |
T8637 |
T8638 |
compound |
trap,analysis |
R5916 |
T8638 |
T8635 |
dobj |
analysis,using |
R5917 |
T8536 |
T8535 |
amod |
treated,animals |
R5918 |
T8639 |
T8638 |
prep |
of,analysis |
R5919 |
T8640 |
T8641 |
amod |
cortical,tissue |
R5920 |
T8641 |
T8639 |
pobj |
tissue,of |
R5921 |
T8537 |
T8538 |
punct |
(,S5 |
R5922 |
T8642 |
T8641 |
prep |
from,tissue |
R5923 |
T8643 |
T8644 |
det |
each,animal |
R5924 |
T8644 |
T8642 |
pobj |
animal,from |
R5925 |
T8538 |
T8527 |
parataxis |
S5,confirmed |
R5926 |
T8645 |
T8617 |
punct |
.,measured |
R5927 |
T8539 |
T8538 |
compound |
Figure,S5 |
R5928 |
T8647 |
T8648 |
prep |
In,passed |
R5929 |
T8648 |
T8658 |
ccomp |
passed,become |
R5930 |
T8649 |
T8650 |
det |
this,assay |
R5931 |
T8540 |
T8538 |
punct |
),S5 |
R5932 |
T8650 |
T8647 |
pobj |
assay,In |
R5933 |
T8651 |
T8648 |
punct |
", ",passed |
R5934 |
T8541 |
T8527 |
punct |
.,confirmed |
R5935 |
T8652 |
T8653 |
amod |
serial,dilutions |
R5936 |
T8653 |
T8648 |
nsubjpass |
dilutions,passed |
R5937 |
T8654 |
T8653 |
prep |
of,dilutions |
R5938 |
T8655 |
T8656 |
compound |
protein,homogenate |
R5939 |
T8656 |
T8654 |
pobj |
homogenate,of |
R5940 |
T8543 |
T8544 |
prep |
As,worsened |
R5941 |
T8657 |
T8648 |
auxpass |
are,passed |
R5942 |
T8659 |
T8648 |
prep |
through,passed |
R5943 |
T8660 |
T8661 |
det |
a,filter |
R5944 |
T8545 |
T8543 |
prep |
in,As |
R5945 |
T8661 |
T8659 |
pobj |
filter,through |
R5946 |
T8662 |
T8661 |
compound |
cellulose,filter |
R5947 |
T8663 |
T8661 |
compound |
acetate,filter |
R5948 |
T8664 |
T8658 |
punct |
;,become |
R5949 |
T8546 |
T8547 |
det |
the,mice |
R5950 |
T8665 |
T8658 |
nsubj |
particles,become |
R5951 |
T8666 |
T8665 |
amod |
larger,particles |
R5952 |
T8547 |
T8545 |
pobj |
mice,in |
R5953 |
T8667 |
T8666 |
prep |
than,larger |
R5954 |
T8668 |
T8669 |
det |
the,size |
R5955 |
T8548 |
T8547 |
nmod |
line,mice |
R5956 |
T8669 |
T8667 |
pobj |
size,than |
R5957 |
T8670 |
T8669 |
compound |
pore,size |
R5958 |
T8549 |
T8548 |
nummod |
107,line |
R5959 |
T8671 |
T8669 |
prep |
of,size |
R5960 |
T8672 |
T8673 |
det |
the,filter |
R5961 |
T8673 |
T8671 |
pobj |
filter,of |
R5962 |
T8550 |
T8547 |
acl |
described,mice |
R5963 |
T8674 |
T8658 |
acomp |
trapped,become |
R5964 |
T8675 |
T8674 |
prep |
in,trapped |
R5965 |
T8551 |
T8550 |
advmod |
above,described |
R5966 |
T8676 |
T8677 |
det |
the,membrane |
R5967 |
T8677 |
T8675 |
pobj |
membrane,in |
R5968 |
T8552 |
T8544 |
punct |
", ",worsened |
R5969 |
T8678 |
T8658 |
cc |
and,become |
R5970 |
T8679 |
T8680 |
auxpass |
are,revealed |
R5971 |
T8553 |
T8554 |
compound |
amyloid,burden |
R5972 |
T8680 |
T8658 |
conj |
revealed,become |
R5973 |
T8681 |
T8680 |
prep |
by,revealed |
R5974 |
T8682 |
T8681 |
pobj |
immunoblotting,by |
R5975 |
T8554 |
T8544 |
nsubj |
burden,worsened |
R5976 |
T8683 |
T8684 |
punct |
[,22 |
R5977 |
T8684 |
T8680 |
parataxis |
22,revealed |
R5978 |
T8555 |
T8544 |
advmod |
substantially,worsened |
R5979 |
T8685 |
T8684 |
punct |
],22 |
R5980 |
T8686 |
T8658 |
punct |
.,become |
R5981 |
T8556 |
T8544 |
prep |
in,worsened |
R5982 |
T8688 |
T8689 |
advcl |
Consistent,had |
R5983 |
T8557 |
T8558 |
det |
the,mice |
R5984 |
T8690 |
T8688 |
prep |
with,Consistent |
R5985 |
T8691 |
T8692 |
poss |
our,analysis |
R5986 |
T8558 |
T8556 |
pobj |
mice,in |
R5987 |
T8692 |
T8690 |
pobj |
analysis,with |
R5988 |
T8693 |
T8692 |
amod |
visual,analysis |
R5989 |
T8694 |
T8692 |
prep |
of,analysis |
R5990 |
T8695 |
T8696 |
det |
the,sections |
R5991 |
T8696 |
T8694 |
pobj |
sections,of |
R5992 |
T8697 |
T8696 |
amod |
histological,sections |
R5993 |
T8559 |
T8558 |
amod |
untreated,mice |
R5994 |
T8698 |
T8689 |
punct |
", ",had |
R5995 |
T8699 |
T8700 |
nmod |
line,mice |
R5996 |
T8560 |
T8558 |
prep |
between,mice |
R5997 |
T8700 |
T8689 |
nsubj |
mice,had |
R5998 |
T8701 |
T8699 |
nummod |
107,line |
R5999 |
T8702 |
T8703 |
compound |
tTA,APP |
R6000 |
T8561 |
T8562 |
nummod |
6,mo |
R6001 |
T8703 |
T8700 |
compound |
APP,mice |
R6002 |
T8704 |
T8703 |
punct |
/,APP |
R6003 |
T8562 |
T8560 |
pobj |
mo,between |
R6004 |
T8705 |
T8700 |
acl |
treated,mice |
R6005 |
T8706 |
T8705 |
prep |
with,treated |
R6006 |
T8707 |
T8706 |
pobj |
dox,with |
R6007 |
T8563 |
T8561 |
cc |
and,6 |
R6008 |
T8564 |
T8561 |
conj |
9,6 |
R6009 |
T8565 |
T8562 |
prep |
of,mo |
R6010 |
T8566 |
T8565 |
pobj |
age,of |
R6011 |
T8708 |
T8705 |
prep |
for,treated |
R6012 |
T8709 |
T8710 |
nummod |
3,mo |
R6013 |
T8567 |
T8544 |
punct |
.,worsened |
R6014 |
T8569 |
T8570 |
nsubj |
Suppression,arrested |
R6015 |
T8571 |
T8569 |
prep |
of,Suppression |
R6016 |
T8710 |
T8708 |
pobj |
mo,for |
R6017 |
T8711 |
T8710 |
cc |
or,mo |
R6018 |
T8712 |
T8710 |
nummod |
6,mo |
R6019 |
T8572 |
T8573 |
compound |
transgene,expression |
R6020 |
T8713 |
T8714 |
det |
the,amount |
R6021 |
T8714 |
T8689 |
dobj |
amount,had |
R6022 |
T8573 |
T8571 |
pobj |
expression,of |
R6023 |
T8715 |
T8714 |
amod |
same,amount |
R6024 |
T8716 |
T8714 |
prep |
of,amount |
R6025 |
T8574 |
T8570 |
advmod |
abruptly,arrested |
R6026 |
T8717 |
T8718 |
amod |
aggregated,Aβ |
R6027 |
T8718 |
T8716 |
pobj |
Aβ,of |
R6028 |
T8575 |
T8570 |
dobj |
progression,arrested |
R6029 |
T8719 |
T8714 |
prep |
as,amount |
R6030 |
T8720 |
T8721 |
advmod |
when,started |
R6031 |
T8576 |
T8575 |
prep |
of,progression |
R6032 |
T8721 |
T8719 |
pcomp |
started,as |
R6033 |
T8722 |
T8721 |
nsubj |
they,started |
R6034 |
T8723 |
T8721 |
dobj |
treatment,started |
R6035 |
T8577 |
T8576 |
pobj |
pathology,of |
R6036 |
T8724 |
T8721 |
prep |
at,started |
R6037 |
T8725 |
T8726 |
nummod |
6,mo |
R6038 |
T8578 |
T8579 |
punct |
(,S6 |
R6039 |
T8726 |
T8724 |
pobj |
mo,at |
R6040 |
T8727 |
T8726 |
prep |
of,mo |
R6041 |
T8728 |
T8727 |
pobj |
age,of |
R6042 |
T8729 |
T8730 |
punct |
(,4A |
R6043 |
T8730 |
T8689 |
parataxis |
4A,had |
R6044 |
T8579 |
T8570 |
parataxis |
S6,arrested |
R6045 |
T8731 |
T8730 |
compound |
Figure,4A |
R6046 |
T8732 |
T8730 |
cc |
and,4A |
R6047 |
T8733 |
T8730 |
conj |
4B,4A |
R6048 |
T8580 |
T8579 |
compound |
Figure,S6 |
R6049 |
T8734 |
T8730 |
punct |
),4A |
R6050 |
T8735 |
T8689 |
punct |
.,had |
R6051 |
T8581 |
T8579 |
punct |
),S6 |
R6052 |
T8737 |
T8738 |
prep |
In,had |
R6053 |
T8582 |
T8570 |
punct |
", ",arrested |
R6054 |
T8739 |
T8737 |
pobj |
contrast,In |
R6055 |
T8740 |
T8738 |
punct |
", ",had |
R6056 |
T8583 |
T8584 |
cc |
but,without |
R6057 |
T8741 |
T8742 |
amod |
untreated,mice |
R6058 |
T8742 |
T8738 |
nsubj |
mice,had |
R6059 |
T8584 |
T8570 |
prep |
without,arrested |
R6060 |
T8743 |
T8744 |
nummod |
9,mo |
R6061 |
T8744 |
T8746 |
npadvmod |
mo,old |
R6062 |
T8745 |
T8744 |
punct |
-,mo |
R6063 |
T8585 |
T8584 |
advmod |
again,without |
R6064 |
T8746 |
T8742 |
amod |
old,mice |
R6065 |
T8747 |
T8746 |
punct |
-,old |
R6066 |
T8586 |
T8587 |
det |
any,sign |
R6067 |
T8748 |
T8749 |
advmod |
almost,twice |
R6068 |
T8749 |
T8750 |
advmod |
twice,much |
R6069 |
T8587 |
T8584 |
pobj |
sign,without |
R6070 |
T8750 |
T8752 |
amod |
much,Aβ |
R6071 |
T8751 |
T8750 |
advmod |
as,much |
R6072 |
T8588 |
T8587 |
prep |
of,sign |
R6073 |
T8752 |
T8738 |
dobj |
Aβ,had |
R6075 |
T8754 |
T8752 |
prep |
as,Aβ |
R6076 |
T8589 |
T8588 |
pobj |
reduction,of |
R6079 |
T8590 |
T8570 |
punct |
.,arrested |
R6080 |
T8757 |
T8758 |
det |
the,groups |
R6082 |
T8759 |
T8758 |
amod |
treated,groups |
R6083 |
T8592 |
T8593 |
preconj |
Both,silver |
R6084 |
T8760 |
T8738 |
punct |
.,had |
R6085 |
T8762 |
T8763 |
compound |
Filter,analysis |
R6086 |
T8593 |
T8594 |
npadvmod |
silver,positive |
R6087 |
T8763 |
T8765 |
nsubj |
analysis,yielded |
R6088 |
T8764 |
T8763 |
compound |
trap,analysis |
R6089 |
T8765 |
T8773 |
ccomp |
yielded,arrested |
R6090 |
T8594 |
T8601 |
amod |
positive,plaques |
R6091 |
T8766 |
T8763 |
prep |
of,analysis |
R6092 |
T8767 |
T8768 |
nmod |
line,mice |
R6093 |
T8768 |
T8766 |
pobj |
mice,of |
R6094 |
T8769 |
T8767 |
nummod |
18,line |
R6095 |
T8595 |
T8593 |
punct |
-,silver |
R6096 |
T8770 |
T8771 |
compound |
tTA,APP |
R6097 |
T8771 |
T8768 |
compound |
APP,mice |
R6098 |
T8772 |
T8771 |
punct |
/,APP |
R6099 |
T8596 |
T8593 |
cc |
and,silver |
R6100 |
T8774 |
T8775 |
amod |
similar,results |
R6101 |
T8597 |
T8598 |
compound |
thioflavin,S |
R6102 |
T8775 |
T8765 |
dobj |
results,yielded |
R6103 |
T8776 |
T8773 |
punct |
: ,arrested |
R6104 |
T8598 |
T8593 |
conj |
S,silver |
R6105 |
T8777 |
T8778 |
det |
the,increase |
R6106 |
T8778 |
T8773 |
nsubjpass |
increase,arrested |
R6107 |
T8599 |
T8598 |
punct |
-,S |
R6108 |
T8779 |
T8778 |
prep |
in,increase |
R6109 |
T8780 |
T8781 |
amod |
aggregated,Aβ |
R6110 |
T8781 |
T8779 |
pobj |
Aβ,in |
R6111 |
T8600 |
T8594 |
punct |
-,positive |
R6112 |
T8782 |
T8778 |
acl |
observed,increase |
R6113 |
T8783 |
T8782 |
prep |
in,observed |
R6114 |
T8601 |
T8602 |
nsubjpass |
plaques,found |
R6115 |
T8784 |
T8785 |
amod |
untreated,animals |
R6116 |
T8785 |
T8783 |
pobj |
animals,in |
R6117 |
T8786 |
T8785 |
prep |
between,animals |
R6118 |
T8814 |
T8811 |
prep |
in,measure |
R6119 |
T8787 |
T8788 |
nummod |
6,mo |
R6120 |
T8788 |
T8786 |
pobj |
mo,between |
R6121 |
T8789 |
T8787 |
cc |
and,6 |
R6122 |
T8790 |
T8787 |
conj |
9,6 |
R6123 |
T8815 |
T8816 |
det |
the,brains |
R6124 |
T8791 |
T8788 |
prep |
of,mo |
R6125 |
T8792 |
T8791 |
pobj |
age,of |
R6126 |
T8793 |
T8773 |
auxpass |
was,arrested |
R6127 |
T8816 |
T8814 |
pobj |
brains,in |
R6128 |
T8794 |
T8773 |
advmod |
completely,arrested |
R6129 |
T8817 |
T8816 |
prep |
of,brains |
R6130 |
T8818 |
T8819 |
det |
each,group |
R6131 |
T8795 |
T8773 |
agent |
by,arrested |
R6132 |
T8796 |
T8797 |
compound |
transgene,suppression |
R6133 |
T8819 |
T8817 |
pobj |
group,of |
R6134 |
T8797 |
T8795 |
pobj |
suppression,by |
R6135 |
T8798 |
T8799 |
punct |
(,S5C |
R6136 |
T8799 |
T8773 |
parataxis |
S5C,arrested |
R6137 |
T8820 |
T8821 |
aux |
to,determine |
R6138 |
T8800 |
T8799 |
compound |
Figure,S5C |
R6139 |
T8801 |
T8799 |
cc |
and,S5C |
R6140 |
T8821 |
T8811 |
advcl |
determine,measure |
R6141 |
T8802 |
T8799 |
conj |
S5D,S5C |
R6142 |
T8803 |
T8799 |
punct |
),S5C |
R6143 |
T8822 |
T8823 |
mark |
whether,occurred |
R6144 |
T8804 |
T8773 |
punct |
.,arrested |
R6145 |
T8806 |
T8807 |
nsubj |
We,used |
R6146 |
T8808 |
T8807 |
advmod |
next,used |
R6147 |
T8823 |
T8821 |
ccomp |
occurred,determine |
R6148 |
T8809 |
T8807 |
dobj |
ELISA,used |
R6149 |
T8810 |
T8811 |
aux |
to,measure |
R6150 |
T8824 |
T8825 |
det |
any,change |
R6151 |
T8811 |
T8807 |
advcl |
measure,used |
R6152 |
T8812 |
T8813 |
amod |
total,Aβ |
R6153 |
T8813 |
T8811 |
dobj |
Aβ,measure |
R6154 |
T8825 |
T8823 |
nsubj |
change,occurred |
R6155 |
T8826 |
T8825 |
prep |
in,change |
R6156 |
T8827 |
T8828 |
det |
the,amount |
R6157 |
T8828 |
T8826 |
pobj |
amount,in |
R6158 |
T8829 |
T8828 |
cc |
or,amount |
R6159 |
T8830 |
T8828 |
conj |
solubility,amount |
R6160 |
T8920 |
T8918 |
prep |
with,Consistent |
R6161 |
T8921 |
T8922 |
det |
the,results |
R6162 |
T8831 |
T8828 |
prep |
of,amount |
R6163 |
T8922 |
T8920 |
pobj |
results,with |
R6164 |
T8923 |
T8922 |
compound |
filter,results |
R6165 |
T8832 |
T8831 |
pobj |
peptide,of |
R6166 |
T8924 |
T8922 |
compound |
trap,results |
R6167 |
T8925 |
T8922 |
acl |
presented,results |
R6168 |
T8926 |
T8925 |
advmod |
above,presented |
R6169 |
T8833 |
T8834 |
mark |
while,suppressed |
R6170 |
T8927 |
T8919 |
punct |
", ",were |
R6171 |
T8928 |
T8919 |
expl |
there,were |
R6172 |
T8834 |
T8823 |
advcl |
suppressed,occurred |
R6173 |
T8929 |
T8930 |
det |
no,differences |
R6174 |
T8930 |
T8919 |
attr |
differences,were |
R6175 |
T8931 |
T8930 |
amod |
significant,differences |
R6176 |
T8835 |
T8836 |
compound |
APPswe,ind |
R6177 |
T8932 |
T8930 |
prep |
in,differences |
R6178 |
T8933 |
T8934 |
npadvmod |
SDS,soluble |
R6179 |
T8836 |
T8838 |
compound |
ind,expression |
R6180 |
T8934 |
T8939 |
amod |
soluble,Aβ |
R6181 |
T8935 |
T8933 |
punct |
-,SDS |
R6182 |
T8936 |
T8933 |
cc |
or,SDS |
R6183 |
T8837 |
T8836 |
punct |
/,ind |
R6184 |
T8937 |
T8933 |
conj |
FA,SDS |
R6185 |
T8938 |
T8934 |
punct |
-,soluble |
R6186 |
T8939 |
T8932 |
pobj |
Aβ,in |
R6187 |
T8838 |
T8834 |
nsubjpass |
expression,suppressed |
R6188 |
T8940 |
T8930 |
prep |
between,differences |
R6189 |
T8941 |
T8942 |
det |
the,cohort |
R6190 |
T8839 |
T8834 |
auxpass |
was,suppressed |
R6191 |
T8942 |
T8940 |
pobj |
cohort,between |
R6192 |
T8943 |
T8944 |
nummod |
6,mo |
R6193 |
T8944 |
T8942 |
nmod |
mo,cohort |
R6194 |
T8840 |
T8807 |
punct |
.,used |
R6195 |
T8945 |
T8942 |
amod |
untreated,cohort |
R6196 |
T8946 |
T8942 |
cc |
and,cohort |
R6197 |
T8947 |
T8948 |
preconj |
either,cohorts |
R6198 |
T8948 |
T8942 |
conj |
cohorts,cohort |
R6199 |
T8949 |
T8948 |
det |
the,cohorts |
R6200 |
T8842 |
T8843 |
amod |
Cortical,homogenates |
R6201 |
T8950 |
T8951 |
nummod |
6,mo |
R6202 |
T8951 |
T8948 |
nmod |
mo,cohorts |
R6203 |
T8952 |
T8951 |
punct |
+,mo |
R6204 |
T8843 |
T8844 |
nsubjpass |
homogenates,extracted |
R6205 |
T8953 |
T8954 |
nummod |
3,mo |
R6206 |
T8954 |
T8951 |
appos |
mo,mo |
R6207 |
T8955 |
T8954 |
acl |
treated,mo |
R6208 |
T8844 |
T8847 |
ccomp |
extracted,measured |
R6209 |
T8956 |
T8951 |
cc |
or,mo |
R6210 |
T8957 |
T8958 |
nummod |
6,mo |
R6211 |
T8958 |
T8951 |
conj |
mo,mo |
R6212 |
T8845 |
T8844 |
auxpass |
were,extracted |
R6213 |
T8959 |
T8958 |
punct |
+,mo |
R6214 |
T8960 |
T8961 |
nummod |
6,mo |
R6215 |
T8846 |
T8844 |
advmod |
sequentially,extracted |
R6216 |
T8961 |
T8958 |
appos |
mo,mo |
R6217 |
T8962 |
T8961 |
acl |
treated,mo |
R6218 |
T8963 |
T8919 |
punct |
.,were |
R6219 |
T8848 |
T8849 |
aux |
to,separate |
R6220 |
T8965 |
T8966 |
advmod |
However,contained |
R6221 |
T8849 |
T8844 |
advcl |
separate,extracted |
R6222 |
T8850 |
T8849 |
dobj |
peptide,separate |
R6223 |
T8967 |
T8966 |
punct |
", ",contained |
R6224 |
T8968 |
T8966 |
nsubj |
brains,contained |
R6225 |
T8851 |
T8849 |
prep |
into,separate |
R6226 |
T8969 |
T8968 |
prep |
of,brains |
R6227 |
T8970 |
T8971 |
preconj |
both,mo |
R6228 |
T8971 |
T8973 |
npadvmod |
mo,treated |
R6229 |
T8852 |
T8853 |
npadvmod |
PBS,soluble |
R6230 |
T8972 |
T8971 |
nummod |
6,mo |
R6231 |
T8973 |
T8983 |
amod |
treated,cohorts |
R6232 |
T8853 |
T8862 |
amod |
soluble,fractions |
R6233 |
T8974 |
T8971 |
punct |
+,mo |
R6234 |
T8975 |
T8976 |
nummod |
3,mo |
R6235 |
T8854 |
T8852 |
punct |
-,PBS |
R6236 |
T8976 |
T8971 |
appos |
mo,mo |
R6237 |
T8977 |
T8971 |
cc |
and,mo |
R6238 |
T8978 |
T8979 |
nummod |
6,mo |
R6239 |
T8855 |
T8852 |
punct |
", ",PBS |
R6240 |
T8979 |
T8971 |
conj |
mo,mo |
R6241 |
T8980 |
T8979 |
punct |
+,mo |
R6242 |
T8981 |
T8982 |
nummod |
6,mo |
R6243 |
T8856 |
T8852 |
conj |
SDS,PBS |
R6244 |
T8982 |
T8979 |
appos |
mo,mo |
R6245 |
T8983 |
T8969 |
pobj |
cohorts,of |
R6246 |
T8857 |
T8856 |
punct |
-,SDS |
R6247 |
T8984 |
T8985 |
advmod |
roughly,twice |
R6248 |
T8985 |
T8986 |
advmod |
twice,much |
R6249 |
T8986 |
T8988 |
amod |
much,Aβ40 |
R6250 |
T8987 |
T8986 |
advmod |
as,much |
R6251 |
T8988 |
T8966 |
dobj |
Aβ40,contained |
R6252 |
T8858 |
T8856 |
punct |
", ",SDS |
R6253 |
T8989 |
T8988 |
nmod |
PBS,Aβ40 |
R6254 |
T8990 |
T8988 |
punct |
-,Aβ40 |
R6255 |
T8991 |
T8988 |
amod |
soluble,Aβ40 |
R6256 |
T8859 |
T8856 |
cc |
and,SDS |
R6257 |
T8992 |
T8988 |
prep |
as,Aβ40 |
R6258 |
T8993 |
T8994 |
amod |
untreated,mice |
R6259 |
T8860 |
T8856 |
conj |
FA,SDS |
R6260 |
T8994 |
T8992 |
pobj |
mice,as |
R6261 |
T8995 |
T8996 |
nummod |
6,mo |
R6262 |
T8996 |
T8998 |
npadvmod |
mo,old |
R6263 |
T8861 |
T8853 |
punct |
-,soluble |
R6264 |
T8997 |
T8996 |
punct |
-,mo |
R6265 |
T8998 |
T8994 |
amod |
old,mice |
R6266 |
T8862 |
T8851 |
pobj |
fractions,into |
R6267 |
T8999 |
T8998 |
punct |
-,old |
R6268 |
T9000 |
T9001 |
punct |
(,5C |
R6269 |
T8863 |
T8847 |
punct |
", ",measured |
R6270 |
T9001 |
T8966 |
parataxis |
5C,contained |
R6271 |
T9002 |
T9001 |
compound |
Figure,5C |
R6272 |
T9003 |
T9001 |
punct |
),5C |
R6273 |
T8864 |
T8847 |
advmod |
then,measured |
R6274 |
T9004 |
T8966 |
punct |
.,contained |
R6275 |
T8865 |
T8866 |
npadvmod |
transgene,derived |
R6276 |
T9006 |
T9007 |
nsubj |
Levels,showed |
R6277 |
T9008 |
T9006 |
prep |
of,Levels |
R6278 |
T8866 |
T8868 |
amod |
derived,Aβ40 |
R6279 |
T9009 |
T9008 |
pobj |
Aβ42,of |
R6280 |
T9010 |
T9011 |
det |
a,trend |
R6281 |
T8867 |
T8866 |
punct |
-,derived |
R6282 |
T9011 |
T9007 |
dobj |
trend,showed |
R6283 |
T9012 |
T9011 |
amod |
similar,trend |
R6284 |
T9013 |
T9007 |
punct |
", ",showed |
R6285 |
T8868 |
T8847 |
nsubjpass |
Aβ40,measured |
R6286 |
T9014 |
T9007 |
cc |
but,showed |
R6287 |
T9015 |
T9016 |
aux |
did,reach |
R6288 |
T8869 |
T8868 |
cc |
and,Aβ40 |
R6289 |
T9016 |
T9007 |
conj |
reach,showed |
R6290 |
T9017 |
T9016 |
neg |
not,reach |
R6291 |
T9018 |
T9019 |
amod |
statistical,significance |
R6292 |
T8870 |
T8868 |
conj |
Aβ42,Aβ40 |
R6293 |
T9019 |
T9016 |
dobj |
significance,reach |
R6294 |
T9020 |
T9007 |
punct |
.,showed |
R6295 |
T8871 |
T8847 |
auxpass |
were,measured |
R6296 |
T9022 |
T9023 |
prep |
In,were |
R6297 |
T8872 |
T8847 |
agent |
by,measured |
R6298 |
T9024 |
T9022 |
pobj |
fact,In |
R6299 |
T8873 |
T8874 |
amod |
human,specific |
R6300 |
T9025 |
T9023 |
punct |
", ",were |
R6301 |
T9026 |
T9023 |
nsubj |
levels,were |
R6302 |
T8874 |
T8876 |
amod |
specific,ELISA |
R6303 |
T9027 |
T9026 |
prep |
of,levels |
R6304 |
T9028 |
T9029 |
npadvmod |
PBS,soluble |
R6305 |
T9029 |
T9031 |
amod |
soluble,Aβ40 |
R6306 |
T8875 |
T8874 |
punct |
-,specific |
R6307 |
T9030 |
T9029 |
punct |
-,soluble |
R6308 |
T9031 |
T9027 |
pobj |
Aβ40,of |
R6309 |
T8876 |
T8872 |
pobj |
ELISA,by |
R6310 |
T9032 |
T9031 |
cc |
and,Aβ40 |
R6311 |
T9033 |
T9031 |
conj |
Aβ42,Aβ40 |
R6312 |
T9034 |
T9026 |
prep |
in,levels |
R6313 |
T8877 |
T8878 |
punct |
[,23 |
R6314 |
T9035 |
T9036 |
det |
the,cohorts |
R6315 |
T9036 |
T9034 |
pobj |
cohorts,in |
R6316 |
T8878 |
T8847 |
parataxis |
23,measured |
R6317 |
T9037 |
T9038 |
nummod |
6,mo |
R6318 |
T9038 |
T9036 |
nmod |
mo,cohorts |
R6319 |
T9039 |
T9038 |
punct |
+,mo |
R6320 |
T8879 |
T8878 |
punct |
],23 |
R6321 |
T9040 |
T9041 |
nummod |
3,mo |
R6322 |
T9041 |
T9038 |
appos |
mo,mo |
R6323 |
T8880 |
T8847 |
punct |
.,measured |
R6324 |
T9042 |
T9038 |
cc |
and,mo |
R6325 |
T9043 |
T9044 |
nummod |
6,mo |
R6326 |
T9044 |
T9038 |
conj |
mo,mo |
R6327 |
T8882 |
T8883 |
prep |
In,found |
R6328 |
T9045 |
T9044 |
punct |
+,mo |
R6329 |
T9046 |
T9047 |
nummod |
6,mo |
R6330 |
T9047 |
T9044 |
appos |
mo,mo |
R6331 |
T9048 |
T9044 |
acl |
treated,mo |
R6332 |
T8884 |
T8885 |
det |
all,animals |
R6333 |
T9049 |
T9050 |
advmod |
most,similar |
R6334 |
T9050 |
T9023 |
acomp |
similar,were |
R6335 |
T9051 |
T9050 |
prep |
to,similar |
R6336 |
T8885 |
T8882 |
pobj |
animals,In |
R6337 |
T8886 |
T8885 |
acl |
harboring,animals |
R6338 |
T9052 |
T9051 |
pobj |
that,to |
R6339 |
T9053 |
T9052 |
prep |
of,that |
R6340 |
T8887 |
T8888 |
compound |
amyloid,deposits |
R6341 |
T9054 |
T9055 |
det |
the,cohort |
R6342 |
T9055 |
T9053 |
pobj |
cohort,of |
R6343 |
T9056 |
T9057 |
nummod |
9,mo |
R6344 |
T8888 |
T8886 |
dobj |
deposits,harboring |
R6345 |
T9057 |
T9055 |
nmod |
mo,cohort |
R6346 |
T9058 |
T9055 |
amod |
untreated,cohort |
R6347 |
T8889 |
T8883 |
punct |
", ",found |
R6348 |
T9059 |
T9023 |
punct |
", ",were |
R6349 |
T9060 |
T9023 |
advcl |
suggesting,were |
R6350 |
T8890 |
T8883 |
nsubj |
we,found |
R6351 |
T9061 |
T9062 |
mark |
that,determine |
R6352 |
T9062 |
T9060 |
ccomp |
determine,suggesting |
R6353 |
T9063 |
T9062 |
nsubj |
age,determine |
R6354 |
T9064 |
T9063 |
punct |
", ",age |
R6355 |
T9065 |
T9063 |
prep |
as,age |
R6356 |
T9066 |
T9065 |
prep |
opposed,as |
R6357 |
T8891 |
T8892 |
mark |
that,extracted |
R6358 |
T9067 |
T9066 |
prep |
to,opposed |
R6359 |
T9068 |
T9069 |
amod |
synthetic,rate |
R6360 |
T8892 |
T8883 |
ccomp |
extracted,found |
R6361 |
T9069 |
T9067 |
pobj |
rate,to |
R6362 |
T9070 |
T9069 |
punct |
(,rate |
R6363 |
T9071 |
T9072 |
dep |
which,be |
R6364 |
T8893 |
T8894 |
det |
the,majority |
R6365 |
T9072 |
T9069 |
relcl |
be,rate |
R6366 |
T9073 |
T9072 |
aux |
would,be |
R6367 |
T8894 |
T8892 |
nsubjpass |
majority,extracted |
R6368 |
T9074 |
T9072 |
acomp |
negligible,be |
R6369 |
T9075 |
T9072 |
prep |
in,be |
R6370 |
T9076 |
T9077 |
det |
the,animals |
R6371 |
T8895 |
T8894 |
amod |
vast,majority |
R6372 |
T9077 |
T9075 |
pobj |
animals,in |
R6373 |
T9078 |
T9077 |
amod |
treated,animals |
R6374 |
T9079 |
T9062 |
punct |
),determine |
R6375 |
T8896 |
T8894 |
prep |
of,majority |
R6376 |
T9080 |
T9062 |
punct |
", ",determine |
R6377 |
T9081 |
T9062 |
aux |
may,determine |
R6378 |
T9082 |
T9083 |
det |
the,fraction |
R6379 |
T8897 |
T8896 |
pobj |
Aβ,of |
R6380 |
T9083 |
T9062 |
dobj |
fraction,determine |
R6381 |
T9084 |
T9083 |
prep |
of,fraction |
R6382 |
T8898 |
T8899 |
punct |
(,% |
R6383 |
T9085 |
T9086 |
npadvmod |
PBS,soluble |
R6384 |
T9086 |
T9088 |
amod |
soluble,Aβ |
R6385 |
T9087 |
T9086 |
punct |
-,soluble |
R6386 |
T8899 |
T8897 |
parataxis |
%,Aβ |
R6387 |
T9088 |
T9084 |
pobj |
Aβ,of |
R6388 |
T9089 |
T9062 |
prep |
in,determine |
R6389 |
T9090 |
T9091 |
det |
these,animals |
R6390 |
T8900 |
T8901 |
punct |
>,99 |
R6391 |
T9091 |
T9089 |
pobj |
animals,in |
R6392 |
T9092 |
T9023 |
punct |
.,were |
R6393 |
T8901 |
T8899 |
nummod |
99,% |
R6394 |
T9094 |
T9095 |
nsubj |
We,assessed |
R6395 |
T8902 |
T8899 |
punct |
),% |
R6396 |
T9096 |
T9095 |
advmod |
also,assessed |
R6397 |
T9097 |
T9098 |
amod |
neuritic,pathology |
R6398 |
T8903 |
T8892 |
auxpass |
was,extracted |
R6399 |
T9098 |
T9095 |
dobj |
pathology,assessed |
R6400 |
T9099 |
T9097 |
cc |
and,neuritic |
R6401 |
T9100 |
T9097 |
conj |
glial,neuritic |
R6402 |
T8904 |
T8892 |
prep |
into,extracted |
R6403 |
T9101 |
T9098 |
acl |
surrounding,pathology |
R6404 |
T9102 |
T9103 |
det |
the,plaques |
R6405 |
T9103 |
T9101 |
dobj |
plaques,surrounding |
R6406 |
T9104 |
T9105 |
aux |
to,determine |
R6407 |
T9105 |
T9095 |
advcl |
determine,assessed |
R6408 |
T8905 |
T8906 |
det |
the,fractions |
R6409 |
T9106 |
T9107 |
mark |
whether,were |
R6410 |
T9107 |
T9105 |
ccomp |
were,determine |
R6411 |
T8906 |
T8904 |
pobj |
fractions,into |
R6412 |
T9108 |
T9107 |
expl |
there,were |
R6415 |
T8907 |
T8906 |
nmod |
SDS,fractions |
R6416 |
T9111 |
T9110 |
prep |
in,changes |
R6417 |
T9112 |
T9113 |
amod |
nearby,tissue |
R6418 |
T8908 |
T8907 |
cc |
and,SDS |
R6419 |
T9113 |
T9111 |
pobj |
tissue,in |
R6420 |
T9114 |
T9107 |
prep |
following,were |
R6421 |
T9115 |
T9116 |
amod |
long,term |
R6422 |
T8909 |
T8907 |
conj |
FA,SDS |
R6423 |
T9116 |
T9118 |
compound |
term,suppression |
R6424 |
T9117 |
T9116 |
punct |
-,term |
R6425 |
T8910 |
T8911 |
punct |
(,5A |
R6426 |
T9118 |
T9114 |
pobj |
suppression,following |
R6427 |
T9119 |
T9118 |
compound |
transgene,suppression |
R6428 |
T9120 |
T9095 |
punct |
.,assessed |
R6429 |
T8911 |
T8892 |
parataxis |
5A,extracted |
R6430 |
T9122 |
T9123 |
preconj |
Both,stain |
R6431 |
T8912 |
T8911 |
compound |
Figure,5A |
R6432 |
T9123 |
T9126 |
nsubj |
stain,showed |
R6433 |
T9124 |
T9123 |
compound |
Hirano,stain |
R6434 |
T9125 |
T9123 |
compound |
silver,stain |
R6435 |
T8913 |
T8911 |
cc |
and,5A |
R6436 |
T9127 |
T9123 |
cc |
and,stain |
R6437 |
T9128 |
T9129 |
compound |
ubiquitin,immunostaining |
R6438 |
T8914 |
T8911 |
conj |
5B,5A |
R6439 |
T9129 |
T9123 |
conj |
immunostaining,stain |
R6440 |
T9130 |
T9131 |
amod |
neuritic,pathology |
R6441 |
T8915 |
T8911 |
punct |
),5A |
R6442 |
T8916 |
T8883 |
punct |
.,found |
R6443 |
T8918 |
T8919 |
advcl |
Consistent,were |
R6444 |
T9131 |
T9126 |
dobj |
pathology,showed |
R6445 |
T9132 |
T9126 |
prep |
in,showed |
R6446 |
T9237 |
T9234 |
auxpass |
was,interrupted |
R6447 |
T9133 |
T9134 |
det |
all,groups |
R6448 |
T9134 |
T9132 |
pobj |
groups,in |
R6449 |
T9135 |
T9134 |
compound |
treatment,groups |
R6450 |
T9238 |
T9210 |
punct |
.,was |
R6451 |
T9136 |
T9137 |
punct |
(,Figure |
R6452 |
T9240 |
T9241 |
advmod |
Unfortunately,compromised |
R6453 |
T9137 |
T9126 |
parataxis |
Figure,showed |
R6454 |
T9138 |
T9137 |
nummod |
6,Figure |
R6455 |
T9139 |
T9137 |
punct |
),Figure |
R6456 |
T9140 |
T9126 |
punct |
.,showed |
R6457 |
T9242 |
T9241 |
punct |
", ",compromised |
R6458 |
T9142 |
T9143 |
advmod |
Similarly,found |
R6459 |
T9144 |
T9143 |
punct |
", ",found |
R6460 |
T9145 |
T9146 |
amod |
activated,astrocytes |
R6461 |
T9243 |
T9241 |
nsubjpass |
efforts,compromised |
R6462 |
T9146 |
T9143 |
nsubjpass |
astrocytes,found |
R6463 |
T9147 |
T9146 |
acl |
immunostained,astrocytes |
R6464 |
T9244 |
T9245 |
aux |
to,characterize |
R6465 |
T9148 |
T9147 |
prep |
for,immunostained |
R6466 |
T9149 |
T9148 |
pobj |
GFAP,for |
R6467 |
T9245 |
T9243 |
acl |
characterize,efforts |
R6468 |
T9150 |
T9143 |
auxpass |
were,found |
R6469 |
T9151 |
T9143 |
prep |
near,found |
R6470 |
T9152 |
T9151 |
pobj |
plaques,near |
R6471 |
T9246 |
T9247 |
amod |
cognitive,behavior |
R6472 |
T9153 |
T9143 |
prep |
in,found |
R6473 |
T9154 |
T9155 |
det |
all,animals |
R6474 |
T9247 |
T9245 |
dobj |
behavior,characterize |
R6475 |
T9155 |
T9153 |
pobj |
animals,in |
R6476 |
T9156 |
T9157 |
punct |
(,Figure |
R6477 |
T9248 |
T9241 |
auxpass |
were,compromised |
R6478 |
T9157 |
T9143 |
parataxis |
Figure,found |
R6479 |
T9158 |
T9157 |
nummod |
6,Figure |
R6480 |
T9159 |
T9157 |
punct |
),Figure |
R6481 |
T9249 |
T9241 |
agent |
by,compromised |
R6482 |
T9160 |
T9143 |
punct |
.,found |
R6483 |
T9162 |
T9163 |
amod |
Neuritic,pathology |
R6484 |
T9250 |
T9251 |
amod |
severe,hyperactivity |
R6485 |
T9163 |
T9166 |
nsubj |
pathology,were |
R6486 |
T9164 |
T9162 |
cc |
and,Neuritic |
R6487 |
T9251 |
T9249 |
pobj |
hyperactivity,by |
R6488 |
T9165 |
T9162 |
conj |
glial,Neuritic |
R6489 |
T9167 |
T9168 |
advmod |
more,severe |
R6490 |
T9252 |
T9251 |
prep |
in,hyperactivity |
R6491 |
T9168 |
T9166 |
acomp |
severe,were |
R6492 |
T9169 |
T9166 |
prep |
in,were |
R6493 |
T9253 |
T9254 |
amod |
untreated,mice |
R6494 |
T9170 |
T9171 |
det |
the,mice |
R6495 |
T9171 |
T9169 |
pobj |
mice,in |
R6496 |
T9172 |
T9171 |
amod |
older,mice |
R6497 |
T9254 |
T9252 |
pobj |
mice,in |
R6498 |
T9173 |
T9171 |
amod |
untreated,mice |
R6499 |
T9174 |
T9166 |
punct |
.,were |
R6500 |
T9255 |
T9256 |
amod |
double,transgenic |
R6501 |
T9176 |
T9177 |
prep |
In,prevented |
R6502 |
T9256 |
T9254 |
amod |
transgenic,mice |
R6503 |
T9178 |
T9176 |
pobj |
contrast,In |
R6504 |
T9179 |
T9177 |
punct |
", ",prevented |
R6505 |
T9180 |
T9181 |
compound |
transgene,suppression |
R6506 |
T9257 |
T9241 |
punct |
.,compromised |
R6507 |
T9181 |
T9177 |
nsubj |
suppression,prevented |
R6508 |
T9182 |
T9183 |
det |
the,growth |
R6509 |
T9183 |
T9177 |
dobj |
growth,prevented |
R6510 |
T9184 |
T9183 |
prep |
of,growth |
R6511 |
T9185 |
T9186 |
amod |
individual,deposits |
R6512 |
T9259 |
T9260 |
det |
The,animals |
R6513 |
T9186 |
T9184 |
pobj |
deposits,of |
R6514 |
T9187 |
T9186 |
relcl |
apparent,deposits |
R6515 |
T9188 |
T9187 |
prep |
in,apparent |
R6516 |
T9189 |
T9190 |
amod |
untreated,mice |
R6517 |
T9260 |
T9264 |
nsubjpass |
animals,seen |
R6518 |
T9190 |
T9188 |
pobj |
mice,in |
R6519 |
T9191 |
T9177 |
punct |
", ",prevented |
R6520 |
T9192 |
T9177 |
cc |
and,prevented |
R6521 |
T9261 |
T9262 |
compound |
tTA,APP |
R6522 |
T9193 |
T9177 |
conj |
limited,prevented |
R6523 |
T9194 |
T9195 |
det |
the,pathology |
R6524 |
T9262 |
T9260 |
compound |
APP,animals |
R6525 |
T9195 |
T9193 |
dobj |
pathology,limited |
R6526 |
T9196 |
T9195 |
amod |
surrounding,pathology |
R6527 |
T9197 |
T9193 |
prep |
to,limited |
R6528 |
T9263 |
T9262 |
punct |
/,APP |
R6529 |
T9198 |
T9199 |
dep |
what,was |
R6530 |
T9199 |
T9197 |
pcomp |
was,to |
R6531 |
T9265 |
T9264 |
auxpass |
were,seen |
R6532 |
T9200 |
T9199 |
advmod |
already,was |
R6533 |
T9201 |
T9199 |
acomp |
present,was |
R6534 |
T9202 |
T9203 |
advmod |
when,began |
R6535 |
T9203 |
T9199 |
advcl |
began,was |
R6536 |
T9266 |
T9264 |
advmod |
often,seen |
R6537 |
T9204 |
T9203 |
nsubj |
treatment,began |
R6538 |
T9267 |
T9264 |
advcl |
running,seen |
R6539 |
T9268 |
T9267 |
prep |
in,running |
R6540 |
T9205 |
T9177 |
punct |
.,prevented |
R6541 |
T9269 |
T9268 |
pobj |
circles,in |
R6542 |
T9207 |
T9208 |
det |
An,question |
R6543 |
T9270 |
T9267 |
prep |
around,running |
R6544 |
T9208 |
T9210 |
nsubj |
question,was |
R6545 |
T9209 |
T9208 |
amod |
obvious,question |
R6546 |
T9271 |
T9272 |
det |
the,perimeter |
R6547 |
T9211 |
T9212 |
nsubj |
we,sought |
R6548 |
T9212 |
T9208 |
advcl |
sought,question |
R6549 |
T9272 |
T9270 |
pobj |
perimeter,around |
R6550 |
T9213 |
T9214 |
aux |
to,address |
R6551 |
T9214 |
T9212 |
xcomp |
address,sought |
R6552 |
T9215 |
T9216 |
mark |
whether,diminished |
R6553 |
T9273 |
T9272 |
prep |
of,perimeter |
R6554 |
T9216 |
T9210 |
attr |
diminished,was |
R6555 |
T9217 |
T9218 |
det |
the,deposition |
R6556 |
T9218 |
T9216 |
nsubj |
deposition,diminished |
R6557 |
T9274 |
T9275 |
poss |
their,cages |
R6558 |
T9219 |
T9218 |
prep |
of,deposition |
R6559 |
T9220 |
T9219 |
pobj |
Aβ,of |
R6560 |
T9221 |
T9222 |
amod |
cognitive,ability |
R6561 |
T9222 |
T9216 |
dobj |
ability,diminished |
R6562 |
T9223 |
T9222 |
prep |
in,ability |
R6563 |
T9275 |
T9273 |
pobj |
cages,of |
R6564 |
T9224 |
T9225 |
amod |
untreated,mice |
R6565 |
T9225 |
T9223 |
pobj |
mice,in |
R6568 |
T9226 |
T9216 |
punct |
", ",diminished |
R6569 |
T9227 |
T9216 |
cc |
and,diminished |
R6570 |
T9278 |
T9279 |
det |
a,pattern |
R6571 |
T9228 |
T9229 |
dep |
what,happen |
R6572 |
T9229 |
T9216 |
conj |
happen,diminished |
R6573 |
T9279 |
T9282 |
nsubjpass |
pattern,noted |
R6574 |
T9230 |
T9229 |
aux |
might,happen |
R6575 |
T9231 |
T9229 |
prep |
to,happen |
R6576 |
T9232 |
T9231 |
pobj |
cognition,to |
R6577 |
T9280 |
T9279 |
amod |
similar,pattern |
R6578 |
T9233 |
T9234 |
advmod |
when,interrupted |
R6579 |
T9281 |
T9279 |
compound |
swimming,pattern |
R6580 |
T9234 |
T9229 |
advcl |
interrupted,happen |
R6581 |
T9235 |
T9236 |
det |
the,process |
R6582 |
T9236 |
T9234 |
nsubjpass |
process,interrupted |
R6583 |
T9282 |
T9264 |
conj |
noted,seen |
R6584 |
T9283 |
T9282 |
auxpass |
was,noted |
R6585 |
T9284 |
T9285 |
advmod |
when,tested |
R6586 |
T9285 |
T9282 |
advcl |
tested,noted |
R6587 |
T9343 |
T9344 |
amod |
certain,criteria |
R6588 |
T9286 |
T9287 |
det |
the,mice |
R6589 |
T9344 |
T9342 |
dobj |
criteria,meet |
R6590 |
T9345 |
T9344 |
compound |
performance,criteria |
R6591 |
T9346 |
T9347 |
punct |
[,30 |
R6592 |
T9287 |
T9285 |
nsubjpass |
mice,tested |
R6593 |
T9347 |
T9319 |
parataxis |
30,dealt |
R6594 |
T9348 |
T9347 |
punct |
],30 |
R6595 |
T9288 |
T9285 |
auxpass |
were,tested |
R6596 |
T9349 |
T9319 |
punct |
.,dealt |
R6597 |
T9289 |
T9285 |
prep |
in,tested |
R6598 |
T9351 |
T9352 |
prep |
In,was |
R6599 |
T9290 |
T9291 |
det |
the,maze |
R6600 |
T9353 |
T9354 |
poss |
our,case |
R6601 |
T9354 |
T9351 |
pobj |
case,In |
R6602 |
T9291 |
T9289 |
pobj |
maze,in |
R6603 |
T9355 |
T9352 |
punct |
", ",was |
R6604 |
T9356 |
T9357 |
det |
the,penetrance |
R6605 |
T9357 |
T9352 |
nsubj |
penetrance,was |
R6606 |
T9292 |
T9291 |
compound |
Morris,maze |
R6607 |
T9358 |
T9357 |
prep |
of,penetrance |
R6608 |
T9359 |
T9358 |
pobj |
hyperactivity,of |
R6609 |
T9293 |
T9291 |
compound |
water,maze |
R6610 |
T9360 |
T9361 |
amod |
close,100 |
R6611 |
T9361 |
T9363 |
nummod |
100,% |
R6612 |
T9362 |
T9361 |
quantmod |
to,100 |
R6613 |
T9363 |
T9352 |
attr |
%,was |
R6614 |
T9364 |
T9352 |
punct |
", ",was |
R6615 |
T9294 |
T9282 |
punct |
.,noted |
R6616 |
T9365 |
T9352 |
advcl |
leaving,was |
R6617 |
T9366 |
T9365 |
dobj |
us,leaving |
R6618 |
T9367 |
T9365 |
prep |
with,leaving |
R6619 |
T9296 |
T9297 |
prep |
In,noted |
R6620 |
T9368 |
T9369 |
det |
no,animals |
R6621 |
T9369 |
T9367 |
pobj |
animals,with |
R6622 |
T9370 |
T9369 |
amod |
testable,animals |
R6623 |
T9298 |
T9299 |
det |
the,maze |
R6624 |
T9371 |
T9352 |
punct |
.,was |
R6625 |
T9373 |
T9374 |
det |
This,phenotype |
R6626 |
T9374 |
T9375 |
nsubj |
phenotype,affected |
R6627 |
T9299 |
T9296 |
pobj |
maze,In |
R6628 |
T9300 |
T9299 |
amod |
radial,maze |
R6629 |
T9376 |
T9375 |
aux |
has,affected |
R6630 |
T9377 |
T9375 |
neg |
not,affected |
R6631 |
T9378 |
T9379 |
amod |
previous,lines |
R6632 |
T9301 |
T9299 |
compound |
water,maze |
R6633 |
T9379 |
T9375 |
dobj |
lines,affected |
R6634 |
T9380 |
T9379 |
prep |
of,lines |
R6635 |
T9302 |
T9297 |
punct |
", ",noted |
R6636 |
T9381 |
T9382 |
compound |
APPswe,mice |
R6637 |
T9382 |
T9380 |
pobj |
mice,of |
R6638 |
T9303 |
T9304 |
amod |
repetitive,patterns |
R6639 |
T9383 |
T9384 |
nsubj |
we,produced |
R6640 |
T9384 |
T9379 |
advcl |
produced,lines |
R6641 |
T9304 |
T9297 |
nsubjpass |
patterns,noted |
R6642 |
T9385 |
T9384 |
aux |
have,produced |
R6643 |
T9386 |
T9379 |
punct |
", ",lines |
R6644 |
T9387 |
T9388 |
amod |
such,as |
R6645 |
T9305 |
T9304 |
compound |
swim,patterns |
R6646 |
T9388 |
T9379 |
prep |
as,lines |
R6647 |
T9389 |
T9390 |
compound |
lines,E1 |
R6648 |
T9306 |
T9297 |
auxpass |
were,noted |
R6649 |
T9390 |
T9388 |
pobj |
E1,as |
R6650 |
T9391 |
T9390 |
punct |
–,E1 |
R6651 |
T9392 |
T9390 |
nummod |
2,E1 |
R6652 |
T9307 |
T9297 |
prep |
with,noted |
R6653 |
T9393 |
T9390 |
cc |
or,E1 |
R6654 |
T9394 |
T9390 |
conj |
C3,E1 |
R6655 |
T9308 |
T9309 |
det |
no,evidence |
R6656 |
T9395 |
T9394 |
punct |
–,C3 |
R6657 |
T9396 |
T9394 |
nummod |
3,C3 |
R6658 |
T9309 |
T9307 |
pobj |
evidence,with |
R6659 |
T9397 |
T9379 |
punct |
", ",lines |
R6660 |
T9398 |
T9399 |
dep |
that,express |
R6661 |
T9399 |
T9379 |
relcl |
express,lines |
R6662 |
T9310 |
T9309 |
prep |
of,evidence |
R6663 |
T9311 |
T9312 |
npadvmod |
choice,motivated |
R6664 |
T9400 |
T9401 |
amod |
lower,levels |
R6665 |
T9401 |
T9399 |
dobj |
levels,express |
R6666 |
T9402 |
T9401 |
prep |
of,levels |
R6667 |
T9312 |
T9314 |
amod |
motivated,actions |
R6668 |
T9403 |
T9404 |
amod |
transgenic,protein |
R6669 |
T9404 |
T9402 |
pobj |
protein,of |
R6670 |
T9313 |
T9312 |
punct |
-,motivated |
R6671 |
T9405 |
T9375 |
punct |
.,affected |
R6672 |
T9314 |
T9310 |
pobj |
actions,of |
R6673 |
T9407 |
T9408 |
advmod |
Indeed,established |
R6674 |
T9409 |
T9408 |
punct |
", ",established |
R6675 |
T9315 |
T9297 |
punct |
.,noted |
R6676 |
T9410 |
T9408 |
prep |
in,established |
R6677 |
T9411 |
T9412 |
amod |
past,studies |
R6678 |
T9317 |
T9318 |
amod |
Other,studies |
R6679 |
T9412 |
T9410 |
pobj |
studies,in |
R6680 |
T9413 |
T9414 |
advmod |
where,was |
R6681 |
T9414 |
T9412 |
relcl |
was,studies |
R6682 |
T9318 |
T9319 |
nsubj |
studies,dealt |
R6683 |
T9415 |
T9414 |
nsubj |
hyperactivity,was |
R6684 |
T9416 |
T9414 |
neg |
not,was |
R6685 |
T9417 |
T9418 |
det |
a,factor |
R6686 |
T9320 |
T9319 |
aux |
have,dealt |
R6687 |
T9418 |
T9414 |
attr |
factor,was |
R6688 |
T9419 |
T9408 |
punct |
", ",established |
R6689 |
T9420 |
T9408 |
nsubj |
we,established |
R6690 |
T9421 |
T9422 |
det |
a,relationship |
R6691 |
T9321 |
T9319 |
prep |
with,dealt |
R6692 |
T9422 |
T9408 |
dobj |
relationship,established |
R6693 |
T9423 |
T9422 |
amod |
clear,relationship |
R6694 |
T9322 |
T9323 |
amod |
similar,problems |
R6695 |
T9424 |
T9422 |
prep |
between,relationship |
R6696 |
T9425 |
T9426 |
compound |
amyloid,load |
R6697 |
T9426 |
T9424 |
pobj |
load,between |
R6698 |
T9323 |
T9321 |
pobj |
problems,with |
R6699 |
T9427 |
T9426 |
cc |
and,load |
R6700 |
T9428 |
T9429 |
amod |
cognitive,ability |
R6701 |
T9324 |
T9319 |
prep |
by,dealt |
R6702 |
T9429 |
T9426 |
conj |
ability,load |
R6703 |
T9430 |
T9431 |
punct |
[,31 |
R6704 |
T9431 |
T9408 |
parataxis |
31,established |
R6705 |
T9325 |
T9324 |
pcomp |
excluding,by |
R6706 |
T9432 |
T9431 |
punct |
],31 |
R6707 |
T9433 |
T9408 |
punct |
.,established |
R6708 |
T9326 |
T9325 |
dobj |
animals,excluding |
R6709 |
T9435 |
T9436 |
advmod |
However,feel |
R6710 |
T9327 |
T9328 |
dep |
that,show |
R6711 |
T9437 |
T9436 |
punct |
", ",feel |
R6712 |
T9438 |
T9436 |
prep |
in,feel |
R6713 |
T9439 |
T9440 |
det |
the,study |
R6714 |
T9328 |
T9326 |
relcl |
show,animals |
R6715 |
T9440 |
T9438 |
pobj |
study,in |
R6716 |
T9441 |
T9440 |
amod |
current,study |
R6717 |
T9442 |
T9436 |
punct |
", ",feel |
R6718 |
T9443 |
T9436 |
nsubj |
we,feel |
R6719 |
T9444 |
T9445 |
mark |
that,made |
R6720 |
T9329 |
T9328 |
aux |
do,show |
R6721 |
T9445 |
T9436 |
ccomp |
made,feel |
R6722 |
T9446 |
T9447 |
mark |
although,scored |
R6723 |
T9447 |
T9445 |
advcl |
scored,made |
R6724 |
T9330 |
T9328 |
neg |
not,show |
R6725 |
T9448 |
T9449 |
det |
the,performance |
R6726 |
T9331 |
T9332 |
amod |
adequate,attention |
R6727 |
T9332 |
T9328 |
dobj |
attention,show |
R6728 |
T9449 |
T9447 |
nsubjpass |
performance,scored |
R6729 |
T9333 |
T9332 |
prep |
to,attention |
R6730 |
T9450 |
T9449 |
amod |
poor,performance |
R6731 |
T9451 |
T9449 |
prep |
of,performance |
R6732 |
T9334 |
T9335 |
det |
the,task |
R6733 |
T9452 |
T9453 |
det |
the,mice |
R6734 |
T9453 |
T9451 |
pobj |
mice,of |
R6735 |
T9454 |
T9455 |
compound |
tTA,APP |
R6736 |
T9335 |
T9333 |
pobj |
task,to |
R6737 |
T9455 |
T9453 |
compound |
APP,mice |
R6738 |
T9456 |
T9455 |
punct |
/,APP |
R6739 |
T9336 |
T9328 |
punct |
", ",show |
R6740 |
T9457 |
T9449 |
prep |
in,performance |
R6741 |
T9458 |
T9459 |
det |
the,tests |
R6742 |
T9459 |
T9457 |
pobj |
tests,in |
R6743 |
T9337 |
T9328 |
advcl |
retaining,show |
R6744 |
T9460 |
T9459 |
compound |
maze,tests |
R6745 |
T9461 |
T9447 |
aux |
could,scored |
R6746 |
T9462 |
T9447 |
advmod |
technically,scored |
R6747 |
T9338 |
T9339 |
advmod |
only,mice |
R6748 |
T9463 |
T9447 |
auxpass |
be,scored |
R6749 |
T9464 |
T9447 |
prep |
as,scored |
R6750 |
T9339 |
T9337 |
dobj |
mice,retaining |
R6751 |
T9465 |
T9466 |
amod |
cognitive,impairment |
R6752 |
T9466 |
T9464 |
pobj |
impairment,as |
R6753 |
T9467 |
T9445 |
punct |
", ",made |
R6754 |
T9340 |
T9339 |
det |
those,mice |
R6755 |
T9468 |
T9469 |
det |
the,animals |
R6756 |
T9469 |
T9470 |
poss |
animals,hyperactivity |
R6757 |
T9341 |
T9342 |
dep |
that,meet |
R6758 |
T9470 |
T9445 |
nsubj |
hyperactivity,made |
R6759 |
T9471 |
T9469 |
case |
',animals |
R6760 |
T9472 |
T9470 |
amod |
severe,hyperactivity |
R6761 |
T9342 |
T9339 |
relcl |
meet,mice |
R6762 |
T9473 |
T9474 |
nsubj |
interpretation,impossible |
R6763 |
T9474 |
T9445 |
ccomp |
impossible,made |
R6764 |
T9475 |
T9473 |
prep |
of,interpretation |
R6765 |
T9555 |
T9554 |
punct |
–,night |
R6766 |
T9476 |
T9477 |
det |
the,tasks |
R6767 |
T9477 |
T9475 |
pobj |
tasks,of |
R6768 |
T9478 |
T9477 |
amod |
cognitive,tasks |
R6769 |
T9479 |
T9436 |
punct |
.,feel |
R6770 |
T9481 |
T9482 |
prep |
In,quantified |
R6771 |
T9556 |
T9532 |
prep |
than,were |
R6772 |
T9483 |
T9481 |
pobj |
order,In |
R6773 |
T9484 |
T9485 |
aux |
to,understand |
R6774 |
T9557 |
T9556 |
pobj |
any,than |
R6775 |
T9485 |
T9483 |
acl |
understand,order |
R6776 |
T9558 |
T9557 |
prep |
of,any |
R6777 |
T9559 |
T9560 |
det |
the,groups |
R6778 |
T9486 |
T9487 |
det |
the,nature |
R6779 |
T9487 |
T9485 |
dobj |
nature,understand |
R6780 |
T9560 |
T9558 |
pobj |
groups,of |
R6781 |
T9488 |
T9487 |
cc |
and,nature |
R6782 |
T9489 |
T9487 |
conj |
extent,nature |
R6783 |
T9490 |
T9487 |
prep |
of,nature |
R6784 |
T9561 |
T9560 |
compound |
control,groups |
R6785 |
T9491 |
T9490 |
pobj |
hyperactivity,of |
R6786 |
T9492 |
T9491 |
prep |
in,hyperactivity |
R6787 |
T9562 |
T9532 |
punct |
.,were |
R6788 |
T9493 |
T9494 |
det |
the,mice |
R6789 |
T9494 |
T9492 |
pobj |
mice,in |
R6790 |
T9564 |
T9565 |
compound |
Activity,levels |
R6791 |
T9495 |
T9496 |
compound |
tTA,APP |
R6792 |
T9496 |
T9494 |
compound |
APP,mice |
R6793 |
T9497 |
T9496 |
punct |
/,APP |
R6794 |
T9498 |
T9482 |
punct |
", ",quantified |
R6795 |
T9565 |
T9566 |
nsubj |
levels,appeared |
R6796 |
T9499 |
T9482 |
nsubj |
we,quantified |
R6797 |
T9500 |
T9501 |
amod |
daily,levels |
R6798 |
T9567 |
T9568 |
aux |
to,follow |
R6799 |
T9501 |
T9482 |
dobj |
levels,quantified |
R6800 |
T9502 |
T9501 |
compound |
activity,levels |
R6801 |
T9503 |
T9501 |
prep |
in,levels |
R6802 |
T9504 |
T9505 |
amod |
double,transgenic |
R6803 |
T9568 |
T9566 |
xcomp |
follow,appeared |
R6804 |
T9505 |
T9506 |
amod |
transgenic,animals |
R6805 |
T9506 |
T9503 |
pobj |
animals,in |
R6806 |
T9569 |
T9570 |
det |
a,cycle |
R6807 |
T9507 |
T9501 |
prep |
along,levels |
R6808 |
T9508 |
T9507 |
prep |
with,along |
R6809 |
T9509 |
T9510 |
poss |
their,siblings |
R6810 |
T9570 |
T9568 |
dobj |
cycle,follow |
R6811 |
T9510 |
T9508 |
pobj |
siblings,with |
R6812 |
T9511 |
T9512 |
amod |
single,transgenic |
R6813 |
T9571 |
T9572 |
advmod |
relatively,normal |
R6814 |
T9512 |
T9510 |
amod |
transgenic,siblings |
R6815 |
T9513 |
T9512 |
cc |
and,transgenic |
R6816 |
T9514 |
T9512 |
conj |
nontransgenic,transgenic |
R6817 |
T9572 |
T9570 |
amod |
normal,cycle |
R6818 |
T9515 |
T9510 |
acl |
using,siblings |
R6819 |
T9516 |
T9517 |
nummod |
four,beam |
R6820 |
T9517 |
T9519 |
compound |
beam,frames |
R6821 |
T9518 |
T9517 |
punct |
-,beam |
R6822 |
T9519 |
T9515 |
dobj |
frames,using |
R6823 |
T9573 |
T9570 |
amod |
diurnal,cycle |
R6824 |
T9520 |
T9519 |
acl |
designed,frames |
R6825 |
T9521 |
T9522 |
aux |
to,monitor |
R6826 |
T9522 |
T9520 |
advcl |
monitor,designed |
R6827 |
T9574 |
T9568 |
punct |
", ",follow |
R6828 |
T9523 |
T9522 |
dobj |
ambulation,monitor |
R6829 |
T9524 |
T9522 |
prep |
within,monitor |
R6830 |
T9575 |
T9568 |
advcl |
decreasing,follow |
R6831 |
T9525 |
T9526 |
det |
an,cage |
R6832 |
T9526 |
T9524 |
pobj |
cage,within |
R6833 |
T9527 |
T9526 |
amod |
enclosed,cage |
R6834 |
T9576 |
T9575 |
advmod |
substantially,decreasing |
R6835 |
T9528 |
T9482 |
punct |
.,quantified |
R6836 |
T9577 |
T9575 |
prep |
during,decreasing |
R6837 |
T9530 |
T9531 |
mark |
As,shown |
R6838 |
T9531 |
T9532 |
advcl |
shown,were |
R6839 |
T9578 |
T9579 |
det |
the,hours |
R6840 |
T9533 |
T9531 |
prep |
in,shown |
R6841 |
T9534 |
T9533 |
pobj |
Figure,in |
R6842 |
T9535 |
T9534 |
nummod |
7,Figure |
R6843 |
T9579 |
T9577 |
pobj |
hours,during |
R6844 |
T9536 |
T9532 |
punct |
", ",were |
R6845 |
T9537 |
T9538 |
det |
the,mice |
R6846 |
T9580 |
T9579 |
compound |
daylight,hours |
R6847 |
T9538 |
T9532 |
nsubj |
mice,were |
R6848 |
T9539 |
T9540 |
amod |
double,transgenic |
R6849 |
T9540 |
T9538 |
nmod |
transgenic,mice |
R6850 |
T9581 |
T9566 |
punct |
.,appeared |
R6851 |
T9541 |
T9542 |
quantmod |
up,10-fold |
R6852 |
T9542 |
T9544 |
advmod |
10-fold,active |
R6853 |
T9543 |
T9542 |
quantmod |
to,10-fold |
R6855 |
T9544 |
T9532 |
acomp |
active,were |
R6856 |
T9545 |
T9544 |
advmod |
more,active |
R6857 |
T9546 |
T9532 |
prep |
during,were |
R6858 |
T9547 |
T9548 |
det |
the,phase |
R6859 |
T9585 |
T9584 |
punct |
", ",remained |
R6860 |
T9548 |
T9546 |
pobj |
phase,during |
R6861 |
T9549 |
T9548 |
compound |
dark,phase |
R6862 |
T9550 |
T9548 |
prep |
of,phase |
R6863 |
T9586 |
T9587 |
advmod |
even,during |
R6864 |
T9551 |
T9552 |
det |
the,cycle |
R6865 |
T9552 |
T9550 |
pobj |
cycle,of |
R6866 |
T9553 |
T9554 |
compound |
day,night |
R6867 |
T9587 |
T9584 |
prep |
during,remained |
R6868 |
T9554 |
T9552 |
compound |
night,cycle |
R6869 |
T9588 |
T9589 |
det |
the,phase |
R6870 |
T9589 |
T9587 |
pobj |
phase,during |
R6871 |
T9590 |
T9589 |
compound |
light,phase |
R6872 |
T9591 |
T9584 |
punct |
", ",remained |
R6874 |
T9592 |
T9593 |
det |
the,mice |
R6877 |
T9593 |
T9584 |
nsubj |
mice,remained |
R6880 |
T9594 |
T9595 |
compound |
tTA,APP |
R6883 |
T9595 |
T9593 |
compound |
APP,mice |
R6886 |
T9596 |
T9595 |
punct |
/,APP |
R6889 |
T9597 |
T9598 |
advmod |
many-fold,more |
R6892 |
T9598 |
T9599 |
advmod |
more,active |
R6895 |
T9599 |
T9584 |
acomp |
active,remained |
R6899 |
T9600 |
T9599 |
prep |
than,active |
R6903 |
T9601 |
T9602 |
amod |
normal,controls |
R6906 |
T9602 |
T9600 |
pobj |
controls,than |
R6910 |
T9603 |
T9584 |
punct |
.,remained |
R6913 |
T9605 |
T9606 |
det |
This,behavior |
R6918 |
T9606 |
T9607 |
nsubjpass |
behavior,reversed |
R6921 |
T9608 |
T9607 |
auxpass |
was,reversed |
R6922 |
T9697 |
T9694 |
pobj |
distinction,with |
R6923 |
T9698 |
T9697 |
prep |
between,distinction |
R6924 |
T9699 |
T9700 |
poss |
their,levels |
R6925 |
T9700 |
T9698 |
pobj |
levels,between |
R6926 |
T9701 |
T9700 |
nmod |
day,levels |
R6927 |
T9702 |
T9701 |
punct |
-,day |
R6928 |
T9703 |
T9701 |
cc |
and,day |
R6929 |
T9609 |
T9607 |
advmod |
partially,reversed |
R6930 |
T9704 |
T9701 |
conj |
nighttime,day |
R6931 |
T9705 |
T9700 |
compound |
activity,levels |
R6932 |
T9706 |
T9674 |
punct |
.,showed |
R6933 |
T9610 |
T9609 |
punct |
", ",partially |
R6934 |
T9611 |
T9609 |
cc |
but,partially |
R6935 |
T9612 |
T9611 |
neg |
not,but |
R6936 |
T9613 |
T9609 |
conj |
consistently,partially |
R6937 |
T9614 |
T9607 |
punct |
", ",reversed |
R6938 |
T9615 |
T9607 |
prep |
by,reversed |
R6939 |
T9616 |
T9617 |
nummod |
1,mo |
R6940 |
T9617 |
T9615 |
pobj |
mo,by |
R6941 |
T9618 |
T9617 |
prep |
of,mo |
R6942 |
T9619 |
T9620 |
compound |
transgene,suppression |
R6943 |
T9620 |
T9618 |
pobj |
suppression,of |
R6944 |
T9621 |
T9617 |
acl |
beginning,mo |
R6945 |
T9622 |
T9621 |
prep |
at,beginning |
R6946 |
T9623 |
T9624 |
quantmod |
4,5 |
R6947 |
T9624 |
T9626 |
nummod |
5,mo |
R6948 |
T9625 |
T9624 |
punct |
–,5 |
R6949 |
T9626 |
T9622 |
pobj |
mo,at |
R6950 |
T9627 |
T9626 |
prep |
of,mo |
R6951 |
T9628 |
T9627 |
pobj |
age,of |
R6952 |
T9629 |
T9630 |
punct |
(,shown |
R6953 |
T9630 |
T9607 |
parataxis |
shown,reversed |
R6954 |
T9631 |
T9630 |
nsubj |
data,shown |
R6955 |
T9632 |
T9630 |
neg |
not,shown |
R6956 |
T9633 |
T9630 |
punct |
),shown |
R6957 |
T9634 |
T9607 |
punct |
.,reversed |
R6958 |
T9636 |
T9637 |
prep |
In,abolished |
R6959 |
T9638 |
T9636 |
pobj |
contrast,In |
R6960 |
T9639 |
T9637 |
punct |
", ",abolished |
R6961 |
T9640 |
T9637 |
nsubjpass |
hyperactivity,abolished |
R6962 |
T9641 |
T9637 |
auxpass |
was,abolished |
R6963 |
T9642 |
T9637 |
advmod |
completely,abolished |
R6964 |
T9643 |
T9637 |
prep |
by,abolished |
R6965 |
T9644 |
T9643 |
pcomp |
rearing,by |
R6966 |
T9645 |
T9646 |
compound |
tTA,APP |
R6967 |
T9646 |
T9648 |
compound |
APP,mice |
R6968 |
T9647 |
T9646 |
punct |
/,APP |
R6969 |
T9648 |
T9644 |
dobj |
mice,rearing |
R6970 |
T9649 |
T9644 |
prep |
on,rearing |
R6971 |
T9650 |
T9649 |
pobj |
dox,on |
R6972 |
T9651 |
T9637 |
punct |
.,abolished |
R6973 |
T9653 |
T9654 |
nsubj |
Animals,showed |
R6974 |
T9655 |
T9653 |
acl |
born,Animals |
R6975 |
T9656 |
T9655 |
cc |
and,born |
R6976 |
T9657 |
T9655 |
conj |
raised,born |
R6977 |
T9658 |
T9657 |
prep |
on,raised |
R6978 |
T9659 |
T9658 |
pobj |
dox,on |
R6979 |
T9660 |
T9661 |
compound |
activity,levels |
R6986 |
T10541 |
T10542 |
nsubj |
We,present |
R6987 |
T10543 |
T10544 |
det |
a,model |
R6988 |
T10544 |
T10542 |
dobj |
model,present |
R6989 |
T10545 |
T10544 |
amod |
new,model |
R6990 |
T10546 |
T10544 |
compound |
mouse,model |
R6991 |
T10547 |
T10544 |
prep |
for,model |
R6992 |
T10548 |
T10547 |
pobj |
AD,for |
R6993 |
T10549 |
T10550 |
dep |
that,designed |
R6994 |
T10550 |
T10544 |
relcl |
designed,model |
R6995 |
T10551 |
T10550 |
auxpass |
was,designed |
R6996 |
T10552 |
T10553 |
aux |
to,test |
R6997 |
T10553 |
T10550 |
advcl |
test,designed |
R6998 |
T10554 |
T10555 |
det |
the,consequences |
R6999 |
T10555 |
T10553 |
dobj |
consequences,test |
R7000 |
T10556 |
T10555 |
prep |
of,consequences |
R7001 |
T10557 |
T10556 |
pcomp |
inhibiting,of |
R7002 |
T10558 |
T10559 |
compound |
Aβ,production |
R7003 |
T10559 |
T10557 |
dobj |
production,inhibiting |
R7004 |
T10560 |
T10557 |
prep |
after,inhibiting |
R7005 |
T10561 |
T10562 |
det |
the,onset |
R7006 |
T10562 |
T10560 |
pobj |
onset,after |
R7007 |
T10563 |
T10562 |
prep |
of,onset |
R7008 |
T10564 |
T10565 |
compound |
amyloid,pathology |
R7009 |
T10565 |
T10563 |
pobj |
pathology,of |
R7010 |
T10566 |
T10542 |
punct |
.,present |
R7011 |
T10568 |
T10569 |
amod |
New,lines |
R7012 |
T10569 |
T10570 |
nsubjpass |
lines,developed |
R7013 |
T10571 |
T10569 |
prep |
of,lines |
R7014 |
T10572 |
T10573 |
amod |
transgenic,mice |
R7015 |
T10573 |
T10571 |
pobj |
mice,of |
R7016 |
T10574 |
T10570 |
auxpass |
were,developed |
R7017 |
T10575 |
T10570 |
prep |
for,developed |
R7018 |
T10576 |
T10577 |
det |
this,study |
R7019 |
T10577 |
T10575 |
pobj |
study,for |
R7020 |
T10578 |
T10579 |
dep |
that,express |
R7021 |
T10579 |
T10570 |
ccomp |
express,developed |
R7022 |
T10580 |
T10581 |
amod |
high,levels |
R7023 |
T10581 |
T10579 |
dobj |
levels,express |
R7024 |
T10582 |
T10581 |
prep |
of,levels |
R7025 |
T10583 |
T10584 |
compound |
APPswe,ind |
R7026 |
T10584 |
T10582 |
pobj |
ind,of |
R7027 |
T10585 |
T10584 |
punct |
/,ind |
R7028 |
T10586 |
T10579 |
prep |
under,express |
R7029 |
T10587 |
T10588 |
det |
the,control |
R7030 |
T10588 |
T10586 |
pobj |
control,under |
R7031 |
T10589 |
T10588 |
prep |
of,control |
R7032 |
T10590 |
T10591 |
det |
a,promoter |
R7033 |
T10591 |
T10589 |
pobj |
promoter,of |
R7034 |
T10592 |
T10593 |
npadvmod |
tetracycline,responsive |
R7035 |
T10593 |
T10591 |
amod |
responsive,promoter |
R7036 |
T10594 |
T10593 |
punct |
-,responsive |
R7037 |
T10595 |
T10570 |
punct |
.,developed |
R7038 |
T10597 |
T10598 |
nsubj |
We,demonstrate |
R7039 |
T10599 |
T10600 |
mark |
that,suppresses |
R7040 |
T10600 |
T10598 |
ccomp |
suppresses,demonstrate |
R7041 |
T10601 |
T10600 |
nsubj |
treatment,suppresses |
R7042 |
T10602 |
T10601 |
prep |
with,treatment |
R7043 |
T10603 |
T10602 |
pobj |
dox,with |
R7044 |
T10604 |
T10605 |
amod |
steady,state |
R7045 |
T10605 |
T10607 |
compound |
state,levels |
R7046 |
T10606 |
T10605 |
punct |
-,state |
R7047 |
T10607 |
T10600 |
dobj |
levels,suppresses |
R7048 |
T10608 |
T10607 |
prep |
of,levels |
R7049 |
T10609 |
T10610 |
preconj |
both,ind |
R7050 |
T10610 |
T10608 |
pobj |
ind,of |
R7051 |
T10611 |
T10610 |
compound |
APPswe,ind |
R7052 |
T10612 |
T10610 |
punct |
/,ind |
R7053 |
T10613 |
T10610 |
cc |
and,ind |
R7054 |
T10614 |
T10615 |
poss |
its,fragments |
R7055 |
T10615 |
T10610 |
conj |
fragments,ind |
R7056 |
T10616 |
T10615 |
nmod |
C,fragments |
R7057 |
T10617 |
T10615 |
punct |
-,fragments |
R7058 |
T10618 |
T10615 |
amod |
terminal,fragments |
R7059 |
T10619 |
T10600 |
punct |
", ",suppresses |
R7060 |
T10620 |
T10600 |
advcl |
indicating,suppresses |
R7061 |
T10621 |
T10622 |
mark |
that,have |
R7062 |
T10622 |
T10620 |
ccomp |
have,indicating |
R7063 |
T10623 |
T10624 |
det |
the,proteins |
R7064 |
T10624 |
T10622 |
nsubj |
proteins,have |
R7065 |
T10625 |
T10624 |
compound |
mutant,proteins |
R7066 |
T10626 |
T10627 |
det |
a,life |
R7067 |
T10627 |
T10622 |
dobj |
life,have |
R7068 |
T10628 |
T10629 |
advmod |
relatively,short |
R7069 |
T10629 |
T10627 |
amod |
short,life |
R7070 |
T10630 |
T10627 |
compound |
half,life |
R7071 |
T10631 |
T10627 |
punct |
-,life |
R7072 |
T10632 |
T10633 |
advmod |
in,vivo |
R7073 |
T10633 |
T10622 |
advmod |
vivo,have |
R7074 |
T10634 |
T10598 |
punct |
.,demonstrate |
R7075 |
T10636 |
T10637 |
amod |
Transgenic,expression |
R7076 |
T10637 |
T10638 |
nsubj |
expression,cause |
R7077 |
T10639 |
T10637 |
prep |
of,expression |
R7078 |
T10640 |
T10641 |
compound |
APPswe,ind |
R7079 |
T10641 |
T10639 |
pobj |
ind,of |
R7080 |
T10642 |
T10641 |
punct |
/,ind |
R7081 |
T10643 |
T10637 |
cc |
and,expression |
R7082 |
T10644 |
T10645 |
amod |
consequent,overproduction |
R7083 |
T10645 |
T10637 |
conj |
overproduction,expression |
R7084 |
T10646 |
T10645 |
prep |
of,overproduction |
R7085 |
T10647 |
T10646 |
pobj |
Aβ42,of |
R7086 |
T10648 |
T10649 |
amod |
early,onset |
R7087 |
T10649 |
T10651 |
compound |
onset,deposition |
R7088 |
T10650 |
T10649 |
punct |
-,onset |
R7089 |
T10651 |
T10638 |
dobj |
deposition,cause |
R7090 |
T10652 |
T10651 |
compound |
amyloid,deposition |
R7091 |
T10653 |
T10638 |
prep |
in,cause |
R7092 |
T10654 |
T10655 |
amod |
untreated,mice |
R7093 |
T10655 |
T10653 |
pobj |
mice,in |
R7094 |
T10656 |
T10655 |
punct |
", ",mice |
R7095 |
T10657 |
T10658 |
prep |
in,appear |
R7096 |
T10658 |
T10655 |
relcl |
appear,mice |
R7097 |
T10659 |
T10657 |
pobj |
which,in |
R7098 |
T10660 |
T10658 |
nsubj |
deposits,appear |
R7099 |
T10661 |
T10662 |
advmod |
as,early |
R7100 |
T10662 |
T10658 |
advmod |
early,appear |
R7101 |
T10663 |
T10662 |
prep |
as,early |
R7102 |
T10664 |
T10665 |
nummod |
2,mo |
R7103 |
T10665 |
T10663 |
pobj |
mo,as |
R7104 |
T10666 |
T10665 |
prep |
of,mo |
R7105 |
T10667 |
T10666 |
pobj |
age,of |
R7106 |
T10668 |
T10638 |
punct |
.,cause |
R7107 |
T10670 |
T10671 |
compound |
Amyloid,burden |
R7108 |
T10671 |
T10672 |
nsubj |
burden,worsens |
R7109 |
T10673 |
T10672 |
advmod |
significantly,worsens |
R7110 |
T10674 |
T10672 |
prep |
with,worsens |
R7111 |
T10675 |
T10674 |
pobj |
age,with |
R7112 |
T10676 |
T10672 |
punct |
", ",worsens |
R7113 |
T10677 |
T10672 |
cc |
and,worsens |
R7114 |
T10678 |
T10679 |
prep |
by,filled |
R7115 |
T10679 |
T10672 |
conj |
filled,worsens |
R7116 |
T10680 |
T10681 |
nummod |
9,mo |
R7117 |
T10681 |
T10678 |
pobj |
mo,by |
R7118 |
T10682 |
T10679 |
punct |
", ",filled |
R7119 |
T10683 |
T10684 |
det |
the,hippocampus |
R7120 |
T10684 |
T10679 |
nsubjpass |
hippocampus,filled |
R7121 |
T10685 |
T10684 |
cc |
and,hippocampus |
R7122 |
T10686 |
T10684 |
conj |
cortex,hippocampus |
R7123 |
T10687 |
T10684 |
prep |
of,hippocampus |
R7124 |
T10688 |
T10689 |
amod |
untreated,mice |
R7125 |
T10689 |
T10687 |
pobj |
mice,of |
R7126 |
T10690 |
T10679 |
auxpass |
are,filled |
R7127 |
T10691 |
T10679 |
advmod |
largely,filled |
R7128 |
T10692 |
T10679 |
prep |
with,filled |
R7129 |
T10693 |
T10694 |
amod |
aggregated,peptide |
R7130 |
T10694 |
T10692 |
pobj |
peptide,with |
R7131 |
T10695 |
T10679 |
punct |
.,filled |
R7132 |
T10697 |
T10698 |
nsubj |
We,find |
R7133 |
T10699 |
T10700 |
mark |
that,halts |
R7134 |
T10700 |
T10698 |
ccomp |
halts,find |
R7135 |
T10701 |
T10700 |
nsubj |
suppression,halts |
R7136 |
T10702 |
T10701 |
prep |
of,suppression |
R7137 |
T10703 |
T10704 |
amod |
transgenic,APP |
R7138 |
T10704 |
T10702 |
pobj |
APP,of |
R7139 |
T10705 |
T10701 |
prep |
by,suppression |
R7140 |
T10706 |
T10707 |
amod |
more,95 |
R7141 |
T10707 |
T10709 |
nummod |
95,% |
R7142 |
T10708 |
T10707 |
quantmod |
than,95 |
R7143 |
T10709 |
T10705 |
pobj |
%,by |
R7144 |
T10710 |
T10700 |
advmod |
abruptly,halts |
R7145 |
T10711 |
T10712 |
det |
the,progression |
R7146 |
T10712 |
T10700 |
dobj |
progression,halts |
R7147 |
T10713 |
T10712 |
prep |
of,progression |
R7148 |
T10714 |
T10715 |
compound |
amyloid,pathology |
R7149 |
T10715 |
T10713 |
pobj |
pathology,of |
R7150 |
T10716 |
T10698 |
punct |
.,find |
R7151 |
T10718 |
T10719 |
advmod |
Importantly,occurs |
R7152 |
T10720 |
T10719 |
punct |
", ",occurs |
R7153 |
T10721 |
T10722 |
det |
this,outcome |
R7154 |
T10722 |
T10719 |
nsubj |
outcome,occurs |
R7155 |
T10723 |
T10719 |
prep |
in,occurs |
R7156 |
T10724 |
T10723 |
pobj |
animals,in |
R7157 |
T10725 |
T10726 |
advmod |
already,harboring |
R7158 |
T10726 |
T10724 |
acl |
harboring,animals |
R7159 |
T10727 |
T10728 |
amod |
considerable,pathology |
R7160 |
T10728 |
T10726 |
dobj |
pathology,harboring |
R7161 |
T10729 |
T10728 |
compound |
amyloid,pathology |
R7162 |
T10730 |
T10719 |
punct |
", ",occurs |
R7163 |
T10731 |
T10732 |
det |
a,situation |
R7164 |
T10732 |
T10719 |
npadvmod |
situation,occurs |
R7165 |
T10733 |
T10732 |
amod |
similar,situation |
R7166 |
T10734 |
T10733 |
prep |
to,similar |
R7167 |
T10735 |
T10736 |
dep |
what,expected |
R7168 |
T10736 |
T10734 |
pcomp |
expected,to |
R7169 |
T10737 |
T10736 |
aux |
might,expected |
R7170 |
T10738 |
T10736 |
auxpass |
be,expected |
R7171 |
T10739 |
T10736 |
prep |
in,expected |
R7172 |
T10740 |
T10739 |
pobj |
patients,in |
R7173 |
T10741 |
T10742 |
aux |
to,treated |
R7174 |
T10742 |
T10740 |
advcl |
treated,patients |
R7175 |
T10743 |
T10742 |
auxpass |
be,treated |
R7176 |
T10744 |
T10742 |
prep |
with,treated |
R7177 |
T10745 |
T10746 |
compound |
secretase,inhibitors |
R7178 |
T10746 |
T10744 |
pobj |
inhibitors,with |
R7179 |
T10747 |
T10719 |
punct |
.,occurs |
R7180 |
T10749 |
T10750 |
advmod |
Somewhat,unexpectedly |
R7181 |
T10750 |
T10751 |
advmod |
unexpectedly,observe |
R7182 |
T10752 |
T10751 |
punct |
", ",observe |
R7183 |
T10753 |
T10751 |
nsubj |
we,observe |
R7184 |
T10754 |
T10755 |
det |
no,clearance |
R7185 |
T10755 |
T10751 |
dobj |
clearance,observe |
R7186 |
T10756 |
T10755 |
amod |
appreciable,clearance |
R7187 |
T10757 |
T10755 |
prep |
of,clearance |
R7188 |
T10758 |
T10759 |
amod |
deposited,amyloid |
R7189 |
T10759 |
T10757 |
pobj |
amyloid,of |
R7190 |
T10760 |
T10761 |
advmod |
even,following |
R7191 |
T10761 |
T10751 |
prep |
following,observe |
R7192 |
T10762 |
T10761 |
pobj |
periods,following |
R7193 |
T10763 |
T10762 |
prep |
of,periods |
R7194 |
T10764 |
T10765 |
compound |
transgene,suppression |
R7195 |
T10765 |
T10763 |
pobj |
suppression,of |
R7196 |
T10766 |
T10762 |
amod |
equal,periods |
R7197 |
T10767 |
T10766 |
prep |
to,equal |
R7198 |
T10768 |
T10769 |
det |
the,time |
R7199 |
T10769 |
T10767 |
pobj |
time,to |
R7200 |
T10770 |
T10769 |
advcl |
taken,time |
R7201 |
T10771 |
T10772 |
mark |
for,form |
R7202 |
T10772 |
T10770 |
advcl |
form,taken |
R7203 |
T10773 |
T10772 |
nsubj |
plaques,form |
R7204 |
T10774 |
T10772 |
aux |
to,form |
R7205 |
T10775 |
T10751 |
punct |
.,observe |
R7206 |
T10777 |
T10778 |
det |
This,finding |
R7207 |
T10778 |
T10780 |
nsubj |
finding,indicates |
R7208 |
T10779 |
T10778 |
amod |
latter,finding |
R7209 |
T10781 |
T10782 |
mark |
that,is |
R7210 |
T10782 |
T10780 |
ccomp |
is,indicates |
R7211 |
T10783 |
T10782 |
prep |
compared,is |
R7212 |
T10784 |
T10783 |
prep |
to,compared |
R7213 |
T10785 |
T10786 |
amod |
other,aggregates |
R7214 |
T10786 |
T10784 |
pobj |
aggregates,to |
R7215 |
T10787 |
T10788 |
npadvmod |
disease,associated |
R7216 |
T10788 |
T10786 |
amod |
associated,aggregates |
R7217 |
T10789 |
T10788 |
punct |
-,associated |
R7218 |
T10790 |
T10786 |
compound |
protein,aggregates |
R7219 |
T10791 |
T10792 |
amod |
such,as |
R7220 |
T10792 |
T10786 |
prep |
as,aggregates |
R7221 |
T10793 |
T10794 |
compound |
mutant,huntingtin |
R7222 |
T10794 |
T10792 |
pobj |
huntingtin,as |
R7223 |
T10795 |
T10794 |
punct |
", ",huntingtin |
R7224 |
T10796 |
T10797 |
dep |
which,clear |
R7225 |
T10797 |
T10794 |
relcl |
clear,huntingtin |
R7226 |
T10798 |
T10797 |
prep |
in,clear |
R7227 |
T10799 |
T10800 |
amod |
less,3 |
R7228 |
T10800 |
T10802 |
nummod |
3,mo |
R7229 |
T10801 |
T10800 |
quantmod |
than,3 |
R7230 |
T10802 |
T10798 |
pobj |
mo,in |
R7231 |
T10803 |
T10804 |
punct |
[,32 |
R7232 |
T10804 |
T10797 |
parataxis |
32,clear |
R7233 |
T10805 |
T10804 |
punct |
],32 |
R7234 |
T10806 |
T10782 |
punct |
", ",is |
R7235 |
T10807 |
T10808 |
det |
the,disaggregation |
R7236 |
T10808 |
T10782 |
nsubj |
disaggregation,is |
R7237 |
T10809 |
T10808 |
prep |
of,disaggregation |
R7238 |
T10810 |
T10811 |
amod |
extracellular,amyloid |
R7239 |
T10811 |
T10809 |
pobj |
amyloid,of |
R7240 |
T10812 |
T10813 |
advmod |
relatively,slow |
R7241 |
T10813 |
T10782 |
acomp |
slow,is |
R7242 |
T10814 |
T10780 |
punct |
.,indicates |
R7243 |
T10816 |
T10817 |
advmod |
Notably,show |
R7244 |
T10818 |
T10817 |
punct |
", ",show |
R7245 |
T10819 |
T10820 |
amod |
pharmaceutical,inhibitors |
R7246 |
T10820 |
T10817 |
nsubj |
inhibitors,show |
R7247 |
T10821 |
T10822 |
punct |
γ,secretase |
R7248 |
T10822 |
T10820 |
compound |
secretase,inhibitors |
R7249 |
T10823 |
T10822 |
punct |
-,secretase |
R7250 |
T10824 |
T10820 |
acl |
published,inhibitors |
R7251 |
T10825 |
T10824 |
prep |
to,published |
R7252 |
T10826 |
T10825 |
pobj |
date,to |
R7253 |
T10827 |
T10828 |
advmod |
less,strict |
R7254 |
T10828 |
T10829 |
amod |
strict,regulation |
R7255 |
T10829 |
T10817 |
dobj |
regulation,show |
R7256 |
T10830 |
T10829 |
prep |
of,regulation |
R7257 |
T10831 |
T10832 |
compound |
Aβ,production |
R7258 |
T10832 |
T10830 |
pobj |
production,of |
R7259 |
T10833 |
T10829 |
prep |
following,regulation |
R7260 |
T10834 |
T10835 |
amod |
chronic,administration |
R7261 |
T10835 |
T10833 |
pobj |
administration,following |
R7262 |
T10836 |
T10837 |
mark |
than,attained |
R7263 |
T10837 |
T10829 |
advcl |
attained,regulation |
R7264 |
T10838 |
T10837 |
nsubj |
we,attained |
R7265 |
T10839 |
T10837 |
aux |
have,attained |
R7266 |
T10840 |
T10837 |
advmod |
here,attained |
R7267 |
T10841 |
T10817 |
punct |
.,show |
R7268 |
T10843 |
T10844 |
nummod |
Two,compounds |
R7269 |
T10844 |
T10846 |
nsubj |
compounds,show |
R7270 |
T10845 |
T10844 |
amod |
independent,compounds |
R7271 |
T10847 |
T10844 |
acl |
tested,compounds |
R7272 |
T10848 |
T10847 |
prep |
in,tested |
R7273 |
T10849 |
T10850 |
npadvmod |
Tg2576,transgenic |
R7274 |
T10850 |
T10859 |
amod |
transgenic,mice |
R7275 |
T10851 |
T10852 |
punct |
[,33 |
R7276 |
T10852 |
T10849 |
parataxis |
33,Tg2576 |
R7277 |
T10853 |
T10852 |
punct |
],33 |
R7278 |
T10854 |
T10849 |
cc |
and,Tg2576 |
R7279 |
T10855 |
T10849 |
conj |
TgCRND8,Tg2576 |
R7280 |
T10856 |
T10857 |
punct |
[,34 |
R7281 |
T10857 |
T10855 |
parataxis |
34,TgCRND8 |
R7282 |
T10858 |
T10857 |
punct |
],34 |
R7283 |
T10859 |
T10848 |
pobj |
mice,in |
R7284 |
T10860 |
T10861 |
neg |
no,85 |
R7285 |
T10861 |
T10864 |
nummod |
85,% |
R7286 |
T10862 |
T10861 |
amod |
more,85 |
R7287 |
T10863 |
T10861 |
quantmod |
than,85 |
R7288 |
T10864 |
T10865 |
compound |
%,suppression |
R7289 |
T10865 |
T10846 |
dobj |
suppression,show |
R7290 |
T10866 |
T10865 |
prep |
of,suppression |
R7291 |
T10867 |
T10868 |
compound |
Aβ40,levels |
R7292 |
T10868 |
T10866 |
pobj |
levels,of |
R7293 |
T10869 |
T10865 |
punct |
", ",suppression |
R7294 |
T10870 |
T10865 |
cc |
and,suppression |
R7295 |
T10871 |
T10872 |
advmod |
where,measured |
R7296 |
T10872 |
T10873 |
advcl |
measured,suppression |
R7297 |
T10873 |
T10865 |
conj |
suppression,suppression |
R7298 |
T10874 |
T10873 |
punct |
", ",suppression |
R7299 |
T10875 |
T10876 |
advmod |
even,less |
R7300 |
T10876 |
T10873 |
amod |
less,suppression |
R7301 |
T10877 |
T10873 |
prep |
of,suppression |
R7302 |
T10878 |
T10877 |
pobj |
Aβ42,of |
R7303 |
T10879 |
T10880 |
punct |
(,% |
R7304 |
T10880 |
T10878 |
parataxis |
%,Aβ42 |
R7305 |
T10881 |
T10882 |
advmod |
approximately,60 |
R7306 |
T10882 |
T10880 |
nummod |
60,% |
R7307 |
T10883 |
T10880 |
punct |
),% |
R7308 |
T10884 |
T10885 |
punct |
[,36 |
R7309 |
T10885 |
T10846 |
parataxis |
36,show |
R7310 |
T10886 |
T10885 |
nummod |
35,36 |
R7311 |
T10887 |
T10885 |
punct |
",",36 |
R7312 |
T10888 |
T10885 |
punct |
],36 |
R7313 |
T10889 |
T10846 |
punct |
.,show |
R7314 |
T10891 |
T10892 |
advmod |
Thus,achieved |
R7315 |
T10893 |
T10892 |
punct |
", ",achieved |
R7316 |
T10894 |
T10895 |
advmod |
even,after |
R7317 |
T10895 |
T10892 |
prep |
after,achieved |
R7318 |
T10896 |
T10895 |
pcomp |
accounting,after |
R7319 |
T10897 |
T10896 |
prep |
for,accounting |
R7320 |
T10898 |
T10899 |
det |
the,levels |
R7321 |
T10899 |
T10897 |
pobj |
levels,for |
R7322 |
T10900 |
T10901 |
advmod |
much,higher |
R7323 |
T10901 |
T10899 |
amod |
higher,levels |
R7324 |
T10902 |
T10899 |
compound |
APP,levels |
R7325 |
T10903 |
T10899 |
compound |
expression,levels |
R7326 |
T10904 |
T10899 |
prep |
in,levels |
R7327 |
T10905 |
T10906 |
poss |
our,mice |
R7328 |
T10906 |
T10904 |
pobj |
mice,in |
R7329 |
T10907 |
T10899 |
prep |
than,levels |
R7330 |
T10908 |
T10907 |
prep |
in,than |
R7331 |
T10909 |
T10910 |
det |
the,lines |
R7332 |
T10910 |
T10908 |
pobj |
lines,in |
R7333 |
T10911 |
T10910 |
nmod |
Tg2576,lines |
R7334 |
T10912 |
T10911 |
cc |
and,Tg2576 |
R7335 |
T10913 |
T10911 |
conj |
TgCRND8,Tg2576 |
R7336 |
T10914 |
T10892 |
punct |
", ",achieved |
R7337 |
T10915 |
T10892 |
nsubj |
we,achieved |
R7338 |
T10916 |
T10892 |
aux |
have,achieved |
R7339 |
T10917 |
T10918 |
advmod |
better,suppression |
R7340 |
T10918 |
T10892 |
dobj |
suppression,achieved |
R7341 |
T10919 |
T10918 |
amod |
absolute,suppression |
R7342 |
T10920 |
T10918 |
prep |
of,suppression |
R7343 |
T10921 |
T10922 |
compound |
Aβ,production |
R7344 |
T10922 |
T10920 |
pobj |
production,of |
R7345 |
T10923 |
T10918 |
prep |
with,suppression |
R7346 |
T10924 |
T10925 |
det |
the,system |
R7347 |
T10925 |
T10923 |
pobj |
system,with |
R7348 |
T10926 |
T10927 |
compound |
tet,off |
R7349 |
T10927 |
T10925 |
compound |
off,system |
R7350 |
T10928 |
T10927 |
punct |
-,off |
R7351 |
T10929 |
T10930 |
mark |
than,is |
R7352 |
T10930 |
T10918 |
advcl |
is,suppression |
R7353 |
T10931 |
T10930 |
advmod |
currently,is |
R7354 |
T10932 |
T10930 |
acomp |
possible,is |
R7355 |
T10933 |
T10930 |
prep |
with,is |
R7356 |
T10934 |
T10935 |
amod |
published,inhibitors |
R7357 |
T10935 |
T10933 |
pobj |
inhibitors,with |
R7358 |
T10936 |
T10937 |
punct |
γ,secretase |
R7359 |
T10937 |
T10935 |
compound |
secretase,inhibitors |
R7360 |
T10938 |
T10937 |
punct |
-,secretase |
R7361 |
T10939 |
T10892 |
punct |
.,achieved |
R7362 |
T10941 |
T10942 |
mark |
Since,are |
R7363 |
T10942 |
T10950 |
advcl |
are,provides |
R7364 |
T10943 |
T10944 |
advmod |
even,agents |
R7365 |
T10944 |
T10942 |
nsubj |
agents,are |
R7366 |
T10945 |
T10944 |
det |
the,agents |
R7367 |
T10946 |
T10947 |
advmod |
most,advanced |
R7368 |
T10947 |
T10944 |
amod |
advanced,agents |
R7369 |
T10948 |
T10944 |
amod |
future,agents |
R7370 |
T10949 |
T10944 |
amod |
pharmaceutical,agents |
R7371 |
T10951 |
T10942 |
acomp |
unlikely,are |
R7372 |
T10952 |
T10953 |
aux |
to,attain |
R7373 |
T10953 |
T10951 |
xcomp |
attain,unlikely |
R7374 |
T10954 |
T10955 |
advmod |
more,complete |
R7375 |
T10955 |
T10956 |
amod |
complete,control |
R7376 |
T10956 |
T10953 |
dobj |
control,attain |
R7377 |
T10957 |
T10956 |
prep |
of,control |
R7378 |
T10958 |
T10959 |
compound |
Aβ,production |
R7379 |
T10959 |
T10957 |
pobj |
production,of |
R7380 |
T10960 |
T10961 |
mark |
than,achieved |
R7381 |
T10961 |
T10956 |
advcl |
achieved,control |
R7382 |
T10962 |
T10961 |
advmod |
here,achieved |
R7383 |
T10963 |
T10950 |
punct |
", ",provides |
R7384 |
T10964 |
T10965 |
det |
this,system |
R7385 |
T10965 |
T10950 |
nsubj |
system,provides |
R7386 |
T10966 |
T10967 |
det |
a,test |
R7387 |
T10967 |
T10950 |
dobj |
test,provides |
R7388 |
T10968 |
T10967 |
amod |
salient,test |
R7389 |
T10969 |
T10967 |
prep |
of,test |
R7390 |
T10970 |
T10971 |
amod |
therapeutic,intervention |
R7391 |
T10971 |
T10969 |
pobj |
intervention,of |
R7392 |
T10972 |
T10971 |
prep |
with,intervention |
R7393 |
T10973 |
T10974 |
npadvmod |
Aβ,lowering |
R7394 |
T10974 |
T10976 |
amod |
lowering,compounds |
R7395 |
T10975 |
T10974 |
punct |
-,lowering |
R7396 |
T10976 |
T10972 |
pobj |
compounds,with |
R7397 |
T10977 |
T10950 |
punct |
.,provides |
R7398 |
T10979 |
T10980 |
mark |
Although,arrested |
R7399 |
T10980 |
T10988 |
advcl |
arrested,found |
R7400 |
T10981 |
T10982 |
det |
the,progression |
R7401 |
T10982 |
T10980 |
nsubjpass |
progression,arrested |
R7402 |
T10983 |
T10982 |
prep |
of,progression |
R7403 |
T10984 |
T10985 |
compound |
amyloid,deposition |
R7404 |
T10985 |
T10983 |
pobj |
deposition,of |
R7405 |
T10986 |
T10980 |
auxpass |
was,arrested |
R7406 |
T10987 |
T10980 |
advmod |
sharply,arrested |
R7407 |
T10989 |
T10980 |
agent |
by,arrested |
R7408 |
T10990 |
T10991 |
det |
this,approach |
R7409 |
T10991 |
T10989 |
pobj |
approach,by |
R7410 |
T10992 |
T10988 |
punct |
", ",found |
R7411 |
T10993 |
T10988 |
nsubj |
we,found |
R7412 |
T10994 |
T10995 |
mark |
that,remained |
R7413 |
T10995 |
T10988 |
ccomp |
remained,found |
R7414 |
T10996 |
T10997 |
det |
a,burden |
R7415 |
T10997 |
T10995 |
nsubj |
burden,remained |
R7416 |
T10998 |
T10997 |
amod |
substantial,burden |
R7417 |
T10999 |
T10997 |
compound |
amyloid,burden |
R7418 |
T11000 |
T11001 |
advmod |
even,after |
R7419 |
T11001 |
T10995 |
prep |
after,remained |
R7420 |
T11002 |
T11003 |
amod |
long,periods |
R7421 |
T11003 |
T11001 |
pobj |
periods,after |
R7422 |
T11004 |
T11003 |
prep |
of,periods |
R7423 |
T11005 |
T11006 |
compound |
transgene,suppression |
R7424 |
T11006 |
T11004 |
pobj |
suppression,of |
R7425 |
T11007 |
T10988 |
punct |
.,found |
R7426 |
T11009 |
T11010 |
nsubj |
We,examined |
R7427 |
T11011 |
T11012 |
det |
a,number |
R7428 |
T11012 |
T11010 |
dobj |
number,examined |
R7429 |
T11013 |
T11012 |
amod |
small,number |
R7430 |
T11014 |
T11012 |
prep |
of,number |
R7431 |
T11015 |
T11014 |
pobj |
animals,of |
R7432 |
T11016 |
T11010 |
prep |
after,examined |
R7433 |
T11017 |
T11018 |
nummod |
12,mo |
R7434 |
T11018 |
T11016 |
pobj |
mo,after |
R7435 |
T11019 |
T11018 |
prep |
of,mo |
R7436 |
T11020 |
T11021 |
compound |
dox,treatment |
R7437 |
T11021 |
T11019 |
pobj |
treatment,of |
R7438 |
T11022 |
T11021 |
punct |
(,treatment |
R7439 |
T11023 |
T11021 |
acl |
beginning,treatment |
R7440 |
T11024 |
T11023 |
prep |
at,beginning |
R7441 |
T11025 |
T11026 |
nummod |
6,mo |
R7442 |
T11026 |
T11024 |
pobj |
mo,at |
R7443 |
T11027 |
T11026 |
prep |
of,mo |
R7444 |
T11028 |
T11027 |
pobj |
age,of |
R7445 |
T11029 |
T11021 |
punct |
),treatment |
R7446 |
T11030 |
T11010 |
punct |
", ",examined |
R7447 |
T11031 |
T11010 |
cc |
and,examined |
R7448 |
T11032 |
T11010 |
conj |
found,examined |
R7449 |
T11033 |
T11034 |
mark |
that,were |
R7450 |
T11034 |
T11032 |
ccomp |
were,found |
R7451 |
T11035 |
T11036 |
compound |
amyloid,deposits |
R7452 |
T11036 |
T11034 |
nsubj |
deposits,were |
R7453 |
T11037 |
T11034 |
advmod |
still,were |
R7454 |
T11038 |
T11039 |
advmod |
relatively,abundant |
R7455 |
T11039 |
T11034 |
acomp |
abundant,were |
R7456 |
T11040 |
T11010 |
punct |
.,examined |
R7457 |
T11042 |
T11043 |
amod |
Longer,term |
R7458 |
T11043 |
T11045 |
compound |
term,treatments |
R7459 |
T11044 |
T11043 |
punct |
-,term |
R7460 |
T11045 |
T11046 |
nsubj |
treatments,are |
R7461 |
T11047 |
T11046 |
advmod |
now,are |
R7462 |
T11048 |
T11046 |
prep |
in,are |
R7463 |
T11049 |
T11048 |
pobj |
progress,in |
R7464 |
T11050 |
T11046 |
punct |
.,are |
R7465 |
T11052 |
T11053 |
prep |
At,showed |
R7466 |
T11054 |
T11055 |
det |
the,interval |
R7467 |
T11055 |
T11052 |
pobj |
interval,At |
R7468 |
T11056 |
T11055 |
amod |
latest,interval |
R7469 |
T11057 |
T11055 |
compound |
treatment,interval |
R7470 |
T11058 |
T11055 |
acl |
analyzed,interval |
R7471 |
T11059 |
T11058 |
agent |
by,analyzed |
R7472 |
T11060 |
T11059 |
pobj |
ELISA,by |
R7473 |
T11061 |
T11053 |
punct |
", ",showed |
R7474 |
T11062 |
T11053 |
nsubj |
animals,showed |
R7475 |
T11063 |
T11062 |
acl |
administered,animals |
R7476 |
T11064 |
T11063 |
dobj |
dox,administered |
R7477 |
T11065 |
T11063 |
prep |
for,administered |
R7478 |
T11066 |
T11067 |
nummod |
6,mo |
R7479 |
T11067 |
T11065 |
pobj |
mo,for |
R7480 |
T11068 |
T11069 |
amod |
elevated,levels |
R7481 |
T11069 |
T11053 |
dobj |
levels,showed |
R7482 |
T11070 |
T11069 |
prep |
of,levels |
R7483 |
T11071 |
T11072 |
npadvmod |
PBS,soluble |
R7484 |
T11072 |
T11074 |
amod |
soluble,Aβ |
R7485 |
T11073 |
T11072 |
punct |
-,soluble |
R7486 |
T11074 |
T11070 |
pobj |
Aβ,of |
R7487 |
T11075 |
T11076 |
punct |
(,see |
R7488 |
T11076 |
T11074 |
parataxis |
see,Aβ |
R7489 |
T11077 |
T11076 |
dobj |
Figure,see |
R7490 |
T11078 |
T11077 |
nummod |
5,Figure |
R7491 |
T11079 |
T11076 |
punct |
),see |
R7492 |
T11080 |
T11081 |
dep |
that,interpreted |
R7493 |
T11081 |
T11069 |
relcl |
interpreted,levels |
R7494 |
T11082 |
T11081 |
aux |
could,interpreted |
R7495 |
T11083 |
T11081 |
auxpass |
be,interpreted |
R7496 |
T11084 |
T11081 |
prep |
as,interpreted |
R7497 |
T11085 |
T11086 |
det |
an,indication |
R7498 |
T11086 |
T11084 |
pobj |
indication,as |
R7499 |
T11087 |
T11088 |
mark |
that,releasing |
R7500 |
T11088 |
T11086 |
acl |
releasing,indication |
R7501 |
T11089 |
T11090 |
det |
the,plaques |
R7502 |
T11090 |
T11088 |
nsubj |
plaques,releasing |
R7503 |
T11091 |
T11088 |
aux |
are,releasing |
R7504 |
T11092 |
T11088 |
advmod |
slowly,releasing |
R7505 |
T11093 |
T11088 |
dobj |
peptide,releasing |
R7506 |
T11094 |
T11093 |
punct |
(,peptide |
R7507 |
T11095 |
T11093 |
cc |
or,peptide |
R7508 |
T11096 |
T11097 |
amod |
oligomeric,Aβ |
R7509 |
T11097 |
T11093 |
conj |
Aβ,peptide |
R7510 |
T11098 |
T11097 |
punct |
),Aβ |
R7511 |
T11099 |
T11088 |
prep |
into,releasing |
R7512 |
T11100 |
T11101 |
det |
the,pool |
R7513 |
T11101 |
T11099 |
pobj |
pool,into |
R7514 |
T11102 |
T11101 |
amod |
soluble,pool |
R7515 |
T11103 |
T11088 |
cc |
and,releasing |
R7516 |
T11104 |
T11105 |
aux |
might,dissolve |
R7517 |
T11105 |
T11088 |
conj |
dissolve,releasing |
R7518 |
T11106 |
T11105 |
advmod |
eventually,dissolve |
R7519 |
T11107 |
T11053 |
punct |
.,showed |
R7520 |
T11109 |
T11110 |
mark |
Whether,result |
R7521 |
T11110 |
T11124 |
csubj |
result,is |
R7522 |
T11111 |
T11110 |
csubj |
inhibiting,result |
R7523 |
T11112 |
T11113 |
compound |
Aβ,production |
R7524 |
T11113 |
T11111 |
dobj |
production,inhibiting |
R7525 |
T11114 |
T11111 |
advmod |
longer,inhibiting |
R7526 |
T11115 |
T11114 |
prep |
than,longer |
R7527 |
T11116 |
T11117 |
nummod |
6,mo |
R7528 |
T11117 |
T11115 |
pobj |
mo,than |
R7529 |
T11118 |
T11116 |
punct |
(,6 |
R7530 |
T11119 |
T11116 |
cc |
or,6 |
R7531 |
T11120 |
T11116 |
conj |
12,6 |
R7532 |
T11121 |
T11117 |
punct |
),mo |
R7533 |
T11122 |
T11110 |
aux |
may,result |
R7534 |
T11123 |
T11110 |
advmod |
ultimately,result |
R7535 |
T11124 |
T11129 |
ccomp |
is,limits |
R7536 |
T11125 |
T11110 |
prep |
in,result |
R7537 |
T11126 |
T11125 |
pobj |
clearance,in |
R7538 |
T11127 |
T11126 |
prep |
of,clearance |
R7539 |
T11128 |
T11127 |
pobj |
amyloid,of |
R7540 |
T11130 |
T11124 |
prep |
under,is |
R7541 |
T11131 |
T11130 |
pobj |
investigation,under |
R7542 |
T11132 |
T11129 |
punct |
;,limits |
R7543 |
T11133 |
T11129 |
advmod |
unfortunately,limits |
R7544 |
T11134 |
T11129 |
punct |
", ",limits |
R7545 |
T11135 |
T11136 |
det |
the,span |
R7546 |
T11136 |
T11129 |
nsubj |
span,limits |
R7547 |
T11137 |
T11136 |
compound |
life,span |
R7548 |
T11138 |
T11136 |
prep |
of,span |
R7549 |
T11139 |
T11140 |
det |
the,model |
R7550 |
T11140 |
T11138 |
pobj |
model,of |
R7551 |
T11141 |
T11129 |
advmod |
eventually,limits |
R7552 |
T11142 |
T11143 |
det |
this,experiment |
R7553 |
T11143 |
T11129 |
dobj |
experiment,limits |
R7554 |
T11144 |
T11129 |
punct |
.,limits |
R7555 |
T11146 |
T11147 |
nsubj |
Therapeutics,have |
R7556 |
T11148 |
T11146 |
acl |
used,Therapeutics |
R7557 |
T11149 |
T11148 |
prep |
in,used |
R7558 |
T11150 |
T11149 |
pobj |
humans,in |
R7559 |
T11151 |
T11147 |
aux |
will,have |
R7560 |
T11152 |
T11153 |
advmod |
considerably,more |
R7561 |
T11153 |
T11154 |
amod |
more,time |
R7562 |
T11154 |
T11147 |
dobj |
time,have |
R7563 |
T11155 |
T11156 |
aux |
to,act |
R7564 |
T11156 |
T11154 |
advcl |
act,time |
R7565 |
T11157 |
T11158 |
mark |
than,is |
R7566 |
T11158 |
T11154 |
advcl |
is,time |
R7567 |
T11159 |
T11158 |
acomp |
possible,is |
R7568 |
T11160 |
T11158 |
prep |
within,is |
R7569 |
T11161 |
T11162 |
det |
the,span |
R7570 |
T11162 |
T11160 |
pobj |
span,within |
R7571 |
T11163 |
T11162 |
compound |
life,span |
R7572 |
T11164 |
T11162 |
prep |
of,span |
R7573 |
T11165 |
T11166 |
compound |
rodent,models |
R7574 |
T11166 |
T11164 |
pobj |
models,of |
R7575 |
T11167 |
T11147 |
punct |
.,have |
R7576 |
T11169 |
T11170 |
amod |
Long,term |
R7577 |
T11170 |
T11172 |
compound |
term,treatments |
R7578 |
T11171 |
T11170 |
punct |
-,term |
R7579 |
T11172 |
T11173 |
nsubj |
treatments,be |
R7580 |
T11174 |
T11173 |
aux |
would,be |
R7581 |
T11175 |
T11173 |
advmod |
certainly,be |
R7582 |
T11176 |
T11173 |
acomp |
possible,be |
R7583 |
T11177 |
T11173 |
cc |
and,be |
R7584 |
T11178 |
T11179 |
aux |
could,be |
R7585 |
T11179 |
T11173 |
conj |
be,be |
R7586 |
T11180 |
T11181 |
det |
a,key |
R7587 |
T11181 |
T11179 |
attr |
key,be |
R7588 |
T11182 |
T11181 |
prep |
to,key |
R7589 |
T11183 |
T11184 |
amod |
effective,therapy |
R7590 |
T11184 |
T11182 |
pobj |
therapy,to |
R7591 |
T11185 |
T11173 |
punct |
.,be |
R7592 |
T11187 |
T11188 |
advmod |
Overall,interpret |
R7593 |
T11189 |
T11188 |
punct |
", ",interpret |
R7594 |
T11190 |
T11188 |
advmod |
however,interpret |
R7595 |
T11191 |
T11188 |
punct |
", ",interpret |
R7596 |
T11192 |
T11188 |
nsubj |
we,interpret |
R7597 |
T11193 |
T11194 |
poss |
our,findings |
R7598 |
T11194 |
T11188 |
dobj |
findings,interpret |
R7599 |
T11195 |
T11188 |
prep |
as,interpret |
R7600 |
T11196 |
T11195 |
pobj |
evidence,as |
R7601 |
T11197 |
T11198 |
mark |
that,reverse |
R7602 |
T11198 |
T11196 |
acl |
reverse,evidence |
R7603 |
T11199 |
T11200 |
compound |
AD,therapies |
R7604 |
T11200 |
T11198 |
nsubj |
therapies,reverse |
R7605 |
T11201 |
T11202 |
dep |
that,lower |
R7606 |
T11202 |
T11200 |
relcl |
lower,therapies |
R7607 |
T11203 |
T11202 |
advmod |
significantly,lower |
R7608 |
T11204 |
T11205 |
det |
the,production |
R7609 |
T11205 |
T11202 |
dobj |
production,lower |
R7610 |
T11206 |
T11205 |
prep |
of,production |
R7611 |
T11207 |
T11206 |
pobj |
Aβ,of |
R7612 |
T11208 |
T11202 |
punct |
(,lower |
R7613 |
T11209 |
T11202 |
prep |
by,lower |
R7614 |
T11210 |
T11211 |
preconj |
either,inhibiting |
R7615 |
T11211 |
T11209 |
pcomp |
inhibiting,by |
R7616 |
T11212 |
T11213 |
compound |
secretase,activity |
R7617 |
T11213 |
T11211 |
dobj |
activity,inhibiting |
R7618 |
T11214 |
T11211 |
cc |
or,inhibiting |
R7619 |
T11215 |
T11211 |
conj |
inhibiting,inhibiting |
R7620 |
T11216 |
T11217 |
compound |
APP,expression |
R7621 |
T11217 |
T11215 |
dobj |
expression,inhibiting |
R7622 |
T11218 |
T11202 |
punct |
),lower |
R7623 |
T11219 |
T11198 |
aux |
may,reverse |
R7624 |
T11220 |
T11198 |
neg |
not,reverse |
R7625 |
T11221 |
T11198 |
advmod |
quickly,reverse |
R7626 |
T11222 |
T11223 |
amod |
preexisting,pathology |
R7627 |
T11223 |
T11198 |
dobj |
pathology,reverse |
R7628 |
T11224 |
T11198 |
punct |
", ",reverse |
R7629 |
T11225 |
T11198 |
cc |
but,reverse |
R7630 |
T11226 |
T11227 |
aux |
should,halt |
R7631 |
T11227 |
T11198 |
conj |
halt,reverse |
R7632 |
T11228 |
T11227 |
advmod |
effectively,halt |
R7633 |
T11229 |
T11230 |
amod |
further,deposition |
R7634 |
T11230 |
T11227 |
dobj |
deposition,halt |
R7635 |
T11231 |
T11230 |
prep |
of,deposition |
R7636 |
T11232 |
T11231 |
pobj |
amyloid,of |
R7637 |
T11233 |
T11188 |
punct |
.,interpret |
R7638 |
T11235 |
T11236 |
prep |
In,remembered |
R7639 |
T11237 |
T11235 |
pcomp |
interpreting,In |
R7640 |
T11238 |
T11239 |
poss |
our,study |
R7641 |
T11239 |
T11237 |
dobj |
study,interpreting |
R7642 |
T11240 |
T11236 |
punct |
", ",remembered |
R7643 |
T11241 |
T11236 |
nsubjpass |
it,remembered |
R7644 |
T11242 |
T11236 |
aux |
should,remembered |
R7645 |
T11243 |
T11236 |
auxpass |
be,remembered |
R7646 |
T11244 |
T11245 |
mark |
that,are |
R7647 |
T11245 |
T11236 |
ccomp |
are,remembered |
R7648 |
T11246 |
T11247 |
det |
the,plaques |
R7649 |
T11247 |
T11245 |
nsubj |
plaques,are |
R7650 |
T11248 |
T11247 |
amod |
earliest,plaques |
R7651 |
T11249 |
T11250 |
aux |
to,appear |
R7652 |
T11250 |
T11247 |
advcl |
appear,plaques |
R7653 |
T11251 |
T11250 |
prep |
in,appear |
R7654 |
T11252 |
T11253 |
det |
these,mice |
R7655 |
T11253 |
T11251 |
pobj |
mice,in |
R7656 |
T11254 |
T11247 |
punct |
", ",plaques |
R7657 |
T11255 |
T11247 |
prep |
like,plaques |
R7658 |
T11256 |
T11257 |
amod |
other,transgenics |
R7659 |
T11257 |
T11255 |
pobj |
transgenics,like |
R7660 |
T11258 |
T11257 |
compound |
APP,transgenics |
R7661 |
T11259 |
T11257 |
acl |
harboring,transgenics |
R7662 |
T11260 |
T11261 |
det |
the,mutation |
R7663 |
T11261 |
T11259 |
dobj |
mutation,harboring |
R7664 |
T11262 |
T11261 |
amod |
Swedish,mutation |
R7665 |
T11263 |
T11264 |
punct |
[,27 |
R7666 |
T11264 |
T11259 |
parataxis |
27,harboring |
R7667 |
T11265 |
T11264 |
punct |
],27 |
R7668 |
T11266 |
T11245 |
punct |
", ",are |
R7669 |
T11267 |
T11245 |
advmod |
predominantly,are |
R7670 |
T11268 |
T11269 |
amod |
fibrillar,deposits |
R7671 |
T11269 |
T11245 |
attr |
deposits,are |
R7672 |
T11270 |
T11269 |
punct |
", ",deposits |
R7673 |
T11271 |
T11272 |
dep |
which,be |
R7674 |
T11272 |
T11269 |
relcl |
be,deposits |
R7675 |
T11273 |
T11272 |
aux |
may,be |
R7676 |
T11274 |
T11275 |
advmod |
less,tractable |
R7677 |
T11275 |
T11272 |
acomp |
tractable,be |
R7678 |
T11276 |
T11275 |
prep |
than,tractable |
R7679 |
T11277 |
T11278 |
det |
the,aggregates |
R7680 |
T11278 |
T11276 |
pobj |
aggregates,than |
R7681 |
T11279 |
T11278 |
amod |
diffuse,aggregates |
R7682 |
T11280 |
T11278 |
acl |
thought,aggregates |
R7683 |
T11281 |
T11282 |
aux |
to,come |
R7684 |
T11282 |
T11280 |
xcomp |
come,thought |
R7685 |
T11283 |
T11282 |
advmod |
first,come |
R7686 |
T11284 |
T11282 |
prep |
in,come |
R7687 |
T11285 |
T11286 |
det |
the,course |
R7688 |
T11286 |
T11284 |
pobj |
course,in |
R7689 |
T11287 |
T11286 |
prep |
of,course |
R7690 |
T11288 |
T11289 |
det |
the,disease |
R7691 |
T11289 |
T11287 |
pobj |
disease,of |
R7692 |
T11290 |
T11289 |
amod |
human,disease |
R7693 |
T11291 |
T11236 |
punct |
.,remembered |
R7694 |
T11293 |
T11294 |
advmod |
However,suggest |
R7695 |
T11295 |
T11294 |
punct |
", ",suggest |
R7696 |
T11296 |
T11297 |
poss |
our,data |
R7697 |
T11297 |
T11294 |
nsubj |
data,suggest |
R7698 |
T11298 |
T11299 |
mark |
that,cleared |
R7699 |
T11299 |
T11294 |
ccomp |
cleared,suggest |
R7700 |
T11300 |
T11301 |
mark |
once,formed |
R7701 |
T11301 |
T11299 |
advcl |
formed,cleared |
R7702 |
T11302 |
T11303 |
amod |
diffuse,deposits |
R7703 |
T11303 |
T11301 |
nsubjpass |
deposits,formed |
R7704 |
T11304 |
T11301 |
auxpass |
are,formed |
R7705 |
T11305 |
T11301 |
prep |
in,formed |
R7706 |
T11306 |
T11307 |
det |
these,mice |
R7707 |
T11307 |
T11305 |
pobj |
mice,in |
R7708 |
T11308 |
T11299 |
punct |
", ",cleared |
R7709 |
T11309 |
T11299 |
nsubjpass |
they,cleared |
R7710 |
T11310 |
T11299 |
auxpass |
are,cleared |
R7711 |
T11311 |
T11312 |
neg |
no,more |
R7712 |
T11312 |
T11313 |
advmod |
more,easily |
R7713 |
T11313 |
T11299 |
advmod |
easily,cleared |
R7714 |
T11314 |
T11299 |
prep |
in,cleared |
R7715 |
T11315 |
T11316 |
poss |
our,system |
R7716 |
T11316 |
T11314 |
pobj |
system,in |
R7717 |
T11317 |
T11299 |
prep |
than,cleared |
R7718 |
T11318 |
T11319 |
amod |
cored,plaques |
R7719 |
T11319 |
T11317 |
pobj |
plaques,than |
R7720 |
T11320 |
T11321 |
punct |
(,see |
R7721 |
T11321 |
T11299 |
parataxis |
see,cleared |
R7722 |
T11322 |
T11323 |
compound |
Figure,S4 |
R7723 |
T11323 |
T11321 |
dobj |
S4,see |
R7724 |
T11324 |
T11321 |
punct |
),see |
R7725 |
T11325 |
T11294 |
punct |
.,suggest |
R7726 |
T11327 |
T11328 |
det |
An,consideration |
R7727 |
T11328 |
T11330 |
nsubj |
consideration,is |
R7728 |
T11329 |
T11328 |
amod |
additional,consideration |
R7729 |
T11331 |
T11332 |
nsubj |
we,recognize |
R7730 |
T11332 |
T11328 |
advcl |
recognize,consideration |
R7731 |
T11333 |
T11334 |
mark |
that,continues |
R7732 |
T11334 |
T11330 |
advcl |
continues,is |
R7733 |
T11335 |
T11336 |
det |
a,amount |
R7734 |
T11336 |
T11334 |
nsubj |
amount,continues |
R7735 |
T11337 |
T11336 |
amod |
small,amount |
R7736 |
T11338 |
T11336 |
prep |
of,amount |
R7737 |
T11339 |
T11340 |
compound |
transgene,expression |
R7738 |
T11340 |
T11338 |
pobj |
expression,of |
R7739 |
T11341 |
T11334 |
prep |
in,continues |
R7740 |
T11342 |
T11343 |
det |
the,presence |
R7741 |
T11343 |
T11341 |
pobj |
presence,in |
R7742 |
T11344 |
T11343 |
prep |
of,presence |
R7743 |
T11345 |
T11344 |
pobj |
dox,of |
R7744 |
T11346 |
T11334 |
cc |
and,continues |
R7745 |
T11347 |
T11348 |
mark |
that,continues |
R7746 |
T11348 |
T11334 |
conj |
continues,continues |
R7747 |
T11349 |
T11350 |
amod |
endogenous,Aβ |
R7748 |
T11350 |
T11348 |
nsubj |
Aβ,continues |
R7749 |
T11351 |
T11350 |
compound |
mouse,Aβ |
R7750 |
T11352 |
T11353 |
aux |
to,produced |
R7751 |
T11353 |
T11348 |
xcomp |
produced,continues |
R7752 |
T11354 |
T11353 |
auxpass |
be,produced |
R7753 |
T11355 |
T11330 |
punct |
.,is |
R7754 |
T11357 |
T11358 |
nsubj |
It,is |
R7755 |
T11359 |
T11358 |
acomp |
possible,is |
R7756 |
T11360 |
T11361 |
mark |
that,are |
R7757 |
T11361 |
T11358 |
ccomp |
are,is |
R7758 |
T11362 |
T11363 |
det |
the,levels |
R7759 |
T11363 |
T11361 |
nsubj |
levels,are |
R7760 |
T11364 |
T11363 |
amod |
combined,levels |
R7761 |
T11365 |
T11363 |
amod |
low,levels |
R7762 |
T11366 |
T11363 |
prep |
of,levels |
R7763 |
T11367 |
T11368 |
amod |
endogenous,Aβ |
R7764 |
T11368 |
T11370 |
nmod |
Aβ,peptide |
R7765 |
T11369 |
T11368 |
nmod |
mouse,Aβ |
R7766 |
T11370 |
T11366 |
pobj |
peptide,of |
R7767 |
T11371 |
T11368 |
cc |
and,Aβ |
R7768 |
T11372 |
T11373 |
amod |
nonsuppressed,human |
R7769 |
T11373 |
T11368 |
conj |
human,Aβ |
R7770 |
T11374 |
T11361 |
acomp |
sufficient,are |
R7771 |
T11375 |
T11376 |
aux |
to,maintain |
R7772 |
T11376 |
T11374 |
xcomp |
maintain,sufficient |
R7773 |
T11377 |
T11378 |
amod |
existing,deposits |
R7774 |
T11378 |
T11376 |
dobj |
deposits,maintain |
R7775 |
T11379 |
T11358 |
punct |
.,is |
R7776 |
T11381 |
T11382 |
advmod |
However,are |
R7777 |
T11383 |
T11382 |
punct |
", ",are |
R7778 |
T11384 |
T11385 |
det |
these,levels |
R7779 |
T11385 |
T11382 |
nsubj |
levels,are |
R7780 |
T11386 |
T11385 |
amod |
low,levels |
R7781 |
T11387 |
T11385 |
prep |
of,levels |
R7782 |
T11388 |
T11387 |
pobj |
peptide,of |
R7783 |
T11389 |
T11382 |
neg |
not,are |
R7784 |
T11390 |
T11382 |
acomp |
sufficient,are |
R7785 |
T11391 |
T11392 |
aux |
to,induce |
R7786 |
T11392 |
T11390 |
xcomp |
induce,sufficient |
R7787 |
T11393 |
T11394 |
amod |
new,formation |
R7788 |
T11394 |
T11392 |
dobj |
formation,induce |
R7789 |
T11395 |
T11394 |
compound |
amyloid,formation |
R7790 |
T11396 |
T11382 |
punct |
", ",are |
R7791 |
T11397 |
T11398 |
mark |
as,develop |
R7792 |
T11398 |
T11382 |
advcl |
develop,are |
R7793 |
T11399 |
T11400 |
nmod |
CaMKIIα,ind |
R7794 |
T11400 |
T11406 |
compound |
ind,mice |
R7795 |
T11401 |
T11400 |
punct |
-,ind |
R7796 |
T11402 |
T11400 |
nmod |
tTA,ind |
R7797 |
T11403 |
T11400 |
punct |
×,ind |
R7798 |
T11404 |
T11400 |
compound |
tetAPPswe,ind |
R7799 |
T11405 |
T11400 |
punct |
/,ind |
R7800 |
T11406 |
T11398 |
nsubj |
mice,develop |
R7801 |
T11407 |
T11406 |
acl |
raised,mice |
R7802 |
T11408 |
T11407 |
prep |
on,raised |
R7803 |
T11409 |
T11408 |
pobj |
dox,on |
R7804 |
T11410 |
T11407 |
prep |
for,raised |
R7805 |
T11411 |
T11412 |
quantmod |
up,a |
R7806 |
T11412 |
T11414 |
nummod |
a,year |
R7807 |
T11413 |
T11412 |
quantmod |
to,a |
R7808 |
T11414 |
T11410 |
pobj |
year,for |
R7809 |
T11415 |
T11398 |
aux |
do,develop |
R7810 |
T11416 |
T11398 |
neg |
not,develop |
R7811 |
T11417 |
T11418 |
compound |
amyloid,lesions |
R7812 |
T11418 |
T11398 |
dobj |
lesions,develop |
R7813 |
T11419 |
T11420 |
punct |
(,shown |
R7814 |
T11420 |
T11398 |
parataxis |
shown,develop |
R7815 |
T11421 |
T11420 |
nsubj |
data,shown |
R7816 |
T11422 |
T11420 |
neg |
not,shown |
R7817 |
T11423 |
T11420 |
punct |
),shown |
R7818 |
T11424 |
T11382 |
punct |
.,are |
R7819 |
T11426 |
T11427 |
nsubj |
It,is |
R7820 |
T11428 |
T11427 |
advmod |
also,is |
R7821 |
T11429 |
T11427 |
acomp |
clear,is |
R7822 |
T11430 |
T11431 |
mark |
that,raised |
R7823 |
T11431 |
T11427 |
ccomp |
raised,is |
R7824 |
T11432 |
T11431 |
prep |
in,raised |
R7825 |
T11433 |
T11434 |
det |
this,system |
R7826 |
T11434 |
T11432 |
pobj |
system,in |
R7827 |
T11435 |
T11434 |
amod |
genetic,system |
R7828 |
T11436 |
T11431 |
punct |
", ",raised |
R7829 |
T11437 |
T11431 |
nsubj |
we,raised |
R7830 |
T11438 |
T11431 |
aux |
have,raised |
R7831 |
T11439 |
T11440 |
det |
the,production |
R7832 |
T11440 |
T11431 |
dobj |
production,raised |
R7833 |
T11441 |
T11440 |
prep |
of,production |
R7834 |
T11442 |
T11441 |
pobj |
Aβ,of |
R7835 |
T11443 |
T11431 |
prep |
to,raised |
R7836 |
T11444 |
T11443 |
pobj |
levels,to |
R7837 |
T11445 |
T11446 |
neg |
not,found |
R7838 |
T11446 |
T11444 |
acl |
found,levels |
R7839 |
T11447 |
T11446 |
prep |
in,found |
R7840 |
T11448 |
T11447 |
pobj |
humans,in |
R7841 |
T11449 |
T11450 |
aux |
to,accelerate |
R7842 |
T11450 |
T11431 |
advcl |
accelerate,raised |
R7843 |
T11451 |
T11450 |
dobj |
pathology,accelerate |
R7844 |
T11452 |
T11450 |
prep |
into,accelerate |
R7845 |
T11453 |
T11454 |
det |
an,frame |
R7846 |
T11454 |
T11452 |
pobj |
frame,into |
R7847 |
T11455 |
T11456 |
advmod |
experimentally,feasible |
R7848 |
T11456 |
T11454 |
amod |
feasible,frame |
R7849 |
T11457 |
T11454 |
compound |
time,frame |
R7850 |
T11458 |
T11427 |
punct |
.,is |
R7851 |
T11460 |
T11461 |
det |
This,system |
R7852 |
T11461 |
T11462 |
nsubj |
system,allowed |
R7853 |
T11462 |
T11463 |
ccomp |
allowed,favored |
R7854 |
T11464 |
T11465 |
nsubj |
us,create |
R7855 |
T11465 |
T11462 |
ccomp |
create,allowed |
R7856 |
T11466 |
T11465 |
aux |
to,create |
R7857 |
T11467 |
T11468 |
det |
an,differential |
R7858 |
T11468 |
T11465 |
dobj |
differential,create |
R7859 |
T11469 |
T11470 |
advmod |
approximately,20-fold |
R7860 |
T11470 |
T11468 |
amod |
20-fold,differential |
R7861 |
T11471 |
T11468 |
prep |
between,differential |
R7862 |
T11472 |
T11473 |
nmod |
APP,Aβ |
R7863 |
T11473 |
T11475 |
nmod |
Aβ,rates |
R7864 |
T11474 |
T11473 |
punct |
/,Aβ |
R7865 |
T11475 |
T11471 |
pobj |
rates,between |
R7866 |
T11476 |
T11475 |
amod |
synthetic,rates |
R7867 |
T11477 |
T11465 |
prep |
before,create |
R7868 |
T11478 |
T11477 |
cc |
and,before |
R7869 |
T11479 |
T11477 |
conj |
after,before |
R7870 |
T11480 |
T11479 |
pobj |
treatment,after |
R7871 |
T11481 |
T11463 |
punct |
", ",favored |
R7872 |
T11482 |
T11463 |
advmod |
yet,favored |
R7873 |
T11483 |
T11484 |
det |
the,equilibrium |
R7874 |
T11484 |
T11463 |
nsubj |
equilibrium,favored |
R7875 |
T11485 |
T11486 |
advmod |
in,vivo |
R7876 |
T11486 |
T11484 |
amod |
vivo,equilibrium |
R7877 |
T11487 |
T11484 |
prep |
between,equilibrium |
R7878 |
T11488 |
T11489 |
amod |
aggregated,states |
R7879 |
T11489 |
T11487 |
pobj |
states,between |
R7880 |
T11490 |
T11488 |
cc |
and,aggregated |
R7881 |
T11491 |
T11488 |
conj |
disaggregated,aggregated |
R7882 |
T11492 |
T11489 |
prep |
of,states |
R7883 |
T11493 |
T11492 |
pobj |
Aβ,of |
R7884 |
T11494 |
T11463 |
advmod |
still,favored |
R7885 |
T11495 |
T11496 |
det |
the,maintenance |
R7886 |
T11496 |
T11463 |
dobj |
maintenance,favored |
R7887 |
T11497 |
T11496 |
prep |
of,maintenance |
R7888 |
T11498 |
T11499 |
compound |
amyloid,deposits |
R7889 |
T11499 |
T11497 |
pobj |
deposits,of |
R7890 |
T11500 |
T11463 |
punct |
.,favored |
R7891 |
T11502 |
T11503 |
prep |
In,seems |
R7892 |
T11504 |
T11505 |
poss |
our,opinion |
R7893 |
T11505 |
T11502 |
pobj |
opinion,In |
R7894 |
T11506 |
T11503 |
punct |
", ",seems |
R7895 |
T11507 |
T11503 |
nsubj |
it,seems |
R7896 |
T11508 |
T11503 |
oprd |
unlikely,seems |
R7897 |
T11509 |
T11510 |
mark |
that,be |
R7898 |
T11510 |
T11503 |
ccomp |
be,seems |
R7899 |
T11511 |
T11512 |
compound |
amyloid,deposits |
R7900 |
T11512 |
T11510 |
nsubj |
deposits,be |
R7901 |
T11513 |
T11512 |
prep |
in,deposits |
R7902 |
T11514 |
T11515 |
amod |
human,brain |
R7903 |
T11515 |
T11513 |
pobj |
brain,in |
R7904 |
T11516 |
T11510 |
aux |
would,be |
R7905 |
T11517 |
T11510 |
advmod |
inherently,be |
R7906 |
T11518 |
T11519 |
advmod |
any,stable |
R7907 |
T11519 |
T11510 |
acomp |
stable,be |
R7908 |
T11520 |
T11519 |
advmod |
less,stable |
R7909 |
T11521 |
T11519 |
prep |
than,stable |
R7910 |
T11522 |
T11521 |
pobj |
those,than |
R7911 |
T11523 |
T11522 |
acl |
formed,those |
R7912 |
T11524 |
T11523 |
prep |
in,formed |
R7913 |
T11525 |
T11526 |
compound |
mouse,brain |
R7914 |
T11526 |
T11524 |
pobj |
brain,in |
R7915 |
T11527 |
T11503 |
punct |
.,seems |
R7916 |
T11529 |
T11530 |
advmod |
However,harbor |
R7917 |
T11531 |
T11530 |
punct |
", ",harbor |
R7918 |
T11532 |
T11533 |
det |
the,brain |
R7919 |
T11533 |
T11530 |
nsubj |
brain,harbor |
R7920 |
T11534 |
T11533 |
amod |
human,brain |
R7921 |
T11535 |
T11530 |
aux |
may,harbor |
R7922 |
T11536 |
T11537 |
compound |
clearance,mechanisms |
R7923 |
T11537 |
T11530 |
dobj |
mechanisms,harbor |
R7924 |
T11538 |
T11539 |
neg |
not,shared |
R7925 |
T11539 |
T11537 |
acl |
shared,mechanisms |
R7926 |
T11540 |
T11539 |
agent |
by,shared |
R7927 |
T11541 |
T11540 |
pobj |
mice,by |
R7928 |
T11542 |
T11543 |
dep |
that,allow |
R7929 |
T11543 |
T11537 |
relcl |
allow,mechanisms |
R7930 |
T11544 |
T11543 |
aux |
would,allow |
R7931 |
T11545 |
T11546 |
advmod |
more,efficient |
R7932 |
T11546 |
T11547 |
amod |
efficient,removal |
R7933 |
T11547 |
T11543 |
dobj |
removal,allow |
R7934 |
T11548 |
T11547 |
prep |
of,removal |
R7935 |
T11549 |
T11550 |
amod |
preexisting,amyloid |
R7936 |
T11550 |
T11548 |
pobj |
amyloid,of |
R7937 |
T11551 |
T11530 |
punct |
.,harbor |
R7938 |
T11553 |
T11554 |
nummod |
One,mechanism |
R7939 |
T11554 |
T11556 |
nsubj |
mechanism,is |
R7940 |
T11555 |
T11554 |
amod |
potential,mechanism |
R7941 |
T11557 |
T11558 |
prep |
by,removed |
R7942 |
T11558 |
T11554 |
relcl |
removed,mechanism |
R7943 |
T11559 |
T11557 |
pobj |
which,by |
R7944 |
T11560 |
T11558 |
nsubjpass |
amyloid,removed |
R7945 |
T11561 |
T11558 |
aux |
may,removed |
R7946 |
T11562 |
T11558 |
auxpass |
be,removed |
R7947 |
T11563 |
T11564 |
advmod |
more,efficiently |
R7948 |
T11564 |
T11558 |
advmod |
efficiently,removed |
R7949 |
T11565 |
T11558 |
prep |
in,removed |
R7950 |
T11566 |
T11567 |
det |
the,disease |
R7951 |
T11567 |
T11565 |
pobj |
disease,in |
R7952 |
T11568 |
T11567 |
amod |
human,disease |
R7953 |
T11569 |
T11558 |
prep |
than,removed |
R7954 |
T11570 |
T11569 |
prep |
in,than |
R7955 |
T11571 |
T11572 |
det |
the,models |
R7956 |
T11572 |
T11570 |
pobj |
models,in |
R7957 |
T11573 |
T11572 |
compound |
mouse,models |
R7958 |
T11574 |
T11556 |
prep |
through,is |
R7959 |
T11575 |
T11576 |
amod |
microglial,phagocytosis |
R7960 |
T11576 |
T11574 |
pobj |
phagocytosis,through |
R7961 |
T11577 |
T11556 |
punct |
.,is |
R7962 |
T11579 |
T11580 |
amod |
Resident,microglia |
R7963 |
T11580 |
T11581 |
nsubj |
microglia,localize |
R7964 |
T11582 |
T11580 |
prep |
in,microglia |
R7965 |
T11583 |
T11584 |
amod |
transgenic,models |
R7966 |
T11584 |
T11582 |
pobj |
models,in |
R7967 |
T11585 |
T11584 |
compound |
mouse,models |
R7968 |
T11586 |
T11581 |
prep |
to,localize |
R7969 |
T11587 |
T11586 |
pobj |
tissue,to |
R7970 |
T11588 |
T11587 |
acl |
surrounding,tissue |
R7971 |
T11589 |
T11588 |
dobj |
plaques,surrounding |
R7972 |
T11590 |
T11581 |
cc |
but,localize |
R7973 |
T11591 |
T11581 |
conj |
show,localize |
R7974 |
T11592 |
T11593 |
amod |
little,evidence |
R7975 |
T11593 |
T11591 |
dobj |
evidence,show |
R7976 |
T11594 |
T11593 |
prep |
of,evidence |
R7977 |
T11595 |
T11596 |
compound |
amyloid,engulfment |
R7978 |
T11596 |
T11594 |
pobj |
engulfment,of |
R7979 |
T11597 |
T11598 |
punct |
[,37 |
R7980 |
T11598 |
T11591 |
parataxis |
37,show |
R7981 |
T11599 |
T11600 |
punct |
–,40 |
R7982 |
T11600 |
T11598 |
prep |
40,37 |
R7983 |
T11601 |
T11598 |
punct |
],37 |
R7984 |
T11602 |
T11581 |
punct |
.,localize |
R7985 |
T11604 |
T11605 |
prep |
In,show |
R7986 |
T11606 |
T11604 |
pobj |
contrast,In |
R7987 |
T11607 |
T11605 |
punct |
", ",show |
R7988 |
T11608 |
T11605 |
nsubj |
microglia,show |
R7989 |
T11609 |
T11608 |
acl |
surrounding,microglia |
R7990 |
T11610 |
T11611 |
compound |
amyloid,plaques |
R7991 |
T11611 |
T11609 |
dobj |
plaques,surrounding |
R7992 |
T11612 |
T11609 |
prep |
in,surrounding |
R7993 |
T11613 |
T11614 |
amod |
human,brain |
R7994 |
T11614 |
T11612 |
pobj |
brain,in |
R7995 |
T11615 |
T11616 |
det |
a,state |
R7996 |
T11616 |
T11605 |
dobj |
state,show |
R7997 |
T11617 |
T11618 |
advmod |
much,higher |
R7998 |
T11618 |
T11616 |
amod |
higher,state |
R7999 |
T11619 |
T11616 |
prep |
of,state |
R8000 |
T11620 |
T11619 |
pobj |
activation,of |
R8001 |
T11621 |
T11605 |
prep |
with,show |
R8002 |
T11622 |
T11623 |
amod |
greater,expression |
R8003 |
T11623 |
T11621 |
pobj |
expression,with |
R8004 |
T11624 |
T11623 |
prep |
of,expression |
R8005 |
T11625 |
T11626 |
compound |
complement,receptor |
R8006 |
T11626 |
T11624 |
pobj |
receptor,of |
R8007 |
T11627 |
T11628 |
punct |
[,40 |
R8008 |
T11628 |
T11605 |
parataxis |
40,show |
R8009 |
T11629 |
T11628 |
punct |
],40 |
R8010 |
T11630 |
T11605 |
punct |
.,show |
R8011 |
T11632 |
T11633 |
advmod |
Thus,is |
R8012 |
T11634 |
T11633 |
punct |
", ",is |
R8013 |
T11635 |
T11636 |
det |
the,role |
R8014 |
T11636 |
T11633 |
nsubj |
role,is |
R8015 |
T11637 |
T11636 |
prep |
of,role |
R8016 |
T11638 |
T11637 |
pobj |
microglia,of |
R8017 |
T11639 |
T11636 |
prep |
in,role |
R8018 |
T11640 |
T11641 |
compound |
amyloid,metabolism |
R8019 |
T11641 |
T11639 |
pobj |
metabolism,in |
R8020 |
T11642 |
T11633 |
acomp |
minor,is |
R8021 |
T11643 |
T11633 |
prep |
in,is |
R8022 |
T11644 |
T11645 |
amod |
transgenic,models |
R8023 |
T11645 |
T11643 |
pobj |
models,in |
R8024 |
T11646 |
T11633 |
prep |
compared,is |
R8025 |
T11647 |
T11646 |
prep |
to,compared |
R8026 |
T11648 |
T11649 |
det |
the,condition |
R8027 |
T11649 |
T11647 |
pobj |
condition,to |
R8028 |
T11650 |
T11649 |
amod |
human,condition |
R8029 |
T11651 |
T11633 |
punct |
.,is |
R8030 |
T11653 |
T11654 |
advmod |
Somewhat,paradoxically |
R8031 |
T11654 |
T11655 |
advmod |
paradoxically,demonstrate |
R8032 |
T11656 |
T11655 |
punct |
", ",demonstrate |
R8033 |
T11657 |
T11658 |
amod |
several,studies |
R8034 |
T11658 |
T11655 |
nsubj |
studies,demonstrate |
R8035 |
T11659 |
T11655 |
advmod |
further,demonstrate |
R8036 |
T11660 |
T11661 |
mark |
that,lowers |
R8037 |
T11661 |
T11655 |
ccomp |
lowers,demonstrate |
R8038 |
T11662 |
T11661 |
nsubj |
treatment,lowers |
R8039 |
T11663 |
T11662 |
prep |
with,treatment |
R8040 |
T11664 |
T11665 |
amod |
anti-inflammatory,drugs |
R8041 |
T11665 |
T11663 |
pobj |
drugs,with |
R8042 |
T11666 |
T11667 |
aux |
to,reduce |
R8043 |
T11667 |
T11662 |
advcl |
reduce,treatment |
R8044 |
T11668 |
T11669 |
amod |
microglial,activation |
R8045 |
T11669 |
T11667 |
dobj |
activation,reduce |
R8046 |
T11670 |
T11661 |
advmod |
actually,lowers |
R8047 |
T11671 |
T11672 |
compound |
amyloid,load |
R8048 |
T11672 |
T11661 |
dobj |
load,lowers |
R8049 |
T11673 |
T11661 |
prep |
in,lowers |
R8050 |
T11674 |
T11675 |
npadvmod |
APP,transgenic |
R8051 |
T11675 |
T11676 |
amod |
transgenic,mice |
R8052 |
T11676 |
T11673 |
pobj |
mice,in |
R8053 |
T11677 |
T11661 |
punct |
", ",lowers |
R8054 |
T11678 |
T11661 |
advcl |
suggesting,lowers |
R8055 |
T11679 |
T11680 |
det |
a,role |
R8056 |
T11680 |
T11678 |
dobj |
role,suggesting |
R8057 |
T11681 |
T11680 |
prep |
for,role |
R8058 |
T11682 |
T11683 |
compound |
mouse,microglia |
R8059 |
T11683 |
T11681 |
pobj |
microglia,for |
R8060 |
T11684 |
T11680 |
prep |
in,role |
R8061 |
T11685 |
T11686 |
det |
the,formation |
R8062 |
T11686 |
T11684 |
pobj |
formation,in |
R8063 |
T11687 |
T11686 |
cc |
and,formation |
R8064 |
T11688 |
T11686 |
conj |
maintenance,formation |
R8065 |
T11689 |
T11686 |
prep |
of,formation |
R8066 |
T11690 |
T11691 |
compound |
amyloid,aggregates |
R8067 |
T11691 |
T11689 |
pobj |
aggregates,of |
R8068 |
T11692 |
T11693 |
punct |
[,41 |
R8069 |
T11693 |
T11661 |
parataxis |
41,lowers |
R8070 |
T11694 |
T11695 |
punct |
–,43 |
R8071 |
T11695 |
T11693 |
prep |
43,41 |
R8072 |
T11696 |
T11693 |
punct |
],41 |
R8073 |
T11697 |
T11655 |
punct |
.,demonstrate |
R8074 |
T11699 |
T11700 |
advmod |
However,explained |
R8075 |
T11701 |
T11700 |
punct |
", ",explained |
R8076 |
T11702 |
T11703 |
det |
this,outcome |
R8077 |
T11703 |
T11700 |
nsubjpass |
outcome,explained |
R8078 |
T11704 |
T11700 |
aux |
may,explained |
R8079 |
T11705 |
T11700 |
auxpass |
be,explained |
R8080 |
T11706 |
T11700 |
advmod |
alternatively,explained |
R8081 |
T11707 |
T11700 |
agent |
by,explained |
R8082 |
T11708 |
T11709 |
amod |
direct,effects |
R8083 |
T11709 |
T11707 |
pobj |
effects,by |
R8084 |
T11710 |
T11709 |
prep |
of,effects |
R8085 |
T11711 |
T11712 |
amod |
many,drugs |
R8086 |
T11712 |
T11710 |
pobj |
drugs,of |
R8087 |
T11713 |
T11712 |
amod |
anti-inflammatory,drugs |
R8088 |
T11714 |
T11709 |
prep |
on,effects |
R8089 |
T11715 |
T11716 |
punct |
γ,secretase |
R8090 |
T11716 |
T11718 |
compound |
secretase,cleavage |
R8091 |
T11717 |
T11716 |
punct |
-,secretase |
R8092 |
T11718 |
T11714 |
pobj |
cleavage,on |
R8093 |
T11719 |
T11720 |
punct |
[,44 |
R8094 |
T11720 |
T11700 |
parataxis |
44,explained |
R8095 |
T11721 |
T11722 |
punct |
–,47 |
R8096 |
T11722 |
T11720 |
prep |
47,44 |
R8097 |
T11723 |
T11720 |
punct |
],44 |
R8098 |
T11724 |
T11700 |
punct |
.,explained |
R8099 |
T11726 |
T11727 |
advmod |
Nonetheless,is |
R8100 |
T11728 |
T11727 |
punct |
", ",is |
R8101 |
T11729 |
T11730 |
det |
the,role |
R8102 |
T11730 |
T11727 |
nsubj |
role,is |
R8103 |
T11731 |
T11730 |
prep |
of,role |
R8104 |
T11732 |
T11731 |
pobj |
microglia,of |
R8105 |
T11733 |
T11730 |
prep |
in,role |
R8106 |
T11734 |
T11735 |
preconj |
both,condition |
R8107 |
T11735 |
T11733 |
pobj |
condition,in |
R8108 |
T11736 |
T11735 |
det |
the,condition |
R8109 |
T11737 |
T11735 |
amod |
human,condition |
R8110 |
T11738 |
T11735 |
cc |
and,condition |
R8111 |
T11739 |
T11740 |
det |
the,models |
R8112 |
T11740 |
T11735 |
conj |
models,condition |
R8113 |
T11741 |
T11740 |
compound |
mouse,models |
R8114 |
T11742 |
T11743 |
advmod |
poorly,understood |
R8115 |
T11743 |
T11727 |
acomp |
understood,is |
R8116 |
T11744 |
T11727 |
punct |
", ",is |
R8117 |
T11745 |
T11727 |
cc |
and,is |
R8118 |
T11746 |
T11747 |
nsubj |
differences,lead |
R8119 |
T11747 |
T11727 |
conj |
lead,is |
R8120 |
T11748 |
T11746 |
prep |
in,differences |
R8121 |
T11749 |
T11750 |
amod |
microglial,reactivity |
R8122 |
T11750 |
T11748 |
pobj |
reactivity,in |
R8123 |
T11751 |
T11746 |
prep |
between,differences |
R8124 |
T11752 |
T11753 |
det |
the,two |
R8125 |
T11753 |
T11751 |
pobj |
two,between |
R8126 |
T11754 |
T11747 |
aux |
could,lead |
R8127 |
T11755 |
T11747 |
prep |
to,lead |
R8128 |
T11756 |
T11757 |
advmod |
significantly,faster |
R8129 |
T11757 |
T11758 |
amod |
faster,clearance |
R8130 |
T11758 |
T11755 |
pobj |
clearance,to |
R8131 |
T11759 |
T11758 |
compound |
amyloid,clearance |
R8132 |
T11760 |
T11758 |
prep |
in,clearance |
R8133 |
T11761 |
T11762 |
det |
the,brains |
R8134 |
T11762 |
T11760 |
pobj |
brains,in |
R8135 |
T11763 |
T11762 |
prep |
of,brains |
R8136 |
T11764 |
T11763 |
pobj |
patients,of |
R8137 |
T11765 |
T11764 |
prep |
with,patients |
R8138 |
T11766 |
T11765 |
pobj |
AD,with |
R8139 |
T11767 |
T11768 |
mark |
than,observe |
R8140 |
T11768 |
T11758 |
advcl |
observe,clearance |
R8141 |
T11769 |
T11768 |
nsubj |
we,observe |
R8142 |
T11770 |
T11768 |
prep |
in,observe |
R8143 |
T11771 |
T11772 |
det |
the,mice |
R8144 |
T11772 |
T11770 |
pobj |
mice,in |
R8145 |
T11773 |
T11774 |
compound |
tet,off |
R8146 |
T11774 |
T11772 |
compound |
off,mice |
R8147 |
T11775 |
T11774 |
punct |
-,off |
R8148 |
T11776 |
T11772 |
compound |
APP,mice |
R8149 |
T11777 |
T11747 |
punct |
.,lead |
R8150 |
T11779 |
T11780 |
prep |
Given,think |
R8151 |
T11781 |
T11782 |
det |
the,role |
R8152 |
T11782 |
T11779 |
pobj |
role,Given |
R8153 |
T11783 |
T11784 |
advmod |
relatively,minor |
R8154 |
T11784 |
T11782 |
amod |
minor,role |
R8155 |
T11785 |
T11782 |
acl |
played,role |
R8156 |
T11786 |
T11785 |
agent |
by,played |
R8157 |
T11787 |
T11786 |
pobj |
microglia,by |
R8158 |
T11788 |
T11785 |
prep |
in,played |
R8159 |
T11789 |
T11790 |
amod |
other,models |
R8160 |
T11790 |
T11788 |
pobj |
models,in |
R8161 |
T11791 |
T11790 |
compound |
mouse,models |
R8162 |
T11792 |
T11790 |
prep |
of,models |
R8163 |
T11793 |
T11792 |
pobj |
amyloidosis,of |
R8164 |
T11794 |
T11780 |
punct |
", ",think |
R8165 |
T11795 |
T11780 |
nsubj |
we,think |
R8166 |
T11796 |
T11797 |
nsubj |
it,unlikely |
R8167 |
T11797 |
T11780 |
advcl |
unlikely,think |
R8168 |
T11798 |
T11799 |
mark |
that,influenced |
R8169 |
T11799 |
T11797 |
advcl |
influenced,unlikely |
R8170 |
T11800 |
T11801 |
det |
these,cells |
R8171 |
T11801 |
T11799 |
nsubj |
cells,influenced |
R8172 |
T11802 |
T11799 |
aux |
have,influenced |
R8173 |
T11803 |
T11804 |
det |
the,rate |
R8174 |
T11804 |
T11799 |
dobj |
rate,influenced |
R8175 |
T11805 |
T11804 |
prep |
of,rate |
R8176 |
T11806 |
T11807 |
compound |
amyloid,clearance |
R8177 |
T11807 |
T11805 |
pobj |
clearance,of |
R8178 |
T11808 |
T11799 |
prep |
in,influenced |
R8179 |
T11809 |
T11810 |
det |
the,mice |
R8180 |
T11810 |
T11808 |
pobj |
mice,in |
R8181 |
T11811 |
T11812 |
compound |
tet,off |
R8182 |
T11812 |
T11810 |
compound |
off,mice |
R8183 |
T11813 |
T11812 |
punct |
-,off |
R8184 |
T11814 |
T11810 |
compound |
APP,mice |
R8185 |
T11815 |
T11780 |
punct |
.,think |
R8186 |
T11817 |
T11818 |
advmod |
Even,so |
R8187 |
T11818 |
T11819 |
advmod |
so,considered |
R8188 |
T11820 |
T11819 |
punct |
", ",considered |
R8189 |
T11821 |
T11819 |
nsubj |
we,considered |
R8190 |
T11822 |
T11823 |
det |
the,possibility |
R8191 |
T11823 |
T11819 |
dobj |
possibility,considered |
R8192 |
T11824 |
T11825 |
mark |
that,altered |
R8193 |
T11825 |
T11823 |
acl |
altered,possibility |
R8194 |
T11826 |
T11827 |
amod |
chronic,treatment |
R8195 |
T11827 |
T11825 |
nsubj |
treatment,altered |
R8196 |
T11828 |
T11827 |
compound |
dox,treatment |
R8197 |
T11829 |
T11825 |
aux |
may,altered |
R8198 |
T11830 |
T11825 |
aux |
have,altered |
R8199 |
T11831 |
T11832 |
det |
the,state |
R8200 |
T11832 |
T11825 |
dobj |
state,altered |
R8201 |
T11833 |
T11832 |
compound |
activation,state |
R8202 |
T11834 |
T11832 |
prep |
of,state |
R8203 |
T11835 |
T11834 |
pobj |
microglia,of |
R8204 |
T11836 |
T11825 |
prep |
in,altered |
R8205 |
T11837 |
T11838 |
poss |
our,mice |
R8206 |
T11838 |
T11836 |
pobj |
mice,in |
R8207 |
T11839 |
T11838 |
amod |
treated,mice |
R8208 |
T11840 |
T11819 |
punct |
.,considered |
R8209 |
T11842 |
T11843 |
nsubj |
Dox,is |
R8210 |
T11844 |
T11845 |
advmod |
structurally,similar |
R8211 |
T11845 |
T11843 |
acomp |
similar,is |
R8212 |
T11846 |
T11845 |
prep |
to,similar |
R8213 |
T11847 |
T11846 |
pobj |
minocycline,to |
R8214 |
T11848 |
T11847 |
punct |
", ",minocycline |
R8215 |
T11849 |
T11850 |
det |
a,drug |
R8216 |
T11850 |
T11847 |
appos |
drug,minocycline |
R8217 |
T11851 |
T11850 |
amod |
reported,drug |
R8218 |
T11852 |
T11850 |
amod |
anti-inflammatory,drug |
R8219 |
T11853 |
T11850 |
cc |
and,drug |
R8220 |
T11854 |
T11850 |
conj |
inhibitor,drug |
R8221 |
T11855 |
T11854 |
prep |
of,inhibitor |
R8222 |
T11856 |
T11857 |
amod |
microglial,activation |
R8223 |
T11857 |
T11855 |
pobj |
activation,of |
R8224 |
T11858 |
T11859 |
punct |
[,48 |
R8225 |
T11859 |
T11843 |
parataxis |
48,is |
R8226 |
T11860 |
T11859 |
punct |
],48 |
R8227 |
T11861 |
T11843 |
punct |
.,is |
R8228 |
T11863 |
T11864 |
advmod |
However,expected |
R8229 |
T11865 |
T11864 |
punct |
", ",expected |
R8230 |
T11866 |
T11867 |
mark |
if,have |
R8231 |
T11867 |
T11864 |
advcl |
have,expected |
R8232 |
T11868 |
T11867 |
nsubj |
dox,have |
R8233 |
T11869 |
T11867 |
aux |
does,have |
R8234 |
T11870 |
T11871 |
amod |
anti-inflammatory,activity |
R8235 |
T11871 |
T11867 |
dobj |
activity,have |
R8236 |
T11872 |
T11864 |
punct |
", ",expected |
R8237 |
T11873 |
T11864 |
advmod |
then,expected |
R8238 |
T11874 |
T11864 |
punct |
", ",expected |
R8239 |
T11875 |
T11864 |
prep |
based,expected |
R8240 |
T11876 |
T11875 |
prep |
on,based |
R8241 |
T11877 |
T11878 |
amod |
previous,studies |
R8242 |
T11878 |
T11876 |
pobj |
studies,on |
R8243 |
T11879 |
T11878 |
prep |
with,studies |
R8244 |
T11880 |
T11881 |
amod |
other,anti-inflammatories |
R8245 |
T11881 |
T11879 |
pobj |
anti-inflammatories,with |
R8246 |
T11882 |
T11864 |
punct |
", ",expected |
R8247 |
T11883 |
T11864 |
nsubj |
we,expected |
R8248 |
T11884 |
T11864 |
aux |
would,expected |
R8249 |
T11885 |
T11864 |
aux |
have,expected |
R8250 |
T11886 |
T11887 |
aux |
to,find |
R8251 |
T11887 |
T11864 |
xcomp |
find,expected |
R8252 |
T11888 |
T11889 |
advmod |
less,amyloid |
R8253 |
T11889 |
T11887 |
dobj |
amyloid,find |
R8254 |
T11890 |
T11887 |
prep |
in,find |
R8255 |
T11891 |
T11892 |
det |
the,animals |
R8256 |
T11892 |
T11890 |
pobj |
animals,in |
R8257 |
T11893 |
T11894 |
npadvmod |
dox,treated |
R8258 |
T11894 |
T11892 |
amod |
treated,animals |
R8259 |
T11895 |
T11894 |
punct |
-,treated |
R8260 |
T11896 |
T11864 |
punct |
.,expected |
R8261 |
T11898 |
T11899 |
advmod |
Clearly,was |
R8262 |
T11900 |
T11899 |
punct |
", ",was |
R8263 |
T11901 |
T11899 |
nsubj |
that,was |
R8264 |
T11902 |
T11899 |
neg |
not,was |
R8265 |
T11903 |
T11904 |
det |
the,case |
R8266 |
T11904 |
T11899 |
attr |
case,was |
R8267 |
T11905 |
T11899 |
punct |
.,was |
R8268 |
T11907 |
T11908 |
mark |
While,is |
R8269 |
T11908 |
T11910 |
advcl |
is,demonstrate |
R8270 |
T11909 |
T11908 |
nsubj |
it,is |
R8271 |
T11911 |
T11908 |
acomp |
possible,is |
R8272 |
T11912 |
T11913 |
mark |
that,acts |
R8273 |
T11913 |
T11908 |
ccomp |
acts,is |
R8274 |
T11914 |
T11913 |
nsubj |
dox,acts |
R8275 |
T11915 |
T11913 |
prep |
in,acts |
R8276 |
T11916 |
T11917 |
det |
some,way |
R8277 |
T11917 |
T11915 |
pobj |
way,in |
R8278 |
T11918 |
T11917 |
amod |
other,way |
R8279 |
T11919 |
T11920 |
aux |
to,slow |
R8280 |
T11920 |
T11913 |
advcl |
slow,acts |
R8281 |
T11921 |
T11922 |
compound |
amyloid,clearance |
R8282 |
T11922 |
T11920 |
dobj |
clearance,slow |
R8283 |
T11923 |
T11910 |
punct |
", ",demonstrate |
R8284 |
T11924 |
T11910 |
nsubj |
data,demonstrate |
R8285 |
T11925 |
T11924 |
prep |
from,data |
R8286 |
T11926 |
T11927 |
amod |
multiple,studies |
R8287 |
T11927 |
T11925 |
pobj |
studies,from |
R8288 |
T11928 |
T11929 |
mark |
that,are |
R8289 |
T11929 |
T11910 |
ccomp |
are,demonstrate |
R8290 |
T11930 |
T11931 |
amod |
microglial,responses |
R8291 |
T11931 |
T11929 |
nsubj |
responses,are |
R8292 |
T11932 |
T11929 |
advmod |
normally,are |
R8293 |
T11933 |
T11929 |
acomp |
weak,are |
R8294 |
T11934 |
T11929 |
prep |
in,are |
R8295 |
T11935 |
T11936 |
det |
the,models |
R8296 |
T11936 |
T11934 |
pobj |
models,in |
R8297 |
T11937 |
T11936 |
compound |
mouse,models |
R8298 |
T11938 |
T11936 |
compound |
AD,models |
R8299 |
T11939 |
T11940 |
punct |
[,37 |
R8300 |
T11940 |
T11929 |
parataxis |
37,are |
R8301 |
T11941 |
T11942 |
punct |
–,40 |
R8302 |
T11942 |
T11940 |
prep |
40,37 |
R8303 |
T11943 |
T11940 |
punct |
],37 |
R8304 |
T11944 |
T11929 |
punct |
", ",are |
R8305 |
T11945 |
T11929 |
cc |
and,are |
R8306 |
T11946 |
T11947 |
advmod |
thus,is |
R8307 |
T11947 |
T11929 |
conj |
is,are |
R8308 |
T11948 |
T11947 |
nsubj |
it,is |
R8309 |
T11949 |
T11947 |
acomp |
doubtful,is |
R8310 |
T11950 |
T11951 |
mark |
that,affected |
R8311 |
T11951 |
T11947 |
ccomp |
affected,is |
R8312 |
T11952 |
T11953 |
npadvmod |
dox,mediated |
R8313 |
T11953 |
T11955 |
amod |
mediated,inhibition |
R8314 |
T11954 |
T11953 |
punct |
-,mediated |
R8315 |
T11955 |
T11951 |
nsubj |
inhibition,affected |
R8316 |
T11956 |
T11955 |
amod |
microglial,inhibition |
R8317 |
T11957 |
T11958 |
det |
the,outcome |
R8318 |
T11958 |
T11951 |
dobj |
outcome,affected |
R8319 |
T11959 |
T11958 |
prep |
of,outcome |
R8320 |
T11960 |
T11961 |
poss |
our,study |
R8321 |
T11961 |
T11959 |
pobj |
study,of |
R8322 |
T11962 |
T11910 |
punct |
.,demonstrate |
R8323 |
T11964 |
T11965 |
det |
The,persistence |
R8324 |
T11965 |
T11966 |
nsubj |
persistence,is |
R8325 |
T11967 |
T11965 |
cc |
and,persistence |
R8326 |
T11968 |
T11965 |
conj |
stability,persistence |
R8327 |
T11969 |
T11965 |
prep |
of,persistence |
R8328 |
T11970 |
T11971 |
compound |
amyloid,deposits |
R8329 |
T11971 |
T11969 |
pobj |
deposits,of |
R8330 |
T11972 |
T11965 |
prep |
in,persistence |
R8331 |
T11973 |
T11974 |
poss |
our,system |
R8332 |
T11974 |
T11972 |
pobj |
system,in |
R8333 |
T11975 |
T11966 |
acomp |
unexpected,is |
R8334 |
T11976 |
T11966 |
prep |
given,is |
R8335 |
T11977 |
T11978 |
det |
the,speed |
R8336 |
T11978 |
T11976 |
pobj |
speed,given |
R8337 |
T11979 |
T11980 |
prep |
with,cleared |
R8338 |
T11980 |
T11978 |
relcl |
cleared,speed |
R8339 |
T11981 |
T11979 |
pobj |
which,with |
R8340 |
T11982 |
T11983 |
compound |
Aβ,aggregates |
R8341 |
T11983 |
T11980 |
nsubjpass |
aggregates,cleared |
R8342 |
T11984 |
T11980 |
auxpass |
are,cleared |
R8343 |
T11985 |
T11980 |
prep |
in,cleared |
R8344 |
T11986 |
T11987 |
amod |
other,models |
R8345 |
T11987 |
T11985 |
pobj |
models,in |
R8346 |
T11988 |
T11987 |
compound |
mouse,models |
R8347 |
T11989 |
T11987 |
prep |
of,models |
R8348 |
T11990 |
T11991 |
amod |
therapeutic,intervention |
R8349 |
T11991 |
T11989 |
pobj |
intervention,of |
R8350 |
T11992 |
T11966 |
punct |
.,is |
R8351 |
T11994 |
T11995 |
amod |
Anti-Aβ,antibodies |
R8352 |
T11995 |
T11996 |
nsubjpass |
antibodies,shown |
R8353 |
T11997 |
T11995 |
acl |
injected,antibodies |
R8354 |
T11998 |
T11997 |
advmod |
directly,injected |
R8355 |
T11999 |
T11997 |
prep |
into,injected |
R8356 |
T12000 |
T12001 |
det |
the,brain |
R8357 |
T12001 |
T11999 |
pobj |
brain,into |
R8358 |
T12002 |
T11996 |
aux |
have,shown |
R8359 |
T12003 |
T11996 |
auxpass |
been,shown |
R8360 |
T12004 |
T12005 |
aux |
to,eliminate |
R8361 |
T12005 |
T11996 |
xcomp |
eliminate,shown |
R8362 |
T12006 |
T12007 |
compound |
amyloid,deposits |
R8363 |
T12007 |
T12005 |
dobj |
deposits,eliminate |
R8364 |
T12008 |
T12005 |
prep |
in,eliminate |
R8365 |
T12009 |
T12010 |
advmod |
as,1 |
R8366 |
T12010 |
T12013 |
nummod |
1,wk |
R8367 |
T12011 |
T12010 |
amod |
little,1 |
R8368 |
T12012 |
T12010 |
quantmod |
as,1 |
R8369 |
T12013 |
T12008 |
pobj |
wk,in |
R8370 |
T12014 |
T12013 |
prep |
after,wk |
R8371 |
T12015 |
T12014 |
pobj |
treatment,after |
R8372 |
T12016 |
T12017 |
punct |
[,49 |
R8373 |
T12017 |
T12005 |
parataxis |
49,eliminate |
R8374 |
T12018 |
T12019 |
punct |
–,51 |
R8375 |
T12019 |
T12017 |
prep |
51,49 |
R8376 |
T12020 |
T12017 |
punct |
],49 |
R8377 |
T12021 |
T11996 |
punct |
.,shown |
R8378 |
T12023 |
T12024 |
amod |
Peripheral,injection |
R8379 |
T12024 |
T12026 |
nsubj |
injection,decreases |
R8380 |
T12025 |
T12024 |
compound |
antibody,injection |
R8381 |
T12027 |
T12028 |
compound |
amyloid,load |
R8382 |
T12028 |
T12026 |
dobj |
load,decreases |
R8383 |
T12029 |
T12030 |
advmod |
more,broadly |
R8384 |
T12030 |
T12026 |
advmod |
broadly,decreases |
R8385 |
T12031 |
T12026 |
punct |
", ",decreases |
R8386 |
T12032 |
T12026 |
cc |
and,decreases |
R8387 |
T12033 |
T12034 |
mark |
although,appear |
R8388 |
T12034 |
T12038 |
advcl |
appear,reduce |
R8389 |
T12035 |
T12034 |
nsubj |
it,appear |
R8390 |
T12036 |
T12034 |
aux |
does,appear |
R8391 |
T12037 |
T12034 |
neg |
not,appear |
R8392 |
T12038 |
T12026 |
conj |
reduce,decreases |
R8393 |
T12039 |
T12040 |
aux |
to,act |
R8394 |
T12040 |
T12034 |
xcomp |
act,appear |
R8395 |
T12041 |
T12042 |
advmod |
as,quickly |
R8396 |
T12042 |
T12040 |
advmod |
quickly,act |
R8397 |
T12043 |
T12042 |
prep |
as,quickly |
R8398 |
T12044 |
T12045 |
amod |
local,injection |
R8399 |
T12045 |
T12043 |
pobj |
injection,as |
R8400 |
T12046 |
T12038 |
punct |
", ",reduce |
R8401 |
T12047 |
T12038 |
aux |
can,reduce |
R8402 |
T12048 |
T12038 |
advmod |
significantly,reduce |
R8403 |
T12086 |
T12084 |
pobj |
area,in |
R8404 |
T12049 |
T12050 |
compound |
amyloid,load |
R8405 |
T12087 |
T12086 |
prep |
of,area |
R8406 |
T12050 |
T12038 |
dobj |
load,reduce |
R8407 |
T12088 |
T12089 |
det |
the,site |
R8408 |
T12051 |
T12038 |
prep |
within,reduce |
R8409 |
T12052 |
T12053 |
nummod |
2,mo |
R8410 |
T12089 |
T12087 |
pobj |
site,of |
R8411 |
T12090 |
T12089 |
compound |
injection,site |
R8412 |
T12053 |
T12051 |
pobj |
mo,within |
R8413 |
T12091 |
T12092 |
punct |
[,54 |
R8414 |
T12092 |
T12073 |
parataxis |
54,reduce |
R8415 |
T12054 |
T12053 |
prep |
of,mo |
R8416 |
T12093 |
T12092 |
punct |
],54 |
R8417 |
T12094 |
T12066 |
punct |
.,shown |
R8418 |
T12055 |
T12056 |
amod |
initial,treatment |
R8419 |
T12096 |
T12097 |
amod |
Careful,study |
R8420 |
T12097 |
T12098 |
nsubj |
study,suggested |
R8421 |
T12056 |
T12054 |
pobj |
treatment,of |
R8422 |
T12099 |
T12097 |
prep |
of,study |
R8423 |
T12057 |
T12058 |
punct |
[,53 |
R8424 |
T12100 |
T12101 |
det |
the,mechanism |
R8425 |
T12101 |
T12099 |
pobj |
mechanism,of |
R8426 |
T12058 |
T12038 |
parataxis |
53,reduce |
R8427 |
T12102 |
T12101 |
prep |
behind,mechanism |
R8428 |
T12103 |
T12102 |
pobj |
several,behind |
R8429 |
T12104 |
T12103 |
prep |
of,several |
R8430 |
T12059 |
T12058 |
nummod |
52,53 |
R8431 |
T12105 |
T12106 |
det |
the,therapies |
R8432 |
T12106 |
T12104 |
pobj |
therapies,of |
R8433 |
T12107 |
T12108 |
npadvmod |
antibody,mediated |
R8434 |
T12108 |
T12106 |
amod |
mediated,therapies |
R8435 |
T12109 |
T12108 |
punct |
-,mediated |
R8436 |
T12060 |
T12058 |
punct |
",",53 |
R8437 |
T12110 |
T12098 |
aux |
has,suggested |
R8438 |
T12111 |
T12112 |
mark |
that,play |
R8439 |
T12112 |
T12098 |
ccomp |
play,suggested |
R8440 |
T12061 |
T12058 |
punct |
],53 |
R8441 |
T12113 |
T12114 |
amod |
activated,microglia |
R8442 |
T12114 |
T12112 |
nsubj |
microglia,play |
R8443 |
T12115 |
T12116 |
det |
an,role |
R8444 |
T12062 |
T12026 |
punct |
.,decreases |
R8445 |
T12116 |
T12112 |
dobj |
role,play |
R8446 |
T12117 |
T12116 |
amod |
important,role |
R8447 |
T12064 |
T12065 |
advmod |
More,recently |
R8448 |
T12118 |
T12112 |
prep |
in,play |
R8449 |
T12119 |
T12120 |
det |
the,removal |
R8450 |
T12120 |
T12118 |
pobj |
removal,in |
R8451 |
T12121 |
T12120 |
prep |
of,removal |
R8452 |
T12065 |
T12066 |
advmod |
recently,shown |
R8453 |
T12122 |
T12123 |
amod |
fibrillar,plaques |
R8454 |
T12123 |
T12121 |
pobj |
plaques,of |
R8455 |
T12124 |
T12112 |
prep |
after,play |
R8456 |
T12067 |
T12066 |
punct |
", ",shown |
R8457 |
T12125 |
T12124 |
pobj |
immunization,after |
R8458 |
T12126 |
T12127 |
punct |
[,55 |
R8459 |
T12127 |
T12098 |
parataxis |
55,suggested |
R8461 |
T12068 |
T12069 |
det |
an,approach |
R8462 |
T12129 |
T12127 |
punct |
",",55 |
R8463 |
T12130 |
T12127 |
nummod |
52,55 |
R8464 |
T12131 |
T12127 |
punct |
",",55 |
R8465 |
T12069 |
T12066 |
nsubj |
approach,shown |
R8466 |
T12132 |
T12127 |
punct |
],55 |
R8467 |
T12133 |
T12098 |
punct |
.,suggested |
R8468 |
T12070 |
T12069 |
amod |
alternative,approach |
R8469 |
T12135 |
T12136 |
advmod |
However,noted |
R8470 |
T12071 |
T12066 |
aux |
has,shown |
R8471 |
T12137 |
T12136 |
punct |
", ",noted |
R8472 |
T12138 |
T12136 |
nsubjpass |
it,noted |
R8473 |
T12139 |
T12136 |
aux |
has,noted |
R8474 |
T12072 |
T12073 |
mark |
that,reduce |
R8475 |
T12140 |
T12136 |
auxpass |
been,noted |
R8476 |
T12141 |
T12142 |
mark |
that,has |
R8477 |
T12073 |
T12066 |
ccomp |
reduce,shown |
R8478 |
T12142 |
T12136 |
ccomp |
has,noted |
R8479 |
T12143 |
T12142 |
nsubj |
deletion,has |
R8480 |
T12144 |
T12143 |
prep |
of,deletion |
R8481 |
T12074 |
T12075 |
amod |
lentiviral,transfer |
R8482 |
T12145 |
T12146 |
det |
the,receptor |
R8483 |
T12146 |
T12144 |
pobj |
receptor,of |
R8484 |
T12147 |
T12146 |
compound |
Fc,receptor |
R8485 |
T12148 |
T12146 |
punct |
(,receptor |
R8486 |
T12149 |
T12150 |
det |
the,receptor |
R8487 |
T12075 |
T12073 |
nsubj |
transfer,reduce |
R8488 |
T12150 |
T12146 |
appos |
receptor,receptor |
R8489 |
T12151 |
T12150 |
amod |
primary,receptor |
R8490 |
T12152 |
T12150 |
prep |
for,receptor |
R8491 |
T12076 |
T12075 |
prep |
of,transfer |
R8492 |
T12153 |
T12154 |
amod |
microglial,opsinization |
R8493 |
T12154 |
T12152 |
pobj |
opsinization,for |
R8494 |
T12155 |
T12154 |
prep |
of,opsinization |
R8495 |
T12077 |
T12076 |
pobj |
neprilysin,of |
R8496 |
T12156 |
T12157 |
compound |
antibody,antigen |
R8497 |
T12157 |
T12159 |
compound |
antigen,complexes |
R8498 |
T12158 |
T12157 |
punct |
–,antigen |
R8499 |
T12078 |
T12073 |
aux |
can,reduce |
R8500 |
T12159 |
T12155 |
pobj |
complexes,of |
R8501 |
T12160 |
T12143 |
punct |
),deletion |
R8502 |
T12079 |
T12073 |
advmod |
also,reduce |
R8503 |
T12161 |
T12143 |
prep |
in,deletion |
R8504 |
T12162 |
T12163 |
npadvmod |
APP,transgenic |
R8505 |
T12163 |
T12164 |
amod |
transgenic,models |
R8506 |
T12080 |
T12081 |
det |
the,number |
R8507 |
T12164 |
T12161 |
pobj |
models,in |
R8508 |
T12165 |
T12164 |
compound |
mouse,models |
R8509 |
T12166 |
T12167 |
det |
no,impact |
R8510 |
T12081 |
T12073 |
dobj |
number,reduce |
R8511 |
T12167 |
T12142 |
dobj |
impact,has |
R8512 |
T12168 |
T12167 |
prep |
on,impact |
R8513 |
T12082 |
T12081 |
prep |
of,number |
R8514 |
T12169 |
T12170 |
det |
the,effectiveness |
R8515 |
T12170 |
T12168 |
pobj |
effectiveness,on |
R8516 |
T12171 |
T12170 |
prep |
of,effectiveness |
R8517 |
T12083 |
T12082 |
pobj |
aggregates,of |
R8518 |
T12172 |
T12173 |
npadvmod |
antibody,mediated |
R8519 |
T12084 |
T12073 |
prep |
in,reduce |
R8520 |
T12085 |
T12086 |
det |
the,area |
R8521 |
T12173 |
T12175 |
amod |
mediated,therapy |
R8522 |
T12192 |
T12191 |
prep |
of,lack |
R8523 |
T12174 |
T12173 |
punct |
-,mediated |
R8524 |
T12175 |
T12171 |
pobj |
therapy,of |
R8525 |
T12176 |
T12177 |
punct |
[,57 |
R8526 |
T12177 |
T12142 |
parataxis |
57,has |
R8527 |
T12193 |
T12194 |
compound |
microglia,activation |
R8528 |
T12178 |
T12177 |
nummod |
56,57 |
R8529 |
T12179 |
T12177 |
punct |
",",57 |
R8530 |
T12180 |
T12177 |
punct |
],57 |
R8531 |
T12194 |
T12192 |
pobj |
activation,of |
R8532 |
T12181 |
T12136 |
punct |
.,noted |
R8533 |
T12195 |
T12196 |
det |
the,difference |
R8534 |
T12183 |
T12184 |
nsubj |
It,is |
R8535 |
T12196 |
T12190 |
attr |
difference,is |
R8536 |
T12185 |
T12184 |
punct |
", ",is |
R8537 |
T12186 |
T12184 |
advmod |
nevertheless,is |
R8538 |
T12187 |
T12184 |
punct |
", ",is |
R8539 |
T12188 |
T12184 |
acomp |
possible,is |
R8540 |
T12189 |
T12190 |
mark |
that,is |
R8541 |
T12190 |
T12184 |
ccomp |
is,is |
R8542 |
T12197 |
T12196 |
amod |
major,difference |
R8543 |
T12191 |
T12190 |
nsubj |
lack,is |
R8544 |
T12198 |
T12196 |
prep |
between,difference |
R8545 |
T12199 |
T12200 |
det |
the,clearance |
R8546 |
T12200 |
T12198 |
pobj |
clearance,between |
R8547 |
T12201 |
T12200 |
amod |
slow,clearance |
R8548 |
T12202 |
T12200 |
acl |
described,clearance |
R8549 |
T12203 |
T12202 |
advmod |
here,described |
R8550 |
T12298 |
T12297 |
punct |
],58 |
R8551 |
T12299 |
T12293 |
cc |
or,expression |
R8552 |
T12204 |
T12200 |
punct |
", ",clearance |
R8553 |
T12300 |
T12301 |
amod |
central,injection |
R8554 |
T12301 |
T12293 |
conj |
injection,expression |
R8555 |
T12302 |
T12301 |
prep |
of,injection |
R8556 |
T12205 |
T12206 |
advmod |
where,expected |
R8557 |
T12303 |
T12302 |
pobj |
lipopolysaccharide,of |
R8558 |
T12304 |
T12305 |
punct |
[,60 |
R8559 |
T12305 |
T12303 |
parataxis |
60,lipopolysaccharide |
R8560 |
T12206 |
T12200 |
relcl |
expected,clearance |
R8561 |
T12306 |
T12305 |
nummod |
59,60 |
R8562 |
T12307 |
T12305 |
punct |
",",60 |
R8563 |
T12207 |
T12208 |
det |
no,perturbation |
R8564 |
T12308 |
T12305 |
punct |
],60 |
R8565 |
T12309 |
T12282 |
aux |
can,reduce |
R8566 |
T12310 |
T12282 |
prep |
by,reduce |
R8567 |
T12208 |
T12206 |
nsubjpass |
perturbation,expected |
R8568 |
T12311 |
T12310 |
pobj |
itself,by |
R8569 |
T12312 |
T12282 |
advmod |
substantially,reduce |
R8570 |
T12209 |
T12208 |
prep |
of,perturbation |
R8571 |
T12313 |
T12314 |
compound |
plaque,burden |
R8572 |
T12314 |
T12282 |
dobj |
burden,reduce |
R8573 |
T12315 |
T12282 |
prep |
in,reduce |
R8574 |
T12210 |
T12211 |
det |
the,system |
R8575 |
T12316 |
T12317 |
npadvmod |
APP,transgenic |
R8576 |
T12317 |
T12318 |
amod |
transgenic,mice |
R8577 |
T12211 |
T12209 |
pobj |
system,of |
R8578 |
T12318 |
T12315 |
pobj |
mice,in |
R8579 |
T12319 |
T12282 |
punct |
.,reduce |
R8580 |
T12212 |
T12211 |
amod |
immune,system |
R8581 |
T12321 |
T12322 |
cc |
But,reaggregates |
R8582 |
T12213 |
T12206 |
auxpass |
is,expected |
R8583 |
T12323 |
T12322 |
prep |
in,reaggregates |
R8584 |
T12324 |
T12325 |
det |
the,case |
R8585 |
T12325 |
T12323 |
pobj |
case,in |
R8586 |
T12214 |
T12200 |
punct |
", ",clearance |
R8587 |
T12326 |
T12325 |
prep |
of,case |
R8588 |
T12327 |
T12328 |
amod |
acute,activation |
R8589 |
T12328 |
T12326 |
pobj |
activation,of |
R8590 |
T12329 |
T12330 |
npadvmod |
antibody,mediated |
R8591 |
T12330 |
T12328 |
amod |
mediated,activation |
R8592 |
T12215 |
T12200 |
cc |
and,clearance |
R8593 |
T12331 |
T12329 |
punct |
-,antibody |
R8594 |
T12332 |
T12329 |
cc |
and,antibody |
R8595 |
T12333 |
T12332 |
punct |
/,and |
R8596 |
T12216 |
T12217 |
det |
the,clearance |
R8597 |
T12334 |
T12332 |
cc |
or,and |
R8598 |
T12335 |
T12329 |
conj |
injury,antibody |
R8599 |
T12336 |
T12330 |
punct |
-,mediated |
R8600 |
T12217 |
T12200 |
conj |
clearance,clearance |
R8601 |
T12337 |
T12322 |
punct |
", ",reaggregates |
R8602 |
T12338 |
T12339 |
mark |
once,passed |
R8603 |
T12339 |
T12322 |
advcl |
passed,reaggregates |
R8604 |
T12218 |
T12217 |
amod |
rapid,clearance |
R8605 |
T12340 |
T12341 |
det |
the,inflammation |
R8606 |
T12341 |
T12339 |
nsubj |
inflammation,passed |
R8607 |
T12219 |
T12217 |
acl |
described,clearance |
R8608 |
T12342 |
T12339 |
aux |
has,passed |
R8609 |
T12220 |
T12219 |
prep |
in,described |
R8610 |
T12343 |
T12339 |
punct |
", ",passed |
R8611 |
T12221 |
T12220 |
pobj |
studies,in |
R8612 |
T12344 |
T12339 |
cc |
and,passed |
R8613 |
T12345 |
T12346 |
det |
the,antibody |
R8614 |
T12346 |
T12347 |
nsubjpass |
antibody,cleared |
R8615 |
T12222 |
T12221 |
acl |
involving,studies |
R8616 |
T12347 |
T12339 |
conj |
cleared,passed |
R8617 |
T12223 |
T12224 |
nmod |
antibody,injection |
R8618 |
T12348 |
T12346 |
cc |
and,antibody |
R8619 |
T12349 |
T12350 |
amod |
bound,peptide |
R8620 |
T12350 |
T12346 |
conj |
peptide,antibody |
R8621 |
T12224 |
T12222 |
dobj |
injection,involving |
R8622 |
T12351 |
T12347 |
aux |
have,cleared |
R8623 |
T12352 |
T12347 |
auxpass |
been,cleared |
R8624 |
T12353 |
T12347 |
cc |
and,cleared |
R8625 |
T12225 |
T12223 |
cc |
or,antibody |
R8626 |
T12354 |
T12347 |
conj |
degraded,cleared |
R8627 |
T12355 |
T12322 |
punct |
", ",reaggregates |
R8628 |
T12356 |
T12357 |
det |
the,Aβ |
R8629 |
T12226 |
T12223 |
conj |
viral,antibody |
R8630 |
T12357 |
T12322 |
nsubj |
Aβ,reaggregates |
R8631 |
T12358 |
T12357 |
amod |
remaining,Aβ |
R8632 |
T12227 |
T12184 |
punct |
.,is |
R8633 |
T12359 |
T12322 |
advmod |
quickly,reaggregates |
R8634 |
T12360 |
T12322 |
cc |
and,reaggregates |
R8635 |
T12361 |
T12362 |
compound |
amyloid,pathology |
R8636 |
T12229 |
T12230 |
prep |
In,be |
R8637 |
T12362 |
T12363 |
nsubjpass |
pathology,reestablished |
R8638 |
T12363 |
T12322 |
conj |
reestablished,reaggregates |
R8639 |
T12364 |
T12363 |
auxpass |
is,reestablished |
R8640 |
T12365 |
T12366 |
punct |
[,49 |
R8641 |
T12366 |
T12363 |
parataxis |
49,reestablished |
R8642 |
T12367 |
T12366 |
punct |
],49 |
R8643 |
T12368 |
T12322 |
punct |
.,reaggregates |
R8644 |
T12231 |
T12229 |
pobj |
isolation,In |
R8645 |
T12370 |
T12371 |
det |
This,finding |
R8646 |
T12371 |
T12372 |
nsubj |
finding,reinforces |
R8647 |
T12232 |
T12230 |
punct |
", ",be |
R8648 |
T12373 |
T12374 |
det |
the,notion |
R8649 |
T12374 |
T12372 |
dobj |
notion,reinforces |
R8650 |
T12375 |
T12376 |
mark |
that,maintain |
R8651 |
T12233 |
T12234 |
amod |
mild,activation |
R8652 |
T12376 |
T12374 |
acl |
maintain,notion |
R8653 |
T12377 |
T12376 |
prep |
without,maintain |
R8654 |
T12234 |
T12230 |
nsubj |
activation,be |
R8655 |
T12378 |
T12379 |
amod |
continued,stimulation |
R8656 |
T12379 |
T12377 |
pobj |
stimulation,without |
R8657 |
T12380 |
T12376 |
punct |
", ",maintain |
R8658 |
T12235 |
T12234 |
prep |
of,activation |
R8659 |
T12381 |
T12376 |
nsubj |
microglia,maintain |
R8660 |
T12382 |
T12381 |
prep |
in,microglia |
R8661 |
T12236 |
T12235 |
pobj |
microglia,of |
R8662 |
T12383 |
T12384 |
compound |
mouse,models |
R8663 |
T12384 |
T12382 |
pobj |
models,in |
R8664 |
T12385 |
T12376 |
aux |
do,maintain |
R8665 |
T12237 |
T12234 |
prep |
by,activation |
R8666 |
T12386 |
T12376 |
neg |
not,maintain |
R8667 |
T12387 |
T12388 |
det |
the,level |
R8668 |
T12388 |
T12376 |
dobj |
level,maintain |
R8669 |
T12238 |
T12239 |
compound |
injection,damage |
R8670 |
T12389 |
T12388 |
amod |
same,level |
R8671 |
T12390 |
T12388 |
prep |
of,level |
R8672 |
T12239 |
T12237 |
pobj |
damage,by |
R8673 |
T12391 |
T12392 |
amod |
sustained,activation |
R8674 |
T12392 |
T12390 |
pobj |
activation,of |
R8675 |
T12393 |
T12394 |
dep |
that,occur |
R8676 |
T12240 |
T12239 |
cc |
or,damage |
R8677 |
T12394 |
T12388 |
relcl |
occur,level |
R8678 |
T12395 |
T12394 |
aux |
may,occur |
R8679 |
T12241 |
T12239 |
conj |
opsinization,damage |
R8680 |
T12396 |
T12394 |
prep |
in,occur |
R8681 |
T12397 |
T12396 |
pobj |
humans,in |
R8682 |
T12398 |
T12372 |
punct |
.,reinforces |
R8683 |
T12242 |
T12230 |
aux |
may,be |
R8684 |
T12400 |
T12401 |
nsubj |
SantaCruz,published |
R8685 |
T12243 |
T12230 |
neg |
not,be |
R8686 |
T12402 |
T12403 |
advmod |
et,al. |
R8687 |
T12403 |
T12400 |
advmod |
al.,SantaCruz |
R8688 |
T12244 |
T12230 |
acomp |
adequate,be |
R8689 |
T12245 |
T12246 |
aux |
to,induce |
R8690 |
T12246 |
T12230 |
advcl |
induce,be |
R8691 |
T12404 |
T12401 |
advmod |
recently,published |
R8692 |
T12247 |
T12248 |
amod |
substantial,phagocytosis |
R8693 |
T12405 |
T12406 |
det |
a,study |
R8694 |
T12406 |
T12401 |
dobj |
study,published |
R8695 |
T12407 |
T12406 |
prep |
of,study |
R8696 |
T12408 |
T12407 |
pobj |
mice,of |
R8697 |
T12409 |
T12410 |
dep |
that,express |
R8698 |
T12410 |
T12408 |
relcl |
express,mice |
R8699 |
T12248 |
T12246 |
dobj |
phagocytosis,induce |
R8700 |
T12411 |
T12412 |
nmod |
P301L,tau |
R8701 |
T12412 |
T12410 |
dobj |
tau,express |
R8702 |
T12249 |
T12230 |
punct |
", ",be |
R8703 |
T12413 |
T12412 |
amod |
human,tau |
R8704 |
T12414 |
T12410 |
prep |
via,express |
R8705 |
T12415 |
T12416 |
det |
a,system |
R8706 |
T12250 |
T12230 |
cc |
but,be |
R8707 |
T12416 |
T12414 |
pobj |
system,via |
R8708 |
T12417 |
T12416 |
amod |
similar,system |
R8709 |
T12251 |
T12252 |
advmod |
when,combined |
R8710 |
T12418 |
T12416 |
compound |
vector,system |
R8711 |
T12419 |
T12420 |
punct |
[,61 |
R8712 |
T12420 |
T12401 |
parataxis |
61,published |
R8713 |
T12252 |
T12253 |
advcl |
combined,work |
R8714 |
T12421 |
T12420 |
punct |
],61 |
R8715 |
T12422 |
T12401 |
punct |
.,published |
R8716 |
T12253 |
T12230 |
conj |
work,be |
R8717 |
T12424 |
T12425 |
prep |
As,found |
R8718 |
T12254 |
T12252 |
prep |
with,combined |
R8719 |
T12426 |
T12424 |
prep |
in,As |
R8720 |
T12427 |
T12428 |
poss |
our,mice |
R8721 |
T12255 |
T12256 |
det |
an,agent |
R8722 |
T12256 |
T12254 |
pobj |
agent,with |
R8723 |
T12428 |
T12426 |
pobj |
mice,in |
R8724 |
T12429 |
T12430 |
compound |
tet,off |
R8725 |
T12257 |
T12258 |
npadvmod |
Aβ,lowering |
R8726 |
T12430 |
T12428 |
compound |
off,mice |
R8727 |
T12431 |
T12430 |
punct |
-,off |
R8728 |
T12258 |
T12256 |
amod |
lowering,agent |
R8729 |
T12432 |
T12428 |
compound |
APP,mice |
R8730 |
T12433 |
T12425 |
punct |
", ",found |
R8731 |
T12434 |
T12425 |
nsubj |
SantaCruz,found |
R8732 |
T12259 |
T12258 |
punct |
-,lowering |
R8733 |
T12435 |
T12436 |
advmod |
et,al. |
R8734 |
T12436 |
T12434 |
advmod |
al.,SantaCruz |
R8735 |
T12437 |
T12438 |
mark |
that,cleared |
R8736 |
T12260 |
T12256 |
punct |
", ",agent |
R8737 |
T12438 |
T12425 |
ccomp |
cleared,found |
R8738 |
T12439 |
T12440 |
nmod |
tau,tangles |
R8739 |
T12261 |
T12262 |
amod |
such,as |
R8740 |
T12440 |
T12438 |
nsubjpass |
tangles,cleared |
R8741 |
T12441 |
T12440 |
amod |
neurofibrillary,tangles |
R8742 |
T12262 |
T12256 |
prep |
as,agent |
R8743 |
T12442 |
T12440 |
punct |
", ",tangles |
R8744 |
T12443 |
T12440 |
prep |
like,tangles |
R8745 |
T12444 |
T12445 |
compound |
amyloid,plaques |
R8746 |
T12445 |
T12443 |
pobj |
plaques,like |
R8747 |
T12446 |
T12438 |
punct |
", ",cleared |
R8748 |
T12263 |
T12264 |
npadvmod |
neprilysin,targeted |
R8749 |
T12447 |
T12438 |
auxpass |
are,cleared |
R8750 |
T12448 |
T12438 |
neg |
not,cleared |
R8751 |
T12449 |
T12438 |
advmod |
efficiently,cleared |
R8752 |
T12450 |
T12438 |
prep |
following,cleared |
R8753 |
T12264 |
T12268 |
amod |
targeted,antibodies |
R8754 |
T12451 |
T12452 |
compound |
transgene,suppression |
R8755 |
T12452 |
T12450 |
pobj |
suppression,following |
R8756 |
T12453 |
T12425 |
punct |
.,found |
R8757 |
T12265 |
T12263 |
cc |
or,neprilysin |
R8758 |
T12455 |
T12456 |
det |
The,lack |
R8759 |
T12456 |
T12457 |
nsubj |
lack,comes |
R8760 |
T12266 |
T12263 |
conj |
Aβ,neprilysin |
R8761 |
T12458 |
T12456 |
prep |
of,lack |
R8762 |
T12267 |
T12264 |
punct |
-,targeted |
R8763 |
T12459 |
T12458 |
pobj |
clearance,of |
R8764 |
T12460 |
T12456 |
prep |
in,lack |
R8765 |
T12461 |
T12462 |
det |
both,models |
R8766 |
T12268 |
T12262 |
pobj |
antibodies,as |
R8767 |
T12462 |
T12460 |
pobj |
models,in |
R8768 |
T12463 |
T12462 |
prep |
of,models |
R8769 |
T12269 |
T12253 |
punct |
", ",work |
R8770 |
T12464 |
T12465 |
compound |
AD,pathology |
R8771 |
T12465 |
T12463 |
pobj |
pathology,of |
R8772 |
T12466 |
T12457 |
prep |
as,comes |
R8773 |
T12270 |
T12271 |
det |
the,two |
R8774 |
T12467 |
T12468 |
det |
a,contrast |
R8775 |
T12468 |
T12466 |
pobj |
contrast,as |
R8776 |
T12271 |
T12253 |
nsubj |
two,work |
R8777 |
T12469 |
T12468 |
amod |
stark,contrast |
R8778 |
T12470 |
T12468 |
prep |
to,contrast |
R8779 |
T12471 |
T12472 |
det |
the,removal |
R8780 |
T12272 |
T12253 |
aux |
may,work |
R8781 |
T12472 |
T12470 |
pobj |
removal,to |
R8782 |
T12473 |
T12472 |
amod |
rapid,removal |
R8783 |
T12273 |
T12253 |
prep |
in,work |
R8784 |
T12474 |
T12472 |
prep |
of,removal |
R8785 |
T12475 |
T12476 |
compound |
protein,aggregates |
R8786 |
T12476 |
T12474 |
pobj |
aggregates,of |
R8787 |
T12274 |
T12273 |
pobj |
concert,in |
R8788 |
T12477 |
T12472 |
acl |
found,removal |
R8789 |
T12478 |
T12477 |
prep |
in,found |
R8790 |
T12479 |
T12480 |
amod |
similar,models |
R8791 |
T12275 |
T12276 |
aux |
to,clear |
R8792 |
T12480 |
T12478 |
pobj |
models,in |
R8793 |
T12481 |
T12482 |
compound |
tet,off |
R8794 |
T12276 |
T12253 |
advcl |
clear,work |
R8795 |
T12482 |
T12480 |
compound |
off,models |
R8797 |
T12484 |
T12480 |
compound |
mouse,models |
R8798 |
T12485 |
T12480 |
prep |
of,models |
R8799 |
T12486 |
T12487 |
nmod |
Huntington,disease |
R8800 |
T12487 |
T12485 |
pobj |
disease,of |
R8801 |
T12277 |
T12278 |
compound |
peptide,deposits |
R8805 |
T12278 |
T12276 |
dobj |
deposits,clear |
R8806 |
T12491 |
T12486 |
cc |
and,Huntington |
R8807 |
T12492 |
T12486 |
conj |
prion,Huntington |
R8809 |
T12279 |
T12253 |
punct |
.,work |
R8810 |
T12494 |
T12487 |
parataxis |
62,disease |
R8811 |
T12495 |
T12494 |
punct |
],62 |
R8812 |
T12281 |
T12282 |
advcl |
Consistent,reduce |
R8813 |
T12496 |
T12457 |
punct |
.,comes |
R8814 |
T12498 |
T12499 |
prep |
In,led |
R8815 |
T12283 |
T12281 |
prep |
with,Consistent |
R8816 |
T12500 |
T12501 |
det |
these,cases |
R8817 |
T12501 |
T12498 |
pobj |
cases,In |
R8818 |
T12502 |
T12499 |
punct |
", ",led |
R8819 |
T12503 |
T12499 |
csubj |
disrupting,led |
R8820 |
T12284 |
T12285 |
det |
this,hypothesis |
R8821 |
T12504 |
T12505 |
det |
the,input |
R8822 |
T12505 |
T12503 |
dobj |
input,disrupting |
R8823 |
T12506 |
T12505 |
prep |
of,input |
R8824 |
T12285 |
T12283 |
pobj |
hypothesis,with |
R8825 |
T12507 |
T12508 |
amod |
new,monomer |
R8826 |
T12508 |
T12506 |
pobj |
monomer,of |
R8827 |
T12509 |
T12505 |
prep |
to,input |
R8828 |
T12286 |
T12282 |
punct |
", ",reduce |
R8829 |
T12287 |
T12288 |
amod |
strong,activation |
R8830 |
T12288 |
T12282 |
nsubj |
activation,reduce |
R8831 |
T12289 |
T12288 |
prep |
of,activation |
R8832 |
T12510 |
T12511 |
det |
the,system |
R8833 |
T12290 |
T12289 |
pobj |
microglia,of |
R8834 |
T12511 |
T12509 |
pobj |
system,to |
R8835 |
T12512 |
T12503 |
prep |
via,disrupting |
R8836 |
T12513 |
T12514 |
npadvmod |
dox,mediated |
R8837 |
T12291 |
T12288 |
prep |
through,activation |
R8838 |
T12292 |
T12293 |
amod |
transgenic,expression |
R8839 |
T12514 |
T12516 |
amod |
mediated,suppression |
R8840 |
T12293 |
T12291 |
pobj |
expression,through |
R8841 |
T12515 |
T12514 |
punct |
-,mediated |
R8842 |
T12516 |
T12512 |
pobj |
suppression,via |
R8843 |
T12517 |
T12516 |
compound |
transgene,suppression |
R8844 |
T12294 |
T12293 |
prep |
of,expression |
R8845 |
T12518 |
T12499 |
prep |
to,led |
R8846 |
T12519 |
T12520 |
advmod |
relatively,rapid |
R8847 |
T12295 |
T12294 |
pobj |
TGFβ,of |
R8848 |
T12520 |
T12521 |
amod |
rapid,clearance |
R8849 |
T12521 |
T12518 |
pobj |
clearance,to |
R8850 |
T12522 |
T12521 |
prep |
of,clearance |
R8851 |
T12523 |
T12524 |
compound |
protein,aggregates |
R8852 |
T12296 |
T12297 |
punct |
[,58 |
R8853 |
T12524 |
T12522 |
pobj |
aggregates,of |
R8854 |
T12525 |
T12499 |
punct |
.,led |
R8855 |
T12297 |
T12295 |
parataxis |
58,TGFβ |
R8856 |
T12527 |
T12528 |
prep |
By,suggest |
R8857 |
T12529 |
T12527 |
pobj |
contrast,By |
R8858 |
T12616 |
T12615 |
punct |
-,off |
R8859 |
T12530 |
T12528 |
punct |
", ",suggest |
R8860 |
T12531 |
T12532 |
poss |
our,study |
R8861 |
T12532 |
T12528 |
nsubj |
study,suggest |
R8862 |
T12617 |
T12613 |
compound |
tau,mice |
R8863 |
T12533 |
T12532 |
cc |
and,study |
R8864 |
T12534 |
T12532 |
conj |
that,study |
R8865 |
T12535 |
T12534 |
prep |
of,that |
R8866 |
T12618 |
T12619 |
mark |
that,required |
R8867 |
T12536 |
T12535 |
pobj |
SantaCruz,of |
R8868 |
T12537 |
T12538 |
advmod |
et,al. |
R8869 |
T12538 |
T12536 |
advmod |
al.,SantaCruz |
R8870 |
T12619 |
T12610 |
ccomp |
required,suggest |
R8871 |
T12539 |
T12540 |
mark |
that,be |
R8872 |
T12540 |
T12528 |
ccomp |
be,suggest |
R8873 |
T12541 |
T12542 |
compound |
protein,aggregates |
R8874 |
T12620 |
T12621 |
compound |
protein,clearance |
R8875 |
T12542 |
T12540 |
nsubj |
aggregates,be |
R8876 |
T12543 |
T12542 |
prep |
in,aggregates |
R8877 |
T12621 |
T12619 |
nsubjpass |
clearance,required |
R8878 |
T12544 |
T12543 |
pobj |
AD,in |
R8879 |
T12545 |
T12540 |
aux |
may,be |
R8880 |
T12546 |
T12547 |
advmod |
more,tenacious |
R8881 |
T12622 |
T12619 |
aux |
may,required |
R8882 |
T12547 |
T12540 |
acomp |
tenacious,be |
R8883 |
T12548 |
T12547 |
prep |
than,tenacious |
R8884 |
T12549 |
T12548 |
prep |
in,than |
R8885 |
T12623 |
T12619 |
prep |
in,required |
R8886 |
T12550 |
T12551 |
amod |
other,disorders |
R8887 |
T12551 |
T12549 |
pobj |
disorders,in |
R8888 |
T12624 |
T12623 |
pobj |
fact,in |
R8889 |
T12552 |
T12551 |
amod |
neurodegenerative,disorders |
R8890 |
T12553 |
T12528 |
punct |
.,suggest |
R8891 |
T12625 |
T12619 |
neg |
not,required |
R8892 |
T12555 |
T12556 |
advmod |
Perhaps,are |
R8893 |
T12626 |
T12619 |
auxpass |
be,required |
R8894 |
T12557 |
T12558 |
mark |
once,aggregated |
R8895 |
T12558 |
T12556 |
advcl |
aggregated,are |
R8896 |
T12627 |
T12619 |
prep |
for,required |
R8897 |
T12559 |
T12556 |
punct |
", ",are |
R8898 |
T12560 |
T12556 |
nsubj |
Aβ,are |
R8899 |
T12561 |
T12560 |
cc |
and,Aβ |
R8900 |
T12628 |
T12629 |
amod |
cognitive,improvement |
R8901 |
T12562 |
T12560 |
conj |
tau,Aβ |
R8902 |
T12563 |
T12564 |
advmod |
either,stable |
R8903 |
T12564 |
T12556 |
acomp |
stable,are |
R8904 |
T12565 |
T12564 |
advmod |
inherently,stable |
R8905 |
T12566 |
T12564 |
advmod |
more,stable |
R8906 |
T12629 |
T12627 |
pobj |
improvement,for |
R8907 |
T12567 |
T12564 |
prep |
than,stable |
R8908 |
T12568 |
T12569 |
amod |
other,aggregates |
R8909 |
T12569 |
T12567 |
pobj |
aggregates,than |
R8910 |
T12630 |
T12619 |
prep |
following,required |
R8911 |
T12570 |
T12569 |
compound |
protein,aggregates |
R8912 |
T12571 |
T12564 |
cc |
or,stable |
R8913 |
T12572 |
T12573 |
advmod |
more,resistant |
R8914 |
T12631 |
T12632 |
compound |
transgene,suppression |
R8915 |
T12573 |
T12564 |
conj |
resistant,stable |
R8916 |
T12574 |
T12573 |
prep |
to,resistant |
R8917 |
T12575 |
T12576 |
advmod |
intra,extracellular |
R8918 |
T12632 |
T12630 |
pobj |
suppression,following |
R8919 |
T12576 |
T12579 |
amod |
extracellular,mechanisms |
R8920 |
T12577 |
T12576 |
punct |
-,extracellular |
R8921 |
T12633 |
T12634 |
punct |
[,61 |
R8922 |
T12578 |
T12576 |
cc |
and,extracellular |
R8923 |
T12579 |
T12574 |
pobj |
mechanisms,to |
R8924 |
T12580 |
T12579 |
compound |
clearance,mechanisms |
R8925 |
T12634 |
T12619 |
parataxis |
61,required |
R8926 |
T12581 |
T12556 |
punct |
.,are |
R8927 |
T12635 |
T12634 |
punct |
],61 |
R8928 |
T12583 |
T12584 |
nummod |
One,question |
R8929 |
T12584 |
T12585 |
nsubj |
question,is |
R8930 |
T12636 |
T12610 |
punct |
.,suggest |
R8931 |
T12586 |
T12587 |
nsubj |
we,were |
R8932 |
T12587 |
T12584 |
advcl |
were,question |
R8933 |
T12638 |
T12639 |
prep |
At,is |
R8934 |
T12588 |
T12587 |
neg |
not,were |
R8935 |
T12589 |
T12587 |
acomp |
able,were |
R8936 |
T12590 |
T12591 |
aux |
to,address |
R8937 |
T12591 |
T12589 |
xcomp |
address,able |
R8938 |
T12640 |
T12638 |
amod |
present,At |
R8939 |
T12592 |
T12591 |
prep |
in,address |
R8940 |
T12593 |
T12594 |
det |
this,study |
R8941 |
T12594 |
T12592 |
pobj |
study,in |
R8942 |
T12595 |
T12596 |
mark |
whether,halts |
R8943 |
T12641 |
T12639 |
punct |
", ",is |
R8944 |
T12596 |
T12585 |
ccomp |
halts,is |
R8945 |
T12597 |
T12596 |
csubj |
abrogating,halts |
R8946 |
T12642 |
T12639 |
prep |
because,is |
R8947 |
T12598 |
T12597 |
dobj |
synthesis,abrogating |
R8948 |
T12599 |
T12598 |
prep |
of,synthesis |
R8949 |
T12643 |
T12642 |
pcomp |
of,because |
R8950 |
T12600 |
T12601 |
amod |
new,Aβ |
R8951 |
T12601 |
T12599 |
pobj |
Aβ,of |
R8952 |
T12644 |
T12645 |
amod |
unexpected,abnormalities |
R8953 |
T12602 |
T12603 |
det |
the,progression |
R8954 |
T12603 |
T12596 |
dobj |
progression,halts |
R8955 |
T12604 |
T12603 |
prep |
of,progression |
R8956 |
T12645 |
T12642 |
pobj |
abnormalities,because |
R8957 |
T12605 |
T12606 |
amod |
cognitive,decline |
R8958 |
T12606 |
T12604 |
pobj |
decline,of |
R8959 |
T12607 |
T12585 |
punct |
.,is |
R8960 |
T12646 |
T12645 |
amod |
noncognitive,abnormalities |
R8961 |
T12609 |
T12610 |
nsubj |
Studies,suggest |
R8962 |
T12647 |
T12645 |
amod |
behavioral,abnormalities |
R8963 |
T12611 |
T12609 |
prep |
from,Studies |
R8964 |
T12612 |
T12613 |
det |
the,mice |
R8965 |
T12648 |
T12639 |
punct |
", ",is |
R8966 |
T12613 |
T12611 |
pobj |
mice,from |
R8967 |
T12614 |
T12615 |
compound |
tet,off |
R8968 |
T12649 |
T12639 |
nsubj |
it,is |
R8969 |
T12615 |
T12613 |
compound |
off,mice |
R8970 |
T12650 |
T12639 |
neg |
not,is |
R8971 |
T12651 |
T12639 |
acomp |
clear,is |
R8972 |
T12652 |
T12653 |
mark |
whether,used |
R8973 |
T12653 |
T12639 |
ccomp |
used,is |
R8974 |
T12722 |
T12723 |
advmod |
when,tested |
R8975 |
T12654 |
T12655 |
det |
the,mice |
R8976 |
T12723 |
T12705 |
advcl |
tested,showed |
R8977 |
T12724 |
T12723 |
prep |
in,tested |
R8978 |
T12655 |
T12653 |
nsubjpass |
mice,used |
R8979 |
T12725 |
T12726 |
det |
the,maze |
R8980 |
T12726 |
T12724 |
pobj |
maze,in |
R8981 |
T12656 |
T12657 |
compound |
tet,off |
R8982 |
T12727 |
T12726 |
compound |
Morris,maze |
R8983 |
T12728 |
T12726 |
compound |
water,maze |
R8984 |
T12729 |
T12705 |
punct |
.,showed |
R8985 |
T12657 |
T12655 |
compound |
off,mice |
R8986 |
T12731 |
T12732 |
nsubj |
Expression,makes |
R8987 |
T12658 |
T12657 |
punct |
-,off |
R8988 |
T12733 |
T12731 |
prep |
of,Expression |
R8989 |
T12734 |
T12735 |
det |
this,phenotype |
R8990 |
T12659 |
T12655 |
compound |
APP,mice |
R8991 |
T12735 |
T12733 |
pobj |
phenotype,of |
R8992 |
T12736 |
T12737 |
amod |
standard,tests |
R8993 |
T12737 |
T12738 |
nsubj |
tests,uninterpretable |
R8994 |
T12660 |
T12653 |
aux |
can,used |
R8995 |
T12738 |
T12732 |
ccomp |
uninterpretable,makes |
R8996 |
T12739 |
T12737 |
prep |
of,tests |
R8997 |
T12740 |
T12739 |
pobj |
learning,of |
R8998 |
T12661 |
T12653 |
auxpass |
be,used |
R8999 |
T12741 |
T12740 |
cc |
and,learning |
R9000 |
T12742 |
T12740 |
conj |
memory,learning |
R9001 |
T12662 |
T12663 |
aux |
to,address |
R9002 |
T12743 |
T12732 |
punct |
.,makes |
R9003 |
T12745 |
T12746 |
nsubj |
Hyperactivity,inhibits |
R9004 |
T12663 |
T12653 |
advcl |
address,used |
R9005 |
T12747 |
T12746 |
advmod |
nonspecifically,inhibits |
R9006 |
T12748 |
T12749 |
npadvmod |
choice,driven |
R9007 |
T12749 |
T12751 |
amod |
driven,changes |
R9008 |
T12664 |
T12665 |
det |
the,question |
R9009 |
T12750 |
T12749 |
punct |
-,driven |
R9010 |
T12751 |
T12746 |
dobj |
changes,inhibits |
R9011 |
T12665 |
T12663 |
dobj |
question,address |
R9012 |
T12752 |
T12751 |
prep |
in,changes |
R9013 |
T12753 |
T12752 |
pobj |
movement,in |
R9014 |
T12666 |
T12665 |
amod |
same,question |
R9015 |
T12754 |
T12751 |
punct |
", ",changes |
R9016 |
T12755 |
T12756 |
det |
the,element |
R9017 |
T12756 |
T12751 |
appos |
element,changes |
R9018 |
T12667 |
T12663 |
prep |
in,address |
R9019 |
T12757 |
T12756 |
amod |
key,element |
R9020 |
T12758 |
T12756 |
prep |
behind,element |
R9021 |
T12759 |
T12760 |
det |
all,paradigms |
R9022 |
T12668 |
T12669 |
det |
the,context |
R9023 |
T12760 |
T12758 |
pobj |
paradigms,behind |
R9024 |
T12761 |
T12760 |
amod |
cognitive,paradigms |
R9025 |
T12669 |
T12667 |
pobj |
context,in |
R9026 |
T12762 |
T12760 |
amod |
behavioral,paradigms |
R9027 |
T12763 |
T12746 |
punct |
.,inhibits |
R9028 |
T12670 |
T12669 |
prep |
of,context |
R9029 |
T12765 |
T12766 |
nsubj |
We,working |
R9030 |
T12671 |
T12672 |
compound |
amyloid,pathology |
R9031 |
T12767 |
T12766 |
aux |
are,working |
R9032 |
T12768 |
T12766 |
advmod |
currently,working |
R9033 |
T12769 |
T12770 |
aux |
to,determine |
R9034 |
T12672 |
T12670 |
pobj |
pathology,of |
R9035 |
T12770 |
T12766 |
xcomp |
determine,working |
R9036 |
T12771 |
T12772 |
mark |
whether,correlates |
R9037 |
T12772 |
T12770 |
ccomp |
correlates,determine |
R9038 |
T12673 |
T12639 |
punct |
.,is |
R9039 |
T12773 |
T12772 |
nsubj |
hyperactivity,correlates |
R9040 |
T12774 |
T12772 |
prep |
with,correlates |
R9041 |
T12675 |
T12676 |
det |
Both,lines |
R9042 |
T12775 |
T12774 |
pobj |
expression,with |
R9043 |
T12776 |
T12775 |
prep |
of,expression |
R9044 |
T12777 |
T12778 |
det |
the,holoprotein |
R9045 |
T12676 |
T12677 |
nsubj |
lines,display |
R9046 |
T12678 |
T12676 |
prep |
of,lines |
R9047 |
T12778 |
T12776 |
pobj |
holoprotein,of |
R9048 |
T12779 |
T12780 |
compound |
APPswe,ind |
R9049 |
T12780 |
T12778 |
compound |
ind,holoprotein |
R9050 |
T12781 |
T12780 |
punct |
/,ind |
R9051 |
T12679 |
T12680 |
compound |
tTA,APP |
R9052 |
T12782 |
T12775 |
cc |
or,expression |
R9053 |
T12783 |
T12784 |
poss |
its,derivatives |
R9054 |
T12784 |
T12775 |
conj |
derivatives,expression |
R9055 |
T12680 |
T12682 |
compound |
APP,mice |
R9056 |
T12785 |
T12784 |
amod |
proteolytic,derivatives |
R9057 |
T12786 |
T12766 |
punct |
.,working |
R9058 |
T12788 |
T12789 |
amod |
Preliminary,studies |
R9059 |
T12681 |
T12680 |
punct |
/,APP |
R9060 |
T12789 |
T12790 |
nsubj |
studies,suggest |
R9061 |
T12791 |
T12792 |
mark |
that,appear |
R9062 |
T12682 |
T12678 |
pobj |
mice,of |
R9063 |
T12792 |
T12790 |
ccomp |
appear,suggest |
R9064 |
T12793 |
T12792 |
nsubj |
hyperactivity,appear |
R9065 |
T12683 |
T12684 |
nsubj |
we,studied |
R9066 |
T12794 |
T12792 |
aux |
does,appear |
R9067 |
T12795 |
T12792 |
neg |
not,appear |
R9068 |
T12684 |
T12676 |
advcl |
studied,lines |
R9069 |
T12796 |
T12792 |
advmod |
quickly,appear |
R9070 |
T12797 |
T12798 |
advmod |
when,shifted |
R9071 |
T12798 |
T12792 |
advcl |
shifted,appear |
R9072 |
T12685 |
T12684 |
advmod |
here,studied |
R9073 |
T12799 |
T12800 |
npadvmod |
dox,reared |
R9074 |
T12800 |
T12802 |
amod |
reared,mice |
R9075 |
T12801 |
T12800 |
punct |
-,reared |
R9076 |
T12686 |
T12687 |
amod |
extreme,hyperactivity |
R9077 |
T12802 |
T12798 |
nsubjpass |
mice,shifted |
R9078 |
T12803 |
T12798 |
auxpass |
are,shifted |
R9079 |
T12687 |
T12677 |
dobj |
hyperactivity,display |
R9080 |
T12804 |
T12798 |
prep |
to,shifted |
R9081 |
T12805 |
T12806 |
amod |
nonmedicated,diets |
R9082 |
T12806 |
T12804 |
pobj |
diets,to |
R9083 |
T12688 |
T12687 |
amod |
visible,hyperactivity |
R9084 |
T12807 |
T12808 |
punct |
(,data |
R9085 |
T12808 |
T12798 |
parataxis |
data,shifted |
R9086 |
T12809 |
T12810 |
compound |
J.,J. |
R9087 |
T12689 |
T12688 |
prep |
as,visible |
R9088 |
T12810 |
T12808 |
dep |
J.,data |
R9089 |
T12811 |
T12810 |
compound |
L.,J. |
R9090 |
T12812 |
T12808 |
punct |
", ",data |
R9091 |
T12690 |
T12691 |
compound |
cage,circling |
R9092 |
T12813 |
T12808 |
amod |
unpublished,data |
R9093 |
T12814 |
T12808 |
punct |
),data |
R9094 |
T12815 |
T12790 |
punct |
.,suggest |
R9095 |
T12691 |
T12689 |
pobj |
circling,as |
R9096 |
T12817 |
T12818 |
det |
These,data |
R9097 |
T12692 |
T12688 |
cc |
and,visible |
R9098 |
T12818 |
T12819 |
nsubj |
data,indicate |
R9099 |
T12820 |
T12819 |
aux |
may,indicate |
R9100 |
T12693 |
T12688 |
conj |
quantified,visible |
R9101 |
T12821 |
T12822 |
mark |
that,is |
R9102 |
T12822 |
T12819 |
ccomp |
is,indicate |
R9103 |
T12694 |
T12693 |
agent |
by,quantified |
R9104 |
T12823 |
T12824 |
det |
the,culprit |
R9105 |
T12824 |
T12822 |
nsubj |
culprit,is |
R9106 |
T12825 |
T12824 |
amod |
neuroactive,culprit |
R9107 |
T12695 |
T12696 |
compound |
activity,monitoring |
R9108 |
T12826 |
T12827 |
neg |
not,immediately |
R9109 |
T12827 |
T12822 |
advmod |
immediately,is |
R9110 |
T12696 |
T12694 |
pobj |
monitoring,by |
R9111 |
T12697 |
T12698 |
punct |
(,see |
R9112 |
T12828 |
T12822 |
acomp |
present,is |
R9113 |
T12698 |
T12677 |
parataxis |
see,display |
R9114 |
T12829 |
T12830 |
mark |
after,initiated |
R9115 |
T12830 |
T12822 |
advcl |
initiated,is |
R9116 |
T12831 |
T12832 |
amod |
transgenic,synthesis |
R9117 |
T12699 |
T12698 |
dobj |
Figure,see |
R9118 |
T12832 |
T12830 |
nsubjpass |
synthesis,initiated |
R9119 |
T12700 |
T12699 |
nummod |
7,Figure |
R9121 |
T12834 |
T12830 |
auxpass |
is,initiated |
R9122 |
T12835 |
T12822 |
punct |
", ",is |
R9123 |
T12701 |
T12698 |
punct |
),see |
R9124 |
T12836 |
T12822 |
cc |
but,is |
R9125 |
T12837 |
T12822 |
conj |
requires,is |
R9126 |
T12702 |
T12677 |
punct |
.,display |
R9129 |
T12704 |
T12705 |
nsubj |
Many,showed |
R9130 |
T12840 |
T12841 |
aux |
to,develop |
R9131 |
T12841 |
T12839 |
advcl |
develop,time |
R9132 |
T12842 |
T12819 |
punct |
.,indicate |
R9133 |
T12706 |
T12704 |
prep |
of,Many |
R9134 |
T12844 |
T12845 |
advmod |
Alternatively,caused |
R9135 |
T12707 |
T12708 |
det |
the,mice |
R9136 |
T12846 |
T12845 |
punct |
", ",caused |
R9137 |
T12847 |
T12845 |
nsubjpass |
hyperactivity,caused |
R9138 |
T12708 |
T12706 |
pobj |
mice,of |
R9139 |
T12848 |
T12845 |
aux |
may,caused |
R9140 |
T12849 |
T12845 |
auxpass |
be,caused |
R9141 |
T12850 |
T12845 |
agent |
by,caused |
R9142 |
T12709 |
T12710 |
amod |
double,transgenic |
R9143 |
T12851 |
T12852 |
amod |
neuronal,alterations |
R9144 |
T12852 |
T12850 |
pobj |
alterations,by |
R9145 |
T12853 |
T12845 |
prep |
due,caused |
R9146 |
T12710 |
T12708 |
amod |
transgenic,mice |
R9147 |
T12854 |
T12853 |
pcomp |
to,due |
R9148 |
T12855 |
T12856 |
compound |
transgene,expression |
R9149 |
T12711 |
T12712 |
amod |
similar,patterns |
R9150 |
T12856 |
T12853 |
pobj |
expression,due |
R9151 |
T12857 |
T12856 |
prep |
during,expression |
R9152 |
T12858 |
T12859 |
amod |
early,postnatal |
R9153 |
T12712 |
T12705 |
dobj |
patterns,showed |
R9154 |
T12859 |
T12860 |
amod |
postnatal,development |
R9155 |
T12860 |
T12857 |
pobj |
development,during |
R9156 |
T12861 |
T12845 |
punct |
.,caused |
R9157 |
T12713 |
T12712 |
amod |
circular,patterns |
R9158 |
T12863 |
T12864 |
amod |
Further,experiments |
R9159 |
T12714 |
T12712 |
prep |
of,patterns |
R9160 |
T12864 |
T12865 |
nsubjpass |
experiments,needed |
R9161 |
T12866 |
T12865 |
auxpass |
are,needed |
R9162 |
T12715 |
T12714 |
pobj |
swimming,of |
R9163 |
T12867 |
T12868 |
aux |
to,distinguish |
R9164 |
T12868 |
T12865 |
advcl |
distinguish,needed |
R9165 |
T12869 |
T12868 |
prep |
between,distinguish |
R9166 |
T12716 |
T12712 |
prep |
near,patterns |
R9167 |
T12870 |
T12871 |
det |
these,possibilities |
R9168 |
T12871 |
T12869 |
pobj |
possibilities,between |
R9169 |
T12717 |
T12718 |
det |
the,edge |
R9170 |
T12872 |
T12865 |
punct |
.,needed |
R9171 |
T12874 |
T12875 |
prep |
In,demonstrate |
R9172 |
T12718 |
T12716 |
pobj |
edge,near |
R9173 |
T12876 |
T12874 |
pobj |
summary,In |
R9174 |
T12719 |
T12718 |
prep |
of,edge |
R9175 |
T12877 |
T12875 |
punct |
", ",demonstrate |
R9176 |
T12878 |
T12875 |
nsubj |
we,demonstrate |
R9177 |
T12720 |
T12721 |
det |
the,tank |
R9178 |
T12879 |
T12880 |
mark |
that,halts |
R9179 |
T12880 |
T12875 |
ccomp |
halts,demonstrate |
R9180 |
T12721 |
T12719 |
pobj |
tank,of |
R9181 |
T12881 |
T12880 |
csubj |
abrogating,halts |
R9182 |
T12882 |
T12883 |
compound |
Aβ,production |
R9183 |
T12883 |
T12881 |
dobj |
production,abrogating |
R9184 |
T12934 |
T12932 |
advcl |
limit,therapies |
R9185 |
T12884 |
T12885 |
det |
the,progression |
R9186 |
T12885 |
T12880 |
dobj |
progression,halts |
R9187 |
T12886 |
T12885 |
prep |
of,progression |
R9188 |
T12887 |
T12888 |
amod |
pathologic,changes |
R9189 |
T12935 |
T12936 |
compound |
Aβ,production |
R9190 |
T12888 |
T12886 |
pobj |
changes,of |
R9191 |
T12889 |
T12885 |
prep |
in,progression |
R9192 |
T12890 |
T12891 |
det |
a,model |
R9193 |
T12936 |
T12934 |
dobj |
production,limit |
R9194 |
T12891 |
T12889 |
pobj |
model,in |
R9195 |
T12892 |
T12891 |
amod |
transgenic,model |
R9196 |
T12937 |
T12934 |
punct |
", ",limit |
R9197 |
T12893 |
T12891 |
compound |
mouse,model |
R9198 |
T12894 |
T12891 |
prep |
of,model |
R9199 |
T12895 |
T12896 |
compound |
Alzheimer,type |
R9200 |
T12938 |
T12934 |
conj |
increase,limit |
R9201 |
T12896 |
T12898 |
compound |
type,amyloidosis |
R9202 |
T12897 |
T12896 |
punct |
-,type |
R9203 |
T12898 |
T12894 |
pobj |
amyloidosis,of |
R9204 |
T12939 |
T12940 |
compound |
Aβ,degradation |
R9205 |
T12899 |
T12875 |
punct |
.,demonstrate |
R9206 |
T12901 |
T12902 |
advmod |
However,are |
R9207 |
T12940 |
T12938 |
dobj |
degradation,increase |
R9208 |
T12903 |
T12902 |
punct |
", ",are |
R9209 |
T12941 |
T12938 |
punct |
", ",increase |
R9210 |
T12904 |
T12902 |
prep |
despite,are |
R9211 |
T12905 |
T12906 |
amod |
dramatic,reductions |
R9212 |
T12906 |
T12904 |
pobj |
reductions,despite |
R9213 |
T12907 |
T12906 |
prep |
in,reductions |
R9214 |
T12908 |
T12909 |
compound |
Aβ,synthesis |
R9215 |
T12909 |
T12907 |
pobj |
synthesis,in |
R9216 |
T12942 |
T12938 |
cc |
and,increase |
R9217 |
T12910 |
T12902 |
punct |
", ",are |
R9218 |
T12911 |
T12912 |
amod |
neuritic,plaques |
R9219 |
T12943 |
T12938 |
conj |
enhance,increase |
R9220 |
T12912 |
T12902 |
nsubj |
plaques,are |
R9221 |
T12913 |
T12914 |
amod |
stable,structures |
R9222 |
T12914 |
T12902 |
attr |
structures,are |
R9223 |
T12944 |
T12943 |
dobj |
phagocytosis,enhance |
R9224 |
T12915 |
T12916 |
advmod |
in,vivo |
R9225 |
T12916 |
T12914 |
advmod |
vivo,structures |
R9226 |
T12945 |
T12944 |
prep |
of,phagocytosis |
R9227 |
T12917 |
T12918 |
dep |
that,disaggregate |
R9228 |
T12918 |
T12914 |
relcl |
disaggregate,structures |
R9229 |
T12919 |
T12918 |
aux |
do,disaggregate |
R9230 |
T12946 |
T12947 |
amod |
deposited,amyloid |
R9231 |
T12920 |
T12918 |
neg |
not,disaggregate |
R9232 |
T12921 |
T12918 |
advmod |
quickly,disaggregate |
R9233 |
T12947 |
T12945 |
pobj |
amyloid,of |
R9234 |
T12922 |
T12902 |
punct |
.,are |
R9235 |
T12948 |
T12928 |
aux |
may,required |
R9236 |
T12924 |
T12925 |
nsubj |
It,is |
R9237 |
T12926 |
T12925 |
acomp |
possible,is |
R9238 |
T12949 |
T12928 |
auxpass |
be,required |
R9239 |
T12927 |
T12928 |
mark |
that,required |
R9240 |
T12928 |
T12925 |
ccomp |
required,is |
R9241 |
T12929 |
T12930 |
det |
a,combination |
R9242 |
T12950 |
T12951 |
aux |
to,reverse |
R9243 |
T12930 |
T12928 |
nsubjpass |
combination,required |
R9244 |
T12931 |
T12930 |
prep |
of,combination |
R9245 |
T12951 |
T12928 |
advcl |
reverse,required |
R9246 |
T12932 |
T12931 |
pobj |
therapies,of |
R9247 |
T12933 |
T12934 |
aux |
to,limit |
R9248 |
T12952 |
T12951 |
dobj |
damage,reverse |
R9249 |
T12953 |
T12952 |
acl |
associated,damage |
R9250 |
T12954 |
T12953 |
prep |
with,associated |
R9251 |
T13040 |
T13028 |
auxpass |
be,required |
R9252 |
T12955 |
T12954 |
pobj |
AD,with |
R9253 |
T12956 |
T12925 |
punct |
.,is |
R9254 |
T13041 |
T13042 |
aux |
to,determine |
R9255 |
T13042 |
T13028 |
advcl |
determine,required |
R9256 |
T12958 |
T12959 |
advmod |
However,provide |
R9257 |
T13043 |
T13044 |
mark |
whether,has |
R9258 |
T13044 |
T13042 |
ccomp |
has,determine |
R9259 |
T13045 |
T13046 |
det |
the,brain |
R9260 |
T12960 |
T12959 |
punct |
", ",provide |
R9261 |
T13046 |
T13044 |
nsubj |
brain,has |
R9262 |
T13047 |
T13046 |
amod |
human,brain |
R9263 |
T13048 |
T13049 |
det |
the,capacity |
R9264 |
T12961 |
T12962 |
mark |
if,started |
R9265 |
T13049 |
T13044 |
dobj |
capacity,has |
R9266 |
T12962 |
T12959 |
advcl |
started,provide |
R9267 |
T13050 |
T13051 |
aux |
to,repair |
R9268 |
T13051 |
T13049 |
acl |
repair,capacity |
R9269 |
T12963 |
T12964 |
advmod |
early,enough |
R9270 |
T13052 |
T13053 |
npadvmod |
amyloid,associated |
R9271 |
T13053 |
T13055 |
amod |
associated,damage |
R9272 |
T13054 |
T13053 |
punct |
-,associated |
R9273 |
T12964 |
T12962 |
advmod |
enough,started |
R9274 |
T13055 |
T13051 |
dobj |
damage,repair |
R9275 |
T13056 |
T13055 |
prep |
of,damage |
R9276 |
T13057 |
T13056 |
pobj |
AD,of |
R9277 |
T12965 |
T12962 |
prep |
in,started |
R9278 |
T13058 |
T13059 |
mark |
once,arrested |
R9279 |
T13059 |
T13051 |
advcl |
arrested,repair |
R9280 |
T12966 |
T12967 |
det |
the,course |
R9281 |
T13060 |
T13061 |
det |
the,progression |
R9282 |
T13061 |
T13059 |
nsubjpass |
progression,arrested |
R9283 |
T13062 |
T13061 |
prep |
of,progression |
R9284 |
T12967 |
T12965 |
pobj |
course,in |
R9285 |
T13063 |
T13062 |
pobj |
pathology,of |
R9286 |
T13064 |
T13059 |
auxpass |
is,arrested |
R9287 |
T13065 |
T13028 |
punct |
.,required |
R9288 |
T12968 |
T12967 |
prep |
of,course |
R9289 |
T12969 |
T12968 |
pobj |
disease,of |
R9290 |
T12970 |
T12959 |
punct |
", ",provide |
R9291 |
T12971 |
T12972 |
compound |
secretase,inhibitors |
R9292 |
T12972 |
T12959 |
nsubj |
inhibitors,provide |
R9293 |
T12973 |
T12972 |
advmod |
alone,inhibitors |
R9294 |
T12974 |
T12959 |
aux |
could,provide |
R9295 |
T12975 |
T12976 |
amod |
substantial,benefit |
R9296 |
T12976 |
T12959 |
dobj |
benefit,provide |
R9297 |
T12977 |
T12976 |
prep |
in,benefit |
R9298 |
T12978 |
T12977 |
pcomp |
slowing,in |
R9299 |
T12979 |
T12980 |
amod |
pathogenic,processes |
R9300 |
T12980 |
T12978 |
dobj |
processes,slowing |
R9301 |
T12981 |
T12980 |
acl |
linked,processes |
R9302 |
T12982 |
T12981 |
prep |
to,linked |
R9303 |
T12983 |
T12984 |
compound |
amyloid,deposition |
R9304 |
T12984 |
T12982 |
pobj |
deposition,to |
R9305 |
T12985 |
T12959 |
punct |
.,provide |
R9306 |
T12987 |
T12988 |
advmod |
Even,at |
R9307 |
T12988 |
T12989 |
prep |
at,suggests |
R9308 |
T12990 |
T12991 |
amod |
later,stages |
R9309 |
T12991 |
T12988 |
pobj |
stages,at |
R9310 |
T12992 |
T12991 |
prep |
in,stages |
R9311 |
T12993 |
T12994 |
det |
the,disease |
R9312 |
T12994 |
T12992 |
pobj |
disease,in |
R9313 |
T12995 |
T12989 |
punct |
", ",suggests |
R9314 |
T12996 |
T12997 |
det |
the,presence |
R9315 |
T12997 |
T12989 |
nsubj |
presence,suggests |
R9316 |
T12998 |
T12997 |
prep |
of,presence |
R9317 |
T12999 |
T13000 |
amod |
substantial,activation |
R9318 |
T13000 |
T12998 |
pobj |
activation,of |
R9319 |
T13001 |
T13000 |
amod |
microglial,activation |
R9320 |
T13002 |
T12997 |
prep |
in,presence |
R9321 |
T13003 |
T13004 |
amod |
human,AD |
R9322 |
T13004 |
T13002 |
pobj |
AD,in |
R9323 |
T13005 |
T13006 |
punct |
[,40 |
R9324 |
T13006 |
T13004 |
parataxis |
40,AD |
R9325 |
T13007 |
T13006 |
punct |
],40 |
R9326 |
T13008 |
T13009 |
mark |
that,allow |
R9327 |
T13009 |
T12989 |
ccomp |
allow,suggests |
R9328 |
T13010 |
T13011 |
advmod |
simply,slowing |
R9329 |
T13011 |
T13009 |
csubj |
slowing,allow |
R9330 |
T13012 |
T13013 |
det |
the,formation |
R9331 |
T13013 |
T13011 |
dobj |
formation,slowing |
R9332 |
T13014 |
T13013 |
prep |
of,formation |
R9333 |
T13015 |
T13016 |
amod |
new,deposits |
R9334 |
T13016 |
T13014 |
pobj |
deposits,of |
R9335 |
T13017 |
T13016 |
compound |
amyloid,deposits |
R9336 |
T13018 |
T13009 |
aux |
may,allow |
R9337 |
T13019 |
T13020 |
amod |
ongoing,phagocytosis |
R9338 |
T13020 |
T13021 |
nsubj |
phagocytosis,diminish |
R9339 |
T13021 |
T13009 |
ccomp |
diminish,allow |
R9340 |
T13022 |
T13021 |
aux |
to,diminish |
R9341 |
T13023 |
T13024 |
amod |
preexisting,lesions |
R9342 |
T13024 |
T13021 |
dobj |
lesions,diminish |
R9343 |
T13025 |
T12989 |
punct |
.,suggests |
R9344 |
T13027 |
T13028 |
advmod |
However,required |
R9345 |
T13029 |
T13028 |
punct |
", ",required |
R9346 |
T13030 |
T13031 |
det |
the,development |
R9347 |
T13031 |
T13028 |
nsubjpass |
development,required |
R9348 |
T13032 |
T13031 |
prep |
of,development |
R9349 |
T13033 |
T13034 |
amod |
safe,inhibitors |
R9350 |
T13034 |
T13032 |
pobj |
inhibitors,of |
R9351 |
T13035 |
T13033 |
cc |
and,safe |
R9352 |
T13036 |
T13033 |
conj |
effective,safe |
R9353 |
T13037 |
T13034 |
compound |
secretase,inhibitors |
R9354 |
T13038 |
T13028 |
aux |
will,required |
R9355 |
T13039 |
T13028 |
advmod |
ultimately,required |
R1499 |
T2237 |
T2234 |
conj |
AS,S36 |
R1575 |
T2317 |
T2315 |
dobj |
offspring,crossing |
R3687 |
T5268 |
T5265 |
parataxis |
samples,Aβ |
R2 |
T139 |
T137 |
prep |
following,Amyloidosis |
R3 |
T140 |
T139 |
pobj |
Suppression,following |
R4 |
T141 |
T140 |
prep |
of,Suppression |
R5 |
T142 |
T143 |
compound |
Aβ,Production |
R6 |
T143 |
T141 |
pobj |
Production,of |
R7 |
T144 |
T140 |
prep |
in,Suppression |
R8 |
T145 |
T146 |
det |
a,Model |
R11 |
T148 |
T146 |
prep |
of,Model |
R12 |
T149 |
T150 |
compound |
Alzheimer,Disease |
R13 |
T150 |
T148 |
pobj |
Disease,of |
R14 |
T155 |
T156 |
det |
The,secretases |
R18 |
T160 |
T156 |
punct |
),secretases |
R19 |
T161 |
T162 |
dep |
that,cleave |
R20 |
T162 |
T156 |
relcl |
cleave,secretases |
R21 |
T163 |
T164 |
nmod |
amyloid,β |
R28 |
T170 |
T162 |
prep |
from,cleave |
R29 |
T171 |
T172 |
det |
the,protein |
R33 |
T175 |
T172 |
punct |
(,protein |
R34 |
T176 |
T172 |
appos |
APP,protein |
R35 |
T177 |
T159 |
punct |
),been |
R36 |
T178 |
T159 |
aux |
have,been |
R37 |
T179 |
T180 |
det |
the,focus |
R38 |
T180 |
T159 |
attr |
focus,been |
R39 |
T181 |
T180 |
prep |
of,focus |
R40 |
T182 |
T183 |
amod |
considerable,investigation |
R41 |
T183 |
T181 |
pobj |
investigation,of |
R42 |
T184 |
T183 |
prep |
in,investigation |
R43 |
T185 |
T186 |
det |
the,development |
R44 |
T186 |
T184 |
pobj |
development,in |
R45 |
T187 |
T186 |
prep |
of,development |
R46 |
T188 |
T187 |
pobj |
treatments,of |
R47 |
T189 |
T188 |
prep |
for,treatments |
R48 |
T190 |
T191 |
compound |
Alzheimer,disease |
R49 |
T191 |
T189 |
pobj |
disease,for |
R50 |
T192 |
T159 |
punct |
.,been |
R51 |
T194 |
T195 |
det |
The,prediction |
R52 |
T195 |
T196 |
nsubj |
prediction,been |
R53 |
T197 |
T196 |
aux |
has,been |
R54 |
T198 |
T199 |
mark |
that,facilitate |
R78 |
T222 |
T223 |
det |
the,repair |
R79 |
T223 |
T199 |
dobj |
repair,facilitate |
R80 |
T224 |
T223 |
prep |
of,repair |
R81 |
T225 |
T226 |
amod |
damaged,tissue |
R82 |
T226 |
T224 |
pobj |
tissue,of |
R83 |
T227 |
T223 |
cc |
and,repair |
R84 |
T228 |
T223 |
conj |
removal,repair |
R85 |
T229 |
T228 |
prep |
of,removal |
R86 |
T230 |
T231 |
compound |
amyloid,lesions |
R87 |
T231 |
T229 |
pobj |
lesions,of |
R88 |
T232 |
T196 |
punct |
.,been |
R89 |
T234 |
T235 |
advmod |
However,performed |
R90 |
T236 |
T235 |
punct |
", ",performed |
R91 |
T237 |
T238 |
det |
no,studies |
R94 |
T240 |
T238 |
compound |
term,studies |
R96 |
T242 |
T238 |
acl |
using,studies |
R97 |
T243 |
T244 |
compound |
animal,models |
R98 |
T244 |
T242 |
dobj |
models,using |
R99 |
T245 |
T244 |
prep |
of,models |
R100 |
T246 |
T247 |
compound |
amyloid,pathology |
R101 |
T247 |
T245 |
pobj |
pathology,of |
R102 |
T248 |
T235 |
aux |
have,performed |
R103 |
T249 |
T235 |
advmod |
yet,performed |
R104 |
T250 |
T235 |
auxpass |
been,performed |
R105 |
T251 |
T252 |
aux |
to,test |
R106 |
T252 |
T235 |
advcl |
test,performed |
R107 |
T253 |
T254 |
det |
this,hypothesis |
R108 |
T254 |
T252 |
dobj |
hypothesis,test |
R109 |
T255 |
T235 |
punct |
.,performed |
R110 |
T258 |
T257 |
cc |
and,Methods |
R111 |
T259 |
T257 |
conj |
Findings,Methods |
R112 |
T261 |
T262 |
nsubj |
We,generated |
R113 |
T263 |
T262 |
aux |
have,generated |
R114 |
T264 |
T265 |
det |
a,model |
R118 |
T268 |
T269 |
dep |
that,mimics |
R121 |
T271 |
T272 |
det |
the,arrest |
R122 |
T272 |
T269 |
dobj |
arrest,mimics |
R123 |
T273 |
T272 |
prep |
of,arrest |
R124 |
T274 |
T275 |
compound |
Aβ,production |
R125 |
T275 |
T273 |
pobj |
production,of |
R126 |
T276 |
T275 |
acl |
expected,production |
R127 |
T277 |
T276 |
prep |
from,expected |
R128 |
T278 |
T277 |
pobj |
treatment,from |
R129 |
T279 |
T278 |
prep |
with,treatment |
R130 |
T280 |
T281 |
compound |
secretase,inhibitors |
R131 |
T281 |
T279 |
pobj |
inhibitors,with |
R132 |
T282 |
T262 |
punct |
.,generated |
R133 |
T284 |
T285 |
det |
These,mice |
R134 |
T285 |
T286 |
nsubj |
mice,overexpress |
R135 |
T287 |
T288 |
compound |
mutant,APP |
R136 |
T288 |
T286 |
dobj |
APP,overexpress |
R137 |
T289 |
T286 |
prep |
from,overexpress |
R138 |
T290 |
T291 |
det |
a,vector |
R139 |
T291 |
T289 |
pobj |
vector,from |
R140 |
T292 |
T293 |
dep |
that,regulated |
R144 |
T296 |
T293 |
agent |
by,regulated |
R145 |
T297 |
T296 |
pobj |
doxycycline,by |
R146 |
T298 |
T286 |
punct |
.,overexpress |
R147 |
T300 |
T301 |
prep |
Under,induces |
R148 |
T302 |
T303 |
amod |
normal,conditions |
R149 |
T303 |
T300 |
pobj |
conditions,Under |
R150 |
T304 |
T301 |
punct |
", ",induces |
R151 |
T305 |
T306 |
amod |
high,level |
R154 |
T308 |
T301 |
nsubj |
expression,induces |
R155 |
T309 |
T308 |
prep |
of,expression |
R156 |
T310 |
T309 |
pobj |
APP,of |
R157 |
T311 |
T301 |
advmod |
quickly,induces |
R158 |
T312 |
T313 |
amod |
fulminant,pathology |
R161 |
T315 |
T301 |
punct |
.,induces |
R162 |
T317 |
T318 |
nsubj |
We,show |
R163 |
T319 |
T320 |
mark |
that,inhibits |
R167 |
T323 |
T324 |
amod |
transgenic,expression |
R170 |
T326 |
T320 |
prep |
by,inhibits |
R171 |
T327 |
T328 |
amod |
greater,95 |
R174 |
T330 |
T326 |
pobj |
%,by |
R175 |
T331 |
T320 |
cc |
and,inhibits |
R176 |
T332 |
T320 |
conj |
reduces,inhibits |
R177 |
T333 |
T334 |
compound |
Aβ,production |
R178 |
T334 |
T332 |
dobj |
production,reduces |
R179 |
T335 |
T332 |
prep |
to,reduces |
R180 |
T336 |
T335 |
pobj |
levels,to |
R181 |
T337 |
T336 |
acl |
found,levels |
R182 |
T338 |
T337 |
prep |
in,found |
R183 |
T339 |
T340 |
amod |
nontransgenic,mice |
R184 |
T340 |
T338 |
pobj |
mice,in |
R185 |
T341 |
T318 |
punct |
.,show |
R186 |
T343 |
T344 |
nsubj |
Suppression,halts |
R187 |
T345 |
T343 |
prep |
of,Suppression |
R188 |
T346 |
T347 |
amod |
transgenic,synthesis |
R191 |
T349 |
T343 |
prep |
in,Suppression |
R192 |
T350 |
T351 |
det |
this,model |
R193 |
T351 |
T349 |
pobj |
model,in |
R194 |
T352 |
T344 |
advmod |
abruptly,halts |
R195 |
T353 |
T354 |
det |
the,progression |
R196 |
T354 |
T344 |
dobj |
progression,halts |
R197 |
T355 |
T354 |
prep |
of,progression |
R198 |
T356 |
T357 |
compound |
amyloid,pathology |
R199 |
T357 |
T355 |
pobj |
pathology,of |
R200 |
T358 |
T344 |
punct |
.,halts |
R201 |
T360 |
T361 |
advmod |
However,appear |
R202 |
T362 |
T361 |
punct |
", ",appear |
R203 |
T363 |
T361 |
nsubj |
formation,appear |
R204 |
T364 |
T363 |
cc |
and,formation |
R205 |
T365 |
T363 |
conj |
disaggregation,formation |
R206 |
T366 |
T363 |
prep |
of,formation |
R207 |
T367 |
T368 |
compound |
amyloid,deposits |
R208 |
T368 |
T366 |
pobj |
deposits,of |
R209 |
T369 |
T370 |
aux |
to,be |
R210 |
T370 |
T361 |
xcomp |
be,appear |
R211 |
T371 |
T370 |
prep |
in,be |
R212 |
T372 |
T371 |
pobj |
disequilibrium,in |
R213 |
T373 |
T374 |
mark |
as,require |
R217 |
T377 |
T378 |
advmod |
far,longer |
R218 |
T378 |
T374 |
advmod |
longer,require |
R219 |
T379 |
T380 |
aux |
to,disperse |
R220 |
T380 |
T374 |
xcomp |
disperse,require |
R221 |
T381 |
T382 |
mark |
than,assemble |
R224 |
T384 |
T361 |
punct |
.,appear |
R225 |
T386 |
T387 |
nsubj |
Mice,retain |
R226 |
T388 |
T389 |
prep |
in,suppressed |
R232 |
T394 |
T389 |
prep |
for,suppressed |
R233 |
T395 |
T396 |
advmod |
as,6 |
R237 |
T399 |
T394 |
pobj |
mo,for |
R238 |
T400 |
T389 |
prep |
after,suppressed |
R239 |
T401 |
T402 |
det |
the,formation |
R240 |
T402 |
T400 |
pobj |
formation,after |
R241 |
T403 |
T402 |
prep |
of,formation |
R242 |
T404 |
T405 |
compound |
Aβ,deposits |
R243 |
T405 |
T403 |
pobj |
deposits,of |
R244 |
T406 |
T407 |
det |
a,load |
R248 |
T410 |
T387 |
punct |
", ",retain |
R249 |
T411 |
T387 |
prep |
with,retain |
R250 |
T412 |
T413 |
amod |
little,sign |
R251 |
T413 |
T411 |
pobj |
sign,with |
R252 |
T414 |
T413 |
prep |
of,sign |
R253 |
T415 |
T416 |
amod |
active,clearance |
R254 |
T416 |
T414 |
pobj |
clearance,of |
R255 |
T417 |
T387 |
punct |
.,retain |
R256 |
T421 |
T422 |
det |
This,study |
R257 |
T422 |
T423 |
nsubj |
study,demonstrates |
R258 |
T424 |
T425 |
mark |
that,are |
R265 |
T431 |
T432 |
advmod |
highly,stable |
R266 |
T432 |
T433 |
amod |
stable,structures |
R267 |
T433 |
T425 |
attr |
structures,are |
R268 |
T434 |
T435 |
advmod |
in,vivo |
R269 |
T435 |
T433 |
advmod |
vivo,structures |
R270 |
T436 |
T437 |
dep |
that,are |
R271 |
T437 |
T433 |
relcl |
are,structures |
R272 |
T438 |
T437 |
acomp |
slow,are |
R273 |
T439 |
T440 |
aux |
to,disaggregate |
R274 |
T440 |
T438 |
xcomp |
disaggregate,slow |
R275 |
T441 |
T423 |
punct |
.,demonstrates |
R276 |
T443 |
T444 |
poss |
Our,findings |
R277 |
T444 |
T445 |
nsubj |
findings,suggest |
R278 |
T446 |
T447 |
mark |
that,halt |
R289 |
T457 |
T458 |
det |
the,progression |
R290 |
T458 |
T447 |
dobj |
progression,halt |
R291 |
T459 |
T458 |
prep |
of,progression |
R292 |
T460 |
T459 |
pobj |
pathology,of |
R293 |
T461 |
T447 |
punct |
", ",halt |
R294 |
T462 |
T447 |
cc |
but,halt |
R295 |
T463 |
T464 |
mark |
that,be |
R300 |
T468 |
T464 |
acomp |
imperative,be |
R301 |
T469 |
T464 |
punct |
", ",be |
R302 |
T470 |
T471 |
mark |
as,appears |
R305 |
T473 |
T474 |
mark |
that,require |
R314 |
T482 |
T483 |
amod |
additional,intervention |
R315 |
T483 |
T474 |
dobj |
intervention,require |
R316 |
T484 |
T485 |
aux |
to,clear |
R317 |
T485 |
T483 |
advcl |
clear,intervention |
R318 |
T486 |
T445 |
punct |
.,suggest |
R2327 |
T3419 |
T3416 |
parataxis |
17,22C11 |
R1141 |
T1769 |
T1774 |
nsubj |
fragment,cloned |
R1172 |
T1801 |
T1799 |
pobj |
fragment,to |
R1395 |
T2032 |
T2029 |
compound |
KS,vector |
R471 |
T861 |
T859 |
pobj |
approaches,of |
R622 |
T1020 |
T1017 |
appos |
enzyme,enzymes |
R8460 |
T12128 |
T12127 |
nummod |
50,55 |
R8796 |
T12483 |
T12482 |
punct |
-,off |
R8802 |
T12488 |
T12489 |
punct |
[,32 |
R8803 |
T12489 |
T12486 |
parataxis |
32,Huntington |
R8804 |
T12490 |
T12489 |
punct |
],32 |
R8808 |
T12493 |
T12494 |
punct |
[,62 |
R9120 |
T12833 |
T12832 |
compound |
APP,synthesis |
R9127 |
T12838 |
T12839 |
amod |
additional,time |
R9128 |
T12839 |
T12837 |
dobj |
time,requires |
R5135 |
T7755 |
T7752 |
prep |
via,expressing |
R5416 |
T8054 |
T8051 |
appos |
mo,mo |
R5417 |
T8055 |
T8051 |
amod |
treated,mo |
R5418 |
T8056 |
T8057 |
punct |
(,5 |
R6074 |
T8753 |
T8752 |
amod |
aggregated,Aβ |
R6077 |
T8755 |
T8754 |
pobj |
either,as |
R6078 |
T8756 |
T8755 |
prep |
of,either |
R6081 |
T8758 |
T8756 |
pobj |
groups,of |
R6413 |
T9109 |
T9110 |
det |
any,changes |
R6414 |
T9110 |
T9107 |
attr |
changes,were |
R6566 |
T9276 |
T9264 |
punct |
", ",seen |
R6567 |
T9277 |
T9264 |
cc |
and,seen |
R6854 |
T9583 |
T9584 |
advmod |
However,remained |
R6873 |
T9661 |
T9654 |
dobj |
levels,showed |
R6875 |
T9662 |
T9661 |
amod |
similar,levels |
R6876 |
T9663 |
T9662 |
prep |
to,similar |
R6878 |
T9664 |
T9665 |
det |
the,controls |
R6879 |
T9665 |
T9663 |
pobj |
controls,to |
R6881 |
T9666 |
T9665 |
amod |
untreated,controls |
R6882 |
T9667 |
T9668 |
punct |
(,7C |
R6884 |
T9668 |
T9654 |
parataxis |
7C,showed |
R6885 |
T9669 |
T9668 |
compound |
Figure,7C |
R6887 |
T9670 |
T9668 |
punct |
),7C |
R6888 |
T9671 |
T9654 |
punct |
.,showed |
R6890 |
T9673 |
T9674 |
advmod |
Intriguingly,showed |
R6891 |
T9675 |
T9674 |
punct |
", ",showed |
R6893 |
T9676 |
T9674 |
nsubj |
all,showed |
R6894 |
T9677 |
T9676 |
prep |
of,all |
R6896 |
T9678 |
T9679 |
det |
the,animals |
R6897 |
T9679 |
T9677 |
pobj |
animals,of |
R6898 |
T9680 |
T9681 |
npadvmod |
dox,reared |
R6900 |
T9681 |
T9679 |
amod |
reared,animals |
R6901 |
T9682 |
T9681 |
punct |
-,reared |
R6902 |
T9683 |
T9676 |
punct |
", ",all |
R6904 |
T9684 |
T9685 |
preconj |
both,transgenic |
R6905 |
T9685 |
T9676 |
amod |
transgenic,all |
R6907 |
T9686 |
T9685 |
cc |
and,transgenic |
R6908 |
T9687 |
T9688 |
amod |
wild,type |
R6909 |
T9688 |
T9685 |
conj |
type,transgenic |
R6911 |
T9689 |
T9688 |
punct |
-,type |
R6912 |
T9690 |
T9674 |
punct |
", ",showed |
R6914 |
T9691 |
T9692 |
amod |
altered,rhythms |
R6915 |
T9692 |
T9674 |
dobj |
rhythms,showed |
R6916 |
T9693 |
T9692 |
amod |
circadian,rhythms |
R6917 |
T9694 |
T9692 |
prep |
with,rhythms |
R6919 |
T9695 |
T9696 |
advmod |
far,less |
R6920 |
T9696 |
T9697 |
amod |
less,distinction |