Id |
Subject |
Object |
Predicate |
Lexical cue |
T6511 |
8-10 |
PRP |
denotes |
We |
T6512 |
11-15 |
VBD |
denotes |
used |
T6513 |
16-19 |
DT |
denotes |
the |
T6514 |
38-44 |
NN |
denotes |
system |
T6515 |
20-23 |
NN |
denotes |
tet |
T6516 |
24-27 |
NN |
denotes |
off |
T6517 |
23-24 |
HYPH |
denotes |
- |
T6518 |
28-37 |
NN |
denotes |
transgene |
T6519 |
45-47 |
TO |
denotes |
to |
T6520 |
48-55 |
VB |
denotes |
express |
T6521 |
56-57 |
DT |
denotes |
a |
T6522 |
72-79 |
NN |
denotes |
version |
T6523 |
58-64 |
JJ |
denotes |
double |
T6524 |
65-71 |
NN |
denotes |
mutant |
T6525 |
80-82 |
IN |
denotes |
of |
T6526 |
83-91 |
JJ |
denotes |
chimeric |
T6527 |
95-103 |
NN |
denotes |
huAPP695 |
T6528 |
92-94 |
NN |
denotes |
mo |
T6529 |
94-95 |
HYPH |
denotes |
/ |
T6530 |
104-105 |
-LRB- |
denotes |
( |
T6531 |
105-108 |
NN |
denotes |
swe |
T6532 |
113-118 |
NN |
denotes |
KM570 |
T6533 |
108-109 |
HYPH |
denotes |
/ |
T6534 |
109-112 |
NN |
denotes |
ind |
T6535 |
118-120 |
, |
denotes |
, |
T6536 |
120-125 |
NN |
denotes |
571NL |
T6537 |
125-127 |
, |
denotes |
, |
T6538 |
127-130 |
CC |
denotes |
and |
T6539 |
131-136 |
NN |
denotes |
V617F |
T6540 |
136-137 |
-RRB- |
denotes |
) |
T6541 |
138-142 |
IN |
denotes |
from |
T6542 |
143-144 |
DT |
denotes |
a |
T6543 |
169-177 |
NN |
denotes |
promoter |
T6544 |
145-157 |
NN |
denotes |
tetracycline |
T6545 |
158-168 |
JJ |
denotes |
responsive |
T6546 |
157-158 |
HYPH |
denotes |
- |
T6547 |
178-179 |
-LRB- |
denotes |
[ |
T6548 |
182-184 |
CD |
denotes |
13 |
T6549 |
179-181 |
CD |
denotes |
12 |
T6550 |
181-182 |
, |
denotes |
, |
T6551 |
184-185 |
-RRB- |
denotes |
] |
T6552 |
185-186 |
. |
denotes |
. |
T6553 |
186-327 |
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 |
187-197 |
JJ |
denotes |
Transgenic |
T6555 |
198-201 |
NN |
denotes |
APP |
T6556 |
202-212 |
NN |
denotes |
expression |
T6557 |
217-226 |
VBN |
denotes |
activated |
T6558 |
213-216 |
VBD |
denotes |
was |
T6559 |
227-229 |
IN |
denotes |
by |
T6560 |
230-238 |
VBG |
denotes |
crossing |
T6561 |
239-242 |
DT |
denotes |
the |
T6562 |
254-258 |
NNS |
denotes |
mice |
T6563 |
243-249 |
NN |
denotes |
APPswe |
T6564 |
250-253 |
NN |
denotes |
ind |
T6565 |
249-250 |
HYPH |
denotes |
/ |
T6566 |
259-261 |
IN |
denotes |
to |
T6567 |
262-269 |
NNS |
denotes |
animals |
T6568 |
270-279 |
VBG |
denotes |
producing |
T6569 |
280-283 |
NN |
denotes |
tTA |
T6570 |
284-289 |
IN |
denotes |
under |
T6571 |
290-297 |
NN |
denotes |
control |
T6572 |
298-300 |
IN |
denotes |
of |
T6573 |
301-304 |
DT |
denotes |
the |
T6574 |
313-321 |
NN |
denotes |
promoter |
T6575 |
305-312 |
NN |
denotes |
CaMKIIα |
T6576 |
322-323 |
-LRB- |
denotes |
[ |
T6577 |
323-325 |
CD |
denotes |
16 |
T6578 |
325-326 |
-RRB- |
denotes |
] |
T6579 |
326-327 |
. |
denotes |
. |
T6580 |
327-521 |
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 |
328-333 |
IN |
denotes |
After |
T6582 |
368-378 |
VBD |
denotes |
identified |
T6583 |
334-341 |
JJ |
denotes |
initial |
T6584 |
342-351 |
NN |
denotes |
screening |
T6585 |
352-354 |
IN |
denotes |
of |
T6586 |
355-363 |
NNS |
denotes |
founders |
T6587 |
363-365 |
, |
denotes |
, |
T6588 |
365-367 |
PRP |
denotes |
we |
T6589 |
379-383 |
CD |
denotes |
four |
T6590 |
384-389 |
NNS |
denotes |
lines |
T6591 |
390-392 |
IN |
denotes |
of |
T6592 |
393-396 |
NN |
denotes |
tet |
T6593 |
404-407 |
NN |
denotes |
ind |
T6594 |
396-397 |
HYPH |
denotes |
- |
T6595 |
397-403 |
NN |
denotes |
APPswe |
T6596 |
403-404 |
HYPH |
denotes |
/ |
T6597 |
408-412 |
NNS |
denotes |
mice |
T6598 |
413-417 |
WDT |
denotes |
that |
T6599 |
418-426 |
VBD |
denotes |
produced |
T6600 |
427-431 |
RB |
denotes |
very |
T6601 |
432-436 |
JJ |
denotes |
high |
T6602 |
437-443 |
NNS |
denotes |
levels |
T6603 |
444-446 |
IN |
denotes |
of |
T6604 |
447-456 |
NN |
denotes |
transgene |
T6605 |
457-464 |
NN |
denotes |
product |
T6606 |
465-467 |
IN |
denotes |
in |
T6607 |
468-477 |
NN |
denotes |
offspring |
T6608 |
478-490 |
VBG |
denotes |
coexpressing |
T6609 |
491-494 |
NN |
denotes |
tTA |
T6610 |
495-496 |
-LRB- |
denotes |
( |
T6611 |
496-503 |
NNS |
denotes |
Figures |
T6612 |
504-505 |
CD |
denotes |
1 |
T6613 |
506-509 |
CC |
denotes |
and |
T6614 |
510-516 |
NN |
denotes |
Figure |
T6615 |
517-519 |
NN |
denotes |
S1 |
T6616 |
519-520 |
-RRB- |
denotes |
) |
T6617 |
520-521 |
. |
denotes |
. |
T6618 |
521-772 |
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 |
522-530 |
VBN |
denotes |
Compared |
T6620 |
645-654 |
VBD |
denotes |
estimated |
T6621 |
531-533 |
IN |
denotes |
to |
T6622 |
534-535 |
DT |
denotes |
a |
T6623 |
560-564 |
NN |
denotes |
line |
T6624 |
536-544 |
JJ |
denotes |
standard |
T6625 |
545-548 |
NN |
denotes |
APP |
T6626 |
549-559 |
JJ |
denotes |
transgenic |
T6627 |
565-569 |
VBN |
denotes |
used |
T6628 |
570-573 |
IN |
denotes |
for |
T6629 |
574-582 |
JJ |
denotes |
previous |
T6630 |
591-598 |
NNS |
denotes |
studies |
T6631 |
583-590 |
NN |
denotes |
amyloid |
T6632 |
599-601 |
IN |
denotes |
by |
T6633 |
602-605 |
PRP$ |
denotes |
our |
T6634 |
606-616 |
NN |
denotes |
laboratory |
T6635 |
617-618 |
-LRB- |
denotes |
( |
T6636 |
636-638 |
CD |
denotes |
27 |
T6637 |
618-622 |
NN |
denotes |
line |
T6638 |
623-625 |
NN |
denotes |
C3 |
T6639 |
625-626 |
HYPH |
denotes |
– |
T6640 |
626-627 |
CD |
denotes |
3 |
T6641 |
627-628 |
: |
denotes |
; |
T6642 |
629-630 |
-LRB- |
denotes |
[ |
T6643 |
630-632 |
CD |
denotes |
15 |
T6644 |
632-633 |
, |
denotes |
, |
T6645 |
633-635 |
CD |
denotes |
26 |
T6646 |
635-636 |
, |
denotes |
, |
T6647 |
638-639 |
-RRB- |
denotes |
] |
T6648 |
639-640 |
-RRB- |
denotes |
) |
T6649 |
640-642 |
, |
denotes |
, |
T6650 |
642-644 |
PRP |
denotes |
we |
T6651 |
655-659 |
IN |
denotes |
that |
T6652 |
688-695 |
VBP |
denotes |
produce |
T6653 |
660-663 |
DT |
denotes |
the |
T6654 |
682-687 |
NNS |
denotes |
lines |
T6655 |
664-668 |
CD |
denotes |
four |
T6656 |
669-681 |
JJ |
denotes |
controllable |
T6657 |
696-706 |
JJ |
denotes |
transgenic |
T6658 |
711-718 |
NN |
denotes |
protein |
T6659 |
707-710 |
NN |
denotes |
APP |
T6660 |
719-721 |
IN |
denotes |
at |
T6661 |
722-724 |
CD |
denotes |
10 |
T6662 |
724-725 |
HYPH |
denotes |
- |
T6663 |
726-728 |
IN |
denotes |
to |
T6664 |
729-736 |
RB |
denotes |
30-fold |
T6665 |
737-741 |
IN |
denotes |
over |
T6666 |
742-752 |
JJ |
denotes |
endogenous |
T6667 |
753-759 |
NNS |
denotes |
levels |
T6668 |
760-761 |
-LRB- |
denotes |
( |
T6669 |
768-770 |
NN |
denotes |
S1 |
T6670 |
761-767 |
NN |
denotes |
Figure |
T6671 |
770-771 |
-RRB- |
denotes |
) |
T6672 |
771-772 |
. |
denotes |
. |
T6673 |
772-1033 |
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 |
773-777 |
DT |
denotes |
This |
T6675 |
778-786 |
NN |
denotes |
estimate |
T6676 |
791-800 |
VBN |
denotes |
confirmed |
T6677 |
787-790 |
VBD |
denotes |
was |
T6678 |
801-803 |
IN |
denotes |
by |
T6679 |
804-810 |
JJ |
denotes |
direct |
T6680 |
811-821 |
NN |
denotes |
comparison |
T6681 |
822-824 |
IN |
denotes |
of |
T6682 |
825-828 |
NN |
denotes |
APP |
T6683 |
829-835 |
NNS |
denotes |
levels |
T6684 |
836-838 |
IN |
denotes |
in |
T6685 |
839-852 |
JJ |
denotes |
nontransgenic |
T6686 |
869-873 |
NNS |
denotes |
mice |
T6687 |
853-856 |
CC |
denotes |
and |
T6688 |
857-860 |
NN |
denotes |
tet |
T6689 |
861-864 |
NN |
denotes |
off |
T6690 |
860-861 |
HYPH |
denotes |
- |
T6691 |
865-868 |
NN |
denotes |
APP |
T6692 |
874-879 |
VBG |
denotes |
using |
T6693 |
880-882 |
DT |
denotes |
an |
T6694 |
883-891 |
NN |
denotes |
antibody |
T6695 |
892-896 |
WDT |
denotes |
that |
T6696 |
897-907 |
VBZ |
denotes |
recognizes |
T6697 |
908-912 |
CC |
denotes |
both |
T6698 |
924-927 |
NN |
denotes |
APP |
T6699 |
913-923 |
JJ |
denotes |
endogenous |
T6700 |
928-929 |
-LRB- |
denotes |
( |
T6701 |
929-932 |
CC |
denotes |
and |
T6702 |
933-940 |
NN |
denotes |
amyloid |
T6703 |
956-963 |
NN |
denotes |
protein |
T6704 |
941-950 |
NN |
denotes |
precursor |
T6705 |
951-955 |
JJ |
denotes |
like |
T6706 |
950-951 |
HYPH |
denotes |
- |
T6707 |
964-965 |
CD |
denotes |
2 |
T6708 |
965-966 |
-RRB- |
denotes |
) |
T6709 |
967-970 |
CC |
denotes |
and |
T6710 |
971-974 |
DT |
denotes |
the |
T6711 |
986-993 |
NN |
denotes |
protein |
T6712 |
975-985 |
JJ |
denotes |
transgenic |
T6713 |
994-995 |
-LRB- |
denotes |
( |
T6714 |
1029-1031 |
NN |
denotes |
1D |
T6715 |
995-1005 |
JJ |
denotes |
monoclonal |
T6716 |
1015-1020 |
NN |
denotes |
22C11 |
T6717 |
1006-1014 |
NN |
denotes |
antibody |
T6718 |
1020-1021 |
: |
denotes |
; |
T6719 |
1022-1028 |
NN |
denotes |
Figure |
T6720 |
1031-1032 |
-RRB- |
denotes |
) |
T6721 |
1032-1033 |
. |
denotes |
. |
T6722 |
1033-2834 |
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 |
2680-2691 |
RB |
denotes |
Importantly |
T6724 |
2732-2738 |
VBD |
denotes |
showed |
T6725 |
2691-2693 |
, |
denotes |
, |
T6726 |
2693-2696 |
DT |
denotes |
all |
T6727 |
2706-2711 |
NNS |
denotes |
lines |
T6728 |
2697-2701 |
CD |
denotes |
four |
T6729 |
2702-2705 |
JJ |
denotes |
new |
T6730 |
2712-2714 |
IN |
denotes |
of |
T6731 |
2715-2718 |
NN |
denotes |
tet |
T6732 |
2719-2722 |
NN |
denotes |
off |
T6733 |
2718-2719 |
HYPH |
denotes |
- |
T6734 |
2727-2731 |
NNS |
denotes |
mice |
T6735 |
2723-2726 |
NN |
denotes |
APP |
T6736 |
2739-2745 |
RB |
denotes |
nearly |
T6737 |
2746-2754 |
JJ |
denotes |
complete |
T6738 |
2755-2766 |
NN |
denotes |
suppression |
T6739 |
2767-2769 |
IN |
denotes |
of |
T6740 |
2770-2773 |
DT |
denotes |
the |
T6741 |
2774-2783 |
NN |
denotes |
transgene |
T6742 |
2784-2793 |
VBG |
denotes |
following |
T6743 |
2794-2797 |
NN |
denotes |
dox |
T6744 |
2798-2807 |
NN |
denotes |
treatment |
T6745 |
2808-2809 |
-LRB- |
denotes |
( |
T6746 |
2809-2816 |
NNS |
denotes |
Figures |
T6747 |
2817-2818 |
CD |
denotes |
1 |
T6748 |
2819-2822 |
CC |
denotes |
and |
T6749 |
2823-2829 |
NN |
denotes |
Figure |
T6750 |
2830-2832 |
NN |
denotes |
S1 |
T6751 |
2832-2833 |
-RRB- |
denotes |
) |
T6752 |
2833-2834 |
. |
denotes |
. |
T6753 |
2834-3017 |
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 |
2835-2837 |
PRP |
denotes |
We |
T6755 |
2838-2845 |
VBD |
denotes |
focused |
T6756 |
2846-2848 |
IN |
denotes |
on |
T6757 |
2849-2852 |
CD |
denotes |
one |
T6758 |
2853-2855 |
IN |
denotes |
of |
T6759 |
2856-2859 |
DT |
denotes |
the |
T6760 |
2865-2870 |
NNS |
denotes |
lines |
T6761 |
2860-2864 |
CD |
denotes |
four |
T6762 |
2870-2872 |
, |
denotes |
, |
T6763 |
2872-2876 |
NN |
denotes |
line |
T6764 |
2877-2880 |
CD |
denotes |
107 |
T6765 |
2880-2882 |
, |
denotes |
, |
T6766 |
2882-2884 |
TO |
denotes |
to |
T6767 |
2885-2892 |
VB |
denotes |
examine |
T6768 |
2893-2895 |
IN |
denotes |
in |
T6769 |
2896-2900 |
JJR |
denotes |
more |
T6770 |
2901-2907 |
NN |
denotes |
detail |
T6771 |
2908-2911 |
DT |
denotes |
the |
T6772 |
2917-2927 |
NN |
denotes |
dependence |
T6773 |
2912-2916 |
NN |
denotes |
time |
T6774 |
2928-2931 |
CC |
denotes |
and |
T6775 |
2932-2938 |
NN |
denotes |
extent |
T6776 |
2939-2941 |
IN |
denotes |
of |
T6777 |
2942-2951 |
NN |
denotes |
transgene |
T6778 |
2952-2963 |
NN |
denotes |
suppression |
T6779 |
2964-2973 |
VBG |
denotes |
following |
T6780 |
2974-2980 |
CC |
denotes |
either |
T6781 |
2998-3007 |
NN |
denotes |
treatment |
T6782 |
2981-2986 |
JJ |
denotes |
acute |
T6783 |
2987-2989 |
CC |
denotes |
or |
T6784 |
2990-2997 |
JJ |
denotes |
chronic |
T6785 |
3008-3012 |
IN |
denotes |
with |
T6786 |
3013-3016 |
NN |
denotes |
dox |
T6787 |
3016-3017 |
. |
denotes |
. |
T6788 |
3017-3297 |
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 |
3018-3021 |
CD |
denotes |
Two |
T6790 |
3034-3040 |
NNS |
denotes |
groups |
T6791 |
3022-3025 |
NN |
denotes |
dox |
T6792 |
3026-3033 |
VBN |
denotes |
treated |
T6793 |
3025-3026 |
HYPH |
denotes |
- |
T6794 |
3046-3054 |
VBN |
denotes |
compared |
T6795 |
3041-3045 |
VBD |
denotes |
were |
T6796 |
3260-3269 |
VBN |
denotes |
harvested |
T6797 |
3055-3057 |
IN |
denotes |
to |
T6798 |
3058-3061 |
CD |
denotes |
two |
T6799 |
3072-3078 |
NNS |
denotes |
groups |
T6800 |
3062-3071 |
JJ |
denotes |
untreated |
T6801 |
3078-3080 |
: |
denotes |
: |
T6802 |
3080-3083 |
CD |
denotes |
one |
T6803 |
3084-3089 |
NN |
denotes |
group |
T6804 |
3102-3106 |
VBN |
denotes |
born |
T6805 |
3090-3092 |
IN |
denotes |
of |
T6806 |
3093-3097 |
NNS |
denotes |
mice |
T6807 |
3098-3101 |
VBD |
denotes |
was |
T6808 |
3107-3110 |
CC |
denotes |
and |
T6809 |
3111-3117 |
VBN |
denotes |
raised |
T6810 |
3118-3120 |
IN |
denotes |
on |
T6811 |
3121-3124 |
NN |
denotes |
dox |
T6812 |
3124-3126 |
, |
denotes |
, |
T6813 |
3126-3127 |
DT |
denotes |
a |
T6814 |
3135-3140 |
NN |
denotes |
group |
T6815 |
3128-3134 |
JJ |
denotes |
second |
T6816 |
3145-3152 |
VBN |
denotes |
treated |
T6817 |
3141-3144 |
VBD |
denotes |
was |
T6818 |
3153-3157 |
IN |
denotes |
with |
T6819 |
3158-3161 |
NN |
denotes |
dox |
T6820 |
3162-3165 |
IN |
denotes |
for |
T6821 |
3166-3167 |
CD |
denotes |
2 |
T6822 |
3168-3170 |
NN |
denotes |
wk |
T6823 |
3171-3179 |
VBG |
denotes |
starting |
T6824 |
3180-3182 |
IN |
denotes |
at |
T6825 |
3183-3184 |
CD |
denotes |
1 |
T6826 |
3185-3187 |
NN |
denotes |
mo |
T6827 |
3188-3190 |
IN |
denotes |
of |
T6828 |
3191-3194 |
NN |
denotes |
age |
T6829 |
3195-3196 |
-LRB- |
denotes |
( |
T6830 |
3198-3200 |
NN |
denotes |
wk |
T6831 |
3196-3197 |
CD |
denotes |
4 |
T6832 |
3201-3202 |
SYM |
denotes |
+ |
T6833 |
3203-3204 |
CD |
denotes |
2 |
T6834 |
3205-3207 |
NN |
denotes |
wk |
T6835 |
3208-3211 |
NN |
denotes |
dox |
T6836 |
3211-3212 |
-RRB- |
denotes |
) |
T6837 |
3212-3213 |
: |
denotes |
; |
T6838 |
3214-3217 |
CD |
denotes |
two |
T6839 |
3228-3234 |
NNS |
denotes |
groups |
T6840 |
3218-3227 |
JJ |
denotes |
untreated |
T6841 |
3235-3239 |
VBN |
denotes |
kept |
T6842 |
3240-3242 |
IN |
denotes |
on |
T6843 |
3243-3249 |
JJ |
denotes |
normal |
T6844 |
3250-3254 |
NN |
denotes |
chow |
T6845 |
3255-3259 |
VBD |
denotes |
were |
T6846 |
3270-3272 |
IN |
denotes |
at |
T6847 |
3273-3279 |
CC |
denotes |
either |
T6848 |
3280-3281 |
CD |
denotes |
4 |
T6849 |
3287-3289 |
NN |
denotes |
wk |
T6850 |
3282-3284 |
CC |
denotes |
or |
T6851 |
3285-3286 |
CD |
denotes |
6 |
T6852 |
3290-3292 |
IN |
denotes |
of |
T6853 |
3293-3296 |
NN |
denotes |
age |
T6854 |
3296-3297 |
. |
denotes |
. |
T6855 |
3297-3368 |
sentence |
denotes |
Animals born and raised on dox harbored no transgenic APP (Figure 1A). |
T6856 |
3298-3305 |
NNS |
denotes |
Animals |
T6857 |
3329-3337 |
VBD |
denotes |
harbored |
T6858 |
3306-3310 |
VBN |
denotes |
born |
T6859 |
3311-3314 |
CC |
denotes |
and |
T6860 |
3315-3321 |
VBN |
denotes |
raised |
T6861 |
3322-3324 |
IN |
denotes |
on |
T6862 |
3325-3328 |
NN |
denotes |
dox |
T6863 |
3338-3340 |
DT |
denotes |
no |
T6864 |
3352-3355 |
NN |
denotes |
APP |
T6865 |
3341-3351 |
JJ |
denotes |
transgenic |
T6866 |
3356-3357 |
-LRB- |
denotes |
( |
T6867 |
3364-3366 |
NN |
denotes |
1A |
T6868 |
3357-3363 |
NN |
denotes |
Figure |
T6869 |
3366-3367 |
-RRB- |
denotes |
) |
T6870 |
3367-3368 |
. |
denotes |
. |
T6871 |
3368-3497 |
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 |
3369-3378 |
VBG |
denotes |
Following |
T6873 |
3445-3452 |
VBN |
denotes |
reduced |
T6874 |
3379-3381 |
RB |
denotes |
as |
T6875 |
3392-3393 |
CD |
denotes |
2 |
T6876 |
3382-3388 |
JJ |
denotes |
little |
T6877 |
3389-3391 |
IN |
denotes |
as |
T6878 |
3394-3396 |
NN |
denotes |
wk |
T6879 |
3397-3399 |
IN |
denotes |
of |
T6880 |
3400-3403 |
NN |
denotes |
dox |
T6881 |
3404-3413 |
NN |
denotes |
treatment |
T6882 |
3413-3415 |
, |
denotes |
, |
T6883 |
3415-3425 |
JJ |
denotes |
transgenic |
T6884 |
3430-3440 |
NN |
denotes |
expression |
T6885 |
3426-3429 |
NN |
denotes |
APP |
T6886 |
3441-3444 |
VBD |
denotes |
was |
T6887 |
3453-3455 |
IN |
denotes |
by |
T6888 |
3456-3460 |
JJR |
denotes |
more |
T6889 |
3466-3468 |
CD |
denotes |
95 |
T6890 |
3461-3465 |
IN |
denotes |
than |
T6891 |
3468-3469 |
NN |
denotes |
% |
T6892 |
3470-3478 |
VBN |
denotes |
compared |
T6893 |
3479-3481 |
IN |
denotes |
to |
T6894 |
3482-3489 |
JJ |
denotes |
pre-dox |
T6895 |
3490-3496 |
NNS |
denotes |
levels |
T6896 |
3496-3497 |
. |
denotes |
. |
T6897 |
3497-3736 |
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 |
3498-3501 |
DT |
denotes |
The |
T6899 |
3511-3521 |
NN |
denotes |
expression |
T6900 |
3502-3510 |
JJ |
denotes |
residual |
T6901 |
3556-3566 |
VBZ |
denotes |
represents |
T6902 |
3522-3531 |
VBG |
denotes |
remaining |
T6903 |
3532-3534 |
IN |
denotes |
in |
T6904 |
3535-3542 |
RB |
denotes |
acutely |
T6905 |
3543-3550 |
VBN |
denotes |
treated |
T6906 |
3551-3555 |
NNS |
denotes |
mice |
T6907 |
3567-3571 |
JJR |
denotes |
less |
T6908 |
3577-3578 |
CD |
denotes |
4 |
T6909 |
3572-3576 |
IN |
denotes |
than |
T6910 |
3578-3579 |
NN |
denotes |
% |
T6911 |
3580-3582 |
IN |
denotes |
of |
T6912 |
3583-3586 |
DT |
denotes |
the |
T6913 |
3598-3605 |
NN |
denotes |
protein |
T6914 |
3587-3597 |
JJ |
denotes |
transgenic |
T6915 |
3606-3614 |
VBN |
denotes |
produced |
T6916 |
3615-3617 |
IN |
denotes |
in |
T6917 |
3618-3621 |
DT |
denotes |
the |
T6918 |
3622-3629 |
NN |
denotes |
absence |
T6919 |
3630-3632 |
IN |
denotes |
of |
T6920 |
3633-3636 |
NN |
denotes |
dox |
T6921 |
3637-3638 |
-LRB- |
denotes |
( |
T6922 |
3645-3647 |
NN |
denotes |
1C |
T6923 |
3638-3644 |
NN |
denotes |
Figure |
T6924 |
3647-3648 |
-RRB- |
denotes |
) |
T6925 |
3648-3650 |
, |
denotes |
, |
T6926 |
3650-3653 |
CC |
denotes |
and |
T6927 |
3654-3660 |
RB |
denotes |
likely |
T6928 |
3661-3668 |
VBZ |
denotes |
results |
T6929 |
3669-3673 |
IN |
denotes |
from |
T6930 |
3674-3680 |
JJ |
denotes |
slight |
T6931 |
3681-3688 |
NN |
denotes |
leakage |
T6932 |
3689-3691 |
IN |
denotes |
at |
T6933 |
3692-3695 |
DT |
denotes |
the |
T6934 |
3696-3701 |
NN |
denotes |
level |
T6935 |
3702-3704 |
IN |
denotes |
of |
T6936 |
3705-3718 |
NN |
denotes |
transcription |
T6937 |
3719-3720 |
-LRB- |
denotes |
( |
T6938 |
3729-3734 |
VBN |
denotes |
shown |
T6939 |
3720-3724 |
NNS |
denotes |
data |
T6940 |
3725-3728 |
RB |
denotes |
not |
T6941 |
3734-3735 |
-RRB- |
denotes |
) |
T6942 |
3735-3736 |
. |
denotes |
. |
T6943 |
3736-4055 |
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 |
3737-3748 |
RB |
denotes |
Importantly |
T6945 |
3867-3870 |
VBD |
denotes |
was |
T6946 |
3748-3750 |
, |
denotes |
, |
T6947 |
3750-3753 |
DT |
denotes |
the |
T6948 |
3760-3766 |
NN |
denotes |
amount |
T6949 |
3754-3759 |
JJ |
denotes |
total |
T6950 |
3767-3769 |
IN |
denotes |
of |
T6951 |
3770-3773 |
NN |
denotes |
APP |
T6952 |
3774-3775 |
-LRB- |
denotes |
( |
T6953 |
3775-3785 |
JJ |
denotes |
endogenous |
T6954 |
3786-3790 |
CC |
denotes |
plus |
T6955 |
3791-3801 |
JJ |
denotes |
transgenic |
T6956 |
3801-3802 |
-RRB- |
denotes |
) |
T6957 |
3803-3806 |
CC |
denotes |
and |
T6958 |
3807-3814 |
JJ |
denotes |
related |
T6959 |
3815-3820 |
NNS |
denotes |
APLPs |
T6960 |
3821-3823 |
IN |
denotes |
in |
T6961 |
3824-3828 |
CC |
denotes |
both |
T6962 |
3829-3834 |
JJ |
denotes |
acute |
T6963 |
3859-3866 |
NNS |
denotes |
animals |
T6964 |
3835-3838 |
CC |
denotes |
and |
T6965 |
3839-3850 |
RB |
denotes |
chronically |
T6966 |
3851-3858 |
VBN |
denotes |
treated |
T6967 |
3871-3884 |
RB |
denotes |
statistically |
T6968 |
3885-3902 |
JJ |
denotes |
indistinguishable |
T6969 |
3903-3907 |
IN |
denotes |
from |
T6970 |
3908-3912 |
DT |
denotes |
that |
T6971 |
3913-3915 |
IN |
denotes |
in |
T6972 |
3916-3929 |
JJ |
denotes |
nontransgenic |
T6973 |
3930-3934 |
NNS |
denotes |
mice |
T6974 |
3935-3936 |
-LRB- |
denotes |
( |
T6975 |
3943-3945 |
NN |
denotes |
1D |
T6976 |
3936-3942 |
NN |
denotes |
Figure |
T6977 |
3945-3946 |
: |
denotes |
; |
T6978 |
3947-3958 |
JJ |
denotes |
statistical |
T6979 |
3959-3967 |
NNS |
denotes |
analyses |
T6980 |
4009-4018 |
VBN |
denotes |
presented |
T6981 |
3968-3971 |
IN |
denotes |
for |
T6982 |
3972-3983 |
NNS |
denotes |
experiments |
T6983 |
3984-3994 |
IN |
denotes |
throughout |
T6984 |
3995-3998 |
DT |
denotes |
the |
T6985 |
3999-4004 |
NN |
denotes |
study |
T6986 |
4005-4008 |
VBP |
denotes |
are |
T6987 |
4019-4021 |
IN |
denotes |
in |
T6988 |
4022-4025 |
DT |
denotes |
the |
T6989 |
4046-4053 |
NNS |
denotes |
legends |
T6990 |
4026-4038 |
VBG |
denotes |
accompanying |
T6991 |
4039-4045 |
NN |
denotes |
figure |
T6992 |
4053-4054 |
-RRB- |
denotes |
) |
T6993 |
4054-4055 |
. |
denotes |
. |
T6994 |
4055-4267 |
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 |
4056-4058 |
TO |
denotes |
To |
T6996 |
4059-4065 |
VB |
denotes |
ensure |
T6997 |
4176-4184 |
VBD |
denotes |
measured |
T6998 |
4066-4070 |
IN |
denotes |
that |
T6999 |
4089-4099 |
VBN |
denotes |
suppressed |
T7000 |
4071-4073 |
NN |
denotes |
Aβ |
T7001 |
4074-4084 |
NN |
denotes |
production |
T7002 |
4085-4088 |
VBD |
denotes |
was |
T7003 |
4100-4102 |
IN |
denotes |
in |
T7004 |
4103-4110 |
NN |
denotes |
concert |
T7005 |
4111-4115 |
IN |
denotes |
with |
T7006 |
4116-4119 |
DT |
denotes |
the |
T7007 |
4133-4143 |
NN |
denotes |
inhibition |
T7008 |
4120-4123 |
NN |
denotes |
dox |
T7009 |
4124-4132 |
VBN |
denotes |
mediated |
T7010 |
4123-4124 |
HYPH |
denotes |
- |
T7011 |
4144-4146 |
IN |
denotes |
of |
T7012 |
4147-4150 |
PRP$ |
denotes |
its |
T7013 |
4151-4160 |
NN |
denotes |
precursor |
T7014 |
4161-4167 |
NN |
denotes |
APPswe |
T7015 |
4168-4171 |
NN |
denotes |
ind |
T7016 |
4167-4168 |
HYPH |
denotes |
/ |
T7017 |
4171-4173 |
, |
denotes |
, |
T7018 |
4173-4175 |
PRP |
denotes |
we |
T7019 |
4185-4189 |
NN |
denotes |
Aβ40 |
T7020 |
4199-4205 |
NNS |
denotes |
levels |
T7021 |
4190-4193 |
CC |
denotes |
and |
T7022 |
4194-4198 |
NN |
denotes |
Aβ42 |
T7023 |
4206-4208 |
IN |
denotes |
by |
T7024 |
4209-4214 |
NN |
denotes |
ELISA |
T7025 |
4215-4217 |
IN |
denotes |
in |
T7026 |
4218-4227 |
NN |
denotes |
forebrain |
T7027 |
4228-4239 |
NNS |
denotes |
homogenates |
T7028 |
4240-4244 |
IN |
denotes |
from |
T7029 |
4245-4250 |
JJ |
denotes |
young |
T7030 |
4259-4266 |
NNS |
denotes |
animals |
T7031 |
4251-4254 |
NN |
denotes |
tet |
T7032 |
4255-4258 |
NN |
denotes |
off |
T7033 |
4254-4255 |
HYPH |
denotes |
- |
T7034 |
4266-4267 |
. |
denotes |
. |
T7035 |
4267-4444 |
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 |
4268-4270 |
IN |
denotes |
At |
T7037 |
4293-4299 |
VBD |
denotes |
lacked |
T7038 |
4271-4272 |
CD |
denotes |
1 |
T7039 |
4273-4275 |
NN |
denotes |
mo |
T7040 |
4276-4278 |
IN |
denotes |
of |
T7041 |
4279-4282 |
NN |
denotes |
age |
T7042 |
4282-4284 |
, |
denotes |
, |
T7043 |
4284-4287 |
DT |
denotes |
the |
T7044 |
4288-4292 |
NNS |
denotes |
mice |
T7045 |
4300-4307 |
JJ |
denotes |
visible |
T7046 |
4316-4326 |
NNS |
denotes |
aggregates |
T7047 |
4308-4315 |
NN |
denotes |
amyloid |
T7048 |
4327-4331 |
WDT |
denotes |
that |
T7049 |
4338-4341 |
VB |
denotes |
act |
T7050 |
4332-4337 |
MD |
denotes |
might |
T7051 |
4342-4344 |
IN |
denotes |
as |
T7052 |
4345-4347 |
DT |
denotes |
an |
T7053 |
4360-4369 |
NN |
denotes |
reservoir |
T7054 |
4348-4359 |
JJ |
denotes |
intractable |
T7055 |
4370-4372 |
IN |
denotes |
of |
T7056 |
4373-4380 |
NN |
denotes |
peptide |
T7057 |
4381-4390 |
VBG |
denotes |
remaining |
T7058 |
4391-4393 |
IN |
denotes |
in |
T7059 |
4394-4397 |
DT |
denotes |
the |
T7060 |
4398-4403 |
NN |
denotes |
brain |
T7061 |
4404-4409 |
IN |
denotes |
after |
T7062 |
4433-4443 |
VBN |
denotes |
suppressed |
T7063 |
4410-4413 |
DT |
denotes |
the |
T7064 |
4414-4423 |
NN |
denotes |
transgene |
T7065 |
4424-4427 |
VBD |
denotes |
had |
T7066 |
4428-4432 |
VBN |
denotes |
been |
T7067 |
4443-4444 |
. |
denotes |
. |
T7068 |
4444-4690 |
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 |
4445-4447 |
TO |
denotes |
To |
T7070 |
4456-4462 |
VB |
denotes |
ensure |
T7071 |
4448-4455 |
RB |
denotes |
further |
T7072 |
4573-4582 |
VBD |
denotes |
performed |
T7073 |
4463-4465 |
PRP |
denotes |
we |
T7074 |
4472-4478 |
VB |
denotes |
detect |
T7075 |
4466-4471 |
MD |
denotes |
could |
T7076 |
4479-4482 |
DT |
denotes |
any |
T7077 |
4498-4508 |
NNS |
denotes |
aggregates |
T7078 |
4483-4487 |
JJ |
denotes |
such |
T7079 |
4488-4497 |
JJ |
denotes |
insoluble |
T7080 |
4509-4513 |
WDT |
denotes |
that |
T7081 |
4520-4524 |
VB |
denotes |
bias |
T7082 |
4514-4519 |
MD |
denotes |
might |
T7083 |
4525-4528 |
PRP$ |
denotes |
our |
T7084 |
4529-4536 |
NN |
denotes |
measure |
T7085 |
4537-4539 |
IN |
denotes |
of |
T7086 |
4540-4547 |
NNS |
denotes |
changes |
T7087 |
4548-4550 |
IN |
denotes |
in |
T7088 |
4551-4558 |
NN |
denotes |
peptide |
T7089 |
4559-4568 |
NN |
denotes |
synthesis |
T7090 |
4568-4570 |
, |
denotes |
, |
T7091 |
4570-4572 |
PRP |
denotes |
we |
T7092 |
4583-4584 |
DT |
denotes |
a |
T7093 |
4607-4617 |
NN |
denotes |
extraction |
T7094 |
4585-4595 |
JJ |
denotes |
sequential |
T7095 |
4596-4601 |
CD |
denotes |
three |
T7096 |
4602-4606 |
NN |
denotes |
step |
T7097 |
4601-4602 |
HYPH |
denotes |
- |
T7098 |
4618-4622 |
IN |
denotes |
with |
T7099 |
4623-4626 |
NN |
denotes |
PBS |
T7100 |
4626-4628 |
, |
denotes |
, |
T7101 |
4628-4629 |
CD |
denotes |
2 |
T7102 |
4629-4630 |
NN |
denotes |
% |
T7103 |
4631-4634 |
NN |
denotes |
SDS |
T7104 |
4634-4636 |
, |
denotes |
, |
T7105 |
4636-4639 |
CC |
denotes |
and |
T7106 |
4640-4642 |
CD |
denotes |
70 |
T7107 |
4642-4643 |
NN |
denotes |
% |
T7108 |
4644-4646 |
NN |
denotes |
FA |
T7109 |
4647-4651 |
WDT |
denotes |
that |
T7110 |
4658-4666 |
VB |
denotes |
separate |
T7111 |
4652-4657 |
MD |
denotes |
would |
T7112 |
4667-4675 |
NNS |
denotes |
peptides |
T7113 |
4676-4678 |
IN |
denotes |
by |
T7114 |
4679-4689 |
NN |
denotes |
solubility |
T7115 |
4689-4690 |
. |
denotes |
. |
T7116 |
4690-5033 |
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 |
4691-4693 |
PRP |
denotes |
We |
T7118 |
4694-4702 |
VBD |
denotes |
compared |
T7119 |
4703-4706 |
DT |
denotes |
the |
T7120 |
4707-4713 |
NNS |
denotes |
levels |
T7121 |
4714-4716 |
IN |
denotes |
of |
T7122 |
4717-4722 |
JJ |
denotes |
human |
T7123 |
4723-4732 |
NN |
denotes |
transgene |
T7124 |
4733-4740 |
VBN |
denotes |
derived |
T7125 |
4732-4733 |
HYPH |
denotes |
- |
T7126 |
4741-4745 |
NN |
denotes |
Aβ40 |
T7127 |
4746-4749 |
CC |
denotes |
and |
T7128 |
4750-4754 |
NN |
denotes |
Aβ42 |
T7129 |
4755-4757 |
IN |
denotes |
in |
T7130 |
4758-4767 |
JJ |
denotes |
untreated |
T7131 |
4768-4772 |
NNS |
denotes |
mice |
T7132 |
4773-4775 |
IN |
denotes |
at |
T7133 |
4776-4777 |
CD |
denotes |
4 |
T7134 |
4784-4786 |
NN |
denotes |
wk |
T7135 |
4778-4781 |
CC |
denotes |
and |
T7136 |
4782-4783 |
CD |
denotes |
6 |
T7137 |
4787-4789 |
IN |
denotes |
of |
T7138 |
4790-4793 |
NN |
denotes |
age |
T7139 |
4794-4796 |
IN |
denotes |
to |
T7140 |
4797-4804 |
NNS |
denotes |
animals |
T7141 |
4805-4809 |
WDT |
denotes |
that |
T7142 |
4826-4830 |
VBN |
denotes |
born |
T7143 |
4810-4813 |
VBD |
denotes |
had |
T7144 |
4814-4820 |
CC |
denotes |
either |
T7145 |
4821-4825 |
VBN |
denotes |
been |
T7146 |
4831-4834 |
CC |
denotes |
and |
T7147 |
4835-4841 |
VBN |
denotes |
raised |
T7148 |
4842-4844 |
IN |
denotes |
on |
T7149 |
4845-4848 |
NN |
denotes |
dox |
T7150 |
4849-4851 |
CC |
denotes |
or |
T7151 |
4852-4856 |
WDT |
denotes |
that |
T7152 |
4866-4870 |
VBN |
denotes |
left |
T7153 |
4857-4860 |
VBD |
denotes |
had |
T7154 |
4861-4865 |
VBN |
denotes |
been |
T7155 |
4871-4880 |
JJ |
denotes |
untreated |
T7156 |
4881-4884 |
IN |
denotes |
for |
T7157 |
4885-4886 |
CD |
denotes |
4 |
T7158 |
4887-4889 |
NN |
denotes |
wk |
T7159 |
4890-4893 |
CC |
denotes |
and |
T7160 |
4894-4898 |
RB |
denotes |
then |
T7161 |
4899-4905 |
VBN |
denotes |
placed |
T7162 |
4906-4908 |
IN |
denotes |
on |
T7163 |
4909-4912 |
NN |
denotes |
dox |
T7164 |
4913-4917 |
NN |
denotes |
chow |
T7165 |
4918-4921 |
IN |
denotes |
for |
T7166 |
4922-4923 |
CD |
denotes |
2 |
T7167 |
4924-4926 |
NN |
denotes |
wk |
T7168 |
4927-4932 |
JJ |
denotes |
prior |
T7169 |
4933-4935 |
IN |
denotes |
to |
T7170 |
4936-4943 |
NN |
denotes |
harvest |
T7171 |
4944-4945 |
-LRB- |
denotes |
( |
T7172 |
5023-5027 |
NN |
denotes |
line |
T7173 |
4945-4948 |
DT |
denotes |
the |
T7174 |
4954-4960 |
NNS |
denotes |
groups |
T7175 |
4949-4953 |
JJ |
denotes |
same |
T7176 |
4961-4970 |
VBN |
denotes |
described |
T7177 |
4971-4976 |
RB |
denotes |
above |
T7178 |
4977-4980 |
IN |
denotes |
for |
T7179 |
4981-4991 |
NN |
denotes |
immunoblot |
T7180 |
4992-5000 |
NN |
denotes |
analysis |
T7181 |
5001-5003 |
IN |
denotes |
of |
T7182 |
5004-5010 |
NN |
denotes |
APPswe |
T7183 |
5011-5014 |
NN |
denotes |
ind |
T7184 |
5010-5011 |
HYPH |
denotes |
/ |
T7185 |
5015-5021 |
NNS |
denotes |
levels |
T7186 |
5021-5023 |
, |
denotes |
, |
T7187 |
5028-5031 |
CD |
denotes |
107 |
T7188 |
5031-5032 |
-RRB- |
denotes |
) |
T7189 |
5032-5033 |
. |
denotes |
. |
T7190 |
5033-5309 |
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 |
5034-5044 |
JJ |
denotes |
Consistent |
T7192 |
5139-5144 |
VBD |
denotes |
found |
T7193 |
5045-5049 |
IN |
denotes |
with |
T7194 |
5050-5053 |
DT |
denotes |
the |
T7195 |
5054-5063 |
NN |
denotes |
reduction |
T7196 |
5064-5066 |
IN |
denotes |
in |
T7197 |
5067-5071 |
JJ |
denotes |
full |
T7198 |
5072-5078 |
NN |
denotes |
length |
T7199 |
5071-5072 |
HYPH |
denotes |
- |
T7200 |
5090-5099 |
NN |
denotes |
synthesis |
T7201 |
5079-5085 |
NN |
denotes |
APPswe |
T7202 |
5086-5089 |
NN |
denotes |
ind |
T7203 |
5085-5086 |
HYPH |
denotes |
/ |
T7204 |
5100-5105 |
VBN |
denotes |
shown |
T7205 |
5106-5108 |
IN |
denotes |
by |
T7206 |
5109-5119 |
NN |
denotes |
immunoblot |
T7207 |
5120-5121 |
-LRB- |
denotes |
( |
T7208 |
5121-5124 |
VB |
denotes |
see |
T7209 |
5125-5131 |
NN |
denotes |
Figure |
T7210 |
5132-5133 |
CD |
denotes |
1 |
T7211 |
5133-5134 |
-RRB- |
denotes |
) |
T7212 |
5134-5136 |
, |
denotes |
, |
T7213 |
5136-5138 |
PRP |
denotes |
we |
T7214 |
5145-5149 |
IN |
denotes |
that |
T7215 |
5194-5204 |
VBN |
denotes |
suppressed |
T7216 |
5150-5159 |
NN |
denotes |
transgene |
T7217 |
5160-5167 |
VBN |
denotes |
derived |
T7218 |
5159-5160 |
HYPH |
denotes |
- |
T7219 |
5171-5177 |
NNS |
denotes |
levels |
T7220 |
5168-5170 |
NN |
denotes |
Aβ |
T7221 |
5178-5182 |
VBD |
denotes |
were |
T7222 |
5183-5193 |
RB |
denotes |
completely |
T7223 |
5205-5207 |
IN |
denotes |
in |
T7224 |
5208-5215 |
NNS |
denotes |
animals |
T7225 |
5216-5220 |
VBN |
denotes |
born |
T7226 |
5221-5224 |
CC |
denotes |
and |
T7227 |
5225-5231 |
VBN |
denotes |
raised |
T7228 |
5232-5234 |
IN |
denotes |
on |
T7229 |
5235-5238 |
NN |
denotes |
dox |
T7230 |
5238-5240 |
, |
denotes |
, |
T7231 |
5240-5243 |
CC |
denotes |
and |
T7232 |
5244-5248 |
VBD |
denotes |
were |
T7233 |
5257-5264 |
VBN |
denotes |
reduced |
T7234 |
5249-5256 |
RB |
denotes |
sharply |
T7235 |
5265-5274 |
VBG |
denotes |
following |
T7236 |
5275-5280 |
JJ |
denotes |
acute |
T7237 |
5299-5308 |
NN |
denotes |
treatment |
T7238 |
5281-5282 |
-LRB- |
denotes |
( |
T7239 |
5284-5286 |
NN |
denotes |
wk |
T7240 |
5282-5283 |
CD |
denotes |
2 |
T7241 |
5286-5287 |
-RRB- |
denotes |
) |
T7242 |
5288-5298 |
JJ |
denotes |
antibiotic |
T7243 |
5308-5309 |
. |
denotes |
. |
T7244 |
5309-5475 |
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 |
5310-5318 |
VBN |
denotes |
Compared |
T7246 |
5378-5385 |
VBD |
denotes |
dropped |
T7247 |
5319-5321 |
IN |
denotes |
to |
T7248 |
5322-5325 |
DT |
denotes |
the |
T7249 |
5326-5332 |
NNS |
denotes |
levels |
T7250 |
5333-5335 |
IN |
denotes |
in |
T7251 |
5336-5345 |
JJ |
denotes |
untreated |
T7252 |
5355-5359 |
NNS |
denotes |
mice |
T7253 |
5346-5347 |
CD |
denotes |
4 |
T7254 |
5348-5350 |
NN |
denotes |
wk |
T7255 |
5347-5348 |
HYPH |
denotes |
- |
T7256 |
5351-5354 |
JJ |
denotes |
old |
T7257 |
5350-5351 |
HYPH |
denotes |
- |
T7258 |
5359-5361 |
, |
denotes |
, |
T7259 |
5361-5364 |
NN |
denotes |
PBS |
T7260 |
5365-5372 |
JJ |
denotes |
soluble |
T7261 |
5364-5365 |
HYPH |
denotes |
- |
T7262 |
5373-5377 |
NN |
denotes |
Aβ42 |
T7263 |
5386-5388 |
IN |
denotes |
by |
T7264 |
5389-5393 |
CD |
denotes |
95.2 |
T7265 |
5393-5394 |
NN |
denotes |
% |
T7266 |
5395-5404 |
VBG |
denotes |
following |
T7267 |
5405-5406 |
CD |
denotes |
2 |
T7268 |
5407-5409 |
NN |
denotes |
wk |
T7269 |
5410-5412 |
IN |
denotes |
of |
T7270 |
5413-5416 |
NN |
denotes |
dox |
T7271 |
5417-5426 |
NN |
denotes |
treatment |
T7272 |
5427-5430 |
CC |
denotes |
and |
T7273 |
5431-5433 |
IN |
denotes |
by |
T7274 |
5440-5444 |
IN |
denotes |
with |
T7275 |
5434-5438 |
CD |
denotes |
99.2 |
T7276 |
5438-5439 |
NN |
denotes |
% |
T7277 |
5445-5452 |
JJ |
denotes |
chronic |
T7278 |
5453-5462 |
NN |
denotes |
treatment |
T7279 |
5463-5464 |
-LRB- |
denotes |
( |
T7280 |
5471-5473 |
NN |
denotes |
2A |
T7281 |
5464-5470 |
NN |
denotes |
Figure |
T7282 |
5473-5474 |
-RRB- |
denotes |
) |
T7283 |
5474-5475 |
. |
denotes |
. |
T7284 |
5475-5586 |
sentence |
denotes |
Similarly, SDS-soluble Aβ42 decreased by 75.2% and 94.8% following 2-wk or lifelong dox treatment (Figure 2B). |
T7285 |
5476-5485 |
RB |
denotes |
Similarly |
T7286 |
5504-5513 |
VBD |
denotes |
decreased |
T7287 |
5485-5487 |
, |
denotes |
, |
T7288 |
5487-5490 |
NN |
denotes |
SDS |
T7289 |
5491-5498 |
JJ |
denotes |
soluble |
T7290 |
5490-5491 |
HYPH |
denotes |
- |
T7291 |
5499-5503 |
NN |
denotes |
Aβ42 |
T7292 |
5514-5516 |
IN |
denotes |
by |
T7293 |
5517-5521 |
CD |
denotes |
75.2 |
T7294 |
5521-5522 |
NN |
denotes |
% |
T7295 |
5523-5526 |
CC |
denotes |
and |
T7296 |
5527-5531 |
CD |
denotes |
94.8 |
T7297 |
5531-5532 |
NN |
denotes |
% |
T7298 |
5533-5542 |
VBG |
denotes |
following |
T7299 |
5543-5544 |
CD |
denotes |
2 |
T7300 |
5545-5547 |
NN |
denotes |
wk |
T7301 |
5544-5545 |
HYPH |
denotes |
- |
T7302 |
5564-5573 |
NN |
denotes |
treatment |
T7303 |
5548-5550 |
CC |
denotes |
or |
T7304 |
5551-5559 |
JJ |
denotes |
lifelong |
T7305 |
5560-5563 |
NN |
denotes |
dox |
T7306 |
5574-5575 |
-LRB- |
denotes |
( |
T7307 |
5582-5584 |
NN |
denotes |
2B |
T7308 |
5575-5581 |
NN |
denotes |
Figure |
T7309 |
5584-5585 |
-RRB- |
denotes |
) |
T7310 |
5585-5586 |
. |
denotes |
. |
T7311 |
5586-5820 |
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 |
5587-5591 |
RB |
denotes |
Only |
T7313 |
5599-5607 |
NN |
denotes |
fraction |
T7314 |
5592-5595 |
DT |
denotes |
the |
T7315 |
5596-5598 |
NN |
denotes |
FA |
T7316 |
5608-5616 |
VBD |
denotes |
revealed |
T7317 |
5617-5618 |
DT |
denotes |
a |
T7318 |
5639-5643 |
NN |
denotes |
pool |
T7319 |
5619-5624 |
JJ |
denotes |
small |
T7320 |
5625-5628 |
NN |
denotes |
dox |
T7321 |
5629-5638 |
JJ |
denotes |
resistant |
T7322 |
5628-5629 |
HYPH |
denotes |
- |
T7323 |
5644-5646 |
IN |
denotes |
of |
T7324 |
5647-5654 |
NN |
denotes |
peptide |
T7325 |
5655-5657 |
IN |
denotes |
in |
T7326 |
5658-5665 |
RB |
denotes |
acutely |
T7327 |
5666-5673 |
VBN |
denotes |
treated |
T7328 |
5674-5681 |
NNS |
denotes |
animals |
T7329 |
5682-5686 |
WDT |
denotes |
that |
T7330 |
5690-5697 |
VBP |
denotes |
believe |
T7331 |
5687-5689 |
PRP |
denotes |
we |
T7332 |
5698-5708 |
VBZ |
denotes |
represents |
T7333 |
5709-5715 |
JJ |
denotes |
stable |
T7334 |
5727-5737 |
NNS |
denotes |
aggregates |
T7335 |
5716-5726 |
JJ |
denotes |
predeposit |
T7336 |
5738-5742 |
WDT |
denotes |
that |
T7337 |
5756-5767 |
VBN |
denotes |
accumulated |
T7338 |
5743-5747 |
VBP |
denotes |
have |
T7339 |
5748-5755 |
RB |
denotes |
already |
T7340 |
5768-5770 |
IN |
denotes |
by |
T7341 |
5771-5772 |
CD |
denotes |
4 |
T7342 |
5773-5775 |
NN |
denotes |
wk |
T7343 |
5776-5778 |
IN |
denotes |
of |
T7344 |
5779-5782 |
NN |
denotes |
age |
T7345 |
5783-5787 |
WRB |
denotes |
when |
T7346 |
5802-5807 |
VBN |
denotes |
begun |
T7347 |
5788-5797 |
NN |
denotes |
treatment |
T7348 |
5798-5801 |
VBD |
denotes |
was |
T7349 |
5808-5809 |
-LRB- |
denotes |
( |
T7350 |
5816-5818 |
NN |
denotes |
2C |
T7351 |
5809-5815 |
NN |
denotes |
Figure |
T7352 |
5818-5819 |
-RRB- |
denotes |
) |
T7353 |
5819-5820 |
. |
denotes |
. |
T7354 |
5820-5982 |
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 |
5821-5827 |
RB |
denotes |
Indeed |
T7356 |
5878-5884 |
VB |
denotes |
harbor |
T7357 |
5827-5829 |
, |
denotes |
, |
T7358 |
5829-5836 |
NNS |
denotes |
animals |
T7359 |
5837-5841 |
WDT |
denotes |
that |
T7360 |
5847-5851 |
VBN |
denotes |
born |
T7361 |
5842-5846 |
VBD |
denotes |
were |
T7362 |
5852-5855 |
CC |
denotes |
and |
T7363 |
5856-5862 |
VBN |
denotes |
raised |
T7364 |
5863-5865 |
IN |
denotes |
on |
T7365 |
5866-5869 |
NN |
denotes |
dox |
T7366 |
5870-5873 |
VBD |
denotes |
did |
T7367 |
5874-5877 |
RB |
denotes |
not |
T7368 |
5885-5889 |
DT |
denotes |
this |
T7369 |
5890-5899 |
NN |
denotes |
reservoir |
T7370 |
5900-5902 |
IN |
denotes |
of |
T7371 |
5903-5912 |
NN |
denotes |
treatment |
T7372 |
5913-5922 |
JJ |
denotes |
resistant |
T7373 |
5912-5913 |
HYPH |
denotes |
- |
T7374 |
5923-5930 |
NN |
denotes |
peptide |
T7375 |
5930-5932 |
, |
denotes |
, |
T7376 |
5932-5936 |
IN |
denotes |
with |
T7377 |
5937-5941 |
CD |
denotes |
96.3 |
T7378 |
5941-5942 |
NN |
denotes |
% |
T7379 |
5943-5947 |
JJR |
denotes |
less |
T7380 |
5948-5952 |
NN |
denotes |
Aβ42 |
T7381 |
5953-5957 |
IN |
denotes |
than |
T7382 |
5958-5967 |
JJ |
denotes |
untreated |
T7383 |
5977-5981 |
NNS |
denotes |
mice |
T7384 |
5968-5969 |
CD |
denotes |
4 |
T7385 |
5970-5972 |
NN |
denotes |
wk |
T7386 |
5969-5970 |
HYPH |
denotes |
- |
T7387 |
5973-5976 |
JJ |
denotes |
old |
T7388 |
5972-5973 |
HYPH |
denotes |
- |
T7389 |
5981-5982 |
. |
denotes |
. |
T7390 |
5982-6227 |
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 |
5983-5994 |
NN |
denotes |
Measurement |
T7392 |
6088-6100 |
VBD |
denotes |
demonstrated |
T7393 |
5995-5997 |
IN |
denotes |
of |
T7394 |
5998-6003 |
JJ |
denotes |
total |
T7395 |
6004-6006 |
NN |
denotes |
Aβ |
T7396 |
6007-6009 |
IN |
denotes |
in |
T7397 |
6010-6021 |
RB |
denotes |
chronically |
T7398 |
6022-6029 |
VBN |
denotes |
treated |
T7399 |
6030-6034 |
NNS |
denotes |
mice |
T7400 |
6034-6036 |
, |
denotes |
, |
T7401 |
6036-6045 |
VBG |
denotes |
including |
T7402 |
6046-6056 |
JJ |
denotes |
endogenous |
T7403 |
6079-6086 |
NN |
denotes |
peptide |
T7404 |
6057-6060 |
CC |
denotes |
and |
T7405 |
6061-6070 |
NN |
denotes |
transgene |
T7406 |
6071-6078 |
VBN |
denotes |
derived |
T7407 |
6070-6071 |
HYPH |
denotes |
- |
T7408 |
6086-6088 |
, |
denotes |
, |
T7409 |
6101-6105 |
IN |
denotes |
that |
T7410 |
6141-6148 |
VBN |
denotes |
reduced |
T7411 |
6106-6108 |
NN |
denotes |
Aβ |
T7412 |
6109-6115 |
NNS |
denotes |
levels |
T7413 |
6116-6118 |
IN |
denotes |
in |
T7414 |
6119-6122 |
NN |
denotes |
tet |
T7415 |
6123-6126 |
NN |
denotes |
off |
T7416 |
6122-6123 |
HYPH |
denotes |
- |
T7417 |
6131-6135 |
NNS |
denotes |
mice |
T7418 |
6127-6130 |
NN |
denotes |
APP |
T7419 |
6136-6140 |
VBD |
denotes |
were |
T7420 |
6149-6151 |
IN |
denotes |
to |
T7421 |
6152-6155 |
DT |
denotes |
the |
T7422 |
6156-6161 |
NN |
denotes |
level |
T7423 |
6162-6164 |
IN |
denotes |
of |
T7424 |
6165-6175 |
JJ |
denotes |
endogenous |
T7425 |
6176-6183 |
NN |
denotes |
peptide |
T7426 |
6184-6189 |
VBN |
denotes |
found |
T7427 |
6190-6192 |
IN |
denotes |
in |
T7428 |
6193-6206 |
JJ |
denotes |
nontransgenic |
T7429 |
6207-6214 |
NNS |
denotes |
animals |
T7430 |
6215-6216 |
-LRB- |
denotes |
( |
T7431 |
6223-6225 |
NN |
denotes |
2D |
T7432 |
6216-6222 |
NN |
denotes |
Figure |
T7433 |
6225-6226 |
-RRB- |
denotes |
) |
T7434 |
6226-6227 |
. |
denotes |
. |
T7435 |
6227-6438 |
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 |
6228-6233 |
VBN |
denotes |
Taken |
T7437 |
6323-6331 |
VBP |
denotes |
indicate |
T7438 |
6234-6242 |
RB |
denotes |
together |
T7439 |
6243-6247 |
IN |
denotes |
with |
T7440 |
6248-6251 |
DT |
denotes |
the |
T7441 |
6267-6271 |
NNS |
denotes |
data |
T7442 |
6252-6266 |
NN |
denotes |
immunoblotting |
T7443 |
6272-6275 |
IN |
denotes |
for |
T7444 |
6276-6280 |
JJ |
denotes |
full |
T7445 |
6281-6287 |
NN |
denotes |
length |
T7446 |
6280-6281 |
HYPH |
denotes |
- |
T7447 |
6295-6298 |
NN |
denotes |
ind |
T7448 |
6288-6294 |
NN |
denotes |
APPswe |
T7449 |
6294-6295 |
HYPH |
denotes |
/ |
T7450 |
6298-6300 |
, |
denotes |
, |
T7451 |
6300-6303 |
DT |
denotes |
the |
T7452 |
6310-6322 |
NNS |
denotes |
measurements |
T7453 |
6304-6309 |
NN |
denotes |
ELISA |
T7454 |
6332-6336 |
IN |
denotes |
that |
T7455 |
6397-6402 |
VBZ |
denotes |
leads |
T7456 |
6337-6340 |
NN |
denotes |
dox |
T7457 |
6341-6349 |
VBN |
denotes |
mediated |
T7458 |
6340-6341 |
HYPH |
denotes |
- |
T7459 |
6350-6361 |
NN |
denotes |
suppression |
T7460 |
6362-6364 |
IN |
denotes |
of |
T7461 |
6365-6375 |
JJ |
denotes |
transgenic |
T7462 |
6387-6396 |
NN |
denotes |
synthesis |
T7463 |
6376-6382 |
NN |
denotes |
APPswe |
T7464 |
6383-6386 |
NN |
denotes |
ind |
T7465 |
6382-6383 |
HYPH |
denotes |
/ |
T7466 |
6403-6405 |
IN |
denotes |
to |
T7467 |
6406-6414 |
JJ |
denotes |
parallel |
T7468 |
6415-6424 |
NN |
denotes |
reduction |
T7469 |
6425-6427 |
IN |
denotes |
of |
T7470 |
6428-6430 |
NN |
denotes |
Aβ |
T7471 |
6431-6437 |
NNS |
denotes |
levels |
T7472 |
6437-6438 |
. |
denotes |
. |
T7473 |
6438-9425 |
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 |
9235-9238 |
DT |
denotes |
The |
T7475 |
9245-9249 |
NNS |
denotes |
data |
T7476 |
9239-9244 |
NN |
denotes |
ELISA |
T7477 |
9255-9264 |
VBD |
denotes |
confirmed |
T7478 |
9250-9254 |
RB |
denotes |
also |
T7479 |
9265-9269 |
IN |
denotes |
that |
T7480 |
9321-9324 |
VBD |
denotes |
led |
T7481 |
9270-9283 |
NN |
denotes |
incorporation |
T7482 |
9284-9286 |
IN |
denotes |
of |
T7483 |
9287-9290 |
DT |
denotes |
the |
T7484 |
9311-9320 |
NNS |
denotes |
mutations |
T7485 |
9291-9298 |
JJ |
denotes |
Swedish |
T7486 |
9299-9302 |
CC |
denotes |
and |
T7487 |
9303-9310 |
NNP |
denotes |
Indiana |
T7488 |
9325-9327 |
IN |
denotes |
to |
T7489 |
9328-9332 |
JJ |
denotes |
high |
T7490 |
9333-9339 |
NNS |
denotes |
levels |
T7491 |
9340-9342 |
IN |
denotes |
of |
T7492 |
9343-9347 |
NN |
denotes |
Aβ42 |
T7493 |
9347-9349 |
, |
denotes |
, |
T7494 |
9349-9354 |
WDT |
denotes |
which |
T7495 |
9358-9367 |
VBD |
denotes |
predicted |
T7496 |
9355-9357 |
PRP |
denotes |
we |
T7497 |
9368-9373 |
MD |
denotes |
would |
T7498 |
9374-9380 |
VB |
denotes |
induce |
T7499 |
9381-9386 |
JJ |
denotes |
rapid |
T7500 |
9394-9403 |
NN |
denotes |
formation |
T7501 |
9387-9393 |
NN |
denotes |
plaque |
T7502 |
9404-9406 |
IN |
denotes |
in |
T7503 |
9407-9416 |
JJ |
denotes |
untreated |
T7504 |
9417-9424 |
NNS |
denotes |
animals |
T7505 |
9424-9425 |
. |
denotes |
. |
T7506 |
9425-9574 |
sentence |
denotes |
Histological characterization of double transgenic (CaMKIIα-tTA × tet-APPswe/ind) mice revealed early-onset amyloid formation in all four new lines. |
T7507 |
9426-9438 |
JJ |
denotes |
Histological |
T7508 |
9439-9455 |
NN |
denotes |
characterization |
T7509 |
9513-9521 |
VBD |
denotes |
revealed |
T7510 |
9456-9458 |
IN |
denotes |
of |
T7511 |
9459-9465 |
JJ |
denotes |
double |
T7512 |
9508-9512 |
NNS |
denotes |
mice |
T7513 |
9466-9476 |
JJ |
denotes |
transgenic |
T7514 |
9477-9478 |
-LRB- |
denotes |
( |
T7515 |
9496-9502 |
NN |
denotes |
APPswe |
T7516 |
9478-9485 |
NN |
denotes |
CaMKIIα |
T7517 |
9485-9486 |
HYPH |
denotes |
- |
T7518 |
9486-9489 |
NN |
denotes |
tTA |
T7519 |
9490-9491 |
SYM |
denotes |
× |
T7520 |
9492-9495 |
NN |
denotes |
tet |
T7521 |
9495-9496 |
HYPH |
denotes |
- |
T7522 |
9502-9503 |
HYPH |
denotes |
/ |
T7523 |
9503-9506 |
JJ |
denotes |
ind |
T7524 |
9506-9507 |
-RRB- |
denotes |
) |
T7525 |
9522-9527 |
JJ |
denotes |
early |
T7526 |
9528-9533 |
NN |
denotes |
onset |
T7527 |
9527-9528 |
HYPH |
denotes |
- |
T7528 |
9542-9551 |
NN |
denotes |
formation |
T7529 |
9534-9541 |
NN |
denotes |
amyloid |
T7530 |
9552-9554 |
IN |
denotes |
in |
T7531 |
9555-9558 |
DT |
denotes |
all |
T7532 |
9568-9573 |
NNS |
denotes |
lines |
T7533 |
9559-9563 |
CD |
denotes |
four |
T7534 |
9564-9567 |
JJ |
denotes |
new |
T7535 |
9573-9574 |
. |
denotes |
. |
T7536 |
9574-9650 |
sentence |
denotes |
Amyloid plaques were seen in mice as young as 8 wk of age (data not shown). |
T7537 |
9575-9582 |
NN |
denotes |
Amyloid |
T7538 |
9583-9590 |
NNS |
denotes |
plaques |
T7539 |
9596-9600 |
VBN |
denotes |
seen |
T7540 |
9591-9595 |
VBD |
denotes |
were |
T7541 |
9601-9603 |
IN |
denotes |
in |
T7542 |
9604-9608 |
NNS |
denotes |
mice |
T7543 |
9609-9611 |
RB |
denotes |
as |
T7544 |
9612-9617 |
JJ |
denotes |
young |
T7545 |
9618-9620 |
IN |
denotes |
as |
T7546 |
9621-9622 |
CD |
denotes |
8 |
T7547 |
9623-9625 |
NN |
denotes |
wk |
T7548 |
9626-9628 |
IN |
denotes |
of |
T7549 |
9629-9632 |
NN |
denotes |
age |
T7550 |
9633-9634 |
-LRB- |
denotes |
( |
T7551 |
9643-9648 |
VBN |
denotes |
shown |
T7552 |
9634-9638 |
NNS |
denotes |
data |
T7553 |
9639-9642 |
RB |
denotes |
not |
T7554 |
9648-9649 |
-RRB- |
denotes |
) |
T7555 |
9649-9650 |
. |
denotes |
. |
T7556 |
9650-9829 |
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 |
9651-9658 |
NNS |
denotes |
Plaques |
T7558 |
9664-9671 |
VBN |
denotes |
limited |
T7559 |
9659-9663 |
VBD |
denotes |
were |
T7560 |
9672-9674 |
IN |
denotes |
to |
T7561 |
9675-9678 |
DT |
denotes |
the |
T7562 |
9679-9688 |
NN |
denotes |
forebrain |
T7563 |
9688-9690 |
, |
denotes |
, |
T7564 |
9690-9699 |
VBG |
denotes |
including |
T7565 |
9700-9703 |
DT |
denotes |
the |
T7566 |
9704-9710 |
NN |
denotes |
cortex |
T7567 |
9710-9712 |
, |
denotes |
, |
T7568 |
9712-9723 |
NN |
denotes |
hippocampus |
T7569 |
9723-9725 |
, |
denotes |
, |
T7570 |
9725-9734 |
JJ |
denotes |
olfactory |
T7571 |
9735-9739 |
NN |
denotes |
bulb |
T7572 |
9739-9741 |
, |
denotes |
, |
T7573 |
9741-9744 |
CC |
denotes |
and |
T7574 |
9745-9753 |
NN |
denotes |
striatum |
T7575 |
9753-9755 |
, |
denotes |
, |
T7576 |
9755-9760 |
WRB |
denotes |
where |
T7577 |
9785-9790 |
VBN |
denotes |
known |
T7578 |
9761-9764 |
DT |
denotes |
the |
T7579 |
9773-9781 |
NN |
denotes |
promoter |
T7580 |
9765-9772 |
NN |
denotes |
CaMKIIα |
T7581 |
9782-9784 |
VBZ |
denotes |
is |
T7582 |
9791-9793 |
TO |
denotes |
to |
T7583 |
9794-9796 |
VB |
denotes |
be |
T7584 |
9797-9801 |
RBS |
denotes |
most |
T7585 |
9802-9808 |
JJ |
denotes |
active |
T7586 |
9809-9810 |
-LRB- |
denotes |
[ |
T7587 |
9813-9815 |
CD |
denotes |
28 |
T7588 |
9810-9812 |
CD |
denotes |
16 |
T7589 |
9812-9813 |
, |
denotes |
, |
T7590 |
9815-9816 |
-RRB- |
denotes |
] |
T7591 |
9817-9818 |
-LRB- |
denotes |
( |
T7592 |
9825-9827 |
NN |
denotes |
S2 |
T7593 |
9818-9824 |
NN |
denotes |
Figure |
T7594 |
9827-9828 |
-RRB- |
denotes |
) |
T7595 |
9828-9829 |
. |
denotes |
. |
T7596 |
9829-9939 |
sentence |
denotes |
By 6 mo of age, amyloid burden became severe, covering large areas of the cortex and hippocampus (Figure S3). |
T7597 |
9830-9832 |
IN |
denotes |
By |
T7598 |
9861-9867 |
VBD |
denotes |
became |
T7599 |
9833-9834 |
CD |
denotes |
6 |
T7600 |
9835-9837 |
NN |
denotes |
mo |
T7601 |
9838-9840 |
IN |
denotes |
of |
T7602 |
9841-9844 |
NN |
denotes |
age |
T7603 |
9844-9846 |
, |
denotes |
, |
T7604 |
9846-9853 |
NN |
denotes |
amyloid |
T7605 |
9854-9860 |
NN |
denotes |
burden |
T7606 |
9868-9874 |
JJ |
denotes |
severe |
T7607 |
9874-9876 |
, |
denotes |
, |
T7608 |
9876-9884 |
VBG |
denotes |
covering |
T7609 |
9885-9890 |
JJ |
denotes |
large |
T7610 |
9891-9896 |
NNS |
denotes |
areas |
T7611 |
9897-9899 |
IN |
denotes |
of |
T7612 |
9900-9903 |
DT |
denotes |
the |
T7613 |
9904-9910 |
NN |
denotes |
cortex |
T7614 |
9911-9914 |
CC |
denotes |
and |
T7615 |
9915-9926 |
NN |
denotes |
hippocampus |
T7616 |
9927-9928 |
-LRB- |
denotes |
( |
T7617 |
9935-9937 |
NN |
denotes |
S3 |
T7618 |
9928-9934 |
NN |
denotes |
Figure |
T7619 |
9937-9938 |
-RRB- |
denotes |
) |
T7620 |
9938-9939 |
. |
denotes |
. |
T7621 |
9939-10068 |
sentence |
denotes |
No lesions were seen in the cerebellum or brain stem even at late ages, consistent with CaMKIIα-controlled transgene expression. |
T7622 |
9940-9942 |
DT |
denotes |
No |
T7623 |
9943-9950 |
NNS |
denotes |
lesions |
T7624 |
9956-9960 |
VBN |
denotes |
seen |
T7625 |
9951-9955 |
VBD |
denotes |
were |
T7626 |
9961-9963 |
IN |
denotes |
in |
T7627 |
9964-9967 |
DT |
denotes |
the |
T7628 |
9968-9978 |
NN |
denotes |
cerebellum |
T7629 |
9979-9981 |
CC |
denotes |
or |
T7630 |
9982-9987 |
NN |
denotes |
brain |
T7631 |
9988-9992 |
NN |
denotes |
stem |
T7632 |
9993-9997 |
RB |
denotes |
even |
T7633 |
9998-10000 |
IN |
denotes |
at |
T7634 |
10001-10005 |
JJ |
denotes |
late |
T7635 |
10006-10010 |
NNS |
denotes |
ages |
T7636 |
10010-10012 |
, |
denotes |
, |
T7637 |
10012-10022 |
JJ |
denotes |
consistent |
T7638 |
10023-10027 |
IN |
denotes |
with |
T7639 |
10028-10035 |
NN |
denotes |
CaMKIIα |
T7640 |
10036-10046 |
VBN |
denotes |
controlled |
T7641 |
10035-10036 |
HYPH |
denotes |
- |
T7642 |
10057-10067 |
NN |
denotes |
expression |
T7643 |
10047-10056 |
NN |
denotes |
transgene |
T7644 |
10067-10068 |
. |
denotes |
. |
T7645 |
10068-10202 |
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 |
10069-10075 |
IN |
denotes |
Unlike |
T7647 |
10173-10176 |
VBP |
denotes |
are |
T7648 |
10076-10080 |
WP |
denotes |
what |
T7649 |
10084-10091 |
VBN |
denotes |
thought |
T7650 |
10081-10083 |
VBZ |
denotes |
is |
T7651 |
10092-10094 |
TO |
denotes |
to |
T7652 |
10095-10100 |
VB |
denotes |
occur |
T7653 |
10101-10103 |
IN |
denotes |
in |
T7654 |
10104-10107 |
DT |
denotes |
the |
T7655 |
10114-10121 |
NN |
denotes |
disease |
T7656 |
10108-10113 |
JJ |
denotes |
human |
T7657 |
10121-10123 |
, |
denotes |
, |
T7658 |
10123-10126 |
DT |
denotes |
the |
T7659 |
10141-10148 |
NNS |
denotes |
plaques |
T7660 |
10127-10132 |
JJ |
denotes |
first |
T7661 |
10133-10140 |
JJ |
denotes |
visible |
T7662 |
10149-10151 |
IN |
denotes |
in |
T7663 |
10152-10155 |
DT |
denotes |
the |
T7664 |
10168-10172 |
NNS |
denotes |
mice |
T7665 |
10156-10159 |
NN |
denotes |
tet |
T7666 |
10160-10163 |
NN |
denotes |
off |
T7667 |
10159-10160 |
HYPH |
denotes |
- |
T7668 |
10164-10167 |
NN |
denotes |
APP |
T7669 |
10177-10186 |
JJ |
denotes |
fibrillar |
T7670 |
10187-10192 |
VBN |
denotes |
cored |
T7671 |
10186-10187 |
HYPH |
denotes |
- |
T7672 |
10193-10201 |
NNS |
denotes |
deposits |
T7673 |
10201-10202 |
. |
denotes |
. |
T7674 |
10202-10337 |
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 |
10203-10205 |
PRP |
denotes |
We |
T7676 |
10211-10216 |
VBN |
denotes |
noted |
T7677 |
10206-10210 |
VBP |
denotes |
have |
T7678 |
10217-10220 |
DT |
denotes |
the |
T7679 |
10232-10242 |
NN |
denotes |
appearance |
T7680 |
10221-10225 |
JJ |
denotes |
same |
T7681 |
10226-10231 |
JJ |
denotes |
early |
T7682 |
10243-10245 |
IN |
denotes |
of |
T7683 |
10246-10251 |
VBN |
denotes |
cored |
T7684 |
10252-10260 |
NNS |
denotes |
deposits |
T7685 |
10261-10263 |
IN |
denotes |
in |
T7686 |
10264-10269 |
JJ |
denotes |
other |
T7687 |
10270-10275 |
NNS |
denotes |
lines |
T7688 |
10276-10278 |
IN |
denotes |
of |
T7689 |
10279-10282 |
NN |
denotes |
APP |
T7690 |
10294-10298 |
NNS |
denotes |
mice |
T7691 |
10283-10293 |
JJ |
denotes |
transgenic |
T7692 |
10299-10303 |
WDT |
denotes |
that |
T7693 |
10304-10310 |
VBP |
denotes |
harbor |
T7694 |
10311-10314 |
DT |
denotes |
the |
T7695 |
10323-10331 |
NN |
denotes |
mutation |
T7696 |
10315-10322 |
JJ |
denotes |
Swedish |
T7697 |
10332-10333 |
-LRB- |
denotes |
[ |
T7698 |
10333-10335 |
CD |
denotes |
27 |
T7699 |
10335-10336 |
-RRB- |
denotes |
] |
T7700 |
10336-10337 |
. |
denotes |
. |
T7701 |
10337-10440 |
sentence |
denotes |
Diffuse plaques were apparent in 6-mo-old tTA/APP mice, and became relatively abundant by 9 mo of age. |
T7702 |
10338-10345 |
NN |
denotes |
Diffuse |
T7703 |
10346-10353 |
NNS |
denotes |
plaques |
T7704 |
10354-10358 |
VBD |
denotes |
were |
T7705 |
10359-10367 |
JJ |
denotes |
apparent |
T7706 |
10368-10370 |
IN |
denotes |
in |
T7707 |
10371-10372 |
CD |
denotes |
6 |
T7708 |
10373-10375 |
NN |
denotes |
mo |
T7709 |
10372-10373 |
HYPH |
denotes |
- |
T7710 |
10376-10379 |
JJ |
denotes |
old |
T7711 |
10375-10376 |
HYPH |
denotes |
- |
T7712 |
10388-10392 |
NNS |
denotes |
mice |
T7713 |
10380-10383 |
NN |
denotes |
tTA |
T7714 |
10384-10387 |
NN |
denotes |
APP |
T7715 |
10383-10384 |
HYPH |
denotes |
/ |
T7716 |
10392-10394 |
, |
denotes |
, |
T7717 |
10394-10397 |
CC |
denotes |
and |
T7718 |
10398-10404 |
VBD |
denotes |
became |
T7719 |
10405-10415 |
RB |
denotes |
relatively |
T7720 |
10416-10424 |
JJ |
denotes |
abundant |
T7721 |
10425-10427 |
IN |
denotes |
by |
T7722 |
10428-10429 |
CD |
denotes |
9 |
T7723 |
10430-10432 |
NN |
denotes |
mo |
T7724 |
10433-10435 |
IN |
denotes |
of |
T7725 |
10436-10439 |
NN |
denotes |
age |
T7726 |
10439-10440 |
. |
denotes |
. |
T7727 |
10440-10594 |
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 |
10441-10443 |
IN |
denotes |
At |
T7729 |
10482-10486 |
VBD |
denotes |
were |
T7730 |
10444-10449 |
JJR |
denotes |
older |
T7731 |
10450-10454 |
NNS |
denotes |
ages |
T7732 |
10455-10456 |
-LRB- |
denotes |
( |
T7733 |
10456-10457 |
CD |
denotes |
9 |
T7734 |
10458-10460 |
CD |
denotes |
12 |
T7735 |
10457-10458 |
SYM |
denotes |
– |
T7736 |
10461-10463 |
NN |
denotes |
mo |
T7737 |
10463-10464 |
-RRB- |
denotes |
) |
T7738 |
10465-10472 |
NN |
denotes |
amyloid |
T7739 |
10473-10481 |
NNS |
denotes |
deposits |
T7740 |
10487-10494 |
JJ |
denotes |
visible |
T7741 |
10495-10497 |
IN |
denotes |
in |
T7742 |
10498-10501 |
DT |
denotes |
the |
T7743 |
10502-10510 |
NN |
denotes |
thalamus |
T7744 |
10510-10512 |
, |
denotes |
, |
T7745 |
10512-10517 |
WDT |
denotes |
which |
T7746 |
10532-10540 |
VBN |
denotes |
observed |
T7747 |
10518-10521 |
VBZ |
denotes |
has |
T7748 |
10522-10526 |
RB |
denotes |
also |
T7749 |
10527-10531 |
VBN |
denotes |
been |
T7750 |
10541-10543 |
IN |
denotes |
in |
T7751 |
10544-10548 |
NNS |
denotes |
mice |
T7752 |
10549-10559 |
VBG |
denotes |
expressing |
T7753 |
10560-10566 |
NN |
denotes |
mutant |
T7754 |
10567-10570 |
NN |
denotes |
APP |
T7755 |
10571-10574 |
IN |
denotes |
via |
T7756 |
10575-10578 |
DT |
denotes |
the |
T7757 |
10585-10593 |
NN |
denotes |
promoter |
T7758 |
10579-10582 |
NN |
denotes |
Thy |
T7759 |
10582-10583 |
HYPH |
denotes |
- |
T7760 |
10583-10584 |
CD |
denotes |
1 |
T7761 |
10593-10594 |
. |
denotes |
. |
T7762 |
10594-10752 |
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 |
10595-10598 |
DT |
denotes |
The |
T7764 |
10599-10607 |
NN |
denotes |
presence |
T7765 |
10653-10663 |
VBN |
denotes |
attributed |
T7766 |
10608-10610 |
IN |
denotes |
of |
T7767 |
10611-10618 |
NN |
denotes |
amyloid |
T7768 |
10619-10628 |
NN |
denotes |
pathology |
T7769 |
10629-10631 |
IN |
denotes |
in |
T7770 |
10632-10636 |
DT |
denotes |
this |
T7771 |
10637-10643 |
NN |
denotes |
region |
T7772 |
10644-10647 |
VBZ |
denotes |
has |
T7773 |
10648-10652 |
VBN |
denotes |
been |
T7774 |
10664-10666 |
IN |
denotes |
to |
T7775 |
10667-10673 |
JJ |
denotes |
axonal |
T7776 |
10674-10683 |
NN |
denotes |
transport |
T7777 |
10684-10686 |
IN |
denotes |
of |
T7778 |
10687-10690 |
NN |
denotes |
APP |
T7779 |
10691-10693 |
NN |
denotes |
Aβ |
T7780 |
10690-10691 |
HYPH |
denotes |
/ |
T7781 |
10694-10696 |
IN |
denotes |
to |
T7782 |
10697-10700 |
DT |
denotes |
the |
T7783 |
10701-10710 |
NNS |
denotes |
terminals |
T7784 |
10711-10713 |
IN |
denotes |
of |
T7785 |
10714-10722 |
JJ |
denotes |
cortical |
T7786 |
10723-10730 |
NNS |
denotes |
neurons |
T7787 |
10731-10733 |
IN |
denotes |
in |
T7788 |
10734-10737 |
DT |
denotes |
the |
T7789 |
10738-10746 |
NN |
denotes |
thalamus |
T7790 |
10747-10748 |
-LRB- |
denotes |
[ |
T7791 |
10748-10750 |
CD |
denotes |
29 |
T7792 |
10750-10751 |
-RRB- |
denotes |
] |
T7793 |
10751-10752 |
. |
denotes |
. |
T7794 |
10752-10870 |
sentence |
denotes |
Most importantly, only double transgenic mice, expressing both the tTA and APP transgenes, developed amyloid lesions. |
T7795 |
10753-10757 |
RBS |
denotes |
Most |
T7796 |
10758-10769 |
RB |
denotes |
importantly |
T7797 |
10844-10853 |
VBD |
denotes |
developed |
T7798 |
10769-10771 |
, |
denotes |
, |
T7799 |
10771-10775 |
RB |
denotes |
only |
T7800 |
10794-10798 |
NNS |
denotes |
mice |
T7801 |
10776-10782 |
JJ |
denotes |
double |
T7802 |
10783-10793 |
JJ |
denotes |
transgenic |
T7803 |
10798-10800 |
, |
denotes |
, |
T7804 |
10800-10810 |
VBG |
denotes |
expressing |
T7805 |
10811-10815 |
CC |
denotes |
both |
T7806 |
10832-10842 |
NNS |
denotes |
transgenes |
T7807 |
10816-10819 |
DT |
denotes |
the |
T7808 |
10820-10823 |
NN |
denotes |
tTA |
T7809 |
10824-10827 |
CC |
denotes |
and |
T7810 |
10828-10831 |
NN |
denotes |
APP |
T7811 |
10842-10844 |
, |
denotes |
, |
T7812 |
10854-10861 |
NN |
denotes |
amyloid |
T7813 |
10862-10869 |
NNS |
denotes |
lesions |
T7814 |
10869-10870 |
. |
denotes |
. |
T7815 |
10870-10953 |
sentence |
denotes |
Single transgenic mice up to 15 mo of age showed no sign of pathology (Figure S3). |
T7816 |
10871-10877 |
JJ |
denotes |
Single |
T7817 |
10878-10888 |
JJ |
denotes |
transgenic |
T7818 |
10889-10893 |
NNS |
denotes |
mice |
T7819 |
10913-10919 |
VBD |
denotes |
showed |
T7820 |
10894-10896 |
IN |
denotes |
up |
T7821 |
10900-10902 |
CD |
denotes |
15 |
T7822 |
10897-10899 |
IN |
denotes |
to |
T7823 |
10903-10905 |
NN |
denotes |
mo |
T7824 |
10906-10908 |
IN |
denotes |
of |
T7825 |
10909-10912 |
NN |
denotes |
age |
T7826 |
10920-10922 |
DT |
denotes |
no |
T7827 |
10923-10927 |
NN |
denotes |
sign |
T7828 |
10928-10930 |
IN |
denotes |
of |
T7829 |
10931-10940 |
NN |
denotes |
pathology |
T7830 |
10941-10942 |
-LRB- |
denotes |
( |
T7831 |
10949-10951 |
NN |
denotes |
S3 |
T7832 |
10942-10948 |
NN |
denotes |
Figure |
T7833 |
10951-10952 |
-RRB- |
denotes |
) |
T7834 |
10952-10953 |
. |
denotes |
. |
T7835 |
10953-11063 |
sentence |
denotes |
Similarly, amyloid pathology can be completely prevented in double transgenic animals born and raised on dox. |
T7836 |
10954-10963 |
RB |
denotes |
Similarly |
T7837 |
11001-11010 |
VBN |
denotes |
prevented |
T7838 |
10963-10965 |
, |
denotes |
, |
T7839 |
10965-10972 |
NN |
denotes |
amyloid |
T7840 |
10973-10982 |
NN |
denotes |
pathology |
T7841 |
10983-10986 |
MD |
denotes |
can |
T7842 |
10987-10989 |
VB |
denotes |
be |
T7843 |
10990-11000 |
RB |
denotes |
completely |
T7844 |
11011-11013 |
IN |
denotes |
in |
T7845 |
11014-11020 |
JJ |
denotes |
double |
T7846 |
11021-11031 |
JJ |
denotes |
transgenic |
T7847 |
11032-11039 |
NNS |
denotes |
animals |
T7848 |
11040-11044 |
VBN |
denotes |
born |
T7849 |
11045-11048 |
CC |
denotes |
and |
T7850 |
11049-11055 |
VBN |
denotes |
raised |
T7851 |
11056-11058 |
IN |
denotes |
on |
T7852 |
11059-11062 |
NN |
denotes |
dox |
T7853 |
11062-11063 |
. |
denotes |
. |
T7854 |
11063-11366 |
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 |
11064-11071 |
NNS |
denotes |
Animals |
T7856 |
11148-11156 |
VBD |
denotes |
harbored |
T7857 |
11072-11076 |
IN |
denotes |
from |
T7858 |
11077-11080 |
PRP$ |
denotes |
our |
T7859 |
11100-11104 |
NN |
denotes |
line |
T7860 |
11081-11088 |
JJS |
denotes |
highest |
T7861 |
11089-11099 |
VBG |
denotes |
expressing |
T7862 |
11105-11106 |
-LRB- |
denotes |
( |
T7863 |
11106-11110 |
NN |
denotes |
line |
T7864 |
11111-11114 |
CD |
denotes |
885 |
T7865 |
11114-11115 |
-RRB- |
denotes |
) |
T7866 |
11116-11126 |
VBN |
denotes |
maintained |
T7867 |
11127-11129 |
IN |
denotes |
on |
T7868 |
11130-11133 |
NN |
denotes |
dox |
T7869 |
11134-11137 |
IN |
denotes |
for |
T7870 |
11138-11140 |
IN |
denotes |
up |
T7871 |
11141-11143 |
IN |
denotes |
to |
T7872 |
11144-11145 |
CD |
denotes |
1 |
T7873 |
11146-11147 |
NN |
denotes |
y |
T7874 |
11157-11159 |
DT |
denotes |
no |
T7875 |
11168-11177 |
NN |
denotes |
pathology |
T7876 |
11160-11167 |
NN |
denotes |
amyloid |
T7877 |
11178-11179 |
-LRB- |
denotes |
( |
T7878 |
11188-11193 |
VBN |
denotes |
shown |
T7879 |
11179-11183 |
NNS |
denotes |
data |
T7880 |
11184-11187 |
RB |
denotes |
not |
T7881 |
11193-11194 |
-RRB- |
denotes |
) |
T7882 |
11194-11196 |
, |
denotes |
, |
T7883 |
11196-11206 |
VBG |
denotes |
indicating |
T7884 |
11207-11211 |
IN |
denotes |
that |
T7885 |
11285-11292 |
VB |
denotes |
provide |
T7886 |
11212-11220 |
JJ |
denotes |
residual |
T7887 |
11221-11228 |
NN |
denotes |
leakage |
T7888 |
11229-11231 |
IN |
denotes |
of |
T7889 |
11232-11241 |
NN |
denotes |
transgene |
T7890 |
11242-11252 |
NN |
denotes |
expression |
T7891 |
11253-11255 |
IN |
denotes |
in |
T7892 |
11256-11259 |
DT |
denotes |
the |
T7893 |
11260-11268 |
NN |
denotes |
presence |
T7894 |
11269-11271 |
IN |
denotes |
of |
T7895 |
11272-11275 |
NN |
denotes |
dox |
T7896 |
11276-11280 |
VBZ |
denotes |
does |
T7897 |
11281-11284 |
RB |
denotes |
not |
T7898 |
11293-11303 |
JJ |
denotes |
sufficient |
T7899 |
11307-11314 |
NN |
denotes |
peptide |
T7900 |
11304-11306 |
NN |
denotes |
Aβ |
T7901 |
11315-11317 |
TO |
denotes |
to |
T7902 |
11318-11324 |
VB |
denotes |
induce |
T7903 |
11325-11332 |
NN |
denotes |
amyloid |
T7904 |
11333-11342 |
NN |
denotes |
formation |
T7905 |
11343-11347 |
RB |
denotes |
even |
T7906 |
11348-11352 |
IN |
denotes |
over |
T7907 |
11353-11357 |
JJ |
denotes |
long |
T7908 |
11358-11365 |
NNS |
denotes |
periods |
T7909 |
11365-11366 |
. |
denotes |
. |
T7910 |
11366-11615 |
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 |
11367-11369 |
TO |
denotes |
To |
T7912 |
11370-11375 |
VB |
denotes |
mimic |
T7913 |
11438-11444 |
VBD |
denotes |
raised |
T7914 |
11376-11387 |
JJ |
denotes |
therapeutic |
T7915 |
11388-11400 |
NN |
denotes |
intervention |
T7916 |
11401-11405 |
IN |
denotes |
with |
T7917 |
11406-11416 |
NNS |
denotes |
inhibitors |
T7918 |
11417-11419 |
IN |
denotes |
of |
T7919 |
11420-11422 |
NN |
denotes |
Aβ |
T7920 |
11423-11433 |
NN |
denotes |
production |
T7921 |
11433-11435 |
, |
denotes |
, |
T7922 |
11435-11437 |
PRP |
denotes |
we |
T7923 |
11445-11446 |
DT |
denotes |
a |
T7924 |
11447-11452 |
NN |
denotes |
group |
T7925 |
11453-11455 |
IN |
denotes |
of |
T7926 |
11456-11458 |
CD |
denotes |
25 |
T7927 |
11477-11481 |
NNS |
denotes |
mice |
T7928 |
11459-11465 |
JJ |
denotes |
double |
T7929 |
11466-11476 |
JJ |
denotes |
transgenic |
T7930 |
11482-11483 |
-LRB- |
denotes |
( |
T7931 |
11497-11500 |
NN |
denotes |
APP |
T7932 |
11483-11490 |
NN |
denotes |
CaMKIIα |
T7933 |
11490-11491 |
HYPH |
denotes |
- |
T7934 |
11491-11494 |
NN |
denotes |
tTA |
T7935 |
11495-11496 |
SYM |
denotes |
× |
T7936 |
11501-11505 |
NN |
denotes |
line |
T7937 |
11506-11509 |
CD |
denotes |
107 |
T7938 |
11509-11510 |
-RRB- |
denotes |
) |
T7939 |
11511-11513 |
IN |
denotes |
on |
T7940 |
11514-11520 |
JJ |
denotes |
normal |
T7941 |
11521-11525 |
NN |
denotes |
food |
T7942 |
11526-11531 |
IN |
denotes |
until |
T7943 |
11532-11533 |
CD |
denotes |
6 |
T7944 |
11534-11536 |
NN |
denotes |
mo |
T7945 |
11537-11539 |
IN |
denotes |
of |
T7946 |
11540-11543 |
NN |
denotes |
age |
T7947 |
11543-11545 |
, |
denotes |
, |
T7948 |
11545-11549 |
WRB |
denotes |
when |
T7949 |
11553-11557 |
VBD |
denotes |
knew |
T7950 |
11550-11552 |
PRP |
denotes |
we |
T7951 |
11558-11565 |
NN |
denotes |
amyloid |
T7952 |
11566-11575 |
NN |
denotes |
formation |
T7953 |
11576-11579 |
VBD |
denotes |
was |
T7954 |
11580-11587 |
RB |
denotes |
already |
T7955 |
11588-11592 |
RB |
denotes |
well |
T7956 |
11593-11601 |
JJ |
denotes |
underway |
T7957 |
11602-11604 |
IN |
denotes |
in |
T7958 |
11605-11608 |
DT |
denotes |
the |
T7959 |
11609-11614 |
NN |
denotes |
brain |
T7960 |
11614-11615 |
. |
denotes |
. |
T7961 |
11615-11760 |
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 |
11616-11618 |
IN |
denotes |
At |
T7963 |
11650-11658 |
VBN |
denotes |
switched |
T7964 |
11619-11620 |
CD |
denotes |
6 |
T7965 |
11621-11623 |
NN |
denotes |
mo |
T7966 |
11623-11625 |
, |
denotes |
, |
T7967 |
11625-11629 |
NN |
denotes |
half |
T7968 |
11630-11632 |
IN |
denotes |
of |
T7969 |
11633-11636 |
DT |
denotes |
the |
T7970 |
11637-11644 |
NNS |
denotes |
animals |
T7971 |
11645-11649 |
VBD |
denotes |
were |
T7972 |
11659-11663 |
IN |
denotes |
from |
T7973 |
11664-11670 |
JJ |
denotes |
normal |
T7974 |
11671-11675 |
NN |
denotes |
chow |
T7975 |
11676-11678 |
IN |
denotes |
to |
T7976 |
11679-11683 |
NN |
denotes |
food |
T7977 |
11684-11694 |
VBG |
denotes |
containing |
T7978 |
11695-11698 |
NN |
denotes |
dox |
T7979 |
11699-11701 |
IN |
denotes |
at |
T7980 |
11702-11705 |
CD |
denotes |
200 |
T7981 |
11706-11708 |
NN |
denotes |
mg |
T7982 |
11708-11709 |
SYM |
denotes |
/ |
T7983 |
11709-11711 |
NN |
denotes |
kg |
T7984 |
11712-11717 |
IN |
denotes |
until |
T7985 |
11728-11738 |
VBN |
denotes |
sacrificed |
T7986 |
11718-11722 |
PRP |
denotes |
they |
T7987 |
11723-11727 |
VBD |
denotes |
were |
T7988 |
11739-11741 |
IN |
denotes |
at |
T7989 |
11742-11743 |
CD |
denotes |
9 |
T7990 |
11750-11752 |
NN |
denotes |
mo |
T7991 |
11744-11746 |
CC |
denotes |
or |
T7992 |
11747-11749 |
CD |
denotes |
12 |
T7993 |
11753-11755 |
IN |
denotes |
of |
T7994 |
11756-11759 |
NN |
denotes |
age |
T7995 |
11759-11760 |
. |
denotes |
. |
T7996 |
11760-11830 |
sentence |
denotes |
The remaining control animals were kept on standard chow (untreated). |
T7997 |
11761-11764 |
DT |
denotes |
The |
T7998 |
11783-11790 |
NNS |
denotes |
animals |
T7999 |
11765-11774 |
VBG |
denotes |
remaining |
T8000 |
11775-11782 |
NN |
denotes |
control |
T8001 |
11796-11800 |
VBN |
denotes |
kept |
T8002 |
11791-11795 |
VBD |
denotes |
were |
T8003 |
11801-11803 |
IN |
denotes |
on |
T8004 |
11804-11812 |
JJ |
denotes |
standard |
T8005 |
11813-11817 |
NN |
denotes |
chow |
T8006 |
11818-11819 |
-LRB- |
denotes |
( |
T8007 |
11819-11828 |
JJ |
denotes |
untreated |
T8008 |
11828-11829 |
-RRB- |
denotes |
) |
T8009 |
11829-11830 |
. |
denotes |
. |
T8010 |
11830-11975 |
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 |
11831-11833 |
IN |
denotes |
In |
T8012 |
11857-11864 |
VBN |
denotes |
created |
T8013 |
11834-11837 |
DT |
denotes |
all |
T8014 |
11837-11839 |
, |
denotes |
, |
T8015 |
11839-11843 |
CD |
denotes |
four |
T8016 |
11844-11851 |
NNS |
denotes |
cohorts |
T8017 |
11852-11856 |
VBD |
denotes |
were |
T8018 |
11864-11866 |
: |
denotes |
: |
T8019 |
11866-11867 |
CD |
denotes |
6 |
T8020 |
11868-11870 |
NN |
denotes |
mo |
T8021 |
11871-11880 |
JJ |
denotes |
untreated |
T8022 |
11881-11882 |
-LRB- |
denotes |
( |
T8023 |
11886-11887 |
CD |
denotes |
7 |
T8024 |
11882-11883 |
NN |
denotes |
n |
T8025 |
11884-11885 |
SYM |
denotes |
= |
T8026 |
11887-11888 |
-RRB- |
denotes |
) |
T8027 |
11888-11890 |
, |
denotes |
, |
T8028 |
11890-11891 |
CD |
denotes |
9 |
T8029 |
11892-11894 |
NN |
denotes |
mo |
T8030 |
11895-11904 |
JJ |
denotes |
untreated |
T8031 |
11905-11906 |
-LRB- |
denotes |
( |
T8032 |
11910-11911 |
CD |
denotes |
5 |
T8033 |
11906-11907 |
NN |
denotes |
n |
T8034 |
11908-11909 |
SYM |
denotes |
= |
T8035 |
11911-11912 |
-RRB- |
denotes |
) |
T8036 |
11912-11914 |
, |
denotes |
, |
T8037 |
11914-11915 |
CD |
denotes |
6 |
T8038 |
11916-11918 |
NN |
denotes |
mo |
T8039 |
11919-11920 |
SYM |
denotes |
+ |
T8040 |
11921-11922 |
CD |
denotes |
3 |
T8041 |
11923-11925 |
NN |
denotes |
mo |
T8042 |
11926-11933 |
VBN |
denotes |
treated |
T8043 |
11934-11935 |
-LRB- |
denotes |
( |
T8044 |
11939-11940 |
CD |
denotes |
8 |
T8045 |
11935-11936 |
NN |
denotes |
n |
T8046 |
11937-11938 |
SYM |
denotes |
= |
T8047 |
11940-11941 |
-RRB- |
denotes |
) |
T8048 |
11941-11943 |
, |
denotes |
, |
T8049 |
11943-11946 |
CC |
denotes |
and |
T8050 |
11947-11948 |
CD |
denotes |
6 |
T8051 |
11949-11951 |
NN |
denotes |
mo |
T8052 |
11952-11953 |
SYM |
denotes |
+ |
T8053 |
11954-11955 |
CD |
denotes |
6 |
T8054 |
11956-11958 |
NN |
denotes |
mo |
T8055 |
11959-11966 |
VBN |
denotes |
treated |
T8056 |
11967-11968 |
-LRB- |
denotes |
( |
T8057 |
11972-11973 |
CD |
denotes |
5 |
T8058 |
11968-11969 |
NN |
denotes |
n |
T8059 |
11970-11971 |
SYM |
denotes |
= |
T8060 |
11973-11974 |
-RRB- |
denotes |
) |
T8061 |
11974-11975 |
. |
denotes |
. |
T8062 |
11975-12098 |
sentence |
denotes |
Full suppression (>95%) of transgenic APPswe/ind levels in the dox-treated animals was confirmed by immunoblot (Figure 3). |
T8063 |
11976-11980 |
JJ |
denotes |
Full |
T8064 |
11981-11992 |
NN |
denotes |
suppression |
T8065 |
12063-12072 |
VBN |
denotes |
confirmed |
T8066 |
11993-11994 |
-LRB- |
denotes |
( |
T8067 |
11997-11998 |
NN |
denotes |
% |
T8068 |
11994-11995 |
SYM |
denotes |
> |
T8069 |
11995-11997 |
CD |
denotes |
95 |
T8070 |
11998-11999 |
-RRB- |
denotes |
) |
T8071 |
12000-12002 |
IN |
denotes |
of |
T8072 |
12003-12013 |
JJ |
denotes |
transgenic |
T8073 |
12025-12031 |
NNS |
denotes |
levels |
T8074 |
12014-12020 |
NN |
denotes |
APPswe |
T8075 |
12021-12024 |
NN |
denotes |
ind |
T8076 |
12020-12021 |
HYPH |
denotes |
/ |
T8077 |
12032-12034 |
IN |
denotes |
in |
T8078 |
12035-12038 |
DT |
denotes |
the |
T8079 |
12051-12058 |
NNS |
denotes |
animals |
T8080 |
12039-12042 |
NN |
denotes |
dox |
T8081 |
12043-12050 |
VBN |
denotes |
treated |
T8082 |
12042-12043 |
HYPH |
denotes |
- |
T8083 |
12059-12062 |
VBD |
denotes |
was |
T8084 |
12073-12075 |
IN |
denotes |
by |
T8085 |
12076-12086 |
NN |
denotes |
immunoblot |
T8086 |
12087-12088 |
-LRB- |
denotes |
( |
T8087 |
12088-12094 |
NN |
denotes |
Figure |
T8088 |
12095-12096 |
CD |
denotes |
3 |
T8089 |
12096-12097 |
-RRB- |
denotes |
) |
T8090 |
12097-12098 |
. |
denotes |
. |
T8091 |
12098-12325 |
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 |
12099-12101 |
TO |
denotes |
To |
T8093 |
12102-12108 |
VB |
denotes |
ensure |
T8094 |
12244-12251 |
VBD |
denotes |
treated |
T8095 |
12109-12113 |
IN |
denotes |
that |
T8096 |
12137-12147 |
VBN |
denotes |
suppressed |
T8097 |
12114-12117 |
DT |
denotes |
the |
T8098 |
12118-12127 |
NN |
denotes |
transgene |
T8099 |
12128-12133 |
MD |
denotes |
could |
T8100 |
12134-12136 |
VB |
denotes |
be |
T8101 |
12148-12150 |
RB |
denotes |
as |
T8102 |
12151-12158 |
RB |
denotes |
rapidly |
T8103 |
12159-12161 |
IN |
denotes |
in |
T8104 |
12162-12163 |
CD |
denotes |
6 |
T8105 |
12164-12166 |
NN |
denotes |
mo |
T8106 |
12163-12164 |
HYPH |
denotes |
- |
T8107 |
12167-12170 |
JJ |
denotes |
old |
T8108 |
12166-12167 |
HYPH |
denotes |
- |
T8109 |
12171-12175 |
NNS |
denotes |
mice |
T8110 |
12176-12180 |
IN |
denotes |
with |
T8111 |
12181-12190 |
JJ |
denotes |
fulminant |
T8112 |
12191-12200 |
NN |
denotes |
pathology |
T8113 |
12201-12203 |
IN |
denotes |
as |
T8114 |
12207-12210 |
MD |
denotes |
can |
T8115 |
12204-12206 |
PRP |
denotes |
it |
T8116 |
12211-12213 |
IN |
denotes |
in |
T8117 |
12214-12219 |
JJ |
denotes |
young |
T8118 |
12232-12239 |
NNS |
denotes |
animals |
T8119 |
12219-12221 |
, |
denotes |
, |
T8120 |
12221-12231 |
JJ |
denotes |
predeposit |
T8121 |
12239-12241 |
, |
denotes |
, |
T8122 |
12241-12243 |
PRP |
denotes |
we |
T8123 |
12252-12254 |
DT |
denotes |
an |
T8124 |
12266-12269 |
NN |
denotes |
set |
T8125 |
12255-12265 |
JJ |
denotes |
additional |
T8126 |
12270-12272 |
IN |
denotes |
of |
T8127 |
12273-12274 |
CD |
denotes |
6 |
T8128 |
12275-12277 |
NN |
denotes |
mo |
T8129 |
12274-12275 |
HYPH |
denotes |
- |
T8130 |
12278-12281 |
JJ |
denotes |
old |
T8131 |
12277-12278 |
HYPH |
denotes |
- |
T8132 |
12282-12289 |
NNS |
denotes |
animals |
T8133 |
12290-12294 |
IN |
denotes |
with |
T8134 |
12295-12298 |
NN |
denotes |
dox |
T8135 |
12299-12302 |
IN |
denotes |
for |
T8136 |
12303-12304 |
CD |
denotes |
1 |
T8137 |
12305-12307 |
NN |
denotes |
wk |
T8138 |
12308-12313 |
JJ |
denotes |
prior |
T8139 |
12314-12316 |
IN |
denotes |
to |
T8140 |
12317-12324 |
NN |
denotes |
harvest |
T8141 |
12324-12325 |
. |
denotes |
. |
T8142 |
12325-12566 |
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 |
12326-12337 |
RB |
denotes |
Importantly |
T8144 |
12401-12411 |
VBN |
denotes |
suppressed |
T8145 |
12337-12339 |
, |
denotes |
, |
T8146 |
12339-12343 |
CC |
denotes |
both |
T8147 |
12351-12354 |
NN |
denotes |
ind |
T8148 |
12344-12350 |
NN |
denotes |
APPswe |
T8149 |
12350-12351 |
HYPH |
denotes |
/ |
T8150 |
12365-12373 |
JJ |
denotes |
terminal |
T8151 |
12355-12358 |
CC |
denotes |
and |
T8152 |
12359-12362 |
NN |
denotes |
APP |
T8153 |
12363-12364 |
NN |
denotes |
C |
T8154 |
12362-12363 |
HYPH |
denotes |
– |
T8155 |
12364-12365 |
HYPH |
denotes |
- |
T8156 |
12383-12389 |
NNS |
denotes |
levels |
T8157 |
12374-12382 |
NN |
denotes |
fragment |
T8158 |
12390-12394 |
VBD |
denotes |
were |
T8159 |
12395-12400 |
RB |
denotes |
fully |
T8160 |
12412-12417 |
IN |
denotes |
after |
T8161 |
12418-12422 |
RB |
denotes |
only |
T8162 |
12425-12427 |
NN |
denotes |
wk |
T8163 |
12423-12424 |
CD |
denotes |
1 |
T8164 |
12428-12430 |
IN |
denotes |
of |
T8165 |
12431-12440 |
NN |
denotes |
treatment |
T8166 |
12440-12442 |
, |
denotes |
, |
T8167 |
12442-12452 |
VBG |
denotes |
indicating |
T8168 |
12453-12457 |
IN |
denotes |
that |
T8169 |
12533-12536 |
VBP |
denotes |
are |
T8170 |
12458-12461 |
DT |
denotes |
the |
T8171 |
12475-12479 |
NN |
denotes |
life |
T8172 |
12462-12464 |
FW |
denotes |
in |
T8173 |
12465-12469 |
FW |
denotes |
vivo |
T8174 |
12470-12474 |
NN |
denotes |
half |
T8175 |
12474-12475 |
HYPH |
denotes |
- |
T8176 |
12480-12482 |
IN |
denotes |
of |
T8177 |
12483-12489 |
NN |
denotes |
APPswe |
T8178 |
12490-12493 |
NN |
denotes |
ind |
T8179 |
12489-12490 |
HYPH |
denotes |
/ |
T8180 |
12494-12497 |
CC |
denotes |
and |
T8181 |
12498-12501 |
PRP$ |
denotes |
its |
T8182 |
12523-12532 |
NNS |
denotes |
fragments |
T8183 |
12502-12511 |
VBN |
denotes |
processed |
T8184 |
12512-12513 |
NN |
denotes |
C |
T8185 |
12514-12522 |
JJ |
denotes |
terminal |
T8186 |
12513-12514 |
HYPH |
denotes |
- |
T8187 |
12537-12547 |
RB |
denotes |
relatively |
T8188 |
12548-12553 |
JJ |
denotes |
short |
T8189 |
12554-12555 |
-LRB- |
denotes |
( |
T8190 |
12562-12564 |
NN |
denotes |
3D |
T8191 |
12555-12561 |
NN |
denotes |
Figure |
T8192 |
12564-12565 |
-RRB- |
denotes |
) |
T8193 |
12565-12566 |
. |
denotes |
. |
T8194 |
12566-14495 |
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 |
14313-14319 |
NN |
denotes |
Tissue |
T8196 |
14320-14328 |
NNS |
denotes |
sections |
T8197 |
14380-14387 |
VBN |
denotes |
stained |
T8198 |
14329-14333 |
IN |
denotes |
from |
T8199 |
14334-14338 |
DT |
denotes |
each |
T8200 |
14339-14345 |
NN |
denotes |
animal |
T8201 |
14346-14348 |
IN |
denotes |
in |
T8202 |
14349-14352 |
DT |
denotes |
the |
T8203 |
14368-14374 |
NNS |
denotes |
groups |
T8204 |
14353-14357 |
CD |
denotes |
four |
T8205 |
14358-14367 |
NN |
denotes |
treatment |
T8206 |
14375-14379 |
VBD |
denotes |
were |
T8207 |
14388-14391 |
IN |
denotes |
for |
T8208 |
14392-14399 |
NN |
denotes |
amyloid |
T8209 |
14400-14409 |
NN |
denotes |
pathology |
T8210 |
14410-14412 |
IN |
denotes |
by |
T8211 |
14413-14419 |
NNP |
denotes |
Hirano |
T8212 |
14420-14426 |
NN |
denotes |
silver |
T8213 |
14426-14428 |
, |
denotes |
, |
T8214 |
14428-14436 |
NNP |
denotes |
Campbell |
T8215 |
14437-14444 |
NNP |
denotes |
Switzer |
T8216 |
14436-14437 |
HYPH |
denotes |
- |
T8217 |
14445-14451 |
NN |
denotes |
silver |
T8218 |
14451-14453 |
, |
denotes |
, |
T8219 |
14453-14463 |
NN |
denotes |
thioflavin |
T8220 |
14464-14465 |
NN |
denotes |
S |
T8221 |
14463-14464 |
HYPH |
denotes |
- |
T8222 |
14465-14467 |
, |
denotes |
, |
T8223 |
14467-14470 |
CC |
denotes |
and |
T8224 |
14471-14473 |
NN |
denotes |
Aβ |
T8225 |
14474-14494 |
NN |
denotes |
immunohistochemistry |
T8226 |
14494-14495 |
. |
denotes |
. |
T8227 |
14495-14641 |
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 |
14496-14498 |
IN |
denotes |
As |
T8229 |
14499-14507 |
VBN |
denotes |
expected |
T8230 |
14535-14544 |
VBD |
denotes |
displayed |
T8231 |
14507-14509 |
, |
denotes |
, |
T8232 |
14509-14512 |
DT |
denotes |
the |
T8233 |
14528-14534 |
NN |
denotes |
cohort |
T8234 |
14513-14514 |
CD |
denotes |
6 |
T8235 |
14515-14517 |
NN |
denotes |
mo |
T8236 |
14518-14527 |
JJ |
denotes |
untreated |
T8237 |
14545-14553 |
JJ |
denotes |
moderate |
T8238 |
14562-14571 |
NN |
denotes |
pathology |
T8239 |
14554-14561 |
NN |
denotes |
amyloid |
T8240 |
14571-14573 |
, |
denotes |
, |
T8241 |
14573-14576 |
CC |
denotes |
and |
T8242 |
14577-14580 |
DT |
denotes |
the |
T8243 |
14596-14602 |
NN |
denotes |
cohort |
T8244 |
14581-14582 |
CD |
denotes |
9 |
T8245 |
14583-14585 |
NN |
denotes |
mo |
T8246 |
14586-14595 |
JJ |
denotes |
untreated |
T8247 |
14603-14613 |
VBD |
denotes |
progressed |
T8248 |
14614-14616 |
IN |
denotes |
to |
T8249 |
14617-14618 |
DT |
denotes |
a |
T8250 |
14634-14640 |
NN |
denotes |
burden |
T8251 |
14619-14625 |
JJ |
denotes |
severe |
T8252 |
14626-14633 |
NN |
denotes |
amyloid |
T8253 |
14640-14641 |
. |
denotes |
. |
T8254 |
14641-14914 |
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 |
14642-14644 |
IN |
denotes |
In |
T8256 |
14763-14772 |
VBD |
denotes |
resembled |
T8257 |
14645-14653 |
NN |
denotes |
contrast |
T8258 |
14653-14655 |
, |
denotes |
, |
T8259 |
14655-14658 |
DT |
denotes |
the |
T8260 |
14659-14665 |
NN |
denotes |
extent |
T8261 |
14666-14668 |
IN |
denotes |
of |
T8262 |
14669-14676 |
NN |
denotes |
amyloid |
T8263 |
14677-14686 |
NN |
denotes |
pathology |
T8264 |
14687-14689 |
IN |
denotes |
in |
T8265 |
14690-14694 |
NNS |
denotes |
mice |
T8266 |
14695-14699 |
IN |
denotes |
from |
T8267 |
14700-14703 |
DT |
denotes |
the |
T8268 |
14747-14754 |
NNS |
denotes |
cohorts |
T8269 |
14704-14705 |
CD |
denotes |
6 |
T8270 |
14706-14708 |
NN |
denotes |
mo |
T8271 |
14716-14723 |
VBN |
denotes |
treated |
T8272 |
14709-14710 |
SYM |
denotes |
+ |
T8273 |
14711-14712 |
CD |
denotes |
3 |
T8274 |
14713-14715 |
NN |
denotes |
mo |
T8275 |
14724-14726 |
CC |
denotes |
or |
T8276 |
14727-14728 |
CD |
denotes |
6 |
T8277 |
14729-14731 |
NN |
denotes |
mo |
T8278 |
14739-14746 |
VBN |
denotes |
treated |
T8279 |
14732-14733 |
SYM |
denotes |
+ |
T8280 |
14734-14735 |
CD |
denotes |
6 |
T8281 |
14736-14738 |
NN |
denotes |
mo |
T8282 |
14755-14762 |
RB |
denotes |
closely |
T8283 |
14773-14777 |
DT |
denotes |
that |
T8284 |
14778-14780 |
IN |
denotes |
of |
T8285 |
14781-14784 |
DT |
denotes |
the |
T8286 |
14800-14806 |
NN |
denotes |
cohort |
T8287 |
14785-14786 |
CD |
denotes |
6 |
T8288 |
14787-14789 |
NN |
denotes |
mo |
T8289 |
14790-14799 |
JJ |
denotes |
untreated |
T8290 |
14806-14808 |
, |
denotes |
, |
T8291 |
14808-14815 |
IN |
denotes |
despite |
T8292 |
14816-14819 |
DT |
denotes |
the |
T8293 |
14836-14846 |
NN |
denotes |
difference |
T8294 |
14820-14831 |
JJ |
denotes |
significant |
T8295 |
14832-14835 |
NN |
denotes |
age |
T8296 |
14847-14854 |
IN |
denotes |
between |
T8297 |
14855-14858 |
DT |
denotes |
the |
T8298 |
14881-14887 |
NNS |
denotes |
groups |
T8299 |
14859-14866 |
VBN |
denotes |
treated |
T8300 |
14867-14870 |
CC |
denotes |
and |
T8301 |
14871-14880 |
JJ |
denotes |
untreated |
T8302 |
14888-14889 |
-LRB- |
denotes |
( |
T8303 |
14889-14896 |
NNS |
denotes |
Figures |
T8304 |
14897-14898 |
CD |
denotes |
4 |
T8305 |
14899-14902 |
CC |
denotes |
and |
T8306 |
14903-14909 |
NN |
denotes |
Figure |
T8307 |
14910-14912 |
NN |
denotes |
S3 |
T8308 |
14912-14913 |
-RRB- |
denotes |
) |
T8309 |
14913-14914 |
. |
denotes |
. |
T8310 |
14914-15086 |
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 |
14915-14919 |
RB |
denotes |
Well |
T8312 |
14920-14926 |
VBN |
denotes |
formed |
T8313 |
14919-14920 |
HYPH |
denotes |
- |
T8314 |
14927-14934 |
NNS |
denotes |
plaques |
T8315 |
14935-14943 |
VBD |
denotes |
remained |
T8316 |
14944-14946 |
IN |
denotes |
in |
T8317 |
14947-14950 |
DT |
denotes |
the |
T8318 |
14959-14966 |
NNS |
denotes |
animals |
T8319 |
14951-14958 |
VBN |
denotes |
treated |
T8320 |
14967-14972 |
IN |
denotes |
after |
T8321 |
14973-14974 |
CD |
denotes |
6 |
T8322 |
14975-14977 |
NN |
denotes |
mo |
T8323 |
14978-14980 |
IN |
denotes |
of |
T8324 |
14981-14990 |
NN |
denotes |
transgene |
T8325 |
14991-15002 |
NN |
denotes |
suppression |
T8326 |
15002-15004 |
, |
denotes |
, |
T8327 |
15004-15008 |
RB |
denotes |
even |
T8328 |
15033-15038 |
VBN |
denotes |
given |
T8329 |
15009-15015 |
IN |
denotes |
though |
T8330 |
15016-15018 |
RB |
denotes |
as |
T8331 |
15019-15023 |
JJ |
denotes |
much |
T8332 |
15024-15028 |
NN |
denotes |
time |
T8333 |
15029-15032 |
VBD |
denotes |
was |
T8334 |
15039-15041 |
TO |
denotes |
to |
T8335 |
15042-15047 |
VB |
denotes |
clear |
T8336 |
15048-15051 |
DT |
denotes |
the |
T8337 |
15052-15059 |
NNS |
denotes |
lesions |
T8338 |
15060-15062 |
IN |
denotes |
as |
T8339 |
15072-15077 |
VBN |
denotes |
taken |
T8340 |
15063-15067 |
PRP |
denotes |
they |
T8341 |
15068-15071 |
VBD |
denotes |
had |
T8342 |
15078-15080 |
TO |
denotes |
to |
T8343 |
15081-15085 |
VB |
denotes |
form |
T8344 |
15085-15086 |
. |
denotes |
. |
T8345 |
15086-15180 |
sentence |
denotes |
Moreover, both types of amyloid, diffuse and fibrillar, remained intact throughout treatment. |
T8346 |
15087-15095 |
RB |
denotes |
Moreover |
T8347 |
15143-15151 |
VBD |
denotes |
remained |
T8348 |
15095-15097 |
, |
denotes |
, |
T8349 |
15097-15101 |
DT |
denotes |
both |
T8350 |
15102-15107 |
NNS |
denotes |
types |
T8351 |
15108-15110 |
IN |
denotes |
of |
T8352 |
15111-15118 |
NN |
denotes |
amyloid |
T8353 |
15118-15120 |
, |
denotes |
, |
T8354 |
15120-15127 |
JJ |
denotes |
diffuse |
T8355 |
15128-15131 |
CC |
denotes |
and |
T8356 |
15132-15141 |
JJ |
denotes |
fibrillar |
T8357 |
15141-15143 |
, |
denotes |
, |
T8358 |
15152-15158 |
JJ |
denotes |
intact |
T8359 |
15159-15169 |
IN |
denotes |
throughout |
T8360 |
15170-15179 |
NN |
denotes |
treatment |
T8361 |
15179-15180 |
. |
denotes |
. |
T8362 |
15180-15338 |
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 |
15181-15186 |
VBG |
denotes |
Using |
T8364 |
15267-15272 |
VBD |
denotes |
found |
T8365 |
15187-15190 |
DT |
denotes |
the |
T8366 |
15215-15220 |
NN |
denotes |
stain |
T8367 |
15191-15199 |
NNP |
denotes |
Campbell |
T8368 |
15200-15207 |
NNP |
denotes |
Switzer |
T8369 |
15199-15200 |
HYPH |
denotes |
- |
T8370 |
15208-15214 |
NN |
denotes |
silver |
T8371 |
15221-15223 |
TO |
denotes |
to |
T8372 |
15224-15235 |
VB |
denotes |
distinguish |
T8373 |
15236-15245 |
JJ |
denotes |
different |
T8374 |
15246-15251 |
NNS |
denotes |
forms |
T8375 |
15252-15254 |
IN |
denotes |
of |
T8376 |
15255-15262 |
NN |
denotes |
amyloid |
T8377 |
15262-15264 |
, |
denotes |
, |
T8378 |
15264-15266 |
PRP |
denotes |
we |
T8379 |
15273-15280 |
JJ |
denotes |
diffuse |
T8380 |
15281-15288 |
NNS |
denotes |
plaques |
T8381 |
15289-15293 |
VBD |
denotes |
were |
T8382 |
15294-15296 |
RB |
denotes |
as |
T8383 |
15297-15307 |
JJ |
denotes |
persistent |
T8384 |
15308-15310 |
IN |
denotes |
as |
T8385 |
15311-15316 |
VBN |
denotes |
cored |
T8386 |
15317-15325 |
NNS |
denotes |
deposits |
T8387 |
15326-15327 |
-LRB- |
denotes |
( |
T8388 |
15334-15336 |
NN |
denotes |
S4 |
T8389 |
15327-15333 |
NN |
denotes |
Figure |
T8390 |
15336-15337 |
-RRB- |
denotes |
) |
T8391 |
15337-15338 |
. |
denotes |
. |
T8392 |
15338-15463 |
sentence |
denotes |
It was nevertheless clear that dox-induced suppression of transgenic APP had completely halted the progression of pathology. |
T8393 |
15339-15341 |
PRP |
denotes |
It |
T8394 |
15342-15345 |
VBD |
denotes |
was |
T8395 |
15346-15358 |
RB |
denotes |
nevertheless |
T8396 |
15359-15364 |
JJ |
denotes |
clear |
T8397 |
15365-15369 |
IN |
denotes |
that |
T8398 |
15427-15433 |
VBN |
denotes |
halted |
T8399 |
15370-15373 |
NN |
denotes |
dox |
T8400 |
15374-15381 |
VBN |
denotes |
induced |
T8401 |
15373-15374 |
HYPH |
denotes |
- |
T8402 |
15382-15393 |
NN |
denotes |
suppression |
T8403 |
15394-15396 |
IN |
denotes |
of |
T8404 |
15397-15407 |
JJ |
denotes |
transgenic |
T8405 |
15408-15411 |
NN |
denotes |
APP |
T8406 |
15412-15415 |
VBD |
denotes |
had |
T8407 |
15416-15426 |
RB |
denotes |
completely |
T8408 |
15434-15437 |
DT |
denotes |
the |
T8409 |
15438-15449 |
NN |
denotes |
progression |
T8410 |
15450-15452 |
IN |
denotes |
of |
T8411 |
15453-15462 |
NN |
denotes |
pathology |
T8412 |
15462-15463 |
. |
denotes |
. |
T8413 |
15463-17367 |
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 |
17135-17137 |
TO |
denotes |
To |
T8415 |
17138-17145 |
VB |
denotes |
confirm |
T8416 |
17243-17251 |
VBD |
denotes |
repeated |
T8417 |
17146-17150 |
IN |
denotes |
that |
T8418 |
17203-17206 |
VBD |
denotes |
was |
T8419 |
17151-17154 |
DT |
denotes |
the |
T8420 |
17155-17161 |
NN |
denotes |
arrest |
T8421 |
17162-17164 |
IN |
denotes |
of |
T8422 |
17165-17172 |
NNS |
denotes |
plaques |
T8423 |
17173-17180 |
IN |
denotes |
without |
T8424 |
17181-17184 |
DT |
denotes |
any |
T8425 |
17185-17189 |
NN |
denotes |
sign |
T8426 |
17190-17192 |
IN |
denotes |
of |
T8427 |
17193-17202 |
NN |
denotes |
clearance |
T8428 |
17207-17210 |
RB |
denotes |
not |
T8429 |
17211-17217 |
JJ |
denotes |
unique |
T8430 |
17218-17220 |
IN |
denotes |
to |
T8431 |
17221-17224 |
DT |
denotes |
the |
T8432 |
17234-17238 |
NNS |
denotes |
mice |
T8433 |
17225-17229 |
NN |
denotes |
line |
T8434 |
17230-17233 |
CD |
denotes |
107 |
T8435 |
17238-17240 |
, |
denotes |
, |
T8436 |
17240-17242 |
PRP |
denotes |
we |
T8437 |
17252-17255 |
DT |
denotes |
the |
T8438 |
17272-17282 |
NN |
denotes |
experiment |
T8439 |
17256-17259 |
NN |
denotes |
dox |
T8440 |
17260-17271 |
NN |
denotes |
suppression |
T8441 |
17259-17260 |
HYPH |
denotes |
- |
T8442 |
17283-17285 |
IN |
denotes |
in |
T8443 |
17286-17287 |
DT |
denotes |
a |
T8444 |
17295-17299 |
NN |
denotes |
line |
T8445 |
17288-17294 |
JJ |
denotes |
second |
T8446 |
17300-17302 |
IN |
denotes |
of |
T8447 |
17303-17306 |
NN |
denotes |
tet |
T8448 |
17307-17310 |
NN |
denotes |
off |
T8449 |
17306-17307 |
HYPH |
denotes |
- |
T8450 |
17315-17319 |
NNS |
denotes |
mice |
T8451 |
17311-17314 |
NN |
denotes |
APP |
T8452 |
17320-17321 |
-LRB- |
denotes |
( |
T8453 |
17350-17354 |
NN |
denotes |
line |
T8454 |
17321-17328 |
NN |
denotes |
CaMKIIα |
T8455 |
17346-17349 |
NN |
denotes |
ind |
T8456 |
17328-17329 |
HYPH |
denotes |
- |
T8457 |
17329-17332 |
NN |
denotes |
tTA |
T8458 |
17333-17334 |
SYM |
denotes |
× |
T8459 |
17335-17338 |
NN |
denotes |
tet |
T8460 |
17338-17339 |
HYPH |
denotes |
- |
T8461 |
17339-17345 |
NN |
denotes |
APPswe |
T8462 |
17345-17346 |
HYPH |
denotes |
/ |
T8463 |
17355-17357 |
CD |
denotes |
18 |
T8464 |
17357-17358 |
: |
denotes |
; |
T8465 |
17359-17360 |
NN |
denotes |
n |
T8466 |
17363-17365 |
CD |
denotes |
22 |
T8467 |
17361-17362 |
SYM |
denotes |
= |
T8468 |
17365-17366 |
-RRB- |
denotes |
) |
T8469 |
17366-17367 |
. |
denotes |
. |
T8470 |
17367-17560 |
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 |
17368-17373 |
RB |
denotes |
Again |
T8472 |
17403-17408 |
VBN |
denotes |
begun |
T8473 |
17373-17375 |
, |
denotes |
, |
T8474 |
17375-17379 |
JJ |
denotes |
long |
T8475 |
17380-17384 |
NN |
denotes |
term |
T8476 |
17379-17380 |
HYPH |
denotes |
- |
T8477 |
17389-17398 |
NN |
denotes |
treatment |
T8478 |
17385-17388 |
NN |
denotes |
dox |
T8479 |
17399-17402 |
VBD |
denotes |
was |
T8480 |
17409-17411 |
IN |
denotes |
at |
T8481 |
17412-17413 |
CD |
denotes |
6 |
T8482 |
17414-17416 |
NN |
denotes |
mo |
T8483 |
17417-17419 |
IN |
denotes |
of |
T8484 |
17420-17423 |
NN |
denotes |
age |
T8485 |
17423-17425 |
, |
denotes |
, |
T8486 |
17425-17428 |
CC |
denotes |
and |
T8487 |
17429-17433 |
NNS |
denotes |
mice |
T8488 |
17439-17448 |
VBN |
denotes |
harvested |
T8489 |
17434-17438 |
VBD |
denotes |
were |
T8490 |
17449-17454 |
IN |
denotes |
after |
T8491 |
17455-17456 |
CD |
denotes |
3 |
T8492 |
17457-17459 |
NN |
denotes |
mo |
T8493 |
17460-17462 |
IN |
denotes |
of |
T8494 |
17463-17472 |
NN |
denotes |
transgene |
T8495 |
17473-17484 |
NN |
denotes |
suppression |
T8496 |
17485-17486 |
-LRB- |
denotes |
( |
T8497 |
17557-17558 |
CD |
denotes |
8 |
T8498 |
17486-17487 |
CD |
denotes |
6 |
T8499 |
17488-17490 |
NN |
denotes |
mo |
T8500 |
17491-17500 |
JJ |
denotes |
untreated |
T8501 |
17506-17507 |
CD |
denotes |
8 |
T8502 |
17500-17502 |
, |
denotes |
, |
T8503 |
17502-17503 |
NN |
denotes |
n |
T8504 |
17504-17505 |
SYM |
denotes |
= |
T8505 |
17507-17508 |
: |
denotes |
; |
T8506 |
17509-17510 |
CD |
denotes |
9 |
T8507 |
17511-17513 |
NN |
denotes |
mo |
T8508 |
17514-17523 |
JJ |
denotes |
untreated |
T8509 |
17529-17530 |
CD |
denotes |
6 |
T8510 |
17523-17525 |
, |
denotes |
, |
T8511 |
17525-17526 |
NN |
denotes |
n |
T8512 |
17527-17528 |
SYM |
denotes |
= |
T8513 |
17530-17531 |
: |
denotes |
; |
T8514 |
17532-17533 |
CD |
denotes |
6 |
T8515 |
17541-17543 |
NN |
denotes |
mo |
T8516 |
17534-17536 |
NN |
denotes |
mo |
T8517 |
17537-17538 |
SYM |
denotes |
+ |
T8518 |
17539-17540 |
CD |
denotes |
3 |
T8519 |
17544-17551 |
VBN |
denotes |
treated |
T8520 |
17551-17553 |
, |
denotes |
, |
T8521 |
17553-17554 |
NN |
denotes |
n |
T8522 |
17555-17556 |
SYM |
denotes |
= |
T8523 |
17558-17559 |
-RRB- |
denotes |
) |
T8524 |
17559-17560 |
. |
denotes |
. |
T8525 |
17560-17656 |
sentence |
denotes |
Immunoblotting for APP confirmed full transgene suppression in the treated animals (Figure S5). |
T8526 |
17561-17575 |
NN |
denotes |
Immunoblotting |
T8527 |
17584-17593 |
VBD |
denotes |
confirmed |
T8528 |
17576-17579 |
IN |
denotes |
for |
T8529 |
17580-17583 |
NN |
denotes |
APP |
T8530 |
17594-17598 |
JJ |
denotes |
full |
T8531 |
17609-17620 |
NN |
denotes |
suppression |
T8532 |
17599-17608 |
NN |
denotes |
transgene |
T8533 |
17621-17623 |
IN |
denotes |
in |
T8534 |
17624-17627 |
DT |
denotes |
the |
T8535 |
17636-17643 |
NNS |
denotes |
animals |
T8536 |
17628-17635 |
VBN |
denotes |
treated |
T8537 |
17644-17645 |
-LRB- |
denotes |
( |
T8538 |
17652-17654 |
NN |
denotes |
S5 |
T8539 |
17645-17651 |
NN |
denotes |
Figure |
T8540 |
17654-17655 |
-RRB- |
denotes |
) |
T8541 |
17655-17656 |
. |
denotes |
. |
T8542 |
17656-17784 |
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 |
17657-17659 |
IN |
denotes |
As |
T8544 |
17713-17721 |
VBD |
denotes |
worsened |
T8545 |
17660-17662 |
IN |
denotes |
in |
T8546 |
17663-17666 |
DT |
denotes |
the |
T8547 |
17676-17680 |
NNS |
denotes |
mice |
T8548 |
17667-17671 |
NN |
denotes |
line |
T8549 |
17672-17675 |
CD |
denotes |
107 |
T8550 |
17681-17690 |
VBN |
denotes |
described |
T8551 |
17691-17696 |
RB |
denotes |
above |
T8552 |
17696-17698 |
, |
denotes |
, |
T8553 |
17698-17705 |
NN |
denotes |
amyloid |
T8554 |
17706-17712 |
NN |
denotes |
burden |
T8555 |
17722-17735 |
RB |
denotes |
substantially |
T8556 |
17736-17738 |
IN |
denotes |
in |
T8557 |
17739-17742 |
DT |
denotes |
the |
T8558 |
17753-17757 |
NNS |
denotes |
mice |
T8559 |
17743-17752 |
JJ |
denotes |
untreated |
T8560 |
17758-17765 |
IN |
denotes |
between |
T8561 |
17766-17767 |
CD |
denotes |
6 |
T8562 |
17774-17776 |
NN |
denotes |
mo |
T8563 |
17768-17771 |
CC |
denotes |
and |
T8564 |
17772-17773 |
CD |
denotes |
9 |
T8565 |
17777-17779 |
IN |
denotes |
of |
T8566 |
17780-17783 |
NN |
denotes |
age |
T8567 |
17783-17784 |
. |
denotes |
. |
T8568 |
17784-17917 |
sentence |
denotes |
Suppression of transgene expression abruptly arrested progression of pathology (Figure S6), but again without any sign of reduction. |
T8569 |
17785-17796 |
NN |
denotes |
Suppression |
T8570 |
17830-17838 |
VBD |
denotes |
arrested |
T8571 |
17797-17799 |
IN |
denotes |
of |
T8572 |
17800-17809 |
NN |
denotes |
transgene |
T8573 |
17810-17820 |
NN |
denotes |
expression |
T8574 |
17821-17829 |
RB |
denotes |
abruptly |
T8575 |
17839-17850 |
NN |
denotes |
progression |
T8576 |
17851-17853 |
IN |
denotes |
of |
T8577 |
17854-17863 |
NN |
denotes |
pathology |
T8578 |
17864-17865 |
-LRB- |
denotes |
( |
T8579 |
17872-17874 |
NN |
denotes |
S6 |
T8580 |
17865-17871 |
NN |
denotes |
Figure |
T8581 |
17874-17875 |
-RRB- |
denotes |
) |
T8582 |
17875-17877 |
, |
denotes |
, |
T8583 |
17877-17880 |
CC |
denotes |
but |
T8584 |
17887-17894 |
IN |
denotes |
without |
T8585 |
17881-17886 |
RB |
denotes |
again |
T8586 |
17895-17898 |
DT |
denotes |
any |
T8587 |
17899-17903 |
NN |
denotes |
sign |
T8588 |
17904-17906 |
IN |
denotes |
of |
T8589 |
17907-17916 |
NN |
denotes |
reduction |
T8590 |
17916-17917 |
. |
denotes |
. |
T8591 |
17917-18021 |
sentence |
denotes |
Both silver- and thioflavin-S-positive plaques could still be found in each of the dox-treated animals. |
T8592 |
17918-17922 |
CC |
denotes |
Both |
T8593 |
17923-17929 |
NN |
denotes |
silver |
T8594 |
17948-17956 |
JJ |
denotes |
positive |
T8595 |
17929-17930 |
HYPH |
denotes |
- |
T8596 |
17931-17934 |
CC |
denotes |
and |
T8597 |
17935-17945 |
NN |
denotes |
thioflavin |
T8598 |
17946-17947 |
NN |
denotes |
S |
T8599 |
17945-17946 |
HYPH |
denotes |
- |
T8600 |
17947-17948 |
HYPH |
denotes |
- |
T8601 |
17957-17964 |
NNS |
denotes |
plaques |
T8602 |
17980-17985 |
VBN |
denotes |
found |
T8603 |
17965-17970 |
MD |
denotes |
could |
T8604 |
17971-17976 |
RB |
denotes |
still |
T8605 |
17977-17979 |
VB |
denotes |
be |
T8606 |
17986-17988 |
IN |
denotes |
in |
T8607 |
17989-17993 |
DT |
denotes |
each |
T8608 |
17994-17996 |
IN |
denotes |
of |
T8609 |
17997-18000 |
DT |
denotes |
the |
T8610 |
18013-18020 |
NNS |
denotes |
animals |
T8611 |
18001-18004 |
NN |
denotes |
dox |
T8612 |
18005-18012 |
VBN |
denotes |
treated |
T8613 |
18004-18005 |
HYPH |
denotes |
- |
T8614 |
18020-18021 |
. |
denotes |
. |
T8615 |
18021-18204 |
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 |
18022-18024 |
PRP |
denotes |
We |
T8617 |
18039-18047 |
VBD |
denotes |
measured |
T8618 |
18025-18038 |
RB |
denotes |
biochemically |
T8619 |
18048-18051 |
DT |
denotes |
the |
T8620 |
18052-18058 |
NN |
denotes |
amount |
T8621 |
18059-18061 |
IN |
denotes |
of |
T8622 |
18062-18072 |
VBN |
denotes |
aggregated |
T8623 |
18073-18075 |
NN |
denotes |
Aβ |
T8624 |
18076-18078 |
IN |
denotes |
in |
T8625 |
18079-18082 |
DT |
denotes |
the |
T8626 |
18083-18089 |
NNS |
denotes |
brains |
T8627 |
18090-18092 |
IN |
denotes |
of |
T8628 |
18093-18096 |
PRP$ |
denotes |
our |
T8629 |
18097-18101 |
NNS |
denotes |
mice |
T8630 |
18102-18108 |
IN |
denotes |
before |
T8631 |
18109-18112 |
CC |
denotes |
and |
T8632 |
18113-18118 |
IN |
denotes |
after |
T8633 |
18119-18128 |
NN |
denotes |
transgene |
T8634 |
18129-18140 |
NN |
denotes |
suppression |
T8635 |
18141-18146 |
VBG |
denotes |
using |
T8636 |
18147-18153 |
NN |
denotes |
filter |
T8637 |
18154-18158 |
NN |
denotes |
trap |
T8638 |
18159-18167 |
NN |
denotes |
analysis |
T8639 |
18168-18170 |
IN |
denotes |
of |
T8640 |
18171-18179 |
JJ |
denotes |
cortical |
T8641 |
18180-18186 |
NN |
denotes |
tissue |
T8642 |
18187-18191 |
IN |
denotes |
from |
T8643 |
18192-18196 |
DT |
denotes |
each |
T8644 |
18197-18203 |
NN |
denotes |
animal |
T8645 |
18203-18204 |
. |
denotes |
. |
T8646 |
18204-18427 |
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 |
18205-18207 |
IN |
denotes |
In |
T8648 |
18263-18269 |
VBN |
denotes |
passed |
T8649 |
18208-18212 |
DT |
denotes |
this |
T8650 |
18213-18218 |
NN |
denotes |
assay |
T8651 |
18218-18220 |
, |
denotes |
, |
T8652 |
18220-18226 |
JJ |
denotes |
serial |
T8653 |
18227-18236 |
NNS |
denotes |
dilutions |
T8654 |
18237-18239 |
IN |
denotes |
of |
T8655 |
18240-18247 |
NN |
denotes |
protein |
T8656 |
18248-18258 |
NN |
denotes |
homogenate |
T8657 |
18259-18262 |
VBP |
denotes |
are |
T8658 |
18356-18362 |
VBP |
denotes |
become |
T8659 |
18270-18277 |
IN |
denotes |
through |
T8660 |
18278-18279 |
DT |
denotes |
a |
T8661 |
18298-18304 |
NN |
denotes |
filter |
T8662 |
18280-18289 |
NN |
denotes |
cellulose |
T8663 |
18290-18297 |
NN |
denotes |
acetate |
T8664 |
18304-18305 |
: |
denotes |
; |
T8665 |
18306-18315 |
NNS |
denotes |
particles |
T8666 |
18316-18322 |
JJR |
denotes |
larger |
T8667 |
18323-18327 |
IN |
denotes |
than |
T8668 |
18328-18331 |
DT |
denotes |
the |
T8669 |
18337-18341 |
NN |
denotes |
size |
T8670 |
18332-18336 |
NN |
denotes |
pore |
T8671 |
18342-18344 |
IN |
denotes |
of |
T8672 |
18345-18348 |
DT |
denotes |
the |
T8673 |
18349-18355 |
NN |
denotes |
filter |
T8674 |
18363-18370 |
JJ |
denotes |
trapped |
T8675 |
18371-18373 |
IN |
denotes |
in |
T8676 |
18374-18377 |
DT |
denotes |
the |
T8677 |
18378-18386 |
NN |
denotes |
membrane |
T8678 |
18387-18390 |
CC |
denotes |
and |
T8679 |
18391-18394 |
VBP |
denotes |
are |
T8680 |
18395-18403 |
VBN |
denotes |
revealed |
T8681 |
18404-18406 |
IN |
denotes |
by |
T8682 |
18407-18421 |
NN |
denotes |
immunoblotting |
T8683 |
18422-18423 |
-LRB- |
denotes |
[ |
T8684 |
18423-18425 |
CD |
denotes |
22 |
T8685 |
18425-18426 |
-RRB- |
denotes |
] |
T8686 |
18426-18427 |
. |
denotes |
. |
T8687 |
18427-18649 |
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 |
18428-18438 |
JJ |
denotes |
Consistent |
T8689 |
18547-18550 |
VBD |
denotes |
had |
T8690 |
18439-18443 |
IN |
denotes |
with |
T8691 |
18444-18447 |
PRP$ |
denotes |
our |
T8692 |
18455-18463 |
NN |
denotes |
analysis |
T8693 |
18448-18454 |
JJ |
denotes |
visual |
T8694 |
18464-18466 |
IN |
denotes |
of |
T8695 |
18467-18470 |
DT |
denotes |
the |
T8696 |
18484-18492 |
NNS |
denotes |
sections |
T8697 |
18471-18483 |
JJ |
denotes |
histological |
T8698 |
18492-18494 |
, |
denotes |
, |
T8699 |
18494-18498 |
NN |
denotes |
line |
T8700 |
18511-18515 |
NNS |
denotes |
mice |
T8701 |
18499-18502 |
CD |
denotes |
107 |
T8702 |
18503-18506 |
NN |
denotes |
tTA |
T8703 |
18507-18510 |
NN |
denotes |
APP |
T8704 |
18506-18507 |
HYPH |
denotes |
/ |
T8705 |
18516-18523 |
VBN |
denotes |
treated |
T8706 |
18524-18528 |
IN |
denotes |
with |
T8707 |
18529-18532 |
NN |
denotes |
dox |
T8708 |
18533-18536 |
IN |
denotes |
for |
T8709 |
18537-18538 |
CD |
denotes |
3 |
T8710 |
18544-18546 |
NN |
denotes |
mo |
T8711 |
18539-18541 |
CC |
denotes |
or |
T8712 |
18542-18543 |
CD |
denotes |
6 |
T8713 |
18551-18554 |
DT |
denotes |
the |
T8714 |
18560-18566 |
NN |
denotes |
amount |
T8715 |
18555-18559 |
JJ |
denotes |
same |
T8716 |
18567-18569 |
IN |
denotes |
of |
T8717 |
18570-18580 |
VBN |
denotes |
aggregated |
T8718 |
18581-18583 |
NN |
denotes |
Aβ |
T8719 |
18584-18586 |
IN |
denotes |
as |
T8720 |
18587-18591 |
WRB |
denotes |
when |
T8721 |
18597-18604 |
VBD |
denotes |
started |
T8722 |
18592-18596 |
PRP |
denotes |
they |
T8723 |
18605-18614 |
NN |
denotes |
treatment |
T8724 |
18615-18617 |
IN |
denotes |
at |
T8725 |
18618-18619 |
CD |
denotes |
6 |
T8726 |
18620-18622 |
NN |
denotes |
mo |
T8727 |
18623-18625 |
IN |
denotes |
of |
T8728 |
18626-18629 |
NN |
denotes |
age |
T8729 |
18630-18631 |
-LRB- |
denotes |
( |
T8730 |
18638-18640 |
NN |
denotes |
4A |
T8731 |
18631-18637 |
NN |
denotes |
Figure |
T8732 |
18641-18644 |
CC |
denotes |
and |
T8733 |
18645-18647 |
NN |
denotes |
4B |
T8734 |
18647-18648 |
-RRB- |
denotes |
) |
T8735 |
18648-18649 |
. |
denotes |
. |
T8736 |
18649-18758 |
sentence |
denotes |
In contrast, untreated 9-mo-old mice had almost twice as much aggregated Aβ as either of the treated groups. |
T8737 |
18650-18652 |
IN |
denotes |
In |
T8738 |
18687-18690 |
VBD |
denotes |
had |
T8739 |
18653-18661 |
NN |
denotes |
contrast |
T8740 |
18661-18663 |
, |
denotes |
, |
T8741 |
18663-18672 |
JJ |
denotes |
untreated |
T8742 |
18682-18686 |
NNS |
denotes |
mice |
T8743 |
18673-18674 |
CD |
denotes |
9 |
T8744 |
18675-18677 |
NN |
denotes |
mo |
T8745 |
18674-18675 |
HYPH |
denotes |
- |
T8746 |
18678-18681 |
JJ |
denotes |
old |
T8747 |
18677-18678 |
HYPH |
denotes |
- |
T8748 |
18691-18697 |
RB |
denotes |
almost |
T8749 |
18698-18703 |
RB |
denotes |
twice |
T8750 |
18707-18711 |
JJ |
denotes |
much |
T8751 |
18704-18706 |
RB |
denotes |
as |
T8752 |
18723-18725 |
NN |
denotes |
Aβ |
T8753 |
18712-18722 |
VBN |
denotes |
aggregated |
T8754 |
18726-18728 |
IN |
denotes |
as |
T8755 |
18729-18735 |
DT |
denotes |
either |
T8756 |
18736-18738 |
IN |
denotes |
of |
T8757 |
18739-18742 |
DT |
denotes |
the |
T8758 |
18751-18757 |
NNS |
denotes |
groups |
T8759 |
18743-18750 |
VBN |
denotes |
treated |
T8760 |
18757-18758 |
. |
denotes |
. |
T8761 |
18758-18985 |
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 |
18759-18765 |
NN |
denotes |
Filter |
T8763 |
18771-18779 |
NN |
denotes |
analysis |
T8764 |
18766-18770 |
NN |
denotes |
trap |
T8765 |
18804-18811 |
VBD |
denotes |
yielded |
T8766 |
18780-18782 |
IN |
denotes |
of |
T8767 |
18783-18787 |
NN |
denotes |
line |
T8768 |
18799-18803 |
NNS |
denotes |
mice |
T8769 |
18788-18790 |
CD |
denotes |
18 |
T8770 |
18791-18794 |
NN |
denotes |
tTA |
T8771 |
18795-18798 |
NN |
denotes |
APP |
T8772 |
18794-18795 |
HYPH |
denotes |
/ |
T8773 |
18930-18938 |
VBN |
denotes |
arrested |
T8774 |
18812-18819 |
JJ |
denotes |
similar |
T8775 |
18820-18827 |
NNS |
denotes |
results |
T8776 |
18827-18829 |
: |
denotes |
: |
T8777 |
18829-18832 |
DT |
denotes |
the |
T8778 |
18833-18841 |
NN |
denotes |
increase |
T8779 |
18842-18844 |
IN |
denotes |
in |
T8780 |
18845-18855 |
VBN |
denotes |
aggregated |
T8781 |
18856-18858 |
NN |
denotes |
Aβ |
T8782 |
18859-18867 |
VBN |
denotes |
observed |
T8783 |
18868-18870 |
IN |
denotes |
in |
T8784 |
18871-18880 |
JJ |
denotes |
untreated |
T8785 |
18881-18888 |
NNS |
denotes |
animals |
T8786 |
18889-18896 |
IN |
denotes |
between |
T8787 |
18897-18898 |
CD |
denotes |
6 |
T8788 |
18905-18907 |
NN |
denotes |
mo |
T8789 |
18899-18902 |
CC |
denotes |
and |
T8790 |
18903-18904 |
CD |
denotes |
9 |
T8791 |
18908-18910 |
IN |
denotes |
of |
T8792 |
18911-18914 |
NN |
denotes |
age |
T8793 |
18915-18918 |
VBD |
denotes |
was |
T8794 |
18919-18929 |
RB |
denotes |
completely |
T8795 |
18939-18941 |
IN |
denotes |
by |
T8796 |
18942-18951 |
NN |
denotes |
transgene |
T8797 |
18952-18963 |
NN |
denotes |
suppression |
T8798 |
18964-18965 |
-LRB- |
denotes |
( |
T8799 |
18972-18975 |
NN |
denotes |
S5C |
T8800 |
18965-18971 |
NN |
denotes |
Figure |
T8801 |
18976-18979 |
CC |
denotes |
and |
T8802 |
18980-18983 |
NN |
denotes |
S5D |
T8803 |
18983-18984 |
-RRB- |
denotes |
) |
T8804 |
18984-18985 |
. |
denotes |
. |
T8805 |
18985-19176 |
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 |
18986-18988 |
PRP |
denotes |
We |
T8807 |
18994-18998 |
VBD |
denotes |
used |
T8808 |
18989-18993 |
RB |
denotes |
next |
T8809 |
18999-19004 |
NN |
denotes |
ELISA |
T8810 |
19005-19007 |
TO |
denotes |
to |
T8811 |
19008-19015 |
VB |
denotes |
measure |
T8812 |
19016-19021 |
JJ |
denotes |
total |
T8813 |
19022-19024 |
NN |
denotes |
Aβ |
T8814 |
19025-19027 |
IN |
denotes |
in |
T8815 |
19028-19031 |
DT |
denotes |
the |
T8816 |
19032-19038 |
NNS |
denotes |
brains |
T8817 |
19039-19041 |
IN |
denotes |
of |
T8818 |
19042-19046 |
DT |
denotes |
each |
T8819 |
19047-19052 |
NN |
denotes |
group |
T8820 |
19053-19055 |
TO |
denotes |
to |
T8821 |
19056-19065 |
VB |
denotes |
determine |
T8822 |
19066-19073 |
IN |
denotes |
whether |
T8823 |
19124-19132 |
VBD |
denotes |
occurred |
T8824 |
19074-19077 |
DT |
denotes |
any |
T8825 |
19078-19084 |
NN |
denotes |
change |
T8826 |
19085-19087 |
IN |
denotes |
in |
T8827 |
19088-19091 |
DT |
denotes |
the |
T8828 |
19092-19098 |
NN |
denotes |
amount |
T8829 |
19099-19101 |
CC |
denotes |
or |
T8830 |
19102-19112 |
NN |
denotes |
solubility |
T8831 |
19113-19115 |
IN |
denotes |
of |
T8832 |
19116-19123 |
NN |
denotes |
peptide |
T8833 |
19133-19138 |
IN |
denotes |
while |
T8834 |
19165-19175 |
VBN |
denotes |
suppressed |
T8835 |
19139-19145 |
NN |
denotes |
APPswe |
T8836 |
19146-19149 |
NN |
denotes |
ind |
T8837 |
19145-19146 |
HYPH |
denotes |
/ |
T8838 |
19150-19160 |
NN |
denotes |
expression |
T8839 |
19161-19164 |
VBD |
denotes |
was |
T8840 |
19175-19176 |
. |
denotes |
. |
T8841 |
19176-19369 |
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 |
19177-19185 |
JJ |
denotes |
Cortical |
T8843 |
19186-19197 |
NNS |
denotes |
homogenates |
T8844 |
19216-19225 |
VBN |
denotes |
extracted |
T8845 |
19198-19202 |
VBD |
denotes |
were |
T8846 |
19203-19215 |
RB |
denotes |
sequentially |
T8847 |
19331-19339 |
VBN |
denotes |
measured |
T8848 |
19226-19228 |
TO |
denotes |
to |
T8849 |
19229-19237 |
VB |
denotes |
separate |
T8850 |
19238-19245 |
NN |
denotes |
peptide |
T8851 |
19246-19250 |
IN |
denotes |
into |
T8852 |
19251-19254 |
NN |
denotes |
PBS |
T8853 |
19270-19277 |
JJ |
denotes |
soluble |
T8854 |
19254-19255 |
HYPH |
denotes |
- |
T8855 |
19255-19257 |
, |
denotes |
, |
T8856 |
19257-19260 |
NN |
denotes |
SDS |
T8857 |
19260-19261 |
HYPH |
denotes |
- |
T8858 |
19261-19263 |
, |
denotes |
, |
T8859 |
19263-19266 |
CC |
denotes |
and |
T8860 |
19267-19269 |
NN |
denotes |
FA |
T8861 |
19269-19270 |
HYPH |
denotes |
- |
T8862 |
19278-19287 |
NNS |
denotes |
fractions |
T8863 |
19287-19289 |
, |
denotes |
, |
T8864 |
19289-19293 |
RB |
denotes |
then |
T8865 |
19294-19303 |
NN |
denotes |
transgene |
T8866 |
19304-19311 |
VBN |
denotes |
derived |
T8867 |
19303-19304 |
HYPH |
denotes |
- |
T8868 |
19312-19316 |
NN |
denotes |
Aβ40 |
T8869 |
19317-19320 |
CC |
denotes |
and |
T8870 |
19321-19325 |
NN |
denotes |
Aβ42 |
T8871 |
19326-19330 |
VBD |
denotes |
were |
T8872 |
19340-19342 |
IN |
denotes |
by |
T8873 |
19343-19348 |
JJ |
denotes |
human |
T8874 |
19349-19357 |
JJ |
denotes |
specific |
T8875 |
19348-19349 |
HYPH |
denotes |
- |
T8876 |
19358-19363 |
NN |
denotes |
ELISA |
T8877 |
19364-19365 |
-LRB- |
denotes |
[ |
T8878 |
19365-19367 |
CD |
denotes |
23 |
T8879 |
19367-19368 |
-RRB- |
denotes |
] |
T8880 |
19368-19369 |
. |
denotes |
. |
T8881 |
19369-19521 |
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 |
19370-19372 |
IN |
denotes |
In |
T8883 |
19416-19421 |
VBD |
denotes |
found |
T8884 |
19373-19376 |
DT |
denotes |
all |
T8885 |
19377-19384 |
NNS |
denotes |
animals |
T8886 |
19385-19394 |
VBG |
denotes |
harboring |
T8887 |
19395-19402 |
NN |
denotes |
amyloid |
T8888 |
19403-19411 |
NNS |
denotes |
deposits |
T8889 |
19411-19413 |
, |
denotes |
, |
T8890 |
19413-19415 |
PRP |
denotes |
we |
T8891 |
19422-19426 |
IN |
denotes |
that |
T8892 |
19462-19471 |
VBN |
denotes |
extracted |
T8893 |
19427-19430 |
DT |
denotes |
the |
T8894 |
19436-19444 |
NN |
denotes |
majority |
T8895 |
19431-19435 |
JJ |
denotes |
vast |
T8896 |
19445-19447 |
IN |
denotes |
of |
T8897 |
19448-19450 |
NN |
denotes |
Aβ |
T8898 |
19451-19452 |
-LRB- |
denotes |
( |
T8899 |
19455-19456 |
NN |
denotes |
% |
T8900 |
19452-19453 |
SYM |
denotes |
> |
T8901 |
19453-19455 |
CD |
denotes |
99 |
T8902 |
19456-19457 |
-RRB- |
denotes |
) |
T8903 |
19458-19461 |
VBD |
denotes |
was |
T8904 |
19472-19476 |
IN |
denotes |
into |
T8905 |
19477-19480 |
DT |
denotes |
the |
T8906 |
19492-19501 |
NNS |
denotes |
fractions |
T8907 |
19481-19484 |
NN |
denotes |
SDS |
T8908 |
19485-19488 |
CC |
denotes |
and |
T8909 |
19489-19491 |
NN |
denotes |
FA |
T8910 |
19502-19503 |
-LRB- |
denotes |
( |
T8911 |
19510-19512 |
NN |
denotes |
5A |
T8912 |
19503-19509 |
NN |
denotes |
Figure |
T8913 |
19513-19516 |
CC |
denotes |
and |
T8914 |
19517-19519 |
NN |
denotes |
5B |
T8915 |
19519-19520 |
-RRB- |
denotes |
) |
T8916 |
19520-19521 |
. |
denotes |
. |
T8917 |
19521-19742 |
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 |
19522-19532 |
JJ |
denotes |
Consistent |
T8919 |
19585-19589 |
VBD |
denotes |
were |
T8920 |
19533-19537 |
IN |
denotes |
with |
T8921 |
19538-19541 |
DT |
denotes |
the |
T8922 |
19554-19561 |
NNS |
denotes |
results |
T8923 |
19542-19548 |
NN |
denotes |
filter |
T8924 |
19549-19553 |
NN |
denotes |
trap |
T8925 |
19562-19571 |
VBN |
denotes |
presented |
T8926 |
19572-19577 |
RB |
denotes |
above |
T8927 |
19577-19579 |
, |
denotes |
, |
T8928 |
19579-19584 |
EX |
denotes |
there |
T8929 |
19590-19592 |
DT |
denotes |
no |
T8930 |
19605-19616 |
NNS |
denotes |
differences |
T8931 |
19593-19604 |
JJ |
denotes |
significant |
T8932 |
19617-19619 |
IN |
denotes |
in |
T8933 |
19620-19623 |
NN |
denotes |
SDS |
T8934 |
19631-19638 |
JJ |
denotes |
soluble |
T8935 |
19623-19624 |
HYPH |
denotes |
- |
T8936 |
19625-19627 |
CC |
denotes |
or |
T8937 |
19628-19630 |
NN |
denotes |
FA |
T8938 |
19630-19631 |
HYPH |
denotes |
- |
T8939 |
19639-19641 |
NN |
denotes |
Aβ |
T8940 |
19642-19649 |
IN |
denotes |
between |
T8941 |
19650-19653 |
DT |
denotes |
the |
T8942 |
19669-19675 |
NN |
denotes |
cohort |
T8943 |
19654-19655 |
CD |
denotes |
6 |
T8944 |
19656-19658 |
NN |
denotes |
mo |
T8945 |
19659-19668 |
JJ |
denotes |
untreated |
T8946 |
19676-19679 |
CC |
denotes |
and |
T8947 |
19680-19686 |
CC |
denotes |
either |
T8948 |
19734-19741 |
NNS |
denotes |
cohorts |
T8949 |
19687-19690 |
DT |
denotes |
the |
T8950 |
19691-19692 |
CD |
denotes |
6 |
T8951 |
19693-19695 |
NN |
denotes |
mo |
T8952 |
19696-19697 |
SYM |
denotes |
+ |
T8953 |
19698-19699 |
CD |
denotes |
3 |
T8954 |
19700-19702 |
NN |
denotes |
mo |
T8955 |
19703-19710 |
VBN |
denotes |
treated |
T8956 |
19711-19713 |
CC |
denotes |
or |
T8957 |
19714-19715 |
CD |
denotes |
6 |
T8958 |
19716-19718 |
NN |
denotes |
mo |
T8959 |
19719-19720 |
SYM |
denotes |
+ |
T8960 |
19721-19722 |
CD |
denotes |
6 |
T8961 |
19723-19725 |
NN |
denotes |
mo |
T8962 |
19726-19733 |
VBN |
denotes |
treated |
T8963 |
19741-19742 |
. |
denotes |
. |
T8964 |
19742-19899 |
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 |
19743-19750 |
RB |
denotes |
However |
T8966 |
19811-19820 |
VBD |
denotes |
contained |
T8967 |
19750-19752 |
, |
denotes |
, |
T8968 |
19752-19758 |
NNS |
denotes |
brains |
T8969 |
19759-19761 |
IN |
denotes |
of |
T8970 |
19762-19766 |
CC |
denotes |
both |
T8971 |
19769-19771 |
NN |
denotes |
mo |
T8972 |
19767-19768 |
CD |
denotes |
6 |
T8973 |
19795-19802 |
VBN |
denotes |
treated |
T8974 |
19772-19773 |
SYM |
denotes |
+ |
T8975 |
19774-19775 |
CD |
denotes |
3 |
T8976 |
19776-19778 |
NN |
denotes |
mo |
T8977 |
19779-19782 |
CC |
denotes |
and |
T8978 |
19783-19784 |
CD |
denotes |
6 |
T8979 |
19785-19787 |
NN |
denotes |
mo |
T8980 |
19788-19789 |
SYM |
denotes |
+ |
T8981 |
19790-19791 |
CD |
denotes |
6 |
T8982 |
19792-19794 |
NN |
denotes |
mo |
T8983 |
19803-19810 |
NNS |
denotes |
cohorts |
T8984 |
19821-19828 |
RB |
denotes |
roughly |
T8985 |
19829-19834 |
RB |
denotes |
twice |
T8986 |
19838-19842 |
JJ |
denotes |
much |
T8987 |
19835-19837 |
RB |
denotes |
as |
T8988 |
19855-19859 |
NN |
denotes |
Aβ40 |
T8989 |
19843-19846 |
NN |
denotes |
PBS |
T8990 |
19846-19847 |
HYPH |
denotes |
- |
T8991 |
19847-19854 |
JJ |
denotes |
soluble |
T8992 |
19860-19862 |
IN |
denotes |
as |
T8993 |
19863-19872 |
JJ |
denotes |
untreated |
T8994 |
19882-19886 |
NNS |
denotes |
mice |
T8995 |
19873-19874 |
CD |
denotes |
6 |
T8996 |
19875-19877 |
NN |
denotes |
mo |
T8997 |
19874-19875 |
HYPH |
denotes |
- |
T8998 |
19878-19881 |
JJ |
denotes |
old |
T8999 |
19877-19878 |
HYPH |
denotes |
- |
T9000 |
19887-19888 |
-LRB- |
denotes |
( |
T9001 |
19895-19897 |
NN |
denotes |
5C |
T9002 |
19888-19894 |
NN |
denotes |
Figure |
T9003 |
19897-19898 |
-RRB- |
denotes |
) |
T9004 |
19898-19899 |
. |
denotes |
. |
T9005 |
19899-19982 |
sentence |
denotes |
Levels of Aβ42 showed a similar trend, but did not reach statistical significance. |
T9006 |
19900-19906 |
NNS |
denotes |
Levels |
T9007 |
19915-19921 |
VBD |
denotes |
showed |
T9008 |
19907-19909 |
IN |
denotes |
of |
T9009 |
19910-19914 |
NN |
denotes |
Aβ42 |
T9010 |
19922-19923 |
DT |
denotes |
a |
T9011 |
19932-19937 |
NN |
denotes |
trend |
T9012 |
19924-19931 |
JJ |
denotes |
similar |
T9013 |
19937-19939 |
, |
denotes |
, |
T9014 |
19939-19942 |
CC |
denotes |
but |
T9015 |
19943-19946 |
VBD |
denotes |
did |
T9016 |
19951-19956 |
VB |
denotes |
reach |
T9017 |
19947-19950 |
RB |
denotes |
not |
T9018 |
19957-19968 |
JJ |
denotes |
statistical |
T9019 |
19969-19981 |
NN |
denotes |
significance |
T9020 |
19981-19982 |
. |
denotes |
. |
T9021 |
19982-20299 |
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 |
19983-19985 |
IN |
denotes |
In |
T9023 |
20079-20083 |
VBD |
denotes |
were |
T9024 |
19986-19990 |
NN |
denotes |
fact |
T9025 |
19990-19992 |
, |
denotes |
, |
T9026 |
19992-19998 |
NNS |
denotes |
levels |
T9027 |
19999-20001 |
IN |
denotes |
of |
T9028 |
20002-20005 |
NN |
denotes |
PBS |
T9029 |
20006-20013 |
JJ |
denotes |
soluble |
T9030 |
20005-20006 |
HYPH |
denotes |
- |
T9031 |
20014-20018 |
NN |
denotes |
Aβ40 |
T9032 |
20019-20022 |
CC |
denotes |
and |
T9033 |
20023-20027 |
NN |
denotes |
Aβ42 |
T9034 |
20028-20030 |
IN |
denotes |
in |
T9035 |
20031-20034 |
DT |
denotes |
the |
T9036 |
20071-20078 |
NNS |
denotes |
cohorts |
T9037 |
20035-20036 |
CD |
denotes |
6 |
T9038 |
20037-20039 |
NN |
denotes |
mo |
T9039 |
20040-20041 |
SYM |
denotes |
+ |
T9040 |
20042-20043 |
CD |
denotes |
3 |
T9041 |
20044-20046 |
NN |
denotes |
mo |
T9042 |
20047-20050 |
CC |
denotes |
and |
T9043 |
20051-20052 |
CD |
denotes |
6 |
T9044 |
20053-20055 |
NN |
denotes |
mo |
T9045 |
20056-20057 |
SYM |
denotes |
+ |
T9046 |
20058-20059 |
CD |
denotes |
6 |
T9047 |
20060-20062 |
NN |
denotes |
mo |
T9048 |
20063-20070 |
VBN |
denotes |
treated |
T9049 |
20084-20088 |
RBS |
denotes |
most |
T9050 |
20089-20096 |
JJ |
denotes |
similar |
T9051 |
20097-20099 |
IN |
denotes |
to |
T9052 |
20100-20104 |
DT |
denotes |
that |
T9053 |
20105-20107 |
IN |
denotes |
of |
T9054 |
20108-20111 |
DT |
denotes |
the |
T9055 |
20127-20133 |
NN |
denotes |
cohort |
T9056 |
20112-20113 |
CD |
denotes |
9 |
T9057 |
20114-20116 |
NN |
denotes |
mo |
T9058 |
20117-20126 |
JJ |
denotes |
untreated |
T9059 |
20133-20135 |
, |
denotes |
, |
T9060 |
20135-20145 |
VBG |
denotes |
suggesting |
T9061 |
20146-20150 |
IN |
denotes |
that |
T9062 |
20241-20250 |
VB |
denotes |
determine |
T9063 |
20151-20154 |
NN |
denotes |
age |
T9064 |
20154-20156 |
, |
denotes |
, |
T9065 |
20156-20158 |
IN |
denotes |
as |
T9066 |
20159-20166 |
VBN |
denotes |
opposed |
T9067 |
20167-20169 |
IN |
denotes |
to |
T9068 |
20170-20179 |
JJ |
denotes |
synthetic |
T9069 |
20180-20184 |
NN |
denotes |
rate |
T9070 |
20185-20186 |
-LRB- |
denotes |
( |
T9071 |
20186-20191 |
WDT |
denotes |
which |
T9072 |
20198-20200 |
VB |
denotes |
be |
T9073 |
20192-20197 |
MD |
denotes |
would |
T9074 |
20201-20211 |
JJ |
denotes |
negligible |
T9075 |
20212-20214 |
IN |
denotes |
in |
T9076 |
20215-20218 |
DT |
denotes |
the |
T9077 |
20227-20234 |
NNS |
denotes |
animals |
T9078 |
20219-20226 |
VBN |
denotes |
treated |
T9079 |
20234-20235 |
-RRB- |
denotes |
) |
T9080 |
20235-20237 |
, |
denotes |
, |
T9081 |
20237-20240 |
MD |
denotes |
may |
T9082 |
20251-20254 |
DT |
denotes |
the |
T9083 |
20255-20263 |
NN |
denotes |
fraction |
T9084 |
20264-20266 |
IN |
denotes |
of |
T9085 |
20267-20270 |
NN |
denotes |
PBS |
T9086 |
20271-20278 |
JJ |
denotes |
soluble |
T9087 |
20270-20271 |
HYPH |
denotes |
- |
T9088 |
20279-20281 |
NN |
denotes |
Aβ |
T9089 |
20282-20284 |
IN |
denotes |
in |
T9090 |
20285-20290 |
DT |
denotes |
these |
T9091 |
20291-20298 |
NNS |
denotes |
animals |
T9092 |
20298-20299 |
. |
denotes |
. |
T9093 |
20299-22627 |
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 |
22454-22456 |
PRP |
denotes |
We |
T9095 |
22462-22470 |
VBD |
denotes |
assessed |
T9096 |
22457-22461 |
RB |
denotes |
also |
T9097 |
22471-22479 |
JJ |
denotes |
neuritic |
T9098 |
22490-22499 |
NN |
denotes |
pathology |
T9099 |
22480-22483 |
CC |
denotes |
and |
T9100 |
22484-22489 |
JJ |
denotes |
glial |
T9101 |
22500-22511 |
VBG |
denotes |
surrounding |
T9102 |
22512-22515 |
DT |
denotes |
the |
T9103 |
22516-22523 |
NNS |
denotes |
plaques |
T9104 |
22524-22526 |
TO |
denotes |
to |
T9105 |
22527-22536 |
VB |
denotes |
determine |
T9106 |
22537-22544 |
IN |
denotes |
whether |
T9107 |
22551-22555 |
VBD |
denotes |
were |
T9108 |
22545-22550 |
EX |
denotes |
there |
T9109 |
22556-22559 |
DT |
denotes |
any |
T9110 |
22560-22567 |
NNS |
denotes |
changes |
T9111 |
22568-22570 |
IN |
denotes |
in |
T9112 |
22571-22577 |
JJ |
denotes |
nearby |
T9113 |
22578-22584 |
NN |
denotes |
tissue |
T9114 |
22585-22594 |
VBG |
denotes |
following |
T9115 |
22595-22599 |
JJ |
denotes |
long |
T9116 |
22600-22604 |
NN |
denotes |
term |
T9117 |
22599-22600 |
HYPH |
denotes |
- |
T9118 |
22615-22626 |
NN |
denotes |
suppression |
T9119 |
22605-22614 |
NN |
denotes |
transgene |
T9120 |
22626-22627 |
. |
denotes |
. |
T9121 |
22627-22743 |
sentence |
denotes |
Both Hirano silver stain and ubiquitin immunostaining showed neuritic pathology in all treatment groups (Figure 6). |
T9122 |
22628-22632 |
CC |
denotes |
Both |
T9123 |
22647-22652 |
NN |
denotes |
stain |
T9124 |
22633-22639 |
NNP |
denotes |
Hirano |
T9125 |
22640-22646 |
NN |
denotes |
silver |
T9126 |
22682-22688 |
VBD |
denotes |
showed |
T9127 |
22653-22656 |
CC |
denotes |
and |
T9128 |
22657-22666 |
NN |
denotes |
ubiquitin |
T9129 |
22667-22681 |
NN |
denotes |
immunostaining |
T9130 |
22689-22697 |
JJ |
denotes |
neuritic |
T9131 |
22698-22707 |
NN |
denotes |
pathology |
T9132 |
22708-22710 |
IN |
denotes |
in |
T9133 |
22711-22714 |
DT |
denotes |
all |
T9134 |
22725-22731 |
NNS |
denotes |
groups |
T9135 |
22715-22724 |
NN |
denotes |
treatment |
T9136 |
22732-22733 |
-LRB- |
denotes |
( |
T9137 |
22733-22739 |
NN |
denotes |
Figure |
T9138 |
22740-22741 |
CD |
denotes |
6 |
T9139 |
22741-22742 |
-RRB- |
denotes |
) |
T9140 |
22742-22743 |
. |
denotes |
. |
T9141 |
22743-22849 |
sentence |
denotes |
Similarly, activated astrocytes immunostained for GFAP were found near plaques in all animals (Figure 6). |
T9142 |
22744-22753 |
RB |
denotes |
Similarly |
T9143 |
22804-22809 |
VBN |
denotes |
found |
T9144 |
22753-22755 |
, |
denotes |
, |
T9145 |
22755-22764 |
VBN |
denotes |
activated |
T9146 |
22765-22775 |
NNS |
denotes |
astrocytes |
T9147 |
22776-22789 |
VBN |
denotes |
immunostained |
T9148 |
22790-22793 |
IN |
denotes |
for |
T9149 |
22794-22798 |
NN |
denotes |
GFAP |
T9150 |
22799-22803 |
VBD |
denotes |
were |
T9151 |
22810-22814 |
IN |
denotes |
near |
T9152 |
22815-22822 |
NNS |
denotes |
plaques |
T9153 |
22823-22825 |
IN |
denotes |
in |
T9154 |
22826-22829 |
DT |
denotes |
all |
T9155 |
22830-22837 |
NNS |
denotes |
animals |
T9156 |
22838-22839 |
-LRB- |
denotes |
( |
T9157 |
22839-22845 |
NN |
denotes |
Figure |
T9158 |
22846-22847 |
CD |
denotes |
6 |
T9159 |
22847-22848 |
-RRB- |
denotes |
) |
T9160 |
22848-22849 |
. |
denotes |
. |
T9161 |
22849-22924 |
sentence |
denotes |
Neuritic and glial pathology were more severe in the older untreated mice. |
T9162 |
22850-22858 |
JJ |
denotes |
Neuritic |
T9163 |
22869-22878 |
NN |
denotes |
pathology |
T9164 |
22859-22862 |
CC |
denotes |
and |
T9165 |
22863-22868 |
JJ |
denotes |
glial |
T9166 |
22879-22883 |
VBD |
denotes |
were |
T9167 |
22884-22888 |
RBR |
denotes |
more |
T9168 |
22889-22895 |
JJ |
denotes |
severe |
T9169 |
22896-22898 |
IN |
denotes |
in |
T9170 |
22899-22902 |
DT |
denotes |
the |
T9171 |
22919-22923 |
NNS |
denotes |
mice |
T9172 |
22903-22908 |
JJR |
denotes |
older |
T9173 |
22909-22918 |
JJ |
denotes |
untreated |
T9174 |
22923-22924 |
. |
denotes |
. |
T9175 |
22924-23119 |
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 |
22925-22927 |
IN |
denotes |
In |
T9177 |
22960-22969 |
VBD |
denotes |
prevented |
T9178 |
22928-22936 |
NN |
denotes |
contrast |
T9179 |
22936-22938 |
, |
denotes |
, |
T9180 |
22938-22947 |
NN |
denotes |
transgene |
T9181 |
22948-22959 |
NN |
denotes |
suppression |
T9182 |
22970-22973 |
DT |
denotes |
the |
T9183 |
22974-22980 |
NN |
denotes |
growth |
T9184 |
22981-22983 |
IN |
denotes |
of |
T9185 |
22984-22994 |
JJ |
denotes |
individual |
T9186 |
22995-23003 |
NNS |
denotes |
deposits |
T9187 |
23004-23012 |
JJ |
denotes |
apparent |
T9188 |
23013-23015 |
IN |
denotes |
in |
T9189 |
23016-23025 |
JJ |
denotes |
untreated |
T9190 |
23026-23030 |
NNS |
denotes |
mice |
T9191 |
23030-23032 |
, |
denotes |
, |
T9192 |
23032-23035 |
CC |
denotes |
and |
T9193 |
23036-23043 |
VBD |
denotes |
limited |
T9194 |
23044-23047 |
DT |
denotes |
the |
T9195 |
23060-23069 |
NN |
denotes |
pathology |
T9196 |
23048-23059 |
VBG |
denotes |
surrounding |
T9197 |
23070-23072 |
IN |
denotes |
to |
T9198 |
23073-23077 |
WP |
denotes |
what |
T9199 |
23078-23081 |
VBD |
denotes |
was |
T9200 |
23082-23089 |
RB |
denotes |
already |
T9201 |
23090-23097 |
JJ |
denotes |
present |
T9202 |
23098-23102 |
WRB |
denotes |
when |
T9203 |
23113-23118 |
VBD |
denotes |
began |
T9204 |
23103-23112 |
NN |
denotes |
treatment |
T9205 |
23118-23119 |
. |
denotes |
. |
T9206 |
23119-23882 |
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 |
23692-23694 |
DT |
denotes |
An |
T9208 |
23703-23711 |
NN |
denotes |
question |
T9209 |
23695-23702 |
JJ |
denotes |
obvious |
T9210 |
23733-23736 |
VBD |
denotes |
was |
T9211 |
23712-23714 |
PRP |
denotes |
we |
T9212 |
23715-23721 |
VBD |
denotes |
sought |
T9213 |
23722-23724 |
TO |
denotes |
to |
T9214 |
23725-23732 |
VB |
denotes |
address |
T9215 |
23737-23744 |
IN |
denotes |
whether |
T9216 |
23766-23776 |
VBD |
denotes |
diminished |
T9217 |
23745-23748 |
DT |
denotes |
the |
T9218 |
23749-23759 |
NN |
denotes |
deposition |
T9219 |
23760-23762 |
IN |
denotes |
of |
T9220 |
23763-23765 |
NN |
denotes |
Aβ |
T9221 |
23777-23786 |
JJ |
denotes |
cognitive |
T9222 |
23787-23794 |
NN |
denotes |
ability |
T9223 |
23795-23797 |
IN |
denotes |
in |
T9224 |
23798-23807 |
JJ |
denotes |
untreated |
T9225 |
23808-23812 |
NNS |
denotes |
mice |
T9226 |
23812-23814 |
, |
denotes |
, |
T9227 |
23814-23817 |
CC |
denotes |
and |
T9228 |
23818-23822 |
WP |
denotes |
what |
T9229 |
23829-23835 |
VB |
denotes |
happen |
T9230 |
23823-23828 |
MD |
denotes |
might |
T9231 |
23836-23838 |
IN |
denotes |
to |
T9232 |
23839-23848 |
NN |
denotes |
cognition |
T9233 |
23849-23853 |
WRB |
denotes |
when |
T9234 |
23870-23881 |
VBN |
denotes |
interrupted |
T9235 |
23854-23857 |
DT |
denotes |
the |
T9236 |
23858-23865 |
NN |
denotes |
process |
T9237 |
23866-23869 |
VBD |
denotes |
was |
T9238 |
23881-23882 |
. |
denotes |
. |
T9239 |
23882-24018 |
sentence |
denotes |
Unfortunately, efforts to characterize cognitive behavior were compromised by severe hyperactivity in untreated double transgenic mice. |
T9240 |
23883-23896 |
RB |
denotes |
Unfortunately |
T9241 |
23946-23957 |
VBN |
denotes |
compromised |
T9242 |
23896-23898 |
, |
denotes |
, |
T9243 |
23898-23905 |
NNS |
denotes |
efforts |
T9244 |
23906-23908 |
TO |
denotes |
to |
T9245 |
23909-23921 |
VB |
denotes |
characterize |
T9246 |
23922-23931 |
JJ |
denotes |
cognitive |
T9247 |
23932-23940 |
NN |
denotes |
behavior |
T9248 |
23941-23945 |
VBD |
denotes |
were |
T9249 |
23958-23960 |
IN |
denotes |
by |
T9250 |
23961-23967 |
JJ |
denotes |
severe |
T9251 |
23968-23981 |
NN |
denotes |
hyperactivity |
T9252 |
23982-23984 |
IN |
denotes |
in |
T9253 |
23985-23994 |
JJ |
denotes |
untreated |
T9254 |
24013-24017 |
NNS |
denotes |
mice |
T9255 |
23995-24001 |
JJ |
denotes |
double |
T9256 |
24002-24012 |
JJ |
denotes |
transgenic |
T9257 |
24017-24018 |
. |
denotes |
. |
T9258 |
24018-24203 |
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 |
24019-24022 |
DT |
denotes |
The |
T9260 |
24031-24038 |
NNS |
denotes |
animals |
T9261 |
24023-24026 |
NN |
denotes |
tTA |
T9262 |
24027-24030 |
NN |
denotes |
APP |
T9263 |
24026-24027 |
HYPH |
denotes |
/ |
T9264 |
24050-24054 |
VBN |
denotes |
seen |
T9265 |
24039-24043 |
VBD |
denotes |
were |
T9266 |
24044-24049 |
RB |
denotes |
often |
T9267 |
24055-24062 |
VBG |
denotes |
running |
T9268 |
24063-24065 |
IN |
denotes |
in |
T9269 |
24066-24073 |
NNS |
denotes |
circles |
T9270 |
24074-24080 |
IN |
denotes |
around |
T9271 |
24081-24084 |
DT |
denotes |
the |
T9272 |
24085-24094 |
NN |
denotes |
perimeter |
T9273 |
24095-24097 |
IN |
denotes |
of |
T9274 |
24098-24103 |
PRP$ |
denotes |
their |
T9275 |
24104-24109 |
NNS |
denotes |
cages |
T9276 |
24109-24111 |
, |
denotes |
, |
T9277 |
24111-24114 |
CC |
denotes |
and |
T9278 |
24115-24116 |
DT |
denotes |
a |
T9279 |
24134-24141 |
NN |
denotes |
pattern |
T9280 |
24117-24124 |
JJ |
denotes |
similar |
T9281 |
24125-24133 |
NN |
denotes |
swimming |
T9282 |
24146-24151 |
VBN |
denotes |
noted |
T9283 |
24142-24145 |
VBD |
denotes |
was |
T9284 |
24152-24156 |
WRB |
denotes |
when |
T9285 |
24171-24177 |
VBN |
denotes |
tested |
T9286 |
24157-24160 |
DT |
denotes |
the |
T9287 |
24161-24165 |
NNS |
denotes |
mice |
T9288 |
24166-24170 |
VBD |
denotes |
were |
T9289 |
24178-24180 |
IN |
denotes |
in |
T9290 |
24181-24184 |
DT |
denotes |
the |
T9291 |
24198-24202 |
NN |
denotes |
maze |
T9292 |
24185-24191 |
NNP |
denotes |
Morris |
T9293 |
24192-24197 |
NN |
denotes |
water |
T9294 |
24202-24203 |
. |
denotes |
. |
T9295 |
24203-24311 |
sentence |
denotes |
In the radial water maze, repetitive swim patterns were noted with no evidence of choice-motivated actions. |
T9296 |
24204-24206 |
IN |
denotes |
In |
T9297 |
24260-24265 |
VBN |
denotes |
noted |
T9298 |
24207-24210 |
DT |
denotes |
the |
T9299 |
24224-24228 |
NN |
denotes |
maze |
T9300 |
24211-24217 |
JJ |
denotes |
radial |
T9301 |
24218-24223 |
NN |
denotes |
water |
T9302 |
24228-24230 |
, |
denotes |
, |
T9303 |
24230-24240 |
JJ |
denotes |
repetitive |
T9304 |
24246-24254 |
NNS |
denotes |
patterns |
T9305 |
24241-24245 |
NN |
denotes |
swim |
T9306 |
24255-24259 |
VBD |
denotes |
were |
T9307 |
24266-24270 |
IN |
denotes |
with |
T9308 |
24271-24273 |
DT |
denotes |
no |
T9309 |
24274-24282 |
NN |
denotes |
evidence |
T9310 |
24283-24285 |
IN |
denotes |
of |
T9311 |
24286-24292 |
NN |
denotes |
choice |
T9312 |
24293-24302 |
VBN |
denotes |
motivated |
T9313 |
24292-24293 |
HYPH |
denotes |
- |
T9314 |
24303-24310 |
NNS |
denotes |
actions |
T9315 |
24310-24311 |
. |
denotes |
. |
T9316 |
24311-24499 |
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 |
24312-24317 |
JJ |
denotes |
Other |
T9318 |
24318-24325 |
NNS |
denotes |
studies |
T9319 |
24331-24336 |
VBN |
denotes |
dealt |
T9320 |
24326-24330 |
VBP |
denotes |
have |
T9321 |
24337-24341 |
IN |
denotes |
with |
T9322 |
24342-24349 |
JJ |
denotes |
similar |
T9323 |
24350-24358 |
NNS |
denotes |
problems |
T9324 |
24359-24361 |
IN |
denotes |
by |
T9325 |
24362-24371 |
VBG |
denotes |
excluding |
T9326 |
24372-24379 |
NNS |
denotes |
animals |
T9327 |
24380-24384 |
WDT |
denotes |
that |
T9328 |
24392-24396 |
VB |
denotes |
show |
T9329 |
24385-24387 |
VBP |
denotes |
do |
T9330 |
24388-24391 |
RB |
denotes |
not |
T9331 |
24397-24405 |
JJ |
denotes |
adequate |
T9332 |
24406-24415 |
NN |
denotes |
attention |
T9333 |
24416-24418 |
IN |
denotes |
to |
T9334 |
24419-24422 |
DT |
denotes |
the |
T9335 |
24423-24427 |
NN |
denotes |
task |
T9336 |
24427-24429 |
, |
denotes |
, |
T9337 |
24429-24438 |
VBG |
denotes |
retaining |
T9338 |
24439-24443 |
RB |
denotes |
only |
T9339 |
24450-24454 |
NNS |
denotes |
mice |
T9340 |
24444-24449 |
DT |
denotes |
those |
T9341 |
24455-24459 |
WDT |
denotes |
that |
T9342 |
24460-24464 |
VBP |
denotes |
meet |
T9343 |
24465-24472 |
JJ |
denotes |
certain |
T9344 |
24485-24493 |
NNS |
denotes |
criteria |
T9345 |
24473-24484 |
NN |
denotes |
performance |
T9346 |
24494-24495 |
-LRB- |
denotes |
[ |
T9347 |
24495-24497 |
CD |
denotes |
30 |
T9348 |
24497-24498 |
-RRB- |
denotes |
] |
T9349 |
24498-24499 |
. |
denotes |
. |
T9350 |
24499-24600 |
sentence |
denotes |
In our case, the penetrance of hyperactivity was close to 100%, leaving us with no testable animals. |
T9351 |
24500-24502 |
IN |
denotes |
In |
T9352 |
24545-24548 |
VBD |
denotes |
was |
T9353 |
24503-24506 |
PRP$ |
denotes |
our |
T9354 |
24507-24511 |
NN |
denotes |
case |
T9355 |
24511-24513 |
, |
denotes |
, |
T9356 |
24513-24516 |
DT |
denotes |
the |
T9357 |
24517-24527 |
NN |
denotes |
penetrance |
T9358 |
24528-24530 |
IN |
denotes |
of |
T9359 |
24531-24544 |
NN |
denotes |
hyperactivity |
T9360 |
24549-24554 |
JJ |
denotes |
close |
T9361 |
24558-24561 |
CD |
denotes |
100 |
T9362 |
24555-24557 |
IN |
denotes |
to |
T9363 |
24561-24562 |
NN |
denotes |
% |
T9364 |
24562-24564 |
, |
denotes |
, |
T9365 |
24564-24571 |
VBG |
denotes |
leaving |
T9366 |
24572-24574 |
PRP |
denotes |
us |
T9367 |
24575-24579 |
IN |
denotes |
with |
T9368 |
24580-24582 |
DT |
denotes |
no |
T9369 |
24592-24599 |
NNS |
denotes |
animals |
T9370 |
24583-24591 |
JJ |
denotes |
testable |
T9371 |
24599-24600 |
. |
denotes |
. |
T9372 |
24600-24757 |
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 |
24601-24605 |
DT |
denotes |
This |
T9374 |
24606-24615 |
NN |
denotes |
phenotype |
T9375 |
24624-24632 |
VBN |
denotes |
affected |
T9376 |
24616-24619 |
VBZ |
denotes |
has |
T9377 |
24620-24623 |
RB |
denotes |
not |
T9378 |
24633-24641 |
JJ |
denotes |
previous |
T9379 |
24642-24647 |
NNS |
denotes |
lines |
T9380 |
24648-24650 |
IN |
denotes |
of |
T9381 |
24651-24657 |
NN |
denotes |
APPswe |
T9382 |
24658-24662 |
NNS |
denotes |
mice |
T9383 |
24663-24665 |
PRP |
denotes |
we |
T9384 |
24671-24679 |
VBN |
denotes |
produced |
T9385 |
24666-24670 |
VBP |
denotes |
have |
T9386 |
24679-24681 |
, |
denotes |
, |
T9387 |
24681-24685 |
JJ |
denotes |
such |
T9388 |
24686-24688 |
IN |
denotes |
as |
T9389 |
24689-24694 |
NNS |
denotes |
lines |
T9390 |
24695-24697 |
NN |
denotes |
E1 |
T9391 |
24697-24698 |
HYPH |
denotes |
– |
T9392 |
24698-24699 |
CD |
denotes |
2 |
T9393 |
24700-24702 |
CC |
denotes |
or |
T9394 |
24703-24705 |
NN |
denotes |
C3 |
T9395 |
24705-24706 |
HYPH |
denotes |
– |
T9396 |
24706-24707 |
CD |
denotes |
3 |
T9397 |
24707-24709 |
, |
denotes |
, |
T9398 |
24709-24713 |
WDT |
denotes |
that |
T9399 |
24714-24721 |
VBP |
denotes |
express |
T9400 |
24722-24727 |
JJR |
denotes |
lower |
T9401 |
24728-24734 |
NNS |
denotes |
levels |
T9402 |
24735-24737 |
IN |
denotes |
of |
T9403 |
24738-24748 |
JJ |
denotes |
transgenic |
T9404 |
24749-24756 |
NN |
denotes |
protein |
T9405 |
24756-24757 |
. |
denotes |
. |
T9406 |
24757-24904 |
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 |
24758-24764 |
RB |
denotes |
Indeed |
T9408 |
24823-24834 |
VBD |
denotes |
established |
T9409 |
24764-24766 |
, |
denotes |
, |
T9410 |
24766-24768 |
IN |
denotes |
in |
T9411 |
24769-24773 |
JJ |
denotes |
past |
T9412 |
24774-24781 |
NNS |
denotes |
studies |
T9413 |
24782-24787 |
WRB |
denotes |
where |
T9414 |
24802-24805 |
VBD |
denotes |
was |
T9415 |
24788-24801 |
NN |
denotes |
hyperactivity |
T9416 |
24806-24809 |
RB |
denotes |
not |
T9417 |
24810-24811 |
DT |
denotes |
a |
T9418 |
24812-24818 |
NN |
denotes |
factor |
T9419 |
24818-24820 |
, |
denotes |
, |
T9420 |
24820-24822 |
PRP |
denotes |
we |
T9421 |
24835-24836 |
DT |
denotes |
a |
T9422 |
24843-24855 |
NN |
denotes |
relationship |
T9423 |
24837-24842 |
JJ |
denotes |
clear |
T9424 |
24856-24863 |
IN |
denotes |
between |
T9425 |
24864-24871 |
NN |
denotes |
amyloid |
T9426 |
24872-24876 |
NN |
denotes |
load |
T9427 |
24877-24880 |
CC |
denotes |
and |
T9428 |
24881-24890 |
JJ |
denotes |
cognitive |
T9429 |
24891-24898 |
NN |
denotes |
ability |
T9430 |
24899-24900 |
-LRB- |
denotes |
[ |
T9431 |
24900-24902 |
CD |
denotes |
31 |
T9432 |
24902-24903 |
-RRB- |
denotes |
] |
T9433 |
24903-24904 |
. |
denotes |
. |
T9434 |
24904-25158 |
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 |
24905-24912 |
RB |
denotes |
However |
T9436 |
24939-24943 |
VBP |
denotes |
feel |
T9437 |
24912-24914 |
, |
denotes |
, |
T9438 |
24914-24916 |
IN |
denotes |
in |
T9439 |
24917-24920 |
DT |
denotes |
the |
T9440 |
24929-24934 |
NN |
denotes |
study |
T9441 |
24921-24928 |
JJ |
denotes |
current |
T9442 |
24934-24936 |
, |
denotes |
, |
T9443 |
24936-24938 |
PRP |
denotes |
we |
T9444 |
24944-24948 |
IN |
denotes |
that |
T9445 |
25104-25108 |
VBD |
denotes |
made |
T9446 |
24949-24957 |
IN |
denotes |
although |
T9447 |
25038-25044 |
VBN |
denotes |
scored |
T9448 |
24958-24961 |
DT |
denotes |
the |
T9449 |
24967-24978 |
NN |
denotes |
performance |
T9450 |
24962-24966 |
JJ |
denotes |
poor |
T9451 |
24979-24981 |
IN |
denotes |
of |
T9452 |
24982-24985 |
DT |
denotes |
the |
T9453 |
24994-24998 |
NNS |
denotes |
mice |
T9454 |
24986-24989 |
NN |
denotes |
tTA |
T9455 |
24990-24993 |
NN |
denotes |
APP |
T9456 |
24989-24990 |
HYPH |
denotes |
/ |
T9457 |
24999-25001 |
IN |
denotes |
in |
T9458 |
25002-25005 |
DT |
denotes |
the |
T9459 |
25011-25016 |
NNS |
denotes |
tests |
T9460 |
25006-25010 |
NN |
denotes |
maze |
T9461 |
25017-25022 |
MD |
denotes |
could |
T9462 |
25023-25034 |
RB |
denotes |
technically |
T9463 |
25035-25037 |
VB |
denotes |
be |
T9464 |
25045-25047 |
IN |
denotes |
as |
T9465 |
25048-25057 |
JJ |
denotes |
cognitive |
T9466 |
25058-25068 |
NN |
denotes |
impairment |
T9467 |
25068-25070 |
, |
denotes |
, |
T9468 |
25070-25073 |
DT |
denotes |
the |
T9469 |
25074-25081 |
NNS |
denotes |
animals |
T9470 |
25090-25103 |
NN |
denotes |
hyperactivity |
T9471 |
25081-25082 |
POS |
denotes |
' |
T9472 |
25083-25089 |
JJ |
denotes |
severe |
T9473 |
25109-25123 |
NN |
denotes |
interpretation |
T9474 |
25147-25157 |
JJ |
denotes |
impossible |
T9475 |
25124-25126 |
IN |
denotes |
of |
T9476 |
25127-25130 |
DT |
denotes |
the |
T9477 |
25141-25146 |
NNS |
denotes |
tasks |
T9478 |
25131-25140 |
JJ |
denotes |
cognitive |
T9479 |
25157-25158 |
. |
denotes |
. |
T9480 |
25158-25447 |
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 |
25159-25161 |
IN |
denotes |
In |
T9482 |
25245-25255 |
VBD |
denotes |
quantified |
T9483 |
25162-25167 |
NN |
denotes |
order |
T9484 |
25168-25170 |
TO |
denotes |
to |
T9485 |
25171-25181 |
VB |
denotes |
understand |
T9486 |
25182-25185 |
DT |
denotes |
the |
T9487 |
25186-25192 |
NN |
denotes |
nature |
T9488 |
25193-25196 |
CC |
denotes |
and |
T9489 |
25197-25203 |
NN |
denotes |
extent |
T9490 |
25204-25206 |
IN |
denotes |
of |
T9491 |
25207-25220 |
NN |
denotes |
hyperactivity |
T9492 |
25221-25223 |
IN |
denotes |
in |
T9493 |
25224-25227 |
DT |
denotes |
the |
T9494 |
25236-25240 |
NNS |
denotes |
mice |
T9495 |
25228-25231 |
NN |
denotes |
tTA |
T9496 |
25232-25235 |
NN |
denotes |
APP |
T9497 |
25231-25232 |
HYPH |
denotes |
/ |
T9498 |
25240-25242 |
, |
denotes |
, |
T9499 |
25242-25244 |
PRP |
denotes |
we |
T9500 |
25256-25261 |
JJ |
denotes |
daily |
T9501 |
25271-25277 |
NNS |
denotes |
levels |
T9502 |
25262-25270 |
NN |
denotes |
activity |
T9503 |
25278-25280 |
IN |
denotes |
in |
T9504 |
25281-25287 |
JJ |
denotes |
double |
T9505 |
25288-25298 |
JJ |
denotes |
transgenic |
T9506 |
25299-25306 |
NNS |
denotes |
animals |
T9507 |
25307-25312 |
IN |
denotes |
along |
T9508 |
25313-25317 |
IN |
denotes |
with |
T9509 |
25318-25323 |
PRP$ |
denotes |
their |
T9510 |
25360-25368 |
NNS |
denotes |
siblings |
T9511 |
25324-25330 |
JJ |
denotes |
single |
T9512 |
25331-25341 |
JJ |
denotes |
transgenic |
T9513 |
25342-25345 |
CC |
denotes |
and |
T9514 |
25346-25359 |
JJ |
denotes |
nontransgenic |
T9515 |
25369-25374 |
VBG |
denotes |
using |
T9516 |
25375-25379 |
CD |
denotes |
four |
T9517 |
25380-25384 |
NN |
denotes |
beam |
T9518 |
25379-25380 |
HYPH |
denotes |
- |
T9519 |
25385-25391 |
NNS |
denotes |
frames |
T9520 |
25392-25400 |
VBN |
denotes |
designed |
T9521 |
25401-25403 |
TO |
denotes |
to |
T9522 |
25404-25411 |
VB |
denotes |
monitor |
T9523 |
25412-25422 |
NN |
denotes |
ambulation |
T9524 |
25423-25429 |
IN |
denotes |
within |
T9525 |
25430-25432 |
DT |
denotes |
an |
T9526 |
25442-25446 |
NN |
denotes |
cage |
T9527 |
25433-25441 |
VBN |
denotes |
enclosed |
T9528 |
25446-25447 |
. |
denotes |
. |
T9529 |
25447-25604 |
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 |
25448-25450 |
IN |
denotes |
As |
T9531 |
25451-25456 |
VBN |
denotes |
shown |
T9532 |
25497-25501 |
VBD |
denotes |
were |
T9533 |
25457-25459 |
IN |
denotes |
in |
T9534 |
25460-25466 |
NN |
denotes |
Figure |
T9535 |
25467-25468 |
CD |
denotes |
7 |
T9536 |
25468-25470 |
, |
denotes |
, |
T9537 |
25470-25473 |
DT |
denotes |
the |
T9538 |
25492-25496 |
NNS |
denotes |
mice |
T9539 |
25474-25480 |
JJ |
denotes |
double |
T9540 |
25481-25491 |
JJ |
denotes |
transgenic |
T9541 |
25502-25504 |
IN |
denotes |
up |
T9542 |
25508-25515 |
RB |
denotes |
10-fold |
T9543 |
25505-25507 |
IN |
denotes |
to |
T9544 |
25521-25527 |
JJ |
denotes |
active |
T9545 |
25516-25520 |
RBR |
denotes |
more |
T9546 |
25528-25534 |
IN |
denotes |
during |
T9547 |
25535-25538 |
DT |
denotes |
the |
T9548 |
25544-25549 |
NN |
denotes |
phase |
T9549 |
25539-25543 |
NN |
denotes |
dark |
T9550 |
25550-25552 |
IN |
denotes |
of |
T9551 |
25553-25556 |
DT |
denotes |
the |
T9552 |
25567-25572 |
NN |
denotes |
cycle |
T9553 |
25557-25560 |
NN |
denotes |
day |
T9554 |
25561-25566 |
NN |
denotes |
night |
T9555 |
25560-25561 |
HYPH |
denotes |
– |
T9556 |
25573-25577 |
IN |
denotes |
than |
T9557 |
25578-25581 |
DT |
denotes |
any |
T9558 |
25582-25584 |
IN |
denotes |
of |
T9559 |
25585-25588 |
DT |
denotes |
the |
T9560 |
25597-25603 |
NNS |
denotes |
groups |
T9561 |
25589-25596 |
NN |
denotes |
control |
T9562 |
25603-25604 |
. |
denotes |
. |
T9563 |
25604-25726 |
sentence |
denotes |
Activity levels appeared to follow a relatively normal diurnal cycle, decreasing substantially during the daylight hours. |
T9564 |
25605-25613 |
NN |
denotes |
Activity |
T9565 |
25614-25620 |
NNS |
denotes |
levels |
T9566 |
25621-25629 |
VBD |
denotes |
appeared |
T9567 |
25630-25632 |
TO |
denotes |
to |
T9568 |
25633-25639 |
VB |
denotes |
follow |
T9569 |
25640-25641 |
DT |
denotes |
a |
T9570 |
25668-25673 |
NN |
denotes |
cycle |
T9571 |
25642-25652 |
RB |
denotes |
relatively |
T9572 |
25653-25659 |
JJ |
denotes |
normal |
T9573 |
25660-25667 |
JJ |
denotes |
diurnal |
T9574 |
25673-25675 |
, |
denotes |
, |
T9575 |
25675-25685 |
VBG |
denotes |
decreasing |
T9576 |
25686-25699 |
RB |
denotes |
substantially |
T9577 |
25700-25706 |
IN |
denotes |
during |
T9578 |
25707-25710 |
DT |
denotes |
the |
T9579 |
25720-25725 |
NNS |
denotes |
hours |
T9580 |
25711-25719 |
NN |
denotes |
daylight |
T9581 |
25725-25726 |
. |
denotes |
. |
T9582 |
25726-25834 |
sentence |
denotes |
However, even during the light phase, the tTA/APP mice remained many-fold more active than normal controls. |
T9583 |
25727-25734 |
RB |
denotes |
However |
T9584 |
25782-25790 |
VBD |
denotes |
remained |
T9585 |
25734-25736 |
, |
denotes |
, |
T9586 |
25736-25740 |
RB |
denotes |
even |
T9587 |
25741-25747 |
IN |
denotes |
during |
T9588 |
25748-25751 |
DT |
denotes |
the |
T9589 |
25758-25763 |
NN |
denotes |
phase |
T9590 |
25752-25757 |
NN |
denotes |
light |
T9591 |
25763-25765 |
, |
denotes |
, |
T9592 |
25765-25768 |
DT |
denotes |
the |
T9593 |
25777-25781 |
NNS |
denotes |
mice |
T9594 |
25769-25772 |
NN |
denotes |
tTA |
T9595 |
25773-25776 |
NN |
denotes |
APP |
T9596 |
25772-25773 |
HYPH |
denotes |
/ |
T9597 |
25791-25800 |
RB |
denotes |
many-fold |
T9598 |
25801-25805 |
RBR |
denotes |
more |
T9599 |
25806-25812 |
JJ |
denotes |
active |
T9600 |
25813-25817 |
IN |
denotes |
than |
T9601 |
25818-25824 |
JJ |
denotes |
normal |
T9602 |
25825-25833 |
NNS |
denotes |
controls |
T9603 |
25833-25834 |
. |
denotes |
. |
T9604 |
25834-25972 |
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 |
25835-25839 |
DT |
denotes |
This |
T9606 |
25840-25848 |
NN |
denotes |
behavior |
T9607 |
25886-25894 |
VBN |
denotes |
reversed |
T9608 |
25849-25852 |
VBD |
denotes |
was |
T9609 |
25853-25862 |
RB |
denotes |
partially |
T9610 |
25862-25864 |
, |
denotes |
, |
T9611 |
25864-25867 |
CC |
denotes |
but |
T9612 |
25868-25871 |
RB |
denotes |
not |
T9613 |
25872-25884 |
RB |
denotes |
consistently |
T9614 |
25884-25886 |
, |
denotes |
, |
T9615 |
25895-25897 |
IN |
denotes |
by |
T9616 |
25898-25899 |
CD |
denotes |
1 |
T9617 |
25900-25902 |
NN |
denotes |
mo |
T9618 |
25903-25905 |
IN |
denotes |
of |
T9619 |
25906-25915 |
NN |
denotes |
transgene |
T9620 |
25916-25927 |
NN |
denotes |
suppression |
T9621 |
25928-25937 |
VBG |
denotes |
beginning |
T9622 |
25938-25940 |
IN |
denotes |
at |
T9623 |
25941-25942 |
CD |
denotes |
4 |
T9624 |
25943-25944 |
CD |
denotes |
5 |
T9625 |
25942-25943 |
SYM |
denotes |
– |
T9626 |
25945-25947 |
NN |
denotes |
mo |
T9627 |
25948-25950 |
IN |
denotes |
of |
T9628 |
25951-25954 |
NN |
denotes |
age |
T9629 |
25955-25956 |
-LRB- |
denotes |
( |
T9630 |
25965-25970 |
VBN |
denotes |
shown |
T9631 |
25956-25960 |
NNS |
denotes |
data |
T9632 |
25961-25964 |
RB |
denotes |
not |
T9633 |
25970-25971 |
-RRB- |
denotes |
) |
T9634 |
25971-25972 |
. |
denotes |
. |
T9635 |
25972-26056 |
sentence |
denotes |
In contrast, hyperactivity was completely abolished by rearing tTA/APP mice on dox. |
T9636 |
25973-25975 |
IN |
denotes |
In |
T9637 |
26015-26024 |
VBN |
denotes |
abolished |
T9638 |
25976-25984 |
NN |
denotes |
contrast |
T9639 |
25984-25986 |
, |
denotes |
, |
T9640 |
25986-25999 |
NN |
denotes |
hyperactivity |
T9641 |
26000-26003 |
VBD |
denotes |
was |
T9642 |
26004-26014 |
RB |
denotes |
completely |
T9643 |
26025-26027 |
IN |
denotes |
by |
T9644 |
26028-26035 |
VBG |
denotes |
rearing |
T9645 |
26036-26039 |
NN |
denotes |
tTA |
T9646 |
26040-26043 |
NN |
denotes |
APP |
T9647 |
26039-26040 |
HYPH |
denotes |
/ |
T9648 |
26044-26048 |
NNS |
denotes |
mice |
T9649 |
26049-26051 |
IN |
denotes |
on |
T9650 |
26052-26055 |
NN |
denotes |
dox |
T9651 |
26055-26056 |
. |
denotes |
. |
T9652 |
26056-26157 |
sentence |
denotes |
Animals born and raised on dox showed activity levels similar to the untreated controls (Figure 7C). |
T9653 |
26057-26064 |
NNS |
denotes |
Animals |
T9654 |
26088-26094 |
VBD |
denotes |
showed |
T9655 |
26065-26069 |
VBN |
denotes |
born |
T9656 |
26070-26073 |
CC |
denotes |
and |
T9657 |
26074-26080 |
VBN |
denotes |
raised |
T9658 |
26081-26083 |
IN |
denotes |
on |
T9659 |
26084-26087 |
NN |
denotes |
dox |
T9660 |
26095-26103 |
NN |
denotes |
activity |
T9687 |
26223-26227 |
JJ |
denotes |
wild |
T9688 |
26228-26232 |
NN |
denotes |
type |
T9689 |
26227-26228 |
HYPH |
denotes |
- |
T9690 |
26232-26234 |
, |
denotes |
, |
T9691 |
26241-26248 |
VBN |
denotes |
altered |
T9692 |
26259-26266 |
NNS |
denotes |
rhythms |
T9693 |
26249-26258 |
JJ |
denotes |
circadian |
T9694 |
26267-26271 |
IN |
denotes |
with |
T9695 |
26272-26275 |
RB |
denotes |
far |
T9696 |
26276-26280 |
JJR |
denotes |
less |
T9697 |
26281-26292 |
NN |
denotes |
distinction |
T9698 |
26293-26300 |
IN |
denotes |
between |
T9699 |
26301-26306 |
PRP$ |
denotes |
their |
T9700 |
26335-26341 |
NNS |
denotes |
levels |
T9701 |
26307-26310 |
NN |
denotes |
day |
T9702 |
26310-26311 |
HYPH |
denotes |
- |
T9703 |
26312-26315 |
CC |
denotes |
and |
T9704 |
26316-26325 |
NN |
denotes |
nighttime |
T9705 |
26326-26334 |
NN |
denotes |
activity |
T9706 |
26341-26342 |
. |
denotes |
. |
T9668 |
26153-26155 |
NN |
denotes |
7C |
T9669 |
26146-26152 |
NN |
denotes |
Figure |
T9670 |
26155-26156 |
-RRB- |
denotes |
) |
T9671 |
26156-26157 |
. |
denotes |
. |
T9672 |
26157-26342 |
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 |
26158-26170 |
RB |
denotes |
Intriguingly |
T9674 |
26234-26240 |
VBD |
denotes |
showed |
T9675 |
26170-26172 |
, |
denotes |
, |
T9676 |
26172-26175 |
DT |
denotes |
all |
T9677 |
26176-26178 |
IN |
denotes |
of |
T9678 |
26179-26182 |
DT |
denotes |
the |
T9679 |
26194-26201 |
NNS |
denotes |
animals |
T9680 |
26183-26186 |
NN |
denotes |
dox |
T9681 |
26187-26193 |
VBN |
denotes |
reared |
T9682 |
26186-26187 |
HYPH |
denotes |
- |
T9683 |
26201-26203 |
, |
denotes |
, |
T9684 |
26203-26207 |
CC |
denotes |
both |
T9685 |
26208-26218 |
JJ |
denotes |
transgenic |
T9686 |
26219-26222 |
CC |
denotes |
and |
T9661 |
26104-26110 |
NNS |
denotes |
levels |
T9662 |
26111-26118 |
JJ |
denotes |
similar |
T9663 |
26119-26121 |
IN |
denotes |
to |
T9664 |
26122-26125 |
DT |
denotes |
the |
T9665 |
26136-26144 |
NNS |
denotes |
controls |
T9666 |
26126-26135 |
JJ |
denotes |
untreated |
T9667 |
26145-26146 |
-LRB- |
denotes |
( |
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 |
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 |