%PDF-1.6
%
1 0 obj
<>
endobj
2 0 obj
<>stream
Eiki Kimura, Ken-ichiro Kubo, Toshihiro Endo, Wenting Ling, Kazunori Nakajima, Masaki Kakeyama, Chiharu Tohyama
Impaired dendritic growth and positioning of cortical pyramidal neurons by activation of aryl hydrocarbon receptor signaling in the developing mouse
www.plosone.org
www.plosone.org
endstream
endobj
3 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 12 0 R/Annots 13 0 R/Contents 14 0 R/TrimBox[0 0 612 792]>>
endobj
13 0 obj
[15 0 R 16 0 R 17 0 R 18 0 R 19 0 R 20 0 R 21 0 R 22 0 R 23 0 R 24 0 R 25 0 R 26 0 R 27 0 R 28 0 R 29 0 R 30 0 R 31 0 R 32 0 R 33 0 R 34 0 R 35 0 R 36 0 R 37 0 R 38 0 R 39 0 R 40 0 R 41 0 R 42 0 R 43 0 R 44 0 R 45 0 R 46 0 R 47 0 R 48 0 R 49 0 R]
endobj
15 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref001)>>
endobj
16 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref002)>>
endobj
17 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref003)>>
endobj
18 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref004)>>
endobj
19 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref005)>>
endobj
20 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref006)>>
endobj
21 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref007)>>
endobj
22 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref008)>>
endobj
23 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref009)>>
endobj
24 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref010)>>
endobj
25 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref011)>>
endobj
26 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref012)>>
endobj
27 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref013)>>
endobj
28 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref014)>>
endobj
29 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref015)>>
endobj
30 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref016)>>
endobj
31 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref018)>>
endobj
32 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref019)>>
endobj
33 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref020)>>
endobj
34 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref021)>>
endobj
35 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref022)>>
endobj
36 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref023)>>
endobj
37 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref024)>>
endobj
38 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref025)>>
endobj
39 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref026)>>
endobj
40 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref028)>>
endobj
41 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref029)>>
endobj
42 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref030)>>
endobj
43 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref031)>>
endobj
44 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref032)>>
endobj
45 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref033)>>
endobj
46 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref034)>>
endobj
47 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref035)>>
endobj
48 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref036)>>
endobj
49 0 obj
<>/Border[0 0 0]/A 50 0 R>>
endobj
50 0 obj
<>
endobj
14 0 obj
[51 0 R 52 0 R 53 0 R 54 0 R 55 0 R 56 0 R 57 0 R 58 0 R 59 0 R 60 0 R 61 0 R 62 0 R 63 0 R 64 0 R 65 0 R 66 0 R 67 0 R 68 0 R 69 0 R 70 0 R 71 0 R 72 0 R 73 0 R 74 0 R 75 0 R 76 0 R 77 0 R 78 0 R 79 0 R 80 0 R 81 0 R 82 0 R 83 0 R 84 0 R 85 0 R 86 0 R]
endobj
51 0 obj
<>stream
q
0.83 0.64 0.02 0 k
225.6378 649.0205 m
230.4 649.0205 l
h
f*
234.822 649.0205 m
239.5843 649.0205 l
h
f*
455.6409 596.9764 m
460.3465 596.9764 l
h
f*
464.8252 596.9764 m
469.5874 596.9764 l
h
f*
541.0772 544.989 m
545.8394 544.989 l
h
f*
550.2614 544.989 m
555.0236 544.989 l
h
f*
347.4142 480.0189 m
352.1764 480.0189 l
h
f*
356.6551 480.0189 m
361.4173 480.0189 l
h
f*
348.2646 466.9795 m
353.0268 466.9795 l
h
f*
415.389 453.9969 m
424.9134 453.9969 l
h
f*
429.3921 453.9969 m
438.8598 453.9969 l
h
f*
221.5559 428.0315 m
231.0236 428.0315 l
h
f*
235.5024 428.0315 m
245.0268 428.0315 l
h
f*
445.1528 414.9921 m
454.6205 414.9921 l
h
f*
459.0992 414.9921 m
468.6236 414.9921 l
h
f*
253.2472 350.022 m
263.0551 350.022 l
h
f*
268.3276 350.022 m
278.1354 350.022 l
h
f*
246.3874 311.0173 m
256.1386 311.0173 l
h
f*
260.7874 311.0173 m
270.5386 311.0173 l
h
f*
315.8362 259.0299 m
325.6441 259.0299 l
h
f*
330.2362 259.0299 m
340.0441 259.0299 l
h
f*
543.5717 245.9906 m
553.3228 245.9906 l
h
f*
537.222 233.0079 m
547.0299 233.0079 l
h
f*
527.3575 167.9811 m
536.8819 167.9811 l
h
f*
203.4142 142.0157 m
212.9386 142.0157 l
h
f*
218.0976 142.0157 m
227.622 142.0157 l
h
f*
487.1055 128.9764 m
496.6299 128.9764 l
h
f*
203.4142 115.9937 m
212.9386 115.9937 l
h
f*
217.3606 115.9937 m
226.885 115.9937 l
h
f*
312.2646 115.9937 m
321.789 115.9937 l
h
f*
326.2677 115.9937 m
335.7354 115.9937 l
h
f*
457.4551 115.9937 m
466.9795 115.9937 l
h
f*
282.3874 103.011 m
291.9118 103.011 l
h
f*
328.252 90.0283 m
337.7764 90.0283 l
h
f*
0 g
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 706.0535 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Introduction)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 689.1023 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(The)Tj
1.7744 0 Td
(mammalian)Tj
5.0343 0 Td
(cerebral)Tj
3.4072 0 Td
(cortex)Tj
2.7043 0 Td
(consists)Tj
3.3335 0 Td
(of)Tj
1.0091 0 Td
(six)Tj
1.304 0 Td
(layers,)Tj
2.7269 0 Td
(each)Tj
2.0182 0 Td
(of)Tj
1.0092 0 Td
(which)Tj
2.6418 0 Td
(harbors)Tj
3.2882 0 Td
(subsets)Tj
3.0501 0 Td
(of)Tj
1.0034 0 Td
(neurons)Tj
-34.3046 -1.3039 Td
(distinguished)Tj
5.5898 0 Td
(by)Tj
1.1792 0 Td
(morphology)Tj
5.1421 0 Td
(and)Tj
1.7347 0 Td
(synaptic)Tj
3.5207 0 Td
(organization:)Tj
5.5105 0 Td
(each)Tj
2.0239 0 Td
(layer)Tj
2.1543 0 Td
(has)Tj
1.5421 0 Td
(specific)Tj
3.1861 0 Td
(pyramidal)Tj
-31.5834 -1.2982 Td
(neurons)Tj
3.4979 0 Td
(that)Tj
1.7688 0 Td
(are)Tj
1.44 0 Td
(endowed)Tj
3.8551 0 Td
(with)Tj
1.9899 0 Td
(characteristic)Tj
5.5388 0 Td
(dendritic)Tj
3.8665 0 Td
(arborization)Tj
5.1363 0 Td
(and)Tj
1.7235 0 Td
(axonal)Tj
2.8459 0 Td
(projection)Tj
4.3314 0 Td
(pat-)Tj
-35.9941 -1.2983 Td
(terns)Tj
2.2223 0 Td
([)Tj
0.83 0.64 0.02 0 k
(1)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2586 0 Td
(2)Tj
0 g
(].)Tj
1.2642 0 Td
(Development)Tj
5.6182 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(cortex)Tj
2.7099 0 Td
(consists)Tj
3.3448 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.6577 0 Td
(series)Tj
2.4264 0 Td
(of)Tj
1.0148 0 Td
(processes)Tj
3.9685 0 Td
(that)Tj
1.7801 0 Td
(are)Tj
1.4457 0 Td
(characterized)Tj
-31.2092 -1.3039 Td
(by)Tj
1.1792 0 Td
(sequential)Tj
4.2576 0 Td
(progenitor)Tj
4.4957 0 Td
(proliferation,)Tj
5.4935 0 Td
(neuronal)Tj
3.8267 0 Td
(migration,)Tj
4.4221 0 Td
(and)Tj
1.7291 0 Td
(dendritic)Tj
3.8778 0 Td
(and)Tj
1.7291 0 Td
(axonal)Tj
2.8573 0 Td
(growth,)Tj
-33.8681 -1.2983 Td
(leading)Tj
3.1294 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4684 0 Td
(establishment)Tj
5.7372 0 Td
(of)Tj
1.0148 0 Td
(functional)Tj
4.3087 0 Td
(cortical)Tj
3.1918 0 Td
(circuits)Tj
3.1577 0 Td
(required)Tj
3.6397 0 Td
(for)Tj
1.389 0 Td
(higher)Tj
2.8006 0 Td
(brain)Tj
2.347 0 Td
(function.)Tj
-33.2104 -1.2982 Td
(These)Tj
2.5681 0 Td
(developmental)Tj
6.0888 0 Td
(processes)Tj
3.9685 0 Td
(are)Tj
1.4456 0 Td
(regulated)Tj
3.9402 0 Td
(by)Tj
1.1792 0 Td
(molecular)Tj
4.2236 0 Td
(signaling)Tj
3.8211 0 Td
(pathways)Tj
3.9287 0 Td
(that)Tj
1.7802 0 Td
(consist)Tj
2.9877 0 Td
(of)Tj
-35.9317 -1.304 Td
(ligand-receptor)Tj
6.3949 0 Td
(interactions)Tj
4.9662 0 Td
(and)Tj
1.7292 0 Td
(transcription)Tj
5.4368 0 Td
(factor)Tj
2.5398 0 Td
(activation)Tj
4.1556 0 Td
([)Tj
0.83 0.64 0.02 0 k
(3)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2585 0 Td
(4)Tj
0 g
(].)Tj
-25.2848 -1.2982 Td
(The)Tj
1.7744 0 Td
(basic)Tj
2.2054 0 Td
(helix-loop-helix)Tj
6.548 0 Td
(\(bHLH\))Tj
3.4696 0 Td
(transcription)Tj
5.4198 0 Td
(factors)Tj
2.897 0 Td
(possess)Tj
3.101 0 Td
(multiple)Tj
3.5547 0 Td
(functions)Tj
3.9798 0 Td
(in)Tj
1.0261 0 Td
(mam-)Tj
-35.172 -1.2983 Td
(malian)Tj
2.9706 0 Td
(brain)Tj
2.3471 0 Td
(development.)Tj
5.6353 0 Td
(They)Tj
2.2336 0 Td
(can)Tj
1.6271 0 Td
(be)Tj
1.1509 0 Td
(divided)Tj
3.2144 0 Td
(into)Tj
1.8425 0 Td
(three)Tj
2.2621 0 Td
(main)Tj
2.2904 0 Td
(subfamilies:)Tj
4.9492 0 Td
(\(1\))Tj
1.3777 0 Td
(the)Tj
1.4683 0 Td
(bHLH)Tj
-33.3692 -1.2983 Td
(domain)Tj
3.3221 0 Td
(only)Tj
1.9786 0 Td
(\(bHLH)Tj
3.1408 0 Td
(only\),)Tj
2.5398 0 Td
(\(2\))Tj
1.3776 0 Td
(bHLH)Tj
2.8006 0 Td
(domain)Tj
3.3222 0 Td
(contiguous)Tj
4.6545 0 Td
(with)Tj
1.9956 0 Td
(a)Tj
0.6519 0 Td
(leucine)Tj
3.0841 0 Td
(zipper)Tj
2.7269 0 Td
(\(bHLH-Zip\),)Tj
-31.5947 -1.3039 Td
(and)Tj
1.7291 0 Td
(\(3\))Tj
1.3776 0 Td
(bHLH)Tj
2.8006 0 Td
(domain)Tj
3.3222 0 Td
(contiguous)Tj
4.6545 0 Td
(with)Tj
1.9955 0 Td
(a)Tj
0.652 0 Td
(Per-Arnt-Sim)Tj
5.743 0 Td
(\(PAS\))Tj
2.6192 0 Td
(domain)Tj
3.3221 0 Td
(\(bHLH-PAS\))Tj
5.5502 0 Td
([)Tj
0.83 0.64 0.02 0 k
(5)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2586 0 Td
(6)Tj
0 g
(].)Tj
-35.0246 -1.2982 Td
(Members)Tj
4.0081 0 Td
(of)Tj
1.0035 0 Td
(these)Tj
2.245 0 Td
(subfamilies)Tj
4.7111 0 Td
(exhibit)Tj
2.9707 0 Td
(region-)Tj
3.1408 0 Td
(and)Tj
1.7235 0 Td
(cell)Tj
1.5477 0 Td
(type-specific)Tj
5.227 0 Td
(effects)Tj
2.7156 0 Td
(on)Tj
1.2642 0 Td
(progenitor)Tj
4.4901 0 Td
(prolif-)Tj
-35.0473 -1.2983 Td
(eration,)Tj
3.2938 0 Td
(neuronal)Tj
3.8267 0 Td
(differentiation,)Tj
6.2022 0 Td
(and)Tj
1.7291 0 Td
(corticogenesis.)Tj
6.0945 0 Td
(The)Tj
1.7858 0 Td
(bHLH)Tj
2.7949 0 Td
(only)Tj
1.9786 0 Td
(subfamily)Tj
4.1272 0 Td
(contains)Tj
-31.8328 -1.3039 Td
(members,)Tj
4.1669 0 Td
(such)Tj
2.0636 0 Td
(as)Tj
1.0148 0 Td
(neurogenin)Tj
4.8528 0 Td
(\(Ngn\),)Tj
2.8744 0 Td
(neurogenic)Tj
4.7224 0 Td
(differentiation)Tj
5.9811 0 Td
(\(Neurod\),)Tj
4.2179 0 Td
(and)Tj
1.7292 0 Td
(hairy)Tj
2.2733 0 Td
(and)Tj
-33.8964 -1.2983 Td
(enhancer)Tj
3.9174 0 Td
(of)Tj
1.0148 0 Td
(split)Tj
1.9105 0 Td
(\(Hes\).)Tj
2.6816 0 Td
(Phosphorylated)Tj
6.48 0 Td
(Ngn2)Tj
2.4434 0 Td
(regulates)Tj
3.7757 0 Td
(the)Tj
1.4684 0 Td
(migration)Tj
4.1952 0 Td
(and)Tj
1.7291 0 Td
(dendritic)Tj
3.8778 0 Td
(morphol-)Tj
-33.4939 -1.2982 Td
(ogy)Tj
1.644 0 Td
(of)Tj
1.0148 0 Td
(mammalian)Tj
5.0457 0 Td
(cortical)Tj
3.1918 0 Td
(neurons)Tj
3.5036 0 Td
([)Tj
0.83 0.64 0.02 0 k
(7)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2642 0 Td
(8)Tj
0 g
(].)Tj
/F11 1 Tf
1.2586 0 Td
[()28()2()12()20()4()]TJ
/F6 1 Tf
(-null)Tj
5.5445 0 Td
(mice)Tj
2.1543 0 Td
(show)Tj
2.2961 0 Td
(histological)Tj
4.7735 0 Td
(degeneration)Tj
-31.6911 -1.304 Td
(of)Tj
1.0147 0 Td
(the)Tj
1.4684 0 Td
(hippocampus)Tj
5.6409 0 Td
(and)Tj
1.7291 0 Td
(cerebellum)Tj
4.6318 0 Td
([)Tj
0.83 0.64 0.02 0 k
(9)Tj
0 g
(].)Tj
1.5987 0 Td
(Hes1)Tj
2.2507 0 Td
(and)Tj
1.7291 0 Td
(Hes5)Tj
2.2507 0 Td
(are)Tj
1.4457 0 Td
(highly)Tj
2.7099 0 Td
(expressed)Tj
4.0932 0 Td
(in)Tj
1.0375 0 Td
(neural)Tj
2.7722 0 Td
(stem)Tj
-34.3726 -1.2982 Td
(cells,)Tj
2.1429 0 Td
(and)Tj
1.7292 0 Td
(inhibit)Tj
2.9083 0 Td
(differentiation)Tj
5.9754 0 Td
(into)Tj
1.8425 0 Td
(mature)Tj
3.0954 0 Td
(neurons)Tj
3.5036 0 Td
([)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7405 0 Td
(11)Tj
0 g
(].)Tj
1.7348 0 Td
(c-Myc)Tj
2.7665 0 Td
(and)Tj
1.7292 0 Td
(N-Myc,)Tj
3.2995 0 Td
(which)Tj
-32.4678 -1.2983 Td
(belong)Tj
2.9139 0 Td
(to)Tj
1.0262 0 Td
(the)Tj
1.4683 0 Td
(bHLH-Zip)Tj
4.5411 0 Td
(subfamily,)Tj
4.3483 0 Td
(control)Tj
3.1238 0 Td
(cellular)Tj
3.1351 0 Td
(proliferation)Tj
5.2667 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(cerebrum)Tj
4.0876 0 Td
(and)Tj
1.7291 0 Td
(cerebel-)Tj
-34.1459 -1.2983 Td
(lum)Tj
1.8141 0 Td
([)Tj
0.83 0.64 0.02 0 k
(12)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(13)Tj
0 g
(].)Tj
1.7348 0 Td
(Sim1)Tj
2.262 0 Td
(and)Tj
1.7292 0 Td
(Sim2,)Tj
2.4831 0 Td
(members)Tj
3.9458 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(bHLH-PAS)Tj
4.8699 0 Td
(subfamily,)Tj
4.3483 0 Td
(have)Tj
2.0636 0 Td
(been)Tj
2.1203 0 Td
(reported)Tj
3.6624 0 Td
(to)Tj
-35.2514 -1.3039 Td
(regulate)Tj
3.4072 0 Td
(neuronal)Tj
3.8267 0 Td
(subtype)Tj
3.3109 0 Td
(specification)Tj
5.244 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(hypothalamus)Tj
5.8791 0 Td
([)Tj
0.83 0.64 0.02 0 k
(14)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7347 0 Td
(15)Tj
0 g
(].)Tj
1.7348 0 Td
(Hence,)Tj
3.0331 0 Td
(clarification)Tj
4.9946 0 Td
(of)Tj
-35.6709 -1.2982 Td
(the)Tj
1.4683 0 Td
(mechanism)Tj
4.8472 0 Td
(of)Tj
1.0148 0 Td
(mammalian)Tj
5.04 0 Td
(cortical)Tj
3.1918 0 Td
(development)Tj
5.4084 0 Td
(requires)Tj
3.4753 0 Td
(a)Tj
0.6519 0 Td
(complete)Tj
3.8778 0 Td
(understanding)Tj
6.0718 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
-36.0621 -1.2983 Td
(functions)Tj
3.9911 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(bHLH)Tj
2.8007 0 Td
(family)Tj
2.7269 0 Td
(genes.)Tj
0.01 Tc
-10.8056 -1.3039 Td
(The)Tj
1.8255 0 Td
(aryl)Tj
1.7858 0 Td
(hydrocarbon)Tj
5.5502 0 Td
(receptor)Tj
3.668 0 Td
(\(AhR\),)Tj
3.0444 0 Td
(which)Tj
2.7212 0 Td
(belongs)Tj
3.3732 0 Td
(to)Tj
1.0545 0 Td
(the)Tj
1.5137 0 Td
(bHLH-PAS)Tj
4.9776 0 Td
(subfamily,)Tj
4.4901 0 Td
(is)Tj
-35.2004 -1.2983 Td
(expressed)Tj
4.2179 0 Td
(in)Tj
1.0658 0 Td
(the)Tj
1.508 0 Td
(mammalian)Tj
5.1704 0 Td
(brain,)Tj
2.6589 0 Td
(including)Tj
4.1669 0 Td
(the)Tj
1.508 0 Td
(cerebral)Tj
3.5319 0 Td
(cortex)Tj
2.795 0 Td
(in)Tj
1.0658 0 Td
(the)Tj
1.508 0 Td
(developing)Tj
4.7395 0 Td
(and)Tj
-33.9361 -1.2983 Td
(adult)Tj
2.3243 0 Td
(stages)Tj
2.6476 0 Td
([)Tj
0.83 0.64 0.02 0 k
(16)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(],)Tj
3.6567 0 Td
(and)Tj
1.7688 0 Td
(acts)Tj
1.7914 0 Td
(as)Tj
1.0432 0 Td
(a)Tj
0.669 0 Td
(receptor)Tj
3.668 0 Td
(for)Tj
1.4286 0 Td
(ligands)Tj
3.1691 0 Td
(to)Tj
1.0545 0 Td
(induce)Tj
3.0217 0 Td
(downstream)Tj
5.3348 0 Td
(signaling.)Tj
4.1839 0 Td
(The)Tj
-35.7616 -1.3039 Td
(liganded)Tj
3.77 0 Td
(AhR)Tj
2.0976 0 Td
(is)Tj
0.8731 0 Td
(activated)Tj
3.9061 0 Td
(by)Tj
1.2132 0 Td
(cofactors)Tj
3.9572 0 Td
(and)Tj
1.7745 0 Td
(translocated)Tj
5.261 0 Td
(from)Tj
2.2621 0 Td
(the)Tj
1.508 0 Td
(cytoplasm)Tj
4.4107 0 Td
(to)Tj
1.0488 0 Td
(the)Tj
1.5137 0 Td
(nucleus,)Tj
-33.596 -1.2982 Td
(where)Tj
2.7212 0 Td
(it)Tj
0.8107 0 Td
(enhances)Tj
4.0252 0 Td
(the)Tj
1.508 0 Td
(transcription)Tj
5.6182 0 Td
(of)Tj
1.0432 0 Td
(target)Tj
2.5908 0 Td
(genes)Tj
2.5115 0 Td
(such)Tj
2.1146 0 Td
(as)Tj
/F11 1 Tf
1.0432 0 Td
[()35( )-13(\n)]TJ
/F6 1 Tf
(,)Tj
/F11 1 Tf
3.4922 0 Td
[()35( )-13(\n)]TJ
/F6 1 Tf
(,)Tj
3.481 0 Td
(and)Tj
/F11 1 Tf
1.7744 0 Td
[(\r)20()18()]TJ
1.7802 0 Td
[()20()2(\n)11()20()8()]TJ
-34.5144 -1.2983 Td
[()-3()11()]TJ
/F6 1 Tf
1.4173 0 Td
(\()Tj
/F11 1 Tf
[(\r)20()18()-9()]TJ
/F6 1 Tf
(\))Tj
2.8629 0 Td
([)Tj
0.83 0.64 0.02 0 k
(19)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7972 0 Td
(20)Tj
0 g
(].)Tj
1.7915 0 Td
(Although)Tj
4.1159 0 Td
(the)Tj
1.508 0 Td
(endogenous)Tj
5.1987 0 Td
(AhR)Tj
2.0976 0 Td
(ligand)Tj
2.795 0 Td
(that)Tj
1.8311 0 Td
(contributes)Tj
4.9096 0 Td
(to)Tj
1.0545 0 Td
(neurodevelop-)Tj
-31.3793 -1.3039 Td
(ment)Tj
2.364 0 Td
(has)Tj
1.5874 0 Td
(not)Tj
1.6158 0 Td
(been)Tj
2.177 0 Td
(identified,)Tj
4.439 0 Td
(loss-)Tj
2.1146 0 Td
(or)Tj
1.1225 0 Td
(gain-of-function)Tj
7.0639 0 Td
(experiments)Tj
5.2951 0 Td
(have)Tj
2.1146 0 Td
(demonstrated)Tj
-29.8939 -1.2983 Td
(important)Tj
4.405 0 Td
(roles)Tj
2.1996 0 Td
(of)Tj
1.0432 0 Td
(AhR)Tj
2.0976 0 Td
(in)Tj
1.0602 0 Td
(nervous)Tj
3.5149 0 Td
(system)Tj
3.0217 0 Td
(development.)Tj
5.7997 0 Td
(In)Tj
/F11 1 Tf
1.1395 0 Td
[()-2()6()2()6()11()8()6()22()4()12()14()7()-4()]TJ
6.3949 0 Td
[()15()4()9()2()16()]TJ
/F6 1 Tf
(,)Tj
/F11 1 Tf
3.3335 0 Td
[()11()18()19()]TJ
/F6 1 Tf
(,)Tj
2.6759 0 Td
(a)Tj
-36.6857 -1.2982 Td
(homolog)Tj
3.8947 0 Td
(of)Tj
1.0375 0 Td
(the)Tj
1.508 0 Td
(mammalian)Tj
5.1647 0 Td
(AhR,)Tj
2.3301 0 Td
(regulates)Tj
3.8948 0 Td
(neuronal)Tj
3.9344 0 Td
(migration,)Tj
4.5581 0 Td
(axonal)Tj
2.9367 0 Td
(branching,)Tj
4.6771 0 Td
(and)Tj
1.7688 0 Td
(neu-)Tj
-35.7049 -1.2983 Td
(ronal)Tj
2.398 0 Td
(subtype)Tj
3.4073 0 Td
(specification)Tj
5.4254 0 Td
([)Tj
0.83 0.64 0.02 0 k
(21)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7915 0 Td
(22)Tj
0 g
(].)Tj
/F11 1 Tf
1.7915 0 Td
[()14(\n)11()12()6()15()4()8()10()]TJ
/F6 1 Tf
(,)Tj
3.9912 0 Td
(the)Tj
/F11 1 Tf
1.5137 0 Td
[()-4()20()7()-3()11(\n)10()18()4()4()]TJ
/F6 1 Tf
4.6431 0 Td
(homolog)Tj
3.9004 0 Td
(of)Tj
1.0432 0 Td
(the)Tj
1.508 0 Td
(mammalian)Tj
-31.4133 -1.3039 Td
(AhR,)Tj
2.3357 0 Td
(controls)Tj
3.5943 0 Td
(the)Tj
1.508 0 Td
(complexity)Tj
4.7849 0 Td
(of)Tj
1.0431 0 Td
(dendritic)Tj
3.9968 0 Td
(arborization)Tj
5.3178 0 Td
(in)Tj
1.0601 0 Td
(sensory)Tj
3.3449 0 Td
(neuron)Tj
3.2315 0 Td
(subtypes)Tj
3.7814 0 Td
([)Tj
0.83 0.64 0.02 0 k
(23)Tj
0 g
(].)Tj
2.1486 0 Td
(In)Tj
-36.1471 -1.2983 Td
(the)Tj
1.508 0 Td
(mouse)Tj
2.931 0 Td
(cerebellum,)Tj
5.0116 0 Td
(AhR)Tj
2.0976 0 Td
(has)Tj
1.5817 0 Td
(been)Tj
2.177 0 Td
(shown)Tj
2.9197 0 Td
(to)Tj
1.0545 0 Td
(regulate)Tj
3.5206 0 Td
(granule)Tj
3.3335 0 Td
(cell)Tj
1.6158 0 Td
(neurogenesis)Tj
5.6182 0 Td
([)Tj
0.83 0.64 0.02 0 k
(24)Tj
0 g
(].)Tj
-33.3692 -1.2983 Td
(Thus,)Tj
2.5398 0 Td
(it)Tj
0.8163 0 Td
(is)Tj
0.8731 0 Td
(plausible)Tj
3.8778 0 Td
(that)Tj
1.8312 0 Td
(AhR-mediated)Tj
6.2985 0 Td
(signaling)Tj
3.9458 0 Td
(regulates)Tj
3.8948 0 Td
(neuronal)Tj
3.9401 0 Td
(differentiation)Tj
6.1908 0 Td
(and)Tj
-34.2082 -1.3039 Td
(maturation)Tj
4.8642 0 Td
(in)Tj
1.0658 0 Td
(the)Tj
1.508 0 Td
(mammalian)Tj
5.1704 0 Td
(cerebral)Tj
3.5319 0 Td
(cortex.)Tj
-0.004 Tc
-14.9441 -1.2982 Td
(Dioxin,)Tj
3.2371 0 Td
(a)Tj
0.6576 0 Td
(persistent)Tj
4.0876 0 Td
(and)Tj
1.7291 0 Td
(highly)Tj
2.7099 0 Td
(toxic)Tj
2.1827 0 Td
(environmental)Tj
6.1114 0 Td
(contaminant,)Tj
5.5729 0 Td
(is)Tj
0.8447 0 Td
(an)Tj
1.2019 0 Td
(extremely)Tj
4.1499 0 Td
(potent)Tj
-33.681 -1.2983 Td
(exogenous)Tj
4.4446 0 Td
(AhR)Tj
2.058 0 Td
(ligand,)Tj
2.931 0 Td
(and)Tj
1.7291 0 Td
(activation)Tj
4.1556 0 Td
(of)Tj
1.0148 0 Td
(AhR)Tj
2.0522 0 Td
(signaling)Tj
3.8211 0 Td
(by)Tj
1.1849 0 Td
(dioxin)Tj
2.8006 0 Td
(has)Tj
1.542 0 Td
(been)Tj
2.126 0 Td
(shown)Tj
2.846 0 Td
(to)Tj
1.0261 0 Td
(induce)Tj
2.9367 0 Td
(a)Tj
-36.6687 -1.3039 Td
(variety)Tj
2.9196 0 Td
(of)Tj
1.0205 0 Td
(toxic)Tj
2.177 0 Td
(effects,)Tj
2.9537 0 Td
(such)Tj
2.0579 0 Td
(as)Tj
1.0148 0 Td
(cancer,)Tj
3.0727 0 Td
(reproductive)Tj
5.3291 0 Td
(toxicity,)Tj
3.4299 0 Td
(and)Tj
1.7292 0 Td
(immunotoxicity)Tj
6.6897 0 Td
([)Tj
0.83 0.64 0.02 0 k
(25)Tj
0 g
(].)Tj
2.0749 0 Td
(Studies)Tj
-34.469 -1.2983 Td
(on)Tj
1.2755 0 Td
(AhR-null)Tj
3.9742 0 Td
(mice)Tj
2.1486 0 Td
(have)Tj
2.0636 0 Td
(demonstrated)Tj
5.76 0 Td
(that)Tj
1.7801 0 Td
(the)Tj
1.4684 0 Td
(AhR)Tj
2.0523 0 Td
(is)Tj
0.8503 0 Td
(necessary)Tj
4.0195 0 Td
(for)Tj
1.3833 0 Td
(these)Tj
2.2564 0 Td
(toxic)Tj
2.1827 0 Td
(effects)Tj
2.7212 0 Td
(of)Tj
1.0148 0 Td
(dioxin)Tj
-34.9509 -1.2983 Td
([)Tj
0.83 0.64 0.02 0 k
(26)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(28)Tj
0 g
(].)Tj
3.5432 0 Td
(In)Tj
1.1112 0 Td
(addition,)Tj
3.8211 0 Td
(adult)Tj
2.2564 0 Td
(rodent)Tj
2.8969 0 Td
(offspring)Tj
3.8325 0 Td
(born)Tj
2.1543 0 Td
(to)Tj
1.0204 0 Td
(dams)Tj
2.3641 0 Td
(exposed)Tj
3.4469 0 Td
(to)Tj
1.0262 0 Td
(dioxin)Tj
2.8006 0 Td
(during)Tj
2.9253 0 Td
(gestation)Tj
-33.1991 -1.3039 Td
(exhibit)Tj
2.9763 0 Td
(cognitive)Tj
3.8721 0 Td
(and)Tj
1.7291 0 Td
(behavioral)Tj
4.3937 0 Td
(abnormalities,)Tj
5.93 0 Td
(such)Tj
2.058 0 Td
(as)Tj
1.0148 0 Td
(spatial)Tj
2.7779 0 Td
(memory)Tj
3.617 0 Td
([)Tj
0.83 0.64 0.02 0 k
(29)Tj
0 g
(],)Tj
2.0806 0 Td
(fear)Tj
1.7348 0 Td
(conditioning)Tj
-32.1843 -1.2982 Td
([)Tj
0.83 0.64 0.02 0 k
(30)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7347 0 Td
(31)Tj
0 g
(],)Tj
1.7348 0 Td
(operant)Tj
3.3222 0 Td
(responses)Tj
4.0932 0 Td
([)Tj
0.83 0.64 0.02 0 k
(32)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7405 0 Td
(33)Tj
0 g
(],)Tj
1.7348 0 Td
(paired-association)Tj
7.5174 0 Td
(learning)Tj
3.5263 0 Td
([)Tj
0.83 0.64 0.02 0 k
(34)Tj
0 g
(],)Tj
2.0749 0 Td
(and)Tj
1.7292 0 Td
(impaired)Tj
3.8494 0 Td
(flexibility)Tj
-33.0574 -1.2983 Td
(and)Tj
1.7291 0 Td
(social)Tj
2.4604 0 Td
(behavior)Tj
3.7077 0 Td
([)Tj
0.83 0.64 0.02 0 k
(35)Tj
0 g
(].)Tj
2.0806 0 Td
(Additionally,)Tj
/F11 1 Tf
5.4539 0 Td
[()12()]TJ
1.0148 0 Td
[()14()11()2()20()]TJ
/F6 1 Tf
2.262 0 Td
(and)Tj
1.7291 0 Td
(lactational)Tj
4.3597 0 Td
(dioxin)Tj
2.8006 0 Td
(exposure)Tj
3.8211 0 Td
(induces)Tj
3.2938 0 Td
(the)Tj
-34.7128 -1.2983 Td
(expression)Tj
4.4617 0 Td
(of)Tj
1.0148 0 Td
(AhR)Tj
2.0579 0 Td
(target)Tj
2.5058 0 Td
(genes)Tj
2.4435 0 Td
([)Tj
0.83 0.64 0.02 0 k
(36)Tj
0 g
(])Tj
1.8538 0 Td
(and)Tj
1.7291 0 Td
(disrupts)Tj
3.4526 0 Td
(dendritic)Tj
3.8721 0 Td
(morphology)Tj
5.142 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(developing)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 314.9858 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Disrupted)Tj
4.422 0 Td
(dendritic)Tj
3.926 0 Td
(growth)Tj
3.1678 0 Td
(and)Tj
1.8567 0 Td
(neuronal)Tj
4.0323 0 Td
(positioning)Tj
4.904 0 Td
(by)Tj
1.2543 0 Td
(AhR)Tj
2.1402 0 Td
(signal)Tj
2.7709 0 Td
(activation)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01834)Tj
4.089 0 Td
(97)Tj
0 g
2.0906 0 Td
(August)Tj
3.2882 0 Td
(18,)Tj
1.5874 0 Td
(2017)Tj
34.0302 0 Td
(2)Tj
0.7654 0 Td
(/)Tj
0.496 0 Td
(18)Tj
/F8 1 Tf
-0.025 Tc
-66.402 84.0904 Td
(Competing)Tj
4.3795 0 Td
(interests)Tj
3.3307 0 Td
(:)Tj
/F9 1 Tf
0.4819 0 Td
(The)Tj
1.5875 0 Td
(authors)Tj
3.0401 0 Td
(have)Tj
1.963 0 Td
(declared)Tj
-14.7827 -1.3748 Td
(that)Tj
1.6228 0 Td
(no)Tj
1.1693 0 Td
(competing)Tj
4.1599 0 Td
(interests)Tj
ET
endstream
endobj
52 0 obj
<>stream
endstream
endobj
53 0 obj
<>stream
endstream
endobj
54 0 obj
<>stream
endstream
endobj
55 0 obj
<>stream
endstream
endobj
56 0 obj
<>stream
endstream
endobj
57 0 obj
<>stream
endstream
endobj
58 0 obj
<>stream
endstream
endobj
59 0 obj
<>stream
endstream
endobj
60 0 obj
<>stream
endstream
endobj
61 0 obj
<>stream
endstream
endobj
62 0 obj
<>stream
endstream
endobj
63 0 obj
<>stream
endstream
endobj
64 0 obj
<>stream
endstream
endobj
65 0 obj
<>stream
endstream
endobj
66 0 obj
<>stream
endstream
endobj
67 0 obj
<>stream
endstream
endobj
68 0 obj
<>stream
endstream
endobj
69 0 obj
<>stream
endstream
endobj
70 0 obj
<>stream
endstream
endobj
71 0 obj
<>stream
endstream
endobj
72 0 obj
<>stream
endstream
endobj
73 0 obj
<>stream
endstream
endobj
74 0 obj
<>stream
endstream
endobj
75 0 obj
<>stream
endstream
endobj
76 0 obj
<>stream
endstream
endobj
77 0 obj
<>stream
endstream
endobj
78 0 obj
<>stream
endstream
endobj
79 0 obj
<>stream
endstream
endobj
80 0 obj
<>stream
endstream
endobj
81 0 obj
<>stream
endstream
endobj
82 0 obj
<>stream
endstream
endobj
83 0 obj
<>stream
endstream
endobj
84 0 obj
<>stream
endstream
endobj
85 0 obj
<>stream
endstream
endobj
86 0 obj
<>stream
BT
10.3394 82.7156 Td
(exist.)Tj
ET
Q
endstream
endobj
87 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 12 0 R/Annots 90 0 R/Contents 91 0 R/TrimBox[0 0 612 792]>>
endobj
90 0 obj
[92 0 R 93 0 R 94 0 R 95 0 R 96 0 R 97 0 R 98 0 R 99 0 R 100 0 R 101 0 R 102 0 R]
endobj
92 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref037)>>
endobj
93 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref037)>>
endobj
94 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref038)>>
endobj
95 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref039)>>
endobj
96 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref041)>>
endobj
97 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref042)>>
endobj
98 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref043)>>
endobj
99 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.g001)>>
endobj
100 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.g001)>>
endobj
101 0 obj
<>/Border[0 0 0]/Dest(Rpone.0183497.ref037)>>
endobj
102 0 obj
<>/Border[0 0 0]/A 103 0 R>>
endobj
103 0 obj
<>
endobj
91 0 obj
[104 0 R 105 0 R 106 0 R 107 0 R 108 0 R 109 0 R 110 0 R 111 0 R 112 0 R 113 0 R 114 0 R 115 0 R]
endobj
104 0 obj
<>stream
q
0.83 0.64 0.02 0 k
255.4583 706.337 m
264.9827 706.337 l
h
f*
435.2315 641.3102 m
444.7559 641.3102 l
h
f*
449.178 641.3102 m
458.7024 641.3102 l
h
f*
267.7606 615.3449 m
277.285 615.3449 l
h
f*
282.4441 615.3449 m
291.9685 615.3449 l
h
f*
511.4835 615.3449 m
521.0079 615.3449 l
h
f*
525.4866 615.3449 m
534.9543 615.3449 l
h
f*
546.6331 263.9055 m
559.2756 263.9055 l
h
f*
200.0126 250.9228 m
211.578 250.9228 l
h
f*
280.063 237.9402 m
289.5874 237.9402 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 200.0125 707.4141 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(mouse)Tj
2.8573 0 Td
(brain)Tj
2.347 0 Td
([)Tj
0.83 0.64 0.02 0 k
(37)Tj
0 g
(].)Tj
2.075 0 Td
(These)Tj
2.5681 0 Td
(exposure)Tj
3.8155 0 Td
(experiments)Tj
5.142 0 Td
(suggest)Tj
3.1237 0 Td
(that)Tj
1.7745 0 Td
(AhR)Tj
2.0523 0 Td
(signaling)Tj
3.8267 0 Td
(is)Tj
0.8447 0 Td
(indeed)Tj
2.9424 0 Td
(involved)Tj
-33.3692 -1.3039 Td
(in)Tj
1.0318 0 Td
(mammalian)Tj
5.0456 0 Td
(corticogenesis.)Tj
-4.8812 -1.2982 Td
(Accordingly,)Tj
5.3687 0 Td
(we)Tj
1.3267 0 Td
(hypothesized)Tj
5.4651 0 Td
(that)Tj
1.7802 0 Td
(activation)Tj
4.1555 0 Td
(of)Tj
1.0148 0 Td
(AhR)Tj
2.0523 0 Td
(signaling)Tj
3.8211 0 Td
(is)Tj
0.8504 0 Td
(linked)Tj
2.7269 0 Td
(to)Tj
1.0261 0 Td
(cortical)Tj
3.1918 0 Td
(develop-)Tj
-33.9758 -1.2983 Td
(mental)Tj
2.9876 0 Td
(in)Tj
1.0375 0 Td
(mice.)Tj
2.3811 0 Td
(In)Tj
1.1055 0 Td
(order)Tj
2.4208 0 Td
(to)Tj
1.0261 0 Td
(test)Tj
1.5988 0 Td
(this)Tj
1.6781 0 Td
(hypothesis,)Tj
4.6884 0 Td
(we)Tj
1.3266 0 Td
(selected)Tj
3.3506 0 Td
(a)Tj
0.6519 0 Td
(constitutively)Tj
5.5956 0 Td
(active)Tj
2.5228 0 Td
(\(CA\)-AhR-)Tj
-32.3714 -1.2983 Td
(expressing)Tj
4.422 0 Td
(transfection)Tj
4.9889 0 Td
(animal,)Tj
3.1975 0 Td
(because)Tj
3.3165 0 Td
(it)Tj
0.788 0 Td
(was)Tj
1.6951 0 Td
(demonstrated)Tj
5.7657 0 Td
(that)Tj
1.7744 0 Td
(CA-AhR)Tj
3.7531 0 Td
(translocates)Tj
4.9266 0 Td
(into)Tj
-34.6278 -1.3039 Td
(the)Tj
1.4683 0 Td
(nucleus)Tj
3.2768 0 Td
(and)Tj
1.7291 0 Td
(induces)Tj
3.2995 0 Td
(AhR)Tj
2.058 0 Td
(target)Tj
2.5058 0 Td
(genes)Tj
2.4434 0 Td
(without)Tj
3.3336 0 Td
(ligands)Tj
3.067 0 Td
([)Tj
0.83 0.64 0.02 0 k
(37)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(38)Tj
0 g
(])Tj
1.5137 0 Td
(and)Tj
1.7291 0 Td
(that)Tj
1.7802 0 Td
(CA-AhR)Tj
3.753 0 Td
(model)Tj
-33.6923 -1.2982 Td
(animals)Tj
3.3278 0 Td
(manifest)Tj
3.6623 0 Td
(signs)Tj
2.2224 0 Td
(of)Tj
1.0148 0 Td
(dioxin)Tj
2.8006 0 Td
(toxicity,)Tj
3.4299 0 Td
(such)Tj
2.0579 0 Td
(as)Tj
1.0148 0 Td
(thymic)Tj
3.0104 0 Td
(involution,)Tj
4.6205 0 Td
(liver)Tj
1.9785 0 Td
(enlargement,)Tj
5.4482 0 Td
(and)Tj
-34.5881 -1.2983 Td
(stomach)Tj
3.5886 0 Td
(cancer)Tj
2.846 0 Td
([)Tj
0.83 0.64 0.02 0 k
(39)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(41)Tj
0 g
(].)Tj
3.5432 0 Td
(Thus,)Tj
2.4718 0 Td
(in)Tj
1.0375 0 Td
(this)Tj
1.6724 0 Td
(study,)Tj
2.6192 0 Td
(we)Tj
1.3266 0 Td
(used)Tj
/F11 1 Tf
2.058 0 Td
[()12()]TJ
1.0148 0 Td
[()14()11()2()20()]TJ
/F6 1 Tf
2.2677 0 Td
(electroporation)Tj
6.3609 0 Td
([)Tj
0.83 0.64 0.02 0 k
(42)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7404 0 Td
(43)Tj
0 g
(])Tj
1.5081 0 Td
(to)Tj
1.0261 0 Td
(trans-)Tj
-35.0813 -1.3039 Td
(fect)Tj
1.6497 0 Td
(CA-AhR)Tj
3.7531 0 Td
(in)Tj
1.0374 0 Td
(cortical)Tj
3.1918 0 Td
(projection)Tj
4.337 0 Td
(neurons)Tj
3.5093 0 Td
(in)Tj
1.0374 0 Td
(the)Tj
1.4684 0 Td
(mouse)Tj
2.8573 0 Td
(brain)Tj
2.3471 0 Td
(and)Tj
1.7291 0 Td
(studied)Tj
3.1578 0 Td
(the)Tj
1.4683 0 Td
(significance)Tj
4.9379 0 Td
(of)Tj
-36.4816 -1.2983 Td
(AhR)Tj
2.0522 0 Td
(signaling)Tj
3.8211 0 Td
(for)Tj
1.389 0 Td
(cerebral)Tj
3.4185 0 Td
(cortical)Tj
3.1918 0 Td
(development.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 561.2598 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Materials)Tj
4.5071 0 Td
(and)Tj
1.989 0 Td
(methods)Tj
/F0 1 Tf
-6.4961 -1.4976 Td
(Reagents)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 526.2803 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Reagents)Tj
3.7927 0 Td
(were)Tj
2.126 0 Td
(special)Tj
2.8913 0 Td
(grade)Tj
2.4434 0 Td
(and)Tj
1.7291 0 Td
(purchased)Tj
4.3314 0 Td
(from)Tj
2.2053 0 Td
(Wako)Tj
2.6249 0 Td
(Pure)Tj
2.1033 0 Td
(Chemicals)Tj
4.3823 0 Td
(\(Osaka,)Tj
3.2598 0 Td
(Japan\),)Tj
3.0501 0 Td
(unless)Tj
-34.9396 -1.3039 Td
(otherwise)Tj
4.0818 0 Td
(stated.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 484.1574 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Animals)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 467.1496 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(All)Tj
1.3946 0 Td
(animal)Tj
2.9707 0 Td
(experiments)Tj
5.1363 0 Td
(were)Tj
2.126 0 Td
(performed)Tj
4.4674 0 Td
(using)Tj
2.3924 0 Td
(protocols)Tj
3.9571 0 Td
(approved)Tj
3.9742 0 Td
(by)Tj
1.1792 0 Td
(the)Tj
1.4683 0 Td
(Animal)Tj
3.2202 0 Td
(Care)Tj
2.1146 0 Td
(and)Tj
-34.401 -1.3039 Td
(Use)Tj
1.7404 0 Td
(Committee)Tj
4.7395 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(University)Tj
4.4051 0 Td
(of)Tj
1.0148 0 Td
(Tokyo)Tj
2.7949 0 Td
(\(No.)Tj
2.0296 0 Td
(P12-41,)Tj
3.2541 0 Td
(PI)Tj
1.1226 0 Td
(=)Tj
0.7993 0 Td
(C.)Tj
1.1055 0 Td
(Tohyama\))Tj
4.3483 0 Td
(and)Tj
1.7348 0 Td
(that)Tj
1.7745 0 Td
(of)Tj
1.0148 0 Td
(Keio)Tj
-34.3613 -1.2982 Td
(University)Tj
4.3993 0 Td
([08065-\(10\),)Tj
5.1477 0 Td
(PI)Tj
1.1168 0 Td
(=)Tj
0.7994 0 Td
(K.)Tj
1.1168 0 Td
(Nakajima])Tj
4.4334 0 Td
(in)Tj
1.0375 0 Td
(accordance)Tj
4.7338 0 Td
(with)Tj
1.9956 0 Td
(Institutional)Tj
5.1647 0 Td
(Guidelines)Tj
4.524 0 Td
(on)Tj
1.2756 0 Td
(Ani-)Tj
-35.7446 -1.2983 Td
(mal)Tj
1.7177 0 Td
(Experimentation)Tj
6.9789 0 Td
(at)Tj
0.9524 0 Td
(the)Tj
1.4684 0 Td
(both)Tj
2.0636 0 Td
(universities)Tj
4.7905 0 Td
(as)Tj
1.0148 0 Td
(well)Tj
1.8198 0 Td
(as)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(Japanese)Tj
3.6906 0 Td
(Government)Tj
5.3291 0 Td
(Law)Tj
1.8766 0 Td
(con-)Tj
-34.1856 -1.3039 Td
(cerning)Tj
3.2654 0 Td
(the)Tj
1.4684 0 Td
(Protection)Tj
4.4277 0 Td
(and)Tj
1.7291 0 Td
(Control)Tj
3.3619 0 Td
(of)Tj
1.0148 0 Td
(Animals)Tj
3.5773 0 Td
(and)Tj
1.7347 0 Td
(Japanese)Tj
3.6907 0 Td
(Government)Tj
5.3291 0 Td
(Notification)Tj
5.0627 0 Td
(of)Tj
-34.6618 -1.2983 Td
(Feeding)Tj
3.4015 0 Td
(and)Tj
1.7291 0 Td
(Safekeeping)Tj
4.9833 0 Td
(of)Tj
1.0148 0 Td
(Animals.)Tj
3.8097 0 Td
(All)Tj
1.3947 0 Td
(efforts)Tj
2.7552 0 Td
(were)Tj
2.126 0 Td
(made)Tj
2.4208 0 Td
(to)Tj
1.0261 0 Td
(reduce)Tj
2.9197 0 Td
(the)Tj
1.4683 0 Td
(total)Tj
2.0013 0 Td
(number)Tj
3.4185 0 Td
(of)Tj
1.0148 0 Td
(ani-)Tj
-35.4838 -1.2982 Td
(mals)Tj
2.0806 0 Td
(used)Tj
2.0579 0 Td
(and)Tj
1.7291 0 Td
(their)Tj
2.109 0 Td
(suffering.)Tj
3.9855 0 Td
(Timed-pregnant)Tj
6.8258 0 Td
(C57BL/6N)Tj
4.4957 0 Td
(mice)Tj
2.1543 0 Td
(were)Tj
2.1203 0 Td
(purchased)Tj
4.337 0 Td
(from)Tj
2.2053 0 Td
(Japan)Tj
-34.1005 -1.2983 Td
(SLC)Tj
1.8935 0 Td
(\(Shizuoka,)Tj
4.439 0 Td
(Japan\))Tj
2.8233 0 Td
(for)Tj
/F11 1 Tf
1.3833 0 Td
[()12()]TJ
1.0148 0 Td
[()14()11()2()20()]TJ
/F6 1 Tf
2.262 0 Td
(electroporation)Tj
6.3666 0 Td
(experiments.)Tj
5.3631 0 Td
(These)Tj
2.5682 0 Td
(mice)Tj
2.1543 0 Td
(were)Tj
2.1203 0 Td
(housed)Tj
3.0954 0 Td
(in)Tj
1.0375 0 Td
(an)Tj
-36.5213 -1.3039 Td
(animal)Tj
2.9706 0 Td
(facility)Tj
2.897 0 Td
(maintained)Tj
4.7906 0 Td
(at)Tj
0.9524 0 Td
(22C)Tj
/F12 1 Tf
[()]TJ
/F6 1 Tf
(24C)Tj
4.8018 0 Td
(and)Tj
1.7292 0 Td
(40%)Tj
/F12 1 Tf
[()]TJ
/F6 1 Tf
(60%)Tj
4.2066 0 Td
(humidity)Tj
3.9117 0 Td
(under)Tj
2.6192 0 Td
(as)Tj
1.0148 0 Td
(12/12)Tj
2.4492 0 Td
(h)Tj
0.7483 0 Td
(light/dark)Tj
-33.0914 -1.2983 Td
(cycle)Tj
2.1883 0 Td
(\(lights)Tj
2.7269 0 Td
(on)Tj
1.2756 0 Td
(from)Tj
2.2053 0 Td
(08:00)Tj
2.3471 0 Td
(to)Tj
1.0261 0 Td
(20:00\).)Tj
2.914 0 Td
(Laboratory)Tj
4.6431 0 Td
(rodent)Tj
2.897 0 Td
(chow)Tj
2.3641 0 Td
(\(Lab)Tj
2.0353 0 Td
(MR)Tj
1.7348 0 Td
(Stock;)Tj
2.6475 0 Td
(Nosan,)Tj
3.0331 0 Td
(Yoko-)Tj
-34.0382 -1.2983 Td
(hama,)Tj
2.6588 0 Td
(Japan\))Tj
2.8233 0 Td
(and)Tj
1.7291 0 Td
(distilled)Tj
3.3846 0 Td
(water)Tj
2.4321 0 Td
(were)Tj
2.126 0 Td
(provided)Tj
/F11 1 Tf
3.8154 0 Td
[()6()]TJ
1.2019 0 Td
[()12()14()11()14()7()12()]TJ
/F6 1 Tf
(.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 308.0125 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Vector)Tj
3.0803 0 Td
(construction)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 291.0047 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(The)Tj
1.7801 0 Td
(AhR)Tj
2.0523 0 Td
(protein)Tj
3.1577 0 Td
(harbors)Tj
3.2939 0 Td
(several)Tj
2.9367 0 Td
(domains,)Tj
3.9117 0 Td
(including)Tj
4.0422 0 Td
(bHLH,)Tj
3.0217 0 Td
(PAS,)Tj
2.1657 0 Td
(ligand-binding,)Tj
6.4176 0 Td
(and)Tj
1.7291 0 Td
(Q-rich)Tj
-34.5087 -1.2982 Td
(domains,)Tj
3.9061 0 Td
(comprising)Tj
4.7621 0 Td
(805)Tj
1.6385 0 Td
(amino)Tj
2.7949 0 Td
(acid)Tj
1.8652 0 Td
(residues,)Tj
3.702 0 Td
(whereas)Tj
3.4412 0 Td
(CA-AhR)Tj
3.7474 0 Td
(lacks)Tj
2.177 0 Td
(142)Tj
1.6384 0 Td
(amino)Tj
2.7893 0 Td
(acid)Tj
1.8709 0 Td
(residues)Tj
-34.333 -1.3039 Td
(spanning)Tj
3.9117 0 Td
(positions)Tj
3.8495 0 Td
(277)Tj
1.6497 0 Td
(to)Tj
1.0261 0 Td
(418,)Tj
1.8709 0 Td
(a)Tj
0.652 0 Td
(region)Tj
2.8062 0 Td
(including)Tj
4.0422 0 Td
(much)Tj
2.5172 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(ligand-binding)Tj
6.1908 0 Td
(domain)Tj
3.3222 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(Fig)Tj
-34.3216 -1.2983 Td
(1A)Tj
0 g
(\).)Tj
1.9445 0 Td
(Plasmid)Tj
3.4356 0 Td
(vectors)Tj
3.0557 0 Td
(pCAGGS1-AhR)Tj
6.65 0 Td
(and)Tj
1.7348 0 Td
(pCAGGS1-CA-AhR)Tj
8.3452 0 Td
(were)Tj
2.1259 0 Td
(identical)Tj
3.6567 0 Td
(to)Tj
1.0205 0 Td
(those)Tj
2.3414 0 Td
(used)Tj
2.0579 0 Td
(in)Tj
-36.3682 -1.2983 Td
(our)Tj
1.627 0 Td
(previous)Tj
3.6454 0 Td
(study)Tj
2.3924 0 Td
([)Tj
0.83 0.64 0.02 0 k
(37)Tj
0 g
(].)Tj
2.0749 0 Td
(Briefly,)Tj
3.0784 0 Td
(a)Tj
0.652 0 Td
(full-length)Tj
4.388 0 Td
(AhR)Tj
2.0523 0 Td
(cDNA)Tj
2.8006 0 Td
(fragment)Tj
3.8721 0 Td
(was)Tj
1.6951 0 Td
(obtained)Tj
3.736 0 Td
(from)Tj
2.2054 0 Td
(a)Tj
0.6519 0 Td
(mouse)Tj
-34.8715 -1.3039 Td
(liver)Tj
1.9842 0 Td
(cDNA)Tj
2.7949 0 Td
(library)Tj
2.8743 0 Td
(by)Tj
1.1793 0 Td
(nested)Tj
2.8062 0 Td
(polymerase)Tj
4.7792 0 Td
(chain)Tj
2.4208 0 Td
(reaction)Tj
3.4922 0 Td
(\(PCR\))Tj
2.744 0 Td
(using)Tj
2.3867 0 Td
(two)Tj
1.7121 0 Td
(primer)Tj
2.9877 0 Td
(pairs:)Tj
/F13 1 Tf
2.3981 0 Td
( \n F F)Tj
-34.5597 -1.2982 Td
( W F F J J J D F J F D J J W J \n \n )Tj
12.9882 0 Td
( D J F D W F W F D J J W D F J J J W W W \n )Tj
/F6 1 Tf
14.3829 0 Td
(and)Tj
/F13 1 Tf
1.7348 0 Td
( \n F W F J D J J F J J J)Tj
-29.1059 -1.2983 Td
( F D F F D W J D J F D J F J J F J F F D )Tj
12.9882 0 Td
( \n \n F W F J D J W F D D F W F W J F D F F)Tj
14.1675 0 Td
( W W J F W \n )Tj
/F6 1 Tf
5.5275 0 Td
(A)Tj
0.9071 0 Td
(CA-AhR)Tj
-33.5903 -1.3039 Td
(cDNA)Tj
2.8006 0 Td
(fragment)Tj
3.8664 0 Td
(was)Tj
1.7008 0 Td
(obtained)Tj
3.7303 0 Td
(by)Tj
1.1849 0 Td
(PCR)Tj
2.0636 0 Td
(amplification)Tj
5.5332 0 Td
(using)Tj
2.3924 0 Td
(pQCXIN-CA-AhR-EGFP)Tj
10.4825 0 Td
(as)Tj
1.0148 0 Td
(a)Tj
0.652 0 Td
(tem-)Tj
-35.4215 -1.2983 Td
(plate)Tj
2.1373 0 Td
(\(a)Tj
0.9921 0 Td
(kind)Tj
2.0636 0 Td
(gift)Tj
1.5364 0 Td
(from)Tj
2.2053 0 Td
(Dr.)Tj
1.5534 0 Td
(Yoshiaki)Tj
3.7133 0 Td
(Fujii-Kuriyama,)Tj
6.6274 0 Td
(then)Tj
2.0126 0 Td
(at)Tj
0.9524 0 Td
(University)Tj
4.405 0 Td
(of)Tj
1.0148 0 Td
(Tsukuba)Tj
3.685 0 Td
(and)Tj
1.7292 0 Td
(Dr.)Tj
-34.6278 -1.2983 Td
(Tomohiro)Tj
4.3369 0 Td
(Ito)Tj
1.3663 0 Td
(at)Tj
0.9525 0 Td
(the)Tj
1.4683 0 Td
(National)Tj
3.6907 0 Td
(Institute)Tj
3.5829 0 Td
(for)Tj
1.389 0 Td
(Environmental)Tj
6.2532 0 Td
(Studies\))Tj
3.4412 0 Td
(and)Tj
1.7292 0 Td
(the)Tj
1.474 0 Td
(specific)Tj
3.1861 0 Td
(primers)Tj
/F13 1 Tf
-32.8703 -1.2982 Td
( \n F W F J D J J F J J J F D F F D W J D)Tj
12.9882 0 Td
( J F D J F J J F J F F D \n)Tj
/F6 1 Tf
9.0708 0 Td
(and)Tj
/F13 1 Tf
1.7291 0 Td
( \n F W F J D J W F D D F W F W)Tj
10.0403 0 Td
( J F D)Tj
-33.8284 -1.3039 Td
( F F W W J F W \n )Tj
/F6 1 Tf
6.7123 0 Td
(The)Tj
1.7802 0 Td
(AhR)Tj
2.0579 0 Td
(and)Tj
1.7292 0 Td
(CA-AhR)Tj
3.7473 0 Td
(fragments)Tj
4.235 0 Td
(were)Tj
2.1203 0 Td
(ligated)Tj
2.88 0 Td
(into)Tj
1.8425 0 Td
(the)Tj
1.4683 0 Td
(pCRII-TOPO)Tj
5.7203 0 Td
(vector)Tj
-34.2933 -1.2983 Td
(using)Tj
2.3867 0 Td
(the)Tj
1.4683 0 Td
(TOPO)Tj
2.8857 0 Td
(TA)Tj
1.5137 0 Td
(Cloning)Tj
3.4696 0 Td
(kit)Tj
1.2812 0 Td
(\(Thermo)Tj
3.8211 0 Td
(Fisher)Tj
2.6986 0 Td
(Scientific,)Tj
4.1272 0 Td
(Carlsbad,)Tj
3.9911 0 Td
(CA,)Tj
1.7915 0 Td
(USA\),)Tj
2.6816 0 Td
(amplified,)Tj
-32.1163 -1.2983 Td
(and)Tj
1.7291 0 Td
(then)Tj
2.0182 0 Td
(excised)Tj
3.1124 0 Td
(by)Tj
/F11 1 Tf
1.1793 0 Td
[()6()]TJ
/F6 1 Tf
(I)Tj
2.1656 0 Td
(digestion)Tj
3.8835 0 Td
(for)Tj
1.3889 0 Td
(insertion)Tj
3.8098 0 Td
(into)Tj
1.8425 0 Td
(the)Tj
/F11 1 Tf
1.4683 0 Td
[()6()]TJ
/F6 1 Tf
(I)Tj
2.1657 0 Td
(site)Tj
1.5703 0 Td
(of)Tj
1.0148 0 Td
(pCAGGS1)Tj
4.4674 0 Td
(to)Tj
1.0261 0 Td
(generate)Tj
-32.8419 -1.3039 Td
(pCAGGS1-AhR)Tj
6.65 0 Td
(and)Tj
1.7291 0 Td
(pCAGGS1-CA-AhR)Tj
8.3508 0 Td
(plasmids,)Tj
3.9798 0 Td
(respectively.)Tj
5.108 0 Td
(These)Tj
2.5682 0 Td
(plasmids)Tj
3.7531 0 Td
(were)Tj
2.1203 0 Td
(subse-)Tj
-34.2593 -1.2982 Td
(quently)Tj
3.2258 0 Td
(used)Tj
2.0579 0 Td
(for)Tj
/F11 1 Tf
1.389 0 Td
[()12()]TJ
1.0148 0 Td
[()14()11()2()20()]TJ
/F6 1 Tf
2.262 0 Td
(electroporation)Tj
6.3666 0 Td
(to)Tj
1.0204 0 Td
(induce)Tj
2.9424 0 Td
(AhR)Tj
2.0522 0 Td
(and)Tj
1.7292 0 Td
(CA-AhR)Tj
3.753 0 Td
(expression)Tj
4.4674 0 Td
(in)Tj
1.0318 0 Td
(cortical)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 314.9858 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Disrupted)Tj
4.422 0 Td
(dendritic)Tj
3.926 0 Td
(growth)Tj
3.1678 0 Td
(and)Tj
1.8567 0 Td
(neuronal)Tj
4.0323 0 Td
(positioning)Tj
4.904 0 Td
(by)Tj
1.2543 0 Td
(AhR)Tj
2.1402 0 Td
(signal)Tj
2.7709 0 Td
(activation)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01834)Tj
4.089 0 Td
(97)Tj
0 g
2.0906 0 Td
(August)Tj
3.2882 0 Td
(18,)Tj
1.5874 0 Td
(2017)Tj
34.0302 0 Td
(3)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
105 0 obj
<>stream
endstream
endobj
106 0 obj
<>stream
endstream
endobj
107 0 obj
<>stream
endstream
endobj
108 0 obj
<>stream
endstream
endobj
109 0 obj
<>stream
endstream
endobj
110 0 obj
<>stream
endstream
endobj
111 0 obj
<>stream
endstream
endobj
112 0 obj
<>stream
endstream
endobj
113 0 obj
<>stream
endstream
endobj
114 0 obj
<>stream
endstream
endobj
115 0 obj
<>stream
BT
66.402 0 Td
(18)Tj
ET
Q
endstream
endobj
116 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 12 0 R/Annots 118 0 R/Contents 119 0 R/TrimBox[0 0 612 792]>>
endobj
117 0 obj
<>/ExtGState<>/Font<>/ProcSet[/PDF/Text/ImageC/ImageI]/Properties<>/XObject<>>>/Length 16325>>stream
/Document /MC1 BDC
/GS1 gs
BT
/F1 1 Tf
20.8295 0 0 20.8295 0 448.389 Tm
.63995 .69274 .68811 .78821 k
0 Tc
0 Tw
(B)Tj
0 -8.6111 TD
(C)Tj
ET
.63992 .69274 .68811 .78821 k
83.184 426.239 151.342 2.087 re
f
1 i
q 1 0 0 1 234.526 426.239 cm 0 0 m
0 .434 l
-150.908 .434 l
-150.908 1.653 l
-.434 1.653 l
-.434 0 l
0 0 l
0 .434 l
0 0 l
.434 0 l
.434 2.521 l
-151.776 2.521 l
-151.776 -.434 l
.434 -.434 l
.434 0 l
0 0 l
f
Q
.52105 .12866 0 0 k
129.244 421.523 24.665 11.519 re
f
BT
9.0155 0 0 9.0155 132.304 424.201 Tm
.63995 .69274 .68811 .78821 k
(Stop)Tj
ET
.63992 .69274 .68811 .78821 k
83.184 324.936 93.827 2.087 re
f
q 1 0 0 1 177.011 324.936 cm 0 0 m
0 .434 l
-93.393 .434 l
-93.393 1.653 l
-.434 1.653 l
-.434 0 l
0 0 l
0 .434 l
0 0 l
.434 0 l
.434 2.521 l
-94.261 2.521 l
-94.261 -.434 l
.434 -.434 l
.434 0 l
0 0 l
f
Q
BT
/F2 1 Tf
33.7714 0 0 33.7714 149.088 358.3929 Tm
.63995 .69274 .68811 .78821 k
(+)Tj
ET
.63992 .69274 .68811 .78821 k
107.358 418.941 .867 1.735 re
f
108.225 415.38 -.867 -3.561 re
107.358 415.38 m
h
108.225 408.258 -.867 -3.561 re
107.358 408.258 m
h
108.225 401.136 -.867 -3.561 re
107.358 401.136 m
h
108.225 394.014 -.867 -3.561 re
107.358 394.014 m
h
108.225 386.892 -.867 -3.561 re
107.358 386.892 m
h
108.225 379.77 -.867 -3.561 re
107.358 379.77 m
h
108.225 372.648 -.867 -3.561 re
107.358 372.648 m
h
108.225 365.526 -.867 -3.561 re
107.358 365.526 m
h
108.225 358.404 -.867 -3.561 re
107.358 358.404 m
h
108.225 351.282 -.867 -3.561 re
107.358 351.282 m
h
108.225 344.16 -.867 -3.561 re
107.358 344.16 m
h
108.225 337.038 -.867 -3.561 re
107.358 337.038 m
f
107.358 328.181 .867 1.735 re
f
q 1 0 0 1 108.833 326.004 cm 0 0 m
1.828 2.951 l
1.09 3.408 l
-.738 .457 l
h
3.656 5.903 m
5.483 8.854 l
4.746 9.311 l
2.918 6.36 l
h
7.311 11.806 m
9.139 14.757 l
8.401 15.214 l
6.573 12.263 l
h
10.967 17.709 m
12.795 20.66 l
12.057 21.117 l
10.229 18.165 l
h
14.623 23.611 m
16.451 26.563 l
15.713 27.02 l
13.885 24.068 l
h
18.279 29.514 m
20.106 32.465 l
19.369 32.922 l
17.541 29.971 l
h
21.934 35.417 m
23.762 38.368 l
23.024 38.825 l
21.196 35.874 l
h
25.59 41.32 m
27.418 44.271 l
26.68 44.728 l
24.852 41.777 l
h
29.246 47.222 m
31.074 50.174 l
30.336 50.631 l
28.508 47.679 l
h
32.902 53.125 m
34.729 56.077 l
33.992 56.534 l
32.164 53.582 l
h
36.557 59.028 m
38.385 61.979 l
37.647 62.436 l
35.82 59.485 l
h
40.213 64.931 m
42.041 67.882 l
41.303 68.339 l
39.475 65.388 l
h
43.869 70.834 m
45.697 73.785 l
44.959 74.242 l
43.131 71.291 l
h
47.525 76.736 m
49.353 79.688 l
48.615 80.145 l
46.787 77.193 l
h
51.18 82.639 m
53.008 85.591 l
52.27 86.048 l
50.443 83.096 l
h
54.836 88.542 m
56.664 91.493 l
55.926 91.95 l
54.098 88.999 l
h
58.492 94.445 m
58.596 94.613 l
57.858 95.07 l
57.754 94.902 l
f
Q
q 1 0 0 1 95.789 314.303 cm 0 0 m
0 24.021 l
31.125 11.503 l
0 0 l
f
Q
BT
/F1 1 Tf
9.0155 0 0 9.0155 97.0659 322.876 Tm
0 0 0 0 k
(loxP)Tj
ET
.63992 .69274 .68811 .78821 k
q 1 0 0 1 95.789 415.272 cm 0 0 m
0 24.021 l
31.125 11.504 l
0 0 l
f
Q
BT
9.0155 0 0 9.0155 97.0659 424.201 Tm
0 0 0 0 k
(loxP)Tj
ET
.63992 .69274 .68811 .78821 k
q 1 0 0 1 160.286 415.272 cm 0 0 m
0 24.021 l
31.126 11.504 l
0 0 l
f
Q
BT
9.0155 0 0 9.0155 161.563 424.201 Tm
0 0 0 0 k
(loxP)Tj
ET
.73971 .03827 1 .001556 k
193.819 421.523 32.168 11.519 re
f
BT
9.0155 0 0 9.0155 197.629 424.201 Tm
.63995 .69274 .68811 .78821 k
-.0002 Tc
(EGFP)Tj
ET
.73971 .03827 1 .001556 k
130.028 320.522 32.167 11.519 re
f
BT
9.0155 0 0 9.0155 133.839 322.875 Tm
.63995 .69274 .68811 .78821 k
0 Tc
(EGFP)Tj
ET
.54311 .45722 .45469 .10706 k
q 1 0 0 1 89.052 427.431 cm 0 0 m
-13.266 12.946 l
-13.266 -13.129 l
0 0 l
f
Q
q 1 0 0 1 89.052 427.431 cm 0 0 m
.606 .621 l
-14.133 15.005 l
-14.133 -15.209 l
1.238 .005 l
.606 .621 l
0 0 l
-.61 .617 l
-12.398 -11.049 l
-12.398 10.886 l
-.606 -.621 l
0 0 l
-.61 .617 l
0 0 l
f
Q
8.0767 418.709 70.628 17.462 re
f
BT
9.0155 0 0 9.0155 12.8257 424.504 Tm
0 0 0 0 k
.0001 Tc
-.0001 Tw
(pCAG promoter)Tj
ET
.54311 .45722 .45469 .10706 k
q 1 0 0 1 89.051 326.117 cm 0 0 m
-13.265 12.948 l
-13.265 -13.128 l
0 0 l
f
Q
q 1 0 0 1 89.051 326.117 cm 0 0 m
.606 .621 l
-14.133 15.008 l
-14.133 -15.208 l
1.238 .005 l
.606 .621 l
0 0 l
-.61 .617 l
-12.397 -11.048 l
-12.397 10.888 l
-.606 -.621 l
0 0 l
-.61 .617 l
0 0 l
f
Q
8.0767 317.395 70.628 17.46 re
f
BT
9.0155 0 0 9.0155 12.8257 323.19 Tm
0 0 0 0 k
(pCAG promoter)Tj
11.2571 0 0 11.2571 185.436 409.192 Tm
.63995 .69274 .68811 .78821 k
-.0002 Tw
(pCALNL-EGFP \(1 mg/mL\))Tj
ET
.63992 .69274 .68811 .78821 k
249.686 369.611 45.137 2.087 re
f
q 1 0 0 1 294.823 369.611 cm 0 0 m
0 .434 l
-44.703 .434 l
-44.703 1.653 l
-.434 1.653 l
-.434 0 l
0 0 l
0 .434 l
0 0 l
.434 0 l
.434 2.521 l
-45.571 2.521 l
-45.571 -.433 l
.434 -.433 l
.434 0 l
0 0 l
f
Q
.54311 .45722 .45469 .10706 k
q 1 0 0 1 255.865 370.822 cm 0 0 m
-13.264 12.944 l
-13.264 -13.129 l
0 0 l
f
Q
q 1 0 0 1 255.865 370.822 cm 0 0 m
.606 .622 l
-14.132 15.004 l
-14.132 -15.21 l
1.238 .005 l
.606 .622 l
0 0 l
-.611 .617 l
-12.396 -11.049 l
-12.396 10.885 l
-.606 -.621 l
0 0 l
-.611 .617 l
0 0 l
f
Q
174.892 362.096 70.628 17.462 re
f
BT
9.0155 0 0 9.0155 179.641 367.892 Tm
0 0 0 0 k
0 Tc
(pCAG promoter)Tj
ET
.31464 .66207 0 0 k
261.193 365.834 22.16 11.52 re
f
BT
9.0155 0 0 9.0155 265.01 368.25 Tm
.63995 .69274 .68811 .78821 k
.0001 Tc
0 Tw
(Cre)Tj
11.2571 0 0 11.2571 250.309 349.453 Tm
-.0002 Tw
(pCAG-M-Cre \(1 g/mL\))Tj
ET
0 0 0 0 k
9.3774 9.687 17.212 101.825 re
f
.63992 .69274 .68811 .78821 k
q 1 0 0 1 9.3774 111.512 cm 0 0 m
-.4338 0 l
-.4338 -102.259 l
17.646 -102.259 l
17.646 .434 l
-.4338 .434 l
-.4338 0 l
0 0 l
0 -.434 l
16.778 -.434 l
16.778 -101.391 l
.434 -101.391 l
.434 0 l
0 0 l
0 -.434 l
0 0 l
f
Q
0 0 0 0 k
9.3784 116.112 17.212 127.499 re
f
.63992 .69274 .68811 .78821 k
q 1 0 0 1 9.3784 243.611 cm 0 0 m
-.434 0 l
-.434 -127.932 l
17.646 -127.932 l
17.646 .434 l
-.434 .434 l
-.434 0 l
0 0 l
0 -.433 l
16.778 -.433 l
16.778 -127.065 l
.4338 -127.065 l
.4338 0 l
0 0 l
0 -.433 l
0 0 l
f
Q
q
264.189 247.886 -237.6 -140.914 re
26.589 247.886 m
W n
28.235 107.383 m
27.023 107.383 l
27.023 111.946 l
27 111.946 l
27 115.679 l
27.024 115.679 l
27.024 244.045 l
27 244.045 l
27 247.475 l
365.4 247.475 l
365.4 114.995 l
363.964 114.995 l
363.964 116.189 l
29.39 116.189 l
29.39 114.995 l
28.235 114.995 l
28.235 107.383 l
W n
q
237.636 0 0 140.946 26.577 106.947 cm
/Im1 Do
Q
Q
q
365.812 247.886 -102.035 -140.914 re
263.777 247.886 m
W n
28.235 107.383 m
27.023 107.383 l
27.023 111.946 l
27 111.946 l
27 115.679 l
27.024 115.679 l
27.024 244.045 l
27 244.045 l
27 247.475 l
365.4 247.475 l
365.4 114.995 l
363.964 114.995 l
363.964 116.189 l
29.39 116.189 l
29.39 114.995 l
28.235 114.995 l
28.235 107.383 l
W n
q
102.066 0 0 140.946 263.757 106.947 cm
/Im2 Do
Q
Q
q
27.023 107.383 m
27 107.383 l
27 111.946 l
27.023 111.946 l
27.023 107.383 l
W n
q
.636 0 0 4.986 26.787 107.157 cm
/Im3 Do
Q
Q
q
27.024 115.679 m
27 115.679 l
27 244.045 l
27.024 244.045 l
27.024 115.679 l
W n
q
.636 0 0 128.826 26.787 115.377 cm
/Im4 Do
Q
Q
BT
0 11.2818 -11.2818 -0 21.4419 134.709 Tm
.63995 .69274 .68811 .78821 k
(Low magnification)Tj
-10.6822 0 TD
(High magnification)Tj
ET
0 0 0 0 k
104.463 120.095 30.376 3.905 re
f
29.39 107.076 334.574 9.113 re
f
q
332.075 115.406 -304.252 -115.817 re
27.823 115.406 m
W n
365.4 0 m
28.235 0 l
28.235 107.383 l
29.39 107.383 l
29.39 107.076 l
363.964 107.076 l
363.964 107.383 l
365.4 107.383 l
365.4 114.995 l
365.4 0 l
W n
q
304.296 0 0 115.836 27.807 -.42301 cm
/Im5 Do
Q
Q
q
365.812 115.406 -34.149 -115.817 re
331.663 115.406 m
W n
365.4 0 m
28.235 0 l
28.235 107.383 l
29.39 107.383 l
29.39 107.076 l
363.964 107.076 l
363.964 107.383 l
365.4 107.383 l
365.4 114.995 l
365.4 0 l
W n
q
34.176 0 0 115.836 331.647 -.423 cm
/Im6 Do
Q
Q
q
365.4 107.383 m
363.964 107.383 l
363.964 114.995 l
365.4 114.995 l
365.4 107.383 l
29.39 107.383 m
28.235 107.383 l
28.235 114.995 l
29.39 114.995 l
29.39 107.383 l
W n
q
337.596 0 0 8.046 28.017 107.157 cm
/Im7 Do
Q
Q
q
363.964 107.076 m
29.39 107.076 l
29.39 114.995 l
363.964 114.995 l
363.964 107.076 l
W n
q
334.926 0 0 8.256 29.247 106.947 cm
/Im8 Do
Q
Q
87.973 13.777 46.866 3.906 re
f
28.956 .75894 334.574 9.112 re
f
142.952 247.54 107.32 15.912 re
f
.63992 .69274 .68811 .78821 k
q 1 0 0 1 250.272 263.452 cm 0 0 m
0 .434 l
-107.754 .434 l
-107.754 -16.346 l
.434 -16.346 l
.434 .434 l
0 .434 l
0 0 l
-.434 0 l
-.434 -15.478 l
-106.886 -15.478 l
-106.886 -.434 l
0 -.434 l
0 0 l
-.434 0 l
0 0 l
f
Q
0 0 0 0 k
254.89 247.54 107.323 15.912 re
f
.63992 .69274 .68811 .78821 k
q 1 0 0 1 362.213 263.452 cm 0 0 m
0 .434 l
-107.757 .434 l
-107.757 -16.346 l
.434 -16.346 l
.434 .434 l
0 .434 l
0 0 l
-.434 0 l
-.434 -15.478 l
-106.889 -15.478 l
-106.889 -.434 l
0 -.434 l
0 0 l
-.434 0 l
0 0 l
f
Q
0 0 0 0 k
30.749 247.54 107.322 15.912 re
f
.63992 .69274 .68811 .78821 k
q 1 0 0 1 138.072 263.452 cm 0 0 m
0 .434 l
-107.756 .434 l
-107.756 -16.346 l
.434 -16.346 l
.434 .434 l
0 .434 l
0 0 l
-.434 0 l
-.434 -15.478 l
-106.889 -15.478 l
-106.888 -.434 l
0 -.434 l
0 0 l
-.434 0 l
0 0 l
f
Q
BT
11.2827 0 0 11.2827 60.582 251.532 Tm
.63995 .69274 .68811 .78821 k
0 Tc
0 Tw
[(tdTomato)-6471.2(EGFP)-7142.9(Merge)]TJ
ET
0 0 0 0 k
91.159 547.333 190.652 18.942 re
f
.72882 .68179 .66461 .88934 k
q 1 0 0 1 281.811 547.333 cm 0 0 m
0 .434 l
-190.218 .434 l
-190.218 18.508 l
-.434 18.508 l
-.434 0 l
0 0 l
0 .434 l
0 0 l
.434 0 l
.434 19.376 l
-191.086 19.376 l
-191.086 -.434 l
.434 -.434 l
.434 0 l
0 0 l
f
Q
0 0 0 0 k
115.277 547.333 65.948 18.942 re
f
.72882 .68179 .66461 .88934 k
q 1 0 0 1 181.225 547.333 cm 0 0 m
0 .434 l
-65.514 .434 l
-65.514 18.508 l
-.434 18.508 l
-.434 0 l
0 0 l
0 .434 l
0 0 l
.434 0 l
.434 19.376 l
-66.382 19.376 l
-66.382 -.434 l
.434 -.434 l
.434 0 l
0 0 l
f
Q
q 1 0 0 1 169.254 547.333 cm 0 0 m
0 .434 l
-11.186 .434 l
-11.186 18.508 l
-.434 18.508 l
-.434 0 l
0 0 l
0 .434 l
0 0 l
.434 0 l
.434 19.376 l
-12.054 19.376 l
-12.054 -.434 l
.434 -.434 l
.434 0 l
0 0 l
f
Q
q 1 0 0 1 131.236 547.333 cm 0 0 m
0 .434 l
-11.184 .434 l
-11.184 18.508 l
-.434 18.508 l
-.434 0 l
0 0 l
0 .434 l
0 0 l
.434 0 l
.434 19.376 l
-12.052 19.376 l
-12.052 -.434 l
.434 -.434 l
.434 0 l
0 0 l
f
Q
0 0 0 0 k
97.736 547.333 12.542 18.942 re
f
.72882 .68179 .66461 .88934 k
q 1 0 0 1 110.278 547.333 cm
0 0 m
0 .434 l
-12.108 .434 l
-12.108 18.508 l
-.434 18.508 l
-.434 0 l
0 0 l
0 .434 l
0 0 l
.434 0 l
.434 19.376 l
-12.976 19.376 l
-12.976 -.434 l
.434 -.434 l
.434 0 l
0 0 l
f
Q
.30646 .24274 .24073 0 k
231.779 547.333 28.593 18.942 re
f
.72882 .68179 .66461 .88934 k
q 1 0 0 1 260.372 547.333 cm 0 0 m
0 .434 l
-28.159 .434 l
-28.159 18.508 l
-.434 18.508 l
-.434 0 l
0 0 l
0 .434 l
0 0 l
.434 0 l
.434 19.376 l
-29.027 19.376 l
-29.027 -.434 l
.434 -.434 l
.434 0 l
0 0 l
f
Q
q 1 0 0 1 157.155 515.417 cm 0 0 m
16.901 -9.594 l
33.626 .001 l
33.194 .754 l
16.899 -8.595 l
.428 .755 l
0 0 l
f
Q
0 0 0 0 k
91.159 506.322 66.475 18.942 re
f
.72882 .68179 .66461 .88934 k
q 1 0 0 1 157.634 506.322 cm 0 0 m
0 .434 l
-66.041 .434 l
-66.041 18.508 l
-.434 18.508 l
-.434 0 l
0 0 l
0 .434 l
0 0 l
.434 0 l
.434 19.376 l
-66.909 19.376 l
-66.909 -.434 l
.434 -.434 l
.434 0 l
0 0 l
f
Q
0 0 0 0 k
190.606 506.322 91.205 18.942 re
f
.72882 .68179 .66461 .88934 k
q 1 0 0 1 281.811 506.322 cm 0 0 m
0 .434 l
-90.771 .434 l
-90.771 18.508 l
-.434 18.508 l
-.434 0 l
0 0 l
0 .434 l
0 0 l
.434 0 l
.434 19.376 l
-91.639 19.376 l
-91.639 -.434 l
.434 -.434 l
.434 0 l
0 0 l
f
Q
.30646 .24274 .24073 0 k
231.779 506.322 28.593 18.942 re
f
.72882 .68179 .66461 .88934 k
q 1 0 0 1 260.372 506.322 cm 0 0 m
0 .434 l
-28.159 .434 l
-28.159 18.508 l
-.434 18.508 l
-.434 0 l
0 0 l
0 .434 l
0 0 l
.434 0 l
.434 19.376 l
-29.027 19.376 l
-29.027 -.434 l
.434 -.434 l
.434 0 l
0 0 l
f
Q
0 0 0 0 k
115.277 506.322 42.357 18.942 re
f
.72882 .68179 .66461 .88934 k
q 1 0 0 1 157.634 506.322 cm 0 0 m
0 .434 l
-41.923 .434 l
-41.923 18.508 l
-.434 18.508 l
-.434 0 l
0 0 l
0 .434 l
0 0 l
.434 0 l
.434 19.376 l
-42.791 19.376 l
-42.791 -.434 l
.434 -.434 l
.434 0 l
0 0 l
f
Q
119.618 506.322 11.618 18.942 re
f
97.605 570.314 12.802 .86792 re
f
97.302 568.38 .8679 2.3682 re
f
109.891 568.38 .868 2.3682 re
f
115.103 570.314 66.165 .86792 re
f
114.843 568.38 .868 2.3682 re
f
180.789 568.38 .86798 2.3682 re
f
231.652 570.314 28.807 .86792 re
f
231.345 568.38 .86801 2.3682 re
f
260.026 568.38 .867 2.3682 re
f
145.62 587.134 45.159 .86792 re
f
145.317 585.202 .867 2.3657 re
f
190.267 585.202 .868 2.3657 re
f
BT
11.5343 0 0 11.5343 91.8101 573.6271 Tm
.63992 .69274 .68811 .78821 k
.0001 Tc
[(bHLH)-1474.5(PAS)]TJ
6.1191 1.44 TD
.0002 Tc
(LB)Tj
6.0078 -1.44 TD
0 Tc
(Q-rich)Tj
12.8159 0 0 12.8159 88.3716 535.4703 Tm
(1)Tj
14.2499 -.1 TD
.0002 Tc
(805)Tj
-14.2499 -3.111 TD
[(1)-13693.7(805)]TJ
4.525 0 TD
.0001 Tc
[(276)-1031.8(419)]TJ
ET
.72882 .68179 .66461 .88934 k
q 1 0 0 1 115.64 547.228 cm 0 0 m
12.325 18.81 l
11.6 19.285 l
-.726 .476 l
f
Q
q 1 0 0 1 115.64 554.732 cm 0 0 m
7.409 11.305 l
6.683 11.781 l
-.726 .476 l
f
Q
q 1 0 0 1 115.64 562.361 cm 0 0 m
2.41 3.676 l
1.685 4.152 l
-.726 .476 l
f
Q
0 0 0 0 k
97.679 547.333 12.99 18.942 re
f
.72882 .68179 .66461 .88934 k
q 1 0 0 1 110.669 547.333 cm 0 0 m
0 .434 l
-12.556 .434 l
-12.556 18.508 l
-.434 18.508 l
-.434 0 l
0 0 l
0 .434 l
0 0 l
.434 0 l
.434 19.376 l
-13.424 19.376 l
-13.424 -.434 l
.434 -.434 l
.434 0 l
0 0 l
f
Q
97.679 563.605 12.969 .8678 re
f
97.679 561.238 12.91 .86792 re
f
97.679 558.869 12.91 .86792 re
f
97.679 556.501 12.969 .86792 re
f
97.679 554.134 12.99 .86786 re
f
97.679 551.767 12.99 .86792 re
f
97.679 549.398 13.03 .86786 re
f
0 0 0 0 k
97.679 506.322 12.99 18.942 re
f
.72882 .68179 .66461 .88934 k
q 1 0 0 1 110.669 506.322 cm 0 0 m
0 .434 l
-12.556 .434 l
-12.556 18.508 l
-.434 18.508 l
-.434 0 l
0 0 l
0 .434 l
0 0 l
.434 0 l
.434 19.376 l
-13.424 19.376 l
-13.424 -.434 l
.434 -.434 l
.434 0 l
0 0 l
f
Q
97.679 522.593 12.969 .86792 re
f
97.679 520.226 12.91 .86786 re
f
97.679 517.859 12.91 .86792 re
f
97.679 515.49 12.969 .86786 re
f
97.679 513.122 12.99 .86804 re
f
97.679 510.754 12.99 .86798 re
f
97.679 508.387 13.03 .86801 re
f
q 1 0 0 1 121.276 547.228 cm 0 0 m
12.326 18.81 l
11.6 19.285 l
-.726 .476 l
f
Q
q 1 0 0 1 127.409 547.228 cm 0 0 m
12.326 18.81 l
11.6 19.285 l
-.726 .476 l
f
Q
q 1 0 0 1 133.542 547.228 cm 0 0 m
12.325 18.81 l
11.599 19.285 l
-.726 .476 l
f
Q
q 1 0 0 1 139.345 547.228 cm
0 0 m
12.326 18.81 l
11.6 19.285 l
-.726 .476 l
f
Q
q 1 0 0 1 145.643 547.228 cm 0 0 m
12.325 18.81 l
11.599 19.285 l
-.726 .476 l
f
Q
q 1 0 0 1 151.611 547.228 cm 0 0 m
12.326 18.81 l
11.6 19.285 l
-.726 .476 l
f
Q
q 1 0 0 1 157.577 547.228 cm 0 0 m
12.325 18.81 l
11.599 19.285 l
-.726 .476 l
f
Q
q 1 0 0 1 163.213 547.228 cm 0 0 m
12.325 18.81 l
11.599 19.285 l
-.726 .476 l
f
Q
q 1 0 0 1 169.263 547.228 cm 0 0 m
12.325 18.81 l
11.599 19.285 l
-.726 .476 l
f
Q
q 1 0 0 1 151.681 506.217 cm 0 0 m
6.316 9.637 l
5.59 10.112 l
-.726 .476 l
f
Q
157.634 547.333 11.62 18.942 re
f
119.618 547.333 11.618 18.942 re
f
BT
12.6286 0 0 12.6286 121.375 552.485 Tm
0 0 0 0 k
2.364 Tc
(AB)Tj
ET
.72882 .68179 .66461 .88934 k
q 1 0 0 1 115.64 506.217 cm 0 0 m
12.325 18.809 l
11.6 19.285 l
-.726 .476 l
f
Q
q 1 0 0 1 115.64 513.719 cm 0 0 m
7.409 11.307 l
6.683 11.783 l
-.726 .476 l
f
Q
q 1 0 0 1 115.64 521.349 cm 0 0 m
2.41 3.677 l
1.685 4.153 l
-.726 .476 l
f
Q
q 1 0 0 1 121.276 506.217 cm 0 0 m
12.326 18.809 l
11.6 19.285 l
-.726 .476 l
f
Q
q 1 0 0 1 127.409 506.217 cm 0 0 m
12.326 18.809 l
11.6 19.285 l
-.726 .476 l
f
Q
q 1 0 0 1 133.542 506.217 cm 0 0 m
12.325 18.809 l
11.599 19.285 l
-.726 .476 l
f
Q
q 1 0 0 1 139.345 506.217 cm 0 0 m
12.326 18.809 l
11.6 19.285 l
-.726 .476 l
f
Q
q 1 0 0 1 145.643 506.217 cm 0 0 m
12.325 18.809 l
11.6 19.285 l
-.726 .476 l
f
Q
q 1 0 0 1 131.236 506.322 cm 0 0 m
0 .434 l
-11.184 .434 l
-11.184 18.508 l
-.434 18.508 l
-.434 0 l
0 0 l
0 .434 l
0 0 l
.434 0 l
.434 19.376 l
-12.052 19.376 l
-12.052 -.434 l
.434 -.434 l
.434 0 l
0 0 l
f
Q
BT
12.6286 0 0 12.6286 121.375 511.473 Tm
0 0 0 0 k
0 Tc
(A)Tj
ET
.72882 .68179 .66461 .88934 k
q 1 0 0 1 175.276 547.228 cm 0 0 m
6.312 9.636 l
5.586 10.111 l
-.726 .476 l
f
Q
BT
18.5653 0 0 18.5653 48.2158 550.9127 Tm
.63995 .69274 .68811 .78821 k
(AhR)Tj
-1.7221 -2.2262 TD
(CA-AhR)Tj
ET
q
0 614.964 367.5 -614.964 re
W n
BT
20.8295 0 0 20.8295 .0317 597.089 Tm
(A)Tj
ET
EMC
Q
endstream
endobj
120 0 obj
[/Indexed/DeviceCMYK 53 133 0 R]
endobj
133 0 obj
<>stream
hD
0C3gf lKĎyH QRLL}l*+6u#O2wAl'IdY)TR+)2Cem
ƫ;[#
endstream
endobj
121 0 obj
<>
endobj
122 0 obj
<>
endobj
134 0 obj
<>
endobj
135 0 obj
<>
endobj
137 0 obj
<>stream
h4WitWI/6$r;U9ULg&HHHH00[xǒlyd.+$
lͲ$[Fe/!1KB:@L&IIɤ)qΔ?U^_֭!m
i-F&DZkH֑