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Md Emon Hossain, Kentaro Matsuzaki, Masanori Katakura, Naotoshi Sugimoto, Abdullah Al Mamun, Rafiad Islam, Michio Hashimoto, Osamu Shido
Direct exposure to mild heat promotes proliferation and neuronal differentiation of neural stem/progenitor cells in vitro
www.plosone.org
www.plosone.org
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-34.7638 -1.2983 Td
(directly)Tj
3.1747 0 Td
(accelerate)Tj
4.0536 0 Td
(the)Tj
1.4399 0 Td
(proliferation)Tj
5.1817 0 Td
(rate)Tj
1.7122 0 Td
(of)Tj
0.9921 0 Td
(NSCs/NPCs)Tj
5.0456 0 Td
(in)Tj
1.0148 0 Td
(rat)Tj
1.2926 0 Td
(hypothalamus.)Tj
6.0151 0 Td
(To)Tj
1.3152 0 Td
(test)Tj
1.5704 0 Td
(this)Tj
1.6384 0 Td
(hypoth-)Tj
-34.4463 -1.2983 Td
(esis,)Tj
1.8255 0 Td
(we)Tj
1.3152 0 Td
(cultured)Tj
3.5206 0 Td
(NSCs/NPCs)Tj
5.0513 0 Td
(under)Tj
2.5909 0 Td
(normal)Tj
3.1067 0 Td
(and)Tj
1.7121 0 Td
(elevated)Tj
3.4073 0 Td
(temperatures,)Tj
5.6352 0 Td
(and)Tj
1.7121 0 Td
(examined)Tj
4.0819 0 Td
(whether)Tj
-33.9588 -1.3039 Td
(direct)Tj
2.4944 0 Td
(heat)Tj
1.8822 0 Td
(exposure)Tj
3.7644 0 Td
(exerts)Tj
2.5285 0 Td
(stimulatory)Tj
4.7395 0 Td
(effects)Tj
2.6815 0 Td
(on)Tj
1.2643 0 Td
(NSC/NPC)Tj
4.3426 0 Td
(proliferation.)Tj
5.4085 0 Td
(Heat)Tj
2.1203 0 Td
(exposure)Tj
3.7701 0 Td
(initi-)Tj
-34.9963 -1.2982 Td
(ates)Tj
1.7121 0 Td
(various)Tj
3.101 0 Td
(cellular)Tj
3.0898 0 Td
(responses)Tj
4.0422 0 Td
(in)Tj
1.0204 0 Td
(cells,)Tj
2.109 0 Td
(including)Tj
3.9912 0 Td
(induction)Tj
4.0818 0 Td
(or)Tj
1.0828 0 Td
(activation)Tj
4.0933 0 Td
(of)Tj
1.0034 0 Td
(heat)Tj
1.8822 0 Td
(shock)Tj
2.5058 0 Td
(proteins)Tj
-33.715 -1.2983 Td
(\(HSPs\))Tj
3.0273 0 Td
([)Tj
0.83 0.64 0.02 0 k
(28)Tj
0 g
(].)Tj
2.0466 0 Td
(Some)Tj
2.4208 0 Td
(of)Tj
1.0035 0 Td
(these)Tj
2.2223 0 Td
(HSPs,)Tj
2.5795 0 Td
(such)Tj
2.0353 0 Td
(as)Tj
1.0034 0 Td
(HSP90,)Tj
3.1635 0 Td
(are)Tj
1.4286 0 Td
(constitutively)Tj
5.5162 0 Td
(expressed,)Tj
4.2576 0 Td
(while)Tj
2.3414 0 Td
(others,)Tj
2.8914 0 Td
(par-)Tj
-35.9374 -1.3039 Td
(ticularly)Tj
3.4355 0 Td
(HSP27)Tj
2.9424 0 Td
(and)Tj
1.7121 0 Td
(HSP70,)Tj
3.1634 0 Td
(are)Tj
1.4287 0 Td
(inducible)Tj
3.9061 0 Td
([)Tj
0.83 0.64 0.02 0 k
(29)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7121 0 Td
(30)Tj
0 g
(].)Tj
1.7121 0 Td
(In)Tj
1.0999 0 Td
(addition)Tj
3.5489 0 Td
(to)Tj
1.0148 0 Td
(their)Tj
2.075 0 Td
(functions)Tj
3.9344 0 Td
(as)Tj
1.0035 0 Td
(molecular)Tj
-32.6889 -1.2983 Td
(chaperones,)Tj
4.9152 0 Td
(both)Tj
2.0353 0 Td
(HSP27)Tj
2.9423 0 Td
(and)Tj
1.7121 0 Td
(HSP70)Tj
2.948 0 Td
(have)Tj
2.0353 0 Td
(been)Tj
2.0976 0 Td
(shown)Tj
2.8176 0 Td
(to)Tj
1.0148 0 Td
(confer)Tj
2.744 0 Td
(cytoprotection)Tj
5.981 0 Td
(against)Tj
2.9877 0 Td
(apopto-)Tj
-34.2309 -1.2983 Td
(sis)Tj
1.1905 0 Td
([)Tj
0.83 0.64 0.02 0 k
(31)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7121 0 Td
(32)Tj
0 g
(])Tj
1.491 0 Td
(and)Tj
1.7121 0 Td
(necrosis)Tj
3.4356 0 Td
([)Tj
0.83 0.64 0.02 0 k
(33)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(35)Tj
0 g
(])Tj
3.2825 0 Td
(by)Tj
1.1679 0 Td
(a)Tj
0.6463 0 Td
(variety)Tj
2.8799 0 Td
(of)Tj
1.0035 0 Td
(stressors.)Tj
3.8041 0 Td
(Further,)Tj
3.4469 0 Td
(HSP27)Tj
2.9423 0 Td
(can)Tj
1.6044 0 Td
(interact)Tj
3.2372 0 Td
(with)Tj
1.9729 0 Td
(the)Tj
-35.5292 -1.3039 Td
(Ser/Thr)Tj
3.2881 0 Td
(kinase)Tj
2.7156 0 Td
(Akt)Tj
1.6781 0 Td
(which)Tj
2.6192 0 Td
(is)Tj
0.839 0 Td
(suggested)Tj
4.0195 0 Td
(to)Tj
1.0148 0 Td
(be)Tj
1.1339 0 Td
(important)Tj
4.2293 0 Td
(for)Tj
1.3662 0 Td
(sustained)Tj
3.9175 0 Td
(Akt)Tj
1.6838 0 Td
(activity)Tj
3.067 0 Td
([)Tj
0.83 0.64 0.02 0 k
(36)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(38)Tj
0 g
(])Tj
3.2769 0 Td
(and)Tj
-34.8489 -1.2982 Td
(Akt)Tj
1.678 0 Td
(has)Tj
1.5251 0 Td
(been)Tj
2.0976 0 Td
(reported)Tj
3.617 0 Td
(to)Tj
1.0091 0 Td
(mediate)Tj
3.3732 0 Td
(promotion)Tj
4.5071 0 Td
(of)Tj
1.0034 0 Td
(cell)Tj
1.5364 0 Td
(proliferation)Tj
5.1874 0 Td
(and)Tj
1.7121 0 Td
(cell)Tj
1.5364 0 Td
(survival)Tj
3.2881 0 Td
([)Tj
0.83 0.64 0.02 0 k
(39)Tj
0 g
(].)Tj
2.0523 0 Td
(Thus,)Tj
2.4378 0 Td
(in)Tj
-36.561 -1.2983 Td
(order)Tj
2.3924 0 Td
(to)Tj
1.0091 0 Td
(elucidate)Tj
3.7417 0 Td
(the)Tj
1.4513 0 Td
(mechanism)Tj
4.7906 0 Td
(of)Tj
1.0034 0 Td
(heat-induced)Tj
5.4255 0 Td
(NSC/NPC)Tj
4.3426 0 Td
(proliferation,)Tj
5.4085 0 Td
(we)Tj
1.3153 0 Td
(investigated)Tj
-30.8804 -1.3039 Td
(HSPs)Tj
2.3584 0 Td
(induction)Tj
4.0818 0 Td
(and)Tj
1.7121 0 Td
(Akt)Tj
1.6781 0 Td
(activation)Tj
4.0932 0 Td
(in)Tj
1.0262 0 Td
(heat-exposed)Tj
5.4084 0 Td
(NSCs/NPCs.)Tj
5.2668 0 Td
(We)Tj
1.5987 0 Td
(also)Tj
1.7461 0 Td
(examined)Tj
4.0819 0 Td
(whether)Tj
-33.0517 -1.2983 Td
(neuronal)Tj
3.7757 0 Td
(differentiation)Tj
5.8903 0 Td
(of)Tj
1.0035 0 Td
(cultured)Tj
3.5149 0 Td
(NSCs/NPCs)Tj
5.057 0 Td
(is)Tj
0.8334 0 Td
(enhanced)Tj
4.0308 0 Td
(by)Tj
1.1679 0 Td
(direct)Tj
2.4945 0 Td
(heat)Tj
1.8822 0 Td
(exposure.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 486.1984 cm
BT
/F3 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
(Ethics)Tj
2.9149 0 Td
(statement)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 451.2188 cm
BT
/F8 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
(in)Tj
1.0374 0 Td
(accordance)Tj
4.7339 0 Td
(with)Tj
2.0012 0 Td
(the)Tj
1.4684 0 Td
(Guidelines)Tj
4.524 0 Td
(for)Tj
1.389 0 Td
(Animal)Tj
3.2201 0 Td
(Experi-)Tj
-34.469 -1.3039 Td
(mentation)Tj
4.3653 0 Td
(of)Tj
1.0148 0 Td
(Shimane)Tj
3.7133 0 Td
(University)Tj
4.405 0 Td
(Faculty)Tj
3.1295 0 Td
(of)Tj
1.0148 0 Td
(Medicine,)Tj
4.2236 0 Td
(which)Tj
2.6475 0 Td
(were)Tj
2.1203 0 Td
(compiled)Tj
3.9515 0 Td
(from)Tj
2.211 0 Td
(the)Tj
1.4683 0 Td
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-34.2649 -1.2982 Td
(lines)Tj
2.0636 0 Td
(for)Tj
1.3889 0 Td
(Animal)Tj
3.2202 0 Td
(Experimentation)Tj
6.9788 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(Japanese)Tj
3.6906 0 Td
(Association)Tj
4.8813 0 Td
(for)Tj
1.3833 0 Td
(Laboratory)Tj
4.6431 0 Td
(Animal)Tj
3.2201 0 Td
(Science.)Tj
-33.9531 -1.2983 Td
(The)Tj
1.7801 0 Td
(protocol)Tj
3.6 0 Td
(for)Tj
1.3833 0 Td
(this)Tj
1.6781 0 Td
(study)Tj
2.3867 0 Td
(was)Tj
1.7008 0 Td
(approved)Tj
3.9685 0 Td
(by)Tj
1.1849 0 Td
(the)Tj
1.4683 0 Td
(Committee)Tj
4.7395 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.474 0 Td
(Ethics)Tj
2.6645 0 Td
(of)Tj
1.0148 0 Td
(Animal)Tj
3.2202 0 Td
(Experi-)Tj
-33.5393 -1.3039 Td
(ments)Tj
2.6702 0 Td
(of)Tj
1.0148 0 Td
(Shimane)Tj
3.7133 0 Td
(University)Tj
4.405 0 Td
(\(Permit)Tj
3.2995 0 Td
(Number:)Tj
3.8325 0 Td
(IZ)Tj
1.1565 0 Td
(2718\).)Tj
3.2088 0 Td
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1.3946 0 Td
(surgeries)Tj
3.7928 0 Td
(were)Tj
2.1203 0 Td
(performed)Tj
4.473 0 Td
(under)Tj
-35.0813 -1.2983 Td
(anesthesia,)Tj
4.524 0 Td
(and)Tj
1.7291 0 Td
(all)Tj
1.1452 0 Td
(efforts)Tj
2.7553 0 Td
(were)Tj
2.126 0 Td
(made)Tj
2.4264 0 Td
(to)Tj
1.0205 0 Td
(minimize)Tj
4.0478 0 Td
(suffering)Tj
3.7587 0 Td
(and)Tj
1.7348 0 Td
(the)Tj
1.4684 0 Td
(number)Tj
3.4185 0 Td
(of)Tj
1.0148 0 Td
(animals)Tj
3.3279 0 Td
(used.)Tj
-34.4974 -1.2982 Td
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1.7801 0 Td
(rats)Tj
1.6838 0 Td
(were)Tj
2.1259 0 Td
(anesthetized)Tj
5.1647 0 Td
(by)Tj
1.1792 0 Td
(intraperitoneal)Tj
6.1795 0 Td
(injection)Tj
3.7587 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.652 0 Td
(mixture)Tj
3.3959 0 Td
(of)Tj
1.0148 0 Td
(medetomidine)Tj
6.0718 0 Td
(hydro-)Tj
-34.0212 -1.2983 Td
(chloride)Tj
3.5149 0 Td
(\(0.15)Tj
2.211 0 Td
(mg/kg\),)Tj
3.3619 0 Td
(midazolam)Tj
4.6884 0 Td
(\(2.0)Tj
1.7348 0 Td
(mg/kg\),)Tj
3.3619 0 Td
(and)Tj
1.7291 0 Td
(butorphanol)Tj
5.2157 0 Td
(tartrate)Tj
3.1465 0 Td
(\(2.5)Tj
1.7348 0 Td
(mg/kg\).)Tj
3.3618 0 Td
(Carbon)Tj
-34.0608 -1.3039 Td
(dioxide)Tj
3.2031 0 Td
(\(CO)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 249.5622 345.5433 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 253.1338 347.1874 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(\))Tj
0.5555 0 Td
(inhalation)Tj
4.303 0 Td
(was)Tj
1.6951 0 Td
(used)Tj
2.0636 0 Td
(for)Tj
1.3833 0 Td
(euthanasia)Tj
4.4787 0 Td
(of)Tj
1.0148 0 Td
(pregnant)Tj
3.8268 0 Td
(rats.)Tj
1.9105 0 Td
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3.7247 0 Td
(of)Tj
1.0148 0 Td
(NSCs/NPCs)Tj
-31.2828 -1.2982 Td
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2.2053 0 Td
(forebrain)Tj
3.9344 0 Td
(cortices)Tj
3.2995 0 Td
(required)Tj
3.6396 0 Td
(decapitation)Tj
5.1647 0 Td
(of)Tj
1.0148 0 Td
(fetuses)Tj
2.9027 0 Td
(with)Tj
1.9956 0 Td
(surgical)Tj
3.3165 0 Td
(scissors.)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
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3.8929 0 Td
(and)Tj
1.8662 0 Td
(culture)Tj
3.1842 0 Td
(of)Tj
1.0441 0 Td
(fetal)Tj
2.0882 0 Td
(NSCs/NPCs)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 291.0047 cm
BT
/F8 1 Tf
1 TL
-0.014 Tc
0 0 Td
(NSCs/NPCs)Tj
5.0116 0 Td
(were)Tj
2.0863 0 Td
(isolated)Tj
3.2031 0 Td
(from)Tj
2.1656 0 Td
(rat)Tj
1.2926 0 Td
(fetuses)Tj
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(on)Tj
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(embryonic)Tj
4.4504 0 Td
(day)Tj
1.6044 0 Td
(14.5)Tj
1.8312 0 Td
(\(E14.5\))Tj
3.0557 0 Td
(and)Tj
1.7008 0 Td
(cultured)Tj
3.4866 0 Td
(by)Tj
1.1622 0 Td
(the)Tj
-35.1437 -1.2982 Td
(neurosphere)Tj
5.1136 0 Td
(method)Tj
3.2598 0 Td
(as)Tj
0.9978 0 Td
(previously)Tj
4.252 0 Td
(described)Tj
3.9628 0 Td
([)Tj
0.83 0.64 0.02 0 k
(40)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.6951 0 Td
(41)Tj
0 g
(].)Tj
1.6951 0 Td
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2.999 0 Td
(rat)Tj
1.2926 0 Td
(forebrain)Tj
3.8494 0 Td
(cortices)Tj
3.2145 0 Td
(were)Tj
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(dis-)Tj
-34.4123 -1.3039 Td
(sected)Tj
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(on)Tj
1.253 0 Td
(E14.5)Tj
2.3924 0 Td
(and)Tj
1.7008 0 Td
(mechanically)Tj
5.3461 0 Td
(dissociated)Tj
4.507 0 Td
(into)Tj
1.8028 0 Td
(single)Tj
2.4718 0 Td
(cells)Tj
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(by)Tj
1.1622 0 Td
(repeated)Tj
3.5603 0 Td
(pipetting)Tj
3.7304 0 Td
(\(trituration\))Tj
-32.4168 -1.2983 Td
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1.0147 0 Td
(a)Tj
0.6463 0 Td
(serum-free)Tj
4.4788 0 Td
(medium)Tj
3.5432 0 Td
(\(N2)Tj
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(medium\))Tj
3.8778 0 Td
(containing)Tj
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(DMEM/F12)Tj
5.0399 0 Td
(\(1:1\),)Tj
2.2451 0 Td
(0.6%)Tj
2.1146 0 Td
(\(w/v\))Tj
2.3187 0 Td
(glucose,)Tj
-31.4473 -1.2983 Td
(0.1125%)Tj
3.5092 0 Td
(\(w/v\))Tj
2.3187 0 Td
(sodium)Tj
3.1692 0 Td
(bicarbonate,)Tj
5.0456 0 Td
(N2)Tj
1.4116 0 Td
(supplement,)Tj
5.023 0 Td
(2)Tj
0.686 0 Td
(mM)Tj
1.9105 0 Td
(L-glutamine,)Tj
5.2441 0 Td
(5)Tj
0.686 0 Td
(mM)Tj
1.9105 0 Td
(HEPES,)Tj
3.3279 0 Td
(and)Tj
-34.2423 -1.3039 Td
(25)Tj
/F14 1 Tf
1.1508 0 Td
[()]TJ
/F8 1 Tf
(g/mL)Tj
2.829 0 Td
(insulin.)Tj
3.1294 0 Td
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1.7575 0 Td
(dissociated)Tj
4.507 0 Td
(cells)Tj
1.8709 0 Td
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(cultured)Tj
3.4866 0 Td
(in)Tj
1.0148 0 Td
(60-mm)Tj
3.1124 0 Td
(dishes)Tj
2.6249 0 Td
(at)Tj
0.9354 0 Td
(a)Tj
0.6406 0 Td
(density)Tj
3.0331 0 Td
(of)Tj
0.9978 0 Td
(5)Tj
/F14 1 Tf
0.6859 0 Td
[()]TJ
/F8 1 Tf
0.7767 0 Td
(10)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 555.6472 230.4566 cm
BT
/F8 1 Tf
1 TL
-0.0186 Tc
0 0 Td
(5)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 212.9952 cm
BT
/F8 1 Tf
1 TL
-0.014 Tc
0 0 Td
(cells)Tj
1.8708 0 Td
(per)Tj
1.5024 0 Td
(dish)Tj
1.8595 0 Td
(in)Tj
1.0204 0 Td
(N2)Tj
1.4117 0 Td
(medium)Tj
3.5433 0 Td
(supplemented)Tj
5.7373 0 Td
(with)Tj
1.9558 0 Td
(20)Tj
1.1509 0 Td
(ng/mL)Tj
2.8687 0 Td
(basic)Tj
2.1656 0 Td
(fibroblast)Tj
3.9061 0 Td
(growth)Tj
3.0161 0 Td
(factor)Tj
2.4774 0 Td
(\(bFGF\))Tj
-34.486 -1.2982 Td
(and)Tj
1.7007 0 Td
(2)Tj
/F14 1 Tf
0.686 0 Td
[()]TJ
/F8 1 Tf
(g)Tj
1.1679 0 Td
(/mL)Tj
1.8822 0 Td
(heparin)Tj
3.2371 0 Td
(\(proliferation)Tj
5.4652 0 Td
(media,)Tj
2.8573 0 Td
(PM\))Tj
1.9842 0 Td
(in)Tj
1.0148 0 Td
(a)Tj
0.6463 0 Td
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