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Lyvianne Decourtye, Maud Clemessy, Erik Mire, Tatiana Ledent, Laurence Périn, Iain C. Robinson, Yves Le Bouc, Laurent Kappeler
Impact of insulin on primary arcuate neurons culture is dependent on early-postnatal nutritional status and neuronal subpopulation
www.plosone.org
www.plosone.org
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h
f*
0 g
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BT
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1 TL
-0.005 Tc
0 0 Td
(Table)Tj
2.5512 0 Td
(1.)Tj
1.1763 0 Td
(Compositio)Tj
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(n)Tj
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(of)Tj
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(the)Tj
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(LasQCdiet)Tj
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(Rod18-R)Tj
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(Main)Tj
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(nutrients)Tj
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(acids)Tj
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(Kg)Tj
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(Protein)Tj
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(18.9)Tj
10.0418 0 Td
(%)Tj
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(Arginine)Tj
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(9.0)Tj
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(g)Tj
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(5.3)Tj
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(%)Tj
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(Cystein)Tj
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(Fibre)Tj
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(%)Tj
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(Histidin)Tj
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(e)Tj
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(4.5)Tj
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(g)Tj
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(Ash)Tj
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(7.0)Tj
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(%)Tj
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(Isoleucine)Tj
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(7.0)Tj
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(g)Tj
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(N-free-Extr)Tj
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(acts)Tj
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(53.1)Tj
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(%)Tj
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(Leucin)Tj
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(e)Tj
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(21.0)Tj
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(g)Tj
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(Dry)Tj
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(matter)Tj
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(88.0)Tj
10.0418 0 Td
(%)Tj
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(Lysine)Tj
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(g)Tj
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(Methion)Tj
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(ine)Tj
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(4.5)Tj
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(g)Tj
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(Energy/kg)Tj
33.3427 0 Td
(Phenyla)Tj
3.2032 0 Td
(lanine)Tj
11.5938 0 Td
(10.0)Tj
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(g)Tj
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(GE)Tj
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(\(gross\))Tj
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(16.6)Tj
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(MJ)Tj
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(Threoni)Tj
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(ne)Tj
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(6.5)Tj
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(g)Tj
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(ME)Tj
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(\(metabolic)Tj
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(13.9)Tj
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(MJ)Tj
9.1985 0 Td
(Tryptopha)Tj
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(n)Tj
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(2.0)Tj
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(g)Tj
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(Tyrosi)Tj
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(ne)Tj
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(g)Tj
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(g)Tj
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(Vitamin)Tj
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(s)Tj
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(Kg)Tj
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(Phosphor)Tj
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(us)Tj
10.2119 0 Td
(6.5)Tj
10.0418 0 Td
(g)Tj
9.1985 0 Td
(Vit.)Tj
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(A)Tj
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(15.000)Tj
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(I.E.)Tj
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(Sodium)Tj
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(g)Tj
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(Vit.)Tj
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(D3)Tj
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(I.E.)Tj
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(m)Tj
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(g)Tj
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(E)Tj
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(K)Tj
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(5)Tj
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(mg)Tj
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(element)Tj
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(kg)Tj
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25.5474 0 Td
(Thiamine)Tj
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(\(B1\))Tj
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(15)Tj
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(mg)Tj
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(mg)Tj
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(\(B2\))Tj
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(mg)Tj
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(Iodine)Tj
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(mg)Tj
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(Pyridoxin)Tj
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(e)Tj
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14.1024 0 Td
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(mg)Tj
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(Cobalami)Tj
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(n)Tj
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(\(B12\))Tj
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(mg)Tj
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(mg)Tj
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[()]TJ
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(20)Tj
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(mg)Tj
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(:0)Tj
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(g)Tj
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(18)Tj
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(:0)Tj
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(3.0)Tj
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(g)Tj
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(C18)Tj
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(:2)Tj
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(21.0)Tj
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(g)Tj
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(:0)Tj
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(0.2)Tj
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(C18)Tj
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(:3)Tj
12.9473 0 Td
(13.0)Tj
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(g)Tj
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1.8 0 Td
(LasQCdiet)Tj
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(Rod18-R)Tj
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(chow)Tj
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(is)Tj
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(provided)Tj
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(ad)Tj
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(libitum)Tj
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(to)Tj
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(mice)Tj
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(and)Tj
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(dedicated)Tj
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(for)Tj
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(gestation,)Tj
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(lactation)Tj
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(and)Tj
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(growth)Tj
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(of)Tj
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(young)Tj
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(animals.)Tj
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(ts)Tj
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(are)Tj
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(Wheat,)Tj
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(corn)Tj
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(gluten,)Tj
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(wheat)Tj
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(meal,)Tj
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(corn,)Tj
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(oats,)Tj
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(barley,)Tj
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(linseed)Tj
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(oil,)Tj
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(carbonate,)Tj
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(brewer's)Tj
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(yeast,)Tj
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(molasses,)Tj
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(Vitamin-)Tj
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(elements)Tj
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(soya,)Tj
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(fish,)Tj
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(coating.)Tj
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(product)Tj
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(is)Tj
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(sterilized)Tj
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(by)Tj
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(a)Tj
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(gamma-i)Tj
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(rradiation)Tj
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(at)Tj
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(minimum)Tj
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(21)Tj
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(https://do)Tj
3.5575 0 Td
(i.org/10.1371/j)Tj
5.4425 0 Td
(ournal.pone)Tj
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(.0193196.t001)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
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(AgRP)Tj
-34.8319 -1.2983 Td
(neurons,)Tj
3.7303 0 Td
(respectively.)Tj
-2.5341 -1.3039 Td
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(grow)Tj
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(uniformly)Tj
4.2406 0 Td
(around)Tj
3.1295 0 Td
(the)Tj
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(explants)Tj
3.5093 0 Td
(on)Tj
1.2699 0 Td
(the)Tj
1.4627 0 Td
(ground)Tj
3.1578 0 Td
(of)Tj
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(the)Tj
1.4627 0 Td
(culture)Tj
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(dish)Tj
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(that)Tj
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(facili-)Tj
-35.3194 -1.2982 Td
(tate)Tj
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(individual)Tj
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(measurements.)Tj
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/F11 1 Tf
3.2371 0 Td
[()12()]TJ
1.0148 0 Td
[()-13()14()7()20( )]TJ
/F6 1 Tf
2.0466 0 Td
(neurons)Tj
3.5093 0 Td
(are)Tj
1.4456 0 Td
(not)Tj
1.5761 0 Td
(as)Tj
1.0148 0 Td
(tightly)Tj
2.7779 0 Td
(oriented)Tj
-33.6753 -1.2983 Td
(as)Tj
/F11 1 Tf
1.0147 0 Td
[()12()]TJ
1.0148 0 Td
[()-13()15()3( )]TJ
/F6 1 Tf
(,)Tj
2.0466 0 Td
(which)Tj
2.6476 0 Td
(facilitate)Tj
3.6 0 Td
(axons)Tj
2.5341 0 Td
(sprouting)Tj
4.0876 0 Td
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(explants.)Tj
3.736 0 Td
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1.9899 0 Td
(is)Tj
0.8448 0 Td
(notably)Tj
3.2201 0 Td
(the)Tj
1.4683 0 Td
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1.3889 0 Td
(GHRH)Tj
-33.6583 -1.3039 Td
(neurons)Tj
3.5035 0 Td
(that)Tj
1.7802 0 Td
(are)Tj
1.4513 0 Td
(already)Tj
3.1124 0 Td
(slightly)Tj
3.0841 0 Td
(oriented)Tj
3.5887 0 Td
(even)Tj
/F11 1 Tf
2.0692 0 Td
[()12()]TJ
1.0148 0 Td
[()-13()15()3( )]TJ
/F6 1 Tf
1.8199 0 Td
(\(see)Tj
0.83 0.64 0.02 0 k
1.7688 0 Td
(S1)Tj
1.1678 0 Td
(Fig)Tj
0 g
(\).)Tj
2.0466 0 Td
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5.1421 0 Td
(of)Tj
1.0148 0 Td
(GHRH)Tj
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(neu-)Tj
-35.6539 -1.2983 Td
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2.0069 0 Td
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/F11 1 Tf
4.6884 0 Td
[()12()]TJ
1.0148 0 Td
[()-13()15()3( )]TJ
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1.8199 0 Td
(has)Tj
1.542 0 Td
(been)Tj
2.126 0 Td
(studied)Tj
3.1521 0 Td
(by)Tj
1.1792 0 Td
(an)Tj
/F11 1 Tf
1.2075 0 Td
[( )11()4()2()]TJ
2.0807 0 Td
[(\r)4( )4( )10()]TJ
/F6 1 Tf
2.0862 0 Td
(approach.)Tj
4.1783 0 Td
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(the)Tj
1.4683 0 Td
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(of)Tj
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/F11 1 Tf
-36.1018 -1.2982 Td
[( )11()4()2()]TJ
2.0806 0 Td
[(\r)4( )4( )10()]TJ
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(,)Tj
2.313 0 Td
(the)Tj
1.474 0 Td
(medio-basal)Tj
5.0967 0 Td
(hypothalamus)Tj
5.8733 0 Td
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1.5421 0 Td
(been)Tj
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(micro-dissected)Tj
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1.4683 0 Td
(brain)Tj
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(7)Tj
0.6973 0 Td
(days-)Tj
-34.8092 -1.2983 Td
(old)Tj
1.5023 0 Td
(male)Tj
2.143 0 Td
(pups)Tj
2.143 0 Td
(normally)Tj
3.8437 0 Td
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1.4627 0 Td
(\(n)Tj
1.1055 0 Td
(=)Tj
0.7994 0 Td
(3\).)Tj
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(nuclei)Tj
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(each)Tj
2.0295 0 Td
(hemisphere)Tj
4.8813 0 Td
(were)Tj
2.1203 0 Td
(open)Tj
2.2167 0 Td
(through)Tj
3.4469 0 Td
(the)Tj
-36.0111 -1.3039 Td
(3)Tj
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Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 204.7748 477.8645 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(rd)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 213.6755 473.3858 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
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(ventricle)Tj
3.6793 0 Td
(while)Tj
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(median)Tj
3.2428 0 Td
(eminence)Tj
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(\(see)Tj
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0.83 0.64 0.02 0 k
1.0318 0 Td
(S1)Tj
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0 g
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(for)Tj
1.389 0 Td
(protocol)Tj
-32.2126 -1.2982 Td
(schema\).)Tj
3.7756 0 Td
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/F11 1 Tf
2.5625 0 Td
[( )11()4()2()]TJ
2.0806 0 Td
[(\r)4( )4( )10()]TJ
/F6 1 Tf
2.4208 0 Td
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2.1259 0 Td
(fixed)Tj
2.1884 0 Td
(in)Tj
1.0375 0 Td
(PFA)Tj
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(4%,)Tj
1.6781 0 Td
(20)Tj
1.1735 0 Td
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1.8538 0 Td
(room)Tj
2.4265 0 Td
(temperature)Tj
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1.0261 0 Td
(be)Tj
1.1509 0 Td
(sub-)Tj
-35.359 -1.2983 Td
(jected)Tj
2.5737 0 Td
(to)Tj
1.0261 0 Td
(an)Tj
1.2019 0 Td
(immunohistochemistry)Tj
9.6151 0 Td
(against)Tj
3.0274 0 Td
(GFP)Tj
2.0239 0 Td
(and)Tj
1.7291 0 Td
(neurofilament)Tj
5.9244 0 Td
(\(NF\))Tj
2.1656 0 Td
(\(see)Tj
1.7688 0 Td
(details)Tj
2.778 0 Td
(above\),)Tj
-33.834 -1.3039 Td
(and)Tj
1.729 0 Td
(counterstained)Tj
6.1795 0 Td
(with)Tj
1.9955 0 Td
(DAPI.)Tj
2.7666 0 Td
(This)Tj
1.99 0 Td
(approach)Tj
3.9514 0 Td
(allows)Tj
2.6986 0 Td
(the)Tj
1.4683 0 Td
(observation)Tj
4.8983 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(start)Tj
1.9842 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(axon,)Tj
-34.6277 -1.2983 Td
(giving)Tj
2.6871 0 Td
(an)Tj
1.2019 0 Td
(idea)Tj
1.8708 0 Td
(of)Tj
1.0148 0 Td
(neurons)Tj
3.5093 0 Td
(orientation.)Tj
4.9152 0 Td
(Rostral)Tj
3.0614 0 Td
(direction)Tj
3.8551 0 Td
(was)Tj
1.6951 0 Td
(considered)Tj
4.6035 0 Td
(as)Tj
1.0148 0 Td
(0,)Tj
1.3096 0 Td
(dorsal)Tj
2.6702 0 Td
(direction)Tj
-33.4088 -1.2982 Td
(as)Tj
1.0148 0 Td
(90,)Tj
1.7857 0 Td
(caudal)Tj
2.8176 0 Td
(direction)Tj
3.8494 0 Td
(as)Tj
1.0148 0 Td
(180)Tj
2.0409 0 Td
(and)Tj
1.7292 0 Td
(ventral)Tj
2.999 0 Td
(direction)Tj
3.8551 0 Td
(as)Tj
1.0148 0 Td
(270.)Tj
2.262 0 Td
(This)Tj
1.9899 0 Td
(experiment)Tj
4.7735 0 Td
(indicates)Tj
3.7758 0 Td
(that)Tj
-34.9225 -1.3039 Td
(GHRH)Tj
3.0896 0 Td
(neurons)Tj
3.5093 0 Td
(are)Tj
1.4456 0 Td
(mainly)Tj
2.9934 0 Td
(dorsally)Tj
3.3675 0 Td
(oriented)Tj
3.5887 0 Td
(but)Tj
1.5534 0 Td
(equally)Tj
3.0557 0 Td
(go)Tj
1.1962 0 Td
(in)Tj
1.0318 0 Td
(rostral)Tj
2.8119 0 Td
(or)Tj
1.0942 0 Td
(caudal)Tj
2.8176 0 Td
(directions)Tj
4.2123 0 Td
(\(see)Tj
-35.7672 -1.2983 Td
(Panel)Tj
2.432 0 Td
(B)Tj
0.7993 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0318 0 Td
(S1)Tj
1.1736 0 Td
(Fig)Tj
0 g
(\).)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 355.9181 cm
BT
/F12 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Biochemical)Tj
5.3527 0 Td
(analysis)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 338.9102 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Insulin)Tj
3.0557 0 Td
(concentration)Tj
5.8223 0 Td
(in)Tj
1.0375 0 Td
(B27)Tj
1.7461 0 Td
(supplement)Tj
4.9039 0 Td
(was)Tj
1.7008 0 Td
(determined)Tj
4.8529 0 Td
(by)Tj
1.1792 0 Td
(ELISA)Tj
2.8289 0 Td
(\(Access)Tj
3.2372 0 Td
(Ultrasensitive)Tj
-30.3645 -1.2982 Td
(Insulin)Tj
3.0557 0 Td
(kit)Tj
1.2869 0 Td
(#33410)Tj
3.0727 0 Td
(on)Tj
1.2756 0 Td
(an)Tj
1.2019 0 Td
(Access)Tj
2.897 0 Td
(2)Tj
0.6916 0 Td
(analyzer,)Tj
3.7758 0 Td
(Beckman-Coulter\),)Tj
7.8972 0 Td
(according)Tj
4.1896 0 Td
(to)Tj
1.0205 0 Td
(manufacturer)Tj
-30.3645 -1.2983 Td
(instructions.)Tj
5.2213 0 Td
(The)Tj
1.7858 0 Td
(sensitivity)Tj
4.218 0 Td
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1.7008 0 Td
(0.03)Tj
/F13 1 Tf
[()]TJ
/F6 1 Tf
(U/mL,)Tj
5.0286 0 Td
(the)Tj
1.4683 0 Td
(intra-assay)Tj
4.5354 0 Td
(CV)Tj
1.5761 0 Td
(was)Tj
1.7008 0 Td
(5.24.2%)Tj
3.8494 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.4683 0 Td
(inter-)Tj
-34.2819 -1.3039 Td
(assay)Tj
2.262 0 Td
(CV)Tj
1.5817 0 Td
(was)Tj
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0 Tc
1.6951 0 Td
(<)Tj
/F6 1 Tf
-0.004 Tc
(10%.)Tj
ET
Q
q
1 j
1 J
0 w
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BT
/F12 1 Tf
1 TL
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(Statistical)Tj
4.3228 0 Td
(analysis)Tj
ET
Q
q
1 j
1 J
0 w
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BT
/F6 1 Tf
1 TL
-0.01 Tc
0 0 Td
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1.3776 0 Td
(data)Tj
1.8878 0 Td
(are)Tj
1.4344 0 Td
(presented)Tj
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(the)Tj
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[()]TJ
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0.7824 0 Td
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3.9572 0 Td
(analyses)Tj
3.4356 0 Td
(were)Tj
2.0976 0 Td
(performed)Tj
4.4163 0 Td
(with)Tj
1.9729 0 Td
(the)Tj
1.4514 0 Td
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-34.1119 -1.3039 Td
(Pad)Tj
1.7234 0 Td
(Prism)Tj
2.5682 0 Td
(5)Tj
0.686 0 Td
(software.)Tj
3.7587 0 Td
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2.2677 0 Td
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2.8516 0 Td
(differences)Tj
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(between)Tj
3.4866 0 Td
(normally-fed)Tj
5.3688 0 Td
(and)Tj
1.7121 0 Td
(underfed)Tj
3.8098 0 Td
(mice)Tj
2.1316 0 Td
(were)Tj
-34.8602 -1.2982 Td
(analyzed)Tj
3.651 0 Td
(by)Tj
1.1735 0 Td
(a)Tj
0.6463 0 Td
(t-test.)Tj
2.4321 0 Td
(Results)Tj
3.016 0 Td
(for)Tj
1.372 0 Td
(explant)Tj
3.1124 0 Td
(cultures)Tj
3.3505 0 Td
(were)Tj
2.0977 0 Td
(analyzed)Tj
3.651 0 Td
(by)Tj
1.1735 0 Td
(two-way)Tj
3.5886 0 Td
(ANOVA)Tj
3.7361 0 Td
(with)Tj
1.9729 0 Td
(a)Tj
0.6463 0 Td
(Bon-)Tj
-35.6199 -1.2983 Td
(ferroni)Tj
2.9536 0 Td
(correction)Tj
4.303 0 Td
(for)Tj
1.3663 0 Td
(multiple)Tj
3.5206 0 Td
(comparisons.)Tj
5.4878 0 Td
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1.7632 0 Td
(precise)Tj
2.965 0 Td
(molar)Tj
2.5682 0 Td
(concentrations-resp)Tj
7.8746 0 Td
(onse)Tj
2.0352 0 Td
(effect)Tj
-34.8375 -1.2983 Td
(within)Tj
2.7779 0 Td
(each)Tj
2.0012 0 Td
(group)Tj
2.5795 0 Td
(was)Tj
1.6838 0 Td
(further)Tj
2.982 0 Td
(analyzed)Tj
3.6567 0 Td
(by)Tj
1.1679 0 Td
(one-way)Tj
3.5829 0 Td
(ANOVA)Tj
3.7361 0 Td
(with)Tj
1.9729 0 Td
(a)Tj
0.6463 0 Td
(Newman-Keuls)Tj
6.3779 0 Td
(multiple)Tj
-33.1651 -1.3039 Td
(comparison)Tj
4.9152 0 Td
(test.)Tj
1.7915 0 Td
(Statistically)Tj
4.6488 0 Td
(non-significant)Tj
6.2475 0 Td
(results)Tj
2.7666 0 Td
(are)Tj
1.4286 0 Td
(abbreviated)Tj
4.8019 0 Td
(NS)Tj
2.1883 0 Td
(in)Tj
1.0262 0 Td
(the)Tj
1.4456 0 Td
(text.)Tj
1.8992 0 Td
(Statistically)Tj
-33.1594 -1.2982 Td
(significant)Tj
4.3199 0 Td
(results)Tj
2.7666 0 Td
(are)Tj
1.4343 0 Td
(marked)Tj
3.2542 0 Td
(with)Tj
1.9729 0 Td
(asterisks,)Tj
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Q
q
1 j
1 J
0 w
6.9998 0 0 6.9998 375.0803 182.0976 cm
BT
/F15 1 Tf
1 TL
0 0 Td
()Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 381.3165 178.4692 cm
BT
/F11 1 Tf
1 TL
-0.01 Tc
0 0 Td
[()]TJ
/F14 1 Tf
0 Tc
0.6859 0 Td
(<)Tj
/F6 1 Tf
-0.01 Tc
0.9921 0 Td
(0.05;)Tj
ET
Q
q
1 j
1 J
0 w
6.9998 0 0 6.9998 418.7905 182.0976 cm
BT
/F15 1 Tf
1 TL
0 0 Td
()Tj
0.575 0 Td
()Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 428.9952 178.4692 cm
BT
/F11 1 Tf
1 TL
-0.01 Tc
0 0 Td
[()]TJ
/F14 1 Tf
0 Tc
0.6916 0 Td
(<)Tj
/F6 1 Tf
-0.01 Tc
0.9921 0 Td
(0.01;)Tj
2.0636 0 Td
(and)Tj
ET
Q
q
1 j
1 J
0 w
6.9998 0 0 6.9998 483.5905 182.0976 cm
BT
/F15 1 Tf
1 TL
0 0 Td
()Tj
0.575 0 Td
()Tj
0.5669 0 Td
()Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 497.8204 178.4692 cm
BT
/F11 1 Tf
1 TL
-0.01 Tc
0 0 Td
[()]TJ
/F14 1 Tf
0 Tc
0.6859 0 Td
(<)Tj
/F6 1 Tf
-0.01 Tc
0.9921 0 Td
(0.001.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 151.9937 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Results)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 134.9858 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Increasing)Tj
4.3993 0 Td
(litter)Tj
2.126 0 Td
(size)Tj
1.6837 0 Td
(from)Tj
2.2054 0 Td
(six)Tj
1.3152 0 Td
(to)Tj
1.0262 0 Td
(10)Tj
1.1735 0 Td
(pups)Tj
2.143 0 Td
(per)Tj
1.5307 0 Td
(dam)Tj
2.0012 0 Td
(delayed)Tj
3.2542 0 Td
(body)Tj
2.2167 0 Td
(weight)Tj
2.8856 0 Td
(gain)Tj
1.9389 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.474 0 Td
(larger)Tj
2.5285 0 Td
(litters)Tj
-34.9339 -1.2982 Td
(relative)Tj
3.135 0 Td
(to)Tj
1.0262 0 Td
(those)Tj
2.3414 0 Td
(with)Tj
1.9956 0 Td
(six)Tj
1.3152 0 Td
(pups.)Tj
2.3641 0 Td
(Underfed)Tj
4.0705 0 Td
(pups)Tj
2.143 0 Td
(weighed)Tj
3.5376 0 Td
(3.51)Tj
/F13 1 Tf
1.8709 0 Td
[()]TJ
/F6 1 Tf
0.788 0 Td
(0.07)Tj
1.8765 0 Td
(g)Tj
0.686 0 Td
(at)Tj
0.9525 0 Td
(seven)Tj
2.4264 0 Td
(days)Tj
2.0012 0 Td
(of)Tj
1.0148 0 Td
(age)Tj
1.5421 0 Td
(vs)Tj
-35.087 -1.2983 Td
(4.13)Tj
/F13 1 Tf
1.8708 0 Td
[()]TJ
/F6 1 Tf
0.788 0 Td
(0.06)Tj
1.8766 0 Td
(g)Tj
0.6803 0 Td
(for)Tj
1.3889 0 Td
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