Phosphorylation of STAT-3 in the hypothalamus.

<p>(A) Representative images for western blot experiement on total (t-) and phosphorylated (p-) STAT-3. n = 9 for Ctrl group, n = 10 for HF group, and n = 11 for HP group, respectively. (B) Measurement of the p-STAT-3/total-STAT-3 ratio in saline injected rats and in leptin injected rats. For clearly comparison, all the p-STAT-3/t-STAT-3 ratios were normalized to the mean value that obtained from the Ctrl group. (C) The sensitivity toward leptin assessed by a significant elevation of the mean p-STAT-3/t-STAT-3 in leptin-injected compared to saline-injected rats. **p<0.001, compared as indicated.</p

Feeding behaviors and locomotor activity of offspring in or after the VDSRL task.

<p>(A) Latencies to collect the food during acquisition (Acq), retention of spatial discrimination (Ret-D), reversal phase (Rev1-3), and retention of reversal 1–3 (Ret-R1-3) in the VDSRL task. A series of three reversals (reversal 1–3: Rev1–3) were performed. Between successive reversals, animals were given a session to test retention of the previous reversal phase (Ret-R1–3). *p<0.05; **p<0.001. (B) Food comsuption during a 30-min test session after the VDSRL task (n = 10 in each group). (C) Number of beam breaks during a 60-min test session after the VDSRL task (n = 9 for Ctrl group, n = 10 for HF group and n = 11 for HP group.).</p

Reversal learning and set shifting in the ASST task.

<p>(A) Schematic representation of the behavioural training and testing protocol. The rewarded and unrewarded bowl is indicated with and without the “+”, respectively. The order of the discriminations and the exemplar pairings were always the same, but the pairs of exemplars were counterbalanced between groups. (B) Trials to reach criterion (six successive correct trials) for each phase of the ASST paradigm. (C) Errors made in each phase of the ASST paradigm. *p<0.05; **p<0.001.</p

Reversal learning in the VDSRL task.

<p>(A) Schematic representation of the behavioral training and testing protocol. The rewarded and unrewarded lever is indicated by the “+” and “−”, respectively. The rewarded lever was counterbalanced across rats. (B–C) Total trials (B) and errors (C) to criterion during acquisition of spatial discrimination (Acq), retention of discrimination (Ret-D) as well as during the reversal phases (reversal 1–3: Rev1–3; retention of reversal 1–3: Ret-R1-3). (D) Perseverative and learning errors accumulated across reversals (perseverative errors accumulated: P-Accum;learning errors accumulated:L-Acuum) and during 3 reversals (perseverative errors of reversal 1–3: P-Ret1-3; learning errors of reversal 1–3: L-Ret1-3) were shown. A series of three reversals were performed by male offspring born to dams fed with the Ctrl diet, HF diet, and HP diet. Between successive reversals, animals were given a session to test retention of the previous reversal phase (Ret-R1-3). (E) Mean probabilities of rats shifting their responding to the other stimulus after making either an incorrect choice (and therefore not receiving reward) or a correct choice and receiving reward. n = 9 for Ctrl group, n = 10 for HF group and n = 11 for HP group. *p<0.05; **p<0.001.</p

Effect of maternal diet on dam, baby and adult offspring.

<p>(A) Mean body weights of dam fed with the control diet (Ctrl), high fatty (HF) or highly palatable diet (HP) (n = 10 in each group). Dam were weighted 6 weeks before mating, at the time of mating and after the delivery of their offspring. (B–C) Mean body weight of offspring born to dams fed with the Ctrl diet (n = 9), HF diet (n = 10), and HP diet (n = 11), measured at birth (day 1), and in adulthood (10 weeks after birth). (D–F) Physiological parameters of offspring born to dams fed with the Ctrl diet (n = 9), HF diet (n = 10), and HP diet (n = 11). *p<0.05; **p<0.001.</p

[125I]RTI-55 binding to striatal dopamine transporter (DAT).

<p>(A) Representative autoradiographs for each group for DAT binding in the striatum of Wistar rats fed with the control diet (Ctrl), high fatty (HF) or highly palatable (HP) diet. Several regions were observed: caudate-putamen (CP), the dorsal (dCP) and ventral (vCP) subdivisions of the CP, and the nucleus accumben (NAc). (B) Values for DAT binding in the striatum of Wistar rats fed with the control diet (Ctrl), high fatty (HF) or highly palatable (HP) diet (n = 9 for Ctrl group, n = 10 for HF group and n = 11 for HP group). Values were generated by quantitative autoradiography of ligand binding. **p<0.001, compared as indicated.</p

In vitro splicing assay of the c.1439+1G>C mutation.

<p>(A) The splice region (c.1439+1, intron 9) of <i>SCNN1A</i> gene was amplified and products were ligated into the pcDNA3.1/Myc-His B vector. (B) RT-PCR of HEK293 cells transfected with either wild-type or mutant <i>SCNN1A.</i> Minigenes showed that the mutation c.1439+1G>C was sufficient to produce a longer band. (C) Lane 1: Empty pcDNA3.1 vector; Lane 2: wild-type <i>SCNN1A</i> (256 bp); Lane 3: c.1439+1G>C mutant (361 bp); Lanes 4, 5, and 6: <i>GAPDH</i> used as control (245 bp).</p

Three novel mutations were identified in the <i>SCNN1A</i> gene.

<p>(A) Sequences showing a compound heterozygous mutations (c.1311delG in exon 8 c.1439+1G>C in intron 9) in PHA1 patient of case 1. (B) Sequences showing a homozygous mutation (c.814_815insG in exon 4) in PHA1 patient of case 2.</p

Additional file 1: of De novo mutations in ARID1B associated with both syndromic and non-syndromic short stature

Supplementary data 1. (DOCX 30 kb

Additional file 1: Table S1. of Copy number variations in 119 Chinese children with idiopathic short stature identified by the custom genome-wide microarray

List of 1469 height-associated candidate genes analyzed by genome-wide association studies. Table S2. Summary of type III and IV CNVs. Table S3. Primers of qPCR. Figure S1. Screenshots of chromosome microarray and qPCR. (DOC 7216 kb