Exercise Prevents Memory Impairment Induced by Arsenic Exposure in Mice: Implication of Hippocampal BDNF and CREB

High concentrations of arsenic, which can be occasionally found in drinking water, have been recognized as a global health problem. Exposure to arsenic can disrupt spatial memory; however, the underlying mechanism remains unclear. In the present study, we tested whether exercise could interfere with the effect of arsenic exposure on the long-term memory (LTM) of object recognition in mice. Arsenic (0, 1, 3, and 10 mg/ kg, i.g.) was administered daily for 12 weeks. We found that arsenic at dosages of 1, 3, and 10 mg/kg decreased body weight and increased the arsenic content in the brain. The object recognition LTM (tested 24 h after training) was disrupted by 3 mg/ kg and 10 mg/ kg, but not 1 mg/ kg arsenic exposure. Swimming exercise also prevented LTM impairment induced by 3 mg/ kg, but not with 10 mg/ kg, of arsenic exposure. The expression of brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP-response element binding protein (pCREB) in the CA1 and dentate gyrus areas (DG) of the dorsal hippocampus were decreased by 3 mg/ kg and 10 mg/ kg, but not by 1 mg/ kg, of arsenic exposure. The decrease in BDNF and pCREB in the CA1 and DG induced by 3 mg/ kg, but not 10 mg/ kg, of arsenic exposure were prevented by swimming exercise. Arsenic exposure did not affect the total CREB expression in the CA1 or DG. Taken together, these results indicated that swimming exercise prevented the impairment of object recognition LTM induced by arsenic exposure, which may be mediated by BDNF and CREB in the dorsal hippocampus.     

Impaired Frontal-Basal Ganglia Connectivity in Male Adolescents with Conduct Disorder

Alack of inhibition control has been found in subjects with conduct disorder (CD), but the underlying neuropathophysiology remains poorly understood. The current study investigated the different mechanism of inhibition control in adolescent-onset CD males (n = 29) and well-matched healthy controls (HCs) (n = 40) when performing a GoStop task by functional magnetic resonance images. Effective connectivity (EC) within the inhibition control network was analyzed using a stochastic dynamic causality model. We found that EC within the inhibition control network was significantly different in the CD group when compared to the HCs. Exploratory relationship analysis revealed significant negative associations between EC between the IFG and striatum and behavioral scale scores in the CD group. These results suggest for the first time that the failure of inhibition control in subjects with CD might be associated with aberrant connectivity of the frontal–basal ganglia pathways, especially between the IFG and striatum.     

Foley Catheter for Induction of Labor at Term: An Open-Label,Randomized Controlled Trial

Objective

This study aimed to determine the optimal Foley catheter balloon volume (30-mL vs. 80-mL) and the maximum time for cervical ripening (12 hours vs. 24 hours) to improve vaginal delivery rate within 24 hours of induction.

Methods

We conducted an open-label, randomized controlled trial in a teaching hospital in China. Women with a term singleton pregnancy, cephalic presentation, intact membrane and an unfavorable cervix (Bishop score <6) were randomly allocated, in 1:1:1:1 ratio, to receive either one of the four treatments: (1) 30-mL balloon for a maximum of 12 hours, (2) 30-mL balloon for a maximum of 24 hours, (3) 80-mL balloon for a maximum of 12 hours, and (4) 80-mL balloon for a maximum of 24 hours. The primary outcome was vaginal delivery within 24 hours. Secondary outcomes included cesarean section rate and maternal/neonatal morbidity. Data were analyzed on a per-protocol basis.

Results

Five hundred and four women were recruited and randomized (126 women in each group); nine women did not receive the assigned intervention. More women achieved vaginal delivery within 24 hours in 12-hour Foley catheter groups than in the 24-hour Foley catheter groups (30-mL/12 hours: 54.5%, 30-mL/24 hours: 33.1%, 80-mL/12 hours: 46.4%, 80-mL/24 hours: 24.0%, p < 0.001). Cesarean section rates and the incidence of chorioaminonitis were comparable among four groups. After adjustment for confounding factors, both ripening time and balloon size did not affect the proportion of women delivered vaginally within 24 hours of induction.

Conclusion

For women with an unfavorable cervix at term, induction of labor with a Foley catheter is safe and effective. Higher balloon volume (80-mL vs. 30-mL) and longer ripening time (24 hours vs. 12 hours) would not shorten induction to delivery interval or reduce cesarean section rate.

Trial Registration

Chinese Clinical trial registry (ChiCTR-TRC-13003044)     

Hyperglycemic Stress Impairs the Stemness Capacity of Kidney Stem Cells in Rats

The incidence of acute kidney injury in patients with diabetes is significantly higher than that of patients without diabetes, and may be associated with the poor stemness capacity of kidney stem cells (KSCs) and limited recovery of injured renal tubules. To investigate the effects of hyperglycemic stress on KSC stemness, KSCs were isolated from the rat renal papilla and analyzed for their self-renewal and differentiation abilities. Our results showed that isolated KSCs expressed the mesenchymal stem cell markers N-cadherin, Nestin, CD133, CD29, CD90, and CD73. Moreover, KSCs co-cultured with hypoxia-injured renal tubular epithelial cell (RTECs) induced the expression of the mature epithelial cell marker CK18, suggesting that the KSCs could differentiate into RTECs in vitro. However, KSC proliferation, differentiation ability and tolerance to hypoxia were decreased in high-glucose cultures. Taken together, these results suggest the high-glucose microenvironment can damage the reparative ability of KSCs. It may result in a decreased of recovery capability of renal tubules from injury.     

Genome-Wide Analysis of Microsatellite Markers Based on Sequenced Database in Chinese Spring Wheat (Triticum aestivum L.)

Microsatellites or simple sequence repeats (SSRs) are distributed across both prokaryotic and eukaryotic genomes and have been widely used for genetic studies and molecular marker-assisted breeding in crops. Though an ordered draft sequence of hexaploid bread wheat have been announced, the researches about systemic analysis of SSRs for wheat still have not been reported so far. In the present study, we identified 364,347 SSRs from among 10,603,760 sequences of the Chinese spring wheat (CSW) genome, which were present at a density of 36.68 SSR/Mb. In total, we detected 488 types of motifs ranging from di- to hexanucleotides, among which dinucleotide repeats dominated, accounting for approximately 42.52% of the genome. The density of tri- to hexanucleotide repeats was 24.97%, 4.62%, 3.25% and 24.65%, respectively. AG/CT, AAG/CTT, AGAT/ATCT, AAAAG/CTTTT and AAAATT/AATTTT were the most frequent repeats among di- to hexanucleotide repeats. Among the 21 chromosomes of CSW, the density of repeats was highest on chromosome 2D and lowest on chromosome 3A. The proportions of di-, tri-, tetra-, penta- and hexanucleotide repeats on each chromosome, and even on the whole genome, were almost identical. In addition, 295,267 SSR markers were successfully developed from the 21 chromosomes of CSW, which cover the entire genome at a density of 29.73 per Mb. All of the SSR markers were validated by reverse electronic-Polymerase Chain Reaction (re-PCR); 70,564 (23.9%) were found to be monomorphic and 224,703 (76.1%) were found to be polymorphic. A total of 45 monomorphic markers were selected randomly for validation purposes; 24 (53.3%) amplified one locus, 8 (17.8%) amplified multiple identical loci, and 13 (28.9%) did not amplify any fragments from the genomic DNA of CSW. Then a dendrogram was generated based on the 24 monomorphic SSR markers among 20 wheat cultivars and three species of its diploid ancestors showing that monomorphic SSR markers represented a promising source to increase the number of genetic markers available for the wheat genome. The results of this study will be useful for investigating the genetic diversity and evolution among wheat and related species. At the same time, the results will facilitate comparative genomic studies and marker-assisted breeding (MAS) in plants.     

Valproate Inhibits Methamphetamine Induced Hyperactivity via Glycogen Synthase Kinase 3β Signaling in the Nucleus Accumbens Core

Valproate (VPA) has recently been shown to influence the behavioral effects of psycho-stimulants. Although glycogen synthase kinase 3β (GSK3β) signaling in the nucleus accumbens (NAc) plays a key role in mediating dopamine (DA)-dependent behaviors, there is less direct evidence that how VPA acts on the GSK3β signaling in the functionally distinct sub-regions of the NAc, the NAc core (NAcC) and the NAc shell (NAcSh), during psycho-stimulant-induced hyperactivity. In the present study, we applied locomotion test after acute methamphetamine (MA) (2 mg/kg) injection to identify the locomotor activity of rats received repeated VPA (300 mg/kg) pretreatment. We next measured phosphor-GSK3β at serine 9 and total GSK3β levels in NAcC and NAcSh respectively to determine the relationship between the effect of VPA on MA-induced hyperlocomotor and changes in GSK3β activity. We further investigated whether microinjection of VPA (300 μg/0.5 μl/side, once daily for 7 consecutive days) into NAcC or NAcSh could affect hyperactivity induced by MA. Our data indicated that repeated VPA treatment attenuated MA-induced hyperlocomotor, and the effect was associated with decreased levels of phosphorylated GSK3β at Ser 9 in the NAcC. Moreover, repeated bilateral intra-NAcC, but not intra-NAcSh VPA treatment, significantly attenuated MA-induced hyperactivity. Our results suggested that GSK3β activity in NAcC contributes to the inhibitory effects of VPA on MA-induced hyperactivity.     

Sense-overlapping lncRNA as a decoy of translational repressor protein for dimorphic gene expression

Long noncoding RNAs (lncRNAs) are vastly transcribed and extensively studied but lncRNAs overlapping with the sense orientation of mRNA have been poorly studied. We analyzed the lncRNA DAPALR overlapping with the 5´ UTR of the Doublesex1 (Dsx1), the male determining gene in Daphnia magna. By affinity purification, we identified an RNA binding protein, Shep as a DAPALR binding protein. Shep also binds to Dsx1 5´ UTR by recognizing the overlapping sequence and suppresses translation of the mRNA. In vitro and in vivo analyses indicated that DAPALR increased Dsx1 translation efficiency by sequestration of Shep. This regulation was impaired when the Shep binding site in DAPALR was deleted. These results suggest that Shep suppresses the unintentional translation of Dsx1 by setting a threshold; and when the sense lncRNA DAPALR is expressed, DAPALR cancels the suppression caused by Shep. This mechanism may be important to show dimorphic gene expressions such as sex determination and it may account for the binary expression in various developmental processes.     

Inactivation of the Sas2 histone acetyltransferase delays senescence driven by telomere dysfunction

Changes in telomere chromatin have been linked to cellular senescence, but the underlying mechanisms and impact on lifespan are unclear. We found that inactivation of the Sas2 histone acetyltransferase delays senescence in Saccharomyces cerevisiae telomerase (tlc1) mutants through a homologous recombination‐dependent mechanism. Sas2 acetylates histone H4 lysine 16 (H4K16), and telomere shortening in tlc1 mutants was accompanied by a selective and Sas2‐dependent increase in subtelomeric H4K16 acetylation. Further, mutation of H4 lysine 16 to arginine, which mimics constitutively deacetylated H4K16, delayed senescence and was epistatic to sas2 deletion, indicating that deacetylated H4K16 mediates the delay caused by sas2 deletion. Sas2 normally prevents the Sir2/3/4 heterochromatin complex from leaving the telomere and spreading to internal euchromatic loci. Senescence was delayed by sir3 deletion, but not sir2 deletion, indicating that senescence delay is mediated by release of Sir3 specifically from the telomere repeats. In contrast, sir4 deletion sped senescence and blocked the delay conferred by sas2 or sir3 deletion. We thus show that manipulation of telomere chromatin modulates senescence caused by telomere shortening.