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Histone demethylase UTX mediates removal of repressive trimethylation of histone H3 lysine 27 (H3K27me3) to establish a mechanistic switch to activate large sets of genes. Mutation of Utx has recently been shown to be associated with Kabuki syndrome, a rare congenital anomaly syndrome with dementia. However, its biological function in the brain is largely unknown. Here, we observe that deletion of Utx results in increased anxiety-like behaviors and impaired spatial learning and memory in mice. Loss of Utx in the hippocampus leads to reduced long-term potentiation and amplitude of miniature excitatory postsynaptic current, aberrant dendrite development and defective synapse formation. Transcriptional profiling reveals that Utx regulates a subset of genes that are involved in the regulation of dendritic morphology, synaptic transmission, and cognition. Specifically, Utx deletion disrupts expression of neurotransmitter 5-hydroxytryptamine receptor 5B (Htr5b). Restoration of Htr5b expression in newborn hippocampal neurons rescues the defects of neuronal morphology by Utx ablation. Therefore, we provide evidence that Utx plays a critical role in modulating synaptic transmission and cognitive behaviors. Utx cKO mouse models like ours provide a valuable means to study the underlying mechanisms of the etiology of Kabuki syndrome.

BackgroundSuicide is the leading cause of death among 15–34 year olds in China, but no national data are available on the suicide and suicide attempts rates of college students, a sub-group of youth with 23 million. Several studies have reported the prevalence of suicide attempts among college students, however, no meta-analysis pooling the prevalence of suicide attempts is found.Objective and MethodsThis study aims to estimate the pooled prevalence of suicide attempts among college students in China. The relevant studies up to August 2014 were systematically searched via electronic databases (PubMed-Medline, Embase, Chinese Wanfang database, Chinese National Knowledge Infrastructure and Chinese VIP database). We only selected original articles that either reported the prevalence of suicide attempts or sufficient data for calculating the prevalence.ResultsA total of 29 eligible studies, with 88,225 college students, were finally included. The maximum and minimum reported prevalences of suicide attempts among college students in China were 0.4% and 10.5%, respectively. The pooled prevalence of suicide attempts was 2.8% (95%CI: 2.3%–3.3%). Subgroup analyses showed that the pooled estimate of prevalence of life time suicide attempts was 2.7% (95%CI: 2.1%–3.3%), and 12-month suicide attempts was 2.9% (95%CI: 2.0%–3.8%). The prevalence for males was 2.4% (95%CI: 1.8%–3.0%), and for females was 2.7% (95%CI: 1.9%–3.7%). The prevalences among college students in grade 1 through 4 were 2.8% (95%CI: 1.7%–3.8%), 1.8% (95%CI: 1.2%–2.3%), 2.0% (95%CI: 0.8%–3.1%), and 2.9% (95%CI: 0.1%–6.7%), respectively. The prevalences among college students from rural and urban areas were 5.1% (95%CI: 2.8%–7.5%) and 3.7% (95%CI: 1.4%–5.9%), respectively.Conclusions2.8% prevalence of suicide attempts and more than 600,000 suicide attempters among college students indicate that suicide attempt among college students is an important public health problem in China. More attention should be paid to the current situation.

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Highlights d DRAK2 is markedly upregulated in the livers of both patients and mice with NAFLD/NASH d DRAK2 regulates RNA alternative splicing through SRPK1mediated SRSF6 phosphorylation d DRAK2 disturbs mitochondrial function in hepatic steatosis via RNA splicing machinery

In this study, we aim to determine the function of miR-124 on gastric cancer (GC) cells and the underlying mechanism that involves jaddeg1 (JAG1) and the Notch signaling pathway. GC tissues and adjacent tissues from 100 patients suffering from GC were selected. GC SGC-7901 and AGS cells were selected and grouped into control, mimic-NC, miR-124 mimic, inhibitor-NC, miR-124 inhibitor, and miR-124 inhibitor + si-JAG1 groups. RT-qPCR and a Western blotting assay were conducted to detect the expression of miR-124, JAG1, and Notch signaling pathway-related proteins (NICD, HES1, and HES5). MTS, wound-healing, transwell assay and flow cytometry were performed to detect cell proliferation, migration, invasion, cell cycle distribution, and apoptosis, respectively. Compared with adjacent tissues, a lower miR-124 expression and higher JAG1 expression were found in GC tissues. JAG1 is a direct target gene of miR-124. Compared with the control group, the expression of JAG1, NICD, HES1, and HES5, cell invasion, migration, and proliferation in the miR-124 mimic group were decreased, while the apoptosis rate was increased and cells were arrested at the G0/G1 phase. Compared with the miR-124 inhibitor group, the expression of JAG1, NICD, HES1, and HES5, cell invasion, migration, and proliferation in the miR-124 inhibitor + si-JAG1 group were decreased, while the apoptosis rate and cell ratio at the G0/G1 phase were increased. The demonstration that miR-124 inhibits GC cell growth supports the concept that miR-124 functions as a tumor suppressor by a mechanism that involves translational repression of the JAG1 and the inhibition of Notch signaling pathway.

As a therapeutic strategy for ischemic stroke, to restore or increase cerebral blood flow (CBF) is the most fundamental option. Laminar shear stress (LS), as an important force generated by CBF, mainly acts on brain microvascular endothelial cells (BMECs). In order to study whether LS was a protective factor in stroke, we investigated LS-intervented ischemic apoptosis of rat BMECs (rBMECs) through PE Annexin V/7-AAD, JC-1 and Hoechst 33258 staining to observe the membranous, mitochondrial and nuclear dysfunction. Real-time PCR and western blot were also used to test the gene and protein expressions of Tie-2, Bcl-2 and Akt, which were respectively related to maintain membranous, mitochondrial and nuclear norm. The results showed that LS could be a helpful stimulus for ischemic rBMECs survival. Simultaneously, membranous, mitochondrial and nuclear regulation played an important role in this process.

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