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Mutations in AT‐rich interactive domain‐containing protein 1A (ARID1A) cause Coffin‐Siris syndrome (CSS), a rare genetic disorder that results in mild to severe intellectual disabilities. However, the biological role of ARID1A in the brain remains unclear. In this study, we report that the haploinsufficiency of ARID1A in excitatory neurons causes cognitive impairment and defects in hippocampal synaptic transmission and dendritic morphology in mice. Similarly, human embryonic stem cell‐derived excitatory neurons with deleted ARID1A exhibit fewer dendritic branches and spines, and abnormal electrophysiological activity. Importantly, supplementation of acetate, an epigenetic metabolite, can ameliorate the morphological and electrophysiological deficits observed in mice with Arid1a haploinsufficiency, as well as in ARID1A ‐null human excitatory neurons. Mechanistically, transcriptomic and ChIP‐seq analyses demonstrate that acetate supplementation can increase the levels of H3K27 acetylation at the promoters of key regulatory genes associated with neural development and synaptic transmission. Collectively, these findings support the essential roles of ARID1A in the excitatory neurons and cognition and suggest that acetate supplementation could be a potential therapeutic intervention for CSS. Synopsis Mutations in ARID1A cause Coffin‐Siris syndrome (CSS), a rare genetic disorder with severe neurodevelopmental deficits. This study investigates the genetic basis of the pathophysiological role of ARID1A in CSS and proposes a potential therapeutic intervention. Arid1a haploinsufficiency in mouse excitatory neurons leads to spatial memory defects. ARID1A is required for neuron dendritic and synapse growth in mice and humans. Acetate supplementation rescues the neuronal deficits by increasing H3K27 acetylation levels at the promoters of neuronal genes in both Arid1a haploinsufficient mice and ARID1A KO hESC‐derived neurons. Graphical Abstract Mutations in ARID1A cause Coffin‐Siris syndrome (CSS), a rare genetic disorder with severe neurodevelopmental deficits. This study investigates the genetic basis of the pathophysiological role of ARID1A in CSS and proposes a potential therapeutic intervention.

Genetic analyses have linked microRNA-137 (MIR137) to neuropsychiatric disorders, including schizophrenia and autism spectrum disorder. miR-137 plays important roles in neurogenesis and neuronal maturation, but the impact of miR-137 loss-of-function in vivo remains unclear. Here we show the complete loss of miR-137 in the mouse germline knockout or nervous system knockout (cKO) leads to postnatal lethality, while heterozygous germline knockout and cKO mice remain viable. Partial loss of miR-137 in heterozygous cKO mice results in dysregulated synaptic plasticity, repetitive behavior, and impaired learning and social behavior. Transcriptomic and proteomic analyses revealed that the miR-137 mRNA target, phosphodiesterase 10a (Pde10a), is elevated in heterozygous knockout mice. Treatment with the Pde10a inhibitor papaverine or knockdown of Pde10a ameliorates the deficits observed in the heterozygous cKO mice. Collectively, our results suggest that MIR137 plays essential roles in postnatal neurodevelopment and that dysregulation of miR-137 potentially contributes to neuropsychiatric disorders in humans.

Neurons in the central nervous system (CNS) lose their intrinsic ability and fail to regenerate, but the underlying mechanisms are largely unknown. Polycomb group (PcG) proteins, which include PRC1 and PRC2 complexes function as gene repressors and are involved in many biological processes. Here we report that PRC1 components (polycomb chromobox (CBX) 2, 7, and 8) are novel regulators of axon growth and regeneration. Especially, knockdown of CBX7 in either embryonic cortical neurons or adult dorsal root ganglion (DRG) neurons enhances their axon growth ability. Two important transcription factors GATA4 and SOX11 are functional downstream targets of CBX7 in controlling axon regeneration. Moreover, knockdown of GATA4 or SOX11 in cultured DRG neurons inhibits axon regeneration response from CBX7 downregulation in DRG neurons. These findings suggest that targeting CBX signaling pathway may be a novel approach for promoting the intrinsic regenerative capacity of damaged CNS neurons.

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 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 results in increased anxiety-like behaviors and impaired spatial learning and memory in mice. Loss of 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 regulates a subset of genes that are involved in the regulation of dendritic morphology, synaptic transmission, and cognition. Specifically, deletion disrupts expression of neurotransmitter 5-hydroxytryptamine receptor 5B ( ). Restoration of expression in newborn hippocampal neurons rescues the defects of neuronal morphology by ablation. Therefore, we provide evidence that plays a critical role in modulating synaptic transmission and cognitive behaviors. cKO mouse models like ours provide a valuable means to study the underlying mechanisms of the etiology of Kabuki syndrome.

ARID1A, an SWI/SNF chromatin-remodeling gene, is commonly mutated in cancer and hypothesized to be a tumor suppressor. Recently, loss-of-function of ARID1A gene has been shown to cause intellectual disability. Here we generate Arid1a conditional knockout mice and investigate Arid1a function in the hippocampus. Disruption of Arid1a in mouse forebrain significantly decreases neural stem/progenitor cells (NSPCs) proliferation and differentiation to neurons within the dentate gyrus (DG), increasing perinatal and postnatal apoptosis, leading to reduced hippocampus size. Moreover, we perform single-cell RNA sequencing (scRNA-seq) to investigate cellular heterogeneity and reveal that Arid1a is necessary for the maintenance of the DG progenitor pool and survival of post-mitotic neurons. Transcriptome and ChIP-seq analysis data demonstrate that ARID1A specifically regulates Prox1 by altering the levels of histone modifications. Overexpression of downstream target Prox1 can rescue proliferation and differentiation defects of NSPCs caused by Arid1a deletion. Overall, our results demonstrate a critical role for Arid1a in the development of the hippocampus and may also provide insight into the genetic basis of intellectual disabilities such as Coffin–Siris syndrome, which is caused by germ-line mutations or microduplication of Arid1a.

Most small homotherms display low leptin level in response to chronic cold exposure. Cold-induced hypoleptinemia was proved to induce hyperphagia. However, it is still not clear whether hypoleptinemia regulates energy expenditure in cold condition. We try to answer this question in chronic cold-acclimated rats. Results showed that 5-day intracerebroventricular(ICV) infusion of leptin (5 μg/day) had no effects on basal and adaptive thermogenesis and uncoupling protein 1 expression. Physical activity was increased by leptin treatment. We further determined whether ghrelin could reverse the increasing effect of leptin on physical activity. Coadministration of ghrelin (1.2 μg/day) completely reversed the effect of leptin on physical activity. Collectively, this study indicated the regulation of leptin on energy expenditure during cold acclimation may be mainly mediated by physical activity but not by thermogenesis. Our study outlined behavioral role of leptin during the adaptation to cold, which adds some new knowledge to promote our understanding of cold-induced metabolic adaptation.

Chronic cold exposure stimulates thermogenesis in brown adipose tissue, resulting in fat mobilization and compensatory hyperphagia. Mostly, these physiological events are accompanied by a remarkable reduction in serum leptin levels. However, the physiological roles of hypoleptinemia in cold adaptation are still not fully clear. We hypothesized that leptin is the keystone of the regulatory systems linking energy balance to cold adaptation. Leptin treatment (5μg/day) decreased food intake, body weight, serum ghrelin levels and hypothalamic melanin-concentrating hormone (MCH) gene expression. Food restriction in the pair-fed group mimicked most of the effects induced by leptin treatment. Central coadministration of ghrelin (1.2 μg/day) partially reversed the effect of leptin on hypothalamic MCH mRNA, but it did not block the reducing effects of leptin on food intake, body weight and serum ghrelin levels. In addition, hypothalamic pro-opiomelanocortin gene expression increased significantly in response to the coadministration of leptin and ghrelin. Collectively, we conclude that the regulatory effects of leptin on energy balance in cold-acclimated rats are dependent on feeding, which may involve the reduction of hypothalamic MCH gene expression. We found no evidence for ghrelin involvement in the regulation of leptin on food intake and body weight during cold acclimation.

This paper is devoted to the formulation of new analytical solutions and exploration of physical interpretation for yarn twist propagation in staple yarn spinning. The wave equation governing the twist propagation is solved by using the complex exponential representation of the rotating angle of a yarn cross-section. Provided that the influence of twist blockage is allowed to be ignorable, the solution of the wave equation can be formulated by the superposition of two counterpropagating waves: one twist wave propagating in the positive s direction with a velocity of v 0 + v and the other one traveling along with the negative s direction with a velocity of v 0 — v. The Doppler effect could be found in the twist propagation process. Further, the proposed method is applied in a false twisting process and a modified low-torque ring spinning frame. Finally, the corresponding twist distribution and the torques of twisting devices are derived.

To the Editor： Chest abdominal wall defects are usually the result of tumor resection, infection, radiation, or trauma. Chest abdominal wall neoplasms are classified as primary, locally invading, or metastatic. The most common primary malignancies in the chest wall are the soft tissue and bone sarcomas.In most patients, the operations of the following defect locations are at the risk of herniation or paradoxical breathing postsurgery： total or subtotal sternal resection including several ribs bilaterally or high lateral resection （more than 3-4 ribs）. In these cases, patients are prone to develop respiratory problems, if the stability is not adequate as early＇ as during the immediate postoperative period .