Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration

RNA exosomes are multi-subunit complexes conserved throughout evolution and are emerging as the major cellular machinery for processing, surveillance and turnover of a diverse spectrum of coding and noncoding RNA substrates essential for viability. By exome sequencing, we discovered recessive mutations in EXOSC3 (encoding exosome component 3) in four siblings with infantile spinal motor neuron disease, cerebellar atrophy, progressive microcephaly and profound global developmental delay, consistent with pontocerebellar hypoplasia type 1 (PCH1; MIM 607596). We identified mutations in EXOSC3 in an additional 8 of 12 families with PCH1. Morpholino knockdown of exosc3 in zebrafish embryos caused embryonic maldevelopment, resulting in small brain size and poor motility, reminiscent of human clinical features, and these defects were largely rescued by co-injection with wild-type but not mutant exosc3 mRNA. These findings represent the first example of an RNA exosome core component gene that is responsible for a human disease and further implicate dysregulation of RNA processing in cerebellar and spinal motor neuron maldevelopment and degeneration.     

扫描法固体低温比热测量系统及其分析

介绍了扫描法测量固体低温比热的实验系统及其出现的问题和解决方法.用此实验系统对纯度为99.7%电介铜的比热测量结果表明,它与美国国家标准参考数据相比,在80K—260K范围内偏差小于7%.     

Phase transitions in the assembly of multivalent signalling proteins

Cells are organized on length scales ranging from ?ngstr?m to micrometres. However, the mechanisms by which ?ngstr?m-scale molecular properties are translated to micrometre-scale macroscopic properties are not well understood. Here we show that interactions between diverse synthetic, multivalent macromolecules (including multi-domain proteins and RNA) produce sharp liquid-liquid-demixing phase separations, generating micrometre-sized liquid droplets in aqueous solution. This macroscopic transition corresponds to a molecular transition between small complexes and large, dynamic supramolecular polymers. The concentrations needed for phase transition are directly related to the valency of the interacting species. In the case of the actin-regulatory protein called neural Wiskott-Aldrich syndrome protein (N-WASP) interacting with its established biological partners NCK and phosphorylated nephrin, the phase transition corresponds to a sharp increase in activity towards an actin nucleation factor, the Arp2/3 complex. The transition is governed by the degree of phosphorylation of nephrin, explaining how this property of the system can be controlled to regulatory effect by kinases. The widespread occurrence of multivalent systems suggests that phase transitions may be used to spatially organize and biochemically regulate information throughout biology.     

充液航天器姿态稳定分析的Casimir方法

充液航天器中的液体燃料晃动将可能导致航天器姿态不稳定性现象的发生．本文采用哈密顿动力学方法研究了半充液航天器姿态运动的稳定性问题．首先将晃动液体等效为弹簧质量块力学模型,建立了液体晃动与航天器姿态多体耦合动力学系统的哈密顿方程,并进一步推导了与耦合动力学系统相关的Casimir函数;借助于Casimir函数并采用李亚普诺夫稳定性理论推导出耦合系统的稳定性和非稳定性条件,最后给出了数值仿真结果及相关结论．     

高压对NiCr—NiCu热电偶的温度影响

在室温和液氮温度下,压强在0—20kbar(1bar=10~5Pa)变化范围内,测量了NiCr-NiCu热电偶的压力热电势随压强的变化关系.测量结果表明:在室温和液氮温度下,压力热电势均随压强增高,在0.1K的温度测量精度、0—20kbar的压强范围内,压力热电势不会对温度测量带来影响.     

Watershed—based Image Segmentation with Region Merging and Edge Detection

The clustering technique is used to examine each pixel in the image which assigned to one of the clusters depending on the minimum distance to obhtain primary classified image into different intensity regions.A watershed transformation technique is then employes.This includes:gradient of the classified image,dividing the image into markers,checking the Marker Image to see if it has zero points(watershed lines).The watershed lines are then deleted in the Marker Image created by watershed algorithm.A Region Adjacency Graph (RAG)and Region Adjacency Boundary(RAB)are created between two regions from Marker Image.Finally region merging is done according to region average intensity and two edge strengths (T1,T2).The approach of the authors is tested on remote sensing and brain MR medical images.The final segmentation result is one closed boundary per actual region in the image.     

Interaction of DISC1 with the PTB domain of Tensin2

The gene for Disrupted-in-Schizophrenia 1 (DISC1) is amongst the most significant risk genes for schizophrenia. The DISC1 protein is an intracellular scaffolding molecule thought to act an important hub for protein interactions involved in signalling for neural cell differentiation and function. Tensin2 is an intracellular actin-binding protein that bridges the intracellular portion of transmembrane receptors to the cytoskeleton, thereby regulating signalling for cell shape and motility. In this study, we probed in molecular detail a novel interaction between DISC1 and Tensin2. Western blot and confocal microscopic analyses revealed widespread expression of both DISC1 and Tensin2 proteins throughout the mouse brain. Furthermore, we have developed novel anti-DISC1 antibodies that verified the predominant expression of a 105-kDa isoform of DISC1 in the rodent brain as well as in human cells. In the mouse brain, both proteins showed region-specific expression patterns, including strong expression in the pyramidal cell layer of the hippocampus and dentate gyrus. DISC1–Tensin2 colocalisation was most clearly observed in the Purkinje cells of the mouse cerebellum. Biochemical coimmunoprecipitation experiments revealed an interaction between endogenous DISC1 and Tensin2 proteins in the mouse brain. Further pulldown studies in human cells using Myc-tagged Tensin2 constructs revealed that DISC1 specifically interacts with the C-terminal PTB domain of Tensin2 in a phosphorylation-independent manner. This new knowledge on the DISC1–Tensin2 interaction, as part of the wider DISC1 interactome, should further elucidate the signalling pathways that are perturbed in schizophrenia and other mental disorders.