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.     

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．     

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.     

Friction stir welding of pure magnesium and polypropylene in a lap-joint configuration:Microstructure and mechanical properties

A hybrid joint with a satisfactory mixture of pure magnesium and polypropylene(PP)was achieved via friction stir joining(FSW)in a lap-joint configuration.The tool rotational and travel speeds used in this work were 500–700 r/min and 50–100 mm/min,respectively.The mechanical properties and microstructural analysis of the resultant hybrid Mg/PP joint were examined.The results show that the maximum tensile shear strength(22.5 MPa)of the joint was attained at 700 r/min and 75 mm/min due to the optimum percentage fraction of mechanical interlocking(48%)and the presence of magnesium oxide.The interfacial joint center exhibits the maximum microhardness values because of the presence of refined and intertwined Mg fragments and density dislocations in the matrix of the PP.The joint failed via two different modes:interfacial line and weld zone fractures,respectively.     

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.     

Chronic hyperesthesia in rats caused by lesions in the dorsal roots of the branchial plexus]

Traumatic avulsions of the brachial plexus in Man is followed by development of hyperesthesia which is known to be reistant to pharmacological medication. We have been able to reproduce this syndrome in the Rat and have used this disturbed animal as a model. This model will give us the possibility of studying nervous mechanisms responsible for these abnormal pains and to look for effective treatments.     

R~(49)A~(50)RGDN~(54)P~(55)突变成I~(49)P~(50)RGDM~(54)P~(55)对华丽蛇毒素活性的影响(英文)

用基因点突变技术将已知具有强抑制血小板凝集作用的去整合蛋白———kistrin的RGD袢区IPRGDMP替换抑制血小板凝集作用较弱的elegantinRGD袢相应部位的RARGDNP,重构一个新的杂合的去整合蛋白,然后,分析该杂合蛋白对血小板凝集的抑制作用。结果表明,重组的杂合去整合蛋白比野生型elegantin具有更强的抑制血小板凝集活性。推测RGD顺序两翼的氨基酸残基在保持去整合蛋白的结构和功能中起重要作用。     

Impact of slip boundary on sloshing motions in partially filled containers

Sloshing is a kind of fluid motion inside partially filled containers. In spacecraft and other partially filled moving containers, sloshing plays an important role. The contact line between the fluid and solid boundary affects the fluid movement and sloshing during motion. A physical model for steady fluid flow with a partial slip boundary is presented and equations for this model are derived for cylindrical (tube-shaped) tanks. This gives a nonlinear system of differential equations that is solved numerically by using a Successive Over-Relaxation (SOR) technique and graphical results are shown. Variations in steady fluid flow are observed with changes in the slip length and some useful results are derived. The effects on the microscopic radius of the fluid layer in a capillary tube are also shown through graphical results.