RIM1alpha is required for presynaptic long-term potentiation.

Two main forms of long-term potentiation (LTP)-a prominent model for the cellular mechanism of learning and memory-have been distinguished in the mammalian brain. One requires activation of postsynaptic NMDA (N-methyl d-aspartate) receptors, whereas the other, called mossy fibre LTP, has a principal presynaptic component. Mossy fibre LTP is expressed in hippocampal mossy fibre synapses, cerebellar parallel fibre synapses and corticothalamic synapses, where it apparently operates by a mechanism that requires activation of protein kinase A. Thus, presynaptic substrates of protein kinase A are probably essential in mediating this form of long-term synaptic plasticity. Studies of knockout mice have shown that the synaptic vesicle protein Rab3A is required for mossy fibre LTP, but the protein kinase A substrates rabphilin, synapsin I and synapsin II are dispensable. Here we report that mossy fibre LTP in the hippocampus and the cerebellum is abolished in mice lacking RIM1alpha, an active zone protein that binds to Rab3A and that is also a protein kinase A substrate. Our results indicate that the long-term increase in neurotransmitter release during mossy fibre LTP may be mediated by a unitary mechanism that involves the GTP-dependent interaction of Rab3A with RIM1alpha at the interface of synaptic vesicles and the active zone.     

The architecture of active zone material at the frog's neuromuscular junction

Active zone material at the nervous system's synapses is situated next to synaptic vesicles that are docked at the presynaptic plasma membrane, and calcium channels that are anchored in the membrane. Here we use electron microscope tomography to show the arrangement and associations of structural components of this compact organelle at a model synapse, the frog's neuromuscular junction. Our findings indicate that the active zone material helps to dock the vesicles and anchor the channels, and that its architecture provides both a particular spatial relationship and a structural linkage between them. The structural linkage may include proteins that mediate the calcium-triggered exocytosis of neurotransmitter by the synaptic vesicles during synaptic transmission.     

正弦形沙丘背风坡回流区特性研究

利用开源计算流体力学软件OpenFOAM的标准k-ε湍流模型,对沙丘表面流场进行数值模拟,获得了距沙丘表面不同高度的流场速度分布曲线,考察了沙丘背风坡回流区特性受沙丘高度和宽度的影响,分析了回流区形成的原因。结果表明:沙丘高度较低时,在背风坡贴近沙丘表面的区域气流速度先降低后增加;随着沙丘高度的增加,背风坡气流速度降低更为迅速,气流不稳定,出现回流区。研究还发现:在沙丘宽度或高度一定的情况下,随着宽高比的增加,回流区尺度减小;回流区尺度不仅取决于宽高比,还取决于沙丘宽度与高度的数值。沙丘背风坡回流区萌生时,贴近沙丘表面出现一系列小涡,减小沙丘宽高比,涡的尺度增大、强度增加,演变为回流区。     

某水库大坝除险加固措施探讨

以某工程为实例,针对水库大坝渗漏严重和坝坡不稳定等问题,探讨和验证水库大坝除险加固措施.通过技术、经济等方面的比较,灵活选取防渗方案.     

对流边界层顶部夹卷层厚度特征及其参数化分析

运用大涡模拟结果分析并讨论了对流边界层顶部夹卷层厚度特征及其参数化．常见的参数化方案是建立归一化夹卷层厚度与对流理查森数（Ri＊）之间的指数对应关系,但不同研究结果得到的幂指数有很大差异．分析表明：“Ri＊方案”本身是造成这种不确定性的原因;另一种理查森数（RiN）,即浮力理查森数,可以较好地表征夹卷层厚度．大涡模拟结果表明：“RiN方案”能够有效地减小夹卷层厚度参数化的不确定性．为消除湍流随机性对参数化的影响,我们对大涡模拟结果进行了时间平均处理,并用所得数据讨论了夹卷层厚度与浮力理查森数之间的关系．结果表明：两者之间有很好的指数对应关系,平均幂指数为-2／5;计算结果同时显示,幂指数仍然存在一定的变化范围（-1／3～-1／2）．夹卷层厚度的这种特性反映出夹卷过程的复杂性,即兼有热泡和界面振荡的特征．     

SOL-1 is a CUB-domain protein required for GLR-1 glutamate receptor function in C. elegans

Ionotropic glutamate receptors (iGluRs) mediate most excitatory synaptic signalling between neurons. Binding of the neurotransmitter glutamate causes a conformational change in these receptors that gates open a transmembrane pore through which ions can pass. The gating of iGluRs is crucially dependent on a conserved amino acid that was first identified in the 'lurcher' ataxic mouse. Through a screen for modifiers of iGluR function in a transgenic strain of Caenorhabditis elegans expressing a GLR-1 subunit containing the lurcher mutation, we identify suppressor of lurcher (sol-1). This gene encodes a transmembrane protein that is predicted to contain four extracellular beta-barrel-forming domains known as CUB domains. SOL-1 and GLR-1 are colocalized at the cell surface and can be co-immunoprecipitated. By recording from neurons expressing GLR-1, we show that SOL-1 is an accessory protein that is selectively required for glutamate-gated currents. We propose that SOL-1 participates in the gating of non-NMDA (N-methyl-D-aspartate) iGluRs, thereby providing a previously unknown mechanism of regulation for this important class of neurotransmitter receptor.     

秋立塔克构造带盐构造形成的传力方式的构造物理模拟

库车坳陷第三系下部库姆格列木群是一套巨厚的膏 (盐 )层 ,该层系不管是在应力传递方面 ,还是在控制构造样式方面都有重要的作用 .秋立塔克构造带是库车前陆褶皱冲断带的变形前缘 ,盐上、盐下构造极不协调 ,盐上层变形强烈 ,发育滑脱断层、大型推覆构造、突发构造和三角带构造 ;盐下变形弱 ,发育小规模的冲断层 .根据构造分析推断 ,在盐上层中 ,应力从变形后缘 (克拉苏构造带 )向变形前缘秋立塔克构造带的传递有 2种方式 ,即重力滑动传递和顺层挤压传递 .构造物理模拟实验证明这种推断是合理的     

Identification of a host protein essential for assembly of immature HIV-1 capsids.

To form an immature HIV-1 capsid, 1,500 HIV-1 Gag (p55) polypeptides must assemble properly along the host cell plasma membrane. Insect cells and many higher eukaryotic cell types support efficient capsid assembly, but yeast and murine cells do not, indicating that host machinery is required for immature HIV-1 capsid formation. Additionally, in a cell-free system that reconstitutes HIV-1 capsid formation, post-translational assembly events require ATP and a subcellular fraction, suggesting a requirement for a cellular ATP-binding protein. Here we identify such a protein (HP68), described previously as an RNase L inhibitor, and demonstrate that it associates post-translationally with HIV-1 Gag in a cell-free system and human T cells infected with HIV-1. Using a dominant negative mutant of HP68 in mammalian cells and depletion-reconstitution experiments in the cell-free system, we demonstrate that HP68 is essential for post-translational events in immature HIV-1 capsid assembly. Furthermore, in cells the HP68-Gag complex is associated with HIV-1 Vif, which is involved in virion morphogenesis and infectivity. These findings support a critical role for HP68 in post-translational events of HIV-1 assembly and reveal a previously unappreciated dimension of host-viral interaction.     

Chaperonin-mediated protein folding at the surface of groEL through a 'molten globule'-like intermediate.

Folding of two monomeric enzymes mediated by groE has been reconstituted in vitro. The groEL protein stabilizes the polypeptides in a conformation resembling the 'molten globule' state. Mg-ATP and groES then promote the acquisition of ordered tertiary structure at the surface of groEL. Folding requires the hydrolysis of about 100 ATP molecules per protein monomer. This active process of surface-mediated chain folding might represent a general mechanism for the formation of protein structure in vivo.     

The mechanism of Z alpha 1-antitrypsin accumulation in the liver.

Most northern Europeans have only the normal M form of the plasma protease inhibitor alpha 1-antitrypsin, but some 4% are heterozygotes for the Z deficiency variant. For reasons that have not been well-understood, the Z mutation results in a blockage in the final stage of processing of antitrypsin in the liver such that in the Z homozygote only 15% of the protein is secreted into the plasma. The 85% of the alpha 1-antitrypsin that is not secreted accumulates in the endoplasmic reticulum of the hepatocyte; much of it is degraded but the remainder aggregates to form insoluble intracellular inclusions. These inclusions are associated with hepatocellular damage, and 10% of newborn Z homozygotes develop liver disease which often leads to a fatal childhood cirrhosis. Here we demonstrate the molecular pathology underlying this accumulation and describe how the Z mutation in antitrypsin results in a unique molecular interaction between the reactive centre loop of one molecule and the gap in the A-sheet of another. This loop-sheet polymerization of Z antitrypsin occurs spontaneously at 37 degrees C and is completely blocked by the insertion of a specific peptide into the A-sheet of the antitrypsin molecule. Z antitrypsin polymerized in vitro has identical properties and ultrastructure to the inclusions isolated from hepatocytes of a Z homozygote. The concentration and temperature dependence of this loop-sheet polymerization has implications for the management of the liver disease of the newborn Z homozygote.     

D32海洋平台用钢在浪溅区腐蚀行为

通过极化实验和阻抗实验研究了D32海洋平台用钢在浪溅区的腐蚀规律,并利用扫描电镜和能量色散谱仪分析了各钢样的腐蚀产物. 结果表明,腐蚀产物的形貌成分和覆盖度的不同导致了模拟全浸区腐蚀速率稍大于钢样在海水中的腐蚀速率,模拟浪溅区腐蚀速率远大于模拟全浸区钢样腐蚀速率. 钢样在青岛海水、埕岛海水的全浸区和浪溅区的Nyquist图中出现的韦伯阻抗是由于表面形成的锈层及钙镁层所致.