A critical role for the protein tyrosine phosphatase receptor type Z in functional recovery from demyelinating lesions

Several lines of evidence suggest that tyrosine phosphorylation is a key element in myelin formation, differentiation of oligodendrocytes and Schwann cells, and recovery from demyelinating lesions. Multiple sclerosis is a demyelinating disease of the human central nervous system, and studies of experimental demyelination indicate that remyelination in vivo requires the local generation, migration or maturation of new oligodendrocytes, or some combination of these. Failure of remyelination in multiple sclerosis could result from the failure of any of these processes or from the death of oligodendrocytes. Ptprz encodes protein tyrosine phosphatase receptor type Z (Ptpz, also designated Rptpbeta), which is expressed primarily in the nervous system but also in oligodendrocytes, astrocytes and neurons. Here we examine the susceptibility of mice deficient in Ptprz to experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. We observe that mice deficient in Ptprz show impaired recovery from EAE induced by myelin oligodendrocyte glycoprotein (MOG) peptide. This sustained paralysis is associated with increased apoptosis of mature oligodendrocytes in the spinal cords of mutant mice at the peak of inflammation. We further demonstrate that expression of PTPRZ1, the human homolog of Ptprz, is induced in multiple sclerosis lesions and that the gene is specifically expressed in remyelinating oligodendrocytes in these lesions. These results support a role for Ptprz in oligodendrocyte survival and in recovery from demyelinating disease.     

Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits

The N-methyl-D-aspartate subtype of glutamate receptor (NMDAR) serves critical functions in physiological and pathological processes in the central nervous system, including neuronal development, plasticity and neurodegeneration. Conventional heteromeric NMDARs composed of NR1 and NR2A-D subunits require dual agonists, glutamate and glycine, for activation. They are also highly permeable to Ca2+, and exhibit voltage-dependent inhibition by Mg2+. Coexpression of NR3A with NR1 and NR2 subunits modulates NMDAR activity. Here we report the cloning and characterization of the final member of the NMDAR family, NR3B, which shares high sequence homology with NR3A. From in situ and immunocytochemical analyses, NR3B is expressed predominantly in motor neurons, whereas NR3A is more widely distributed. Remarkably, when co-expressed in Xenopus oocytes, NR3A or NR3B co-assembles with NR1 to form excitatory glycine receptors that are unaffected by glutamate or NMDA, and inhibited by D-serine, a co-activator of conventional NMDARs. Moreover, NR1/NR3A or -3B receptors form relatively Ca2+-impermeable cation channels that are resistant to Mg2+, MK-801, memantine and competitive antagonists. In cerebrocortical neurons containing NR3 family members, glycine triggers a burst of firing, and membrane patches manifest glycine-responsive single channels that are suppressible by D-serine. By itself, glycine is normally thought of as an inhibitory neurotransmitter. In contrast, these NR1/NR3A or -3B 'NMDARs' constitute a type of excitatory glycine receptor.     

Annexin II light chain regulates sensory neuron-specific sodium channel expression

The tetrodotoxin-resistant sodium channel Na(V)1.8/SNS is expressed exclusively in sensory neurons and appears to have an important role in pain pathways. Unlike other sodium channels, Na(V)1.8 is poorly expressed in cell lines even in the presence of accessory beta-subunits. Here we identify annexin II light chain (p11) as a regulatory factor that facilitates the expression of Na(V)1.8. p11 binds directly to the amino terminus of Na(V)1.8 and promotes the translocation of Na(V)1.8 to the plasma membrane, producing functional channels. The endogenous Na(V)1.8 current in sensory neurons is inhibited by antisense downregulation of p11 expression. Because direct association with p11 is required for functional expression of Na(V)1.8, disrupting this interaction may be a useful new approach to downregulating Na(V)1.8 and effecting analgesia.     

基于WEB的数字信号处理虚拟系统

基于WEB的虚拟系统为研究数字信号处理提供了一种新的方式,采用虚拟系统对数字信号的频谱分析及语音编码进行研究,通过ASP和ActiveX技术实现系统的动态交互和实时传输,初步实现了信号在网上的实时交互处理,该系统的研究成果已开始应用于教学,科研中。     

比喻义的训释与比喻义的形成--《现代汉语词典》比喻义计量研究之一

运用计量统计的方法,分析了<现代汉语词典>(1983年版)中2488条比喻义的释义特点及所反映的词义性质.概括出了六种释义类型,反映出两种不同性质的比喻义固定比喻义与语境比喻义.固定比喻义是指已经凝固为稳定词义成分的比喻义,已成为词典释义中的一部分.语境比喻义是指靠具体上下文来显示的比喻义,以例句的形式来体现.<现代汉语词典>对比喻义的处理方法在词汇学与词典学有着独到的贡献再现了词义形成、稳定的过程;扩大了规范语文词典反映语言事实的范围,加强了语文词典的"引导"功能;丰富了词典的编纂技巧,完善了语文词典的表现手段.     

旋风预热器预热过程数值模拟试验研究

本文通过"三传一反"基本原理,建立了四级旋风预热器系统的预热过程气体平衡、物料平衡、热量平衡与流体、传热动动力学过程耦合的数学模型,并确立了其求解方法,通过对某厂实例的具体分析计算,表明该方法计算结果能较好地反应实际情况,为设计和优化预热器系统提供了一条有效的途径和方法.     

中日铁路项目国民经济评价方法比较与分析

以日本《铁路费用效益分析手册 (99版 )》和中国《铁路建设项目经济评价办法 (第 2版 )》为参照 ,通过对比分析中日铁路项目国民经济评价方法的差异 ,提出日本铁路费用效益分析方法中的可借鉴之处 :借鉴日本评价方法分 3类界定受益群体的思路 ,解决我国现行方法存在的效益重复计算问题 ;以福利经济学和“有无对比法”作为项目评价的基本指导原则 ,解决我国由于评价原则模糊导致的同一项目不同评价结论的问题等     

工科大学物理实验教学模式的探讨

主要阐述在做好基础实验的基础上 ,同时开设综合实验 ,进而鼓励应用计算机软件进行设计性实验。提出撰写实验报告的能力是实验教学不可忽视的教学环节 ,以最终趋向于“实践型、设计型”为目标来探讨工科物理实验教学模式     

Insight into a natural Diels-Alder reaction from the structure of macrophomate synthase

The Diels-Alder reaction, which forms a six-membered ring from an alkene (dienophile) and a 1,3-diene, is synthetically very useful for construction of cyclic products with high regio- and stereoselectivity under mild conditions. It has been applied to the synthesis of complex pharmaceutical and biologically active compounds. Although evidence on natural Diels-Alderases has been accumulated in the biosynthesis of secondary metabolites, there has been no report on the structural details of the natural Diels-Alderases. The function and catalytic mechanism of the natural Diels-Alderase are of great interest owing to the diversity of molecular skeletons in natural Diels-Alder adducts. Here we present the 1.70 A resolution crystal structure of the natural Diels-Alderase, fungal macrophomate synthase (MPS), in complex with pyruvate. The active site of the enzyme is large and hydrophobic, contributing amino acid residues that can hydrogen-bond to the substrate 2-pyrone. These data provide information on the catalytic mechanism of MPS, and suggest that the reaction proceeds via a large-scale structural reorganization of the product.     

广义系统的可靠最优调节器设计

在实践应用过程中,控制元件(包括执行器或传感器)的失效往往会造成系统不稳定或性能指标难以达到·因此研究如何利用仅存的有效控制元件来实现控制目标十分必要·由此"可靠控制"应运而生,即无论特定集合中的某些控制元器件失效与否,都要求所设计的控制器能保证系统的稳定性和各项性能指标的实现·针对执行器失效的线性广义系统,给出可靠最优调节器设计方法,所设计的状态反馈控制器能够使执行器故障系统具有正则、渐近稳定、无脉冲,且此时的二次性能指标小于正常情况下的二次性能指标·