Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration

Cyclin-dependent kinase 5 (Cdk5) is required for proper development of the mammalian central nervous system. To be activated, Cdk5 has to associate with its regulatory subunit, p35. We have found that p25, a truncated form of p35, accumulates in neurons in the brains of patients with Alzheimer's disease. This accumulation correlates with an increase in Cdk5 kinase activity. Unlike p35, p25 is not readily degraded, and binding of p25 to Cdk5 constitutively activates Cdk5, changes its cellular location and alters its substrate specificity. In vivo the p25/Cdk5 complex hyperphosphorylates tau, which reduces tau's ability to associate with microtubules. Moreover, expression of the p25/Cdk5 complex in cultured primary neurons induces cytoskeletal disruption, morphological degeneration and apoptosis. These findings indicate that cleavage of p35, followed by accumulation of p25, may be involved in the pathogenesis of cytoskeletal abnormalities and neuronal death in neurodegenerative diseases.     

Gigaxonin-controlled degradation of MAP1B light chain is critical to neuronal survival

Giant axonal neuropathy (GAN) is a devastating sensory and motor neuropathy caused by mutations in the GAN gene, which encodes the ubiquitously expressed protein gigaxonin. Cytopathological features of GAN include axonal degeneration, with accumulation and aggregation of cytoskeletal components. Little is currently known about the molecular mechanisms underlying this recessive disorder. Here we show that gigaxonin controls protein degradation, and is essential for neuronal function and survival. We present evidence that gigaxonin binds to the ubiquitin-activating enzyme E1 through its amino-terminal BTB domain, while the carboxy-terminal kelch repeat domain interacts directly with the light chain (LC) of microtubule-associated protein 1B (MAP1B). Overexpression of gigaxonin leads to enhanced degradation of MAP1B-LC, which can be antagonized by proteasome inhibitors. Ablation of gigaxonin causes a substantial accumulation of MAP1B-LC in GAN-null neurons. Moreover, we show that overexpression of MAP1B in wild-type cortical neurons leads to cell death characteristic of GAN-null neurons, whereas reducing MAP1B levels significantly improves the survival rate of null neurons. Our results identify gigaxonin as a ubiquitin scaffolding protein that controls MAP1B-LC degradation, and provide insight into the molecular mechanisms underlying human neurodegenerative disorders.     

EPS8 and E3B1 transduce signals from Ras to Rac.

The small guanine nucleotide (GTP)-binding protein Rac regulates mitogen-induced cytoskeletal changes and c-Jun amino-terminal kinase (JNK), and its activity is required for Ras-mediated cell transformation. Epistatic analysis placed Rac as a key downstream target in Ras signalling; however, the biochemical mechanism regulating the cross-talk among these small GTP-binding proteins remains to be elucidated. Eps8 (relative molecular mass 97,000) is a substrate of receptors with tyrosine kinase activity which binds, through its SH3 domain, to a protein designated E3b1/Abi-1. Here we show that Eps8 and E3b1/Abi-1 participate in the transduction of signals from Ras to Rac, by regulating Rac-specific guanine nucleotide exchange factor (GEF) activities. We also show that Eps8, E3b1 and Sos-1 form a tri-complex in vivo that exhibits Rac-specific GEF activity in vitro. We propose a model in which Eps8 mediates the transfer of signals between Ras and Rac, by forming a complex with E3b1 and Sos-1.     

超混沌时序加密数字信号的应用

给出一个超混沌系统模型,利用此系统生成的超混沌时序作为密钥,采用模２加法的方式对数字信号进行重新编码,实现了对文本、图像和声音等数字信号的加密与解密。     

APC(Cdc20) promotes exit from mitosis by destroying the anaphase inhibitor Pds1 and cyclin Clb5

Ubiquitin-mediated proteolysis due to the anaphase-promoting complex/cyclosome (APC/C) is essential for separation of sister chromatids, requiring degradation of the anaphase inhibitor Pds1, and for exit from mitosis, requiring inactivation of cyclin B Cdk1 kinases. Exit from mitosis in yeast involves accumulation of the cyclin kinase inhibitor Sic1 as well as cyclin proteolysis mediated by APC/C bound by the activating subunit Cdh1/Hct1 (APC(Cdh1)). Both processes require the Cdc14 phosphatase, whose release from the nucleolus during anaphase causes dephosphorylation and thereby activation of Cdh1 and accumulation of another protein, Sic1 (refs 4-7). We do not know what determines the release of Cdc14 and enables it to promote Cdk1 inactivation, but it is known to be dependent on APC/C bound by Cdc20 (APC(Cdc20)) (ref. 4). Here we show that APC(Cdc20) allows activation of Cdc14 and promotes exit from mitosis by mediating proteolysis of Pds1 and the S phase cyclin Clb5 in the yeast Saccharomyces cerevisiae. Degradation of Pds1 is necessary for release of Cdc14 from the nucleolus, whereas degradation of Clb5 is crucial if Cdc14 is to overwhelm Cdk1 and activate its foes (Cdh1 and Sic1). Remarkably, cells lacking both Pds1 and Clb5 can proliferate in the complete absence of Cdc20.     

倒谱技术在人体脉搏信号分析中的应用

运用倒谱理论讨论了正常心律和非正常心律受检者的脉搏信号在倒谱域中的特征表现．通过对２８６例脉搏信号的倒谱分析，发现代脉信号与其他正常心律脉搏信号的倒谱特征差别显著     

热活化过硫酸钠降解水中1-萘酚的研究

通过热活化过硫酸钠降解水中的1-萘酚,考察了温度、过硫酸钠(PS)投加量、初始p H值和1-萘酚初始浓度对降解过程的影响;并对自由基进行了鉴定.实验结果表明:1-萘酚初始浓度为20 mg/L,PS投加量为1.65 g/L,溶液初始p H为5.8,温度为60℃时,20 min 1-萘酚的降解率可达86.30%.1-萘酚的降解率随着温度的升高及PS投加量的增加而增大.自由基鉴定实验表明,热活化过硫酸钠降解1-萘酚的过程中,SO4-·和·OH均有生成并参与反应,而SO4-·起主导作用.     

固溶体Zn_xCd_(1-x)S光催化降解甲基橙水溶液

采用共沉淀法制备固溶体ZnxCd1-xS光催化剂,采用X线衍射仪(XRD),扫描电子显微镜(SEM)和紫外-可见漫反射光谱仪(UV-Vis DRS)对ZnxCd1-xS光催化剂的结构和性能进行表征。以甲基橙水溶液为模型反应物,通过可见光催化降解甲基橙水溶液,对固溶体ZnxCd1-xS光催化剂的可见光催化活性进行评价。探讨Zn的摩尔分率(x)对ZnxCd1-xS光催化剂的能带结构、导带电位、价带电位及光催化活性的影响,考察降解温度、催化剂用量、甲基橙水溶液的初始浓度和p H对可见光催化降解甲基橙性能的影响,并对ZnxCd1-xS光催化剂的光催化活性的提高进行了机制分析。结果表明:与Cd S相比,ZnxCd1-xS不仅光催化活性高,而且光稳定性好,可多次循环使用。     

FFT频谱分析在微震信号识别中的应用

 为识别采场大爆破信号与岩石破裂大震级微震信号,运用MATLAB 的快速傅里叶变换(FFT)频谱分析,对采场大爆破信号和大震级微震信号的功率谱和幅频特性进行分析,并对比两者能量在频带上的分布差异。研究表明,大震级微震信号频带分布较宽,且在30～50 Hz 达到了最大幅值,采场大爆破信号频带更窄、幅值更大、且一般在10 Hz 就能达到最大幅值。由于爆破释放的能量较大且释放的非常快,采场大爆破信号能量大多分布在0～30 Hz 的低频区域,大震级微震信号的能量大多分布于30～50 Hz 区域。利用信号特性实现对两种信号快速有效的辨识,为后期微震监测对地压风险区域的预测预报提供了准确的数据支撑。     

V2O5/CeF3光催化降解丙酮的性能研究

利用浸渍法制备了一系列不同掺杂量的V2O5/CeF3光催化剂,通过光催化降解丙酮实验考察了催化剂的光催化性能,并采用X射线衍射(XRD)、BET比表面积和紫外可见光谱(UV-vis)等方法表征了催化剂的物理化学性质.结果表明:少量(摩尔分数≤15%)V2O5的掺杂有利于催化剂比表面积的增加,有利于催化剂光催化性能的提高;而当V2O5含量进一步增加时,由于CeVO4晶相的出现,使催化剂的比表面积减小、禁带宽度增加,从而降低了催化剂的光催化活性.其中,摩尔分数为15%的V2O5/CeF3催化剂具有最佳的光催化性能,丙酮降解率可达85%.     

Ti-5Al-5Mo-5V-1Cr-1Fe合金热加工图及其组织演变

采用热模拟试验机对Ti-5Al-5Mo-5V-1Cr-1Fe合金进行等温压缩试验,获得变形温度为750~900℃和应变速率为0.001~1 s 1时的真应力真应变曲线,并运用修正后的试验数据建立真应变为0.7的热加工图。通过显微组织观察,分析合金的变形机理,确定热变形失稳区。研究结果表明:Ti-5Al-5Mo-5V-1Cr-1Fe合金加工温度范围较宽,当加工温度低于800℃且变形速率大于0.1 s 1时易发生绝热剪切,造成流变失稳;随着变形温度升高,功率耗散因子η有增大趋势,合金的流动软化机制由动态回复逐渐变为动态再结晶,显微组织也随之细化、均匀。     

Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis

Human osteoarthritis is a progressive disease of the joints characterized by degradation of articular cartilage. Although disease initiation may be multifactorial, the cartilage destruction appears to be a result of uncontrolled proteolytic extracellular matrix destruction. A major component of the cartilage extracellular matrix is aggrecan, a proteoglycan that imparts compressive resistance to the tissue. Aggrecan is cleaved at a specific 'aggrecanase' site in human osteoarthritic cartilage; this cleavage can be performed by several members of ADAMTS family of metalloproteases. The relative contribution of individual ADAMTS proteases to cartilage destruction during osteoarthritis has not been resolved. Here we describe experiments with a genetically modified mouse in which the catalytic domain of ADAMTS5 (aggrecanase-2) was deleted. After surgically induced joint instability, there was significant reduction in the severity of cartilage destruction in the ADAMTS5 knockout mice compared with wild-type mice. This is the first report of a single gene deletion capable of abrogating the course of cartilage destruction in an animal model of osteoarthritis. These results demonstrate that ADAMTS5 is the primary 'aggrecanase' responsible for aggrecan degradation in a murine model of osteoarthritis, and suggest rational strategies for therapeutic intervention in osteoarthritis.