Role of ERAB/L-3-hydroxyacyl-coenzyme A dehydrogenase type II activity in Abeta-induced cytotoxicity

Endoplasmic reticulum-associated amyloid beta-peptide (Abeta)-binding protein (ERAB)/L-3-hydroxyacyl-CoA dehydrogenase type II (HADH II) is expressed at high levels in Alzheimer's disease (AD)-affected brain, binds Abeta, and contributes to Abeta-induced cytotoxicity. Purified recombinant ERAB/HADH II catalyzed the NADH-dependent reduction of S-acetoacetyl-CoA with a Km of approximately 68 microM and a Vmax of approximately 430 micromol/min/mg. The contribution of ERAB/HADH II enzymatic activity to Abeta-mediated cellular dysfunction was studied by site-directed mutagenesis in the catalytic domain (Y168G/K172G). Although COS cells cotransfected to overexpress wild-type ERAB/HADH II and variant beta-amyloid precursor protein (betaAPP(V717G)) showed DNA fragmentation, cotransfection with Y168G/K172G-altered ERAB and betaAPP(V717G) was without effect. We thus asked whether the enzyme might recognize alcohol substrates of which the aldehyde products could be cytotoxic; ERAB/HADH II catalyzed oxidation of a variety of simple alcohols (C2-C10) to their respective aldehydes in the presence of NAD+ and NAD-dependent oxidation of 17beta-estradiol. Addition of micromolar levels of synthetic Abeta(1-40) to purified ERAB/HADH II inhibited, in parallel, reduction of S-acetoacetyl-CoA (Ki approximately 1.6 microM), as well as oxidation of 17beta-estradiol (Ki approximately 3.2 microM) and (-)-2-octanol (Ki approximately 2.6 microM). Because micromolar levels of Abeta were required to inhibit ERAB/HADH II activity, whereas Abeta binding to ERAB/HADH II occurred at much lower concentrations (Km approximately 40-70 nM), the latter more closely simulating Abeta levels within cells, Abeta perturbation of ERAB/HADH II was likely to result from mechanisms other than the direct modulation of enzymatic activity. Cells cotransfected to overexpress ERAB/HADH II and betaAPP(V717G) generated malondialdehyde-protein and 4-hydroxynonenal-protein epitopes, which were detectable only at the lowest levels in cells overexpressing either ERAB/HADH II or betaAPP(V717G) alone. Generation of such toxic aldehydes was not observed in cells contransfected to overexpress Y168G/K172G-altered ERAB and betaAPP(V717G). We conclude that the generalized alcohol dehydrogenase activity of ERAB/HADH II is central to the cytotoxicity observed in an Abeta-rich environment.     

Up?Scalable Fabrication of -SnO2 with Multifunctional Interface for High Performance Perovskite Solar Modules

Tin dioxide -(SnO2) has been demonstrated as one of the promising electron transport layers for highefficiency perovskite solar cells (PSCs). However, scalable ...     

电弧保护装置的设计

本文分析了故障电弧导致火灾的可能性与严重性,简述了目前国内外相关保护装置的发展与现状。详细介绍了故障电弧保护装置的设计流程与技术关键点。     

Design and Validation of an Efficient Authentication Scheme with Anonymity for Roaming Service in Global Mobility Networks

Designing a user authentication protocol with anonymity for the global mobility network (GLOMONET) is a difficult task because wireless networks are susceptible to attacks and each mobile user has limited power, processing and storage resources. In this paper, a secure and lightweight user authentication protocol with anonymity for roaming service in the GLOMONET is proposed. Compared with other related approaches, our proposal has many advantages. Firstly, it uses low-cost functions such as one-way hash functions and exclusive-OR operations to achieve security goals. Having this feature, it is more suitable for battery-powered mobile devices. Secondly, it uses nonces instead of timestamps to avoid the clock synchronization problem. Therefore, an additional clock synchronization mechanism is not needed. Thirdly, it only requires four message exchanges between the user, foreign agent and home agent. Further, the security properties of our protocol are formally validated by a model checking tool called AVISPA. We also demonstrate that this protocol enjoys important security attributes including prevention of various attacks, single registration, user anonymity, no password table, and high efficiency in password authentication. Security and performance analyses show that compared with other related authentication schemes, the proposed scheme is more secure and efficient.     

异步电动机取消线圈间接头连续嵌线工艺

介绍显极接法的异步电动机取消线圈间接头连续嵌线工艺,是1998年第1期《防爆电机》刊载的多极异步电动机线圈间不接头一条龙嵌线工艺的续篇。     

移动互联网用户标识管理技术的研究

移动互联网业务中,网络地址转换(NAT,Network Address Translation)技术使得公网增值服务提供商(SP)无法获取用户标识及其基础信息、业务使用信息,因此无法实现业务使用计费及用户管理,极大地限制了移动互联网业务的发展。文章针对这一问题,提出一种全新的移动互联网用户标识解决方案,运营商通过对用户转换前、后标识信息的匹配及对用户的统一管理,形成用户访问信息的完整记录,实现公网SP对移动互联网用户信息的识别和管理。     

混合卫星-地面协同网络的误符号性能

该文研究了直达径满足阴影莱斯分布,中继链路满足阴影莱斯/瑞利分布的混合卫星-地面协同网络的误符号性能。基于最大比合并准则,首先推导了直达径和中继链路的矩生成函数解析式。然后,计算出系统平均误符号率的理论表达式和高信噪比条件下的渐进解来分析系统的分集度和阵列增益。最后,通过仿真验证了理论分析的正确性。