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.     

空气污染排放视角下中国核电的健康效益

核电在改善空气质量方面具有重要的作用。本文对比了核电与煤电的空气污染物排放系数,根据空气污染物引起的死亡率与人均燃煤发电量的负指数幂关系,评估了中国通过发展核电在改善空气质量方面对居民的健康效益,并对未来的健康效益进行了分析。结果显示,发展核电能够避免的死亡人数在增加。据估算,1995—2018年,中国核电累计可避免约4.7万人因空气污染物死亡,可避免约22.6万人因空气污染物患病。2020—2030年,预计会避免8.3万~9.4万人死亡,避免39.7万~45.1万人患病。     

Nitrogen utilization and transformation in red soil fertilized with urea and ryegrass

The influence of fertilization with urea and ryegrass on nitrogen utilization and transformation in red soil has been studied by using ^15N tracer method.When urea and ryegrass were applied alone or in combination,the percentage of N uptaken by ryegrass from labelled urea was 3 and 1.7 times that from labelled ryegrass for the application rate of 200mgN.kg^-1 and 100mgN.kg^-1,respectively;combining application of ryegrass and ureareduced uptake of urea N and increased uptake of ryegrass N by ryegrass plant,but the percentage of N residued in soil increased for urea and decreased for ryegrass.when urea and ryegrass were applied alone,the percentage of N residued in soil from labelled ryegrass was more than 69% while that from labelled urea was less than 25%,and much more ryegrass N was incorporated into humus than urea N.     

高铁混凝土简支预应力箱梁施工技术研究

结合我国某高铁预应力混凝土简支箱梁采用后张法施工的过程,简要论述三项关键工序、高性能混凝土耐久性指标的保证措施、减小箱梁后期徐变的相关施工措施及注意要点,以确保满足高速铁路运营的安全性、高速度、高平顺性和舒适度.     

除盐水制备技术进展

介绍了几种水除盐技术(蒸馏、离子交换、电渗析、反渗透、电去离子和电吸附)的原理、发展及应用现状,分析了水除盐技术发展的整体脉络,并预测了发展前景.     

天基发射与载人登月初探

登月是载人航天向深空探测的延续，它与载人飞船工程相比，可靠性要求更高，工程规模更大，资金投入更多。结合国外登月历程和我国航天事业取得的重大成就，探讨了利用现有运载技术，分批次将登月飞船和航天员送入近地轨道，并在天基发射平台上进行组装发射，实现载人登月的设想；并就天基发射平台和天基发射方式进行了初步探讨。     

高流动性星型尼龙12的合成与表征

在均苯三甲酸的存在下,进行十二内酰胺的水解聚合,合成了四种不同臂长的三臂星型尼龙12,对产物的分子量进行了测定,并对其力学性能和流变行为进行了研究。结果表明,星型尼龙12的分子量随着均苯三甲酸含量的提高而降低,与相应分子量的线型尼龙12相比,星型尼龙12的拉伸强度和弯曲强度基本保持,冲击强度保持率在80%以上,断裂伸长...