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991.
Role of ERAB/L-3-hydroxyacyl-coenzyme A dehydrogenase type II activity in Abeta-induced cytotoxicity
SD Yan Y Shi A Zhu J Fu H Zhu Y Zhu L Gibson E Stern K Collison F Al-Mohanna S Ogawa A Roher SG Clarke DM Stern 《Canadian Metallurgical Quarterly》1999,274(4):2145-2156
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. 相似文献
992.
将化学计量比1∶2的Al粉和B粉混合均匀后压制成Φ12 mm的圆柱锭,在流通Ar气气氛下,分别于650,700,800,900和1000℃下烧结4 h后随炉冷却至室温,利用X射线衍射仪(XRD)和扫描电子显微镜(SEM)分别研究了合成的样品的物相组成和微观形貌。结果表明,烧结温度的升高不仅会使样品中AlB2的相含量发生变化,还伴随有AlB2颗粒的长大;在800℃时烧结可以得到相含量较多、颗粒尺寸相对较小的AlB2。此外,研究了在800℃时保温不同时间对AlB2合成反应的影响。在流通Ar气气氛中,将压制好的圆柱锭在800℃下分别保温0.5,2.0,4.0,6.0和10.0 h后将样品装置移出管式炉并于Ar气气氛中冷却至室温。物相和形貌分析表明保温时间也会使AlB2的相含量和颗粒尺寸发生变化,且AlB颗粒随保温时间的延长有明显长大的趋势;综合考虑在800℃烧结时保温6 h效果最好。 相似文献
993.
994.
995.
在Thermecmastor-Z型热模拟试验机上对BT20钛合金进行了变形温度800~1 100℃及应变速率0.001~70 s-1的热模拟压缩实验。以实验数据为基础,运用BP神经网络算法原理,建立了BT20钛合金在高温变形条件下的应力与应变、应变速率和变形温度关系的预测模型,并对模型的泛化能力进行了误差评价。结果表明:通过BP神经网络建立的合金本构关系模型具有较高的预测精度,预测结果的相对误差均在3%以内,能很好地满足实际应用的需求。此外,该模型能够客观、真实地描述BT20钛合金的高温动态变形行为,为材料高温本构关系模型的建立提供了快捷、有效的工具。 相似文献
996.
997.
In a quasi-two-dimensional model, the scattering of incident ordinary electromag- netic waves by a dipole-electrostatic drift vortex is studied with first-order Born approximation. The distribution of the scattering cross-section and total cross-section are evaluated analytically in different approximate conditions, and the physical interpretations are discussed. When the wavelength of incident wave is much longer than the vortex radius (kia〈〈1), it is found that the angle at which the scattering cross-section reaches its maxim depends significantly on the approximation of the parameters of the vortex used. It is also found that the total scattering cross-section has an affinitive relation with the parameters of the plasma, while it is irrelevant to the frequency of the incident wave in a wide range of parameters of the vortex. In a totally different range of parameters when incident wave is in the radar-frequency range (then kia 〈〈 1, the wavelength of incident wave is much shorter than the vortex radius), the numerical procedure is conducted with computer in order to obtain the distribution and the total expression of the scattering crosssection. Then it is found that the total scattering cross-section in the low frequency range is much larger than that in high frequency range, so the scattering is more effective in the low frequency range than in high frequency range. 相似文献
998.
WuGang HeZhen-Li 《核技术(英文版)》1998,9(3):176-180
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. 相似文献
999.
Guo-Qing Zhang Shuai Wang Hai-Qing Zhang Xing-Wang Zhu Chao Peng Jun Cai Zhao-Zhong He Kun Chen 《核技术(英文版)》2017,28(3)
The release of fission products from coated particle fuel to primary coolant,as well as the activation of coolant and impurities,were analysed for a fluoride salt-cooled high-temperature reactor (FHR) system,and the activity of radionuclides accumulated in the coolant during normal operation was calculated.The release rate (release fraction per unit time) of fission products was calculated with STACY code,which is modelled mainly based on the Fick's law,while the activation of coolant and impurities was calculated with SCALE code.The accumulation of radionuclides in the coolant has been calculated with a simplified model,which is generally a time integration considering the generation and decay of radionuclides.The results show that activation products are the dominant gamma source in the primary coolant system during normal operation of the FHR while fission products become the dominant source after shutdown.In operation condition,health-impacts related nuclides such as 3H,and 14C originate from the activation of lithium and coolant impurities including carbon,nitrogen,and oxygen.According to the calculated effective cross sections of neutron activation,6Li and 14N are the dominant 3H production source and 14C production source,respectively.Considering the high production rate,3H and 14C should be treated before being released to the environment. 相似文献
1000.