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71.
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. 相似文献
72.
本文报导了双—N(2—羟基乙基)β—雷锁醛亚胺合镍(Ⅱ)和双—N(2—羟基乙基)β—雷锁醛亚胺合铜(Ⅱ)的合成,它们的组成已由元素分析和红外光谱所证实。抗癌活性试验表明,双—N(2—羟基乙基)β—雷锁醛亚胺合镍(Ⅱ)对肿瘤模型S_(180)(A)及艾氏腹水癌均有较好的抑制作用. 相似文献
73.
本文采用回归设计和电算机离线调优运算,对我国某大型铜矿含多种重金属离子废水的处理进行了研究。提出了“阶段中和沉淀—浮选分离”的处理废水新工艺。建立了氢氧化铜和石膏浮选分离的数学模型,并进行了计算机绘图。最终获得了符合国家排放标准的处理水,并逐一回收了有价金属化合物氢氧化铁、氢氧化铜和石膏产品。 相似文献
74.
Based on the qualitative theory of atmospheric dynamical equations, a new method for simplifying equations, the operator constraint principle, is presented. The general rule of the method and its mathematical strictness are discussed. Moreover, the way that how to use the method to simplify equations rationally and how to get the simplified equations with harmonious and consistent dynamics is given. 相似文献
75.
76.
Interdiffusion in the Fe2O3-TiO2 system was investigated by the diffusion couple method in the temperature range of 1323 to 1473 K. The diffusion concentration curves of Ti4+ cations were obtained by electron probe microanalysis, according to which the Boltzmann-Matano method optimized by Broeder was used to calculate the interdiffusion coefficients. The interdiffusion coefficients almost increased linearly with the mole fraction of Ti4+ cations increasing, and they were in the range of 10?12–10?11cm2·s?1. The increase of temperature could also lead to the increase of the interdiffusion coefficients at a constant concentration of Ti4+ cations. It was also found that the thickness growth of the diffusion layer obeyed the parabolic rate law. 相似文献
77.
Ben-Chaung Wang Fang-Yi Chou Yung-Jaan Lee 《Systemic Practice and Action Research》2010,23(2):157-172
Chung-Sheng Community in Taoyuan City, Taiwan is a typical urban community. By adopting participatory action research, this study examines resident awareness regarding the feasibility of transforming Chung-Sheng Community into a sustainable community. Action research can help avoid constant “trial and error” in constructing sustainable communities and enhance process efficiency. Meanwhile, an active research approach can help communities better achieve sustainable development. Constructing a sustainable urban community requires energy, effective frameworks, and professional assistance. Achieving these requires a continuous and participatory action research process, and careful exploration of the awareness of community residents, which is the focus of this investigation. 相似文献
78.
针对工件到达时间与加工时间不确定,且存在紧急工件的并行机开放车间调度问题,以TWC(total weighted completion time)与TWT(total weighted tardiness)为优化目标,设计了一种集成FlexSim仿真模型与NSGA-Ⅱ算法的自适应动态调度方法。该方法以FlexSim模型仿真工件的生成和加工为基础,根据车间实时负荷确定动态调度周期,对紧急工件进行右移重调度,利用NSGA-Ⅱ算法生成双目标优化的调度方案。某晶粒拣选车间生产数据的实验结果表明,相较于利用规则的实时动态调度与固定周期重调度,提出的方法能够在最小化调度偏离度的同时获得满意解。 相似文献
79.
Yuk-Man Leung Kar-Lok Wong Chia-Huei Lin Chia-Chia Chao Chun-Hsiao Chou Li-Yun Chang Siao-Wei Chen Tzu-Hurng Cheng Yueh-Hsiung Kuo 《Cellular and molecular life sciences : CMLS》2010,67(1):147-156
Voltage-gated K+ (Kv) channels exhibit slow or C-type inactivation during continuous depolarization. A selective pharmacological agent targeting
C-type inactivation is hitherto lacking. Here, we report that 6β-acetoxy-7α-hydroxyroyleanone (AHR), a diterpenoid compound
isolated from Taiwania cryptomerioides, can selectively modify C-type inactivation of Kv1.2 channels. Extracellular, but not intracellular, AHR (50 μM) dramatically
accelerated the slow decay of Kv currents and left-shifted the steady-state inactivation curve. AHR blocked Kv currents with
an IC50 of 17.7 μM. AHR did not affect the kinetics and voltage-dependence of Kv1.2 channel activation. Channel block by AHR was
independent of intracellular K+ concentration. In addition, effect of AHR was much attenuated in a Kv1.2 V370G mutant defective in C-type inactivation. Therefore,
block of Kv1.2 channels by AHR did not appear to involve direct occlusion of the outer pore but depended on C-type inactivation.
AHR could thus be a probe targeting Kv channel C-type inactivation gate. 相似文献
80.