HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS

A prominent feature of late-onset neurodegenerative diseases is accumulation of misfolded protein in vulnerable neurons. When levels of misfolded protein overwhelm degradative pathways, the result is cellular toxicity and neurodegeneration. Cellular mechanisms for degrading misfolded protein include the ubiquitin-proteasome system (UPS), the main non-lysosomal degradative pathway for ubiquitinated proteins, and autophagy, a lysosome-mediated degradative pathway. The UPS and autophagy have long been viewed as complementary degradation systems with no point of intersection. This view has been challenged by two observations suggesting an apparent interaction: impairment of the UPS induces autophagy in vitro, and conditional knockout of autophagy in the mouse brain leads to neurodegeneration with ubiquitin-positive pathology. It is not known whether autophagy is strictly a parallel degradation system, or whether it is a compensatory degradation system when the UPS is impaired; furthermore, if there is a compensatory interaction between these systems, the molecular link is not known. Here we show that autophagy acts as a compensatory degradation system when the UPS is impaired in Drosophila melanogaster, and that histone deacetylase 6 (HDAC6), a microtubule-associated deacetylase that interacts with polyubiquitinated proteins, is an essential mechanistic link in this compensatory interaction. We found that compensatory autophagy was induced in response to mutations affecting the proteasome and in response to UPS impairment in a fly model of the neurodegenerative disease spinobulbar muscular atrophy. Autophagy compensated for impaired UPS function in an HDAC6-dependent manner. Furthermore, expression of HDAC6 was sufficient to rescue degeneration associated with UPS dysfunction in vivo in an autophagy-dependent manner. This study suggests that impairment of autophagy (for example, associated with ageing or genetic variation) might predispose to neurodegeneration. Morover, these findings suggest that it may be possible to intervene in neurodegeneration by augmenting HDAC6 to enhance autophagy.     

一种包边模边界缩进控制方法

 将确定性优化方法用于板料包边设计.汽车板料包边仿真中变形区域小导致有限元模型在变形区域的网格很小,模型计算时间太长.本文针对影响板料包边后边界缩进较大的3个参数,建立目标函数的径向基函数近似模型,并用确定性优化方法对近似模型进行优化,近似模型计算效率高,提高了优化方法计算效率,使板料包边的优化设计成为可能,并为生产中的汽车板料控制包边后的边界缩进提供了一种新的思路.     

基于信息平台整合对高职院校毕业设计过程监控信息化研究

随着社会的发展,信息技术的进步,教育信息化特别是实践教学信息化具有重要研究意义.基于地方信息平台的整合,提出了高职高专院校毕业论文(设计)过程监控网络信息化.先设计了毕业论文(设计)信息平台结构,从而把政、校、企对学生进行共同培养模式进行了有机的结合;再从出题、选题、论文答辩、论文成果转化等方面对毕业论文(设计)管理实现了信息化;通过理论分析与实践证明此信息化过程有一定的理论意义和实用价值.     

公路工程中常见地质灾害的分析及防治

公路是遇到地质灾害危害最严重的工程建筑之一,常常会遇到诸如泥石流、滑坡、崩塌、岩溶等地质灾害。文章针对这些地质灾害展开了探究。     

一种检测氯胺酮的新方法

目的:寻找检验氯胺酮的试剂。方法:用化学方法进行检验,根据颜色反应进行识别。结果:氯胺酮与硫氰酸钴混合溶液反应,出现了特征性的紫色沉淀物。结论:该方法具有操作简便,结果准确,特异性强,便于推广的优势,可用于氯胺酮的初步检验。     

基于深度贝叶斯网络学习的不确定性建模方法

战场态势评估涉及很多不确定因素,对不确定性进行仿真建模能够提高态势评估的能力。针对参战对象多元、不确定性增多导致的无法全面准确表达不确定性问题,提出了基于记忆模块和变分自编码器的深度贝叶斯网络模型。采用生成模型设计了基于深度贝叶斯网络学习的态势评估模型;阐述了融合记忆模块的深度生成模型原理和模型的学习与推理过程;以某空袭行动为例构建贝叶斯网络,对所提方法进行了验证。结果表明:深度神经网络能够逼近隐变量的非线性变换,设计的记忆模块能存储深度神经网络提取的大量局部特征,通过学习自动得到了贝叶斯网络条件概率,增强了不确定性建模能力。     

小麦中与低脱氧雪腐镰刀菌烯醇含量关联的抗性基因类似物

脱氧雪腐镰刀菌烯醇(Deoxynivalenol,DON)是小麦遭受赤霉病危害后由赤霉病菌———禾谷镰刀菌产生的一种真菌毒素,这种毒素对人类和家畜的健康产生危害,严重地影响小麦的利用价值.种植低DON含量的品种是减少这种毒素危害的有效措施,而分子标记辅助育种技术能加速低DON品种的选育进程.在采用AFLP、SSR分子标记的基础上,进一步利用抗性基因类似物(RGA)对‘宁7840’(低DON含量的品种)和‘Clark’(高DON含量的品种)建立的133个重组自交系进行了DON含量的遗传特性分析.研究结果发现两个DON含量的数量特性位点(QTL),它们中含有4个与低DON含量密切相关RGAs,其中三个RGAs(RGA14-1,RGA16-1,RGA18-1)座落在染色体1A的长臂上,另一个(RGA14-2)座落在染色体5B的长臂上.座落在1AL和5BL上的QTL分别解释16.81%和7.84%的DON含量变异.DNA序列分析表明这些RGAs均与现已发现的抗性基因同源/类似,它们可能在小麦的低DON含量和赤霉病抗性上扮演着重要的角色.     

基于MSP430F5438A的工业排污督察管理终端设计

工业排污占环境污染高达70％,传统水质监测方法效率低且排污企业暗自偷排、突排污水问题严重,为此设计了一款基于MSP430F5438A和北斗的工业排污督察管理终端.工业排污督察管理终端以MSP430F5438A为核心控制器,利用北斗定位模块定位排污口位置并借助水质检测单元实时采集pH值、温度、浑浊度、溶解氧、氨氮浓度等信...     

Analysis for MIMO correlated frequency-selective channel in the presence of interference

The space time spreading, superimposed training sequences, and space-time coding are used to present a multiple input and multiple output （MIMO） systems model, and a closed-form of average error probability upper bound expression for MIMO correlated frequency-selective channel in the presence of interference （co-channel interference and jamming signals） is derived. Moreover, the correlation at both ends of the wireless link that can be incorporated equivalently into correlation at the transmit end is also derived, which is significant to analyze space-time link algorithm of MIMO systems.     

数字化创新:回顾与展望

结合数字化创新的特征与发展趋势,基于5W2H的分析思路,本文从数字化创新特征(WHAT)、数字化创新研究时间线(WHEN)、数字化创新场景(WHERE)、数字化创新动因(WHY)、数字化创新参与者(WHO)、数字化创新途径(HOW)以及数字化创新代价(HOW MUCH)七个方面对数字化创新相关文献进行了梳理.研究发现,...