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.     

基于扩散模型的ZnO/p-Si异质结伏安特性研究

为了揭示ZnO/p-Si异质结的导电机理,基于p-n结扩散模型和Anderson扩散模型推导了ZnO/p-Si异质结在理想情况下的伏安特性,并分析了掺杂浓度、工作温度以及能带补偿的影响.结果表明:当正向偏压超过势垒高度时,界面两边多数载流子由耗尽变为堆积,形成反向势垒,对异质结的正向电流起阻碍作用;当外加正向电压等于内...     

退火温度对ZnO薄膜晶体管电特性的影响

针对非晶硅和有机薄膜晶体管的低迁移率问题,以高纯Zn为靶材,反应磁控溅射沉积、且在不同温度下退火的ZnO薄膜作为半导体活性层,成功地制备出基于ZnO材料的薄膜晶体管(ZnO-TFT),研究了退火温度对ZnO -TFT电特性的影响.结果表明:ZnO- TFT的载流子迁移率随退火温度的升高而明显增大,700℃退火的样品迁移...     

一株产纤维素酶和植酸酶的米曲霉的诱变筛选和固体发酵

通过紫外诱变和微波辐射米曲霉菌株,筛选出高产纤维素酶和植酸酶米曲霉菌株ZQH48,并进行了固体发酵条件的优化.优化后的培养基配方为:菌渣:麸皮=1:1,氯化铵12%,蛋白胨2%,硫酸镁0.07%,氯化钠0.5%,磷酸二氢钾0.02%,固水比为1:1;最佳培养温度35℃.优化后纤维素酶活力可达161.55 U/g,较原始...     

云黄连不同部位生物量及生物碱含量个体差异初探

以道地产区3个不同居群云黄连为研究材料,对不同单株不同部位(根茎、须根、叶)生物量及主要生物碱(小檗碱、药根碱、巴马汀)含量进行比较分析.结果表明:3个不同居群单株生物量及生物碱含量均存在较大个体差异,其中,单株根茎最稳定,叶次之,须根个体差异最大;作为非传统用药部位的叶和须根中的主要生物碱总量约占整株中将近1/3,可...     

对外跨国并购能否为中国企业创造价值?

以1995—2010年发生的275起中国公司海外并购为样本,采用事件研究法就对外跨国并购对中国并购方企业价值的影响进行了探究。研究发现并购公告发布前后中国并购方公司获得了正累计超额收益。细分发现,较小规模的公司和国有性质的公司相对于大规模公司和非国有公司超额收益更加显著;另外当并购方公司能够在跨国并购中获得目标公司的控制权时,累计超额收益更为显著。上述现象表明大型企业应当以更加谨慎理性的态度对待对外跨国并购,政府方面也应加强对民营企业对外跨国并购的监管和扶持力度。     

我国高等职业教育发展困境分析与对策

高等职业教育是我国高等教育事业的重要组成,大力发展高等职业教育是加快我国人力资源开发,提高人文素质,培养创新型、复合型人才的重要途径。通过对我国高等职业教育发展中存在问题的分析,进而提出了解决策略和建议,期待我国高职教育又快又好的健康发展。     

聚天冬氨酸修饰玻碳电极伏安法检测阿魏酸

通过在水溶液中直接电聚合的方法制备了聚天冬氨酸修饰玻碳电极.在pH为4.5,0.1 mol.L-1HAc-NaAc缓冲溶液中,修饰电极对阿魏酸表现出良好的吸附能力,显著地提高了阿魏酸的电信号强度.探讨了聚天冬氨酸修饰玻碳电极的作用机理,建立了阿魏酸的快速检测方法.在浓度为9.1×10-7～3.0×10-3mol.L-1范围内,阿魏酸的微分脉冲氧化峰电流与其浓度呈线性关系,检出限为3.1×10-7mol.L-1.此方法用于中成药逍遥丸中痕量阿魏酸的检测,回收率为97.9%～102.2%.     

上海建设海上人工岛及长江口亚三角洲体系的战略意义

近代上海的崛起,依靠的是地处我国弓箭型江海格局关节点的独特区位优势.在上海发展的历史轨迹中,有三个重要的交汇点:即苏州河与黄浦江、黄浦江与长江、长江与东海的汇合处.在第一个交汇点上,形成了以外滩为标志的近代繁华;在第二个交汇点处,包括宝钢、外高桥以及浦东新区,带动了上海改革开放30年的蓬勃发展;而第三个交汇点,就是浩瀚的长江口.