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.     

The development of a protoplanetary disk from its natal envelope

Class 0 protostars, the youngest type of young stellar objects, show many signs of rapid development from their initial, spheroidal configurations, and therefore are studied intensively for details of the formation of protoplanetary disks within protostellar envelopes. At millimetre wavelengths, kinematic signatures of collapse have been observed in several such protostars, through observations of molecular lines that probe their outer envelopes. It has been suggested that one or more components of the proto-multiple system NGC 1333-IRAS 4 (refs 1, 2) may display signs of an embedded region that is warmer and denser than the bulk of the envelope. Here we report observations that reveal details of the core on Solar System dimensions. We detect in NGC 1333-IRAS 4B a rich emission spectrum of H2O, at wavelengths 20-37 microm, which indicates an origin in extremely dense, warm gas. We can model the emission as infall from a protostellar envelope onto the surface of a deeply embedded, dense disk, and therefore see the development of a protoplanetary disk. This is the only example of mid-infrared water emission from a sample of 30 class 0 objects, perhaps arising from a favourable orientation; alternatively, this may be an early and short-lived stage in the evolution of a protoplanetary disk.     

光电混合式电流互感器的研究设计与实现

电流互感器是电力系统中的重要设备,光电混合式电流互感器避免了传统电流互感器的缺点,具有广泛的应用前景.对光电混合式电流互感器做了具体的分析,提出了一种系统设计方案,并详细介绍了方案的具体实现方法.整个系统方案具有可行性,可以达到预想的要求,具有高集成度、高处理速度、高可靠性以及良好的实时性等优点,在电力系统中具有一定的研究价值与应用价值.     

计算机化自适应诊断测验新的选题策略

提出了一种既能满足属性平衡又能有效处理相似属性模式的新方法——改进的极大化整体判别认知诊断模型信息量指标法(MGCDI).对无结构型的属性,讨论定长CD-CAT的选题策略.研究结果表明,使用相同选题策略选题时,先选择可达矩阵的所有列对应的项目比不使用这些项目的诊断准确率高.     

不同热解温度生物炭改良铅和镉污染土壤的研究

 为了探究热解温度对生物炭修复重金属污染土壤的影响,将300℃、500℃和700℃下制备的生物炭加入铅（Pb）和镉（Cd）污染土壤进行培养,检测重金属形态的变化。结果表明,加入生物炭培养60d后,Pb和Cd污染土壤pH值较对照上升0.35—0.86单位值,土壤中重金属的酸可提取态含量下降,残渣态含量上升,对目标重金属生物有效性降低的改良效果700℃>500℃>300℃;在生物炭添加量相同的情况下,复合污染土壤中Pb的残渣态含量比对应单一污染高50.60%—72.79%,而复合污染土壤中Cd的酸可提取态含量较对应单一污染高7.53%—12.99%;热解温度影响生物炭的表面特征和吸附重金属机制,进而影响生物炭改良土壤中目标重金属形态分布。     

Model evaluations for winter orographic clouds with observations

The Real-Time Four-Dimensional Data Assimilation (RT-FDDA) system is used for orographic snowpack enhancement.The model has three nested domains with the grid spacing of 18,6 and 2 km.To evaluate the simulations of winter orographic clouds and precipitation,comparisons are made between model simulations and observations to determine how the model simulates the cloud distribution,cloud height,cloud vertical profiles and snow precipitation.The simulated results of the 02:00 UTC cycling with 2-km resolution are used in the comparison.The observations include SNOTEL,ceilometer,sounding and satellite data,from the ground to air.The verification of these observations indicates that the Weather Research and Forecast (WRF) RT-FDDA system provides good simulations.It is better to use data within the forecast period of 2-16 h simulations.Although the horizontal wind component near the ground has some bias,and the simulated clouds are a little higher and have a little more coverage than observed,the simulated precipitation is a little weaker than observed.The results of the comparison show that the WRF RT-FDDA model provides good simulations and can be used in orographic cloud seeding.     

分光光度法检测不同地区和类型稻种功能性成分的初步研究

 为研究不同地区和类型水稻品种糙米中γ-氨基丁酸和总黄酮等功能性成分,本实验采用分光光度法准确测定了中国、日本、韩国、国际稻作所和云南品种及云南野生稻γ-氨基丁酸和总黄酮的含量.结果表明:① 用分光光度法测定水稻籽粒中γ-氨基丁酸和总黄酮含量的方法是可靠的;② 不同地区和类型水稻品种功能成分含量存在差异;③ 相关分析表明,氨基丁酸与总黄酮的相关系数较高(r=0.575^**),在育种上可以实现多个相关性状间的遗传改良;④ 鉴定出墨江黄皮饵块谷、明恢86、墨江饵块谷、疣粒野生稻等18份高GABA和高总黄酮的水稻品种,可作为选育高黄酮和γ-氨基丁酸品种的亲本或直接作为功能稻开发利用.首次报道疣粒野生稻总黄酮质量分数达0.751%,在所有水稻品种中黄酮含量最高.     

基于块背景建模的运动目标检测

运动目标检测是计算机视觉中目标识别、目标跟踪和场景理解的前提.文中提出一种基于块的混合高斯背景建模方法,采用图像块的均值和块内方差作为块的特征对场景进行建模,并对前景块根据它的邻域块处理以得到更精确的目标区.新方法不仅考虑了像素在时间域上的分布信息,还利用了像素邻域间的信息消除虚警数,改善了传统混合高斯背景建模方法处理...     

新弱化缓冲算子的构造及其运用

将已有的弱化缓冲算子进行一些简单的数学运算后构造出新的弱化缓冲算子.在预测工作中如果系统行为数据出现前阶段增长(衰减)速度过快而后阶段增长(衰减)速度过慢的,以文章所构造的弱化缓冲算子再建模预测能使预测精度有显著提高,预测值也能更好的逼近观测值.     

论建筑工程的施工管理对成本核算的重要性

文章对工民建工程的施工管理到成本核算进行了较为完整的阐述,对当前工民建工程施工管理现状及存在的问题进行了分析、对比,并结合实际提出了管理的相关措施,阐述了从施工管理上下功夫对降低成本是一种有效的方法。