Loss of autophagy in the central nervous system causes neurodegeneration in mice

Protein quality-control, especially the removal of proteins with aberrant structures, has an important role in maintaining the homeostasis of non-dividing neural cells. In addition to the ubiquitin-proteasome system, emerging evidence points to the importance of autophagy--the bulk protein degradation pathway involved in starvation-induced and constitutive protein turnover--in the protein quality-control process. However, little is known about the precise roles of autophagy in neurons. Here we report that loss of Atg7 (autophagy-related 7), a gene essential for autophagy, leads to neurodegeneration. We found that mice lacking Atg7 specifically in the central nervous system showed behavioural defects, including abnormal limb-clasping reflexes and a reduction in coordinated movement, and died within 28 weeks of birth. Atg7 deficiency caused massive neuronal loss in the cerebral and cerebellar cortices. Notably, polyubiquitinated proteins accumulated in autophagy-deficient neurons as inclusion bodies, which increased in size and number with ageing. There was, however, no obvious alteration in proteasome function. Our results indicate that autophagy is essential for the survival of neural cells, and that impairment of autophagy is implicated in the pathogenesis of neurodegenerative disorders involving ubiquitin-containing inclusion bodies.     

HDACs link the DNA damage response, processing of double-strand breaks and autophagy

Protein acetylation is mediated by histone acetyltransferases (HATs) and deacetylases (HDACs), which influence chromatin dynamics, protein turnover and the DNA damage response. ATM and ATR mediate DNA damage checkpoints by sensing double-strand breaks and single-strand-DNA-RFA nucleofilaments, respectively. However, it is unclear how acetylation modulates the DNA damage response. Here we show that HDAC inhibition/ablation specifically counteracts yeast Mec1 (orthologue of human ATR) activation, double-strand-break processing and single-strand-DNA-RFA nucleofilament formation. Moreover, the recombination protein Sae2 (human CtIP) is acetylated and degraded after HDAC inhibition. Two HDACs, Hda1 and Rpd3, and one HAT, Gcn5, have key roles in these processes. We also find that HDAC inhibition triggers Sae2 degradation by promoting autophagy that affects the DNA damage sensitivity of hda1 and rpd3 mutants. Rapamycin, which stimulates autophagy by inhibiting Tor, also causes Sae2 degradation. We propose that Rpd3, Hda1 and Gcn5 control chromosome stability by coordinating the ATR checkpoint and double-strand-break processing with autophagy.     

人类HDAC4和MIF4GD蛋白相互作用的初步研究

以HDAC4为“诱饵”,利用酵母双杂交系统筛选人肝cDNA文库得到“猎物”蛋白,通过GST Pull-down,Co-IP,荧光共定位等技术验证HDACA和“猎物”的特异性结合,并通过成人多组织cDNAPanel确定“猎物”的组织表达谱．通过体内、外蛋白结合实验证实了HDACA与MIF4GD（MIF4G domaincontaining）蛋白特异性互作,且两者亚细胞共定位于细胞质内,并确定了MIF4GD在胎盘、肝脏和胰腺中有特异性表达．本实验发现并验证了HDACA与MIF4GD的特异性互作,并确定了MIF4GD的特异性表达谱,为深入研究两种蛋白的功能及其所参与的生理过程提供了新的线索．     

关于超立方体与Mbius立方体的连接

新型并行计算系统的研制依赖于对新型互连网络结构及其性质的研究.超立方体及其变型——Mbius立方体两者都具有优点,也具有缺点.本文给出了在超立方体与Mbius立方体的顶点之间的一种连接,从而得到一种称为HMm-立方体的新型网络,证明了HMn-立方体不仅保持了超立方体和Mbius立方体的低顶点度数和高连通度以及其直径至多比Mbius立方体大2的性质,而且它克服了超立方体对圈模拟能力的不足.     

IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling

Neural Wiskott-Aldrich syndrome protein (N-WASP) functions in several intracellular events including filopodium formation, vesicle transport and movement of Shigella frexneri and vaccinia virus, by stimulating rapid actin polymerization through the Arp2/3 complex. N-WASP is regulated by the direct binding of Cdc42 (refs 7, 8), which exposes the domain in N-WASP that activates the Arp2/3 complex. A WASP-related protein, WAVE/Scar, functions in Rac-induced membrane ruffling; however, Rac does not bind directly to WAVE, raising the question of how WAVE is regulated by Rac. Here we demonstrate that IRSp53, a substrate for insulin receptor with unknown function, is the 'missing link' between Rac and WAVE. Activated Rac binds to the amino terminus of IRSp53, and carboxy-terminal Src-homology-3 domain of IRSp53 binds to WAVE to form a trimolecular complex. From studies of ectopic expression, we found that IRSp53 is essential for Rac to induce membrane ruffling, probably because it recruits WAVE, which stimulates actin polymerization mediated by the Arp2/3 complex.     

凉山州用地与养地结合模式浅析

通过对凉山州不同地区、不同生产条件用地与养地模式的探讨,提出了应采取的农业耕作法则,总的目的是达到土地生产能力的持续稳定提高,为人类提供丰富的食品资源,满足人类生产、生活和社会发展的需求。     

变幅杆连接结构对超声能量传递效果的影响

旋转超声加工是加工硬脆材料的一种较好方法,要实现良好的旋转超声加工,必须设计满足多方面要求的超声振动系统,以实现超声能量传递的最大化。超声振动系统的变幅杆连接结构分为传统连接结构、锥面定位连接结构、两面定位连接结构。在理论分析的基础上,对3种连接结构的变幅杆超声能量传递效果进行了对比实验研究,结果表明:在相同的实验条件下,传统连接结构最有利于超声能量的传递,但兼顾超声能量传递和回转精度两方面指标,两面定位的变幅杆连接结构最为合理。     

关于大学英语与中学英语教学衔接的实证研究

针对目前大学英语与中学英语教学衔接脱节的情况,分别对一些中学生和大学生英语学习的动机、缺课原因、英语学习上缺乏成就感的主要原因、对中学阶段与大学阶段自身状况的评价、参与课堂教学情况以及整理、复习课堂笔记、课外学习情况等学生自身因素,以及对中学英语教师与大学英语教师的评价等教师因素进行了调查,并提出了做好大学英语与中学英语教学的衔接的具体措施。     

三种纳米材料C_(70),C_(60)Cl_6和C_(60)Ph_6引起细胞自噬的现象

为了进一步研究富勒烯家族及其衍生物引起细胞自噬的现象,运用荧光显微镜、透射电子显微镜、蛋白免疫印迹等技术,对水溶性的纳米C70,C60Cl6和C60Ph6诱导的细胞自噬现象进行了初步探讨.实验结果显示,C70,C60Cl6和C60Ph6稳定分散于水中形成的纳米颗粒,均能诱导HeLa细胞产生自噬现象,揭示了富勒烯家族及其衍生物在生物医药领域更广泛的研究和应用价值.     

Functional link between ataxia-telangiectasia and Nijmegen breakage syndrome gene products

Ataxia-telangiectasia (A-T) and Nijmegen breakage syndrome (NBS) are recessive genetic disorders with susceptibility to cancer and similar cellular phenotypes. The protein product of the gene responsible for A-T, designated ATM, is a member of a family of kinases characterized by a carboxy-terminal phosphatidylinositol 3-kinase-like domain. The NBS1 protein is specifically mutated in patients with Nijmegen breakage syndrome and forms a complex with the DNA repair proteins Rad50 and Mrel1. Here we show that phosphorylation of NBS1, induced by ionizing radiation, requires catalytically active ATM. Complexes containing ATM and NBS1 exist in vivo in both untreated cells and cells treated with ionizing radiation. We have identified two residues of NBS1, Ser 278 and Ser 343 that are phosphorylated in vitro by ATM and whose modification in vivo is essential for the cellular response to DNA damage. This response includes S-phase checkpoint activation, formation of the NBS1/Mrel1/Rad50 nuclear foci and rescue of hypersensitivity to ionizing radiation. Together, these results demonstrate a biochemical link between cell-cycle checkpoints activated by DNA damage and DNA repair in two genetic diseases with overlapping phenotypes.     

如何做好大学物理与中学物理教学的有效衔接

针对目前大学物理教学存在的现状,通过大学物理与中学物理在研究内容、研究对象、研究手段的对比研究,给出了大学物理与中学物理教学的有效衔接措施,使学生尽快地从中学物理学习过渡到大学物理学习。     

UPS网络控制和电压波形显示的研究

对目前在UPS方面研究的焦点问题作了阐述 ,并重点介绍了UPS网络控制系统的实现方法、系统功能和技术特点     

论柳永词作与宋初赋风的内在联系

论柳永词作与宋初赋风的内在联系@崔海正$济南大学中文系!山东济南250002 @刘培$山东大学文学院!山东济南250002     

A genetic link between co-suppression and RNA interference in C. elegans

Originally discovered in plants, the phenomenon of co-suppression by transgenic DNA has since been observed in many organisms from fungi to animals: introduction of transgenic copies of a gene results in reduced expression of the transgene as well as the endogenous gene. The effect depends on sequence identity between transgene and endogenous gene. Some cases of co-suppression resemble RNA interference (the experimental silencing of genes by the introduction of double-stranded RNA), as RNA seems to be both an important initiator and a target in these processes. Here we show that co-suppression in Caenorhabditis elegans is also probably mediated by RNA molecules. Both RNA interference and co-suppression have been implicated in the silencing of transposons. We now report that mutants of C. elegans that are defective in transposon silencing and RNA interference (mut-2, mut-7, mut-8 and mut-9) are in addition resistant to co-suppression. This indicates that RNA interference and co-suppression in C. elegans may be mediated at least in part by the same molecular machinery, possibly through RNA-guided degradation of messenger RNA molecules.     

A link between prompt optical and prompt gamma-ray emission in gamma-ray bursts

The prompt optical emission that arrives with the gamma-rays from a cosmic gamma-ray burst (GRB) is a signature of the engine powering the burst, the properties of the ultra-relativistic ejecta of the explosion, and the ejecta's interactions with the surroundings. Until now, only GRB 990123 had been detected at optical wavelengths during the burst phase. Its prompt optical emission was variable and uncorrelated with the prompt gamma-ray emission, suggesting that the optical emission was generated by a reverse shock arising from the ejecta's collision with surrounding material. Here we report prompt optical emission from GRB 041219a. It is variable and correlated with the prompt gamma-rays, indicating a common origin for the optical light and the gamma-rays. Within the context of the standard fireball model of GRBs, we attribute this new optical component to internal shocks driven into the burst ejecta by variations of the inner engine. The correlated optical emission is a direct probe of the jet isolated from the medium. The timing of the uncorrelated optical emission is strongly dependent on the nature of the medium.     

UPS监控及其状态数据库管理

随着计算机网络的发展,服务器的不间断运行已经成为了必然的要求,为此开发研制了智能UPS,可以单机或通过网络对于各节点UPS进行监控和管理.并且将UPS的状态记录在数据库中.该系统的研制过程中使用了VB作为工具,完成通过网络对串口设备的控制以及设备的状态数据库进行访问.