The LRRK2 G2019S mutant exacerbates basal autophagy through activation of the MEK/ERK pathway

Mutations in leucine-rich repeat kinase 2 (LRRK2) are a major cause of familial Parkinsonism, and the G2019S mutation of LRRK2 is one of the most prevalent mutations. The deregulation of autophagic processes in nerve cells is thought to be a possible cause of Parkinson’s disease (PD). In this study, we observed that G2019S mutant fibroblasts exhibited higher autophagic activity levels than control fibroblasts. Elevated levels of autophagic activity can trigger cell death, and in our study, G2019S mutant cells exhibited increased apoptosis hallmarks compared to control cells. LRRK2 is able to induce the phosphorylation of MAPK/ERK kinases (MEK). The use of 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene (U0126), a highly selective inhibitor of MEK1/2, reduced the enhanced autophagy and sensibility observed in G2019S LRRK2 mutation cells. These data suggest that the G2019S mutation induces autophagy via MEK/ERK pathway and that the inhibition of this exacerbated autophagy reduces the sensitivity observed in G2019S mutant cells.     

Hormonal control of Sertoli cell metabolism regulates spermatogenesis

Hormonal regulation is essential to spermatogenesis. Sertoli cells (SCs) have functions that reach far beyond the physical support of germ cells, as they are responsible for creating the adequate ionic and metabolic environment for germ cell development. Thus, much attention has been given to the metabolic functioning of SCs. During spermatogenesis, germ cells are provided with suitable metabolic substrates, in a set of events mediated by SCs. Multiple signaling cascades regulate SC function and several of these signaling pathways are hormone-dependent and cell-specific. Within the seminiferous tubules, only SCs possess receptors for some hormones rendering them major targets for the hormonal signaling that regulates spermatogenesis. Although the mechanisms by which SCs fulfill their own and germ cells metabolic needs are mostly studied in vitro, SC metabolism is unquestionably a regulation point for germ cell development and the hormonal control of these processes is required for a normal spermatogenesis.     

一类非单调关联系统的率模可靠性分析

实际的生产和生活中存在着大量的非单调关联系统 ,对其进行可靠性分析就需要有相应的非单调关联系统理论支持 ,现有的率模 (probabilityandfuzzystate ,Profust)可靠性理论仅仅对单调关联系统进行了讨论。因此 ,首先建立了Profust非单调关联系统的相关理论 ,然后针对一类典型的非单调关联系统 (“n中取r至s”系统 )进行了具体的可靠性分析 ,从而在非单调关联系统领域对蔡的Profust可靠性理论进行了进一步的确证和推广     

中国芯片发展现状（四）

阐述了我国芯片产业的现状，介绍了我国自行研制开发的光子芯片、“神芯”芯片、“华厦网芯”、IC卡芯片、3G手机芯片的用途、性能和发展前景。     

供应链中二级分销网络优化设计的随机规划模型

给出供应链中二级分销网络优化设计的机会约束规划模型。模型中将各个分销中心的需求量和各工厂的生产能力设为随机参数，并进一步讨论如何将模型中的机会约束转化为确定性等价类问题。     

Study of the mechanism of inhibition produced by hexoses on histamine release activity of dextran

Zusammenfassung Die Hemmung der Histaminfreisetzung durch Hexosen wurde untersucht. Es gelang, nachzuweisen bzw. graphisch darzustellen, dass ein Zusammenhang zwischen dem Prozentgehalt der Histaminfreisetzung und der Dextrankonzentration besteht, wenn nachLineweaver undBurk analysiert wurde.     

Model of the interaction between trypsin and alpha 2-macroglobulin of porcine serum]

A comparative study of the dissociation into subunits of Porcine alpha2 M, either native or bound to trypsin (Tn), has been carried out in order to determine the modifications of the alpha2 M structure due to the formation of the Tn-alpha2 M complex. Analytical ultra-centrifugation at pH 3.5 shows that the dissociation is smaller when alpha 2 M is bound to trypsin. Electrophoresis in 4% polyacrylamide gels, in presence of 0.1% SDS, of alpha2 M and Tn-alpha2 M incubated in 1% SDS leads to the same conclusion; the enzyme must stabilize the quaternay structure of alpha2 M. In presence of SDS + beta-mercaptoethanol, only a molecular weight (M.W.) 200,000 band is revealed in electrophoresis pattern of native alpha2 M. In the case of reduced Tn-alpha2 M, some other bands of M.W. 100,000, 50,000, 30,000 appear. When trypsin is inactivated by TLCK 100,000 M.W. band is present, accompanied by the 200,000 M.W. band whose intensity is function of the alpha2 M concentration. The 100,000 M.W. band appears therefore characteristic of the formation of the complex which must imply a proteolytic cleavage in the middle of the 100,000 polypeptidic chain of alpha2 M. A model of the complex is proposed in which the enzyme forms a proteic bridge between the two halves of the alpha2 M molecule.