The role of presenilin cofactors in the gamma-secretase complex

Mutations in presenilin genes account for the majority of the cases of the familial form of Alzheimer's disease (FAD). Presenilin is essential for gamma-secretase activity, a proteolytic activity involved in intramembrane cleavage of Notch and beta-amyloid precursor protein (betaAPP). Cleavage of betaAPP by FAD mutant presenilin results in the overproduction of highly amyloidogenic amyloid beta42 peptides. gamma-Secretase activity requires the formation of a stable, high-molecular-mass protein complex that, in addition to the endoproteolysed fragmented form of presenilin, contains essential cofactors including nicastrin, APH-1 (refs 15-18) and PEN-2 (refs 16, 19). However, the role of each protein in complex formation and the generation of enzymatic activity is unclear. Here we show that Drosophila APH-1 (Aph-1) increases the stability of Drosophila presenilin (Psn) holoprotein in the complex. Depletion of PEN-2 by RNA interference prevents endoproteolysis of presenilin and promotes stabilization of the holoprotein in both Drosophila and mammalian cells, including primary neurons. Co-expression of Drosophila Pen-2 with Aph-1 and nicastrin increases the formation of Psn fragments as well as gamma-secretase activity. Thus, APH-1 stabilizes the presenilin holoprotein in the complex, whereas PEN-2 is required for endoproteolytic processing of presenilin and conferring gamma-secretase activity to the complex.     

Reactions of Benzo[ b ]cyclobuta[ d ]pyran-3-one Derivatives with Sulfur Ylide

1 Introduction Small ring size cycloalkanes such as cyclopropanes and cyclobutanes have been found as a basic structural constituent in a wide rang of natural products~([1]). In organic synthesis, their cycloalkanes also play an important role owing to their diversity of reaction.1IntroductionSmall ring size cycloalkanes such as cyclopropanes and cyclobutanes have beenfound as a basic structuralconstituent in a wide rang of natural products[1].In organic synthesis ,their cycloalkanes also pla…     

Development of thermodynamic and kinetic databases in micro-soldering alloy systems and their applications

Recent progress in the development of thermodynamic and kinetic databases of micro-soldering alloys,which were constructed within the framework of the Thermo-Calc and DICTRA software,was presented.Especially,a thermodynamic tool, ADAMIS(alloy database for micro-solders) was developed by combining the thermodynamic databases of micro-solders with Pandat,a multi-component phase diagram calculation software program.ADAMIS contains 11 elements,namely,Ag,Al,Au,Bi,Cu, In,Ni,Sb,Sn,Zn and Pb,and can handle all c...     

Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human

Free fatty acids provide an important energy source as nutrients, and act as signalling molecules in various cellular processes. Several G-protein-coupled receptors have been identified as free-fatty-acid receptors important in physiology as well as in several diseases. GPR120 (also known as O3FAR1) functions as a receptor for unsaturated long-chain free fatty acids and has a critical role in various physiological homeostasis mechanisms such as adipogenesis, regulation of appetite and food preference. Here we show that GPR120-deficient mice fed a high-fat diet develop obesity, glucose intolerance and fatty liver with decreased adipocyte differentiation and lipogenesis and enhanced hepatic lipogenesis. Insulin resistance in such mice is associated with reduced insulin signalling and enhanced inflammation in adipose tissue. In human, we show that GPR120 expression in adipose tissue is significantly higher in obese individuals than in lean controls. GPR120 exon sequencing in obese subjects reveals a deleterious non-synonymous mutation (p.R270H) that inhibits GPR120 signalling activity. Furthermore, the p.R270H variant increases the risk of obesity in European populations. Overall, this study demonstrates that the lipid sensor GPR120 has a key role in sensing dietary fat and, therefore, in the control of energy balance in both humans and rodents.     

双臂移动机器人的图形化编程与仿真控制系统

介绍一种双臂移动机器人的图形化编程与仿真控制系统。用户通过图形编程界面对机器人编程和任务规划，在三维仿真环境中预宽和分析规划结果，最后将优化程序下载到真实机器人中进行控制。采用Java3D和VRML实现三维仿真；基于RT-Linux平台保证仿真控制的实时性；实现了多机器人机制以支持机器人的流水线协作。该系统现在支持日本安川电机株式会社的双臂移动机器人产品。     

冶金反应器内三维流动模拟计算软件及应用

介绍了一个自行开发，用于冶金反应器过程模拟的三维计算软件ＴＰＳ－３Ｄ的基本设计原理、构成和求解技术及在吹氩精炼钢包中的应用情况。     

基于关联规则的ABC库存分类方法

库存管理是工业工程中普遍存在的基础管理,由于库存项目繁多,一般需要进行有重点的分类管理.ABC分类法一直被广泛应用于很多场合,其基础是将库存项目按照某类价值进行由高到低的排序,然后根据2-8原则分段划分ABC类型.然而,商品项目的价值不仅仅来源其自身的销售价值,还受到其它项目的影响,如"交叉销售"效应(cross-sal e effect).本文研究了在考虑交叉销售效应影响下的项目重要度评价问题,给出了一种基于关联规则的项目重要度评价指标,称为"期望金额占用",并在此基础上给出了新的库存 ABC分类方法.通过简单算例和benchmark数据集的计算,验证了算法的效率和效果.实验计算表明,新算法下的分类结果与传统ABC分类结果之间存在着不可忽略的较大差异.     

Calculation of the self-formation driving force for composite microstructure in liquid immiscible alloy system

Using Becker's method, we calculate the interfacial energy between two liquid phases in an immiscible system. Based on the Gibbs-Thomson equation, the force acting on the droplet towards the thermal center can be obtained by integrating the interfacial energy between the droplet and matrix liquid phase, which is related to both the radius of a droplet and the temperature gradient. In addition, the forces of gravitation and buoyancy also act on the droplet. The calculated results indicate that the resultant for these forces together mainly decides the microstructure morphology of the solidified alloy. The calculated results are in good agreement with the corresponding experimental results.