Phospholipids and the origin of cationic gating charges in voltage sensors

Cells communicate with their external environment through physical and chemical processes that take place in the cell-surrounding membrane. The membrane serves as a barrier as well as a special environment in which membrane proteins are able to carry out important processes. Certain membrane proteins have the ability to detect the membrane voltage and regulate ion conduction or enzyme activity. Such voltage-dependent processes rely on the action of protein domains known as voltage sensors, which are embedded inside the cell membrane and contain an excess of positively charged amino acids, which react to an electric field. How does the membrane create an environment suitable for voltage sensors? Here we show under a variety of conditions that the function of a voltage-dependent K+ channel is dependent on the negatively charged phosphodiester of phospholipid molecules. A non-voltage-dependent K+ channel does not exhibit the same dependence. The data lead us to propose that the phospholipid membrane, by providing stabilizing interactions between positively charged voltage-sensor arginine residues and negatively charged lipid phosphodiester groups, provides an appropriate environment for the energetic stability and operation of the voltage-sensing machinery. We suggest that the usage of arginine residues in voltage sensors is an adaptation to the phospholipid composition of cell membranes.     

Removal of phospho-head groups of membrane lipids immobilizes voltage sensors of K+ channels

A fundamental question about the gating mechanism of voltage-activated K+ (Kv) channels is how five positively charged voltage-sensing residues in the fourth transmembrane segment are energetically stabilized, because they operate in a low-dielectric cell membrane. The simplest solution would be to pair them with negative charges. However, too few negatively charged channel residues are positioned for such a role. Recent studies suggest that some of the channel's positively charged residues are exposed to cell membrane phospholipids and interact with their head groups. A key question nevertheless remains: is the phospho-head of membrane lipids necessary for the proper function of the voltage sensor itself? Here we show that a given type of Kv channel may interact with several species of phospholipid and that enzymatic removal of their phospho-head creates an insuperable energy barrier for the positively charged voltage sensor to move through the initial gating step(s), thus immobilizing it, and also raises the energy barrier for the downstream step(s).     

银杏叶的药理及临床应用

银杏叶作为传统植物药具有润肺、平喘、止咳之功效.自20世纪60年代起,国内外学者对银杏叶进行了大量研究.近年来,中药银杏叶对冠心病、心绞痛、大脑退化及心血管疾病引起的脑功能障碍、老年痴呆等症有确切疗效,引起医药界的广泛关注,各种研究成果常见于诸报刊.就国内外关于中药银杏叶药理作用及临床应用方面的研究进展做了总结性的综述.并就中药银杏叶的深入开发的前景进行讨论.     

高校信息系统建设中的兼容性和可移植性策略研究

从操作系统、数据库、应用服务器、业务流程等几个方面,讨论了在高校信息系统建设中的兼容性和可移植性策略,并结合复旦大学虚拟校园系统实例进行了分析和实践.     

猪用饲喂器拨片式供料装置机理分析与参数优化

为提高我国生猪养殖业应用的饲喂器的工作性能,对设计的一种猪用饲喂器拨片式供料装置进行了机理分析与试验.通过对其主要结构的理论分析以及离散元模拟仿真,确定杆绳斜置式破拱单元和拨片式排料单元的结构.在实现稳定排料基础上,以影响其排料性能的主要因素为试验因素,以排料速率和排料均匀性(以变异系数表示)为评价指标进行三因素五水平二次回归正交旋转组合试验,获得最优参数组合.试验结果表明:杆绳斜置式破拱单元实现了料斗内颗粒饲料连续、稳定排料;在填充率为80％,且拨片转速为55.5 r·min-1、出口间距为14.5 mm、排料段最大后倾角为31.5°时,对应排料速率和变异系数分别为166.75 g·s-1和4.39％;饲槽内颗粒饲料分布均匀,饲喂器排料性能较佳.     

Integrin cytoplasmic tyrosine motif is required for outside-in alphaIIbbeta3 signalling and platelet function.

Integrins not only bind adhesive ligands, they also act as signalling receptors. Both functions allow the integrin alphaIIbbeta3 to mediate platelet aggregation. Platelet agonists activate alphaIIbbeta3 (inside-out signalling) to allow the binding of soluble fibrinogen. Subsequent platelet aggregation leads to outside-in alphaIIbbeta3 signalling, which results in calcium mobilization, tyrosine phosphorylation of numerous proteins including beta3 itself, increased cytoskeletal reorganisation and further activation of alphaIIbbeta3. Thus, outside-in signals enhance aggregation, although the mechanisms and functional consequences of specific signalling events remain unclear. Here we describe a mouse that expresses an alphaIIbbeta3 in which the tyrosines in the integrin cytoplasmic tyrosine motif have been mutated to phenylalanines. These mice are selectively impaired in outside-in alphaIIbbeta3 signalling, with defective aggregation and clot-retraction responses in vitro, and an in vivo bleeding defect which is characterized by a pronounced tendency to rebleed. These data provide evidence for an important role of outside-in signalling in platelet physiology. Furthermore, they identify the integrin cytoplasmic tyrosine motif as a key mediator of beta-integrin signals and a potential target for new therapeutic agents.     

消除电压互感器二次回路压降问题的方法

为了解决电力系统中电压互感器的二次回路压降问题,提出一种从原理上能够彻底解决该问题的方法。该方法通过将电压互感器的二次输出端电压进行就地数字化处理,并将电信号转换成光信号,采用光纤作为传输媒质将该信息传输至控制室,在控制室再将光信号转变为电信号,供二次电力设备使用。试验结果表明:就地数字化装置在80%~120%额定电压下,比差小于0.01%,角差小于±2;′通过与标准电压互感器的对比试验,验证了该方法的有效性,为解决电压互感器二次回路压降问题提供了一种方法。     

电力系统静态电压稳定的三维分析与临界电压

从统一关联的角度,重新审视静态电压稳定的机理,并以图形的方式加以直观解释,获得静态电压稳定判据.通过三维图形分析,指出静态电压稳定是由电源侧特性与负荷侧特性共同决定的,各种二维平面分析可以统一到三维空间中.     

三柱式倍压整流在高压电源中的应用

介绍高压电源的设计方法 ,阐述了高压电源中采取的几种措施 ,分析了应用电路 .     

称重传感器弹性体的分析与研究

运用材料力学理论和有限元法,分析某型号称重传感器弹性体的应变位移。用间接法测定数据,通过对比得到:材料力学理论在求解空间结构的弹性体应变时存在缺陷,计算结果误差比较大,而有限元解却接近真实解。利用ANSYS Workbench优化设计模块,发现改变孔径尺寸就可迅速设计出系列产品,节约成本,提高效率。     

药理学课堂教学形式及方法问卷调查分析

目的了解各专业医学生对药理学课堂教学形式及方法的要求,以便在今后教学过程中选择合适的教学方法及形式,提高教学效果和教学质量.方法对井冈山学院医学院2004级各专业568名学生进行了问卷.结果绝大多数学生希望药理学课堂教学时,教师能根据教学内容联系临床有关问题进行讲授并分析讨论.结论改革传统课堂教学形式及方法,可激发学生学习药理学的兴趣,有效调动学生学习的积极性和主动性.     

药理学课堂教学形式及方法问卷调查分析

目的了解各专业医学生对药理学课堂教学形式及方法的要求,以便在今后教学过程中选择合适的教学方法及形式,提高教学效果和教学质量.方法对井冈山学院医学院2004级各专业568名学生进行了问卷.结果绝大多数学生希望药理学课堂教学时,教师能根据教学内容联系临床有关问题进行讲授并分析讨论.结论改革传统课堂教学形式及方法,可激发学生学习药理学的兴趣,有效调动学生学习的积极性和主动性.     

BD-FACS Calibur流式细胞仪在药理学中的应用与管理

流式细胞仪(flow cytometry,FCM)是采用激光束激发单行流动的细胞,对它的散射光和携带的或自发的荧光强度进行探测,从而完成细胞分析和分选的重要仪器。结合工作实际,从分析FCM在药理学中的应用入手,探讨实验中心大型仪器的科学管理问题。在管理上引入统一、有偿、共享等方式,重视操作人员的培训,将有利于充分发挥大型仪器的作用,使之更好地服务于教学、科研和社会。     

禾谷炭疽菌效应分子motif序列研究

禾谷炭疽菌侵染玉米、小麦等粮食作物而引起的炭疽病,给各国农业生产造成了巨大经济损失。植物病原菌可以利用效应分子来操控寄主植物的防卫反应,从而实现其对植物的侵染、定殖和扩展等过程。研究基于前人对禾谷炭疽菌中已报道的177个候选效应分子(CE)的氨基酸数据,利用MEME对全部CE和不同氨基酸类别的CE进行在线motif分析,未获得较满意结果。随后,结合已报道效应分子(E)所具有保守motif的氨基酸位置范围,对82个具有典型特征E的信号肽序列后30~60 aa进行获取,并将信号肽位置大于28、氨基酸数量较小的E进行剔除,最终明确64个E存在着保守的PAAX motif。该研究丰富了真菌保守motif的类型,为进一步开展禾谷炭疽菌效应分子的motif功能研究提供重要的理论指导。     

甘草多糖的化学与药理研究

综述了甘草多糖的提取方法、化学组分、药理作用等方面的研究进展.现代提取方法较传统方法简便快捷,甘草多糖产量高,且不会影响多糖的结构和活性.研究表明,甘草多糖主要由鼠李糖、葡聚糖、阿拉伯糖和半乳糖组成,但其主链结构的研究结论不尽相同.药理研究发现,甘草多糖具有免疫调节、抗肿瘤、抗病毒等作用,而且无细胞毒作用.     

细胞光电型传感器及其在毒性评价中的应用

20世纪60年代以来,体外细胞培养技术不断成熟,体外细胞毒性评价由于实验周期短、成本低和毒性机制易于探明等优点得到快速发展。当前对体外培养的细胞系的性质检测手段也是多种多样,其中细胞活性检测法是最常见的方法之一。对当今比较主流且研究较为广泛的光电型细胞传感器的类型及应用进行综述,主要包括电流型细胞传感器、阻抗型细胞传感器、电位型细胞传感器和光学细胞传感器。     

Sweep Coverage中的节点移动控制

作为无线传感器网络中一种新的覆盖类型,Sweep Coverage与其他覆盖类型相比,可以使用较少的节点满足特定区域的监控需求.为了改进Sweep Coverage机制的性能,本文以Vehicle Routing Problem with Time Windows问题的模型,对Sweep coverage问题进行了分析,提出了一种基于模拟退火算法的Sweep Coverage机制(VRP-Sweep).实验结果表明,在相同的网络场景下,VRP-Sweep机制较以往的Sweep Coverage机制取得更好的性能表现.