Crystal structure of a voltage-gated sodium channel in two potentially inactivated states

In excitable cells, voltage-gated sodium (Na(V)) channels activate to initiate action potentials and then undergo fast and slow inactivation processes that terminate their ionic conductance. Inactivation is a hallmark of Na(V) channel function and is critical for control of membrane excitability, but the structural basis for this process has remained elusive. Here we report crystallographic snapshots of the wild-type Na(V)Ab channel from Arcobacter butzleri captured in two potentially inactivated states at 3.2?? resolution. Compared to previous structures of Na(V)Ab channels with cysteine mutations in the pore-lining S6 helices (ref. 4), the S6 helices and the intracellular activation gate have undergone significant rearrangements: one pair of S6 helices has collapsed towards the central pore axis and the other S6 pair has moved outward to produce a striking dimer-of-dimers configuration. An increase in global structural asymmetry is observed throughout our wild-type Na(V)Ab models, reshaping the ion selectivity filter at the extracellular end of the pore, the central cavity and its residues that are analogous to the mammalian drug receptor site, and the lateral pore fenestrations. The voltage-sensing domains have also shifted around the perimeter of the pore module in wild-type Na(V)Ab, compared to the mutant channel, and local structural changes identify a conserved interaction network that connects distant molecular determinants involved in Na(V) channel gating and inactivation. These potential inactivated-state structures provide new insights into Na(V) channel gating and novel avenues to drug development and therapy for a range of debilitating Na(V) channelopathies.     

以资源节约促进生态文明

当前我国正处在工业化和城市化发展的加快时期,对资源和能源的需求不断增加,因此环境污染也日益严重。只有重视资源节约,减少和消除经济发展对环境的破坏,实现可持续发展,推动绿色GDP的增长,才能切实促进生态文明的建设。     

利用8098单片机的热电偶参比端温度的全补偿方法

本文介绍在采用微机来进行热电偶测温处理时,通过查表的方法实现参比端温度的完全补偿,并完成热电势到温度的处理。     

胰岛素缓控释制剂的研究进展

糖尿病是目前患病率较高的疾病,皮下注射胰岛素是治疗糖尿病的主要方法.天然胰岛素属于多肽蛋白类药物,体内半衰期较短,维持长时间的稳态血药浓度,需要频繁给药,患者的顺应性低.将胰岛素包封在生物相容性好的材料中制成微球或原位植入系统,可在注射部位缓慢持续释放胰岛素,减少注射给药的次数,增加患者的依从性.分析了目前胰岛素注射缓控释制剂的设计思路及相关研究进展.     

Dual effects of spatial updating in both real and virtual environments

When people move around in their environment, spatial updating, which is an automatic cognitive process, is essential to ensuring people can keep track of their relations between them and the surrounding objects, and to "recalculating" the relative position and orientation of those objects with regard to the current position of the persons. Despite the facilitating effect of spatial updating to people’s mental representation in most circumstances as demonstrated in most of the existing literature, the effect sometimes can be adversarial. For instance, some research suggested that even though people were asked to ignore their locomotion, it is difficult to suppress updating of the spatial representation during movement. The current two studies were conducted to systematically investigate the dual effects of spatial updating in both real and virtual environments. We used a typical spatial updating paradigm to explore the effects of scene familiarity (familiar vs. novel) and person’s locomotion (stationary vs. moving) on change detection accuracy (target object moved or not). The results indicated a facilitating effect of spatial updating in the novel scene condition, but an adversarial effect in the familiar scene condition-the dual effects, in both real and virtual environments.     

船舶上层建筑纵向振动固有频率估算

在参考了当的国内外常用的上层建筑纵向振动固有频率估算公式的基础上，运用统计回归和力学分析相结合的方法，提出了一个新的上层建筑纵向振动固有频率公式。该公式能够较全面的反映出影响上层建筑纵向振动的各种主要因素，不仅考虑剪切影响，而且还考虑回转影响。经对多条船上层建筑激振试验验证，用本文公式计算出上层建筑纵向振动固有频率与实测值接近，可满足工程上计算精度要求。本文公式可供船舶方案设计阶段使用。     

弹塑性边界元中强奇异积分的一种新的计算方法

采用边界元法分析弹塑性问题时,需要解决塑性域剖分单元上的强奇异积分汁算问题。本文以二维问题为例,建议一种任意等参体单元上强奇异积分的新的计算方法。其主要原理是引入一种恒等分解,使含强奇异部分的积分与坐标变换无关。利用基本解性质,该积分的奇异性可以消除并可降阶,本文的方法是半解析的,计算精度高。方法的基本思想普遍适用于任意二维和三维等参体单元。     

方便、实用的免费电子邮件

以Ｈｏｔｍａｉｌ公司免费电子邮件为例,介绍了免费电子邮件的申请、收发和管理等问题     

Lymphotactin enhances the in-vitro immune efficacy of dendritoma formed by dendritic cells and mouse hepatocellular carcinoma cells

Objective: To investigate the in-vitro antitumor immune responses of dendritoma formed by mouse hepatocellular carcinoma (HCC) cells and lymphotactin (Lptn) gene modified dendritic cells (DCs). Method: DCs prepared from mouse bone marrow were genetically modified by lymphotactin adenovirus, and fused with H22 cells by polyethylene glycol (PEG). RT-PCR and ELISA were employed to identify lymphotactin expression at mRNA and protein level. Cell phenotypes and fusion efficiency was detected by FACS. The stimulatory effect of DC on T cells was detected by mixed lymphocyte reaction. The cytotoxicity activity against H22 cells was assayed by LDH method. Results: Lymphotactin could be efficiently expressed by DCLptn/H22 hybridoma. DCLptn/H22 cells could induce potent T cell proliferation effect and generate strong cytotoxic T lymphocyte (CTL) reaction against allogenic H22 cells. Conclusion: Lymphotactin genetic modification could enhance the in vitro immune activity of the dendritoma.     

SEM analysis of the changes of carbon layer structure of mesocarbon microbeads heat-treated at different temperatures

Mesocarbon microbeads (MCMB) with narrow size distribution, excellent sphericity and no obvious conglutination have been prepared with a coal tar pitch containing quinoline insolubles (QI) as the raw material. Optical microscopy and scanning electron microscopy (SEM) are used to examine the structure of the MCMB. It has been found that SEM technique shows the structural information of MCMB clearly in the form of micrographs even when the structure of MCMB is complex, while the optical technique is useful for analysis of the regular structure of the mesophase spheres but cannot be effectively used to analyze either the complex structure of the green MCMB or the structures of the further heat-treated ones at different temperatures. According to the characteristics of the carbon layers, the structures of the as-prepared MCMB in the present experiment could be classified as (I) Parallel Layer type structure and (2) Bent Layer type structure with the carbon layers gathering at one or two points in the MCMB. In the experiments, SEM is also utilized to investigate the structures of MCMB that are heat-treated at different temperatures. It has been found that the MCMB without any further heat-treatment show no layered-carbons, while the ones heat-treated at temperaturehigher than 1000℃ exhibit obvious layered carbons across their sections. When increasing the heat-treatment temperature, the carbon layers become thinner and flatter.