Granzyme B is recovered by natural killer cells via clathrin-dependent endocytosis

When they recognize a target cell, natural killer (NK) cells mount an attack to kill the target by exerting their cytotoxicity via the exocytosis of cytotoxic granules. Although the details of this process (which includes the movement of cytotoxic granules in the immune synapse and their fusion with the plasma membrane, releasing granzymes and perforin into the synaptic cleft) are relatively better understood, the post-exocytosis regulation of the process is still largely unknown. Here we show that a clathrin-dependent endocytosis stimulated by target cell occurs in NK92 cell line, which is closely correlated with granzyme B recovery. Inhibition of the endocytosis significantly attenuates the cytotoxicity of NK92 cells. The NK cell recovery of its released effector molecules, in turn, suggests that endocytosis may well play a key role in the post exocytosis regulation of immune cells.     

A genome-wide association study in Han Chinese identifies new susceptibility loci for ankylosing spondylitis

To identify susceptibility loci for ankylosing spondylitis, we performed a two-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 1,356,350 autosomal SNPs in 1,837 individuals with ankylosing spondylitis and 4,231 controls; in the validation stage, we analyzed 30 suggestive SNPs in an additional 2,100 affected individuals and 3,496 controls. We identified two new susceptibility loci between EDIL3 and HAPLN1 at 5q14.3 (rs4552569; P = 8.77 × 10(-10)) and within ANO6 at 12q12 (rs17095830; P = 1.63 × 10(-8)). We also confirmed previously reported associations in Europeans within the major histocompatibility complex (MHC) region (top SNP, rs13202464; P < 5 × 10(-324)) and at 2p15 (rs10865331; P = 1.98 × 10(-8)). We show that rs13202464 within the MHC region mainly represents the risk effect of HLA-B*27 variants (including HLA-B*2704, HLA-B*2705 and HLA-B*2715) in Chinese. The two newly discovered loci implicate genes related to bone formation and cartilage development, suggesting their potential involvement in the etiology of ankylosing spondylitis.     

Cdk5 targets active Src for ubiquitin-dependent degradation by phosphorylating Src(S75)

The non-receptor tyrosine kinase Src is a critical regulator of cytoskeletal contraction, cell adhesion, and migration. In normal cells, Src activity is stringently controlled by Csk-dependent phosphorylation of Src(Y530), and by Cullin-5-dependent ubiquitinylation, which affects active Src(pY419) exclusively, leading to its degradation by the proteosome. Previous work has shown that Src activity is also limited by Cdk5, a proline-directed kinase, which has been shown to phosphorylate Src(S75). Here we show that this phosphorylation promotes the ubiquitin-dependent degradation of Src, thus restricting the availability of active Src. We demonstrate that Src(S75) phosphorylation occurs in vivo in epithelial cells, and like ubiquitinylation, is associated only with active Src. Preventing Cdk5-dependent phosphorylation of Src(S75), by site-specific mutation of S75 or by Cdk5 inhibition or suppression, increases Src(Y419) phosphorylation and kinase activity, resulting in Src-dependent cytoskeletal changes. In transfected cells, ubiquitinylation of Src(S75A) is about 35% that of wild-type Src-V5, and its half-life is approximately 2.5-fold greater. Cdk5 suppression leads to a comparable decrease in the ubiquitinylation of endogenous Src and a similar increase in Src stability. Together, these findings demonstrate that Cdk5-dependent phosphorylation of Src(S75) is a physiologically significant mechanism of regulating intracellular Src activity.     

大宁河两种小型鱼类个体和器官代谢率的比较

[目的]考察三峡库区两种小型鲤科(Cyprinidae)鱼类的个体和器官代谢率.[方法]对大宁河水域分布的红尾副鳅(Paracobitis variegatus)和云南盘鮈(Discogobio yunnanensis)的体质量、器官质量、个体代谢率和器官代谢率进行测定和比较.[结果]在校正体质量后,红尾副鳅在个体静止...     

复合土钉墙中搅拌桩对变形及土钉拉力的影响

复合土钉墙中的水泥搅拌桩对于减小基坑水平位移、改善土钉的受力状态有重要作用,但目前对于搅拌桩在复合土钉墙中这一作用的研究多局限在定性探讨,未进行较为量化的分析,在复合土钉墙的设计中也一般将搅拌桩作为安全储备.文中通过对复合土钉墙的有限元分析,对复合土钉墙中不同搅拌桩排数、长度及不同土层情况进行了对比研究.结果表明,设置不同排数的搅拌桩对于复合土钉墙的受力机理、变形特性、土钉拉力大小及分布均有较大影响,1~2排搅拌桩较为合理,过多的搅拌桩排数可能会导致复合土钉墙出现重力式挡墙的受力、变形性态,增加上部土钉的拉力.     

土的地震液化概率评估模型

基于278个土的地震液化或非液化实测数据,运用二元回归方法推导出两个对数模型.这两个模型将液化概率表示成地震荷载和土阻力参数的函数,以修正的标准贯入锤击数来量度土的抗液化能力.文中将所提出的对数模型与确定性液化判别标准进行了比较,并将模型应用于典型场地的分析.结果表明,所提出的两个对数模型能客观地评价数据中的相关信息,可直接量化基于统计数据的条件液化概率.     

DRD1基因敲除影响雄鼠生育的分子机理研究

目的 研究DRD1基因敲除引起雄鼠生殖功能下降的机制.方法 本研究以DRD1基因敲除鼠(KO)和野生鼠(WT)为研究对象,对8周龄KO与WT雄鼠进行基因型鉴定,测体质量并计算睾丸系数,一侧睾丸HE染色观察形态,另一侧睾丸TRIzol法提取RNA,通过qRT-PCR反应,采用相对定量法,分析与生殖密切相关基因的表达差异倍...     

双向认知网络物理层安全策略建模及仿真研究

为提高移动通信系统的性能,构建了一个存在主网络干扰和窃听者时双向认知中继网络时物理层安全传输模型,设计了一种中继选择和功率分配的联合优化策略,用于对抗窃听者,保护收发节点的信息传输.通过仿真分析得出,此非凸优化问题限制条件较多,难以保证粒子群优化算法随机生成的初始解的可行性,从而造成求解困难.提出了一种基于可变网格优化...     

包含制度因素的湖南省经济增长因素的实证分析

通过运用现代经济增长理论和经济计量方法,实证分析了制度变迁、产业结构转变、资本等要素对湖南省经济增长的贡献率。     

通用试题库的研究与开发

介绍了通用试题库的设计与实现,利用这种方法开发的试题库可以实现考试工作的现代化管理。