IFT54 regulates IFT20 stability but is not essential for tubulin transport during ciliogenesis

Intraflagellar transport (IFT) is required for ciliogenesis by ferrying ciliary components using IFT complexes as cargo adaptors. IFT54 is a component of the IFT-B complex and is also associated with cytoplasmic microtubules (MTs). Loss of IFT54 impairs cilia assembly as well as cytoplasmic MT dynamics. The N-terminal calponin homology (CH) domain of IFT54 interacts with tubulins/MTs and has been proposed to transport tubulin during ciliogenesis, whereas the C-terminal coiled-coil (CC) domain binds IFT20. However, the precise function of these domains in vivo is not well understood. We showed that in Chlamydomonas, loss of IFT54 completely blocks ciliogenesis but does not affect spindle formation and proper cell cycle progression, even though IFT54 interacts with mitotic MTs. Interestingly, IFT54 lacking the CH domain allows proper flagellar assembly. The CH domain is required for the association of IFT54 with the axoneme but not with mitotic MTs, and also regulates the flagellar import of IFT54 but not IFT81 and IFT46. The C-terminal CC domain is essential for IFT54 to bind IFT20, and for its recruitment to the basal body and incorporation into IFT complexes. Complete loss of IFT54 or the CC domain destabilizes IFT20. ift54 mutant cells expressing the CC domain alone rescue the stability of IFT20 and form stunted flagella with accumulation of both IFT-A component IFT43 and IFT-B component IFT46, indicating that IFT54 also functions in IFT turn-around at the flagellar tip.     

探月工程三期月地高速再入返回飞行器防热系统设计与验证

本文针对月地高速再入返回的高焓、二次大气层再入、高热流密度峰值与长加热时间耦合的气动加热环境特点,提出了飞行器防热系统设计方案,研制了七种新型碳硅复合烧蚀防热材料,建立了防热系统分析模型,并完成了地面试验验证.经对飞行试验数据的详细分析,结果表明防热系统的实际性能与设计预期一致.     

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.     

Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder

Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.     

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.     

虚拟示波器及其信号源构建

文章以测控系统中虚拟示波器和信号源的构建为例,详细地讨论了虚拟仪器系统的功能特点,并给出了虚拟仪器系统构建所需要的硬件及软件技术。     

我国工业企业技术创新能力研究

技术创新能力是入世后我国工业企业得以持续发展的根本保证。在介绍了我国工业企业技术创新能力的现状的基础上,分析了影响我国工业企业技术创新能力的因素,最后提出了改进建议。     

基于小波能量加权的医学图像融合新算法

目前的大多数基于小波变换的医学图像融合算法,由于没有细致考虑低频分量融合规则以及高频分量邻域特征对于融合效果的重要性,因而得到的融合效果有时并不理想.现提出一种小波域按邻域加窗能量加权的融合准则,该准则根据人体颅部18F-FDG和MRI-T1图像的特点,充分考虑到了低频分量和高频分量邻域特征,对原图像高、低频小波系数分别选用具有不同物理意义的窗矩阵进行邻域加窗能量计算,以归一化加窗能量为权值对各小波系数进行加权,得到融合小波系数,经过小波反变换重构出融合图像.实验证明,采用提出的融合算法得到的融合图像很好地包含了源图像的信息,该算法在医学图像融合应用中比传统的小波系数取大算法、加权平均算法及按邻域方差加权算法效果更好.     

试论图书馆联盟在信息网格应用中的作用

介绍了信息网格和图书馆联盟的涵义,阐述了网格技术应用过程中的问题,探讨了图书馆联盟在信息网格应用中的作用,指出图书馆联盟作为图书馆际合作组织,在信息网格时代应利用信息网格技术推动图书馆际间资源共享,提高图书馆信息服务质量和能力,促进信息网格的信息连通,使其逐渐成熟。     

新时期我国经济技术开发区发展的形势、方向和任务研究

经济技术开发区作为一种特殊类型经济功能区,在我国改革开放和经济发展过程中发挥着重要作用,同时也存在许多突出问题。在新形势下,来自经济全球化国际大背景和全面建设小康社会国内大环境的双重影响,使得经济技术开发区面临着新的机遇和挑战。立足国内外经济社会发展变化趋势,应进一步明确我国经济技术开发区中长期发展方向和定位,并在此基础上提出“十一五”及今后一段时期面临的重点任务。