Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome

Protein-protein interaction analyses have uncovered a ciliary and basal body protein network that, when disrupted, can result in nephronophthisis (NPHP), Leber congenital amaurosis, Senior-L?ken syndrome (SLSN) or Joubert syndrome (JBTS). However, details of the molecular mechanisms underlying these disorders remain poorly understood. RPGRIP1-like protein (RPGRIP1L) is a homolog of RPGRIP1 (RPGR-interacting protein 1), a ciliary protein defective in Leber congenital amaurosis. We show that RPGRIP1L interacts with nephrocystin-4 and that mutations in the gene encoding nephrocystin-4 (NPHP4) that are known to cause SLSN disrupt this interaction. RPGRIP1L is ubiquitously expressed, and its protein product localizes to basal bodies. Therefore, we analyzed RPGRIP1L as a candidate gene for JBTS and identified loss-of-function mutations in three families with typical JBTS, including the characteristic mid-hindbrain malformation. This work identifies RPGRIP1L as a gene responsible for JBTS and establishes a central role for cilia and basal bodies in the pathophysiology of this disorder.     

Segregation of MHC class II molecules from MHC class I molecules in the Golgi complex for transport to lysosomal compartments.

Traffic of MHC molecules dictates the source of peptides that are presented to T cells. The intracellular distribution of MHC class I and class II molecules reflects the dichotomy in presentation of antigen from endogenous and exogenous origin, respectively. In human B lymphoblastoid cells, class I molecules are present in compartments constituting the biosynthetic pathway, whereas class II molecules enter structures related to lysosomes during their biosynthesis.     

大众体育思潮冲击下足球策略调整研究

通过问卷调查发现，现代青年对体育项目的喜爱中反映出的相对应的体育文化类型，首先是在休闲的生活方式的锻炼中有所追求展示技艺的体育项目，在此基础上分析足球运动项目不被现代青年所钟爱的原因为：社会发展的必然趋势；足球自身的特点限制了它的大众化传播；我国足球事业发展缺乏大众化策略．最后相应给出了一些对策．     

身体素质引导课存在的问题与改进办法

每学期初的两次体育课,称为身体素质引导课较为适当.目前,这类课型存在着“运动负荷安排不合理“、“练习顺序安排不适当“等问题;改进的方法是:分析问题存在的根本原因,提高教师素质,强化教学管理.     

采用WD倒谱法分析人体肾组织的超声散射微结构特征

提出了一种对超声散射信号分析的新方法———WD倒谱法 .利用该方法对人体正常肾和肾肿瘤组织的回波信号进行分析 ,与用AR倒谱法所得结果进行了比较 .结果表明 ,两种肾组织散射子的平均间距明显不同 ,WD倒谱比AR倒谱更能反映软组织的微观结构特征 ,说明WD倒谱是软组织超声散射信号分析与软组织散射子平均间距定征的一种有效方法     

杆系结构静/动力学计算的直接方法

针对有限单元法计算精度受网格密度制约的问题,提出一种求任意复杂杆系静、动力学问题精确解的方法.该方法基于节点分析法,逐个节点列位移相容方程和内力平衡方程,以谱系数作为未知数,杆件变形和截面内力则采用相应问题的精确解来描述.用代数符号化的方式,对方程系数矩阵的组建过程进行了详细描述,为通用程序编制提供依据.对建模过程中的分布式载荷和铰接接头的处理方法进行了探讨并给出处理方法.通过平面钢架屈曲分析和空间管路谐响应分析,证实所提方法具有计算精度高、划分单元数少的特点,特别适合于需要精确解的场合.     

Epigenetic regulation of telomere length in mammalian cells by the Suv39h1 and Suv39h2 histone methyltransferases

Telomeres are capping structures at the ends of eukaryotic chromosomes composed of TTAGGG repeats bound to an array of specialized proteins. Telomeres are heterochromatic regions. Yeast and flies with defects in activities that modify the state of chromatin also have abnormal telomere function, but the putative role of chromatin-modifying activities in regulating telomeres in mammals is unknown. Here we report on telomere length and function in mice null with respect to both the histone methyltransferases (HMTases) Suv39h1 and Suv39h2 (called SUV39DN mice). Suv39h1 and Suv39h2 govern methylation of histone H3 Lys9 (H3-Lys9) in heterochromatic regions. We show that primary cells derived from SUV39DN mice have abnormally long telomeres relative to wild-type controls. Using chromatin immunoprecipitation (ChIP) analysis, we found that telomeres were enriched in di- and trimethylated H3-Lys9 but that telomeres of SUV39DN cells had less dimethylated and trimethylated H3-Lys9 but more monomethylated H3-Lys9. Concomitant with the decrease in H3-Lys9 methylation, telomeres in SUV39DN cells had reduced binding of the chromobox proteins Cbx1, Cbx3 and Cbx5, homologs of Drosophila melanogaster heterochromatin protein 1 (HP1). These findings indicate substantial changes in the state of telomeric heterochromatin in SUV39DN cells, which are associated with abnormal telomere elongation. Taken together, the results indicate epigenetic regulation of telomere length in mammals by Suv39h1 and Suv39h2.