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91.
Mishra SK Ammon T Popowicz GM Krajewski M Nagel RJ Ares M Holak TA Jentsch S 《Nature》2011,474(7350):173-178
Alternative splicing of pre-messenger RNAs diversifies gene products in eukaryotes and is guided by factors that enable spliceosomes to recognize particular splice sites. Here we report that alternative splicing of Saccharomyces cerevisiae SRC1 pre-mRNA is promoted by the conserved ubiquitin-like protein Hub1. Structural and biochemical data show that Hub1 binds non-covalently to a conserved element termed HIND, which is present in the spliceosomal protein Snu66 in yeast and mammals, and Prp38 in plants. Hub1 binding mildly alters spliceosomal protein interactions and barely affects general splicing in S. cerevisiae. However, spliceosomes that lack Hub1, or are defective in Hub1-HIND interaction, cannot use certain non-canonical 5' splice sites and are defective in alternative SRC1 splicing. Hub1 confers alternative splicing not only when bound to HIND, but also when experimentally fused to Snu66, Prp38, or even the core splicing factor Prp8. Our study indicates a novel mechanism for splice site utilization that is guided by non-covalent modification of the spliceosome by an unconventional ubiquitin-like modifier. 相似文献
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93.
A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans 总被引:27,自引:0,他引:27
Prokunina L Castillejo-López C Oberg F Gunnarsson I Berg L Magnusson V Brookes AJ Tentler D Kristjansdóttir H Gröndal G Bolstad AI Svenungsson E Lundberg I Sturfelt G Jönssen A Truedsson L Lima G Alcocer-Varela J Jonsson R Gyllensten UB Harley JB Alarcón-Segovia D Steinsson K Alarcón-Riquelme ME 《Nature genetics》2002,32(4):666-669
94.
黄土环境意义的研究对全球环境变化的研究具有重要的意义。而通过研究黄土磁化率曲线又是研究黄土环境变化的一种重要方法。该文运用便携式可变能量动力触探仪,现场测试了黄土的力学性能。通过具体实例,比较分析了黄土的触探曲线和磁化率曲线,探讨了这两类曲线可比性的原因。比较结果表明,黄土触探曲线不仅能反映黄土力学强度的变化,而且比磁化率曲线更细微、更精确。黄土触探曲线和磁化率曲线的良好比较性使得可以通过研究黄土触探曲线来间接地研究黄土的气候环境变化 相似文献
95.
Hillmer AM Brockschmidt FF Hanneken S Eigelshoven S Steffens M Flaquer A Herms S Becker T Kortüm AK Nyholt DR Zhao ZZ Montgomery GW Martin NG Mühleisen TW Alblas MA Moebus S Jöckel KH Bröcker-Preuss M Erbel R Reinartz R Betz RC Cichon S Propping P Baur MP Wienker TF Kruse R Nöthen MM 《Nature genetics》2008,40(11):1279-1281
We carried out a genome-wide association study in 296 individuals with male-pattern baldness (androgenetic alopecia) and 347 controls. We then investigated the 30 best SNPs in an independent replication sample and found highly significant association for five SNPs on chromosome 20p11 (rs2180439 combined P = 2.7 x 10(-15)). No interaction was detected with the X-chromosomal androgen receptor locus, suggesting that the 20p11 locus has a role in a yet-to-be-identified androgen-independent pathway. 相似文献
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97.
Geometry sensing by dendritic cells dictates spatial organization and PGE2-induced dissolution of podosomes 总被引:1,自引:1,他引:0
van den Dries K van Helden SF Riet Jt Diez-Ahedo R Manzo C Oud MM van Leeuwen FN Brock R Garcia-Parajo MF Cambi A Figdor CG 《Cellular and molecular life sciences : CMLS》2012,69(11):1889-1901
Assembly and disassembly of adhesion structures such as focal adhesions (FAs) and podosomes regulate cell adhesion and differentiation. On antigen-presenting dendritic cells (DCs), acquisition of a migratory and immunostimulatory phenotype depends on podosome dissolution by prostaglandin E(2) (PGE(2)). Whereas the effects of physico-chemical and topographical cues have been extensively studied on FAs, little is known about how podosomes respond to these signals. Here, we show that, unlike for FAs, podosome formation is not controlled by substrate physico-chemical properties. We demonstrate that cell adhesion is the only prerequisite for podosome formation and that substrate availability dictates podosome density. Interestingly, we show that DCs sense 3-dimensional (3-D) geometry by aligning podosomes along the edges of 3-D micropatterned surfaces. Finally, whereas on a 2-dimensional (2-D) surface PGE(2) causes a rapid increase in activated RhoA levels leading to fast podosome dissolution, 3-D geometric cues prevent PGE(2)-mediated RhoA activation resulting in impaired podosome dissolution even after prolonged stimulation. Our findings indicate that 2-D and 3-D geometric cues control the spatial organization of podosomes. More importantly, our studies demonstrate the importance of substrate dimensionality in regulating podosome dissolution and suggest that substrate dimensionality plays an important role in controlling DC activation, a key process in initiating immune responses. 相似文献
98.
Over the last years it has become evident that the nuclear envelope (NE) is more than a passive membrane barrier that separates
the nucleus from the cytoplasm. The NE not only controls the trafficking of macromolecules between the nucleoplasm and the
cytosol, but also provides anchoring sites for chromosomes and cytoskeleton to the nuclear periphery. Targeting of chromatin
to the NE might actually be part of gene expression regulation in eukaryotes. Mutations in certain NE proteins are associated
with a diversity of human diseases, including muscular dystrophy, neuropathy, lipodistrophy, torsion dystonia and the premature
aging condition progeria. Despite the importance of the NE for cell division and differentiation, relatively little is known
about its biogenesis and its role in human diseases. It is our goal to provide a comprehensive view of the NE and to discuss
possible implications of NE-associated changes for gene expression, chromatin organization and signal transduction.
Received 8 August 2005; received after revision 13 October 2005; accepted 13 October 2005 相似文献
99.
100.