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Evolving concepts of rheumatoid arthritis 总被引:80,自引:0,他引:80
Firestein GS 《Nature》2003,423(6937):356-361
Rheumatoid arthritis is the most common inflammatory arthritis and is a major cause of disability. It existed in early Native American populations several thousand years ago but might not have appeared in Europe until the 17th century. Early theories on the pathogenesis of rheumatoid arthritis focused on autoantibodies and immune complexes. T-cell-mediated antigen-specific responses, T-cell-independent cytokine networks, and aggressive tumour-like behaviour of rheumatoid synovium have also been implicated. More recently, the contribution of autoantibodies has returned to the forefront. Based on the pathogenic mechanisms, specific therapeutic interventions can be designed to suppress synovial inflammation and joint destruction in rheumatoid arthritis. 相似文献
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Identification of a host protein essential for assembly of immature HIV-1 capsids. 总被引:18,自引:0,他引:18
Concepcion Zimmerman Kevin C Klein Patti K Kiser Aalok R Singh Bonnie L Firestein Shannyn C Riba Jaisri R Lingappa 《Nature》2002,415(6867):88-92
To form an immature HIV-1 capsid, 1,500 HIV-1 Gag (p55) polypeptides must assemble properly along the host cell plasma membrane. Insect cells and many higher eukaryotic cell types support efficient capsid assembly, but yeast and murine cells do not, indicating that host machinery is required for immature HIV-1 capsid formation. Additionally, in a cell-free system that reconstitutes HIV-1 capsid formation, post-translational assembly events require ATP and a subcellular fraction, suggesting a requirement for a cellular ATP-binding protein. Here we identify such a protein (HP68), described previously as an RNase L inhibitor, and demonstrate that it associates post-translationally with HIV-1 Gag in a cell-free system and human T cells infected with HIV-1. Using a dominant negative mutant of HP68 in mammalian cells and depletion-reconstitution experiments in the cell-free system, we demonstrate that HP68 is essential for post-translational events in immature HIV-1 capsid assembly. Furthermore, in cells the HP68-Gag complex is associated with HIV-1 Vif, which is involved in virion morphogenesis and infectivity. These findings support a critical role for HP68 in post-translational events of HIV-1 assembly and reveal a previously unappreciated dimension of host-viral interaction. 相似文献
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Vertebrate odorant receptors 总被引:3,自引:0,他引:3
Olfactory transduction begins with the binding of an odorous molecule to a protein receptor--odorant receptor--on the cell surface of olfactory neuron. Odorant receptors are encoded by a large gene family belonging to the superfamily of G-protein-coupled, seven-transmembrane-domain receptors. Since the identification of the receptor gene family in 1991, a considerable amount of progress has been made in the study of odorant receptors, including aspects of spatial and temporal expression pattern, the genomic organization of the receptor genes, regulation of expression, and receptor function. These studies are of critical importance in understanding how the olfactory system recognizes and distinguishes thousands of odors. 相似文献
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Rb targets histone H3 methylation and HP1 to promoters 总被引:78,自引:0,他引:78
Nielsen SJ Schneider R Bauer UM Bannister AJ Morrison A O'Carroll D Firestein R Cleary M Jenuwein T Herrera RE Kouzarides T 《Nature》2001,412(6846):561-565
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How the olfactory system makes sense of scents 总被引:38,自引:0,他引:38
Firestein S 《Nature》2001,413(6852):211-218
The human nose is often considered something of a luxury, but in the rest of the animal world, from bacteria to mammals, detecting chemicals in the environment has been critical to the successful organism. An indication of the importance of olfactory systems is the significant proportion - as much as 4% - of the genomes of many higher eukaryotes that is devoted to encoding the proteins of smell. Growing interest in the detection of diverse compounds at single-molecule levels has made the olfactory system an important system for biological modelling. 相似文献
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