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61.
Butland G Peregrín-Alvarez JM Li J Yang W Yang X Canadien V Starostine A Richards D Beattie B Krogan N Davey M Parkinson J Greenblatt J Emili A 《Nature》2005,433(7025):531-537
Proteins often function as components of multi-subunit complexes. Despite its long history as a model organism, no large-scale analysis of protein complexes in Escherichia coli has yet been reported. To this end, we have targeted DNA cassettes into the E. coli chromosome to create carboxy-terminal, affinity-tagged alleles of 1,000 open reading frames (approximately 23% of the genome). A total of 857 proteins, including 198 of the most highly conserved, soluble non-ribosomal proteins essential in at least one bacterial species, were tagged successfully, whereas 648 could be purified to homogeneity and their interacting protein partners identified by mass spectrometry. An interaction network of protein complexes involved in diverse biological processes was uncovered and validated by sequential rounds of tagging and purification. This network includes many new interactions as well as interactions predicted based solely on genomic inference or limited phenotypic data. This study provides insight into the function of previously uncharacterized bacterial proteins and the overall topology of a microbial interaction network, the core components of which are broadly conserved across Prokaryota. 相似文献
62.
One of the most important considerations when planning the next generation of ground-based optical astronomical telescopes is to choose a site that has excellent 'seeing'--the jitter in the apparent position of a star that is caused by light bending as it passes through regions of differing refractive index in the Earth's atmosphere. The best mid-latitude sites have a median seeing ranging from 0.5 to 1.0 arcsec (refs 1-5). Sites on the Antarctic plateau have unique atmospheric properties that make them worth investigating as potential observatory locations. Previous testing at the US Amundsen-Scott South Pole Station has, however, demonstrated poor seeing, averaging 1.8 arcsec (refs 6, 7). Here we report observations of the wintertime seeing from Dome C (ref. 8), a high point on the Antarctic plateau at a latitude of 75 degrees S. The results are remarkable: the median seeing is 0.27 arcsec, and below 0.15 arcsec 25 per cent of the time. A telescope placed at Dome C would compete with one that is 2 to 3 times larger at the best mid-latitude observatories, and an interferometer based at this site could work on projects that would otherwise require a space mission. 相似文献
63.
Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster 总被引:28,自引:0,他引:28
Dews M Homayouni A Yu D Murphy D Sevignani C Wentzel E Furth EE Lee WM Enders GH Mendell JT Thomas-Tikhonenko A 《Nature genetics》2006,38(9):1060-1065
Human adenocarcinomas commonly harbor mutations in the KRAS and MYC proto-oncogenes and the TP53 tumor suppressor gene. All three genetic lesions are potentially pro-angiogenic, as they sustain production of vascular endothelial growth factor (VEGF). Yet Kras-transformed mouse colonocytes lacking p53 formed indolent, poorly vascularized tumors, whereas additional transduction with a Myc-encoding retrovirus promoted vigorous vascularization and growth. In addition, VEGF levels were unaffected by Myc, but enhanced neovascularization correlated with downregulation of anti-angiogenic thrombospondin-1 (Tsp1) and related proteins, such as connective tissue growth factor (CTGF). Both Tsp1 and CTGF are predicted targets for repression by the miR-17-92 microRNA cluster, which was upregulated in colonocytes coexpressing K-Ras and c-Myc. Indeed, miR-17-92 knockdown with antisense 2'-O-methyl oligoribonucleotides partly restored Tsp1 and CTGF expression; in addition, transduction of Ras-only cells with a miR-17-92-encoding retrovirus reduced Tsp1 and CTGF levels. Notably, miR-17-92-transduced cells formed larger, better-perfused tumors. These findings establish a role for microRNAs in non-cell-autonomous Myc-induced tumor phenotypes. 相似文献