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排序方式: 共有175条查询结果,搜索用时 15 毫秒
101.
Jäger S Cimermancic P Gulbahce N Johnson JR McGovern KE Clarke SC Shales M Mercenne G Pache L Li K Hernandez H Jang GM Roth SL Akiva E Marlett J Stephens M D'Orso I Fernandes J Fahey M Mahon C O'Donoghue AJ Todorovic A Morris JH Maltby DA Alber T Cagney G Bushman FD Young JA Chanda SK Sundquist WI Kortemme T Hernandez RD Craik CS Burlingame A Sali A Frankel AD Krogan NJ 《Nature》2012,481(7381):365-370
Human immunodeficiency virus (HIV) has a small genome and therefore relies heavily on the host cellular machinery to replicate. Identifying which host proteins and complexes come into physical contact with the viral proteins is crucial for a comprehensive understanding of how HIV rewires the host's cellular machinery during the course of infection. Here we report the use of affinity tagging and purification mass spectrometry to determine systematically the physical interactions of all 18 HIV-1 proteins and polyproteins with host proteins in two different human cell lines (HEK293 and Jurkat). Using a quantitative scoring system that we call MiST, we identified with high confidence 497 HIV-human protein-protein interactions involving 435 individual human proteins, with ~40% of the interactions being identified in both cell types. We found that the host proteins hijacked by HIV, especially those found interacting in both cell types, are highly conserved across primates. We uncovered a number of host complexes targeted by viral proteins, including the finding that HIV protease cleaves eIF3d, a subunit of eukaryotic translation initiation factor 3. This host protein is one of eleven identified in this analysis that act to inhibit HIV replication. This data set facilitates a more comprehensive and detailed understanding of how the host machinery is manipulated during the course of HIV infection. 相似文献
102.
Neutrophils are an essential component of the innate immune response and a major contributor to inflammation. Consequently,
neutrophil homeostasis in the blood is highly regulated. Neutrophil number in the blood is determined by the balance between
neutrophil production in the bone marrow and release from the bone marrow to blood with neutrophil clearance from the circulation.
This review will focus on mechanisms regulating neutrophil release from the bone marrow. In particular, recent data demonstrating
a central role for the chemokines CXCL12 and CXCL2 in regulating neutrophil egress from the bone marrow will be discussed. 相似文献
103.
Safe handling of nanotechnology 总被引:7,自引:0,他引:7
Maynard AD Aitken RJ Butz T Colvin V Donaldson K Oberdörster G Philbert MA Ryan J Seaton A Stone V Tinkle SS Tran L Walker NJ Warheit DB 《Nature》2006,444(7117):267-269
104.
Ngo VN Young RM Schmitz R Jhavar S Xiao W Lim KH Kohlhammer H Xu W Yang Y Zhao H Shaffer AL Romesser P Wright G Powell J Rosenwald A Muller-Hermelink HK Ott G Gascoyne RD Connors JM Rimsza LM Campo E Jaffe ES Delabie J Smeland EB Fisher RI Braziel RM Tubbs RR Cook JR Weisenburger DD Chan WC Staudt LM 《Nature》2011,470(7332):115-119
The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) remains the least curable form of this malignancy despite recent advances in therapy. Constitutive nuclear factor (NF)-κB and JAK kinase signalling promotes malignant cell survival in these lymphomas, but the genetic basis for this signalling is incompletely understood. Here we describe the dependence of ABC DLBCLs on MYD88, an adaptor protein that mediates toll and interleukin (IL)-1 receptor signalling, and the discovery of highly recurrent oncogenic mutations affecting MYD88 in ABC DLBCL tumours. RNA interference screening revealed that MYD88 and the associated kinases IRAK1 and IRAK4 are essential for ABC DLBCL survival. High-throughput RNA resequencing uncovered MYD88 mutations in ABC DLBCL lines. Notably, 29% of ABC DLBCL tumours harboured the same amino acid substitution, L265P, in the MYD88 Toll/IL-1 receptor (TIR) domain at an evolutionarily invariant residue in its hydrophobic core. This mutation was rare or absent in other DLBCL subtypes and Burkitt's lymphoma, but was observed in 9% of mucosa-associated lymphoid tissue lymphomas. At a lower frequency, additional mutations were observed in the MYD88 TIR domain, occurring in both the ABC and germinal centre B-cell-like (GCB) DLBCL subtypes. Survival of ABC DLBCL cells bearing the L265P mutation was sustained by the mutant but not the wild-type MYD88 isoform, demonstrating that L265P is a gain-of-function driver mutation. The L265P mutant promoted cell survival by spontaneously assembling a protein complex containing IRAK1 and IRAK4, leading to IRAK4 kinase activity, IRAK1 phosphorylation, NF-κB signalling, JAK kinase activation of STAT3, and secretion of IL-6, IL-10 and interferon-β. Hence, the MYD88 signalling pathway is integral to the pathogenesis of ABC DLBCL, supporting the development of inhibitors of IRAK4 kinase and other components of this pathway for the treatment of tumours bearing oncogenic MYD88 mutations. 相似文献
105.
106.
107.
Hinch AG Tandon A Patterson N Song Y Rohland N Palmer CD Chen GK Wang K Buxbaum SG Akylbekova EL Aldrich MC Ambrosone CB Amos C Bandera EV Berndt SI Bernstein L Blot WJ Bock CH Boerwinkle E Cai Q Caporaso N Casey G Cupples LA Deming SL Diver WR Divers J Fornage M Gillanders EM Glessner J Harris CC Hu JJ Ingles SA Isaacs W John EM Kao WH Keating B Kittles RA Kolonel LN Larkin E Le Marchand L McNeill LH Millikan RC Murphy A Musani S Neslund-Dudas C Nyante S Papanicolaou GJ Press MF Psaty BM 《Nature》2011,476(7359):170-175
Recombination, together with mutation, gives rise to genetic variation in populations. Here we leverage the recent mixture of people of African and European ancestry in the Americas to build a genetic map measuring the probability of crossing over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans. At intervals of more than three megabases it is nearly identical to a map built in Europeans. At finer scales it differs significantly, and we identify about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans. The probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at PRDM9 (P?value 10(-245)). We identify a 17-base-pair DNA sequence motif that is enriched in these hotspots, and is an excellent match to the predicted binding target of PRDM9 alleles common in West Africans and rare in Europeans. Sites of this motif are predicted to be risk loci for disease-causing genomic rearrangements in individuals carrying these alleles. More generally, this map provides a resource for research in human genetic variation and evolution. 相似文献
108.
Hoffmann AA Montgomery BL Popovici J Iturbe-Ormaetxe I Johnson PH Muzzi F Greenfield M Durkan M Leong YS Dong Y Cook H Axford J Callahan AG Kenny N Omodei C McGraw EA Ryan PA Ritchie SA Turelli M O'Neill SL 《Nature》2011,476(7361):454-457
Genetic manipulations of insect populations for pest control have been advocated for some time, but there are few cases where manipulated individuals have been released in the field and no cases where they have successfully invaded target populations. Population transformation using the intracellular bacterium Wolbachia is particularly attractive because this maternally-inherited agent provides a powerful mechanism to invade natural populations through cytoplasmic incompatibility. When Wolbachia are introduced into mosquitoes, they interfere with pathogen transmission and influence key life history traits such as lifespan. Here we describe how the wMel Wolbachia infection, introduced into the dengue vector Aedes aegypti from Drosophila melanogaster, successfully invaded two natural A. aegypti populations in Australia, reaching near-fixation in a few months following releases of wMel-infected A. aegypti adults. Models with plausible parameter values indicate that Wolbachia-infected mosquitoes suffered relatively small fitness costs, leading to an unstable equilibrium frequency <30% that must be exceeded for invasion. These findings demonstrate that Wolbachia-based strategies can be deployed as a practical approach to dengue suppression with potential for area-wide implementation. 相似文献
109.
Evidence that decomposition rates of organic carbon in mineral soil do not vary with temperature 总被引:75,自引:0,他引:75
It has been suggested that increases in temperature can accelerate the decomposition of organic carbon contained in forest mineral soil (Cs), and, therefore, that global warming should increase the release of soil organic carbon to the atmosphere. These predictions assume, however, that decay constants can be accurately derived from short-term laboratory incubations of soil or that in situ incubations of fresh litter accurately represent the temperature sensitivity of Cs decomposition. But our limited understanding of the biophysical factors that control Cs decomposition rates, and observations of only minor increases in Cs decomposition rate with temperature in longer-term forest soil heating experiments and in latitudinal comparisons of Cs decomposition rates bring these predictions into question. Here we have compiled Cs decomposition data from 82 sites on five continents. We found that Cs decomposition rates were remarkably constant across a global-scale gradient in mean annual temperature. These data suggest that Cs decomposition rates for forest soils are not controlled by temperature limitations to microbial activity, and that increased temperature alone will not stimulate the decomposition of forest-derived carbon in mineral soil. 相似文献
110.
Pinus aristata Engelm. forest vegetation in Colorado was studied to determine vegetation composition and the relationship between vegetation and environment. Species percent cover, tree size class, and environmental variables were recorded for 49 plots. Previously collected data for 4 plots form New Mexico were included. Environmental variables included latitude, longitude, elevation, slope, aspect, topographic position, parent material, percent rock cover, mean rock size, litter depth, estimated plot age class, and evidence of anthropogenic disturbance. Soils were analyzed for texture, depth, and percent carbon and nitrogen. Pinus aristata foliage was analyzed for percent nitrogen and phosphorus. Direct and indirect gradient analyses (CANOCO) were used to determine environmental factors associated with community composition. Vegetation in P. aristata forests is influenced primarily by elevation and soil pH. Substrate, soil texture, topographic position, and geographic location are secondary factors. Six plant associations were identified using cluster analysis (listed in an elevational sequence from low to high): Pinus aristata/ Festuca arizonica Vasey, Pinus aristata / Festuca thurberi Vasey, Pinus aristata / Juniperus communis L., Pinus aristata / Vaccinium myrtilus L., Pinus aristata / Ribes montigenum McClatchie, and Pinus aristata / Trifolium dasyphyllum Torr. & Gray. 相似文献