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排序方式: 共有1447条查询结果,搜索用时 15 毫秒
81.
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Steed PM Tansey MG Zalevsky J Zhukovsky EA Desjarlais JR Szymkowski DE Abbott C Carmichael D Chan C Cherry L Cheung P Chirino AJ Chung HH Doberstein SK Eivazi A Filikov AV Gao SX Hubert RS Hwang M Hyun L Kashi S Kim A Kim E Kung J Martinez SP Muchhal US Nguyen DH O'Brien C O'Keefe D Singer K Vafa O Vielmetter J Yoder SC Dahiyat BI 《Science (New York, N.Y.)》2003,301(5641):1895-1898
Tumor necrosis factor (TNF) is a key regulator of inflammatory responses and has been implicated in many pathological conditions. We used structure-based design to engineer variant TNF proteins that rapidly form heterotrimers with native TNF to give complexes that neither bind to nor stimulate signaling through TNF receptors. Thus, TNF is inactivated by sequestration. Dominant-negative TNFs represent a possible approach to anti-inflammatory biotherapeutics, and experiments in animal models show that the strategy can attenuate TNF-mediated pathology. Similar rational design could be used to engineer inhibitors of additional TNF superfamily cytokines as well as other multimeric ligands. 相似文献
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84.
Hillenmeyer ME Fung E Wildenhain J Pierce SE Hoon S Lee W Proctor M St Onge RP Tyers M Koller D Altman RB Davis RW Nislow C Giaever G 《Science (New York, N.Y.)》2008,320(5874):362-365
Genetics aims to understand the relation between genotype and phenotype. However, because complete deletion of most yeast genes ( approximately 80%) has no obvious phenotypic consequence in rich medium, it is difficult to study their functions. To uncover phenotypes for this nonessential fraction of the genome, we performed 1144 chemical genomic assays on the yeast whole-genome heterozygous and homozygous deletion collections and quantified the growth fitness of each deletion strain in the presence of chemical or environmental stress conditions. We found that 97% of gene deletions exhibited a measurable growth phenotype, suggesting that nearly all genes are essential for optimal growth in at least one condition. 相似文献
85.
Sexual selection is a potent evolutionary force. However, very few models have considered the evolution of female preferences for traits expressed in both sexes. Here we explore how female preferences coevolve with sexually antagonistic traits, which involve alleles that are beneficial to one sex but harmful to the other. We show that with a sexually antagonistic trait on the X chromosome (males XY, females XX), females evolve to prefer mates carrying alleles beneficial to daughters. In contrast, with a Z-linked trait (males ZZ, females ZW), females more often evolve mating preferences for mates carrying alleles beneficial to sons (that is, flashy displays). 相似文献
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El-Sayed NM Myler PJ Blandin G Berriman M Crabtree J Aggarwal G Caler E Renauld H Worthey EA Hertz-Fowler C Ghedin E Peacock C Bartholomeu DC Haas BJ Tran AN Wortman JR Alsmark UC Angiuoli S Anupama A Badger J Bringaud F Cadag E Carlton JM Cerqueira GC Creasy T Delcher AL Djikeng A Embley TM Hauser C Ivens AC Kummerfeld SK Pereira-Leal JB Nilsson D Peterson J Salzberg SL Shallom J Silva JC Sundaram J Westenberger S White O Melville SE Donelson JE Andersson B Stuart KD Hall N 《Science (New York, N.Y.)》2005,309(5733):404-409
A comparison of gene content and genome architecture of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major, three related pathogens with different life cycles and disease pathology, revealed a conserved core proteome of about 6200 genes in large syntenic polycistronic gene clusters. Many species-specific genes, especially large surface antigen families, occur at nonsyntenic chromosome-internal and subtelomeric regions. Retroelements, structural RNAs, and gene family expansion are often associated with syntenic discontinuities that-along with gene divergence, acquisition and loss, and rearrangement within the syntenic regions-have shaped the genomes of each parasite. Contrary to recent reports, our analyses reveal no evidence that these species are descended from an ancestor that contained a photosynthetic endosymbiont. 相似文献
88.
Brilliant plumage is typical of male birds, reflecting differential enhancement of male traits when females are the limiting sex. Brighter females are thought to evolve exclusively in response to sex role reversal. The striking reversed plumage dichromatism of Eclectus roratus parrots does not fit this pattern. We quantify plumage color in this species and show that very different selection pressures are acting on males and females. Male plumage reflects a compromise between the conflicting requirements for camouflage from predators while foraging and conspicuousness during display. Females are liberated from the need for camouflage but compete for rare nest hollows. 相似文献
89.
Cruz-Migoni A Hautbergue GM Artymiuk PJ Baker PJ Bokori-Brown M Chang CT Dickman MJ Essex-Lopresti A Harding SV Mahadi NM Marshall LE Mobbs GW Mohamed R Nathan S Ngugi SA Ong C Ooi WF Partridge LJ Phillips HL Raih MF Ruzheinikov S Sarkar-Tyson M Sedelnikova SE Smither SJ Tan P Titball RW Wilson SA Rice DW 《Science (New York, N.Y.)》2011,334(6057):821-824
The structure of BPSL1549, a protein of unknown function from Burkholderia pseudomallei, reveals a similarity to Escherichia coli cytotoxic necrotizing factor 1. We found that BPSL1549 acted as a potent cytotoxin against eukaryotic cells and was lethal when administered to mice. Expression levels of bpsl1549 correlate with conditions expected to promote or suppress pathogenicity. BPSL1549 promotes deamidation of glutamine-339 of the translation initiation factor eIF4A, abolishing its helicase activity and inhibiting translation. We propose to name BPSL1549 Burkholderia lethal factor 1. 相似文献
90.
Hoskins AA Friedman LJ Gallagher SS Crawford DJ Anderson EG Wombacher R Ramirez N Cornish VW Gelles J Moore MJ 《Science (New York, N.Y.)》2011,331(6022):1289-1295
The spliceosome is the complex macromolecular machine responsible for removing introns from precursors to messenger RNAs (pre-mRNAs). We combined yeast genetic engineering, chemical biology, and multiwavelength fluorescence microscopy to follow assembly of single spliceosomes in real time in whole-cell extracts. We find that individual spliceosomal subcomplexes associate with pre-mRNA sequentially via an ordered pathway to yield functional spliceosomes and that association of every subcomplex is reversible. Further, early subcomplex binding events do not fully commit a pre-mRNA to splicing; rather, commitment increases as assembly proceeds. These findings have important implications for the regulation of alternative splicing. This experimental strategy should prove widely useful for mechanistic analysis of other macromolecular machines in environments approaching the complexity of living cells. 相似文献