Inactivation of TNF signaling by rationally designed dominant-negative TNF variants     

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   

A homolog of Drosophila grainy head is essential for epidermal integrity in mice   总被引：1，自引：0，他引：1  

Ting SB  Caddy J  Hislop N  Wilanowski T  Auden A  Zhao LL  Ellis S  Kaur P  Uchida Y  Holleran WM  Elias PM  Cunningham JM  Jane SM 《Science (New York, N.Y.)》2005,308(5720):411-413

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The chemical genomic portrait of yeast: uncovering a phenotype for all genes     

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   

Sexual selection can resolve sex-linked sexual antagonism     

Albert AY  Otto SP 《Science (New York, N.Y.)》2005,310(5745):119-121

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   

THE TRANSITION FROM THE INDIVIDUAL TO THE SOCIAL LEVEL     

Jennings HS 《Science (New York, N.Y.)》1941,94(2446):447-453

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Parks and factors in their success     

Bhagwat S  Brown N  Evans T  Jennings S  Savill P 《Science (New York, N.Y.)》2001,293(5532):1045-1047

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Behavior. A narrow road to cooperation     

Boyd R  Mathew S 《Science (New York, N.Y.)》2007,316(5833):1858-1859

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Germination, genetics, and growth of an ancient date seed     

Sallon S  Solowey E  Cohen Y  Korchinsky R  Egli M  Woodhatch I  Simchoni O  Kislev M 《Science (New York, N.Y.)》2008,320(5882):1464

An ancient date seed (Phoenix dactylifera L.) excavated from Masada and radiocarbon-dated to the first century Common Era was germinated. Climatic conditions at the Dead Sea may have contributed to the longevity of this oldest, directly dated, viable seed. Growth and development of the seedling over 26 months was compatible with normal date seedlings propagated from modern seeds. Preliminary molecular characterization demonstrated high levels of genetic variation in comparison to modern, elite date cultivars currently growing in Israel. As a representative of an extinct date palm population, this seedling can provide insights into the historic date culture of the Dead Sea region. It also has importance for seed banking and conservation and may be of relevance to modern date palm cultivation.  相似文献   

Comparative genomics of trypanosomatid parasitic protozoa     

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   

Human chromosome 7: DNA sequence and biology     

Scherer SW  Cheung J  MacDonald JR  Osborne LR  Nakabayashi K  Herbrick JA  Carson AR  Parker-Katiraee L  Skaug J  Khaja R  Zhang J  Hudek AK  Li M  Haddad M  Duggan GE  Fernandez BA  Kanematsu E  Gentles S  Christopoulos CC  Choufani S  Kwasnicka D  Zheng XH  Lai Z  Nusskern D  Zhang Q  Gu Z  Lu F  Zeesman S  Nowaczyk MJ  Teshima I  Chitayat D  Shuman C  Weksberg R  Zackai EH  Grebe TA  Cox SR  Kirkpatrick SJ  Rahman N  Friedman JM  Heng HH  Pelicci PG  Lo-Coco F  Belloni E  Shaffer LG  Pober B  Morton CC  Gusella JF  Bruns GA  Korf BR 《Science (New York, N.Y.)》2003,300(5620):767-772

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