Glycosylation of nucleocytoplasmic proteins: signal transduction and O-GlcNAc     

Wells L  Vosseller K  Hart GW 《Science (New York, N.Y.)》2001,291(5512):2376-2378

The dynamic glycosylation of serine or threonine residues on nuclear and cytosolic proteins by O-linked beta-N-acetylglucosamine (O-GlcNAc) is abundant in all multicellular eukaryotes. On several proteins, O-GlcNAc and O-phosphate alternatively occupy the same or adjacent sites, leading to the hypothesis that one function of this saccharide is to transiently block phosphorylation. The diversity of proteins modified by O-GlcNAc implies its importance in many basic cellular and disease processes. Here we systematically examine the current data implicating O-GlcNAc as a regulatory modification important to signal transduction cascades.  相似文献   

Medicine. The future of personal genomics     

McGuire AL  Cho MK  McGuire SE  Caulfield T 《Science (New York, N.Y.)》2007,317(5845):1687

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The concern with numbers: a calculating people     

Wells RV 《Science (New York, N.Y.)》1983,221(4607):255-256

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Extinction and ecosystem function in the marine benthos     

Solan M  Cardinale BJ  Downing AL  Engelhardt KA  Ruesink JL  Srivastava DS 《Science (New York, N.Y.)》2004,306(5699):1177-1180

Rapid changes in biodiversity are occurring globally, yet the ecological impacts of diversity loss are poorly understood. Here we use data from marine invertebrate communities to parameterize models that predict how extinctions will affect sediment bioturbation, a process vital to the persistence of aquatic communities. We show that species extinction is generally expected to reduce bioturbation, but the magnitude of reduction depends on how the functional traits of individual species covary with their risk of extinction. As a result, the particular cause of extinction and the order in which species are lost ultimately govern the ecosystem-level consequences of biodiversity loss.  相似文献   

Environmental economics. Development and conservation goals in World Bank projects     

Kareiva P  Chang A  Marvier M 《Science (New York, N.Y.)》2008,321(5896):1638-1639

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Little evidence for developmental plasticity of adult hematopoietic stem cells     

Wagers AJ  Sherwood RI  Christensen JL  Weissman IL 《Science (New York, N.Y.)》2002,297(5590):2256-2259

To rigorously test the in vivo cell fate specificity of bone marrow (BM) hematopoietic stem cells (HSCs), we generated chimeric animals by transplantation of a single green fluorescent protein (GFP)-marked HSC into lethally irradiated nontransgenic recipients. Single HSCs robustly reconstituted peripheral blood leukocytes in these animals, but did not contribute appreciably to nonhematopoietic tissues, including brain, kidney, gut, liver, and muscle. Similarly, in GFP+:GFP- parabiotic mice, we found substantial chimerism of hematopoietic but not nonhematopoietic cells. These data indicate that "transdifferentiation" of circulating HSCs and/or their progeny is an extremely rare event, if it occurs at all.  相似文献   

Constraints on neon and argon isotopic fractionation in solar wind     

Meshik A  Mabry J  Hohenberg C  Marrocchi Y  Pravdivtseva O  Burnett D  Olinger C  Wiens R  Reisenfeld D  Allton J  McNamara K  Stansbery E  Jurewicz AJ 《Science (New York, N.Y.)》2007,318(5849):433-435

To evaluate the isotopic composition of the solar nebula from which the planets formed, the relation between isotopes measured in the solar wind and on the Sun's surface needs to be known. The Genesis Discovery mission returned independent samples of three types of solar wind produced by different solar processes that provide a check on possible isotopic variations, or fractionation, between the solar-wind and solar-surface material. At a high level of precision, we observed no significant inter-regime differences in 20Ne/22Ne or 36Ar/38Ar values. For 20Ne/22Ne, the difference between low- and high-speed wind components is 0.24 +/- 0.37%; for 36Ar/38Ar, it is 0.11 +/- 0.26%. Our measured 36Ar/38Ar ratio in the solar wind of 5.501 +/- 0.005 is 3.42 +/- 0.09% higher than that of the terrestrial atmosphere, which may reflect atmospheric losses early in Earth's history.  相似文献   

Human-specific gain of function in a developmental enhancer     

Prabhakar S  Visel A  Akiyama JA  Shoukry M  Lewis KD  Holt A  Plajzer-Frick I  Morrison H  Fitzpatrick DR  Afzal V  Pennacchio LA  Rubin EM  Noonan JP 《Science (New York, N.Y.)》2008,321(5894):1346-1350

Changes in gene regulation are thought to have contributed to the evolution of human development. However, in vivo evidence for uniquely human developmental regulatory function has remained elusive. In transgenic mice, a conserved noncoding sequence (HACNS1) that evolved extremely rapidly in humans acted as an enhancer of gene expression that has gained a strong limb expression domain relative to the orthologous elements from chimpanzee and rhesus macaque. This gain of function was consistent across two developmental stages in the mouse and included the presumptive anterior wrist and proximal thumb. In vivo analyses with synthetic enhancers, in which human-specific substitutions were introduced into the chimpanzee enhancer sequence or reverted in the human enhancer to the ancestral state, indicated that 13 substitutions clustered in an 81-base pair module otherwise highly constrained among terrestrial vertebrates were sufficient to confer the human-specific limb expression domain.  相似文献   

Comparative genome and proteome analysis of Anopheles gambiae and Drosophila melanogaster     

Zdobnov EM  von Mering C  Letunic I  Torrents D  Suyama M  Copley RR  Christophides GK  Thomasova D  Holt RA  Subramanian GM  Mueller HM  Dimopoulos G  Law JH  Wells MA  Birney E  Charlab R  Halpern AL  Kokoza E  Kraft CL  Lai Z  Lewis S  Louis C  Barillas-Mury C  Nusskern D  Rubin GM  Salzberg SL  Sutton GG  Topalis P  Wides R  Wincker P  Yandell M  Collins FH  Ribeiro J  Gelbart WM  Kafatos FC  Bork P 《Science (New York, N.Y.)》2002,298(5591):149-159

Comparison of the genomes and proteomes of the two diptera Anopheles gambiae and Drosophila melanogaster, which diverged about 250 million years ago, reveals considerable similarities. However, numerous differences are also observed; some of these must reflect the selection and subsequent adaptation associated with different ecologies and life strategies. Almost half of the genes in both genomes are interpreted as orthologs and show an average sequence identity of about 56%, which is slightly lower than that observed between the orthologs of the pufferfish and human (diverged about 450 million years ago). This indicates that these two insects diverged considerably faster than vertebrates. Aligned sequences reveal that orthologous genes have retained only half of their intron/exon structure, indicating that intron gains or losses have occurred at a rate of about one per gene per 125 million years. Chromosomal arms exhibit significant remnants of homology between the two species, although only 34% of the genes colocalize in small "microsyntenic" clusters, and major interarm transfers as well as intra-arm shuffling of gene order are detected.  相似文献   

Dimerization of the extracellular domain of the human growth hormone receptor by a single hormone molecule   总被引：51，自引：0，他引：51  

B C Cunningham  M Ultsch  A M De Vos  M G Mulkerrin  K R Clauser  J A Wells 《Science (New York, N.Y.)》1991,254(5033):821-825

Human growth hormone (hGH) forms a 1:2 complex with the extracellular domain of its receptor-binding protein (hGHbp) as studied by crystallization, size exclusion chromatography, calorimetry, and a previously undescribed fluorescence quenching assay. These and other experiments with protein engineered variants of hGH have led to the identification of the binding determinants for two distinct but adjacent sites on hGH for the hGHbp, and the data indicated that there are two overlapping binding sites on the hGHbp for hGH. Furthermore, the binding of hGH to the hGHbp occurred sequentially; a first hGHbp molecule bound to site 1 on hGH and then a second hGHbp bound to site 2. Hormone-induced receptor dimerization is proposed to be relevant to the signal transduction mechanism for the hGH receptor and other related cytokine receptors.  相似文献