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81.
82.
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
83.
Temporal variability of the Atlantic meridional overturning circulation at 26.5 degrees N 总被引:4,自引:0,他引:4
Cunningham SA Kanzow T Rayner D Baringer MO Johns WE Marotzke J Longworth HR Grant EM Hirschi JJ Beal LM Meinen CS Bryden HL 《Science (New York, N.Y.)》2007,317(5840):935-938
The vigor of Atlantic meridional overturning circulation (MOC) is thought to be vulnerable to global warming, but its short-term temporal variability is unknown so changes inferred from sparse observations on the decadal time scale of recent climate change are uncertain. We combine continuous measurements of the MOC (beginning in 2004) using the purposefully designed transatlantic Rapid Climate Change array of moored instruments deployed along 26.5 degrees N, with time series of Gulf Stream transport and surface-layer Ekman transport to quantify its intra-annual variability. The year-long average overturning is 18.7 +/- 5.6 sverdrups (Sv) (range: 4.0 to 34.9 Sv, where 1 Sv = a flow of ocean water of 10(6) cubic meters per second). Interannual changes in the overturning can be monitored with a resolution of 1.5 Sv. 相似文献
84.
85.
Giovannoni SJ Tripp HJ Givan S Podar M Vergin KL Baptista D Bibbs L Eads J Richardson TH Noordewier M Rappé MS Short JM Carrington JC Mathur EJ 《Science (New York, N.Y.)》2005,309(5738):1242-1245
The SAR11 clade consists of very small, heterotrophic marine alpha-proteobacteria that are found throughout the oceans, where they account for about 25% of all microbial cells. Pelagibacter ubique, the first cultured member of this clade, has the smallest genome and encodes the smallest number of predicted open reading frames known for a free-living microorganism. In contrast to parasitic bacteria and archaea with small genomes, P. ubique has complete biosynthetic pathways for all 20 amino acids and all but a few cofactors. P. ubique has no pseudogenes, introns, transposons, extrachromosomal elements, or inteins; few paralogs; and the shortest intergenic spacers yet observed for any cell. 相似文献
86.
The large variation in the ratio of uranium-234 to uranium-238 (234U/238U) in rivers is not well understood, but may provide information about past weathering and rainfall and is important because it controls seawater (234U/238U). Here, we demonstrate the importance of physical weathering and rainfall for (234U/238U), using rivers from South Island, New Zealand. These data allow interpretation of an existing speleothem (234U/238U) record and suggest that New Zealand glacier advance 13,000 years ago was influenced by increased rainfall rather than by Younger Dryas-like cooling. A model of seawater (234U/238U) during glacial cycles indicates that rejection of corals based on modern (234U/238U) +/- <0.01 is not merited and may reject the highest quality ages. 相似文献
87.
RNA silencing genes control de novo DNA methylation 总被引:1,自引:0,他引:1
Chan SW Zilberman D Xie Z Johansen LK Carrington JC Jacobsen SE 《Science (New York, N.Y.)》2004,303(5662):1336
88.
Mangale VS Hirokawa KE Satyaki PR Gokulchandran N Chikbire S Subramanian L Shetty AS Martynoga B Paul J Mai MV Li Y Flanagan LA Tole S Monuki ES 《Science (New York, N.Y.)》2008,319(5861):304-309
The earliest step in creating the cerebral cortex is the specification of neuroepithelium to a cortical fate. Using mouse genetic mosaics and timed inactivations, we demonstrated that Lhx2 acts as a classic selector gene and essential intrinsic determinant of cortical identity. Lhx2 selector activity is restricted to an early critical period when stem cells comprise the cortical neuroepithelium, where it acts cell-autonomously to specify cortical identity and suppress alternative fates in a spatially dependent manner. Laterally, Lhx2 null cells adopt antihem identity, whereas medially they become cortical hem cells, which can induce and organize ectopic hippocampal fields. In addition to providing functional evidence for Lhx2 selector activity, these findings show that the cortical hem is a hippocampal organizer. 相似文献
89.
Murphy WJ Larkin DM Everts-van der Wind A Bourque G Tesler G Auvil L Beever JE Chowdhary BP Galibert F Gatzke L Hitte C Meyers SN Milan D Ostrander EA Pape G Parker HG Raudsepp T Rogatcheva MB Schook LB Skow LC Welge M Womack JE O'brien SJ Pevzner PA Lewin HA 《Science (New York, N.Y.)》2005,309(5734):613-617
The genome organizations of eight phylogenetically distinct species from five mammalian orders were compared in order to address fundamental questions relating to mammalian chromosomal evolution. Rates of chromosome evolution within mammalian orders were found to increase since the Cretaceous-Tertiary boundary. Nearly 20% of chromosome breakpoint regions were reused during mammalian evolution; these reuse sites are also enriched for centromeres. Analysis of gene content in and around evolutionary breakpoint regions revealed increased gene density relative to the genome-wide average. We found that segmental duplications populate the majority of primate-specific breakpoints and often flank inverted chromosome segments, implicating their role in chromosomal rearrangement. 相似文献
90.