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71.
Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor 总被引:2,自引:0,他引:2
Adams GB Chabner KT Alley IR Olson DP Szczepiorkowski ZM Poznansky MC Kos CH Pollak MR Brown EM Scadden DT 《Nature》2006,439(7076):599-603
During mammalian ontogeny, haematopoietic stem cells (HSCs) translocate from the fetal liver to the bone marrow, where haematopoiesis occurs throughout adulthood. Unique features of bone that contribute to a microenvironmental niche for stem cells might include the known high concentration of calcium ions at the HSC-enriched endosteal surface. Cells respond to extracellular ionic calcium concentrations through the seven-transmembrane-spanning calcium-sensing receptor (CaR), which we identified as being expressed on HSCs. Here we show that, through the CaR, the simple ionic mineral content of the niche may dictate the preferential localization of adult mammalian haematopoiesis in bone. Antenatal mice deficient in CaR had primitive haematopoietic cells in the circulation and spleen, whereas few were found in bone marrow. CaR-/- HSCs from fetal liver were normal in number, in proliferative and differentiative function, and in migration and homing to the bone marrow. Yet they were highly defective in localizing anatomically to the endosteal niche, behaviour that correlated with defective adhesion to the extracellular matrix protein, collagen I. CaR has a function in retaining HSCs in close physical proximity to the endosteal surface and the regulatory niche components associated with it. 相似文献
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73.
Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma 总被引:1,自引:0,他引:1
Varela I Tarpey P Raine K Huang D Ong CK Stephens P Davies H Jones D Lin ML Teague J Bignell G Butler A Cho J Dalgliesh GL Galappaththige D Greenman C Hardy C Jia M Latimer C Lau KW Marshall J McLaren S Menzies A Mudie L Stebbings L Largaespada DA Wessels LF Richard S Kahnoski RJ Anema J Tuveson DA Perez-Mancera PA Mustonen V Fischer A Adams DJ Rust A Chan-on W Subimerb C Dykema K Furge K Campbell PJ Teh BT Stratton MR Futreal PA 《Nature》2011,469(7331):539-542
74.
Yalcin B Wong K Agam A Goodson M Keane TM Gan X Nellåker C Goodstadt L Nicod J Bhomra A Hernandez-Pliego P Whitley H Cleak J Dutton R Janowitz D Mott R Adams DJ Flint J 《Nature》2011,477(7364):326-329
Structural variation is widespread in mammalian genomes and is an important cause of disease, but just how abundant and important structural variants (SVs) are in shaping phenotypic variation remains unclear. Without knowing how many SVs there are, and how they arise, it is difficult to discover what they do. Combining experimental with automated analyses, we identified 711,920 SVs at 281,243 sites in the genomes of thirteen classical and four wild-derived inbred mouse strains. The majority of SVs are less than 1?kilobase in size and 98% are deletions or insertions. The breakpoints of 160,000 SVs were mapped to base pair resolution, allowing us to infer that insertion of retrotransposons causes more than half of SVs. Yet, despite their prevalence, SVs are less likely than other sequence variants to cause gene expression or quantitative phenotypic variation. We identified 24 SVs that disrupt coding exons, acting as rare variants of large effect on gene function. One-third of the genes so affected have immunological functions. 相似文献
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76.
澳大利亚和新西兰都是英语国家且在文化和经济上历来与英国和美国有着紧密的联系,同时他们又都是依靠资源和农业的传统型经济体.最近的一篇关于新西兰创新体制的OECD报告中提到这样一段话:“过去,新西兰经济主要是依靠农业、林业、渔业、加工及服务业而发展的典型的自然资源经济.而近年来随着农业食品生物技术、旅游业以及影视制作等新兴... 相似文献
77.
Fred Adams 《Foundations of Science》2014,19(2):133-135
In this commentary to Serrano et al. (2013), I applaud this foundation article for being a breath of fresh air because it addresses the question “What is cognition?” Too often in the cognitive sciences, we leave that question unanswered or worse, unasked. I come not to criticize but to offer a helpful suggestion aimed a pulling together some of the separate strands weaved throughout this article. 相似文献
78.
Everitt AR Clare S Pertel T John SP Wash RS Smith SE Chin CR Feeley EM Sims JS Adams DJ Wise HM Kane L Goulding D Digard P Anttila V Baillie JK Walsh TS Hume DA Palotie A Xue Y Colonna V Tyler-Smith C Dunning J Gordon SB;GenISIS Investigators;MOSAIC Investigators Smyth RL Openshaw PJ Dougan G Brass AL Kellam P 《Nature》2012,484(7395):519-523
The 2009 H1N1 influenza pandemic showed the speed with which a novel respiratory virus can spread and the ability of a generally mild infection to induce severe morbidity and mortality in a subset of the population. Recent in vitro studies show that the interferon-inducible transmembrane (IFITM) protein family members potently restrict the replication of multiple pathogenic viruses. Both the magnitude and breadth of the IFITM proteins' in vitro effects suggest that they are critical for intrinsic resistance to such viruses, including influenza viruses. Using a knockout mouse model, we now test this hypothesis directly and find that IFITM3 is essential for defending the host against influenza A virus in vivo. Mice lacking Ifitm3 display fulminant viral pneumonia when challenged with a normally low-pathogenicity influenza virus, mirroring the destruction inflicted by the highly pathogenic 1918 'Spanish' influenza. Similar increased viral replication is seen in vitro, with protection rescued by the re-introduction of Ifitm3. To test the role of IFITM3 in human influenza virus infection, we assessed the IFITM3 alleles of individuals hospitalized with seasonal or pandemic influenza H1N1/09 viruses. We find that a statistically significant number of hospitalized subjects show enrichment for a minor IFITM3 allele (SNP rs12252-C) that alters a splice acceptor site, and functional assays show the minor CC genotype IFITM3 has reduced influenza virus restriction in vitro. Together these data reveal that the action of a single intrinsic immune effector, IFITM3, profoundly alters the course of influenza virus infection in mouse and humans. 相似文献
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80.
Charon's radius and atmospheric constraints from observations of a stellar occultation 总被引:1,自引:0,他引:1
Gulbis AA Elliot JL Person MJ Adams ER Babcock BA Emilio M Gangestad JW Kern SD Kramer EA Osip DJ Pasachoff JM Souza SP Tuvikene T 《Nature》2006,439(7072):48-51
The physical characteristics of Pluto and its moon, Charon, provide insight into the evolution of the outer Solar System. Although previous measurements have constrained the masses of these bodies, their radii and densities have remained uncertain. The observation of a stellar occultation by Charon in 1980 established a lower limit on its radius of 600 km (ref. 3) (later refined to 601.5 km; ref. 4) and suggested a possible atmosphere. Subsequent, mutual event modelling yielded a range of 600-650 km (ref. 5), corresponding to a density of 1.56 +/- 0.22 g cm(-3) (refs 2, 5). Here we report multiple-station observations of a stellar occultation by Charon. From these data, we find a mean radius of 606 +/- 8 km, a bulk density of 1.72 +/- 0.15 g cm(-3), and rock-mass fraction 0.63 +/- 0.05. We do not detect a significant atmosphere and place 3sigma upper limits on atmospheric number densities for candidate gases. These results seem to be consistent with collisional formation for the Pluto-Charon system in which the precursor objects may have been differentiated, and they leave open the possibility of atmospheric retention by the largest objects in the outer Solar System. 相似文献