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排序方式: 共有410条查询结果,搜索用时 531 毫秒
401.
Houlston RS Cheadle J Dobbins SE Tenesa A Jones AM Howarth K Spain SL Broderick P Domingo E Farrington S Prendergast JG Pittman AM Theodoratou E Smith CG Olver B Walther A Barnetson RA Churchman M Jaeger EE Penegar S Barclay E Martin L Gorman M Mager R Johnstone E Midgley R Niittymäki I Tuupanen S Colley J Idziaszczyk S;COGENT Consortium Thomas HJ Lucassen AM Evans DG Maher ER;CORGI Consortium;COIN Collaborative Group;COINB Collaborative Group Maughan T Dimas A Dermitzakis E Cazier JB 《Nature genetics》2010,42(11):973-977
Genome-wide association studies (GWAS) have identified ten loci harboring common variants that influence risk of developing colorectal cancer (CRC). To enhance the power to identify additional CRC risk loci, we conducted a meta-analysis of three GWAS from the UK which included a total of 3,334 affected individuals (cases) and 4,628 controls followed by multiple validation analyses including a total of 18,095 cases and 20,197 controls. We identified associations at four new CRC risk loci: 1q41 (rs6691170, odds ratio (OR) = 1.06, P = 9.55 × 10?1? and rs6687758, OR = 1.09, P = 2.27 × 10??, 3q26.2 (rs10936599, OR = 0.93, P = 3.39 × 10??), 12q13.13 (rs11169552, OR = 0.92, P = 1.89 × 10?1? and rs7136702, OR = 1.06, P = 4.02 × 10??) and 20q13.33 (rs4925386, OR = 0.93, P = 1.89 × 10?1?). In addition to identifying new CRC risk loci, this analysis provides evidence that additional CRC-associated variants of similar effect size remain to be discovered. 相似文献
402.
Gudmundsson J Sulem P Manolescu A Amundadottir LT Gudbjartsson D Helgason A Rafnar T Bergthorsson JT Agnarsson BA Baker A Sigurdsson A Benediktsdottir KR Jakobsdottir M Xu J Blondal T Kostic J Sun J Ghosh S Stacey SN Mouy M Saemundsdottir J Backman VM Kristjansson K Tres A Partin AW Albers-Akkers MT Godino-Ivan Marcos J Walsh PC Swinkels DW Navarrete S Isaacs SD Aben KK Graif T Cashy J Ruiz-Echarri M Wiley KE Suarez BK Witjes JA Frigge M Ober C Jonsson E Einarsson GV Mayordomo JI Kiemeney LA 《Nature genetics》2007,39(5):631-637
Prostate cancer is the most prevalent noncutaneous cancer in males in developed regions, with African American men having among the highest worldwide incidence and mortality rates. Here we report a second genetic variant in the 8q24 region that, in conjunction with another variant we recently discovered, accounts for about 11%-13% of prostate cancer cases in individuals of European descent and 31% of cases in African Americans. We made the current discovery through a genome-wide association scan of 1,453 affected Icelandic individuals and 3,064 controls using the Illumina HumanHap300 BeadChip followed by four replication studies. A key step in the discovery was the construction of a 14-SNP haplotype that efficiently tags a relatively uncommon (2%-4%) susceptibility variant in individuals of European descent that happens to be very common (approximately 42%) in African Americans. The newly identified variant shows a stronger association with affected individuals who have an earlier age at diagnosis. 相似文献
403.
404.
Edith Jones Norma Gaytan Iraselia Garcia Alan Herrera Manuel Ramos Divya Agarwala Maahrose Rana Wendy Innis-Whitehouse Erin Schuenzel Robert Gilkerson 《Cellular and molecular life sciences : CMLS》2017,74(7):1347-1363
As an organellar network, mitochondria dynamically regulate their organization via opposing fusion and fission pathways to maintain bioenergetic homeostasis and contribute to key cellular pathways. This dynamic balance is directly linked to bioenergetic function: loss of transmembrane potential across the inner membrane (Δψ m) disrupts mitochondrial fission/fusion balance, causing fragmentation of the network. However, the level of Δψ m required for mitochondrial dynamic balance, as well as the relative contributions of fission and fusion pathways, have remained unclear. To explore this, mitochondrial morphology and Δψ m were examined via confocal imaging and tetramethyl rhodamine ester (TMRE) flow cytometry, respectively, in cultured 143B osteosarcoma cells. When normalized to the TMRE value of untreated 143B cells as 100%, both genetic (mtDNA-depleted ρ0) and pharmacological [carbonyl cyanide m-chlorophenyl hydrazone (CCCP)-treated] cell models below 34% TMRE fluorescence were unable to maintain mitochondrial interconnection, correlating with loss of fusion-active long OPA1 isoforms (L-OPA1). Mechanistically, this threshold is maintained by mechanistic coordination of DRP1-mediated fission and OPA1-mediated fusion: cells lacking either DRP1 or the OMA1 metalloprotease were insensitive to loss of Δψ m, instead maintaining an obligately fused morphology. Collectively, these findings demonstrate a mitochondrial ‘tipping point’ threshold mediated by the interaction of Δψ m with both DRP1 and OMA1; moreover, DRP1 appears to be required for effective OPA1 maintenance and processing, consistent with growing evidence for direct interaction of fission and fusion pathways. These results suggest that Δψ m below threshold coordinately activates both DRP1-mediated fission and OMA1 cleavage of OPA1, collapsing mitochondrial dynamic balance, with major implications for a range of signaling pathways and cellular life/death events. 相似文献
405.
Van Houdt JK Nowakowska BA Sousa SB van Schaik BD Seuntjens E Avonce N Sifrim A Abdul-Rahman OA van den Boogaard MJ Bottani A Castori M Cormier-Daire V Deardorff MA Filges I Fryer A Fryns JP Gana S Garavelli L Gillessen-Kaesbach G Hall BD Horn D Huylebroeck D Klapecki J Krajewska-Walasek M Kuechler A Lines MA Maas S Macdermot KD McKee S Magee A de Man SA Moreau Y Morice-Picard F Obersztyn E Pilch J Rosser E Shannon N Stolte-Dijkstra I Van Dijck P Vilain C Vogels A Wakeling E Wieczorek D 《Nature genetics》2012,44(4):445-9, S1
406.
Iain R. Murray Christopher C. West Winters R. Hardy Aaron W. James Tea Soon Park Alan Nguyen Tulyapruek Tawonsawatruk Lorenza Lazzari Chia Soo Bruno Péault 《Cellular and molecular life sciences : CMLS》2014,71(8):1353-1374
Mesenchymal stem/stromal cells (MSCs) can regenerate tissues by direct differentiation or indirectly by stimulating angiogenesis, limiting inflammation, and recruiting tissue-specific progenitor cells. MSCs emerge and multiply in long-term cultures of total cells from the bone marrow or multiple other organs. Such a derivation in vitro is simple and convenient, hence popular, but has long precluded understanding of the native identity, tissue distribution, frequency, and natural role of MSCs, which have been defined and validated exclusively in terms of surface marker expression and developmental potential in culture into bone, cartilage, and fat. Such simple, widely accepted criteria uniformly typify MSCs, even though some differences in potential exist, depending on tissue sources. Combined immunohistochemistry, flow cytometry, and cell culture have allowed tracking the artifactual cultured mesenchymal stem/stromal cells back to perivascular anatomical regions. Presently, both pericytes enveloping microvessels and adventitial cells surrounding larger arteries and veins have been described as possible MSC forerunners. While such a vascular association would explain why MSCs have been isolated from virtually all tissues tested, the origin of the MSCs grown from umbilical cord blood remains unknown. In fact, most aspects of the biology of perivascular MSCs are still obscure, from the emergence of these cells in the embryo to the molecular control of their activity in adult tissues. Such dark areas have not compromised intents to use these cells in clinical settings though, in which purified perivascular cells already exhibit decisive advantages over conventional MSCs, including purity, thorough characterization and, principally, total independence from in vitro culture. A growing body of experimental data is currently paving the way to the medical usage of autologous sorted perivascular cells for indications in which MSCs have been previously contemplated or actually used, such as bone regeneration and cardiovascular tissue repair. 相似文献
407.
Alan C. Taye 《西北部美国博物学家》2011,43(4)
Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 st1\:*{behavior:url(#ieooui) } /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} The Stansbury Mountains of north central Utah rise over 2000 m above surrounding desert valleys to a maximum elevation of 3362 m on Deseret Peak. Because of the great variety of environmental conditions that can be found in the Stansburys, a wide range of plant species and vegetation types (from shadscale desert to alpine meadow) exist there. This paper presents an annotated list of 594 vascular plant species in 315 genera and 78 families. The largest families are Asteraceae (98 species), Poaceae (71), Brassicaceae (33), Fabaceae (27), and Rosaceae (26). Elymus flavescens was previously unreported from Utah. Statistical comparison of the Stansbury flora with neighboring mountain floras indicates that the Wasatch Mountains lying 65 km to the east have probably been the primary source area for development of the Stansbury flora. Many lowland species, especially those inhabiting sandy areas, apparently have migrated to the area from the south. 相似文献
408.
Bicknell LS Bongers EM Leitch A Brown S Schoots J Harley ME Aftimos S Al-Aama JY Bober M Brown PA van Bokhoven H Dean J Edrees AY Feingold M Fryer A Hoefsloot LH Kau N Knoers NV Mackenzie J Opitz JM Sarda P Ross A Temple IK Toutain A Wise CA Wright M Jackson AP 《Nature genetics》2011,43(4):356-359
Meier-Gorlin syndrome (ear, patella and short-stature syndrome) is an autosomal recessive primordial dwarfism syndrome characterized by absent or hypoplastic patellae and markedly small ears1?3. Both pre- and post-natal growth are impaired in this disorder, and although microcephaly is often evident, intellect is usually normal in this syndrome. We report here that individuals with this disorder show marked locus heterogeneity, and we identify mutations in five separate genes: ORC1, ORC4, ORC6, CDT1 and CDC6. All of these genes encode components of the pre-replication complex, implicating defects in replication licensing as the cause of a genetic syndrome with distinct developmental abnormalities. 相似文献
409.
Loveday C Turnbull C Ramsay E Hughes D Ruark E Frankum JR Bowden G Kalmyrzaev B Warren-Perry M Snape K Adlard JW Barwell J Berg J Brady AF Brewer C Brice G Chapman C Cook J Davidson R Donaldson A Douglas F Greenhalgh L Henderson A Izatt L Kumar A Lalloo F Miedzybrodzka Z Morrison PJ Paterson J Porteous M Rogers MT Shanley S Walker L;Breast Cancer Susceptibility Collaboration 《Nature genetics》2011,43(9):879-882
Recently, RAD51C mutations were identified in families with breast and ovarian cancer. This observation prompted us to investigate the role of RAD51D in cancer susceptibility. We identified eight inactivating RAD51D mutations in unrelated individuals from 911 breast-ovarian cancer families compared with one inactivating mutation identified in 1,060 controls (P = 0.01). The association found here was principally with ovarian cancer, with three mutations identified in the 59 pedigrees with three or more individuals with ovarian cancer (P = 0.0005). The relative risk of ovarian cancer for RAD51D mutation carriers was estimated to be 6.30 (95% CI 2.86-13.85, P = 4.8 × 10(-6)). By contrast, we estimated the relative risk of breast cancer to be 1.32 (95% CI 0.59-2.96, P = 0.50). These data indicate that RAD51D mutation testing may have clinical utility in individuals with ovarian cancer and their families. Moreover, we show that cells deficient in RAD51D are sensitive to treatment with a PARP inhibitor, suggesting a possible therapeutic approach for cancers arising in RAD51D mutation carriers. 相似文献
410.