排序方式: 共有61条查询结果,搜索用时 15 毫秒
21.
Berger MF Hodis E Heffernan TP Deribe YL Lawrence MS Protopopov A Ivanova E Watson IR Nickerson E Ghosh P Zhang H Zeid R Ren X Cibulskis K Sivachenko AY Wagle N Sucker A Sougnez C Onofrio R Ambrogio L Auclair D Fennell T Carter SL Drier Y Stojanov P Singer MA Voet D Jing R Saksena G Barretina J Ramos AH Pugh TJ Stransky N Parkin M Winckler W Mahan S Ardlie K Baldwin J Wargo J Schadendorf D Meyerson M Gabriel SB Golub TR Wagner SN Lander ES Getz G Chin L Garraway LA 《Nature》2012,485(7399):502-506
Melanoma is notable for its metastatic propensity, lethality in the advanced setting and association with ultraviolet exposure early in life. To obtain a comprehensive genomic view of melanoma in humans, we sequenced the genomes of 25 metastatic melanomas and matched germline DNA. A wide range of point mutation rates was observed: lowest in melanomas whose primaries arose on non-ultraviolet-exposed hairless skin of the extremities (3 and 14 per megabase (Mb) of genome), intermediate in those originating from hair-bearing skin of the trunk (5-55 per Mb), and highest in a patient with a documented history of chronic sun exposure (111 per Mb). Analysis of whole-genome sequence data identified PREX2 (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2)--a PTEN-interacting protein and negative regulator of PTEN in breast cancer--as a significantly mutated gene with a mutation frequency of approximately 14% in an independent extension cohort of 107 human melanomas. PREX2 mutations are biologically relevant, as ectopic expression of mutant PREX2 accelerated tumour formation of immortalized human melanocytes in vivo. Thus, whole-genome sequencing of human melanoma tumours revealed genomic evidence of ultraviolet pathogenesis and discovered a new recurrently mutated gene in melanoma. 相似文献
22.
Raychaudhuri S Remmers EF Lee AT Hackett R Guiducci C Burtt NP Gianniny L Korman BD Padyukov L Kurreeman FA Chang M Catanese JJ Ding B Wong S van der Helm-van Mil AH Neale BM Coblyn J Cui J Tak PP Wolbink GJ Crusius JB van der Horst-Bruinsma IE Criswell LA Amos CI Seldin MF Kastner DL Ardlie KG Alfredsson L Costenbader KH Altshuler D Huizinga TW Shadick NA Weinblatt ME de Vries N Worthington J Seielstad M Toes RE Karlson EW Begovich AB Klareskog L Gregersen PK Daly MJ Plenge RM 《Nature genetics》2008,40(10):1216-1223
To identify rheumatoid arthritis risk loci in European populations, we conducted a meta-analysis of two published genome-wide association (GWA) studies totaling 3,393 cases and 12,462 controls. We genotyped 31 top-ranked SNPs not previously associated with rheumatoid arthritis in an independent replication of 3,929 autoantibody-positive rheumatoid arthritis cases and 5,807 matched controls from eight separate collections. We identified a common variant at the CD40 gene locus (rs4810485, P = 0.0032 replication, P = 8.2 x 10(-9) overall, OR = 0.87). Along with other associations near TRAF1 (refs. 2,3) and TNFAIP3 (refs. 4,5), this implies a central role for the CD40 signaling pathway in rheumatoid arthritis pathogenesis. We also identified association at the CCL21 gene locus (rs2812378, P = 0.00097 replication, P = 2.8 x 10(-7) overall), a gene involved in lymphocyte trafficking. Finally, we identified evidence of association at four additional gene loci: MMEL1-TNFRSF14 (rs3890745, P = 0.0035 replication, P = 1.1 x 10(-7) overall), CDK6 (rs42041, P = 0.010 replication, P = 4.0 x 10(-6) overall), PRKCQ (rs4750316, P = 0.0078 replication, P = 4.4 x 10(-6) overall), and KIF5A-PIP4K2C (rs1678542, P = 0.0026 replication, P = 8.8 x 10(-8) overall). 相似文献
23.
Combinatorial microRNA target predictions 总被引:59,自引:0,他引:59
Krek A Grün D Poy MN Wolf R Rosenberg L Epstein EJ MacMenamin P da Piedade I Gunsalus KC Stoffel M Rajewsky N 《Nature genetics》2005,37(5):495-500
24.
We provide examples of the extent and nature of environmental and human health problems and show why in the United States
prevailing scientific and legal burden of proof requirements usually cannot be met because of the pervasiveness of scientific
uncertainty. We also provide examples of how may assumptions, judgments, evaluations, and inferences in scientific methods
are value-laden and that when this is not recognized results of studies will appear to be more factual and value-neutral than
warranted. Further, we show that there is a "tension" between the use of the 95 percent confidence rule as a normative basis
to reduce speculation in scientific knowledge and other public policy and moral concerns embodied by the adoption of a precautionary
principle. Finally, although there is no precise agreement regarding what a precautionary principle might entail, we make
several recommendations regarding the placement of the burden of proof and the standard of proof that ought to be required
in environmental and human health matters.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
25.
Systemic Practice and Action Research - Action research literature promotes broad participation in order to gain better insights into prevailing issues and cope with both present and future... 相似文献
26.
Banerji S Cibulskis K Rangel-Escareno C Brown KK Carter SL Frederick AM Lawrence MS Sivachenko AY Sougnez C Zou L Cortes ML Fernandez-Lopez JC Peng S Ardlie KG Auclair D Bautista-Piña V Duke F Francis J Jung J Maffuz-Aziz A Onofrio RC Parkin M Pho NH Quintanar-Jurado V Ramos AH Rebollar-Vega R Rodriguez-Cuevas S Romero-Cordoba SL Schumacher SE Stransky N Thompson KM Uribe-Figueroa L Baselga J Beroukhim R Polyak K Sgroi DC Richardson AL Jimenez-Sanchez G Lander ES Gabriel SB Garraway LA Golub TR 《Nature》2012,486(7403):405-409
27.
J L Davèze A Di Pietro J Frappa R Deloince Y Beaudry R Fontanges 《Comptes rendus des séances de l'Académie des sciences. Série D, Sciences naturelles》1978,286(22):1621-1624
5'-nucleotidase activity of cultured diplo?d cells was measured using intact suspended cells. This depended on the substrate amount, but did not vary with Mg ++ concentration-Kinetic data were determined using Con. A,a specific inhibitor. 相似文献
28.
Eggan K Baldwin K Tackett M Osborne J Gogos J Chess A Axel R Jaenisch R 《Nature》2004,428(6978):44-49
Cloning by nuclear transplantation has been successfully carried out in various mammals, including mice. Until now mice have not been cloned from post-mitotic cells such as neurons. Here, we have generated fertile mouse clones derived by transferring the nuclei of post-mitotic, olfactory sensory neurons into oocytes. These results indicate that the genome of a post-mitotic, terminally differentiated neuron can re-enter the cell cycle and be reprogrammed to a state of totipotency after nuclear transfer. Moreover, the pattern of odorant receptor gene expression and the organization of odorant receptor genes in cloned mice was indistinguishable from wild-type animals, indicating that irreversible changes to the DNA of olfactory neurons do not accompany receptor gene choice. 相似文献
29.
30.