排序方式: 共有64条查询结果,搜索用时 15 毫秒
31.
Finlayson C Pacheco FG Rodríguez-Vidal J Fa DA Gutierrez López JM Santiago Pérez A Finlayson G Allue E Baena Preysler J Cáceres I Carrión JS Fernández Jalvo Y Gleed-Owen CP Jimenez Espejo FJ López P López Sáez JA Riquelme Cantal JA Sánchez Marco A Guzman FG Brown K Fuentes N Valarino CA Villalpando A Stringer CB Martinez Ruiz F Sakamoto T 《Nature》2006,443(7113):850-853
The late survival of archaic hominin populations and their long contemporaneity with modern humans is now clear for southeast Asia. In Europe the extinction of the Neanderthals, firmly associated with Mousterian technology, has received much attention, and evidence of their survival after 35 kyr bp has recently been put in doubt. Here we present data, based on a high-resolution record of human occupation from Gorham's Cave, Gibraltar, that establish the survival of a population of Neanderthals to 28 kyr bp. These Neanderthals survived in the southernmost point of Europe, within a particular physiographic context, and are the last currently recorded anywhere. Our results show that the Neanderthals survived in isolated refuges well after the arrival of modern humans in Europe. 相似文献
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33.
Nurieva R Yang XO Martinez G Zhang Y Panopoulos AD Ma L Schluns K Tian Q Watowich SS Jetten AM Dong C 《Nature》2007,448(7152):480-483
34.
Amary MF Damato S Halai D Eskandarpour M Berisha F Bonar F McCarthy S Fantin VR Straley KS Lobo S Aston W Green CL Gale RE Tirabosco R Futreal A Campbell P Presneau N Flanagan AM 《Nature genetics》2011,43(12):1262-1265
Ollier disease and Maffucci syndrome are characterized by multiple central cartilaginous tumors that are accompanied by soft tissue hemangiomas in Maffucci syndrome. We show that in 37 of 40 individuals with these syndromes, at least one tumor has a mutation in isocitrate dehydrogenase 1 (IDH1) or in IDH2, 65% of which result in a R132C substitution in the protein. In 18 of 19 individuals with more than one tumor analyzed, all tumors from a given individual shared the same IDH1 mutation affecting Arg132. In 2 of 12 subjects, a low level of mutated DNA was identified in non-neoplastic tissue. The levels of the metabolite 2HG were measured in a series of central cartilaginous and vascular tumors, including samples from syndromic and nonsyndromic subjects, and these levels correlated strongly with the presence of IDH1 mutations. The findings are compatible with a model in which IDH1 or IDH2 mutations represent early post-zygotic occurrences in individuals with these syndromes. 相似文献
35.
CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer 总被引:19,自引:0,他引:19
Weisenberger DJ Siegmund KD Campan M Young J Long TI Faasse MA Kang GH Widschwendter M Weener D Buchanan D Koh H Simms L Barker M Leggett B Levine J Kim M French AJ Thibodeau SN Jass J Haile R Laird PW 《Nature genetics》2006,38(7):787-793
Aberrant DNA methylation of CpG islands has been widely observed in human colorectal tumors and is associated with gene silencing when it occurs in promoter areas. A subset of colorectal tumors has an exceptionally high frequency of methylation of some CpG islands, leading to the suggestion of a distinct trait referred to as 'CpG island methylator phenotype', or 'CIMP'. However, the existence of CIMP has been challenged. To resolve this continuing controversy, we conducted a systematic, stepwise screen of 195 CpG island methylation markers using MethyLight technology, involving 295 primary human colorectal tumors and 16,785 separate quantitative analyses. We found that CIMP-positive (CIMP+) tumors convincingly represent a distinct subset, encompassing almost all cases of tumors with BRAF mutation (odds ratio = 203). Sporadic cases of mismatch repair deficiency occur almost exclusively as a consequence of CIMP-associated methylation of MLH1 . We propose a robust new marker panel to classify CIMP+ tumors. 相似文献
36.
Amos CI Wu X Broderick P Gorlov IP Gu J Eisen T Dong Q Zhang Q Gu X Vijayakrishnan J Sullivan K Matakidou A Wang Y Mills G Doheny K Tsai YY Chen WV Shete S Spitz MR Houlston RS 《Nature genetics》2008,40(5):616-622
To identify risk variants for lung cancer, we conducted a multistage genome-wide association study. In the discovery phase, we analyzed 315,450 tagging SNPs in 1,154 current and former (ever) smoking cases of European ancestry and 1,137 frequency-matched, ever-smoking controls from Houston, Texas. For replication, we evaluated the ten SNPs most significantly associated with lung cancer in an additional 711 cases and 632 controls from Texas and 2,013 cases and 3,062 controls from the UK. Two SNPs, rs1051730 and rs8034191, mapping to a region of strong linkage disequilibrium within 15q25.1 containing PSMA4 and the nicotinic acetylcholine receptor subunit genes CHRNA3 and CHRNA5, were significantly associated with risk in both replication sets. Combined analysis yielded odds ratios of 1.32 (P < 1 x 10(-17)) for both SNPs. Haplotype analysis was consistent with there being a single risk variant in this region. We conclude that variation in a region of 15q25.1 containing nicotinic acetylcholine receptors genes contributes to lung cancer risk. 相似文献
37.
Dispersal characteristics were measured for a population of yucca weevils ( Scyphophorus yuccae ) in a plot consisting of flowering and nonflowering Yucca whipplei . We compared weevil dispersal to yucca distribution, pheonolgy, and caudex temperature. We also compared weevil movement to wind patterns and time of day. Captured weevils were marked and released into both flowering and nonflowering home plants in the field. Distance traveled, weevil flight direction, and target plant characteristics were recorded. We found that yucca weevils moved only between 1600 h on the release day and 0600 h of the following day. We recorded movement from both nonflowering and old flowering (> 1/2 stalk had reached anthesis) yuccas to new flowering (> 1/2 stalk pre-anthesis) yuccas. The pattern of weevil movement did not match the pattern of flowering yuccas in the field. Yucca weevils moved a mean distance of 33 ± 8 m. Caudex temperature appeared to be important to maintain a population of weevils on a plant. Wind direction was the best predictor of weevil dispersal direction. Weevils consistently moved into the wind, suggesting that they are active fliers. Dispersal characteristics of the yucca weevil have implications for the evolution of the semelparous flowering strategy of Y. whipplei and S. yuccae life history. 相似文献
38.
Landscape of transcription in human cells 总被引:3,自引:0,他引:3
S Djebali CA Davis A Merkel A Dobin T Lassmann A Mortazavi A Tanzer J Lagarde W Lin F Schlesinger C Xue GK Marinov J Khatun BA Williams C Zaleski J Rozowsky M Röder F Kokocinski RF Abdelhamid T Alioto I Antoshechkin MT Baer NS Bar P Batut K Bell I Bell S Chakrabortty X Chen J Chrast J Curado T Derrien J Drenkow E Dumais J Dumais R Duttagupta E Falconnet M Fastuca K Fejes-Toth P Ferreira S Foissac MJ Fullwood H Gao D Gonzalez A Gordon H Gunawardena C Howald S Jha R Johnson P Kapranov B King 《Nature》2012,489(7414):101-108
Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene. 相似文献
39.
Poulikakos PI Persaud Y Janakiraman M Kong X Ng C Moriceau G Shi H Atefi M Titz B Gabay MT Salton M Dahlman KB Tadi M Wargo JA Flaherty KT Kelley MC Misteli T Chapman PB Sosman JA Graeber TG Ribas A Lo RS Rosen N Solit DB 《Nature》2011,480(7377):387-390
Activated RAS promotes dimerization of members of the RAF kinase family. ATP-competitive RAF inhibitors activate ERK signalling by transactivating RAF dimers. In melanomas with mutant BRAF(V600E), levels of RAS activation are low and these drugs bind to BRAF(V600E) monomers and inhibit their activity. This tumour-specific inhibition of ERK signalling results in a broad therapeutic index and RAF inhibitors have remarkable clinical activity in patients with melanomas that harbour mutant BRAF(V600E). However, resistance invariably develops. Here, we identify a new resistance mechanism. We find that a subset of cells resistant to vemurafenib (PLX4032, RG7204) express a 61-kDa variant form of BRAF(V600E), p61BRAF(V600E), which lacks exons 4-8, a region that encompasses the RAS-binding domain. p61BRAF(V600E) shows enhanced dimerization in cells with low levels of RAS activation, as compared to full-length BRAF(V600E). In cells in which p61BRAF(V600E) is expressed endogenously or ectopically, ERK signalling is resistant to the RAF inhibitor. Moreover, a mutation that abolishes the dimerization of p61BRAF(V600E) restores its sensitivity to vemurafenib. Finally, we identified BRAF(V600E) splicing variants lacking the RAS-binding domain in the tumours of six of nineteen patients with acquired resistance to vemurafenib. These data support the model that inhibition of ERK signalling by RAF inhibitors is dependent on levels of RAS-GTP too low to support RAF dimerization and identify a novel mechanism of acquired resistance in patients: expression of splicing isoforms of BRAF(V600E) that dimerize in a RAS-independent manner. 相似文献
40.
Hillier LW Fulton RS Fulton LA Graves TA Pepin KH Wagner-McPherson C Layman D Maas J Jaeger S Walker R Wylie K Sekhon M Becker MC O'Laughlin MD Schaller ME Fewell GA Delehaunty KD Miner TL Nash WE Cordes M Du H Sun H Edwards J Bradshaw-Cordum H Ali J Andrews S Isak A Vanbrunt A Nguyen C Du F Lamar B Courtney L Kalicki J Ozersky P Bielicki L Scott K Holmes A Harkins R Harris A Strong CM Hou S Tomlinson C Dauphin-Kohlberg S Kozlowicz-Reilly A Leonard S Rohlfing T Rock SM Tin-Wollam AM Abbott A 《Nature》2003,424(6945):157-164