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51.
Cassan A Kubas D Beaulieu JP Dominik M Horne K Greenhill J Wambsganss J Menzies J Williams A Jørgensen UG Udalski A Bennett DP Albrow MD Batista V Brillant S Caldwell JA Cole A Coutures Ch Cook KH Dieters S Prester DD Donatowicz J Fouqué P Hill K Kains N Kane S Marquette JB Martin R Pollard KR Sahu KC Vinter C Warren D Watson B Zub M Sumi T Szymański MK Kubiak M Poleski R Soszynski I Ulaczyk K Pietrzyński G Wyrzykowski L 《Nature》2012,481(7380):167-169
Most known extrasolar planets (exoplanets) have been discovered using the radial velocity or transit methods. Both are biased towards planets that are relatively close to their parent stars, and studies find that around 17-30% (refs 4, 5) of solar-like stars host a planet. Gravitational microlensing, on the other hand, probes planets that are further away from their stars. Recently, a population of planets that are unbound or very far from their stars was discovered by microlensing. These planets are at least as numerous as the stars in the Milky Way. Here we report a statistical analysis of microlensing data (gathered in 2002-07) that reveals the fraction of bound planets 0.5-10?AU (Sun-Earth distance) from their stars. We find that 17(+6)(-9)% of stars host Jupiter-mass planets (0.3-10?M(J), where M(J) = 318?M(⊕) and M(⊕) is Earth's mass). Cool Neptunes (10-30?M(⊕)) and super-Earths (5-10?M(⊕)) are even more common: their respective abundances per star are 52(+22)(-29)% and 62(+35)(-37)%. We conclude that stars are orbited by planets as a rule, rather than the exception. 相似文献
52.
Shah SP Roth A Goya R Oloumi A Ha G Zhao Y Turashvili G Ding J Tse K Haffari G Bashashati A Prentice LM Khattra J Burleigh A Yap D Bernard V McPherson A Shumansky K Crisan A Giuliany R Heravi-Moussavi A Rosner J Lai D Birol I Varhol R Tam A Dhalla N Zeng T Ma K Chan SK Griffith M Moradian A Cheng SW Morin GB Watson P Gelmon K Chia S Chin SF Curtis C Rueda OM Pharoah PD Damaraju S Mackey J Hoon K Harkins T Tadigotla V Sigaroudinia M Gascard P Tlsty T Costello JF Meyer IM Eaves CJ Wasserman WW 《Nature》2012,486(7403):395-399
Primary triple-negative breast cancers (TNBCs), a tumour type defined by lack of oestrogen receptor, progesterone receptor and ERBB2 gene amplification, represent approximately 16% of all breast cancers. Here we show in 104 TNBC cases that at the time of diagnosis these cancers exhibit a wide and continuous spectrum of genomic evolution, with some having only a handful of coding somatic aberrations in a few pathways, whereas others contain hundreds of coding somatic mutations. High-throughput RNA sequencing (RNA-seq) revealed that only approximately 36% of mutations are expressed. Using deep re-sequencing measurements of allelic abundance for 2,414 somatic mutations, we determine for the first time-to our knowledge-in an epithelial tumour subtype, the relative abundance of clonal frequencies among cases representative of the population. We show that TNBCs vary widely in their clonal frequencies at the time of diagnosis, with the basal subtype of TNBC showing more variation than non-basal TNBC. Although p53 (also known as TP53), PIK3CA and PTEN somatic mutations seem to be clonally dominant compared to other genes, in some tumours their clonal frequencies are incompatible with founder status. Mutations in cytoskeletal, cell shape and motility proteins occurred at lower clonal frequencies, suggesting that they occurred later during tumour progression. Taken together, our results show that understanding the biology and therapeutic responses of patients with TNBC will require the determination of individual tumour clonal genotypes. 相似文献
53.
The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups 总被引:1,自引:0,他引:1
Curtis C Shah SP Chin SF Turashvili G Rueda OM Dunning MJ Speed D Lynch AG Samarajiwa S Yuan Y Gräf S Ha G Haffari G Bashashati A Russell R McKinney S;METABRIC Group Langerød A Green A Provenzano E Wishart G Pinder S Watson P Markowetz F Murphy L Ellis I Purushotham A Børresen-Dale AL Brenton JD Tavaré S Caldas C Aparicio S 《Nature》2012,486(7403):346-352
54.
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
55.
Noel Edwards Catriona M. H. Anderson Nichola J. Conlon Andrew K. Watson Rebecca J. Hall Timothy R. Cheek T. Martin Embley David T. Thwaites 《Cellular and molecular life sciences : CMLS》2018,75(5):921-938
Amino acid transporters are essential components of prokaryote and eukaryote cells, possess distinct physiological functions, and differ markedly in substrate specificity. Amino acid transporters can be both drug targets and drug transporters (bioavailability, targeting) with many monogenic disorders resulting from dysfunctional membrane transport. The largest collection of amino acid transporters (including the mammalian SLC6, SLC7, SLC32, SLC36, and SLC38 families), across all kingdoms of life, is within the Amino acid-Polyamine-organoCation (APC) superfamily. The LeuT-fold is a paradigm structure for APC superfamily amino acid transporters and carriers of sugars, neurotransmitters, electrolytes, osmolytes, vitamins, micronutrients, signalling molecules, and organic and fatty acids. Each transporter is specific for a unique sub-set of solutes, specificity being determined by how well a substrate fits into each binding pocket. However, the molecular basis of substrate selectivity remains, by and large, elusive. Using an integrated computational and experimental approach, we demonstrate that a single position within the LeuT-fold can play a crucial role in determining substrate specificity in mammalian and arthropod amino acid transporters within the APC superfamily. Systematic mutation of the amino acid residue occupying the equivalent position to LeuT V104 titrates binding pocket space resulting in dramatic changes in substrate selectivity in exemplar APC amino acid transporters including PAT2 (SLC36A2) and SNAT5 (SLC38A5). Our work demonstrates how a single residue/site within an archetypal structural motif can alter substrate affinity and selectivity within this important superfamily of diverse membrane transporters. 相似文献
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57.
58.
Structure of yeast phosphoglycerate kinase 总被引:13,自引:0,他引:13
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60.
The history of the Earth has been characterized by a series of major transitions separated by long periods of relative stability. The largest chemical transition was the 'Great Oxidation', approximately 2.4 billion years ago, when atmospheric oxygen concentrations rose from less than 10(-5) of the present atmospheric level (PAL) to more than 0.01 PAL, and possibly to more than 0.1 PAL. This transition took place long after oxygenic photosynthesis is thought to have evolved, but the causes of this delay and of the Great Oxidation itself remain uncertain. Here we show that the origin of oxygenic photosynthesis gave rise to two simultaneously stable steady states for atmospheric oxygen. The existence of a low-oxygen (less than 10(-5) PAL) steady state explains how a reducing atmosphere persisted for at least 300 million years after the onset of oxygenic photosynthesis. The Great Oxidation can be understood as a switch to the high-oxygen (more than 5 x 10(-3) PAL) steady state. The bistability arises because ultraviolet shielding of the troposphere by ozone becomes effective once oxygen levels exceed 10(-5) PAL, causing a nonlinear increase in the lifetime of atmospheric oxygen. Our results indicate that the existence of oxygenic photosynthesis is not a sufficient condition for either an oxygen-rich atmosphere or the presence of an ozone layer, which has implications for detecting life on other planets using atmospheric analysis and for the evolution of multicellular life. 相似文献