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排序方式: 共有113条查询结果,搜索用时 15 毫秒
41.
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
42.
Andersen EC Gerke JP Shapiro JA Crissman JR Ghosh R Bloom JS Félix MA Kruglyak L 《Nature genetics》2012,44(3):285-290
The nematode Caenorhabditis elegans is central to research in molecular, cell and developmental biology, but nearly all of this research has been conducted on a single strain of C. elegans. Little is known about the population genomic and evolutionary history of this species. We characterized C. elegans genetic variation using high-throughput selective sequencing of a worldwide collection of 200 wild strains and identified 41,188 SNPs. Notably, C. elegans genome variation is dominated by a set of commonly shared haplotypes on four of its six chromosomes, each spanning many megabases. Population genetic modeling showed that this pattern was generated by chromosome-scale selective sweeps that have reduced variation worldwide; at least one of these sweeps probably occurred in the last few hundred years. These sweeps, which we hypothesize to be a result of human activity, have drastically reshaped the global C. elegans population in the recent past. 相似文献
43.
The application of fractal dimension-based constructs to probe the protein interior dates back to the development of the concept
of fractal dimension itself. Numerous approaches have been tried and tested over a course of (almost) 30 years with the aim
of elucidating the various facets of symmetry of self-similarity prevalent in the protein interior. In the last 5 years especially,
there has been a startling upsurge of research that innovatively stretches the limits of fractal-based studies to present
an array of unexpected results on the biophysical properties of protein interior. In this article, we introduce readers to
the fundamentals of fractals, reviewing the commonality (and the lack of it) between these approaches before exploring the
patterns in the results that they produced. Clustering the approaches in major schools of protein self-similarity studies,
we describe the evolution of fractal dimension-based methodologies. The genealogy of approaches (and results) presented here
portrays a clear picture of the contemporary state of fractal-based studies in the context of the protein interior. To underline
the utility of fractal dimension-based measures further, we have performed a correlation dimension analysis on all of the
available non-redundant protein structures, both at the level of an individual protein and at the level of structural domains.
In this investigation, we were able to separately quantify the self-similar symmetries in spatial correlation patterns amongst
peptide–dipole units, charged amino acids, residues with the π-electron cloud and hydrophobic amino acids. The results revealed
that electrostatic environments in the interiors of proteins belonging to ‘α/α toroid’ (all-α class) and ‘PLP-dependent transferase-like’
domains (α/β class) are highly conducive. In contrast, the interiors of ‘zinc finger design’ (‘designed proteins’) and ‘knottins’
(‘small proteins’) were identified as folds with the least conducive electrostatic environments. The fold ‘conotoxins’ (peptides)
could be unambiguously identified as one type with the least stability. The same analyses revealed that peptide–dipoles in
the α/β class of proteins, in general, are more correlated to each other than are the peptide–dipoles in proteins belonging
to the all-α class. Highly favorable electrostatic milieu in the interiors of TIM-barrel, α/β-hydrolase structures could explain
their remarkably conserved (evolutionary) stability from a new light. Finally, we point out certain inherent limitations of
fractal constructs before attempting to identify the areas and problems where the implementation of fractal dimension-based
constructs can be of paramount help to unearth latent information on protein structural properties. 相似文献
44.
45.
V. Gopalakrishnan S. Ramaswamy N. Padmanabha Pillai S. Ranganathan M. N. Ghosh 《Cellular and molecular life sciences : CMLS》1980,36(12):1423-1425
Summary Incubation of red cells with higher concentrations of prolactin in vitro enhanced the cellular sodium level and produced a significant reduction in erythrocyte membrane adenosine triphosphatase activity. This effect was dose and time-dependent. It is the result of an inhibition of the active sodium pump similar to that produced by ouabain, suggesting altered red cell function and electrolyte balance in hyperprolactinemic states.Acknowledgments. Ovine prolactin was generously supplied by Ferring (Malmö, Sweden) and NPA, NIH (Maryland, USA). Thanks are also due to Prof. S. Dutta, Wayne State University, Detroit, for the gift, of ouabain octahydrate and Dr M. Ramachandran and Prof. S. Ramakrishnan, Department of Biochemistry, JIPMER, Pondicherry, for their encouragement and keen interest in this study. 相似文献
46.
47.
48.
Zusammenfassung Männliche Albino-Ratten, 45 Tage bei riboflavinarmer Nahrung, zeigten erhöhten Gehalt freien Aminosäure-Stickstoffs in Leber, Muskel und Plasma. Die Erhöhung scheint durch eine gesteigerte Aktivität der Nebennierenrinde beim Riboflavinmangel herbeigeführt zu sein. 相似文献
49.
Summary Injection of cadmium chloride in a toad increases both the
5-3-hydroxy-steroid dehydrogenase and 17-hydroxysteroid dehydrogenase activities in Bidder's organ. 相似文献
50.
Harsha HC Suresh S Amanchy R Deshpande N Shanker K Yatish AJ Muthusamy B Vrushabendra BM Rashmi BP Chandrika KN Padma N Sharma S Badano JL Ramya MA Shivashankar HN Peri S Choudhury DR Kavitha MP Saravana R Niranjan V Gandhi TK Ghosh N Chandran S Menezes M Joy M Mohan SS Katsanis N Deshpande KS Raghothama C Prasad CK Pandey A 《Nature genetics》2005,37(4):331-332