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排序方式: 共有214条查询结果,搜索用时 62 毫秒
81.
Ellis MJ Ding L Shen D Luo J Suman VJ Wallis JW Van Tine BA Hoog J Goiffon RJ Goldstein TC Ng S Lin L Crowder R Snider J Ballman K Weber J Chen K Koboldt DC Kandoth C Schierding WS McMichael JF Miller CA Lu C Harris CC McLellan MD Wendl MC DeSchryver K Allred DC Esserman L Unzeitig G Margenthaler J Babiera GV Marcom PK Guenther JM Leitch M Hunt K Olson J Tao Y Maher CA Fulton LL Fulton RS Harrison M Oberkfell B Du F Demeter R Vickery TL Elhammali A Piwnica-Worms H McDonald S Watson M Dooling DJ 《Nature》2012,486(7403):353-360
To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies of neoadjuvant aromatase inhibitor therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five genes (RUNX1, CBFB, MYH9, MLL3 and SF3B1) previously linked to haematopoietic disorders. Mutant MAP3K1 was associated with luminal A status, low-grade histology and low proliferation rates, whereas mutant TP53 was associated with the opposite pattern. Moreover, mutant GATA3 correlated with suppression of proliferation upon aromatase inhibitor treatment. Pathway analysis demonstrated that mutations in MAP2K4, a MAP3K1 substrate, produced similar perturbations as MAP3K1 loss. Distinct phenotypes in oestrogen-receptor-positive breast cancer are associated with specific patterns of somatic mutations that map into cellular pathways linked to tumour biology, but most recurrent mutations are relatively infrequent. Prospective clinical trials based on these findings will require comprehensive genome sequencing. 相似文献
82.
Yooseph S Nealson KH Rusch DB McCrow JP Dupont CL Kim M Johnson J Montgomery R Ferriera S Beeson K Williamson SJ Tovchigrechko A Allen AE Zeigler LA Sutton G Eisenstadt E Rogers YH Friedman R Frazier M Venter JC 《Nature》2010,468(7320):60-66
The understanding of marine microbial ecology and metabolism has been hampered by the paucity of sequenced reference genomes. To this end, we report the sequencing of 137 diverse marine isolates collected from around the world. We analysed these sequences, along with previously published marine prokaryotic genomes, in the context of marine metagenomic data, to gain insights into the ecology of the surface ocean prokaryotic picoplankton (0.1-3.0?μm size range). The results suggest that the sequenced genomes define two microbial groups: one composed of only a few taxa that are nearly always abundant in picoplanktonic communities, and the other consisting of many microbial taxa that are rarely abundant. The genomic content of the second group suggests that these microbes are capable of slow growth and survival in energy-limited environments, and rapid growth in energy-rich environments. By contrast, the abundant and cosmopolitan picoplanktonic prokaryotes for which there is genomic representation have smaller genomes, are probably capable of only slow growth and seem to be relatively unable to sense or rapidly acclimate to energy-rich conditions. Their genomic features also lead us to propose that one method used to avoid predation by viruses and/or bacterivores is by means of slow growth and the maintenance of low biomass. 相似文献
83.
84.
Published fish blood parameters are limited to commercially cultured species (e.g. rainbow trout [ Oncorhynchus mykiss ] and channel catfish [ Ictalurus punctatus ]). However, as walleye ( Stizostedion vitreum ) and other fish increase in value to the angler, hatchery and fish managers will require data on these species. Blood sera were collected from live walleye in the field, creatinine values were determined colorimetrically, and health range values were established from these data. Creatinine levels of walleye serum (0.06-0.72 mg/dl) were higher in three species but lower than recognized in a recent catfish study. Creatinine levels may be important in predicting diseases in which the kidney is adversely affected. 相似文献
85.
Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss 总被引:1,自引:0,他引:1
Klein CJ Botuyan MV Wu Y Ward CJ Nicholson GA Hammans S Hojo K Yamanishi H Karpf AR Wallace DC Simon M Lander C Boardman LA Cunningham JM Smith GE Litchy WJ Boes B Atkinson EJ Middha S B Dyck PJ Parisi JE Mer G Smith DI Dyck PJ 《Nature genetics》2011,43(6):595-600
DNA methyltransferase 1 (DNMT1) is crucial for maintenance of methylation, gene regulation and chromatin stability. DNA mismatch repair, cell cycle regulation in post-mitotic neurons and neurogenesis are influenced by DNA methylation. Here we show that mutations in DNMT1 cause both central and peripheral neurodegeneration in one form of hereditary sensory and autonomic neuropathy with dementia and hearing loss. Exome sequencing led to the identification of DNMT1 mutation c.1484A>G (p.Tyr495Cys) in two American kindreds and one Japanese kindred and a triple nucleotide change, c.1470-1472TCC>ATA (p.Asp490Glu-Pro491Tyr), in one European kindred. All mutations are within the targeting-sequence domain of DNMT1. These mutations cause premature degradation of mutant proteins, reduced methyltransferase activity and impaired heterochromatin binding during the G2 cell cycle phase leading to global hypomethylation and site-specific hypermethylation. Our study shows that DNMT1 mutations cause the aberrant methylation implicated in complex pathogenesis. The discovered DNMT1 mutations provide a new framework for the study of neurodegenerative diseases. 相似文献
86.
Brown KM Macgregor S Montgomery GW Craig DW Zhao ZZ Iyadurai K Henders AK Homer N Campbell MJ Stark M Thomas S Schmid H Holland EA Gillanders EM Duffy DL Maskiell JA Jetann J Ferguson M Stephan DA Cust AE Whiteman D Green A Olsson H Puig S Ghiorzo P Hansson J Demenais F Goldstein AM Gruis NA Elder DE Bishop JN Kefford RF Giles GG Armstrong BK Aitken JF Hopper JL Martin NG Trent JM Mann GJ Hayward NK 《Nature genetics》2008,40(7):838-840
We conducted a genome-wide association pooling study for cutaneous melanoma and performed validation in samples totaling 2,019 cases and 2,105 controls. Using pooling, we identified a new melanoma risk locus on chromosome 20 (rs910873 and rs1885120), with replication in two further samples (combined P < 1 x 10(-15)). The per allele odds ratio was 1.75 (1.53, 2.01), with evidence for stronger association in early-onset cases. 相似文献
87.
88.
A subfamily of stress proteins facilitates translocation of secretory and mitochondrial precursor polypeptides 总被引:242,自引:0,他引:242
Depletion of a subset of 70K stress proteins in yeast mutants shows that they are involved in the post-translational import of precursor polypeptides into both mitochondria and the lumen of the endoplasmic reticulum. The identification of such a basic function may explain the remarkable evolutionary conservation of the gene family encoding these proteins. 相似文献
89.
M. Wurzel L. C. Craig B. W. Zweifach 《Cellular and molecular life sciences : CMLS》1969,25(8):824-826
Résumé La «nouvelle»-vasoconstrictine (SVPx 1962), une hormone vasoconstrictrice du plasma, a été préparée par distribution à contre-courant en quantité suffisante pour l'étude de sa structure chimique et de ses propriétés biologiques. 相似文献
90.
Role of thiols in human peripheral blood natural killer and killer lymphocyte activities 总被引:1,自引:0,他引:1
The thiol reagents, dithiothreitol, diethyldithiocarbamate and reduced glutathione were each found to inhibit Natural Killer and Killer lymphocyte-mediated cytotoxicities. A biphasic aspect to the inhibition with increasing concentration was observed with diethyldithiocarbamate and reduced glutathione. The inhibition observed in response to reduced glutathione, a non-permeant compound, suggests that cell surface thiols may be critical functional groups in the processes of NK and K lymphocyte-mediated cytotoxicities. 相似文献