排序方式: 共有49条查询结果,搜索用时 857 毫秒
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Greenman C Stephens P Smith R Dalgliesh GL Hunter C Bignell G Davies H Teague J Butler A Stevens C Edkins S O'Meara S Vastrik I Schmidt EE Avis T Barthorpe S Bhamra G Buck G Choudhury B Clements J Cole J Dicks E Forbes S Gray K Halliday K Harrison R Hills K Hinton J Jenkinson A Jones D Menzies A Mironenko T Perry J Raine K Richardson D Shepherd R Small A Tofts C Varian J Webb T West S Widaa S Yates A Cahill DP Louis DN Goldstraw P Nicholson AG Brasseur F Looijenga L Weber BL Chiew YE DeFazio A 《Nature》2007,446(7132):153-158
Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNA corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers. There was substantial variation in the number and pattern of mutations in individual cancers reflecting different exposures, DNA repair defects and cellular origins. Most somatic mutations are likely to be 'passengers' that do not contribute to oncogenesis. However, there was evidence for 'driver' mutations contributing to the development of the cancers studied in approximately 120 genes. Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated. 相似文献
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Tawk M Araya C Lyons DA Reugels AM Girdler GC Bayley PR Hyde DR Tada M Clarke JD 《Nature》2007,446(7137):797-800
The development of cell polarity is an essential prerequisite for tissue morphogenesis during embryogenesis, particularly in the development of epithelia. In addition, oriented cell division can have a powerful influence on tissue morphogenesis. Here we identify a novel mode of polarized cell division that generates pairs of neural progenitors with mirror-symmetric polarity in the developing zebrafish neural tube and has dramatic consequences for the organization of embryonic tissue. We show that during neural rod formation the polarity protein Pard3 is localized to the cleavage furrow of dividing progenitors, and then mirror-symmetrically inherited by the two daughter cells. This allows the daughter cells to integrate into opposite sides of the developing neural tube. Furthermore, these mirror-symmetric divisions have powerful morphogenetic influence: when forced to occur in ectopic locations during neurulation, they orchestrate the development of mirror-image pattern formation and the consequent generation of ectopic neural tubes. 相似文献
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Tom Addis Jan Townsend Addis Dave Billinge David Gooding Bart-Floris Visscher 《Foundations of Science》2008,13(1):5-16
We argue from the Church-Turing thesis (Kleene Mathematical logic. New York: Wiley 1967) that a program can be considered as equivalent to a formal language similar to predicate calculus where predicates can be taken as functions. We can relate such a calculus to Wittgenstein’s first major work, the Tractatus, and use the Tractatus and its theses as a model of the formal classical definition of a computer program. However, Wittgenstein found flaws in his initial great work and he explored these flaws in a new thesis described in his second great work; the Philosophical Investigations. The question we address is “can computer science make the same leap?” We are proposing, because of the flaws identified by Wittgenstein, that computers will never have the possibility of natural communication with people unless they become active participants of human society. The essential difference between formal models used in computing and human communication is that formal models are based upon rational sets whereas people are not so restricted. We introduce irrational sets as a concept that requires the use of an abductive inference system. However, formal models are still considered central to our means of using hypotheses through deduction to make predictions about the world. These formal models are required to continually be updated in response to peoples’ changes in their way of seeing the world. We propose that one mechanism used to keep track of these changes is the Peircian abductive loop. 相似文献
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Frezza C Zheng L Folger O Rajagopalan KN MacKenzie ED Jerby L Micaroni M Chaneton B Adam J Hedley A Kalna G Tomlinson IP Pollard PJ Watson DG Deberardinis RJ Shlomi T Ruppin E Gottlieb E 《Nature》2011,477(7363):225-228
Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid cycle (TCA cycle) that catalyses the hydration of fumarate into malate. Germline mutations of FH are responsible for hereditary leiomyomatosis and renal-cell cancer (HLRCC). It has previously been demonstrated that the absence of FH leads to the accumulation of fumarate, which activates hypoxia-inducible factors (HIFs) at normal oxygen tensions. However, so far no mechanism that explains the ability of cells to survive without a functional TCA cycle has been provided. Here we use newly characterized genetically modified kidney mouse cells in which Fh1 has been deleted, and apply a newly developed computer model of the metabolism of these cells to predict and experimentally validate a linear metabolic pathway beginning with glutamine uptake and ending with bilirubin excretion from Fh1-deficient cells. This pathway, which involves the biosynthesis and degradation of haem, enables Fh1-deficient cells to use the accumulated TCA cycle metabolites and permits partial mitochondrial NADH production. We predicted and confirmed that targeting this pathway would render Fh1-deficient cells non-viable, while sparing wild-type Fh1-containing cells. This work goes beyond identifying a metabolic pathway that is induced in Fh1-deficient cells to demonstrate that inhibition of haem oxygenation is synthetically lethal when combined with Fh1 deficiency, providing a new potential target for treating HLRCC patients. 相似文献
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Kleta R Romeo E Ristic Z Ohura T Stuart C Arcos-Burgos M Dave MH Wagner CA Camargo SR Inoue S Matsuura N Helip-Wooley A Bockenhauer D Warth R Bernardini I Visser G Eggermann T Lee P Chairoungdua A Jutabha P Babu E Nilwarangkoon S Anzai N Kanai Y Verrey F Gahl WA Koizumi A 《Nature genetics》2004,36(9):999-1002
Hartnup disorder, an autosomal recessive defect named after an English family described in 1956 (ref. 1), results from impaired transport of neutral amino acids across epithelial cells in renal proximal tubules and intestinal mucosa. Symptoms include transient manifestations of pellagra (rashes), cerebellar ataxia and psychosis. Using homozygosity mapping in the original family in whom Hartnup disorder was discovered, we confirmed that the critical region for one causative gene was located on chromosome 5p15 (ref. 3). This region is homologous to the area of mouse chromosome 13 that encodes the sodium-dependent amino acid transporter B(0)AT1 (ref. 4). We isolated the human homolog of B(0)AT1, called SLC6A19, and determined its size and molecular organization. We then identified mutations in SLC6A19 in members of the original family in whom Hartnup disorder was discovered and of three Japanese families. The protein product of SLC6A19, the Hartnup transporter, is expressed primarily in intestine and renal proximal tubule and functions as a neutral amino acid transporter. 相似文献
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Sharp ZD 《Cellular and molecular life sciences : CMLS》2011,68(4):587-597
Longstanding results with calorie and growth factor restriction plus recent results with the first interventional drug suggest
that retarding the pace of aging to improve the quality of life of older people is at hand. The biological system targeted
by these approaches is the target of rapamycin (TOR), which is central for cellular responses to a variety of stimuli including
stressors, growth factors, and nutrients and energy states. That the life-extending response to reducing its activity is highly
conserved from yeast to mammals is consistent with the evolution of aging as a strategy to preserve reproductive potential
of young cells and animals. 相似文献