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排序方式: 共有183条查询结果,搜索用时 15 毫秒
61.
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
62.
The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth 总被引:1,自引:0,他引:1
Christofk HR Vander Heiden MG Harris MH Ramanathan A Gerszten RE Wei R Fleming MD Schreiber SL Cantley LC 《Nature》2008,452(7184):230-233
Many tumour cells have elevated rates of glucose uptake but reduced rates of oxidative phosphorylation. This persistence of high lactate production by tumours in the presence of oxygen, known as aerobic glycolysis, was first noted by Otto Warburg more than 75 yr ago. How tumour cells establish this altered metabolic phenotype and whether it is essential for tumorigenesis is as yet unknown. Here we show that a single switch in a splice isoform of the glycolytic enzyme pyruvate kinase is necessary for the shift in cellular metabolism to aerobic glycolysis and that this promotes tumorigenesis. Tumour cells have been shown to express exclusively the embryonic M2 isoform of pyruvate kinase. Here we use short hairpin RNA to knockdown pyruvate kinase M2 expression in human cancer cell lines and replace it with pyruvate kinase M1. Switching pyruvate kinase expression to the M1 (adult) isoform leads to reversal of the Warburg effect, as judged by reduced lactate production and increased oxygen consumption, and this correlates with a reduced ability to form tumours in nude mouse xenografts. These results demonstrate that M2 expression is necessary for aerobic glycolysis and that this metabolic phenotype provides a selective growth advantage for tumour cells in vivo. 相似文献
63.
Structural changes in glycogen phosphorylase induced by phosphorylation 总被引:27,自引:0,他引:27
S R Sprang K R Acharya E J Goldsmith D I Stuart K Varvill R J Fletterick N B Madsen L N Johnson 《Nature》1988,336(6196):215-221
A comparison of the refined crystal structures of dimeric glycogen phosphorylase b and a reveals structural changes that represent the first step in the activation of the enzyme. On phosphorylation of serine-14, the N-terminus of each subunit assumes an ordered helical conformation and binds to the surface of the dimer. The consequent structural changes at the N- and C-terminal regions lead to strengthened interactions between subunits and alter the binding sites for allosteric effectors and substrates. 相似文献
64.
65.
在过去的20年,科研工作者已经在分子肿瘤领域取得了划时代的重大发现,这很大程度上归功于免疫组织化学方法的应用。这一方法在脑肿瘤研究中也已经从试验阶段走向了成熟。 相似文献
66.
Limited heterogeneity of rearranged T-cell receptor V alpha transcripts in brains of multiple sclerosis patients 总被引:49,自引:0,他引:49
J R Oksenberg S Stuart A B Begovich R B Bell H A Erlich L Steinman C C Bernard 《Nature》1990,345(6273):344-346
67.
爱德华·霍尔于 2 0 0 1年 8月 1 1日病逝 ,享年 77岁。霍尔不仅是一位伟大的物理学家 ,还是一位有独创性的发明家和手艺超群的工匠。他建造了世界上最为精确的单摆钟 ,并在科学研究上也颇有建树 ,他认为自己对科学工作纯粹都是为了兴趣而完成的。在过去的 45年里 ,霍尔的主要兴趣 (至少是在技术方面 )在考古学上。考古学主要是通过发明、建造和利用各种方法来发现古代物品 ,确定它们的年代并对其进行鉴定。考古学可以使我们了解古代的技术状况。近些年来 ,在世界范围内掀起了一场考古热 ,它是科学和艺术的结合 ,现在称为“考古定年学”。这… 相似文献
68.
Generation of a transient, amplified response to the dimming of light in the visual system of the barnacle involves two synaptic stages. It is accomplished primarily by decrementally conducting neurones that are similar to bipolar cells of the vertebrate retina. 相似文献
69.
Carlton JM Adams JH Silva JC Bidwell SL Lorenzi H Caler E Crabtree J Angiuoli SV Merino EF Amedeo P Cheng Q Coulson RM Crabb BS Del Portillo HA Essien K Feldblyum TV Fernandez-Becerra C Gilson PR Gueye AH Guo X Kang'a S Kooij TW Korsinczky M Meyer EV Nene V Paulsen I White O Ralph SA Ren Q Sargeant TJ Salzberg SL Stoeckert CJ Sullivan SA Yamamoto MM Hoffman SL Wortman JR Gardner MJ Galinski MR Barnwell JW Fraser-Liggett CM 《Nature》2008,455(7214):757-763
The human malaria parasite Plasmodium vivax is responsible for 25-40% of the approximately 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non-human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species. 相似文献
70.
González-Maeso J Ang RL Yuen T Chan P Weisstaub NV López-Giménez JF Zhou M Okawa Y Callado LF Milligan G Gingrich JA Filizola M Meana JJ Sealfon SC 《Nature》2008,452(7183):93-97
The psychosis associated with schizophrenia is characterized by alterations in sensory processing and perception. Some antipsychotic drugs were identified by their high affinity for serotonin 5-HT2A receptors (2AR). Drugs that interact with metabotropic glutamate receptors (mGluR) also have potential for the treatment of schizophrenia. The effects of hallucinogenic drugs, such as psilocybin and lysergic acid diethylamide, require the 2AR and resemble some of the core symptoms of schizophrenia. Here we show that the mGluR2 interacts through specific transmembrane helix domains with the 2AR, a member of an unrelated G-protein-coupled receptor family, to form functional complexes in brain cortex. The 2AR-mGluR2 complex triggers unique cellular responses when targeted by hallucinogenic drugs, and activation of mGluR2 abolishes hallucinogen-specific signalling and behavioural responses. In post-mortem human brain from untreated schizophrenic subjects, the 2AR is upregulated and the mGluR2 is downregulated, a pattern that could predispose to psychosis. These regulatory changes indicate that the 2AR-mGluR2 complex may be involved in the altered cortical processes of schizophrenia, and this complex is therefore a promising new target for the treatment of psychosis. 相似文献