排序方式: 共有120条查询结果,搜索用时 15 毫秒
111.
Scherer SE Muzny DM Buhay CJ Chen R Cree A Ding Y Dugan-Rocha S Gill R Gunaratne P Harris RA Hawes AC Hernandez J Hodgson AV Hume J Jackson A Khan ZM Kovar-Smith C Lewis LR Lozado RJ Metzker ML Milosavljevic A Miner GR Montgomery KT Morgan MB Nazareth LV Scott G Sodergren E Song XZ Steffen D Lovering RC Wheeler DA Worley KC Yuan Y Zhang Z Adams CQ Ansari-Lari MA Ayele M Brown MJ Chen G Chen Z Clerc-Blankenburg KP Davis C Delgado O Dinh HH Draper H Gonzalez-Garay ML Havlak P Jackson LR Jacob LS 《Nature》2006,440(7082):346-351
Human chromosome 12 contains more than 1,400 coding genes and 487 loci that have been directly implicated in human disease. The q arm of chromosome 12 contains one of the largest blocks of linkage disequilibrium found in the human genome. Here we present the finished sequence of human chromosome 12, which has been finished to high quality and spans approximately 132 megabases, representing approximately 4.5% of the human genome. Alignment of the human chromosome 12 sequence across vertebrates reveals the origin of individual segments in chicken, and a unique history of rearrangement through rodent and primate lineages. The rate of base substitutions in recent evolutionary history shows an overall slowing in hominids compared with primates and rodents. 相似文献
112.
Rachel V Baxter Kamel Ben Othmane Julie M Rochelle Jason E Stajich Christine Hulette Susan Dew-Knight Faycal Hentati Mongi Ben Hamida S Bel Judy E Stenger John R Gilbert Margaret A Pericak-Vance Jeffery M Vance 《Nature genetics》2002,30(1):21-22
We previously localized and fine-mapped Charcot Marie Tooth 4A (CMT4A), the autosomal recessive, demyelinating peripheral neuropathy, to chromosome 8. Through additional positional cloning, we have identified a good candidate gene, encoding ganglioside-induced differentiation-associated protein-1 (GDAP1). We found three different mutations in four different Tunisian families-two nonsense and one missense mutation. How mutations in GDAP1 lead to CMT4A remains to be understood. 相似文献
113.
Viré E Brenner C Deplus R Blanchon L Fraga M Didelot C Morey L Van Eynde A Bernard D Vanderwinden JM Bollen M Esteller M Di Croce L de Launoit Y Fuks F 《Nature》2006,439(7078):871-874
The establishment and maintenance of epigenetic gene silencing is fundamental to cell determination and function. The essential epigenetic systems involved in heritable repression of gene activity are the Polycomb group (PcG) proteins and the DNA methylation systems. Here we show that the corresponding silencing pathways are mechanistically linked. We find that the PcG protein EZH2 (Enhancer of Zeste homolog 2) interacts-within the context of the Polycomb repressive complexes 2 and 3 (PRC2/3)-with DNA methyltransferases (DNMTs) and associates with DNMT activity in vivo. Chromatin immunoprecipitations indicate that binding of DNMTs to several EZH2-repressed genes depends on the presence of EZH2. Furthermore, we show by bisulphite genomic sequencing that EZH2 is required for DNA methylation of EZH2-target promoters. Our results suggest that EZH2 serves as a recruitment platform for DNA methyltransferases, thus highlighting a previously unrecognized direct connection between two key epigenetic repression systems. 相似文献
114.
Ro DK Paradise EM Ouellet M Fisher KJ Newman KL Ndungu JM Ho KA Eachus RA Ham TS Kirby J Chang MC Withers ST Shiba Y Sarpong R Keasling JD 《Nature》2006,440(7086):940-943
Malaria is a global health problem that threatens 300-500 million people and kills more than one million people annually. Disease control is hampered by the occurrence of multi-drug-resistant strains of the malaria parasite Plasmodium falciparum. Synthetic antimalarial drugs and malarial vaccines are currently being developed, but their efficacy against malaria awaits rigorous clinical testing. Artemisinin, a sesquiterpene lactone endoperoxide extracted from Artemisia annua L (family Asteraceae; commonly known as sweet wormwood), is highly effective against multi-drug-resistant Plasmodium spp., but is in short supply and unaffordable to most malaria sufferers. Although total synthesis of artemisinin is difficult and costly, the semi-synthesis of artemisinin or any derivative from microbially sourced artemisinic acid, its immediate precursor, could be a cost-effective, environmentally friendly, high-quality and reliable source of artemisinin. Here we report the engineering of Saccharomyces cerevisiae to produce high titres (up to 100 mg l(-1)) of artemisinic acid using an engineered mevalonate pathway, amorphadiene synthase, and a novel cytochrome P450 monooxygenase (CYP71AV1) from A. annua that performs a three-step oxidation of amorpha-4,11-diene to artemisinic acid. The synthesized artemisinic acid is transported out and retained on the outside of the engineered yeast, meaning that a simple and inexpensive purification process can be used to obtain the desired product. Although the engineered yeast is already capable of producing artemisinic acid at a significantly higher specific productivity than A. annua, yield optimization and industrial scale-up will be required to raise artemisinic acid production to a level high enough to reduce artemisinin combination therapies to significantly below their current prices. 相似文献
115.
Stephens P Edkins S Davies H Greenman C Cox C Hunter C Bignell G Teague J Smith R Stevens C O'Meara S Parker A Tarpey P Avis T Barthorpe A Brackenbury L Buck G Butler A Clements J Cole J Dicks E Edwards K Forbes S Gorton M Gray K Halliday K Harrison R Hills K Hinton J Jones D Kosmidou V Laman R Lugg R Menzies A Perry J Petty R Raine K Shepherd R Small A Solomon H Stephens Y Tofts C Varian J Webb A West S Widaa S Yates A Brasseur F Cooper CS Flanagan AM Green A Knowles M Leung SY Looijenga LH 《Nature genetics》2005,37(6):590-592
We examined the coding sequence of 518 protein kinases, approximately 1.3 Mb of DNA per sample, in 25 breast cancers. In many tumors, we detected no somatic mutations. But a few had numerous somatic mutations with distinctive patterns indicative of either a mutator phenotype or a past exposure. 相似文献
116.
Penetration by an object through a dense granular medium (for example, by a finger pushing slowly into the sand on a beach) presents an interesting physics problem that is closely related to issues of practical importance in soil science. Here we measure the penetration-resistance force for an object approaching the solid bottom boundary of a granular sample--analogous to the finger approaching a flat rock buried in the beach. We find that the penetration resistance near the boundary increases exponentially, which demonstrates the existence of an intrinsic length scale to the 'jamming' caused by a locally applied stress. 相似文献
117.
The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes 总被引:2,自引:0,他引:2
Skaletsky H Kuroda-Kawaguchi T Minx PJ Cordum HS Hillier L Brown LG Repping S Pyntikova T Ali J Bieri T Chinwalla A Delehaunty A Delehaunty K Du H Fewell G Fulton L Fulton R Graves T Hou SF Latrielle P Leonard S Mardis E Maupin R McPherson J Miner T Nash W Nguyen C Ozersky P Pepin K Rock S Rohlfing T Scott K Schultz B Strong C Tin-Wollam A Yang SP Waterston RH Wilson RK Rozen S Page DC 《Nature》2003,423(6942):825-837
118.
Atlas R Campbell P Cozzarelli NR Curfman G Enquist L Fink G Flanagin A Fletcher J George E Hammes G Heyman D Inglesby T Kaplan S Kennedy D Krug J Levinson R Marcus E Metzger H Morse SS O'Brien A Onderdonk A Poste G Renault B Rich R Rosengard A Salzberg S Scanlan M Shenk T Tabor H Varmus H Wimmer E Yamamoto K;Journal Editors Authors Group 《Nature》2003,421(6925):771
119.
Flierl MA Rittirsch D Nadeau BA Chen AJ Sarma JV Zetoune FS McGuire SR List RP Day DE Hoesel LM Gao H Van Rooijen N Huber-Lang MS Neubig RR Ward PA 《Nature》2007,449(7163):721-725
It is becoming increasingly clear that the autonomic nervous system and the immune system demonstrate cross-talk during inflammation by means of sympathetic and parasympathetic pathways. We investigated whether phagocytes are capable of de novo production of catecholamines, suggesting an autocrine/paracrine self-regulatory mechanism by catecholamines during inflammation, as has been described for lymphocytes. Here we show that exposure of phagocytes to lipopolysaccharide led to a release of catecholamines and an induction of catecholamine-generating and degrading enzymes, indicating the presence of the complete intracellular machinery for the generation, release and inactivation of catecholamines. To assess the importance of these findings in vivo, we chose two models of acute lung injury. Blockade of alpha2-adrenoreceptors or catecholamine-generating enzymes greatly suppressed lung inflammation, whereas the opposite was the case either for an alpha2-adrenoreceptor agonist or for inhibition of catecholamine-degrading enzymes. We were able to exclude T cells or sympathetic nerve endings as sources of the injury-modulating catecholamines. Our studies identify phagocytes as a new source of catecholamines, which enhance the inflammatory response. 相似文献
120.