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排序方式: 共有126条查询结果,搜索用时 46 毫秒
1.
RNA polymerase is poised for activation across the genome 总被引:2,自引:0,他引:2
Muse GW Gilchrist DA Nechaev S Shah R Parker JS Grissom SF Zeitlinger J Adelman K 《Nature genetics》2007,39(12):1507-1511
2.
Water capture by a desert beetle. 总被引:15,自引:0,他引:15
Some beetles in the Namib Desert collect drinking water from fog-laden wind on their backs. We show here that these large droplets form by virtue of the insect's bumpy surface, which consists of alternating hydrophobic, wax-coated and hydrophilic, non-waxy regions. The design of this fog-collecting structure can be reproduced cheaply on a commercial scale and may find application in water-trapping tent and building coverings, for example, or in water condensers and engines. 相似文献
3.
The enzyme uracil DNA glycosylase (UNG) excises unwanted uracil bases in the genome using an extrahelical base recognition mechanism. Efficient removal of uracil is essential for prevention of C-to-T transition mutations arising from cytosine deamination, cytotoxic U*A pairs arising from incorporation of dUTP in DNA, and for increasing immunoglobulin gene diversity during the acquired immune response. A central event in all of these UNG-mediated processes is the singling out of rare U*A or U*G base pairs in a background of approximately 10(9) T*A or C*G base pairs in the human genome. Here we establish for the human and Escherichia coli enzymes that discrimination of thymine and uracil is initiated by thermally induced opening of T*A and U*A base pairs and not by active participation of the enzyme. Thus, base-pair dynamics has a critical role in the genome-wide search for uracil, and may be involved in initial damage recognition by other DNA repair glycosylases. 相似文献
4.
5.
Bivona TG Hieronymus H Parker J Chang K Taron M Rosell R Moonsamy P Dahlman K Miller VA Costa C Hannon G Sawyers CL 《Nature》2011,471(7339):523-526
Human lung adenocarcinomas with activating mutations in EGFR (epidermal growth factor receptor) often respond to treatment with EGFR tyrosine kinase inhibitors (TKIs), but the magnitude of tumour regression is variable and transient. This heterogeneity in treatment response could result from genetic modifiers that regulate the degree to which tumour cells are dependent on mutant EGFR. Through a pooled RNA interference screen, we show that knockdown of FAS and several components of the NF-κB pathway specifically enhanced cell death induced by the EGFR TKI erlotinib in EGFR-mutant lung cancer cells. Activation of NF-κB through overexpression of c-FLIP or IKK (also known as CFLAR and IKBKB, respectively), or silencing of IκB (also known as NFKBIA), rescued EGFR-mutant lung cancer cells from EGFR TKI treatment. Genetic or pharmacologic inhibition of NF-κB enhanced erlotinib-induced apoptosis in erlotinib-sensitive and erlotinib-resistant EGFR-mutant lung cancer models. Increased expression of the NF-κB inhibitor IκB predicted for improved response and survival in EGFR-mutant lung cancer patients treated with EGFR TKI. These data identify NF-κB as a potential companion drug target, together with EGFR, in EGFR-mutant lung cancers and provide insight into the mechanisms by which tumour cells escape from oncogene dependence. 相似文献
6.
The X-linked chronic granulomatous disease gene codes for the beta-chain of cytochrome b-245 总被引:2,自引:0,他引:2
Chronic granulomatous disease (CGD) is a rare inherited disorder associated with a profound predisposition to infection due to the lack of a microbicidal oxidase system in the phagocytes of these patients. This syndrome is most commonly inherited through a defect on the X chromosome and the only clearly defined component of the oxidase system, the very unusual cytochrome b (b-245), has been shown to be missing from the cells of these patients. This cytochrome is a heterodimer composed of an alpha-chain of relative molecular mass (Mr) 23,000 (23K) and a 76-92K beta-chain; neither are detectable in neutrophils from X-linked CGD subjects. The defective X-CGD gene has recently been cloned by 'reverse genetics' but the protein predicted from the proposed complementary DNA sequence was not identified. We have purified the beta-chain of the cytochrome and sequenced 43 amino acids from the N terminus. Almost complete homology was obtained between this sequence and that of the complementary nucleotides 19-147 of the sequence of the X-CGD gene, originally designated as a non-coding region. 相似文献
7.
Mutations of the BRAF gene in human cancer 总被引:2,自引:0,他引:2
Davies H Bignell GR Cox C Stephens P Edkins S Clegg S Teague J Woffendin H Garnett MJ Bottomley W Davis N Dicks E Ewing R Floyd Y Gray K Hall S Hawes R Hughes J Kosmidou V Menzies A Mould C Parker A Stevens C Watt S Hooper S Wilson R Jayatilake H Gusterson BA Cooper C Shipley J Hargrave D Pritchard-Jones K Maitland N Chenevix-Trench G Riggins GJ Bigner DD Palmieri G Cossu A Flanagan A Nicholson A Ho JW Leung SY Yuen ST Weber BL Seigler HF Darrow TL Paterson H Marais R Marshall CJ Wooster R 《Nature》2002,417(6892):949-954
Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma. 相似文献
8.
Gene expression: Oestrogen receptor hijacked 总被引:1,自引:0,他引:1
9.
The benthic macroinvertebrate fauna of southern Saskatchewan, Canada, has received little attention relative to other regions of western North America. Therefore, little is known of the related aquatic ecosystem health and biogeography of regional aquatic insects. Here we present the results of an aquatic macroinvertebrate survey for the Pipestone Creek watershed in southeastern Saskatchewan. We qualitatively sampled aquatic macroinvertebrates in 5 sites on 4 dates through spring, summer, and fall 2006. Sampling produced 294 taxa of macroinvertebrates including 25 provincial range extensions to the southeast corner of the province. Presence/absence data of taxa grouped the sites into lentic and lotic sites. However, the relative proportions of the taxa varied greatly among sites, with no 2 sites having a community similarity greater than 50%. Functional feeding group analyses separated the sites into collector-dominated and scraper/grazer-dominated sites. However, the taxonomic make-up of the feeding groups varied among sites and also among dates. A modified Hilsenhoff Biotic Index of the site communities indicated that all were influenced by organic pollution. Results of this study suggest that although the watershed is enormously diverse, its biological communities are likely influenced by organic pollution. Further, range expansions of species found here, such as the stonefly Perlesta placida , have implications for invasion pathways and post-glaciation species islands in a prairie landscape. 相似文献
10.
Alcázar R García AV Kronholm I de Meaux J Koornneef M Parker JE Reymond M 《Nature genetics》2010,42(12):1135-1139
Accumulation of genetic incompatibilities within species can lead to reproductive isolation and, potentially, speciation. In this study, we show that allelic variation at SRF3 (Strubbelig Receptor Family 3), encoding a receptor-like kinase, conditions the occurrence of incompatibility between Arabidopsis thaliana accessions. The geographical distribution of SRF3 alleles reveals that allelic forms causing epistatic incompatibility with a Landsberg erecta allele at the RPP1 resistance locus are present in A. thaliana accessions in central Asia. Incompatible SRF3 alleles condition for an enhanced early immune response to pathogens as compared to the resistance-dampening effect of compatible SRF3 forms in isogenic backgrounds. Variation in disease susceptibility suggests a basis for the molecular patterns of a recent selective sweep detected at the SRF3 locus in central Asian populations. 相似文献