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排序方式: 共有210条查询结果,搜索用时 15 毫秒
31.
Genomics: massively parallel sequencing 总被引:1,自引:0,他引:1
32.
Antifertility action and metabolism of hexamethylphosphoramide 总被引:3,自引:0,他引:3
33.
34.
Hao HX Xie Y Zhang Y Charlat O Oster E Avello M Lei H Mickanin C Liu D Ruffner H Mao X Ma Q Zamponi R Bouwmeester T Finan PM Kirschner MW Porter JA Serluca FC Cong F 《Nature》2012,485(7397):195-200
R-spondin proteins strongly potentiate Wnt signalling and function as stem-cell growth factors. Despite the biological and therapeutic significance, the molecular mechanism of R-spondin action remains unclear. Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6. Inhibition of ZNRF3 enhances Wnt/β-catenin signalling and disrupts Wnt/planar cell polarity signalling in vivo. Notably, R-spondin mimics ZNRF3 inhibition by increasing the membrane level of Wnt receptors. Mechanistically, R-spondin interacts with the extracellular domain of ZNRF3 and induces the association between ZNRF3 and LGR4, which results in membrane clearance of ZNRF3. These data suggest that R-spondin enhances Wnt signalling by inhibiting ZNRF3. Our study provides new mechanistic insights into the regulation of Wnt receptor turnover, and reveals ZNRF3 as a tractable target for therapeutic exploration. 相似文献
35.
An RNA virus population does not consist of a single genotype; rather, it is an ensemble of related sequences, termed quasispecies. Quasispecies arise from rapid genomic evolution powered by the high mutation rate of RNA viral replication. Although a high mutation rate is dangerous for a virus because it results in nonviable individuals, it has been hypothesized that high mutation rates create a 'cloud' of potentially beneficial mutations at the population level, which afford the viral quasispecies a greater probability to evolve and adapt to new environments and challenges during infection. Mathematical models predict that viral quasispecies are not simply a collection of diverse mutants but a group of interactive variants, which together contribute to the characteristics of the population. According to this view, viral populations, rather than individual variants, are the target of evolutionary selection. Here we test this hypothesis by examining the consequences of limiting genomic diversity on viral populations. We find that poliovirus carrying a high-fidelity polymerase replicates at wild-type levels but generates less genomic diversity and is unable to adapt to adverse growth conditions. In infected animals, the reduced viral diversity leads to loss of neurotropism and an attenuated pathogenic phenotype. Notably, using chemical mutagenesis to expand quasispecies diversity of the high-fidelity virus before infection restores neurotropism and pathogenesis. Analysis of viruses isolated from brain provides direct evidence for complementation between members in the quasispecies, indicating that selection indeed occurs at the population level rather than on individual variants. Our study provides direct evidence for a fundamental prediction of the quasispecies theory and establishes a link between mutation rate, population dynamics and pathogenesis. 相似文献
36.
R. Walter G. Schaechtelin L. C. Craig 《Cellular and molecular life sciences : CMLS》1974,30(3):306-308
Zusammenfassung Der Effekt von Na+-, NH4
+- und Ca++-Ionen auf die Blutdruckaktivität von Arginin-Vasopressom wurde untersucht und mit analogen Experimenten (Val5-Angiotensin II-Asp1--Amid) verglichen. Die Wirkungsweise der Ionen-induzierten Potenzierung von Vasopressin wird diskutiert.
Supported by USPHS Grant No. AM-13567.
Abbreviations used are: AVP, arginine-vasopressin; bp, blood pres sure; U, unit;n, number of experiments; , mean value; S.E. standard error;p, level of significance; NS, not significant. 相似文献
Supported by USPHS Grant No. AM-13567.
Abbreviations used are: AVP, arginine-vasopressin; bp, blood pres sure; U, unit;n, number of experiments; , mean value; S.E. standard error;p, level of significance; NS, not significant. 相似文献
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38.
Tsai WW Wang Z Yiu TT Akdemir KC Xia W Winter S Tsai CY Shi X Schwarzer D Plunkett W Aronow B Gozani O Fischle W Hung MC Patel DJ Barton MC 《Nature》2010,468(7326):927-932
Recognition of modified histone species by distinct structural domains within 'reader' proteins plays a critical role in the regulation of gene expression. Readers that simultaneously recognize histones with multiple marks allow transduction of complex chromatin modification patterns into specific biological outcomes. Here we report that chromatin regulator tripartite motif-containing 24 (TRIM24) functions in humans as a reader of dual histone marks by means of tandem plant homeodomain (PHD) and bromodomain (Bromo) regions. The three-dimensional structure of the PHD-Bromo region of TRIM24 revealed a single functional unit for combinatorial recognition of unmodified H3K4 (that is, histone H3 unmodified at lysine 4, H3K4me0) and acetylated H3K23 (histone H3 acetylated at lysine 23, H3K23ac) within the same histone tail. TRIM24 binds chromatin and oestrogen receptor to activate oestrogen-dependent genes associated with cellular proliferation and tumour development. Aberrant expression of TRIM24 negatively correlates with survival of breast cancer patients. The PHD-Bromo of TRIM24 provides a structural rationale for chromatin activation through a non-canonical histone signature, establishing a new route by which chromatin readers may influence cancer pathogenesis. 相似文献
39.
Wheeler DA Srinivasan M Egholm M Shen Y Chen L McGuire A He W Chen YJ Makhijani V Roth GT Gomes X Tartaro K Niazi F Turcotte CL Irzyk GP Lupski JR Chinault C Song XZ Liu Y Yuan Y Nazareth L Qin X Muzny DM Margulies M Weinstock GM Gibbs RA Rothberg JM 《Nature》2008,452(7189):872-876
The association of genetic variation with disease and drug response, and improvements in nucleic acid technologies, have given great optimism for the impact of 'genomic medicine'. However, the formidable size of the diploid human genome, approximately 6 gigabases, has prevented the routine application of sequencing methods to deciphering complete individual human genomes. To realize the full potential of genomics for human health, this limitation must be overcome. Here we report the DNA sequence of a diploid genome of a single individual, James D. Watson, sequenced to 7.4-fold redundancy in two months using massively parallel sequencing in picolitre-size reaction vessels. This sequence was completed in two months at approximately one-hundredth of the cost of traditional capillary electrophoresis methods. Comparison of the sequence to the reference genome led to the identification of 3.3 million single nucleotide polymorphisms, of which 10,654 cause amino-acid substitution within the coding sequence. In addition, we accurately identified small-scale (2-40,000 base pair (bp)) insertion and deletion polymorphism as well as copy number variation resulting in the large-scale gain and loss of chromosomal segments ranging from 26,000 to 1.5 million base pairs. Overall, these results agree well with recent results of sequencing of a single individual by traditional methods. However, in addition to being faster and significantly less expensive, this sequencing technology avoids the arbitrary loss of genomic sequences inherent in random shotgun sequencing by bacterial cloning because it amplifies DNA in a cell-free system. As a result, we further demonstrate the acquisition of novel human sequence, including novel genes not previously identified by traditional genomic sequencing. This is the first genome sequenced by next-generation technologies. Therefore it is a pilot for the future challenges of 'personalized genome sequencing'. 相似文献
40.
Abundance and diversity of microbial life in ocean crust 总被引:2,自引:0,他引:2
Santelli CM Orcutt BN Banning E Bach W Moyer CL Sogin ML Staudigel H Edwards KJ 《Nature》2008,453(7195):653-656
Oceanic lithosphere exposed at the sea floor undergoes seawater-rock alteration reactions involving the oxidation and hydration of glassy basalt. Basalt alteration reactions are theoretically capable of supplying sufficient energy for chemolithoautotrophic growth. Such reactions have been shown to generate microbial biomass in the laboratory, but field-based support for the existence of microbes that are supported by basalt alteration is lacking. Here, using quantitative polymerase chain reaction, in situ hybridization and microscopy, we demonstrate that prokaryotic cell abundances on seafloor-exposed basalts are 3-4 orders of magnitude greater than in overlying deep sea water. Phylogenetic analyses of basaltic lavas from the East Pacific Rise (9 degrees N) and around Hawaii reveal that the basalt-hosted biosphere harbours high bacterial community richness and that community membership is shared between these sites. We hypothesize that alteration reactions fuel chemolithoautotrophic microorganisms, which constitute a trophic base of the basalt habitat, with important implications for deep-sea carbon cycling and chemical exchange between basalt and sea water. 相似文献