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排序方式: 共有203条查询结果,搜索用时 78 毫秒
51.
Shi Y Li Z Xu Q Wang T Li T Shen J Zhang F Chen J Zhou G Ji W Li B Xu Y Liu D Wang P Yang P Liu B Sun W Wan C Qin S He G Steinberg S Cichon S Werge T Sigurdsson E Tosato S Palotie A Nöthen MM Rietschel M Ophoff RA Collier DA Rujescu D Clair DS Stefansson H Stefansson K Ji J Wang Q Li W Zheng L Zhang H Feng G He L 《Nature genetics》2011,43(12):1224-1227
Schizophrenia is a severe mental disorder affecting ~1% of the world population, with heritability of up to 80%. To identify new common genetic risk factors, we performed a genome-wide association study (GWAS) in the Han Chinese population. The discovery sample set consisted of 3,750 individuals with schizophrenia and 6,468 healthy controls (1,578 cases and 1,592 controls from northern Han Chinese, 1,238 cases and 2,856 controls from central Han Chinese, and 934 cases and 2,020 controls from the southern Han Chinese). We further analyzed the strongest association signals in an additional independent cohort of 4,383 cases and 4,539 controls from the Han Chinese population. Meta-analysis identified common SNPs that associated with schizophrenia with genome-wide significance on 8p12 (rs16887244, P = 1.27 × 10(-10)) and 1q24.2 (rs10489202, P = 9.50 × 10(-9)). Our findings provide new insights into the pathogenesis of schizophrenia. 相似文献
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Bass AJ Lawrence MS Brace LE Ramos AH Drier Y Cibulskis K Sougnez C Voet D Saksena G Sivachenko A Jing R Parkin M Pugh T Verhaak RG Stransky N Boutin AT Barretina J Solit DB Vakiani E Shao W Mishina Y Warmuth M Jimenez J Chiang DY Signoretti S Kaelin WG Spardy N Hahn WC Hoshida Y Ogino S Depinho RA Chin L Garraway LA Fuchs CS Baselga J Tabernero J Gabriel S Lander ES Getz G Meyerson M 《Nature genetics》2011,43(10):964-968
Prior studies have identified recurrent oncogenic mutations in colorectal adenocarcinoma and have surveyed exons of protein-coding genes for mutations in 11 affected individuals. Here we report whole-genome sequencing from nine individuals with colorectal cancer, including primary colorectal tumors and matched adjacent non-tumor tissues, at an average of 30.7× and 31.9× coverage, respectively. We identify an average of 75 somatic rearrangements per tumor, including complex networks of translocations between pairs of chromosomes. Eleven rearrangements encode predicted in-frame fusion proteins, including a fusion of VTI1A and TCF7L2 found in 3 out of 97 colorectal cancers. Although TCF7L2 encodes TCF4, which cooperates with β-catenin in colorectal carcinogenesis, the fusion lacks the TCF4 β-catenin-binding domain. We found a colorectal carcinoma cell line harboring the fusion gene to be dependent on VTI1A-TCF7L2 for anchorage-independent growth using RNA interference-mediated knockdown. This study shows previously unidentified levels of genomic rearrangements in colorectal carcinoma that can lead to essential gene fusions and other oncogenic events. 相似文献
54.
Gesche K. Gerresheim Nadia Dünnes Anika Nieder-Röhrmann Lyudmila A. Shalamova Markus Fricke Ivo Hofacker Christian Höner zu Siederdissen Manja Marz Michael Niepmann 《Cellular and molecular life sciences : CMLS》2017,74(4):747-760
We have analyzed the binding of the liver-specific microRNA-122 (miR-122) to three conserved target sites of hepatitis C virus (HCV) RNA, two in the non-structural protein 5B (NS5B) coding region and one in the 3′ untranslated region (3′UTR). miR-122 binding efficiency strongly depends on target site accessibility under conditions when the range of flanking sequences available for the formation of local RNA secondary structures changes. Our results indicate that the particular sequence feature that contributes most to the correlation between target site accessibility and binding strength varies between different target sites. This suggests that the dynamics of miRNA/Ago2 binding not only depends on the target site itself but also on flanking sequence context to a considerable extent, in particular in a small viral genome in which strong selection constraints act on coding sequence and overlapping cis-signals and model the accessibility of cis-signals. In full-length genomes, single and combination mutations in the miR-122 target sites reveal that site 5B.2 is positively involved in regulating overall genome replication efficiency, whereas mutation of site 5B.3 showed a weaker effect. Mutation of the 3′UTR site and double or triple mutants showed no significant overall effect on genome replication, whereas in a translation reporter RNA, the 3′UTR target site inhibits translation directed by the HCV 5′UTR. Thus, the miR-122 target sites in the 3′-region of the HCV genome are involved in a complex interplay in regulating different steps of the HCV replication cycle. 相似文献
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Coping with complexity is at the heart of management and leadership in the turbulent environments faced by the organizations and societies of our day. The systems approach provides transdisciplinary theories and tools for dealing with this challenge more effectively than efforts merely based on disciplinary insights or pragmatic recipes. In this paper, a concept of "intelligent organizations" is introduced. A framework for the design of intelligent organizations is proposed that links three organizational cybernetic models: the Model for Systemic Control, the Viable System Model, and the Team Syntegrity model.2 The proposition is that a combined use of these models, guided by the integrative conceptual framework, enables a more effective response to complex situations than merely pragmatic approaches to "integrative management." Provisional empirical evidence gathered from applied research indicates that the proposed framework is capable of enhancing such superior potential for effective response. As such, it promises to meet the specific needs of the new types of organizations that have already begun to emerge in the knowledge societies. 相似文献
57.
One hundred years ago Albert Einstein introduced the concept of the photon. Although in the early years after 1905 the evidence for the quantum nature of light was not compelling, modern experiments--especially those using photon pairs--have beautifully confirmed its corpuscular character. Research on the quantum properties of light (quantum optics) triggered the evolution of the whole field of quantum information processing, which now promises new technology, such as quantum cryptography and even quantum computers. 相似文献
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Silencing of microRNAs in vivo with 'antagomirs' 总被引:2,自引:0,他引:2
Krützfeldt J Rajewsky N Braich R Rajeev KG Tuschl T Manoharan M Stoffel M 《Nature》2005,438(7068):685-689
MicroRNAs (miRNAs) are an abundant class of non-coding RNAs that are believed to be important in many biological processes through regulation of gene expression. The precise molecular function of miRNAs in mammals is largely unknown and a better understanding will require loss-of-function studies in vivo. Here we show that a novel class of chemically engineered oligonucleotides, termed 'antagomirs', are efficient and specific silencers of endogenous miRNAs in mice. Intravenous administration of antagomirs against miR-16, miR-122, miR-192 and miR-194 resulted in a marked reduction of corresponding miRNA levels in liver, lung, kidney, heart, intestine, fat, skin, bone marrow, muscle, ovaries and adrenals. The silencing of endogenous miRNAs by this novel method is specific, efficient and long-lasting. The biological significance of silencing miRNAs with the use of antagomirs was studied for miR-122, an abundant liver-specific miRNA. Gene expression and bioinformatic analysis of messenger RNA from antagomir-treated animals revealed that the 3' untranslated regions of upregulated genes are strongly enriched in miR-122 recognition motifs, whereas downregulated genes are depleted in these motifs. Analysis of the functional annotation of downregulated genes specifically predicted that cholesterol biosynthesis genes would be affected by miR-122, and plasma cholesterol measurements showed reduced levels in antagomir-122-treated mice. Our findings show that antagomirs are powerful tools to silence specific miRNAs in vivo and may represent a therapeutic strategy for silencing miRNAs in disease. 相似文献
60.
Senderek J Krieger M Stendel C Bergmann C Moser M Breitbach-Faller N Rudnik-Schöneborn S Blaschek A Wolf NI Harting I North K Smith J Muntoni F Brockington M Quijano-Roy S Renault F Herrmann R Hendershot LM Schröder JM Lochmüller H Topaloglu H Voit T Weis J Ebinger F Zerres K 《Nature genetics》2005,37(12):1312-1314
SIL1 (also called BAP) acts as a nucleotide exchange factor for the Hsp70 chaperone BiP (also called GRP78), which is a key regulator of the main functions of the endoplasmic reticulum. We found nine distinct mutations that would disrupt the SIL1 protein in individuals with Marinesco-Sj?gren syndrome, an autosomal recessive cerebellar ataxia complicated by cataracts, developmental delay and myopathy. Identification of SIL1 mutations implicates Marinesco-Sj?gren syndrome as a disease of endoplasmic reticulum dysfunction and suggests a role for this organelle in multisystem disorders. 相似文献