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排序方式: 共有230条查询结果,搜索用时 15 毫秒
101.
The ELF4-ELF3-LUX complex links the circadian clock to diurnal control of hypocotyl growth 总被引:1,自引:0,他引:1
Nusinow DA Helfer A Hamilton EE King JJ Imaizumi T Schultz TF Farré EM Kay SA 《Nature》2011,475(7356):398-402
102.
Yokoyama S Woods SL Boyle GM Aoude LG MacGregor S Zismann V Gartside M Cust AE Haq R Harland M Taylor JC Duffy DL Holohan K Dutton-Regester K Palmer JM Bonazzi V Stark MS Symmons J Law MH Schmidt C Lanagan C O'Connor L Holland EA Schmid H Maskiell JA Jetann J Ferguson M Jenkins MA Kefford RF Giles GG Armstrong BK Aitken JF Hopper JL Whiteman DC Pharoah PD Easton DF Dunning AM Newton-Bishop JA Montgomery GW Martin NG Mann GJ Bishop DT Tsao H Trent JM Fisher DE Hayward NK Brown KM 《Nature》2011,480(7375):99-103
103.
104.
Xiao B Sanders MJ Underwood E Heath R Mayer FV Carmena D Jing C Walker PA Eccleston JF Haire LF Saiu P Howell SA Aasland R Martin SR Carling D Gamblin SJ 《Nature》2011,472(7342):230-233
The heterotrimeric AMP-activated protein kinase (AMPK) has a key role in regulating cellular energy metabolism; in response to a fall in intracellular ATP levels it activates energy-producing pathways and inhibits energy-consuming processes. AMPK has been implicated in a number of diseases related to energy metabolism including type 2 diabetes, obesity and, most recently, cancer. AMPK is converted from an inactive form to a catalytically competent form by phosphorylation of the activation loop within the kinase domain: AMP binding to the γ-regulatory domain promotes phosphorylation by the upstream kinase, protects the enzyme against dephosphorylation, as well as causing allosteric activation. Here we show that ADP binding to just one of the two exchangeable AXP (AMP/ADP/ATP) binding sites on the regulatory domain protects the enzyme from dephosphorylation, although it does not lead to allosteric activation. Our studies show that active mammalian AMPK displays significantly tighter binding to ADP than to Mg-ATP, explaining how the enzyme is regulated under physiological conditions where the concentration of Mg-ATP is higher than that of ADP and much higher than that of AMP. We have determined the crystal structure of an active AMPK complex. The structure shows how the activation loop of the kinase domain is stabilized by the regulatory domain and how the kinase linker region interacts with the regulatory nucleotide-binding site that mediates protection against dephosphorylation. From our biochemical and structural data we develop a model for how the energy status of a cell regulates AMPK activity. 相似文献
105.
Temporal dynamics and genetic control of transcription in the human prefrontal cortex 总被引:1,自引:0,他引:1
Colantuoni C Lipska BK Ye T Hyde TM Tao R Leek JT Colantuoni EA Elkahloun AG Herman MM Weinberger DR Kleinman JE 《Nature》2011,478(7370):519-523
106.
Hundreds of variants clustered in genomic loci and biological pathways affect human height 总被引:2,自引:0,他引:2
Lango Allen H Estrada K Lettre G Berndt SI Weedon MN Rivadeneira F Willer CJ Jackson AU Vedantam S Raychaudhuri S Ferreira T Wood AR Weyant RJ Segrè AV Speliotes EK Wheeler E Soranzo N Park JH Yang J Gudbjartsson D Heard-Costa NL Randall JC Qi L Vernon Smith A Mägi R Pastinen T Liang L Heid IM Luan J Thorleifsson G Winkler TW Goddard ME Sin Lo K Palmer C Workalemahu T Aulchenko YS Johansson A Zillikens MC Feitosa MF Esko T Johnson T Ketkar S Kraft P Mangino M Prokopenko I Absher D Albrecht E 《Nature》2010,467(7317):832-838
Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P?0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways. 相似文献
107.
Neale BM Kou Y Liu L Ma'ayan A Samocha KE Sabo A Lin CF Stevens C Wang LS Makarov V Polak P Yoon S Maguire J Crawford EL Campbell NG Geller ET Valladares O Schafer C Liu H Zhao T Cai G Lihm J Dannenfelser R Jabado O Peralta Z Nagaswamy U Muzny D Reid JG Newsham I Wu Y Lewis L Han Y Voight BF Lim E Rossin E Kirby A Flannick J Fromer M Shakir K Fennell T Garimella K Banks E Poplin R Gabriel S DePristo M Wimbish JR Boone BE Levy SE Betancur C Sunyaev S Boerwinkle E Buxbaum JD Cook EH Devlin B 《Nature》2012,485(7397):242-245
Autism spectrum disorders (ASD) are believed to have genetic and environmental origins, yet in only a modest fraction of individuals can specific causes be identified. To identify further genetic risk factors, here we assess the role of de novo mutations in ASD by sequencing the exomes of ASD cases and their parents (n = 175 trios). Fewer than half of the cases (46.3%) carry a missense or nonsense de novo variant, and the overall rate of mutation is only modestly higher than the expected rate. In contrast, the proteins encoded by genes that harboured de novo missense or nonsense mutations showed a higher degree of connectivity among themselves and to previous ASD genes as indexed by protein-protein interaction screens. The small increase in the rate of de novo events, when taken together with the protein interaction results, are consistent with an important but limited role for de novo point mutations in ASD, similar to that documented for de novo copy number variants. Genetic models incorporating these data indicate that most of the observed de novo events are unconnected to ASD; those that do confer risk are distributed across many genes and are incompletely penetrant (that is, not necessarily sufficient for disease). Our results support polygenic models in which spontaneous coding mutations in any of a large number of genes increases risk by 5- to 20-fold. Despite the challenge posed by such models, results from de novo events and a large parallel case-control study provide strong evidence in favour of CHD8 and KATNAL2 as genuine autism risk factors. 相似文献
108.
In 1997, the rediscovery of Sus bucculentus in Laos was announced by Groves et al.--this wild pig species had gone unrecorded since first being described in 1892. Although the identification of the new specimen was based initially on morphology, the authors also used a 7% sequence divergence from the common Eurasian pig S. scrofa (based on their analysis of 327 base pairs of the gene encoding mitochondrial 12S ribosomal RNA) as support for the species status of S. bucculentus. Concerned about the large divergence reported for a relatively conserved gene, and the absence of the sequence in any public database, we analysed an additional tissue sample from the specimen and found only 0.6% divergence from S. scrofa. Our more extensive analysis places the sample within the S. scrofa clade, calling into question the species status of S. bucculentus and demonstrating the need for both phylogenetic and morphological evidence in defining species. 相似文献
109.
Zusammenfassung Unsere Alltagssprache ist nur zur Beschreibung von Phänomenen, welche im menschlichen Wahrnehmungsbereich der Gleichzeitigkeit liegen, geeignet. Die Diskussion von Begriffen, wie z. B. Kausalität und Zufall, erfordert eine sprachlichea-priori-Begrenzung der Signalfortbewegung (Wilkinson). Eine solche neue Sprache muss auch informationstheoretische Konzepte enthalten. 相似文献
110.
Résumé Après 7 semaines de surcharge saline administrée par gavage, l'augmentation de tension artérielle systolique de 3 groupes de rats uninephrectomisés soumis à différents régimes d'hydratation s'avéra être en meilleure corrélation avec le rapport NaCl/H20 ingéré qu'avec la quantité absolue de sodium ingéré. La soif pourrait possiblement potentialiser d'autres formes d'hypertension expérimentale. 相似文献