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71.
MAP kinase signalling cascade in Arabidopsis innate immunity 总被引:29,自引:0,他引:29
Asai T Tena G Plotnikova J Willmann MR Chiu WL Gomez-Gomez L Boller T Ausubel FM Sheen J 《Nature》2002,415(6875):977-983
72.
Strigolactone inhibition of shoot branching 总被引:16,自引:0,他引:16
Gomez-Roldan V Fermas S Brewer PB Puech-Pagès V Dun EA Pillot JP Letisse F Matusova R Danoun S Portais JC Bouwmeester H Bécard G Beveridge CA Rameau C Rochange SF 《Nature》2008,455(7210):189-194
A carotenoid-derived hormonal signal that inhibits shoot branching in plants has long escaped identification. Strigolactones are compounds thought to be derived from carotenoids and are known to trigger the germination of parasitic plant seeds and stimulate symbiotic fungi. Here we present evidence that carotenoid cleavage dioxygenase 8 shoot branching mutants of pea are strigolactone deficient and that strigolactone application restores the wild-type branching phenotype to ccd8 mutants. Moreover, we show that other branching mutants previously characterized as lacking a response to the branching inhibition signal also lack strigolactone response, and are not deficient in strigolactones. These responses are conserved in Arabidopsis. In agreement with the expected properties of the hormonal signal, exogenous strigolactone can be transported in shoots and act at low concentrations. We suggest that endogenous strigolactones or related compounds inhibit shoot branching in plants. Furthermore, ccd8 mutants demonstrate the diverse effects of strigolactones in shoot branching, mycorrhizal symbiosis and parasitic weed interaction. 相似文献
73.
GoDARTS UKPDS Diabetes Pharmacogenetics Study Group;Wellcome Trust Case Control Consortium Zhou K Bellenguez C Spencer CC Bennett AJ Coleman RL Tavendale R Hawley SA Donnelly LA Schofield C Groves CJ Burch L Carr F Strange A Freeman C Blackwell JM Bramon E Brown MA Casas JP Corvin A Craddock N Deloukas P Dronov S Duncanson A Edkins S Gray E Hunt S Jankowski J Langford C Markus HS Mathew CG Plomin R Rautanen A Sawcer SJ Samani NJ Trembath R Viswanathan AC Wood NW;MAGIC investigators 《Nature genetics》2011,43(2):117-120
Metformin is the most commonly used pharmacological therapy for type 2 diabetes. We report a genome-wide association study for glycemic response to metformin in 1,024 Scottish individuals with type 2 diabetes with replication in two cohorts including 1,783 Scottish individuals and 1,113 individuals from the UK Prospective Diabetes Study. In a combined meta-analysis, we identified a SNP, rs11212617, associated with treatment success (n = 3,920, P = 2.9 × 10(-9), odds ratio = 1.35, 95% CI 1.22-1.49) at a locus containing ATM, the ataxia telangiectasia mutated gene. In a rat hepatoma cell line, inhibition of ATM with KU-55933 attenuated the phosphorylation and activation of AMP-activated protein kinase in response to metformin. We conclude that ATM, a gene known to be involved in DNA repair and cell cycle control, plays a role in the effect of metformin upstream of AMP-activated protein kinase, and variation in this gene alters glycemic response to metformin. 相似文献
74.
Sanna S Jackson AU Nagaraja R Willer CJ Chen WM Bonnycastle LL Shen H Timpson N Lettre G Usala G Chines PS Stringham HM Scott LJ Dei M Lai S Albai G Crisponi L Naitza S Doheny KF Pugh EW Ben-Shlomo Y Ebrahim S Lawlor DA Bergman RN Watanabe RM Uda M Tuomilehto J Coresh J Hirschhorn JN Shuldiner AR Schlessinger D Collins FS Davey Smith G Boerwinkle E Cao A Boehnke M Abecasis GR Mohlke KL 《Nature genetics》2008,40(2):198-203
75.
Stoetzel C Laurier V Davis EE Muller J Rix S Badano JL Leitch CC Salem N Chouery E Corbani S Jalk N Vicaire S Sarda P Hamel C Lacombe D Holder M Odent S Holder S Brooks AS Elcioglu NH Silva ED Da Silva E Rossillion B Sigaudy S de Ravel TJ Lewis RA Leheup B Verloes A Amati-Bonneau P Mégarbané A Poch O Bonneau D Beales PL Mandel JL Katsanis N Dollfus H 《Nature genetics》2006,38(5):521-524
Bardet-Biedl syndrome (BBS) is a genetically heterogeneous ciliopathy. Although nine BBS genes have been cloned, they explain only 40-50% of the total mutational load. Here we report a major new BBS locus, BBS10, that encodes a previously unknown, rapidly evolving vertebrate-specific chaperonin-like protein. We found BBS10 to be mutated in about 20% of an unselected cohort of families of various ethnic origins, including some families with mutations in other BBS genes, consistent with oligogenic inheritance. In zebrafish, mild suppression of bbs10 exacerbated the phenotypes of other bbs morphants. 相似文献
76.
Lounkine E Keiser MJ Whitebread S Mikhailov D Hamon J Jenkins JL Lavan P Weber E Doak AK Côté S Shoichet BK Urban L 《Nature》2012,486(7403):361-367
Discovering the unintended 'off-targets' that predict adverse drug reactions is daunting by empirical methods alone. Drugs can act on several protein targets, some of which can be unrelated by conventional molecular metrics, and hundreds of proteins have been implicated in side effects. Here we use a computational strategy to predict the activity of 656 marketed drugs on 73 unintended 'side-effect' targets. Approximately half of the predictions were confirmed, either from proprietary databases unknown to the method or by new experimental assays. Affinities for these new off-targets ranged from 1 nM to 30 μM. To explore relevance, we developed an association metric to prioritize those new off-targets that explained side effects better than any known target of a given drug, creating a drug-target-adverse drug reaction network. Among these new associations was the prediction that the abdominal pain side effect of the synthetic oestrogen chlorotrianisene was mediated through its newly discovered inhibition of the enzyme cyclooxygenase-1. The clinical relevance of this inhibition was borne out in whole human blood platelet aggregation assays. This approach may have wide application to de-risking toxicological liabilities in drug discovery. 相似文献
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78.
Sladek R Rocheleau G Rung J Dina C Shen L Serre D Boutin P Vincent D Belisle A Hadjadj S Balkau B Heude B Charpentier G Hudson TJ Montpetit A Pshezhetsky AV Prentki M Posner BI Balding DJ Meyre D Polychronakos C Froguel P 《Nature》2007,445(7130):881-885
Type 2 diabetes mellitus results from the interaction of environmental factors with a combination of genetic variants, most of which were hitherto unknown. A systematic search for these variants was recently made possible by the development of high-density arrays that permit the genotyping of hundreds of thousands of polymorphisms. We tested 392,935 single-nucleotide polymorphisms in a French case-control cohort. Markers with the most significant difference in genotype frequencies between cases of type 2 diabetes and controls were fast-tracked for testing in a second cohort. This identified four loci containing variants that confer type 2 diabetes risk, in addition to confirming the known association with the TCF7L2 gene. These loci include a non-synonymous polymorphism in the zinc transporter SLC30A8, which is expressed exclusively in insulin-producing beta-cells, and two linkage disequilibrium blocks that contain genes potentially involved in beta-cell development or function (IDE-KIF11-HHEX and EXT2-ALX4). These associations explain a substantial portion of disease risk and constitute proof of principle for the genome-wide approach to the elucidation of complex genetic traits. 相似文献
79.
Bruno Mesmin Bruno Antonny Guillaume Drin 《Cellular and molecular life sciences : CMLS》2013,70(18):3405-3421
In cells, the levels of sterol vary greatly among organelles. This uneven distribution depends largely on non-vesicular routes of transfer, which are mediated by soluble carriers called lipid-transfer proteins (LTPs). These proteins have a domain with a hydrophobic cavity that accommodates one sterol molecule. However, a demonstration of their role in sterol transport in cells remains difficult. Numerous LTPs also contain membrane-binding elements, but it is not clear how these LTPs couple their ability to target organelles with lipid transport activity. This issue appears critical, since many sterol transporters are thought to act at contact sites between two membrane-bound compartments. Here, we emphasize that biochemical and structural studies provide precious insights into the mode of action of sterol-binding proteins. Recent studies on START, Osh/ORP and NPC proteins suggest models on how these proteins could transport sterol between organelles and, thereby, influence cellular functions. 相似文献
80.
NAUGOLNYKH Serge V 《科学通报(英文版)》2012,57(27):3603-3609
A new species Lepidopteris baodensis sp.nov.belonging to the family Peltaspermaceae and represented by two ultimate pinnae in the collection under study,was recently discovered at the Baijiagou of Baode,Shanxi,China,from the Upper Permian Sunjiagou Formation.The lower surface of the ultimate rachis,the midrib and secondary veins is covered with triangular,trapezoid,rounded,or ligulate subepidermal swellings,which show different natures from intercalary pinnules.Lepidopteris is one of typical elements of the Late Permian Euramerican flora.Since Schimper erected the genus Lepidopteris in 1869,the entire epidermal structure of subepidermal swellings had been unclear.The new species L.baodensis clearly showing the distinguished epidermal structure of subepidermal swellings,not only enlarges and supplements our knowledge in biology and taxonomy of Lepidopteris as well as the Upper Permian stratigraphy of China,but also provides an opportunity to understand the relationship between Euramerican floras and Cathaysian floras in paleoclimatic,paleoenvironmental and paleogeographic context. 相似文献