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41.
Sung BJ Hwang KY Jeon YH Lee JI Heo YS Kim JH Moon J Yoon JM Hyun YL Kim E Eum SJ Park SY Lee JO Lee TG Ro S Cho JM 《Nature》2003,425(6953):98-102
Phosphodiesterases (PDEs) are a superfamily of enzymes that degrade the intracellular second messengers cyclic AMP and cyclic GMP. As essential regulators of cyclic nucleotide signalling with diverse physiological functions, PDEs are drug targets for the treatment of various diseases, including heart failure, depression, asthma, inflammation and erectile dysfunction. Of the 12 PDE gene families, cGMP-specific PDE5 carries out the principal cGMP-hydrolysing activity in human corpus cavernosum tissue. It is well known as the target of sildenafil citrate (Viagra) and other similar drugs for the treatment of erectile dysfunction. Despite the pressing need to develop selective PDE inhibitors as therapeutic drugs, only the cAMP-specific PDE4 structures are currently available. Here we present the three-dimensional structures of the catalytic domain (residues 537-860) of human PDE5 complexed with the three drug molecules sildenafil, tadalafil (Cialis) and vardenafil (Levitra). These structures will provide opportunities to design potent and selective PDE inhibitors with improved pharmacological profiles. 相似文献
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For spatial based decision making such as choice of best place to construct a new department store, spatial data warehousing system is required more and more previous spatial data warehousing systems; however, provided decision making of non-spatial data on a map and so those cannot support enough spatial based decision making. The spatial aggregations are proposed for spatial based decision making in spatial data warehouses. The meaning of aggregation operators for applying spatial data was modified and new spatial aggregations were defined. These aggregations can support hierarchical concept of spatial measure. Using these aggregations, the spatial analysis classified by non-spatial data is provided. In case study, how to use these aggregations and how to support spatial based decision making are shown. 相似文献
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Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease 总被引:2,自引:0,他引:2
Barrett JC Hansoul S Nicolae DL Cho JH Duerr RH Rioux JD Brant SR Silverberg MS Taylor KD Barmada MM Bitton A Dassopoulos T Datta LW Green T Griffiths AM Kistner EO Murtha MT Regueiro MD Rotter JI Schumm LP Steinhart AH Targan SR Xavier RJ;NIDDK IBD Genetics Consortium Libioulle C Sandor C Lathrop M Belaiche J Dewit O Gut I Heath S Laukens D Mni M Rutgeerts P Van Gossum A Zelenika D Franchimont D Hugot JP de Vos M Vermeire S 《Nature genetics》2008,40(8):955-962
Several risk factors for Crohn's disease have been identified in recent genome-wide association studies. To advance gene discovery further, we combined data from three studies on Crohn's disease (a total of 3,230 cases and 4,829 controls) and carried out replication in 3,664 independent cases with a mixture of population-based and family-based controls. The results strongly confirm 11 previously reported loci and provide genome-wide significant evidence for 21 additional loci, including the regions containing STAT3, JAK2, ICOSLG, CDKAL1 and ITLN1. The expanded molecular understanding of the basis of this disease offers promise for informed therapeutic development. 相似文献
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Prodigiosin condensing enzyme (PCE) activities were present in Serratia marcescens wild type 08, mutants OF, WF and 9-3-3. Their specific activities exhibited different maxima and at different times during the late log phase or the early stationary phase of cell growth. The levels of prodigiosin and its precursors also showed a significant increase at this period. The results support that prodigiosin and/or its precursors are secondary metabolites. The ubiquity of the PCE activity in mutants deficient in prodigiosin biosynthesis suggest that this particular enzyme may also be present in non-pigmented clinical isolates. 相似文献
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Y. W. Cho M. Akbari-Fard E. J. Dugge 《Cellular and molecular life sciences : CMLS》1966,22(4):242-244
Zusammenfassung
Escherichia coli-Endotoxin (1 mg per kg) wurde in die Ohrvene von Kaninchen injiziert: Die Succinat-dehydrogenase- und Cytochromoxydase-Aktivität in den Mitochondrien des Herzmuskels wurde nach 15 min verändert. Es ist wahrscheinlich, dass das Endotoxin sowohl auf das Herz, als auch auf die peripheren Gefässe direkt wirkt.
This study was supported by the Research Grant HE-09016 from the National Heart Institute, US Public Health Service; and the General Research Support Funds from the Philadelphia General Hospital. 相似文献
This study was supported by the Research Grant HE-09016 from the National Heart Institute, US Public Health Service; and the General Research Support Funds from the Philadelphia General Hospital. 相似文献
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Summary Zinc sulphate pretreatment i.p. produces dose-related reductions in stress ulcer incidence in pylorus-occluded rats. The associated increases in gastric wall mucus, in stressed and nonstressed animals, suggest that a similar effect may contribute to its ulcer-reducing ability in man. 相似文献