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Yue Shi Guang Yang Jia Yu Lina Yu Ruth Westenbroek William A. Catterall Lisa Juntti-Berggren Per-Olof Berggren Shao-Nian Yang 《Cellular and molecular life sciences : CMLS》2014,71(7):1289-1303
Apolipoprotein CIII (ApoCIII) not only serves as an inhibitor of triglyceride hydrolysis but also participates in diabetes-related pathological events such as hyperactivation of voltage-gated Ca2+ (CaV) channels in the pancreatic β cell. However, nothing is known about the molecular mechanisms whereby ApoCIII hyperactivates β cell CaV channels. We now demonstrate that ApoCIII increased CaV1 channel open probability and density. ApoCIII enhanced whole-cell Ca2+ currents and the CaV1 channel blocker nimodipine completely abrogated this enhancement. The effect of ApoCIII was not influenced by individual inhibition of PKA, PKC, or Src. However, combined inhibition of PKA, PKC, and Src counteracted the effect of ApoCIII, similar results obtained by coinhibition of PKA and Src. Moreover, knockdown of β1 integrin or scavenger receptor class B type I (SR-BI) prevented ApoCIII from hyperactivating β cell CaV channels. These data reveal that ApoCIII hyperactivates β cell CaV1 channels through SR-BI/β1 integrin-dependent coactivation of PKA and Src. 相似文献
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Yang J Ferreira T Morris AP Medland SE;Genetic Investigation of ANthropometric Traits 《Nature genetics》2012,44(4):369-75, S1-3
We present an approximate conditional and joint association analysis that can use summary-level statistics from a meta-analysis of genome-wide association studies (GWAS) and estimated linkage disequilibrium (LD) from a reference sample with individual-level genotype data. Using this method, we analyzed meta-analysis summary data from the GIANT Consortium for height and body mass index (BMI), with the LD structure estimated from genotype data in two independent cohorts. We identified 36 loci with multiple associated variants for height (38 leading and 49 additional SNPs, 87 in total) via a genome-wide SNP selection procedure. The 49 new SNPs explain approximately 1.3% of variance, nearly doubling the heritability explained at the 36 loci. We did not find any locus showing multiple associated SNPs for BMI. The method we present is computationally fast and is also applicable to case-control data, which we demonstrate in an example from meta-analysis of type 2 diabetes by the DIAGRAM Consortium. 相似文献
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J. A. Ruth M. J. Gershten J. K. Disbrow 《Cellular and molecular life sciences : CMLS》1984,40(7):692-694
Summary The accumulation of3H-dopamine by synaptic vesicles from rat striatum was significantly stabilized in a membrane impermeant medium. The characteristics of dopamine accumulation by striatal vesicles were quite similar to those reported for dopamine accumulation by a whole brain vesicle preparation in the same medium, and were siginificantly different from the characteristics previously reported for vesicular accumulation of norepinephrine.Acknowledgments. This work was supported by grant NS 18752 (NIH) of the United States Public Health Service. Reprint requests to J. A. R. 相似文献
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Summary With the aid of the differential interference contrast microscope (systemNomarski), the pollen grains ofAlnus rugosa were examined. The characteristic surface structure, the arci and certain structures in the vestibules of the pores are thus very clearly visible. A further use of this microscopic method may be possible for the investigation of pollen grains. 相似文献
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J. K. Disbrow M. J. Gershten J. A. Ruth 《Cellular and molecular life sciences : CMLS》1982,38(11):1323-1324
Summary The biochemical lifetime of noradrenergic storage vesicles from rat brain is greatly extended in a medium based upon the membrane impermeable anion D-tartrate. Examination of the MgATP-dependent accumulation of (–)-3H-norepinephrine suggests that this medium may more closely approximate the intracellular environment of the storage vesicle, and may better support electrochemical gradients existing across the vesicle membrane.Acknowledgments. This work was supported by grant NS 15374 (NIH) of the United States Public Heath Service. 相似文献
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Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans 总被引:18,自引:0,他引:18
Robertson SP Twigg SR Sutherland-Smith AJ Biancalana V Gorlin RJ Horn D Kenwrick SJ Kim CA Morava E Newbury-Ecob R Orstavik KH Quarrell OW Schwartz CE Shears DJ Suri M Kendrick-Jones J Wilkie AO;OPD-spectrum Disorders Clinical Collaborative Group 《Nature genetics》2003,33(4):487-491
Remodeling of the cytoskeleton is central to the modulation of cell shape and migration. Filamin A, encoded by the gene FLNA, is a widely expressed protein that regulates re-organization of the actin cytoskeleton by interacting with integrins, transmembrane receptor complexes and second messengers. We identified localized mutations in FLNA that conserve the reading frame and lead to a broad range of congenital malformations, affecting craniofacial structures, skeleton, brain, viscera and urogenital tract, in four X-linked human disorders: otopalatodigital syndrome types 1 (OPD1; OMIM 311300) and 2 (OPD2; OMIM 304120), frontometaphyseal dysplasia (FMD; OMIM 305620) and Melnick-Needles syndrome (MNS; OMIM 309350). Several mutations are recurrent, and all are clustered into four regions of the gene: the actin-binding domain and rod domain repeats 3, 10 and 14/15. Our findings contrast with previous observations that loss of function of FLNA is embryonic lethal in males but manifests in females as a localized neuronal migration disorder, called periventricular nodular heterotopia (PVNH; refs. 3-6). The patterns of mutation, X-chromosome inactivation and phenotypic manifestations in the newly described mutations indicate that they have gain-of-function effects, implicating filamin A in signaling pathways that mediate organogenesis in multiple systems during embryonic development. 相似文献
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In this report we analyze patterns of size-assortative mating in an insect genus by (1) describing the consistency and strength of assortative mating among populations of a species and among species of a genus, and (2) determining the role of sampling artifacts in generating this nonrandom pattern of mating. Our data consist of 18 samples of soldier beetles (8 species of the genus Chauliognathus ) from 17 sites within the southwestern United States. Of the 18 samples, just 6 exhibited significant correlations between elytron lengths of mating pairs. We show how these and other significant correlations are generated by 3 kinds of sampling artifacts: mixed-species samples, mixed-population samples, and mixed-microsite samples. 相似文献
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