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Sökning: WFRF:(Wessel Jennifer)

  • Resultat 11-13 av 13
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11.
  • Mack, Jennifer, Associate Professor, et al. (författare)
  • Att bygga om Sverige
  • 2015
  • Ingår i: Arkitektur. ; , s. 82-87
  • Tidskriftsartikel (populärvet., debatt m.m.)
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12.
  • Rana, Brinda K., et al. (författare)
  • Natural variation within the neuronal nicotinic acetylcholine receptor cluster on human chromosome 15q24 : influence on heritable autonomic traits in twin pairs
  • 2009
  • Ingår i: Journal of Pharmacology and Experimental Therapeutics. - 0022-3565 .- 1521-0103. ; 331:2, s. 419-428
  • Tidskriftsartikel (refereegranskat)abstract
    • Nicotinic acetylcholine receptors (nAChRs) are combinations of subunits arranged as pentamers encircling a central cation channel. At least nine α and four β subunits are expressed in the central and peripheral nervous systems; their presence in autonomic ganglia, the adrenal medulla, and central nervous system, with accompanying responses elicited by nicotinic agonists, point to their involvement in cardiovascular homeostasis. nAChRs formed by α3, α5, and β4 subunits may regulate blood pressure (BP) by mediating release of catestatin, the endogenous nicotinic antagonist fragment of chromogranin A (CHGA) and potent inhibitor of catecholamine secretion. Genes encoding these subunits (CHRNA3, CHRNA5, and CHRNB4) are clustered on human chromosome 15q24. Because variation in this cluster may alter autonomic regulation of BP, we sequenced ∼15 kilobase pairs in 15q24 containing their coding and 5′- and 3′-untranslated regions in 80 individuals. We identified 63 variants: 25 in coding regions of CHRNA3, CHRNA5, and CHRNB4 and 48 noncoding single-nucleotide polymorphisms (SNPs). Haplotype frequencies varied across ethnic populations. We assessed the contribution of six SNPs in the putative catestatin binding region of CHRNA3 and CHRNB4 to autonomic traits. In twins, catestatin and BP were heritable. CHRNA3 SNPs and haplotypes containing K95K (G285A) associated with circulating plasma catestatin, epinephrine levels, as well as systolic BP, suggesting altered coupling of the nAChRs to BP. Studies of chromaffin cells in vitro reveal that nicotinic agonist stimulation releases catecholamines and CHGA, a process augmented by overexpression of CHRNA3 and blocked by catestatin. These cellular events suggest a homeostatic mechanism underlying the pleiotropic actions of CHRNA3 genetic variation on autonomic function observed in twins.
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13.
  • Wen, Gen, et al. (författare)
  • An ancestral variant of Secretogranin II confers regulation by PHOX2 transcription factors and association with hypertension
  • 2007
  • Ingår i: Human Molecular Genetics. - 0964-6906 .- 1460-2083. ; 16:14, s. 1752-1764
  • Tidskriftsartikel (refereegranskat)abstract
    • Granins regulate secretory vesicle formation in neuroendocrine cells and granin-derived peptides are co-released with neurotransmitters as modulatory signals at sympathetic sites. We report evidence for association between a regulatory polymorphism in Secretogranin II (SCG2) and hypertension in African-American subjects. The minor allele is ancestral in the human lineage and is associated with disease risk in two case-control studies and with elevated blood pressure in a separate familial study. Mechanistically, the ancestral allele acts as a transcriptional enhancer in cells that express endogenous Scg2, whereas the derived allele does not. ARIX (PHOX2A) and PHOX2B are identified as potential transactivating factors by oligonucleotide affinity chromatography and mass spectrometry and confirmed by chromatin immunoprecipitation. Each of these transcription factors preferentially binds the risk allele, both in vitro and in vivo. Population genetic considerations suggest positive selection of the protective allele within the human lineage. These results identify a common regulatory variation in SCG2 and implicate granin gene expression in the control of human blood pressure and susceptibility to hypertension.
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  • Resultat 11-13 av 13
  • Föregående 1[2]
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