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Articles by C Daly
Total Records ( 2 ) for C Daly
  J. D McCully , M. K Bhasin , C Daly , M. C Guerrero , S Dillon , T. A Liberman , D. B Cowan , J. D Mably , F. X McGowan and S. Levitsky

Cardioplegia is used to partially alleviate the effects of surgically induced global ischemia injury; however, the molecular mechanisms involved in this cardioprotection remain to be elucidated. To improve the understanding of the molecular processes modulating the effects of global ischemia and the cardioprotection afforded by cardioplegia, we constructed rabbit heart cDNA libraries and isolated, sequenced, and identified a compendium of nonredundant cDNAs for use in transcriptomic and proteomic analyses. New Zealand White rabbits were used to compare the effects of global ischemia and cardioplegia compared with control (nonischemic) hearts. The effects of RNA and protein synthesis on the cardioprotection afforded by cardioplegia were investigated separately by preperfusion with either -amanitin or cycloheximide. Our results demonstrate that cardioplegia partially ameliorates the effects of global ischemia and that the cardioprotection is modulated by RNA- and protein-dependent mechanisms. Transcriptomic and proteomic enrichment analyses indicated that global ischemia downregulated genes/proteins associated with mitochondrial function and energy production, cofactor catabolism, and the generation of precursor metabolites of energy. In contrast, cardioplegia significantly increased differentially expressed genes/proteins associated with the mitochondrion and mitochondrial function and significantly upregulated the biological processes of muscle contraction, involuntary muscle contraction, carboxylic acid and fatty acid catabolic processes, fatty acid β-oxidation, and fatty acid metabolic processes.

  C. R Sussman , J Zhao , C Plata , J Lu , C Daly , N Angle , J DiPiero , I. A Drummond , J. O Liang , W. F Boron , M. F Romero and M. H. Chang

Mutations in the electrogenic Na+/nHCO3 cotransporter (NBCe1, SLC4A4) cause severe proximal renal tubular acidosis, glaucoma, and cataracts in humans, indicating NBCe1 has a critical role in acid-base homeostasis and ocular fluid transport. To better understand the homeostatic roles and protein ontogeny of NBCe1, we have cloned, localized, and downregulated NBCe1 expression in zebrafish, and examined its transport characteristics when expressed in Xenopus oocytes. Zebrafish NBCe1 (zNBCe1) is 80% identical to published mammalian NBCe1 cDNAs. Like other fish NBCe1 clones, zebrafish NBCe1 is most similar to the pancreatic form of mammalian NBC (Slc4a4-B) but appears to be the dominant isoform found in zebrafish. In situ hybridization of embryos demonstrated mRNA expression in kidney pronephros and eye by 24 h postfertilization (hpf) and gill and brain by 120 hpf. Immunohistochemical labeling demonstrated expression in adult zebrafish eye and gill. Morpholino knockdown studies demonstrated roles in eye and brain development and caused edema, indicating altered fluid and electrolyte balance. With the use of microelectrodes to measure membrane potential (Vm), voltage clamp (VC), intracellular pH (pHi), or intracellular Na+ activity (aNai), we examined the function of zNBCe1 expressed in Xenopus oocytes. Zebrafish NBCe1 shared transport properties with mammalian NBCe1s, demonstrating electrogenic Na+ and HCO3 transport as well as similar drug sensitivity, including inhibition by 4,4'-diiso-thiocyano-2,2'-disulfonic acid stilbene and tenidap. These data indicate that NBCe1 in zebrafish shares many characteristics with mammalian NBCe1, including tissue distribution, importance in systemic water and electrolyte balance, and electrogenic transport of Na+ and HCO3. Thus zebrafish promise to be useful model system for studies of NBCe1 physiology.

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