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Articles by H Song
Total Records ( 5 ) for H Song
  H Song , M Wohltmann , S Bao , J. H Ladenson , C. F Semenkovich and J. Turk

Phospholipases A2 (PLA2) play important roles in metabolic processes, and the Group VI PLA2 family is comprised of intracellular enzymes that do not require Ca2+ for catalysis. Mice deficient in Group VIA PLA2 (iPLA2β) develop more severe glucose intolerance than wild-type (WT) mice in response to dietary stress. Group VIB PLA2 (iPLA2) is a related enzyme distributed in membranous organelles, including mitochondria, and iPLA2 knockout (KO) mice exhibit altered mitochondrial morphology and function. We have compared metabolic responses of iPLA2-KO and WT mice fed a Western diet (WD) with a high fat content. We find that KO mice are resistant to WD-induced increases in body weight and adiposity and in blood levels of cholesterol, glucose, and insulin, even though WT and KO mice exhibit similar food consumption and dietary fat digestion and absorption. KO mice are also relatively resistant to WD-induced insulin resistance, glucose intolerance, and altered patterns of fat vs. carbohydrate fuel utilization. KO skeletal muscle exhibits impaired mitochondrial β-oxidation of fatty acids, as reflected by accumulation of larger amounts of long-chain acylcarnitine (LCAC) species in KO muscle and liver compared with WT in response to WD feeding. This is associated with increased urinary excretion of LCAC and much reduced deposition of triacylglycerols in liver by WD-fed KO compared with WT mice. The iPLA2-deficient genotype thus results in a phenotype characterized by impaired mitochondrial oxidation of fatty acids and relative resistance to the metabolic abnormalities induced by WD.

  L Wei , P. E Gravitt , H Song , A. M Maldonado and M. A. Ozbun

High-risk human papillomavirus (HPV) infections are necessary but insufficient causes of cervical cancers. Other risk factors for cervical cancer (e.g., pregnancy, smoking, infections causing inflammation) can lead to high and sustained nitric oxide (NO) concentrations in the cervix, and high NO levels are related to carcinogenesis through DNA damage and mutation. However, the effects of NO exposure in HPV-infected cells have not been investigated. In this study, we used the NO donor DETA-NO to model NO exposure to cervical epithelium. In cell culture media, 24-hour exposure to 0.25 to 0.5 mmol/L DETA-NO yielded a pathologically relevant NO concentration. Exposure of cells maintaining episomal high-risk HPV genomes to NO increased HPV early transcript levels 2- to 4-fold but did not increase viral DNA replication. Accompanying increased E6 and E7 mRNA levels were significant decreases in p53 and pRb protein levels, lower apoptotic indices, increased DNA double-strand breaks, and higher mutation frequencies when compared with HPV-negative cells. We propose that NO is a molecular cofactor with HPV infection in cervical carcinogenesis, and that modifying local NO cervical concentrations may constitute a strategy whereby HPV-related cancer can be reduced.[Cancer Res 2009;69(11):4878–84]

  H Song , W Qian , H Wang and B. Qiu

The initial steps in N-linked glycosylation involve the synthesis of a lipid-linked core oligosaccharide followed by the transfer of the core glycan to nascent polypeptides in the endoplasmic reticulum (ER). In this study, we have identified two genes, HpALG11and HpRFT1, in the metylotrophic yeast Hansenula polymorpha. Detailed analysis of the glycan structures of the N-linked glycans of secreted recombinant glucose oxidase in mutant strains Hpalg3, Hpalg11, and Hpalg3alg11 with the assistance of over-expression of RFT1 was performed by linkage-specific mannosidase digestion. The results suggest that HpALG11 and HpRFT1 were responsible for catalyzing the sequential transfer of terminal -1,2-Man residues to form the Man5GlcNAc2-PP-Dol intermediate at the cytosolic side of the ER before flipping to the luminal side and encoding an evolutionarily conserved protein required for the translocation of Man5GlcNAc2-PP-Dol from the cytoplasmic to the lumenal leaflet of the ER membrane, respectively. Deletion of the HpALG11 gene leads to poor growth and temperature-sensitive lethality, whereas over-expression of HpRft1p can improve growth of the Hpalg11 and Hpalg3alg11 strains. Furthermore, deletion of the HpALG11 gene in the Hpalg3 strain resulted in the secretion of glycoproteins with a predicted structure mainly containing trimannosyl core N-linked glycans (Man3GlcNAc2).

  H Song , S. J Ramus , S. K Kjaer , R. A DiCioccio , G Chenevix Trench , C. L Pearce , E Hogdall , A. S Whittemore , V McGuire , C Hogdall , J Blaakaer , A. H Wu , D. J Van Den Berg , D. O Stram , U Menon , A Gentry Maharaj , I. J Jacobs , P. M Webb , J Beesley , X Chen , The Australian Ovarian Cancer Study Group the Australian Cancer (Ovarian) Study , J. A Doherty , J Chang Claude , S Wang Gohrke , M. T Goodman , G Lurie , P. J Thompson , M. E Carney , R. B Ness , K Moysich , E. L Goode , R. A Vierkant , J. M Cunningham , S Anderson , J. M Schildkraut , A Berchuck , E. S Iversen , P. G Moorman , M Garcia Closas , S Chanock , J Lissowska , L Brinton , H Anton Culver , A Ziogas , W. R Brewster , B. A.J Ponder , D. F Easton , S. A Gayther , P. D.P Pharoah and on behalf of the Ovarian Cancer Association Consortium (OCAC)

Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case–control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially, three SNPs (rs2107425 in MRPL23, rs7313833 in PTHLH, rs3803662 in TNRC9) were weakly associated with ovarian cancer risk and one SNP (rs4954956 in NXPH2) was associated with serous ovarian cancer in non-Hispanic white subjects (P-trend < 0.1). These four SNPs were then genotyped in an additional 4060 cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95% CI 1.01–1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07–1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast cancer susceptibility variants we tested was associated with ovarian cancer risk. Further work will be needed to identify the causal variant associated with rs4954956 or elucidate its function.

  H Song , R Ji , C Stock and Z. Wang

Remotely sensed ocean color data and numerical modeling have been used to study the phenology of both spring and fall phytoplankton blooms (FPBs) in the Nova Scotian Shelf (NSS)–Gulf of Maine (GoM) region. The ocean color data reveal a general pattern of westward progression of the spring phytoplankton bloom (SPB), and an eastward progression of the FPB in the NSS–GoM region. The spatial pattern of mean chlorophyll concentration in spring is similar to that in fall, with a lower concentration in the NSS and higher in the GoM. Interannually, there is a weak but significant tendency for years with earlier (delayed) SPBs to be followed by delayed (earlier) FPBs, but the mean chlorophyll concentrations during SPBs are not correlated with those during FPBs. The interannual variability of SPB timing is significantly correlated with sea surface salinity (SSS), but the FPB timing is correlated with both SSS and sea surface temperature. The process-oriented numerical modeling experiments suggest that (i) salinity is the main factor influencing the bloom timing and magnitude in the NSS–GoM region, especially for the timing of SPBs; (ii) compared to buoyancy forcing induced by vertical salinity gradients, the impact of surface heating and surface wind stress on the blooms variability is much weaker; and (iii) the nutrient level controls the bloom magnitude, but only has a minor effect on bloom timing. This study provides a quantitative estimation of relationship between changes in local/remote environmental forcing and phytoplankton phenological shifts, thus improving our understanding on the possible impact of climate change on coastal/shelf ecosystems.

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