published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

Liver fibrosis is an important reversible stage in progress of most chronic liver diseases (CLDs). The excess hepatic wound healing response against chronic liver injury results in extracellular matrix proteins accumulation and fibrosis. Oxidative stress, liver inflammation and/or hepatic steatosis contribute to this process. Until now, little is known how dietary lipids can influence liver’s pathophysiology. The effects of lipids on CLD progression may depend on their amount and the quality of fatty acids as well as the degrees of saturation. The investigation of liver fibrosis will help to understand the pathogenesis of CLDs and develop potential nutritional therapeutic approaches. The specific aim of this study was to investigate the effects of different high fats consumption in liver fibrosis by feeding the normal and carbon tetrachloride (CCl4)-treated animals with the diets enriched with following oils: corn oil rich in ω-6 polyunsaturated fatty acids (PUFAs), extra virgin olive oil (EVOO) high in ω-9 monounsaturated fatty acids (MUFAs), and lard enriched with saturated fatty acids (SFAs) for 4 weeks. The differentially expressed liver proteins in this process were identified by two-dimensional gel electrophoresis based proteomics to explore the molecular mechanisms. The proteomic analysis revealed characteristic differences between (i) normal and fibrotic livers (Chapter 3), and between the fibrotic livers treated with (ii) low fat versus high fat (20% w/w corn oil, Chapter 4) and among the high fats, between the diet enriched with corn oil versus (iii) EVOO (Chapter 5) and lard (Chapter 6). Among the identified proteins, collagen synthesis related protein prolyl 4-hydroxylase, oxidative stress related protein alpha-1-antitrypsin, free radical scavenger Cu/Zn superoxide dismutase and Calcium homeostasis regulator calreticulin and regucalcin were found to involve in CCl4-induced liver fibrosis. The results show that corn oil enhanced the hepatic steatosis but had no significant effects on fibrogenesis; the expression of several stress proteins like heat shock protein 75 kDa, and lipid metabolism related protein enoyl-CoA hydratase domain-containing protein 3 were found increased in high corn oil consumption animals with CCl4-treatment. Histological evaluations showed that olive oil could attenuate, and lard oil aggravate the liver damage induced by CCl4. Compared to corn oil, high EVOO diet rich in MUFAs decreased the lipid peroxidation and collagen accumulation in liver. Several protein related to antioxidant effects, including peroxiredoxin-1, thiosulfate sulfurtransferase and thioredoxin domain-containing protein 12 were found have higher expression level in high EVOO intake animals. In contrast, lard rich in SFAs intake leaded to macrovesicular steatosis and advanced fibrosis, and decreased the expression of antioxidant related glutathione S-transferases. Interestingly, S-adenosylmethionine synthesis related enzyme methionine adenosyltransferase was found up-regulated in lard intake animals, suggests the modification of DNA methylation was implicated in lard fed animals, while the demethylation on the promoter of profibrogenic gene was found, confirmed the lard consumption has the epigenetic modification effects in liver injury. Together, these findings give further insight into the pathobiology of CLDs. The data also helped to address the issue that different degrees of saturation of dietary lipids may affect liver fibrosis with different mechanistic actions. / published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

he chlorinated methanes carbon tetrachloride (CT), chloroform (CF), dichloromethane (DCM) and chloromethane (CM) are widespread groundwater pollutants that pose risks to human and ecosystem health. Although some progress has been made in elucidating the microbiology contributing to the aerobic degradation of DCM and CM, these efforts have had little impact on bioremediation practices aimed at restoring anoxic aquifers impacted by chlorinated methanes. Remaining knowledge gaps include the lack of understanding of the microbial mechanisms and pathways contributing to chlorinated methane transformations under anoxic conditions. Thus, the major goals of this research effort were to identify microbes that can contribute to the transformation of chlorinated methanes in the absence of oxygen, and to develop monitoring tools to assess anaerobic chlorinated methane bioremediation at contaminated sites. To accomplish these goals, freshwater and estuarine sediment samples from 45 geographically distinct locations, including 3 sites with reported chlorinated-methane contamination, were collected and screened for CT-, CF-, DCM- and/or CM-degrading activity. DCM degradation was observed in microcosms established with sediment materials from 15 locations, and the sediment-free, DCM-degrading enrichment culture RM was obtained from Rio Mameyes sediment. 16S rRNA-gene based community analysis characterized consortium RM, and identified a Dehalobacter sp. involved in DCM fermentation to non-toxic products. Organism- and process-specific monitoring tools were designed that target the 16S rRNA gene of the DCM-fermenting Dehalobacter sp. and the consortium’s specific 13C-DCM enrichment factor, respectively. Treatability studies using site materials that showed no chlorinated methane degradation activity demonstrated the feasibility of using CF- and DCM-degrading consortia for bioaugmentation applications. Collectively, this study expands our understanding of bacteria contributing to chlorinated methane degradation, provides new tools for monitoring anaerobic DCM degradation, and demonstrates that microbial remedies at chlorinated methane contaminated sites are feasible.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1952. / Typescript. Vita. Includes: Effect of density and average atomic number of the medium on the counting yield of beta and gamma radiation in a solution-type Geiger counter / Robert Sieh-Hsuan Chiang and John E. Willard. Reprinted from Science, vol. 112, no, 2899 (21 July 1950), p. 81-84 -- Some effects of temperature, phase and nature of chemical species on halogen atom reactions initiated by radiative neutron capture and by isomeric transition / By S. Goldhaber, R.S.H. Chiang and J.E. Willard. Reprinted from Journal of the American Chemical Society, vol. 73 (1951), p. 2271-2275. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of Pennsylvania, 1928.

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Typescript. / Digitized by Kansas Correctional Industries

Thesis (Ph. D.)--University of Washington, 1993. / Vita. Includes bibliographical references (leaves 243-254).

Thesis (Ph. D.)--University of Washington, 1998. / Vita. Includes bibliographical references (leaves [166]-175).