Thesis (M. Phil.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.

Thesis (Ph.D.)--Hong Kong University of Science and Technology, 2005. / Includes bibliographical references (leaves 112-133). Also available in electronic version.

Thesis (Ph. D.)--Illinois State University, 1995. / Title from title page screen, viewed May 8, 2006. Dissertation Committee: Hou Tak Cheung (chair), David W. Borst, Herman E. Brockman, Alan J. Katz, Anthony J. Otsuka. Includes bibliographical references (leaves 98-110) and abstract. Also available in print.

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 117-135).

Th. doct.-ing.--Génie chim.--Grenoble--I.N.P., 1981. N°: DI 237.

The effects of altered membrane fatty acid composition on the toxic interactions of heavy metals with Saccharomyces cerevisiae were examined. Saccharomyces cerevisiae was enriched with the polyunsaturated fatty acids (PUFAs) linoleate (18:2) and linolenate (18:3) by growth in 18:2- or 18:3-supplemented medium. Incorporation of the exogenous PUF As resulted in them comprising greater than 65% and 40% of the total fatty acids in whole-cell and plasma membrane lipids, and nuclear membrane lipids, respectively. Incorporation of the exogenous PUF As had no discernible adverse effects on cell division. However, inhibition of cell division in the presence of Cd(N03)2 was accentuated by growth in the presence of the di-unsaturated fatty acid linoleate. Furthermore, susceptibility to both Cd2+ - and Cu2+ -induced plasma membrane permeabilisation and whole cell toxicity was markedly accentuated in PUF A-enriched cells, and increased with the degree of fatty acid unsaturation. The increased sensitivity ofPUFA-enriched cells to membrane permeabilisation and whole-cell toxicity was correlated with increased levels of lipid peroxidation in these cells. Cu2+ - and Cd2+_ induced lipid peroxidation was rapid and associated with a decline in plasma membrane lipid order, detected by fluorescence depolarization measurements. Levels of the lipid peroxidation products thiobarbituric acid-reactive substances (TBARS) and conjugated dienes were markedly higher in PUF A-enriched cells, compared with unsupplemented cells, following exposure to cadmium or copper. Thus, lipid peroxidation was demonstrated as a major means of heavy metal toxicity in a microorganism for the first time. In addition, the effects ofPUFA-enrichment on the interactions of heavy metals with cellular nucleic acids were examined. Exposure ofPUFA-enriched cells to the redox-active metals chromium and copper resulted in the uncoupling of DNA synthesis from cell division, leading to sequential S phases. For example, DNA levels of up to 8C were evident in 18:3-enriched cells after only 4.5 h exposure to 100 JJ.M Cu(N03h. Using flow cytometry, the heterogeneity in susceptibility to copper toxicity of exponential phase S. cerevisiae was also examined. Susceptibility towards copper toxicity was demonstrated to be cell cycle stage-dependent, whereby G2/M phase cells were found to be the most susceptible towards copper toxicity. Staining with the oxidantsensitive probe 2',7' -dichlorodihydrofluorescein diacetate (H2DCFDA) revealed that the greater copper sensitivity of G2/M phase cells correlated with elevated endogenous levels of reactive oxygen species in these cells.

No description available.

Kyoto University (京都大学) / 0048 / 新制・課程博士 / 博士(工学) / 甲第13842号 / 工博第2946号 / 新制||工||1435(附属図書館) / 26058 / UT51-2008-C758 / 京都大学大学院工学研究科高分子化学専攻 / (主査)教授 増田 俊夫, 教授 中條 善樹, 教授 木村 俊作 / 学位規則第4条第1項該当

Antibacterial agents are composed of a diverse group and many such agents have entered common usage through experience with little information on their mechanism of action. Study of the mechanism of action of an antimicrobial agent provides an insight into resistance mechanisms, toxicological problems and the design and development of new agents or combinations. The primary target of most antimicrobial agents (excluding antibiotics) is the cytoplasmic membrane and associated enzymes. Membrane-active agents can cause a change in the fluidity and/or permeability of the cytoplasmic membrane. Such changes can be determined by the leakage of cellular constituents such as potassium ions, nucleotides and their constituents and amino acids. The effect of an anti bacterial agent on the cytoplasmic membrane can also be determined by elucidating the effect of the antibacterial agent on the activity of membrane-bound enzymes and substrate uptake.

No description available.