Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 121-147).

This thesis presents results obtained from the investigation of secondary metabolites through screening of marine organisms, marine-derived microbes, and microbes form under-explored habitats. The first part includes the isolation of eight cytotoxic diterpene derivatives of which four were new from the organic extract of the sponge <i>Spongionella </i>sp. obtained from the U.S. National Cancer Institute’s Open Repository Program, the isolation of three new antibacterial dibenzofuran derivatives and a known butyrolactone from ascomycete Super1F1-09 isolated from the Indo-Pacific sponge <i>Acanthella cavernosa. </i>An attempt to synthesize these compounds was conducted. This part also includes the isolation of five known pyrroloiminoquinone alkaloids, from the Fijian sponge <i>Zyzzya</i> sp., which showed potent antiprotozoal activity. The second part comprises the use of OSMAC approach for the isolation of four new ansamycin-type polyketides, three new macrolactones and one known siderophore from <i>Streptomyces </i>strain C34 isolated from Atacama Desert, Chile. These compounds showed good antibacterial activity with one of the ansamycins showed pronounced antibacterial activity against a panel of clinical isolates of methicillin-sensitive as well as methicillin-resistant <i>S. aureus</i> (MRSA). This part also contains the use of microbial co-culture for the induction of secondary metabolites. It comprises the isolation of ten antiprotozoal fungal metabolites, of which one was new, from <i>Aspergillus fumigatus </i>when co-cultured with the novel strain <i>Streptomyces </i>C2 isolated from Atacama Desert. In conclusion, natural products from diverse sources proved to be the major resource of drug discovery. This thesis describes the isolation and structural characterisation of 35 compounds, 15 of which were new. Extremophiles proved to be a good source for new secondary metabolites.

Thesis (Ph. D.)--University of Hong Kong, 1999. / Includes bibliographical references (leaves 206-229).

Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 176-203). Also available online.

Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 176-203). Also available in print.

Thesis (M. Phil.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 120-140) Also available in print.

Thesis (Ph.D.)--Aberdeen University, 2009. / Title from web page (viewed on Dec. 2, 2009). Includes bibliographical references.

published_or_final_version / Ecology and Biodiversity / Doctoral / Doctor of Philosophy

Anthropogenically driven climate change not only results in rising of sea temperature but also leads to more frequent and longer-lasting cold and heat waves. Meanwhile, coastal marine ecosystems are constantly challenged by increasing threats of chemical pollution. Temperature and chemical stressors can jointly affect the livelihood of marine organisms, but their combined effects are still poorly understood. Therefore, this study aimed to investigate the effects of thermal stress and chemical exposure on the marine medaka Oryzias melastigma, copepod Tigriopus japonicus and rotifer Brachionus koreanus. The four selected chemical contaminants included copper sulphate pentahydrate (Cu), dichlorophenyltrichloroethane (DDT), triphenyltin chloride and copper pyrithione. It was hypothesized that marine organisms are more susceptible to chemical exposure at both cold and warm extremes. In vivo acute ecotoxicity tests were conducted over a wide temperature range to ascertain the relationship between thermal stress and chemical toxicity. For O. melastigma larvae, the lowest toxicity occurred at an optimum temperature range; the chemical toxicity further increased with temperature increase or decrease from this optimum, and exacerbated at extremely low and high temperatures. For T. japonicus and B. koreanus, the chemical toxicity generally increased with increasing temperature. Such inter-species dissimilarities were possibly due to differences in the uptake route, detoxification mechanism, avoidance behaviour and physiological response between the fish and the copepod or rotifer. Experiments were conducted to evaluate the temperature-dependent physiological and biochemical responses, and thermal tolerance of O. melastigma larvae. The growth in the fish larvae showed an inverse and negatively skewed V-shape relationship with temperature, with a significant reduction in performance at both low and high thermal extremes. A mismatch between demand and supply of oxygen and energy under extremely cold and warm conditions was probably the primary cause of growth inhibition and metabolic impairment, leading to a temporary adaptation by a shift to anaerobiosis and an induction of heat shock proteins (HSPs). Temperatures at both cold and warm extremes increased toxicities of DDT and Cu to O. melastigma larvae, resulting in restricted growth and interrupted oxygen consumption rate. The fish larvae modulated their metabolic pathway and produced stress proteins (i.e., HSPs and metallothioneins) for adaptation to the combined stress. However, such responses were disrupted by combinations of thermal extremes, in particular high temperature, and high chemical concentration. Most importantly, both DDT and Cu exposure significantly reduced the thermal tolerance of the fish larvae. The interacting effect of temperature and Cu was also investigated on T. japonicus. The results showed that their combined effect could significantly reduce the survival, lengthen the developmental time and change the sex ratio of the copepod. Transcriptions of several stress-related genes (i.e., glutathione reductase, glutathione S-transferases and HSPs) in the adult T. japonicus were significantly affected by the joint-effect of temperature and Cu exposure, implying that these genes played essential roles in protecting the cellular integrity against the stresses. This study advanced the understanding on the temperature-dependent toxicity of chemical contaminants to marine organisms, and provided valuable information and empirical models for deriving water quality criteria of chemical contaminants at various temperatures. / published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

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