Bibliography: leaves 348-366. / x, 366 leaves : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Elucidates the nature and extent of genetic and environmental contributions to variation in permanent tooth crown size. Sibling correlations are compared to find evidence of sex-linked genes contributing to crown size. This hypothesis was tested by comparing mean tooth size in female-male opposite-sex twins with same-sex twins, and singletons. / Thesis (Ph.D.)--University of Adelaide, Dept. of Dentistry, 1998

Corrigenda pasted onto back end-papers. / Bibliography: leaves 163-182. / [xiii], 183, [155] leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Analyses the proteins involved in Shigella flexneri O-antigen biosynthesis at the molecular level in order to gain a more concise understanding of the biosynthesis machinery and how it functions. / Thesis (Ph.D.)--University of Adelaide, Dept. of Microbiology and Immunology, 1999

Copies of author's previously published articles inserted. / Includes bibliographical references. / xv, 210 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / A chemical and pharmacological investigation of compounds derived from amphibian skin. Isolates novel amphibian peptides and further investigates the biological activity of some of the peptides discovered. / Thesis (Ph.D.)--University of Adelaide, Dept. of Chemistry, 2000

[Truncated abstract] The placenta forms a barrier regulating the transfer of gases, nutrients and wastes between the mother and the developing conceptus, and also produces hormones affecting both the fetus and the mother. This barrier is formed by the differentiation of the outer layer of the blastocyst- the trophoblast- to facilitate implantation and subsequent invasion of the uterus. The trophoblast consists of an underlying proliferative pool of cytotrophoblasts, which differentiate to replenish the overlying continuous, multi-nucleated syncytiotrophoblast that forms the barrier between the mother and fetus. Moreover, the location of the syncytiotrophoblast directly in contact with the maternal circulation suggests an endothelial role for the trophoblast regulating blood flow, thrombosis and immune cell adhesion. Disruption to the function of the human trophoblast may result in preeclampsia, a maternally manifested disorder of pregnancy characterised by hypertension and proteinurea. Blood flow to preeclamptic placentae is reduced and the cytotrophoblast pool is diminished; however the exact cause (or causes) remains elusive. Many potential causes are hypothesised, including endothelial damage, premature remodelling of maternal spiral arteries, increased oxidative stress and impaired trophoblast differentiation and apoptosis. Caspase-14 is an unusual caspase in that it is not involved in apoptosis. Furthermore, it possesses a limited, predominantly epithelial, tissue distribution. In the epidermis, caspase-14 is expressed in the apical differentiating layers. Here it cleaves profilaggrin to stabilise intracellular keratin intermediate filaments, and indirectly provides natural hydration and UV protection to the corneocytes. Thus, caspase-14 is vital to the maintenance of the barrier function of the skin. ... As differentiation-associated genes were elevated in the absence of caspase-14, this implies that caspase-14 suppresses biochemical trophoblast differentiation. The cytoskeletal keratin network was also examined following RNA Interference. The synthesis of cytokeratin 18 was significantly enhanced after caspase-14 suppression during BeWo differentiation, linking caspase-14 with keratin homeostasis. Therefore caspase-14 suppresses trophoblast differentiation, potentially through modulation of the cytoskeletal keratin filament network. The precise mechanism remains to be elucidated, however the identification of pathways regulated by caspase-14 advances our knowledge of trophoblast differentiation and potential causes of disorders of pregnancy. In summary, caspase-14 appears to be involved in the suppression of differentiation in the human trophoblast. As disorders of pregnancy such as preeclampsia often feature disturbed differentiation and a diminished cytotrophoblast pool, a greater understanding of caspase-14 biology in the human placenta could lead potential therapies for various disorders of pregnancy.

Bibliography: leaves 189-205. / xi, 205 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The aim of this PhD project is to screen feral goat rumen fluid for the presence of new organisms that may play a role in the detoxification of tannins and to investigate their mechanisms of action. An enrichment experiment is conducted to screen rumen fluid for anaerobic bacteria capable of growing in the presence of high levels of "Acacia" condensed tannin. Four morphologically-distinct bacteria are isolated, confirming that resistance is a property shared by more than one organism. One isolate is chosen at random for further characterisation and is identified as a strain of "Selenomonas ruminantium" subspecies "ruminantium". It is arbitrarily designated strain K2. "Selenomonas ruminantium" K2 is shown to be not only tannin-resistant but also able to grow on tannic acid. It is proposed that this bacterium obtained energy for growth from tannic acid. The thesis examines the molecular mechanisms controlling tannin resistance or tannin degradation in rumen microorganisms. / Thesis (Ph.D.)--University of Adelaide, Dept. of Animal Science, 1997

Bibliography: leaves 348-366. / x, 366 leaves : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Elucidates the nature and extent of genetic and environmental contributions to variation in permanent tooth crown size. Sibling correlations are compared to find evidence of sex-linked genes contributing to crown size. This hypothesis was tested by comparing mean tooth size in female-male opposite-sex twins with same-sex twins, and singletons. / Thesis (Ph.D.)--University of Adelaide, Dept. of Dentistry, 1998

Thesis (PhD)--Macquarie University, Division of Environmental & Life Sciences, Department of Biological Sciences, 2008. / Bibliography: p. 257-274. / Literature review -- General materials and methods -- Characterisation of strain collection -- Distribution of integrons and gene cassettes in pseudomonas -- Genomic context of pseudomonas integrons -- Evolutionary analysis of pseudomonas spp. integrons 199 -- Final discussion -- Appendix -- References. / Integrons associated with mobile genetic elements have played a central role in the emergence and spread of multiple antibiotic resistance in many pathogenic bacteria. However, the discovery of integrons in the chromosomes of diverse, non-pathogenic bacteria suggests that integrons have a broader role in bacterial evolution. The Pseudomonas stutzeri species complex is a well studied model for bacterial diversity. Members of the complex are genetically closely related, but sub-taxa are not able to be defined by exclusively shared sets of phenotypic characters. Rather, on the basis of total DNA:DNA similarity, Ps. stutzeri strains have been divided into 17 different groups (termed genomovars). Two Ps. stutzeri strains have been found to contain Chromosomal Integrons (CIs). This thesis involved exploration of the hypothesis that a CI was present in the common ancestor of the Ps. stutzeri species complex and assessed the impact of integrons on diversity across all Pseudomonads. The history and significance of integrons is discussed in Chapter 1 as part of a literature review, and general materials and methods are provided in Chapter 2. Chapters 3 - 6 comprise the sections in which data generated during my PhD project are presented. A comprehensive analysis of the relationships between the strains being analysed is presented in Chapter 3. In Chapter 4, results of PCR and hybridisation screening for integrons across the strain collection are presented. In Chapter 5 the recovery of additional integrons and in depth sequence analysis of the recovered integrons are described. Finally, Chapter 6 contains statistical analyses of integron-associated genes and Chapter 7 contains a final discussion the most significant findings. Twenty-three Pseudomonas spp. strains were screened for the presence of integrons. All but three were found to contain integron-like sequences; however, most integron sequences recovered contained inactivated core integrons. viii Despite having a chromosomal locus, integrons in Pseudomonas were found to have properties indicative of frequent horizontal transfer. Evidence was also obtained which suggests that integrons have been acquired at the same locus on multiple independent occasions. This has not been observed in other families of chromosomal integrons and suggests that the loci at which integrons in Pseudomonas are found are hotspots for recombination. / Mode of access: World Wide Web. / xiii, 274 p. ill

[Truncated abstract] The hepatitis C virus (HCV) is a significant human pathogen for which there are limited post-infection therapies and no effective vaccine. Research into HCV is notoriously difficult due to the absence of suitable in vitro and in vivo model systems with which to study the virus. Furthermore, our understanding of HCV host interaction is limited and the mechanisms by which it subverts the host immune system remains largely unknown. Due to the difficult nature associated with studying HCV, the work presented in this thesis was designed to addresses a broad range of issues relating to both clinical and molecular aspects of HCV. Chronic HCV infection is often associated with the development of cirrhosis, end stage liver disease and hepatocellular carcinoma. To date, histological examination of liver biopsies provides the only approved method with which to assess the level of liver damage. While clinically informative, liver biopsies are highly invasive and may be contraindicative for patients such as haemophiliacs. Cytokine specific ELISPOT assays were used to determine whether cytokine secretion from PBMCs isolated from chronically infected HCV patients could be used as a non-invasive method to assess liver damage. Chronically infected patients with sever liver fibrosis demonstrated a significantly reduced ability to produce IFN-γ in response to HCV Core, but not other unrelated antigens, indicating that decreased IFN-γ secretion by PBMCs in response to HCV antigen could be used as a non-invasive marker for the development of liver fibrosis ... A series of HCV expression vectors covering the full length of the HCV ORF were constructed and their expression extensively tested before being used to assess the ability of HCV proteins to interact with Jak/STAT mediated Type I IFN signalling. Additionally, an alternative set of HCV IRES-EGFP reporter vectors were developed and used to access HCV IRES functionality between different eukaryotic cell lines. HCV Core protein expressed alone or in concert with E1-P7 and non-structural protein NS5B were shown to significantly reduce Jak/STAT mediated IFN expression. While the influence of HCV Core on Type I IFN signalling is consistent with previous reports in the literature, these results identify a new role for NS5B as a possible candidate protein involved in inhibition of Type I IFN signalling.

[Truncated abstract] During development of the visual system, topographic connections between the retina and the superior colliculus are established using guidance molecules. The EphA family of tyrosine kinase receptors and their ephrin-A ligands are important for establishing topography between the temporo-nasal axis of the retina and the rostro-caudal axis of the superior colliculus. After injury to the visual system via unilateral optic nerve transection, adult mammalian retinal ganglion cells fail to regenerate axons spontaneously to their main visual centre, which in rodents, is the superior colliculus. The EphA5 gradient is down-regulated from a temporalhigh to nasallow gradient to a uniform low level in the few surviving retinal ganglion cells, but ephrin-A2 is upregulated back to a significant rostrallow to caudalhigh gradient in the superior colliculus, similar to that seen during development. In this thesis, a number of experiments have been undertaken to investigate further how EphA5 and ephrin-A2 are regulated after injury and how they may play a role once regeneration has been encouraged through surgical intervention. In the first study, targeted unilateral retinal laser lesions were used to ablate either dorso-nasal or ventro-temporal quadrants of the retina. ... Surviving and regenerating retinal ganglion cells in the retina, and axons in the optic nerve, were analysed. The data suggest that metallothionein-I/II increases axonal regeneration through the optic nerve injury site but, at the dose administered, had no neuroprotective effects on retinal ganglion cells. This thesis provides further insight into the response of guidance molecules to injury, and the potential of metallothionein-I/II as a neuroregenerative factor in the adult mammalian visual system. The regulation of both EphA5 and ephrin-A2 through transsynaptic connections may be a response common to other guidance molecules. Such connectivity now needs to be studied further to understand how it may impact on various treatments designed to increase re-connectivity after other brain injuries, including stroke. The ectopic expression of ephrin-A2 at the insertion site of a peripheral nerve graft in the superior colliculus, implicate this guidance molecule in the glial scar for the first time. Therefore, to overcome inhibition by the glial scar, axons must also overcome ephrin-A2 mediated inhibition, potentially by the addition of EphA5 fusion proteins. Metallothionein-I/II?s effect of increasing axonal regeneration through the optic nerve injury site suggests that it could be used to increase the number of regenerating axons reaching their target. Such strategies to increase the absolute number of regenerated axons should enable these axons to better use the EphA5 and ephrin-A2 topographic gradients to optimize regenerative success.

[Truncated abstract] The Phase II clinical candidate, [(trans-Pt(NH3)2Cl)2{μ-trans-Pt(NH3)2(H2N(CH2)6NH2)2}]4+ (BBR3464 or 1,0,1/t,t,t) shows a unique binding profile when compared to the anticancer agent cis-[Pt(NH3)2Cl2] (cisplatin) and dinuclear platinum complexes of the general formula [(trans-Pt(NH3)2Cl)2(H2N(CH2)nNH2)]2+. There is evidence that the increased efficacy of 1,0,1/t,t,t results from the presence of the charged central linker, which can alter the mode of binding to DNA. This alternate binding mode may be due to an electrostatic and hydrogen bonding association of the central platinum moiety in the minor groove that occurs prior to covalent binding (termed “pre-association”) . . . This research shows that 0,0,0/t,t,t is an adequate model to study the pre-association process of 1,0,1/t,t,t and that it binds in the minor groove of DNA. Therefore it is likely that 1,0,1/t,t,t pre-associates in the minor groove of DNA prior to covalent binding. This work supports the conclusions reached in NMR studies of the binding of 1,0,1/t,t,t with the 1,4-GG sequence (Qu et al. JBIC. 8, 19-28 (2003)), which showed simultaneous binding in the major and minor groove. The findings of the current work may also explain the observed binding mode of 1,0,1/t,t,t, which can bind to DNA in both the 3',3' and 5',5' directions (Kasparkova et al. JBC. 277, 48076-48086 (2002)). These unique binding characteristics are thought to be responsible for the increased efficacy of 1,0,1/t,t,t, and in light of the current results the observed binding mode most likely stems from the electrostatic pre-association of the central platinum moiety.