This research involved a rigorous implementation of the conceptual framework of Australia's National Strategy for Quality Use of Medicines through a planned sequence of studies across a large defined geographical region to test the hypothesis that: The National Strategy for Quality Use of Medicines can be used to design, implement and evaluate a research program to achieve sustained improvement in health care in a regional setting.

Pseudomonas fluorescens SBW25 is a gram-negative soil bacterium capable of growing on histidine as the sole source of carbon and nitrogen. Expression of histidine utilization (hut) genes is controlled by the HutC repressor with urocanate, the first intermediate of the histidine degradation pathway, as the direct inducer. Recent genome sequencing of P. fluorescens SBW25 revealed the presence of hutD in the hut locus, which encodes a highly conserved hypothetical protein. Previous genetic analysis showed that hutD is involved in hut regulation, in such a way that it prevents overproduction of the hut enzymes. Deletion of hutD resulted in a slow growth phenotype in minimal medium with histidine as the sole carbon and nitrogen source. While the genetic evidence supporting a role of hutD in hut regulation is strong, nothing is known of the mechanism of HutD action. Here I have cloned and expressed the P. fluorescens SBW25 hutD in E. coli. Purified HutD was subjected to chemical and structural analysis. Analytic size-exclusion chromatography indicated that HutD forms a dimer in the elution buffer. The crystal structure of HutD was solved at 1.80 Å (R = 19.3% and Rfree = 22.3%) by using molecular replacement based on HutD from P. aeruginosa PAO1. P. fluorescens SBW25 HutD has two molecules in an asymmetric unit and each monomer consists of one subdomain and two ß-barrel domains. Comparative structural analysis revealed a conserved binding pocket. The interaction of formate with a highly conserved residue Arg61 via salt-bridges in the pocket suggests HutD binds to small molecules with carboxylic group(s) such as histidine, urocanate or formyl-glutamate. The hypothesis that HutD functions via binding to urocanate, the hut inducer, was tested. Experiments using a thermal shift assay and isothermal titration calorimetry (ITC) analysis suggested that HutD binds to urocanate but not to histidine. However, the signal of HutD-urocanate binding was very weak and detected only at high urocanate concentration (53.23 mM), which is not physiologically relevant. The current data thus does not support the hypothesis of HutD-urocanate binding in vivo. Although the HutD-urocanate binding was not confirmed, this work has laid a solid foundation for further testing of the many alternative hypotheses regarding HutD function.

Bibliography :leaves 149-172. / vii, 172,[60] leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The investigations centre on the use of [beta]-aminothiols (cysteine, cysteamine and penicillamine) to decrease endogenous oxalate production by forming adducts with glyoxylate, the immediate precursor of oxalate. They indicate that cysteine delivery drugs like OTC have the potential to aid in management of calcium oxalate stone disease, thereby reducing endogenous oxalate production and urinary oxalate excretion. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 1995?

Includes bibliographical references (leaves 290-333). / xxiv, 333 leaves : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Describes research into the nutritional value of aquatic plants as novel or non-conventional feedstuffs for ruminants in general and for sheep in particular, with especial reference to those which are available in high amount in southern Australia, such as the seagrass, Posidonia australis. / Thesis (Ph.D.)--University of Adelaide, Dept. of Animal Science, 1996?

Bibliography: p. 320-341. / xvii, 341 p. : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Addresses the documented variation in dental service rates and the questions of appropriateness of care arising from this variation. Examines the association of services provided with dentists, practice and patient factors. Based on a survey pf private general practice dentists who provided a data log for one typical day. / Thesis (Ph.D.)--University of Adelaide, Dept. of Dentistry, 2000

[Truncated abstract] Saltbush is one of the few types of forage that will grow on salt affected land but, sheep struggle to maintain weight when grazing saltbush mainly because of its high salt content. Therefore, a strategy to improve salt tolerance of sheep would be beneficial to the profitable use of revegetated saline land. This could be done by manipulating the dietary salt load of pregnant or lactating ewes which could 'program', or permanently alter the physiology of their offspring to allow them to cope better with a high-salt diet as adults. When rat dams consume a high amount of salt during pregnancy, the salt balance mechanisms of their offspring are 'programmed' due to suppression of the offspring's renin-angiotensin system in early development. If this occurs in offspring from ewes grazing saltbush, beneficial adaptations may be programmed in these offspring which could allow them to better cope with the high-salt content of saltbush. I tested the general hypothesis that offspring born to ewes that consumed a high-salt or saltbush diet from mid-pregnancy to early lactation would have an increased capacity to cope with salt that would allow them gain weight when grazing saltbush in later life. To test this hypothesis, I pair-fed ewes either a high-salt diet (14% NaCl) or control diet (2% NaCl) in an animal house from day 60 of gestation until day 21 of lactation. During the same period, I also conducted a field experiment where ewes grazed on saltbush (supplemented with barley) or on pasture (supplemented with lupins). ... This led to the high-salt offspring retaining more salt than control animals. In contrast, the renin activity of saltbush was consistently lower than pasture offspring which allowed them to excrete salt more rapidly. In experiment three, the saltbush offspring gained tissue weight after grazing saltbush for 8 weeks, whereas the offspring in the other three treatments lost weight. High-salt and saltbush offspring also had higher greasy fleece weights at 22 months of age than their respective control groups. Feeding saltbush to ewes from mid-pregnancy to early lactation induces physiological adaptations in their offspring that allow them to cope better with salt and gain weight when grazing saltbush as adults, supporting my hypothesis. However, contrary to expectations, the high-salt offspring did not gain weight when grazing saltbush because their physiological adaptations, such as salt retention, did not allow them to cope better with a salt load. The reason that saltbush offspring showed different adaptations to highsalt offspring is likely to be because saltbush contains not only NaCl but also high amounts of other minerals such as potassium, and other plant compounds, which may influence the adaptive responses of the offspring. This research has direct implications for farmers because it shows they could utilize otherwise unproductive saltland by grazing pregnant ewes on saltbush to 'program' their offspring to gain weight when they graze saltbush later in life.

Thesis (Ph.D.)--University of Wisconsin--Madison, 2006. / Includes bibliographical references (p. 155-163). Also available on the Internet.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2007. / Härtill 4 uppsatser.

Thesis (M.A.)--University of Toronto, 2006. / Source: Masters Abstracts International, Volume: 44-06, page: 2503.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.