Model studies toward the total synthesis of thebaine by an intramolecular cycloaddition strategy

The present studies describe recent progress toward the synthesis of the thebaine. Model substrates were synthesized using pyridazine derivatives as a starting material, which allowed to assess the key Diels-Alder reaction as a route to construct the thebaine core.

Aspergillus flavus infections in Galleria mellonella : a pathogen-host model system for the study of emerging diseases

To study emerging diseases, I employed a model pathogen-host system involving infections of insect larvae with the opportunistic fungus Aspergillus flavus, providing insight into three mechanisms ofpathogen evolution namely de novo mutation, genome decay, and virulence factoracquisition In Chapter 2 as a foundational experiment, A. flavus was serially propagated through insects to study the evolution of an opportunistic pathogen during repeated exposure to a single host. While A. flavus displayed de novo phenotypic alterations, namely decreased saprobic capacity, analysis of genotypic variation in Chapter 3 signified a host-imposed bottleneck on the pathogen population, emphasizing the host's role in shaping pathogen population structure. Described in Chapter 4, the serial passage scheme enabled the isolation of an A. flavus cysteine/methionine auxotroph with characteristics reminiscent of an obligate insect pathogen, suggesting that lost biosynthetic capacity may restrict host range based on nutrient availability and provide selection pressure for further evolution. As outlined in Chapter 6, cysteine/methionine auxotrophy had the pleiotrophic effect of increasing virulence factor production, affording the slow-growing auxotroph with a modified pathogenic strategy such that virulence was not reduced. Moreover in Chapter 7, transformation with a virulence factor from a facultative insect pathogen failed to increase virulence, demonstrating the necessity of an appropriate genetic background for virulence factor acquisition to instigate pathogen evolution.

A model of personality and health : coping styles as a moderator in the perfectionism-health connection

The purpose of this study was to examine a model of personality and health. Specifically, this thesis examined perfectionism as a predictor of health status and health behaviours, as moderated by coping styles. A community sample of 813 young adults completed the Multidimensional Perfectionism Scale, the Coping Strategy Indicator, and measures of health symptoms, health care utilization, and various health behaviours. Multiple regression analyses revealed a number of significant findings. First, perfectionism and coping styles contributed significant main effects in predicting health status and health behaviours, although coping styles were not shown to moderate the perfectionism-health relationship. The data showed that perfectionism did constitute a health risk, both in terms of health status and health behaviours. Finally, an unexpected finding was that perfectionism also included adaptive features related to health. Specifically, some dimensions of perfectionism were also associated with reports of better health status and involvement in some positive health behaviours.