A Short and efficient syntheses of chiral 2, 2¡¦- bipyridine derivatives by Kröhnke reaction. The bipyridines allow well defined in self- assembly of double stranded helicates by coordinating with silver(¢¹).

Thesis (Ph.D.) - Simon Fraser University, 2004. / Theses (Dept. of Biological Sciences) / Simon Fraser University. Bibliography : leaves 134-154.

Thesis (Ph. D.) in Biochemistry and Molecular Biology--University of Maine, 2001. / Includes vita. Includes bibliographical references (leaves 71-83).

Thesis (Ph. D.)--Cornell University, May, 2008. / Vita. Includes bibliographical references (leaves 162-177).

Background: Genetic recombination is a driving force in genome evolution. Among viruses it has a dual role. For genomes with higher fitness, it maintains genome integrity in the face of high mutation rates. Conversely, for genomes with lower fitness, it provides immediate access to sequence space that cannot be reached by mutation alone. Understanding how recombination impacts the cohesion and dissolution of individual whole genomes within viral sequence space is poorly understood across double-stranded DNA bacteriophages (a.k.a phages) due to the challenges of obtaining appropriately scaled genomic datasets. Results: Here we explore the role of recombination in both maintaining and differentiating whole genomes of 142 wild double-stranded DNA marine cyanophages. Phylogenomic analysis across the 51 core genes revealed ten lineages, six of which were well represented. These phylogenomic lineages represent discrete genotypic populations based on comparisons of intra-and inter-lineage shared gene content, genome-wide average nucleotide identity, as well as detected gaps in the distribution of pairwise differences between genomes. McDonald-Kreitman selection tests identified putative niche-differentiating genes under positive selection that differed across the six well-represented genotypic populations and that may have driven initial divergence. Concurrent with patterns of recombination of discrete populations, recombination analyses of both genic and intergenic regions largely revealed decreased genetic exchange across individual genomes between relative to within populations. Conclusions: These findings suggest that discrete double-stranded DNA marine cyanophage populations occur in nature and are maintained by patterns of recombination akin to those observed in bacteria, archaea and in sexual eukaryotes.

Antibiotics are a foundation of modern medicine, helping to save millions of lives since their discovery in 1928. But the improper and excessive use of these drugs over the last few decades has led to an alarming increase in antimicrobial resistance; coupled with the recent decrease in antibiotic discovery, it is widely thought that we are approaching a post-antibiotic era. A less well-understood problem is that of drug tolerance. Even at high doses, antibiotics often cannot kill all the bacteria in an infection because of cells that are able to tolerate antibiotic treatment. Evidence points to drug-tolerant cells, also called persisters, to be a major cause of treatment failure and chronic and recurring infections It is imperative that we develop insight and methods to prevent the spread of antimicrobial resistance and combat antimicrobial tolerance. One key effort is characterizing bacterial responses to antibiotic drug treatment to generate a more comprehensive understanding of the factors that contribute to cell death and to elucidate potential targets for new therapies. Quinolones are an important class of antibiotics that target DNA replication. They bind to topoisomerase II and IV, leading to eventual DNA fragmentation and death. However, the precise mechanism by which they work is not well understood. Because they inhibit DNA replication, quinolones lead to up-regulation of the SOS response, which allows for increased mutagenesis and the potential for increased antimicrobial resistance, thus making quinolones an interesting class of antibiotics to study. Although quinolones are one of the most effective classes of antibiotics, there are many conditions in which they do not kill, such as in stationary-phase cultures. Understanding the mechanism behind quinolone killing, quinolone-induced mutagenesis and tolerance to quinolones is important to improve quinolone efficacy. Here I have presented my work on understanding quinolones: sensitivity, mutagenesis and tolerance. In understanding quinolone sensitivity, I focus on DNA repair and its involvement in quinolone-mediated death. I then probe the field of stress-induced mutagenesis by quinolones, uncovering phenotypes of dose-dependent mutagenesis that have previously been uncharacterized. Finally, I focus on drug tolerance and how density-dependent tolerance to quinolones can be reversed by up-regulating cellular respiration through the addition of a carbon source and electron acceptor. / 2018-11-02T00:00:00Z

Thesis (M. Phil.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

Thesis (M. Phil.)--University of Hong Kong, 2006. / Also available online.

Thesis (Ph. D.)--Cornell University, May, 2008. / Vita. Includes bibliographical references (leaves 125-133).

Thesis (Ph. D.)--Oregon State University, 2009. / Printout. Titles called 1 and 2. Includes bibliographical references (leaves 174-197). Also available on the World Wide Web.