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Thesis (M.E.S.)--York University, 2000. Graduate Programme in Environmental Studies. / Typescript. Includes bibliographical references (leaves 157-167). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://wwwlib.umi.com/cr/yorku/fullcit?pMQ59545.

Thesis (doctoral)--Ludwig-Maximilians-Universität, Munich, Germany.

Thesis (doctoral)--Ludwig-Maximilians-Universität, Munich, Germany.

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DNA in eukaryotes is packaged into nucleosomes, which present steric impediments to many of the factors and enzymes that act on DNA, including DNA repair enzymes. Within the nucleosome, DNA remains vulnerable to oxidative damage that can result from normal cellular metabolism, ionizing radiation, and various chemical agents. Oxidatively damaged DNA is repaired in a stepwise fashion via the base excision repair (BER) pathway. Other DNA repair pathways, including Nucleotide Excision Repair (NER), Mismatch Repair (MMR), Homologous Recombination (HR), and Non-homologous End-Joining (NHEJ) are all thought to require nucleosome remodeling or disruption. In contrast, it was reported that the first step of BER does not require or induce nucleosome disruption. For example, the human DNA glycosylase hNTH1 (human Endonuclease III) was discovered to excise thymine glycol lesions from nucleosomes without nucleosome disruption, and could excise optimally oriented lesions with an efficiency approaching that seen for naked DNA (Prasad, Wallace, and Pederson 2007). To determine if the properties of hNTH1 are shared by other human DNA glycosylases, we compared hNTH1 with NEIL1, a human DNA glycoylase that also excises thymine glycol from DNA, with respect to their activities on nucleosome substrates. We found that the cellular concentrations and apparent kcat/KM ratios for hNTH1 and NEIL1 are similar. However, NEIL1 and hNTH1 differ in that NEIL1 binds undamaged DNA far more avidly than hNTH1. After adjustment for non-specific DNA binding, hNTH1 and NEIL1 proved to have similar intrinsic activities towards nucleosome substrates. We next wanted to examine the effects of nucleosomes on enzymes that catalyze the remaining steps in BER. We therefore assembled the entire four-step BER reaction with model, lesion-containing nucleosomes. The rates of substrate processing during the first three steps in BER, catalyzed by a DNA glycosylase, AP endonuclease, and DNA Polymerase Pol), varied with the helical orientation of the substrate relative to the underlying histone octamer. In contrast, the rate of action by DNA Ligase III- (in association with XRCC1) was independent of lesion orientation. These results are consistent with structural studies of BER enzymes and the previously proposed DNA unwrapping model for how BER enzymes gain access to lesions in nucleosomes (Prasad, Wallace, and Pederson 2007). During these investigations, we also discovered a synergistic interaction between Pol and Ligase III- complexed with XRCC1 that enhances the repair of lesions in nucleosomes. Together, our results support the hypothesis that DNA glycosylases have evolved to function in specific cellular environments (e.g. NEIL1 may function exclusively during DNA replication), but also possess DNA binding motifs and mechanisms of substrate recognition that impart a similar intrinsic activity on nucleosomes. In addition to hNTH1 and NEIL1, we have discovered that lesion orientation is also an important factor to the activities of APE and Pol and that the complete BER reaction can occur without requiring or inducing nucleosome disruption. Finally, protein-protein interactions between XRCC1 and Pol may be important for the efficient in vivo repair of lesions in nucleosomes.

There is a drive for improving the surface uniformity of optical waveguide devices in the photonics lab. This report focuses on the exploration of annealed proton exchange (APE) waveguide fabrication on lithium niobate crystal as a method of producing optical waveguides. These waveguides aim to have little variation in step height or surface roughness in the transition area from the waveguide location to that of the bulk crystal, providing a uniform surface amenable to vertical device integration. This is a substantial improvement over the titanium diffused waveguide process, which can have surface variations in excess of 100nm. It is anticipated that the smoother surface will enable light to couple more easily into photonic devices, such as ring resonators, as compared to the current Ti diffused waveguide process. This work explores the design and fabrication aspects of annealed proton exchange waveguides. A review of literature on modeling hydrogen diffusion into lithium niobate is presented, as well as computer models for simulating the bidimensional fractional hydrogen proton concentration distribution. This is used to determine the change in refractive index of the waveguide needed to simulate the mode propagation and profile in the device. Fabrication processes involved in proton exchange waveguide formation are outlined, and measurements for working devices are presented. Best case loss for current devices are 0.5 dB/cm. These samples exhibit smooth surfaces with only ±60A in variation of surface uniformity. Concluding remarks present ideas to further the work by lowering propagation losses, improving mode matching to single mode fiber, and improving the consistency of fabrication conditions.

I examined fission-fusion sociality in dusky dolphins (Lagenorhynchus obscurus), and investigated aspects of social convergence between dolphins and great apes. I used boat-based group focal follows and photo-identification to collect data in Admiralty Bay, New Zealand during 2005-2006. I used generalized estimating equations to examine relationships between party (group) size, rate of party fission-fusion, activity, and location; and relationships between leaping frequency and behavior. Using photo-identification images from 2001-2006, I analyzed the strength and temporal patterning of associations, short- and long-term association patterns, preferred/avoided associations, and behaviorally-specific preferred associations. To analyze social convergence between dolphins and great apes, I compared female bottlenose dolphin (Tursiops spp.) and chimpanzee (Pan troglodytes) social strategies through literature review. I conducted 171 group focal follows, totaling 157 observation hours. Mean party size was 7.0±6.0 individuals. Party size changed every 5±.47.6 min on average. The most frequent activity was resting (37%), followed by traveling (29%), foraging (18%), and socializing (15%). Foraging was positively related to party size and rate of fission-fusion. Near mussel farms, foraging increased, traveling decreased, and rate of party fusion increased. "Clean" leaps were the most frequent leap type (84%) and were positively related to party size and foraging. Noisy and coordinated leaps were positively related to party size; noisy leaps were negatively related to foraging. Associations during 2001-2006 (N = 228 individuals) were nonrandom for 125 days; associations within one field season were nonrandom for 60 days. Individuals formed preferred/avoided associations during most years. The strongest associations occurred during foraging and socializing; the weakest associations occurred during traveling. Individuals formed preferred associations during foraging, resting, and socializing. Review of female bottlenose dolphin and chimpanzee sociality revealed that: 1) females form weaker bonds and are less social than males, 2) females associate mostly with other females, 3) mothers are often alone with their offspring, 4) mothers (vs. non-mothers) and non-cycling (vs. cycling) females associate less with males, and 5) non-cycling (vs. cycling) females occur in smaller parties. Female dolphins may be more social than female chimpanzees due to decreased scramble competition, increased predation risk, and decreased cost of transport for dolphins vs. chimpanzees.

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