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To determine if the disruption of the MMR pathway results in the reduced conservation of methylated adenines as well as an increased tolerance for mutations that result in the loss or gain of new GATC sites, we surveyed individual clones isolated from experimentally evolving wild-type and MMR-deficient (mutL- ;conferring an 150x increase in mutation rate) populations of E. coli with whole-genome sequencing. Initial analysis revealed a lack of mutations affecting methylation sites (GATC tetranucleotides) in wild-type clones. However, the inherent low mutation rates conferred by the wild-type background render this result inconclusive, due to a lack of statistical power, and reveal a need for a more direct measure of changes in methylation status. Thus as a first step to comparative methylomics, we benchmarked four different methylation-calling pipelines on three biological replicates of the wildtype progenitor strain for our evolved populations.
While it is understood that these methylated sites play a role in the MMR pathway, it is not fully understood the full extent of their effect on the genome. Thus the goal of this thesis was to better understand the forces which maintain the genome, specifically concerning m6A within the GATC motif.
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Past studies have shown that exercise in the form of high intensity interval training (HIIT) is the "ideal form of exercise to improve health and performance without overstressing the immune system" (Fisher et. al, 2011, p. 5). Additionally, HIIT has been found to promote cardiovascular health and immunity (Fisher et. al, 2011). The proposed study will evaluate the neuropsychological effects of HIIT on breast cancer patients undergoing anthracycline-based chemotherapy. The intervention group (n = 17) will receive a HIIT protocol concurrent with chemotherapy treatment. There will also be a control group (n= 17) to compare the effects of the intervention. Breast cancer survivorship is often ridden with various health and mental problems, the implementation of HIIT procedures could help to reduce these issues. It is expected that knowledge from this study will be useful in the healthcare setting to benefit breast cancer patients. This study will uniquely add to the limited research base by introducing an intervention for neuropsychological declines in breast cancer patients.