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Carbohydrates And Fungal Toxin Exposure Influence The Vaginal Microbiota, Metabolome, And Reproductive Health Of Women, Stephanie L. Collins

Electronic Thesis and Dissertation Repository

The reproductive health of women is influenced by microorganisms and their metabolites, namely those representing the vaginal microbiota and those producing toxins that are ingested. To manipulate the vaginal microbiota toward a health-associated, Lactobacillusdominant state, an approach adopting prebiotic lactulose was taken. Using batch culture, lactulose supported Lactobacillus maintenance and positively altered metabolites, while not disrupting indigenous L. crispatus epithelial adherence. The vagina also harbours abundant glycogen, but initial assumptions that lactobacilli utilize it were incorrect. I have now shown that glycogen selectively stimulates organisms associated with dysbiosis and L. iners in a self-limiting manner. Other compounds such as environmental …

Crispr Screen For Identification Of Kinases That Mediate Prostate Cancer Cell Invasion, Hamad Aldhafeeri

Electronic Thesis and Dissertation Repository

Metastasis is the primary cause of mortality in cancer patients. Inhibition of proteins that are involved in the regulation of metastasis are expected to suppress metastasis and represent treatment targets. Our focus is on prostate cancer metastasis and we have developed a novel high-throughput means of performing in vitro screens for regulators of prostate cancer metastasis. We propose to use a focused CRISPR library screen that will “knock out” all human kinases to determine which ones are responsible for prostate cancer metastasis. CRISPR is a potent genetic editing tool and was used to silence all kinases in prostate cells (BPH …

Postnatal Β1 Integrin Deficiency In Pancreatic Beta-Cells Impairs Function And Survival, Jason E. Peart

Electronic Thesis and Dissertation Repository

Integrin β1 is essential for pancreatic beta-cell development and maintenance throughout life in rodents and human fetal islets. However, the effects of a postnatal β1 integrin knockout (β1KO) specific to pancreatic beta-cells of mice is undetermined. We generated mice with CreERT recombinase specific to the mouse insulin promoter (MIP), allowing us to induce a β1KO upon injection of tamoxifen (MIPβ1KO model).

At 3-4 weeks of age tamoxifen was injected and mice were sacrificed at 8 (male) and 16 weeks (female) post-tamoxifen. MIPβ1KO mice had impaired glucose tolerance, reduced beta-cell mass and islet density. The impairment in glucose tolerance remained in …