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Background: Approximately 40% of global human immunodeficiency virus-1 (HIV) transmission occurs in the female genital tract (FGT). Epithelial cells lining the FGT comprise the first barrier to HIV-1 entry. The functions of these cells are influenced by female sex hormones and the mucosal microbiota. Studies have suggested that hormonal environment and a dysbiosis of the FGT microbiota may lead to inflammation in the genital mucosa and enhance HIV acquisition. A Lactobacillus dominant microenvironment in the FGT is considered to have protective functions against sexually transmitted pathogens, however the interaction between sex hormones and lactobacilli and their effect on epithelial cell functions remains to be determined. Methods of Study: For these studies, primary genital epithelial cells (GECs) were isolated from hysterectomy tissues obtained following patient consent. GEC cultures were grown to confluence on cell culture inserts in the presence or absence of the female sex hormones estrogen (E2), progesterone (P4), or medroxyprogesterone acetate (MPA). Polarized monolayers were exposed to two probiotic strains of Lactobacillus: L. reuteri (RC-14) or L. rhamnosus (GR-1), or the most common strain of bacteria found in the FGT, L. crispatus in the presence or absence of HIV-1. Cell viability, barrier integrity, and innate inflammatory factors were among the primary measures performed. Results: In our system, cell viability was unaltered in the presence of Lactobacillus species and/or female sex hormones. All three strains of bacteria (L. crispatus and probiotic lactobacilli GR-1 and RC-14) significantly increased GEC barrier integrity, as measured by transepithelial electrical resistance (TER). Both GR-1 and RC-14 significantly reduced GEC barrier permeability as measured by a dextran dye leakage assay, whereas L. crispatus did not. Conversely, hormones did not alter barrier integrity nor barrier permeability. However, hormones did alter secretion of cytokines and chemokins by GECs. GECs grown in the presence of estrogen decreased TNF-α, IL-1α, IL-1β and IL-8 secretion in comparison to no hormone treatment, while GECs grown in the presence of MPA significantly decreased MIP-1α and TNF-α secretion. In the presence of HIV both GR-1 and RC-14 were able to confer an increase in barrier integrity similar to that observed with GR-1 and RC-14 treatment alone. Addionally, GECs grown in the presence of E2 and MPA displayed a less inflammatory (TNF-α, IL-1α, and IL-1β) environment when exposed to HIV compared to no hormone and P4. Interstingly, the decrease in inflammation was not observed when measuring chemokines such as IL-8 and RANTES. Furthermore, probiotic bacteria were able to significantly reduce HIV mediated increases in TNF-α when grown in the presence of no hormone, P4, and MPA. A similar trend was observed for GECs grown in the presence of E2 however, given that E2 reduced the TNF-α response mediated by HIV, results were not significant. Overall, probiotic lactobacilii GR-1 and RC-14 enhanced GEC barrier functions while E2 and MPA appeared to exert an anti-inflammatory effect on epithelial cell innate responses in both the presence and absence of HIV. Conclusions: In our system, probiotic lactobacilli enhanced GEC barrier functions and estrogen appeared to exert an anti-inflammatory effect on epithelial innate responses. Enhanced barrier function and decreased inflammation correlate with decreased in HIV acquisition and replication. These studies provide an insight into how factors in the genital microenvironment can affect HIV acquisition in the FGT, and will subsequently assist in the development of prophylactic strategies to reduce HIV transmission. / Thesis / Master of Science (MSc) / Approximately 40% of global HIV transmission occurs in the female genital tract. Although women make up more than 50% of infected individuals worldwide, the details regarding how HIV infection starts in the female genital tract remains poorly understood. The cells that line the genital tract are the first barrier against HIV entry. These cells are influenced by common factors within the genital tract microenvironment such as female sex hormones and natural bacterial populations. Previous studies have suggested that certain hormonal contraceptives or a build-up of pathogenic bacteria within the genital tract, leads to an inflammatory microenvironment and may enhance HIV acquisition. Comparatively, ‘good bacteria’ within the microenvironment have been shown to have protective effects against sexually transmitted infections. For this study, we were interested in understanding how different hormones (estrogen, progesterone and progesterone based hormonal contraceptives) and ‘good bacteria’ (specifically probiotic strains of lactobacilli), affect the cells that line the genital tract and local inflammation in the presence and absence of HIV. Therefore, we obtained cells that line the genital tract (epithelial cells) from women undergoing hysterectomies. The cells were grown in the presence or absence of hormones, exposed to ‘good bacteria’ and then challenged with HIV. In our system, probiotic lactobacilli enhanced genital epithelial cell barrier functions and estrogen appeared to exert an anti-inflammatory effect on epithelial cells. Furthermore, when genital epithelial cells were pre-treated with lactobacilli and exposed to HIV, lactobacilli treatment was able to protect against HIV mediated barrier disruption. Lactobacilli treated genital epithelial cells also reduced inflammatory markers in the presence HIV. Enhanced barrier function and decreased inflammation correlate with decrease in HIV infection and replication. This study provides insight into how factors in the genital microenvironment can affect HIV infection in the female genital tract and suggests potential prophylactic strategies to reduce HIV infection.

Acute aerobic exercise alters neurotrophic and growth factor concentrations, increases neural activity and improves cognitive and motor function. Additionally, acute exercise increases excitation and reduces inhibition in the motor cortex as assessed via transcranial magnetic stimulation (TMS). The propensity for exercise-induced neuroplasticity may be greater in females, as females show greater neuroplasticity induction following non-invasive brain stimulation (NIBS) compared to males. In females, NIBS yields greater neuroplasticity during ovulation, when estradiol levels are higher, compared to menstruation, suggesting that ovarian hormones may also impact exercise-induced neuroplasticity. To date, it is unknown whether biological sex and ovarian hormones impact neuroplasticity induced by acute aerobic exercise. The present thesis investigated the effects of biological sex and ovarian hormones on the magnitude and direction of neuroplasticity induced by acute aerobic exercise. Fourteen females and fourteen age- and fitness-matched males participated in two sessions in which dependent measures were acquired before and following a single bout of aerobic exercise. Females were tested in the follicular (~day 7) and luteal (~day 21) phases of the menstrual cycle and males were also tested on two occasions separated by ~14 days. The exercise intervention consisted of 5 minutes of warm up, 20 minutes of moderate intensity continuous cycling at 65-70% maximal heart rate, and 5 minutes cool down. TMS was used to obtain motor evoked potential (MEP) recruitment curves and short interval intracortical inhibition (SICI) from the right first dorsal interosseous muscle. Blood measures of estradiol, progesterone, testosterone, and brain-derived neurotrophic factor were assessed before exercise on both testing sessions. Results indicated that only females showed increases in MEP recruitment curve following exercise, and this occurred regardless of menstrual cycle phase. SICI did not change following exercise for males or females on either testing session. The estrogen to progesterone ratio in females was greater in the follicular phase compared to the luteal phase. There was a trend towards greater serum BDNF levels in females in the luteal phase compared to the follicular phase. Sex hormones and BDNF levels did not vary across sessions in males. These findings indicate biological sex, but not ovarian hormones, is an important factor to consider when inducing neuroplasticity using acute exercise. / Thesis / Master of Science (MSc)

A series of studies were conducted to examine the antioxidant status, drought and disease tolerance, and growth response to foliar application of soluble seaweed (Ascophyllum nodosum) extracts (SE) and humic acid (HA; 25% active HA or 2.9% active HA) in tall fescue (Festuca arundinacea Schreb), Kentucky bluegrass (Poa pratensis L.) and creeping bentgrass (Agrostis palusttis Huds.) grown under low (-0.5 MPa) and high (-0.03 MPa) soil moisture environments. Foliar application of humic acid (2.9 % active HA) at 23.7 and 47.4 l/ha improved leaf water status, shoot and root development in tall fescue, Kentucky bluegrass and creeping bentgrass grown under drought. Humic acid (2.9% active HA) at 15.5 l/ha or SE at 326 g/ha significantly reduced dollarspot incidence and improved turf quality in creeping bentgrass. Drought stress induced an increase of antioxidants alpha-tocopherol and ascorbic acid concentrations in the three turfgrass species. In the experiment with Kentucky bluegrass, drought stress increased beta-carotene concentration, but did not significantly influence superoxide dismutase (SOD) activity. Foliar application of humic acid (25% active HA) at 5 l/ha and/or SE at 326 g/ha consistently enhanced alpha-tocopherol and ascorbic acid concentrations, leaf water status, and growth in the three cool-season turfgrass species grown under low and high soil moisture environments. In the experiment with Kentucky bluegrass, application of HA at 5 l/ha plus SE at 326 g/ha also increased beta-carotene content and SOD activity under low and high soil moisture environments. There were close positive correlations between the antioxidant status and shoot or root growth in the three turfgrass species regardless of soil moisture levels. The antioxidant SOD activity, photosynthetic capacity in terms of Fvm690, and chlorophyll content in terms of Fm730/Fm690 exhibited a seasonal fluctuation in endophyte [Neotiphodium coenophialum (Morgan Jones and Gams) Glenn, Bacon, Price and Hanlin] -free and endophyte-infected tall fescue. Application of SE enhanced SOD activity, photosynthetic capacity, and chlorophyll content in tall fescue, especially at 4 weeks after SE treatment. The SOD activity, photosynthetic capacity and chlorophyll content were not significantly influenced by the endophyte infection. A close positive correlation between SOD and photosynthetic capacity during the summer was found in endophyte-free and endophyte-infected tall fescue. / Ph. D.

Inosine monophosphate (IMP) is a precursor of the two purine nucleotides, adenosine monophosphate (AMP) and guanosine monophosphate (GMP)e through DEAE-Scphacex, and the reaction IMP~ XMP is catalyzed by: IMP dehydrogenase which was purified in a manner similar to adenylosuccinate synthetase. Adenylosuccinate synthetase of rat liver is stimulated maximally with 10-9 M L-T 3 or 10-5 M L-T4 , but not by D in vivo effects. Further correlation to in vivo studies was obtained from brain and testes tissues. / Ph. D.

Seventy five mature and 520 prepuberal Dublin Disease Resistant rats were utilized to study the effects of exogenous hormones upon various reproductive phenomena. Ovulation was induced in 45 day old females by means of PMS and HCG. Progesterone (1.5, 2.5, 3.5, 5.0, or 10.0 mg) was dissolved in peanut oil and administered subcutaneously daily from day 2 to day 20 post coitus. Estradiol (0.2 mcg) was dissolved in peanut oil and administered subcutaneously on day 3 post coitus. Control rats received oil only. / Ph. D.

In this thesis, I develop a history of thyroid hormone treatment (THT) that centers on the bodies of animals and women between 1890 and 1970. This history contextualizes the current debate between two forms of THT, desiccated and synthetic. Drawing on the discourses present in biomedical journals, I trace how medical practitioners used the animals and women to demonstrate and make sense of THT's effectiveness over time. As such, I study what Catherine Waldby terms the "biomedical imaginary" or the speculative fabric of scientific thought, to demonstrate how an "ordinary" medical technology crosses and reinforces the conceptions of gender and animality. THT emerged in the 1890s as an organotherapy, or a medicine made from animal organs. Like other organotherapies, general physicians used THT for a wide variety of ailments that had not been scientifically proven through the practices of vivisection or animal experimentation. From its emergence, THT served as a site of tension between scientific researchers and general practitioners. This tension only increased when a synthetic form of THT was invented in the 1920s, when scientific researchers embraced synthetic THT and general practitioners continued using desiccated THT. At the center of the controversy were the productive and subversive relationships of animals and women to biomedical meaning-making. Over the twentieth century, methods of defining THT's effectiveness and purity were defined in opposition to these bodies. These chemical measures combined the specialist and physician's measurement of THT's clinical effectiveness, which led to a preference for synthetic THT. / Master of Science