Human preterm labor is the single most significant issue in modern obstetrics andgynecology, affecting ten percent of pregnancies, constituting the leading cause of infant death, and contributing significantly to chronic childhood disease. Obstetricians and reproductive scientists are faced with the major challenge of trying to increase the understanding of the complex molecular and cellular signals that regulate uterine activity during human pregnancy and labor. Even though preterm labor accounts for a large portion of perinatal mortality and morbidity, there still is not an effective therapeutic strategy for the treatment or prevention of preterm labor. This dissertation presents tyramine as an alternative modulator of uterine activity. In this dissertation the aims were as follows: 1) to investigate the localization of tyramine and trace amine associated receptor 1 (TAAR1) in the mouse uterine horn using immunohistochemistry as well as confirm the presence of tyramine in the uterine tissue using high performance liquid chromatography, 2) identify which TAAR 1-9 subtypes were present in the mouse uterine horn using RT-qPCR, 3) investigate ultrastructural differences in the mouse uterine horn following tyramine and dopamine treatment using transmission electron microscopy and 4) investigate pinopod ultrastructure as well as pinopod ultrastructural differences following tyramine and dopamine treatment. The research presented in this dissertation showed: 1) tyramine has very specific localization in the mouse endometrium, mainly in the uterine glands, TAAR1 is localized all throughout the perimetrium, myometrium and endometrium, and that tyramine was confirmed and quantified using HPLC, 2) TAAR 1- 9 genes are expressed in trace levels in the mouse uterine horn, 3) tyramine influences changes in endometrial ultrastructure, and 4) tyramine influences changes in pinopod ultrastructure. Ultimately these findings can help with identifying novel treatment options not only for spontaneous preterm labor contractions but also for other uterine related disorders.

The branching dynamics and navigation of filamentous fungi that have an apical vesical crescent (AVC) are poorly understood. Here, Rhizopus oryzae (Mucoromycota), which has an AVC, is compared to Neurospora crassa (Ascomycota), which has a Spitzenkörper (Spk), as they navigated microfluidic maze environments varying in pattern. The different maze patterns (diamonds, squares, and chevrons) presented increasing angles of impact, and degrees of obstruction. This investigation addressed questions regarding advantages or disadvantages that a Spk or AVC may provide in hyphal growth. All branching phenomena were compared to the regular branching of unobstructed growth to determine obstacle induced branching. Neurospora crassa generated more branches per impact amongst all three maze types and was unable to complete the chevron maze types. Rhizopus oryzae generated less branches per impact but was able to complete every maze type. The greatest difference in branch formation was seen in the chevron maze design where N. crassa generated a greater number than R. oryzae. Neurospora crassa exhibited a hyperbranching response in the chevron mazes not seen in R. oryzae. Closer inspection of the hyperbranching events revealed that they were composed of initial branching events followed by secondary and tertiary branching events. The directional memory of N. crassa was also observed, and was a characteristic of R. oryzae. While the branching dynamics and navigation of N. crassa and R. oryzae were different, and N. crassa exhibited branching and navigational phenomenon that R. oryzae did not, R. oryzae seemingly had the advantage with its use of an AVC over N. crassa, as it was able to complete every maze type, which N. crassa was unable to do.

The desire to start a family is something millions of people around the globe strive to achieve. However, many factors such as the societal changes in family planning due to increasing maternal age, use of birth control, and ever-changing lifestyles have increased the number of infertility cases seen in the United States each year. Infertility can manifest as a prolonged inability to conceive, or inability to carry a pregnancy full-term. Modern advancements in the field of reproductive medicine have begun to promote the use of Assisted Reproductive Technologies (ART) to circumvent reduced fertility in both men and women. Implementation of techniques such as In Vitro Fertilization, Intracytoplasmic Sperm Injection, and Pre-Implantation Genetic Testing have allowed many couples to conceive. There is continual effort being made towards developing more effective and personalized fertility treatments. This often begins in the form of animal research—a fundamental step in biomedical research. This dissertation examines infertility as a medical condition through the characterization of normal reproductive anatomy and physiology in the introductory overview of reproduction. Specific pathologies of male and female-factor infertility are described, which necessitates the use of ARTs. The various forms of ARTs currently utilized in a clinical setting are addressed including history, preparations, and protocols for each technology. To promote continual advancement of the field, both animal studies and human trials provide fundamental stepping-stones towards the execution of new techniques and protocols. Examples of research conducted for the betterment of human reproductive medicine are explored, including an animal study conducted in mice exploring the role of tyramine in ovulation. With the development and implementation of new technologies and protocols in the field, this also unearths ethical dilemmas that further complicate the addition of new technologies in the field. Combining an extensive review in assisted reproduction, research and clinical fieldwork, this study investigates the history and development of novel research conducted in reproductive medicine and explores the broader implications of new technologies in the field.

According to the World Health Organization, obesity has nearly tripled since 1975 and forty-one million children under the age of 5 are overweight or obese (World Health Organization, 2018). Exercise is a potential intervention to prevent obesity-induced cardiovascular complications as exercise training has been shown to aid nitric oxide (NO) production as well as preserving endothelial function in obese mice (Silva et al., 2016). A soil-derived organic mineral compound (OMC) has been shown to lower blood sugar in diabetic mice (Deneau et al., 2011). Prior research has shown that, while OMC did not prevent high fat diet (HFD)-induced increases in body fat in male Sprague-Dawley rats, it was effective at preventing HFD-induced impaired vasodilation (M. S. Crawford et al., 2019). Six-weeks of HFD has been shown to impair vasodilation through oxidative-stress mediated scavenging of NO as well as upregulation of inflammatory pathways including inducible nitric oxide synthase (iNOS) and cyclooxygenase (Karen L. Sweazea et al., 2010). Therefore, the aim of the present study was to determine whether OMC alters protein expression of iNOS and endothelial NOS (eNOS) in the vasculature of rats fed a control or HFD with and without OMC supplementation. Six-week old male Sprague-Dawley rats were fed either a standard chow diet (CHOW) or a HFD composed of 60% kcal from fat for 10 weeks. The rats were administered OMC at doses of 0 mg/mL (control), 0.6 mg/mL, or 3.0 mg/mL added to their drinking water. Following euthanasia with sodium pentobarbital (200 mg/kg, i.p.), mesenteric arteries and the surrounding perivascular adipose tissue were isolated and prepared for Western Blot analyses. Mesenteric arteries from HFD rats had more uncoupled eNOS (p = 0.006) and iNOS protein expression (p = 0.027) than rats fed the control diet. OMC was not effective at preventing the uncoupling of eNOS or increase in iNOS induced by HFD. Perivascular adipose tissue (PVAT) showed no significant difference in iNOS protein expression between diet or OMC treatment groups. These findings suggest that OMC is not likely working through the iNOS or eNOS pathways to improve vasodilation in these rats, but rather, appears to be working through another mechanism.

Pregnancy and childbirth are both natural occurring events, but still little is known about the signaling mechanisms that induce contractions. Throughout the world, premature labor occurs in 12% of all pregnancies with 36% of infant deaths resulting from preterm related causes. Even though the cause of preterm labor can vary, understanding alternative signaling pathways, which affect muscle contraction, could provide additional treatment options in stopping premature labor. The uterus is composed of smooth muscle, which is innervated, with a plexus of nerves that cover the muscle fibers. Smooth muscle can be stimulated or modulated by many sources such as neurotransmitters [i.e. dopamine], hormones [i.e. estrogen], peptides [i.e. oxytocin] and amines. This study focuses on the biogenic monoamine tyramine, which is produced in the tyrosine catecholamine biosynthesis pathway. Tyramine is known to be associated with peripheral vasoconstriction, increased cardiac output, increased respiration, elevated blood glucose and the release of norepinephrine. This research has found tyramine, and its specific receptor TAAR1, to be localized within mouse uterus and that this monoamine can induce uterine contractions at levels similar to oxytocin.

Thrombus (blood clot) formation is at the roots of hemostasis and pathological thrombosis. Although many studies have successfully elucidated the cellular and molecular mechanisms underlying thrombus formation, there is still a void in understanding the processes limiting thrombus growth beyond that needed for stabilization. As a hemostatic thrombus grows, its surface consisting primarily of platelets changes to that composed of fibrin, which mechanically stabilizes the thrombus. Formation of fibrin ceases after some time; however, it is unclear why this fibrin is non-thrombogenic. This is puzzling since fibrin is known to support strong integrin-mediated adhesion of both platelets and leukocytes in vitro. Therefore, it would be expected that the fibrin surface of hemostatic thrombi in the circulation also support accumulation of these cells and thus continuous thrombus growth or degradation. Nevertheless, many in vivo studies did not detect any accumulation of blood cells including platelets at the fibrin surfaces of thrombi. This finding suggests the existence of natural processes that modulate the adhesive properties of fibrin to ensure proper regulation of thrombus growth, stability and degradation. In this dissertation, I document and discuss the findings supporting the existence of anti-adhesive mechanisms and their physiological relevance in surface-mediated control of thrombus growth and stability. The studies discussed in my dissertation have the potential to establish a novel aspect of hemostasis. Furthermore, it may provide new insights into the intricate and dynamic interplay between the mechanisms underlying hemostatic balance, which is essential to understanding the dysfunction of this process during pathological conditions.

Blind and visually impaired individuals have historically demonstrated a low participation in the fields of science, engineering, mathematics, and technology (STEM). This low participation is reflected in both their education and career choices. Despite the establishment of the Americans with Disabilities Act (ADA) and the Individuals with Disabilities Education Act (IDEA), blind and visually impaired (BVI) students continue to academically fall below the level of their sighted peers in the areas of science and math. Although this deficit is created by many factors, this study focuses on the lack of adequate accessible image based materials. Traditional methods for creating accessible image materials for the vision impaired have included detailed verbal descriptions accompanying an image or conversion into a simplified tactile graphic. It is very common that no substitute materials will be provided to students within STEM courses because they are image rich disciplines and often include a large number images, diagrams and charts. Additionally, images that are translated into text or simplified into basic line drawings are frequently inadequate because they rely on the interpretations of resource personnel who do not have expertise in STEM. Within this study, a method to create a new type of tactile 3D image was developed using High Density Polyethylene (HDPE) and Computer Numeric Control (CNC) milling. These tactile image boards preserve high levels of detail when compared to the original print image. To determine the discernibility and effectiveness of tactile images, these customizable boards were tested in various

university classrooms as well as in participation studies which included BVI and sighted students. Results from these studies indicate that tactile images are discernable and were found to improve performance in lab exercises as much as 60% for those with visual impairment. Incorporating tactile HDPE 3D images into a classroom setting was shown to increase the interest, participation and performance of BVI students suggesting that this type of 3D tactile image should be incorporated into STEM classes to increase the participation of these students and improve the level of training they receive in science and math.