Physiology Commons^™

The Role Of Neurotrophin Signaling In Urinary Bladder Dysfunction With Cyclophosphamide-Induced Cystitis, Harrison Wood Hsiang

Graduate College Dissertations and Theses

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory pelvic pain syndrome characterized by urinary frequency and urgency, bladder discomfort, decreased bladder capacity, and pelvic pain. A positive feedback loop of bladder inflammation and afferent hypersensitization is currently thought to underlie IC/BPS. Inflammation increases bladder afferent excitability, which in turn releases inflammatory neuropeptides, growth factors, cytokines, and chemokines throughout the micturition pathway, leading to altered bladder function and sensation. There currently exists no effective therapy for IC/BPS.

While its etiology remains unknown, a large body of evidence suggests a role for changes in neurotrophin signaling, particularly that of nerve growth …

Implications Of Population Genetics And Physiological Responses On The Conservation Of Moose (Alces Alces Americana), Elias Rosenblatt

Graduate College Dissertations and Theses

Wildlife populations around the globe are facing numerous, complex challengesto their persistence, yet conservation efforts are hindered by limited information about these populations and the anthropogenic pressures they face. North American moose (Alces alces americana), despite being of ecological, cultural, and economical importance, inhabit remote landscapes, making population monitoring difficult. At the same time, many moose populations, including in Vermont and eastern North America, have experienced recent declines mainly due to winter tick (Dermacentor albipictus) epizootics. Anthropogenic landscape change and climate-mediated pressures pose future challenges for moose across the southern extent of their distribution. Though impacts of winter tick infestation …

Autonomic Reactivity In Emerging Adulthood : Relationships Between Cyberbullying , The Autonomic Nervous System, And Clinical Outcomes., Aya Cheaito

Graduate College Dissertations and Theses

With the advent of the COVID-19 pandemic, online environments have become critical ways of connecting among college students. With the increase in online interactions, cybervictimization has been identified as a public health issue. This study aims to examine whether cybervictimization among college students is associated with clinical adjustment outcomes such as depression and alcohol consumption. This study also aims to examine whether reactivity in the two branches of the autonomic nervous system (sympathetic and parasympathetic) jointly moderate the relationship between cyberbullying and depression/alcohol consumption, indicating sensitivity to the environment. Participants (n =164, 69% female, M age = 19.92, SD = …

Transcriptional Programming By Thyroid Hormone Receptor Beta Maintains Normal Cell Identity And Suppresses Tumor Growth, Noelle Elizabeth Gillis

Graduate College Dissertations and Theses

The overall incidence of thyroid cancer has more than tripled over the past several decades, as has aggressive disease and mortality. The direct relationship between thyroid disease, thyroid hormone levels, and development of thyroid cancer is incomplete. Recent meta-analyses have indicated a higher risk of thyroid cancer for patients with thyroid diseases that reflect an altered thyroid-pituitary signaling axis, which can have profound impacts on the physiology of the thyroid gland. These largely unanswered questions regarding altered thyroid hormone signaling and its consequences for thyroid tumor growth present a significant clinical challenge. This dilemma may come from a lack of …

Mediators Of Bladder Dysfunction In A Rat Model Of Cyclophosphamide-Induced Cystitis, Katharine Beca

Graduate College Dissertations and Theses

The urinary bladder relies on complex and interconnected neural circuits in the peripheral and central nervous systems to properly coordinate micturition. Local sensory signals in the bladder produce neurochemical changes that are relayed and integrated to allow a switch from the storage phase to the elimination phase of the micturition reflex. These local signals can result from mechanical distension that occurs during bladder filling or can be the result of maladaptive neurotransmission due to noxious stimuli and/or inflammation. The latter occurs frequently in individuals with a chronic pain pathology called interstitial cystitis (IC)/bladder pain syndrome (BPS). Patients with IC/BPS typically …

Effects Of Tumor-Related Factors And Chemotherapy On Skeletal Muscle And The Protective Effects Of Exercise, Blas Anselmo Guigni

Graduate College Dissertations and Theses

Cancer patients often experience cachexia, a form of weight loss consisting mostly of skeletal muscle wasting. Muscle wasting leads to physical disability, poor quality of life, reduced tolerance to treatments and shorter survival. Although the causes of cancer-related muscle atrophy have been studied for decades, the exact mechanisms through which cancer and its treatments promote muscle wasting have yet to be defined.

The overall aim of this dissertation is to examine the mediators of muscle wasting in cancer patients during their treatment and examine the modulatory role of exercise to maintain muscle size and function. To address these aims, we …

Association Of Sickle Cell Trait With Exertional Rhabdomyolysis And Atrial Fibrillation., Daniel R. Douce

Graduate College Dissertations and Theses

Sickle cell trait (SCT), sickle cell disease’s carrier status, is a common genetic variant found in many people of African, South Asian, Middle Eastern and Mediterranean descent. While overall considered a benign carrier status, it has been associated with an increased risk of several diseases, including exertional rhabdomyolysis (ER), and chronic kidney disease. While epidemiological evidence links SCT with ER, the actual pathophysiological mechanism less understood. Additionally, while there is an increased prevalence of atrial fibrillation (AF) documented in people with sickle cell disease, studies in individuals with SCT are lacking.

The objectives of this thesis are twofold: The first …

Investigation Of Transforming Growth Factor-Alpha And Its Potential Role In Promoting Ovarian Follicular Dominance, Allie Lynn Lundberg

Graduate College Dissertations and Theses

Intraovarian growth factors play a vital role in influencing the fate of ovarian follicles. They affect proliferation versus apoptosis of granulosa cells (GCs), and can influence whether small antral follicles continue their growth or undergo atresia. Transforming Growth Factor-alpha (TGFα), an oocyte-derived growth factor, is thought to regulate granulosa cell function, yet has been largely overshadowed by current interest in TGF-beta superfamily members, such as bone morphogenetic proteins (BMPs) and anti-Mullerian hormone (AMH). In the current study, effects of TGFα on bovine GC proliferation, intracellular signaling and cytokine-induced apoptosis were evaluated. Briefly, all small antral follicles (3-5mm) from bovine ovaries …

Altered Gastrointestinal Motility In Multiple Sclerosis, Estelle Trego Spear

Graduate College Dissertations and Theses

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that causes motor, visual, and sensory symptoms. Patients also experience constipation, which is not yet understood, but could involve dysfunction of the enteric nervous system (ENS). Autoimmune targeting of the ENS occurs in other autoimmune diseases that exhibit gastrointestinal (GI) symptoms, and similar mechanisms could lead to GI dysfunction in MS. Here, we characterize GI dysmotility in the experimental autoimmune encephalomyelitis (EAE) model of MS and test whether autoantibodies targeting the ENS are present in the serum of MS patients.

Male SJL or B6 mice were induced with …

Evolutionary Innovations In Ants To Thermally Stressful Environments, Andrew D. Nguyen

Graduate College Dissertations and Theses

Temperature is a fundamental environmental force shaping species abundance and distributions through its effects on biochemical reaction rates, metabolism, activity, and reproduction. In light of future climate shifts, mainly driven by temperature increases, how will organisms persist in warmer environments? One molecular mechanism that may play an important role in coping with heat stress is the heat shock response (HSR), which protects against molecular damage. To prevent and repair protein damage specifically, Hsps activate and become up-regulated. However, the functional diversity and relevance of heat shock proteins (Hsps) in extending upper thermal limits in taxonomic groups outside marine and model …

A Role For Transforming Growth Factor-Beta In Urinary Bladder Dysfunction With Cyclophosphamide-Induced Cystitis, Eric James Gonzalez

Graduate College Dissertations and Theses

Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a chronic pain disorder characterized by at least six weeks of lower urinary tract symptoms and unpleasant sensations (pain, pressure and discomfort) thought to be related to the urinary bladder and not meeting exclusion criteria. While the etiology is not known, BPS/IC may involve a "vicious circle" of uroepithelial dysfunction, inflammation and peripheral and central sensitization. We propose that the urinary bladder inflammatory insult partly mediates voiding dysfunction and visceral neurogenic pain characteristic of BPS/IC. Several studies from our laboratory have already demonstrated the role(s) of cytokines and their downstream targets in the …

Contributions Of Trpm4 And Rho Kinase To Myogenic Tone Development In Cerebral Parenchymal Arterioles, Yao Li

Graduate College Dissertations and Theses

Cerebral parenchymal arterioles (PAs) play a critical role in assuring appropriate blood flow and perfusion pressure within the brain. PAs are unique in contrast to upstream pial arteries, as defined by their critical roles in neurovascular coupling, distinct sensitivities to vasoconstrictors, and enhanced myogenic responsiveness. Dysfunction of these blood vessels is implicated in numerous cardiovascular diseases. However, treatments are limited due to incomplete understanding of the fundamental control mechanisms at this level of the circulation. One of the key elements within most vascular networks, including the cerebral circulation, is the presence of myogenic tone, an intrinsic process whereby resistance arteries …

Traumatic Brain Injury Causes Endothelial Dysfunction In Mesenteric Arteries 24 Hrs After Injury, Ivette Ariela Nunez

Graduate College Dissertations and Theses

Traumatic brain injury (TBI) is the most frequent cause of death in children and young adults in the United States. Besides emergency neurosurgical procedures, there are few medical treatment options to improve recovery in people who have experienced a TBI. Management of patients who survive TBI is complicated by both central nervous system and peripheral systemic effects. The pathophysiology of systemic inflammation and coagulopathy following TBI has been attributed to trauma-induced endothelial cell dysfunction; however, there is little knowledge of the mechanisms by which trauma might impact the functions of the vascular endothelium at sites remote from the injury. The …

Facilitative Glucose Transporter And Its Regulation By Insulin/Igf-Like Signaling In Caenorhabditis Elegans, Shun Kitaoka

Graduate College Dissertations and Theses

In humans, the functional regulation of facilitative glucose transporters (GLUTs) by insulin plays a central role in the maintenance of glucose homeostasis. The insensitivity of tissues to this regulation results in diabetes mellitus, however, the underlying mechanisms remain largely unknown. To establish Caenorhabditis elegans (C. elegans) as a model system to study the mechanisms of insulin regulation of GLUTs because of the well-conserved insulin/IGF-like signaling (IIS) and many unique advantages of this organism, we functionally characterized 9 candidate genes of human GLUT homologues in C. elegans based on their sequence homologies to GLUTs. We found that FGT-1 is the only …

Carnitine And O-Acylcarnitines In Pseudomonas Aerguinosa: Metabolism, Transport, And Regulation, Jamie Meadows

Graduate College Dissertations and Theses

Pseudomonas aeruginosa is found in numerous environments and is an opportunistic pathogen affecting those who are immunocompromised. Its large genome encodes tremendous metabolic and regulatory diversity that enables P. aeruginosa to adapt to various environments. We are interested in how P. aeruginosa senses and responds to the host-derived compounds, carnitine and acylcarnitines. Acylcarnitines can be hydrolyzed to carnitine, where the liberated carnitine and its catabolic product glycine betaine can be used as osmoprotectants, for induction of the virulence factor phospholipase C, and as sole carbon, nitrogen, and energy sources. P. aeruginosa is incapable of de novo synthesis of carnitine and …