Medicine and Health Sciences Commons^™

The Effect Of Tryptamine Producing Bacteria On Gut Motility In Mice, Emilia Sofia Norberg

Graduate College Dissertations and Theses

It has become increasingly clear that there is bidirectional communication between the microbes that exist in the lumen of the gastrointestinal (GI) tract and the nervous system. Research within the last 20 years has revealed GI bacterial metabolites to have a significant effect on gut motility, and some of these actions involve influencing serotonin signaling in the epithelial layer of the intestines. Serotonin, abbreviated as 5- HT, has many functions within the gut including propulsive and segmentation motility, vasodilation, and epithelial cell secretion. There are several bacterial species that have been discovered to synthesize one of 5-HT’s precursory molecules, including …

The Evaluation Of The Prokinetic Action Of A Luminally Restricted 5-Ht4 Receptor Agonist In Mice, Emma Schoeling

Graduate College Dissertations and Theses

Serotonin (5-HT) is a neurotransmitter mainly produced in the enteric nervous system (ENS) of the gastrointestinal (GI) system. Serotonin has widespread function throughout the body including regulating mood, cognition, sleep, sex, and appetite. In the context of the gut, the monoamine modulates vasodilation, mucus secretion, pain, and peristaltic reflexes for motility. The 5-HT4 receptor is expressed on enteric epithelial cells and nerve terminals in the intestinal mucosa. The agonists available to act on these receptors are a favorable target to promote epithelial healing, recovery from colitis or constipation, and epithelial cell proliferation. The non-absorbable, luminally restricted, 5-HT4R agonist (5HT4-LA1; Takeda …

Context, Goals, And Operant Behavior: The Role Of The Prelimbic Cortex And Associated Neural Circuitry, Callum Mark Piper Thomas

Graduate College Dissertations and Theses

Operant (instrumental) conditioning is a laboratory model of voluntary behavior. In its simplest form, performing a particular response, such as a lever press, leads to delivery of a reinforcing outcome (e.g., a sucrose pellet). Operant behaviors can be associated with preceding stimuli (“habits”) or outcomes (“goal-directed actions”). A factor that influences performance of operant behaviors is the context in which they are learned. Contexts can be defined as background stimuli that are present during behavior. For example, eating dessert may occur in the context of a restaurant and the sated feeling of a finished meal. The context for eating dessert, …

Experiences Participating In Federal Nutrition Assistance Programs During The Early Months Of The Covid-19 Pandemic: A Mixed Methods Study In Vermont, Emma Haven Spence

Graduate College Dissertations and Theses

For many Americans, the impacts of the COVID-19 pandemic have extended far beyond its overt health risks, spanning from economic shocks to new social realities. Elevated rates of both novel and continued food insecurity during the pandemic have been well-documented, and this burden has not been equally shared. Examination of food insecurity at the present moment offers a unique opportunity to give voice to those affected during this unprecedented time and understand the ability of existing social services to meet increased needs. This research aims to delve into the experiences of individuals at risk for food insecurity. Specifically, (1) to …

Characterization And Manipulation Of O-Glcnacylation In Granulosa Cells Of Bovine Ovarian Antral Follicles, Abigail Marie Maucieri

Graduate College Dissertations and Theses

Glucose is widely recognized as the preferred energy substrate for metabolism by granulosa cells (GCs). Yet in most cells, 2-5% of glucose is shunted through the hexosamine biosynthesis pathway (HBP) for O-linked N-acetylglucosaminylation (O-GlcNAcylation). O-GlcNAcylation is an evolutionarily-conserved, post-translational process that modifies serine and threonine residues on a variety of proteins. O-GlcNAcylation is also considered a nutrient sensor that can regulate cellular processes such as metabolism, signal transduction, and proliferation. In this respect, O-GlcNAcylation may be similar to, and possibly mediate, AMP-activated protein kinase (AMPK) signaling and its nutrient-sensing actions. However, the occurrence of O-GlcNAcylation and its relative importance to …

Building A Learning Healthcare System: A Path To Optimizing Big Health Data To Inform Clinical Care Decisions, Danne Charlotte Emily Elbers

Graduate College Dissertations and Theses

The explosive growth of data and computing power of the last decades has had large impacts on a myriad of domains, not in the least on one of society’s most complex systems: healthcare. In this work, a version of the resulting Learning Healthcare System (LHS) is explored and elements of it have been implemented and are in use at the Department of Veterans’ Affairs today. After an overview of what a LHS is and what it could be once executed in its full form, the chapters will describe in detail some of the individual elements and how they address cogs …

Mitochondrial Dynamics Regulation Of The Lung Epithelial Response To Complex Allergen, Sierra White

Graduate College Dissertations and Theses

Asthma is a chronic inflammatory disease of the lungs that affects roughly 25 million Americans, costing the United States upwards of $80 billion annually in management and economic loss. The airway epithelium, which serves as the first line of defense against insults in the lung, are now appreciated as key contributors to initiation of this disease. A key regulator of the epithelial response to allergens and other inhaled irritants that can induce an allergic asthmatic response is the mitochondria. During an allergic response, the airway epithelial energy requirement changes, and mitochondrial function is altered, enhancing production of reactive oxygen species, …

The Effect Of Amphibian Host Ecology And Evolution On The Pathogen Dynamics Of Ranavirus, Lauren V. Ash

Graduate College Dissertations and Theses

Emerging infectious diseases threaten amphibian species around the globe. Ranavirus (Family: Iridoviridae) is associated with the majority of amphibian deaths in North America, with some species exhibiting mass mortality events in short periods of time. In contrast, some amphibian species show the capacity to resist or tolerate infection. Resistant individuals exhibit reduced infection intensity, while tolerant individuals display reduced fitness effects given the infection intensity. My research focused on how amphibian host dynamics at community, population, and individual-level scales relate to the wide variation in Ranavirus prevalence and severity. Through my work, I documented the first reports of Ranavirus in …

The Role Of Infralimbic Cortex In Switching Between An Instrumental Behavior’S Status As A Goal-Directed Action Or Habit, Matthew Broomer

Graduate College Dissertations and Theses

In instrumental learning, extensive training of a response typically generates a habit. The transition from goal-directed to habitual behavioral control is often considered unidirectional; however, recent evidence suggests this is not the case. Under certain conditions, goal-directed control may be restored to a behavior that was previously habitual. We identify the infralimbic cortex (IL) as a participant in this process and draw on both instrumental learning and fear extinction literatures to further our understanding of IL function.

Four experiments explored the role of IL in flexible behavior. Experiments 1a and 1b were instrumental learning experiments. Experiment 1a used a previously …

Examining Sex Differences In Habit Formation: Effects Of Methamphetamine Sensitization And Contributions Of Ovarian Hormones, Hannah Schoenberg Book

Graduate College Dissertations and Theses

In the early stages of instrumental learning, behavior is goal-directed and sensitive to changes in the value of the instrumental outcome. As learning progresses, an association forms between the response and stimuli within the learning environment, such that after sufficient repetition, responding is evoked automatically in the presence of these stimuli and is insensitive to changes in outcome value. The reflexive nature of these types of behaviors has led to their classification as instrumental habits. The emergence of habitual behavior is thought to involve parallel processes that are mediated by distinct neural substrates. Regions of the prefrontal cortex, amygdala, and …

Microevolution In Staphylococcus Aureus: Does Exposure To Sub-Lethal Levels Of Cinnamon Bark Oil Lead To Changes In Antimicrobial Susceptibility?, Heather Sandra Schuettner

Graduate College Dissertations and Theses

The emergence of antibiotic-resistant and multi-drug resistant bacteria presents a growing global health issue recognized by the World Health Organization and the Centers for Disease Control and Prevention. Infections caused by drug-resistant bacteria are associated with longer hospital stays, higher treatments costs, and increased mortality compared to infections caused by antibiotic-susceptible pathogens. The global increase in antibiotic resistance is driven in part by the misuse and overuse of antibiotics in healthcare and agriculture. Staphylococcus aureus can infect humans and animals, and strains that are resistant to one or more antibiotics are common. Many plant essential oils have antimicrobial properties. Essential …

Microevolution In Staphylococcus Aureus: Does Exposure To Sub-Lethal Levels Of Cinnamon Bark Oil Lead To Changes In Antimicrobial Susceptibility?, Heather Sandra Schuettner

Graduate College Dissertations and Theses

The emergence of antibiotic-resistant and multi-drug resistant bacteria presents a growing global health issue recognized by the World Health Organization and the Centers for Disease Control and Prevention. Infections caused by drug-resistant bacteria are associated with longer hospital stays, higher treatments costs, and increased mortality compared to infections caused by antibiotic-susceptible pathogens. The global increase in antibiotic resistance is driven in part by the misuse and overuse of antibiotics in healthcare and agriculture. Staphylococcus aureus can infect humans and animals, and strains that are resistant to one or more antibiotics are common. Many plant essential oils have antimicrobial properties. Essential …

Designer Biologics Composed Of Hepatocyte Growth Factor, Fibroblast Growth Factor 2 And Immunoglobulin G For Treatment Of Acute Myocardial Infarction, Benjamin Liebman

Graduate College Dissertations and Theses

ABSTRACT Coronary artery disease leading to myocardial infarction (a.k.a. MI, heart attack) is one of the leading causes of death globally. Each year an estimated 605,000 Americans suffer a heart attack, which equates to one MI every 40 seconds. As such, MI represents one of the largest health burdens to society. The current standard of care is revascularization therapy achieved by fibrinolytics and Percutaneous Coronary Intervention (PCI); both of which re-open occluded proximal arteries to restore blood flow to the affected areas. Despite revascularization therapy, 30-50% of patients exhibit a form of reperfusion injury termed “no/low-reflow” in which the blood …

Effect Of Long-Term Dietary Fat Quality On Metabolic Health With A Special Focus On Dairy Fat, Allison L. Unger

Graduate College Dissertations and Theses

Diet, and particularly dietary fat quality (i.e., fatty acid composition), is a significant modifiable risk factor in the development of metabolic diseases. However, whether the manipulation of long-term dietary fat quality may serve as an effective dietary strategy to mitigate metabolic disease risk during aging is not well defined. Accordingly, this work sought to investigate the role of life-long consumption of bioactive fatty acids from various food sources, and particularly dairy fat, on health maintenance and metabolic disease risk later in life. To address this issue, I assessed how long-term supplementation of dairy fat (butter oil), echium oil, or fish …

Genetic And Functional Approaches To Understanding Autoimmune And Inflammatory Pathologies, Abbas Raza

Graduate College Dissertations and Theses

Our understanding of genetic predisposition to inflammatory and autoimmune diseases has been enhanced by large scale quantitative trait loci (QTL) linkage mapping and genome-wide association studies (GWAS). However, the resolution and interpretation of QTL linkage mapping or GWAS findings are limited. In this work, we complement genetic predictions for several human diseases including multiple sclerosis (MS) and systemic capillary leakage syndrome (SCLS) with genetic and functional data in model organisms to associate genes with phenotypes and diseases.

Focusing on MS, an autoimmune inflammatory disease of the central nervous system (CNS), we experimentally tested the effect of three of the GWAS …

Redox Regulation Of Src Kinase: Implications For Innate Il-33 Signaling In Allergen Responses, Christopher Michael Dustin

Graduate College Dissertations and Theses

The proto-oncogene tyrosine kinase Src is a ubiquitously expressed non-receptor tyrosine kinase involved in critical cellular functions including wound healing, migration, survival, and proliferation. Accordingly, aberrant Src signaling is also significantly involved in many diseases. Src is most well known as an oncogenic protein, however, there are emerging roles for Src signaling in various tissues involved in inflammatory diseases. One such tissue is the respiratory epithelium, which comprises the first line of defense against inhaled microbial, particulate, and chemical insults and is a critical nexus of innate immune signaling. Recent work has detailed the involvement of Src in many innate …

Regulation Of Neuroinflammation After Ischemic Stroke By Astroglial Endothelin Receptor Type-B Signaling, John Mcinnis

Graduate College Dissertations and Theses

A large body of neuroscientific research has focused on reactive gliosis and glial scar formation because these are among the most prominent features of the cellular response to central nervous system (CNS) injury. Despite much progress in our understanding, controversy remains regarding the relative balance between the protective nature of the astroglial scar and its anti-regenerative features. Recent work suggests that astrocytes are heterogeneous in their resting state and in their reactivity. In traumatic injuries such as stroke and spinal cord injury, proliferative reactive astrocytes protect CNS tissue. By contrast, under neuroinflammatory and/or neurodegenerative conditions, neurotoxic astrocyte phenotypes may contribute …

Exosomes And Their Role In Asbestos Exposure And Mesothelioma, Phillip Blake Munson

Graduate College Dissertations and Theses

Malignant mesothelioma (MM) is a locally invasive and highly aggressive cancer arising on the mesothelial surface of organ cavities (mainly pleural) as a direct result of asbestos exposure. The latency period of MM is long (20-50yrs) after initial asbestos exposure, and the prognostic outcomes are dismal with median life expectancy of 6-12 months post-diagnosis. There are no useful biomarkers for early MM diagnosis, no successful therapeutic interventions. These vast voids of knowledge led to our hypotheses that secreted vesicles, termed exosomes, play an important role in MM development and tumorigenic properties. Exosomes are nano-sized particles secreted from all cell types …

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 …

An Analysis Of Beverage Consumption In The United States Using The National Health And Examination Survey 2007-2017, Sean Morris

Graduate College Dissertations and Theses

Sugar-Sweetened Beverages (SSBs) are liquids sweetened with various forms of added sugar. They are the leading source of calories and added sugar in the American diet (Drewnowski & Rehm, 2014; National Cancer Institute, 2016; Powell, Chriqui, Khan, Wada, & Chaloupka, 2013). The health and nutrition literature has increasingly identified added sugars and SSBs as a key potential contributor to a host of public health issues including obesity, type 2 diabetes, hypertension, and cardiovascular disease (Johnson et al., 2009; Malik, Popkin, Bray, Despres, & Hu, 2010; Vartanian, Schwartz, & Brownell, 2007). Concern about these public health crises has recently animated regional …

Genotypes And Phenotypes Of Staphylococci On Selected Dairy Farms In Vermont, Robert Mugabi

Graduate College Dissertations and Theses

The genus Staphylococcus contains at least 47 species and 23 subspecies. Bacteria in this genus are ubiquitous; many are commensals on human and animal skin and can be opportunistic pathogens. In dairy cattle, staphylococci are the leading cause of intramammary infections (IMI) and mastitis. Mastitis is the inflammation of the mammary gland, and is one of the leading infectious diseases causing production losses in the dairy industry. Based on the ability to clot blood plasma in vitro, members of the genus can be divided into two groups: coagulase positive staphylococci (CPS) and coagulase negative staphylococci (CNS). In the dairy industry, …

Methylation Controlled J Protein Is A Master Regulator Of Mitochondrial Metabolism, Devin Pierre Champagne

Graduate College Dissertations and Theses

Methylation controlled J protein (MCJ) is a negative regulator of mitochondrial metabolism that has a substantial impact on overall cell metabolism and function. MCJ is highly expressed by naïve CD8+ T cells, however its role in their immune effector functions was unknown. In this dissertation, it will be demonstrated that MCJ restricts the mitochondrial metabolism of CD8+ T cells, in part by reducing respiratory supercomplex formation. MCJ deficiency enhances the immune effector functions and memory responses of CD8+ T cells in a mitochondrial ATP dependent manner. As a consequence, protection to influenza virus infection is substantially improved. Reduced expression of …

21st Century Approaches To Addressing Childhood Diarrhea In Low And Middle-Income Countries: Zinc As A Cornerstone Of New Prevention Strategies, Elizabeth Ross Colgate

Graduate College Dissertations and Theses

During the 20th century, significant strides were made in curtailing the burden of childhood diarrhea, including advances in vaccine research, the advent of antibiotics, improved water and sanitation, and expanded access to health information across the globe. Despite this progress, today diarrhea ranks second only to pneumonia as a leading cause of mortality in children under five years, with a disproportionate burden of 90% of diarrheal deaths in South Asia and Sub-Saharan Africa. Additionally, substantial morbidity due to diarrhea persists in young children, with more than 45 million disability-adjusted life years (DALYs) lost due to diarrhea in 2015. Long-term consequences …

Methods To Identify And Develop Drugs For Cryptosporidiosis, Rajiv Satish Jumani

Graduate College Dissertations and Theses

Cryptosporidiosis is a common diarrheal disease caused by intestinal infection with the apicomplexan parasite Cryptosporidium, in humans usually either with C. hominis or C. parvum. Unfortunately, given a large burden of disease in children and immunocompromised people like AIDS patients, the only currently approved treatment, nitazoxanide, is unreliable for these patient populations. To address the urgent need for new drugs for the most vulnerable populations, large phenotypic screening efforts have been established to identify anti-Cryptosporidium growth inhibitors in vitro (hits). However, in the absence of a gold standard drug, the in vitro and in vivo characteristics that should be used …

Assessing Community Dynamics And Colonization Patterns Of Tritatoma Dimidiata And Other Biotic Factors Associated With Chagas Disease Prevalence In Central America, Lucia Consuelo Orantes

Graduate College Dissertations and Theses

Chagas disease is caused by the parasite Trypanosoma cruzi and transmitted by multiple triatomine vectors across the Americas. In Central America, the predominant vector is Triatoma dimidiata, a highly adaptable and genetically diverse Hemiptera. In this research, we used a novel reduced-representation DNA sequencing approach to discover community dynamics among multiple biotic factors associated with Chagas disease in Central America, and assess the infestation patterns of T. dimidiata after seasonal and chemical disturbances in Jutiapa, Guatemala. For our first study, we used a hierarchical sampling design to obtain multi-species DNA data found in the abdomens of 32 T. dimidiata …

Thyroid Hormone Receptor Ss (Trß) Regulation Of Runt-Related Transcription Factor 2 (Runx2) In Thyroid Tumorigenesis: Determination Of The Trß Nuclear Protein Complexes That Associate With The Runx2 Gene., Thomas Howland Taber

Graduate College Dissertations and Theses

Thyroid Tumorigenesis is typically a well understood process, with well delineated oncogenic factors. Follicular and papillary thyroid cancers are typically survivable, with 5-year survival rates being >95% for Stage I-III of both cancer types. Anaplastic thyroid cancer, in contrast, lacks this prognosis, and is the most lethal of all endocrine-related cancers. The median survival time after a diagnosis is generally between 6-8 months, with a 5-year survival rate of <10%. Current treatment for anaplastic thyroid cancers routinely meet roadblocks, as resistance is quickly developed. Even non-discriminatory kinase inactivators, such as sorafenib, which are generally considered a drug of last resort, are unable to effect survival rates. As such, there is a clear need for further investigation of the causes of anaplastic thyroid cancer mechanisms.

Previous work in the Carr lab revealed a novel regulatory pathway of an oncogene that is associated with several other endocrine-related cancers, as well as other non-endocrine-related cancers. Specifically, the Runt-related …

Magnesium Intake And Depression In U.S. Adults, Emily Tarleton

Graduate College Dissertations and Theses

Research has focused extensively on the negative health effects of inadequate Mg intake, but the extent of the problem of deficiency deserves further exploration. The notion that U.S. adults consume an inadequate amount of magnesium, leading to increased risk for chronic diseases such as depression, is plausible. National Health and Nutrition Examination Surveys (NHANES), which are large, cross-sectional, population-based data sets that assess the health and nutritional status of U.S. adults and children, indicate over half the adult population does not consume adequate amounts of magnesium based on the estimated average requirement (EAR) established by the Institute of Medicine. Using …

The Cardiovascular Epidemiology And Genome-Wide Associations Of Biomarkers Of Innate And Adaptive Immunity: Scd163 And Sil2ra, Jon Peter Durda

Graduate College Dissertations and Theses

Cardiovascular disease (CVD) is a major cause of morbidity and mortality in the U.S. and worldwide. Atherosclerosis, the buildup of plaque in the arteries, is a common cause of CVD. For many years, research in atherosclerosis was focused on lipid metabolism and the accumulation of low-density lipoprotein in the arteries. While this research set public health guidelines for lipid management, lipid concentration was not the only factor influencing atherosclerosis and CVD events. Many scientists, as far back as the 1850’s recognized the role of inflammation in the progression of atherosclerotic disease. The continuous low levels of immune activation in the …

Co-Localization Of Basal And Proliferative Cells In The Murine Main Olfactory Epithelium And Vomeronasal Organ After Injury With Cyclophosphamide, Kyle Barnes Joseph

Graduate College Dissertations and Theses

ABSTRACT

In humans, advanced malignancies are often targeted with broad-spectrum cytotoxic drugs that engender several detrimental side effects, in addition to their primary usage for eradicating cancerous cells. One of the lesser-researched of these effects, histological distortion of the olfactory system impedes a patient's ability to smell, perceive flavor, and ultimately may interfere with their nutritional intake and recovery from chemotherapy. Recent studies have indicated that cytotoxic drugs can damage gustatory epithelia immediately following administration (Mukherjee & Delay, 2011, 2013). We sought to observe the histological effects that cyclophosphamide (CYP), one of the oldest and most popular alkylating antineoplastic agents, …

Transdermal Testosterone For Menopause-Related Hyposexual Desire Disorder: Current Guidelines And Provider Perceptions, Knowledge, And Practice, Kelly Christine White

Graduate College Dissertations and Theses

Hypoactive sexual desire or low libido in women are collectively referred to as hypoactive sexual desire disorder (HSDD). HSDD is estimated to occur in 10% to 15% of adult women. HSDD is likely the most common female sexual dysfunction (FSD) in menopausal women. The hallmark of the diagnosis is personal distress and interpersonal difficulties resulting from low sex drive. Most women will not seek help for this problem. Studies have suggested that primary care providers and gynecologic healthcare providers report not feeling qualified to treat patients with sexual dysfunction, especially HSDD. Testosterone, specifically transdermal testosterone, has been suggested to play …