Life Sciences Commons^™

Quality Of Life For Women With Chronic Lyme Disease: A Socioeconomic Investigation, Dale M. Jones

Doctoral Dissertations

This is a mixed methods investigation of how chronic Lyme disease, including Lyme-like diseases and co-infections, affects the quality of life of women who have chronic Lyme. Both quantitative and qualitative methods were used during three phases of research: a 91-question survey instrument followed by focus group discussions and written narratives. The research considered the socioeconomic impact on quality of life in five areas: obtaining a diagnosis, relationships and personal support systems, struggles with the medical system, the ability to work, and access to treatment. There were 500 responses to the survey, of which 373 were analyzed; 11 participants in …

Cat Covid, Cmv And Chemokines, Oh My!, Trevor Hancock

Doctoral Dissertations

Cytomegalovirus (CMV) is an important pathogen infecting most humans worldwide. CMV infection within immunocompromised individuals can cause severe morbidity and potential mortality. Disease during CMV infection is due to virus dissemination and subsequent inflammation. Host immune cells lie at the intersection potentially mediating both. The CMV-encoded viral chemokine vCXCL-1 is a proposed virulence factor in mouse models increasing immune cell recruitment and disease. However, the primary immune cell mediator is undetermined. To identify targets, Chapter 2 examines CXCR2 expression (receptor for vCXCL-1) among various mouse tissues and human peripheral blood under steady-state conditions. In vitro, isoforms of HCMV’s vCXCL-1 …

Design And Development Of The Urban Population Health Observatory To Improve Disease Surveillance And Response, Whitney Brakefield

Doctoral Dissertations

Chronic and infectious diseases have a profound impact on the quality and length of life of populations that suffer from these conditions. Scientists, physicians, and health officials are seeking innovative approaches to decrease the morbidity and mortality of deadly diseases. Incorporating artificial intelligence and data science techniques across the health science domain could improve disease surveillance, intervention planning, and policymaking. In this dissertation, we describe the design and development of the Urban Population Health Observatory (UPHO), an explainable knowledge-based multimodal big data analytics platform. A common challenge for conducting multimodal big data analytics is integrating multidimensional heterogeneous data sources, which …

Oxybenzone And The Mammary Gland: Impact Of An Environmental Pollutant On Health, Disease & Ethical Decision-Making, Klara Matouskova

Doctoral Dissertations

The environmental pollutant and common sunscreen compound oxybenzone is a benzophenone type UV light chemical filter used in industrial and consumer goods. This chemical widely contaminates human tissues, non-human species, and environmental matrices. In this dissertation, oxybenzone is investigated for its effects on the mouse mammary gland in the offspring following perinatal exposure; after perinatal and prepubertal exposures as a dual environmental insult during two sensitive times of development; and in adults after exposure during pregnancy & lactation as an environmental factor potentially increasing the tissue susceptibility to mammary tumors. Chapter 1 introduces the mammary gland. Chapter 2 reviews UV …

Investigating The Developmental Impacts Of 3,3’-Dichlorobiphenyl (Pcb-11) In Zebrafish (Danio Rerio), Monika A. Roy

Doctoral Dissertations

The environmental pollutant 3,3’-dichlorobiphenyl (PCB-11) is a lower-chlorinated polychlorinated biphenyl (PCB) congener present in air and water samples. Both PCB-11 and its metabolite, 4-PCB-11-Sulfate, are detected in humans, including in pregnant women. The work conducted for this dissertation takes a developmental toxicology approach and uses zebrafish (Danio rerio) to investigate PCB-11’s potential impacts to the liver and pancreas. Chapter 1 introduces PCBs and the current knowledge gaps. Chapter 2 investigates PCB-11 interactions in short-term 4-day exposures with the Aryl hydrocarbon receptor (Ahr) pathway in both 0-20 mM individual and mixture exposures with other Ahr agonists. In Chapter 3, …

Anti-Inflammatory And Chemopreventive Activity Of Lunasin From Tofu Whey For The Management Of Gastrointestinal Diseases, Cindy Andrea Nieto Veloza

Doctoral Dissertations

Gastrointestinal diseases such as inflammatory bowel diseases (IBD) and colorectal cancer (CRC) are pathological conditions associated with chronic inflammation, characterized by intestinal damage, debilitating symptoms, and detrimental health consequences. The increased risk of CRC in IBD patients, and the adverse effects associated with current therapeutic strategies, point out the need for safer alternatives to reduce chronic inflammation in the bowel. Lunasin is a bioactive peptide naturally occurring in soybeans, with chemopreventive and anti-inflammatory properties demonstrated in several extra-intestinal diseases. However, to date, there is no evidence of the biological activity of lunasin on the gastrointestinal tract as a target site. …

Prevalence Of Rats And Rodent Borne Pathogens Across Post-Katrina New Orleans, Bruno Marco Ghersi

Doctoral Dissertations

Disasters are happening at an increasingly higher rate and intensity a trend that is expected to continue as more humans migrate to coastal urban areas. Disasters, and as importantly, disaster recovery can affect how native and pest populations will recover. My aim was to improve understanding of disease risk by evaluating the socioecological conditions that have shaped commensal rat recovery and distribution, as well as the pathogens they carry, across New Orleans after Hurricane Katrina. I first estimated relative abundance and distribution of commensal rats from rodent trapping conducted between mid-2014 and early-2017 across 96 sites in 10 areas of …

Redox Signaling In The Zebrafish Embryo And Implications For Endocrine Pancreas Morphogenesis, Archit Rastogi

Doctoral Dissertations

The glutathione (GSH) system evolved to combat oxygen toxicity in nearly all living organisms, and serves as the predominant cellular redox buffer in vertebrates. This dissertation explores the roles of GSH during embryogenesis using the zebrafish (Danio rerio). The first agnostic in vivo characterization of GSH utilization in the embryo revealed strict spatiotemporal GSH profiles in developing organ systems. Interruption of these GSH profiles by exogenous xenobiotics led to organ specific adverse developmental outcomes; pancreatic β-cells were found to be especially susceptible and developed atypical morphologies following redox active xenobiotic exposures. Pancreatic β-cells lacked expression of Nrf2a (Nuclear …

Cytochrome P450 Monooxygenase-Mediated Lipid Metabolism In Obesity And Colon Tumorigenesis, Weicang Wang

Doctoral Dissertations

Colon cancer is a major public health issue: it is expected to have 140,250 new cases and 50,630 deaths during 2018, making colon cancer the third most common type of cancer and the second leading cause of cancer death in the United States. Obesity is associated with enhanced colonic inflammation, which is a major risk factor of colorectal cancer. Currently, more than 35% of adults and nearly 17% of children are obese. Considering the obesity and colon cancer epidemic in the United States, there is an urgent need to identify novel therapeutic targets for obesity and colon cancer. Here, using …

Hybridized Polymeric Nano-Assemblies: Key Insights Into Addressing Mdr Infections, Ryan Landis

Doctoral Dissertations

Multidrug-resistant (MDR) bacteria contribute to more than 700,000 annual deaths world-wide. Millions more suffer from limb amputations or face high healthcare treatment costs where prolonged and costly therapeutic regimens are used to counter MDR infections. While there is an international push to develop novel and more powerful antimicrobials to address the impending threat, one particularly interesting approach that has re-emerged are essential oils, phytochemical extracts derived from plant sources. While their antimicrobial activity demonstrates a promising avenue, their stability in aqueous media, limits their practical use in or on mammals. Inspired by the versatility of polymer nanotechnology and the sustainability …

Extrinsic And Intrinsic Factors In Liver Development, Amrita Palaria

Doctoral Dissertations

Liver is the largest internal organ of the human body. It performs a multitude of functions. Therefore, it is provided with a huge regenerative capacity however, because of the same reason it is also prone to various diseases. Hence, it is essential to understand liver development in order to understand liver regeneration and liver diseases to provide better therapeutic targets and solutions. Liver development is orchestrated by a variety of intrinsic and extrinsic factors. The major focus of this dissertation thesis is to elucidate the role of BMP signals and YY1/VEGFA regulated signals in liver development. Liver organogenesis initiates with …

Sleep, And Its Relation To Non-Motor Deficits In Patients With Cerebellar Ataxia, Akshata Sonni

Doctoral Dissertations

The cerebellum is a highly connected structure, and its involvement in sleep – which is a dynamic process that is modulated by a complex set of neural systems – can come about through a number of neural pathways. We conducted two studies aimed at furthering our understanding of cerebellar involvement in sleep behavior and physiology, as well as measuring the impact of poor sleep on mood and cognition in patients with cerebellar degeneration. First, by means of an online battery including measures of sleep and neuropsychiatric function, we collected data from 176 patients with cerebellar ataxia. We found strong evidence …

Investigating The Regulation Of Indole-3-Acetic Acid Production By The Plant Associated Microbe Pantoea Sp. Yr343, Kasey Noel Estenson

Doctoral Dissertations

The auxin indole-3-acetic acid (IAA) plays a central role in plant growth and development and many plant-associated microbes produce IAA. Several IAA biosynthetic pathways have been identified in microbes which use the precursor tryptophan. Pantoea sp. YR343, which was isolated from the Populus deltoides rhizosphere, is a robust plant root colonizer that produces IAA. Using genomic and metabolomics analyses, we predicted that the indole-3-pyruvate (IPA) pathway is the major pathway in Pantoea sp. YR343 for IAA production. To better understand IAA biosynthesis and the effects of IAA exposure on cell physiology, we performed proteomics on Pantoea sp. YR343 grown in …

Colicins - A Sound Antimicrobial Approach For The Prevention Of Catheter-Associated Urinary Tract Infections, Sandra M. Roy

Doctoral Dissertations

The emergence and spread of antibiotic resistance has created one of the greatest challenges in fighting infectious disease. We address the rise of antibiotic-resistant pathogens by examining the evolutionary history of a class of resistance determinants, the SHV b-lactamases. We isolated the genes that encode the SHV beta-lactamases (bla_SHV genes) from clinical settings and from an environment essentially devoid of antibiotic use. Our data suggests that, counter to current dogma, the use of antibiotics in the clinic is not creating these resistance genes; genes for antibiotic resistance already exist in nature and our use of antibiotics in clinical …

Health Assessment Of Two Reintroduced Populations Of American Martens (Martes Americana) In Michigan, Maria Catherine Spriggs

Doctoral Dissertations

The American marten (Martes americana) was extirpated from Michigan during the early-20th century due to loss of vast areas of mature conifer forest and unregulated trapping. The species was reintroduced into the Upper Peninsula (UP) and Northern Lower Peninsula (NLP) during the mid-20th century. While the American marten population in the UP has grown and is doing well, the population in the NLP has been less successful. The reasons for the limited success of the NLP population are unknown, but may include lack of suitable habitat, limited reproductive success, poor genetic diversity, disease, or negative environmental impacts. American …

Brown And Beige Adipocytes: Effects Of Inflammation And Nutritional Intervention, Jiyoung Bae

Doctoral Dissertations

Recent findings of brown adipocytes and brown-like or beige adipocytes, capable of dissipating energy as heat, in adult humans have promised new hope for obesity treatment and prevention. Understanding of the regulation of brown and beige adipocytes will provide novel strategies to reach the goal. Pattern recognition receptors (PRR) are responsible for inflammation in adipose tissue, which leads to adipose dysfunction and obesity associated chronic diseases. It has been shown that PRR activation induces inflammation, leading to insulin resistance in white adipocytes and white adipose tissue (WAT). However, the roles of PRR activation in brown adipocytes and brown adipose tissue …

Epidemiology Of Select Species Of Filarial Nematodes In Free-Ranging Moose (Alces Alces) Of North America, Caroline Mae Grunenwald

Doctoral Dissertations

North American moose (Alces alces) are a culturally and economically valued species. Recent population declines raise concern for the survivability of this natural resource. The Minnesota population has experienced the most dramatic decline, with a 60% loss in total numbers since 2006. Nematode parasites, particularly some species of filarids, are important pathogens of moose and could be contributing to morbidity and mortality. This study investigates the eco-epidemiology of two filarial parasites of moose: Rumenfilaria andersoni and Elaeophora schneideri. By surveying cervid species from six U.S. states, we discovered R. andersoni was present in moose from all sample locations …

Mimicking The Arterial Microenvironment With Peg-Pc To Investigate The Roles Of Physicochemical Stimuli In Smc Phenotype And Behavior, William G. Herrick

Doctoral Dissertations

The goal of this dissertation was to parse the roles of physical, mechanical and chemical cues in the phenotype plasticity of smooth muscle cells (SMCs) in atherosclerosis. We first developed and characterized a novel synthetic hydrogel with desirable traits for studying mechanotransduction in vitro. This hydrogel, PEG-PC, is a co-polymer of poly(ethylene glycol) and phosphorylcholine with an incredible range of Young’s moduli (~1 kPa - 9 MPa) that enables reproduction of nearly any tissue stiffness, exceptional optical and anti-fouling properties, and support for covalent attachment of extracellular matrix (ECM) proteins. To our knowledge, this combination of mechanical range, low …

A Novel Population Of Natural Killer Cells Plays A Critical Role In The Depletion Of Splenic B2 B Cells During Experimental African Trypanosomiasis, Deborah Frenkel

Doctoral Dissertations

Loss of humoral immune competence in T. brucei-infected mice is associated with the apoptotic depletion of splenic transitional, marginal zone and follicular B cells as well as a depletion of CD8⁺ T cells. This occurs rapidly after infection and impairs responses to vaccine antigens in addition to responses to newly arising VSG antigenic variants, leading to uncontrolled parasite growth and death of the infected mice. Infection-induced B2 B cell and CD8⁺ T cell loss requires the presence of a novel population of natural killer (NK) cells and is mediated by a perforin-dependent process consistent with perforin- and …

Elucidating Cellular Signaling Pathways That Contribute To The Immunopathogenesis Of Aplastic Anemia, Christina M. Kuksin

Doctoral Dissertations

Aplastic Anemia is a rare immune mediated bone marrow failure disease that is mediated by autoreactive T cells that cause destruction to the stem, progenitor, and stromal cells in the bone marrow. Because little is known about the etiology of the disease, our lab has developed a major MHC mismatch GVHD model to examine cellular pathways in autoreactive T cells that contribute to disease. We examined three pathways that are important in T cell activation and differentiation and asked if they were important in the development of Aplastic Anemia. First, we were able to show that expression of active PKCθ …

Associations Of Total Activity Counts And Physical Activity Intensity Levels With The Metabolic Syndrome: A Structural Equation Modeling Approach, Dana Lizbeth Wolff

Doctoral Dissertations

To clarify the protective benefits of physical activity (PA), epidemiologists and public health researchers continue to seek improved methods of assessing PA. In particular, accelerometers have gained acceptance with researchers as they provide reliable estimates of PA and can record both the amount and intensity of ambulatory movement. However, there is concern that accelerometer data reduction techniques may not provide quantitatively accurate measurements of time spent in various PA intensity categories. One way to circumvent these inaccuracies is to use the accelerometer-derived total activity counts (TAC), which is a more direct expression of what the monitor records.

In order to …

Effects Of Increased Step Width On Knee Joint Biomechanics In Healthy And Knee Osteoarthritis Older Adults During Stair Descent, Maxime Robert Paquette

Doctoral Dissertations

Stair negotiation is one of the most challenging tasks for older adults especially for those suffering from knee osteoarthritis (OA). To date, no studies have investigated the effects of increased step width (SW) on knee joint biomechanics. The purpose of Study One was to investigate the effects of increased SW on peak internal knee abduction moment and other lower extremity variables during stair descent in healthy older adults. The purpose of Study Two was to investigate the effects of increased SW on peak internal knee abduction moment, knee pain and other lower extremity variables during stair descent in medial compartment …

Diagnosis And Management Of Horses With Equine Metabolic Syndrome (Ems), Kelly Ann Chameroy

Doctoral Dissertations

In horses, a painful and often debilitating disease known as laminitis can result in impaired function and, in severe cases, euthanasia. Equine Metabolic Syndrome (EMS) is a syndrome in horses that results in development of laminitis and is characterized by the presence of general and/or regional adiposity (“cresty neck”), aberrations in blood lipid concentrations, insulin resistance (IR) and/ or hyperinsulinemia. Therapies have focused on improving the state of obesity and insulin resistance with the goal of diminishing the likelihood of laminitis development. A definitive cause for laminitis has not been established, but hyperinsulinemia and IR are likely candidates as experimental …