Medicine and Health Sciences Commons^™

Impairment Of The Glial Phagolysosomal System Drives Prion-Like Propagation Of Huntington’S Disease, Graham Davis

Theses and Dissertations

The ability of glia to tightly regulate neuronal health and homeostasis in the CNS is conserved across species. Yet, despite the ability to degrade protein aggregates, glia are vulnerable to the accumulation of neurotoxic amyloid aggregates during neurodegenerative disease progress, and even exacerbate their spread. A developing narrative highlights glia as a double-edged sword in neurodegenerative diseases: initially capable of dynamically responding to amyloid aggregate-ladened dying neurons but also capable of inducing chronic inflammation and creating seeding-competent amyloid oligomers. Thus, uncovering the mechanisms that allow glia to control aggregate deposition while preventing the neurotoxic effects and seed generation is vital …

Chronic Adolescent Stress As A Predictive Factor For The Risk Of Developing Ptsd-Like Symptoms In Adulthood, Grace K. Young

Theses and Dissertations

Post-traumatic stress disorder is a stress and trauma based psychological disorder that is defined by the DSM-IV as an anxiety disorder that affects approximately 7.8% of people in the United States. PTSD is when those who suffer a traumatic event have intense and distressing feelings, emotions, and memories for a prolonged period of time after the event. A prominent feature of PTSD is the impaired ability to properly extinguish a fear response after a dangerous trigger or stressor is no longer present, also known as safety learning. Stressors are threats perceived within the environment that activate a response within the …

Understanding An Inflammatory Pathway In Diabetic Retinopathy, Reanna Raye Rodriguez

Theses and Dissertations

Diabetic Retinopathy (DR) is the leading cause of blindness in the U.S. However, not much is known of its molecular pathway and how it attributes to increases in inflammatory response in the eye. One avenue we will investigate is the transforming growth factor beta (TGFB) signaling pathway and its effect of vascular endothelial growth factor (VEGF) secretion and cell viability. VEGF is the hallmark that exacerbates DR progression in prolonged diabetes. Some major concern that have arisen are the underlying effects of oxidants and antioxidants in elevating VEGF secretion in diabetes. In attempt to learn more, we evaluated how an …

Investigating Bmp7 Expression In Glioblastoma Multiforme, Yajaira Janett Macias

Theses and Dissertations

The PI3K/AKT/mTOR pathway regulates important cell processes such as growth, survival, motility, inflammation, proliferation, and apoptosis. In Glioblastoma multiforme (GBM) the PI3K/AKT/mTOR pathway is aberrant as it is almost always active. This results in the deregulation of downstream molecules and ultimately leads to cancer progression and maintenance in GBM tumors. In this study, we used RNA-sequencing to identify differentially expressed genes (DEGs) in U87MG GBM cells treated with NVP-BEZ235, a dual inhibitory drug targeting PI3K and mTOR. A total of 7,803 differentially expressed genes were identified via RNA-seq. GEPIA2 online tool was used to assess differential gene expression …

Impact Of Targeting Glycosylated Ceramides On Tumorigenic Properties, And Characterization Of Sphingolipids In Head And Neck Tumors, Katherine E. Hylton

Theses and Dissertations

Sphingolipids play a crucial role in signaling, membrane structure, and migration, making them important molecules in cancer development, metastasis, and drug resistance. While some sphingolipids have been associated with pro-apoptotic or pro-survival behaviors, the role of many sphingolipids in cancer remains poorly defined. Chapter 1 of this study investigated the impact of three enzymes that compose most of the ceramide to Lc3 ceramide pathway – UGCG, GBA, and B3GNT5 – and how their alteration impacts chemoresistance and basal membrane invasion in vitro. It was found that the CΒE-induced inhibition of GBA, which converts glucosylceramide to ceramide, has no effects on …

The Long-Term Persistence And Tissue Tropism Of Brazilian Zika Virus In Monodelphis Domestica, Marisol Morales

Theses and Dissertations

Zika virus (ZIKV) rose as a major public health concern due to the congenital abnormalities of infants born to infected mothers during the 2015 Latin American outbreak. While animal models such as transgenic mice and nonhuman primates are used to study ZIKV pathogenesis, they display various limitations. Additionally, the persistence and tissue distribution of long-term ZIKV infection remains unknown. We describe the laboratory opossum, Monodelphis domestica, as a potential new model for ZIKV pathogenesis research to address these issues. We utilized immunohistochemistry, RT-PCR, and ELISA to show that: infant animals inoculated intracerebrally were susceptible to infection, ZIKV infection persisted …

Vertical Transmission And Venereal Transmission Of Zika Virus In A Population Of South Texas Aedes Aegypti, Jeremy Marshall

Theses and Dissertations

Zika virus has become a greater global public health concern from the occurrence of outbreaks in 2007 and its expansion to the Americas in 2015. The presence of Aedes aegypti in the Lower Rio Grande Valley and evidence of local transmission of Zika in Brownsville, Texas provides a need to research transmission dynamics of local populations. In these experiments, a locally acquired, laboratory colony of Aedes aegypti mosquitoes were infected with a blood meal featuring a Mexican isolate of Zika virus to display vector competency, vertical transmission, venereal transmission. Here, we infected 39 females, with 34 of them displaying evidence …

Using Genetic Diversity To Differentiate Mosquito Populations, Rachel Christine Malampy

Theses and Dissertations

Experiment 1: Little is known about Aedes aegypti females sharing oviposition sites. We examined four different oviposition sites in McAllen, TX. A mitochondrial gene was used to analyze the variation within the oviposition site to understand how many egg-laying females are sharing oviposition sites. These results will aid in the understanding of Aedes. aegypti oviposition behavior and contribute to more effective mosquito control techniques.

Experiment 2: Mosquito flight patterns and movement from habitat to habitat can drastically influence the spread of diseases. The anthropophilic Aedes aegypti mosquito has historically been identified as having a very limited flight range. Studies also …

Characterization Of Plasmids Harbored By Vibrio Cholerae Isolates Endemic To The Rio Grande Delta, Viviana Trevino

Theses and Dissertations

Cholera is a diarrheal disease responsible for considerable morbidity and mortality globally. Epidemics along the Rio Grande Delta were reported during the 1850s, and the etiological agent Vibrio cholerae, remains endemic, thus presenting a unique opportunity for a study of historical and biological relevance. V. cholerae strains were isolated from two locations: the Rio Grande River under a bridge linking Brownsville to Matamoros (site 21) and where the river empties into the Gulf of Mexico (site 42). Two strains from site 21, and one from site 42 were selected to isolate, subclone, sequence, assemble and annotate extra-chromosomal elements. Results …

Temperature Influence On Insecticide Resistance In Aedes Aegypti And Aedes Albopictus Mosquitoes From South Texas, Wendy Soledad Salinas

Theses and Dissertations

Aedes aegypti and Aedes albopictus are vectors for several emerging arboviruses including Zika, chikungunya and dengue. Both mosquitoes are found along the Rio Grande River in South Texas, along the border between Mexico and the United States of America. These mosquito species typically reside near human settlements. A preventative measure public health official use to help halt the spread of diseases is by controlling vector population with the use of insecticides, but as temperature vary, and with the constant exposure to commonly used insecticides, mosquitoes from South Texas may be developing a resistance to the insecticides. Resistance to insecticides may …

The Role Of Sphingosine Kinase 2 In Alcoholic Liver Disease, Eric K. Kwong

Theses and Dissertations

Alcoholic liver disease (ALD) is one of the most common liver diseases worldwide characterized by the accumulation of lipids within the liver, inflammation and the possibility of progressing to cirrhosis and liver failure. More importantly, there are currently no effective treatments for ALD and liver transplantation remains the only therapeutic option for end-stage liver disease. Previous studies have shown that ALD is a result of a combination of endoplasmic reticulum (ER) stress, lipid metabolism dysregulation and inflammation. It has been previously reported that alcohol disrupts gut microbiota homeostasis and causes increased endotoxins that contribute to the pathology of ALD. However, …

Differential Migration Of Cd4+ And Cd8+ T Cells During An Immune Response, Jacob Parrott

Theses and Dissertations

ABSTRACT

DIFFERENTIAL MIGRATION OF CD4+ AND CD8+ T CELLS DURING AN IMMUNE RESPONSE

by

Jacob Parrott

The University of Wisconsin-Milwaukee, 2018

Under the Supervision of Professor Douglas Steeber

Lymphocyte migration is critical for recognizing pathogenic challenges in a timely manner and generating effective, rapid immune responses. Lymphocyte numbers in secondary lymphoid tissues such as lymph nodes are rapidly and dramatically increased during an immune response. Lymphocytes use specific adhesion molecules and intracellular signaling cascades to migrate and enter secondary lymphoid tissues under resting conditions. It is not clear if the same migration and/or entry pathways are utilized when secondary lymphoid …

Survey Assessment Of Community Knowledge And Prevention Of Chagas Disease And Its Vector In Hidalgo And Cameron Counties, Adam Dennis Wiejaczka

Theses and Dissertations

Chagas disease, caused by the parasite Trypanosoma cruzi, kills thousands of people annually and is the dominant cause of infectious myocarditis worldwide. Kissing bugs are vectors that carry T. cruzi . and are found in the Lower Rio Grande Valley (LRGV). There is no vaccination nor cure for Chagas. The best mechanism of prevention is to control vector infestations. Little research is available regarding the level of understanding local communities have about Chagas.

Our goal was to test the knowledge of several communities in the LRGV on Chagas disease. Our hypothesis states that local communities do not have sufficient …

Novel Insights Into The Contribution Of Cellular Senescence To Cancer Therapy: Reversibility, Dormancy And Senolysis., Tareq Saleh

Theses and Dissertations

Cellular senescence a specialized form of growth arrest that contributes to the pathogenesis of several aging-related disorders including cancer. While by definition tumor cells are considered immortalized, they can undergo senescence when exposed to conventional and targeted cancer therapy. Therapy-Induced Senescence (TIS) represents a fundamental response to therapy and impacts its outcomes. However, TIS has been considered a positive therapeutic goal since senescent tumor cells are expected to enter a state of permanent growth abrogation. In this work we examined the hypothesis that a subpopulation of senescent cells can re-acquire proliferative potential after a state of senescent dormancy, indicating that …

Interactive Effects Of Domoic Acid Allelopathy, Salinity, And Eutrophication On Estuarine Phytoplankton Community Structure, Elise Van Meerssche

Theses and Dissertations

Coastal regions and estuaries are particularly sensitive to the increase in nutrient loading and river runoff, threatening the ecosystems with possible spreads in harmful algal blooms (HABs). As an example, blooms of toxic Pseudo-nitzschia species can release acute concentrations of the neurotoxin domoic acid (DA) in the water column. When ingested at concentrations higher than 20 ppm, DA can cause the death of marine birds, marine mammals and even humans. The main objectives of my research were to determine the drivers of Pseudo-nitzschia abundance and toxicity and to assess how these drivers influenced the phytoplankton community structure and DA allelopathy. …

Evaluation And Adaptation Of Live-Cell Interferometry For Applications In Basic, Translational, And Clinical Research, Kevin A. Leslie

Theses and Dissertations

Cell mass is an important indicator of cell health and status. A diverse set of techniques have been developed to precisely measure the masses of single cells, with varying degrees of technical complexity and throughput. Here, the development of a non-invasive, label-free optical technique, termed Live-Cell Interferometry (LCI), is described. Several applications are presented, including an evaluation of LCI’s utility for assessing drug response heterogeneity in patient-derived melanoma lines and the measurement of CD3+ T cell kinetics during hematopoietic stem cell transplantation. The characterization of mast cells during degranulation, the measurement of viral reactivation kinetics in Kaposi’s Sarcoma, and drug …

Exogenous Fniii 12-14 Regulates Tgf-Β1-Induced Markers, Hilmi M. Humeid

Theses and Dissertations

The extracellular matrix protein Fibronectin (FN) plays an important role in cell contractility, differentiation, growth, adhesion, and migration. The 12th -14th Type III repeats of FN (FNIII 12-14), also referred to as the Heparin-II domain, comprise a highly promiscuous growth factor (GF) binding region. This binding domain aids in cellular signaling initiated from the ECM. Additionally, FN has the ability to assemble into fibrils under certain conditions, mostly observed during cell contractile processes such as those that initiate due to upregulation of Transforming Growth Factor Beta 1 (TGF-β1) [1], [2]. Previous work from our lab has shown that self-assembly of …

Resolution Of Inflammation Rescues Axon Initial Segment Disruption, Nicholas M. George

Theses and Dissertations

Axonal domains are required for proper neuron function. These domains are unstable and degenerate concurrent with the inflammation in multiple sclerosis (MS) and the inflammatory disease models experimental autoimmune encephalomyelitis (EAE) and lipopolysaccharide (LPS) induced inflammation. Previous studies from our laboratory have shown that the axon initial segment (AIS) is maintained independently of the presence of myelin, but that AIS disruption is seen in MS as well as EAE and LPS-mediated inflammation. AIS loss can be interrupted in the early stage of EAE using the anti-inflammatory drug Didox. However, the potential for Didox directed repair of the AIS in later …

Stains Induce Apoptosis And Autophagy In Primary And Transformed Mast Cells, Patrick A. Paez

Theses and Dissertations

Statin drugs are widely employed in the clinic to reduce serum low density lipoproteins (LDLs) in patients with hypocholesteremia. In addition to their cholesterol-lowering effects through HMG CoA reductase antagonism, isoprenyl lipids necessary for membrane anchorage and signaling of small G-proteins are abrogated. We previously found that statins suppress mast cell activation in murine and human cells, suggesting these drugs might be useful in treating allergic disease. While mast cell function is critical to allergic inflammation, mast cell hyperplasia and survival also impact these diseases, and were not studied in our previous work. In this study, we describe Fluvastatin-mediated apoptosis …

Activation Of Microglia In The Rotenone Lymnaea Stagnalis Model Of Parkinson's Disease, Xiomara Galvan

Theses and Dissertations

Parkinson’s disease (PD) is the most common irreversible neurodegenerative movement disorder affecting approximately ten million people worldwide. In the central nervous system (CNS), PD is known by the selective loss of Dopamine (DA) cells of the substantia nigra pars compacta. Although the disease has been very widely studied, the underlying mechanisms are not yet understood. Several hypotheses have arisen as result of injury of the mitochondria, some experiments include microglia activation, microtubule damage, and reactive oxidative species, which all result in the death of DA cells. The theory of microglia activation upon inflammation was explored in this study. Using the …

Bacterially-Based Immune Challenges And Trauma Elicit Terminal Investment In Male Aedes Aegypti, Molly K. Schumacher

Theses and Dissertations

Investment in life history traits such as immune function and reproduction is constrained by finite available resources. A cost-of-immunity trade-off may occur in response to infection when resources are diverted away from reproductive effort and into an immune response. Alternatively, an infected individual may enhance reproductive effort to maximize terminal reproductive success in response to the survival threat inherent to infection (terminal investment). We measured male Aedes aegypti reproductive behavior following inoculations with: living bacteria; killed bacteria as an immune elicitor; and a sham control. Mating competitiveness relative to naïve males was also determined through a binary mate choice experiment …

The Effects Of Antibodies In Disease Progression Of Mog-Induced Experimental Autoimmune Encephalomyelitis, Melissa Marie Riter

Theses and Dissertations

Abstract: Multiple sclerosis (MS) is an auto-inflammatory disease of the central nervous system (CNS), affecting over 400,000 people in the US. MS is primarily studied in the animal model experimental autoimmune encephalomyelitis (EAE). MS is a T cell mediated disease but there is mounting evidence for a role for B cells in MS. Previous studies have established that rMOG Induction depends on the presence of B cells, while induction using the MOG peptide covering amino acids 35-55 does not require B cells to cause disease. When plasma from the rMOG and MOG35-55 immunized WT mice was analyzed by ELISA there …

Proof-Of-Concept Of Environmental Dna Tools For Atlantic Sturgeon Management, Jameson Hinkle

Theses and Dissertations

Abstract

The Atlantic Sturgeon (Acipenser oxyrinchus oxyrinchus, Mitchell) is an anadromous species that spawns in tidal freshwater rivers from Canada to Florida. Overfishing, river sedimentation and alteration of the river bottom have decreased Atlantic Sturgeon populations, and NOAA lists the species as endangered. Ecologists sometimes find it difficult to locate individuals of a species that is rare, endangered or invasive. The need for methods less invasive that can create more resolution of cryptic species presence is necessary. Environmental DNA (eDNA) is a non-invasive means of detecting rare, endangered, or invasive species by isolating nuclear or mitochondrial DNA (mtDNA) from the …

Effects Of Tgf-Β1 And Il-33 On Mast Cell Function, Victor S. Ndaw

Theses and Dissertations

TGFβ is involved in many pathological conditions, including autoimmune disorders, cancer, and cardiovascular and allergic diseases. We have previously found that TGFβ can suppress IgE-mediated mast cell activation in human and mouse mast cells in vitro. IL-33 is a recently discovered member of the IL-1 family capable of inducing mast cell responses and enhancing IgE-mediated activation. In this study, we investigated the effects of TGFβ on IL-33-mediated mast cell activation. Bone marrow-derived mast cells cultured in TGFβ -1, -2, or -3 showed reduced IL-33-mediated production of TNF, IL-6, IL-13 and MCP-1, in a concentration-dependent manner. Furthermore, TGFβ also reduced …

Marine Population Connectivity: Range Boundaries And Climate Change, Rhiannon Leigh Rognstad

Theses and Dissertations

Population connectivity, particularly in open systems, is an important metric for understanding population-level processes on both ecological and evolutionary timescales. In coastal marine systems, adults are typically sedentary and dispersal occurs primarily during a larval stage when individuals are transported in ocean currents. Because coastal marine populations exist as networks of interconnected subpopulations, variation in the magnitude and extent of population connectivity can have profound effects on population dynamics and species distribution limits. Connectivity is a complex process, affected by a multitude of factors, including adult inputs and physical dispersal, which operate at multiple scales and may interact. This dissertation …

Life After Adhesion: L-Selectin Throughout The T Cell Lifespan, Abner Garcia Fernandez

Theses and Dissertations

Lymphocytes require antigenic encounter to activate and proliferate, eventually clearing the source of antigenic challenge. The peripheral lymph nodes (PLN) are the primary sites of antigenic encounter and thus the ability of lymphocytes to migrate to this tissue is a requirement for mounting effective immune responses. The process of lymphocyte migration to the PLN is known as the "adhesion cascade". Specifically, lymphocytes are captured from the blood through the adhesion molecule, L-selectin, followed by CC chemokine receptor 7 (CCR7)-mediated integrin activation, which ultimately results in cell transmigration into the PLN. Because the PLN is the site where antigenic encounter is …

Adhesion Molecule Regulation Of Regulatory T Cell Migration, Jessica Jean Loppnow

Theses and Dissertations

Regulatory T (Treg) cells mediate tumor immune evasion by suppressing anti-tumor effector T cell responses in peripheral lymphoid tissues and within the tumor. While elevated Treg cell numbers have been shown to correlate with increased tumor growth, mechanisms that regulate their distribution within secondary lymphoid tissue and tumor tissue are not well understood. L-selectin, an adhesion molecule constitutively expressed on all classes of leukocytes, functions early in the adhesion cascade and regulates the migration of lymphocytes to lymph nodes through high endothelial venules. In addition, L-selectin can mediate migration of lymphocytes to sites of inflammation by binding to ligands present …

Identification Of Immunomodulatory Cells Induced By 670 Nm Light Therapy In An Animal Model Of Multiple Sclerosis, Erin Christine Koester

Theses and Dissertations

Multiple sclerosis is an autoimmune, demyelinating disease characterized by neurodegeneration and inflammation of the central nervous system. It affects approximately 250,000 people in the United States alone, with women being affected two times more than men. Experimental Autoimmune Encephalomyelitis (EAE) is the primary animal model of MS, sharing clinical signs and histopathology with MS. The current paradigm supports MS/EAE induction by myelin reactive CD4+ T cells that cross the blood brain barrier to induce an inflammatory response that leads to the destruction of the myelin sheath and eventual loss of axons. Recent data suggest that axonal loss and disease progression …

Biochemical And Molecular Nutrition Blocks As Dietary Supplements In Llamas (Lama Glama) In The Last Third Of The Gestation Period Of The Ceac, Janette Illanes Callejas

Theses and Dissertations

The present work consisted in the use of biochemical and molecular nutrition blocks (BMN) in llamas during the last third of the gestation period, at the Agricultural Experiment Center of Condori (CEAC), located 49 km north of the city of Oruro, and 12 km north of the Caracollo population, in the province of Cercado. For this research work, we used 20 pregnant llamas in the last third of their gestation period, between the ages of 2 and 3 years old, 10 of which belonged to the Khara breed, and 10 to the Thampulli breed. Two corrals of 7 x 7 …