Life Sciences Commons^™

Perivascular Waste Metabolites Clearance In Central Nervous System (Cns), Yiming Cheng

Dissertations

Efficient clearance of interstitial waste metabolites is essential for normal brain homeostasis. Such effective clearance is hampered by the lack of a lymphatic system in the brain, and the cerebrospinal fluid (CSF) is unable to clear large size waste metabolites in the brain. Here, a novel idea that brain arterial endothelium and smooth muscle cells reactivity regulates the clearance of these water-insoluble large size waste metabolites through the perivascular dynamic exchange, and that low dose ethanol promotes this perivascular clearance is proposed.

In Aim 1, the biodistribution of a large size waste metabolite (Amyloid-β protein mimic) in rat perivascular space …

Generation And Utilization Of Diverse Memory B Cells After Flavivirus Challenges, Rachel Wong

Arts & Sciences Electronic Theses and Dissertations

Over the course of an effective immune response to an infection, two distinct B cell populations are generated to provide protection against reinfection, long-lived plasma cells (LLPCs) and memory B cells (MBCs). LLPCs and MBCs originate from germinal center (GC) B cells that have undergone B cell receptor (BCR) affinity maturation through iterative rounds of somatic hypermutation, proliferation, and selection. Thus, LLPCs and MBCs can bind to their antigen with higher affinity than their naïve B cell precursors. LLPCs constitutively secrete antibodies and can provide sterilizing immunity that pre-exists subsequent infections. MBCs, on the other hand, are quiescent and provide …

Investigating Biological Mechanisms Of Radiation Resistance In Advanced Stage Cervical Cancer, Fiona Ruiz

Arts & Sciences Electronic Theses and Dissertations

The current standard of care treatment for locally advanced cervical cancer is curative intent pelvic radiation with concurrently administered platinum chemotherapy (CRT). This treatment strategy is effective for many patients, but 33-50% of patients treated with CRT develop disease recurrence. Metastatic and recurrent cervical cancer is an incurable condition, and many of the currently available treatments are associated with significant morbidity and mortality. Identifying these patients upfront is a challenge that clinicians face when developing treatment strategies. Previous studies used to catalog the genomic and transcriptomic landscape of cervical cancer lacked high quality corresponding clinical follow up data for patients, …

The Transcription Factor Bhlhe40 Regulates Tissue-Resident Macrophages And Type 2 Immunity, Nicholas N. Jarjour

Arts & Sciences Electronic Theses and Dissertations

Transcriptional control of gene expression is essential for life, tailoring protein production to development and environment to maintain organismal homeostasis. A limited set of proteins termed transcription factors are critical to this process. As our understanding of these central regulators has improved, new aspects of cell and organismal biology have been revealed. Herein, we demonstrate the importance of the transcription factor Bhlhe40 to tissue-resident macrophages, T helper type 2 cells, and type 2 immune responses, revealing novel transcriptional control of macrophages and unexpected cytokine regulation of helminth infection. We find that Bhlhe40 is cell-intrinsically required for normal proliferation of large …

T Cell Immunity In Pancreatic Cancer Is Undermined By Dendritic Cell Dysfunction, Samarth Hegde

Arts & Sciences Electronic Theses and Dissertations

Pancreatic cancer carries a dismal prognosis, and desperately needs viable therapeutic interventions beyond chemo-radiation. T cell-dependent immunotherapies have shown great promise in several tumor types, but have not been effective for the vast majority of pancreatic cancer patients. This is, in part, due to our limited understanding of how antigenicity of pancreatic lesions is recognized, and how adaptive immunity is overcome in this disease. We sought to study tumor-immune interactions and identify mechanisms for this immune-failure using several spontaneous and unperturbed mouse models of pancreatic adenocarcinoma. We found that early pancreatic lesions fail to elicit tumor-limiting CD4+ TH1 and CD8+ …

Examining The Relationship Of Exercise And Sleep In Students Across Multiple Academic Disciplines, Taylor Zewe

Honors Projects

Students in college learn the importance of balancing their academic studies with their sleep and exercise habits. The amount of sleep and exercise a student recieves has been examined in previous research studies. In these studies it was found that exercise had a postive affect on the amount of sleep received. However, there is little research on the affect academic discipline has on sleep habits and/or exercise habits of students in college. The purpose of this study is to examine the sleep and exercise habits among students in multiple academic majors at Bowling Green State University.

Functional Characterization Of Lt-Hsc Metabolic Activity Dependent On Ahr Activity, Everett Tate

Theses and Dissertations

The cells of the immune system are descended from multipotent hematopoietic stem cells (HSCs) that emerge during development. Multipotency means that a single progenitor HSC can differentiate into any cell of the immune system. HSCs are required to do this for the lifetime of the organism through a process called self-renewal, and as such, any perturbation during development or in the bone marrow can have a trickle-down effect, affecting the self-renewal capacity or ability to terminally differentiate. The aryl hydrocarbon receptor (AHR) is a known regulator of HSCs. The AHR is a transcription factor required for the detoxification of numerous …

Role Of Regulatory T Cells In The Development And Progression Of Lyme Disease In Balb/C Mice, Kaitlyn Nielsen

Theses and Dissertations

Lyme disease, caused by Borrelia burgdorferi, is an increasingly important public health concern, with tens of thousands of new cases being diagnosed each year, even in previously non-endemic areas. It is known that symptoms of Lyme disease are caused by an inflammatory immune response initiated to aid in clearance of the pathogen. Left unchecked, these inflammatory responses can potentially increase tissue damage, leading to increased disease severity. Mechanisms responsible for the control of the inflammatory response to infection with B. burgdorferi are not entirely understood. Evidence exists that regulatory T (Treg) cells, a population of Foxp3-expressing CD4+ T cells known …

Investigating The Effects Of Excitotoxic Stimuli On The Suprachiasmatic Nucleus, Rachel A. Brandes

Chancellor’s Honors Program Projects

No abstract provided.

The Identification Of Long Non-Coding Rna Zfas1 Through An Exploratory Rna-Sequencing Analysis And Its Association With Epithelial-To-Mesenchymal Transition In Colon Cancer Adenocarcinoma., Stephen J. O'Brien

Electronic Theses and Dissertations

Colorectal adenocarcinoma is the fourth most common cancer diagnosed worldwide and is a significant cause of morbidity and mortality. This dissertation performed an exploratory RNA-sequencing analysis comparing gene expression between colon adenocarcinoma tissue and paired normal colon epithelium. After identification of a number of lncRNAs that were increased in expression in colon adenocarcinoma compared to normal colon epithelium, we aimed to validate the expression and investigate their function in vitro. Specifically, we focused on the lncRNA ZFAS1 and its association with epithelial-to-mesenchymal transition. These studies found the following: 1. Seven candidate lncRNAs were identified from the exploratory RNA-sequencing analysis to …

The Role Of Atypical Protein Kinase C In Colorectal Cancer Cells Carcinogenesis, S M Anisul Islam

USF Tampa Graduate Theses and Dissertations

Colorectal cancer (CRC) is the third most common malignancy and the fourth most common cause of cancer-related death worldwide. CRC is a life-threatening disease due to therapy-resistant cancerous cells. The exact mechanisms of cell growth, survival, metastasis and inter & intracellular signaling pathways involved in CRC are still a significant challenge. Moreover, the treatment of metastatic CRC considered palliative for many years aimed for an improved life, with little hope of a cure, highlighting the need for developing novel targeted therapy for CRC. Hence, investigating new molecular mechanism(s) that lead to colorectal carcinogenesis may give insight into the therapeutic target. …

Understanding The Influence Of The Cancer Microenvironment On Metabolism And Metastasis, Shonagh Russell

USF Tampa Graduate Theses and Dissertations

Cancer is a complex and heterogeneous disease. Not only is there considerable variability between different cancer types, but there is enormous variability between and within patients who have the same type of cancer. Within tumors, there are multiple cell types, including cancer cells, stromal cells, and immune cells. The tumor microenvironment often induces the healthy cells to become pro-tumorigenic. Cell metabolism is exquisitely sensitive to changes in the tumor microenvironment and can be measured to infer the aggressiveness of cancer and predict response to therapy. In this dissertation, we aim to understand how the microenvironment, specifically low pH, affects the …

Mesothelium-Derived Factors Shape Tissue Resident Macrophage, Chin-Wen Lai

Arts & Sciences Electronic Theses and Dissertations

The studies outlined in this thesis provide several new insights into Msln-related pathways necessary for peritoneal immune responses and mucosal repair. We found that Msln and its binding partner mucin 16 from mesothelium influenced peritoneal and pleural macrophage differentiation. We found that Msln was required for proper tissue repair after colonic biopsy injury and was required for maximal polyp growth in APCMin/+ mice. Overall, this work describes mesothelial and epithelial-derived factors that are important for tissue resident macrophage differentiation and wound repair after colonic mucosal injury. Understanding the complex interactions between stromal cells and immune cells will lead to better …

Quantitatively Studying Tissue Damage In Multiple Sclerosis Using Gradient Recalled Echo Mri Sequences, Biao Xiang

Arts & Sciences Electronic Theses and Dissertations

Multiple Sclerosis (MS) is an unpredictable, often disabling disease of the central nervous system (CNS) that disrupts the flow of information within the brain, and between the brain the body. MS is the most common progressive neurologic disease of young adults, affecting approximately 2.3 million people worldwide. It is estimated that more than 700,000 individuals are affected by MS in United States. While MS has been studied for decades, the cause of it is still not definite and a fully effective treatment for MS is not yet available. Magnetic resonance imaging (MRI) has been used extensively in MS diagnosis and …

Secretory Iga Enhances Gut B Cells Priming And Systemic Igg Responses Towards Commensals, You Zhou

Arts & Sciences Electronic Theses and Dissertations

IgA is the primary antibody response at mucosal surfaces and is reported to inhibit adaptive immune responses against gut bacteria. Here, we utilize an in vitro system to expand and screen IgA memory B cells for their ability to recognize gut bacteria in the context of secretory IgA (sIgA) deficiency in polymeric Ig receptor (Pigr–/–) mice. Contrary to the prevailing hypothesis that IgA provides an immune exclusionary function, we found that mice lacking sIgA showed decreased anti-bacterial IgA specificities as assessed using flow cytometry. IgA B cell responses against certain taxa such as those of order Bacteriodales showed greater dependence …

Understanding The Transcriptional Mechanisms Underlying Dendritic Cell Development, Prachi Bagadia

Arts & Sciences Electronic Theses and Dissertations

Dendritic cells (DCs) comprise an important immune lineage that plays a critical role in initiating and sustaining the proper immune response. They can be divided into two distinct branches, classical/conventional DCs (cDCs) or plasmacytoid DCs (pDCs). cDCs can further be classified as cDC1 or cDC2. Each DC subset exerts unique functions in vivo and are necessary for a complete immune response. The precise transcriptional programs underlying DC specification and commitment remain unclear. cDC1, cDC2, and pDC all arise from the common DC progenitor (CDP) in the bone marrow. How the CDP gives rise to all three DC subsets in an …

Vanadium Compounds Modulate Osteoblast Proliferation And Function, Bryan Sosa

Seton Hall University Dissertations and Theses (ETDs)

Osteoblastogenesis is an essential part of the bone healing process. Insulin has been shown to improve bone healing in both normal and diabetic bone healing models. In addition, insulin mimetic compounds such as Zinc chloride (ZnCl₂) and Vanadyl acetylacetonate (VAC) have also been shown to improve bone healing in these models as well. The purpose of this study was to determine the effects of vanadium compounds VAC and Vanadium (II) sulfate (VSO₄) in osteoblast proliferation and function. In addition the mechanisms by which growth and function are facilitated by these Vanadium compounds were also evaluated. In …

Neurodevelopmental Outcomes Of Infantile Hydrocephalus: An Fmri Case Study, Ikhlas Ahmed Hashi

Electronic Thesis and Dissertation Repository

Ventricle dilatation caused by infantile hydrocephalus may result in extensive damage of the posterior cortex (parietal and occipital lobes). We hypothesize that pathological changes in the development of the posterior cortex can be linked to non-verbal learning disabilities in children with previous infantile hydrocephalus. This case study will investigate the neurodevelopmental outcomes of 3 treated hydrocephalus patients, when compared to a group of healthy control children (n = 12). Within the hydrocephalus group, patients displayed differences in non-verbal test performance as well as parietal brain activation during an fMRI number comparison task. We associated these differences with clinical variables such …

Relationship Between One Repetition Maximum Parallel Squat And Jump Squat Peak Power, Corey Klitzke

Masters Theses

Jump squats are a simple exercise that can be used to train lower body power. Unlike many other methods of power training, jump squats do not require any specialized equipment (platforms, bumper plates, etc.). Jump squats can be used when other forms of power training are not available or are not allowed. In order to most efficiently train power, the intensity must balance force and velocity. The purpose of this study was to find the intensity that yields the peak power output of a jump squat. 12 participants (9 males, 3 female) participated in the study. Each participant completed a …

Fasting Reduces Intestinal Radiotoxicity Enabling Dose-Escalated Radiotherapy For Pancreatic Cancer, Marimar De La Cruz Bonilla

Dissertations & Theses (Open Access)

Surgical resection is the only potentially curative treatment for pancreatic cancer, but only 15-20% of patients have resectable tumors. In unresectable cases, stereotactic body radiotherapy (SBRT) may be used to give tumor-directed radiotherapy (RT). Unfortunately, this can cause severe gastrointestinal (GI) toxicity due to proximity of the pancreatic head to the duodenum. Protecting the intestine from the toxic side-effects of radiation may enable dose-escalation that could achieve more effective local control of disease. We and others have previously shown that a fast of 24 hours protects mice from lethal doses of the DNA-damaging agent etoposide. In this study, we demonstrate …

Maternal Nicotine Exposure Induces Congenital Heart Defects In The Offspring Of Mice, Elizabeth Greco

Electronic Thesis and Dissertation Repository

Congenital heart defects are the most prevalent birth defect, and maternal cigarette smoking is a known risk factor. Nicotine replacement therapies are recommended to pregnant women who smoke to aid in smoking cessation, as this alternative is thought to be much safer compared to cigarette smoking. However, these products contain nicotine, and the safety of nicotine on the developing heart is not well known. In this thesis, a mouse model was used to test the hypothesis that maternal nicotine exposure (MNE) during pregnancy leads to congenital heart defects and coronary artery defects in the offspring of mice. MNE resulted in …

Development And Cross-Validation Of A Cadence-Based Metabolic Equation For Walking, Christopher C. Moore

Masters Theses

The ACSM Metabolic Equation is a widely recognized equation for predicting metabolic intensity from walking speed. However, an equation that uses an observable metric (i.e., cadence [steps/min]), accounts for individual characteristics, and is validated across walking conditions may enable more accessible and accurate predictions of walking intensity. PURPOSE: To develop metabolic equations that predict metabolic intensity (oxygen consumption; mL/kg/min) from cadence using a large treadmill walking dataset (Study One) and cross-validate these equations during overground unconstrained and cadence-constrained walking conditions (Study Two). METHODS: In Study One, 193 adults (21-81 years) completed treadmill walking bouts while oxygen consumption was measured with …

Mutations In The Human Follicle Stimulating Hormone Receptor Caveolin Interaction Motif Cause Increased Basal Activation, Elizabeth Altman

Honors Theses

Over twelve percent of women aged fifteen to forty-five in America suffer from infertility and/or impaired fecundity and over seven million women have used infertility services, such as intrauterine insemination and in vitro fertilization. Some cases of infertility may be due to dysfunctional human follicle stimulating hormone (hFSH) signaling. hFSH plays a role in spermatogenesis in males, as well as follicle maturation and estrogen production in females. Problems with either hFSH or the hFSH receptor (hFSHR) decrease fertility in males and cause complete infertility in females. As part of the hypothalamic-pituitary-gonadal axis, hFSH is released from the pituitary gland and …

The Role Of Tumor Stromal Discoidin Domain Receptor 2 (Ddr2) In Breast Cancer Metastasis., Samantha Van Hove Bayer

Arts & Sciences Electronic Theses and Dissertations

Characteristics of breast tumor stroma, including altered collagen architecture and increased stiffness, are known to contribute to tumor invasion and metastasis. However, the cellular and molecular mechanisms by which these changes occur are not fully understood. To address this question, we used a mouse genetic model to delete Discoidin Domain Receptor 2 (DDR2) from mouse tumor stromal cells and interrogated breast cancer associated fibroblasts (CAFs) to determine the molecular events downstream of DDR2 action that may lead to changes in the tumor extracellular matrix (ECM). Our work revealed that the action of DDR2 in breast stromal cells is required for …

Exploring Infant Leukemia Through Exome Sequencing And An In Vitro Model Of Hematopoietic Development, Mark Cannon Valentine

Arts & Sciences Electronic Theses and Dissertations

Cancer is a heterogeneous disease with myriad causes and outcomes. Many of the cancers that occur in adult populations have become increasingly well characterized with the advent of affordable high-throughput sequencing. These studies have revealed that cancer is largely a disease of somatic mutation in the adult population. In strong contrast to this, childhood cancers have an exceedingly low rate of somatic mutation. At the extreme end of this spectrum is Infant Leukemia (IL). Sequencing of IL has revealed that these tumors frequently have one or fewer somatic SNP. In the absence of a somatic explanation for IL, many other …

Improved Orthopaedic Repairs Through Mechanically Optimized, Adhesive Biomaterials, Stephen Wheeler Linderman

McKelvey School of Engineering Theses & Dissertations

Despite countless surgical advances over the last several decades refining surgical approaches, repair techniques, and tools to treat tendon and tendon-to-bone injuries, we are still left with repair solutions that rely on fairly crude underlying mechanical principles. Musculoskeletal soft tissues have evolved to transfer high loads by optimizing stress distribution profiles across the tissue at each length scale. However, instead of mimicking these natural load transfer mechanisms, conventional suture approaches are limited by high load transfer across only a small number of anchor points within tissue. This leads to stress concentrations at anchor points that often cause repair failure as …

Characterizing The Humoral Response To Flavivirus Infection, Estefania Fernandez

Arts & Sciences Electronic Theses and Dissertations

Flaviviruses are positive (+) sense, single-stranded RNA viruses of the Flaviviridae family that are transmitted by mosquitoes. For our studies, we focused on Zika virus (ZIKV) and Japanese encephalitis virus (JEV). Most human infections with ZIKV historically resulted in a mild self-limiting febrile illness. However, since 2013, a worldwide spread and increase in ZIKV infections has been observed. Notably, ZIKV has been associated with autoimmune ascending paralysis (Guillain-Barré Syndrome) and ophthalmologic effects in adults and intrauterine growth restriction and microcephaly in developing fetuses. Current vaccine efforts utilize technologies implemented for related flaviviruses (yellow fever virus (YFV), Dengue virus (DENV), and …

Activation Of Toll-Like Receptor 3 Translates To Long-Term Post-Viral Lung Disease, Xinyu Wang

Arts & Sciences Electronic Theses and Dissertations

Chronic obstructive lung disease (COPD) causes substantial human and economic costs both in the US and worldwide. To identify the molecular mechanisms to allow for targeted therapies for COPD, we developed a high-fidelity mouse model of chronic lung inflammation using the natural rodent pathogen Sendai virus (SeV). While nucleic acid-sensing pattern recognition receptors are important for innate immune responses to viral pathogens, there have been few studies investigating their role in the context of chronic disease. Here we show that Toll-like receptor 3 (Tlr3) signaling is required for the development of chronic lung disease in a postviral mouse model. Activation …

Dissemination Of The Apicomplexan Parasite, Toxoplasma Gondii, Lisa L. Drewry

Arts & Sciences Electronic Theses and Dissertations

The parasitic protist Toxoplasma gondii is a common pathogen of rodents and felines that also infects humans. The most severe clinical manifestations of toxoplasmosis in humans derive from the systemic dissemination of T. gondii, during which the parasite penetrates biological barriers and accesses protected host compartments such as the central nervous system. T. gondii dissemination is enabled by the intrinsic gliding motility of extracellular parasites, which allows for travel to new host cells and tissues, and also powers the invasion of diverse host cells including migratory leukocytes. Dissemination is further advanced when migrating infected leukocytes shuttle intracellular parasites to new …

Development Of Enteric Neurons And Muscularis Macrophages, Marina Avetisyan

Arts & Sciences Electronic Theses and Dissertations

The enteric nervous system (ENS) is a complex interconnected network of neurons and glia in the bowel wall that regulates intestinal motility, blood flow, and epithelial function. The ENS also controls aspects of inflammatory signaling within the bowel. To perform these tasks, there are at least 20 types of enteric neuron and four types of enteric glia. Although much is known about early events in ENS development, signals governing the development of specific neuronal subtypes and communication with neighboring cell types within the bowel remain poorly understood. One fundamental hypothesis is that diverse trophic factors support distinct neuronal populations in …