Life Sciences Commons^™

Telomeric Regulation Of Chromosomal Instability In Colorectal Cancer, Kyle Labella, Kyle A Labella

Dissertations and Theses (Open Access)

Telomere dysfunction drives chromosomal instability (CIN) during the transition from benign adenoma to malignant adenocarcinoma. While CIN provides a mutator mechanism for cancer-relevant genomic events, its role in shaping tumor biology during carcinogenesis is not well understood. Here, we explored the molecular and biological impact of telomere dysfunction and associated CIN in vivo in a faithful model of CRC. In vivo lineage tracing revealed that CIN increased neoplastic cell competition and clonal expansion through accelerated differentiation of neighboring stem cells, resulting in increased number of adenomas and decreased survival in CIN-high Apc^min mice. Mechanistically, CIN represses EZH2 leading to …

Cortical Representation Of Learning Social Interactions In Freely Moving Non-Human Primates, Melissa Franch

Dissertations and Theses (Open Access)

The motivation and capacity to be social is necessary for human survival. Successful learning of complex, prosocial behavior stems from the ability to perceive and respond to visual cues, such as the body language and facial expressions, from others in our environment. This dependence on visual information to guide social interaction is especially true for humans and non-human primates. Although recent studies in primate neurophysiology discovered neurons that can encode socially relevant variables, like reward and social actions, the underlying neural mechanisms of learning advanced social concepts, such as cooperation, are not well understood. Further, previous work has identified …

Role Of The Immune System In The Modulation Of The Mmr-Deficient Intestinal Stem Cell Niche, Shepard Conner

Dissertations and Theses (Open Access)

Mismatch Repair (MMR) is a crucial DNA repair system to maintain genomic integrity in cells that is integrated by specific genes including MLH1, MSH2, MSH6, and PMS2. These genes play a critical role in repairing errors that occur in base pairing by stabilizing the genetic material. When the MMR system fails to correct those errors, MMR deficiency occurs where monoallelic mutations in the MMR genes result in a condition known as Lynch Syndrome (LS). LS makes up approximately 3% of all colorectal cancer (CRC) and is regarded as a hereditary form of CRC, which progresses from MMR-deficient …

Downregulation Of Mir-10a-5p As A Potential Therapeutic Target To Improve The Detrimental Effects Of Post-Stroke Social Isolation, Patrick Mooz

Dissertations and Theses (Open Access)

Introduction

Social isolation is detrimental to health. Isolation and loneliness are linked to all-cause mortality and accelerated disease progression in patients with cancer, dementia, and vascular disease. The number of individuals that live alone is increasing in our society, especially in the elderly, and loneliness and isolation represent a profound growing public health challenge. Previous studies have found that the detrimental effects of social isolation can be recapitulated in animal models. Mice that are socially isolated (SI) prior to an experimental stroke have larger infarcts and significantly worse outcomes. Importantly, animals that remain pair housed (PH) when an experimental stroke …

A Signal To Divide: Apoptotic Extracellular Vesicles As Carriers Of Mitogenic And Immunogenic Signals, Safia Essien, Safia Essien

Dissertations and Theses (Open Access)

Efficient replacement of dead cells in epithelial tissue is crucial for maintaining barrier function and tissue homeostasis. Apoptotic cells can signal to neighboring cells to stimulate proliferation and compensate for cell loss and maintain overall cell numbers in normal physiology and cancer. While dying cells can transmit instructive cues to neighboring cells, the molecular mechanisms that induce cell division are not well understood. Recent evidence suggests that apoptotic bodies (ABs) or apoptotic extracellular vesicles (AEVs) mediate cell-to-cell communication and carry diverse biologically active cellular cargo which can influence cell proliferation. This dissertation visualizes and characterizes AEVs in larval zebrafish and …

Identification And Delineation Of Neuronal Pathways Underlying Hypophagia, Jing Cai

Dissertations and Theses (Open Access)

In terms of metabolism, eating disorders manifest in two extreme directions: overnutrition, which can lead to obesity, and malnutrition, which can result in underweight or even starvation. Both extremes compromise the quality of life. According to the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) standard, eating disorders affect up to 17.9% of young women and 2.4% of young men. Although eating disorders are primarily defined as mental disorders rather than metabolic disorders, they are intertwined with complex emotions and sensory perceptions. However, in contemporary animal research related to eating disorders and feeding behaviors, the majority of neuroscientists still examine …

Analyzing Extracellular Vesicles For Disease Monitoring In Metastatic Colorectal Cancer Patients, Vahid Bahrambeigi

Dissertations and Theses (Open Access)

Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. Metastases are the main cause of cancer-related death, and the most frequent metastatic sites in patients with CRCs are liver and lung. To confirm the diagnosis of metastatic CRC (mCRCs) and to classify mCRCs, tumor biopsy of a suspected metastasis is often required. The consensus molecular subtype (CMS) classification which is based on gene expression profiles of CRC tumor specimens, is a predictive factor for treatment outcomes of standard chemotherapies for mCRCs. The practicality of repeated tumor biopsies for disease monitoring in mCRC patients is …

Genomic Characterization Of Adolescent And Young Adult Cancers: Investigation Of Ewing Sarcoma Susceptibility And Chornobyl Thyroid Tumors, Olivia Lee

Dissertations and Theses (Open Access)

Adolescent and young adult (AYA) cancers, diagnosed between the ages of 15 and 39, can exhibit distinctive genetic and molecular characteristics. Reported epidemiologic findings and treatment outcomes based on pediatric and adult cancer studies are often not suitable for application to the AYA population, underscoring the need for more thorough genomic research. Advances in sequencing technologies have enabled comprehensive analyses of complex genomic characteristics of AYA cancers, crucial for understanding the underlying biology of these malignancies. Here, I have utilized advanced sequencing techniques and integrated analytic approaches to describe important genomic features in two different AYA cancer types: Ewing Sarcoma …

Oncogenic Kras And Telomere Biology In Crc Progression, Ronald Depinho

Dissertations and Theses (Open Access)

While colorectal cancer (CRC) patients diagnosed with localized stage disease (as defined by SEER) have a 5-year survival rate of 90%, this rate plunges to 14% for patients diagnosed with metastatic CRC. Consequently, there is an immediate imperative to elucidate the mechanisms that drive the transition to advanced CRC.

Human CRCs carrying oncogenic mutations in the KRAS oncogene, henceforth referred to as KRAS*, exhibit a 25% higher propensity for developing liver metastases. Similarly, in our CRC mouse model, engineered with an inducible Kras* transgene and conditional null alleles of Apc and Tp53 (referred to as iKAP), KRAS* has been …

Biochemical And Kinetic Analysis Of Phosphofructokinase In The Eukaryotic Human Pathogen Entamoeba Histolytica, Jin Cho

All Dissertations

Entamoeba histolytica is a water- and food-borne intestinal parasite that causes amoebiasis and liver abscess in ~100 million people each year leading to ~100,000 deaths. This amitochondriate parasite lacks many metabolic pathways including the tricarboxylic acid cycle and oxidative phosphorylation, and cannot synthesize purines, pyrimidines, or most amino acids. As a result, E. histolytica is presumed to rely on its modified pyrophosphate (PP_i)-dependent glycolytic pathway for ATP production during growth on glucose. This pathway relies on a PP_i-dependent rather than ATP-dependent phosphofructokinase (PFK) and thus has a net production of three ATP per glucose. However, in …

Structural Characterization Of Cardiomyocyte Microenvironment In Murine Myocardium By Multimodal Stimulated Emission Depletion Microscopy, Zhao Zhang

All Dissertations

Cardiomyopathy, a disease of the heart muscle, is characterized by structural and functional abnormalities of the myocardium, in the absence of coronary artery disease, hypertension, valvular disease or congenital heart disease. In 2020, there were approximately 6.11 million prevalent cases of cardiomyopathy and myocarditis, and 0.37 million related deaths worldwide. Many affected individuals are asymptomatic, and chronically treated patients are at risk of heart failure. Within the myocardium, cardiomyocytes reside in a complex and dynamic extracellular matrix (ECM), consisting of basement membrane and interstitial matrix. The interactions between cardiomyocytes and myocardial ECM play a critical role in maintaining cardiac geometry …

Interpretable Mechanistic And Machine Learning Models For Pre-Dicting Cardiac Remodeling From Biochemical And Biomechanical Features, Anamul Haque

All Dissertations

Biochemical and biomechanical signals drive cardiac remodeling, resulting in altered heart physiology and the precursor for several cardiac diseases, the leading cause of death for most racial groups in the USA. Reversing cardiac remodeling requires medication and device-assisted treatment such as Cardiac Resynchronization Therapy (CRT), but current interventions produce highly variable responses from patient to patient. Mechanistic modeling and Machine learning (ML) approaches have the functionality to aid diagnosis and therapy selection using various input features. Moreover, 'Interpretable' machine learning methods have helped make machine learning models fairer and more suited for clinical application. The overarching objective of this doctoral …

Impact Of Copper-Containing Products And Irrigation On Hybrid Bermudagrass (Cynodon Dactylon (L.) Pers X C. Transvaalensis Burtt-Davy), Adam Gore

All Dissertations

Copper (Cu) is an often-seen component in various turf industry products including fungicides, algaecides, and colorants. Though an essential micronutrient in plants, excessive levels of Cu has been shown in various plant commodities to cause phytotoxicity and plant death. With the increasing use of pigments on hybrid bermudagrass [Cynodon dactylon (L.) Pers x. C. transvaalensis Burtt-Davy] putting greens to replace overseeding practices during traditional dormant periods combined with regular applications of fungicide, algaecide and spray additives containing Cu, the objective of this study was to investigate the potential impact of individual and combined copper-containing treatments on hybrid bermudagrass and …

Engineering Next-Generation Cardiovascular Therapies, Ryan Walker Barrs

All Dissertations

Cardiovascular diseases are the leading cause of death worldwide. Heart disease, in particular, accounted for 1 in every 5 deaths in the United States in 2021, representing a substantial public health burden that will require more effective treatment options to alleviate. Heart transplant surgery is currently the only option to completely restore cardiac function, but many patients die while waiting for a transplant due to a longstanding organ donor shortage. Thus, there is a dire need for accessible treatment options that can repair damaged hearts. Recent advances in tissue engineering and regenerative medicine have accelerated the development of therapies for …

Cellular Mechanism Of Pentagalloyl Glucose-Mediated Prevention And Reversal Of Abdominal Aortic Aneurysms, Greg Halsey

All Dissertations

Abdominal aortic aneurysm (AAA) has been the 15th leading cause of death in persons older than 55 for the past ten years in several Western countries, with rupture resulting in an almost 100% mortality rate. AAA is a focal dilation of the aorta characterized by progressive loss of elastin and vascular smooth muscle cells (SMCs), as well as persistent inflammatory response [1]. The only treatment for AAA is surgery; however, the mortality post-procedure is still 1-4%, with a 15-30% chance of morbidity [2].

Pentagalloyl glucose (PGG) treatment is effective in the reversal of AAA. While its stabilizing interactions with extracellular …

Characterization Of The Effects Of The Pyrazolopyrimidine Inhibitor Grassofermata (Nav-2729) In The Eukaryotic Pathogen Trypanosoma Brucei, Kristina Marie Parman

All Dissertations

The protozoan pathogen, Trypanosoma brucei, is the causative agent of sleeping sickness in humans and nagana in livestock in sub-Saharan Africa. T. brucei cycles between tsetse fly and mammalian hosts, and it is adapted to survive in diverse host tissues. Variant Surface Glycoprotein (VSG) plays a key role in immune evasion in the mammalian host. The VSG membrane anchor requires two myristates, 14-carbon saturated fatty acids (FAs) that are scarce in the host. T. brucei can synthesize FAs de novo, but also readily takes up exogenous FAs, despite lacking homologs to fatty acid uptake proteins found in other …

Integrated Techniques To Identify And Characterize Resistance To Fusarium Wilt Caused By Fusarium Oxysporum, F. Sp. Vasinfectum Race 4 In Two Domesticated Gossypium Species, Stephen Parris

All Dissertations

Fusarium wilt of cotton (Gossypium hirsutum and G. barbadense), caused by Fusarium oxysporum f. sp. vasinfectum race 4 (FOV4), is the most threatening disease faced by today’s cotton breeders. During the past 20 years, over $7 million have been dedicated to efforts in breeding upland cotton for resistance to FOV4 while yielding little to no results. To counteract this, we conducted a study in Clint, TX, that utilized control plots and geostatistical methods to adjust phenotypic data for the heterogeneous distribution of FOV4 in the field, improving the accuracy of genetic resistance assessments. Concurrently, early-generation genetic mapping in …

Economic Analysis Of Sod-Seeded Summer Annuals For Forage And Grazing, Ivanelle Meyer

Graduate Theses and Dissertations

Forage and pasture trials were conducted over the summers of 2021 and 2022 to assess how forage production and nutritive value of sorghum sudangrass, cowpea, and sorghum sudangrass-cowpea mixtures, sod-seeded to bermudagrass pasture would impact stocker cattle performance. The forage trials compared forage production and quality when poultry litter was surface or sub-surface applied biennially in comparison to a no poultry litter control. Poultry litter is a nutrient dense fertilizer utilized on pastures in the mid-southern United States to increase forage nutritive value and yield. Broadcasting poultry litter results in more nutrient losses due to runoff and nitrogen volatilization compared …

Effect Of Plant Genotype On Plant-Microbe Interactions And Multi-Generation Ecosystem Selection Of Microbial Communities Associated With Plant Biomass In Arabidopsis Thaliana, Nachiket Shankar

Graduate Doctoral Dissertations

The microbiome's role in shaping host phenotypes is a critical area of investigation, with implications for ecology, evolution, and host health. Dynamic plant-microbe interactions are influenced by factors like soil type, environment, and genotype. Understanding their impact on microbial communities is key for tailored plant benefits. An artificial ecosystem selection experiment was done for eight generations with Arabidopsis thaliana Ler and Cvi. This revealed distinct microbial communities shaped by genotypes and biomass treatments. Initially, environment dominated, but over time, genotype and biomass gained influence, explaining ~40% of the variation. Moreover, genotype-specific rhizobacterial associations were observed, enhancing understanding of community dynamics …

E-Cigarettes: What Is The Relationship Between E-Cigarette Usage And Periodontal Disease?, Deborah Rose

Electronic Theses and Dissertations

The dental community has a broad understanding of how traditional combustible cigarettes affect the oral cavity of the dental patient but there is little research available on the effects that e-cigarettes have on the patient’s dental health. Vaping products have been marketed as a healthier option over traditional combustible cigarettes. Since they were first introduced in 2003, very little research has been performed to understand their dental implications. This project was executed to investigate the chemicals associated with these vaping products and how they possibly contribute to the progression of periodontal disease. This research project was conducted with the contribution …

Evaluating The Impact Of Oyster Reef Breakwaters On Hydrodynamics, Morphodynamics, And Sediment Transport Using Xbeach, Tabassum Islam

Graduate Theses and Dissertations (2019 - present)

Alabama Port is a unique marsh and sandy beach shoreline. Since the 1950s, substantial erosion has occurred along this shoreline due to storms, wind-generated waves, and ship wakes. This research focuses on evaluating the effect of oyster reef breakwaters on wave height attenuation and sediment stabilization through numerical modeling (XBeach) under three different synthetic storm scenarios coupled with three unique sea level rise projections near Alabama Port. This has been accomplished by comparing a with and without project condition using XBeach in a two-dimensional (2D) mode by analyzing wave height, velocity, and cumulative bed-level changes at the study site. The …

Unlocking The Mysteries Of Opportunism: Neuroendocrine Insights From An Aseasonal Breeder (Taeniopygia Guttata), Jessica A. Moodie

Graduate Theses and Dissertations (2019 - present)

The regulation of reproductive physiology in animals is mediated by the Hypothalamus-Pituitary-Gonad (HPG) axis. In seasonal breeders, a conserved reciprocal switching of deiodinase enzymes alters thyroid hormone signaling, which controls HPG activity. This study tested the hypothesis that neural regulation of the HPG axis as described in seasonal systems is conserved and repurposed to respond to other cues in aseasonal species. Using water deprivation and nest restriction in the opportunistic Zebra Finch, we were able to create a breeding group and non-breeding group, confirmed by egg laying and changes in ovarian anatomy. Breeding females had clear follicular hierarchy, increased ovary …

Interactions Between Sediment Mechanical Structure And Infaunal Community Structure Following Physical Disturbance, William Cyrus Roger Clemo

Graduate Theses and Dissertations (2019 - present)

Shallow, river-influenced coastal sediments are important for global carbon storage and nutrient cycling and provide a habitat for diverse communities of invertebrates (infauna). Elevated bed shear stress from extreme storms can resuspend, transport, and deposit sediments, disrupting the cohesive structure of muds, and sorting and depositing sand eroded from beaches. These physical disruptions can also resuspend or smother infauna, decreasing abundances and changing community structure. Infaunal activities such as burrowing, tube construction, and feeding can impact sediment structure and stability. However, little is known about how physical disturbance impacts short and long-term sediment habitat suitability and whether disturbance-tolerant infauna influence …

Preparing Teaching Assistants To Facilitate Course-Based Undergraduate Research Experiences (Cures) In The Biological Sciences: A Call To Action, Erin Shortlidge, Amie M. Kern, Emma Goodwin, Jeffrey T. Olimpo

Biology Faculty Publications and Presentations

Course-based undergraduate research experiences (CUREs) offer an expanding avenue to engage students in real-world scientific practices. Increasingly, CUREs are instructed by graduate teaching assistants (TAs), yet TAs may be underprepared to facilitate and face unique barriers when teaching CUREs. Consequently, unless TAs are provided professional development (PD) and resources to teach CUREs effectively, they and their students may not reap the assumed benefits of CURE instruction. Here, we describe three perspectives – that of the CURE TA, the CURE designer/facilitator, and the CURE student – that are collectively intended to inform the development of tentative components of CURE TA PD. …

Characterization Of Developmental Phenotypes In Zebrafish With Mutations In Mmachc, Briana Elise Pinales

Open Access Theses & Dissertations

Methylmalonic aciduria and homocystinuria, CblC type (cblC) syndrome (MIM 277400) is a genetic disorder resulting from a mutation in the MMACHC gene. This gene plays a crucial role as a chaperone in the conversion of vitamin B12 into its active form, which is essential for proper cellular metabolism. cblC syndrome is heterogenous by nature, primarily attributed to the extensive damage it causes across multiple bodily systems. In cases of early onset of cblC syndrome, patients may exhibit a diverse range of clinical symptoms including difficulties with feeding, dysmorphic features, microcephaly, brain abnormalities, hypotonia, developmental delays, and seizures. The study of …

Evaluation Of Evapotranspiration Estimates Using An Existing Hybrid Machine Learning Model In A Natural And A Managed Dryland Site, Katya Esquivel Herrera

Open Access Theses & Dissertations

Evapotranspiration (ET) is a critical component of the hydrologic cycle, encompassing both evaporative water loss from surfaces and transpiration through plant stomata. The environmental factors influencing ET include water and energy availability, atmospheric capacity for water uptake, and various meteorological variables. ET serves as a unique climate variable linking water, energy, and carbon cycles. In agroecosystems, accurate ET quantification is vital for optimizing water use efficiency, irrigation management, and crop yield. Traditional methods for ET estimation involve direct measurements and indirect models, with both presenting limitations.

Recent years have witnessed the integration of remote sensing and machine learning (ML) algorithms …

Development Of Synthetic Glycobiomarkers For The Follow-Up Of Chagas Disease Chemotherapy And Serological And Molecular Assays For Evaluation Of Trypanosoma Cruzi Infections In The U.S-Mexico Border, Igor L. Estevao

Open Access Theses & Dissertations

Chagas disease (CD), caused by the protozoan parasite Trypanosoma cruzi, affects 7-8 million people worldwide. Lately, the disease has been spread to nonendemic countries and regions, like the U.S. and Europe. The disease can be divided into two phases: the acute and chronic phases, which continue for years or even decades. There are two available drugs for CD treatment: benznidazole (BNZ) and nifurtimox (NFX). These drugs are highly effective in the acute phase but less efficient in the chronic stage. Other limitations of these drugs are their toxicity, leading to serious adverse events and premature treatment termination. Newer clinical trial …

Evaluation Of The Efficacy Of Synthetic Glycovaccines Against Both Murine Acute Chagas Disease And Cutaneous Leishmaniasis, Colin D. Knight

Open Access Theses & Dissertations

Chagas disease (CD) and cutaneous leishmaniasis (CL) are neglected tropical diseases caused by the protozoan trypanosomatids, Trypanosoma cruzi and Leishmania spp., respectively. There are approximately 6-8 million people infected with T. cruzi worldwide and ~300,000 people in the US. Between 700,000 and 1.2 million new cases of CL occur worldwide yearly. The approved chemotherapies for both diseases are partially effective and may cause serious adverse events, resulting in premature treatment interruption. Moreover, no effective vaccine for either disease is available. Therefore, developing a vaccine that would provide effective cross-protection against both diseases would provide a cost-effective alternative to the existing …

Repositioning Propranolol To Block Mitogenic Signaling In Breast Cancer, Alexa Noel Montoya

Open Access Theses & Dissertations

Breast cancer is the second most diagnosed cancer among women and is about 30% of all new cases of female cancers each year. It is projected that 1 in 8 every U.S. woman (about 13%) develop invasive breast cancer over the course of her lifetime. While advances in cancer research have made it possible to elucidate several breast cancer genomic subtypes, and develop new novel therapies, many of these agents are associated with significant toxicity, as well as high costs. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor …

Lizard Communities In A Shifting Landscape: The Current State Of Insectivorous Lizard Communities In The Jornada Basin Between Grassland, Mesquite Dune, And Creosote Bush Habitats In A Semi-Arid Landscape Undergoing Shrubification, Julie Marie Schlichte

Open Access Theses & Dissertations

Lizard communities in arid lands can act as model systems of how diversity and abundance are impacted in the face of ongoing climate variability and change, as they are sensitive to shifts in precipitation, temperature, and changing vegetation structure. The main research question we hope to answer is how the community composition of lizards varies between dominant vegetation types (Mesquite dunes, grasslands, and Creosote Bush flats). Nine sites (3 of each dominant vegetation type) with 16 pitfall traps each (n = 144) were surveyed from June 2016 -- June 2017. 12 lizard species were captured, consisting of 923 total captures …