Life Sciences Commons^™

Size Structure And Intraguild Interactions Between Two Ambystoma Species, Gwyneth Daunton

Theses and Dissertations

Intraguild interactions affect population and community structure through a combination of competition and predation. Changes in size structure influence intraguild interactions by affecting the strength and direction of these species’ interactions. I tested for size-structured intraguild interactions in temporary pond ecosystems between marbled salamanders (Ambystoma opacum) and tiger salamanders (Ambystoma tigrinum) using an outdoor mesocosm experiment. I hypothesized that 1) A. opacum survivorship and growth would be negatively impacted when both species start at a similar size because tiger salamanders grow faster and are more aggressive 2) A. tigrinum will grow slower and have lower survivorship …

Statistical Modeling Of Drug Properties, Host Clinical And Genetic Factors In Drug-Induced Liver Injury, Kristin Ashby

Theses and Dissertations

Drug-induced liver injury (DILI) is a rare adverse reaction that can result in liver transplant or death. Currently, there are no reliable methods to identify which individuals are at risk of developing severe or chronic DILI prior to drug administration. Here, we investigated the interplay between drug properties, clinical, and genetic factors and DILI risk, severity, and trajectory. First, we used a large, published dataset of 1036 drugs to examine the relationship between DILI risk and two drug properties, lipophilicity and extent of metabolism. Each drug property was tested alone and in combination with daily dose using five different DILI …

Behavioral And Physiological Effects Of Heavy Metals On Fish: A Review And Preliminary Results, Diana V. Morales

Theses and Dissertations

Pollution, specifically heavy metal pollution, in various bodies of water has been a significant issue for decades. Research has been conducted on heavy metals and their effects on the environment, larger fish species, and humans since the 1970s (Skidmore, 1964; Adeniyi et al., 2007; Adeosun et al., 2015; Bawuro et al., 2018). It is known that zinc is a neurotoxin in some species and causes harm to the environment. It is also known that it causes harm to people if it is ingested or if they are exposed to it for long periods of time (Mahurpawar, 2015; Mizuno and Kawahara, …

Improving Capture Methods For Neonate Ungulates, Matthew T. Turnley

Theses and Dissertations

The capture of neonate ungulates has played an integral role in studies of habitat selection, phenology, survival, and other topics of ecological interest. However, neonates can be difficult for researchers to locate and capture. Neonate ungulates are born in habitats with reduced visibility, frequently spend time in a concealed, prone position, and may display cryptic coloration. In an attempt to improve researchers' likelihood of locating and capturing neonate ungulates, multiple capture methods have been developed. Much remains unknown about biases associated with capture methods and how to further improve capture methods once biases are understood. Our objectives were to determine …

The Effects Of Curricular Change On Student Learning And Well-Being In Biomedical And Clinical Education, Rachel Jalaire Tomco Novak

Theses and Dissertations

The implementation of curriculum change, and innovative pedagogical theory, can help educators and administrators in higher education further the learning gains of students in the sciences. But the introduction of new methods of teaching, or curricular restructuring, can be interpreted by students differently, potentially affecting students' emotional states as well as their relationships with peers. To support not only the learning of students, but also their emotional and social well-being, pedagogical and curricular theory should be enacted in ways that take into consideration the full scope of the student experience. In this dissertation, the implementation of curriculum and pedagogical theory, …

Combating Fungal Pathogens (Helminthosporium Solani, Pythium Ultimum) With Secondary Metabolites Of Streptomyces Bacteria, Erik W. Kemp

Theses and Dissertations

Fungal diseases, Pythium ultimum (Pythium leak) and Helminthosporium solani (silver scurf) have detrimental effects on potato tuber (Solanum tuberosum) quality and yield. Tubers are the world’s fourth largest agricultural food crop and are crucial for feeding a growing population. Bacteria from the genus Streptomyces are known for producing a wide variety of secondary metabolites with antifungal properties. Isolates of Streptomyces have recently shown inhibitory effects towards P. ultimum and H. solani in Petri dish assays. These data suggest that Streptomyces may work as a biocontrol to protect tubers from P. ultimum and H. solani. We tested talc-based powder formulas for …

Development Of A Methodology For The Quantification Of Reaerosolization Of A Biological Contaminant Surrogate Particle From Military Uniform Fabric, George D. Cooksey

Theses and Dissertations

During a mass casualty medical evacuation after a bioaerosol attack, a decontamination method is needed that is effective at both decontamination and preventing the secondary hazard of biological particles reaerosolizing from contaminated clothing. However, neither the efficacy of current decontamination methods nor the risk of biological particle reaerosolization is significantly explored in existing literature. The goals of this thesis were to develop a repeatable methodology to quantify the reaerosolization of a biological contaminate off Airman Battle Uniform (ABU) fabric swatches, and to test the efficacy of one decontamination method (high-volume, low-pressure water) using 1 mpolystyrene latex (PSL) spheres as a …

Taxonomic And Phylogenetic Diversity Of Pitcher Plant Bogs In Georgia's Coastal Plain, Melanie Flood

Theses and Dissertations

Diversity studies via floristic survey and taxonomic metrics have proven essential for discerning community composition and biodiversity, however, phylogenetic analyses are necessary to reveal underlying evolutionary change and potential community assembly patterns. Pitcher plant bogs are highly diverse, highly understudied habitats that contain numerous listed and at-risk plant and animal species of Georgia.

In this study I investigated the taxonomic and phylogenetic diversity of pitcher plant bogs by asking the following questions:

1) What is the taxonomic diversity of pitcher plant bogs,

2) What is the dispersion of phylogenetic diversity within bog habitats, and

3) Does taxonomic and phylogenetic diversity …

Characterization Of Testis-Derived Mesenchymal Cells And The Hunt For Universal Stemness Markers, Myret Ghabriel

Theses and Dissertations

Mesenchymal stromal/stem cells (MSCs) are multipotent cells residing in multiple tissues with the capacity for self-renewal and differentiation into various cell types. Due to the myriad sources of MSCs the International Society for Cellular Therapy (ISCT) proposed certain criteria for their characterization. Here, we isolate adult MSCs from mouse testes and demonstrate that these testis-derived MSCs (tMSCs) follow some of the ISCT’s criteria. tMSCs expressed the MSCs surface markers CD44, CD73, and CD29 and lacked the expression of the hematopoietic cell marker CD45. Moreover, the cells displayed the capacity for self-renewal and in vitro differentiation into adipocytes. Since the isolation …

Knockdown Of Mdm2 In Hepg2 Cell Line: A Step Towards Understanding The Relation Between Mirna590-3p And Its Downstream Target Gene, Mdm2, In Hepatocellular Carcinoma, Jihad Mahmoud

Theses and Dissertations

Background: miRNA 590-3p is a small non-coding RNA that has previously been associated with the occurrence and progression of several cancer types. Its expression pattern and biological role in Hepatocellular carcinoma (HCC), however, remain controversial. Interestingly, a previous study in our lab revealed a tumor suppressing activity of miR-590-3p in HCC and identified the MDM2 gene as the miR-590-3p target gene.

Aim: The current study aimed to knock down the expression of MDM2 in HepG2 cells to understand how the inhibition of MDM2, as a validated downstream target of miR-590-3p, would affect different functional pathways in HCC. In …

A Predictive Model For Geographical Location Using Microbiome Composition And Covid-19 Based Analysis, Ahmed Adel Aboushanab

Theses and Dissertations

The human microbiome is a main contributor for the health and welfare of the human body. It is affected by many factors like diet and hygiene. These factors differ between different populations. Testing the population-microbiome differences using healthy samples from different countries is the first objective of this study. This data was then used in training and testing machine learning models (Random Forest and L2-logistic Regression Classifiers) for the prediction of the geographical location based on the microbiome data. Random Forest Classifier had the highest accuracy. Feature importance analysis showed that the data for Proteobacteria, Actinobacteria, and Bacteroidetes improved the …

Selective Gsk3Β Inhibition Mediates An Nrf2-Independent Anti-Inflammatory Microglial Response, Mohamed H. Yousef

Theses and Dissertations

Glycogen Synthase Kinase 3 (GSK3) is associated with the proinflammatory phenotype of microglia and has been shown to act in concert with Nuclear factor kappa B (NF-κB). . GSK3 is also a suppressor of Nuclear factor erythroid 2-related factor 2 (Nrf2), the principal regulator of redox homeostasis. Agreeing with the oxidative paradigm of aging, Nrf2 is often deregulated in parainflammatory and neurodegenerative diseases. In this study, we aimed to explore a multimodal disease-modifying utility of GSK3 inhibition, beyond neuronal proteopathologies, Furthermore, we aimed to underscore the difference in therapeutic value between the two GSK3 paralogs by isoform-selective chemical inhibition.

The …

Repurposing Metformin And Antifolates For The Treatment Of Hepatocellular Carcinoma, Sherouk Mohamed Tawfik

Theses and Dissertations

Hepatocellular carcinoma (HCC), one of the most prevalent types of cancers worldwide, continues to maintain high levels of resistance to standard therapy. As clinical data revealed poor response rates, the need for developing new methods has increased to improve the overall wellbeing of patients with HCC. Due to its safety, wide availability and previously reported anti-cancer effects, metformin (MET) serves to be a possible therapeutic agent when combined with other well-known anti-cancer agents. The aim of this study was to investigate the potential anti-cancer effects of MET, an anti-diabetic agent, when combined with two antifolate drugs: trimethoprim (TMP) or methotrexate …

Molecular Characterization Of Antibiotic Resistant Shiga Toxin-Producing Escherichia Coli From Clinical And Food Samples, Khulud Alotaibi

Theses and Dissertations

Antimicrobial resistance (AMR) in foodborne pathogens can be a consequence of using antimicrobial drugs in food-producing animals. The emergence of antimicrobial resistance in foodborne pathogens is of great concern due to adverse patient health outcomes and the possibility of transferring genes encoding AMR to other clinically relevant pathogens. One of these bacteria is Shiga toxin-producing Escherichia coli (STEC), which can cause serious illness in humans for a haemolytic uremic syndrome (HUS). This study characterized and determined the mechanism of antibiotic resistance in 46 Shiga toxin-producing Escherichia coli strains collected by the U.S. Food and Drug Administration from food and clinical …

Heterologous Production Of Plant Secondary Metabolites Resveratrol And Caffeic Acid In E.Coli And Synechocystis Sp. Pcc 6803, Yong Xue

Theses and Dissertations

Caffeic acid and resveratrol are polyphenol compounds produced by plants as secondary metabolites to protect against biotic and abiotic stresses. In the last decades, numerous studies have demonstrated the beneficial effects of these compounds on human health as anticancer, antioxidant, anti-virus and anti-inflammatory agents. In plants, both caffeic acid and resveratrol are synthesized either from phenylalanine or tyrosine. Recently, heterologous production of phenylpropanoids using genetically engineered bacteria is gaining more and more attentions from industry because it can dramatically improve the yield with reduced costs. The major aim of the work is to explore the possibility of using Synechocystis or …

Design Of A Synthetic Temperature-Activated Epigenetic Biocontainment System, Owen Rivers Page

Theses and Dissertations

The need for an internal control to govern engineered strain survival is becoming apparent when considering the biosafety and ethics within biotechnological research. Using understudied regulatory elements known as RNA thermometers (RNATs) that can modulate protein translation based on temperature changes and a Type II restriction modification system, we posit the creation of a synthetic temperature-activated epigenetic biocontainment system, termed the ‘sentinel switch’. We have mined a wide variety of bacteria from Yersinia pestis to Synechocystis sp. looking for novel RNATs. A complementary synthetic biology approach based on library generation and screening of chimeric RNATs (ChRNATs) was also conducted. RNATs …

Identification Of Novel Phosphorylation Sites In Sars-Cov-2 Nucleocapsid Protein, Josie Daldegan Rezende

Theses and Dissertations

COVID-19, the 2019 disease outbreak, continues to cause severe mortality worldwide. Fast and reliable tests that identify the SARS-CoV-2 virus, which is responsible for causing the COVID-19 disease, are crucial for controlling the spread of the virus. Antigen tests are ideal for the rapid diagnosis of COVID-19. Current antigen tests for COVID-19 detect the SARS-CoV-2 nucleocapsid (N) protein. The nucleocapsid is the most abundant protein produced by the virus upon infection, which makes it a superior target for detection by an antigen test. Nucleocapsid proteins from several coronaviruses, including SARS, have previously been shown to be modified by posttranslational modification …

N, N-Dimethylacetamide Targets Neuroinflammation In Alzheimer’S Disease In In Vitro And Ex Vivo Models, Zenghui Wei

Theses and Dissertations

Alzheimer’s disease (AD) is a neurodegenerative disorder with no cure, accounting for 60-80% of cases of dementia. While the two pathologic hallmarks of AD, senile plaques from extracellular deposition of amyloid β-protein (Aβ) and tau-based neurofibrillary tangles (NFT), have been known for decades, the pathogenesis of AD remains unclear. In recent years, anti-neuroinflammatory treatment has entered the spotlight in AD research. In previous studies, we have shown that N,N-dimethylacetamide (DMA), a common drug excipient, is a potent anti-inflammatory agent. In the current work, we investigate the effect of DMA on neuroinflammation and its mechanism of action in in-vitro and ex-vivo …

Human Otop1 Proton Channel Can Function As A Monomer, Gabriella Abigail Ulloa

Theses and Dissertations

Otopetrins (OTOP) represent a new family of eukaryotic proton channels that do not share structural similarities with other renowned ion channels. Otop1 was initially known for its involvement in vestibular function and its significance for otoconia formation before it was established as a bona fide sour taste receptor. The cryo-EM structures for several Otop channels have been determined and demonstrated Otop1 as a homodimer comprised of two subunits. Each subunit constitutes twelve transmembrane helices that can be further partitioned into two structurally similar six transmembrane domains designated as the N and C domains. Molecular dynamic simulations have also previously shown …

Regulation Of Interferon- Induced Interleukin-8 And Pd-L1 Expression In Ovarian Cancer Cells, Sveta Padmanabhan

Theses and Dissertations

Interferon-γ (IFNγ) is a pleiotropic cytokine that has a crucial role in immune response and tumor immunity. Because of its anti-tumor effects, IFNγ has been used in cancer treatment. However, IFNγ also has tumor-promoting functions that are less well understood. Here, I show that IFNγ induces expression of the pro-inflammatory and pro-angiogenic chemokine interleukin-8 (IL-8, CXCL8) in ovarian cancer (OC) cells. The IFNγ-induced IL-8 expression is dependent on JAK1, STAT1, and p65 NFκB, and is associated with an increased occupancy of K314/ 315 acetylated p65 NFκB and Ser-727 phosphorylated STAT1 at the IL-8 promoter. Neutralization of IL-8 using anti-IL-8 antibody …

Dithiocarbamates Mancozeb And Disulfiram Induce Striated Muscle Myopathy And Neuropathy In Long-Evans Rats, Olivia Stephenson

Theses and Dissertations

Mancozeb (MZ), an ethylene bis-dithiocarbamate complexed with the metals manganese and zinc, is a broad-spectrum fungicide used primarily on orchards and vineyards. Disulfiram (DS, Antabuse®), a diethyldithiocarbamate, is an FDA-approved drug used for alcohol aversion therapy. Both dithiocarbamates (DTCs) have shown neurological effects including motor impairment, muscle weakness, and hind-limb paralysis, although the mechanism of toxicity is not understood. The purpose of this study is to determine how these neurotoxic compounds are damaging striated muscle of rats. Adult, male Long-Evans rats were administered either 250mg/kg MZ or 750mg/kg DS via oral gavage 3x/week for four weeks. Animals were euthanized 24 …

Functional Modulation Of The Cav3.1 Calcium Channel By Alternative Splicing At The C-Terminus, Ruizhi Wang

Theses and Dissertations

The CACNA1G gene encodes for Cav3.1, the alpha-1G subunit of a low-voltage-activated T-type calcium channel, which plays crucial roles in cardiac and smooth muscle cells and neurons by influencing the transmembrane potentials and regulating intracellular Ca2+ signaling. Heterozygous missense mutations in the CACNA1G gene cause spinocerebellar ataxia-42 (SCA42), a heterogeneous group of neurodegenerative disorders characterized by brainstem and cerebellum degeneration, and mice that are null for this gene present severe motor coordination defects, abnormal electrical conductance in the heart, aberrant action potentials in the brain, disrupted sleeping patterns, and absence epilepsy. Different splice variants of Cav3.1 have been described, and …

Repurposing An Anti-Epileptic Drug For The Treatment Of Glioblastoma, Anjali Yadav

Theses and Dissertations

Glioblastoma multiforme (GBM) is a grade IV malignant glioma. It is a highly proliferative form of brain tumor with 5-year survival rate ~ 5% indicating a high mortality rate. Current treatment strategies for GBM include surgery, radiation, and chemotherapy. Surgical resection is challenging due to vital function of brain and as GBM often metastasizes in different brain regions. Additionally, development of resistance against the standard of care drug temozolomide (TMZ) is a major challenge in GBM management. GBM is also shielded with the blood brain barrier (BBB) which prevents the entry of several drugs. Therefore, a new drug must overcome …

Development Of Novel, Miniaturized Sperm Cell Isolation Techniques For Sexual Assault Samples, Brittany Celeste Hudson

Theses and Dissertations

The ever-increasing sexual assault evidence collection kit backlog within the United States has prompted the search (and desperate need) for a more efficient, cost-effective, and rapid processing technique that can separate male and female contributions from evidentiary samples. Although backlogs have largely been tackled across the United States and many technological advancements have made the forensic DNA analysis workflow quicker, techniques for handling sexual assault samples remain time-consuming, tedious, and inefficient at separating cellular fractions from the victim and perpetrator. Thus, this research sought to identify a reproducible sperm isolation method using antibodies and/or alternative differential cell lysis techniques as …

Developmental Validation Of A Bacterial Signature-Based Identification Method Of Forensically Relevant Human Biological Samples, Denise M. Wohlfahrt

Theses and Dissertations

The confirmatory identification of body fluids is one of the most critical steps in criminal investigations, as it provides not only information on the source of the DNA, but it can corroborate evidence, aid in the reconstruction of a crime, and associate evidence with a person of interest. Current serological methods utilize biochemistry and immunology to identify biological evidence; however, these serological tests are mostly presumptive while only testing for one fluid at a time, potentially wasting precious evidence. More recently, forensic investigators have suggested the use of molecular methods such as mRNA, miRNA, or DNA methylation. While each of …

The Role Of Slu7 In Spliceosome Function In Saccharomyces Cerevisiae, Sovira A. Chaudhry

Theses and Dissertations

The removal of introns from pre-messenger RNA via splicing in the nucleus is an essential step in gene expression. In recent decades, significant effort has been made to understand the chemical mechanisms of splicing reactions and the composition of the spliceosome that catalyzes them. Yet very little is known about the exact function of many splicing factors and small proteins within the spliceosome. Slu7, a pre-mRNA splicing factor, is essential during the second catalytic step of splicing because it interacts with several proteins and stabilizes the active site conformation. It has been found that Slu7 is involved in 3' splice …

Evaluating The Effects Of Mechlorethamine On The Dermal-Epidermal Junction, Trishaal Janardhanam Raghavendra Rao

Theses and Dissertations

Sulfur Mustard (SM) is a chemical warfare agent first utilized on the battlefield more than 100 years ago. To the present time, no antidote to combat the dermatotoxicity of SM exists. Mechlorethamine (HN2) is a derivative of SM which is used in anticancer therapy. Dermal exposure of HN2 is associated with dermal-epidermal junction (DEJ) disruption (vesication) which limits its clinical usefulness. The primary purpose of the present study was to investigate the mechanisms of vesication caused by HN2 using an in vivo mouse ear vesicant model (MEVM). The ears of male or female C57BL/ 6J mice were exposed to a …

Theta Burst Brain Stimulation In Painful Diabetic Neuropathy Patients: Investigating Neural Mechanisms, Bhushan Thakkar

Theses and Dissertations

Chronic pain (CP) is a significant contributor to disability and disease burden globally. In 2019, approximately 50.2 million adults (20.4% of the US population) experienced chronic pain, contributing to $560-635 billion in direct medical costs. In addition, the worldwide prevalence of diabetes mellitus has reached epidemic proportions and is set to increase to 629 million by 2045. Almost 50% of patients with diabetes present with diabetic neuropathy (DN), and one in five patients with diabetes presents with painful DN (pDN) which is the most common cause of neuropathic pain (NP) in the US. Symptomatic treatment is the mainstay of management …

The Influence Of Salinity On The Structure And Function Of Soil Prokaryotic Communities In Coastal Freshwater Wetlands, Joseph C. Morina Ii

Theses and Dissertations

Microbial communities are critical biological components of the world’s ecosystems, and their respiratory pathways are directly involved in the biogeochemical cycling of essential nutrients. As genomic technologies advance, allowing for more detailed profiling of microbial communities, efforts have successfully linked microbial community composition to ecosystem-level functions and have shown microbial communities are susceptible and resistant to disturbance events. The goal of this dissertation is to address the temporal scales in which microbial communities respond to the disturbance of salinization, and the repercussions this has on microbially-meditated carbon and nitrogen cycling. Coastal freshwater wetlands are an excellent study system to investigate …

Antiviral Effects Of Metalloshielding: Differential Antiviral Activity Of Polynuclear Platinum And Cobalt Compounds, Mary Zoepfl

Theses and Dissertations

The majority of antiviral drug development has focused on virus-specific discovery targeting discrete steps in the individual life cycles. Although great strides have been made for a number of clinically relevant diseases such as human immunodeficiency virus, influenza virus, and hepatitis B, broad spectrum antivirals do not exist. Broad spectrum antivirals would offer (1) treatment for viruses without specifically-targeted antivirals, (2) treatment for viruses which have developed resistance to their available treatments, and (3) a rapidly deployable treatment option in viral epidemics. Many viruses including human cytomegalovirus (HCMV), HIV, and SARS-CoV-2. rely on heparan sulfate (HS), a highly sulfated glycosaminoglycan …