Early Onset Alzheimer’S Disease Markers In Mouse Hippocampus Unveiled By Single-Cell Transcriptomic Analysis Following Cranial Radiotherapy, Tuba Aksoy

Dissertations and Theses (Open Access)

Cranial radiation therapy plays an integral role in the treatment of brain tumors but can lead to progressive cognitive deficits in survivors by mechanisms that are poorly understood. To develop preventive or mitigative strategies, it is crucial to better understand the underlying pathogenesis of radiation-induced cognitive impairments. The study investigated single-cell transcriptomics and DNA methylation changes as potential drivers of persistent cellular dysfunction after radiation exposure, specifically concentrating on the CA1-3 regions of the hippocampus and the prefrontal cortex due to their role in cognitive functions. Thirteen-week-old mice underwent whole-brain radiation at clinically relevant doses. Following whole-brain radiation, an assessment …

Genetics Of Mdh In Humans, Adam Haberman, Celeste N. Peterson

Biology: Faculty Scholarship

Malate dehydrogenase (MDH) performs key roles in metabolism, but little is known about its function specifically in human health and disease. In this minireview, we describe the incomplete state of our knowledge of human MDH genetics. Humans have three MDH genes with a total of four validated isoforms. MDH1 and MDH2 are widely expressed, while MDH1B is only expressed in a small subset of tissues. Many mutations in MDH1 and MDH2 have been identified in patients, but only a few have been studied to determine what symptoms they cause. MDH1 has been associated with cancer and a neurodevelopmental disorder. MDH2 …

Conservation Genomic Investigation Of A Threatened Trout Species Endemic To The Gila River, David Thomas Camak

Biology ETDs

Climate change is a looming threat to the persistence of species, especially aquatic, imperiled species. Species native to desert streams are at a particular disadvantage, as many species already face drought, floods, wildfires, and threats from nonnative species, all of which are thought to be exacerbated by climate change. Species such as the threatened Gila Trout (Oncorhynchus gilae) already have small ranges and persist in fragmented and isolated habitats that limits gene flow between populations. Therefore, it is important to understand the current genomic status of such populations to be able to predict the future effects of climate …

Genetic Diversity Of 1,845 Rhesus Macaques Improves Genetic Variation Interpretation And Identifies Disease Models, Jun Wang, Meng Wang, Ala Moshiri, R Alan Harris, Muthuswamy Raveendran, Tracy Nguyen, Soohyun Kim, Laura Young, Keqing Wang, Roger Wiseman, David H O'Connor, Zach Johnson, Melween Martinez, Michael J Montague, Ken Sayers, Martha Lyke, Eric Vallender, Tim Stout, Yumei Li, Sara M Thomasy, Jeffrey Rogers, Rui Chen

Faculty, Staff and Students Publications

Understanding and treating human diseases require valid animal models. Leveraging the genetic diversity in rhesus macaque populations across eight primate centers in the United States, we conduct targeted-sequencing on 1845 individuals for 374 genes linked to inherited human retinal and neurodevelopmental diseases. We identify over 47,000 single nucleotide variants, a substantial proportion of which are shared with human populations. By combining rhesus and human allele frequencies with established variant prediction methods, we develop a machine learning-based score that outperforms established methods in predicting missense variant pathogenicity. Remarkably, we find a marked number of loss-of-function variants and putative deleterious variants, which …

Ocular Gene Transfer In The Spotlight: Implications Of Newspaper Content For Clinical Communications, Shelly Benjaminy, Tania M. Bubela

Office of the Provost

Background: Ocular gene transfer clinical trials are raising hopes for blindness treatments and attracting media attention. News media provide an accessible health information source for patients and the public, but are often criticized for overemphasizing benefits and underplaying risks of novel biomedical interventions. Overly optimistic portrayals of unproven interventions may influence public and patient expectations; the latter may cause patients to downplay risks and over-emphasize benefits, with implications for informed consent for clinical trials. We analyze the news media communications landscape about ocular gene transfer and make recommendations for improving communications between clinicians and potential trial participants in light of …

The Influence Of Childhood Trauma On Dna Methylation Patterns And Sex-Specific Cortisol Stress Reactivity: A Secondary Analysis, Isabella F. Correia

USF Tampa Graduate Theses and Dissertations

Childhood trauma has been shown to significantly impact physical and mental health outcomes, leading to conditions such as heart disease, diabetes, depression, and difficulties in decision-making and maintaining relationships. Exposure to such trauma has the potential to dysregulate an individual’s stress response system, resulting in abnormal cortisol levels. Many studies suggest a lasting impact of early-life stress on DNA methylation patterns and, separately, cortisol stress reactivity. In addition, there are known sex differences in exposure to childhood trauma and cortisol reactivity; yet studies to date have not investigated whether there is an association to DNA methylation. This study utilized a …

Mutating Lysine 336 In Msh6 Does Not Appear To Affect Dna Mismatch Repair In Saccharomyces Cerevisiae, Anthony Thompson, Daniel Reese, Noa Bennafield, Kalila Daveron, Christopher Bolden, Joanna E. Haye-Bertolozzi

XULAneXUS

Defects in the DNA mismatch repair process results in the accumulation of mutations and disease. Mutations in MSH6 and MSH2, encoding for the subunits of the MutSα complex, are often responsible for Constitutional Mismatch Repair Deficiency (CMMRD) and Lynch Syndrome (LS), respectively. This work focused on DNA mismatch repair through analysis of the MSH6 missense variant msh6-K336T. The mutation examined in this study is msh6-K336T in Saccharomyces cerevisiae, which is equivalent to msh6-K431T in humans. The mutation results in the replacement of lysine with threonine, an amino acid with different properties. It was therefore hypothesized that the mutation …

An Unexpected Path For Malat1 In Neurons: Trafficking Out Of The Nucleus For Translation, Bradley W Wright, Jeremy E Wilusz

Faculty, Staff and Students Publications

The Malat1 (metastasis-associated lung adenocarcinoma transcript 1) long noncoding RNA is highly and broadly expressed in mammalian tissues, accumulating in the nucleus where it modulates expression and pre-mRNA processing of many protein-coding genes. In this issue of Genes & Development, Xiao and colleagues (doi:10.1101/gad.351557.124) report that a significant fraction of Malat1 transcripts in cultured mouse neurons are surprisingly exported from the nucleus. These transcripts are packaged with Staufen proteins in RNA granules and traffic down the lengths of neurites. They then can be released in a stimulus-dependent manner to be locally translated into a microprotein that alters neuronal gene …

The Tissue-Specific Role Of Smn-1 In C. Elegans, Lindsey Philips

Biological Sciences Theses and Dissertations

Spinal muscular atrophy (SMA) is an autosomal recessive disease that results from mutations in the Survival Motor Neuron (SMN-1) gene. Although SMN is a ubiquitously expressed protein that acts as an RNA-binding protein (RBP), SMA is characterized by the selective degeneration of motor neurons of the lower spinal cord. Despite a clear understanding of the genetic causes underlying SMA, the mechanisms associated with low SMN levels to disease pathogenesis remains unclear. Here, we investigate the role SMN-1 has in different tissues to begin understanding possible mechanisms. This project has three aims that has guided our experiments. The first aim is …

Screen For Beneficial Genetic And Chemical Modifiers In Drosophila Models Of Als And Traumatic Brain Injury, Will Bonderer

Biological Sciences Theses and Dissertations

The underlying molecular processes of aberrant protein expression in neurodegeneration are intricate and multifaceted, with ribosome-associated quality control (RQC) emerging as a promising avenue of exploration. Ribosome-associated quality control is integral to cellular function. Its evolutionarily conserved pathway encompasses a network of mechanisms designed to ensure the fidelity of protein synthesis, folding, and degradation within the cells of all eukaryotes. The ribosome, central to protein synthesis, plays a pivotal role in this quality control network, and its malfunction can lead to the accumulation of misfolded or aberrant proteins. In the context of neurodegenerative disorders, this dysfunction can have dire consequences. …

The Greenbeard Gene Tgrb1 Regulates Altruism And Cheating In Dictyostelium Discoideum, Mariko Katoh-Kurasawa, Peter Lehmann, Gad Shaulsky

Faculty, Staff and Students Publications

Greenbeard genetic elements encode rare perceptible signals, signal recognition ability, and altruism towards others that display the same signal. Putative greenbeards have been described in various organisms but direct evidence for all the properties in one system is scarce. The tgrB1-tgrC1 allorecognition system of Dictyostelium discoideum encodes two polymorphic membrane proteins which protect cells from chimerism-associated perils. During development, TgrC1 functions as a ligand-signal and TgrB1 as its receptor, but evidence for altruism has been indirect. Here, we show that mixing wild-type and activated tgrB1 cells increases wild-type spore production and relegates the mutants to the altruistic stalk, whereas mixing …

Omani Camels From A Cultural And Genomics Perspective, Al Muatasim Al Zadjali

Electronic Theses and Dissertations

The Dromedarian camel, Camelus dromedarius, is native to the Arabian Peninsula, including the Sultanate of Oman. These camels are used for food, milk, as well as show and racing competitions. Despite their economic and cultural importance research on camels in Oman is limited. The goal of this study was to examine their genomic variation, relationship with camels in other parts of the Arabian Peninsula, and to determine if selective breeding has led to the establishment of distinct breeds in Oman. Information was compiled from multiple sources to produce a comprehensive review on the breeding, management, economic and cultural use, …

West Coast Rock Lobster Resource Harvest Strategy, Department Of Primary Industries And Regional Development, Western Australia

Fisheries Management Papers

Harvest strategies for Western Australia’s (WA) aquatic resources are formal documents developed by the Department of Primary Industries and Regional Development (DPIRD, the Department) to support decision-making processes that ensure the outcomes are consistent with the principles of Ecologically Sustainable Development (ESD; Fletcher 2002a) and Ecosystem Based Fisheries Management (EBFM; Fletcher et al. 2012). Harvest strategies are a key component of all contemporary fishery management systems and a requirement for certification under the Marine Stewardship Council (MSC). The objectives of ESD are reflected in the objectives of the Fish Resources Management Act 1994 (FRMA) and the Aquatic Resources Management Act …

The Study Of Dmrt1 In Zebrafish And How It Impacts Sex Determination, Raymond Michael Poirier

Graduate Masters Theses

The dmrt1 gene is common amongst most animals and functions to determine or maintain male sex during development. Similarly, in zebrafish dmrt1 is important for male sex determination and maintaining proper testis morphology. This gene is expressed in two different cell types of the testis in zebrafish, germ cells and Sertoli cells. While we know where this gene is expressed and what its role is, it is not known if it is sufficient to drive male fate. If so, then in which cells is it sufficient to drive male fate in the testis? I aimed to answer this question by …

The Anti-Diabetic Drug Metformin Disrupts Feeding And Sleeping Behaviors In Drosophila Melanogaster., Lucas Fitzgerald

College of Arts & Sciences Senior Theses

Dimethylbiguanide, also known as metformin, is the single most prescribed oral treatment for non-insulin dependent diabetes mellitus, or type 2 diabetes, in Western countries. The primary mechanism of action that metformin acts through is the activation of AMP kinase, an important regulator of energy homeostasis. While the anti-diabetic effects of metformin are well documented, its effects on feeding and sleeping behaviors are not well characterized. Using the model organism Drosophila melanogaster, the mean daily quantity of food consumed was measured and compared between groups treated with several dosages of metformin. Feeding interactions such as meal frequency and length were …

Conserving One Of Hawai'i'S Last Endemic Ducks: Genetics And Habitat Associations Of Koloa, Feral Mallards, And Their Hybrids, Kristi Fukunaga

Open Access Theses & Dissertations

Increases in anthropogenic hybridization through introduced species have accelerated the loss of genetic diversity and reductions in population size of native species that are already threatened by population and genetic diversity decline. Fertile hybrids that are common among waterfowl (order Anseriformes) are especially worrisome. A prime example is the endangered Hawaiian duck (Anas wyvilliana; “koloa maoli”), which is the remaining endemic duck species on the main Hawaiian Islands and is threatened by genetic extinction through ongoing hybridization with feral mallards (Anas platyrhynchos). Of note, koloa populations are known to be strongly male-biased (3:1), and this sex bias is known to …

Survey Of The Bolctes From Fish River Nature Preserve, Noah T. Nelson

Honors Theses

Boletes are a special kind of mushroom inside of the Kingdom Fungi that are distinguished from other mushrooms by their uniquely pored hymenium, as opposed to gills. Many boletes are ectomycorrhizal, meaning they are mutualists with vascular plants, and thus beneficial to the overall health of the terrestrial ecosystem. Some are well-known for their edibility and are of economic importance. In the United States 59 genus-level clades comprising 290 operational taxonomic units have been reported. The southeastern US and Gulf Coast regions however are less researched and recorded for their mushroom ecology. In Alabama, only 56 bolete species have been …

Acute Pain Prediction In Oral Cavity And Oropharyngeal Cancer Patients Receiving Radiation Therapy, Vivian Salama

Dissertations and Theses (Open Access)

Oral-Cavity and oropharyngeal cancers (OC/OPC) are types of head and neck cancers that are increasing in incidence domestically. Radiation therapy (RT) is crucial in OC/OPC management. Pain is a common and challenging symptom for most patients during therapy, as nearly all patients undergoing locoregional RT in OC/OPC require analgesia for acute iatrogenic pain. Moreover, about 45% of long-term survivors report chronic pain, with more than 10% exhibiting severe chronic pain. Pain control is challenging due to the multifactorial clinical, molecular, and cellular etiology of cancer/therapy pain, as well as variation in pain assessment and the non-uniform management of pain between …

How Dna Reveals God’S Design, Alan L. Gillen

Faculty Publications and Presentations

Codes are big in today’s world: QR codes, barcodes, computer codes, cell phone codes, and more. Specific information is needed to identify, diagnose, and inform. DNA is the code for life: microbes, plants, parasites, animals, and man. DNA Day is April 25 because it was this day in history (April 25, 1953) when James Watson and Francis Crick described DNA as the double helix and the code for life. Although we consider DNA the genetic blueprint for life, it has only been known for 80 years. On February 1, 1944, Oswald Avery, Colin MacLeod, and Maclyn McCarty wrote a revolutionary …

Annotation Of Hypothetical Genes In Lactococcus Lactis Ssp. Il403, Jennifer A. Tangires

Student Scholar Showcase

The human gastrointestinal tract (GIT) harnesses various microbial organisms involved in almost all processes of physiological homeostasis, among these are lactic acid bacteria (LAB). These bacteria, almost all of which belong to the order Lactobacillales, are able to produce lactic acid, and play an important role in food preservation because they produce bacteriocins. Bacteriocins are antimicrobial proteins that are used to fight off related bacteria in their environment that are competing for the same resources. This study focuses on a specific LAB strain, Lactococcus lactis ssp. IL1403 where 21.9% of its predicted genes have not yet been assigned a function. …

Structural Basis Of Dna Crossover Capture By Escherichia Coli Dna Gyrase, Marlène Vayssières, Nils Marechal, Long Yun, Brian Lopez Duran, Naveen Kumar Murugasamy, Jonathan M Fogg, Lynn Zechiedrich, Marc Nadal, Valérie Lamour

Faculty, Staff and Students Publications

DNA supercoiling must be precisely regulated by topoisomerases to prevent DNA entanglement. The interaction of type IIA DNA topoisomerases with two DNA molecules, enabling the transport of one duplex through the transient double-stranded break of the other, remains elusive owing to structures derived solely from single linear duplex DNAs lacking topological constraints. Using cryo–electron microscopy, we solved the structure of Escherichia coli DNA gyrase bound to a negatively supercoiled minicircle DNA. We show how DNA gyrase captures a DNA crossover, revealing both conserved molecular grooves that accommodate the DNA helices. Together with molecular tweezer experiments, the structure shows that the …

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …

Recovering Ancient Dna Using The Polymerase Chain Reaction, Rose Jennings

Undergraduate Research Symposium

Investigations into aDNA offer a window into the past that modern DNA and paleontological studies alone cannot provide and help address the evolution and connections between hominids, domestication timelines, the analysis of populations over time, and general diversity. Progress in aDNA research has been inherently technology-driven, with modern molecular biology methods, such as the inventions of Polymerase Chain Reaction (PCR) and Next Generation Sequencing (NGS), substantially increasing the analysis possibilities of aDNA. My research this semester has taken me along two parallel paths of investigation: literary research into aDNA and practical exposure to the laboratory techniques used in its analysis. …

Development Of A Novel Edna Sampling Method For Macroinvertebrate Species Of Greatest Conservation Need (Sgcn) In Texas, James York

Biology Theses

Environmental DNA (eDNA) sampling is a new sampling technique that allows for non-invasive sampling of target species or the characterization of entire communities based on barcoding genes. The goal of this study was to sequence common barcoding genes such as 28S rRNA and Cytochrome C Oxidase I (COI), and then develop species-specific primers for eight macroinvertebrates listed as Species of Greatest Conservation Need (SGCN) in Texas. After sampling for the target species, five were not found, all of which were in the Order Trichoptera (caddisflies). A sixth target species, Isoperla sagittata, was found to have only one gap and …

The Effects Of Early Exposure To Prescription/Illicit Drugs And Drug Metabolites On Larval Zebrafish Behavioral And Motor Function Development, Jacob Thomas, Dena Weinberger, Bikram Subedi, Brandon Capps

Murray State Theses and Dissertations

THE EFFECTS OF EARLY EXPOSURE TO PRESCRIPTION/ILLICIT DRUGS AND DRUG METABOLITES ON LARVAL ZEBRAFISH BEHAVIORAL AND MOTOR FUNCTION DEVELOPMENT

A Thesis Presented to the Faculty of the Department of Biology

Murray State University

Murray, Kentucky

In Partial Fulfillment of the Requirements for the Degree of Masters In Science

By Jacob Thomas, B.S., Murray State University

December 2024

Acknowledgements

Brandon Capps, who pretty much did a whole third of the legwork on this project and saved me lots of headaches;

Chandler Maddox, one of the University of Kentucky’s finest undergrads who came in from the top rope with a folding chair …

Do Duckweeds Adapt To Water And Microbes?, Ava M. Rose

Honors Theses and Capstones

Organisms in their home environment sometimes outperform transplanted individuals native to other areas, in a phenomenon termed local adaptation. While local adaptation is traditionally considered to be driven by the abiotic factors of an environment, scientists have recently increased consideration of biotic factors. Specifically, of interest to many is host-associated microbiomes, which can alter host trait expression. As the desire to commercialize microbiome treatments for agriculture and medicine grows, it is important to analyze the potential value of local microbiomes, which may be adapted to their hosts, or to which local hosts may have adapted. Using Lemna minor (duckweed) as …

Genetic Diversity Of Paxistima Canbyi A. Gray: Conserving A Rare Plant Species Endemic To The Eastern United States, Isaac Buabeng

Master’s Theses

Premise: The glacial cycles of the Pleistocene period likely had a profound impact on the genetic diversity and phylogeographic patterns of numerous plant taxa in North America. However, the genetic diversity of rare, limestone-endemic woody species has not been highlighted. This study assesses genetic diversity in Paxistima canbyi A. Gray (Canby’s mountain lover or rat stripper), a rare limestone endemic small woody plant.

Methods: We investigated the genetic diversity of P. canbyi using genomic Single Nucleotide Polymorphism (SNP) data from 165 individuals from 14 populations sampled from across the entire range distribution. We first; de novo assembled the SNP …

Ribosome Hibernation Factor Induces Antibiotic Persisters Of Mycobacterium Tuberculosis In Neutrophil-Rich Lung Lesions, Jamie Corro

Electronic Theses & Dissertations (2024 - present)

Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, is a prescient global health threat and the leading cause of death by an infectious agent. Treatment of Mtb infection involves administering 2-4 antibiotics for a minimum of 6 months. This extended drug regimen is required to target a subpopulation of persistent bacilli. As their name implies, these bacteria can “persist” by acquiring nonhereditary and transient antibiotic tolerance. Although the precise mechanism is unknown, it’s often attributed to slowing cellular growth and metabolic processes. During zinc deprivation, bacteria can remodel their ribosomes by replacing their zinc-binding paralogues containing the CXXC motif (C+) …

Developing Cellular Systems To Elucidate Rna Structural Dynamics Of Cag Expansion Transcripts In Spinocerebellar Ataxias, Victoria Demeo

Electronic Theses & Dissertations (2024 - present)

Spinocerebellar ataxias (SCAs) are a diverse group of over 40 genetically heterogeneous neurodegenerative disorders, many of which are caused by a trinucleotide CAG repeat expansion in the coding region of specific genes. These expansions lead to the production of polyglutamine (polyQ) tracts that interfere with normal protein function, triggering cellular dysfunction and contributing to disease pathogenesis. The most well-known of these SCAs, such as SCA1, SCA2, and SCA3, exhibit progressive neurodegeneration, yet the precise mechanisms through which these mutations cause disease remain poorly understood.

A significant challenge in studying CAG repeat expansion disorders lies in the complexity of the disease …

Csn-5: A Tumor's Friend Or Foe In The C. Elegans Germline?, Kellie C. Kuch

Graduate Student Theses, Dissertations, & Professional Papers

The COP9 signalosome is a highly conserved eukaryotic complex regulating protein degradation via deneddylation of Cullin-RING E3 ligases. CSN5, the COP9’s fifth component, contains the catalytically active domain for CSN deneddylation. The complex is inactive without CSN5; however, CSN5 engages in COP9-independent binding with several other proteins, typically promoting either destruction or stabilization of its partners. Many of its confirmed interaction partners are also implicated in tumorigenesis (prominent examples being p27 and p53) and a complex cancer interactome has been established for CSN5. Additionally, CSN5 overexpression has been documented in a staggering array of cancers of diverse origins. This discovery …