Molecular Genetics Commons^™

Mechanisms Of Trinucleotide Repeat Instability During Dna Synthesis, Kara Y. Chan

Theses and Dissertations--Toxicology and Cancer Biology

Genomic instability, in the form of gene mutations, insertions/deletions, and gene amplifications, is one of the hallmarks in many types of cancers and other inheritable genetic disorders. Trinucleotide repeat (TNR) disorders, such as Huntington’s disease (HD) and Myotonic dystrophy (DM) can be inherited and repeats may be extended through subsequent generations. However, it is not clear how the CAG repeats expand through generations in HD. Two possible repeat expansion mechanisms include: 1) polymerase mediated repeat extension; 2) persistent TNR hairpin structure formation persisting in the genome resulting in expansion after subsequent cell division. Recent in vitro studies suggested that a …

Exploration Of Sonic Hedgehog Gene Expression In Fathead Minnows (Pimephales Promelas), Brooke Renee Greiner

Undergraduate Honors Theses

Pollutants, as a result of wastewater treatments, have been shown to have negative impacts on aquatic ecosystems. To better understand the possible consequences caused by effluents on ecosystems, it is important to examine ecotoxicology data. One of the most commonly used species for water quality testing is the fathead minnow, Pimephales promelas. Ecotoxicology can then be taken one step further to understand the effects of pollutants on a molecular level. Previous research had identified effluents as causes for abnormal minnow fin morphology. In order to collect additional data on development, tanks with fathead minnows were placed at the Charleston …

Effects Of A Systemic High Urea Concentration On The Endometrial And Embryonic Transcriptomes Of The Mare, Yatta Linhares Boakari

Theses and Dissertations--Veterinary Science

Pregnancy loss remains a major source of economic cost to the equine industry. Frequently, the exact causes of pregnancy loss remain unknown. It has been shown, in other species, that increased dietary protein leading to elevated blood urea nitrogen concentrations (BUN) can be a factor in decreased survival of the early embryo. Our studies provided novel information regarding the effects of elevated BUN on endometrium and embryos from mares as well as insights on changes in their gene expression. Our first objective was to develop an experimental model to elevate BUN during diestrus using intravenous urea infusion. We analyzed the …

Genome-Wide Systems Genetics Of Alcohol Consumption And Dependence, Kristin Mignogna

Theses and Dissertations

Widely effective treatment for alcohol use disorder is not yet available, because the exact biological mechanisms that underlie this disorder are not completely understood. One way to gain a better understanding of these mechanisms is to examine the genetic frameworks that contribute to the risk for developing this disorder. This dissertation examines genetic association data in combination with gene expression networks in the brain to identify functional groups of genes associated with alcohol consumption and dependence.

The first study took advantage of the behavioral complexity of human samples, and experimental capabilities provided by mouse models, by co-analyzing gene expression networks …

Phenotypic Characterization Of Pnpase Mutation And Overexpression In C. Elegans, Brian J. Hur

Theses and Dissertations

PNPase, polynucleotide phosphorylase, is a multifunctional exoribonuclease protein with 3` terminal oligonucleotide polymerase activity. Coded by the PNPT1 gene, the protein is associated with mitochondrial homeostasis and functions as a possible target for cancer therapy. In this study, C. elegans was used to investigate the effect of mutation and overexpression of pnpt-1, the gene that encodes PNPase. It was determined that two specific mutations in pnpt-1 did not affect PNPase expression nor did they produce deleterious phenotypes that affected polycistronic transcript accumulation or ROS production. Creation of a stable overexpression model was achieved through Fusion PCR. However, different transgenic …

Testing For Cryptic Diversity And Inference Of Population Structure In The Cosmopolitan Hoplonemertean Emplectonema Gracile (Nemertea), Paul L. Delaney Iv

Theses and Dissertations

Emplectonema gracile (Johnston 1837) is a hoplonemertean of marine intertidal hard-bottom communities and is distributed throughout the Northern Hemisphere. Although possessing a planktonic larval stage in its life history, the range of such cosmopolitan marine invertebrate species is often explained by cryptic speciation and anthropogenic transport. The purpose of this study is to test for possible cryptic species using mtDNA markers (COI and 16S rDNA) and to investigate population structure in E. gracile over a portion of its geographic range using mtDNA markers and ddRADseq nuclear SNP data. The results of both phylogenetic- and tree-based species delimitation revealed that E. …

Regulation Of Cancer-Specific Mirnas By Mda-7/Il-24, Danielle Scheunemann

Theses and Dissertations

Melanoma differentiation associated gene 7/Interleukin-24 (MDA-7/IL-24) is a secreted cytokine which acts as a tumor suppressor. It is capable of selectively killing cancer cells, regardless of anatomic origin, while sparing normal cells. miRNAs are master regulators of gene expression that can play two roles in cancer: tumor-suppression and oncogenesis. We identified a number of miRNAs that are regulated by MDA-7/IL-24 using a PCR plate array containing probes for miRNAs known to play a role in prostate cancer. We independently validated the array with qRT-PCR to identify three miRNAs which are downregulated by MDA-7/IL-24 treatment in DU145, PC3, and PC3ML prostate …

Genetic And Environmental Factors Influence Drosophila Ethanol Sedation, Rebecca E. Schmitt

Theses and Dissertations

Alcohol use disorder is a global health issue that affects a significant portion of the population, with affects including both negative mental and physical consequences. Currently, there are few treatment options available to those who suffer from alcohol use disorder, alcohol abuse, or alcohol dependence. Identifying candidate genes or environmental influences would therefore improve the means for possible treatments or identification of those people at risk for alcohol use disorder. Previous studies in humans have demonstrated an inverse association between initial sensitivity and risk for alcohol abuse. This connection allows investigators, and our laboratory, to investigate genetic and environmental factors …

Aeg-1 Knockout Sensitizes Hepatocellular Carcinoma (Hcc) Cells To Ionizing Radiation, Maheen Khan

Theses and Dissertations

Liver cancer is the fourth leading cause of cancer-associated deaths globally, and among primary liver cancers, hepatocellular carcinoma (HCC) encompasses 75-85% of all cases. HCC is a highly lethal disease due to limited treatment options – only a small subset of patients qualify for surgical resection or transplantation; the remaining patients often display resistance to radiation therapy or chemotherapy. Overexpression of the oncogene astrocyte elevated gene-1 (AEG-1) is associated with poorer survival and increased tumor recurrence in HCC, and numerous studies show its role in initiation of hepatocarcinogenesis. A prior study also demonstrated AEG-1 expression inhibits senescence by diminishing the …

Characterization Of Nodule-Specific, Slac And Mate Membrane Transporters In Medicago Truncatula, Lina Yang

Graduate Theses, Dissertations, and Problem Reports (ETD)

Legumes play a crucial role in sustainable agriculture because of their intrinsic ability to reduce atmospheric N₂ into NH₃ via symbiotic nitrogen fixation (SNF). SNF is carried out in the symbiosome, a quasi-organelle containing endosymbiotic rhizobial bacteria in the cytoplasm of infected cells of the nodule. Therefore, the bacteria are surrounded by a symbiosome membrane (SM), which is derived from the plant plasma membrane during infection. SNF requires constant nutritional exchanges between symbionts, including reduced carbon (dicarboxylates) from the plant for reduced nitrogen (NH₄⁺) from the bacteroids. This exchange of nutrients and signals is fundamental …

Genetic Regulation Of The Elicitation Of Glyceollin Biosynthesis In Soybean, Md. Asraful Jahan

Graduate Theses, Dissertations, and Problem Reports (ETD)

Glyceollin phytoalexins are the pathogen-elicited defense metabolites that belong to the isoflavonoid family of molecules of soybean (Glycine max L. Merr). Phytophthora root and stem rot of soybean caused by Phytophthora sojae is a destructive disease throughout the soybean-growing regions worldwide causing devastating economic damages (globally $1-2 billion and over $250 million in the USA) every year. Engineering soybean plants that produce higher levels of glyceollins could confer resistance against this pathogen. Glyceollins also show anticancer and neuroprotective activities in mammals, therefore they are important for agriculture and medical research. Firstly, we were interested in understanding how biotic and …

Exploring The Efficacy Of Natural Products In Alleviating Alzheimer’S Disease Using Animal Models, Prajakta Deshpande, Neha Gogia, Amit Singh

Biology Faculty Publications

Alzheimer’s disease (hereafter AD) is a progressive neurodegenerative disorder that affects the central nervous system. There are multiple factors that cause AD, viz., accumulation of extracellular Amyloid-beta 42 plaques, intracellular hyper-phosphorylated Tau tangles, generation of reactive oxygen species due to mitochondrial dysfunction and genetic mutations. The plaques and tau tangles trigger aberrant signaling, which eventually cause cell death of the neurons. As a result, there is shrinkage of brain, cognitive defects, behavioral and psychological problems. To date, there is no direct cure for AD. Thus, scientists have been testing various strategies like screening for the small inhibitor molecule library …

The Impact Of Household Biocides And Antibiotics On Aquatic Microbial Community Composition, Abdulaziz Saud M Alrashdi

Dissertations, Master's Theses and Master's Reports

Triclosan (TCS) is antimicrobial agent that is used in a lot of consumer products, including toothpaste, liquid and bar soap, and cosmetics. TCS has been found in many lakes and rivers in the United States. However, The Food and Drug Administration (FDA) banned TCS recently and it will no longer be used in household products. Despite the recent ban, TCS is known to persist in the environment and may have long-term impacts. We conducted an experiment on using fresh water from three locations Houghton, Green Bay and the Huron Mountains. Our goals in the study is to assess the impact …

Mutations Of Fus Cause Aggregation Of Rna Binding Proteins, Disruptions In Protein Synthesis, And Dysregulation Of Nonsense Mediated Decay, Marisa Elizabeth Kamelgarn

Theses and Dissertations--Toxicology and Cancer Biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron death and subsequent muscle atrophy. Approximately 15% of ALS cases are inheritable, and mutations in the Fused in Sarcoma (FUS) gene contribute to approximately 5% of these cases, as well as about 2% of sporadic cases. FUS performs a diverse set of cellular functions, including being a major regulator of RNA metabolism. FUS undergoes liquid- liquid phase transition in vitro, allowing for its participation in stress granules and RNA transport granules. Phase transition also contributes to the formation of cytoplasmic inclusions found in the …

Impact Of Seasonal And Host-Related Factors On The Intestinal Microbiome And Cestode Community Of Sorex Cinereus And Sorex Monticola, Katelyn D. Cranmer

College of Graduate Studies: Theses & Dissertations

The intestinal microbiome of mammals plays a significant role in host health and response to environmental stimuli and can include both beneficial native bacteria as well as parasitic worms. In this study, I examined the intestinal cestode and bacterial communities of two closely related species of shrew, Sorex monticola and Sorex cinereus, over a six month period in 2016. Specimens were collected approximately every three weeks from May to October from the Sangre de Cristo Mountains in Cowles, New Mexico. A total of 79 shrews were prepared with the gastrointestinal tracts removed and flash-frozen in liquid nitrogen. An additional …

Glial Cell Expansion And Intercellular Signaling In The Developing Medial Nucleus Of The Trapezoid Body (Mntb), Ashley N. Brandebura

Graduate Theses, Dissertations, and Problem Reports (ETD)

Neural circuit formation is a complex process involving coordinated communication between neurons, glia and vascular-associated cells (VACs). Each cell type is responsible for a unique transcriptional and translational contribution to tissue maturation. Deciphering the intercellular signaling patterns which guide neural circuit formation during normal development is thus an essential step in understanding which components of neural circuit formation go awry in neurodevelopmental disorders. The medial nucleus of the trapezoid body (MNTB), located in the auditory brainstem, was used as a model system to study the dynamics of neural circuit formation because it contains a mostly homogeneous population of postsynaptic neurons …

Enhancing Water Stress Tolerance In Floriculture Crops, Suejin Park

Graduate Theses, Dissertations, and Problem Reports (ETD)

Water deficit is one of the major constraints on plant growth and development, causing reduction of crop productivity. To minimize water loss, among many adaptation strategies, plants close their stomata to reduce transpiration. The stomatal closure is regulated by light, internal CO2 concentration, and plant hormones, mainly abscisic acid. Plants’ response mechanisms to water deficit are complex processes involving numerous genes and various signaling pathways. Floriculture crops are often exposed to water deficit during shipping and retailing, and these periods often result in damaged crops and profit loss. Understanding of plant responses to water deficit stress will provide us an …

Effects Of Commercial Formulations Of Glyphosate On Saccharomyces Cerevisiae, Apoorva Ravi Shankar

Graduate Theses, Dissertations, and Problem Reports (ETD)

Commercial formulations of glyphosate are among the most extensively used herbicides around the world. The active ingredient, glyphosate, targets the aromatic amino acid pathway. This pathway is absent in mammals, resulting in low toxicity. Different formulations contain varying adjuvants and surfactants, whose synergistic effects are yet to be extensively studied at the cellular level. In this study, I tested multiple commercial formulations that showed a variation in growth phenotype among different yeast strains. To gain a better understanding of response and resistance mechanisms at the genome and transcriptome level, I carried out an in-lab evolution study, along with a transcriptome …

Association Genetics And Local Adaptation Of Populus Trichocarpa Torr. & Gray, Hari Bahadur Chhetri

Graduate Theses, Dissertations, and Problem Reports (ETD)

A major goal in plant science is overcoming the recalcitrance of plant biomass to cellulose extraction, to enable efficient production of cellulosic biofuel. We have started to understand the genetic basis of some important traits such as cell wall chemistry, but we do not know anything about the key structural and functional traits such as wood anatomy that greatly affect plant biomass recalcitrance. Furthermore, biofuel feedstocks have to be adapted to varied environmental conditions to ensure high productivity in plantations, but little is known about the molecular mechanisms underlying local adaptation. With the advancement in sequencing and genotyping technologies, association …

Insects And The Evolution Of Developmental Pathways: Functional Analysis Of Genetic Sex Determination Mechanisms In Oncopeltus Fasciatus, Josefine Just

Honors Theses

Natural selection alters genetic pathways over evolutionary time. However, different pathways have been shown to maintain mutations at varying rates, leading to different levels of conservation across developmental pathways. Sex determination pathways, in particular, show vast diversity across animals despite the fundamental conservation of biological sex itself. Here, I investigated the sex determination pathway of the hemimetabolous insect, Oncopeltus fasciatus. The large milkweed bug, O. fasciatus, is part of the order Hemiptera, which provides a relevant outgroup study to other insects in which sex determination has been studied to date. I studied three sex determination genes, intersex, fruitless …