Life Sciences Commons^™

Dengue Virus Modulation Of Genome Instability In Vero E6 Cells, Erica Nicole Lamkin

Graduate College Dissertations and Theses

Dengue virus (DENV) is the fastest-spreading arthropod-borne virus in the world. Dengue is characterized as a major global public health challenge in tropical and subtropical nations by the World Health Organization. The number of dengue cases globally has increased 8-fold in the past two decades, with 100 to 400 million cases occurring annually. While most patients with dengue fever are asymptomatic, dengue infection carries the possibility of severe and potentially fatal febrile illness. Approximately 1 in 4 individuals infected with dengue virus develop symptomatic dengue infection, often presenting as mild to moderate, nonspecific, acute febrile illness. A smaller subset of …

Implications Of Population Genetics And Physiological Responses On The Conservation Of Moose (Alces Alces Americana), Elias Rosenblatt

Graduate College Dissertations and Theses

Wildlife populations around the globe are facing numerous, complex challengesto their persistence, yet conservation efforts are hindered by limited information about these populations and the anthropogenic pressures they face. North American moose (Alces alces americana), despite being of ecological, cultural, and economical importance, inhabit remote landscapes, making population monitoring difficult. At the same time, many moose populations, including in Vermont and eastern North America, have experienced recent declines mainly due to winter tick (Dermacentor albipictus) epizootics. Anthropogenic landscape change and climate-mediated pressures pose future challenges for moose across the southern extent of their distribution. Though impacts of winter tick infestation …

Systems Approaches For Gene And Drug Discovery In Alzheimer’S Disease, Jeffrey Brabec

Graduate College Dissertations and Theses

Alzheimer’s Disease (AD) is a devastating neurodegenerative disorder affecting all tissues and cell types of brain leading to emotional dysregulation and cognitive dysfunction. From genome-wide association studies (GWAS), to date we have identified forty-two genome-wide significant genes for AD that influence overall disease risk or endophenotypes, including neuroimaging and gene expression profiles. Nevertheless, the currently known AD genes do not account for a significant proportion of the heritability of disease risk, implying the existence of many weak-effect variants in potentially thousands of genes as drivers of AD outcomes. This genetic architecture, composed of many small effects, is partly due to …

Characterization Of Higher Order Chromatin Structures And Chromatin States In Cell Models Of Human Herpesvirus Infection, Michael Mariani

Graduate College Dissertations and Theses

Human herpesviruses are ubiquitous pathogens worldwide with 90% of the global population infected with one or more Human herpesviruses (HHV’s) by adulthood. All herpesviruses have three unique life cycle stages. Upon resolution of a primary acute stage infection, they can establish a latent stage infection within the host cell nucleus. This stage is characterized primarily by transcriptional quiescence of the viral genome. Specific physiological conditions (e.g., cell stress) can cause the latent virus to enter the reactivation stage, often many years after resolution of the acute infection, in which the virus becomes replicationally active again. HHV’s are known to cause …

Mutations In Ikaros Lead To An Altered Epigenetic And Chromatin Landscape Contributing To The Manifestation Of B-Cell Related Disorders, Princess Rodriguez

Graduate College Dissertations and Theses

IKAROS is expressed throughout the entire hematopoietic system and is required for lymphoid commitment and subsequent differentiation towards the B-lymphoid fate. If absent, progenitor and mature B-cell subsets are not expressed. IKAROS (encoded by IKZF1) is a zinc-finger transcription factor shown to regulate gene expression either directly or through the recruitment of chromatin remodeling complexes. The epigenetic gene regulatory mechanisms, including the posttranslational modification to histone proteins, as well as the expression of noncoding RNAs (ncRNAs) are important to control as perturbations in these processes contribute to the manifestation of human diseases. If left unregulated, uncontrolled growth, aberrant cell activation, …

Rapid Evolution In Agroecosystems: Transposable Elements And Epigenetics In The Colorado Potato Beetle, Kristian Brevik

Graduate College Dissertations and Theses

Within agricultural ecosystems, humans and insects enter into complex relationships. Humans consider many of these insects to be pests, and exert significant pressures upon them, such as efforts to kill them using insecticides. One of the ways insects respond to these efforts is by rapidly evolving resistance to insecticides - but how they do this is not fully understood. DNA methylation, an epigenetic mechanism, and transposable elements, which are mobile genetic elements within genomes, may each play a role in shaping the way insects rapidly evolve in response to exposure to insecticides. Understanding the role of transposable elements and DNA …

The Utilization Of Host-Derived Compounds By Gram-Negative Bacteria, Lauren Alexandra Hinkel

Graduate College Dissertations and Theses

The increase in multidrug resistance (MDR) among bacterial pathogens is an ongoing threat to public health, with the CDC estimating more than 2.8 million MDR infections in the United States each year, and greater than 35,000 deaths annually. Gram-negative bacteria possess intrinsic mechanisms to resist available therapeutics and are frequently responsible for difficult-to-treat nosocomial, blood stream, and soft tissue infections. In addition to biophysical and genetic MDR mechanisms, Gram negatives are metabolically versatile, enabling them to utilize host-derived nutrients to promote proliferation and colonization within the host. The metabolic versatility of Gram-negative bacteria is due, in part, to the transcription …

The Potential Of Refugee Seed Systems To Promote Contemporary Adaptation In Traditional Crops: A Case Study Of African Maize In New England, Andi Kur

Graduate College Dissertations and Theses

There are many mechanisms by which landraces evolve in a contemporary agricultural setting; however, the influence of forced human migration on landrace redistribution and evolution has received little attention in comparison to the stochastic effects of drift, mutation, and gene flow in the centers of origin. Although the seed systems of forcedly-displaced people remain poorly understood, evidence suggests that refugees often continue to grow traditional crops after resettlement. From a genetics perspective, the crops that are transported to highly disparate environments provide an interesting opportunity to study adaptation.

This research addresses how forced human migration has impacted contemporary landrace evolution …

Genetic And Functional Approaches To Understanding Autoimmune And Inflammatory Pathologies, Abbas Raza

Graduate College Dissertations and Theses

Our understanding of genetic predisposition to inflammatory and autoimmune diseases has been enhanced by large scale quantitative trait loci (QTL) linkage mapping and genome-wide association studies (GWAS). However, the resolution and interpretation of QTL linkage mapping or GWAS findings are limited. In this work, we complement genetic predictions for several human diseases including multiple sclerosis (MS) and systemic capillary leakage syndrome (SCLS) with genetic and functional data in model organisms to associate genes with phenotypes and diseases.

Focusing on MS, an autoimmune inflammatory disease of the central nervous system (CNS), we experimentally tested the effect of three of the GWAS …

Maintenance Of Mammary Epithelial Phenotype By Transcription Factor Runx1 Through Mitotic Gene Bookmarking, Joshua Rose

Graduate College Dissertations and Theses

Breast cancer arises from a series of acquired mutations that disrupt normal mammary epithelial homeostasis and create multi-potent cancer stem cells that can differentiate into clinically distinct breast cancer subtypes. Despite improved therapies and advances in early detection, breast cancer remains the leading diagnosed cancer in women.

A predominant mechanism initiating invasion and migration for a variety of cancers including breast, is epithelial-to-mesenchymal transition (EMT). EMT— a trans-differentiation process through which mammary epithelial cells acquire a more aggressive mesenchymal phenotype—is a regulated process during early mammary gland development and involves many transcription factors involved in cell lineage commitment, proliferation, and …

Understanding The Role Of Androgen Receptor Signaling In Modulating P38-Alpha Mitogen-Activated Protein Kinase In Experimental Autoimmune Encephalomyelitis, Grace Kathryn Voorhees

Graduate College Dissertations and Theses

Multiple Sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system, characterized by axonal demyelination and multifocal inflammation. Like many autoimmune diseases, it is a sexually dimorphic disease, being 3-4 times more common in females than in males. p38α MAP kinase (MAPK) has an integral role in modulating inflammatory processes in autoimmunity. Conditionally ablating p38α MAPK in myeloid cells in B6 mice shows a sex difference in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). In the absence of sex hormones, this sex difference was reversed, suggesting a role for sex hormones in modulating p38α MAPK signaling …

Cisco Science: Using Omics To Answer A Range Of Key Questions, Hannah Lachance

Graduate College Dissertations and Theses

Coregonines, including cisco (Coregonus artedi), kiyi (Coregonus kiyi), and bloater (Coregonus hoyi), are a focus for prey fish conservation and restoration efforts throughout the Laurentian Great Lakes. However, fundamental questions about coregonine ecology and genetics remain. For example, we know little about how the early life stages of coregonines respond to environmental change at either the genotypic or phenotypic level. We also have limited knowledge about how to identify different species at the larval stage and the genetic relationships among species, which makes the different species difficult to study at the larval stage. To increase the probability for success in …

Evidence For The Involvement Of Runx1 And Runx2 In Maintenance Of The Breast Cancer Stem Cell Phenotype, Mark Fitzgerald

Graduate College Dissertations and Theses

In the United States, metastatic breast cancer kills approximately 40,000 women and 400 men annually, and approximately 200,000 new cases of breast cancer are diagnosed each year. Worldwide, breast cancer is the leading cause of cancer deaths among women. Despite advances in the detection and treatment of metastatic breast cancer, mortality rates from this disease remain high because the fact is that once metastatic, it is virtually incurable. It is widely accepted that a major reason breast cancer continues to exhibit recurrence after remission is that current therapies are insufficient for targeting and eliminating therapy-resistant cancer cells. Emerging research has …

Genetic And Demographic Consequences Of Lake And River Habitat Fragmentation On Fishes In Vermont, Peter T. Euclide

Graduate College Dissertations and Theses

Globally, habitat fragmentation has had a major impact on the conservation and management of many species and is one of the primary causes of species extinction. Habitat fragmentation is loosely defined as a process in which a continuous habitat is reduced to smaller, disconnected patches as the result of habitat loss, restriction of migration or the construction of barriers to movement. Aquatic systems are particularly vulnerable to habitat fragmentation, and today an estimated 48% of rivers are fragmented worldwide. My dissertation evaluates how habitat fragmentation has influenced the populations of four different species of fish in the Lake Champlain basin. …

Characterization Of A Novel Vps26c-Retromer Complex And Its Interaction With An Endosomal Trafficking Pathway Regulated By The Snare Vti13 In Controlling Polarized Growth And Cell Wall Organization In Arabidopsis Thaliana, Suryatapa Ghosh Jha

Graduate College Dissertations and Theses

The endosomal trafficking system is a network of highly coordinated cellular pathways that control the growth and function of cells. The coordination of secretion and endocytosis in cells is one of the primary drivers of polarized growth, where new plasma membrane and cell wall components are deposited at the growing apex. In plants, one of the cell types exhibiting polarized growth are the root hairs. Root hairs are regulated extensions of epidermal cells called trichoblasts and are essential for anchorage, absorption of water and nutrients, and plant-microbe interactions. In this thesis, I characterize a previously undescribed protein involved in retromer …

Evolution Of Duplicated Han-Like Genes In Petunia X Hybrida., Beck Powers

Graduate College Dissertations and Theses

Gene duplications generate critical components of genetic variation that can be selected upon to affect phenotypic evolution. The angiosperm GATA transcription factor family has undergone both ancient and recent gene duplications, with the HAN-like clade displaying divergent functions in organ boundary establishment and lateral organ growth. To better determine the ancestral function within core eudicots, and to investigate their potential role in floral diversification, I conducted HAN-like gene expression and partial silencing analyses in the asterid species petunia (Petunia x hybrida). My results indicate duplication of HAN-like genes at the base of Solanaceae followed by expression diversification within the flower. …

Target Identification Strategies For Mmv Malaria Box Inhibitors Of Toxoplasma Gondii Growth, Jenna Elizabeth Foderaro

Graduate College Dissertations and Theses

Small molecule screening is commonly used to discover lead compounds for drug development, but it can also be a powerful way to identify chemical probes for studying biological mechanisms. Our lab uses small molecules to study the mechanisms by which the protozoan parasite Toxoplasma gondii infects and replicates within its hosts. In this work, we employed a fluorescence-based assay to screen the Medicines for Malaria Venture (MMV) Open Access Malaria box for compounds that affect T. gondii growth. The box contains 400 previously identified small-molecule inhibitors of the related parasite, Plasmodium falciparum. We identified 79 hits, including a 2,4-diaminoquinazoline (MMV006169; …

Assessing Community Dynamics And Colonization Patterns Of Tritatoma Dimidiata And Other Biotic Factors Associated With Chagas Disease Prevalence In Central America, Lucia Consuelo Orantes

Graduate College Dissertations and Theses

Chagas disease is caused by the parasite Trypanosoma cruzi and transmitted by multiple triatomine vectors across the Americas. In Central America, the predominant vector is Triatoma dimidiata, a highly adaptable and genetically diverse Hemiptera. In this research, we used a novel reduced-representation DNA sequencing approach to discover community dynamics among multiple biotic factors associated with Chagas disease in Central America, and assess the infestation patterns of T. dimidiata after seasonal and chemical disturbances in Jutiapa, Guatemala. For our first study, we used a hierarchical sampling design to obtain multi-species DNA data found in the abdomens of 32 T. dimidiata …

The Cardiovascular Epidemiology And Genome-Wide Associations Of Biomarkers Of Innate And Adaptive Immunity: Scd163 And Sil2ra, Jon Peter Durda

Graduate College Dissertations and Theses

Cardiovascular disease (CVD) is a major cause of morbidity and mortality in the U.S. and worldwide. Atherosclerosis, the buildup of plaque in the arteries, is a common cause of CVD. For many years, research in atherosclerosis was focused on lipid metabolism and the accumulation of low-density lipoprotein in the arteries. While this research set public health guidelines for lipid management, lipid concentration was not the only factor influencing atherosclerosis and CVD events. Many scientists, as far back as the 1850’s recognized the role of inflammation in the progression of atherosclerotic disease. The continuous low levels of immune activation in the …

Integrating Human Population Genetics And Genomics To Elucidate The Etiology Of Brain Disorders, Arvis Sulovari

Graduate College Dissertations and Theses

Brain disorders present a significant burden on affected individuals, their families and society at large. Existing diagnostic tests suffer from a lack of genetic biomarkers, particularly for substance use disorders, such as alcohol dependence (AD). Numerous studies have demonstrated that AD has a genetic heritability of 40-60%. The existing genetics literature of AD has primarily focused on linkage analyses in small family cohorts and more recently on genome-wide association analyses (GWAS) in large case-control cohorts, fueled by rapid advances in next generation sequencing (NGS). Numerous AD-associated genomic variations are present at a common frequency in the general population, making these …

Mechanisms And Dynamics Of Oxidative Dna Damage Repair In Nucleosomes, Wendy J. Cannan

Graduate College Dissertations and Theses

DNA provides the blueprint for cell function and growth, as well as ensuring continuity from one cell generation to the next. In order to compact, protect, and regulate this vital information, DNA is packaged by histone proteins into nucleosomes, which are the fundamental subunits of chromatin. Reactive oxygen species, generated by both endogenous and exogenous agents, can react with DNA, altering base chemistry and generating DNA strand breaks. Left unrepaired, these oxidation products can result in mutations and/or cell death. The Base Excision Repair (BER) pathway exists to deal with damaged bases and single-stranded DNA breaks. However, the packaging of …

The Molecular Evolution Of Non-Coding Dna And Population Ecology Of The Spiny Softshell Turtle (Apalone Spinifera) In Lake Champlain, Lucas Edward Bernacki

Graduate College Dissertations and Theses

ABSTRACT

Spiny softshell turtles (Apalone spinifera) occur at the northwest limit of their range in Lake Champlain. This species, although widespread across North America, is listed as threatened in Vermont due to habitat destruction and disturbances of anthropogenic origin. The population of spiny softshell turtles in Lake Champlain is isolated from other North American populations and is considered as an independent management unit. Efforts to obtain information on the biology of spiny softshell turtles in Lake Champlain precede 1936 with conservation measures being initiated in 1987.

Methods of studying spiny softshell turtles in Lake Champlain have included direct …

Meckelin Functions In The Guided Movement And Orientation Of Basal Bodies Prior To Duplication In Paramecium Tetraurelia, Tyler August Picariello

Graduate College Dissertations and Theses

Ciliopathies are a group of disorders that arise from ciliary dysfunction. Meckelin (MKS3 or TMEM67) is a conserved transmembrane protein found at the transition zone of ciliated cells. In humans MKS3 is one of 3 genes linked to the ciliopathy Meckel Syndrome. This disease is characterized by occipital meningioencephalocoele, polycystic kidneys, fibrotic changes to the liver, postnatal polydactyly and situs inversus.

Paramecium tetraurelia is a single celled ciliated eukaryote. Its surface is organized of a meshwork of cortical units that run the length of the cell. At the center of the cortical units are either one or two basal bodies. …