Life Sciences Commons^™

Conservation And Variation Of Dna Methylation In Lactuca Sativa And Lactuca Serriola, Trudi A. Baker

Graduate Doctoral Dissertations

Molecular techniques for guiding plant breeding have successfully used wild progenitors of domestic crops as sources of genetic variants conveying desirable traits. However, epigenetic variation, in particular DNA methylation, is a significant source of phenotypic variation and epigenetic effects of plant domestication are poorly understood. Described herein are the first single-base pair resolution methylomes of the highly valued crop iceberg lettuce (Lactuca sativa cv. Salinas) and its close relative, and ubiquitous weed, L. serriola. This work suggests several roles for acquisition and inheritance of methylation in the evolution of Lactuca spp. in response to stress. The Lactuca spp. have conserved …

Analysis Of Argonaute-Small Rna-Transcription Factor Circuits Controlling Leaf Development, John Steen Hoyer

Arts & Sciences Electronic Theses and Dissertations

Experimental studies of plant development have yielded many insights into gene regulation, revealing interactions between core transcriptional and post-transcriptional regulatory pathways present in all land plants. This work describes a direct connection between the three main small RNA-transcription factor circuits controlling leaf shape dynamics in the reference plant Arabidopsis thaliana. We used a high-throughput yeast 1-hybrid platform to identify factors directly binding the promoter of the highly specialized ARGONAUTE7 silencing factor. Two groups of developmentally significant microRNA-targeted transcription factors were the clearest hits from these screens, but transgenic complementation analysis indicated that their binding sites make only a small contribution …

Prospective Associations Of Homocysteine, Executive Function, And Depressive Symptoms, Peter J. Dearborn

Electronic Theses and Dissertations

Associations of cardiovascular risk factors, cognitive performance, and depressive symptoms have been well established. However, the directionality of these associations as well as the specificity of these associations with respect to executive function are less clear. Additionally few studies have determined whether genetic risk factors, such as apolipoprotein-E4 (APOE-E4) genotype, and age moderate the associations of cardiovascular risk factors such as homocysteine with changes in depressive symptoms and how these associations may be mediated by cognitive performance. The primary aim of this study was to analyze the bidirectional associations of a full range of cognitive domains and symptoms of depression …

Knowledge Driven Approaches And Machine Learning Improve The Identification Of Clinically Relevant Somatic Mutations In Cancer Genomics, Benjamin John Ainscough

Arts & Sciences Electronic Theses and Dissertations

For cancer genomics to fully expand its utility from research discovery to clinical adoption, somatic variant detection pipelines must be optimized and standardized to ensure identification of clinically relevant mutations and to reduce laborious and error-prone post-processing steps. To address the need for improved catalogues of clinically and biologically important somatic mutations, we developed DoCM, a Database of Curated Mutations in Cancer (http://docm.info), as described in Chapter 2. DoCM is an open source, openly licensed resource to enable the cancer research community to aggregate, store and track biologically and clinically important cancer variants. DoCM is currently comprised of 1,364 variants …

Mechanism Of Gene Regulation By Coding Polya Tracks, Laura Lea Arthur

Arts & Sciences Electronic Theses and Dissertations

Regulation of gene expression is essential for cellular development and survival. The great variety and complexity of regulatory mechanisms underscores this fact. Messenger RNA stability and translational efficiency are often key determinants of gene expression. mRNA surveillance pathways, discovered for their role in degradation of aberrant mRNA, are now known to be instrumental in the regulation of physiologically correct mRNA stability. Thus, the study of cis elements in a transcript that can induce mRNA surveillance pathways has become an area of particular interest.

Here I report on the mechanism of gene regulation by coding polyA tracks, defined as a sequence …

The Role Of Orphan Nuclear Receptor Dax-1 (Nr0b1) In Human Breast Cancer Cells: Expression, Proliferation And Metastasis, Erin Dishington

Master's Theses

The orphan nuclear hormone receptor DAX-1 (Dosage Sensitive Sex Reversal, Adrenal Hypoplasia Congenita on the X Chromosome, gene 1) plays an important role in the development of adrenal and gonadal tissues and functions as a global negative-regulator of steroidogenesis. In addition, it is known to be involved in several diseases including some cancers. Herein, we describe our examination of the role of DAX-1 in breast cancer, specifically its influence on proliferation and metastasis and its expression during progressive stages of disease. In an effort to understand how DAX-1 influences breast cancer cell proliferation and metastasis, we used MCF7 breast cancer …

Analysis Of Diagnostic, Preventive, And Disease-Modifying Therapeutic Measures Of Alzheimer’S Disease, Ghazal Habib Havoutis

HCNSO Student Capstones

Alzheimer’s disease (AD) is the most common late-onset neurodegenerative disorder and cause of dementia, characterized by the formation of neurofibrillary tangles and senile plaque deposits. The heterogeneous nature of the disease (both genetically and environmentally) makes it difficult to prevent or cure. Without prevention, the prevalence of AD is expected to triple by 2050. However, because the diagnosis of AD is usually preceded by years of cognitive impairment, early detection may aid in reducing prevalence. Thus, there is a need for validated diagnostic measures for early and improved diagnosis and prevention. In this review, current and ongoing classifiers of early …

Systematics And Biogeography Of The Cortinarius Violaceus Group And Sequestrate Evolution In Cortinarius (Agaricales), Emma Harrower

Doctoral Dissertations

Phylogenetics is a powerful tool used for illuminating the diversity of life on Earth, their evolution and their ecology. I created a multi-gene phylogenetic tree of Cortinarius section Cortinarius and uncovered five previously overlooked species, increasing the number of species in the section from seven to twelve. All members of the clade possess both cheilocystidia and pleurocystidia and possess a pigment known as (R)-39,49-dihydroxybphenylalanine. Ancestral state reconstruction estimated that the ancestral host was most likely an angiosperm, switching hosts when encountering novel host species in new lands, and only C. violaceus associating with the Pinaceae in North America. Biogeographic analysis …

Role Of Incompatibility Group 1 (Inci1) Plasmid-Encoded Factors On Salmonella Enterica Antimicrobial Resistance And Virulence, Pravin Raghunath Kaldhone

Graduate Theses and Dissertations

Foodborne illnesses are a leading cause of infectious diseases in the world. Among enteric organisms Salmonella is a key pathogen. It’s high prevalence in poultry and other food-animal sources make it imperative to study. Salmonella has the ability to modify its genetic content with help of mobile genetic elements such as plasmids. Incompatibiltiy group 1 (IncI1) plasmids are commonly reported in Salmonella. This study evaluates role on IncI1 plasmids in antimicrobial resistance and virulence in Salmonella. Genetic determinants of resistance and virulence are noted among our IncI1-containing Salmonella isolates. These genetic elements are also transferable and reported to carry respective …

Development Of New Bioinformatic Approaches For Human Genetic Studies, Jose Andres Guevara Coto

All Dissertations

The development of bioinformatics methods for human genetic studies utilizes the vast amount of data to generate new valuable information. Machine learning and statistical coupling analysis can be used in the study of human diseases. These diseases include intellectual disabilities (ID), prevalent in 1-3% of the population and caused primarily by genetics. Although many cases of ID are caused by mutations in protein-coding genes, the possible involvement of long non-coding RNAs (lncRNAs) in ID due to their role in gene expression regulation, has been explored. In this study, we used machine learning to develop a new expression-based model trained using …

Quality Of Life: Socio-Demographic And Genetic Determinants As Well As Links With Cancer Outcomes, Jeanne Pierzynski

Dissertations & Theses (Open Access)

Quality of life (QOL) is an independent prognostic factor for cancer. Lung cancer is the leading cause of cancer death. Breast cancer is the most diagnosed. Bladder cancer is the most expensive cancer to treat because of its high recurrence rate. We set to perform comprehensive analyses of predictors of QOL in these cancer sites with the future goal of improving QOL and outcomes.

In 6,456 newly diagnosed lung cancer patients, we investigated the relationship between baseline patient characteristics and QOL to identify determinants of QOL. A QOL questionnaire (SF-12v1) measured patients’ physical component summary (PCS) and mental component summary …

This Is Just A Phase : The Impact Of Population Structure On Haplotype Phasing And Linkage Disequilibrium Measures At Functional Genetic Sites., Roxanne Kaaren Leiter

Electronic Theses and Dissertations

The block-like structure of the human genome has been the subject of many scientific papers and is of practical significance in large-scale genome-wide association studies. How stringent haplotype block boundaries are within and between populations has been the subject of ongoing debate within human population genetics. This thesis will contribute to the description of universal and population-specific haplotype blocks at functional sites, namely across the IL-10 gene family (including IL-10, IL-19, IL-20 and IL-24), which is involved in a number of immune system processes, and MAPKAP-K2, an adjacent and functionally significant kinase gene. Beyond the description of blocks across these …

Chromatin Accessibility Dynamics In The Arabidopsis Root Epidermis And Endodermis During Cold Acclimation, Shawn Hoogstra

Electronic Thesis and Dissertation Repository

Understanding cell-type specific transcriptional responses to environmental conditions is limited by a lack of knowledge of transcriptional control due to epigenetic dynamics. Additionally, cell-type analyses are limited by difficulties in applying current technologies to single cell-types. A novel DNase-seq protocol and analysis procedure, deemed DNase-DTS, was developed to identify DHSs in the Arabidopsis epidermis and endodermis under control and cold acclimation conditions. Results identified thousands of DHSs within each cell-type and experimental condition. DHSs showed strong association to gene expression, DNA methylation, and histone modifications. A priori mapping of existing DNA binding motifs within accessible genes and the cold C-repeat/dehydration …

Characterizing Mekk1: Candidate Behavioural Isolation Gene, Caryn Dooner

Electronic Thesis and Dissertation Repository

Behavioural isolation can occur due to divergence in aspects of courtship and mating, and can contribute to reproductive isolation. The purpose of this study is to determine how a gene, Mekk1, contributes to female rejection behaviour between D. melanogaster and D. simulans. Unique polymorphisms were identified within D. simulans Mekk1 that could contribute to behaviour, most of which are non-coding. Both transcripts of Mekk1 appear to be expressed at similar levels in D. simulans and D. melanogaster. These data also indicate that Mekk1 may be expressed in a specific region of the brain called the mushroom body, …

Exploiting Fission Yeast Genetic Interaction Data To Identify Disease-Specific Drug Targets For Tuberous Sclerosis Complex, Ashyad Rayhan

Electronic Thesis and Dissertation Repository

Tuberous sclerosis complex (TSC) is an inherited genetic disorder caused by loss-of-function mutations in either TSC1 or TSC2. Their respective gene products regulate the mechanistic target of rapamycin (mTOR) signaling pathway, which serves as an activator of cellular proliferation, metabolism, and cell survival. Orthologs of the TSC1 and TSC2 genes exist in a wide range of organisms, including the commonly used and genetically tractable model eukaryote, Schizosaccharomyces pombe. To better understand the functional roles of S. pombe tsc1 and tsc2, I exploited recent advances in genetic interaction biology to identify and characterize genes that modulate the phenotypic …

Gene Expression Changes In The Mushroom Body Of Drosophila Melanogaster During A Time Course Of Long-Term Memory Formation And Maintenance, Spencer G. Jones

Electronic Thesis and Dissertation Repository

Long-term memory (LTM) requires gene transcription. However, there is still much to learn about which genes are transcriptionally regulated during LTM and the biological roles they play. Here, gene expression changes were characterized in Drosophila melanogaster over a time course of LTM formation and maintenance in neurons of the mushroom body (MB), a structure required for normal learning and memory. I identified 120 genes differentially expressed (q < 0.2, fold change > 1.3) 24h after LTM induction. Among these were 13 potential downstream targets for RNA localization by the known memory genes pumilo, staufen and oskar, several genes encoding chromatin regulators and seven genes with …

All Roads Lead To Weediness: Stories About Weedy Rice Origins, Weedy Genes And Weed Competitiveness, Zhongyun Huang

Doctoral Dissertations

Weedy rice (Oryza spp.), a weedy relative of cultivated rice (O.sativa), infests and persists in cultivated rice fields worldwide. Many weedy rice populations have evolved similar adaptive traits, considered part of the ‘agricultural weed syndrome’, making this an ideal model to study the genetic basis of parallel evolution. Using population genetics analyses of South Asian and US weedy rice, my research reveals multiple independent evolution events giving rise to weed groups in the two geographic areas. Weeds in South Asia have highly heterogenous genetic backgrounds, with contributions from both cultivated varieties (aus and indica) …

Uncovering Tasselsheath3. A Genomic And Phenotypic Analysis Of A Maize Floral Mutant., Thompson Zhang

Masters Theses

In the modern era, maize has become the most successful crop grown in the United States. According to the USDA over 90 million acres of land are planted to corn and 96.2% of the U.S feed grain production is made up of the cereal. Part of the success of maize is due to its floral architecture, and its pollination technique in which the flower opens, exposing stamens containing pollen into the air. A unique organ called the lodicule functions as a release mechanism, forcing the flower to open. Lodicules from grasses and eudicot petals are homologous, yet there is little …

Characterization Of Plant-Spider Mite Interactions And Establishment Of Tools For Spider Mite Functional Genetic Studies, Nicolas Bensoussan

Electronic Thesis and Dissertation Repository

The two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae), is one of the most polyphagous herbivores feeding on cell contents of over 1100 plant species including more than 150 crops. However, despite its important pest status and a growing understanding of the molecular basis of its interactions with plant hosts, knowledge of the way mites interface with the plant while feeding and the plant damage directly inflicted by mites is lacking. Likewise, while the use of the reverse genetic tools in plants facilitated our understanding of the establishment of defense mechanisms against spider mite herbivory, such tools are lacking for …

Characterization Of Acaricide Resistance, Plant-Mediated Rnai Against Two-Spotted Spider Mites (Tetranychus Urticae Koch), And Assessing Off- And Non-Target Effects, Hooman Hosseinzadeh Namin

Electronic Thesis and Dissertation Repository

The two-spotted spider mite (TSSM), Tetranychus urticae (Koch), is one of the most damaging agricultural pests in the world. It feeds on over 150 crops, causing considerable yield losses in greenhouses and agricultural fields. Currently, using synthetic acaricides is the main method to control TSSM. However, it can develop resistance to acaricides with repeated exposure, and typically resistance can occur within two to four years. To understand the underlying mechanisms of spider mite adaptation to acaricides is an essential part of resistance management strategy. The resistance ratio of the pyridaben-selected strain compared with the pre-selection strain was estimated at greater …

Tracing The Genetic Footprints Of The Redbelly Yellowtail Fusilier, Caesio Cuning, Across Multiple Spatial And Evolutionary Scales, Amanda Susanne Ackiss

Biological Sciences Theses & Dissertations

Overfishing is one of the most pervasive threats to coral reef ecosystems, and management of these multi-species resources is hampered by limited species-specific population level information. The reefs in the western tropical Pacific Ocean, including the Coral Triangle, are the most bio-diverse in the world. Home to more than 400 million people, this region contains some of the most threatened coral reef ecosystems. Presented here is the first comprehensive analysis of the genetic structure of Caesio cuning, planktivorous fish inhabiting reefs in the Coral Triangle and western Pacific Ocean. Data from both classical Sanger and next-generation sequencing were analyzed …

Population Structure Of Lethrinus Lentjan (Lethrinidae, Percoidei) Across The South China Sea And The Philippines Is Detected With Lane-Affected Radseq Data, Ellen E. Biesack

Biological Sciences Theses & Dissertations

Southeast Asia includes the Coral Triangle, a marine biodiversity hotspot that supports important fishery resources experiencing varied threats. Patterns of speciation and population structure in the Coral Triangle have been examined to test hypotheses relating to the historical geologic processes that may have influenced this biodiversity phenomenon. This study investigates the genetic population structure of the Pink-ear Emperor Snapper, Lethrinus lentjan (Lacepède, 1802), across the Philippines and the South China Sea. The species is fished throughout the Coral Triangle by subsistence and commercial fishers and their landings have been in decline for several years, which could be indicative of depleted …

Robust Algorithms For Detecting Hidden Structure In Biological Data, Roman Sloutsky

Arts & Sciences Electronic Theses and Dissertations

Biological data, such as molecular abundance measurements and protein

sequences, harbor complex hidden structure that reflects its underlying

biological mechanisms. For example, high-throughput abundance measurements

provide a snapshot the global state of a living cell, while homologous

protein sequences encode the residue-level logic of the proteins' function

and provide a snapshot of the evolutionary trajectory of the protein family.

In this work I describe algorithmic approaches and analysis software I

developed for uncovering hidden structure in both kinds of data.

Clustering is an unsurpervised machine learning technique commonly used

to map the structure of data collected in high-throughput experiments,

such …

Type 1 And F17-Like Pili Promote The Establishment Of The Uropathogenic E. Coli Intestinal Reservoir, Caitlin Nicole Spaulding

Arts & Sciences Electronic Theses and Dissertations

Urinary tract infections (UTI) affect over 150 million individuals worldwide every year. These infections are associated with significant morbidity and have a sizeable economic impact, with $5 billion being spent on UTI treatment in the USA annually. Uropathogenic E. coli (UPEC) are responsible for 80% of community acquired UTIs and 65% of nosocomial UTI. The current standard of care for UTI is antibiotic therapy. However, 30-50% of women experience recurrent UTI (rUTI) despite receiving antibiotic therapy. The prevalence of single and multi-drug resistant UPEC strains has led to increased reliance on carbepenems, which are primarily reserved for multi-drug resistant infections, …

Neurogenetics Of The Externalizing Spectrum, Caitlin E. Carey

Arts & Sciences Electronic Theses and Dissertations

Externalizing spectrum disorders, which include attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder, alcohol and substance use disorders, and antisocial personality disorder, are characterized by behavioral disinhibition and are thought to be manifestations of a common heritable liability factor throughout the lifespan. However, relatively little is known about their underlying etiology. Here, I probe genetic and neural risk mechanisms for externalizing psychopathology in three complementary studies. First, I report an indirect association between genetic risk for childhood attention-deficit/hyperactivity disorder (ADHD) and problem drinking in young adulthood, mediated by heightened reward-related neural activity within the ventral striatum, among 404 college students. I …

Reevaluating The Occurrence And Phylogeny Of The Pigtoe Unionid Mussels Fusconaia Askewi, Fusconaia Lananensis, Fusconaia Flava, And Pleurobema Riddelli In Texas, Charles J. Pratt

Biology Theses

The recent development of DNA-based species classification methods has led to the revision of many morphology-based species designations as genetic data has provided new information for species delineation. Analysis of standardized DNA ‘barcoding’ gene regions has proven particularly effective in resolving the taxonomic status of taxa that display phenotypic and habitat overlap.

Freshwater Unionid and Margaritiferid mussels comprise one of the most diverse aquatic taxa in North America, but are also among the most threatened, with over 70% of the approximately 300 native species considered at-risk or in decline. Although mussels face extensive threats from anthropogenic activity, conservation efforts have …

New Insights Into The Role Of Antimicrobials Of Xenorhabdus In Interspecies Competition, Kristin Jean Ciezki

Theses and Dissertations

Xenorhabdus spp. are symbionts of entomopathogenic nematodes and pathogens of susceptible insects. The nematodes penetrate the insect midgut to enter the hemocoel where Xenorhabdus bacteria are released, transitioning to their pathogenic stage. During nematode invasion microbes from the insect gut translocate into the hemocoel. In addition, different species of nematodes carrying specific strains of Xenorhabdus can invade a single insect. Xenorhabdus spp thereby engage in competition with both related strains and nonrelated gut microbes. In complex media Xenorhabdus spp produce diverse antimicrobial compounds whose functions in biological systems remain poorly understood. R-type bacteriocins are contractile phage-tail-like structures that are bactericidal …

Identifying Three-Way Gene Interactions From Microarray Data Using Kolmogorov-Smirnov And Cross-Match Tests, Shubhashree Khadka

Graduate Theses and Dissertations

Human gene network is much more complex than just pairwise interaction among the genes. Zhang et al. [6] extracted microarray data from International Genomics Consortium (IGC), and presented the detection of three-way gene interactions in their paper using Fisher’s z-transformation test. Three-way gene interactions are closer than pairwise correlations in representing the complex gene structures. Additionally, it was more tractable than assessing four or more gene interactions. In this paper, we are simulating different models where Fisher’s test might not be as effective. Zhang et al.’s approach utilized Pearson’s correlation coefficients and involved detection of linear interactions only. Since gene …

Comprehensive Assessments Of The Genetic Determinants In Salmonella Typhimurium For Fitness Under Host Stressors: Oxidative Stress And Iron Restriction, Sardar Abdullah

Graduate Theses and Dissertations

Salmonella is an intracellular pathogen that infects a wide range of hosts. The infected host utilizes reactive oxygen species (ROS) and iron-restriction to eliminate the pathogen. We used proteogenomics to determine the candidate genes and proteins that have a role in resistance of S. Typhimurium to H2O2. For Tn-seq, a highly saturated Tn5 library was grown in vitro under either 2.5 (H2O2L) or 3.5 mM H2O2 (H2O2H). We identified two sets of overlapping genes that are required for resistance of S. Typhimurium to H2O2L and H2O2H, and the results were validated via phenotypic evaluation of 50 selected mutants. The enriched …

Functional Consequences Of Rna Exosome Complex Alteration By Conformational Changes And Cofactor Binding, Jaeil Han

Dissertations & Theses (Open Access)

The RNA exosome is an essential 3’-5 ribonuclease that processes or degrades a variety of RNA species in eukaryotes. It is composed of nine structural cores and one catalytic subunit, Rrp44. Structural studies captured two different conformations of Rrp44, Rrp44^ch (channel) and Rrp44^da (direct-access). The Rrp44^ch appears to recruit RNA substrates from the central channel formed by the core subunits, while the substrate is directly recruited to Rrp44^da bypassing the central channel. Although in vivo function of the Rrp44^ch-exosome is extensively studied, the function or even the presence of the Rrp44^da-exosome in …