Digital Commons Network^™

Comparisons Of Eating Disorder Presentation, Research Participation, And Treatment Utilization Between Racial And Ethnic Groups Of College Women With Eating Disorders, Grace Monterubio

Arts & Sciences Electronic Theses and Dissertations

The inclusion of racial and ethnic minority individuals in research is imperative in furthering generalizable and comprehensive research on eating disorder (ED) populations and improving the disparities for minorities with EDs. The current study investigates such disparities by 1) assessing the presentation of EDs and comorbidities across racial and ethnic groups, as well as 2) assessing whether minority individuals are less likely to participate in a research study, or utilize the offered interventions versus their majority counterparts in the Healthy Body Image Program (HBI), a study of an online, guided self-help, ED intervention vs. referral to in-person care among college …

The Essential Roles Of The Chromatin Factor Gon4l In Heart Development, Terin Elise Budine

Arts & Sciences Electronic Theses and Dissertations

Heart development and the genetic pathways underlying it are highly conserved among vertebrates. During heart development, an embryo must induce mesoderm formation, pattern the mesoderm, specify cardiomyocytes, increase the population of cardiomyocytes through proliferation, and pattern the cardiac chambers. It is becoming increasingly clear that chromatin modifications help mediate the complex processes of heart development by providing spatiotemporal regulation of gene expression. My thesis work focuses on characterizing functions of the chromatin factor Gonad-4-like (Gon4l), encoded by the gene ugly duckling (udu), in zebrafish heart development. Previous works established a requirement for Gon4l in the formation of many mesoderm derivatives …

Modeling The Bioactivation And Subsequent Reactivity Of Drugs, Tyler Brian Hughes

Arts & Sciences Electronic Theses and Dissertations

Metabolism can convert drugs to harmful reactive metabolites that conjugate to DNA and off-target proteins. Reactive metabolites are a significant driver of both drug candidate attrition and withdrawal from the market of already approved drugs. Unfortunately, reactive metabolites are difficult to study in vivo, because they are transitory and generally do not circulate. Instead, this work computationally models both metabolism and reactivity. Using deep learning, predictive models were developed for the metabolic formation of quinones and epoxides, which together account for about half of known reactive metabolites. Additionally, an accurate model of DNA and protein reactivity was constructed, which predicts …

A Mouse Model Of Börjeson-Forssman-Lehmann Syndrome Reveals A Potential Link With Autism Spectrum Disorder, Cheng Cheng

Arts & Sciences Electronic Theses and Dissertations

ABSTRACT OF THE DISSERTATION

A Mouse Model of Börjeson-Forssman-Lehmann Syndrome reveals a potential link with Autism Spectrum Disorder

By

Cheng Cheng

Doctor of Philosophy in Biology and Biomedical Sciences

Developmental, Regenerative and Stem Cell Biology

Washington University in St. Louis, 2018

Dr. Azad Bonni, Chair

Intellectual disability (ID) is a prevalent neurodevelopmental disorder that affects 1% to 3% of the general population. ID is characterized by developmental deficiencies in cognitive function and adaptive behaviors. Lacking effective treatments, ID currently presents an immense burden to affected families and the economy. Therefore, there is an urgent need to elucidate the pathogenesis of …

Sequence Analysis Methods For The Design Of Cancer Vaccines That Target Tumor-Specific Mutant Antigens (Neoantigens), Jasreet Hundal

Arts & Sciences Electronic Theses and Dissertations

The human adaptive immune system is programmed to distinguish between self and non-self proteins and if trained to recognize markers unique to a cancer, it may be possible to stimulate the selective destruction of cancer cells. Therapeutic cancer vaccines aim to boost the immune system by selectively increasing the population of T cells specifically targeted to the tumor-unique antigens, thereby initiating cancer cell death.. In the past, this approach has primarily focused on targeted selection of ‘shared’ tumor antigens, found across many patients. The advent of massively parallel sequencing and specialized analytical approaches has enabled more efficient characterization of tumor-specific …

Mechanistic Characterization Of Resistome And Microbiome Dynamics Across Diverse Microbial Habitats, Andrew John Gasparrini

Arts & Sciences Electronic Theses and Dissertations

Increasing antibiotic resistance in pathogens is a serious public health challenge, with over two million antibiotic resistant infections in the United States leading to at least 23,000 deaths and an estimated $55 billion in excess healthcare and societal costs. Antibiotic resistance has risen steadily in both pathogenic and benign bacteria since antibiotics’ introduction to agriculture and medicine 70 years ago. A dramatic reduction in the number of antibiotics approved for human use has accompanied this rise in antibiotic resistance, leading to the alarming prospect of a post-antibiotic era. Understanding the evolutionary origins, genetic contexts, and molecular mechanisms of antibiotic resistance …

Grammar And Variation: Understanding How Cis-Regulatory Information Is Encoded In Mammalian Genomes, Dana Michele King

Arts & Sciences Electronic Theses and Dissertations

Understanding how genotype leads to phenotype is key to understand both the development and dysfunction of complex organisms. In the context of regulating the gene expression patterns that contribute to cell identity and function, the goal of my thesis research is to how changes in genome sequence may impact impact gene expression by determining how sequence features contribute to regulatory potential. To accomplish this goal, I first leveraged the key regulatory role of pluripotency transcription factors (TFs) in mouse embryonic stem cells (mESCs) and tested synthetically generated and genomic identified combinations of binding site for four TFs, OCT4, SOX2, KLF4, …

Genetic Basis Of Thermal Divergence In Saccharomyces Species, Xueying C. Li

Arts & Sciences Electronic Theses and Dissertations

The genetic architecture of phenotypic divergence is a central question in evolutionary biology. Genetic architecture is impacted by whether evolution occurs through accumulation of many small-effect or a few large-effect changes, the relative contribution of coding and cis-regulatory changes, and the prevalence of epistatic effects. Our empirical understanding of the genetic basis of evolutionary change remains incomplete, largely because reproductive barriers limit genetic analysis to those phenotypes that distinguish closely related species. In this dissertation, I use hybrid genetic analysis to examine the basis of thermal divergence between two post-zygotically isolated species, Saccharomyces cerevisiae and S. uvarum. S. cerevisiae is …

Radiolabeled Nanohydroxyapatite As A Platform For The Development Of New Pet Imaging Agents, Stacy Lee Queern

Arts & Sciences Electronic Theses and Dissertations

Positron emission tomography (PET) imaging utilizes drugs labeled with positron emitters to target and evaluate different biological processes occurring in the body. Tailoring medicine to the individual allows for higher quality of care with better diagnosis and treatment and is a key purpose for advancing research into developing new platforms for PET imaging agents. A PET nuclide of high interest for the development of these agents is 89Zr. This can be attributed to the long half-life of 3.27 days and low positron energy of 89Zr.

In this work, we developed a production method for 89Zr using Y sputtered coins that …

Fast Objective Coupled Planar Illumination Microscopy, Cody Jonathan Greer

Arts & Sciences Electronic Theses and Dissertations

Among optical imaging techniques light sheet fluorescence microscopy stands out as one of the most attractive for capturing high-speed biological dynamics unfolding in three dimensions. The technique is potentially millions of times faster than point-scanning techniques such as two-photon microscopy. This potential is especially poignant for neuroscience applications due to the fact that interactions between neurons transpire over mere milliseconds within tissue volumes spanning hundreds of cubic microns. However current-generation light sheet microscopes are limited by volume scanning rate and/or camera frame rate. We begin by reviewing the optical principles underlying light sheet fluorescence microscopy and the origin of these …

Intersecting Variables Of Second And Foreign Language Reading: Self-Assessment And Comprehension With Adolescents And Adults Across Languages, Haley Dolosic

Arts & Sciences Electronic Theses and Dissertations

Today, more individuals are seeking to learn a second language (L2) or foreign language (FL) than ever before. These individuals are language learners who intend to use their growing L2 knowledge to traverse linguistic and national boundaries in order to achieve their personal and professional goals (Callahan & Gándara, 2014). To realize these goals in the digital era, L2 learners must be more prepared than ever to use their knowledge with written media, making L2 reading a central skill to successful use of their L2 knowledge. Yet, when language learners attempt to use their L2 skills in their daily lives, …

Ming China As A Gunpowder Empire: Military Technology, Politics, And Fiscal Administration, 1350-1620, Weicong Duan

Arts & Sciences Electronic Theses and Dissertations

This dissertation explores the transformation of Ming China in the gunpowder age. Focusing on the relation between military technology, politics, and fiscal administration, it closely traces the change of the Ming state in association with the gunpowder revolution. Two aspects of institutional change receive special attention. The first aspect is the formation of an absolute authority in the Ming period, a development exhibiting many parallels with the absolute monarchies of other major gunpowder states in Europe and the Islamic world. The second is the modification of the Confucian bureaucratic government. The revolutions in gunpowder technology had a complex impact on …

Freezing Of Gait: Mechanisms, Mechanics, And Management, Peter S. Myers

Arts & Sciences Electronic Theses and Dissertations

Parkinson disease (PD) is a neurodegenerative disease with multiple motor and non-motor symptoms, including postural instability, gait impairments, and cognitive deficits. More than 50% of individuals with PD experience a symptom called freezing of gait (FOG), described as a transient inability to take another step forward. Individuals with PD who experience FOG (freezers) have further postural, gait, and cognitive impairments compared to individuals with PD without FOG (non-freezers). While degeneration of the dopaminergic neurons in the substantia nigra is accepted as the primary etiology of the disease, research shows that the disease has a global impact on the brain, accounting …

The Effect Of Talker And Contextual Variability On Memory For Words In Sentences, Nichole Runge

Arts & Sciences Electronic Theses and Dissertations

Previous research has found that adding different forms of variability during study can affect later memory at test. For example, having words spoken by different talkers has been shown to improve recall of known and novel words (Goldinger et al., 1999; Barcroft & Sommers, 2005), and varying the cues in cue-target related word pairs has been found to improve recall of the targets (Glenberg, 1979; Bevan et al., 1966). It was unclear, however, whether benefits of variability would extend to more naturalistic stimuli, such as sentences, which have higher working memory demands. The present set of experiments investigated how talker …

Tunable Electronic And Optical Properties Of Low-Dimensional Materials, Shiyuan Gao

Arts & Sciences Electronic Theses and Dissertations

Two-dimensional (2D) materials with single or a few atomic layers, such as graphene, hexagonal boron nitride (h-BN) and transition metal dichalcogenides (TMDCs), and the heterostructures or one-dimensional (1D) nanostructures they form, have attracted much attention recently as unique platforms for studying many condensed-matter phenomena and holds great potentials for nanoelectronics and optoelectronic applications. Apart from their unique intrinsic properties which has been intensively studied for over a decade by now, they also allow external control of many degrees of freedom, such as electrical gating, doping and layer stacking. In this thesis, I present a theoretical study of the electronic and …

Protein Structure-Guided Approaches To Identify Functional Mutations In Cancer, Sohini Sengupta

Arts & Sciences Electronic Theses and Dissertations

Distinguishing driver mutations from passenger mutations within tumor cells continues to be a major challenge in cancer genomics. Many computational tools have been developed to address this challenge; however, they rely heavily on primary protein sequence context and frequency/mutation rate. Rare driver mutations not found in many cancer patients may be missed with these traditional approaches. Additionally, the structural context of mutations on tertiary/quaternary protein structures is not taken into account and may play a more prominent role in determining phenotype and function. This dissertation first presents a novel computational tool called HotSpot3D, which identifies regions of protein structures that …

The Splice Is Not Right: Splice-Site-Creating Mutations In Cancer Genomes, Reyka Glencora Jayasinghe

Arts & Sciences Electronic Theses and Dissertations

Accurate interpretation of cancer mutations in individual tumors is a prerequisite for precision medicine. Large-scale sequencing studies, such as The Cancer Genome Atlas (TCGA) project, have worked to address the functional consequences of genomic mutations, with the larger goal of determining the underlying mechanisms of cancer initiation and progression. Many studies have focused on characterizing non-synonymous somatic mutations that alter amino acid sequence, as well as splice disrupting mutations at splice donors and acceptors. Current annotation methods typically classify mutations as disruptors of splicing if they fall on the consensus intronic dinucleotide splice donor, GT, the splice acceptor, AG. Splice …

The Role Of Fibrillin-1 In Eye Development And Disease, Wendell Brooks Jones

Arts & Sciences Electronic Theses and Dissertations

The ciliary zonule of the human eye consists of a circumferential array of fibers that connect the ocular lens to the nonpigmented ciliary epithelium (NPCE) located at the inner wall of the eye. Zonular fibers consist of bundles of beaded filaments called microfibrils. Microfibrils are major structural elements of the extracellular matrix and are present in pure form in the ciliary zonule. Microfibrils are composed principally of fibrillin-1 (FBN-1); a large extracellular matrix glycoprotein. In humans, mutations in FBN1 underlie Marfan syndrome; a pleiotropic connective tissue disorder that profoundly affects the eye. Ocular manifestations include ectopia lentis (dislocated lenses), cataracts, …

A Recombinant Virus And Reporter Mouse System To Study Chronic Chikungunya Virus Pathogenesis, Alissa Roxanne Young

Arts & Sciences Electronic Theses and Dissertations

Chikungunya virus (CHIKV) is an arthritogenic alphavirus that during acute disease causes fever as well as severe joint and muscle pain. Chronic joint and muscle pain persists in a significant subset of patients, yet we still have a poor understanding of what drives this chronic disease. While replicating virus has not been detected in the joints of patients with chronic arthritis or in various animal models at chronic time points, persistent viral RNA can be detected for months after acute infection.

To identify the cells that could be contributing to chronic CHIKV pathogenesis, we developed recombinant viruses that express Cre …

The Role Of Apolipoprotein E In Regulating Tau Pathogenesis And Neurodegeneration In A Tauopathy Mouse Model, Yang Shi

Arts & Sciences Electronic Theses and Dissertations

APOE4 is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). APOE4 increases brain amyloid-β (Aβ) pathology relative to other APOE isoforms. However, whether APOE independently influences tau pathology, the other pathological hallmark of AD and other tauopathies, or tau-mediated neurodegeneration, is not clear. By generating P301S tau transgenic mice on either a human APOE knock in (KI) or APOE knockout (KO) background, we show that the presence of human APOE, regardless of APOE isoforms, leads to various degrees of brain atrophy in 9-month old P301S mice, whereas APOE ablation strongly protects against neurodegeneration. In particular, P301S/E4 mice develop …

Neural Mechanisms Of Drosophila Circadian Rhythms, Xitong Liang

Arts & Sciences Electronic Theses and Dissertations

Animals show circadian rhythms in a variety of physiological functions and behaviors. In Drosophila melanogaster, behavioral rhythms are driven by circadian clock genes that are oscillating in ~150 circadian pacemaker neurons. To explain how circadian neurons encode time and regulate different behavioral rhythms, I performed 24-hour in vivo whole-brain calcium imaging using light-sheet microscopy. First, I found that different groups of circadian neurons show circadian rhythms in spontaneous neural activity with diverse phases. The neural activity phases of the M and E pacemaker groups, which are associated with the morning and evening locomotor activities respectively, occur ~4 hours before their …

Singing As A Therapeutic Technique To Improve Gait For People With Parkinson Disease, Elinor Harrison

Arts & Sciences Electronic Theses and Dissertations

Abstract of the Dissertation

Singing as a Therapeutic Technique to

Improve Gait for People with Parkinson Disease

by

Elinor Clare Harrison

Doctor of Philosophy in Movement Science

Neurosciences

Washington University in St. Louis, 2018

Professor Gammon Earhart, Chair

Gait impairment is common in older adults and even more prevalent for people with Parkinson disease (PD). Gait dysfunction is often characterized by reductions in speed, step frequency, and step length. In addition, decreased ability to regulate step length and step frequency may contribute to increased gait variability, making walking less stable and increasing risk for falls. As gait deficits are often …

Unsettling Geographies: Primitivist Utopias In Queer American Literature From Walt Whitman To Willa Cather, Benjamin Meiners

Arts & Sciences Electronic Theses and Dissertations

In “Unsettling Geographies: Primitivist Utopias in Queer American Literature from Walt Whitman to Willa Cather,” I argue that the colonial discourse of primitivism played a central role in the queer literary imaginaries of both canonical and non-canonical U.S. authors. Building on the work of historians of sexuality who trace the complex development of the twentieth-century homo-/hetero- binary, I show how literary works produced in this historical moment—roughly 1860 to 1925—explored and in some instances even advocated alternative queer modes of citizenship and erotic imagination and practice. Focusing on the works of Walt Whitman, Emily Dickinson, Charles Warren Stoddard, and Willa …

Combining Footprinting Mass Spectrometry And Molecular Dynamics Simulation For Structural Studies In Membrane Proteins, Fengbo Zhou

Arts & Sciences Electronic Theses and Dissertations

Membrane proteins are essential in many cellular processes and represent ~60% of all current drug targets. Due to technical limits, membrane proteins of various types were not studied extensively in the past and the biochemistry and functionality of them remain unclear. The structural biology methodologies require pure isolated protein samples for us to resolve their structure and study their biochemical functions. For such in vitro studies, however, membrane proteins often become unstable when isolated from their native lipid bilayer environment. To overcome the challenge, I employed a novel methodology of solubilizing membrane proteins in solution without detergent. I reconstituted ferroportin, …

A Tail Of Two Pancancer Projects: Somatic Variant Identification And Driver Gene Discovery Using Tcga, Matthew Hawkins Bailey

Arts & Sciences Electronic Theses and Dissertations

The implementation of next-generation genomic sequencing has exploded over the past dozen years. Large consortia, such as The Cancer Genome Atlas (TCGA); the International Cancer Genetics Consortium (ICGC); and the Pediatric Cancer Genome Projects (PCGP), made great strides in democratizing big data for the scientific community. These data sets provide a rich resource to build tools for somatic variant discovery and exploratory analysis. Public repositories hold the answer to many novel biological and clinical revelations i.e., the discovery of complex indels, splice creating mutations, alternative super enhancer binding sites, machine learning models to predict mutation impact, and cancer subtype classification …

Photophysical Characterization And Wavelength Tuning Of Natural And Synthetic Oxobacteriochlorins And Biohybrids, Don Hood

Arts & Sciences Electronic Theses and Dissertations

ABSTRACT OF THE DISSERTATION

Photophysical Characterization and Wavelength Tuning of Natural and Synthetic Oxobacteriochlorins and Biohybrids

By

Donald L. Hood

Doctor of Philosophy in Chemistry

Washington University in St. Louis, 2018

Dr. Dewey Holten, Chairperson

Herein is discussed the theoretical and practical unpinnings of photophysical behaviors and kinetic constants for tetrapyrrole macrocycles, to wit, porphyrins, chlorins, and bacteriochlorins. Understanding the characteristic photophysical response of tetrapyrroles to changes in environment or substituents is important to designing synthetic chromophores with tunable absorption wavelengths and for preparing useful biohybrids of natural photosynthetic light antennas combined with unnatural chromophores attached to the light antenna …

Anodic Cyclization Reaction: Manipulation Of Reaction Pathway And Efforts To Radical Cation And Radical Intermediate, Ruozhu Feng

Arts & Sciences Electronic Theses and Dissertations

In recent years, synthetic chemists have been expressing significant interest in electro-organic synthetic methods. This interest is being fueled by the existence of an increasing number of successful methods in the literature and the availability of new electrochemical equipment that removes the barrier to attempting an electrolysis reaction for the first time. Yet while these developments have fueled growth in some areas of electro-organic synthesis (the recycling of chemical catalysts for example), other areas remain underdeveloped. One such area is the exploration of reactions that can be triggered directly as an electrode surface without the use of any chemical reagent. …

Linking Structure And Dynamics In Metallic Liquids: A Combined Experimental And Molecular Dynamics Approach, Robert Ashcraft

Arts & Sciences Electronic Theses and Dissertations

A major outstanding problem in condensed matter physics is the nature of the glass transition, in which a rapidly cooled liquid can bypass the transition into a crystalline state and the liquid structure is "frozen-in" due to kinetic arrest. To characterize the fundamental features behind this transition the liquid, both in the high temperature (equilibrium) and supercooled state, needs to be better understood. By examining the relationship between structure and dynamics a better characterization of the liquid state and a determination of the mechanisms that are ultimately important for the formation of the glass can be gained. In this dissertation, …

Understanding Adolescent Physical Activity In The Early Nutrition Transitioning Country Of Haiti, Haley V. Becker

Arts & Sciences Electronic Theses and Dissertations

The nutrition transition is underway in Haiti, giving rise to the dual burden of malnutrition. Physical activity (PA) plays an important role in mitigating the negative health consequences of nutrition transition and the dual burden, but heretofore this data has been unavailable for Haiti. This dissertation undertook an exploratory needs assessment providing baseline PA data for Haitian adolescents. It evaluated two different PA data collection methodologies: a cross-sectional survey adapted from the IPAQ long-form and objectively measured PA via Actigraph GT1M accelerometers. Next, it identified initial covariates of self-reported and objectively-assessed PA behaviors; data was operationalized as meeting the World …

Lexical Retrieval Inhibition From Semantically Related Retrieval Primes, Abhilasha Ashok Kumar

Arts & Sciences Electronic Theses and Dissertations

The phenomenological experience of lexical retrieval involves conscious and active attempts to retrieve semantically related information, but the direct influence of this retrieval process on subsequent retrieval is presently unknown. We investigated the influence of passively viewing or actively retrieving different types of information at the critical moment preceding lexical retrieval through a novel priming paradigm. Participants attempted to retrieve target words (e.g., FOLIAGE) from their low-frequency definitions or descriptions (e.g., the leafy parts of a plant or tree, collectively). Across five experiments, target retrieval was preceded by the brief presentation of a prime word (Experiment 1), progressive demasking of …