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Spag17 Deficiency Impairs Neuronal Cell Differentiation In Developing Brain, Olivia J. Choi

Theses and Dissertations

The development of the nervous system is a multi-level, time-sensitive process that relies heavily on cell differentiation. However, the molecular mechanisms that control brain development remain poorly understood. We generated a knockout (KO) mouse for the cilia associated gene Spag17. These animals develop hydrocephalus and enlarged ventricles consistent with the role of Spag17 in the motility of ependymal cilia. However, other phenotypes that cannot be explained by this role were also present. Recently, a mutation in Spag17 has been associated with brain malformations and severe intellectual disability in humans. Therefore, we hypothesized that Spag17 plays a crucial role in …

Class/Act Embodied Practices For Performative Pedagogy, Chauntee Irving

Theses and Dissertations

Class/Act: Embodied Practices for Performative Pedagogy is a personal and practical exploration of embodiment’s role in higher education acting pedagogy. In my thesis, I propose that embodied acting practices rooted in phenomenology and corporeal dramaturgy surpass conventional acting curricula. Embodied training is often confused with movement curricula and is regularly considered a shallow and/or unintelligent means to approaching acting work. However, I will argue the efficiency and effectiveness of embodied teaching techniques in four parts. Part One: Seeing is a retrospective of how my personal experiences outside of the classroom have drawn me toward embodied aesthetics. Part Two: Knowing unveils …

Humans Aren't Boxes, Art Isn't Finite, Brianne Alta Humphreys

Theses and Dissertations

I am bored. All around me are systems that perpetuate repetitive, reductive, and mundane modes of living. In an attempt to counter a culture obsessed with singular ways of existence and bite-sized perfection, I utilize moving mediums of video and performance to dive head first into a vast array of sloppy sincerity. The crisp, white-washed, analytical, and restrictive is loudly replaced with the empirical, haphazard, and instinctual. My intention is to create and encourage raw, performative-based work that is as multifaceted as unbridled life itself. This alive and physical practice hosts a conglomeration of sweat, memories, heartbreaks, hymn singing, line …

Manufactured By Nature: Growing Generatively Designed Products, Mohammad Jawad

Theses and Dissertations

Mass production and assembly lines are yesterday’s manufacturing methods. They have exhausted Earth’s resources and limited the possibilities of design in terms of both form and material, prompting designers to search for new processes. A new generation of making includes biomimicry-inspired technologies such as 3D printing and parametric simulation, which have transformed the production paradigm. Utilizing nature as industry, this thesis explores the possibility of “growing” designed objects by employing nature’s own processes and resources. It integrates bio materials, generative design and additive manufacturing to produce objects for a post-industrial world. The project outcomes employ natural minerals, crystallization and 3D …

Graphic Intimacies: Identity, Humor, And Trauma In Autobiographical Comics By Women Of Color, Francesca Lyn

Theses and Dissertations

Graphic Intimacies: Identity, Humor, and Trauma in Autobiographical Comics by Women of Color examines works of comics art about the lived experience of the comics’ creator. These graphic narratives address racialized difference and the construction of identity while also using humor to negotiate their narrations of traumatic events. I argue that these creators employ the structure of comics to replicate the fragmentary nature of memory. Comics allow for the representation of trauma as being intimately linked to corporeality. The comics medium allows creators to make visible and present fractured versions of the self, a product of traumatic fragmentation. Drawing traumatic …

An Evaluation Of Induced Shear Stress On Endothelial Cellular Adhesion Molecules, Edward B. Crabb

Theses and Dissertations

The pathophysiology of atherosclerotic cardiovascular disease (CVD) is highlighted by vascular dysfunction and low-grade vascular inflammation. Furthermore, the site-specific distribution of atherosclerosis throughout the arterial vasculature is primarily determined by local hemodynamic force. Therefore, this dissertation outlines three experiments designed to investigate the role of acute mental and physical (i.e., aerobic exercise), and vascular wall shear stress (SS) on the inflammatory aspects of atherosclerosis. Chapter 2 examines the effect of acute laboratory-induced mental stress on intracellular pro-inflammatory signaling pathways in peripheral blood mononuclear cells. Chapter 3 investigates the impact of acute laboratory-induced mental stress and maximal aerobic exercise on the …

Singing The Landscape: A Meditation On Song, Sound And Community At The Fall Line Of The James River, Sara Bouchard

Theses and Dissertations

I work in the medium of song. A multidisciplinary artist and composer, I make work that is immersive, time-based and often participatory. I interact with landscape and the complexities of American history, bringing into focus local ecologies through the lens of song.

This document accompanies my thesis performance The Sound of a Stone, an immersive exploration of song, language, ecology and locational listening performed in a 4-channel surround format. In the semi-improvised composition, I sample live vocals, mandolin and found natural objects in a combination of roots music traditions and experimental techniques. Utilizing the software Ableton Live to process …

The Wild Beasts, Peter Cochrane

Theses and Dissertations

The Wild Beasts springs from my desire to thank my ever-expanding queer chosen family and mentors for their strength. Working through the often violent and othering aspects of the lens and photographic histories I create floral portraits responding to each person’s being and our relationship. Using the 19th century, 8x10 large format view camera—the same used by colonialists and ethnographers to “capture” the divinity of Nature—I erect each as a traditional still life studio setup at the threshold between the natural world and that constructed by humans. These environments speak both to the character of each friend and also to …

Long-Term Effects Of Notch1 Signaling On Neural Stem Cells Following Traumatic Brain Injury, Cruz Sevilla Jr

Theses and Dissertations

Traumatic brain injury (TBI) is a devastating problem which stands as a leading cause of death and disability. The elderly is significantly affected by TBI, typically as the result of falls, and recovery is especially limited. This, in part, is associated with decreased tissue-specific stem cell regeneration and replacement of damaged cells in the aged brain. The diminished ability of the aged brain to recover is especially devastating after TBI, likely leading to permanent loss of sensory, motor, and cognitive functions. Studies have shown that the mature mammalian brain contains Neural Stem Cells (NSCs), found in specific regions of the …

The Puppets Look Like Flowers At Last, Evie Metz

Theses and Dissertations

The urge to uncover aspects of human condition permeates my work, from the fundamental curiosity of a child tearing apart their doll to uncover what lies within to continuing a quest in uncovering basic human urges through my puppet animated dramas and tragedies. There is a controversial line between the childlike and the adult-like that can be ambiguous, and at some times more discernible while other times less. I create handcrafted stop-frame puppet animations that explore self-conscious emotions such as embarrassment, shame, and envy within unpredictable life scenarios. These are animations about inner life, attempting to resolve conflicting elements of …

The Analgesic-Like Properties Of Alcohol In Animal Models Of Chronic Pain, Bradley Neddenriep

Theses and Dissertations

Chronic pain and excessive alcohol consumption are individually problems in our society today. Alcohol Use Disorder (AUD) affects 15.1 million adult Americans each year. Chronic pain affects over 100 million people annually in the United States. However, there is growing evidence suggesting that these two conditions can often be interrelated with chronic pain increasing consumption of alcohol, and excessive alcohol consumption increasing pain that leaves a feedback cycle trapping millions of patients in an ever worsening spiral. Large population-based studies show an association between pain and alcohol abuse, suggesting a link between increased alcohol use and reduced pain. While rodent …

Au@Tio2 Nanocomposites Synthesized By X-Ray Radiolysis As Potential Radiosensitizers, Maria C. Molina Higgins

Theses and Dissertations

Radiosensitization is a novel targeted therapy strategy where chemical compounds are being explored to enhance the sensitivity of the tissue to the effects of ionizing radiation. Among the different radiosensitizers alternatives, nanomaterials have shown promising results by enhancing tumor injury through the production of free radicals and reactive oxygen species (ROS). In this work, Gold-supported titania (Au@TiO₂) nanocomposites were synthesized through an innovative strategy using X-ray irradiation, and their potential as radiosensitizers was investigated. Radiosensitization of Au@TiO₂ nanocomposites was assessed by monitoring the decomposition of Methylene Blue (MB) under X-ray irradiation in the presence of the nanomaterial. …

Parallel Narrative: Short-Video Social Media Platforms’ Influences On Contemporary Narrative, Ruiqi Zhang

Theses and Dissertations

Through the study of Kwai, a popular short-video social media platform in China, this thesis investigates the social issues, media class divides and aesthetics specific to Kwai culture. It further proposes a strategy of artistic practice - parallel narrative - an experiment in video art production and editing techniques that explores new possibilities of narrative in video art. Integrating theoretical research on Post-Internet art and object-oriented ontology, this thesis reveals people’s ability to digest multisource information and shows how mobile technologies and open-source materials contribute to the formation of parallel narratives.

The Role Of Tumor And Tumor Microenvironment On Breast Cancer-Associated Adipocyte Plasticity, Janina V. Pearce

Theses and Dissertations

Cancer-associated cachexia is a condition defined by a sustained net-negative energy imbalance. Although the different types of adipose tissue – white, beige, and brown – have been implicated in contributing to cancer-associated cachexia, the mechanisms of these maladaptive changes and their impact on whole-body energy expenditure have not been fully elucidated. Using breast cancer as our model, we demonstrate white adipose tissue browning in murine and human breast cancer; furthermore, we demonstrate that this effect is extremely localized and takes place early in tumor progression. We utilized in vitro cell culture techniques and demonstrate that cancer secreted factors and cross-talk …

A Computational Assessment Of Lisfranc Injuries And Their Surgical Repairs, Michael Perez

Theses and Dissertations

While Lisfranc injuries in the mid foot are less common than other ankle and mid foot injuries, they pose challenges in both properly identifying them and treating them. When Lisfranc injuries are ligamentous and do not include obvious fractures, they are very challenging for clinicians to identify unless weight bearing radiographs are used. The result is that 20%-40% of Lisfranc injuries are missed in the initial evaluation. Even when injuries are correctly identified the outcomes of surgical procedures remain poor. Existing literature has compared the different surgical procedures but has not had a standard approach or procedures across studies. This …

Targeted Therapies For Ewsr1-Fli1 Translocated Ewing Family Of Tumors, Daniel A.R. Heisey

Theses and Dissertations

The EWSR1-FLI1 t(11;22)(q24;q12) translocation is the pathognomonic genomic alteration in 85% of the Ewing Family of Tumors (EWFT) a malignancy of the bone and the surrounding tissue, predominantly affecting children and adolescents. This translocation results in the formation of a chimeric oncoprotein which acts as an aberrant transcription factor that is currently not pharmaceutically druggable, driving the need for more effective targeted therapies. The EWSR1-FLI1 translocation induces a variety of changes including dysregulation of the epigenome and altered gene expression to drive tumorigenesis, and consequently contributes to the hypersensitivity of EWFT to several classes of chemotherapeutics. We sought to exploit …

Structure-Activity Relationship Studies Of Synthetic Cathinones And Related Agents, Rachel A. Davies

Theses and Dissertations

Synthetic cathinones and related agents represent an international drug abuse problem, and at the same time an important class of clinically useful compounds. Structure-activity relationship studies are needed to elucidate molecular features underlying the pharmacology of these agents. Illicit methcathinone (i.e., MCAT), the prototype of the synthetic cathinone class, exists as a racemic mixture. Though the differences in potency and target selectivity between the positional and optical isomers of synthetic cathinones and related agents have been demonstrated to have important implications for abuse and therapeutic potential, the two MCAT isomers have never been directly compared at their molecular targets: the …

From Sunrise To Sunset: A Lifespan Approach To Understanding The Mental Health Of A Subset Of American Farmers, Janna L. Imel

Theses and Dissertations

Prior research has indicated higher risk of suicide for farmers and identified depression and anxiety as mental health concerns, though the majority of research was conducted in the 1980s-1990s. In today’s economic, social, and political climate, farmers are exposed to situations and stressors reminiscent of the 1980s Farm Crisis. An added risk is the aging workforce of farmers, as age-related conditions can make farming even riskier. This study investigated the mental health of a subset of American farmers by exploring farm-related stressors, coping mechanisms, and mental health outcomes. Dispositional mindfulness was explored as a specific coping mechanism. Participants (N …

The Role Of The Mechanical Environment On Cd117+ Endothelial Cell Angiogenesis, Patrick Link

Theses and Dissertations

Angiogenesis is a complex process coordinating cell migration, proliferation, and lumen formation. Changes to the microenvironment regulate angiogenesis through mechanotransduction and cytokine signals. In pulmonary hypertension, something in the process becomes abnormal, resulting in changes to the microenvironment and the formation of a glomerulus of dysfunctional capillaries, called a plexiform lesion. Endothelial cells, expressing CD117 (CD117+ EC clones) increase in the plexiform lesions of pulmonary hypertension, independent of pro-angiogenic VEGF signaling. We hypothesize that the mechanical environment and the macromolecular composition of the extracellular matrix, both, contribute to the aberrant angiogenesis. When we changed the mechanical environment, we changed the …

Embryonic Stem Cell-Derived Exosomes Increase The Antiproliferative Activity Of Doxorubicin In Breast Cancer, Alexander M. Hirsch

Theses and Dissertations

The field of cancer research has grown immensely in recent decades and has led to a better understanding of the causes of the disease, as well as greatly improved treatment for various types of cancers, especially breast cancer. One of the most effective treatments involves the chemotherapeutic drug doxorubicin (DOX). DOX is an effective tool against all types of breast cancer, especially against triple negative breast cancer. However, DOX causes adverse side effects that include damage to the heart and skeletal muscle, particularly above specific cumulative doses. Recent evidence suggests that embryonic stem cell-derived (ES) exosomes, nanoscale extracellular vesicles that …

A Hybrid Molecule Of Melatonin And Curcumin For Therpeutic Use In Pulmonary Fibrosis, Varsha V. Nair

Theses and Dissertations

Pulmonary fibrosis (PF) is a serious lung disease, as its life expectancy is only 3-5 years upon occurrence and more than 50 % of the cases are idiopathic, i.e., unknown cause. Two drugs, pirfenidone (PIR) and nintedanib, have recently been approved; however, their efficacies are moderate without evidence of prolonged survival. While this is primarily due to our insufficient knowledge about key PF pathogenesis, inductions of oxidative stress and transforming growth factor-b1 (TGF-b1) have been suggested in PF lungs. Hence, anti-oxidative melatonin (MEL) and curcumin (CUR) have been studied yet their efficacies remain moderate without clear understanding about the mechanisms …

Endogenous Opioid Peptides And Brain Development: Endomorphin-1 And Nociceptin Play A Sex-Specific Role In The Control Of Oligodendrocyte Maturation And Brain Myelination, Esraa M. Mohamed

Theses and Dissertations

Myelin is an extensive cell membrane produced by oligodendrocytes to ensheath neuronal axons in the central nervous system with the primary goal of maximizing the efficiency of electrochemical impulse transmission. During brain development, oligodendrocytes differentiate into myelin forming cells in a tightly regulated process which makes them vulnerable to multiple insults. Previous results from the laboratory showed that the timing of oligodendrocyte differentiation and rat brain myelination were altered by perinatal exposure to buprenorphine and methadone, opioid analogues used for treating pregnant addicts. The mechanism by which these opioids exerted their effects involved two opioid receptors, the μ-opioid receptor (MOR) …

Cellular And Molecular Mechanisms Of Collective Migration In Facial Branchiomotor Neurons, Jane K. Rebman

Theses and Dissertations

The directed migration of neurons is influenced by multiple guidance cues, that may include soluble attractive chemotactic factors and cell-cell contact mediated collective migration. The nature of these neuron-neuron interactions and their integration with chemotaxis remains unclear. Contact inhibition of locomotion (CIL), a process whereby cells undergoing a collision cease their migration towards the colliding cell, has been identified as a driving force behind the collective migration of several cell populations in vivo, but has not been described for neurons in the central nervous system. We have established that Cadherin2 (Cdh2), a cell adhesion molecule, mediates the physical interactions …

Axon Initial Segment Integrity In Aging And Traumatic Brain Injury, Mazen M. Gouda

Theses and Dissertations

According to the Center for Disease Control’s (CDC) report to the Congress, there are 2.2 million emergency department visits; 80,000 hospitalizations; and 50,000 deaths each year due to traumatic brain injury. Adults 65 years and older account substantially for the majority of the hospitalization and deaths. Over 70% of the traumatic brain injuries of the older adults are classified as mild to moderate; however, even with these milder injuries, older adults present with a significantly higher morbidity and mortality compared to all other age groups (LeBlanc et al., 2006). With that in mind, it seems essential to develop a deeper …

Fluoxetine Attenuates Mast Cell Function By Targeting Purinergic Signaling, Tamara T. Haque

Theses and Dissertations

Mast cells are tissue resident, innate immune cells that provide protection against parasitic and bacterial infections and venom poisoning. Mast cells also play a pathogenic role in atopy and allergic diseases. Atopy and allergic diseases are increasing in the developed world and are predicted to continue to increase at an alarming rate. Current treatment options include corticosteroids, anti-histamines, anti-IgE and avoidance of allergen. These interventions have limitations: some patients are steroid resistant; anti-histamines have low efficacy since they need to be administered early during allergen exposure; and anti-IgE is costly. Thus there is a clinical need for new treatment options. …

Latent Growth Model Approach To Characterize Maternal Prenatal Dna Methylation Trajectories, Dana Lapato

Theses and Dissertations

Background. DNA methylation (DNAm) is a removable chemical modification to the DNA sequence intimately associated with genomic stability, cellular identity, and gene expression. DNAm patterning reflects joint contributions from genetic, environmental, and behavioral factors. As such, differences in DNAm patterns may explain interindividual variability in risk liability for complex traits like major depression (MD). Hundreds of significant DNAm loci have been identified using cross-sectional association studies. This dissertation builds on that foundational work to explore novel statistical approaches for longitudinal DNAm analyses. Methods. Repeated measures of genome-wide DNAm and social and environmental determinants of health were collected up to six …

The Effects Of Notch Signaling On Functional Recovery Following Traumatic Brain Injury, Jyoti Lodha

Theses and Dissertations

2.5 million people sustain a traumatic brain injury (TBI) annually in the United States. Although there is potential for functional recovery following TBI, there is no definitive treatment to improve recovery after TBI. Our lab has shown that TBI enhances an endogenous neurogenic response in the subventricular zone and hippocampus. TBI-induced neural stem cells (NSCs) can integrate into regions such as the hippocampus and olfactory bulb. Although the mechanism behind TBI-enhanced neurogenesis remains unknown, the Notch signaling pathway has been implicated as a regulator in the maintenance and survival of NSCs.

This thesis explores the effects of Notch pathway manipulation …

Illumination Of The Golgi Apparatus Of Pathogenic And Nonpathogenic Naegleria Species, Tyler M. Poe

Theses and Dissertations

In this study, Naegleria fowleri, a pathogenic amoeba and the causative agent of Primary Amebic Meningoencephalitis (PAM), was utilized to determine the presence or absence of classically conserved Golgi molecules featured in the expression of a Golgi apparatus. Previous studies concluded no Golgi expression via light microscopy and transmission electron microscopy, but a recent report on Naegleria gruberi indicated the presence of dispersed Golgi tubules. Non-pathogenic species of the Naegleria genus such as Naegleria gruberi 30540 and Naegleria lovaniensis 30569 were utilized in Western immunoblot analysis compared to reduced whole-cell lysate proteins of two strains of N. fowleri and …

Analyzing Interactions Between Methcathinone Analogs And The Human Monoamine Transporters, Vy Nguyen

Theses and Dissertations

Psychostimulants elicit their psychological and behavioral effects through interactions with the monoamine transporters. These compounds are classified as either substrates or reuptake inhibitors, depending on their mechanism of action, and have varying potencies at the three human monoamine transporters, hDAT, hSERT, and hNET. Substrates and reuptake inhibitors also have distinct electrophysiological signatures: reuptake inhibitors cause hyperpolarization in HEK293 cells stably expressing the monoamine transporters, whereas substrate transport mediates a depolarizing current. Recent studies have shown that substrate-mediated depolarization is sufficient to activate L-type calcium channels, a characteristic which has been used to develop a novel calcium assay which uses calcium …

Molecular Targets Of Psychedelics And Their Role In Behavioral Models Of Hallucinogenic Action, Hiba Z. Vohra

Theses and Dissertations

Psychedelics are a subset of hallucinogenic drugs that exert their characteristic effects through agonist activity at the serotonin receptor 2A (5-HT_2A). In this study, I aimed to characterize the modulatory role of the metabotropic glutamate subtype 2 receptor (mGluR2) in the 5-HT_2A-specific rodent model of hallucinogenic action, head-twitch response (HTR). Secondly, I aimed to explore if 5-HT_2A agonist-induced deficits in prepulse inhibition (PPI) of the startle response, an additional model of hallucinogenic action, could be produced in mice. Though 5-HT_2A agonist-induced PPI deficits, which represent interruptions in normal sensorimotor gating, have been described in …