Digital Commons Network^™

The Functional Importance Of Methyl Cpg Binding Domain Proteins 2 And 3 In Regulating Fetal Hemoglobin Expression In Human Adult Erythroid Cells, Alexander Azzo

Theses and Dissertations

Humans undergo two developmental switches in the predominantly expressed β-like globin chain during embryogenesis and fetal development. The first switch from embryonic (ε) to fetal (γ) occurs around week 5 of embryonic development, while the second switch from fetal to adult (β) globin occurs shortly after birth. By adulthood, fetal hemoglobin represents only 1-2% of total hemoglobin in the blood. As sufficiently elevated levels of fetal hemoglobin are beneficial for improving clinical outcomes in sickle cell disease and β-thalassemia, the mechanisms that enforce silencing of fetal hemoglobin expression postnatally are of great clinical significance. The methyl-CpG binding domain protein MBD2 …

Quantification And Modeling Of Bladder Biomechanics Mechanisms Linking Spontaneous Rhythmic Contractions And Dynamic Elasticity To Detrusor Overactivity, Zachary E. Cullingsworth

Theses and Dissertations

Overactive bladder (OAB) is a chronic condition affecting approximately 20% of adults in the United States. Detrusor overactivity (DO) is the presence of non-voiding contractions in the detrusor (bladder) muscle during filling and is present in some individuals with OAB. DO is currently identified visually during a urodynamics (UD) study involving pressure catheters and filling and voiding of the bladder to evaluate function. UD provides limited subtyping of DO, and an incomplete understanding of mechanisms contributing to OAB.

Aim 1 of this study was to develop objective tools to quantify, subgroup and better understand …

A Study On The Mechanism Of Clp290 Restoration Of Kcc2 And Neuroprotection After Traumatic Brain Injury, Ekaterina Stepanova

Theses and Dissertations

The research of this thesis investigated the mechanism of action for the therapeutic compound CLP290, which our laboratory has previously demonstrated to reverse degradation of the protein potassium-chloride co-transporter 2 (KCC2) and restore neuronal function following modeled traumatic brain injury (TBI) in the rat. The loss of membranous KCC2 from the plasma membrane after TBI worsens the excitation/inhibition imbalance common in neurotrauma. Addressed here were the specific aims to: 1) assess that CLP290 treatment restores the functional oligomeric form of KCC2 to the neuronal plasma membrane as necessary to provide chloride homeostasis; 2) investigate the signaling mechanism by which CLP290 …

Disruption Of The Dream Complex Results In Cell Cycle Deregulation, Hayley C. Walston

Theses and Dissertations

The Dimerization Partner, Rb-like, E2F, And MuvB (DREAM) complex was identified in humans due to homology of the genes involved in the D. melanogaster dREAM complex. It assembles during cellular arrest, or G0, to function as a transcriptional repressor of cell cycle genes. It is known that phosphorylation of LIN52 at serine 28 is necessary for the critical DREAM forming interaction between LIN52 and the pocket protein p130. Our laboratory has previously shown that gene editing of LIN52 to replace serine 28 with alanine (S28A) prevents phosphorylation by the kinase DYRK1A and inhibits DREAM formation. Here we have confirmed this …

Accounting For The Uncertainty Due To Chemicals Below The Detection Limit In Mixture Analysis, Paul M. Hargarten

Theses and Dissertations

Humans are exposed to multiple chemicals every day. Epidemiological studies have shown that chemical mixtures are associated with cancers, allergies, neurodevelopmental disorders, and other adverse health effects. To assess these associations, investigators are increasingly using chemical mixture approaches like weighted quantile sum (WQS) regression. In these studies, the research objectives are to determine whether a mixture of correlated chemicals is associated with an adverse health outcome and to identify the important chemicals. However, as experimental equipment measures each exposure to a chemical-specific detection limit, the exposures are unknown between zero and the detection limit. Indeed, the number of exposures below …

Enhancing Chemosensitivity Of Lung Cancers By Manipulating The Tumor Microenvironment: Local Lung Delivery And Nanocarrier-Based Therapies, Hanming Zhang

Theses and Dissertations

Cancer is the second leading cause of death in United States causing an estimated six hundred thousand death in 2019. Among different types of cancer, lung cancer is the leading cause of cancer related death in both male and female. While targeted therapy and immunotherapy have shown promising clinical outcomes, currently there remain a significant proportion of patients who do not benefit from these strategies or who cannot tolerate them, making Pt based doublet chemotherapy still an indispensable component in almost all stages of treatment. However, partially due to the poor tumor distribution of small molecule drug, the development of …

The Utilization Of Eukaryotic Cell Types In Microbiomes For Semen, Vaginal Fluid, And Menstrual Blood Identification Using 18s Rdna, Ines Benaissa

Master of Science in Forensic Science Directed Research Projects

The accurate identification of body fluids is vital for crime scene investigation and forensic analysis. While many body fluids can be presumptively identified, there is a lack of confirmatory testing for verification. Therefore, the purpose of this study was to determine if body fluids (menstrual blood, vaginal fluid, and semen) could be differentiated based on their eukaryotic microbial communities. The target area of interest was the V9 hyper-variable region of 18S ribosomal DNA (18S rDNA). The samples were extracted, barcoded using a duel-index strategy, and PCR amplified before undergoing high throughput sequencing using the Illumina Miseq FGx instrument. The samples …

Prediction Of Minimum Postmortem Submersion Interval (Pmsimin) Based On Eukaryotic Community Succession On Skeletal Remains Recovered From Aquatic Environments, Sala Randall

Master of Science in Forensic Science Directed Research Projects

Many recent studies were conducted concerning bacterial succession in decomposing animal carrion in terrestrial system. However, not much is known about the microorganisms involved in aquatic decomposition. To the best of our knowledge, there are currently no published studies which estimate minimum postmortem submersion interval PMSI_min based on eukaryotic community succession in aquatic system. The main goal of this study was to determine the eukaryotic community succession associated with porcine skeletal remains in a lentic environment, and to derive a statistical model for PMSI_min prediction. Henleys Lake in Crozet, VA was the location chosen for this research. Fresh …

Food Park, Houria Boumzairig

Theses and Dissertations

If climate change and population growth progress at their current pace, in roughly 50 years farming as we know it will no longer exist (Despommier, 2009). This means that the majority of people could soon be without enough food or water. But there is a solution that is surprisingly within reach: Move most farming into cities, and grow crops in tall, specially constructed buildings. It’s called vertical farming. “There is a close relation between the beginning of agriculture and the birth of architecture. Our cities were shaped by food” (Precht, 2019). The agricultural revolution ended our presence as hunters and …

Preventative And Therapeutic Effects Of Bmsc Exosome On Periodontal Disease, Jin Ha Kim

Theses and Dissertations

Periodontitis is an inflammatory disease caused by the imbalance between host immune response and bacterial infection. Strategies to manage the uncontrolled, excessive immune response and to promote tissue healing are in great demand. Therapies based on mesenchymal stem cells (MSCs) are promising and the clinical effects of MSCs are largely mediated by their secretome, especially exosomes. Previously, we isolated and purified exosomes secreted by human bone marrow mesenchymal stem cells (hBMSC). These exosomes have proliferative, chemotactic, anti-inflammatory and anti-osteoclastic function in vitro. In this study, we had two hypotheses: 1) hBMSC exosomes would prevent periodontal inflammation and alveolar bone loss …

Mass Grave Localization Prediction With Geographical Information Systems In Guatemala And Future Impacts, Perla Santillan

Master of Science in Forensic Science Directed Research Projects

Conducting physical searches for mass grave locations based on anecdotal evidence is a time consuming and resource intensive endeavor in circumstances that often pose a threat to personal safety. The development of tools and procedures to speed such searches can greatly reduce the risk involved, increase the number of individuals whose remains are recovered and identified; and, more importantly, reunite these remains with their loved ones to provide them with a proper burial. Geographic information systems (GIS) software, which can analyze and manipulate the spatial characteristics of known mass grave data, represents a powerful tool that can be used to …

Homecoming, Claes Tholand

Mighty Pen Project Anthology & Archive

A young Navy SK3 experiences his last mission before coming home to a country with very different opinions about his service.

Articles, stories, and other compositions in this archive were written by participants in the Mighty Pen Project. The program, developed by author David L. Robbins, and in partnership with Virginia Commonwealth University and the Virginia War Memorial in Richmond, Virginia, offers veterans and their family members a customized twelve-week writing class, free of charge. The program encourages, supports, and assists participants in sharing their stories and experiences of military experience so both writer and audience may benefit.

Peep Show, Joe Maslanka

Mighty Pen Project Anthology & Archive

An Army veteran reaches out to protect the younger generation when a teen wanders into an adult video shop.

Articles, stories, and other compositions in this archive were written by participants in the Mighty Pen Project. The program, developed by author David L. Robbins, and in partnership with Virginia Commonwealth University and the Virginia War Memorial in Richmond, Virginia, offers veterans and their family members a customized twelve-week writing class, free of charge. The program encourages, supports, and assists participants in sharing their stories and experiences of military experience so both writer and audience may benefit.

New Car Smell, Ken Mick

Mighty Pen Project Anthology & Archive

An Army pilot recounts the initiation of a new helicopter during a mission.

Articles, stories, and other compositions in this archive were written by participants in the Mighty Pen Project. The program, developed by author David L. Robbins, and in partnership with Virginia Commonwealth University and the Virginia War Memorial in Richmond, Virginia, offers veterans and their family members a customized twelve-week writing class, free of charge. The program encourages, supports, and assists participants in sharing their stories and experiences of military experience so both writer and audience may benefit.

In-Danger Animals, James Crawford

Mighty Pen Project Anthology & Archive

An Army Ranger reflects on his experiences with wild animals during his military career, especially an encounter with a tiger in the DMZ.

Articles, stories, and other compositions in this archive were written by participants in the Mighty Pen Project. The program, developed by author David L. Robbins, and in partnership with Virginia Commonwealth University and the Virginia War Memorial in Richmond, Virginia, offers veterans and their family members a customized twelve-week writing class, free of charge. The program encourages, supports, and assists participants in sharing their stories and experiences of military experience so both writer and audience may benefit.

How Much Wood Could A Woodchuck Chuck If This Wood Was Sediment: The Effect Of Marmota Monax On The Archaeological Record, Megan Scalzo

UROP Posters

How Much Wood Could a Woodchuck Chuck if this Wood was Sediment: The Effect of Marmota monax on the Archaeological Record

Megan Scalzo, Dept. of Anthropology, with Dr. Bernard Means, Dept. of Anthropology

Geomorphology is the study of the topographic effects of different physical, chemical, biological processes occurring along and within the landscape. Biological processes can occur from different faunal influences and subsequently get called geomorphic agents. In the majority of North American woodlands, Marmota monax (common names include: groundhog, woodchuck) can be found and thus can be assumed to be geomorphic agents of these woodland areas. In this poster, …

A Game-Theoretic Model Of Monkeypox To Assess Vaccination Strategies, Sri Vibhaav Bankaru, Samuel Kossol, William Hou, Parsa Mahmoudi, Jan Rychtar

UROP Posters

A Game-Theoretic Model of Monkeypox to Assess Vaccination Strategies

Sri Vibhaav Bankaru, Depts. of Biomedical Engineering, Math, & Chemistry, Samuel Kossol, William Hou, & Parsa Mahmoudi, with Dr. Jan Rychtar, Dept. of Mathematics

Monkeypox (MPX) is a zoonotic disease similar to smallpox. Its fatality rate is about 11% and it is endemic to the Central and West African countries. In this paper, we analyze a compartmental model of MPX dynamics. Our goal is to see whether MPX can be controlled and eradicated by voluntary vaccinations. We show that there are three equilibria - disease free, fully endemic and previously neglected …

Exploration Of The Neuronal Subtype Specificity Of An Ethanol Responsive Gene: Glycogen Synthase Kinase 3 Beta (Gsk3b), Dalton Huey, A Van Der Vaart, G M. Harris, M F. Miles

UROP Posters

Exploration of the Neuronal Subtype Specificity of an Ethanol Responsive Gene: Glycogen Synthase Kinase 3 Beta (Gsk3b)

Dalton Huey, Depts. of Bioinformatics, Biology & Chemistry, A. van der Vaart, G. M. Harris, and M. F. Miles, with Dr. Sarah Golding, Dept. of Biology

Previous work done in our laboratory revealed that Glycogen Synthase Kinase 3 Beta (Gsk3b) functions as a hub gene in a network of genes regulated by acute ethanol in the medial prefrontal cortex (mPFC) across a mouse genetic panel. Adult mice treated with acute ethanol showed increased phosphorylation of GSK3B on the Ser9 residue in prefrontal cortex. …

Epigenetic Alterations At Synaptic Plasticity Genes In A Genetically Heterogeneous Rat Model Of Neuropsychiatric Disorders, Doan M. On

Theses and Dissertations

Sensorimotor gating impairments are observed across a range of neuropsychiatric conditions. The prepulse inhibition of the acoustic startle response (PPI) is a validated measure of sensorimotor gating. Genetic and pharmacological manipulations in rodents have shown PPI is regulated by specific brain monoaminergic systems. Using genetically heterogeneous NIH-HS rats, we stratified individuals by %PPI. In low PPI animals, we observed elevated mRNA levels of certain neurotransmitter receptors, including metabotropic glutamate receptor Grm2, dopamine receptors Drd1 and Drd2, serotonin receptors Htr1a and Htr2a, and scaffolding protein Homer1, in the frontal cortex (FC) and striatum (STR). We found Drd2 …

From Bedside To Bench: Use Of Patient-Derived Xenograft Models To Develop Novel Therapeutic Strategies For Triple-Negative Breast Cancer, Tia H. Turner

Theses and Dissertations

Triple-negative breast cancer (TNBC) is a clinically aggressive disease that is associated with bleak outcomes due to its metastatic propensity, frequent failure to respond to chemotherapy, and lack of alternative treatment options. Despite decades of major translational research efforts, there has been very little success thus far in the development of effective targeted therapies for this disease. It is imperative to develop novel therapeutic strategies to improve patient outcomes, as well as minimize the toxicity associated with standard-of-care chemotherapeutics. Given that metastatic disease accounts for the vast majority of TNBC-related deaths, a better understanding of therapeutic responses within common sites …

The Effect Of Intermittent Theta Burst Stimulation On Biceps Corticomotor Excitability In Non-Impaired Individuals And Individuals With Tetraplegia, Blaize Majdic

Theses and Dissertations

Neuromodulation of the primary motor cortex (M1) in pair with physical therapy may be a promising method for improving motor outcomes after spinal cord injury (SCI). Increased excitability of the corticospinal motor pathways (i.e. corticomotor excitability) has shown to be associated with improved motor learning and skill acquisition. Intermittent theta burst stimulation (iTBS) is a form of non-invasive brain stimulation which can increase corticomotor excitability, as measured by an increase in the amplitude of motor evoked potentials (MEPs). However, the ability for iTBS to increase the corticomotor excitability of proximal muscles such as the biceps, and muscles affected by spinal …

Exploring The Use Of Pulsed Erbium Lasers To Retrieve A Zirconia Crown From A Zirconia Implant Abutment, Ahmed Elkharashi

Theses and Dissertations

Removal of zirconia crowns, commonly used as cement-retained implant fixed restorations, can be challenging. Conventional methods of crown removal are time consuming and often leave irreparable damage to the crown, which can be costly to patients and practitioners. This research explored the use of two different types of pulsed erbium lasers, erbium-doped yttrium aluminum garnet laser (Er:YAG) and erbium, chromium-doped yttrium, scandium, gallium and garnet (Er,Cr:YSGG), as non-invasive tools to retrieve cemented zirconia crowns from zirconia implant abutments. Times needed to remove the crowns were recorded and analyzed using ANOVA (��=0.05). No statistical differences between the debond times of each …

Characterization Of The Tsc/Dyrk1a Interaction, Supriya Joshi

Theses and Dissertations

The Tuberous sclerosis complex (TSC) includes TSC1, TSC2 and the TBC1D7 subunits that together function as a principal inhibitor of the mTOR protein kinase complex 1 (mTORC1). mTORC1 is a master regulator of cell growth and proliferation that responds to signaling cues such as growth factors and nutrient availability. Proteomic studies in our lab revealed an interaction between the TSC subunits and DYRK1A, a ubiquitous protein kinase encoded by a gene located in the Down syndrome (DS) region on human chr21. In this study, we sought to validate the interaction of the TSC components with DYRK1A and to determine the …

Dna Analysis And The Postmortem Submersion Interval From The Microbiome Of Waterlogged Sus Scrofa Skeletal Remains, Claire Cartozzo

Theses and Dissertations

Following water-related deaths, soft tissue on victims’ remains may be entirely absent after a temperature dependent period of time. Due to their physical and chemical components, which protect them from environmental deterioration and biological attack, bones preserve DNA for longer periods of time. Therefore, the ability to both identify an individual and estimate the postmortem submersion interval (PMSI) may depend on DNA obtained from skeletal remains. The goals of the dissertation were to examine differences in both the degradation of skeletal DNA and the microbiome inhabiting bone in freshwater aquatic environments (e.g., Henley Lake and the James River). At each …

Characteristics Of Alveolar Bone Marrow Cells From Patients Undergoing Dental Extractions Or Dental Implant Therapy, Meng H. Lee

Theses and Dissertations

Alveolar bone marrow stromal cells (aBMSCs) play important roles in craniofacial wound healing. To establish an easy, efficient and reliable method to harvest aBMSCs, we compared three different methods: extraction socket aspiration, osteotomy aspiration and bone core digestion. Samples of aBMSC were collected from two groups of subjects. Group 1 (dental extraction): after dental extraction, 22.5-gauge needles were used to collect 0.5-1cc marrow aspirate. Group 2 (dental implant): during implant surgeries, bone core and 0.5-1cc marrow aspirate were obtained from the osteotomy. Samples were cultured in petri dishes and attached cells were expanded. The population doubling time (PDT), surface markers, …

The Future In The Instant: Time As The Essence Of Dramatic Tension In Shakespeare's Plays And Their Contemporary Stage Appropriations, Amalia Oswald

Theses and Dissertations

This project looks at the similarities and differences between three Shakespeare plays and their companion contemporary stage appropriations: Othello and Toni Morrisons’s Desdemona, The Winter’s Tale and Mary Elizabeth Hamilton’s 16 Winters or the Bear’s Tale, and Macbeth and Daivd Grieg’s Dunsinane. The specific lens used to examine these texts is the dramatic concept of time, taking the form of different variations throughout the work such as chronology, remembrance, fate, and futurity. This project argues that the multifaceted dramatic concept of time is the foundation for dramatic tension and the principal connecting motif between the three sets of early modern/contemporary …

Characterizing Glycosaminoglycan And Glycosaminoglycan-Oligo Interactions With Cancer Stem Cells And Their Regulators, Rahaman Navaz Gangji

Theses and Dissertations

Tumor metastasis and recurrence account for more than 90% of cancer-associated deaths and are thought to occur due to a small subpopulation of neoplastic cells known as cancer stem cells (CSCs). Because CSCs are resistant to conventional chemotherapy, there is a critical need to develop CSC-targeting agents. Microenvironmental components, especially glycosaminoglycans (GAGs), play a key role in regulating CSC phenotype. GAGs such as heparan sulfate (HS) interact with hundreds of proteins and influence a variety of biological processes including tumor proliferation, angiogenesis, metastasis and stem cell biology.

Recently, the Desai and Patel laboratories have demonstrated that a hexasaccharide form of …

Robert Catherine, Sarah Nelson Rupp

Theses and Dissertations

Robert Catherine is an experimental augmented reality novel engaged in the speculative realist question: What is the point to anything if everything?

A perverted and downwardly mobile Richmond millennial man quarantined because of the Coronavirus writes a series of creative non-fiction essays for his girlfriend about suicide, panic attacks, ADHD, DNA testing, capitalism, depression, and sexual repression.

Effects Of (R,S)-Ketamine And (2r,6r)-Hydroxynorketamine: A Preclinical Study, Remington Rice

Theses and Dissertations

In 2017, 7.1% of US adults were diagnosed with depression, and 50% of patients received medication to treat their depression. Depression can cause severe interruptions in an individual's cognitive functioning and behaviors like sleeping, eating, working, and socializing. Unfortunately, approximately 40% of patients do not respond to treatment with monoaminergic medications (e.g. Prozac) and therapeutic effects may be delayed 2-8 weeks. Due to these therapeutic shortcomings, faster acting and more efficacious treatments are needed. Recent preclinical findings indicate potential for glutamatergic drugs like (R,S)-ketamine and (2R,6R) hydroxynorketamine to produce more rapid and longer-acting therapeutic effects. The antidepressant effectiveness of (R,S)-ketamine …

Molecular And Behavioral Mechanisms Mediated Paclitaxel-Induced Changes In Affect-Like Behavior In Mice, Julia Meade

Theses and Dissertations

Paclitaxel and oxaliplatin are two chemotherapeutics that cause acute neurotoxicity and chemotherapy-induce peripheral neuropathy (CIPN) in 70-90% of cancer patients. Chemotherapy-induced sensory changes are correlated with depression and anxiety. We characterized the effects of these drugs on sensation and various mood-related behaviors in mice, to determine if changes in sensation are associated with depression-like behavior, to explore putative mechanisms of chemotherapy-induced depression-like behavior (Aim 1), and to develop a mouse model of chemotherapy-induced operant responding deficit (Aim 2). In Aim 1, we observed that a cumulative dose of 32 mg/kg paclitaxel induced mechanical hypersensitivity and transiently reduced preference for sucrose …