Digital Commons Network^™

Utilizing Voltage-Gated Calcium Channels To Assess The Activity Of Cathinone Derivatives At Human Monoamine Transporters, Brian A. Ruiz

Theses and Dissertations

Cathinones are psychostimulant compounds heavily implicated as drugs of abuse. They exert their physiological actions at the monoamine transporters, which are responsible for maintaining synaptic neurotransmitter homeostasis. Monoamine transporters produce currents during transport and have been shown to depolarize cell membranes and activate voltage-gated calcium channels in mammalian expression systems. This phenomenon is harnessed in an assay which measures these induced calcium transients, allowing for quantification of pharmacodynamic effects of compounds at monoamine transporters. It is unknown if this electrical coupling occurs in neurons, but the implications if it does are significant. In the current work, fluorescent resonance energy transfer …

Improving The Conservation Of A Cryptic Endangered Freshwater Mussel (Parvaspina Collina) Through The Use Of Environmental Dna And Species Distribution Modeling, Bonnie A. Roderique

Theses and Dissertations

Conservation efforts that involve habitat protection, population augmentation, and species reintroductions require knowledge of the habitat requirements, distribution, and abundance of a species—information that can be challenging to acquire, especially for rare organisms with patchy distributions. In this thesis, I develop a protocol for the use of environmental DNA (eDNA) and create a Species Distribution Model for the endangered James spinymussel, Parvaspina collina (Unionidae). The results of this work show that eDNA is a robust tool for identifying species presence but not for estimating the relative abundance of populations. This study found that P. collina’s distribution is influenced by abiotic …

Placental Eicosanoids And Sphingolipids In Preeclampsia, Daniel T. Reep

Theses and Dissertations

Placental dysfunction is implicated in the pathogenesis of preeclampsia. Chemical signals between the placenta and maternal circulation are a suspect cause of endothelial dysfunction and maternal hypertension. This study examined select lipid mediators of inflammation produced by the placenta. Patients were recruited from Virginia Commonwealth University’s pregnancy clinics and placentas were collected at delivery. Forty-eight-hour explant cultures of villous placental tissue were used to model lipid production. Electrospray ionization mass spectrometry was used to quantify concentrations of free lipids in the culture media. Bicinchoninic acid assays were performed to quantify protein in each culture for normalization of lipid data. After …

Aerobic Exercise Exposure Targeting Anxiety Sensitivity: Effects On Associated Health Behaviors In Young Adults, Autumn Lanoye

Theses and Dissertations

Anxiety sensitivity (AS) is associated with health behaviors such as low rates of physical activity, overeating, alcohol use, and poor sleep; however, interventions targeting AS via exercise-based interoceptive exposure have not assessed these as outcomes. In addition, previous studies are limited by brief follow-up periods. This study aimed to replicate previous aerobic exercise interoceptive exposures with an extended (6-week) follow-up and measurement of health behaviors.

Participants were 44 sedentary young adults with elevated AS randomized to intervention (6 20-minute sessions of moderate-intensity treadmill walking) or assessment-only control. Assessments took place at baseline, week 2 (post-treatment), week 4, and week 8 …

Integral Measurement Of Atmospheric Particulate Matter (Pm), Di Liu

Theses and Dissertations

Atmospheric aerosol particles also known as atmospheric particulate matter or particulate matter (PM) are microscopic particles (solid or liquid) suspended in air, which is one of six air pollutants in US air quality standard. PM is classified as coarse particles with diameters between 2.5 to 10 mm, fine particles with a diameter less than 2.5 mm (PM_2.5), and ultrafine particles with the diameter less than 0.1 mm (PM_0.1). Epidemiological studies have already showed the adverse health effects (such as asthma, lung cancer and respiratory and cardiovascular disease) resulted from exposure to the fine and ultrafine particles. …

Role Of C121a In Mglur2 Homodimeric Expression And Function, Jong M. Shin

Theses and Dissertations

The group II metabotropic glutamate receptors are known for their involvement in various psychiatric disorders. The mGluR2 in particular is linked with etiology of schizophrenia especially in the context of crosstalk with 5-HT2A. Thus, the mGluR2 has attracted attentions for its potential therapeutic applications. Despite numerous physiological evidences on the actions of mGluR2, its mechanism is still unclear to this day. It is partially due to the lack of understanding in characteristics of mGluR2 homodimer which is its functionally active form. Therefore, the characterization of dimeric interaction serves as a foundation to advanced understanding of the role of mGluR2. On …

Exploring Literacies In The Assemblage Of Adult Education English For Speakers Of Other Languages Classrooms, Susan Watson

Theses and Dissertations

The purpose of this dissertation is to provide a posthuman perspective of adult second language and literacy learning using the philosophy of Gilles Deleuze and his collaborative work with Félix Guattari, Masny’s (2005/6) multiple literacies theory or MLT, and DeLanda’s (2016) assemblage theory. Thinking with these scholars, I employ a post-qualitative, posthuman MLT conceptual framework to study literacy as a process that flows through and connects with globally-diverse students, languages, worldviews, and texts in the assemblage of adult education, English for speakers of other languages (ESOL) classrooms. I posit this assemblage as a remarkable and important context for literacy research …

Novel Insights Into The Contribution Of Cellular Senescence To Cancer Therapy: Reversibility, Dormancy And Senolysis., Tareq Saleh

Theses and Dissertations

Cellular senescence a specialized form of growth arrest that contributes to the pathogenesis of several aging-related disorders including cancer. While by definition tumor cells are considered immortalized, they can undergo senescence when exposed to conventional and targeted cancer therapy. Therapy-Induced Senescence (TIS) represents a fundamental response to therapy and impacts its outcomes. However, TIS has been considered a positive therapeutic goal since senescent tumor cells are expected to enter a state of permanent growth abrogation. In this work we examined the hypothesis that a subpopulation of senescent cells can re-acquire proliferative potential after a state of senescent dormancy, indicating that …

Women In Music: Letting A Long Story Be Long Contemplating Women’S Sonic, Musical, And Spiritual Experiences In Prehistory, Deborah J. Saidel

Theses and Dissertations

Situated within deep history, this study explores the auditory and spiritual lives of Paleolithic women. It considers their personal agency in mediating the spiritual power of sound and how doing so contributes to a multifaceted musicality. The theoretical framework involves a wide spectrum of topics, from ways of rethinking the writing of history and reckoning with time, to sound studies and the study of acoustics in ancient sites, to a critical examination through a feminist lens of normative disciplinary scholarship in anthropology and archaeology, religious studies, and musicology. I explore potential audio-visual-lithic relationships for their implications for deepening an understanding …

Trna Profiling Of Mesenchymal Stem Cell Exosome, Khin Mimi San

Theses and Dissertations

Background: Exosomes have great potential in regenerative medicine through the

transfer of their bioactive cargos, such as RNA. tRF RNA and tiRNA are tRNAderived

non-coding RNA. Here, we sought to identify the tRF/tiRNA profile in human

mesenchymal stem cell (hMSC) exosomes. Methods: Bone marrow hMSCs were

cultured with/without osteogenic differentiation medium and exosomes were

harvested. RNA was extracted from: 1) control cells (Cell-NT); 2) control exosomes

(EXO-NT); 3) differentiated cells (Cell-OM); 4) exosomes produced by differentiated

cells (EXO-OM). RNA was sequenced to profile the small RNA with a focus on

tRF/tiRNA. Results: tRF/tiRNA was highly enriched in hMSC exosomes. Less …

Secondary Student Information Literacy Self-Efficacy Vs. Performance, Jen Spisak

Theses and Dissertations

The amount of information in the world has grown exponentially in the last generation. Students often believe that growing up as digital natives means they have advanced information literacy skills. However, school librarians are not seeing evidence of this in their schools. The purpose of this study was to determine if secondary students overestimate their information literacy (IL) abilities, if relationships exist between IL self-efficacy and performance, and if grade level or self-efficacy level changes those relationships. To accomplish this, data were collected from two middle schools and three high schools from a total of 397 students in grades 6, …

Water Dynamics And The Effect Of Static And Alternating Electric Fields, Mohammadmahdi Shafiei Alavijeh

Theses and Dissertations

Having a net dipole moment, water molecules tend to align with an external electric field. The re-orientation of water molecules to align with the field direction can result in structural and dynamic changes in liquid water. Studying these changes can help us to understand the role of an E-field in many biological systems, chemical reactions, and many technological advancements.

In short, the application of static electric fields causes molecules to stay aligned with the field, so, fewer hydrogen bonds break, and molecules have slower dynamics. This type of field can be used when the mobility of water molecules needs to …

Rep-Dna Complexes And Their Role In Aav Dna Transactions, Vishaka Santosh

Theses and Dissertations

Adeno-associated Virus (AAV) Rep proteins are multifunctional proteins that carry out various DNA transactions required for the life cycle of AAV. The Rep proteins have been found to be important for genome replication, gene regulation, site-specific integration and play an essential role in genome packaging. There are two main groups of Rep proteins: large and small Reps; both groups are SF3 helicase family members. During DNA packaging, studies have shown that the small Rep proteins are critical to produce fully packed particles. Using stopped-flow kinetic analysis, we show a significant difference in helicase activity between the small and large Rep …

Examination Of The Role Of Dehumanization As A Potential Mechanism Underlying The Racial Disparities In School Disciplinary Measures., Ebony A. Lambert

Theses and Dissertations

Schools should be safe and supportive spaces for all students, yet Black students tend to face biased treatment in the education system, which often results in harsh disciplinary measures. This research examined the role of animalistic dehumanization (i.e., perceiving others as animal-like and uncultured and denying uniquely human characteristics), in predicting choice of harsher disciplinary measures for Black students as opposed to White students. It was hypothesized that individuals who dehumanize Black students to a greater degree would be more likely to believe that Black students need to be disciplined through harsher measures. Additionally, it was hypothesized that the link …

Shared Genetic And Environmental Influences On Fear, Anxiety, Posttraumatic Stress, And Brain Morphometry, Chelsea Sawyers

Theses and Dissertations

Anxiety disorders (ADs) and stress-related disorders are some of the most common psychiatric disorders in the United States. Like other c0mplex psychiatric illness, genetics and neuroimaging research has focused on understanding their underlying neurobiology. Areas within the fear-network play important roles in threat perception, fear conditioning/learning, cognitive processing, and modulation of fear responses including contextual modulation and extinction and have been implicated in ADs as well as stress disorders such as posttraumatic stress disorder (PTSD). The primary gap in the current search for underlying biological mechanisms is in whether biomarkers associated with disorders share genetic influences with the disorders they …

Effects Of A 2-Week Exercise Intervention On Heart Rate Variability In Individuals With Low And High Anxiety Sensitivity, Hannah M. Kotarski

Theses and Dissertations

Anxiety Sensitivity (AS), the belief that anxiety-related sensations may have harmful implications, can alter autonomic nervous system (ANS) function. Exercise has previously been shown to reduce AS; however, the effects of an exercise intervention on heart rate variability (HRV), a measure of ANS function, has not been evaluated in individuals with high AS. This study sought to 1) compare resting HRV in individuals with either low (LAS) or high AS (HAS) and 2) evaluate the effects of a 2-week exercise intervention on HRV and AS. Using the Anxiety Sensitivity Index (ASI-3), participants were identified as LAS (n=9; ASI-3=5.89±1.39) or HAS …

Nicotinic Acetylcholine Receptor Dependent Effects Of Nicotine On Hek293t And Hbo Cells, James D. Larsen

Theses and Dissertations

T2R receptors are the classical bitter taste receptors which detect and transduce bitter taste in a subset of taste receptor cells (TRCs). The TRPM5-dependent T2Rs are G-protein coupled receptors (GPCRs) and are linked to G protein, gustducin to initiate an intracellular signaling cascade for the transduction of bitter tastants. Nicotine is bitter. However, at present the transduction mechanisms for the detection of nicotine in are poorly understood. Previous studies from our laboratory using TRPM5 knockout (KO) mice demonstrated that the T2R pathway is insufficient in explaining the taste perception of nicotine. TRPM5 KO mice elicited chorda tympani (CT) taste nerve …

The Effect Of Biologic Materials And Oral Steroids On Radiographic And Clinical Outcomes Of Horizontal Alveolar Ridge Augmentation., Amy Reichert

Theses and Dissertations

The purpose of this study was to investigate if the addition of biologic materials and/or oral steroids would affect horizontal bone gain, or the bone density of the grafted bone in horizontal alveolar ridge augmentations. A retrospective chart review was completed to assess the clinical and radiographic outcomes of 53 ridge augmentation patients. An average bone gain of 3.6mm of width was found in our study based on radiographic analysis. There were no statistically significant differences found in the linear bone gain with the addition of biologic materials and steroids. A marginally statistically significant difference was found in the bone …

Investigation Of Gold(Iii) Complexes With Hiv-Ncp7 And Models, James Beaton

Theses and Dissertations

The medicinal uses of gold date as far back as 2500 B.C. in China. In modern times, gold has been used in the treatment of a number of different human diseases including rheumatoid arthritis, cancer, and viral infections. This dissertation will focus on the development of gold complexes for the purpose of selective inhibition of HIV NCp7, a 55 amino acid zinc finger protein with two Cys₃His zinc binding domains.

NCp7 is involved in a number of viral life cycle processes including activation of reverse transcription, integration, DNA recognition, RNA packaging, and formation of the viral envelope. The …

Mechanisms Of B-Myb Oncogenicity In Ovarian Cancer, Audra N. Iness

Theses and Dissertations

High expression of B-Myb (encoded by MYBL2), an oncogenic transcription factor, is associated with cell cycle deregulation and poor prognosis in several cancers, including ovarian cancer. However, the mechanism by which B-Myb alters the cell cycle is not fully understood. In proliferating cells, B-Myb interacts with the MuvB core complex including LIN9, LIN37, LIN52, RBBP4, and LIN54, forming the MMB (Myb-MuvB) complex, and promotes transcription of genes required for mitosis. Alternatively, the MuvB core interacts with Rb-like protein p130 and E2F4-DP1 to form the DREAM complex that mediates global repression of cell cycle genes in G0/G1, including a subset …

The Role Of Adam10 And Adam17 In Humoral And Type 2 Immunity, Joseph C. Lownik

Theses and Dissertations

The proper regulation of inducible costimulator (ICOS) and its ligand (ICOSL) have been shown to be essential for maintaining immune homeostasis. Loss of either protein results in defective humoral immunity, and overexpression of ICOS results in aberrant antibody production resembling lupus. How ICOSL is regulated in response to ICOS interaction is still unclear. We demonstrate that ADAM10 is the primary physiological sheddase of ICOSL in both mouse and human. Using an in vivo system in which ADAM10 is deleted only on B cells (ADAM10^B-/-), elevated levels of ICOSL were seen. This increase is also seen when ADAM10 is …

5-Ht2b Receptor-Mediated Cardiac Valvulopathy, Pallavi Nistala

Theses and Dissertations

5-HT_2B receptor agonism causes cardiac valvulopathy, a condition characterized by thickening of the heart valves and as a result, regurgitation of blood within the heart. The anti-obesity drug fenfluramine, which was originally prescribed as an anorectic, was withdrawn from the market due to causing cardiac valvulopathy. Fenfluramine, after metabolism by N-dealkylation, produces the metabolite norfenfluramine, which acts as a more potent valvulopathogen. The same was seen with MDMA (ecstasy), a popular drug of abuse, which is metabolized by N-dealkylation to produce MDA, a more potent valvulopathogen. Glennon and co-workers. studied a series of 2,5-dimethoxy-4- substituted phenylisopropylamines (DOX type) hallucinogens …

Family Planning And Hiv Interventions Among Women In Low-Income Settings, Steven P. Masiano

Theses and Dissertations

This dissertation examines the effectiveness of interventions related to family planning and the uptake of HIV-related preventive services among women in low-income settings. Women in low-income settings and living with HIV face many barriers to care, including limited access to services for family planning and HIV-related preventive care. At the same time, national, regional, and global efforts are looking for interventions to help control rapid population growth, create an HIV-free generation, and provide adequate preventive care for those living with HIV. This dissertation cuts across these issues and can help to inform debate and policies to address these issues.

This …

Drug Delivery With Light, Patrick S. Dupart

Theses and Dissertations

Cancer is responsible for about 25% of deaths in developed countries and for 15% of all deaths worldwide. Cancer is a devastating disease and while there have been great advances in the development of anticancer drugs, off-target toxicity is a major limitation with conventional cancer chemotherapy. The consequence of this form of treatment results in the killing of healthy and rapidly-growing non-cancerous cells including cells in the bone marrow; hair follicles; and cells in the mouth, digestive tract, and reproductive system. In addition to these general effects, certain anticancer drugs can have other associated toxicities. For instance, the anticancer drug …

Decellularized Matrices Effect On The Adaptive Immune Response, Kegan Sowers

Theses and Dissertations

Decellularized extracellular matrices have been a growing area of interest in the biomedical engineering fields of tissue engineering and regenerative medicine.As these materials move toward clinical applications, the immune response to these materials will be a driving force toward their success in clinical approaches. Fully digested decellularized matrix constructs derived from porcine liver, muscle and lung were created to test the adaptive immune response. Hydrogel characterization ensured that the materials had relatively similar stiffness levels to reduce variability, and in vitro studies were conducted. Each individual construct as well as a gelatin control were plated with a co-culture of macrophages …

Decoding The Signaling Of The D2r-2ar Heteromer: Relevance To Schizophrenia, Miao Huang

Theses and Dissertations

Schizophrenia is a severe mental disorder affecting ~1% of world population. Two G protein coupled receptors (GPCRs): Gi-coupled dopamine D2 receptor (D₂R), and Gq-coupled serotonin 2A receptor (2AR), are targeted by the typical and atypical antipsychotic drugs to treat schizophrenia. These two receptors have been shown to co-localize in brain regions relevant to schizophrenia, including the ventral tegmental area (VTA), striatum, and prefrontal cortex (PFC). Studies in our lab characterized the integrated signaling of the D₂R-2AR heteromer and found that both the Gi activity of D₂R and the Gq activity of 2AR were potentiated …

Forest Structural Complexity And Net Primary Production Resilience Across A Gradient Of Disturbance In A Great Lakes Ecosystem, Lisa T. Haber

Theses and Dissertations

Forests are an important component of the global carbon (C) cycle and contribute to climate change mitigation through atmospheric C uptake and storage in biomass and soils. However, the forest C sink is susceptible to disturbance, which modifies physical and biological structure and limits spatial extent of forests. Unlike severe, stand-replacing disturbances that reset forest successional trajectories and may simplify ecosystem structure, moderate severity disturbances may instead introduce complexity in ways that sustain net primary production (NPP), leading to the phenomenon of “NPP resilience.” In this study, we examined the linkage between disturbance severity and ecosystem biological and physical structural …

Gastrointestinal Microbiota Modulate Antinociceptive Tolerance Development In Mice With Chronic Morphine Exposure, Ryan A. Mischel

Theses and Dissertations

In October 2017, the United States government declared a state of public health emergency in response to the burgeoning prescription opioid epidemic. Opioid analgesics are the gold standard of therapy for moderate to severe pain, but their clinical utility is greatly limited by analgesic tolerance – a primary driver of diminished pain control and opioid dose escalations. Integral in this process are primary afferent sensory neurons in dorsal root ganglia (DRG), the first-order components of nociceptive sensation. With surmounting evidence that morphine and other narcotics can alter gut microbial composition and promote bacterial translocation to other tissues, a question arises …

Climate Change And Mountaintop Removal Mining: A Maxent Assessment Of The Potential Dual Threat To West Virginia Fishes, Lindsey R F Hendrick

Theses and Dissertations

Accounts of species’ range shifts in response to climate change, most often as latitudinal shifts towards the poles or upslope shifts to higher elevations, are rapidly accumulating. These range shifts are often attributed to species ‘tracking’ their thermal niches as temperatures in their native ranges increase. Our objective was to estimate the degree to which climate change-driven shifts in water temperature may increase the exposure of West Virginia’s native freshwater fishes to mountaintop removal surface coal mining. Mid-century shifts in habitat suitability for nine non-game West Virginia fishes were projected via Maximum Entropy species distribution modeling, using a combination of …

Strengthening Social Networks Of Youth Aging Out Of Foster Care: Promoting Positive Adult Outcomes, Rachel D. Rosenberg

Theses and Dissertations

During the transition to adulthood, youth often rely on the people in their life for support. However, for transition-aged foster youth, these supports may not be available or may look different than supports available to youth in the general population. Relationships with supportive adults have been found to help former foster youth transition to adulthood, but little is known about the adults youth have in their network. Foster youth who report increased levels of social capital have been shown to experience higher levels of success in young adulthood. However, as former foster youth transition to adulthood, a lack of in-depth …