Life Sciences Commons^™

Glucocorticoid Receptor Dysregulation Underlies 5-Ht2a Receptor-Dependent Synaptic And Behavioral Deficits In A Mouse Neurodevelopmental Disorder Model, Justin M. Saunders

Theses and Dissertations

Schizophrenia is a severe neuropsychiatric disorder that presents with diverse symptoms, some of which remain resistant to treatment. Increased risk of neurodevelopmental disorders such as schizophrenia has been observed following gestational infection in humans, leading to development of maternal immune activation (MIA) animal models. Increased density of the serotonin 5-HT2AR receptor (5-HT2AR), the primary target of hallucinogenic drugs and a key target of atypical antipsychotics, has been observed in postmortem antipsychotic-free prefrontal cortex samples from schizophrenia subjects, a change reflected in frontal cortex of adult MIA offspring. To model MIA, we administered 20 mg/kg i.p. of the viral mimetic poly-(I:C) …

Comparing The Sensitivity And Specificity Of Cbct And Mri In Detecting Osteoarthritis Of The Tmj: A Systematic Review, Gabriel R. Saavedra

Theses and Dissertations

The aim of this systematic review was to compare the sensitivity and specificity of cone-beam computed tomography (CBCT) and magnetic resonance imaging (MRI) in detecting osteoarthritis (OA) of the temporomandibular joint (TMJ). This was done by using computed tomography (CT) and the research diagnostic criteria for temporomandibular disorders (RDC/TMD) as reference methods and using CBCT and MRI as index methods. A specific search strategy was developed and applied to these electronic databases: PubMed, Embase, DOSS, and Cochrane. The search results returned 802 articles, which were then narrowed down using the inclusion/exclusion criteria, to four final articles that were included in …

A Computational Model Relating Tissue Oxygen Consumption To Oxygen Delivery In A Krogh Cylinder Model Of Skeletal Muscle, Raghad A. Alqahtani

Theses and Dissertations

Oxygen transport from a capillary to skeletal muscle tissue is a complex process that involves convective and diffusive mechanisms to deliver adequate oxygen to meet tissue metabolic activities. Typically, oxygen uptake in tissue is set by oxygen demand, which is set by metabolic activity. The relationship between the oxygen consumption (VO₂) of an isolated perfused tissue and the rate of delivery of oxygen (QO₂) to the tissue has been a subject of interest to many investigators over the past century. Experiments have shown that there is a critical value of QO₂ below which tissue VO …

Qualitative And Quantitative Characterization Of Epithelial Cell Mixtures Using Hormone Antibody Probes And Flow Cytometry, Luke Baldridge

Theses and Dissertations

“Touch” DNA is evidence that consists of epidermal cells deposited by handling objects and it is becoming more common in evidence samples processed in crime labs. Because “touch” DNA evidence samples may be low-template DNA and are often mixtures, there is a need to both nondestructively estimate the amount of DNA present prior to DNA purification and to identify and characterize mixtures prior to DNA typing. The purpose of this study was to test the use of FITC-labeled anti-testosterone antibodies as a potential tool to estimate the number of contributors in two-, three-, and four-person mixtures of epidermal skin cells, …

Quantitative Pcr And Sanger Sequencing Of Mitochondrial Dna Recovered From Waterlogged Bone, Kailey Babcock

Theses and Dissertations

In forensic contexts, samples containing heavily fragmented DNA are commonly encountered. Compromised biological samples are especially prevalent in instances where human remains have been submerged in an aqueous environment for extended periods of time. Nuclear DNA is particularly vulnerable to the prolonged exposure to heat, moisture, and bacterial degradation that are prevalent in aquatic settings. Paired with the difficulty of recovering DNA from skeletal remains, which are often the only remaining component after the soft tissues have been stripped away, mitochondrial DNA (mtDNA) analysis serves as an invaluable alternative. In this multifaceted study, mtDNA analysis was performed on waterlogged bone …

Comparison Of Semi-Automated And Manual Differential Separation Methods For Mock Sexual Assault Samples, Stephanie Rink

Theses and Dissertations

In the event of a sexual assault, separation of suspect from victim DNA is possible through differential extraction if the evidentiary mixture consists of female epithelial cells and male spermatozoa. The basis of differential extraction is the differing properties of epithelial and sperm cell membranes, specifically the comparative sturdiness of the proteins making up the sperm head containing the male DNA. Effective retrieval and separation of male and female DNA fractions is important in generating high-quality STR profiles that can be utilized in identifying suspects in a sexual assault case. Differential extraction has been conventionally performed using Proteinase K (PK) …

Development And Evaluation Of A Combinatorial Rt-Qpcr Multiplex For Forensic Body Fluid Identification, Carolyn A. Lewis

Theses and Dissertations

Body fluid identification is essential in the forensic biology workflow that assists DNA analysts in determining where to collect DNA evidence. Current presumptive tests lack the sensitivity and specificity molecular techniques can achieve; therefore, molecular methods, such as microRNA and microbial signatures, have been extensively researched in the forensic community. Limitations of each method suggest combining molecular markers to increase discrimination efficiency of multiple body fluids from a single assay. While microbial signatures have been successful in identifying fluids with high bacterial abundances, microRNAs have shown promise in fluids with low microbial abundance. A disadvantage of RNA analysis in forensic …

Microrna In The Mammalian Growth Plate: Matrix Vesicles And 1Α,25-Dihydroxyvitamin D3, Niels C. Asmussen

Theses and Dissertations

Growth plate chondrocytes are the driving force of long bone elongation and they accomplish this vital task, in part, by producing, remodeling, and finally mineralizing the cartilage tissue that makes up the growth plate. This mineralized tissue is turned over again as bone forming cells invade and began the process of turning mineralized cartilage into bone. Chondrocytes undergo a distinct series of observable phases as they move through this process transitioning from a stage of proliferation to one of hypertrophy and finally capillary invasion. Chondrocytes produce matrix vesicles (MVs) that they release into the growth plate and that attach to …

Water Clarity At The River-Estuary Transition Zone: A Comparative Study Of The James, Mattaponi, And Pamunkey Sub-Estuaries, Rachel Henderson

Theses and Dissertations

Water clarity is a key parameter for monitoring water quality and often used to assess habitat suitability for submerged aquatic vegetation (SAV). Light attenuation, a measure of water clarity, is impacted by colored dissolved organic matter (CDOM), and by suspended particulates which include living and non-living components. We anticipated that the relative importance of these factors in regulating light attenuation would vary among the upper portions of three sub-estuaries differing in morphometry, hydrology, and degree of human influence. The James is characterized by eutrophic conditions and high algal abundance, whereas the Mattaponi and Pamunkey exhibit lower phytoplankton production. The Mattaponi …

Influence Of Metal Sleeves In The Accuracy Of Dental Implant Placement Using Guided Implant Surgery, Coleman Adams

Theses and Dissertations

The fabrication of implant surgical guides through stereolithographic 3D printing has become a staple in dental implant guided surgery over the last couple decades. These surgical guides have typically utilized metal sleeves to assist in guidance of the drills during osteotome preparation. The metal sleeves can be costly and potentially cause deviations if improperly placed during post-processing of the guide. This research explored a novel method for the utilization of sleeve-free surgical guides by comparing the dimensional and angulational deviations between the implant guides with and without a metal sleeve. To achieve this goal, two separate aims were pursued. Our …

Searching For Gold: Using A Novel Land Cover Classification To Identify Multiscale Drivers Of Site Occupancy By A Flagship Species For Early-Successional Habitat Conservation, Baron Lin

Theses and Dissertations

Understanding habitat selection at multiple scales is an important step in guiding conservation programs and reversing species declines. This, however, is difficult for species that occupy early-successional habitats (ESH) due to a lack of accurate representation of shrub cover in publicly available land cover data. The Golden-winged Warbler (Vermivora chrysoptera; GWWA) is a threatened species of conservation concern and a flagship for ESH conservation. We used a novel, LIDAR-derived land cover classification that accurately identifies shrubs at a fine resolution (1m) to investigate how habitat composition and configuration influence GWWA site occupancy. We aggregated this same land cover …

Comparison Of Antibiotic Resistance In Biofilm, Sediment, And Planktonic Communities Of The James River, Mary Bernadette Coughter

Theses and Dissertations

Antibiotic resistance spread within aquatic bacterial communities, particularly ones in urban areas, is in part driven by wastewater inflows that may contain both elevated concentrations of antibiotics and increased abundance of antibiotic resistant bacteria. These can be transmitted into the environment via release of treated wastewater, since removal of these compounds by most wastewater treatment facilities is inadequate, or by release of untreated waste from leaking wastewater treatment networks and overflow of combined sewer systems. This study used the James River and the City of Richmond wastewater network as a model urban waterway to study both types of impacts. Shotgun …

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …

Computational Analysis And Prediction Of Intrinsic Disorder And Intrinsic Disorder Functions In Proteins, Akila I. Katuwawala

Theses and Dissertations

COMPUTATIONAL ANALYSIS AND PREDICTION OF INTRINSIC DISORDER AND INTRINSIC DISORDER FUNCTIONS IN PROTEINS

By Akila Imesha Katuwawala

A dissertation submitted in partial fulfillment of the requirements for the degree of Engineering, Doctor of Philosophy with a concentration in Computer Science at Virginia Commonwealth University.

Virginia Commonwealth University, 2021

Director: Lukasz Kurgan, Professor, Department of Computer Science

Proteins, as a fundamental class of biomolecules, have been studied from various perspectives over the past two centuries. The traditional notion is that proteins require fixed and stable three-dimensional structures to carry out biological functions. However, there is mounting evidence regarding a “special” class …

Muscarinic Excitation Of Dopamine Neurons In The Ventral Tegmental Area Via Activation Of A Trpc-Like Cation Conductance, Yu Tzu Chen

Theses and Dissertations

Dopaminergic (DA) neurons in the ventral tegmental area (VTA) play a crucial role in reward and motivational behaviors, including the development of drug addictions. VTA DA neurons receive excitatory cholinergic inputs from the mesopontine tegmentum. Blockage of the M5 muscarinic receptor in DA neurons has been shown to attenuate drug-induced DA release and abuse-related behaviors, but the molecular mechanism is unknown. In this study, experiments were designed to identify the electrophysiological effects of muscarinic agonism in the modulation of action potential kinetics and firing patterns in VTA DA neurons of mice. Pharmacology of the muscarinic receptor-evoked current was also characterized. …

A Novel Immunostimulatory Platform For Amplifying The Abscopal Response Rates Of Radiation Therapy, Patrick A. Paez

Theses and Dissertations

Radiation therapy (RT) is one of the primary treatment modalities for head and neck squamous cell carcinoma (HNSCC). At the time of diagnosis two-thirds of HNSCC patients have local-advanced disease and 50-60% of these patients will experience a local-regional or metastatic relapse within three years. Improving the immunogenic response of RT may help address this clinical problem. However, current RT regimens have failed to reliably generate robust antitumor immunity as evidenced by the rarity of clinical abscopal responses. Recently we engineered a chimeric fusion molecule called Flagrp170, a novel immunostimulatory agent highly capable of promoting antigen presentation and T-cell activation. …

Interclass Gpcr Heteromerization Affects Localization And Trafficking, Rudy Toneatti

Theses and Dissertations

Class A serotonin (5-hydroxytryptamine) 2A (5-HT_2AR) and class C metabotropic glutamate 2 receptors (mGluR2) are seven transmembrane receptors (7TMRs or G protein-coupled receptors – GPCRs) involved in multiple neuropsychiatric disorders including schizophrenia. Previous findings from our laboratory reported that 5-HT_2AR and mGluR2 are dysregulated in the prefrontal cortex of patients suffering from this psychiatric condition, although 5-HT_2AR’s expression was recovered in antipsychotic-medicated patients. Genome-wide association studies on schizophrenia reported that endosomal trafficking that regulates cell surface abundance of another 7TMR implicated in this disease (dopamine D2 receptor) can be altered. Ligand-activated receptors, including the …

Plant Communities In Dynamic Systems: How Disturbance Influences Coastal Plant Community Structure And Function, Joseph K. Brown

Theses and Dissertations

As the climate continues to change it is difficult to predict how barrier island function will respond to global change drivers accompanying predicted climate change. Disturbance frequency and nutrient enrichment in coastal regions are drivers of plant community change that increase with climate change. Plant communities on barrier islands are not only tightly connected to barrier island function but are also some of the first communities affected by environmental change, making them a critical piece in understanding how current drivers of global change will impact the future of barrier islands. The objective of my dissertation was to observe and manipulate …

Radioimmunoconjugate For Cancer Molecular Imaging, Nouri Elmekharam

Theses and Dissertations

Over expression of Sperm Acrosomal SLLP1 Binding protein (SAS1B) on the surface of uterine cancer and the availability of different anti-SAS1B monoclonal antibodies (mAbs) that specifically bind to it, offered an opportunity to label these antibodies with radionuclides for cancer imaging. Although optimizing in vivo stable radiolabeling is challenging, imaging this type of aggressive cancer will improve the treatment strategy. The objective of this work is to develop a radiolabeled anti-SAS1B antibodies with Zircunum-89 (⁸⁹Zr) and Copper-67 (⁶⁷Cu) and determine, in vitro and in vivo their uptake and biodistribution. Two anti-SAS1B monoclonal antibodies (SB2, and SB5) …

Phenotypic Characterization Of Table Mountain (Pinus Pungens) And Pitch Pine (Pinus Rigida) Hybrids Along An Elevational Gradient In The Blue Ridge Mountains, Virginia, Alexander L. Brown

Theses and Dissertations

Hybridization has played a long-standing role in the evolution of both plant and animal species and allows for the sharing of genetic information between lineages. Here, potential hybridization of a species endemic to the Appalachian Mountains, Table Mountain pine (Pinus pungens), and pitch pine (Pinus rigida) was investigated along an elevational gradient, through the use of phenotypic measurements: cone length, cone width, and needle length. Phenotypes were used to identify hybrids in a three-tiered elevational sampling method at two sites in Shenandoah National Park with the use of linear discriminant analysis. It was found that hybridization …

Modeling Vegetation Effects On Barrier Island Evolution, Eric W. Schoen

Theses and Dissertations

Barrier islands play a significant role in protecting coastlines and harboring coastal habitats. In an effort to study and better understand the evolution of barrier island systems, a cellular model capturing various meteorological and environmental processes is proposed. Erosion due to wind, gravity, and marine processes are coupled with plant population effects. We demonstrate the inhibition of plant cover on sediment mobility, island migration, and erosion in the presence of sea level rise.

Investigating Cannabinoid Type-1 Receptor (Cb1r) Positive Allosteric Modulators (Pams) In Mouse Models Of Overt Cannabimimetic Activity, Subjective Drug Effects, And Neuropathic Pain, Jayden Elmer

Theses and Dissertations

Chronic pain affects between 20 and 30 percent of the adult population in western countries and represents a wide array of specific etiologies (Berge, 2011). Neuropathic pain secondary to traumatic nerve injury, chemotherapeutic toxicity, or diseases (e.g., diabetes mellitus) is often refractory to conventional analgesics, with patients receiving less than 50% pain relief compared to placebo (Finnerup et al. 2010). The endocannabinoid system has shown potential as a therapeutic target for neuropathic pain wherein CB1 agonism via administration of exogenous agonists or pharmacological blockade of endocannabinoid catabolic enzymes exhibits efficacy in reversing allodynia in the chronic constriction injury (CCI) model …

Evaluating Neuromuscular Function Of The Biceps Brachii After Spinal Cord Injury: Assessment Of Voluntary Activation And Motor Evoked Potential Input-Output Curves Using Transcranial Magnetic Stimulation, Thibault Roumengous

Theses and Dissertations

Activation of upper limb muscles is important for independent living after cervical spinal cord injury (SCI) that results in tetraplegia. An emerging, non-invasive approach to address post-SCI muscle weakness is modulation of the nervous system. A long-term goal is to develop neuromodulation techniques to reinnervate (i.e. resupply nerve to) muscle fiber and thereby increase muscle function in individuals with tetraplegia. Towards this goal, developing monitoring techniques to quantify neuromuscular function is needed to better direct neurorehabilitation. Assessment of voluntary activation (VA) is a promising approach because the location of the stimulus can be applied cortically using transcranial magnetic stimulation (TMS) …

Single Molecule Investigations Of Holliday Junction Binding Protein Ruva, Dalton Reed Gibbs

Theses and Dissertations

DNA breaks are inevitable as they mainly occur due to cells’ own reactive oxygen species (ROS). While DNA breaks can be single-stranded or double-stranded, the double-stranded DNA (dsDNA) breaks are more dangerous. If such damage is not repaired, it can lead to genetic instability and serious health issues including cancers. One way dsDNA breaks can be repaired is via a process called homologous recombination (HR), which involves several DNA-binding proteins. Therefore, to have a better insight into the repair mechanism and origin of repair defects, we need a better understanding of how these proteins interact with DNA itself and DNA …

Pushing The Limits: Increasing The Speed And Specificity Of Sars-Cov-2 Testing, Grayson Way

Theses and Dissertations

The prevalence and spread of the current COVID-19 pandemic have highlighted the importance of continual improvements upon current microbiological testing methods. Rapid and accurate testing can help mitigate spread by improving on the time to quarantine and quarantine duration required. As of the writing of this thesis, COVID-19 has been responsible for more than 500,000 deaths in the United States of America, and greater than 2 million deaths globally. The work done in this thesis has shown improvements in the current SARS-CoV-2 testing methodology by reducing the time it takes for patient testing while maintaining accuracy and the sensitivity required …

A Mechanism Behind The Mechanotransduction Of Surface Characteristics In Osteoblasts, Otto J. Juhl Iv

Theses and Dissertations

Biomaterials for use in bone regeneration and healing range from metal and metal alloy implants to hydrogel-based solutions. These materials can be optimized to increase bone healing and integration by improving the mechanical and biological properties. Regardless of the material itself, the cell-substrate interaction is key to the success of the biomaterial once implanted. Substrate surface characteristics such as roughness, wettability, and particle density are well-known contributors to a substrate’s overall osteogenic potential, and therefore the substrate's overall success. Unfortunately, it is still unknown how these substrate surface characteristics are transduced into intracellular signals by cells, preventing specific tailoring of …

Mathematical Modeling Of Lung Inflammation: Macrophage Polarization And Ventilator-Induced Lung Injury With Methods For Predicting Outcome, Sarah B. Minucci

Theses and Dissertations

Lung insults, such as respiratory infections and lung injuries, can damage the pulmonary epithelium, with the most severe cases needing mechanical ventilation for effective breathing and survival. Furthermore, despite the benefits of mechanical ventilators, prolonged or misuse of ventilators may lead to ventilation-associated/ventilation-induced lung injury (VILI). Damaged epithelial cells within the alveoli trigger a local immune response. A key immune cell is the macrophage, which can differentiate into a spectrum of phenotypes ranging from pro- to anti-inflammatory. To gain a greater understanding of the mechanisms of the immune response in the lungs and possible outcomes, we developed several mathematical models …

Il-36g Cytokine Induction In Oral Epithelial Cells Triggered By Treponema Denticola And Their Role In Chronic Periodontitis, Christopher Blake

Theses and Dissertations

Periodontal disease is a polymicrobial disease affecting 10-15% of the population. Periodontal disease affects the quality of life by reducing mastication and potentially causing tooth loss. Periodontal disease is also linked to more severe, systemic diseases such as cardiovascular disease and rheumatoid arthritis. Development of the diseased state occurs when the plaque biofilm shifts from healthy to dysbiotic. The shift to a dysbiotic biome brings with it a shift in bacterial presence, specifically an increase in gram-negative bacteria, such as T. denticola. T. denticola is a gram-negative, anaerobic spirochete whose relationship with oral epithelial cells is poorly understood. Preliminary data …

Nature-Inspired Material Strategies Towards Functional Devices, Sayantan Pradhan

Theses and Dissertations

Naturally sourced, renewable biomaterials possess outstanding advantages for a multitude of biomedical applications owing to their biodegradability, biocompatibility, and excellent mechanical properties. Of interest in this dissertation are silk (protein) and chitin (polysaccharide) biopolymers for the fabrication of functional biodevices. One of the major challenges restricting these materials beyond their traditional usage as passive substrate materials is the ability to combine them with high-resolution fabrication techniques. Initial research work is directed towards the fabrication of micropatterned, flexible 2D substrates of silk fibroin and chitin using bench-top photolithographic techniques. Research is focused on imparting electrochemical properties to silk proteins using conducting …

A Novel Review Of Heat Shock Protein 110 Kda: A Basis For Research And Continued Experimentation Through Biochemical Analysis, Crist W. Cuffee

Theses and Dissertations

Heat shock protein 110 kDa, Hsp110, is a distinct cellular protector, different in form and function from Hsp70, a close relative of Hsp110. Functioning primarily as a holdase or in tandem with other molecular chaperones, a review of current accomplishments elucidates the uniqueness of this protein and the continued mysteries that surrounds it. Found only in eukaryotes, Hsp110 has been linked to many diseases, ranging from parasitic infection to neurodegenerative disorders. While still lacking, studies of this protein have provided much in the realm of speculation on the mechanisms behind Hsp110s’ contribution to different pathologies. This review will serve as …