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Depth And Development Of The Sonic System In Deep-Sea Macrourid Fishes On The Continental Slope, Jonothan Wrenn

Theses and Dissertations

Work on sound production of deep-sea fishes has been limited to anatomy, and no sounds from identified species have been recorded on the continental slope. Here I examined the sonic muscles of six species in the family Macrouridae by depth (Coelorhincus carminatus, Nezumia bairdii, Coryphaenoides rupestris, Nezumia equalis, Coryphaenoides armatus, Coryphaenoides carapinus,). Due to increasingly limited food with depth, I hypothesized that sonic muscle development would decrease with depth. Sonic muscles were intrinsic and occurred in males and females. Swimbladder and sonic muscle dimensions increased linearly with fish size, but there were no clear differences with depth suggesting …

Discriminative Stimulus Properties Of Endogenous Cannabinoid Degradative Enzyme Inhibitors, Robert Owens Ii

Theses and Dissertations

Inhibition of fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL), the chief degradative enzymes of N-arachidonoyl ethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG), respectively, elicits no or partial substitution for Δ⁹-tetrahydrocannabinol (THC) in drug discrimination procedures. However, combined inhibition of both enzymes fully substitutes for THC, as well as produces a full constellation of cannabimimetic effects. Because no published report to date have investigated whether an inhibitor of endocannabinoid hydrolysis will serve as a discriminative stimulus, the purpose of this doctoral dissertation was to investigate whether C57BL/6J mice would learn to discriminate SA-57 (4-[2-(4-Chlorophenyl)ethyl]-1-piperidinecarboxylic acid 2-(methylamino)-2-oxoethyl ester), a …

Probing Allosteric, Partial Inhibition Of Thrombin Using Novel Anticoagulants, Stephen S. Verespy Iii

Theses and Dissertations

Thrombin is the key protease that regulates hemostasis; the delicate balance between procoagulation and anticoagulation of blood. In clotting disorders, like deep vein thrombosis or pulmonary embolism, procoagulation is up-regulated, but propagation of clotting can be inhibited with drugs targeting the proteases involved, like thrombin. Such drugs however, have serious side effects (e.g., excessive bleeding) and some require monitoring during the course of treatment. The reason for these side effects is the mechanism by which the drugs’ act. The two major mechanisms are direct orthosteric and indirect allosteric inhibition, which will completely abolish the protease’s activity. Herein we sought an …

Effects Of Olfactory Cues On The Movement Behavior Of The Predatory Beetle Calosoma Wilcoxi, Kennesha Myrick-Bragg

Theses and Dissertations

Arthropod predators often use prey and conspecific cues to make foraging decisions. Calosoma wilcoxi (Leconte) is a voracious predatory beetle that specializes on lepidopteran larvae often found in the forest canopy, including the fall cankerworm. This study tested the hypothesis that C. wilcoxi uses olfactory cues to detect prey and conspecifics. A Y-tube olfactometer was used to test attractiveness to larvae, larval frass, conspecific cues, and volatiles from herbivore-damaged white oak leaves. C. wilcoxi did not preferentially choose the treatment in any of the experiments. There was no difference in mean time spent in the treatment or control arm for …

Investigating The Mechanism Of The Compartmentalized Cbp (Creb-Binding Protein) Ubiquitin Ligase Activities, Oluwatoyin E. Akande

Theses and Dissertations

CBP (CREB Binding Protein) is global transcriptional co-activator and histone acetyltransferase. CBP is involved in the modulation of the transcription of many genes via histone acetylation at the promoter regions of the target genes. Also, non-histone proteins and transcription factors can be acetylated by CBP to promote their transcriptional activation. In addition to its transcription co-activator role, CBP is involved in many other pathological and physiological cellular processes such as cell growth and differentiation, cell transformation and development, response to stress, cell cycle regulation and apoptosis.

CBP and its paralogue p300, play double-edged roles in the regulation of p53, a …

Allosteric Effects Of G-Protein Coupled Receptor Heteromerization: Relevance To Psychosis, Jason W. Younkin

Theses and Dissertations

G-protein coupled receptors (GPCRs) implicated in disease are the predominant pharmaceutical targets. Growing evidence suggests that GPCRs form homo- and heteromeric complexes, resulting in allosteric functional changes. Ligands targeting one receptor can alter the function of the other receptor or receptors. Knowledge of these functional changes will provide unique opportunities to treat diseases. We examined two GPCR heteromers implicated in psychosis: mGlu2R-5HT2AR and D2R-5HT2AR. Using whole-cell patch clamp, we studied HEK-293 cells stably transfected with mGlu2R and 5HT2AR. Maximal heteromer formation allows inverse agonists to increase the G-protein activity of the opposite receptor, while sub-maximal heteromer formation does not. However, …

Response Of Soil Microbial Communities To Saltwater Intrusion In Tidal Freshwater Wetlands, Chansotheary Dang

Theses and Dissertations

Saltwater intrusion due to global change is expected to have a detrimental effect on the biogeochemistry of tidal freshwater wetlands. Of particular concern is that fact that salinization can alter the role of these ecosystems in the global carbon cycling by causing shifts in microbial metabolism that alter greenhouse gas emissions and increase carbon mineralization rates. However, our understanding of how wetland microbial community dynamics will respond to saltwater intrusion is limited. To address this knowledge gap and increase our understanding of how microbial communities in tidal freshwater wetlands change over time (1, 3, 12, and 49 weeks) under elevated …

Role Of The Exopolysaccharide Alginate In Adherence To And Inflammation Of Pulmonary Epithelial Cells, Brian E. Crossley

Theses and Dissertations

Pseudomonas aeruginosa (PA) infections in Cystic Fibrosis (CF) patients are not easily cleared due to the conversion from a nonmucoid to a mucoid phenotype. Alginate is an acetylated exopolysaccharide produced by mucoid PA that is responsible for increased resistance to antibiotics, host phagocytic killing, and propagating biofilm formation. Understanding the interaction between PA and host cells is critical to understanding chronic infection and inflammation in CF. In order to investigate this, we used A549 pulmonary epithelial cells and murine alveolar macrophages (MH-S) to examine host response to nonmucoid versus mucoid PA infection. Adhesion assays in A549 pulmonary epithelial cells revealed …

Host Densities And Parasitism Rates In A Forest Defoliator Across A Rural-Urban Landscape, Abigail J. Nelson

Theses and Dissertations

Fall cankerworm (FCW) outbreaks have recently increased in frequency and intensity in the mid-Atlantic region of the United States, especially around cities of Charlotte, NC and Richmond, VA. This study evaluated the effects of two landscape features associated with urbanization, impervious surface and forest cover, on population patterns of FCW and its parasitoids across eastern Virginia. Forest cover was positively related to parasitism rates while impervious surface was positively related to FCW abundance, suggesting that FCW outbreaks may be amplified in urban areas. FCW abundance declined over the two-year period of this study, but parasitism rate increased at most sites. …

Power Analysis In Applied Linear Regression For Cell Type-Specific Differential Expression Detection, Edmund Glass

Theses and Dissertations

The goal of many human disease-oriented studies is to detect molecular mechanisms different between healthy controls and patients. Yet, commonly used gene expression measurements from any tissues suffer from variability of cell composition. This variability hinders the detection of differentially expressed genes and is often ignored. However, this variability may actually be advantageous, as heterogeneous gene expression measurements coupled with cell counts may provide deeper insights into the gene expression differences on the cell type-specific level. Published computational methods use linear regression to estimate cell type-specific differential expression. Yet, they do not consider many artifacts hidden in high-dimensional gene expression …

Identification Of Size And Shape Changes In Orofacial Development And Disease, Allyson E. Kennedy

Theses and Dissertations

Among the most prevalent and devastating types of human birth defects are those affecting the mouth and face, such as orofacial clefts. Children with malformed orofacial structures undergo multiple surgeries throughout their lifetime and struggle with facial disfigurements, speech, hearing, and eating problems. Therefore, facilitating new research in cranio- and orofacial development is paramount to prevention and treatment of these types of birth defects in humans. Xenopus laevis has emerged as a new tool for dissecting the mechanisms governing facial development. Thus, molecular analyses accompanied by quantitative assessment of morphological changes during orofacial development of this species could be very …

The Study Of The Regulon Of Oxyr In Escherichia Coli And Porphyromonas Gingivalis, Christopher K. Pham

Theses and Dissertations

The facultative anaerobe, Escherichia coli and the obligate anaerobe, Porphyromonas gingivalis are two bacteria that reside in our body. Although they reside in separate environments, they are both subject to hydrogen peroxide stress and have mechanisms to regulate the stress. OxyR is the primary transcriptional regulator/sensor of oxidative stress response caused by hydrogen peroxide. OxyR in P. gingivalis is not well-characterized compared to OxyR in E. coli. We sought to characterize and compare the two forms of OxyR in order to gain a better understanding of the protein. We determined the oligomeric state of both proteins: primarily a tetramer for …

Investigating The Molecular Etiologies Of Sporadic Als (Sals) Using Rna-Sequencing, David G. Brohawn

Theses and Dissertations

ALS is an often lethal disease involving degeneration of motor neurons in the brain and spinal cord. Current treatments only extend life by several months, and novel therapies are needed. We combined RNA-Sequencing, systems biology analyses, and molecular biology assays to elucidate sporadic ALS group-specific differences in postmortem cervical spinal sections (7 sALS and 8 control samples) that may be relevant to disease pathology. >55 million 2X150 RNA-sequencing reads per sample were generated and processed.

In Chapter 2, we used bioinformatics tools to identify nuclear differentially expressed genes (DEGs) between our two groups. Further, we used Weighted Gene Co-Expression Network …

The Microbiome In Light Of Host Evolution, Alexander M. Waldrop Jr.

Theses and Dissertations

Recent advances in sequencing technologies have provided an unprecedented window in the unseen biological world. Accompanying this revolution is a growing appreciation for the ubiquity and diversity of beneficial interactions between animals and the microbes they carry. Given the symbiotic roles of microbes in host nutrition, immunity, behavior, development, and nearly every other facet of host biology, it is becoming increasingly clear that any understanding of hosts and their evolution would be incomplete without also considering the microbial dimension. Yet despite the growing body of evidence that many of these partnerships are rooted deep in evolutionary time, the majority of …

The Role Of E-Cadherin Force In The Maintenance Of Homeostasis In Epithelial Acini, Fnu Vani Narayanan

Theses and Dissertations

Numerous three-dimensional model systems have emerged for emulating the biochemical and physiological states of native tissue. Yet little is known about the effects of mechanical forces on cell behavior in the context of an organized tissue structure in three-dimensional cell-culture. Epithelial cells cultured in a three-dimensional environment comprised of extracellular matrix proteins form spheroids of polarized cells. Cellular responses to mechanical cues, generated from dynamic interactions with the extracellular matrix and neighboring cells, are known to influence cellular behavior to a great extent. Previous studies have shown that tumorigenic progression has been frequently linked to the down regulation of E-cadherin, …

Influence Of Historic Landscapes And Contemporary Species Management On Chesapeake Bay Bald Eagles And Osprey, Catherine B. Viverette

Theses and Dissertations

Influence of historic landscapes and contemporary species management on Chesapeake Bay Bald Eagles and Osprey

Catherine B. Viverette

Co-distributed species with well documented demographic histories can provide good models for testing alternative hypotheses about the impact of evolutionary history, contemporary landscapes, and species management on current distribution and population structure. The Osprey (Pandion haliaetus) and Bald Eagle (Haliaeetus leucocephalus) have been extensively studied, managed and monitored across their North American breeding range, particularly in the Chesapeake Bay. We used a combination of ecological niche modelling, diet reconstruction, and population genetic modeling to understand the role of …

Seasonal Variation Of Fish And Macroinvertebrate Biomass Spectra In Southern West Virginia Streams, Andrew J. Kirk

Theses and Dissertations

The biomass size spectrum - the power-law scaling relationship between average individual size and total biomass - has often been studied in lake and marine ecosystems, but rarely in lotic systems. The objective of this study was to test for characteristic biomass spectra in small temperate streams. Seasonal fish and macroinvertebrate data, including population abundance and biomass estimates, were collected in three wadeable, southern West Virginia streams from October 2013 to May 2015. Fish abundances were estimated with 3-pass electrofishing (depletion) surveys and individuals were weighed in the field. Macroinvertebrates were collected with a Hess sampler and returned to the …

Plant Functional Trait And Hyperspectral Reflectance Responses To Comp B Exposure: Efficacy Of Plants As Landmine Detectors, Paul V. Manley Ii

Theses and Dissertations

At least 110 million landmines have been planted since the 1970s in about 70 nations, many of which remain in place today. Some risk of detection may be mitigated using currently available remote sensing techniques when vegetation is present. My study focused on using plants as phytosensors to detect buried explosives. I exposed three species representing different functional types (Cyperus esculentus (sedge), Ulmus alata (tree), Vitis labrusca (vine)) to 500 mg kg^-1 of Composition B (Comp B; 60/40 mixture of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and 2,4,6-trinitrotoluene (TNT)), a commonly used explosive mixture, and measured functional traits and reflectance over …

Celecoxib Enhances Sorafenib/Sildenafil Lethality In Cancer Cells And Reverts Platinum Chemotherapy Resistance, Timothy A. Webb

Theses and Dissertations

The present studies sought to determine whether the lethality of the drug combination [sorafenib + sildenafil] could be enhanced by the anti-inflammatory agent celecoxib, using ovarian cancer and other tumor cell lines as models. Also, in a dose dependent fashion celecoxib enhanced [sorafenib + sildenafil] lethality in multiple ovarian cancer cell lines. In a dose dependent fashion celecoxib enhanced the ability of [sorafenib + sildenafil] to reduce expression of multiple chaperone proteins in parallel with lower levels of the drug efflux pumps ABCB1 and ABCG2. Over-expression of GRP78 and HSP27 maintained pump expression in the presence of drugs. Cell killing …

The Effect Of Depth On Development And Sexual Dimorphism Of The Sonic System In Deep Sea Neobythitine Fishes: The Upper Continental Slope, Heba Ali

Theses and Dissertations

Abstract

Background: Cusk-eels from the subfamily Neobythiitinae are one of the major groups of sound-producing fishes on the continental slope. Sounds have never been recorded from a member of this subfamily, and sonic anatomy is considered a proxy for sound production. As the first part of a study on the effects of depth on sonic anatomy, we examined three relatively shallow species from the upper continental slope.

Methods: Three species (Hoplobrotula armata, Neobythites longipes and Neobythites unimaculatus) were examined for sonic anatomy (skeleton, swimbladder and sonic muscles), and sonic and epaxial muscle fibers were measured for diameter. …

The Effect Of Pre-Deployment Physiology As A Predictor Of Post-Traumatic Stress Disorder Among A Sample Of United States Army National Guard And Reserve Soldiers, David J. Rothman

Theses and Dissertations

Potential risk factors for development of Post-Traumatic Stress Disorder (PTSD) are still unclear. One potential risk factor for the development of PTSD is an individual’s cardiovascular reactivity and recovery in response to stressor tasks. The current study was conducted with 763 Army National Guard and Army Reserve soldiers. Participants completed a stressful induction along with self-report measures prior to deployment. Post-deployment, self-report measures were completed to assess PTSD symptomatology and experiences related to deployment and combat. Multiple regression was used to determine the ability of blood pressure response to stress to predict PTSD symptoms immediately and one-year after return from …

System Genetic Analysis Of Mechanisms Underlying Excessive Alcohol Consumption, Maren L. Smith

Theses and Dissertations

Increased alcohol consumption over time is one of the characteristic symptoms of Alcohol Use Disorder (AUD). The molecular mechanisms underlying this escalation in intake is still the subject of study. However, the mesocortical and mesolimbic dopamine pathways, and the extended amygdala, because of their involvement in reward and reinforcement are believed to play key roles in these behavioral changes. Multiple gene expression studies have shown that alcohol affects the expression of thousands of genes in the brain. The studies discussed in this document use the systems biology technique of co-expression network analysis to attempt to find

patterns within genome-wide expression …

Genomic Comparisons And Genome Architecture Of Divergent Trypanosoma Species, Katie Bradwell

Theses and Dissertations

Virulent Trypanosoma cruzi, and the non-pathogenic Trypanosoma conorhini and Trypanosoma rangeli are protozoan parasites with divergent lifestyles. T. cruzi and T. rangeli are endemic to Latin America, whereas T. conorhini is tropicopolitan. Reduviid bug vectors spread these parasites to mammalian hosts, within which T. rangeli and T. conorhini replicate extracellularly, while T. cruzi has intracellular stages. Firstly, this work compares the genomes of these parasites to understand their differing phenotypes. Secondly, genome architecture of T. cruzi is examined to address the effect of a complex hybridization history, polycistronic transcription, and genome plasticity on this organism, and study its highly …

Mechanisms Of Native Shrub Encroachment On A Virginia Barrier Island, Joseph Thompson

Theses and Dissertations

Species composition, temperature, soil nutrients, and leaf area index (LAI) were recorded across three encroaching Morella cerifera thicket edges and three free- standing shrubs on Hog Island, Virginia to characterize the effect of shrub thickets on the plant community and microclimate. Electron transport rate (ETR) was taken on shrub leaves to determine if microclimate benefits M. cerifera physiology. Species richness was lowest inside shrub thickets. Soil water content and LAI were higher in shrub thickets compared to grassland. Soil organic matter, N, and C were higher inside shrub thickets. Summer and fall maximum temperatures were more moderate in shrub thickets …

Exploring Pharmacological And Behavioral Mechanisms Involved In Alcohol Dependence During Adolescence, Rabha Mousa Younis

Theses and Dissertations

Alcoholism is a serious illness that is marked by uncontrollable drinking and physical dependence to alcohol. Long-term alcoholism has been linked to many health concerns such as cirrhosis of the liver and cardiovascular disease. Alcohol is one of the most commonly used drugs among adolescent populations. Given that adolescence is a unique developmental stage during which alcohol has long-term effects on future drug-taking behavior; it is essential to understand how early exposure to alcohol during adolescence may affect the abuse liability of the drug later in life. Indeed, most alcohol users start during adolescence suggesting that exposure to alcohol during …

Conditional Cardiac-Specific Akap13 Knockout Induces Sex Dependent Biventricular Dilated Cardiomyopathy With Sarcomeric And Mitochondrial Defects, Kimberlyn M. Baig-Ward

Theses and Dissertations

Heart disease is a complex and heterogeneous disease. Notably, studies have demonstrated gender differences in the expression and types of cardiovascular disease, such as dilated cardiomyopathy (DCM), a major underlying cause of heart failure. Previously we showed that loss of A-Kinase Anchoring Protein 13 (Akap13), a unique proto-oncogene and estrogen receptor modulator, resulted in enlarged embryonic hearts, defective cardiac sarcomere formation, and embryonic lethality in mice. Data have also shown cAMP-dependent Protein Kinase A (PKA) to be involved in DCM pathophysiology. Given the established role of AKAP13 in cell signaling, its ability to bind and modulate ligand-activated nuclear hormone …

Role Of Vav2 In Podocyte Inflammasome Activation And Glomerular Injury During Hyperhomocysteinemia, Sabena Conley

Theses and Dissertations

Hyperhomocysteinemia (hHcys) is a widely known pathogenic factor in the progression of end-stage renal disease (ESRD) and it is also associated with an increased risk for injurious cardiovascular pathologies during ESRD. HHcys is linked to the formation and activation of the NOD-like receptor protein 3 (NLRP3) inflammasome, characterized as a critical early mechanism initiating the inflammatory response. NADPH oxidase (NOX)-derived reactive oxygen species (ROS) mediate the activation of the NLRP3 inflammasome in podocytes in response to elevated levels of homocysteine (Hcys) in vitro and in vivo. However, it remains unknown how NLRP3 inflammasome activation is triggered by NOX. The …

Acute And Chronic Effects Of Inhalants In Intracranial Self-Stimulation, Matthew Tracy

Theses and Dissertations

Inhalants are a loosely defined diverse group of volatile substances which people abuse. Despite widespread misuse of inhalants, there are limited preclinical methods available to study the reinforcement-like properties of inhalants. One procedure which has demonstrated substantial promise as a tool to investigate inhalant pharmacology is the intracranial self-stimulation (ICSS) procedure. ICSS utilizes pulses of electrical stimulation to the mesolimbic reward pathway to serve as a temporally defined and controlled operant reinforcer with a highly adjustable efficacy. The first aim of the project was to characterize the effects of commonly abused inhalants: including toluene, trichloroethane, nitrous oxide, isoflurane and R134a …

Dynamic Regulation Of Mitochondrial Stat3 And Its Association With Cypd, Jeremy A. Meier

Theses and Dissertations

In recent years, a number of nuclear transcription factors have been shown to be present in the mitochondria where they have distinct roles in regulating mitochondrial function. Signal Transducer and Activator of Transcription 3 (STAT3), classically activated by the JAK family of receptor associated tyrosine kinases to drive nuclear gene expression, is one such transcription factor with a unique mitochondrial role. There, it has been shown to support oxidative phosphorylation, regulate mitochondrial-encoded transcripts, and be key for the transformation and growth of a number of different cancers. Despite its well-characterized functional importance at the level of the mitochondria, the mechanism …

A Mechanistic Study Of An Ipsc Model For Leigh’S Disease Caused By Mtdna Mutataion (8993 T>G), John P. Galdun

Theses and Dissertations

Mitochondrial diseases encompass a broad range of devastating disorders that typically affect tissues with high-energy requirements. These disorders have been difficult to diagnose and research because of the complexity of mitochondrial genetics, and the large variability seen among patient populations. We have devised and carried out a mechanistic study to generate a cell based model for Leigh’s disease caused by mitochondrial DNA mutation 8993 T>G. Leigh’s disease is a multi-organ system disorder that depends heavily on the mutation burden seen within various tissues. Using new reprogramming and sequencing technologies, we were able to show that Leigh’s disease patient fibroblasts …