Life Sciences Commons^™

Stains Induce Apoptosis And Autophagy In Primary And Transformed Mast Cells, Patrick A. Paez

Theses and Dissertations

Statin drugs are widely employed in the clinic to reduce serum low density lipoproteins (LDLs) in patients with hypocholesteremia. In addition to their cholesterol-lowering effects through HMG CoA reductase antagonism, isoprenyl lipids necessary for membrane anchorage and signaling of small G-proteins are abrogated. We previously found that statins suppress mast cell activation in murine and human cells, suggesting these drugs might be useful in treating allergic disease. While mast cell function is critical to allergic inflammation, mast cell hyperplasia and survival also impact these diseases, and were not studied in our previous work. In this study, we describe Fluvastatin-mediated apoptosis …

Independent Origination Of Floral Zygomorphy, A Predicted Adaptive Response To Pollinators: Developmental And Genetic Mechanisms, Ghadeer Bukhari, Wenheng Zhang

Theses and Dissertations

Observations of floral development indicate that floral organ initiation in pentapetalous flowers more commonly results in a medially positioned abaxial petal (MAB) than in a medially positioned adaxial petal (MAD), where the medial plane is defined by the stem and the bract during early floral development. It was proposed that the dominant MAB petal initiation might impose a developmental constraint that leads to the evolution of limited patterns of floral zygomorphy in Asteridae, a family in which the floral zygomorphy develops along the medial plane and results in a central ventral (CV) petal in mature flowers. Here, I investigate whether …

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 …

Functional Significance Of Mtdna Cytosine Modification Tested By Genome Editing, Jason M. Robinson

Theses and Dissertations

The field of epigenetics is gaining popularity and speed, due in part to its capability to answer lingering questions about the root cause of certain diseases. Epigenetics plays a crucial role in regulation of the cell and cell survival, particularly by cytosine methylation. It remains controversial if DNMT’s which facilitate methylation are present in mammalian mitochondria and what the functional significance they may have on modification of mitochondrial DNA. CRISPR-Cas9 technology enabled genome editing to remove the MTS (mitochondrial targeting sequence) from DNMT1 of HCT116 cells, purposefully minimizing effects on nuclear cytosine methylation, while exclusively impacting mitochondrial modification. Removal of …

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 …

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 …

Emergent Interactions Influence Functional Traits And Success Of Dune Building Ecosystem Engineers, Joseph K. Brown

Theses and Dissertations

Stability of coastal systems are threatened by oceanic and atmospheric drivers of climate change. Sea-level rise compounded with increased frequency and intensity of storms emphasizes need for protection of inner island systems by dune formations. Dune building processes are affected by interactions between growth of ecosystem engineering dune grasses and environmental factors associated with disturbance such as sand burial and salt spray. Climate change may also cause latitudinal expansion of some species, resulting in emergence of competitive interactions that were previously absent. Topographic structure of coastlines, traditionally influenced by sand burial, could change as a result of competition emergence. My …

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 …

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 …

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 …

Resolution Of Inflammation Rescues Axon Initial Segment Disruption, Nicholas M. George

Theses and Dissertations

Axonal domains are required for proper neuron function. These domains are unstable and degenerate concurrent with the inflammation in multiple sclerosis (MS) and the inflammatory disease models experimental autoimmune encephalomyelitis (EAE) and lipopolysaccharide (LPS) induced inflammation. Previous studies from our laboratory have shown that the axon initial segment (AIS) is maintained independently of the presence of myelin, but that AIS disruption is seen in MS as well as EAE and LPS-mediated inflammation. AIS loss can be interrupted in the early stage of EAE using the anti-inflammatory drug Didox. However, the potential for Didox directed repair of the AIS in later …

Atm Phosphorylates Subunit A Of Pp2a Resulting In Its Nuclear Export And Spatiotemporal Regulation Of The Dna Damage Response, Amrita D. Sule

Theses and Dissertations

Ataxia telangiectasia mutated (ATM) is a serine-threonine protein kinase and major regulator of the DNA damage response (DDR). One critical ATM target is protein phosphatase 2A (PP2A) known to regulate diverse cellular processes such as mitosis and cell growth as well as dephosphorylation of many proteins during the recovery from the DDR while returning the cell to normalcy. Interestingly, ATM and PP2A are known to form an auto-regulatory yin-yang kinase-phosphatase relationship. Herein, we show that the phosphorylation of the PP2A-Aα structural subunit at S401 by ATM results in nuclear export, which regulates the DDR at multiple levels and affects genomic …

Reduction Of Oxidative Stress And Storage Lesions (Rcsl) In Red Blood Cells - Analysis Of Ascorbic Acid (Aa), N-Acetylcysteine Amide (Ad4), And Serotonin (5-Ht), Shanmuka Gadiraju

UROP Posters

Oxidative stress is a common occurrence in red blood cell (RBC) storage in blood banks throughout the world. Typically RBC units stored under routine standard protocol (stored in SAGM-CPD additive solution) can only be kept up to 42 days for transfusion usage before being discarded. I am studying the effects of Ascorbic Acid (AA), N-acetylcysteine amide (AD4), and Serotonin (5-HT) as additives in blood bank storage because I want to find out if these additives can reduce storage-induced oxidative stress on red blood cells (RBCs), in order to help my reader understand how potential blood storage additives can affect the …

The Relationship Between Exercise And Depression And Anxiety In College Students, Joshua Frank, Dr. Amy Adkins, Nathan Thomas, Dr. Danielle Dick

UROP Posters

The literature shows an inverse association between exercise and mental disorders. The aim of this study is to further elaborate on this association with regards to exercise and its relationship with anxiety and depression in a college sample. The subject group focused on seniors in the Spit for Science data set which incorporated a total of 821 students. Physical activity was assessed using the International Physical Activity Questionnaire (IPAQ) to estimate the overall metabolic equivalents (MET’s) each student spent in walking, moderate, or vigorous activity levels in the previous week. Sum scores were used to measure depression and anxiety. Overall,the …

Axon Initial Segment Loss Is Not Observed In The Hippocampus Of A Experimental Autoimmune Encephalomyelitis Mouse Model, Praveen Mohanraju

UROP Posters

The axon initial segment (AIS) is fundamental for neuronal communication and action potential initiation, a characteristic which has been shown to be disrupted in inflammatory diseases such as Multiple Sclerosis (MS). Previous work from our lab has shown AIS breakdown in layer 5 of the cortex in a mouse model of MS known as experimental autoimmune encephalomyelitis (EAE). Moreover, it was shown that AIS breakdown was independent of demyelination but temporally correlated with microglial inflammatory reactivity. In order to determine if this pathology is specific to the cortex or affects other regions of the brain, we exploited these EAE induced …

Plant Functionality Across An Environmental Gradient, Taylor L. Price, Julie Zinnert

UROP Posters

Community assemblages provide insight into ecosystem processes, both spatially and temporally. They interact with biotic and abiotic factors that vary with habitat structure, influencing community composition. Ecological theory demonstrates that species have the potential for a wide fundamental niche, but habitat range may be restricted by factors exposed to species in their realized niche. In barrier island ecosystems, edaphic and environmental characteristics (e.g. elevation and distance to shoreline) are major drivers determining where and how plant communities establish. Physical stressors, such as salt stress and drought influence community grouping and can alter plant function within the environment. With projected increases …

The Effects Of Pet Ownership On Anxiety And Depression Among Trauma-Exposed College Students, Dung N. Nguyentran, Marlene A. Michniak, James J. Jung, Christine Q. Do

UROP Posters

Rates of anxiety and depression are prevalent in college students and can be attributed in part to stress and trauma-related events. However, studies suggest that pet ownership has the possibility of alleviating symptoms of anxiety, depression, negative emotions, and suicide. The purpose of this study was to determine the relationship between pet ownership and levels of anxiety and depression among those who have experienced a traumatic event. The sample was comprised of five hundred and forty-seven VCU students who completed an online survey from Spit for Science during their junior year. Linear regressions were performed to determine the nature and …

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 …

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 …

Examining Genetic And Environmental Influences On Alcohol Use And Externalizing Behaviors In African American Adolescents, Neeru Goyal

Theses and Dissertations

The aim of this thesis is to expand our understanding of the etiology of alcohol misuse and related disorders in African Americans using genetically informative study designs. Specifically, we take advantage of the candidate-gene approach and polygenic score analysis to extend the literature specific to African American populations. Chapter 2 explores gene x environment (GxE) interactions through the candidate gene approach to explore the relationship between two genes chosen on their potential relevance to stress response and adolescent alcohol use and misuse, among African American youth living in highly impoverished neighborhoods, as moderated by stressful life events. Chapter 3 implements …

The Curiosity Of Con, Petrified Breath, And An Accident Known As Blue., Steven Randall

Theses and Dissertations

My thesis installation emerged from an interest in visualizing breath. The resulting work came to exist at the intersection between art, biology, and performance.

The unicorn tapestries were used as a generative point of departure to explore the preservation and transformation of images through time, by time, and with time. Reproductions of the six tapestries were each etched into paper and then submerged into solutions of Phenol Red dye, Ferric Ferrocyanide (also known as Prussian Blue), and various forms of sodium chloride. Exhaled breath was used to encrust these images of the tapestries into physical objects which gradually crystallized and …

Dietary Adaptations And Intra- And Interspecific Variation In Dental Occlusal Shape In Hominin And Non-Hominin Primates, Kelsey O'Neill

Theses and Dissertations

Dental morphology and tooth shape have been used to recreate the

dietary adaptations for extinct species, and thus dental variation can provide

information on the relationship between fossil species and their

paleoenvironments. Variation in living species with known behaviors can provide

a baseline for interpreting morphology, and behavior, in the fossil record.

Tooth occlusal surface outlines in hominins and non-hominin primates, and other

mammals, have been used for assessments of taxonomic significance, with

variability often considered as being primarily phylogenetic. Few studies have

attempted to assess how diet might influence the pattern of variability in closely

related species. Here the …

Optimizing Cobalt Carbide Based Nanomaterials By Using Nucleating Agents And Statistical Routes, Turki I. Almugaiteeb

Theses and Dissertations

The continuous high demand on permanent magnets in industries opened new research plateau to develop alternative magnetic material. The current used permanent magnet materials in the market still suffer from high cost and insufficient magnetic or thermal properties. The central focus of this dissertation work is the optimization of cobalt carbide based nanomaterial by means of modifying polyol synthesis assisted by nucleation agent and systematic statistics using JMP software tool. In most existing literatures, producing cobalt carbide (Co₂C or Co₃C) lack reproducibility and consistency resulting in nonsolid magnetic properties results. The practical requirements for cobalt carbide …

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 …

Forest Stand Structure And Primary Production In Relation To Ecosystem Development, Disturbance, And Canopy Composition, Cynthia M. Scheuermann

Theses and Dissertations

Temperate forests are complex ecosystems that sequester carbon (C) in biomass. C storage is related to ecosystem-scale forest structure, changing over succession, disturbance, and with community composition. We quantified ecosystem biological and physical structure in two forest chronosequences varying in disturbance intensity, and three late successional functional types to examine how multiple structural expressions relate to ecosystem C cycling. We quantified C cycling as wood net primary production (NPP), ecosystem structure as Simpson’s Index, and physical structure as leaf quantity (LAI) and arrangement (rugosity), examining how wood NPP-structure relates to light distribution and use-efficiency. Relationships between structural attributes of biodiversity, …

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 …

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. …

Genome Wide Epigenetic Analyses Of Araptus Attenuatus, A Bark Beetle, Chitra Seshadri

Theses and Dissertations

Phylogeographic studies have relied on surveying neutral genetic variation in natural populations as a way of gaining better insights into the evolutionary processes shaping present day population demography. Recent emphasis on understanding putative adaptive variation have brought to light the role of epigenetic variation in influencing phenotypes and the mechanisms underlying local adaptation. While much is known about how methylation acts at specific loci to influence known phenotypes, there is little information on the spatial genetic structure of genome-wide patterns of methylation and the extent to which it can extend our understanding of both neutral and putatively adaptive processes. This …

Grunt Variation In The Oyster Toadfish Opsanus Tau: Effect Of Size And Sex, Michael L. Fine, Tyler D. Waybright

Biology Publications

As in insects, frogs and birds, vocal activity in fishes tends to be more developed in males than in females, and sonic swimbladder muscles may be sexually dimorphic, i.e., either larger in males or present only in males. Male oyster toadfish Opsanus tau L produce a long duration, tonal boatwhistle advertisement call, and both sexes grunt, a short duration more pulsatile agonistic call. Sonic muscles are present in both sexes but larger in males. We tested the hypothesis that males would call more than females by inducing grunts in toadfish of various sizes held in a net and determined incidence …