Life Sciences Commons^™

The Effects Of Tidal Forcing On Nutrient Fluxes In The Tidal, Freshwater James River Estuary, Va, Dana L. Devore

Theses and Dissertations

A 12-month study (January to December 2015) focused on the effects of tidal forcing on nutrient fluxes in the tidal, freshwater segment of the James River Estuary (JRE). Discrete sampling of nutrient chemistry and continuous monitoring of tidal discharge were used to determine the volume and timing of the tides, and differences in nutrient concentrations between incoming and outgoing tides. The goal of this study was to improve understanding of tidal influence on nutrient fluxes and their role in nutrient transport to the lower estuary. Results suggested that differences in nutrient concentrations between incoming and outgoing tides were small throughout …

The Role Of Matrix Metalloproteinase 9 And Osteopontin In Synaptogenesis And Reinnervation Of The Olfactory Bulb Following Brain Injury, Melissa A. Powell

Theses and Dissertations

Traumatic brain injury (TBI) is a serious health concern, causing cognitive, motor, and sensory deficits, including olfactory dysfunction. This dissertation explores the effects of TBI on synaptic plasticity within the olfactory system, seeking to define mechanisms guiding postinjury sensory reinnervation. Physical forces induced by TBI can axotomize olfactory receptor neurons (ORNs), which innervate olfactory bulb (OB). These axons regenerate OB projections after injury, a process involving growth through a complex extracellular matrix (ECM). As such, we investigated a potential molecular mechanism capable of modifying local OB ECM to support postinjury synaptogenesis. Since matrix metalloproteinases (MMPs) and their ECM substrates are …

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 …

Investigation Of Anaplasma Phagocytophilum And Anaplasma Marginale Adhesin-Host Cell Interactions, Kathryn S. Hebert

Theses and Dissertations

Anaplasma phagocytophilum and A. marginale are the etiologic agents of bovine anaplasmosis and human granulocytic anaplasmosis, respectively. As obligate intracellular pathogens, binding and entry of host cells is a prerequisite for survival. The molecular events associated with these processes are poorly understood. Identifying the adhesins mediating binding, delineating their key functional domains, and determining the molecular determinants to which they bind not only benefits better understanding of Anaplasma spp. pathobiology, but could also benefit the development of novel approaches for protecting against infection. We previously demonstrated that A. phagocytophilum outer membrane protein A (ApOmpA) is critical for bacterial binding and …

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 …

Characterizing The Oncogenic Properties Of C-Terminal Binding Protein, Evan T. Sumner

Theses and Dissertations

The paralogous C-terminal binding proteins (CtBP) 1 and 2 are evolutionarily conserved transcriptional coregulators that target and disrupt the expression of several genes essential for multiple cellular processes critical to regulating tumor formation. CtBP’s ability to govern the transcription of genes necessary for apoptosis, tumor suppression, invasion/migration and EMT gives rise to its oncogenic activities. Both isoforms of CtBP are found to be overexpressed in cancers including colorectal, pancreatic, ovarian, and breast, with higher levels correlating to lower overall median survival. Although multiple lines of evidence suggest CtBP plays a role in tumorigenesis, it has never been formally characterized as …

A Neural Circuit Of Appetite Control In C. Elegans, Kristen C. Davis

Theses and Dissertations

Feeding behavior and its associated neural circuitry is complex and intricate in mammalian systems, however, a simple model organism, such as C. elegans provides a more basic approach to understand factors and molecules involved. The fruit-dwelling nematode provides a unique set of resources; it only consists of 959 cells, 302 of which are neurons. In addition, each neuron’s connectivity and position within the worm is known and consistent between animals. Conservation of neurotransmitters and biochemical processes add to this impressive list. These resources provide an excellent background to address feeding behavior and the neural structures governing it.

Feeding behavior in …

Functional Consequences Of Mtdna Methylation On Mitochondrial Transcription Factor Binding And Transcription Initiation, Elliot N. Burton

Theses and Dissertations

The role of cytosine modifications on nuclear transcription has been well characterized, but the function of DNA methylation in the mitochondrial genome has not been determined. Previous studies conducted by the Taylor laboratory have shown overexpression of the mitochondrial isoform of DNMT1 leads to strand-specific changes in gene expression. Here, we show that increased mtDNMT1 expression leads to an increase in the polycistronic transcript encoding the ND1 and Cox1 sequences. In order to understand the mechanistic basis of these changes, we investigated the effects of CpG methylation in the heavy strand promoter on transcription initiation and TFAM binding. Methylation was …

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 …

Roles Of Planar Cell Polarity Proteins In Copa Axon Pathfinding, Ashley Morgan Purdy

Theses and Dissertations

In zebrafish, CoPA (Commissural Primary Ascending) is the first among ascending commissural axons to pathfind anteriorly and form the spinal commissure. One pathway that guides their anterior growth is the planar cell polarity (PCP) signaling pathway, but it is not fully known how PCP signaling regulates anterior guidance. We examined CoPA pathfinding in various PCP mutants to determine if anterior-posterior (A-P) guidance of CoPAs is dependent on PCP signaling. We found that certain PCP mutants exhibited anterior pathfinding defects, with approximately half of all affected CoPAs migrating incorrectly posteriorly. By using a translation-blocking DCC (Deleted in …

Evaluating And Improving The Efficiency Of Software And Algorithms For Sequence Data Analysis, Hugh L. Eaves

Theses and Dissertations

With the ever-growing size of sequence data sets, data processing and analysis are an increasingly large portion of the time and money spent on nucleic acid sequencing projects. Correspondingly, the performance of the software and algorithms used to perform that analysis has a direct effect on the time and expense involved. Although the analytical methods are widely varied, certain types of software and algorithms are applicable to a number of areas. Targeting improvements to these common elements has the potential for wide reaching rewards. This dissertation research consisted of several projects to characterize and improve upon the efficiency of several …

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 …

Adducins Are Negative Regulators Of Migration And Invasion Of Normal Lung Epithelial Cells And Lung Cancer Cells, Parth Hitenbhai Amin, Parth Amin

Theses and Dissertations

Cell migration is an important component of many physiological and pathological processes such as tissue and organ morphogenesis during development, wound healing, inflammatory immune response, and tumor metastasis. The actin cytoskeleton is the basic engine driving cell migration. In the present study, we elucidate the role of an important actin interacting proteins, Adducins, in motility of normal lung epithelium and lung cancer cells. Adducins are the family of cytoskeleton protein capping the fast growing end and facilitating the bundling of actin filaments. Adducins are encoded by the three closely related genes namely alpha (ADD1), beta (ADD2) and gamma (ADD3) Adducin. …

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 …

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 …

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 …

Upper Thermal Limits Differ Among Component Species In A Host-Parasitoid-Hyperparasitoid System, Kanchan A. Joshi

Theses and Dissertations

Among the predicted impacts associated with global climate change, warming is of special interest because the rates of physiological processes are temperature-dependent. Insects and other ectotherms are likely to be affected due to their limited ability to control body temperature. In this study, I measured the tolerance to extreme high temperatures, i.e., critical thermal maximum (CT_max), of component species in a tri-trophic system, including an herbivore (Manduca sexta), a primary larval parasitoid (Cotesia congregata) and a hyperparasitoid (genus Silochalcis). For wild insects, the parasitoid had the lowest CT_max, the hyperparasitoid had …

Evaluation Of Redox Potential As A Novel Biomarker Of Oxidative Stress, Inflammatory Response, And Shock Using Nanoporous Gold Electrodes, Matthew C. Ellenberg

Theses and Dissertations

EVALUATION OF REDOX POTENTIAL AS A NOVEL BIOMARKER OF OXIDATIVE STRESS, INFLAMMATORY RESPONSE, AND SHOCK USING NANOPOROUS GOLD ELECTRODES

Background: Redox potential is a chemical species’ affinity for electrons. Increased oxidant concentration is associated with disease1,2, yet there is not a way to measure systemic redox status.3 Redox potentiometry uses metal electrodes that do not work in blood because protein molecules adhere on the metal surface, blocking electron exchange.

Methods: Nanoporous gold electrodes have large surface areas that allowed electron exchange to continue in blood.4 Redox potential was measured in blood with ascorbic acid, in cardiac bypass patients and pigs …

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 …

From Seed To Sky: Impacts Of Explosive Compounds On Vegetation Across Spatial And Developmental Scales, Stephen M. Via

Theses and Dissertations

Explosive compounds are broadly distributed across the globe as a result of nearly two centuries of munitions use in warfare and military activities. Two explosive compounds have seen disproportionate use; RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) and TNT (2-methyl- 1,3,5-trinitrobenzene), being the most commonly found explosives in the environment. The effects of explosives on biota have been studied in great detail; however, there is a general lack of understanding with regard to broader ecological impacts of these contaminants. My dissertation objective was to follow the impacts of explosive compounds on vegetation across scales. Impacts on vegetation at the species scale alter community composition via …

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 …

Introducing Novel Combinatorial Targeted Therapies In Multiple Types Of Cancer, Mehrad Tavallai

Theses and Dissertations

The cancers of liver, colon and breast are amongst the top five most prevalent and most fatal worldwide. As the Raf/MEK/ERK pathway is frequently deregulated in hepatocellular carcinoma (HCC), sorafenib, a Raf kinase inhibitor, became the first systemic therapy approved for the treatment of patients with HCC. However, sorafenib only produced modest effects with low response rates in the clinic. Similarly, regorafenib, which was approved for the treatment of metastatic colorectal cancer (CRC), has had a poor response rate in the clinic. Since phosphodiesterase type 5 has been reported to be overexpressed in HCC and CRC, we hypothesized that sildenafil, …

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. …

Differential Response Of Barrier Island Dune Grasses To Species Interactions And Burial, April Harris

Theses and Dissertations

Dune grasses are integral to biogeomorphic feedbacks that create and alter foredunes and barrier island stability. In a glasshouse study, Ammophila breviligulata Fern. and Uniola paniculata L. were planted together and subjected to sand burial to quantify morphological and physiological response. Ammophila breviligulata physiological and morphological performance declined when planted with U. paniculata but U. paniculata was not affected when planted with A. breviligulata. Burial had a positive effect on A. breviligulata and U. paniculata as indicated by electron transport rate and total biomass at the end of the experiment. Due to their different growth strategies, A. breviligulata and …

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 …

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 …

High Affinity Block Of Icl,Swell By Thiol-Reactive Small Molecules, Sung H. Park

Theses and Dissertations

Ebselen (Ebs) is considered as a glutathione peroxidase (GPx) mimetic and primarily thought to function by scavenging intracellular reactive oxygen species (ROS). Previous to our work, Deng et al. (2010a) demonstrated complete block of I_Cl,swell with 15 microM Ebs following endothelin-1 (ET-1) induced activation of the current in cardiomyocytes. This block was presumed to take effect mainly via the quenching of ROS. Nonetheless, our work with DI TNC1 astrocytes strongly emphasizes that Ebs might function by an alternative mechanism based on its kinetic profile in blocking I_Cl,swell. Our experiments showed that 45 nM Ebs can fully block …

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 …

Predictors Of Caffeine-Related Withdrawal Symptoms In College Freshmen, David J. Pomm

Theses and Dissertations

While caffeine withdrawal has been well-characterized, research on caffeine intake and factors associated with withdrawal has been limited. The present study examined prevalence rates of caffeine use and identified psychosocial factors associated with having caffeine withdrawal headaches (CWH). Participants were N = 1,989 college freshmen who participated in the 2011 Spit for Science project. Caffeine use was reported by 80% of the sample. Females were more likely than males to consume caffeine, and soda was the primary source of caffeine for both genders. As hypothesized, daily caffeine users were more likely to report CWH than non-daily users. When multivariable analyses …