Life Sciences Commons^™

Comparing Low Salinity Transcriptomic Profiles Among Hard Clam, Mercenaria Mercenaria, Lines, Leslie Speight Youtsey

Dissertations, Theses, and Masters Projects

The hard clam is an important ecological and economic resource along the U.S. Eastern Seaboard. In Virginia alone, farm gate sales were estimated at $38.8 million in 2018 and $57.8 million in 2021, making Virginia the largest producer of hard clams in the U.S. This industry is primarily limited to higher salinity habitats on the seaside of the Eastern Shore of Virginia and lower Chesapeake Bay. Although the hard clam can be found in lower salinity habitats, they do not grow or survive at rates that are practical for productive aquaculture. Even in areas of higher salinity, hard clams are …

Synthesis And Biological Testing Of Small-Molecule Mitochondrial Complex I Inhibitors, Willough Sloan

Undergraduate Honors Theses

This thesis delineates two main projects: the first outlines the structure elucidation efforts toward a Diels-Alder adduct of a novel reaction for the synthesis of chimaphilin, a naphthoquinone-based natural product with apoptotic or antiproliferative activity in certain cancer cells^1,2. The structure elucidation extends to derivatives of chimaphilin synthesized by the same cyclization reaction. While Diels-Alder reactions are usually regioselective, ¹H-NMR and ¹³C-NMR of the adducts was inconclusive and indicated the possibility of regioisomer presence, with one regioisomer being chimaphilin (or derivatives). A multitude of crystallization methods were carried out in order to be able to analyze …

Honey As A Biomonitor For Air Pollutant Deposition In The Eastern United States Using Ion Chromatography And Scanning Electron Microscopy, Cole Cochran

Undergraduate Honors Theses

Anthropogenic activities generate metal, acid, and particulate air pollutants which negatively impact human and ecological health. In the United States, power plant, industrial, and vehicle emissions are leading causes of air pollution, however, the measurement of air pollution at high-resolution spatial regimes remains a challenge. Honey has emerged as a powerful biomonitoring tool to effectively quantify contaminants without the need for a large array of monitoring instruments. I hypothesized that honey could be used to effectively measure and map modern air pollutant spatiotemporal relationships over the Eastern U.S. Using ion chromatography with sulfate as an indicator for air pollution and …

Transcriptomes Of Electrophysiologically Recorded Dbx1-Derived Respiratory Neurons Of The Prebötzinger Complex In Neonatal Mice, Prajkta S. Kallurkar, Maria Cristina D. Picardo, Yae K. Sugimura, Margaret Saha, Gregory D. Conradi Smith, Christopher A. Del Negro

Arts & Sciences Articles

Breathing depends on interneurons in the preBötzinger complex (preBötC) derived from Dbx1-expressing precursors. Here we investigate whether rhythm- and pattern-generating functions reside in discrete classes of Dbx1 preBötC neurons. In a slice model of breathing with ~ 5 s cycle period, putatively rhythmogenic Type-1 Dbx1 preBötC neurons activate 100–300 ms prior to Type-2 neurons, putatively specialized for output pattern, and 300–500 ms prior to the inspiratory motor output. We sequenced Type-1 and Type-2 transcriptomes and identified differential expression of 123 genes including ionotropic receptors (Gria3, Gabra1) that may explain their preinspiratory activation profiles and Ca2+ signaling ( …

Limitations Of 16s Rrna Gene Sequencing To Characterize Lactobacillus Species In The Upper Genital Tract, Jessica L. O'Callaghan, Dana Willner, Melissa Buttini, Flavia Huygens, Elise S. Pelzer

Arts & Sciences Articles

The endometrial cavity is an upper genital tract site previously thought as sterile, however, advances in culture-independent, next-generation sequencing technology have revealed that this low-biomass site harbors a rich microbial community which includes multiple Lactobacillus species. These bacteria are considered to be the most abundant non-pathogenic genital tract commensals. Next-generation sequencing of the female lower genital tract has revealed significant variation amongst microbial community composition with respect to Lactobacillus sp. in samples collected from healthy women and women with urogenital conditions. The aim of this study was to evaluate our ability to characterize members of the genital tract microbial community …

Proteomic Analysis Of Mycobacteriophage Crimd, William Moeller

Undergraduate Honors Theses

Bacteriophages represent a large portion of the biomatter on our planet, and many of them have yet to be fully characterized. Here we discuss the proteomic analysis of a particular Bacteriophage, Mycobacteriophage CrimD. This phage was discovered on the Campus of William & Mary and has had its genome characterized. We took the next logical step of proteomic analysis.

In our analyses we made use high pressure liquid chromatography paired with linear ion trap mass spectrometry to analyze the proteome of CrimD at specific time points after the infection of its host, Mycobacterium smegmatis. Additionally, we used nanospray ionization with …

A Simple Method For Sphingolipid Analysis Of Tissues Embedded In Optimal Cutting Temperature Compound, Timothy Rohrbach, April E. Boyd, Pamela J. Grizzard, Sarah Speigel, Jeremy Allegood, Santiago Lima

Richard Bland Faculty Works

MS-assisted lipidomic tissue analysis is a valuable tool to assess sphingolipid metabolism dysfunction in disease. These analyses can reveal potential pharmacological targets or direct mechanistic studies to better understand the molecular underpinnings and influence of sphingolipid metabolism alterations on disease etiology. But procuring sufficient human tissues for adequately powered studies can be challenging. Therefore, biorepositories, which hold large collections of cryopreserved human tissues, are an ideal retrospective source of specimens. However, this resource has been vastly underutilized by lipid biologists, as the components of OCT compound used in cryopreservation are incompatible with MS analyses. Here, we report results indicating that …

Modeling Hybrid Novel Traits: A Case Study In Complex Petal Pigment Patterning In Hybrid Mimulus, Xingyu Zheng

Undergraduate Honors Theses

Hybridization between species, by introducing dramatic trait variation into the population and creating viable, transgressive offsprings with novel phenotypes, can have huge evolutionary implications. Some hybrid traits have been studied in the classical genetics or population genetics context, but most complex traits are determined by multiple causes, e.g. the number of loci involved, the rewiring of the genetic circuitries, and the changes in gene expression pattern. Using the hybrid monkeyflower petal pigment patterning as an example, we present a case study to investigate complex hybrid traits in a systematic manner that includes empirical data analysis and quantitative mathematical modeling of …

Regenerative Ionic Currents And Bistability, Gregory D. Conradi Smith

Arts & Sciences Book Chapters

What every neuroscientist should know about the mathematical modeling of excitable cells. Combining empirical physiology and nonlinear dynamics, this text provides an introduction to the simulation and modeling of dynamic phenomena in cell biology and neuroscience. It introduces mathematical modeling techniques alongside cellular electrophysiology. Topics include membrane transport and diffusion, the biophysics of excitable membranes, the gating of voltage and ligand-gated ion channels, intracellular calcium signalling, and electrical bursting in neurons and other excitable cell types. It introduces mathematical modeling techniques such as ordinary differential equations, phase plane, and bifurcation analysis of single-compartment neuron models. With analytical and computational problem …

A Likelihood Ratio Test For Changes In Homeolog Expression Bias, Ronald D. Smith, Taliesin J. Kinser, Gregory D. Conradi Smith, Joshua R. Puzeyn

Arts & Sciences Articles

Background

Gene duplications are a major source of raw material for evolution and a likely contributor to the diversity of life on earth. Duplicate genes (i.e., homeologs, in the case of a whole genome duplication) may retain their ancestral function, sub- or neofunctionalize, or be lost entirely. A primary way that duplicate genes evolve new functions is by altering their expression patterns. Comparing the expression patterns of duplicate genes gives clues as to whether any of these evolutionary processes have occurred.

Results

We develop a likelihood ratio test for the analysis of the expression ratios of duplicate genes across two …

Modeling The Effects Of Supercomplex Formation And Stress Response On Alzheimer’S Disease Progression, Morgan Griffin Shelton

Dissertations, Theses, and Masters Projects

Alzheimer’s disease is a specific form of dementia characterized by the aggregation of Amyloid-β plaques and tau tangles. New research has found that the formation of these aggregates occurs after dysregulation of respiratory activity and the production of radical oxygen species. Proteomic data shows that these changes are also related to unique gene expression patterns. We investigate the impact of these findings on new therapeutic options via metabolic flux analysis of sirtuin stress response pathways and respiratory supercomplex formation. Our results indicate CRISPR Cas-based gene therapy focused on upregulating stable CIII expression, and protective changes in SIRT1 and AMPK expression …

Utilization Of Unnatural Amino Acids To Modulate Protein Structure And Function, John Halonski

Dissertations, Theses, and Masters Projects

Proteins are capable of an astounding array of functions using only the 20 canonical amino acids; however, the ability to add new functional groups to the genetic code through the utilization of unnatural amino acids (UAAs) has greatly expanded our ability to study and manipulate proteins. By expanding the diversity of functional groups within proteins, a wide variety of applications in industry as well as in fields such as diagnostics, biochemistry, and materials science are now possible. These applications have further been expanded through the development and optimization of bioorthogonal reactions which can occur under physiological conditions with a high …

Acetylation Controls Thyroid Hormone Receptor Intracellular Localization And Intranuclear Mobility, Cyril S. Anyetei-Anum

Dissertations, Theses, and Masters Projects

Thyroid hormone receptor (TR) is responsible for mediating the expression of genes involved in growth, development, and homeostatic regulation, in response to thyroid hormone. There are two main subtypes of TR, TRα1 and TRβ1, that mediate these physiological processes. Dysregulation of TR mediated processes is a contributing factor in disease pathology. Our prior studies show that TR is shuttled rapidly between the nucleus and cytosol, while localizing primarily to the nucleus. TRα1 contains two nuclear localization signals (NLSs) that act together to confer strong nuclear localization, while TRβ1 only contains one NLS (NLS-1). Recently, we found that the intracellular localization …

Spread And Interaction Of Epidemics And Information On Adaptive Social Networks, Yunhan Long

Dissertations, Theses, and Masters Projects

The spread of diseases and opinions has profoundly affected the development of human societies. The structure of the underlying social network may change as a result of individuals changing their social connections in response to an ongoing epidemic or opinion spreading, either for self protection or as an expression of personal values. The interaction of spreading processes and the underlying network structure has been a focus of many recent studies. In this dissertation, we construct models to better incorporate heterogeneous responses to disease spread and attempted opinion spread.;We first model the simultaneous spread of an epidemic and awareness about the …

Langevin, Population Density And Moment-Based Modeling Of Local And Global Aspects Of Intercellular Calcium Signaling, Xiao Wang

Dissertations, Theses, and Masters Projects

Markov chain models of the coupled gating of intracellular calcium (Ca 2+) channels are often used to study the stochastic dynamic of local Ca2+ release events and whole cell Ca2+ homeostasis. However, the runtime of the Markov chain description of Ca2+ channel gating is exponential in the number of Ca2+ channel states and may thus result in a combinatorial state space explosion when the number of channel states is large. This dissertation presents several novel stochastic modeling approaches that capture important aspects of Ca 2+ signaling while improving computational efficiency. This dissertation presents several novel stochastic modeling approaches that capture …

A Mathematical Model Of Tau Protein Hyperphosphorylation: The Effects Of Kinase Inhibitors As A Theoretical Alzheimer's Disease Therapy, Patrick Neil Blank

Dissertations, Theses, and Masters Projects

No abstract provided.

Identifying Sumo Protease Targets And Investigating E3 Ligase Interactions, Mark Guillotte

Dissertations, Theses, and Masters Projects

No abstract provided.

Investigating Heat Shock Protein 70 As A Binding Partner Of Mk-Styx, And The Role Of Mk-Styx In Neuronal Differentiation, Lauren Elizabeth Rusnak

Dissertations, Theses, and Masters Projects

No abstract provided.

Investigation Of Microwave Technologies For Biochemical Applications, Valerie Terynn Tripp

Dissertations, Theses, and Masters Projects

No abstract provided.

Automated Reductions Of Markov Chain Models Of Calcium Release Site Models, Yan Hao

Dissertations, Theses, and Masters Projects

Markov chain models have played an important role in understanding the relationship between single channel gating of intracellular calcium (Ca2+) channels, specifically 1,4,5-trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs), and the stochastic dynamics of Ca2+ release events, known as Ca2+ puffs and sparks. Mechanistic Ca2+ release site models are defined by the composition of single channel models whose transition probabilities depend on the local calcium concentration and thus the state of the other channels. Unfortunately, the large state space of such compositional models impedes simulation and computational analysis of the whole cell Ca2+ signaling in which the stochastic dynamics of …

Thermochemistry Of Amino Acids And Constrained Diamines, Erica Jane Tullo

Dissertations, Theses, and Masters Projects

The gas-phase proton affinities of several highly basic amino acids and diamines were determined using the extended kinetic method in an ESI-quadrupole ion trap instrument. The non-protein amino acid L-canavanine is structurally related to L-arginine with an oxygen substituted for the terminal methylene group of L-arginine and is highly toxic to humans. The proton affinity of L-arginine, a protein amino acid, was determined to be 1036 kJ mol -1, whereas the proton affinity of L-canavanine was determined to be 1005 kJ mol-1. Thus, substitution of an oxyguanidino group for the guanidine group in L-arginine results in a large decrease in …

Spe-7, A Novel Regulator Of Msp Assembly In C Elegans Spermatocytes, Kari Lynn Messina

Dissertations, Theses, and Masters Projects

No abstract provided.

Hydrogen/Deuterium Exchange Studies Of Protein And Non-Protein Amino Acids Using Electrospray Ionization Mass Spectrometry, Justine Victoria Arrington

Dissertations, Theses, and Masters Projects

No abstract provided.

Reactive Sulfur: Redox Reactions Of Cysteines And Methionines In The Cytoskeletal Protein Tubulin, Tara Dawn Hagedorn

Dissertations, Theses, and Masters Projects

No abstract provided.

Investigations Of The Fragmentation Spectra Of Dipeptides Containing Lysine And Its Non-Protein Amino Acid Homologs, Omar Hamdy

Dissertations, Theses, and Masters Projects

No abstract provided.

Understanding The Origins, Dispersal, And Evolution Of Bonamia Species (Phylum Haplosporidia) Based On Genetic Analyses Of Ribosomal Rna Gene Regions, Kristina M. Hill

Dissertations, Theses, and Masters Projects

No abstract provided.

Molecular Marker Development For The Discrimination Of Atlantic And Pacific Blue Marlin (Makaira Nigricans), Laurie Sorenson

Dissertations, Theses, and Masters Projects

No abstract provided.

The Sumo-Targeted Ubiquitin Ligase Subunit Slx5 Functional Interacts With The Sumo E3 Ligase Siz1, Jason William Westerbeck

Dissertations, Theses, and Masters Projects

No abstract provided.

Sumo-Dependent Substrate Targeting Of The Sumo Protease Ulp1, Zachary Cole Elmore

Dissertations, Theses, and Masters Projects

No abstract provided.

An Investigation Of The Polymorphic Arss Gene Of Helicobacter Pylori, Daniel Ross Hallinger

Dissertations, Theses, and Masters Projects

No abstract provided.