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Quantum Computations And Molecular Dynamics Simulations: From The Fundamentals Of Antimicrobial Resistance To Neurological Diseases, Angel Tamez

Electronic Theses and Dissertations

Biophysical phenomena are modeled using a combination of quantum and classical methods to interpret and supplement three distinct and diverse problems in this dissertation. In the first project, decarboxylation reactions are ubiquitous across chemical and biological disciplines, yet the origin of non-catalytic solvent effects remains elusive. Specific solvent structure and energetics have not been well described for the monoanion of malonate, nor corrected from the gas-phase charge-assisted intramolecular hydrogen bond model known as “pseudochair”. In the aqueous phase, a low-lying energy conformer known as the “orthogonal conformation” is computed to be preferred by a three-water cluster of hydrogen bonding over …

Metabolic Foundations Of Exercise-Induced Cardiac Growth., Kyle Fulghum

Electronic Theses and Dissertations

Regular aerobic exercise promotes physiological cardiac growth, which is an adaptive response thought to enable the heart to meet higher physical demands. Cardiac growth involves coordination of catabolic and anabolic activities to support ATP generation, macromolecule biosynthesis, and myocyte hypertrophy. Although previous studies suggest that exercise-induced reductions in cardiac glycolysis are critical for physiological myocyte hypertrophy, it remains unclear how exercise influences the many interlinked pathways of metabolism that support adaptive remodeling of the heart. In this thesis project, we tested the general hypothesis that aerobic exercise promotes physiological cardiac growth by coordinating myocardial metabolism to promote glucose-supported anabolic pathway …

Regulation Of Line-1 In Developing Oocytes And The Impact On The Ovarian Reserve, Rose Besen-Mcnally

Electronic Theses and Dissertations

In humans and mice, the ovarian reserve (OR) is established during a lengthy process that starts during early embryogenesis with germ cell specification and culminates in the first weeks after birth when primordial follicles (PF) are formed. OR establishment is an important process which influences the fertile lifespan and fecundity of the individual. Fetal oocyte attrition (FOA) has been identified as a critical developmental event that regulates how many oocytes survive and contribute to the final OR. In addition to FOA, OR size and quality also depend on efficiency of meiotic recombination. Chromosome asynapsis and unrepaired meiotic double-strand breaks (DSB) …

Applications Of Nuclear Magnetic Resonance Spectroscopy: From Drug Discovery To Protein Structure And Dynamics., Mark Vincent C. Dela Cerna

Electronic Theses and Dissertations

The versatility of nuclear magnetic resonance (NMR) spectroscopy is apparent when presented with diverse applications to which it can contribute. Here, NMR is used i) as a screening/ validation tool for a drug discovery program targeting the Phosphatase of Regenerating Liver 3 (PRL3), ii) to characterize the conformational heterogeneity of p53 regulator, Murine Double Minute X (MDMX), and iii) to characterize the solution dynamics of guanosine monophosphate kinase (GMPK). Mounting evidence suggesting roles for PRL3 in oncogenesis and metastasis has catapulted it into prominence as a cancer drug target. Yet, despite significant efforts, there are no PRL3 small molecule inhibitors …

Lipophilic Probes For Cellular Ethylene Detection, Morgan R. Brown

Electronic Theses and Dissertations

The structure of ethylene is simple, yet its biological effects are significant. When considering its role in biology it is almost exclusively regarded as a plant hormone. Research on ethylene from plants was progressed by several advancements in analytical instrumentation, from its discovery to elucidation of its signaling pathway. There is currently limited understanding of ethylene’s role in mammals, but evidence suggests that it may be a biomarker for oxidative stress! Additional tools and technology are crucial to study this surprising and important signaling role in mammals. Our group has developed molecular ethylene probes as a strategy to detect ethylene …

Structural And Functional Characterization Of Two Poly(Aspartic Acid) Hydrolases, Amanda Jansch

Electronic Theses and Dissertations

Due to the accumulation of polymers in the environment, biodegradable alternatives should be used in place of commonly used polymers like poly(carboxylates). Poly(carboxylates) are water-soluble polymers (WSPs) that make up a variety of consumer products, such as detergents, descaling agents, and superabsorbent materials commonly found in diapers and feminine hygiene products. While the visible accumulation of these products may not be obvious, it is necessary to reduce the amount entering the environment. Poly(aspartic acid) (PAA) is an alternative WSP that is biodegradable through the action of three different enzymes, PahZ1_KT-1, PahZ2_KT-1, and PahZ1_KP-2. Originally …

Elucidating Mechanisms For S-Nitrosoglutathione Reductase Activity And Control In Plants Using O-Aminobenzoyl-S-Nitrosoglutathione And A Novel Photo-Sensitive Probe, Leslie Ventimiglia

Electronic Theses and Dissertations

S-nitrosoglutathione reductase, (GSNOR) is widely accepted as the master regulator of stress through NO signaling and protein S-nitrosylation. GSNOR mediates stress response through the catalysis of its principal substrate S-nitrosoglutathione (GSNO). The instigation of various stressors in plants cause observable changes in plant phenotype, which are associated with changes in GSNOR activity. There are no current methods for measuring GSNOR activity directly in living plants. In this paper, a previously developed fluorogenic pseudo-substrate for human GSNOR, OAbz-GSNO, was applied to the Solanum lycopersicum plant model. OAbz-GSNO was identified as a promising novel pseudo- substrate to study changes …

Rnp Granules In Toxoplasma Gondii: Function And Formation, Scott Roscoe

Electronic Theses and Dissertations

Toxoplasma gondii is an obligate intracellular parasite capable of infecting mammals, birds, reptiles, and fish. T. gondii only undergoes sexual reproduction in a feline host. In all other organisms the parasite reproduces asexually, either as fast growing tachyzoites or slow growing bradyzoites. Bradyzoites form latent cysts inside the host cell that can lay dormant for years and convert back to tachyzoites when the host’s immune system becomes weakened. Tachyzoites rapidly replicate in the host cell, eventually causing it to lyse. While extracellular, tachyzoites repress their own translation by phosphorylating the eukaryotic initiation factor eIF2α and form microscopically visible aggregates of …

Inhibition Of De Novo And The Prion-Like Spread Of Amyloidogenesis Using In Vitro And In Vivo Disease Models, Johnson Anazoba Joseph

Electronic Theses and Dissertations

The aberrant fibrous, extracellular, and intracellular proteinaceous deposits in cells, organs and tissues are referred to as amyloids. These deposits are dominated by β-sheet structures that have been implicated in several neurodegenerative diseases and cancer. In this work, the types of amyloidosis studied include Parkinson’s disease (PD) using UA196 and NL5901 strains of Caenorhabditis elegans (C. elegans), Alzheimer’s disease (AD) using GMC101 strain of C. elegans, and cancer-associated mutant p53 aggregation in MIA PaCa-2 mutant cells. Several molecules including SK-129, NS132, NS163, bexarotene, a polyphenol (-)-epi-gallocatechine gallate (EGCG), ADH40, RD148, and RD242 were screened in vitro and in …

Development Of Novel Pyridazine Derivatives And Drug Delivery Systems Against Dengue, Janae A. Culmer

Electronic Theses and Dissertations

The lack of approved vaccines, medications and treatment regimens has significantly contributed to the rapid spread of mosquito-borne viruses such as Dengue and Zika virus. The complex immunopathology of these viruses presents limitations for the development and implementation of a definitive, safe and effective approach to combat infections.Previous research has demonstrated that vector control strategies such as the elimination of larval habitats, larviciding with insecticides, the use of biological agents and the application of adulticides have been unsuccessful in the reduction of viral transmission leading to the need for the continued development of antivirals. This research proposes an approach for …

Biomimetic Synthesis Of Palladium Nanoparticles For Catalytic Application, Emily A. Groover

Electronic Theses and Dissertations

The synthesis of palladium nanoparticles (Pd NPs) using materials-directed peptides is a novel, nontoxic approach which exerts a high level of control over the particle size and shape. This biomimetic technique is environmentally benign, featuring nonhazardous ligands and ambient conditions. Nanoparticles are extremely reactive catalysts, boasting a large surface-to-volume ratio when compared to their bulk counterparts. The rational design of these nanoparticles using peptides has been very successful in aqueous environments, but no research has been done to apply it in organic systems. As such, the biomimetic synthesis of Pd NPs in an organic system is here investigated, with ethanol …

Understanding The Impact Of Human Germline Single-Nucleotide Variants, Samuel Adjei

Electronic Theses and Dissertations

All genetic variations in the human genome are due to mutations, and therefore determining the impact of the different categories of mutations, particularly nonsynonymous single nucleotide variants (SNVs) which are the most abundant in the population is essential for understanding the genetics of human diseases. Generations of mutation studies have focused on a relatively small number, partly due to technological limitations. However, advances in next-generation sequencing have allowed for empirical assessments of genome-wide mutations. genome sequence of any individual contains extensive protein-altering genetic variation (missense mutations) and of which only a few are unambiguously deleterious. Characterizing the phenotypes of these …

Investigating Spatiotemporal Kinetics, Dynamics, And Mechanism Of Exosome Release, Anarkali Mahmood

Electronic Theses and Dissertations

Exosomes are small lipid-based vesicles that can carry biomolecules from one cell to another. While exosomes are crucial to maintain homeostasis in healthy cells, they are exploited by unhealthy cells to aid disease progression. Exosomes likely facilitate disease progression via the transfer of disease-causing biomolecules from unhealthy to healthy cells. Exosomes are generated in Multivesicular endosomes (MVEs) and are then secreted into the extracellular space to travel to other cells. Despite being a crucial step, very little is known about exosomes release mechanism and dynamics. To further our understanding of exosomes, specifically their secretion, my work has focused on investigating …

Structure And Mechanics Of Biomembrane Mimics In The Presence Of Vitamin E, Mitchell Dipasquale

Electronic Theses and Dissertations

Over the course of this dissertation, the fundamental behaviours and interactions between various analogs of vitamin E and biologically-relevant membranes will be explored. These analogs include the biologically active form, α-tocopherol; the most naturally abundant form γ-tocopherol; an oxidized product, α-tocopheryl quinone; and the synthetic stabile form, vitamin E acetate.

Beginning in Chapter 1, a foundation in membrane biophysics is established from a historical progression of the field. The importance of biomembranes is argued and a deep connection is established between structure and function. Key structural features of lipid assemblies, and role of lipid composition is defined, and with the …