Physical Sciences and Mathematics Commons^™

Structural Insights Into The Cl-Par-4 Protein: Ionic Requirements, Conformational Transitions, And Interaction With Cisplatin, Krishna Kumar Raut

Chemistry & Biochemistry Theses & Dissertations

Cancer continues to be the leading global cause of death, with challenges in early diagnosis, drug resistance, non-specific drug targeting, and cancer recurrence and metastasis posing formidable obstacles in cancer therapy. In this context, Prostate Apoptosis Response-4 (Par-4), a pro-apoptotic tumor suppressor protein, emerged as a promising therapeutic target due to its ability to selectively induce apoptosis in cancer cells, thereby minimizing the drug-associated adverse effects. However, a comprehensive understanding of the structural features of Par-4, specifically the caspase-cleaved fragment (cl-Par-4), is crucial for therapeutic advancements.

This dissertation investigated the effects of various ions, both monovalent and divalent, on the …

Clostridioides Difficile Biofilm And Spore Production In Response To Antibiotics And Immune Stress, Adenrele M. Oludiran

Chemistry & Biochemistry Theses & Dissertations

The development of new therapeutic options against Clostridioides difficile (C. difficile) infection is a critical public health concern, as the causative bacterium is highly resistant to multiple classes of antibiotics. C. difficile, an anaerobic spore-forming Gram-positive pathogenic bacterium, is a major cause of hospital-acquired infections. C. difficile persists in the environment and spreads the infection to new hosts in the form of dormant spores and can persist within hosts as surface-attached biofilms. These studies investigate bacterial vegetative cell survival, biofilm formation, and sporulation in response to stress. Antimicrobial host-defense peptides (HDPs) are highly effective at simultaneously modulating …

Genetically Engineered Thermosynechococcus Elongatus Bp1: Assessment Of Potential Biorisks And Biofuel Production, Thu Ho Anh Nguyen-Jones

Chemistry & Biochemistry Theses & Dissertations

According to the International Energy Outlook 2019, released by the U.S. Energy Information Administration, it is projected that the energy consumption will increase up to 50% between 2018 and 2050 worldwide. As fossil fuel being a finite source of energy with the risk of depletion, many countries are now facing an energy security crisis. Therefore, it is important to develop other renewable and sustainable energy sources that will allow countries to shift away from depending on fossil fuels. Among several types of renewable energy, biofuel production using genetically engineered cyanobacteria is capturing much interest due to its many advantages. Different …

Computational Analysis Of Type 3 Iodothyronine Deiodinase: Potential Inhibitors, Substrate Binding, And Dimer Structure, Eric Scott Marsan

Chemistry & Biochemistry Theses & Dissertations

Thyroid hormones (THs) in mammalian tissues are crucial for development and maintaining metabolic homeostasis. Iodothyronine deiodinases (Dios) remove iodines from THs by a selenocysteine (Sec) residue, which either activates or inactivates them. Halogen bonding (XB) has been proposed to describe the interaction between the Se and I atoms of the T4-Dio complex. Disruption of TH homeostasis by xenobiotics, such as polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) can cause deleterious effects on the endocrine system. Experimental studies have indicated that PBDEs and PCBs could disrupt TH homeostasis by inhibiting Dio through XB formation. However, no current quantitative study exists …

Improvement Of Biochar Through Ozonization And Biosafety Of Genetically Engineered Cyanobacteria, Oumar Sacko

Chemistry & Biochemistry Theses & Dissertations

Through the innovative technique of biochar post-production surface oxygenation by ozonization, we were able to improve certain properties of biochar. In project one, the incubation of an insoluble phosphate rock material (hydroxyapatite) with the wet ozonized pine 400 biochar and its filtrate resulted in a solubilization of 80 times more phosphate from hydroxyapatite (569.0 mg/L ± 6.4) compared to the pure water-hydroxyapatite control (7.2 mg/L ± 0.3). The ozonized biochar may provide a new possible way to unlock the phosphorus from insoluble phosphate mineral phases. The cation exchange capacity (CEC) is a key property of biochar when used as a …

Electrohydrodynamic Simulations Of Capsule Deformation Using A Dual Time-Stepping Lattice Boltzmann Scheme, Charles Leland Armstrong

Mathematics & Statistics Theses & Dissertations

Capsules are fluid-filled, elastic membranes that serve as a useful model for synthetic and biological membranes. One prominent application of capsules is their use in modeling the response of red blood cells to external forces. These models can be used to study the cell’s material properties and can also assist in the development of diagnostic equipment. In this work we develop a three dimensional model for numerical simulations of red blood cells under the combined influence of hydrodynamic and electrical forces. The red blood cell is modeled as a biconcave-shaped capsule suspended in an ambient fluid domain. Cell deformation occurs …

Biophysical Characterization Of The Par-4 Tumor Suppressor: Evidence Of Structure Outside The Coiled Coil Domain And Interactions With Platinum Chemotherapeutics, Andrea Megan Clark

Chemistry & Biochemistry Theses & Dissertations

Prostate apoptosis response-4 (Par-4) is an apoptosis-inducing tumor suppressor protein. Full-length Par-4 has previously been shown to be a predominantly intrinsically disordered protein (IDP) under neutral conditions, with significant regular secondary structure evident only within the C-terminal coiled coil domain. However, IDPs can gain ordered structure through the process of induced folding, which often occurs under non-neutral conditions. Previous work has shown that the Par-4 leucine zipper, which is a subset of the C-terminal coiled coil domain, is disordered under neutral conditions, but forms a dimeric coiled coil at acidic pH. Increase in ionic strength was also shown to increase …

Evaluating The Role Of The Stringent Response Mechanism In Clostridioides Difficile Survival And Pathogenesis, Astha Pokhrel

Chemistry & Biochemistry Theses & Dissertations

The human pathogen Clostridioides difficile is increasingly tolerant of multiple antibiotics and causes infections with a high rate of recurrence, creating an urgent need for new preventive and therapeutic strategies. The stringent response, a universal bacterial response to extracellular stresses, governs antibiotic survival and pathogenesis in diverse organisms but has not previously been characterized in C. difficile. This dissertation explores the ability of C. difficile to mount the stringent response. The bacteria encode a full-length, canonical bifunctional Rel/Spo Homolog or RSH enzyme. C. difficile RSH is incapable of utilizing GTP as a substrate but readily synthesizes putative 5’-pGpp-3’ alarmones. …

Computational And Experimental Investigation Into The Determinants Of Protein Structure, Folding, And Stability In The Β-Grasp Superfamily, John T. Bedford Ii

Chemistry & Biochemistry Theses & Dissertations

Elucidating the mechanisms of protein folding and unfolding is one of the greatest scientific challenges in basic science. The overarching goal is to predict three-dimensional structures from their amino acid sequences. Understanding the determinants of protein folding and stability can be facilitated through the study of evolutionarily related but diverse proteins. Insights can also be gained through the study of proteins from extremophiles that may more closely resemble the primordial proteins. In this doctoral research, three aims were accomplished to characterize the structure, folding and unfolding behavior within the β-grasp superfamily. We propose that the determinants of structure, stability, and …

Not Too Hot, Not Too Cold, But Moderately Variable: The Influence Of Environmental Variability On Coral Thermal Tolerance, Courtney Nicole Klepac

Biological Sciences Theses & Dissertations

Anthropogenic climate change is causing an increase in the frequency and severity of marine heat waves, resulting in declining health of coral reef ecosystems worldwide. Coral bleaching events – the breakdown in symbiosis between the coral host and their intracellular photosynthetic algae – are increasingly common in recent years and contribute to widespread losses in coral cover. However, bleaching and heat stress responses vary across spatial scales both within and among coral species. Coral populations native to highly variable environments can have greater bleaching resistance than corals from more stable habitats and corals transplanted into these variable reef sites can …

Study Of The Effects Of Silver Ions And Silver Nanoparticles On Embryonic Development, Martha Sharisha Johnson

Biomedical Sciences Theses & Dissertations

This dissertation focuses on the study of the toxicity of metal nanoparticles (NPs) and their ions on the development of zebrafish embryos, aiming to understand unique biological effects of NPs and ions, and design new in vivo assays to characterize the toxicity of these metal NPs and metal ions. Currently, the underlying molecular mechanisms of biological effects of nanomaterials are partially understood. Some studies assume that the toxic effects of NPs can be attributed to the release of their ions. We investigate the effects of silver NPs (Ag NPs) and silver ions (Ag+ ions) on the embryonic development of zebrafish …

Characterizing The Activity Of Antimicrobial Peptides Against The Pathogenic Bacterium Clostridium Difficile In An Anaerobic Environment, Adenrele Mojeed Oludiran

Chemistry & Biochemistry Theses & Dissertations

Clostridium difficile is an anaerobic Gram-positive pathogen with high treatment costs and mortality and very high antibiotic tolerance. Antimicrobial host-defense peptides (HDPs) produced naturally by animal immune systems are promising candidates to develop novel therapies for bacterial infection because they cause oxidative stress that damages multiple targets in bacterial cells, so it is difficult for bacteria to evolve resistance to these attacks.

Piscidins, fish-derived HDPs that can also form complexes with copper (Cu) to enhance their activities, are very active against multiple bacterial species in an aerobic environment. We examined their activity against C. difficile and other species in an …

Advances In Amino Acid Analysis For Marine Related Matrices And Its Application To Coastal Shelf Settings In The Canadian Arctic, Rachel M. Mcmahon

OES Theses and Dissertations

Amino acids comprise up to 50% of organic matter in cellular material and are a major fraction of oceanic organic carbon. Amino acids are also considered highly labile during organic matter recycling, making them useful proxies for organic carbon cycling. Nevertheless, analysis of individual amino acids has been burdened by lengthy derivatization and complex analysis since the 1950s. In this thesis, I describe the modification of advanced analytical techniques, developed in the biomedical field, for analysis of marine matrices which allow the determination of at least 40 amino acids without the need for lengthy sample preparation and derivatization, twice the …

Structure Of The Picornavirus Replication Platform: A Potential Drug Target For Inhibiting Virus Replication, Meghan Suzanne Warden

Chemistry & Biochemistry Theses & Dissertations

Picornaviruses are small, positive-stranded RNA viruses, divided into twelve different genera. Members of the Picornaviridae family cause a wide range of human and animal diseases including the common cold, poliomyelitis, foot and mouth disease, and dilated cardiomyopathy. The picornavirus genome is replicated via a highly conserved mechanism involving a presumed cloverleaf structure located at the 5’ noncoding region of the virus genome. The 5’ cloverleaf consists of three stem loops (B, C, and D) and one stem (A), which interact with a variety of virus and host cell proteins during replication. In this dissertation, human rhinovirus serotype 14 (HRV-14) SLB …

Marine Reserves Promote Coral Reef Resilience By Mitigating Human Impacts Through The Restoration Of Parrotfish Populations, Increasing Their Reproductive Output And Seeding Neighboring Overfished Reefs, Brian L. Stockwell

Biological Sciences Theses & Dissertations

Coral reefs are some of the most productive ecosystems on the planet, providing fisheries resources for over a billion people with billions of dollars in revenue from tourism for developing nations. Coral reefs are under threat from overfishing and water pollution, resulting in less productive algae dominated reefs. Marine reserves are widely expected to promote the resilience of reefs by protecting and increasing the abundance of herbivorous fishes that can graze on algae, therefore directly or indirectly preventing coral to algal phase shifts. However, the ability of marine reserves to mitigate human impacts, restore herbivorous fish populations and seed nearby …

Bioenergetics: Experimental Demonstration Of Excess Protons And Related Features, Haitham A. Saeed

Chemistry & Biochemistry Theses & Dissertations

Over the last 50 years, ever since the Nobel-prize work of Peter Mitchell’s Chemiosmotic theory, the question whether bioenergetics energy transduction occurs through localized or delocalized protons has been a controversial issue among scientists. Recently, a proton-electrostatics localization hypothesis was formulated which may provide a new and clear understanding of localized and delocalized proton-coupling energy transduction in many biological systems. The aim of this dissertation was to test this new hypothesis.

To demonstrate the fundamental behavior of localized protons in a pure water-membrane-water system in relation to the newly derived pmf equation, excess protons and excess hydroxyl anions were generated …

Synthesis And Mechanistic Investigations Of Transition Metal Complexes And Ligands For Chemotherapeutic Applications, Jimmie Lee Bullock Jr.

Chemistry & Biochemistry Theses & Dissertations

Transition metal complexes have played a critical role in antitumor therapy with many complexes incorporating platinum, ruthenium, and lanthanum having been investigated in preclinical and clinical trials. The best known transition metal therapeutic is cisplatin, which is utilized in nearly 50% of all cancer therapies, despite its significant toxic side effects. The toxic side effects of current FDA approved platinum-based chemotherapeutics are often overlooked due to the “special status” granted to these drugs due to their ability to fight, what is often considered an incurable disease with life expectancies often measured in months. Oncology drug development has therefore now focused …

Exploring The Effect Of Climate Change On Biological Systems, Nardos Sori

Chemistry & Biochemistry Theses & Dissertations

The present and potential future effect of global warming on the ecosystem has brought climate change to the forefront of scientific inquiry and discussion. For our investigation, we selected two organisms, one from cyanobacteria and one from a cereal plant to determine how climate change may impact these biological systems. The study involved understanding the physiological and adaptive responses at both the genetic and protein function levels to counteract environmental stresses. An increase in atmospheric carbon dioxide is a key factor in global climate change and can lead to alterations in ocean chemistry. Cyanobacteria are important, ancient and ubiquitous organisms …

Density Functional Theory Modeling Of It-Stacking And Electrophilic Donor-Acceptor Interactions With Application To Therapeutic Targeting Of Zinc-Finger Proteins, Patricia Beall Lutz

Chemistry & Biochemistry Theses & Dissertations

Several viruses, including viruses that cause cancer, contain conserved zinc finger (ZF) proteins that are essential for viral reproduction, making them attractive drug targets for cancer and viral treatment. ZFs are small protein domains that have Zn²⁺ tetrahedrally coordinated to at least 2 Cys and His. They form three classes of ZFs depending on the amino acid ligands, CCHH, CCCH, and CCCC. Zn²⁺ is stable towards redox reactions; however, the Cys thiolates are redox active. Oxidation of the Cys thiolates release Zn²⁺, and the ZF loses its tertiary structure and can no longer bind DNA or …

Comparison Of Two Separation Methods For Biological Particles: Field-Flow Fractionation (Fff) And Sucrose Density Gradients, Cody E. Garrison

OES Theses and Dissertations

Sucrose gradient centrifugation and Field-flow fractionation (FFF) are two different particle separation methods that overcome the problems of similar size microorganisms clumping together during standard filtration methods. FFF separates particles based on size and density via the parabolic velocity profile of laminar flow in a ribbon-like channel. The sucrose method separates particles via centrifugation in a density gradient. Both techniques worked well in separating eukaryotic from prokaryotic microbes, with the preferred method depending on the type and relative abundance of organisms to be separated. Minicells were separated from mother cells in transformed Escherichia coli cultures, heterotrophic flagellates (e.g., Diplonema papillatum …

Identification Of Persistent Long Range Interactions In GA95 And GB95 Through Thermal Unfolding Simulations, Milen Redai Tesfamariam

Chemistry & Biochemistry Theses & Dissertations

For over five decades, different experiments have been performed to research how proteins attain their native three dimensional structures. However, the folding problem continues to be a puzzle in modern science. The design of two proteins that have maximal sequence identity but different folds and functions is one method that is being used to study the relationship between protein structure and amino acid sequence. In particular, mutant proteins of Streptococcus protein G, G_A and G_B, have 95% sequence identity and a 3a helix fold and β4/a fold, respectively. Molecular dynamics simulations of G_A95 …

Design Of In Vivo Assays For Study Of Transport, Biocompatibility And Toxicity Of Nanoparticles, Kerry Jean Lee

Theses and Dissertations in Biomedical Sciences

This dissertation focuses on the design of new in vivo assays for study of transport, biocompatibility and toxicity of nanoparticles (NPs) in zebrafish embryos. We synthesized and purified spherical silver (Ag) NPs with diameters, ranging from 12 to 95 nm, that are stable (non-aggregated) in egg-water media. We developed new imaging approaches to characterize the sizes of single Ag NPs in zebrafish embryos at nanometer resolution by measuring their size-dependent plasmonic spectra and scattering intensity using dark-field optical microscopy and spectroscopy (DFOMS). We used single Ag NPs because they exhibit the high quantum yield (QY) of Rayleigh scattering and resist …

Computational Investigation Of The Bioactive Selenium Compounds Ebselen And Selenious Acid, Sonia Antony

Chemistry & Biochemistry Theses & Dissertations

Selenium, a toxic element, is required in trace quantities for the proper functioning of biological systems. The experimental mechanistic study of the reactions of ebselen and selenious acid is difficult due to complexity of the reaction mixtures and the presence of short-lived intermediates. Computational modeling of the reactivity of these species can give us an insight into their mechanisms, but the process is complicated by proton exchanges associated with the mechanistic steps. In gas phase modeling, this may be corrected to a certain level using the solvent assisted proton exchange (SAPE) method. SAPE is a modeling technique that mimics solvent …

Bioinformatics, Thermodynamics And Kinetics Analysis Of An All Alpha Helical Protein With A Gree-Key Topology, Hai Li

Chemistry & Biochemistry Theses & Dissertations

Computational and experimental studies focusing on the role of conserved residues for folding and stability is an active and promising area of research. To further expand our understanding we present the results of a bioinformatics analysis of the death domain superfamily. The death domain superfamily fold consists of six α-helices arranged in a Greek-key topology, which is shared by the all β-sheet immunoglobulin and mixed α/β-plait superfamilies. Our sequence and structural studies have identified a group of conserved hydrophobic residues and corresponding long-range interactions, which we propose are important in the formation and stabilization of the hydrophobic core and native …

Characterization Of Metastasis-Associated Cell Surface Glycoproteins In Prostate Cancer, Lifang Yang

Theses and Dissertations in Biomedical Sciences

Prostate cancer (PCa) is a major health problem in males in the United States. Its lethality is mostly attributed to the primary tumor metastasizing to distant sites that are highly resistant to conventional therapies. Serum Prostate Specific Antigen (PSA) is the only protein biomarker used in clinic for prediction of prostate cancer recurrence following local therapies. Nonetheless, PSA lacks the ability to predict the behavior of an individual tumor in an individual patient. Therefore, development of reliable biomarkers for detection of metastatic potential in primary tumors, as well as discovery of new therapeutic targets, is in a great need for …

Phosphorus Uptake In Rhodomonas Salina (Wislouch) And Its Effect On Allocation And Elimination In Acartia Tonsa (Dana), Danna Palladino

OES Theses and Dissertations

Phosphorus is a key element in important biochemical compounds, such as RNA and phospholipids, and can become limiting in a variety of marine systems. The uptake of phosphorus into biochemical fractions (protein, low molecular weight (LMW) compounds, lipid, polysaccharide and nucleic acid) in Acartia tonsa fed ³³P -labeled Rhodomonas salina was examined. R. salina was cultured on two variations of one media that in one case contained phosphorus in balance and the other out of balance with relation to other standard f/2 components. The P-balanced (PB) media had a N:P ratio of 24.5, which is higher than that found …

Experimental Investigation Of A Non-Thermal Atmospheric Pressure Plasma Jet, Asma Begum

Electrical & Computer Engineering Theses & Dissertations

The main objective of this dissertation is to understand the formation of the plasma jet from the plasma pencil, and the propagation of the plasma jet in the ambient atmosphere where the effect of the external electric field is almost zero. Before investigating the formation and propagation phenomenon of the plasma jet, common physical properties of plasma jets are determined by using the imaging technique and optical emission spectroscopy. The first goal of this dissertation is to establish the laminar helium gas flow channel through a plasma pencil.

The formation position, formation time, and the criterion of the plasma jet …

Conformational Change And Topological Stability Of Proteins, Jeffrey Andrew Tibbitt

Chemistry & Biochemistry Theses & Dissertations

The conformation and topology of a protein changes when stabilizing forces are absent, but the mechanisms by which these changes occur remains elusive. This dissertation aims to broaden the understandings. On the conformational level, the M20 loop conformers of E. coli dihydrofolate reductase are interrogated to identify factors responsible for their stability as well as to determine how one conformer might change into another. Molecular dynamics is used to simulate the open, closed and occluded conformers (observed in X-ray crystal structures) under a series of different single ligand conditions. Analysis shows that all open conformers move to a similar new …

Characterization Of Antibiotic Resistance In Vibrio Cholerae Isolated From Ships' Ballast And Other Environmental Sources, Frank Kornegay Thomson Iii

OES Theses and Dissertations

Ships' ballast has been implicated as a vector in the dispersal of invasive species into new environments. Numerous cases have been documented for the introduction of macroorganisms via ballasting operations, but what is less known is the role of ballast water and residuals in the spread of potentially harmful microbes, especially with reference to novel genotypes. Of particular interest are the genes encoding for various forms of antibiotic resistance, many of which are carried on mobile genetic elements. A four-year sampling effort has yielded over 300 putative isolates of Vibrio cholerae from ships' ballast tanks and various environmental sources, of …

Improved Constrained Global Optimization For Estimating Molecular Structure From Atomic Distances, Terri Marie Grant

Mathematics & Statistics Theses & Dissertations

Determination of molecular structure is commonly posed as a nonlinear optimization problem. The objective functions rely on a vast amount of structural data. As a result, the objective functions are most often nonconvex, nonsmooth, and possess many local minima. Furthermore, introduction of additional structural data into the objective function creates barriers in finding the global minimum, causes additional computational issues associated with evaluating the function, and makes physical constraint enforcement intractable. To combat the computational problems associated with standard nonlinear optimization formulations, Williams et al. (2001) proposed an atom-based optimization, referred to as GNOMAD, which complements a simple interatomic distance …