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An Investigation Into The Structural Features That Control Factor Xiii Stability And Substrate Specificity., Rameesa Darul Amne Syed Mohammed May 2024

An Investigation Into The Structural Features That Control Factor Xiii Stability And Substrate Specificity., Rameesa Darul Amne Syed Mohammed

Electronic Theses and Dissertations

Factor XIII (FXIII) is a transglutaminase enzyme with multiple physiological roles that is found in plasma and cells of bone marrow origin. The catalytic A subunit (FXIII-A) is made of an N-terminal activation peptide (AP), β-sandwich, catalytic core, and two β-barrel domains. FXIII crosslinks the sidechains of glutamine (Q) and lysine (K) residues across plasmatic and cellular substrates. Because of its involvement in clot stabilization and determining fibrin clot size, FXIII-A is regarded as a target for developing new anticoagulants with minimal bleeding risks. However, the FXIII-A structural features that control its stability and substrate specificity largely remain unknown. Plasma …


Elucidating The Role Of Sialic Acid In Tumorigenic Pathways, Kakali Das Jan 2024

Elucidating The Role Of Sialic Acid In Tumorigenic Pathways, Kakali Das

Electronic Theses and Dissertations

Hypersialylation is a prognostic biomarker in cancer cells. The upregulated sialic acid expression on cancer cells facilitates tumorigenesis by playing a critical role in cancer cell proliferation and growth, immune evasion, cell signaling, and metastasis by interacting with various carbohydrate-binding molecules. Sialic acids on cancer cell surface undergo various modifications like O-acetylation at positions 4,7,9 de-acetylation and addition of glycolyl group at position 5. In our first chapter we analyzed the effect of de-acetylated sialic acid on migration via selectin binding in colon cancer cell line HCT116 and in lung cancer cell line A549. Selectins are calcium-dependent cell adhesion molecules …


Development Of Innovative Flocculation Technologies For Agricultural Water Treatment, Noor Haleem Jan 2024

Development Of Innovative Flocculation Technologies For Agricultural Water Treatment, Noor Haleem

Electronic Theses and Dissertations

The development of innovative flocculation technologies is essential for addressing the challenges of agricultural water treatment. These technologies play a crucial role in removing contaminants such as suspended solids and nutrients, thereby ensuring safer water for irrigation and livestock consumption. By enhancing water quality and wastewater management, they contribute significantly to environmental sustainability and public health in agricultural communities. This comprehensive thesis extensively explores various dimensions of flocculation, with a focused effort on methodologies and resources aimed at strengthening sustainability and efficiency. A pivotal aspect of the research involves synthesizing cationic starch (CS), a flocculant derived from an underutilized resource, …


On The Anti-Adipogenic Function Of Collagen Triple Helix Repeat-Containing Protein 1, Matthew E. Siviski Dec 2023

On The Anti-Adipogenic Function Of Collagen Triple Helix Repeat-Containing Protein 1, Matthew E. Siviski

Electronic Theses and Dissertations

Adipogenesis is regulated by the coordinated activity of adipogenic transcription factors, including PPAR-gamma (PPARG) and C/EBP alpha (CEBPA). Thus, dysregulated adipogenesis predisposes adipose tissues to adipocyte hypertrophy and hyperplasia. We have previously reported that mice possessing a homozygous null gene mutation in collagen triple helix repeat-containing protein 1 (CTHRC1) have increased adiposity compared to wildtype mice, supporting the concept that CTHRC1 regulates body composition. Herein, we investigated the anti-adipogenic activity of CTHRC1. Using 3T3-L1 preadipocytes, we showed significantly reduced adipogenic differentiation in the presence of CTHRC1 commensurate to marked suppression of Cebpa and Pparg gene expression. In addition, CTHRC1 increased …


Synthesis Of Bacterial Glycerophospholipids For Biomembrane Model Studies: A Means To Advanced Biofuels, Felix Adulley Dec 2023

Synthesis Of Bacterial Glycerophospholipids For Biomembrane Model Studies: A Means To Advanced Biofuels, Felix Adulley

Electronic Theses and Dissertations

To reduce reliance on fossil fuels, sustainable biofuels are being pursued, especially advanced biofuels like 1-butanol that have higher energy content and greater compatibility with existing infrastructure than ethanol. A persistent challenge is the yield-limiting toxicity of biofuels and process solvents, such as tetrahydrofuran, to the microbes that ferment biomass into biofuel. The cell membrane is a focal point of toxicity, and understanding how it interacts with fuels and solvents is key to improving yield. Phospholipid bilayers are the core of biomembranes, and model biomembranes of defined composition provide the ideal platform for biophysical studies. To this end, glycerophospholipids characteristic …


Flavonol Glucosylation: A Structural Investigation Of The Flavonol Specific 3-O Glucosyltransferase Cp3gt, Aaron S. Birchfield Dec 2023

Flavonol Glucosylation: A Structural Investigation Of The Flavonol Specific 3-O Glucosyltransferase Cp3gt, Aaron S. Birchfield

Electronic Theses and Dissertations

Flavonoid glycosyltransferases (GTs), enzymes integral to plant ecological responses and human pharmacology, necessitate rigorous structural elucidation to decipher their mechanistic function and substrate specificity, particularly given their role in the biotransformation of diverse pharmacological agents and natural products. This investigation delved into a comprehensive exploration of the flavonol 3-O GT from Citrus paradisi (Cp3GT), scrutinizing the impact of a c-terminal c-myc/6x histidine tag on its enzymatic activity and substrate specificity, and successfully achieving its purification to apparent homogeneity. This established a strong foundation for potential future crystallographic and other structure/function analyses. Through the strategic implementation of site-directed mutagenesis, a thrombin …


A Tale Of Two Mechanisms: Is The P53 Modulator Coti-2 A Zinc Chaperone Instead?, Irem Simsek Sep 2023

A Tale Of Two Mechanisms: Is The P53 Modulator Coti-2 A Zinc Chaperone Instead?, Irem Simsek

Electronic Theses and Dissertations

The tumor protein p53 plays a vital role in regulating protein pathways that determine the fate of cells. Any interference with p53 function can cause disruptive cell proliferation and carcinogenesis. The p53 protein experiences a high frequency of mutation in human cancers, leading to significant research efforts to target mutant p53 and restore the normal functioning of p53. The COTI-2 small molecule, developed by COTINGA Pharmaceuticals through a computational program, has entered Phase I clinical trials. Although the mechanism of action is not fully understood, it has shown considerable promise in targeting cell lines with mutant p53. COTI-2 is believed …


Mechanisms Behind The Chaperone Activity Of Nucleic Acids, Theodore J. Litberg Aug 2023

Mechanisms Behind The Chaperone Activity Of Nucleic Acids, Theodore J. Litberg

Electronic Theses and Dissertations

Understanding the interplay between nucleic acids and protein aggregation is integral to the understanding of proteostasis, aging, and neurodegenerative disease progression. Nucleic acids are known to modulate the aggregation of PrP, tau, ⍺-synuclein, and other disease relevant proteins. Although the interactions between misfolded protein and nucleic acids can play a role in disease, this interaction may potentially be beneficial as well. Our group and others have shown nucleic acids can be powerful chaperones. Previous work has shown both RNA and DNA can prevent protein aggregation and RNA can pass off protein clients to the heat shock protein (Hsp) system. Here …


Epitranscriptomic Regulation In Breast Cancer And Pcb-Induced Liver Disease., Belinda Petri Aug 2023

Epitranscriptomic Regulation In Breast Cancer And Pcb-Induced Liver Disease., Belinda Petri

Electronic Theses and Dissertations

Post-transcriptional RNA modifications including N6-methyladenosine (m6A) regulate mRNA stability, splicing, and translation. My research examined m6A in two disease models: breast cancer (BCa) and non-alcoholic fatty liver disease (NAFLD). Acquired resistance to endocrine therapies (ET) develops in approximately 20% of BCa patients with estrogen receptor α positive (ER+) tumors following treatment. The mechanisms by which tumor cells evade ET are not completely understood. Using a cell line model, we investigated the role of an m6A reader protein, HNRNPA2B1 (A2B1) that is upregulated in ET-resistant ER+ BCa cells. Stable overexpression of A2B1 in ET-sensitive MCF-7 cells (MCF-7-A2B1), results in ET resistance, …


Fbg Αc 389 – 402 Modulates Factor Xiii Crosslinking In The Fibrinogen Αc Region., Francis Dean Orlina Ablan Aug 2023

Fbg Αc 389 – 402 Modulates Factor Xiii Crosslinking In The Fibrinogen Αc Region., Francis Dean Orlina Ablan

Electronic Theses and Dissertations

Fibrinogen (Fbg) is a coagulation protein critical for clot formation. Coagulation Factor XIII (FXIII) is a calcium-dependent transglutaminase that crosslinks reactive glutamines (Q) and lysines (K) between fibrin and other anti-fibrinolytic proteins. In the presence of Ca2+, FXIII could be activated non-proteolytically (FXIII-A°), or proteolytically by thrombin (FXIII-A*). Significant increases in clot stability and red blood cell retention are linked to FXIII activity in the fibrinogen αC region (Fbg Aα 221 – 610). This region contains several FXIII-reactive glutamines and lysines, as well as a binding site for FXIII-A* (Fbg αC 389 – 402) that includes a key …


Investigating Structural Determinants Of The Hyvh1-Hsp70 Interaction Using High Resolution Mass Spectrometry, Adrian A. Luiso Jul 2023

Investigating Structural Determinants Of The Hyvh1-Hsp70 Interaction Using High Resolution Mass Spectrometry, Adrian A. Luiso

Electronic Theses and Dissertations

The protein tyrosine phosphatase hYVH1 (also known as DUSP12) is an atypical member of the DUSP subfamily of PTPs that possesses a unique Cterminal zinc-binding domain and demonstrates functions in cell survival, cell cycle regulation, stress granule disassembly, and ribosome biogenesis. hYVH1 has been shown to associate with the ATPase domain of Hsp70 to amplify its cell survival capability, and recent studies have suggested that this complex can be dissociated by Src kinase phosphorylation. This study demonstrates the relevancy of Src-mediated hYVH1 phosphorylation at the endogenous level, supporting the conclusion that hYVH1 is a novel Src substrate. Label-free quantitative mass …


Exploring The Impact Of Src-Directed Phosphorylation On Hyvh1’S Intracellular Function, Griffin Lotze Jun 2023

Exploring The Impact Of Src-Directed Phosphorylation On Hyvh1’S Intracellular Function, Griffin Lotze

Electronic Theses and Dissertations

Human hYVH1, also referred to as DUSP12, is a dual specificity protein tyrosine phosphatase that is highly conserved across species and has been demonstrated to be overexpressed in various cancerous states.1–4 Prior investigation of hYVH1 has implicated it in numerous cellular functions including stress response, cell survival, and cell cycle modulation.5–7 Recently, novel evidence has suggested that hYVH1 also plays a role in ribosome biogenesis, functioning in the maturation of the pre-60S ribosomal subunit by mediating its nuclear export and the ejection of Mrt4.8,9 Additionally, the well characterized tyrosine kinase Src has been suggested to trigger hYVH1 to localize into …


Non-Destructive Imaging Of Phytosulfokine Trafficking In Plants Using Fiber-Optic Fluorescence Microscopy, Bernard Abakah May 2023

Non-Destructive Imaging Of Phytosulfokine Trafficking In Plants Using Fiber-Optic Fluorescence Microscopy, Bernard Abakah

Electronic Theses and Dissertations

Plants secrete peptide ligands and use receptor signaling to respond to stress and control development. Understanding these phenomena is key to improving plant health and productivity for food, fiber, and energy applications. Phytosulfokine (PSK), a sulfated peptide hormone, regulates plant cell division, growth, and stress tolerance via specific phytosulfokine receptors (PSKRs). This study uses fiber-optic fluorescence microscopy to elucidate trafficking of PSK in live plants. The microscope features two-color optics and an objective lens connected to a 1-m coherent imaging fiber mounted on either a conventional upright microscope body or 5-axis positioning system (X–Y–Z plus pitch and yaw). PSK and …


Small Gtpase Regulated Intracellular Protein Trafficking In Endothelium, Caitlin Francis Mar 2023

Small Gtpase Regulated Intracellular Protein Trafficking In Endothelium, Caitlin Francis

Electronic Theses and Dissertations

Intracellular protein trafficking is the movement of membrane-bound organelles to and from requisite locations within the cell. Small GTPases are a critical component to the spatiotemporal accuracy of intracellular trafficking pathways as they determine the specificity and direction of organelle transport. There exists over 150 small GTPases categorized into 5 sub-families and are employed across all cell types. Despite their universal expression and relevance to cellular function, small GTPases remain incompletely understood across tissue types. In various instances, the trafficking pathway of a particular Rab in one cell type may belong to a completely disparate pathway in another cell type. …


Development Of Novel Cellular Assay Model And Therapeutic Deep Eutectic Solvents To Optimize The Activity Of Anticancer Agents, Nizam Uddin Jan 2023

Development Of Novel Cellular Assay Model And Therapeutic Deep Eutectic Solvents To Optimize The Activity Of Anticancer Agents, Nizam Uddin

Electronic Theses and Dissertations

Multidrug resistance (MDR) is the major burden behind chemotherapeutic treatment failure. It is the principal mechanism by which cancer cells evade chemotherapeutic treatment. As a result, aggressive cancer cells survive and continue uncontrolled cell division. Multidrug resistance affects survival rate of almost all types of cancer patients and death toll rises at an alarming rate. There are seven different mechanisms for evolving MDR. The most common mechanism in efflux activity of overexpressed ABC transporters. MRP1 is a prominent ABC transporter that pumps out a wide variety of anticancer drugs from the cells and thereby reduces intracellular drug concentrations and develops …


The Role Of Cadherins And Ryk On Metastasis And Invasion In Triple Negative Breast Cancer Cell Model: Hs578t/Hs578ts(I)8, Ibis Iser Jan 2023

The Role Of Cadherins And Ryk On Metastasis And Invasion In Triple Negative Breast Cancer Cell Model: Hs578t/Hs578ts(I)8, Ibis Iser

Electronic Theses and Dissertations

Breast cancer is a major cause of death among women in European and North American countries, even with improved methods for diagnosis and therapy. The mortality of breast cancer is mainly due to the migration of the primary tumor to distinct sites in the body and is very common in triple negative breast cancer (TNBC). This type of breast cancer affects younger woman and has a high recurrence rate. Unfortunately, TNBC is extremely difficult to control because of the absence of specific targets for treatment. Therefore, our research aim is to discover new therapeutic targets and identify novel approaches for …


Post-Translational Modification Of Proteins Via Ambient Air Pollutants And Endogenous Reactive Species, Rachel Lauren Davey Jan 2023

Post-Translational Modification Of Proteins Via Ambient Air Pollutants And Endogenous Reactive Species, Rachel Lauren Davey

Electronic Theses and Dissertations

Proteins can react with reactive oxygen species (ROS) and reactive nitrogen species (RNS) to form post-translational modifications (PTMs), which can affect protein structure and function. The formation of 3-nitrotyrosine (NTyr) and dityrosine (DiTyr) upon reaction of proteins with ROS/RNS are two common PTMs studied due to their stability and irreversibility, as well as their ability to enhance the allergenicity of pollen allergens upon formation. Many common techniques used to study the formation of these PTMs can reliably detect the PTMs but can only provide semi-quantitative information due to many assumptions and limitations. In Chapter 2 we present an analysis of …


Mechanistic Insights Into Mftr-Dependent Regulation Of The Redox Cofactor Mycofactocin, Aigera Mendauletova Jan 2023

Mechanistic Insights Into Mftr-Dependent Regulation Of The Redox Cofactor Mycofactocin, Aigera Mendauletova

Electronic Theses and Dissertations

Organic redox cofactors are essential for life. While classic flavins and nicotinamides are widely distributed across all domains of life, nature has also evolved niche cofactors in subsets of life domains. For example, in Actinobacteria, coenzyme F420 is commonly used in place of flavin mononucleotide in enzymes associated with carbon fixation and oxidation of secondary alcohols. The importance of niche cofactors has long been recognized however, detailed understanding about their biosynthesis and physiological uses has been lagging. One class of niche cofactors is derived from ribosomally synthesized and posttranslationally modified peptides (RiPPs). To achieve their mature form, the genetically …


Modulatory Effects Of Deacetylated Sialic Acids (A Sugar Residue) In Nk-Mediated Cytotoxicity And Targeted Therapy By Receptor Tyrosine Kinase Inhibitors, Mathias Tawiah Anim Jan 2023

Modulatory Effects Of Deacetylated Sialic Acids (A Sugar Residue) In Nk-Mediated Cytotoxicity And Targeted Therapy By Receptor Tyrosine Kinase Inhibitors, Mathias Tawiah Anim

Electronic Theses and Dissertations

The complex nature of the biology of cancer is still an unraveling science, yielding several biomarkers that have served as molecular targets for detection and treatment of the disease. How sugars, glycans, play a role has remained relatively uninvestigated. Sialic acid (Sia), a sugar residue on the surface of cells, has been identified as a hallmark of cancer and its progression. Sialic acid can be highly functionalized, but we became interested in acetylated Sias. This functional group is modulated by Sialate O- acetylesterase (encoded by the gene SIAE) and Sialate O-acetyltransferase (encoded by CASD1), enzymes that play a crucial role …


Modulatory Effects Of Deacetylated Sialic Acids On Breast Cancer Resistance Protein-Mediated Multidrug Resistance And Receptor Tyrosine Kinase-Targeted Therapy, Isaac Tuffour Jan 2023

Modulatory Effects Of Deacetylated Sialic Acids On Breast Cancer Resistance Protein-Mediated Multidrug Resistance And Receptor Tyrosine Kinase-Targeted Therapy, Isaac Tuffour

Electronic Theses and Dissertations

Multidrug resistance (MDR) remains a major challenge in cancer treatment, accounting for over 90% of chemotherapeutic failures. Cancers utilize sugar residues to engage in multidrug resistance. The underlying mechanism of action involving glycans, specifically the glycan sialic acid (Sia) and its various functional group alterations, has not been explored. ATP-binding cassette (ABC) transporter proteins, key proteins utilized by cancers to engage in MDR pathways, contain Sias in their extracellular domains. Modulating the expression of acetylated-Sias on Breast Cancer Resistance Protein (BCRP), a significant ABC transporter implicated in MDR, in lung and colon cancer cells directly impacted the ability of cancer …


Biophysical Insights Into Peptide And Alcohol Perturbations On Biomimetic Membranes, Michael Hai Nguen Jan 2023

Biophysical Insights Into Peptide And Alcohol Perturbations On Biomimetic Membranes, Michael Hai Nguen

Electronic Theses and Dissertations

Biological membranes exist in every domain of life. Life exists due to the presence of these special structures for which we take for granted. They are composed of fatty lipids and workhorse proteins and act as the premier interface of biological processes. Due to the sheer quantity and complexity within their thin boundary, studying their actions and properties pose challenges to researchers. As a result, simplified biomembrane mimics are employed regularly. We will use several types of biomembrane mimics to understand fundamental properties of membranes. In the present thesis, we also attempt to move beyond the canonical structure-based theories upon …


Quantum Computations And Molecular Dynamics Simulations: From The Fundamentals Of Antimicrobial Resistance To Neurological Diseases, Angel Tamez Dec 2022

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 Dec 2022

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 Aug 2022

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 Aug 2022

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 Jan 2022

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 Jan 2022

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, PahZ1KT-1, PahZ2KT-1, and PahZ1KP-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 Jan 2022

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 Jan 2022

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 Jan 2022

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 …