Elucidating The Impact Of Sos-Response Timing In On Escherichia Coli Survival Following Treatment With Fluoroquinolone Topoisomerase Inhibitors,
2023
University of Connecticut
Elucidating The Impact Of Sos-Response Timing In On Escherichia Coli Survival Following Treatment With Fluoroquinolone Topoisomerase Inhibitors, Stephanie Schofield
Honors Scholar Theses
Antibiotic treatment failure is a public health crisis, with a 2019 report stating that roughly 35,000 deaths occur in the United States yearly due to bacterial infections that are unresponsive to antibiotics (1). One complication in the treatment of bacterial infection is antibiotic persistence which further compromises our battle to effectively treat infection. Bacterial persisters can exist in clonal bacterial cultures and can tolerate antibiotic treatment by undergoing reversible phenotypic changes. They can survive drug concentrations that their genetically identical kin cannot. Some persisters remain in a slow growing state and are difficult to target with current antibiotics. A specific …
Analyzing Conformational Changes In The Binding Of Hiv-1 Matrix Protein, N And C Terminals, To Calmodulin,
2023
Chapman University
Analyzing Conformational Changes In The Binding Of Hiv-1 Matrix Protein, N And C Terminals, To Calmodulin, Nousha Karimi, Fabian Valdez, Davis Mau, K. Sakamaki
Student Scholar Symposium Abstracts and Posters
Worldwide, more than 38 million people are living with human immunodeficiency virus (HIV), about 84 million people have become infected with HIV since the start of the epidemic, and 40.1 million of those diagnoses led to death. HIV Type-1 is the most common type of HIV, attacking the body’s immune system by destroying CD4 cells. The virus attaches itself to the CD4 cell, taking control of its DNA and replicating itself to release more HIV into the bloodstream. The Gag proteins of HIV-1 are crucial players in the virus’ assembly, release, and maturation; it utilizes its essential matrix protein (MA) …
Is Vdac1 A Novel Bcl2 Family Member That Binds Bax?,
2023
University of Mississippi
Is Vdac1 A Novel Bcl2 Family Member That Binds Bax?, Claire Pearson
Honors Theses
Apoptosis is a type of regulated cell death important for normal embryonic development and maintenance of adult tissues by removing excess or dysfunctional cells to ensure proper functioning of organs. The Bcl-2 family of proteins determines whether apoptosis remains suppressed or becomes activated through the balance of interactions among pro-survival and pro-death members. A defining feature of the Bcl-2 family is a BH3 domain that drives interactions between the family members. Isoform 1 of the voltage dependent anion channel (VDAC1) has an important role in metabolism, but was recently found to have high homology with known BH3 domains. This study …
Mitochondrial Roles In Developmentally Programmed Heart Disease,
2023
University of South Dakota
Mitochondrial Roles In Developmentally Programmed Heart Disease, Eli John Louwagie
Dissertations and Theses
Offspring of diabetic and obese mothers (ODOM) have greater risks of heart disease at birth and later in life. However, prevention is hindered because underlying mechanisms are poorly understood. Mounting studies in the Developmental Origins of Health and Disease field suggest that mitochondria play key roles in developmentally programmed heart disease similar to the roles they play in cardiomyopathy in adults with diabetes and obesity. However, whether mitochondria are responsible for the short[1]and long-term cardiac disease seen in ODOM remains unknown. Here, we sought to delineate the roles of mitochondria in the hearts of ODOM, determine whether mitochondria are playing …
Poop! There It Is! Anti-Germinants And Biological Variables As Modulators Of Clostridioides Difficile Infection (Cdi),
2023
University of Nevada, Las Vegas
Poop! There It Is! Anti-Germinants And Biological Variables As Modulators Of Clostridioides Difficile Infection (Cdi), Jacqueline Renee Phan
UNLV Theses, Dissertations, Professional Papers, and Capstones
Clostridioides difficile infection (CDI) is a major cause of antibiotic-associated diarrhea. Due to its insidious nature, the Centers for Disease Control and Prevention (CDC) has declared CDI an urgent threat. A key characteristic of C. difficile is its ability to form dormant spores that act as the infectious vehicles for disease. In the gut, spores recognize bile salts to germinate into toxin-producing cells.Dysbiosis of the gut microbiome is a key factor in allowing the C. difficile spores to germinate. Normal gut microbiota naturally protects from CDI. However, biological variables such as diet and sex have been found to modulate to …
Nicotinamide Riboside And Beta-Hydroxybutyrate Activate Parallel Pathways For C. Elegans Lifespan Extension,
2023
East Tennessee State University
Nicotinamide Riboside And Beta-Hydroxybutyrate Activate Parallel Pathways For C. Elegans Lifespan Extension, Mckenzie Peters
Undergraduate Honors Theses
Supplementation with nicotinamide riboside (NR), a form of vitamin B3 and a precursor of nicotinamide adenine dinucleotide (NAD+) extends lifespan in the nematode C. elegans and delays aging-related pathologies in mammals. During aging, levels of NAD+ decline causing metabolic dysfunction and oxidative damage. Studies in C. elegans found that when NR was administered during larval development it induced the mitochondrial unfolded protein response (UPRmt), which is frequently associated with lifespan extension. Both calorie restriction (CR) and ketogenic diets (KD) have been shown to extend lifespan, in part through increasing NAD+ and through increasing levels …
Review Of Biomedical Applications Of Cardiovascular Tissue Engineering,
2023
Murray State University
Review Of Biomedical Applications Of Cardiovascular Tissue Engineering, Natalie M. Howard
Honors College Theses
Tissue engineering can be defined as processes that aim to generate three-dimensional functional tissues in vitrothat have been favorably altered according to the structural, biochemical, electrophysiological, and biomechanical properties of the desired tissue before implantation into the human body. In relation to cardiac tissues, these properties would include the ability to conduct action potentials, withstand systolic pressure, permit sufficient O2 and CO2penetration, sufficient vascularization to supply nutrients for cellular activity, surface topology that enables cellular communication, and more. As heart diseases and instances of myocardial infarction continue to rise worldwide, there is an increasing need for …
Impact Of The Pre-A Motif On Truncated Hemoglobin N Activity,
2023
University of Wisconsin-Milwaukee
Impact Of The Pre-A Motif On Truncated Hemoglobin N Activity, Alexander Shayne Drena
Theses and Dissertations
Tuberculosis (TB) remains the leading cause of death by an infectious agent and therefore a global health crisis, according to the most recent report by the World Health Organization. This is due, in part, to Mycobacterium tuberculosis’ impressive defensive mechanisms against immune response, as well as the rise of Multi-Drug Resistant strains that have recently developed. Towards the turn of the century, a small heme protein called truncated hemoglobin N (trHbN) was discovered to protect the bacteria against reactive nitrogen species by converting nitric oxide (NO) to nitrate at rates far exceeding those of myoglobin and closer to those of …
Using Nmr Chemical Shift Perturbations To Map Interactions Between Acyl-Acyl Carrier Proteins And Acyl Homoserine Lactone Synthases,
2023
Boise State University
Using Nmr Chemical Shift Perturbations To Map Interactions Between Acyl-Acyl Carrier Proteins And Acyl Homoserine Lactone Synthases, Madison N. Rizzo
Boise State University Theses and Dissertations
A pandemic of antibiotic resistance is underway and affecting multiple industries, including veterinary, agricultural, and healthcare. High bacterial population density is a major form of defense for bacterial cells against drugs, contributes to antibiotic resistance, and is one of the requirements for the formation of biofilms. Quorum sensing is a form of cell-to-cell communication that both gram-negative and gram-positive bacteria use to account for density behavior. When the population density of bacteria reaches a certain level (a “quorum”), there is an observed coordinated shift in gene expression that leads to optimized growth or virulence. Acyl carrier proteins (ACP) and the …
Studies Of The Reaction Of Rongalite With Epoxides,
2023
Montclair State University
Studies Of The Reaction Of Rongalite With Epoxides, Anuj Aryal
Theses, Dissertations and Culminating Projects
Reactions between Rongalite (Na+O-SOCH2OH) and epoxides were studied with the aim of developing new synthetic routes for the procurement of sulfone diols. This class of compounds contains essential building blocks in the construction of sulfur heterocycles, which have been implied in the development of several medicinal compounds. Thus far, the desired diols have not been isolated. During control experiments with bromo alcohols, an unknown product was isolated but remains to be identified.
Methyltransferase, Glucose Adaptation, And Import Complex In Trypanosoma Brucei,
2023
Clemson University
Methyltransferase, Glucose Adaptation, And Import Complex In Trypanosoma Brucei, Emily Knight
All Dissertations
Trypanosoma brucei is a kinetoplastid parasite responsible for human African trypanosomiasis (HAT) and nagana, a livestock wasting disease, which both endemic to sub-Saharan Africa. Unique to kinetoplastids are the specialized peroxisomes, named glycosomes, which compartmentalize the first several steps of glycolysis and gluconeogenesis, nucleotide sugar biosynthesis, and many other metabolic processes. Kinetoplastids are unique in that they have a single mitochondrion. In this work, I present the first study into SET domain proteins in any kinetoplastid parasites. We have characterized a predicted SET domain protein, TbSETD3, that localizes to the mitochondrion and a depletion of the protein results in growth …
New Dna Repair And Demethylation Functions In Uracil Dna Glycosylase Superfamily,
2023
Clemson University
New Dna Repair And Demethylation Functions In Uracil Dna Glycosylase Superfamily, Chenyan Chang
All Dissertations
Uracil-DNA glycosylase (UDG) superfamily, which consists of several groups of enzymes that recognize the damaged DNA bases and initiate the base excision repair (BER) pathway, is most important in dealing with DNA deamination and other base modifications. Thymine DNA glycosylase (TDG), which belongs to family 2 in the UDG superfamily, is able to specifically recognize and cleave the 5-methylcytosine (mC) oxidative derivatives including 5-formylcytosine (fC), 5-carboxylcytosine (caC), 5-hydromethyluracil (hmU) caused by active demethylation or DNA damage. My dissertation work is mainly focused on the fC and caC glycosylase activity within UDG superfamily. Chapter 1 is a general introduction to the …
Glycolytic Inhibitors As Leads For Drug Discovery In The Pathogenic Free-Living Amoebae,
2023
Clemson University
Glycolytic Inhibitors As Leads For Drug Discovery In The Pathogenic Free-Living Amoebae, Jillian Milanes
All Dissertations
The free-living amoeba, Naegleria fowleri, can cause a rare yet usually lethal infection of the brain called primary amebic meningoencephalitis. Because of poor diagnostics and limited treatment options, the mortality rate associated with the disease is >97%. Due to our finding that glucose is critical for trophozoite growth in culture, we have been interested in exploiting amoebae glucose metabolism to identify new potential drug targets. We have characterized the first enzyme of the glycolytic pathway, glucokinase (Glck), from N. fowleri and two other pathogenic free-living amoeba, Acanthamoeba castellanii and Balamuthia mandrillaris. We have assessed their biochemical properties and …
Studying The Phosphorylation Of Isocitrate Dehydrogenase In Humans,
2023
University of Arkansas, Fayetteville
Studying The Phosphorylation Of Isocitrate Dehydrogenase In Humans, Hannah Smith
Chemistry & Biochemistry Undergraduate Honors Theses
Isocitrate dehydrogenase is an important enzyme in the citric acid cycle where it catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate. While there are three isoforms of isocitrate dehydrogenase (IDH1, IDH2, and IDH3), this research will focus on IDH1. The phosphorylation of isocitrate dehydrogenase is a process that has been linked to the formation of both luminal-like and basal-like breast cancer. Despite these correlations, the mechanisms that cause breast cancer development are unknown. To examine this, an enzyme activity assay for each phosphorylation variant and crystallization were conducted. The results of these indicate that phosphorylation at each site (IDH1-T77, IDH1-S188, …
Quantum Chemistry–Machine Learning Approach For Predicting Properties Of Lewis Acid–Lewis Base Adducts,
2023
Loyola Marymount University
Quantum Chemistry–Machine Learning Approach For Predicting Properties Of Lewis Acid–Lewis Base Adducts, Hieu Huynh, Thomas J. Kelly, Linh Vu, Tung Hoang, Phuc An Nguyen, Tu C. Le, Emily Jarvis, Hung Phan
Chemistry and Biochemistry Faculty Works
Synthetic design allowing predictive control of charge transfer and other optoelectronic properties of Lewis acid adducts remains elusive. This challenge must be addressed through complementary methods combining experimental with computational insights from first principles. Ab initio calculations for optoelectronic properties can be computationally expensive and less straightforward than those sufficient for simple ground-state properties, especially for adducts of large conjugated molecules and Lewis acids. In this contribution, we show that machine learning (ML) can accurately predict density functional theory (DFT)-calculated charge transfer and even properties associated with excited states of adducts from readily obtained molecular descriptors. Seven ML models, built …
Differential Electrostatic Interaction Patterns In Sars-Cov-1 And Sars-Cov-2 Variants: A Molecular Dynamics Simulation Study,
2023
University of Arkansas-Fayetteville
Differential Electrostatic Interaction Patterns In Sars-Cov-1 And Sars-Cov-2 Variants: A Molecular Dynamics Simulation Study, Ugochi Hope Isu
Graduate Theses and Dissertations
The SARS-related coronavirus (SARS-rCoV) is a highly contagious virus that has raised significant worldwide health concerns. It caused outbreaks in 2002-2003 and more recently in 2019-2020 with SARS-CoV-2. SARS-CoV-2 is responsible for the COVID-19 pandemic, which has resulted in a significant global impact on health and the economy. The spike protein of the virus plays a critical role in its infectivity and transmission, and the receptor-binding domain (RBD) within the spike protein is of particular interest, as it is responsible for binding to the human angiotensin-converting enzyme 2 (ACE2) receptor. In this study, we used Molecular dynamics (MD) simulations to …
Targeting Metabolic Alterations Associated With Smooth Muscle Α-Actin Pathogenic Variant Attenuates Moyamoya-Like Cerebrovascular Disease,
2023
The Texas Medical Center Library
Targeting Metabolic Alterations Associated With Smooth Muscle Α-Actin Pathogenic Variant Attenuates Moyamoya-Like Cerebrovascular Disease, Anita Kaw
Dissertations & Theses (Open Access)
Heterozygous pathogenic variants in ACTA2, encoding smooth muscle α-actin (α-SMA), predispose to thoracic aortic aneurysms and dissections. De novo missense variants disrupting ACTA2 arginine 179 (p.Arg179) cause a multisystemic disease termed smooth muscle dysfunction syndrome (SMDS), which is characterized by early onset thoracic aortic disease and moyamoya disease-like (MMD) cerebrovascular disease. The MMD-like cerebrovascular disease in SMDS patients is marked by bilateral steno-occlusive lesions in the distal internal carotid arteries (ICAs) and their branches. To study the molecular mechanisms that underlie the ACTA2 p.Arg179 variants, a smooth muscle-specific Cre-lox knock-in mouse model of the heterozygous Acta2 R179C variant, termed …
Rational Design, Synthesis And Biology Of Immunostimulatory Peptides,
2023
Seton Hall University
Rational Design, Synthesis And Biology Of Immunostimulatory Peptides, Nelson Casanova
Seton Hall University Dissertations and Theses (ETDs)
This dissertation reports the design, synthesis, characterization, and biological studies of three uniquely structured peptides, derived from ubiquitinated multiple myeloma proteins and ubiquitinated B7H6 ligand. The peptides were made into linear or branched shapes, with the branched peptides containing both major histocompatibility complex (MHC) class two and NKp30 binding motifs properties in one peptide. This results in an immunocytotoxic response (via cytokines and chemokines) of both natural killer cells and cytotoxic T lymphocytes (CTLs). These shapes were determined for data comparison but also to increase cytokine proliferation, the shapes help with healthy cell aviation. Thus, the linear monomer (contains a …
Acetate Metabolism In The Fungal Pathogen Cryptococcus Neoformans,
2023
Clemson University
Acetate Metabolism In The Fungal Pathogen Cryptococcus Neoformans, Oly Ahmed
All Dissertations
Cryptococcus neoformans is an environmental basidiomycetous fungus with a worldwide distribution and a wide range of habitats. Inhalation of the desiccated yeasts or spores of C. neoformans often leads to opportunistic pulmonary infections in immunocompromised individuals, and in severe cases causes lethal meningitis following hematogenous dissemination. During infection, depending on the tissue and disease state, the invading fungi experience a range of nutrient microenvironments within the host body. As a result, rapid metabolic adaptations geared towards efficient utilization of carbon sources alternative to glucose become one of the prime determinants of survival and growth for the pathogen. Incidentally, cryptococcal infection …
Expression, Purification, And Characterization Of Fibroblast Growth Factor 19,
2023
University of Arkansas, Fayetteville
Expression, Purification, And Characterization Of Fibroblast Growth Factor 19, Elizabeth Ford
Chemistry & Biochemistry Undergraduate Honors Theses
Fibroblast growth factors (FGFs) are a family of signaling proteins with diverse biological functions. Fibroblast growth factor 19 (FGF19) regulates several vital physiological processes, including bile acid, glucose, and lipid homeostasis. However, its therapeutic potential is limited by its structural instability. The purpose of this study is to express, purify, and characterize recombinant FGF19 to build the foundation for the creation of stable mutants, which can be used to treat a variety of common diseases including type 2 diabetes, atherosclerosis, and nonalcoholic fatty liver disease. The parameters for overexpression in Escherichia coli were optimized according to optical density, inducer concentration, …
