Structural And Functional Insight Of Helicobacter Pylori Translation Initiation Factor If1 (Hpif1) In Protein Biosynthesis And Rational Design Of New Antimicrobial Candidates,
2023
The University of Texas Rio Grande Valley
Structural And Functional Insight Of Helicobacter Pylori Translation Initiation Factor If1 (Hpif1) In Protein Biosynthesis And Rational Design Of New Antimicrobial Candidates, Asif Shahriar
Theses and Dissertations
Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the human gastric mucosa and is associated with peptic ulcer disease and gastric cancer. Bacterial protein synthesis is a fundamental metabolic process occurring in all bacteria and is a validated target of antibiotics; however, the precise structural mechanism of H. pylori protein biosynthesis remains unknown. Protein synthesis contains four stages, and translational initiation is the most important and highly regulated critical step, involving three initiation factors (IF1, IF2, IF3) and other key components. IF1 plays a vital role in regulating this step by binding to the 30S ribosomal subunit cooperatively …
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 and 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 …
Elucidating The Direct Role Of M6a In The Human Transcriptome,
2023
The University of Texas MD ANderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences
Elucidating The Direct Role Of M6a In The Human Transcriptome, Lana Al Hasani
Dissertations and Theses (Open Access)
The best characterized and most abundant internal RNA modification is the methylation of adenosine at position 6 to give N6-methyladenosine (m6A). m6A modification on cellular RNAs was discovered in the 1970s. The past decade has witnessed major progress that illustrated important roles of this mark in various aspects of gene control. Due to its pleiotropic roles, the direct effect of m6A regulation of gene expression has remained incompletely understood. Traditional methods of understanding protein function, like CRISPR/Cas9 and RNA interference, have many limitations and have halted the process of fully understanding the direct functions of m6A. Here, we attempt alternative …
Regulation And Function Of Zeb1 Acetylation In Lung Adenocarcinoma Progression And Metastasis,
2023
The Texas Medical Center Library
Regulation And Function Of Zeb1 Acetylation In Lung Adenocarcinoma Progression And Metastasis, Mabel Perez-Oquendo
Dissertations and Theses (Open Access)
Lung cancer metastasis is leading the causes of cancer-related mortality in the United States and worldwide. Epithelial-to-mesenchymal transition (EMT) is a model for metastasis that results in loss of specialized epithelial cell contacts and acquisition of mesenchymal invasive capacity. Zinc finger E-box-binding homeobox 1 (ZEB1) recognizes and binds to E-boxes of epithelial gene promoters to repress its transcription. ZEB1 has inconsistent molecular weights, which have been attributed to post-translational modifications (PTMs). In the presented dissertation, I specifically addressed the gap in the molecular mechanisms by which PTMs of ZEB1 regulate its ability to induce EMT and how its activity might …
Neuronal Or Intestinal Knockdown Of C. Elegans Nadk-1 Decreases Oxygen Consumption And Reactive Oxygen Species,
2023
East Tennessee State University
Neuronal Or Intestinal Knockdown Of C. Elegans Nadk-1 Decreases Oxygen Consumption And Reactive Oxygen Species, Jake Regan
Electronic Theses and Dissertations
Reactive oxygen species (ROS) such as H2O2 can damage cellular components and are formed as a byproduct of mitochondrial oxidative metabolism. Studies using the nematode C. elegans have found that increasing ROS during development or early adulthood can extend lifespan, while increasing ROS during later adulthood normally decreases lifespan. NADPH provides the reducing power for several cellular antioxidants and is synthesized in a two-step reaction from NAD+ with the first step being catalyzed by NAD kinase (NADK). In this study, the effects of knocking down C. elegans cytoplasmic NADK, nadk-1 globally or in a neuron or intestine-specific manner starting from …
Determination Of Cadmium Uptake In Crassostrea Virginica Shell Under Controlled Conditions,
2023
University of South Alabama
Determination Of Cadmium Uptake In Crassostrea Virginica Shell Under Controlled Conditions, Joseph John Pavelites Ii
Graduate Theses and Dissertations (2019 - present)
The objective of this thesis was to meet growing demand for the development of environmental biomonitors that protect ecosystems and public health. To do this, I determined the potential of oyster shell as a bioindicator of cadmium (Cd) in the environment by determining the mode of Cd uptake and relationships between Cd concentrations in the environment, shell, and soft tissues of juvenile eastern oysters (Crassostrea virginica Gmelin). I performed a review of the literature on the ability of oyster shell to retain metal contaminants and the factors that could affect this process (Chapter 2). I then reared C. virginica …
Cyclic-Di-Gmp Regulates Salmonella Typhimurium Infection Of Epithelial Cells And Macrophages,
2023
East Tennessee State University
Cyclic-Di-Gmp Regulates Salmonella Typhimurium Infection Of Epithelial Cells And Macrophages, Abdulafiz Musa
Electronic Theses and Dissertations
Regulation of the bacterial second messenger cyclic-di-GMP in Salmonella Typhimurium allows it to delicately alter phenotypes to optimize invasion and survive intracellularly in epithelial cells and macrophages to become virulent and cause infection. Cyclic-di-GMP concentration is regulated by the presence of external stimuli, sensory diguanylate cyclases (DGCs) and phosphodiesterases (PDEs), and cyclic-di-GMP binding effectors. Previous studies established that maintenance of low cyclic-di-GMP concentrations is required for survival in macrophages, and that deletion of 3 active PDEs reduces this survival. Here I showed that these 3 PDEs also influenced the infection of epithelial cells. Further studies re-established the decreased survival in …
Expression, Characterization, And Investigation Of The Thermal Stability Of Fibroblast Growth Factor (Fgf) 19,
2023
University of Arkansas, Fayetteville
Expression, Characterization, And Investigation Of The Thermal Stability Of Fibroblast Growth Factor (Fgf) 19, Ridhikaanth Kalaiselvan
Chemistry & Biochemistry Undergraduate Honors Theses
Fibroblast growth factors are a family of cell signaling proteins that have the ability to bind to heparin and are involved in a wide range of physiological functions, such as angiogenesis, cell differentiation, cell proliferation, cell morphogenesis, and wound healing. Fibroblast growth factor (FGF) 19 is a signaling protein belonging to this large family of fibroblast growth factors (FGFs). FGF19 has a pronounced effect on various biological processes, including cell proliferation, cholesterol and lipid catabolism, and glucose homeostasis. As such, FGF19 is known to play an integral role in regulating many metabolic diseases, which piques the interest of the science …
A Characterization Of The Quadruple Mutant Of The Fgf1-Fgf2 Heterodimer,
2023
University of Arkansas, Fayetteville
A Characterization Of The Quadruple Mutant Of The Fgf1-Fgf2 Heterodimer, Kenlee Claborn
Chemistry & Biochemistry Undergraduate Honors Theses
Human Fibroblast Growth Factor (FGF) was first identified as a protein whose function was to aid in cell proliferation, but now, FGF has been determined to consist of over 23 different proteins in 7 different subfamilies with three different types of cell-signaling purposes.1 In the first subfamily are the two most notable and studied proteins, Fibroblast Growth Factor 1 (FGF1) and Fibroblast Growth Factor 2 (FGF2). Respectively, they are known for their unique capabilities of cell proliferation/mitogenesis and angiogenesis.2 To induce the cell-signaling pathway that leads to the function of these proteins, FGF1 and FGF2 binds to their …
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, …
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, …
Microorganisms In Extreme Environmental Conditions,
2023
University of Arkansas, Fayetteville
Microorganisms In Extreme Environmental Conditions, Khanh Mai Nguyen
Graduate Theses and Dissertations
Organisms are known to be able to prosper under normal and extreme environmental conditions, which are classified as mesophile and extremophile, respectively. Extremophiles can thrive under a large array of conditions, from pressures, temperatures, salinity, and pH to a combination of them. For example, to survive on the ocean floor, marine biomass must have its biomolecular machinery adapted to the high pressures and high salinity environment. Moreover, around the hydrothermal vents, aside from pressure and salinity, the microbes that live there also need to adjust to the temperature as well as the pH level. Aside from high temperatures, researchers also …
Development Of A Cannabinoid Testing Method Using Blood Collection Cards And Lc-Ms/Ms,
2023
Lipscomb University
Development Of A Cannabinoid Testing Method Using Blood Collection Cards And Lc-Ms/Ms, Lindsey K. Reynolds, Matt J. Vergne
Student Works
Cannabis is one of the most widely used drugs in the world. Marijuana is a type of cannabis with high amount of Δ9-tetrahydrocannabinol (Δ9-THC) which is psychoactive and intoxicating. Δ9-THC affects alertness and concentration, reducing driving skills when one is intoxicated. Law enforcement of driving under the influence of drugs (DUID) is difficult for police because there is no rapid way to test for Δ9- THC intoxication at the scene of an accident or police stop. Currently, police have to take suspects to a facility to acquire blood samples for testing and the average time before testing is more than …
Non-Destructive Imaging Of Phytosulfokine Trafficking In Plants Using Fiber-Optic Fluorescence Microscopy,
2023
East Tennessee State University
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 …
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 …
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 …
Effects Of Cations And Dipicolinic Acid On B. Anthracis Spore Physiology And Cytotoxicity,
2023
University of Nevada, Las Vegas
Effects Of Cations And Dipicolinic Acid On B. Anthracis Spore Physiology And Cytotoxicity, Chandler P. Hassan
UNLV Theses, Dissertations, Professional Papers, and Capstones
Inhalation of Bacillus anthracis spores leads to the most severe form of anthrax. Following phagocytosis by alveolar macrophages, spores germinate inside the phagolysosome. The mechanism used by the newly germinated B. anthracis cells to survive within macrophages is not completely understood.B. anthracis spores contain large concentrations of calcium in complex with dipicolinic acid (Ca-DPA). Upon germination, the cell excretes the large depot of Ca-DPA. DPA is an amphipathic molecule that could act as a buffer and modulate phagolysosome acidification. Intracellular calcium overload can disrupt signaling pathways required for normal macrophage function and trigger cell death. We hypothesized the release of …
Biochemical Characterization Of Fsa1572 From Fervidibacter Sacchari, The First Hyperthermophilic Gh50 With Β-1, 4-Glucanase Activity,
2023
University of Nevada, Las Vegas
Biochemical Characterization Of Fsa1572 From Fervidibacter Sacchari, The First Hyperthermophilic Gh50 With Β-1, 4-Glucanase Activity, Jonathan Covington
UNLV Theses, Dissertations, Professional Papers, and Capstones
The bacterium Fervidibacter sacchari is an aerobic hyperthermophile that catabolizes various polysaccharides and is the only cultivated member of the class Fervidibacteria within the phylum Armatimonadota. Among its glycoside hydrolase (GH) cache is an enzyme from GH family 50 (GH50), an understudied family with only 25 characterized representatives and two known activities from 1,518 predicted members in the Carbohydrate-Active EnZyme (CAZy) Database. Here, we expressed, purified, and functionally characterized an extracellular GH50 from F. sacchari called Fsa1572. Using colorimetric assays, we show it has novel β-1,4-glucanase activity and only weak agarose activity that is typical for GH50 enzymes. The purified …
Long-Range Regulation By The Shigella Virulence Gene Regulator, Virb,
2023
University of Nevada, Las Vegas
Long-Range Regulation By The Shigella Virulence Gene Regulator, Virb, Cody Cris
UNLV Theses, Dissertations, Professional Papers, and Capstones
Nucleoid-structuring proteins (NSPs) in bacterial cells can exert gene regulatory effects over great distances on DNA. This contrasts with the traditional view of bacterial transcriptional regulation, where transcription factors bind cis-acting regulatory sites proximal (<250 bp) to promoters to influence gene expression. In Shigella species, the histone-like nucleoid-structuring protein (H-NS) transcriptionally silences many genes on the large (~220 kb) virulence plasmid. During host colonization, however, silencing by H-NS is alleviated by the anti-silencer protein, VirB, which remodels the H-NS:DNA complex. This transcriptional anti-silencing is mediated by VirB:DNA interactions and the modulation of DNA supercoiling, which lead to the up-regulation of virulence genes. VirB is a central regulator of Shigella virulence, but the mechanistic basis for transcriptional regulation is incompletely characterized. Here, I focus on the potential for VirB to regulate transcription from remotely located DNA binding sites. Employing complementary in vivo approaches, I assessed the spatial stringency of the VirB binding site and elucidated how varying cellular VirB levels impacts regulation over different distances. I also evaluated how a molecular roadblock on DNA influences remote regulation by VirB. Additionally, I developed control tools to validate the ability of VirB to spread along DNA, an activity of VirB that putatively drives transcriptional regulation. These data are consistent with transcriptional anti-silencing being driven by VirB spreading along DNA. Overall, these findings highlight how VirB is not a conventional transcriptional regulator and broaden our perspective on transcriptional control in bacteria. Furthermore, this work contributes to our understanding of long-range gene regulatory effects, which are frequently overlooked and poorly characterized in bacteria.
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 …
