Sequencing And Functional Characterization Of A Latrodectus Geometricus Defensin, Lg-Defensin,
2022
Stephen F Austin State University
Sequencing And Functional Characterization Of A Latrodectus Geometricus Defensin, Lg-Defensin, Jacklyn Victoria Thompson
Electronic Theses and Dissertations
Defensins are small, cysteine-rich, immune related proteins described to be the most widespread family of invertebrate antimicrobial peptides. Presently, there is limited information regarding spider defensins. In this study, a new defensin peptide was described in Latrodectus geometricus, Lg-defensin. The full open reading frame was resolved using RACE and de novo assembly, followed by a bioinformatical analysis and phylogenetic alignment to determine conserved sequence patterns and structural similarities to other defensins. Next, the functionality of Lg-defensin was determined using in vitro RNA interference to assess what impact silencing had on the spider’s ability to control a gram-positive and gram-negative bacterial …
Dna Origami Scaffold Development For Digital Nucleic Acid Memory,
2022
Boise State University
Dna Origami Scaffold Development For Digital Nucleic Acid Memory, Sarah Elizabeth Kobernat
Boise State University Theses and Dissertations
Recently, DNA nanotechnology has emerged as a promising and rapidly expanding method to utilize nucleic acids as a nanoscale building material. DNA origami is a major structural application of DNA nanotechnology, using DNA to construct two- and three-dimensional shapes. These structures have been employed for a variety of uses including DNA data storage. DNA is a promising material to address the impending shortage of silicon-based storage as data demands increase. There are many sequence-based methods of data storage, but digit Nucleic Acid Memory (dNAM) uses DNA origami as a breadboard and is read by super-resolution microscopy instead. dNAM uses DNA …
Structure, Function, And Immunogenic Applications Of Ab5-Type Adp-Ribosylating Bacterial Toxins,
2022
Boise State University
Structure, Function, And Immunogenic Applications Of Ab5-Type Adp-Ribosylating Bacterial Toxins, Elise Marie Overgaard
Boise State University Theses and Dissertations
Bacterial mono-ADP-ribosyltransferases (ARTs) catalyze the singular transfer of an ADP-ribose moiety from an NAD+ molecule onto a target molecule. ARTs contain an ancient and highly conserved tertiary structure and have a wide variety of intracellular targets and effects. Some, but not all, bacterial ARTs have an AB5-type multimeric structure consisting of an enzymatically active subunit non-covalently situated atop of a non-toxic pentamer. The active, or A, subunit of AB5-type toxins has a catalytic action that contributes to bacterial pathogenicity, and it is sometimes, but not always, an ART. ArtAB is an ART with AB5-type …
Ankyrin Dependent Mitochondrial Function And Bioenergetics In The Heart,
2022
The Texas Medical Center Library
Ankyrin Dependent Mitochondrial Function And Bioenergetics In The Heart, Janani Subramaniam, Janani Subramaniam
Dissertations and Theses (Open Access)
ANK2 mutations in patients are associated with numerous arrhythmias, cardiomyopathies, and other heart defects. In the heart, AnkB, the protein encoded by ANK2, clusters relevant ion channels and cell adhesion molecules in several important domains; however, its role at Mitochondria Associated ER/SR Membranes (MAMs) has yet to be investigated. MAMs are crucial to mitochondrial function and metabolism and are signaling hubs implicated in various cardiac pathologies. Among several functions, these sites mediate the direct transfer of calcium from the ER/SR to the mitochondria to modulate ATP synthesis. Given that mitochondrial function and energy production are paramount to cardiovascular heath, …
The Antimicrobial Resistance Plasmid Mobilome Of Salmonella Enterica And Related Enteric Species And Factors That Influence The Transfer Efficiency.,
2022
University of Arkansas, Fayetteville
The Antimicrobial Resistance Plasmid Mobilome Of Salmonella Enterica And Related Enteric Species And Factors That Influence The Transfer Efficiency., Suad Algarni
Graduate Theses and Dissertations
The dynamic distribution of antimicrobial resistance genes in Salmonella enterica is considered a public health risk. S. enterica is one of the most important etiological agents of foodborne illness and has a critical impact on global human health. In S. enterica and related species, mobile genetic elements (MGEs) serve as primary vehicles for the dissemination of antibiotic resistance genes in the bacterial evolution. This dissemination can be impacted by different selective pressures that leads to diverse antibiotic response phenotypes. This project focusses on the dynamics of antimicrobial resistance genes, particularly exploring the transfer efficiency of multidrug resistance plasmids in S. …
Exploring The Anticancer Mechanism Of Thienopyrazole Derivative Tpz-1 In Acute Myeloid Leukemia,
2022
University of Texas at El Paso
Exploring The Anticancer Mechanism Of Thienopyrazole Derivative Tpz-1 In Acute Myeloid Leukemia, Jessica Dyanne Hess
Open Access Theses & Dissertations
Anticancer drug discovery is a time and resource-consuming process for which exceedingly reliable and efficient modern approaches are needed. Phenotypic drug screenings can generate highly potent and innovative drug candidates; however, deconvolution of the drugâ??s target often presents significant barriers to drug development. To overcome this hurdle, we have originally combined in vitro and in silico analyses to uncover the molecular mechanism(s) driving the anticancer activity of the uniquely structured small molecule drug candidate, Tpz-1. Our study revealed that Tpz-1 is a multitargeted agent which induces the programmed death of HL-60 acute myeloid leukemia cells primarily through disruption of microtubule …
Using Molecular Dynamics Simulations To Decipher Mechanistic Details Of Biomolecular Processes Of Biology And Biotechnology Oriented Applications,
2022
University of Arkansas, Fayetteville
Using Molecular Dynamics Simulations To Decipher Mechanistic Details Of Biomolecular Processes Of Biology And Biotechnology Oriented Applications, Adithya Polasa
Graduate Theses and Dissertations
Researchers in chemistry and biology often utilize computer simulations, in conjunction with experimental data, to model and predict the structures, energies, kinetics, processes, and functions of the systems that are their focus of study, ranging from single molecules to whole viruses. Here, we use molecular dynamics (MD) techniques to gain a deeper understanding of biomolecular processes in biology and biotechnology-oriented applications. Using a mixture of equilibrium and non-equilibrium MD simulations, this work describes the insertion process of YidC at the atomic level. In order to better comprehend the insertion process, several docking models of YidC-Pf3 in the lipid bilayer were …
Re-Engineering Cardio-Oncology Testing Using Biomimetic Heart Slice Cultures.,
2022
University of Louisville
Re-Engineering Cardio-Oncology Testing Using Biomimetic Heart Slice Cultures., Jessica Miller
Electronic Theses and Dissertations
28% of drug withdrawal from the market are due to unforeseen disruptions in cardiomyocyte contractility and electrophysiology. The most commonly used platforms for drug testing are in vivo animal models and in vitro cell culture models. While both have been of paramount importance for the discovery and detection of many cardiotoxicities and mechanisms of action, they lack the ability to model an intact human myocardium. This work aims to establish cardiac tissue slices, which are 300-micron thin tissue sections taken from the left ventricular myocardium, as an alternative platform for cardio-oncology studies, specifically cardiotoxicity testing. Additionally, this work aims to …
Molecular Characterization Of Nitrogenase Regulation In Methanosarcina Acetivorans,
2022
University of Arkansas, Fayetteville
Molecular Characterization Of Nitrogenase Regulation In Methanosarcina Acetivorans, Melissa Chanderban
Graduate Theses and Dissertations
Nitrogenase is the metalloenzyme only found in bacteria and archaea that is essential for biological nitrogen fixation (diazotrophy), but it can also serve as a catalyst in biofuel production. All diazotrophs contain a molybdenum (Mo) nitrogenase, while some species contain additional alternative nitrogenases where either vanadium (V) or iron (Fe) replace Mo in the active site cofactor. Nitrogen fixation by bacteria has been extensively studied. The limited investigation of nitrogen fixation in methanogenic archaea (methanogens) indicates production of nitrogenase is simpler than in bacteria and methanogen nitrogenase has different biochemical properties. Thus, methanogen nitrogenases provide a promising alternative for genetic …
Comparative Analysis Of Conformational Transition Pathways In Homologous Proteins,
2022
University of Arkansas, Fayetteville
Comparative Analysis Of Conformational Transition Pathways In Homologous Proteins, Dylan Sebastien Ogden
Graduate Theses and Dissertations
Molecular dynamics (MD) simulations are routinely used to study the dynamics of proteins. However, conventional MD limited to the sampling of local conformational changes as the functionally important conformational transitions of proteins often extend beyond the timescales of the simulations employed, for example, membrane transport proteins. We have determined the combination of multiple MD based techniques that allows for a rigorous characterization of energetics and kinetics of large-scale conformational changes in membrane proteins. The methodology is based on biased, nonequilibrium collective variable based simulations including nonequilibrium pulling, string method with swarms of trajectories, bias-exchange umbrella sampling, and rate estimation techniques. …
Investigations Into Prg-2 And Its Involvement In Developing Gallus Gallus Retinal Neurons,
2022
Winthrop University
Investigations Into Prg-2 And Its Involvement In Developing Gallus Gallus Retinal Neurons, Jeffrey Parham
Graduate Theses
I am interested in the development of the nervous system, especially since during development nerves grow and extend, but in adults, they do not regenerate if damaged. We are specifically interested in the molecules that guide nerves to the correct target during their development. Lysophosphatidic acid (LPA) is a bioactive molecule that has been shown to play a role in neural development. LPA, through repeated studies, has been shown to stop neurons from growing by causing a physical change in a neuron’s growth cone (a structure used for navigation and growth). Recently, a novel set of genes, called PRGs, have …
T-Cell Antigen Receptors In Multiple Sclerosis,
2022
Old Dominion University
T-Cell Antigen Receptors In Multiple Sclerosis, Lisa Lanée Keyes Jones
Biomedical Sciences Theses & Dissertations
Multiple Sclerosis (MS) is T-cell mediated autoimmune disease characterized by inflammation, demyelination, and degeneration of axons in the brain and spinal cord. A T cell-mediated immune response in MS is directed against myelin components and possibly other antigens in genetically susceptible individuals and is triggered by a viral infection. The T-cell antigen receptor (TCR) on T cells is responsible for antigen recognition and determines specificity. Our overall hypothesis is to determine whether clonally expanded T cells in patients with MS recognize viral or self-antigens and to determine whether molecular mimicry is involved in the development of the disease. To study …
Cell Division Dynamics Of Escherichia Coli In Extreme Environments,
2022
University of Arkansas, Fayetteville
Cell Division Dynamics Of Escherichia Coli In Extreme Environments, Steven P. Murray
Graduate Theses and Dissertations
Life is remarkable in how resilient it can be. Many organism, classified as ex- tremophiles, can not only survive in extreme environments, but they can thrive in them. In the search for extraterrestrial life, the best candidates to harbor life exist with some kind of extreme condition. Europa, for example, is a favorite for the possibility of accommodating life as we know it within our solar system. Thought there is believed to be a liquid ocean under its icy surface, this habitat would be under immense pressures and high salinity. To best know where to look for extraterrestrial life, it …
Gating Intermediates Reveal Inhibitory Role Of The Voltage Sensor In A Cyclic Nucleotide-Modulated Ion Channel,
2022
The Texas Medical Center Library
Gating Intermediates Reveal Inhibitory Role Of The Voltage Sensor In A Cyclic Nucleotide-Modulated Ion Channel, Xiaolong Gao, Philipp A M Schmidpeter, Vladimir Berka, Ryan J Durham, Chen Fan, Vasanthi Jayaraman, Crina M Nimigean
Faculty, Staff and Student Publications
Understanding how ion channels gate is important for elucidating their physiological roles and targeting them in pathophysiological states. Here, we used SthK, a cyclic nucleotide-modulated channel from Spirochaeta thermophila, to define a ligand-gating trajectory that includes multiple on-pathway intermediates. cAMP is a poor partial agonist for SthK and depolarization increases SthK activity. Tuning the energy landscape by gain-of-function mutations in the voltage sensor domain (VSD) allowed us to capture multiple intermediates along the ligand-activation pathway, highlighting the allosteric linkage between VSD, cyclic nucleotide-binding (CNBD) and pore domains. Small, lateral displacements of the VSD S4 segment were necessary to open the …
Structural And Biochemical Characterization Of Epigenetic And Fusion Tyrosine Kinase Cancer Targets For Drug Development,
2022
University of South Florida
Structural And Biochemical Characterization Of Epigenetic And Fusion Tyrosine Kinase Cancer Targets For Drug Development, Melissa Bikowitz
USF Tampa Graduate Theses and Dissertations
Cancer is a significant global health burden, as ~40% of the human population is diagnosed with cancer over a lifetime, half of which succumb to the disease. To develop novel compounds as potential cancer therapeutics, an in-depth structural and biochemical understanding of proteins involved in oncogenesis is key. This dissertation centers around the comprehensive structural and biochemical characterization of two classes of proteins critical for cancer cell survival: bromodomain-containing proteins (BRDs) and fusion tyrosine kinases (FTKs).In 2010, small molecule inhibitors targeting bromodomains (epigenetic reader proteins) became heavily popularized due to the druggability and potent anticancer effects of BET inhibitors. …
The Childhood Acute Illness And Nutrition (Chain) Network Nested Case-Cohort Study Protocol: A Multi-Omics Approach To Understanding Mortality Among Children In Sub-Saharan Africa And South Asia,
2022
The Childhood Acute Illness and Nutrition Network, Kenya
The Childhood Acute Illness And Nutrition (Chain) Network Nested Case-Cohort Study Protocol: A Multi-Omics Approach To Understanding Mortality Among Children In Sub-Saharan Africa And South Asia, James M. Njunge, Kirkby Tickell, Abdoulaye Hama Diallo, Abu Sadat Mohammad Sayeem Bin Shahi, Md Amran Gazi, Ali Faisal Saleem, Zaubina Kazi, Syed Ali, Caroline Tigoi, Ezekiel Mupere
Department of Paediatrics and Child Health
Introduction: Many acutely ill children in low- and middle-income settings have a high risk of mortality both during and after hospitalisation despite guideline-based care. Understanding the biological mechanisms underpinning mortality may suggest optimal pathways to target for interventions to further reduce mortality. The Childhood Acute Illness and Nutrition (CHAIN) Network ( www.chainnnetwork.org) Nested Case-Cohort Study (CNCC) aims to investigate biological mechanisms leading to inpatient and post-discharge mortality through an integrated multi-omic approach.
Methods and analysis; The CNCC comprises a subset of participants from the CHAIN cohort (1278/3101 hospitalised participants, including 350 children who died and 658 survivors, and …
Occurrence Of Kanamycin-Resistant Bacteria Relative To Anthropogenic Pollution Along Richland Creek In Nashville, Tn,
2022
Belmont University
Occurrence Of Kanamycin-Resistant Bacteria Relative To Anthropogenic Pollution Along Richland Creek In Nashville, Tn, Jolene Ho Mach, Annie Le, Brandon Torres Ramirez
Science University Research Symposium (SURS)
The overuse of antibiotics has caused an increase in antibiotic-resistant (AR) bacteria, which is a serious public health concern. Previous studies showed a significant correlation between anthropogenic pollution and AR bacteria. This project aims to identify AR bacteria in Richland Creek relative to local anthropogenic pollution. Water samples were collected at four locations along Richland Creek in Nashville, Tennessee. Bacteria resistant to the antibiotic kanamycin were isolated from the water samples, identified to genera using DNA barcoding, and compared among the sites. We expect to see a greater abundance and diversity of kanamycin-resistant bacteria closer to the end than near …
The Effect Of Licogliflozin (Sglt1/2 Inhibitor) On Diabetes And Cardiac Complications,
2022
United Arab Emirates University
The Effect Of Licogliflozin (Sglt1/2 Inhibitor) On Diabetes And Cardiac Complications, Alanoud Gharib Alblooshi
Theses
Diabetes mellitus (DM) is a chronic endocrine disease affecting millions of people worldwide. In spite of the advances made in the management of DM, poor glycemic control and diabetes complications are still very common. There is a continuous search for new and more effective drugs to treat DM. One of the drugs currently in clinical trials for the treatment of DM is licogliflozin (LIK066), a dual SGLT1/2 inhibitor, which can be used to treat obesity and diabetes. LIK066 inhibits glucose reabsorption in the kidney and small intestine, thereby reducing hyperglycemia. This study aims to investigate the efficacy of licogliflozin on …
Distribution Of Erm Proteins In The Stomach Mucosa Of Normal And Diabetic Rats,
2022
United Arab Emirates University
Distribution Of Erm Proteins In The Stomach Mucosa Of Normal And Diabetic Rats, Asmaa Salem Al Sereidi
Theses
Diabetes mellitus (DM), or simply diabetes, refers to a group of metabolic disorders that include a variety of diseases that disrupt our body's metabolism. The long-term uncontrolled disease can lead to stomach complications such as gastroparesis, as well as disruption in several proteins, such as ERM (Ezrin, radixin, moesin) proteins. ERM proteins are three proteins that are structurally and functionally related. ERM proteins have molecular masses of 82, 80, and 75 kDa, respectively. Ezrin is highly expressed in the stomach, especially in parietal cells that secrete gastric acid. ERM proteins function as scaffolding proteins in lipid rafts and granule trafficking …
To Be Or Not To Be: A Tale Of Staphylococcal Gpsb,
2022
University of South Florida
To Be Or Not To Be: A Tale Of Staphylococcal Gpsb, Lauren R. Hammond
USF Tampa Graduate Theses and Dissertations
There are two big drivers motivating studies into bacterial cell division. The first is a desire to understand life around us. One of the defining characteristics of life is the ability for a cell to grow and divide, and without in-depth knowledge of this process, we cannot truly understand the complexities that allow for life on this planet. The second motivator is to identify new drug targets in the ongoing fight against antimicrobial resistance. Many infectious organisms have become resistant to commonly used antibiotics, and the bacterial cell division machinery is a largely untapped essential process with many potential therapeutic …
