An Elf4 Hypomorphic Variant Results In Nk Cell Deficiency,
2022
The Texas Medical Center Library
An Elf4 Hypomorphic Variant Results In Nk Cell Deficiency, Sandra Andrea Salinas, Emily M Mace, Matilde I Conte, Chun Shik Park, Yu Li, Joshua I Rosario-Sepulveda, Sanjana Mahapatra, Emily K Moore, Evelyn R Hernandez, Ivan K Chinn, Abigail E Reed, Barclay J Lee, Alexander Frumovitz, Richard A Gibbs, Jennifer E Posey, Lisa R Forbes Satter, Akaluck Thatayatikom, Eric J Allenspach, Theodore G Wensel, James R Lupski, H Daniel Lacorazza, Jordan S Orange
Faculty, Staff and Students Publications
NK cell deficiencies (NKD) are a type of primary immune deficiency in which the major immunologic abnormality affects NK cell number, maturity, or function. Since NK cells contribute to immune defense against virally infected cells, patients with NKD experience higher susceptibility to chronic, recurrent, and fatal viral infections. An individual with recurrent viral infections and mild hypogammaglobulinemia was identified to have an X-linked damaging variant in the transcription factor gene ELF4. The variant does not decrease expression but disrupts ELF4 protein interactions and DNA binding, reducing transcriptional activation of target genes and selectively impairing ELF4 function. Corroborating previous murine models …
Lpa Disruption With Aav-Crispr Potently Lowers Plasma Apo(A) In Transgenic Mouse Model: A Proof-Of-Concept Study,
2022
The Texas Medical Center Library
Lpa Disruption With Aav-Crispr Potently Lowers Plasma Apo(A) In Transgenic Mouse Model: A Proof-Of-Concept Study, Alexandria M Doerfler, So Hyun Park, Julia M Assini, Amer Youssef, Lavanya Saxena, Adam B Yaseen, Marco De Giorgi, Marcel Chuecos, Ayrea E Hurley, Ang Li, Santica M Marcovina, Gang Bao, Michael B Boffa, Marlys L Koschinsky, William R Lagor
Faculty, Staff and Students Publications
Lipoprotein(a) (Lp(a)) represents a unique subclass of circulating lipoprotein particles and consists of an apolipoprotein(a) (apo(a)) molecule covalently bound to apolipoprotein B-100. The metabolism of Lp(a) particles is distinct from that of low-density lipoprotein (LDL) cholesterol, and currently approved lipid-lowering drugs do not provide substantial reductions in Lp(a), a causal risk factor for cardiovascular disease. Somatic genome editing has the potential to be a one-time therapy for individuals with extremely high Lp(a). We generated an LPA transgenic mouse model expressing apo(a) of physiologically relevant size. Adeno-associated virus (AAV) vector delivery of CRISPR-Cas9 was used to disrupt the LPA transgene in …
Screening Anti-Pd-L2 Peptides As Antitumor Ligands Using Phage Display,
2022
Bowling Green State University
Screening Anti-Pd-L2 Peptides As Antitumor Ligands Using Phage Display, Chien Tran Phuoc
Honors Projects
Cancer still remains one of the top leading causes of death in America. Recently, programmed cell death protein 1 (PD-1) blockades have been demonstrated to be highly effective against various types of cancer. By blocking PD-1 from binding with their ligands (PD-L1 and PD-L2), the “off” signal to the immune system is inhibited, hence reinvigorating the immune cells to kill tumor cells. To date, despite PD-L1 and PD-L2 both interacting with PD-1, research efforts have only been focused on developing anti-PD-L1 inhibitors. Therefore, the work of this honor project has focused on finding anti-PD-L2 peptides by phage display, with the …
Designing And Synthesizing A Warhead-Fragment Inhibitory Ligand For Ivyp1 Through Fragment-Based Drug Discovery,
2022
Kennesaw State University
Designing And Synthesizing A Warhead-Fragment Inhibitory Ligand For Ivyp1 Through Fragment-Based Drug Discovery, Samuel Moore
Symposium of Student Scholars
Fragment-based drug discovery (FBDD) is a powerful tool for developing anticancer and antimicrobial agents. Within this, magnetic resonance spectroscopy (NMR) provides a comprehensive qualitative and quantitative approach to screening and validating weak and robust binders with targeted proteins, making NMR among the most attractive strategies in FBDD. Inhibitor of vertebrate lysozyme (Ivyp1) of P. aeruginosa serves as an excellent target because of its active cellular location and implications in clinical prognosis for cystic fibrosis and immunocompromised patients. This study uses current NMR and biophysical techniques to develop a covalent, fragment-linked warhead inhibitor for Ivyp1 through synthetic methods, warhead linking, and …
Chemical Control And Understanding Of Horizontal Gene Transfers, Drug-Resistance Development, And Filament And Biofilm Formation,
2022
Syracuse University
Chemical Control And Understanding Of Horizontal Gene Transfers, Drug-Resistance Development, And Filament And Biofilm Formation, Yuchen Jin
Dissertations - ALL
Biofilms formed by microbes on surfaces are the sources for persistent infectious diseases and environmental problems. The mechanism and details of how antibiotics promote biofilm formation is largely unknown. For instance, it not clear what stages of biofilm growth are promoted to proceed faster than without antibiotics, what phenotypes of bacteria form in an antibiotic-promoted biofilm, and what different biofilm compositions and structures are caused by the presence of antibiotics. Among other effects, antibiotics can cause bacteria to form filaments of living bacteria. Here, we conduct a real-time study of the adherence of bacteria and antibiotic-induced filamentous bacteria on surfaces …
Caribbean Reef-Building Coral-Symbiodiniaceae Network: Identifying Symbioses Critical For System Stability In A Changing Climate,
2022
Nova Southeastern University
Caribbean Reef-Building Coral-Symbiodiniaceae Network: Identifying Symbioses Critical For System Stability In A Changing Climate, Shaman Patel
All HCAS Student Capstones, Theses, and Dissertations
Increasing global ocean temperatures and frequency of marine heatwaves pose dire consequences for coral reefs. High temperatures often lead to disruptions in coral symbiosis resulting in coral bleaching, increasing the mortality of corals. However, corals can potentially avoid bleaching peril by associating with thermally tolerant symbionts. Here we provide a tool for understanding symbiosis network stability of Caribbean reef-building corals. We created a network of Caribbean hermatypic corals and their associated Symbiodiniaceae phylotypes. A bleaching model was applied to this network to test for resilience and robustness (R50) to thermal stress. It was also layered with trait data for coral …
Wrack Lines Volume 22, Number 2, Fall-Winter 2022-2023,
2022
University of Connecticut-Avery Point
Wrack Lines Volume 22, Number 2, Fall-Winter 2022-2023, Nancy C. Balcom, Juliana Barrett, Judy Benson, Ben Crnic, Sto Len
Wrack Lines
With the theme, "Looking Ahead: People and Projects Shaping the Future," the Fall-Winter 2022-2023 leads with the first in what will be a series of articles about offshore wind development impacting Connecticut. That is followed by the inspiring story of how a dying forest was replanted for climate resilience. Next, a profile of longtime marine educator Tim Visel tells about his lasting impact on Connecticut schools and students. Lastly, the complex challenge of dealing with Contaminants of Emerging Concern is examined, with descriptions of how Sea Grant is involved and the particularly troublesome group of substances called PFAS.
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 …
Dpc29 Promotes Mitochondrial Translation Post-Initation In Saccharomyces Cerevisiae,
2022
Rowan University
Dpc29 Promotes Mitochondrial Translation Post-Initation In Saccharomyces Cerevisiae, Kyle Andrew Hubble
Graduate School of Biomedical Sciences Theses and Dissertations
Although the cytosolic and bacterial translation systems are well studied, much less is known about translation in mitochondria. In the yeast Saccharomyces cerevisiae, mitochondrial gene expression is predominately regulated by translational activators. These regulators are thought to promote translation by binding the elongated 5’-UTRs on their target mRNAs. Since mammalian mitochondrial mRNAs generally lack 5’-UTRs, they must regulate translation by other mechanisms. As expected, most yeast translational activators lack orthologues in mammals. Recently, a mitochondrial gene-specific translational activator, TACO1, was reported in mice and humans. To better define its role in mitochondrial translation I examined the yeast TACO1 orthologue, DPC29. …
Functional Analysis Of Legionella Pneumophila Effector Protein,
2022
Western Kentucky University
Functional Analysis Of Legionella Pneumophila Effector Protein, Shreya Neupane
Masters Theses & Specialist Projects
Legionella pneumophila is a gram-negative bacterium that causes Legionnaire’s disease (a severe form of pneumonia) in humans. L. pneumophila can cause infection by utilizing its Type IV secretion system, a protein secretion system that transports proteins from the bacterial cytosol into the infected macrophage. Effectors released from the Type Iv secretion system allow L. pneumophila to create a safe environment to survive, replicate and cause infection. One such effector, RavQ, inhibits cell proliferation of mammalian HEK 293T cells and localizes to the cell’s nucleus, leading us to hypothesize that RavQ interferes with cellular activity in the nucleus. To detect its …
Metabolic Foundations Of Exercise-Induced Cardiac Growth.,
2022
University of Louisville
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 …
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 …
The Role Of Vsmc Mir-33a Expression On Apoa-I Mediated Cholesterol Efflux And Macrophage-Like Cell Transdifferentiation,
2022
Clemson University
The Role Of Vsmc Mir-33a Expression On Apoa-I Mediated Cholesterol Efflux And Macrophage-Like Cell Transdifferentiation, Ikechukwu Esobi
All Dissertations
Atherosclerosis is a condition caused by cholesterol accumulating in arterial intimal cells and is a disease that kills more people in the United States and globally than any other disease. Atherosclerosis is commonly recognized to arise from arterial intimal macrophage cholesterol accumulation, but cell lineage tracing technology has shown that a large majority of cholesterol-laden intimal cells found in atherosclerotic arteries are actually vascular smooth muscle cells that have switched phenotypes to a macrophage-like cell. This vascular smooth muscle cell to macrophage-like cell phenotypic switch is known as transdifferentiation and can be triggered by vascular smooth muscle cell cholesterol accumulation. …
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 …
Functional Characterization Of The Newly Discovered Type V Crispr-Cas Protein Cas12a2,
2022
Utah State University
Functional Characterization Of The Newly Discovered Type V Crispr-Cas Protein Cas12a2, Dylan J. Keiser
All Graduate Theses and Dissertations, Spring 1920 to Summer 2023
Similarly to people, bacteria are under the treat of infection by viruses. To circumvent these threats, bacteria evolve complex immune systems. Our understanding of some of these immune systems has led to many advancements in the field of Biotechnology including tools that made expressing proteins for study in a lab easier, tools that revolutionized the feasibility of gene editing, and tools that could change the way we think about viral diagnostics and cancer therapeutics. A certain type of immune system that bacteria use to fight virus is called a CRISPR system. Presented here is work to understand the function of …
Vircy-Seq : A Protocol For Characterizing Viral Activity,
2022
University at Albany, State University of New York
Vircy-Seq : A Protocol For Characterizing Viral Activity, Tyler James Dion
Legacy Theses & Dissertations (2009 - 2024)
The main purpose of pharmaceutical production is to produce safe effective medicine for patient use. In an effort to ensure patient safety constant surveillance for viruses takes place. The detection of a viral nucleic acid in a pharmaceutical production setting results in investigations to assess its infectious potential. This is an intensive, expensive process that entails many tests such as the observation of hemadsorption, cytopathic effects (CPE), and more. These tests are typically specific and only capture certain viruses, as factors like CPE can only be observed in some viral species. A new investigational method that is effective on all …
Understanding SjöGren's Syndrome As A Systemic Autoimmune Disorder,
2022
University at Albany, State University of New York
Understanding SjöGren's Syndrome As A Systemic Autoimmune Disorder, Gaietchyne Chery
Legacy Theses & Dissertations (2009 - 2024)
Sjögren’s syndrome is an autoimmune condition characterized by a dysfunction in the lachrymal and salivary glands which results in dry eyes and dry mouth. Since its first description in 1892, the disease is one of the most common autoimmune diseases after lupus erythematosus and rheumatoid arthritis in the United States. Despite its high prevalence in the general population, Sjögren’s syndrome remains hard to diagnose due to the wide range of symptoms associated with the disease that is also shared by other conditions. Furthermore, the mechanisms behind the pathogenesis are not properly understood even though multiple factors have been proposed to …
Development Of Nucleic Acid Diagnostics For Targeted And Non-Targeted Biosensing,
2022
University at Albany, State University of New York
Development Of Nucleic Acid Diagnostics For Targeted And Non-Targeted Biosensing, Christopher William Smith
Legacy Theses & Dissertations (2009 - 2024)
The field of nucleic acid technology is rapidly expanding with new impactful discoveriesbeing made each year. Starting from the discovery of the double-helix structure, cloning, gene editing, polymerase chain reaction (PCR), CRISPR technology, and even the late mRNA vaccines; nucleic acid technology is at the forefront of improving medicine. Nucleic acid technology is extremely versatile due to its easy programmability, automated cheap synthesis, and even its catalog for numerous chemical modifications that can be used to alter structure stability. For example, the number of permutations that can be made with DNA just by altering the code for adenine (A), cytosine …
Characterizing And Epitope Mapping Single-Domain Antibodies On Borrelia Burgdorferi Protein Ospa,
2022
University at Albany, State University of New York
Characterizing And Epitope Mapping Single-Domain Antibodies On Borrelia Burgdorferi Protein Ospa, Saiful Basir
Legacy Theses & Dissertations (2009 - 2024)
Epitope mapping a protein that enables pathogenesis is crucial for the development of therapies and prophylactics that can inhibit the pathogen’s function and its transmission of disease. The lipoprotein OspA enables Lyme Disease etiologic pathogen, Borrelia burgdorferi, to inhabit the tick midgut until transmission occurs. Anti-OspA mAbs and their smaller VHH counterparts are highly specific and tailored to bind proteins such as OspA, reproducibly, at established binding sites or epitopes. Previous studies found an array of mAbs that successfully bound OspA and have already been used in epitope mapping. To our knowledge, this is the first use of VHHs in …
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 …
