Toward The Yeast Surface Display Of Microviridin B,
2023
University of New Mexico - Main Campus
Toward The Yeast Surface Display Of Microviridin B, Jillian Leigh Stafford
Chemistry and Chemical Biology ETDs
Humans have turned to natural products for medicinal therapeutics for millennia. In recent years, the ribosomally synthesized and post-translationally modified peptide (RiPP) class of natural products have garnered a lot of attention due to their ability for heterologous expression, relative ease of mutation, and vast biological activates. Microviridins are a family of RiPPs that contain a tricyclic cage-like structure through the formation of two lactone rings and one lactam ring catalyzed by two ATP-grasp ligase family enzymes. Microviridins are potent inhibitors of serine proteases and mutational studies of a small number of residues indicates the potential of peptide engineering protease …
Lipid Nanoparticle-Mediated Mrna Delivery In Lung Fibrosis,
2023
The Texas Medical Center Library
Lipid Nanoparticle-Mediated Mrna Delivery In Lung Fibrosis, Matteo Massaro, Suhong Wu, Gherardo Baudo, Haoran Liu, Scott Collum, Hyunho Lee, Cinzia Stigliano, Victor Segura-Ibarra, Harry Karmouty-Quintana, Elvin Blanco
Faculty, Staff and Student Publications
mRNA delivery enables the specific synthesis of proteins with therapeutic potential, representing a powerful strategy in diseases lacking efficacious pharmacotherapies. Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by excessive extracellular matrix (ECM) deposition and subsequent alveolar remodeling. Alveolar epithelial type 2 cells (AEC2) and fibroblasts represent important targets in IPF given their role in initiating and driving aberrant wound healing responses that lead to excessive ECM deposition. Our objective was to examine a lipid nanoparticle (LNP)-based mRNA construct as a viable strategy to target alveolar epithelial cells and fibroblasts in IPF. mRNA-containing LNPs measuring ∼34 nm had …
Characterization And Genomic Analysis Of Two Escherichia Coli O157:H7 Bacteriophages Isolated From Pigeons,
2023
United Arab Emirates University
Characterization And Genomic Analysis Of Two Escherichia Coli O157:H7 Bacteriophages Isolated From Pigeons, Mohamad I. Alolama
Dissertations
Enterohemorrhagic Escherichia coli, also known as EHEC, is a subset of Shiga toxin-producing E. coli (STEC), and it has recently been identified as one of the principal foodborne pathogens. E. coli O157:H7 is the most important serotype of STEC for its role in causing foodborne illnesses. E. coli O157:H7 could cause various gastroenteritis symptoms such as diarrhea, hemolytic uremic syndrome, hemorrhagic colitis, and thrombotic thrombocytopenic purpura and may cause death. Elimination of E. coli O157:H7 during food processing and storage is a possible solution. Bacteriophages have a significant impact on bacterial populations in nature due to their ability to …
The Function Of Transport Protein Mfl1 In Arabidopsis Thaliana,
2023
Louisiana State University and Agricultural and Mechanical College
The Function Of Transport Protein Mfl1 In Arabidopsis Thaliana, Joseph Qian
LSU Master's Theses
Photosynthesis serves as the primary process for plants to synthesize ATP and sugar molecules, however, this reaction requires many cofactors such as heme, plastoquinone, and iron-sulfur clusters to assist in energy gathering and electron transfer steps. Many of these require trace metals, such as iron, to cross across the chloroplast membranes and be incorporated into proteins and other organic molecules to form useable cofactors. The light-independent reactions of photosynthesis are also inefficient, with up to 25% of the photosynthetic energy wasted to metabolize the toxic waste product glycolate. The cellular logistics of both photorespiration and iron transport have been studied, …
A Forward Genetic Screen Identifies Genes Involved In Gametocyte Development Of The Human Malaria Parasite Plasmodium Falciparum.,
2023
University of South Florida
A Forward Genetic Screen Identifies Genes Involved In Gametocyte Development Of The Human Malaria Parasite Plasmodium Falciparum., Jyotsna Chawla
USF Tampa Graduate Theses and Dissertations
Transmission of the deadly malaria parasite Plasmodium falciparum from human to mosquito is achieved by specialized intraerythrocytic sexual forms called gametocytes. Circulating in the vertebrate host, relatively few intraerythrocytic gametocytes are picked up during a bloodmeal to continue sexual development in the mosquito vector. Human-to-vector transmission thus represents an infection bottleneck in the parasite's life cycle for therapeutic interventions to prevent malaria. Though the crucial regulatory mechanisms leading to gametocyte commitment have recently come to light, networks of genes that control sexual development remain to be elucidated. Here, we report a forward genetic approach to identify genes associated with gametocyte …
Synthesis, Characterization, And Cytotoxicity Studies Of A Copper(Ii) Complex With Vanillin 3-Ethyl-Thiosemcarbazone A Ligand,
2023
Old Dominion University
Synthesis, Characterization, And Cytotoxicity Studies Of A Copper(Ii) Complex With Vanillin 3-Ethyl-Thiosemcarbazone A Ligand, Novia Mann, Ifeoluwa Oyeyemi, Duaa R. Alajroush, Elizabeth A. Tonsel-White, Stephen J. Beebe, Alvin Holder
Undergraduate Research Symposium
Triple-negative breast cancer (TNBC) is one of the most aggressive and challenging breast cancer subtypes to treat, as these cancer cells lack three common receptors: estrogen, progesterone, and human epidermal growth factor receptor 2. The multiple oxidation states transition metals can occupy have made this narrowly explored group popular for anti-cancer research in recent decades. Furthermore, the success of cisplatin, which has platinum as a metal center, while being a cancer-fighting agent with serious side effects, has caused other metal centers to be investigated as possible alternatives as chemotherapeutic drugs. Copper, as a biologically essential metal, makes an attractive candidate …
Neuronal Sirt3 Deletion Predisposes To Female-Specific Alterations In Cellular Metabolism, Memory, And Network Excitability,
2023
The Texas Medical Center Library
Neuronal Sirt3 Deletion Predisposes To Female-Specific Alterations In Cellular Metabolism, Memory, And Network Excitability, Jennifer N Pearson-Smith, Ruth Fulton, Christopher Q Huynh, Anna G Figueroa, Gia B Huynh, Li-Ping Liang, Lindsey B Gano, Cole R Michel, Nichole Reisdorph, Richard Reisdorph, Kristofer S Fritz, Eric Verdin, Manisha Patel
Faculty, Staff and Students Publications
Mitochondrial dysfunction is an early event in the pathogenesis of neurologic disorders and aging. Sirtuin 3 (SIRT3) regulates mitochondrial function in response to the cellular environment through the reversible deacetylation of proteins involved in metabolism and reactive oxygen species detoxification. As the primary mitochondrial deacetylase, germline, or peripheral tissue-specific deletion of SIRT3 produces mitochondrial hyperacetylation and the accelerated development of age-related diseases. Given the unique metabolic demands of neurons, the role of SIRT3 in the brain is only beginning to emerge. Using mass spectrometry-based acetylomics, high-resolution respirometry, video-EEG, and cognition testing, we report targeted deletion of SIRT3 from select neurons …
Characterization Of Tick And Host-Associated Factors Linked To Induction Of Alpha-Gal Syndrome.,
2023
University of Southern Mississippi
Characterization Of Tick And Host-Associated Factors Linked To Induction Of Alpha-Gal Syndrome., Surendra Raj Sharma, Surendra Raj Sharma
Dissertations
Alpha-Gal Syndrome (AGS) is a delayed allergic reaction caused by specific IgE antibodies to the oligosaccharide galactose-α-1,3-galactose (α-gal) present in red meat. AGS is a growing concern globally, with over 34,000 confirmed cases in the United States alone. Studies have linked AGS to tick bites, which sensitizes hosts against α-gal antigens and elevates α-gal specific IgE. This dissertation investigates the role of tick and host-associated factors in AGS development. Microbiome analysis of Am. americanum ticks revealed a comprehensive core microbiome profile and showed that new Fransiella-like endosymbionts dominate and outcompete conventional tick Coxiella endosymbionts. Ticks subjected to tetracycline treatment showed …
The Molecular And Cellular Response To Acat1/Soat1 Inhibition,
2023
Dartmouth College
The Molecular And Cellular Response To Acat1/Soat1 Inhibition, Taylor C. Harned
Dartmouth College Ph.D Dissertations
Cholesterol is an important component of all mammalian cell membranes. It governs the membrane’s physical properties and creates the membrane order and heterogeneity required for complex membrane-related processes. Tight regulation of cholesterol levels and distribution are necessary for maintaining proper cell health. Likewise, disruptions in cholesterol homeostasis have been implicated in a variety of diseases, including Alzheimer’s disease (AD). Our lab, and others, have demonstrated the benefits of blocking acyl-CoA:cholesterol acyltransferase1/sterol O:acyltransferase 1 (ACAT1/SOAT1) in AD models by genetic ablation or pharmacological inhibition. We understand that blocking ACAT1/SOAT1 activity reduces amyloid and tau pathology, and that this is, at least …
Anterior And Posterior Tongue Regions And Taste Papillae: Distinct Roles And Regulatory Mechanisms With An Emphasis On Hedgehog Signaling And Antagonism.,
2023
Rowan University
Anterior And Posterior Tongue Regions And Taste Papillae: Distinct Roles And Regulatory Mechanisms With An Emphasis On Hedgehog Signaling And Antagonism., Archana Kumari, Charlotte M. Mistretta
Rowan-Virtua School of Osteopathic Medicine Departmental Research
Sensory receptors across the entire tongue are engaged during eating. However, the tongue has distinctive regions with taste (fungiform and circumvallate) and non-taste (filiform) organs that are composed of specialized epithelia, connective tissues, and innervation. The tissue regions and papillae are adapted in form and function for taste and somatosensation associated with eating. It follows that homeostasis and regeneration of distinctive papillae and taste buds with particular functional roles require tailored molecular pathways. Nonetheless, in the chemosensory field, generalizations are often made between mechanisms that regulate anterior tongue fungiform and posterior circumvallate taste papillae, without a clear distinction that highlights …
Small Gtpase Regulated Intracellular Protein Trafficking In Endothelium,
2023
University of Denver
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. …
Uncovering Zn2+ And Ca2+ Homeostasis And Crosstalk In Primary Hippocampal Neurons,
2023
University of Denver
Uncovering Zn2+ And Ca2+ Homeostasis And Crosstalk In Primary Hippocampal Neurons, Chen Zhang
Electronic Theses and Dissertations
Zn2+ has been suggested to act as an intracellular signaling molecule due to its regulatory effects on numerous protein targets including enzymes, transcription factors, ion channels, neurotrophic factors, and postsynaptic scaffolding proteins. However, intracellular Zn2+ concentration is tightly maintained at steady levels under natural physiological conditions. Dynamic changes in intracellular Zn2+ concentration have only been detected in cells exposed to pathologic stimuli or upon receptor ligand binding. In the first project of my dissertation, for the first time, we revealed that developing neurons fire spontaneous and synchronous Zn2+ spikes at a specific time window (from 14 …
A Single-Cell Gene Expression Atlas Of Human Follicular Aspirates: Identification Of Leukocyte Subpopulations And Their Paracrine Factors,
2023
University of Kentucky
A Single-Cell Gene Expression Atlas Of Human Follicular Aspirates: Identification Of Leukocyte Subpopulations And Their Paracrine Factors, Yohan Choi, Hayce Jeon, Mats Brännström, James W. Akin, Thomas E. Curry, Misung Jo
UK CARES Faculty Publications
Leukocytes are in situ regulators critical for ovarian function. However, little is known about leukocyte subpopulations and their interaction with follicular cells in ovulatory follicles, especially in humans. Single-cell RNA sequencing (scRNA- seq) was performed using follicular aspirates obtained from four IVF patients and identified 13 cell groups: one granulosa cell group, one thecal cell group, 10 subsets of leukocytes, and one group of RBC/platelet. RNA velocity analyses on five granulosa cell populations predicted developmental dynamics denoting two projections of differentiation states. The cell type-specific transcriptomic profiling analyses revealed the presence of a diverse array of leukocyte-derived factors that can …
Loss Of Peroxiredoxin Iv Protects Mice From Azoxymethane/Dextran Sulfate Sodium-Induced Colorectal Cancer Development,
2023
University of Kentucky
Loss Of Peroxiredoxin Iv Protects Mice From Azoxymethane/Dextran Sulfate Sodium-Induced Colorectal Cancer Development, Pratik Thapa, Hong Jiang, Na Ding, Yanning Hao, Aziza Alshahrani, Eun Young Lee, Junichi Fujii, Qiou Wei
Markey Cancer Center Faculty Publications
Peroxiredoxin IV (Prx4), a typical two-cysteine-containing member of the peroxidase family, functions as an antioxidant to maintain cellular redox homeostasis through the reduction of reactive oxygen species (ROS) via cycles of oxidation–reduction reactions. Under oxidative stress, all Prxs including Prx4 are inactivated as their catalytic cysteines undergo hyperoxidation, and hyperoxidized two-cysteine Prxs can be exclusively repaired and revitalized through the reduction cycle catalyzed by sulfiredoxin (Srx). Previously, we showed that Prx4 is a preferred substrate of Srx, and knockout of Srx in mice leads to resistance to azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon carcinogenesis. To further understand the significance of the …
Latexin Regulates Sex Dimorphism In Hematopoiesis Via Gender-Specific Differential Expression Of Microrna 98-3p And Thrombospondin 1,
2023
University of Kentucky
Latexin Regulates Sex Dimorphism In Hematopoiesis Via Gender-Specific Differential Expression Of Microrna 98-3p And Thrombospondin 1, Xiaojing Cui, Cuiping Zhang, Fang Wang, Xinghui Zhao, Shuxia Wang, Jinpeng Liu, Daheng He, Chi Wang, Feng-Chun Yang, Sheng Tong, Ying Liang
Markey Cancer Center Faculty Publications
Hematopoietic stem cells (HSCs) have the ability to self-renew and differentiate to all blood cell types. HSCs and their differentiated progeny show sex/gender differences. The fundamental mechanisms remain largely unexplored. We previously reported that latexin (Lxn) deletion increased HSC survival and repopulation capacity in female mice. Here, we find no differences in HSC function and hematopoiesis in Lxn knockout (Lxn-/- male mice under physiologic and myelosuppressive conditions. We further find that Thbs1, a downstream target gene of Lxn in female HSCs, is repressed in male HSCs. Male-specific high expression of micro- RNA 98-3p (miR98-3p) contributes to Thbs1 suppression in male …
Ferric Chloride-Induced Arterial Thrombosis And Sample Collection For 3d Electron Microscopy Analysis,
2023
University of Kentucky
Ferric Chloride-Induced Arterial Thrombosis And Sample Collection For 3d Electron Microscopy Analysis, Smita Joshi, Alexis N. Smith, Kanakanagavalli Shravani Prakhya, Hammodah Rawhi Hammodah Alfar, Joshua Lykins, Ming Zhang, Irina D. Pokrovskaya, Maria A. Aronova, Richard D. Leapman, Brian Storrie, Sidney W. Whiteheart
Saha Cardiovascular Research Center Faculty Publications
Cardiovascular diseases are a leading cause of mortality and morbidity worldwide. Aberrant thrombosis is a common feature of systemic conditions like diabetes and obesity, and chronic inflammatory diseases like atherosclerosis, cancer, and autoimmune diseases. Upon vascular injury, usually the coagulation system, platelets, and endothelium act in an orchestrated manner to prevent bleeding by forming a clot at the site of the injury. Abnormalities in this process lead to either excessive bleeding or uncontrolled thrombosis/insufficient antithrombotic activity, which translates into vessel occlusion and its sequelae. The FeCl3-induced carotid injury model is a valuable tool in probing how thrombosis initiates and progresses …
An Improved Germline Genome Assembly For The Sea Lamprey Petromyzon Marinus Illuminates The Evolution Of Germline-Specific Chromosomes,
2023
University of Kentucky
An Improved Germline Genome Assembly For The Sea Lamprey Petromyzon Marinus Illuminates The Evolution Of Germline-Specific Chromosomes, Nataliya Timoshevskaya, Kaan İ. Eşkut, Vladimir A. Timoshevskiy, Sofia M.C. Robb, Carson Holt, Jon E. Hess, Hugo J. Parker, Cindy F. Baker, Allison K. Miller, Cody Saraceno, Mark Yandell, Robb Krumlauf, Shawn R. Narum, Ralph T. Lampman, Neil J. Gemmell, Jacquelyn Mountcastle, Bettina Haase, Jennifer R. Balacco, Giulio Formenti, Sarah Pelan, Ying Sims, Kerstin Howe, Olivier Fedrigo, Erich D. Jarvis, Jeramiah James Smith
Markey Cancer Center Faculty Publications
Programmed DNA loss is a gene silencing mechanism that is employed by several vertebrate and nonvertebrate lineages, including all living jawless vertebrates and songbirds. Reconstructing the evolution of somatically eliminated (germline-specific) sequences in these species has proven challenging due to a high content of repeats and gene duplications in eliminated sequences and a corresponding lack of highly accurate and contiguous assemblies for these regions. Here, we present an improved assembly of the sea lamprey (Petromyzon marinus) genome that was generated using recently standardized methods that increase the contiguity and accuracy of vertebrate genome assemblies. This assembly resolves highly contiguous, somatically …
Chalcone Derivative Cx258 Suppresses Colorectal Cancer Via Inhibiting The Top2a/Wnt/Β-Catenin Signaling,
2023
Hebei Normal University
Chalcone Derivative Cx258 Suppresses Colorectal Cancer Via Inhibiting The Top2a/Wnt/Β-Catenin Signaling, Xi Chen, Xiaocheng Lv, Lijie Gao, Jiawei Liu, Wei Wang, Lichao Guo, Mykhaylo S. Frasinyuk, Wen Zhang, David S. Watt, Chunming Liu, Xifu Liu
Markey Cancer Center Faculty Publications
The deregulation in the Wnt/β-catenin signaling pathway is associated with many human cancers, particularly colorectal cancer (CRC) and, therefore, represents a promising target for drug development. We have screened over 300 semisynthetic and natural compounds using a Wnt reporter assay and identified a family of novel chalcone derivatives (CXs) that inhibited Wnt signaling and CRC cell proliferation. Among them, we selected CX258 for further in vitro and in vivo study to investigate the molecular mechanisms. We found that CX258 significantly inhibited β-catenin expression and nuclear translocation, inducing cell cycle arrest at the G2/M phase in CRC cells. Additionally, CX258 reduced …
Endogenous Glycoprotein Gpm6a Is Involved In Neurite Outgrowth In Rat Dorsal Root Ganglion Neurons,
2023
University of Kentucky
Endogenous Glycoprotein Gpm6a Is Involved In Neurite Outgrowth In Rat Dorsal Root Ganglion Neurons, Gabriela I. Aparicio, Antonella León, Rocío Gutiérrez Fuster, Baylen Ravenscraft, Paula V. Monje, Camila Scorticati
Markey Cancer Center Faculty Publications
The peripheral nervous system (PNS) has a unique ability for self-repair. Dorsal root ganglion (DRG) neurons regulate the expression of different molecules, such as neurotrophins and their receptors, to promote axon regeneration after injury. However, the molecular players driving axonal regrowth need to be better defined. The membrane glycoprotein GPM6a has been described to contribute to neuronal development and structural plasticity in central-nervous-system neurons. Recent evidence indicates that GPM6a interacts with molecules from the PNS, although its role in DRG neurons remains unknown. Here, we characterized the expression of GPM6a in embryonic and adult DRGs by combining analysis of public …
Kegg_Pull: A Software Package For The Restful Access And Pulling From The Kyoto Encyclopedia Of Gene And Genomes,
2023
University of Kentucky
Kegg_Pull: A Software Package For The Restful Access And Pulling From The Kyoto Encyclopedia Of Gene And Genomes, Erik D. Huckvale, Hunter N. B. Moseley
Markey Cancer Center Faculty Publications
Background: The Kyoto Encyclopedia of Genes and Genomes (KEGG) provides organized genomic, biomolecular, and metabolic information and knowledge that is reasonably current and highly useful for a wide range of analyses and modeling. KEGG follows the principles of data stewardship to be findable, accessible, interoperable, and reusable (FAIR) by providing RESTful access to their database entries via their web-accessible KEGG API. However, the overall FAIRness of KEGG is often limited by the library and software package support available in a given programming language. While R library support for KEGG is fairly strong, Python library support has been lacking. Moreover, there …
