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Articles 1 - 18 of 18
Full-Text Articles in Life Sciences
Breaking Virulent: The Coincidental Evolution Of Virulence Factors In Bacteria., Rhiannon Emmanuelle Cecil
Breaking Virulent: The Coincidental Evolution Of Virulence Factors In Bacteria., Rhiannon Emmanuelle Cecil
Electronic Theses and Dissertations
Understanding how innocuous organisms can evolve to be pathogenic to humans is of increasing global concern. Further, understanding how existing pathogens may evolved to be more virulent is also vital to our ability to provide healthcare to people afflicted with diseases that promote chronic bacterial infections, such as cystic fibrosis. With the rise of antibiotic resistance in both bacteria and fungi it is paramount that new therapeutics are identified. Understanding what mutations occur that result in increased virulence in microbes can potentially provide new targets for antimicrobial drugs to combat antibiotic resistance. The Coincidental Evolution Hypothesis is a fundamental hypothesis …
Determination Of The Functional Role Of Rab-Ggt In Physcomitrium Patens., Hyun Jin Jung
Determination Of The Functional Role Of Rab-Ggt In Physcomitrium Patens., Hyun Jin Jung
Electronic Theses and Dissertations
Protein prenylation, a common lipid post-translational modification, is required for growth and development in eukaryotes. Rab geranylgeranylation involves the addition of one or two 20-carbon geranylgeranyl moieties to Rab-GTPase target proteins, which regulate intracellular vesicle trafficking. The reaction is carried out by heterodimeric Rab geranylgeranyltransferase (Rab-GGT), which is composed of two associated α- and β-subunits, with the assistance of an additional protein called Rab escort protein (REP). Loss of function of the Rab-GGT α subunit RGTA1 has not been reported in any plant. While knockout of either of the two β subunits RGTB1 or RGTB2 results in …
A Computational Model Of The Line-1 Retrotransposon Life Cycle And Visualization Of Metabolic Networks In 3-Dimensions., Michael D. Martin
A Computational Model Of The Line-1 Retrotransposon Life Cycle And Visualization Of Metabolic Networks In 3-Dimensions., Michael D. Martin
Electronic Theses and Dissertations
Computational modeling of metabolic reactions and cellular systems is evolving as a tool for quantitative prediction of metabolic parameters and reaction pathway analysis. In this work, the basics of computational cell biology are presented as well as a summary of physical processes within the cell, and the algorithmic methods used to find time dependent solutions. Protein-protein and enzyme-substrate interactions are mathematically represented via mass action kinetics to construct sets of linear differential equations that describe reaction rates and formation of protein complexes. Using mass action methods, examples of reaction networks and their solutions are presented within the Virtual Cell simulation …
Role Of Galactose, Thiazolidinediones, And Neet Proteins In Mitochondrial Physiology And Therapeutic Development., Robert Anthony Skolik
Role Of Galactose, Thiazolidinediones, And Neet Proteins In Mitochondrial Physiology And Therapeutic Development., Robert Anthony Skolik
Electronic Theses and Dissertations
This dissertation explores the relationship between mitochondrial physiology and development of therapeutics. Mitochondrial dysfunction is associated with both acute and chronic forms of pathophysiology. This work aims to address development efforts at the cell culture and drug-target levels with respect to mitochondria. At the cell culture level, I characterize an approach that has been shown to improve the physiological dependency on mitochondria in tumor-derived cells. I demonstrate that prolonged replacement of glucose with galactose in culture medium induces a global metabolic shift in hepatocellular carcinoma (HepG2) cells to closer reflect a primary hepatocyte phenotype (Chapter 2). I characterize this shift …
Cannabinoids And Retinal Fibrotic Disorders., Lucy June Sloan
Cannabinoids And Retinal Fibrotic Disorders., Lucy June Sloan
Electronic Theses and Dissertations
Retinal fibrosis is detrimental to vision. Retinal pigment epithelial (RPE) cells contribute to several retinal fibrotic diseases. Upon exposure to TGF-β, a key fibrotic cytokine, RPE cells trans-differentiate to myofibroblasts marked by the integration of α-SMA fibers into F-actin stress fibers, which confer strong contractility. Myofibroblasts produce and contract the collagen-rich fibrotic scar and disrupt retinal architecture. In this study, we investigated the in vitro effects of the putative endocannabinoid compound N-oleoyl dopamine (OLDA) on TGF-β2 induced porcine RPE cell contraction and α-SMA expression. Using an in vitro collagen matrix contraction assay, we found that OLDA inhibited TGF-β2 induced contraction …
Visualizing Anhydrobiosis: Liquid-Liquid Phase Separation, Membraneless Organelles, And Cellular Reorganization., Clinton J. Belott
Visualizing Anhydrobiosis: Liquid-Liquid Phase Separation, Membraneless Organelles, And Cellular Reorganization., Clinton J. Belott
Electronic Theses and Dissertations
Water is an integral and necessary component of life. It is then, exceedingly remarkable that some species are capable of surviving virtually complete water loss for extended periods of time. Several decades of intense research into anhydrobiosis, or life without water, have given significant insights into the molecular mechanisms governing this phenomenon. Anhydrobiosis-related intrinsically disordered (ARID) proteins have been demonstrated to be critically important for desiccation tolerance in many anhydrobiotic species and exhibit a considerably wide range of protective properties that include membrane stabilization, reinforcing bioglass formation, and protein stabilization. This dissertation begins with cellular dielectrophoresis suggesting that two ARID …
Tissue-Resident Myeloid-Derived Suppressor Cells Modulate Immune Homeostasis In Healthy Adipose., Katlin Brooke Stivers
Tissue-Resident Myeloid-Derived Suppressor Cells Modulate Immune Homeostasis In Healthy Adipose., Katlin Brooke Stivers
Electronic Theses and Dissertations
Our goal with this study was to gain insight into the homeostatic immune cell network in healthy adipose tissue. Specifically, we sought to determine if the immature myeloid cells found in healthy and inflamed adipose were, in fact, tissue-resident myeloid-derived suppressor cells (MDSCs). Using various in vitro and in vivo methods, we have uncovered a population of CD11bHi Ly6CHi Ly6G- MDSCs resident in healthy adipose tissue. To the best of our knowledge this is the first time that these cells have been investigated and described in healthy adipose tissue. Systemic MDSC depletion lead to the accumulation of …
Development Of In Vitro Models To Study The Rapid Extraintestinal Dissemination Of Salmonella., Adarsh Gopinath
Development Of In Vitro Models To Study The Rapid Extraintestinal Dissemination Of Salmonella., Adarsh Gopinath
Electronic Theses and Dissertations
Salmonella appears in the bloodstream of mice in as little as 15 minutes after oral inoculation and establishes persistent colonies in the spleen and liver. While its pathway to blood is undetermined, this phenomenon is dependent on the activity of Salmonella pathogenicity island 2 (SPI-2) coded type III secretion system (T3SS) and CD18+ phagocytes. We hypothesize that dendritic cells associated with the basal face of the gut epithelium, that are naturally migratory and known to sample for luminal antigens directly transport Salmonella to the bloodstream. This process comprises of at least two phases, dissociation and reverse transmigration. We define dissociation …
Epidermal Growth Factor-Like Ligands Regulate Dimer Selection., Jamie S. Rush
Epidermal Growth Factor-Like Ligands Regulate Dimer Selection., Jamie S. Rush
Electronic Theses and Dissertations
There are thirteen known endogenous EGF-like ligands. We previously reported that Betacellulin (BTC) increases ligand-mediated corneal wound healing more than Epidermal Growth Factor (EGF) [Peterson et al. (2014) IOVS 55(5):2870-80], although the molecular reason for this is unknown. Despite being better at promoting wound healing via enhanced cell migration, BTC has reduced receptor affinity and weaker induction of EGFR phosphorylation. These data indicate that BTC’s response is not due to enhanced affinity or EGFR-kinase activity. Receptor phosphorylation and proximity ligation assays indicate that BTC treatment significantly increases ErbB3 phosphorylation and EGFR:ErbB3 heterodimers. BTC traffics EGFR at a faster rate than …
Egfr Signaling From The Early Endosome., Julie A. Gosney
Egfr Signaling From The Early Endosome., Julie A. Gosney
Electronic Theses and Dissertations
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is an integral component of proliferative signaling. When activated by a ligand at the plasma membrane, EGFR dimerizes with another ErbB family receptor, leading to kinase domain activation and transphosphorylation of C-terminus tyrosine residues. These phosphotyrosines act as crucial regulators of EGFR signaling as effector proteins dock to the receptor at these sites. The receptor undergoes clathrin-mediated endocytosis into early endosomes, where it can then be trafficked to a lysosome for degradation. However, the kinase domain of EGFR retains its activity during trafficking, suggesting that EGFR can continue …
Unfolded Protein Response Pathways In Skeletal Muscle Homeostasis., Kyle R. Bohnert
Unfolded Protein Response Pathways In Skeletal Muscle Homeostasis., Kyle R. Bohnert
Electronic Theses and Dissertations
Skeletal muscle mass, contractile properties, and metabolic function are regulated through the coordinated activation of multiple intracellular signaling pathways and genetic reprogramming. The endoplasmic reticulum (ER) plays a pivotal role in protein folding and calcium homeostasis in many cell types, including skeletal muscle. Disruption of calcium levels or accumulation of misfolded proteins in the ER lumen leads to stress, which results in the activation of a signaling network called the unfolded protein response (UPR). Further, recent studies have suggested that in certain conditions, UPR pathways can be activated independent of ER stress. However, the role of ER stress and the …
The Dlk1-Meg3 Locus In Malignant Cells Of Proposed Primordial Germ Cell Origins., Zachariah Payne Sellers
The Dlk1-Meg3 Locus In Malignant Cells Of Proposed Primordial Germ Cell Origins., Zachariah Payne Sellers
Electronic Theses and Dissertations
Primordial germ cells (PGCs) are hypothesized to deposit hematopoietic stem cells (HSCs) along their migration route through the embryo during the early stages of embryogenesis. PGCs also undergo global chromatin remodeling, including the erasure and reestablishment of genomic imprints, during this migration. While PGCs do not spontaneously form teratomas, their malignant development into germ cell tumors (GCTs) in vivo is often accompanied by the retention of hypomethylation at the IGF2-H19 imprinting control differentially methylated region (DMR). Previous studies in bimaternal embryos determined that proper genomic imprinting at two paternally imprinted loci was necessary for their growth and development: Igf2-H19 and …
Identifying The Signaling Mechanisms Of Egfr-Mediated Apoptosis., Nicole Marion Jackson
Identifying The Signaling Mechanisms Of Egfr-Mediated Apoptosis., Nicole Marion Jackson
Electronic Theses and Dissertations
The Epidermal Growth Factor Receptor (EGFR) is a 170-kilodalton transmembrane protein that belongs to the ErbB family of receptor tyrosine kinases. Upon ligand-mediated activation, the EGFR is responsible for cell growth, proliferation, and tissue homeostasis; however, the EGFR is overexpressed in many human malignancies, including MDA-MB-468 cells, a metastatic breast epithelial cell line. Studies within this cell line, and other cell lines characterized with high EGFR levels, have shown that EGF stimulation results in the induction of apoptosis. However, the mechanisms and signaling effectors implicated in this process have yet to be elucidated. The overarching research goal of this dissertation …
Isolation Of Egfr-Containing Early Endosomes., Julie A. Gosney
Isolation Of Egfr-Containing Early Endosomes., Julie A. Gosney
Electronic Theses and Dissertations
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) that is an integral component of proliferative signaling. When activated by a ligand at the plasma membrane, EGFR undergoes clathrin-mediated endocytosis. This spatial regulation of the receptor is an important regulator of receptor expression as it mediates its degradation. Endocytosis also has implications on EGFR downstream signaling, though the details are not fully understood. The goal of this thesis is to develop a method to isolate early endosomes in order to study downstream effectors associated with activated EGFR in this compartment. HeLa cells were used to test various …
Identification Of Host Factors Required For Yersinia Pestis Macrophage Intracellular Survival And Their Impact On Vacuole Maturation, Acidification And Trafficking., Michael Graylin Connor
Identification Of Host Factors Required For Yersinia Pestis Macrophage Intracellular Survival And Their Impact On Vacuole Maturation, Acidification And Trafficking., Michael Graylin Connor
Electronic Theses and Dissertations
Y. pestis is a facultative intracellular pathogen and the causative agent of plague. This bacterium, while most noted or the Black Death during the European 14th century, is not a historic pathogen but a re-emerging pandemic with both domestic and global impact. Y. pestis is capable of colonizing the macrophage, and actively subverts phagolysosome maturation to establish a replicative niche known as the Yersinia containing vacuole (YCV). The exploited host factors required to support the YCV are unknown. Here we identified a comprehensive list of host factors required for Y. pestis survival through a genome-wide RNAi high-throughput screen. We …
Modulation Of Cell Death Signaling And Cell Proliferation By The Interaction Of Homoserine Lactones And Paraoxonase 2., Aaron Mackallan Neely
Modulation Of Cell Death Signaling And Cell Proliferation By The Interaction Of Homoserine Lactones And Paraoxonase 2., Aaron Mackallan Neely
Electronic Theses and Dissertations
Pseudomonas aeruginosa produces N-(3-oxododecanoyl)-homoserine lactone (C12) as a quorum-sensing molecule that functions to facilitate bacteria-bacteria communication. C12 has also been reported to affect many aspects of human host cell physiology, including evoking cell death in various types of cells. However, the signaling pathway(s) leading to C12-triggerred cell death remains unclear. To clarify cell death signaling induced by C12, we examined mouse embryonic fibroblasts (MEFs) deficient in one or more caspases. Our data indicate that, unlike most apoptotic inducers, C12 evokes a novel form of apoptosis in cells, probably through the direct induction of mitochondrial membrane permeabilization. Previous studies indicate that …
The Role Of Stem Cells In Adipose Tissue Remodeling., Candice Reshay Holden 1988-
The Role Of Stem Cells In Adipose Tissue Remodeling., Candice Reshay Holden 1988-
Electronic Theses and Dissertations
The work presented in this dissertation outlines the role of stem cells in the remodeling of adipose tissue under conditions of nutrient excess. Obesity-induced variations in adipose tissue stem cell distribution were uncovered by analysis of the stromal vascular fraction isolated from mice fed a high fat diet for several weeks. Bone marrow cell transplantation was used to determine the derivation of progenitor cells found in adipose tissue; and supplementation of depleted progenitor cell populations achieved via direct cell transplantation, helped to determine the contribution of these progenitor cells to the remodeling process. The dissertation is presented in five chapters …
The Effect Of Sodium Chloride Upon The Fission Rate Within A Single Clone Of Paramecium Caudatum And The Heritability Of That Effect., Mary C. Adolph
The Effect Of Sodium Chloride Upon The Fission Rate Within A Single Clone Of Paramecium Caudatum And The Heritability Of That Effect., Mary C. Adolph
Electronic Theses and Dissertations
No abstract provided.