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The Worlds Of Splicing And Chromatin Collide, J. Adam Hall, Philippe T. Georgel 2019 Marshall University

The Worlds Of Splicing And Chromatin Collide, J. Adam Hall, Philippe T. Georgel

Philippe T. Georgel

Both transcription and splicing take place in a nuclear environment which, at face value, may seem refractory to the efficiency afforded by the coupling of both processes. This environment, chromatin, was once viewed as only a passive packaging system for genetic material, with very little contribution to the variety of nuclear activities occurring within and around it. However, overwhelming evidence now points to the chromatin environment as being highly dynamic, and an active player in nuclear activities.


Spatial Reorganization Of Histone-Like Nucleoid Structuring Proteins Caused By Silver Nanoparticles, Meaad Alqahtany 2019 University of Arkansas, Fayetteville

Spatial Reorganization Of Histone-Like Nucleoid Structuring Proteins Caused By Silver Nanoparticles, Meaad Alqahtany

Theses and Dissertations

Silver nanoparticles (AgNPs) and ions (Ag+) can be the new generation of antibiotics due to their antimicrobial effects against bacteria and other microbes. Many studies have shown that AgNPs and suppress the growth of bacteria and damage the cell walls of the microbes; therefore, treating bacterial cells with AgNPs may be a promising method to terminate multi-resistant bacteria. In this work, the effect of AgNPs with two different surface coatings on the spatial reorganization of histone-like nucleoid structuring (H-NS) proteins in Escherichia coli bacteria was investigated using quantitative super-resolution fluorescence microscopy to understand the toxicity and antimicrobial mechanism of AgNPs ...


Biotransformation Of Natural Antioxidants Osajin And Pomiferin By Cunninghamella Elegans (Atcc® 9245tm), Stephen Luis 2019 University of the Incarnate Word

Biotransformation Of Natural Antioxidants Osajin And Pomiferin By Cunninghamella Elegans (Atcc® 9245tm), Stephen Luis

Theses & Dissertations

Osajin and pomiferin, prenylated isoflavones extracted from the fruit of the osage orange tree (Maclura pomifera) have been reported as antioxidant compounds. The purpose of this study is to analyze the metabolization of osajin and pomiferin by the fungi Cunninghamella elegans (ATCC 9245) and supporting strains Umbelopsis ramanniana and Aspergillus fumigatus fresnius.

HPLC analysis of the extracts showed new, more polar compounds were formed, evidenced by peaks at lower retention times for each strain of fungi. To further investigate the metabolites produced, HPLC-guided chromatographic purification will be performed, and the pure metabolites will be analyzed through nuclear magnetic resonance and ...


Pre-Administration Of Medium Chain Triglycerides In Vivo Can Attenuate Or Block The Effects Of Recurrent Hypoglycemia, Dhanisha Nandigama 2019 University at Albany, State University of New York

Pre-Administration Of Medium Chain Triglycerides In Vivo Can Attenuate Or Block The Effects Of Recurrent Hypoglycemia, Dhanisha Nandigama

Biological Sciences

Hypoglycemia is a state of abnormally low blood glucose. Many patients who use insulin, primarily for the treatment of diabetes, experience multiple bouts of hypoglycemia, termed recurrent hypoglycemia (RH). Because RH impairs cognitive function and ability to appropriately respond to a subsequent episode of hypoglycemia, it is critical to develop treatments. One approach, which we have taken here, is to attempt to preserve neuronal fuel supply during a hypoglycemic episode. Medium-chain triglycerides are medium-chain fatty acid (MCT) esters of glycerol that can provide an alternative fuel source to the brain via ketones; the hippocampus is known to express transporters for ...


The Effect Of Cysteine-Reactive Catechol Antioxidants On Alcohol Dehydrogenase As A Model For Oxidative Stress In Neurodegenerative Disease, Rachel Smith 2019 William & Mary

The Effect Of Cysteine-Reactive Catechol Antioxidants On Alcohol Dehydrogenase As A Model For Oxidative Stress In Neurodegenerative Disease, Rachel Smith

Undergraduate Honors Theses

The cellular mechanisms underlying age-related neurodegeneration, especially in disease states, are poorly understood. Oxidative stress has been heavily implicated as one factor both produced by and contributing to the progression of neurodegenerative diseases such as Alzheimer’s disease. In particular, it can destroy a cell’s ability to produce energy through aerobic and anaerobic respiration, thus leading to the death of individual cells and brain tissues as a whole. This study focuses on the relationship between oxidative stress and energy production in disease states. In particular, we examine the ability of catechol molecules to take on pro-oxidative properties and modify ...


Targeting Sec61Α By Ipomoeassin F Leads To Highly Cytotoxic Effect, Zhijian Hu 2019 University of Arkansas, Fayetteville

Targeting Sec61Α By Ipomoeassin F Leads To Highly Cytotoxic Effect, Zhijian Hu

Theses and Dissertations

Ipomoeassin F is a flagship congener of a resin glycoside family that inhibits growth of many tumor cell lines with only single-digital nanomolar IC50 values. However, biological and pharmacological mechanisms of ipomoeassin F have been undefined. To facilitate exploration of the biological and pharmacological properties, we performed sophisticate SAR (Structure–activity relationship) studies of ipomoeassin F to understand its pharmacophore and structure properties so that we can design favorable probes for further biological investigation. By applying appropriate deviates that possess fluorescent groups and similar bio-activity, the target protein was found to be localized in endoplasmic reticulum (ER). Through biotin affinity ...


Glycine Receptor Expression Across Identified Retinal Ganglion Cell Types., Ian Scot Pyle 2019 University of Louisville

Glycine Receptor Expression Across Identified Retinal Ganglion Cell Types., Ian Scot Pyle

Electronic Theses and Dissertations

Retinal ganglion cells (RGCs) represent the culmination of all retinal signaling and their output forms the substrate for vision throughout the rest of the brain. About 40 different RGC types have been defined by differences in their visually evoked responses, morphology, and genetic makeup. These responses arise from interactions between inhibition and excitation throughout the retinal circuit (Franke et al., 2017; Masland, 2012; Sanes & Masland, 2015; Werblin, 2011). Unlike most other areas of the central nervous system (CNS), the retina utilizes both GABA and glycine inhibitory neurotransmitters to refine glutamatergic excitatory signals (Franke & Baden, 2017; Werblin, 2011; C. Zhang, Nobles, & McCall, 2015). Glycine receptors (GlyRs) are heteromers composed of a single β subunit and one of four α subunits, with a stoichiometry of 3β:2α (Grudzinska et al., 2005; Heinze, Harvey, Haverkamp, & Wassle, 2007; Lynch ...


Paraoxonase 2 Is Critical For Non-Small Cell Lung Carcinoma Proliferation., Aaron Whitt 2019 University of Louisville

Paraoxonase 2 Is Critical For Non-Small Cell Lung Carcinoma Proliferation., Aaron Whitt

Electronic Theses and Dissertations

Non-small cell lung carcinoma (NSCLC) comprises 85% of lung cancer diagnoses and is plagued by drug resistance. Thus, elucidating the underlying mechanisms of NSCLC is paramount to expand future treatment options. Paraoxonase 2 (PON2), an intracellular enzyme with arylesterase and lactonase functions, has well-established anti-atherosclerotic activity. Recent studies show PON2 is overexpressed in a variety of tumors and confers drug resistance, although these interactions have not been thoroughly examined in NSCLC. Thus, we sought to investigate the role of PON2 in cellular proliferation using PON2-knockout mice, primary mouse cells, and NSCLC cell lines. Using these approaches, we demonstrate that PON2 ...


Development Of A Lectin-Fc Fusion Protein With Antiviral And Anti-Cancer Activity., Matthew William Dent 2019 University of Louisville

Development Of A Lectin-Fc Fusion Protein With Antiviral And Anti-Cancer Activity., Matthew William Dent

Electronic Theses and Dissertations

This thesis describes the development of a novel lectin-Fc fusion protein and its antiviral and anti-cancer activity. The molecule, Avaren-Fc (AvFc), is a fusion of a variant of the actinomycete lectin actinohivin (Avaren) and the Fc region of human IgG1, and is selective for the terminal α1,2-mannose residues found at the ends of high-mannose-type glycans that can be found on the surface of certain heavily glycosylated viruses and cancer cells. Here, AvFc was found to be able to neutralize simian immunodeficiency virus as well as Hepatitis C virus with nanomolar IC50 values. Furthermore, AvFc recognizes a number of ...


Relationships Of Protein Biomarkers Of The Urokinase Plasminogen Activator System With Expression Of Their Cognate Genes In Primary Breast Carcinomas., Seth B. Sereff 2019 University of Louisville

Relationships Of Protein Biomarkers Of The Urokinase Plasminogen Activator System With Expression Of Their Cognate Genes In Primary Breast Carcinomas., Seth B. Sereff

College of Arts & Sciences Senior Honors Theses

Background: Urokinase plasminogen activator (uPA), its receptor uPAR and serine protease inhibitors PAI-1 or PAI-2 play key roles in tissue membrane remodeling and invasion of basement membranes by induction of a fibrinolytic pathway. Earlier studies reported that uPA and PAI-1 protein levels in breast carcinomas assist in prediction of response to chemotherapy. Our goal is to develop molecular signatures of candidate genes and identify novel relationships with these four protein biomarkers that demonstrate clinical utility for assessment of breast carcinoma outcomes.

Methods: This retrospective study used de-identified biomarker results and clinical outcomes from primary breast cancers that were stored in ...


The Effects Of Eicosapentaenoic Acid (Epa) And Docosahexaenoic Acid (Dha) On Brown Adipogenesis In Stem Cell Culture, Darynne Dahlem 2019 University of Arkansas, Fayetteville

The Effects Of Eicosapentaenoic Acid (Epa) And Docosahexaenoic Acid (Dha) On Brown Adipogenesis In Stem Cell Culture, Darynne Dahlem

Animal Science Undergraduate Honors Theses

Polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are major maternal dietary supplements due to their positive benefits on neurological tissue growth during the first 12 weeks of gestation. Previous studies show that EPA and DHA inhibit muscle formation but promote adipogenesis. However, no research has addressed the question whether high intake of EPA and DHA affects brown fat development during gestation. The objective of this study was to measure the effect of EPA and DHA supplement on brown adipogenesis and potential pathways related to mitochondrial biosynthesis using fibroblasts as in vitro model. Using Oil-Red-O staining ...


The Q Rule In Bacteriodetes And The Identification And Characterization Of Porphyromonas Gingivalis Glutaminyl Cyclase., John Andrew Houston 2019 University of Louisville

The Q Rule In Bacteriodetes And The Identification And Characterization Of Porphyromonas Gingivalis Glutaminyl Cyclase., John Andrew Houston

Electronic Theses and Dissertations

Background: Porphyromonas gingivalis, a major pathogen associated with chronic periodontitis, secretes variety of proteins, majority of which begins with glutamine. Several of these proteins were found with pyroglutamate (pGlu) at N-terminus suggesting the presence of this posttranslational modification pathway in P.gingivalis. The observation that N-terminal glutamine is over-represented as the first amino acid after signal peptide cleavage, and subsequent confirmation of pGlu formation on the nascent protein via mass spectrometry, led us to conclude that an enzyme must be present as the executor of this reaction. Hypothesis: PG2157 is a glutaminyl cyclase and is responsible for the cyclization of ...


Effect Of Turmeric On The Promoter Activity Of The Cyp6a8 Gene Of Drosophila Melanogaster, Alexa Stroh 2019 University of Tennessee, Knoxville

Effect Of Turmeric On The Promoter Activity Of The Cyp6a8 Gene Of Drosophila Melanogaster, Alexa Stroh

Chancellor’s Honors Program Projects

No abstract provided.


Thiol-Based Misfolding: Linking Redox Balance To Cytosolic Proteostasis, Ford Amy 2019 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Thiol-Based Misfolding: Linking Redox Balance To Cytosolic Proteostasis, Ford Amy

UT GSBS Dissertations and Theses (Open Access)

The eukaryotic cytosolic proteome is vulnerable to changes in proteostatic and redox balance caused by temperature, pH, oxidants and xenobiotics. Cysteine-containing proteins are especially at risk as the thiol side chain is subject to oxidation, adduction and chelation by thiol-reactive compounds. All of these thiol-modifiers have been demonstrated to induce the heat shock response and recruit protein chaperones to sites of presumed protein aggregation in the budding yeast Saccharomyces cerevisiae. However, endogenous targets of thiol stress toxicity responsible for these outcomes are largely unknown. Furthermore, I hypothesize proteins identified as redox-active are prone to misfolding and aggregation by thiol-specific stress ...


Transformation Of Model Organisms With Munc13-1 For Subcloning And Protein Harvesting, Grace Dittmar 2019 The University of Southern Mississippi

Transformation Of Model Organisms With Munc13-1 For Subcloning And Protein Harvesting, Grace Dittmar

Honors Theses

Exocytosis is the process by which cells release various molecules into the extracellular space. This mechanism is accomplished by membrane fusion, in which the membrane of the transport vesicle and that of the cell itself fuse to create one continuous membrane, allowing the release of the molecules inside the vesicle. A family of proteins, known as SNARE proteins, is responsible for facilitating membrane fusion. SNARE proteins form a complex between the vesicle membrane and the plasma membrane. For various cells, such as mast cells and neurons, exocytosis is essential to carry out their vital functions. Various accessory proteins are known ...


Regulation Of The Drosophila Imd Pathway By Signaling Amyloids, Anni Kleino, Neal S. Silverman 2019 Aarhus University

Regulation Of The Drosophila Imd Pathway By Signaling Amyloids, Anni Kleino, Neal S. Silverman

Open Access Articles

Fruit flies elicit effective defense responses against numerous microbes. The responses against Gram-negative bacteria are mediated by the Imd pathway, an evolutionarily conserved NF-kappaB pathway recognizing meso-diaminopimelic acid (DAP)-type peptidoglycan from bacterial cell walls. Several reviews already provide a detailed view of ligand recognition and signal transduction during Imd signaling, but the formation and regulation of the signaling complex immediately downstream of the peptidoglycan-sensing receptors is still elusive. In this review, we focus on the formation of the Imd amyloidal signaling center and post-translational modifications in the assembly and disassembly of the Imd signaling complex.


Brown Fat Organogenesis And Maintenance Requires Akt1 And Akt2, Joan Sanchez-Gurmaches, Camila Martinez Calejman, Su Myung Jung, Huawei Li, David A. Guertin 2019 University of Massachusetts Medical School

Brown Fat Organogenesis And Maintenance Requires Akt1 And Akt2, Joan Sanchez-Gurmaches, Camila Martinez Calejman, Su Myung Jung, Huawei Li, David A. Guertin

Open Access Articles

OBJECTIVE: Understanding the signaling mechanisms that control brown adipose tissue (BAT) development is relevant to understanding energy homeostasis and obesity. The AKT kinases are insulin effectors with critical in vivo functions in adipocytes; however, their role in adipocyte development remains poorly understood. The goal of this study was to investigate AKT function in BAT development.

METHODS: We conditionally deleted Akt1 and Akt2 either individually or together with Myf5-Cre, which targets early mesenchymal precursors that give rise to brown adipocytes. Because Myf5-Cre also targets skeletal muscle and some white adipocyte lineages, comparisons were made between AKT function in BAT versus white ...


Hormone Signaling, Gene Expression, And Mitochondrial Hormone Receptor Expression In Avian Muscle (Cells), Kentu Rushadd Lassiter 2019 University of Arkansas, Fayetteville

Hormone Signaling, Gene Expression, And Mitochondrial Hormone Receptor Expression In Avian Muscle (Cells), Kentu Rushadd Lassiter

Theses and Dissertations

Mitochondria are vital to the proper growth and function of muscle cells since they’re responsible for the majority of ATP production used for cellular energy. Previous studies have investigated how differences in mitochondrial function affects feed efficiency (FE) in broilers phenotyped for High and Low FE. Low FE broilers have been shown to have increased levels of reactive oxygen species (ROS), thus contributing to higher levels of oxidative stress and damage seen in these birds. Global gene and protein expression studies conducted on breast muscle of the High FE and Low FE phenotypes have suggested that differences in mitochondrial ...


Paper Spray High-Resolution Accurate Mass Spectrometry For Quantitation Of Voriconazole In Equine Tears, Jonathan P. Mochel 2019 Iowa State University

Paper Spray High-Resolution Accurate Mass Spectrometry For Quantitation Of Voriconazole In Equine Tears, Jonathan P. Mochel

Jonathan Mochel

Paper spray high-resolution accurate mass spectrometry is a fast and versatile analysis method. This ambient ionization technique enables the quantitation of xenobiotics in complex biological matrices without chromatography or conventional sample extraction. The simplicity, rapidity, and affordability of the paper spray mass spectrometry (PS-MS) method make the technique especially attractive for clinical investigations where fast and affordable sample analysis is crucial. A new PS-MS method for the quantitation of voriconazole in equine tears was developed and validated. For a concentration range of 10 to 1000 ng/mL, good linearity (R2 > 0.99), inter- and intra-run precision (coefficient of variation ...


Ouabain Enhances Cell-Cell Adhesion Mediated By Beta1 Subunits Of The Na(+),K(+)-Atpase In Cho Fibroblasts, Claudia Andrea Vilchis-Nestor, Maria Luisa Roldan, Angelina Leonardi, Juan G. Navea, Teresita Padilla-Benavides, Liora Shoshani 2019 University of Massachusetts Medical School

Ouabain Enhances Cell-Cell Adhesion Mediated By Beta1 Subunits Of The Na(+),K(+)-Atpase In Cho Fibroblasts, Claudia Andrea Vilchis-Nestor, Maria Luisa Roldan, Angelina Leonardi, Juan G. Navea, Teresita Padilla-Benavides, Liora Shoshani

Open Access Articles

Adhesion is a crucial characteristic of epithelial cells to form barriers to pathogens and toxic substances from the environment. Epithelial cells attach to each other using intercellular junctions on the lateral membrane, including tight and adherent junctions, as well as the Na(+),K(+)-ATPase. Our group has shown that non-adherent chinese hamster ovary (CHO) cells transfected with the canine beta1 subunit become adhesive, and those homotypic interactions amongst beta1 subunits of the Na(+),K(+)-ATPase occur between neighboring epithelial cells. Ouabain, a cardiotonic steroid, binds to the alpha subunit of the Na(+),K(+)-ATPase, inhibits the pump activity and induces ...


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