Avicin Is A Potent Sphingomyelinase Inhibitor That Blocks K-Ras Plasma Membrane Interaction And Its Oncogenic Activity,
2018
Wright State University
Avicin Is A Potent Sphingomyelinase Inhibitor That Blocks K-Ras Plasma Membrane Interaction And Its Oncogenic Activity, Christian M. Garrido
Browse all Theses and Dissertations
Ras proteins are small GTPases that regulate cell growth, differentiation and apoptosis. There are three main isoforms: H-, N-, and K-Ras in mammalian cells, and they cycle between an active GTP- and inactive GDP-bound states. Constitutively active Ras mutations are found in ~15% of all human cancers. Of those, oncogenic K-Ras is found in ~98% of pancreatic, ~52% colorectal, and ~32% of lung cancers. In nearly 30 years since its discovery, there are no anti-K-Ras drugs currently available for clinical use. Since K-Ras must be localized to the plasma membrane (PM) for its full biological activity, targeting K-Ras PM interaction …
A Novel Method To Analyze Dna Breaks And Repair In Human Cells,
2018
Wright State University
A Novel Method To Analyze Dna Breaks And Repair In Human Cells, Caitlin Elizabeth Goodman
Browse all Theses and Dissertations
Microsatellites repeat sequences are prone to forming non-canonical DNA structures and mutations. These areas of the genome can undergo expansions and contractions and are responsible for a variety of inherited neurological and neuromuscular disorders. Hairpin structures formed by trinucleotide repeats can lead to replication fork stalling, and fork collapse causing DNA double strand breaks. Various mechanisms are involved in processing microsatellites including mismatch repair, base excision repair, and crossover junction endonuclease cleavage. These processes, which are supposed to protect the genome, could also be the culprits which are causing mutations. In order to test and study this hypothesis, the use …
Influence Of Dietary Ractopamine And Supranutritional Supplementation Of Vitamin E On Proteome Profile Of Postmortem Beef Longissimus Lumborum Muscle,
2018
University of Kentucky
Influence Of Dietary Ractopamine And Supranutritional Supplementation Of Vitamin E On Proteome Profile Of Postmortem Beef Longissimus Lumborum Muscle, Hyun Mok Kim
Theses and Dissertations--Animal and Food Sciences
The effects of dietary ingredients on the proteome profile of postmortem beef longissimus lumborum (LL) muscle were evaluated. In the first experiment, the influence of dietary ractopamine on the whole-muscle proteome of beef LL was examined. Five proteins were differentially abundant between ractopamine-fed (RAC) and non-ractopamine fed (CON) groups. The differentially abundant proteins were over-abundant in RAC and were related to muscle structure development (F-actin-capping protein subunit beta-2 and PDZ and LIM domain protein-3), chaperone (heat shock protein beta-1), oxygen transportation (myoglobin), and glycolysis (L-lactate dehydrogenase A chain). These findings indicated that ractopamine influences the abundance of proteins associated with …
Studies On E2 Conjugation Enzyme Partners Of Mulan E3 Ubiquitin Ligase,
2018
University of Central Florida
Studies On E2 Conjugation Enzyme Partners Of Mulan E3 Ubiquitin Ligase, Rebekah J. Fitzpatrick
Honors Undergraduate Theses
Mulan is an E3 ubiquitin ligase embedded in the outer mitochondria membrane. Mulan’s participation in the ubiquitination process is conducted through its cytosol exposed RING finger domain, and its ability to modulate protein ubiquitination makes it a key player in mitochondrial and cellular homeostasis. Mulan is known to be involved in mitochondrial fission, fusion, mitochondrial stress, apoptosis, and Parkin-independent mitophagy. Dysregulation of Mulan in mice has been shown to correlate with human neurodegenerative disorders and heart disease. Accumulation of Mulan is predicted to be responsible for the motor neuron degeneration 2 (mnd2) phenotype in mutant mice through the deregulation of …
Determination Of The Sivmac Vif-Human Apobec3b Interaction,
2018
Minnesota State University, Mankato
Determination Of The Sivmac Vif-Human Apobec3b Interaction, Oumar Sanogo
All Graduate Theses, Dissertations, and Other Capstone Projects
The APOBEC3 family of enzymes are DNA cytosine deaminases, some of which restrict replication of HIV-‐1. This viral restriction is caused by deamination of cytosines to uracils in the viral cDNA, resulting in lethal mutation. HIV-‐1 counteracts this deamination by producing the protein Vif, which targets the restricting APOBEC3 enzymes for proteosomal degradation. Previous studies have demonstrated that HIV-‐1 Vif mediates degradation of APOBEC3D (A3D), APOBEC3F (A3F), APOBEC3G (A3G), and APOBEC3H (A3H). Other lentiviruses may also encode a Vif protein, however not all Vif proteins can degrade the same APOBEC3 proteins. For example, SIVmac (simian immunodeficiency virus that infects rhesus …
Manipulation Of Genes Involved In Secondary Cell Wall Development During Wood Formation In Poplar,
2018
Michigan Technological University
Manipulation Of Genes Involved In Secondary Cell Wall Development During Wood Formation In Poplar, Kavitha Satish Kumar
Dissertations, Master's Theses and Master's Reports
Lignins are second most abundant components of vascular plant cell walls. They provide plants with structural rigidity and are polymers of monolignols. Lignin polymerization is catalyzed by peroxidases and/or laccases. These enzymes are suggested to share functional overlap and mechanism by which they coordinate this process is not clearly understood. There are about 100 peroxidases and 50 laccase genes known in poplar genome out of which some stem differentiating xylem-specific (SDX) enzymes were selected for our study. The main objective was to genetically manipulate genes expressed in the SDX region in the cell wall to see the effects on lignin …
Altering Oligomerization Of Epha2 Via Mutations In The Intracellular Domain,
2018
The University of Akron
Altering Oligomerization Of Epha2 Via Mutations In The Intracellular Domain, Ryan W. Lingerak
Williams Honors College, Honors Research Projects
Eph receptor tyrosine kinases (RTKs) are activated by membrane-bound ligands called ephrins. Eph RTKs are divided into two subclasses, each activated by a specific classes of the ligand ephrin. The overexpression of Eph receptors is correlated to cancer cell metastasis in several different types of cancers. Studies with the EphA2 extracellular domain (ECD) and ephrinA1 ligand have shown that upon binding of ephrin to the receptor, EphA2 undergoes increased oligomerization and activation. This indicates that oligomerization is intimately connected to kinase activity. High resolution crystal structures of the EphA2 ECD have revealed some details of these ligand bound oligomers, as …
Targeting Ovarian Cancer And Endothelium With An Allosteric Ptp4a3 Phosphatase Inhibitor,
2018
Old Dominion University
Targeting Ovarian Cancer And Endothelium With An Allosteric Ptp4a3 Phosphatase Inhibitor, Kelley E. Mcqueeney, Joseph M. Salamoun, James C. Burnett, Nektarios Barabutis, Paula Pekic, Sophie L. Lewandowski, Danielle C. Llaneza, Robert Cornelison, Yunpeng Bai, Zhong-Yin Zhang, John D. Catravas
Bioelectrics Publications
Overexpression of protein tyrosine phosphatase PTP4A oncoproteins is common in many human cancers and is associated with poor patient prognosis and survival. We observed elevated levels of PTP4A3 phosphatase in 79% of human ovarian tumor samples, with significant overexpression in tumor endothelium and pericytes. Furthermore, PTP4A phosphatases appear to regulate several key malignant processes, such as invasion, migration, and angiogenesis, suggesting a pivotal regulatory role in cancer and endothelial signaling pathways. While phosphatases are attractive therapeutic targets, they have been poorly investigated because of a lack of potent and selective chemical probes. In this study, we disclose that a potent, …
Esope-Equivalent Pulsing Protocols For Calcium Electroporation: An In Vitro Optimization Study On 2 Cancer Cell Models,
2018
Old Dominion University
Esope-Equivalent Pulsing Protocols For Calcium Electroporation: An In Vitro Optimization Study On 2 Cancer Cell Models, Stefania Romeo, Anna Sannino, Maria Rosaria Scarfi, P. Thomas Vernier, Ruggero Cadossi, Julie Gehl, Olga Zeni
Bioelectrics Publications
Reversible electroporation is used to increase the uptake of chemotherapeutic drugs in local tumor treatment (electrochemotherapy) by applying the pulsing protocol (8 rectangular pulses, 1000 V/cm, 100 µs) standardized in the framework of the European Standard Operating Procedure on Electrochemotherapy multicenter trial. Currently, new electrochemotherapy strategies are under development to extend its applicability to tumors with different histology. Electrical parameters and drug type are critical factors. A possible approach is to test pulse parameters different from European Standard Operating Procedure on Electrochemotherapy but with comparable electroporation yield (European Standard Operating Procedure on Electrochemotherapy-equivalent protocols). Moreover, the use of non-toxic drugs …
Availability Of Fermentable Nutrients Affect Gut Microbiota Composition,
2018
Wright State University
Availability Of Fermentable Nutrients Affect Gut Microbiota Composition, Trupthi Mehta
Browse all Theses and Dissertations
Recent studies have increasingly established the role of gut microbiota in human health and disease. Diseases such as inflammatory bowel disease, colon cancer, cardiovascular disease and many neurological disorders have been linked to specific gut microbiota composition and disturbances. There have also been attempts in recent years to modulate gut microbial composition with the use of prebiotics and probiotics to promote healthy gut and prevent diseases. This thesis investigates whether the availability of fermentable nutrients high in fiber and antioxidants such as found in green coffee, roasted coffee, and salami infused with various prebiotics altered the composition and abundance of …
Lipin1 Regulates Skeletal Muscle Differentiation Through The Pkc/Hdac5/Mef2c:Myod -Mediated Pathway,
2018
Wright State University
Lipin1 Regulates Skeletal Muscle Differentiation Through The Pkc/Hdac5/Mef2c:Myod -Mediated Pathway, Abdulrahman M. Jama
Browse all Theses and Dissertations
Our previous characterization of global lipin1-deficient (fld) mice demonstrated that lipin1 played a novel role in skeletal muscle (SM) regeneration. The clinical relevance of lipin1 has been observed in patients with lipin1 null mutations where they exhibited severe rhabdomyolysis with aggregated and dysfunctional mitochondria. Lipin1 is a key gene that plays an important role in lipid biosynthesis and metabolism. It has dual functions as it contains a phosphatase activity that converts phosphatidic acid (PA) to diacylglycerol (DAG), the penultimate step in triglycerides (TAG) biosynthesis as well as transcriptional co-activator function. In the cytosol and ER, lipin1 carries out its lipid …
Discovery Of Small Molecules Blocking Oncogenic K-Ras Activity,
2018
Wright State University
Discovery Of Small Molecules Blocking Oncogenic K-Ras Activity, Sarah E. Kovar
Browse all Theses and Dissertations
Ras proteins were the first human oncogenes discovered. Although Ras has been found to be the most frequently mutated oncogene, there are currently no anti-Ras-specific drugs available in the clinic. Ras is responsible for initiating cellular pathways that include proliferation, survival, and apoptosis. There are three ubiquitously expressed Ras isoforms in mammalian cells: H-, N-, and K-Ras. Interaction with the plasma membrane is required for Ras biological activity. When Ras interaction with the plasma membrane is blocked, Ras activity is inhibited. Two compounds (from Dr. Ketcha, WSU Chemistry Department) were tested and shown to dissociate K-Ras, but not H-Ras from …
Role Of Sirna Pathway In Epigenetic Modifications Of The Drosophila Melanogaster X Chromosome,
2018
Wayne State University
Role Of Sirna Pathway In Epigenetic Modifications Of The Drosophila Melanogaster X Chromosome, Nikita Deshpande
Wayne State University Dissertations
Eukaryotic genomes are organized into large domains of coordinated regulation. The role of small RNAs in formation of these domains is largely unexplored. An extraordinary example of domain-wide regulation is X chromosome compensation in Drosophila melanogaster males. This process occurs by hypertranscription of genes on the single male X chromosome. Extensive research in this field has shown that the Male Specific Lethal (MSL) complex binds X-linked genes and modifies chromatin to increase expression. The components of this complex, and their actions on chromatin, are well studied. In contrast, the mechanism that results in exclusive recruitment to the X chromosome is …
Optimisation Of Ion Exchange Chromatography Purification Protocols For A Staphylococcal Peptidoglycan Degrading Hydrolase Enzyme,
2018
Department of Biological Sciences, Cork Institute of Technology, Cork, Ireland
Optimisation Of Ion Exchange Chromatography Purification Protocols For A Staphylococcal Peptidoglycan Degrading Hydrolase Enzyme, Fiona Maher
Theses
Bacteriophage (phage) are the most abundant biological entities on earth and were first discovered by d’Herelle in 1917. They are found wherever their hosts live and, like all viruses they do not have the ability to make their own protein. Therefore, in order to reproduce, phage must invade and infect bacterial cells. This project focused on the optimisation of Ion Exchange Chromatography purification protocols for a staphylococcal peptidoglycan degrading hydrolase enzyme (CHAPk). The project objective was to obtain the greatest yield of enzyme from the growth of the E.coU XL 1-Blue expression system into which the vector pQE60 was previously …
The Effects Of Oxidative Stress On P75ntr Signaling In Dopaminergic Neurons,
2018
Eastern Kentucky University
The Effects Of Oxidative Stress On P75ntr Signaling In Dopaminergic Neurons, Cassandra Marie Escobedo
Online Theses and Dissertations
The p75 neurotrophin receptor (p75NTR) is responsible for implementing cellular death during embryonic development and in response to cellular injury. The receptor has been recognized as a contributor of neurodegeneration in numerous pathological conditions. Cleavage of p75NTR by Tumor Necrosis Factor converting enzyme (TACE) and γ-secretase has been observed to be associated with an increase in neurodegeneration. In a previous study, p75NTR was discovered to become activated in sympathetic neurons in response to oxidative stress induced by 4-hydroxynonenal (HNE) in a ligand-independent mechanism. Furthermore, cleavage of the receptor was demonstrated to contribute to the death of sympathetic neurons following oxidative …
Implementation And Performance Comparison Of Some Heuristic Algorithms For Block Sorting,
2018
University of North Florida
Implementation And Performance Comparison Of Some Heuristic Algorithms For Block Sorting, Sandhya Turlapaty
UNF Graduate Theses and Dissertations
An implementation framework has been developed in this thesis for a well-known APX-hard combinatorial optimization problem known as Block Sorting. The motivation for the study of this problem comes from applications such as computational biology and optical character recognition. While existing Block Sorting research has been theoretically focused on the development and analysis of several approximation algorithms for Block Sorting, little or no work has been carried out thus far on the implementation of the proposed approximation algorithms. The conceptualization of an implementation framework and illustrating its use by experimenting with the existing approximation algorithms will provide means for discovering …
Chronic Clozapine Treatment Impairs Functional Activation Of Metabotropic Glutamate Receptor 2 Via An Hdac2-Depedent Mechanism,
2018
Virginia Commonwealth University
Chronic Clozapine Treatment Impairs Functional Activation Of Metabotropic Glutamate Receptor 2 Via An Hdac2-Depedent Mechanism, Travis M. Cuddy
Theses and Dissertations
Schizophrenia is a chronic mental disorder affecting millions worldwide. It has no known cure. Current pharmaceutical treatments have shown efficacy in only one of the three symptom clusters of schizophrenia, providing little or no benefit in the other two. Furthermore, the current standard-of-care drugs, known as atypical antipsychotics, carry risks of severe side effects affecting multiple body systems. Most patients opt to discontinue drug therapy within two years of initiation due to lack of efficacy and/or preponderance of adverse effects. Previous findings have shown that chronic usage of atypical antipsychotics causes a 5-HT2A-dependent upregulation of histone deacetylase 2 …
Wnt Secretion Proteins Modulate Rankl-Induced Expression Of Aire In Thymic Epithelial Cells,
2018
CUNY City College
Wnt Secretion Proteins Modulate Rankl-Induced Expression Of Aire In Thymic Epithelial Cells, Daniel Pollack
Dissertations and Theses
Thymic epithelial cells (TEC) are essential for a proper adaptive immune response by regulating thymocyte development and establishing central tolerance. In the thymus, TECs differentially express Wnt proteins, which activate canonical and non-canonical Wnt signaling pathways. Wnt signaling is thought to regulate cell survival, proliferation, and development although the direct molecular mechanisms in TECs have yet to be elucidated. The inducible inhibition of canonical Wnt signaling with Dkk1 leads to a rapid loss of TEC progenitors as well as a decline in mature Aire-expressing mTECs. Therefore, we explore the role of Wnt ligands potentially responsible for stimulating and/or regulating Wnt …
Processing Of 3′-Blocked Dna Double-Strand Breaks By Tyrosyl-Dna Phosphodiesterase 1, Artemis And Polynucleotide Kinase/ Phosphatase,
2018
Virginia Commonwealth University
Processing Of 3′-Blocked Dna Double-Strand Breaks By Tyrosyl-Dna Phosphodiesterase 1, Artemis And Polynucleotide Kinase/ Phosphatase, Ajinkya S. Kawale
Theses and Dissertations
DNA double-strand breaks (DSBs) containing unligatable termini are potent cytotoxic lesions leading to growth arrest or cell death. The Artemis nuclease and tyrosyl-DNA phosphodiesterase (TDP1) are each capable of resolving protruding 3′-phosphoglycolate (PG) termini of DNA double-strand breaks (DSBs). Consequently, a knockout of Artemis and a knockout/knockdown of TDP1 rendered cells sensitive to the radiomimetic agent neocarzinostatin (NCS), which induces 3′-PG-terminated DSBs. Unexpectedly, however, a knockdown or knockout of TDP1 in Artemis-null cells did not confer any greater sensitivity than either deficiency alone, indicating a strict epistasis between TDP1 and Artemis. Moreover, a deficiency in Artemis, but not TDP1, resulted …
Assembly And Trafficking Of The Cystic Fibrosis Transmembrane Conductance Regulator And Associated Proteins,
2018
University of Kentucky
Assembly And Trafficking Of The Cystic Fibrosis Transmembrane Conductance Regulator And Associated Proteins, Zhihui Zhang
Theses and Dissertations--Chemistry
Cystic Fibrosis (CF) is an autosomal recessive genetic disease that leads to severe malfunction in many organs, but particularly the lungs. The primary cause of this malfunction is the decrease of the airway surface liquid layer on the lung epithelium. The lack of hydration leads to mucus build up on the epithelial lining, leading to blockage of airways. The underlying cause of CF is the dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR), which results from mutations in the protein. Almost 90% of CF patients are caused by the deletion of the phenylalanine at position 508 of CFTR, which …
