Interaction Between Brk And Her2 In Breast Cancer, 2013 The University of Texas Graduate School of Biomedical Sciences at Houston
Interaction Between Brk And Her2 In Breast Cancer, Midan Ai
Dissertations & Theses (Open Access)
INTERACTION BETWEEN BRK AND HER2 IN BREAST CANCER
Midan Ai, Ph.D.
Supervisory Professor: Zhen Fan, M.D.
Breast tumor kinase (Brk) is a nonreceptor protein-tyrosine kinase that is highly expressed in approximately two thirds of breast cancers but is not detectable or is expressed at very low levels in normal mammary epithelium. Brk plays important roles in promoting proliferation, survival, invasion, and metastasis of breast cancer cells, but the mechanism(s) of which remain largely unknown. Recent studies showed that Brk is frequently co-overexpressed with human epidermal growth factor receptor-2 (HER2) and is physically associated with HER2 in breast cancer. The mechanism …
Enabling Sum Frequency Spectroscopy And Fluorescence Correlation Spectroscopy Of Model Cellular Membranes, 2013 The University of Maine
Enabling Sum Frequency Spectroscopy And Fluorescence Correlation Spectroscopy Of Model Cellular Membranes, Sarah M. Sterling
Electronic Theses and Dissertations
The majority of proteins secreted from cells contain a signal peptide sequence that is required for secretion mediated by the endoplasmic reticulum and Golgi apparatus. However, many proteins lack the essential signal peptide sequence, yet still undergo secretion. Such proteins are known to regulate cell proliferation, differentiation, and migration. Fibroblast growth factor 1 (FGF-1) is one protein which undergoes non-classical protein transport. The role of its interactions with the cellular membrane during non-classical protein transport is not fully understood, although FGF-1 has shown preferential destabilizing effects on artificial membranes composed of acidic phospholipids. In the present work, physiologically relevant model …
Molecular Diagnosis Of Metabolic Fast Growth Related Diseases In Broiler, 2013 University of Arkansas, Fayetteville
Molecular Diagnosis Of Metabolic Fast Growth Related Diseases In Broiler, Adnan Ali Khalaf Al-Rubaye
Graduate Theses and Dissertations
Pulmonary Hypertension Syndrome (PHS) and lameness are important metabolic diseases that affect rapidly growing broilers. The research reported in the first section of this dissertation focused on developing qPCR assays to identify differences in the expression levels of four candidate genes possibly associated with PHS: angiotensin II type 1 receptor (AGTR1): urotensin receptor 2D (UTS2D); serotonin receptor/transporter type 2Bn (HTR2B); and angiotensinogen cleaving enzyme (ACE). Expression levels of these candidate genes were examined in four different tissues. We established ribosomal protein S14 (RPS14) and RNA polymerase subunit 2B (RP2B) as suitable reference genes because they showed the most consistent deltaCt …
Bio-Separation Process Improvement Via Genomic Manipulation: Development Of Novel Strains For Use In Immobilized Metal Affinity Chromatography (Imac), 2013 University of Arkansas, Fayetteville
Bio-Separation Process Improvement Via Genomic Manipulation: Development Of Novel Strains For Use In Immobilized Metal Affinity Chromatography (Imac), Ryan Curtis Haley
Graduate Theses and Dissertations
The dissertation is comprised of three parts. Part I describes proteomic analysis of native bacterial proteins from Escherichia coli (E.coli) that bind during Immobilized Metal Affinity Chromatography (IMAC). Part II describes the value in exploiting proteome based data as a tool toward the design an E. coli expression strain that is particularly useful when Immobilized Metal Affinity Chromatography is employed as the initial capture step of a homologous protein purification process. Part III describes a methodology of chromosomal mapping of all contaminant gene products.
The objective of Part I was to identify all E. coli proteins that bind to Co(II), …
Effects Of Ergot Alkaloids And Bovine Bodily Fluids On Cytochrome P450 Activity, 2013 University of Arkansas, Fayetteville
Effects Of Ergot Alkaloids And Bovine Bodily Fluids On Cytochrome P450 Activity, Nicholas Scott Ezell
Graduate Theses and Dissertations
This thesis evaluates the PromegaTM P450-Glo assay (PromegaTM V9800) as a tool for quantifying ergot alkaloid concentration. Current techniques used for detection of ergot alkaloids are slow and expensive, do not detect all ergot alkaloids, or are not effective on bovine bodily fluids. The first study was conducted to determine effects of commercial ergot alkaloids (n = 6; 0 - 400 μM) on the PromegaTM P450-Glo assay. Cytochrome P450 (CYP450) activity in assay had a differential response to each ergot alkaloid and concentration. As concentrations of ergotamine, dihydroergotamine, ergocornine, and ergocryptine increased CYP450 activity was inhibited (P …
Spectroscopic Investigation Of The Interaction Of Fadh In Dna Photolyase With Uv-Damaged Dna, 2013 Montclair State University
Spectroscopic Investigation Of The Interaction Of Fadh In Dna Photolyase With Uv-Damaged Dna, Kyle Luke Williams
Theses, Dissertations and Culminating Projects
Skin cancer is the most prevalent malignancy found in humans, with the diagnosis rate continuing to steadily increase. The primary cause of this disease is overexposure to harmful ultraviolet (UV) radiation from sunlight, which can induce damage to the nitrogenous bases in DNA via dimerization. The most prevalent UV-induced photoproducts in DNA are cyclobutane pyrimidine dimers (CPDs), most commonly between adjacent thymidines.
Organisms have implemented methods by which to repair these CPDs, the primary of which are nucleotide excision repair (NER) and photoreactivation by photolyases. Photolyases are blue-light activated flavoproteins that are more efficient at recognizing and repairing CPDs than …
Prolonged Glucose Deprivation Sensitizes Snf1 To Negative Regulation By Pka To Delay Entry Into Quiescence, 2013 University of Wisconsin-Milwaukee
Prolonged Glucose Deprivation Sensitizes Snf1 To Negative Regulation By Pka To Delay Entry Into Quiescence, Leah Bernadette Doughty
Theses and Dissertations
AMPK, the fuel gauge of the cell, and its upstream kinase, LKB1, have been implicated in cancer prevention and stress response associated with energy exhaustion. In the yeast Saccharomyces cerevisiae, Snf1 is the ortholog of mammalian AMPK. In S. cerevisiae, Snf1 is activated by phosphorylation of its T–loop at Thr210, primarily by its upstream kinase Sak1, in absence of the preferred carbon source, glucose, or during some other stress responses. Cyclic AMP–dependent protein kinase A, PKA, is involved in nutrient signaling largely antagonistically to Snf1. Using yeast strains of the Sigma 1278b genetic background, which have a high basal level …
High-Throughput Approaches For The Assessment Of Factors Influencing Bioavailability Of Small Molecules In Pre-Clinical Drug Development, 2013 University of Wisconsin-Milwaukee
High-Throughput Approaches For The Assessment Of Factors Influencing Bioavailability Of Small Molecules In Pre-Clinical Drug Development, Megan Marie Mccallum
Theses and Dissertations
A bioactive molecule must pass many hurdles to be designated as a "good" pharmaceutical lead or hit compound. It should have a significant activity, selectivity, bioavailability, and metabolic half-life. Many factors have been identified that influence the free drug concentration or bioavailability of orally administered drugs in the earliest development stages. In vitro pre-clinical assays have been developed to measure these parameters. The small molecule properties that are investigated here include aqueous solubility, permeability, reactivity (electrophilicity), small molecule-protein binding, and displacement of protein-bound molecules (drug-drug interactions). The development of rapid and miniaturized assays to quantify these factors is presented herein. …
Methods In Metallomics, Proteomics, And Toxicology: Development And Applications Of Laser Ablation Inductively Coupled Plasma Mass Spectrometry And Native Sds-Page, 2013 University of Wisconsin-Milwaukee
Methods In Metallomics, Proteomics, And Toxicology: Development And Applications Of Laser Ablation Inductively Coupled Plasma Mass Spectrometry And Native Sds-Page, William John Wobig
Theses and Dissertations
Polyacrylamide gel electrophoresis (PAGE) is a bio-analytical method used to separate proteins in solution into an array of individual bands of proteins in a gel matrix. Current PAGE methods, however, have severe limitations in simultaneously maintaining a protein's native structure and association with transition metals while providing adequate resolution. Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) provides a means to perform trace to ultra-trace level inorganic analysis of solid samples such as dried PAGE gels containing metallo-protein arrays. Current LA-ICP-MS methods involving the analysis of PAGE gels, however, have been limited in their effective use by inadequate limits of …
Dynamics And Model Of The Pore-Forming Protein Lysenin, 2013 University of Arkansas, Fayetteville
Dynamics And Model Of The Pore-Forming Protein Lysenin, Eric Krueger
Graduate Theses and Dissertations
Membrane transporters are a class of membrane proteins that function to provide a pathway across a cell membrane for the movement of ions and biomolecules. Investigations into the regulatory mechanism of these systems are hindered by their extensive preparation requirements compounded by their fragility and instability. However, lysenin, a pore-forming protein extracted from the earthworm Eisenia foetida, provided a unique opportunity to study a protein which is stable in both a soluble and membrane phase. Lysenin channels possess several important properties characteristic of ion channels without the inherent difficulties that plague investigations with biologically vital membrane transporters like voltage-gated ion …
The Geometry And Sensitivity Of Ion-Beam Sculpted Nanopores For Single Molecule Dna Analysis, 2013 University of Arkansas, Fayetteville
The Geometry And Sensitivity Of Ion-Beam Sculpted Nanopores For Single Molecule Dna Analysis, Ryan Connor Rollings
Graduate Theses and Dissertations
In this dissertation, the relationship between the geometry of ion-beam sculpted solid-state nanopores and their ability to analyze single DNA molecules using resistive pulse sensing is investigated. To accomplish this, the three dimensional shape of the nanopore is determined using energy filtered and tomographic transmission electron microscopy. It is shown that this information enables the prediction of the ionic current passing through a voltage biased nanopore and improves the prediction of the magnitude of current drop signals when the nanopore interacts with single DNA molecules. The dimensional stability of nanopores in solution is monitored using this information and is improved …
Modeling Amyloid-Ss Self-Assembly : Stability Of On-Pathway Aggregate Formation, 2013 Montclair State University
Modeling Amyloid-Ss Self-Assembly : Stability Of On-Pathway Aggregate Formation, Andrew Kevin Mauro
Theses, Dissertations and Culminating Projects
Protein misfolding and concomitant aggregation towards amyloid formation is the underlying biochemical commonality among a wide range of human pathologies. Amyloid formation involves the conversion of proteins from their native monomeric states (intrinsically disordered or globular) to well-organized, fibrillar aggregates in a nucleation-dependent manner. Understanding the mechanism of aggregation is important not only to gain better insight into amyloid pathology but also to simulate and predict molecular pathways. One of the main impediments in doing so is the highly stochastic nature of interactions that complicates the development of meaningful insights. In this study, we have utilized a well-characterized intermediate along …
Investigation Of Ghrelin Acylation By Ghrelin O-Acyltransferase, 2013 Syracuse University
Investigation Of Ghrelin Acylation By Ghrelin O-Acyltransferase, Edward P. Prybolsky
Honors Capstone Projects - All
Ghrelin is a peptide hormone involved in hunger signaling and other physiological processes. To become active, ghrelin first must be acylated by ghrelin O-acyltransferase (GOAT). This enzyme carries out a post-translational modification that attaches an octanoyl group to the side chain of the serine 3 (S3) residue of ghrelin. With ghrelin linked to hunger signaling, memory, and other physiological processes, GOAT has been identified as a potential drug target. However, inhibitor design is difficult because not much is known regarding the active site structure and catalytic mechanism of GOAT. This study reports the design of a novel fluorescence-based assay that …
Design Of Metalloproteins For Catalysis And Bioimaging, 2013 Syracuse University
Design Of Metalloproteins For Catalysis And Bioimaging, Krystyna Zhezherya
Honors Capstone Projects - All
Abstract
Metalloenzymes constitute a large subclass of proteins with diverse functions including metal-sensing, signal transduction pathways, and metal transport. In this report, I aim to study the intricate relationship between structure and function as it relates to metalloproteins in the fields of catalysis and bioimaging. For catalysis, I used existing platforms in addition to de novo design to study small scaffolds with varying secondary structure, and their function in catalyzing the hydrolysis of a p-nitrophenol ester. For bioimaging, I used an existing enzyme known as human carbonic anhydrase I, hCA, to develop a bioimaging agent that can be fused to …
The Role Of Oswrky71 And Its Interacting Proteins In Seed Germination And Early Growth Of Cereal Grains, 2013 University of Nevada, Las Vegas
The Role Of Oswrky71 And Its Interacting Proteins In Seed Germination And Early Growth Of Cereal Grains, Margaret Ja Shin
UNLV Theses, Dissertations, Professional Papers, and Capstones
During seed germination and early seedling growth, complex molecular and physiological events occur in rice (Oryza sativa) and other cereal grains. As the seed transitions to vegetative tissue, it responds to both favorable and unfavorable environmental conditions and is vulnerable to attack by predation and disease. Although seeds are relatively small and tender in size, extensive and sophisticated molecular networks enables the immobile seed to grow, survive and adapt in its environment. One of the networks I am interested in is in the crosstalk between the gibberellin (GA) and abscisic acid (ABA) signaling pathways. These pathways are interesting because they …
Increased Production And Extraction Efficiency Of Triacylglycerides From Microorganisms And An Enhanced Understanding Of The Pathways Involved In The Production Of Triacylglycerides And Fatty Alcohols, 2013 Utah State University
Increased Production And Extraction Efficiency Of Triacylglycerides From Microorganisms And An Enhanced Understanding Of The Pathways Involved In The Production Of Triacylglycerides And Fatty Alcohols, Robert M. Willis
All Graduate Theses and Dissertations, Spring 1920 to Summer 2023
The continued increase in the demand for fossil fuels combined with their ever dwindling supply has prompted the search for a suitable alternative fuel. The research contained within this dissertation seeks to increase the lipid (fat) content of cellular feedstocks, improve extraction efficiencies of lipids, and to understand the pathways involved in the production of fatty alcohols and triacylglycerides, compounds commonly used in many industrial processes, from microbial feedstocks. This work has been done in an attempt to increase the overall economic viability of microbial biofuels production.
The production of biofuels from microalgae used as a feedstock allows for the …
Characterization And Potential Utility Of Porcine Trophoblast-Derived Stem-Like Cells, 2013 Utah State University
Characterization And Potential Utility Of Porcine Trophoblast-Derived Stem-Like Cells, Edison A. Suasnavas
All Graduate Theses and Dissertations, Spring 1920 to Summer 2023
In mammalian pregnancy, the placenta is a very important organ which helps to establish a healthy pregnancy. Its functions could be described in four points: 1) It allows the fetus to receive gases and nutrients from the mother in a safe way; 2) it lets the fetus get rid of waste through the mother's kidneys; 3) it releases essential pregnancy-related hormones and growth factors that let the uterus hold the fetus; 4) it secretes immune response regulators to give the fetus immune protection against the mother. Abnormalities in the placenta can be the cause of death to the fetus. Mammalian …
Amphetamine Elicits Opposing Actions On Readily Releasable And Reserve Pools For Dopamine, 2013 Illinois State University
Amphetamine Elicits Opposing Actions On Readily Releasable And Reserve Pools For Dopamine, Dan P. Covey, Steven A. Juliano, Paul A. Garris
Faculty Publications – Biological Sciences
Amphetamine, a highly addictive drug with therapeutic efficacy, exerts paradoxical effects on the fundamental communication modes employed by dopamine neurons in modulating behavior. While amphetamine elevates tonic dopamine signaling by depleting vesicular stores and driving non-exocytotic release through reverse transport, this psychostimulant also activates phasic dopamine signaling by up-regulating vesicular dopamine release. We hypothesized that these seemingly incongruent effects arise from amphetamine depleting the reserve pool and enhancing the readily releasable pool. This novel hypothesis was tested using in vivo voltammetry and stimulus trains of varying duration to access different vesicular stores. We show that amphetamine actions are stimulus dependent …
Oxidation Of Thrombomodulin Methionine 388 In Cigarette Smokers, 2013 University of Arkansas, Fayetteville
Oxidation Of Thrombomodulin Methionine 388 In Cigarette Smokers, Samrat B. Thapa
Graduate Theses and Dissertations
This work tested the hypothesis that oxidation of methionine 388 in thrombomodulin is higher in cigarette smokers, and thus a likely contributor towards the hypercoagulable state in smokers. Thrombomodulin, a protein cofactor found on endothelial cell surfaces, regulates the activity of thrombin. Thrombin bound to thrombomodulin no longer converts fibrinogen to fibrin, but instead activates Protein C which, in turn, stops the coagulation cascade by inactivation of clotting factors. The oxidation of methionine 388 of thrombomodulin has been shown in vitro to dramatically decrease the anticoagulant cofactor activity of thrombomodulin. The blood of cigarette smokers is more prone to clot …
Interactions Between Ions And Lysenin Nanochannels And Their Potential Applications As Biosensors, 2013 University of Arkansas, Fayetteville
Interactions Between Ions And Lysenin Nanochannels And Their Potential Applications As Biosensors, Radwan Awwad Al Faouri
Graduate Theses and Dissertations
Lysenin is classified as a pore-forming toxin protein that is isolated from the earthworm Eisenia fetida and consists of 297 amino acids [1]. Lysenin inserts large conducting pores (3.0-4.7 nm in diameter) into artificial membranes (BLM) which include sphingomyelin. These pores (channels) are open and oriented upon insertion into the bilayer lipid membrane. Lysenin channels gate at positive voltages (voltage-induced gating), but not at negative voltages. Lysenin pores also exhibit activity modulation in response to changes in ionic strength and pH, indicating that electrostatic interaction is responsible for Lysenin conductance activities. In this line of inquiries, and by modulating Lysenin …