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Extension Of The Ergot Alkaloid Gene Cluster, Samantha Joy Fabian
Extension Of The Ergot Alkaloid Gene Cluster, Samantha Joy Fabian
Graduate Theses, Dissertations, and Problem Reports
Specialized metabolites produced by fungi impact human health. A large portion of the pharmaceuticals currently on the market are derived from metabolites biosynthesized by microbes. Ergot alkaloids are a class of fungal metabolites that are important in the interactions of environmental fungi with insects and mammals and also are used in the production of pharmaceuticals. In animals, ergot alkaloids can act as partial agonists or antagonists at receptors for 5-hydroxytryptamine (serotonin), dopamine, and noradrenaline as ergot alkaloids have chemical structures similar to those neurotransmitters. Therefore, they affect insects and mammals that consume them and can be used to produce drugs …
A Streptozotocin-Induced Model Of Alzheimer's Disease In Mice With Wild-Type Human Tau, Carolyn C. Rudy
A Streptozotocin-Induced Model Of Alzheimer's Disease In Mice With Wild-Type Human Tau, Carolyn C. Rudy
Graduate Theses, Dissertations, and Problem Reports
Alzheimer's disease (AD) accounts for 60 to 80% of all dementias, affects over 5 million Americans, and incurs annual healthcare costs of over {dollar}200 billion (Alzheimer's Association, 2012). Hyperphosphorylation of tau, the main component of neurofibrillary tangles observed in AD, leads to deficits in cell structure and function. Because recent data suggest impairments in cerebral glucose utilization and energy metabolism play a prominent role in the pathogenesis of AD, we sought to create a mouse model that emulates the metabolic changes using intracerebroventricular infusions of streptozotocin (ICV-STZ) in transgenic mice expressing human tau. The Barnes maze, a test of spatial …
Hydrogen-Deuterium Exchange Studies By Mass Spectrometry: A Method For Obtaining Conformational Structures Of Proteins In Solution, Teerapat Rojsajjakul
Hydrogen-Deuterium Exchange Studies By Mass Spectrometry: A Method For Obtaining Conformational Structures Of Proteins In Solution, Teerapat Rojsajjakul
Graduate Theses, Dissertations, and Problem Reports
Hydrogen-deuterium exchange (HDX) coupled with electrospray ionization (ESI) in mass spectrometry (MS) has become an important method in the study of protein structure and dynamics. It provides an opportunity for obtaining conformational structures of protein motions in physiological conditions and offers unparalleled limits of detection. This method relies on the fact that the accessibility of exchangeable amide hydrogens of a protein to D2O induces H/D isotopic exchange. The exchangeable amide hydrogens that lack hydrogen bonding when exposed to solvent are exchanged rapidly. Protected amide hydrogens from tightly folded elements and have hydrogen bonding exchange slow and can be detected by …
Analysis And Interpretation Of Complex Biological Signal Transduction Networks, Holly N. Currie
Analysis And Interpretation Of Complex Biological Signal Transduction Networks, Holly N. Currie
Graduate Theses, Dissertations, and Problem Reports
Cellular signaling is a complex system of biological communication that coordinates cellular activities via biochemical reactions. The passing of an extracellular signal across a cell membrane to intracellular signaling molecules is referred to as signal transduction. Signals transduced across a cell's membrane influence its function, and allow the cell to respond to its local environment. Within the cell, proteins are key responders to, and carriers of, the transduced signal. A class of proteins called kinases mediate most of the signal transduction in eukaryotic cells by catalyzing the phosphorylation of substrate proteins. The post-translational modification of proteins by phosphorylation regulates protein …
Exploring The Mechanism Of Shp2 And Egfr/Her2 Cooperation In Breast Cancer Cell Signaling, Zachary Raymond Hartman
Exploring The Mechanism Of Shp2 And Egfr/Her2 Cooperation In Breast Cancer Cell Signaling, Zachary Raymond Hartman
Graduate Theses, Dissertations, and Problem Reports
The Src homology 2-containing protein tyrosine phosphatase 2 (SHP2) has been established as a critical mediator of cancer-related cell signaling downstream of receptor tyrosine kinases like EGFR and HER2. As such, targeting of SHP2 is being recognized as a potentially viable therapeutic option in HER2-positive and triple-negative breast cancers. In this report, I employed molecular and cellular biology techniques to further elucidate the role of SHP2 downstream of receptor tyrosine kinases in breast cancer cell lines. In this way, I was able to contribute knowledge to how SHP2 controls triple-negative cell motility. In addition, the mechanism of SHP2 control of …
Absorption Of Marine Vs Non-Marine Sources Of Epa And Dha, John S. Ketz
Absorption Of Marine Vs Non-Marine Sources Of Epa And Dha, John S. Ketz
Graduate Theses, Dissertations, and Problem Reports
Docosahexaenoic acid (DHA) from algae oil has been incorporated into tissues at a lower level and has been less effective than fish oil (FO) at reducing body fat. Our objective was to determine fecal excretion of eicosapentaenoic acid (EPA) and DHA from different dietary sources. Male mice (n=100) were fed a 12% lipid diet containing soy oil (SO), FO, yeast oil (YO) algae oil (AO), or AO+YO. The AO diet was fed to contain amounts of DHA equal to the FO diet, and the YO diet was fed to contain amounts of EPA equal to the FO diet. To measure …
Disulfide Bridging The Gap Between Src And Cortactin: A New Paradigm In Sh2 Domain-Mediated Signaling, Jason Vanburen Evans
Disulfide Bridging The Gap Between Src And Cortactin: A New Paradigm In Sh2 Domain-Mediated Signaling, Jason Vanburen Evans
Graduate Theses, Dissertations, and Problem Reports
Src and cortactin are cytoplasmic proteins that are implicated in cancer progression and metastasis. Src is a non-receptor tyrosine kinase that also regulates normal cell homeostasis through phosphorylation of multiple downstream substrates. Cortactin is an actin binding protein and nucleation promoting factor that promotes the formation of stable branching networks within the actin cytoskeleton. Together, these proteins work in concert to promote the invasive and metastatic potential of tumor cells due to tyrosine phosphorylation of cortactin by Src. However, the mechanistic details of the interaction between Src and cortactin have never been elucidated. Collectively, this work aims to define how …
The Inhibition Of Splicing Of Glucose-6-Phosphate Dehydrogenase Mrna During Starvation By Heterogeneous Nuclear Ribonucleoprotein K, Travis Cyphert
The Inhibition Of Splicing Of Glucose-6-Phosphate Dehydrogenase Mrna During Starvation By Heterogeneous Nuclear Ribonucleoprotein K, Travis Cyphert
Graduate Theses, Dissertations, and Problem Reports
Splicing of nascent RNA transcripts is an essential step in gene expression and a target of nutrient regulation. Glucose-6-phosphate dehydrogenase (G6PD) is a lipogenic gene whose expression is regulated exclusively at this posttranscriptional stage. Expression of G6PD mRNA increases 15- to 17-fold during refeeding and is inhibited 80-90% by starvation and the addition of polyunsaturated fat to the diet. The large changes in the accumulation of G6PD mRNA are due to changes the rate of pre-mRNA splicing and not changes in its transcription. In this regard, dietary carbohydrate enhances intron removal, which increases the accumulation of G6PD mRNA. Starvation alters …
Characterization Of The Unique Flagellar Hook Structure Of The Spirochetes Borrelia Burgdorferi And Treponema Denticola, Kelly Ann Heintzelman Miller
Characterization Of The Unique Flagellar Hook Structure Of The Spirochetes Borrelia Burgdorferi And Treponema Denticola, Kelly Ann Heintzelman Miller
Graduate Theses, Dissertations, and Problem Reports
The long-term goal of this project is to better understand Borrelia burgdorferi and Treponema denticola motility as it relates to pathogenesis. The structure of the spirochete periplasmic flagella is unique when compared to externally located flagella. One unusual characteristic is the flagellar hook, which serves as a universal joint coupling rotation of the membrane bound motor complex to the flagellar filament. The hook is composed of approximately 120 FlgE monomers, and in bacteria with externally located flagella, these structures readily disassociate into monomers (~50 kDa) when treated with heat and detergent. However, in spirochetes the FlgE monomers form a large …
Investigations In Molecular Recognition Element Selection And Single-Wall Carbon Nanotube Properties, Ryan Martin Williams
Investigations In Molecular Recognition Element Selection And Single-Wall Carbon Nanotube Properties, Ryan Martin Williams
Graduate Theses, Dissertations, and Problem Reports
The in vitro selection of Molecular Recognition Elements (MREs) is a powerful tool for identifying molecules useful in numerous applications. This is achieved using the iterative Systematic Evolution of Ligands by EXponential Enrichment (SELEX) process. This technique utilizes a large library of 10 9-1015 different molecules which is enriched for those that bind to a target of interest. It also can be designed to enrich for molecules which do not bind to other, closely-related negative targets. We have developed a novel variation of this process called Decoy-SELEX. This enriches molecules that bind to the target of interest, but focuses on …
Network Dynamics, Synchronization, And Self-Propelled Particles In Chemical Systems, Hua Ke
Network Dynamics, Synchronization, And Self-Propelled Particles In Chemical Systems, Hua Ke
Graduate Theses, Dissertations, and Problem Reports
Neural networks are a class of biological networks of great importance. They are a key component of the central nervous system that coordinates body functions. The exploration of the detailed mechanism of biological neural networks remains extremely active. Inspired by the structure of biological neural networks, artificial neural networks have been designed to solve a variety of problems in pattern recognition, prediction, optimization and control. However, few studies have been reported that explore the dynamics of biological neural networks using chemical systems. As part of this thesis, an experimentally trainable network based on the photosensitive Belousov-Zhabotinsky reaction is developed, where …
Role Of Chaperonin Cct In G-Protein Biosynthesis, Catherine Woodard
Role Of Chaperonin Cct In G-Protein Biosynthesis, Catherine Woodard
Graduate Theses, Dissertations, and Problem Reports
Chaperonins are ubiquitous molecular chaperones that are found in all animal kingdoms. They all share a common structure and function to assist the folding of other proteins. All chaperonins consist of two stacked rings, which come together to form a central cavity where folding can take place. The eukaryotic cytosolic chaperonin containing TCP1 (CCT) is a member of the group II chaperonins, which are defined as having octameric or nonameric rings composed of more than one type of subunit.;CCT is an essential part of eukaryotic cell function, and it has been estimated that it folds up to 10% of newly …
Mass Spectrometric Approaches To Characterization Of Chemical Species Containing Metallic Ions, Guodong Gu
Mass Spectrometric Approaches To Characterization Of Chemical Species Containing Metallic Ions, Guodong Gu
Graduate Theses, Dissertations, and Problem Reports
Mass spectrometry is a widely used analytical technique for both qualitative and quantitative analysis of physical, chemical, and biological compounds by measuring mass to charge ratio (m/z) of particles. It can supply elemental composition, molecular weight, and structure information of chemical compounds. The high sensitivity and analysis speed enable it to be an outstanding tool for chemical analysis. A Quadrupole Ion Trap Mass Spectrometry (QITMS) and a pulsed Glow Discharge Time-of-Flight Mass Spectrometry (GD-TOFMS) are employed in this study.;Internal energy distribution, P(E), of collision induced dissociation in QITMS is studied by using "thermometer molecules", whose fragmentation pathway consists of several …
Glycan Characterization And Manipulation Using Phospholipid Additives For Capillary Electrophoresis, Stephanie A. Archer-Hartmann
Glycan Characterization And Manipulation Using Phospholipid Additives For Capillary Electrophoresis, Stephanie A. Archer-Hartmann
Graduate Theses, Dissertations, and Problem Reports
Protein glycosylation is of interest in a number of emerging fields, and plays important functional roles in cellular biology. The analysis of these molecules is nontrivial because they exhibit great complexity in both monomer makeup and linkages of these monomers. As a result, a common challenge that analytical techniques face is the separation of linkage glycan isomers. This dissertation is based on the research leading to the development of a phospholipid-capillary electrophoresis method that allows for highly efficient separations and the non-covalent incorporation of enzymes and lectins for in-capillary interactions. Glycans were removed from glycoproteins through enzymatic means, then labeled …
Rescue Of Inherited Retinal Degeneration Associated With Aipl1 Defects, Cristy Ann Ku
Rescue Of Inherited Retinal Degeneration Associated With Aipl1 Defects, Cristy Ann Ku
Graduate Theses, Dissertations, and Problem Reports
Since groundbreaking clinical trials treating Leber congenital amaurosis (LCA) patients with retinal pigmented epithelium-specific 65 kDa protein (Rpe65) defects, which were the most successful gene therapy studies to date, much effort has been put into finding other candidate genes associated with inherited retinal degeneration to treat. Animal models with Rpe65 defects demonstrate an unusual circumstance that greatly favors treatment, where dramatic vision loss is disproportionately greater than the ensuing slow photoreceptor degeneration. This pattern is also believed to occur in Rpe65-LCA patients, and stems from the primary defect in retinal pigmented epithelial (RPE) cells that subsequently perturbs photoreceptors. However, a …
Can Changes In Sr Protein Acetylation Affect Alternative Splicing?, Heather E. Knupp
Can Changes In Sr Protein Acetylation Affect Alternative Splicing?, Heather E. Knupp
Graduate Theses, Dissertations, and Problem Reports
Cellular phenotype and function is determined by the cellular proteome. Within the cellular proteome there are processes that have a potential to significantly alter the composition of the proteome. One such process is called alternative splicing. Splicing is the removal of introns from a pre-mRNA sequence and the remaining pre-mRNA sequences, called exons, are combined. Alternative splicing modifies the intron-exon combination, and can form novel products from the different arrangement of the coding sequences. This process, due to the high potential for new, possibly unwanted products, is highly regulated and can occur in a tissue and developmental-specific fashion. The misreguation …
Role Of Nitric Oxide And Reactive Oxygen Species In Apoptotic, Inflammatory And Migratory Signaling Pathways In Cancer, Siera Jo Talbott
Role Of Nitric Oxide And Reactive Oxygen Species In Apoptotic, Inflammatory And Migratory Signaling Pathways In Cancer, Siera Jo Talbott
Graduate Theses, Dissertations, and Problem Reports
Cancer represents over 200 different diseases of different cell and tissue type origins. The heterogeneity of tumors presents challenges in finding effective treatments for the different diseases. Therefore, understanding the molecular events that promote tumorgenesis can assist in the development of better targeted treatments and therapies. Reduction/oxidation (redox) biology has become increasingly important as high levels of nitric oxide (NO) and reactive oxygen species (ROS) are reported in both the development of cancer and in response to treatment. In addition to their known potential biotoxic effects on DNA, proteins and lipids, NO and ROS are recognized as secondary messengers within …
De Novo Asymmetric Synthesis Of Biologically Active Carbohydrate Natural Products And Related Sar Studies, Bulan Wu
Graduate Theses, Dissertations, and Problem Reports
The carbohydrate portion of natural products plays an important role in its biological activity, such as solubility, target binding, tissue targeting, and membrane transportation. Over the last fourteen years, Dr. O'Doherty's group has been developing de novo methodologies to build the desired carbohydrate functionality and stereochemistry within each sugar from simple achiral starting materials in stark contrast to the traditional carbohydrate approach using known sugar isomers as starting materials. The methodologies depend on a highly diasteroselective palladium-catalyzed glycosylation reaction to control the anomeric stereochemistry, and a highly enantioselective Noyori reduction to install the sugar absolute stereochemistry. Appropriate post-glycosylation transformations create …
Systemic Lipopolysaccharide Stimulates Airway Transepithelial Na+ Transport By Increasing Enac And Na+,K+ -Pump Activity, Michael W. Dodrill
Systemic Lipopolysaccharide Stimulates Airway Transepithelial Na+ Transport By Increasing Enac And Na+,K+ -Pump Activity, Michael W. Dodrill
Graduate Theses, Dissertations, and Problem Reports
Our laboratory found that systemic administration of lipopolysaccharide (LPS; 4 mg/kg) hyperpolarized the transepithelial potential difference (V t) of tracheal epithelium in the isolated, perfused trachea (IPT) of the guinea pig 18 h after injection. We hypothesized that LPS stimulates the transepithelial movement of Na+ via the epithelial sodium channel (ENaC)/Na+,K+-pump axis, leading to hyperpolarization of Vt. LPS increased the Vt response to amiloride, i.e., offset the effect of LPS, indicating that Na+ transport was increased. The functional activity of ENaC was measured in the IPT after short-circuiting the Na+,K+-pump with basolateral amphotericin B. LPS had no effect on the …
Regulation Of Anoikis By Ankyrin Complexes, Sanjeev Kumar
Regulation Of Anoikis By Ankyrin Complexes, Sanjeev Kumar
Graduate Theses, Dissertations, and Problem Reports
Anoikis is a subset of apoptosis, suppressed by cell-extracellular matrix association. It is a safeguard mechanism against tumor metastasis. The present study was designed to understand the role of cortical cytoskeletal protein ankyrin-G and its interacting proteins in anoikis. E-cadherin and ankyrin-G are function partners and during epithelial-mesenchymal-transition (EMT), both gets downregulated. During cell-extracellular matrix dissociation, ankyrin-G shifts to cytoplasm from cytoskeleton and loses spectrin interaction. Overexpression of ankyrin-G induced apoptosis in death domain dependent manner, promoted by the presence of ankyrin-G death domain interacting partner, RIP1 (Receptor Interacting Protein with death domain). Ankyrin-G also interacted with a MAGE family …
Phospholipid Enhanced Separation With Capillary Electrophoresis, Ruijuan Luo
Phospholipid Enhanced Separation With Capillary Electrophoresis, Ruijuan Luo
Graduate Theses, Dissertations, and Problem Reports
Phospholipids were used as an additive in capillary electrophoresis to enhance the separation of glycans derived from alpha1-acid glycoprotein, fetuin, and ribonuclease B. The properties of phospholipid preparations were dependent upon composition, hydration, and temperature. Separation performance was evaluated as a function of these variables. A preparation of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dihexanoyl-snglycero-3-phosphocholine (DHPC), with [DMPC]/[DHPC] = 2.5, in 10% lipid/aqueous buffer at 25 °C provided the best separation efficiency at an electric field strength of 400 V/cm. Resolution was enhanced with the additive as well.;Phospholipids were also investigated as an additive for capillary electrophoresis separation of DNA molecules. Lipid preparations …
Development Of Nanofluidic/Microfluidic Interfaces As Analyte Concentrators For Proteomic Samples, Kathleen C. Reschke
Development Of Nanofluidic/Microfluidic Interfaces As Analyte Concentrators For Proteomic Samples, Kathleen C. Reschke
Graduate Theses, Dissertations, and Problem Reports
We have developed a nanofluidic microfluidic analyte concentrator for application to proteomic samples. This dissertation includes a study investigating the current rectification behavior of the device including a temporal characterization of the ON state to OFF state transition and the OFF state to ON state transition as a function of device design. An analyte concentrator compatible with proteomic samples is presented and the current rectifying phenomenon is utilized to ensure adequate analyte delivery for the enrichment process. Finally, characterization of a coating technique to alter the surface charge of the nanofluidic element from anionic to cationic is presented.
The Effects Of Fungal Pigments On Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectral Peak Formation, Amanda Dawn Buskirk
The Effects Of Fungal Pigments On Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectral Peak Formation, Amanda Dawn Buskirk
Graduate Theses, Dissertations, and Problem Reports
Fungi are ubiquitous microorganisms that commonly cause diseases with high mortality rates in immunocompromised hosts. In order to successfully treat the infection and subsequently decrease mortality rates, it is necessary to rapidly identify the causal organism(s) and promptly begin the proper treatment. Common identification methods, such as viable culture characterization, are often time consuming or not species-specific, as is the case with many molecular or immunodiagnostic assays. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been used to discriminate between many clinically relevant microorganisms. Recently, MALDI-TOF MS has been used to discriminate between monilaceous fungal species, however, darkly pigmented …
Mechanisms Of Iron Reduction And Phosphorus Solubilization In An Intermittently Wet Pasture Soil, Jared L. Wilmoth
Mechanisms Of Iron Reduction And Phosphorus Solubilization In An Intermittently Wet Pasture Soil, Jared L. Wilmoth
Graduate Theses, Dissertations, and Problem Reports
Microbial Fe-reduction in pasture soils may be of agronomic importance, because it has been shown to influence P cycling. The present study investigated the behavior of Fe and P in an intermittently wet, Appalachian pasture soil during a 42 day anaerobic incubation. Native humic acid (HA) extracted from the sampling location and anthraquinone-2,6-disulfonic acid (AQDS) were used in the experiment to determine their electron-mediating effects on Fe(III) reduction and P solubilization over time. Extracted HA and the International Humic Substance Society (IHSS) Elliott Soil HA standard were compared using 13C-NMR, FT-IR, SEM, and CHNS analysis. Soil samples treated with 1.24 …
The Identification Of Molecular Guidance Cues Necessary For Development Of The Central Auditory System, David M. Howell
The Identification Of Molecular Guidance Cues Necessary For Development Of The Central Auditory System, David M. Howell
Graduate Theses, Dissertations, and Problem Reports
Developing neurons utilize multiple guidance cues to reach their appropriate destination. Although much is known about the anatomy and electrophysiology of auditory brainstem neurons, the molecular factors directing migration of these cells and the targeting of their axons are only beginning to be explored. Ventral cochlear nucleus (VCN) neurons have axons that project bilaterally to the superior olivary complex (SOC) in the ventral acoustic stria (VAS). The circumferential trajectory taken by developing VCN axons is similar to the path of spinal commissural neurons (SCNs). Therefore, we reasoned that netrin-DCC and slit-robo signaling systems may function, similar to SCNs, in the …
The Roles Of The Phosducin Family Proteins In The Regulation Of Heterotrimeric G Proteins In Vertebrate Photoreceptors, Hongman Song
The Roles Of The Phosducin Family Proteins In The Regulation Of Heterotrimeric G Proteins In Vertebrate Photoreceptors, Hongman Song
Graduate Theses, Dissertations, and Problem Reports
Phosducin (Pdc) and phosducin-like protein 1 (PhLP1) are homologous proteins of the phosducin gene family that specifically interact with heterotrimeric G proteins. Both Pdc and PhLP1 are expressed in photoreceptors, sensory neurons of the retina responsible for acquisition of visual information; however their functions in these cells remains enigmatic. Photoreceptors maintain remarkably high and tightly controlled levels of the heterotrimeric G protein, transducin, utilized by these cells for visual signal transduction. Our central hypothesis was that Pdc and PhLP1 are engaged in the maintenance of transducin homeostasis in the photoreceptors.;To test this hypothesis, we have studied phosphorylation of Pdc, which …
The Effect Of Nutrients Upon The Activity Of Sr Proteins, Callee Mcconnell Walsh
The Effect Of Nutrients Upon The Activity Of Sr Proteins, Callee Mcconnell Walsh
Graduate Theses, Dissertations, and Problem Reports
RNA splicing is an important component of gene expression that contributes immensely to the biological complexity of higher eukaryotes. The regulation of splicing by external stimuli, such as nutrients, is poorly understood, however. The experiments contained herein sought to understand how the activity of splicing factors called SR proteins is regulated by insulin and polyunsaturated fatty acids in the liver using the model mRNA glucose-6-phosphate dehydrogenase (G6PD). RNA affinity and chromatin immunoprecipitation experiments demonstrated that refeeding of rodents stimulates the binding of SR proteins to the splicing regulatory element of G6PD; and this was especially relevant for SRp20. In vitro …
Determination Of The Nutritional Value, Protein Quality And Safety Of Krill Protein Concentrate Isolated Using An Isolelectric Solubilization/Precipitation Technique, Joseph Christopher Gigliotti
Determination Of The Nutritional Value, Protein Quality And Safety Of Krill Protein Concentrate Isolated Using An Isolelectric Solubilization/Precipitation Technique, Joseph Christopher Gigliotti
Graduate Theses, Dissertations, and Problem Reports
Despite its abundance and nutritional value, krill has not been widely utilized for human consumption due to the lack of proper technology for protein recovery. The study objectives were to isolate krill protein concentrate (KPC) and to determine the nutritional value, health benefits, and safety of KPC for human consumption. Proximate analysis indicated KPC on a dry basis is composed of ∼78% protein and ∼8% fat of which ∼27% are omega-3 polyunsaturated fatty acids (o-3 PUFAs). The amino acid composition of KPC indicated that all nine essential amino acids were present in amounts that met the requirements for adult humans …
Differential Binding Of Hnrnp K, L And A2/B1 To An Exonic Splicing Silencer Element Located Within Exon 12 Of Glucose -6 -Phosphate Dehydrogenase Mrna, Brian Nelson Griffith
Differential Binding Of Hnrnp K, L And A2/B1 To An Exonic Splicing Silencer Element Located Within Exon 12 Of Glucose -6 -Phosphate Dehydrogenase Mrna, Brian Nelson Griffith
Graduate Theses, Dissertations, and Problem Reports
The expression of most lipogenic enzymes is regulated through the effects of dietary polyunsaturated fatty acids on transcription. However, we have observed that the regulation of Glucose-6-phosphate dehydrogenase (G6PD) by polyunsaturated fatty acids occurs through a novel posttranscriptional mechanism. RNA reporter assays were used to map the cis-acting element by measuring the regulation of each RNA reporter construct transfected into primary rat hepatocytes. All RNA reporter constructs were regulated by polyunsaturated fatty acids with the exception of RNA reporter constructs lacking exon 12. Therefore, polyunsaturated fatty acids regulate the constitutive splicing of G6PD mRNA through a cis-acting element located within …
Analysis Of The Mechanisms Mediating The Regulation Of Acetyl -Coa Carboxylase Transcription By The Liver X Receptor And Chenodeoxycholic Acid, Saswata Talukdar
Analysis Of The Mechanisms Mediating The Regulation Of Acetyl -Coa Carboxylase Transcription By The Liver X Receptor And Chenodeoxycholic Acid, Saswata Talukdar
Graduate Theses, Dissertations, and Problem Reports
Agonists of the liver X receptor (LXR) prevent and decrease arterial plaque formation in experimental models of atherosclerosis. The anti-atherosclerotic effects of LXR agonists are mediated by an increase in expression of genes involved in cholesterol export. Currently, the therapeutic utility of LXR agonists is limited by the fact that these agents increase triglyceride levels in the blood and liver. These undesired effects are caused by an increase in transcription of genes controlling triglyceride synthesis, such as acetyl CoA carboxylasealpha (ACCalpha). We have demonstrated that a synthetic LXR agonist, T0-901317 increases ACCalpha via both a direct mechanism involving the activation …