The New Role Of Proprotein Convertase Subtilisin/Kexin Type 9: A Connection Of Proprotein Convertase Subtilisin/Kexin Type 9, Apolipoprotein B, And Autophagy,
2012
The University of Texas Graduate School of Biomedical Sciences at Houston
The New Role Of Proprotein Convertase Subtilisin/Kexin Type 9: A Connection Of Proprotein Convertase Subtilisin/Kexin Type 9, Apolipoprotein B, And Autophagy, Hua Sun
Dissertations and Theses (Open Access)
Plasma low-density lipoprotein (LDL) levels are positively correlated with the incidence of coronary artery disease. In the circulation, the plasma LDL clearance is mainly achieved by the uptake via LDL receptor (LDLR). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a newly discovered gene, playing an important role in LDL metabolism. Gain-of-function mutations of PCSK9 lead to hypercholesterolemia and loss-of-function mutations of PCSK9 are associated with decrease of LDL cholesterol. The effects of PCSK9 on cholesterol levels are the consequence of a strong interaction between the catalytic domain of PCSK9 and epidermal growth factor-like repeat A (EGF-A) domain of …
Metabolic Regulation Of Mtor Activation And Endoplasmic Reticulum Stress In The Heart,
2012
The University of Texas Graduate School of Biomedical Sciences at Houston
Metabolic Regulation Of Mtor Activation And Endoplasmic Reticulum Stress In The Heart, Shiraj Sen
Dissertations and Theses (Open Access)
When subjected to increased workload, the heart responds metabolically by increasing its reliance on glucose and structurally by increasing the size of myocytes. Whether changes in metabolism regulate the structural remodeling process is unknown. A likely candidate for a link between metabolism and growth in the heart is the mammalian target of rapamycin (mTOR), which couples energy and nutrient metabolism to cell growth. Recently, sustained mTOR activation has also been implicated in the development of endoplasmic reticulum (ER) stress. We explored possible mechanisms by which acute metabolic changes in the hemodynamically stressed heart regulate mTOR activation, ER stress and cardiac …
Regulation Of Protein Degradation In The Heart By Amp-Activated Protein Kinase,
2012
The University of Texas Graduate School of Biomedical Sciences at Houston
Regulation Of Protein Degradation In The Heart By Amp-Activated Protein Kinase, Kedryn K. Baskin
Dissertations and Theses (Open Access)
The degradation of proteins by the ubiquitin proteasome system is essential for cellular homeostasis in the heart. An important regulator of metabolic homeostasis is AMP-activated protein kinase (AMPK). During nutrient deprivation, AMPK is activated and intracellular proteolysis is enhanced through the ubiquitin proteasome system (UPS). Whether AMPK plays a role in protein degradation through the UPS in the heart is not known. Here I present data in support of the hypothesis that AMPK transcriptionally regulates key players in the UPS, which, under extreme conditions can be detrimental to the heart. The ubiquitin ligases MAFbx /Atrogin-1 and MuRF1, key regulators of …
Regulation Of Iron-Related Molecules In The Rat Hippocampus: Sex- And Age-Associated Differences,
2012
Marshall University
Regulation Of Iron-Related Molecules In The Rat Hippocampus: Sex- And Age-Associated Differences, Srinivasarao Thulluri, Miaozong Wu, Eric R. Blough, Nandini D.P.K. Manne, Ashley B. Litchfield, Bin Wang
MIIR Faculty Research
Iron accumulation, especially that of free oxidized ferrous iron, has been shown to induce tissue oxidative damage and contribute to brain aging and the development of neurodegenerative disease. Here we examine whether sex and advanced age affect the expression of iron-related molecules that participate in regulating free iron levels (heme oxygenase I (HOI), iron-regulatory protein I (IRPI), and ferritin heavy chain (FTH)) and whether changes in the expression of these molecules are associated with differences in the expression of alpha-synuclein (ASN) which is thought to be a critical regulator in the pathogenesis of neurodegeneration. Using a well-established aging animal model, …
Single-Chain Vαvβ T Cell Receptors Function Without
Mispairing With Endogenous Tcr Chains1,
2012
University of Illinois
Single-Chain Vαvβ T Cell Receptors Function Without Mispairing With Endogenous Tcr Chains1, David H. Aggen, Adam S. Chervin, Thomas M. Schmitt, Boris Engels, Jennifer D. Stone, Sarah A. Richman, Kurt H. Piepenbrink, Brian M. Baker, Philip D. Greenberg, Hans Schreiber, David M. Kranz
Food for Health: Publications
Transduction of exogenous T cell receptor (TCR) genes into patients’ activated peripheral blood T cells is a potent strategy to generate large numbers of specific T cells for adoptive therapy of cancer and viral diseases. However, the remarkable clinical promise of this powerful approach is still being overshadowed by a serious potential consequence: mispairing of the exogenous TCR chains with endogenous TCR chains. These “mixed” heterodimers can generate new specificities that result in graft-versus-host reactions. Engineering TCR constant regions of the exogenous chains with a cysteine promotes proper pairing and reduces the mispairing, but, as we show here, does not …
Conformational Melding Permits A Conserved Binding Geometry
In Tcr Recognition Of Foreign And Self Molecular Mimics,
2012
University of Notre Dame
Conformational Melding Permits A Conserved Binding Geometry In Tcr Recognition Of Foreign And Self Molecular Mimics, Oleg Y. Borbulevych, Kurt H. Piepenbrink, Brian M. Baker
Food for Health: Publications
Molecular mimicry between foreign and self antigens is a mechanism of T cell receptor cross reactivity and is thought to contribute to the development of autoimmunity. The αβ TCR A6 recognizes the foreign antigen Tax from the virus HTLV-1 when presented by the class I MHC HLA-A2. In a possible link with the autoimmune disease HAM/TSP, A6 also recognizes a self peptide from the neuronal protein HuD in the context of HLA-A2. We found here that the complexes of the HuD and Tax epitopes with HLA-A2 are close but imperfect structural mimics, and that in contrast with other recent structures …
The Role Of Vascular Endothelial Growth Factor At The Blood-Brain Barrier In Diabetes,
2012
Marshall University
The Role Of Vascular Endothelial Growth Factor At The Blood-Brain Barrier In Diabetes, Aileen J. Marcelo
Theses, Dissertations and Capstones
Diabetes is a risk factor for stroke and vascular dementia. Clinical studies using gadolinium-magnetic resonance imaging techniques have shown diabetic patients exhibit a permeability increase at the blood-brain barrier (BBB) (Starr et al, 2003). The BBB, a vascular interface at the level of brain microvascular vessels, functions to provide nutrients and oxygen from the peripheral circulation, mediates waste efflux from the brain, and protects the brain from toxins. These functions are due to the presence of tight junction proteins. Animal studies have shown increased BBB permeability is due to a decrease in these proteins (Hawkins et al, 2007). Based on …
Effects Of Adipocyte Deficiency Of Angiotensin Type 1a Receptors In Models Of Obesity And Hypercholesterolemia,
2012
University of Kentucky
Effects Of Adipocyte Deficiency Of Angiotensin Type 1a Receptors In Models Of Obesity And Hypercholesterolemia, Kelly Anne Putnam
Theses and Dissertations--Nutritional Sciences
Adipocytes express angiotensin II (AngII) receptors; however the direct effects of AngII at the adipocyte remain unclear. Knockout mouse models of renin-angiotensin system components exhibit reduced body weight, reduced adiposity, improved glucose tolerance, and improved blood pressure when fed high fat diets, which may be due to reduced action of AngII through the AT1aR in adipocytes. Additionally, hypercholesterolemic AT1aR deficient mice are protected from AngII-induced increases in atherosclerosis and abdominal aortic aneurysm (AAA) formation. We hypothesized that deficiency of AT1aR in adipocytes would reduce the development of obesity, obesity-induced disorders, and vascular diseases. To test this hypothesis, we created a …
Synthesis And Flame Retardant Testing Of New Boronated And Phosphonated Aromatic Compounds,
2012
University of Dayton
Synthesis And Flame Retardant Testing Of New Boronated And Phosphonated Aromatic Compounds, Vladimir Benin, Sravanthi Durganala, Alexander Morgan
Chemistry Faculty Publications
The present report describes the preparation and use of some dimethyl terephthalate derivatives in transition metal-catalyzed coupling reactions to produce new reactive flame retardants. Dimethyl iodoterephthalate and dimethyl 2,5-diiodoterephthalate were successfully employed in the preparation of phosphonic and boronic esters and acids. The latter were tested for heat release with a microcombustion calorimeter (ASTM D7309) to determine the potential for heat release reduction of these flame retardant molecules. The results showed that the addition of boronic or phosphonic acids greatly lowered the heat release, due to a condensed phase (char formation) mechanism. Adding ester groups to the boronic acids or …
The Emerging Role Of Acyl-Coa Thioesterases And Acyltransferases In Regulating Peroxisomal Lipid Metabolism,
2012
Technological University Dublin
The Emerging Role Of Acyl-Coa Thioesterases And Acyltransferases In Regulating Peroxisomal Lipid Metabolism, Mary Hunt, Marina Siponen, Stefan Alexson
Articles
The importance of peroxisomes in lipid metabolism is now well established and peroxisomes contain approximately 60 enzymes involved in these lipid metabolic pathways. Several acyl-CoA thioesterase enzymes (ACOTs) have been identified in peroxisomes that catalyze the hydrolysis of acyl-CoAs (short-, medium-, long- and very long-chain), bile acid-CoAs, and methyl branched-CoAs, to the free fatty acid and coenzyme A. A number of acyltransferase enzymes, which are structurally and functionally related to ACOTs, have also been identified in peroxisomes, which conjugate (or amidate) bile acid-CoAs and acyl-CoAs to amino acids, resulting in the production of amidated bile acids and fatty acids. The …
Map Kinases Couple Hindbrain-Derived Catecholamine Signals To Hypothalamic Adrenocortical Control Mechanisms During Glycemia-Related Challenges,
2011
University of Texas at El Paso
Map Kinases Couple Hindbrain-Derived Catecholamine Signals To Hypothalamic Adrenocortical Control Mechanisms During Glycemia-Related Challenges, Arshad Khan, Kimberly Kaminski, Graciela Sanchez-Watts, Todd Ponzio, J. Kuzmiski, Jaideep Bains, Alan Watts
Selected Works Temporary Series
No abstract provided.
Map Kinases Couple Hindbrain-Derived Catecholamine Signals To Hypothalamic Adrenocortical Control Mechanisms During Glycemia-Related Challenges,
2011
University of Texas at El Paso
Map Kinases Couple Hindbrain-Derived Catecholamine Signals To Hypothalamic Adrenocortical Control Mechanisms During Glycemia-Related Challenges, Khan, Kimberly Kaminski, Graciela Sanchez-Watts, Todd Ponzio, J. Kuzmiski, Jaideep Bains, Alan Watts
Departmental Papers (Biology)
No abstract provided.
Disparate Degrees Of Hypervariable Loop Flexibility Control T Cell
Receptor Cross-Reactivity, Specificity, And Binding Mechanism,
2011
University of Notre Dame
Disparate Degrees Of Hypervariable Loop Flexibility Control T Cell Receptor Cross-Reactivity, Specificity, And Binding Mechanism, Daniel R. Scott, Oleg Y. Borbulevych, Kurt H. Piepenbrink, Steven A. Corcelli, Brian M. Baker
Food for Health: Publications
αβ T cell receptors recognize multiple antigenic peptides bound and presented by major histocompatibility complex molecules. TCR cross-reactivity has been attributed in part to flexibility of the complementarity-determining region loops, yet there have been limited direct studies of loop dynamics to determine the extent of its role. Here we studied the flexibility of the binding loops of the αβ TCR A6 utilizing crystallographic, spectroscopic, and computational methods. A significant role for flexibility in binding and cross-reactivity was indicated only for the CDR3α and CDR3β hypervariable loops. Examination of the energy landscapes of these two loops indicated that CDR3β possesses a …
The Tetrafluoroborate Salt Of 4-Methoxybenzyl N-2-(Dimethylamino)Ethyl-N-Nitrosocarbamate: Synthesis, Crystal Structure And Dft Calculations,
2011
University of Dayton
The Tetrafluoroborate Salt Of 4-Methoxybenzyl N-2-(Dimethylamino)Ethyl-N-Nitrosocarbamate: Synthesis, Crystal Structure And Dft Calculations, Helene Hedian, Vladimir Benin
Chemistry Faculty Publications
The tetrafluoroborate salt of 4-methoxybenzyl N-2-(dimethylamino)ethyl-N-nitrosocarbamate was prepared in two steps, via the corresponding carbamate. Its crystal structure is monoclinic, space group P21/c. The unit cell dimensions are: a = 19.499(8) Å, b = 5.877(3) Å, c = 15.757(7) Å, α = 90°, β = 110.019(7)°, γ = 90°, V = 1696.5(12) Å3, Z = 4. The structure exhibits an unexpected, pseudo-gauche conformation with respect to the C2–C3 bond, due to a stabilizing hydrogen bond between the carbonyl oxygen (O1) and the hydrogen atom at the trialkylammonium center (H3n), with a distance between them of …
Using Lectinmicroarrays To Identify Regulatory Mechanisms For Mammalian Glycosylation,
2011
Marshall University
Using Lectinmicroarrays To Identify Regulatory Mechanisms For Mammalian Glycosylation, John F. Rakus
Chemistry Faculty Research
Glycosylation involves the post-translational addition of carbohydrates to protein molecules and is an intricate and indispensable biochemical process. Study of this complicated network of interactions is hindered by the lack of a coding template analogous to the genetic code, and by the vast structural complexity inherent to carbohydrate polymers. We use lectins (non-enzymatic carbohydrate-binding proteins of non-immunological origin) as microarray probes to identify carbohydrate features expressed on cellular surfaces. Specifically, we utilized lectin microarray technology to investigate the differences in carbohydrates expressed by the cell lines of the Nation Cancer Institute’s NCI-60 panel. Our investigation identified tissue-specific expression differences in …
Application Of Raman Spectroscopy To Lubricants, Lubricated Surfaces And Lubrication Phenomena,
2011
University of Dayton
Application Of Raman Spectroscopy To Lubricants, Lubricated Surfaces And Lubrication Phenomena, David W. Johnson
Chemistry Faculty Publications
Recent advances in lasers and detector technologies and the development of low-cost instruments and fiber-optic probes have brought about an explosion in the lubrication systems being studied by Raman spectroscopy. This article provides examples of the use of Raman spectroscopy in the study of lubrication phenomena, including the characterization of liquid lubricants, lubricant additives, and solid lubricants; the study of vapor-phase lubrication; and the use of coated nanoparticles as lubricants.
The Effects Of Curcumin On Body Composition Of Patients With Advanced Pancreatic Cancer,
2011
The University of Texas Graduate School of Biomedical Sciences at Houston
The Effects Of Curcumin On Body Composition Of Patients With Advanced Pancreatic Cancer, Henrique A. Parsons Md
Dissertations and Theses (Open Access)
Cachexia is very common among patients with advanced pancreatic cancer and is a marker of poor prognosis. Weight loss in cachexia is due to both adipose and muscle compartments, and sarcopenia (severe muscle depletion) is associated with worse outcomes. Curcumin has shown a myriad of biological effects, including anti-cancer and anti-inflammatory. The ability of curcumin to attenuate cachexia and muscle loss has been tested in animal models, with conflicting results so far. The hypothesis of this study was that patients with advanced pancreatic cancer treated with curcumin for two months have less fat and muscle loss as compared to matched …
Identification And Engineering Of Human
Variable Regions That Allow Expression Of
Stable Single-Chain T Cell Receptors,
2011
University of Illinois
Identification And Engineering Of Human Variable Regions That Allow Expression Of Stable Single-Chain T Cell Receptors, David H. Aggen, Adam S. Chervin, Francis K. Insaidoo, Kurt H. Piepenbrink, Brian M. Baker, David M. Kranz
Food for Health: Publications
Single-chain antibody fragments (scFv), consisting of two linked variable regions (VH and VL), are a versatile format for engineering and as potential antigen-specific therapeutics. Although the analogous format for T cell receptors (TCRs), consisting of two linked V regions (Vα and Vβ; referred to here as scTv), could provide similar opportunities, all wild-type scTv proteins examined to date are unstable. This obstacle has prevented scTv fragments from being widely used for engineering or therapeutics. To further explore whether some stable human scTv fragments could be expressed, we used a yeast system in which display of properly folded …
Chelation Therapy As A Treatment For Autism,
2011
University of Nevada, Las Vegas
Chelation Therapy As A Treatment For Autism, Cassandra Baty, Rachel Terharr
Festival of Communities: UG Symposium (Posters)
As medical advances continue to be made, there has yet to be an effectively consistent cure to the commonly known condition, Autism. Some researchers and physicians state that by using chelation therapy, it could help cure mercury poisoning in autistic individuals who were affected by vaccines or other sources. Because of the lack of research and knowledge of chelation therapy, there has been some controversy as to the ethics of providing chelation therapy to autistic children. The families that are put through these trials are faced with high costs, and no guarantee that their child could be cured. But to …
A Sodium Salt Of The Dimer Of Boronoterephthalic Acid Anhydride,
2011
University of Dayton
A Sodium Salt Of The Dimer Of Boronoterephthalic Acid Anhydride, Scott Simmons, Albert Fratini, Vladimir Benin
Chemistry Faculty Publications
The title compound, sodium bis(6-carboxy-1-hydroxy-3-oxo-1,3-dihydro-2,1-benzoxaborol-1-yl)oxidanium, Na+·C16H15B2O13-, was prepared in two steps from 2-bromo-p-xylene. Its crystal structure was determined at 140 K and has triclinic (P) symmetry. The compound presents a unique structural motif, including two units of the cyclic anhydride of boronoterephthalic acid, joined by a protonated, and thereby trivalent, oxonium center. Association in the crystal is realized by complementary hydrogen bonding of the carboxyl groups, as well as by coordination of the sodium cations to the oxygen centers on the five-membered rings.
