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2009

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Articles 241 - 270 of 279

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Generation Of A Reporter Library Of Eralpha Interacting Dna Sequences, Cormac Jennings Jan 2009

Generation Of A Reporter Library Of Eralpha Interacting Dna Sequences, Cormac Jennings

Masters

Oestrogens are a group of steroid hormones of which oestradiol is the major form. Oestrogens are present in men and women and some of their main physiological roles involve female and male reproduction, bone metabolism and homeostasis. Oestrogens carry out their actions by diffusing across the cell membrane and binding to their receptor called the oestrogen receptor (ER), of which two types exist, ERα and ERβ. ERs regulate gene expression through the binding of DNA, most notably the estrogen response element (ERE). Breast cancer is the most common malignancy in women in industrialised countries and 65 percent of breast cancers …


Probing The Urea Dependence Of Residual Structure In Denatured Human Α-Lactalbumin, Victoria A. Higman, Heike I. Rösner, Raffaella Ugolini, Lesley H. Greene, Christina Redfield, Lorna J. Smith Jan 2009

Probing The Urea Dependence Of Residual Structure In Denatured Human Α-Lactalbumin, Victoria A. Higman, Heike I. Rösner, Raffaella Ugolini, Lesley H. Greene, Christina Redfield, Lorna J. Smith

Chemistry & Biochemistry Faculty Publications

Backbone 15N relaxation parameters and 15N–1HN residual dipolar couplings (RDCs) have been measured for a variant of human α-lactalbumin (α-LA) in 4, 6, 8 and 10 M urea. In the α-LA variant, the eight cysteine residues in the protein have been replaced by alanines (all-Ala α-LA). This protein is a partially folded molten globule at pH 2 and has been shown previously to unfold in a stepwise non-cooperative manner on the addition of urea. 15N R2 values in some regions of all-Ala α-LA show significant exchange broadening which is reduced as the urea …


Comparative Efficacy Of Bioud To Other Commercially Available Arthropod Repellants Against The Ticks Amblyomma Americanum And Dermacentor Variabilis On Cotton Cloth, Brooke W. Bissinger, Jiwei Zhu, Charles S. Apperson, Daniel E. Sonenshine, D. Wesley Watson, R. Michael Roe Jan 2009

Comparative Efficacy Of Bioud To Other Commercially Available Arthropod Repellants Against The Ticks Amblyomma Americanum And Dermacentor Variabilis On Cotton Cloth, Brooke W. Bissinger, Jiwei Zhu, Charles S. Apperson, Daniel E. Sonenshine, D. Wesley Watson, R. Michael Roe

Biological Sciences Faculty Publications

BioUD is an arthropod repellent that contains the active ingredient 2-undecanone originally derived from wild tomato plants. Repellency of BioUD was compared with five commercially available arthropod repellents against the ticks Amblyomma americanum (L.) and Dermacentor variabilis Say in two-choice bioassays on treated versus untreated cotton cheesecloth. Overall mean percentage repellency against both species was greatest for and did not differ significantly between BioUD (7.75% 2-undecanone) and products containing 98.1% DEET, 19.6% IR3535, and 30% oil of lemon eucalyptus. Products containing 5% and 15% Picaridin and 0.5% permethrin were also repellent compared with untreated controls but to a lesser degree …


Substrate And Regulation Of Mitochondrial Μ-Calpain, Aashish Joshi Jan 2009

Substrate And Regulation Of Mitochondrial Μ-Calpain, Aashish Joshi

University of Kentucky Doctoral Dissertations

μ -Calpain is localized to the mitochondrial intermembrane space. Apoptosisinducing factor (AIF), which executes caspase-independent cell death, is also localized to the mitochondrial intermembrane space. Following processing at the N-terminus, AIF becomes truncated (tAIF) and is released from mitochondria. The protease responsible for AIF processing has not been established. The same submitochondrial localization of mitochondrial μ-calpain and AIF gives support to the hypothesis that mitochondrial μ-calpain may be responsible for processing AIF. Atractyloside-induced tAIF release in rat liver mitochondria was inhibited by cysteine protease inhibitor MDL28170, but not by calpain inhibitors PD150606 or calpastatin. Moreover, μ-calpain immunoreactivity was difficult to …


Due-B, A New Human Dna Replication Protein, Is The Functional Homolog Of S. Cerevisiae Sld3, Jianhong Yao Jan 2009

Due-B, A New Human Dna Replication Protein, Is The Functional Homolog Of S. Cerevisiae Sld3, Jianhong Yao

Browse all Theses and Dissertations

DNA unwinding elements (DUEs) are commonly found at DNA replication origins. The DUE binding protein (DUE-B) is crucial for the initiation of DNA replication in eukaryotes. The unique 59 amino acid C-terminal part of DUE-B shares nearly 50% similarity with yeast the C-terminus of Sld3. DUE-B plays a key role in eukaryotic DNA replication because it is required for the loading of Cdc45, the MCM helicase activator, on chromatin. Here we show that DUE-B, just like yeast Sld3, binds to Cdc45 and TopBP1 through its C-terminus in Sf9 cells and in vitro. We also show that DUE-B, Cdc45 and TopBP1 …


Dose-Dependent Effects Of Oxygen On Metabolism In Rat Cortico-Hippocampal Brain Tissue Slices, Jennifer Lynne Hollyfield Jan 2009

Dose-Dependent Effects Of Oxygen On Metabolism In Rat Cortico-Hippocampal Brain Tissue Slices, Jennifer Lynne Hollyfield

Browse all Theses and Dissertations

Studies have shown that 95% oxygen increases neuronal excitability and ROS production. We wanted to investigate the dose-dependent effects of oxygen on brain slice metabolism. We exposed rat brain cortico-hippocampal tissue slices to 0.40, 0.95, and 4.50 ATA O2 for 60 minutes, made dual-phase tissue extracts, and used multi-nuclear NMR experiments to elucidate the slice metabolism. We found that low doses of oxygen may shift metabolism toward anaerobic glycolysis. Elevated lactate suggests this shift, along with elevated ratios of NAD+/NADH which may drive the reactions toward the production of lactate. The results also suggest that high doses of oxygen may …


A Herpesvirus Encoded Deubiquitinase Is A Novel Neuroinvasive Determinant, Joy I. Lee, Patricia J. Sollars, Scott B. Baver, Gary E. Pickard, Mindy Leelawong, Gregory A. Smith Jan 2009

A Herpesvirus Encoded Deubiquitinase Is A Novel Neuroinvasive Determinant, Joy I. Lee, Patricia J. Sollars, Scott B. Baver, Gary E. Pickard, Mindy Leelawong, Gregory A. Smith

School of Veterinary and Biomedical Sciences: Faculty Publications

The neuroinvasive property of several alpha-herpesviruses underlies an uncommon infectious process that includes the establishment of life-long latent infections in sensory neurons of the peripheral nervous system. Several herpesvirus proteins are required for replication and dissemination within the nervous system, indicating that exploiting the nervous system as a niche for productive infection requires a specialized set of functions encoded by the virus. Whether initial entry into the nervous system from peripheral tissues also requires specialized viral functions is not known. Here we show that a conserved deubiquitinase domain embedded within a pseudorabies virus structural protein, pUL36, is essential for initial …


Regulation Of Innate Immune Responses By Bovine Herpesvirus 1 And Infected Cell Protein 0 (Bicp0), Clinton Jones Jan 2009

Regulation Of Innate Immune Responses By Bovine Herpesvirus 1 And Infected Cell Protein 0 (Bicp0), Clinton Jones

School of Veterinary and Biomedical Sciences: Faculty Publications

Bovine herpesvirus 1 (BoHV-1) infected cell protein 0 (bICP0) is an important transcriptional regulatory protein that stimulates productive infection. In transient transfection assays, bICP0 also inhibits interferon dependent transcription. bICP0 can induce degradation of interferon stimulatory factor 3 (IRF3), a cellular transcription factor that is crucial for activating beta interferon (IFN-β) promoter activity. Recent studies also concluded that interactions between bICP0 and IRF7 inhibit trans-activation of IFN-β promoter activity. The C3HC4 zinc RING (really important new gene) finger located near the amino terminus of bICP0 is important for all known functions of bICP0. A recombinant virus that contains a single …


Spontaneous Idiopathic Arteritis Of The Testicular Artery In Raccoons (Procyon Lotor), A. N. Hamir, M. V. Palmer, H. Li, J. Stasko, D. G. Rogers Jan 2009

Spontaneous Idiopathic Arteritis Of The Testicular Artery In Raccoons (Procyon Lotor), A. N. Hamir, M. V. Palmer, H. Li, J. Stasko, D. G. Rogers

School of Veterinary and Biomedical Sciences: Faculty Publications

The testes and the spermatic cord of raccoons (Procyon lotor, kits to adult breeders; n = 48) were examined. Segmental arteritis confined to the extratesticular portions of the testicular artery was present in raccoons of all ages. The arterial changes were seen in laboratory-confined experimental and control animals as well as in wild-caught raccoons. The lesions consisted of proliferative endarteritis with presence of inflammatory cells within the intima, media, and the adventitial regions of most affected vessels. Some aspects of the proliferative arterial lesions were reminiscent of systemic necrotizing vasculitis (polyarteritis nodosa), an immunologically mediated condition of animals and humans. …


The Selenoproteome Of Clostridium Sp. Ohilas: Characterization Of Anaerobic Bacterial Selenoprotein Methionine Sulfoxide Reductase A, Hwa Young, Yan Zhang, Byung Cheon Lee, Jae-Ryong Kim, Vadim N. Gladyshev Jan 2009

The Selenoproteome Of Clostridium Sp. Ohilas: Characterization Of Anaerobic Bacterial Selenoprotein Methionine Sulfoxide Reductase A, Hwa Young, Yan Zhang, Byung Cheon Lee, Jae-Ryong Kim, Vadim N. Gladyshev

Vadim Gladyshev Publications

Selenocysteine (Sec) is incorporated into proteins in response to UGA codons. This residue is frequently found at the catalytic sites of oxidoreductases. In this study, we characterized the selenoproteome of an anaerobic bacterium, Clostridium sp. (also known as Alkaliphilus oremlandii) OhILA, and identified 13 selenoprotein genes, five of which have not been previously described. One of the detected selenoproteins was methionine sulfoxide reductase A (MsrA), an antioxidant enzyme that repairs oxidatively damaged methionines in a stereospecific manner. To date, little is known about MsrA from anaerobes. We characterized this selenoprotein MsrA which had a single Sec residue at the catalytic …


X-Ray Fluorescence Microscopy Reveals The Role Of Selenium In Spermatogenesis, Sebastian Kehr, Mikalai I. Malinouski, Lydia Finney, Stefan Vogt, Vyacheslav M. Labunskyy, Marina V. Kasaikina, Bradley A. Carlson, You Zhou, Dolph L. Hatfield, Vadim N. Gladyshev Jan 2009

X-Ray Fluorescence Microscopy Reveals The Role Of Selenium In Spermatogenesis, Sebastian Kehr, Mikalai I. Malinouski, Lydia Finney, Stefan Vogt, Vyacheslav M. Labunskyy, Marina V. Kasaikina, Bradley A. Carlson, You Zhou, Dolph L. Hatfield, Vadim N. Gladyshev

Vadim Gladyshev Publications

Selenium (Se) is a trace element with important roles in human health. Several selenoproteins have essential functions in development. However, the cellular and tissue distribution of Se remains largely unknown because of the lack of analytical techniques that image this element with sufficient sensitivity and resolution. Herein, we report that X-ray fluorescence microscopy (XFM) can be used to visualize and quantify the tissue, cellular and subcellular topography of Se. We applied this technique to characterize the role of Se in spermatogenesis and identified a dramatic Se enrichment specifically in late spermatids, a pattern that was not seen in any other …


Comparative Genomic Analyses Of Nickel, Cobalt And Vitamin B12 Utilization, Yan Zhang, Dmitry Rodionov, Mikhail Gelfand, Vadim N. Gladyshev Jan 2009

Comparative Genomic Analyses Of Nickel, Cobalt And Vitamin B12 Utilization, Yan Zhang, Dmitry Rodionov, Mikhail Gelfand, Vadim N. Gladyshev

Vadim Gladyshev Publications

Background: Nickel (Ni) and cobalt (Co) are trace elements required for a variety of biological processes. Ni is directly coordinated by proteins, whereas Co is mainly used as a component of vitamin B12. Although a number of Ni and Co-dependent enzymes have been characterized, systematic evolutionary analyses of utilization of these metals are limited. Results: We carried out comparative genomic analyses to examine occurrence and evolutionary dynamics of the use of Ni and Co at the level of (i) transport systems, and (ii) metalloproteomes. Our data show that both metals are widely used in bacteria and archaea. Cbi/NikMNQO …


Eukaryotic Selenoproteins And Selenoproteomes, Alexey V. Lobanov, Dolph L. Hatfield, Vadim N. Gladyshev Jan 2009

Eukaryotic Selenoproteins And Selenoproteomes, Alexey V. Lobanov, Dolph L. Hatfield, Vadim N. Gladyshev

Vadim Gladyshev Publications

Selenium is an essential trace element for which both beneficial and toxic effects in human health have been described. It is now clear that the importance of having adequate amounts of this micronutrient in the diet is primarily due to the fact that selenium is required for biosynthesis of selenocysteine, the twenty first naturally occurring amino acid in protein. In this review, we provide an overview of eukaryotic selenoproteins and selenoproteomes, which are sets of selenoproteins in these organisms. In eukaryotes, selenoproteins show a mosaic occurrence, with some organisms, such as vertebrates and algae, having dozens of these proteins, while …


Overexpression Of Methionine-R-Sulfoxide Reductases Has No Influence On Fruit Fly Aging, Valentina A. Shchedrina, Gerd Vorbrüggen, Byung Cheon Lee, Hwa-Young Kim, Hadise Kabil, Lawrence G. Harshman, Vadim N. Gladyshev Jan 2009

Overexpression Of Methionine-R-Sulfoxide Reductases Has No Influence On Fruit Fly Aging, Valentina A. Shchedrina, Gerd Vorbrüggen, Byung Cheon Lee, Hwa-Young Kim, Hadise Kabil, Lawrence G. Harshman, Vadim N. Gladyshev

Vadim Gladyshev Publications

Methionine sulfoxide reductases (Msrs) are enzymes that repair oxidized methionine residues in proteins. This function implicated Msrs in antiox¬idant defense and the regulation of aging. There are two known Msr types in animals: MsrA specific for the reduction of methionine-S-sulfoxide, and MsrB that catalyzes the reduction of methionine-R-sulfoxide. In a previous study, overexpression of MsrA in the nervous system of Drosophila was found to extend lifespan by 70%. Overexpression of MsrA in yeast also extended lifespan, whereas MsrB overexpression did so only under cal¬orie restriction conditions. The effect of MsrB overexpression on lifespan has not yet been characterized in animal …


Characterization And Performance Of A Near-Infrared 2-Deoxyglucose Optical Imaging Agent For Mouse Cancer Models, Joy L. Kovar, William Volcheck, Eva Sevick-Muraca, Melanie A. Simpson, D. Michael Olive Jan 2009

Characterization And Performance Of A Near-Infrared 2-Deoxyglucose Optical Imaging Agent For Mouse Cancer Models, Joy L. Kovar, William Volcheck, Eva Sevick-Muraca, Melanie A. Simpson, D. Michael Olive

Department of Biochemistry: Faculty Publications

Malignant neoplasms exhibit an elevated rate of glycolysis over normal cells. This characteristic can be exploited for optical imaging of tumors in mice. A near-infrared fluorophore, IRDye 800CW, emission maximum 794 nm, was conjugated to 2-deoxyglucose (2-DG). An immunofluorescent cell-based assay was used to evaluate specificity and sensitivity of the conjugate in cultured cell monolayers. Dose-dependent uptake was established with increasing concentrations of IRDye 800CW 2-DG for epithelial and prostate carcinomas. IRDye 800CW 2-DG was specifically blocked by an antibody against GLUT1 glucose transporter, and by excess unlabeled 2-DG or d-glucose. Signal was increased by a phorbol ester activator of …


Hyaluronan-Binding Proteoglycans, Ed Harris, Paul H. Weigel Jan 2009

Hyaluronan-Binding Proteoglycans, Ed Harris, Paul H. Weigel

Department of Biochemistry: Faculty Publications

Molecular components of the extracellular matrix (ECM) are critical for matrix stabilization, cellular differentiation, and tissue morphogenesis. Once thought to function only as the extracellular glue that primarily binds cells together, proteoglycans in the ECM carry out a diverse array of activities and can be grouped into five functionally based families: (i) hyalectins (lecticans), which contain lectin-like carbohydrate-recognition domains (CRDs) and bind hyaluronan (HA); (ii) heparan sulfate (HS) proteoglycans that sequester growth factors via their HS chains; (iii) small leucine-rich proteoglycans (SLRPs) containing leucine-rich domains that interact with collagens and other ECM proteins; (iv) phosphacans that function primarily as receptor-like …


Functional Aspects Of The Hyaluronan And Chondroitin Sulfate Receptors, Ed Harris, Paul H. Weigel Jan 2009

Functional Aspects Of The Hyaluronan And Chondroitin Sulfate Receptors, Ed Harris, Paul H. Weigel

Department of Biochemistry: Faculty Publications

Glycosaminoglycans (GAGs) are distinct from other sugars/oligosaccharides in that they are polymers of disaccharide units composed of an amino sugar, N-acetylglucosamine (GlcNAc), or N-acetylgalactosamine (GalNAc), and uronic acid, glucuronic acid (GlcUA), or iduronic acid (IdUA). The exception is keratan sulfate (KS) in which the uronic acid is replaced by the neutral sugar galactose. Initially, GAGs were thought to be just part of an extracellular glue or ground substance that held tissues together and provided a liquid-like space between cells for the transport of nutrients. However, research using new technologies and techniques over the last two decades has revealed that the …


Polyploidy Creates Higher Diversity Among Cynodon Accessions As Assessed By Molecular Markers, Osman Gulsen, Songul Sever-Mutlu, Nedim Mutlu, Metin Tuna, Osman Karaguzel, Robert C. Shearman, Terrance P. Riordan, Tiffany M. Heng-Moss Jan 2009

Polyploidy Creates Higher Diversity Among Cynodon Accessions As Assessed By Molecular Markers, Osman Gulsen, Songul Sever-Mutlu, Nedim Mutlu, Metin Tuna, Osman Karaguzel, Robert C. Shearman, Terrance P. Riordan, Tiffany M. Heng-Moss

Department of Biochemistry: Faculty Publications

Developing a better understanding of associations among ploidy level, geographic distribution, and genetic diversity of Cynodon accessions could be beneficial to bermudagrass breeding programs, and would enhance our understanding of the evolutionary biology of this warm season grass species. This study was initiated to: (1) determine ploidy analysis of Cynodon accessions collected from Turkey, (2) investigate associations between ploidy level and diversity, (3) determine whether geographic and ploidy distribution are related to nuclear genome variation, and (4) correlate among four nuclear molecular marker systems for Cynodon accessions’ genetic analyses. One hundred and eighty-two Cynodon accessions collected in Turkey from an …


Copper Transport Into The Secretory Pathway Is Regulated By Oxygen In Macrophages, Carine White, Taiho Kambe, Yan G. Fulcher, Sherri W. Sachdev, Ashley I. Bush, Kevin Fritsche, Jaekwon Lee, Thomas P. Quinn, Michael J. Petris Jan 2009

Copper Transport Into The Secretory Pathway Is Regulated By Oxygen In Macrophages, Carine White, Taiho Kambe, Yan G. Fulcher, Sherri W. Sachdev, Ashley I. Bush, Kevin Fritsche, Jaekwon Lee, Thomas P. Quinn, Michael J. Petris

Department of Biochemistry: Faculty Publications

Copper is an essential nutrient for a variety of biochemical processes; however, the redox properties of copper also make it potentially toxic in the free form. Consequently, the uptake and intracellular distribution of this metal is strictly regulated. This raises the issue of whether specific pathophysiological conditions can promote adaptive changes in intracellular copper distribution. In this study, we demonstrate that oxygen limitation promotes a series of striking alterations in copper homeostasis in RAW264.7 macrophage cells. Hypoxia was found to stimulate copper uptake and to increase the expression of the copper importer, CTR1. This resulted in increased copper delivery to …


Targeting The Fatty Acid Transport Proteins (Fatp) To Understand The Mechanisms Linking Fatty Acid Transport To Metabolism, Paul N. Black, Angel Sandoval, Elsa Arias-Barrau, Concetta C. Dirusso Jan 2009

Targeting The Fatty Acid Transport Proteins (Fatp) To Understand The Mechanisms Linking Fatty Acid Transport To Metabolism, Paul N. Black, Angel Sandoval, Elsa Arias-Barrau, Concetta C. Dirusso

Department of Biochemistry: Faculty Publications

One principal process driving fatty acid transport is vectorial acylation, where fatty acids traverse the membrane concomitant with activation to CoA thioesters. Current evidence is consistent with the proposal that specific fatty acid transport (FATP) isoforms alone or in concert with specific long chain acyl CoA synthetase (Acsl) isoforms function to drive this energy-dependent process. Understanding the details of vectorial acylation is of particular importance as disturbances in lipid metabolism many times leads to elevated levels of circulating free fatty acids, which in turn increases fatty acid internalization and ectopic accumulation of triglycerides. This is associated with changes in fatty …


Glucose Promotes Stress Resistance In The Fungal Pathogen Candida Albicans, Alexandra Rodaki, Iryna M. Bohovych, Brice Enjalbert, Tim Young, Frank C. Odds, Neil A.R. Gow, Alistair J.P. Brown Jan 2009

Glucose Promotes Stress Resistance In The Fungal Pathogen Candida Albicans, Alexandra Rodaki, Iryna M. Bohovych, Brice Enjalbert, Tim Young, Frank C. Odds, Neil A.R. Gow, Alistair J.P. Brown

Department of Biochemistry: Faculty Publications

Metabolic adaptation, and in particular the modulation of carbon assimilatory pathways during disease progression, is thought to contribute to the pathogenicity of Candida albicans. Therefore, we have examined the global impact of glucose upon the C. albicans transcriptome, testing the sensitivity of this pathogen to wide-ranging glucose levels (0.01, 0.1, and 1.0%). We show that, like Saccharomyces cerevisiae, C. albicans is exquisitely sensitive to glucose, regulating central metabolic genes even in response to 0.01% glucose. This indicates that glucose concentrations in the bloodstream (approximate range 0.05–0.1%) have a significant impact upon C. albicans gene regulation. However, in contrast …


A Role For The Atp7a Copper-Transporting Atpase In Macrophage Bactericidal Activity, Carine White, Jaekwon Lee, Taiho Kambe, Kevin Fritsche, Michael J. Petris Jan 2009

A Role For The Atp7a Copper-Transporting Atpase In Macrophage Bactericidal Activity, Carine White, Jaekwon Lee, Taiho Kambe, Kevin Fritsche, Michael J. Petris

Department of Biochemistry: Faculty Publications

Copper is an essential micronutrient that is necessary for healthy immune function. This requirement is underscored by an increased susceptibility to bacterial infection in copper-deficient animals; however, a molecular understanding of its importance in immune defense is unknown. In this study, we investigated the effect of proinflammatory agents on copper homeostasis in RAW264.7 macrophages. Interferon-γ was found to increase expression of the high affinity copper importer, CTR1, and stimulate copper uptake. This was accompanied by copper-stimulated trafficking of the ATP7A copper exporter from the Golgi to vesicles that partially overlapped with phagosomal compartments. Silencing of ATP7A expression attenuated bacterial killing, …


Copper Transport Activity Of Yeast Ctr1 Is Down-Regulated Via Its C Terminus In Response To Excess Copper, Xiaobin Wu, Devis Sinani, Heejeong Kim, Jaekwon Lee Jan 2009

Copper Transport Activity Of Yeast Ctr1 Is Down-Regulated Via Its C Terminus In Response To Excess Copper, Xiaobin Wu, Devis Sinani, Heejeong Kim, Jaekwon Lee

Department of Biochemistry: Faculty Publications

Copper is an essential yet toxic trace element. The Ctr1 family of proteins plays a critical role for copper uptake in eukaryotes. However, the mechanisms of action of Ctr1 are largely unknown. Our previous data demonstrated that copper transport induces conformational changes in the cytosolic C terminus of the yeast Saccharomyces cerevisiae Ctr1. To define the physiological significance of this molecular event and gain better insights into the mechanism of Ctr1-mediated copper uptake, we have characterized the functional roles of the Ctr1 C terminus.ACtr1 mutant lacking the entire C-terminal cytosolic tail is functional in high affinity copper uptake; however, yeast …


Contribution Of Impaired Myocardial Insulin Signaling To Mitochondrial Dysfunction And Oxidative Stress In The Heart, Sihem Boudina, Heiko Bugger, Sandra Sena, Brian T. O'Neill, Vlad G. Zaha, Olesya Ilkun, Jordan J. Wright, Pradip K. Mazumber, Eric Palfreyman, Timothy J. Tidwell, Heather Theobald, Oleh Khalimonchuk, Benjamin Wayment, Xiaoming Sheng, Kenneth J. Rodnick, Ryan Centini, Dong Chen, Sheldon E. Litwin, Bart E. Weimer, E. Dale Abel Jan 2009

Contribution Of Impaired Myocardial Insulin Signaling To Mitochondrial Dysfunction And Oxidative Stress In The Heart, Sihem Boudina, Heiko Bugger, Sandra Sena, Brian T. O'Neill, Vlad G. Zaha, Olesya Ilkun, Jordan J. Wright, Pradip K. Mazumber, Eric Palfreyman, Timothy J. Tidwell, Heather Theobald, Oleh Khalimonchuk, Benjamin Wayment, Xiaoming Sheng, Kenneth J. Rodnick, Ryan Centini, Dong Chen, Sheldon E. Litwin, Bart E. Weimer, E. Dale Abel

Department of Biochemistry: Faculty Publications

Background—Diabetes-associated cardiac dysfunction is associated with mitochondrial dysfunction and oxidative stress, which may contribute to LV dysfunction. The contribution of altered myocardial insulin action, independently of associated changes in systemic metabolism is incompletely understood. The present study tested the hypothesis that perinatal loss of insulin signaling in the heart impairs mitochondrial function.

Methods and Results—In 8-week-old mice with cardiomyocyte deletion of insulin receptors (CIRKO), inotropic reserves were reduced and mitochondria manifested respiratory defects for pyruvate that was associated with proportionate reductions in catalytic subunits of pyruvate dehydrogenase. Progressive age-dependent defects in oxygen consumption and ATP synthesis with the substrates glutamate …


Sdh5, A Gene Required For Flavination Of Succinate Dehydrogenase, Is Mutated In Paraganglioma, Huai-Xiang Hao, Oleh Khalimonchuk, Margit Schraders, Noah Dephoure, Jean-Pierre Bayley, Henricus Kunst, Peter Devilee, Cor W.R.J. Cremers, Joshua D. Schiffman, Brandon G. Bentz, Steven P. Gygi, Dennis R. Winge, Hannie Kremer, Jared Rutter Jan 2009

Sdh5, A Gene Required For Flavination Of Succinate Dehydrogenase, Is Mutated In Paraganglioma, Huai-Xiang Hao, Oleh Khalimonchuk, Margit Schraders, Noah Dephoure, Jean-Pierre Bayley, Henricus Kunst, Peter Devilee, Cor W.R.J. Cremers, Joshua D. Schiffman, Brandon G. Bentz, Steven P. Gygi, Dennis R. Winge, Hannie Kremer, Jared Rutter

Department of Biochemistry: Faculty Publications

Mammalian mitochondria contain about 1100 proteins, nearly 300 of which are uncharacterized. Given the well-established role of mitochondrial defects in human disease, functional characterization of these proteins may shed new light on disease mechanisms. Starting with yeast as a model system, we investigated an uncharacterized but highly conserved mitochondrial protein (named here Sdh5). Both yeast and human Sdh5 interact with the catalytic subunit of the succinate dehydrogenase (SDH) complex, a component of both the electron transport chain and the tricarboxylic acid cycle. Sdh5 is required for SDH-dependent respiration and for Sdh1 flavination (incorporation of the flavin adenine dinucleotide cofactor). Germline …


Chemchains: A Platform For Simulation And Analysis Of Biochemical Networks Aimed To Laboratory Scientists, Tomáš Helikar, Jim A. Rogers Jan 2009

Chemchains: A Platform For Simulation And Analysis Of Biochemical Networks Aimed To Laboratory Scientists, Tomáš Helikar, Jim A. Rogers

Department of Biochemistry: Faculty Publications

Background: New mathematical models of complex biological structures and computer simulation software allow modelers to simulate and analyze biochemical systems in silico and form mathematical predictions. Due to this potential predictive ability, the use of these models and software has the possibility to compliment laboratory investigations and help refine, or even develop, new hypotheses. However, the existing mathematical modeling techniques and simulation tools are often difficult to use by laboratory biologists without training in high-level mathematics, limiting their use to trained modelers.

Results: We have developed a Boolean network-based simulation and analysis software tool, ChemChains, which combines the advantages of …


Ulk-Atg13-Fip200 Complexes Mediate Mtor Signaling To The Autophagy Machinery, Chang Hwa Jung, Chang Bong Jun, Seung-Hyun Ro, Young-Mi Kim, Neil Michael Otto, Jing Cao, Mondira Kundu, Do-Hyung Kim Jan 2009

Ulk-Atg13-Fip200 Complexes Mediate Mtor Signaling To The Autophagy Machinery, Chang Hwa Jung, Chang Bong Jun, Seung-Hyun Ro, Young-Mi Kim, Neil Michael Otto, Jing Cao, Mondira Kundu, Do-Hyung Kim

Department of Biochemistry: Faculty Publications

Autophagy, the starvation-induced degradation of bulky cytosolic components, is up-regulated in mammalian cells when nutrient supplies are limited. Although mammalian target of rapamycin (mTOR) is known as the key regulator of autophagy induction, the mechanism by which mTOR regulates autophagy has remained elusive. Here, we identify that mTOR phosphorylates a mammalian homologue of Atg13 and the mammalian Atg1 homologues ULK1 and ULK2. The mammalian Atg13 binds both ULK1 and ULK2 and mediates the interaction of the ULK proteins with FIP200. The binding of Atg13 stabilizes and activates ULK and facilitates the phosphorylation of FIP200 by ULK, whereas knockdown of Atg13 …


Editorial: Dietary Lipid Absorption, Concetta Dirusso, Paul N. Black Jan 2009

Editorial: Dietary Lipid Absorption, Concetta Dirusso, Paul N. Black

Department of Biochemistry: Faculty Publications

The composition of dietary fat influences tissue fatty acid composition, which in turn impacts cellular function through a number of different processes. This includes changes in signaling, lipid metabolism, and transcriptional activities that normally function to maintain intracellular fatty acid homeostasis. The consumption of high levels of dietary fat in excess of caloric expenditure is linked with obesity and the disruption of normal homeostatic mechanisms governing lipid metabolism. Data from the Centers for Disease Control and Prevention show that obesity (defined as a BMI≥30) represents a considerable health concern in the United States. Of particular note is that for adult …


Physiological Responses Of Resistant And Susceptible Barley, Hordeum Vulgare To The Russian Wheat Aphid, Diurpahis Noxia (Mordvilko), Andrea R. Gutsche, Tiffany M. Heng-Moss, Leon G. Higley, Gautam Sarath, Dolores W. Mornhinweg Jan 2009

Physiological Responses Of Resistant And Susceptible Barley, Hordeum Vulgare To The Russian Wheat Aphid, Diurpahis Noxia (Mordvilko), Andrea R. Gutsche, Tiffany M. Heng-Moss, Leon G. Higley, Gautam Sarath, Dolores W. Mornhinweg

Gautam Sarath Publications

Knowledge of the physiological responses of barley, Hordeum vulgare L., to the Russian wheat aphid, Diuraphis noxia (Mordvilko) (Hemiptera: Aphididae) is critical to understanding the defense response of barley to aphid injury and identifying resistance mechanisms. This study documented the impact of D. noxia feeding on resistant (‘Sidney’) and susceptible (‘Otis’) barley through chlorophyll fluorescence measurements, chlorophyll content, and carbon assimilation (A–Ci) curves recorded at 1, 3, 6, 10, and 13 days after aphid introduction. All chlorophyll fluorescence parameters evaluated were similar between aphid-infested and control plants for both cultivars. A–Ci curves showed that D. noxia feeding …


Improved Sugar Conversion And Ethanol Yield For Forage Sorghum (Sorghum Bicolor L. Moench) Lines With Reduced Lignin Contents, Bruce S. Dien, Gautam Sarath, Jeffrey F. Pedersen, Scott E. Sattler, Han Chen, Deanna L. Funnell-Harris, Nancy N. Nichols, Michael A. Cotta Jan 2009

Improved Sugar Conversion And Ethanol Yield For Forage Sorghum (Sorghum Bicolor L. Moench) Lines With Reduced Lignin Contents, Bruce S. Dien, Gautam Sarath, Jeffrey F. Pedersen, Scott E. Sattler, Han Chen, Deanna L. Funnell-Harris, Nancy N. Nichols, Michael A. Cotta

Gautam Sarath Publications

Lignin is known to impede conversion of lignocellulose into ethanol. In this study, forage sorghum plants carrying brown midrib (bmr) mutations, which reduce lignin contents, were evaluated as bioenergy feedstocks.