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https://www.readbyqxmd.com/read/27913695/a-randomized-double-blind-placebo-controlled-trial-of-coenzyme-q10-in-huntington-disease
#1
Andrew McGarry, Michael McDermott, Karl Kieburtz, Elisabeth A de Blieck, Flint Beal, Karen Marder, Christopher Ross, Ira Shoulson, Peter Gilbert, William M Mallonee, Mark Guttman, Joanne Wojcieszek, Rajeev Kumar, Mark S LeDoux, Mary Jenkins, H Diana Rosas, Martha Nance, Kevin Biglan, Peter Como, Richard M Dubinsky, Kathleen M Shannon, Padraig O'Suilleabhain, Kelvin Chou, Francis Walker, Wayne Martin, Vicki L Wheelock, Elizabeth McCusker, Joseph Jankovic, Carlos Singer, Juan Sanchez-Ramos, Burton Scott, Oksana Suchowersky, Stewart A Factor, Donald S Higgins, Eric Molho, Fredy Revilla, John N Caviness, Joseph H Friedman, Joel S Perlmutter, Andrew Feigin, Karen Anderson, Ramon Rodriguez, Nikolaus R McFarland, Russell L Margolis, Eric S Farbman, Lynn A Raymond, Valerie Suski, Sandra Kostyk, Amy Colcher, Lauren Seeberger, Eric Epping, Sherali Esmail, Nancy Diaz, Wai Lun Alan Fung, Alan Diamond, Samuel Frank, Philip Hanna, Neal Hermanowicz, Leon S Dure, Merit Cudkowicz
OBJECTIVE: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD. METHODS: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months...
December 2, 2016: Neurology
https://www.readbyqxmd.com/read/27856619/coq-deficiency-causes-disruption-of-mitochondrial-sulfide-oxidation-a-new-pathomechanism-associated-with-this-syndrome
#2
Marta Luna-Sánchez, Agustín Hidalgo-Gutiérrez, Tatjana M Hildebrandt, Julio Chaves-Serrano, Eliana Barriocanal-Casado, Ángela Santos-Fandila, Miguel Romero, Ramy Ka Sayed, Juan Duarte, Holger Prokisch, Markus Schuelke, Felix Distelmaier, Germaine Escames, Darío Acuña-Castroviejo, Luis C López
Coenzyme Q (CoQ) is a key component of the mitochondrial respiratory chain, but it also has several other functions in the cellular metabolism. One of them is to function as an electron carrier in the reaction catalyzed by sulfide:quinone oxidoreductase (SQR), which catalyzes the first reaction in the hydrogen sulfide oxidation pathway. Therefore, SQR may be affected by CoQ deficiency. Using human skin fibroblasts and two mouse models with primary CoQ deficiency, we demonstrate that severe CoQ deficiency causes a reduction in SQR levels and activity, which leads to an alteration of mitochondrial sulfide metabolism...
November 17, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27856618/coenzyme-q-deficiency-causes-impairment-of-the-sulfide-oxidation-pathway
#3
Marcello Ziosi, Ivano Di Meo, Giulio Kleiner, Xing-Huang Gao, Emanuele Barca, Maria J Sanchez-Quintero, Saba Tadesse, Hongfeng Jiang, Changhong Qiao, Richard J Rodenburg, Emmanuel Scalais, Markus Schuelke, Belinda Willard, Maria Hatzoglou, Valeria Tiranti, Catarina M Quinzii
Coenzyme Q (CoQ) is an electron acceptor for sulfide-quinone reductase (SQR), the first enzyme of the hydrogen sulfide oxidation pathway. Here, we show that lack of CoQ in human skin fibroblasts causes impairment of hydrogen sulfide oxidation, proportional to the residual levels of CoQ. Biochemical and molecular abnormalities are rescued by CoQ supplementation in vitro and recapitulated by pharmacological inhibition of CoQ biosynthesis in skin fibroblasts and ADCK3 depletion in HeLa cells. Kidneys of Pdss2(kd/kd) mice, which only have ~15% residual CoQ concentrations and are clinically affected, showed (i) reduced protein levels of SQR and downstream enzymes, (ii) accumulation of hydrogen sulfides, and (iii) glutathione depletion...
November 17, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27852445/a-metabolomics-driven-approach-reveals-metabolic-responses-and-mechanisms-in-the-rat-heart-following-myocardial-infarction
#4
Miso Nam, Youngae Jung, Do Hyun Ryu, Geum-Sook Hwang
BACKGROUND: Myocardial infarction (MI) is caused by myocardial necrosis resulting from prolonged ischemia. However, the biological mechanisms underlying MI remain unclear. METHODS: We evaluated metabolic and lipidomic changes in rat heart tissue from sham and MI at 1h, 1day and 10day after coronary ligation, using global profiling based on metabolomics. RESULTS: A time-dependent increase or decrease in polar and lipid metabolite levels was measured...
November 11, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27837315/cloning-and-characterization-of-decaprenyl-diphosphate-synthase-from-three-different-fungi
#5
Daisuke Moriyama, Tomohiro Kaino, Kazuyoshi Yajima, Ryota Yanai, Yasuhiro Ikenaka, Junzo Hasegawa, Motohisa Washida, Hirokazu Nanba, Makoto Kawamukai
Coenzyme Q (CoQ) is composed of a benzoquinone moiety and an isoprenoid side chain of varying lengths. The length of the side chain is controlled by polyprenyl diphosphate synthase. In this study, dps1 genes encoding decaprenyl diphosphate synthase were cloned from three fungi: Bulleromyces albus, Saitoella complicata, and Rhodotorula minuta. The predicted Dps1 proteins contained seven conserved domains found in typical polyprenyl diphosphate synthases and were 528, 440, and 537 amino acids in length in B. albus, S...
November 11, 2016: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27732833/hypothesis-driven-versus-hypothesis-free-filling-the-gaps-in-coq-biosynthesis
#6
José Antonio Enríquez, Fátima Sánchez-Cabo, Jesús Vázquez
Two independent investigations based on the power of yeast genetics, but using radically different discovery-driven approaches, have solved a long-pursued goal: the understanding of the early steps in CoQ biosynthesis, which may help diagnose CoQ deficiencies of unknown origin (Payet et al., 2016; Stefely et al., 2016).
October 11, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27669165/mitochondrial-protein-functions-elucidated-by-multi-omic-mass-spectrometry-profiling
#7
Jonathan A Stefely, Nicholas W Kwiecien, Elyse C Freiberger, Alicia L Richards, Adam Jochem, Matthew J P Rush, Arne Ulbrich, Kyle P Robinson, Paul D Hutchins, Mike T Veling, Xiao Guo, Zachary A Kemmerer, Kyle J Connors, Edna A Trujillo, Jacob Sokol, Harald Marx, Michael S Westphall, Alexander S Hebert, David J Pagliarini, Joshua J Coon
Mitochondrial dysfunction is associated with many human diseases, including cancer and neurodegeneration, that are often linked to proteins and pathways that are not well-characterized. To begin defining the functions of such poorly characterized proteins, we used mass spectrometry to map the proteomes, lipidomes, and metabolomes of 174 yeast strains, each lacking a single gene related to mitochondrial biology. 144 of these genes have human homologs, 60 of which are associated with disease and 39 of which are uncharacterized...
November 2016: Nature Biotechnology
https://www.readbyqxmd.com/read/27651221/deciphering-how-lip2-and-pox2-promoters-can-optimally-regulate-recombinant-protein-production-in-the-yeast-yarrowia-lipolytica
#8
Hosni Sassi, Frank Delvigne, Tambi Kar, Jean-Marc Nicaud, Anne-Marie Crutz-Le Coq, Sebastien Steels, Patrick Fickers
BACKGROUND: In recent years, the non-conventional model yeast species Yarrowia lipolytica has received much attention because it is a useful cell factory for producing recombinant proteins. In this species, expression vectors involving LIP2 and POX2 promoters have been developed and used successfully for protein production at yields similar to or even higher than those of other cell factories, such as Pichia pastoris. However, production processes involving these promoters can be difficult to manage, especially if carried out at large scales in fed-batch bioreactors, because they require hydrophobic inducers, such as oleic acid or methyl oleate...
2016: Microbial Cell Factories
https://www.readbyqxmd.com/read/27564375/quantification-of-the-fungal-fraction-released-from-various-preloaded-fibrous-filters-during-a-simulated-ventilation-restart
#9
K Morisseau, A Joubert, L Le Coq, Y Andres
This study aimed to demonstrate that particles, especially those associated with fungi, could be released from fibrous filters used in the air-handling unit (AHU) of heating, ventilation and air-conditioning (HVAC) systems during ventilation restarts. Quantification of the water retention capacity and SEM pictures of the filters was used to show the potential for fungal proliferation in unused or preloaded filters. Five fibrous filters with various particle collection efficiencies were studied: classes G4, M5, M6, F7, and combined F7 according to European standard EN779:2012...
August 26, 2016: Indoor Air
https://www.readbyqxmd.com/read/27510225/dietary-and-microbiome-factors-determine-longevity-in-caenorhabditis-elegans
#10
Adolfo Sánchez-Blanco, Alberto Rodríguez-Matellán, Ana González-Paramás, Susana González-Manzano, Stuart K Kim, Faustino Mollinedo
Diet composition affects organismal health. Nutrient uptake depends on the microbiome. Caenorhabditis elegans fed a Bacillus subtilis diet live longer than those fed the standard Escherichia coli diet. Here we report that this longevity difference is primarily caused by dietary coQ, an antioxidant synthesized by E. coli but not by B. subtilis. CoQ-supplemented E. coli fed worms have a lower oxidation state yet live shorter than coQ-less B. subtilis fed worms. We showed that mutations affecting longevity for E...
July 2016: Aging
https://www.readbyqxmd.com/read/27503795/a-clock-network-for-geodesy-and-fundamental-science
#11
C Lisdat, G Grosche, N Quintin, C Shi, S M F Raupach, C Grebing, D Nicolodi, F Stefani, A Al-Masoudi, S Dörscher, S Häfner, J-L Robyr, N Chiodo, S Bilicki, E Bookjans, A Koczwara, S Koke, A Kuhl, F Wiotte, F Meynadier, E Camisard, M Abgrall, M Lours, T Legero, H Schnatz, U Sterr, H Denker, C Chardonnet, Y Le Coq, G Santarelli, A Amy-Klein, R Le Targat, J Lodewyck, O Lopez, P-E Pottie
Leveraging the unrivalled performance of optical clocks as key tools for geo-science, for astronomy and for fundamental physics beyond the standard model requires comparing the frequency of distant optical clocks faithfully. Here, we report on the comparison and agreement of two strontium optical clocks at an uncertainty of 5 × 10(-17) via a newly established phase-coherent frequency link connecting Paris and Braunschweig using 1,415 km of telecom fibre. The remote comparison is limited only by the instability and uncertainty of the strontium lattice clocks themselves, with negligible contributions from the optical frequency transfer...
2016: Nature Communications
https://www.readbyqxmd.com/read/27499296/mitochondrial-protein-interaction-mapping-identifies-regulators-of-respiratory-chain-function
#12
Brendan J Floyd, Emily M Wilkerson, Mike T Veling, Catie E Minogue, Chuanwu Xia, Emily T Beebe, Russell L Wrobel, Holly Cho, Laura S Kremer, Charlotte L Alston, Katarzyna A Gromek, Brendan K Dolan, Arne Ulbrich, Jonathan A Stefely, Sarah L Bohl, Kelly M Werner, Adam Jochem, Michael S Westphall, Jarred W Rensvold, Robert W Taylor, Holger Prokisch, Jung-Ja P Kim, Joshua J Coon, David J Pagliarini
Mitochondria are essential for numerous cellular processes, yet hundreds of their proteins lack robust functional annotation. To reveal functions for these proteins (termed MXPs), we assessed condition-specific protein-protein interactions for 50 select MXPs using affinity enrichment mass spectrometry. Our data connect MXPs to diverse mitochondrial processes, including multiple aspects of respiratory chain function. Building upon these observations, we validated C17orf89 as a complex I (CI) assembly factor...
August 18, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27499294/cerebellar-ataxia-and-coenzyme-q-deficiency-through-loss-of-unorthodox-kinase-activity
#13
Jonathan A Stefely, Floriana Licitra, Leila Laredj, Andrew G Reidenbach, Zachary A Kemmerer, Anais Grangeray, Tiphaine Jaeg-Ehret, Catherine E Minogue, Arne Ulbrich, Paul D Hutchins, Emily M Wilkerson, Zheng Ruan, Deniz Aydin, Alexander S Hebert, Xiao Guo, Elyse C Freiberger, Laurence Reutenauer, Adam Jochem, Maya Chergova, Isabel E Johnson, Danielle C Lohman, Matthew J P Rush, Nicholas W Kwiecien, Pankaj K Singh, Anna I Schlagowski, Brendan J Floyd, Ulrika Forsman, Pavel J Sindelar, Michael S Westphall, Fabien Pierrel, Joffrey Zoll, Matteo Dal Peraro, Natarajan Kannan, Craig A Bingman, Joshua J Coon, Philippe Isope, Hélène Puccio, David J Pagliarini
The UbiB protein kinase-like (PKL) family is widespread, comprising one-quarter of microbial PKLs and five human homologs, yet its biochemical activities remain obscure. COQ8A (ADCK3) is a mammalian UbiB protein associated with ubiquinone (CoQ) biosynthesis and an ataxia (ARCA2) through unclear means. We show that mice lacking COQ8A develop a slowly progressive cerebellar ataxia linked to Purkinje cell dysfunction and mild exercise intolerance, recapitulating ARCA2. Interspecies biochemical analyses show that COQ8A and yeast Coq8p specifically stabilize a CoQ biosynthesis complex through unorthodox PKL functions...
August 18, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27493029/the-coq2-genotype-predicts-the-severity-of-coenzyme-q10-deficiency
#14
Maria Andrea Desbats, Valeria Morbidoni, Micol Silic-Benussi, Mara Doimo, Vincenzo Ciminale, Matteo Cassina, Sabrina Sacconi, Michio Hirano, Giuseppe Basso, Fabien Pierrel, Placido Navas, Leonardo Salviati, Eva Trevisson
COQ2 (p-hydroxybenzoate polyprenyl transferase) encodes the enzyme required for the second step of the final reaction sequence of Coenzyme Q10 (CoQ) biosynthesis. Its mutations represent a frequent cause of primary CoQ deficiency and have been associated with the widest clinical spectrum, ranging from fatal neonatal multisystemic disease to late-onset encephalopathy. However, the reasons of this variability are still unknown.We have characterized the structure of human COQ2, defined its subcellular localization and developed a yeast model to validate all the mutant alleles reported so far...
August 4, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27472605/direct-laser-writing-of-a-low-loss-waveguide-with-independent-control-over-the-transverse-dimension-and-the-refractive-index-contrast-between-the-core-and-the-cladding
#15
Pascal Masselin, Eugène Bychkov, David Le Coq
In this Letter, we present the realization of a low-loss waveguide in a chalcogenide glass by direct laser writing technique in a particular configuration that allows the independent control over the diameter of the core and the magnitude of the refractive index contrast with the cladding. The waveguide is of multicore type and composed of 19 channels arranged on a hexagonal lattice. Each channel is obtained by stacking voxels of refractive index variation obtained by static exposure to femtosecond laser pulse burst...
August 1, 2016: Optics Letters
https://www.readbyqxmd.com/read/27464616/impact-of-surgical-technique-on-long-term-complication-rate-after-laparoscopic-adjustable-gastric-banding-lagb-results-of-a-single-blinded-randomized-controlled-trial-anosean-study
#16
Benjamin Le Coq, Vincent Frering, Mohammed Ghunaim, Pierre Campan, André Dabrowski, Emmanuel Mulliez, Eric Loridan, Frédéric Combemale, Franck Denimal, Fanelly Torres, Gregory Baud, Camille Thibault, Guelareh Dezfoulian, Laurent Arnalsteen, Alain Duhamel, François Pattou, Robert Caiazzo
OBJECTIVE: The aim of the study was to explore the impact of the absence of band fixation on the reoperation rate and to identify other risk factors for long-term complications. BACKGROUND: Laparoscopic adjustable gastric banding has been demonstrated to permit important weight loss and comorbidity improvement, but some bands will have to be removed mainly for failure or in case of planned 2-step surgery. Then, the absence of a gastro-gastric suture (GGS) would allow easier band removal...
November 2016: Annals of Surgery
https://www.readbyqxmd.com/read/27429412/the-validity-and-reliability-study-of-the-turkish-version-of-the-evidence-based-practice-evaluation-competence-questionnaire
#17
Esra Yildiz, Zeynep Güngörmüş
INTRODUCTION: Identifying the competence of nursing students in evidence-based practice in nursing is important in planning education to train nurses to know, apply and improve evidence-based practice. PURPOSE: To perform a validity and reliability study for the Turkish version of the "Evidence-based Practice Competence of Nursing Students" questionnaire. DESIGN: This methodological study was conducted with 199 undergraduate nursing students in a university located in eastern Turkey, between April 1 2014 and February 4 2016...
October 2016: Nurse Education Today
https://www.readbyqxmd.com/read/27396355/metabolic-engineering-of-yarrowia-lipolytica-to-produce-chemicals-and-fuels-from-xylose
#18
Rodrigo Ledesma-Amaro, Zbigniew Lazar, Magdalena Rakicka, Zhongpeng Guo, Florian Fouchard, Anne-Marie Crutz-Le Coq, Jean-Marc Nicaud
Yarrowia lipolytica is a biotechnological chassis for the production of a range of products, such as microbial oils and organic acids. However, it is unable to consume xylose, the major pentose in lignocellulosic hydrolysates, which are considered a preferred carbon source for bioprocesses due to their low cost, wide abundance and high sugar content. Here, we engineered Y. lipolytica to metabolize xylose to produce lipids or citric acid. The overexpression of xylose reductase and xylitol dehydrogenase from Scheffersomyces stipitis were necessary but not sufficient to permit growth...
July 7, 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/27374853/secondary-coenzyme-q10-deficiencies-in-oxidative-phosphorylation-oxphos-and-non-oxphos-disorders
#19
Delia Yubero, Raquel Montero, Miguel A Martín, Julio Montoya, Antonia Ribes, Manuela Grazina, Eva Trevisson, Juan Carlos Rodriguez-Aguilera, Iain P Hargreaves, Leonardo Salviati, Plácido Navas, Rafael Artuch, Cristina Jou, Cecilia Jimenez-Mallebrera, Andres Nascimento, Belén Pérez-Dueñas, Carlos Ortez, Federico Ramos, Jaume Colomer, Mar O'Callaghan, Mercè Pineda, Angels García-Cazorla, Carmina Espinós, Angels Ruiz, Alfons Macaya, Anna Marcé-Grau, Judit Garcia-Villoria, Angela Arias, Sonia Emperador, Eduardo Ruiz-Pesini, Ester Lopez-Gallardo, Viruna Neergheen, Marta Simões, Luisa Diogo, Alberto Blázquez, Adrián González-Quintana, Aitor Delmiro, Cristina Domínguez-González, Joaquín Arenas, M Teresa García-Silva, Elena Martín, Pilar Quijada, Aurelio Hernández-Laín, María Morán, Eloy Rivas Infante, Rainiero Ávila Polo, Carmen Paradas Lópe, Juan Bautista Lorite, Eva M Martínez Fernández, Ana B Cortés, Ana Sánchez-Cuesta, Maria V Cascajo, María Alcázar, Gloria Brea-Calvo
We evaluated the coenzyme Q₁₀ (CoQ) levels in patients who were diagnosed with mitochondrial oxidative phosphorylation (OXPHOS) and non-OXPHOS disorders (n=72). Data from the 72 cases in this study revealed that 44.4% of patients showed low CoQ concentrations in either their skeletal muscle or skin fibroblasts. Our findings suggest that secondary CoQ deficiency is a common finding in OXPHOS and non-OXPHOS disorders. We hypothesize that cases of CoQ deficiency associated with OXPHOS defects could be an adaptive mechanism to maintain a balanced OXPHOS, although the mechanisms explaining these deficiencies and the pathophysiological role of secondary CoQ deficiency deserves further investigation...
September 2016: Mitochondrion
https://www.readbyqxmd.com/read/27353847/resection-of-hepatocellular-carcinoma-in-elderly-patients-and-the-role-of-energy-balance
#20
Marco Cannistrà, Raffaele Grande, Michele Ruggiero, Matteo Novello, Alessandra Zullo, Elisabetta Bonaiuto, Sebastiano Vaccarisi, Giuseppe Cavallari, Raffaele Serra, Bruno Nardo
INTRODUCTION: Progressive functional impairment with age has a significant impact on perioperative risk management. Chronic liver diseases induce a strong oxidative stress; in the elderly, in particular, impaired elimination of free radicals leads to insufficient DNA repair. The events associated with a weak response to growth factors after hepatectomy leads to a decline in liver regeneration. Hypercholesterolemia is highly prevalent in the elderly, which may alter the coenzyme Q10 (CoQ) levels and in turn the cellular energy balance...
September 2016: International Journal of Surgery
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