Mary-Ellen Harper

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Mary-Ellen Harper
Professor, University Research Chair in Mitochondrial Bionergetics, Director, Ottawa Institute of Systems Biology and Director of MATRIX (NSERC-Create) (See biography below)

BSc, University of Guelph
PhD, University of Ottawa
Postdoc Cambridge University, UK

Room: Roger Guindon Hall, Room 3510B (office), 3522 (lab)
Office: 613-562-5800 ext. 8458
Lab: 613-562-5800 ext. 8459
Work E-mail: mharper@uottawa.ca

Dr. Mary-Ellen Harper

Biography

Dr. Mary-Ellen Harper is a University Research Chair in Mitochondrial Bionergetics. She is also Director, Metabolomics Advanced Training and International Exchange (Matrix), an NSERC-CREATE program http://www.matrixmetabolomics.ca; as well as, Interim Director, Ottawa Institute of Systems Biology https://med.uottawa.ca/oisb/

 

Research Interests

Mammalian Bioenergetics: Metabolic Significance and Control of Uncoupling Proteins

Energy conversion processes in mammalian cells are far from perfect. The research conducted in Dr Harper's laboratory focuses specifically on the metabolic pathways that affect efficiency of energy transduction processes within different cells of the body. The cellular organelle 'charged' with the responsibility of energy conversion is the mitochondrion. It is there that the oxidation of various energy substrates converges for the production of the universal energy currency of cells, ATP. The efficiency of mitochondrial ATP synthesis, or oxidative phosphorylation, varies between different tissues of the body; between different metabolic states; and between different disease states (e.g., thyroid disorders).

The overall aim of the research projects conducted in the Harper lab is to better understand the control of cellular energy transduction processes in health and disease.

In particular, Dr. Harper's laboratory investigates the metabolic significance and control of uncoupling proteins (UCPs). UCPs are a subfamily of the mitochondrial carrier protein family and are located in the mitochondrial inner membrane. They have been hypothesized to cause a mitochondrial proton leak, and thereby allow protons to return to the mitochondrial matrix, bypassing ATP synthase. Thus energy substrates are oxidized, and the energy is released (or "wasted") as heat, instead of being converted to ATP. The function of such seemingly wasteful processes is a major interest of the lab. The role of uncoupling proteins in protection from reactive oxygen species, and cell death, is an expanding research interest of the laboratory group, and has implications for an improved understanding of cell death and aging processes.

Dr. Harper's research group uses integrative approaches spanning from bioenergetic studies of isolated mitochondria, to transfected cell cultures, to transgenic mice, and to clinical investigations. Clinical projects are conducted in collaboration with Dr. Robert Dent (Ottawa Hospital), and Dr. Ruth McPherson (University of Ottawa Heart Institute). Experimental techniques include: gene transfection, transgenics and knockouts, self-referencing microelectrode technologies, metabolic control analysis, oxygen and ion-selective electrodes, real-time PCR, Western blotting, and various forms of fluorescence microscopy.

Graduate Student and Postdoctoral Fellow Supervisions

Completed:

13 M.Sc. Shadi MONEMDJOU, 1998; Manon GAGNÉ, 1999; Andreas ANTONIOU, 2001; Darcy MacLELLAN 2007; Sean CRAWFORD, 2009; Carmen ESTEY 2009; Adrienne GOWING, 2010; Cynthia MOFFAT, 2010; Rui ZHANG, 2012; Cyril ADJEITEY, 2013, Skye McBRIDE, 2014; Lucien NADEAU, 2017(co-supervised with Dr. Céline Aguer); Awa LIAGHATI, 2017.

8 Ph.D. Shadi MONEMDJOU, 2002; Tia MOFFAT, 2007 (co-supervised with Steffany Bennett); Lisa BEVILACQUA, 2007, Sheila COSTFORD, 2008; Brittany BEAUCHAMP, 2015; Ghadi ANTOUN, 2017 (MD-PhD); Abi RAJKUMAR, 2018 (co-supervised with Dr. Frédérique Tesson); Georges KANAAN, 2018.

10 PDF. Dr. Céline AGUER; Dr. Véronic BEZAIRE; Dr. Martin GERRITS; Dr. Ryan MAILLOUX; Dr. Fiona McMURRAY; Dr. Erin SEIFERT; Dr. Brianne THRUSH; Dr. Neoma BOARDMAN; Dr. Denis BLONDIN; Dr. David PATTEN; Dr. Jens Frey HALLING (visiting for 6 mo from University of Copenhagen)

Current (In progress):

4 PhD.; Rajaa SEBAA; Nidhi KUKSAL; Michel KANAAN; Alessandra GENTILE (visiting from University of Naples)

3 MSc: Nina HADZIMUSTAFIC, Gaganvir Singh PARMAR, Claire FONG-McMASTER

1 PDF. Dr. Chantal PILEGGI

Undergraduate Research Thesis Student Supervision:

2016-17: Megan MacFarlane; Karan Gandhi; 2015-2016: Bianca ICHIM; Kijoo KIM; Cecile LE; 2014-15: Kris KOMM; Alyssa PEIXOTO; Jessica QUIZI; 2013-14: Olivier CHARETTE; 2012-13: Dhiya HASSAN, William CHEN, 2011-12: Melissa PASQUA, Aline PFEFFERLE; 2010-11: Naveen VENAYAK; 2009-10: Mark BASTIENELLI; Cyril ADJEITEY; Daniela GAMBAROTTA; 2008-9: Marisa ROSSI; Brittany BEAUCHAMP; 2007-8: Sean CRAWFORD, Samantha PREVOST, Benny HILL, Neha SARNA; 2006-7: Carmen ESTEY, Anastasia TOUR; 2005-6: Mitra ABAIEAN, Dimitre RANEV; 2004-5: Basil HUBBARD, Shehla CHAUDHRY; 2003-4: Matthew NIEDZWIECKI, Julie BEAULIEU; 2002-3: Nausheen SIDDIQUI, Marianne McGEE; 2001-2: Audrey NUK, Lorenne DOUCET; 2000-1: Lisa BEVILACQUA; 1999-2000: Veronic BEZAIRE; 1998-9: Andreas ANTONIOU, 1997-8: Shirin LAL; 1996-7: Manon GAGNE, 1995-6: Shadi MONEMDJOU

Current Research Funding

Canadian Institutes of Health Research (CIHR),Natural Sciences and Engineering Research Council (NSERC)  

Distinctions:

  • University Research Chair in Mitochondrial Bioenergetics. 2016-2021
  • College of Reviewers, Canadian Institutes of Health Research (CIHR) 2014 -
  • Visiting Research Scholar, Joslin Diabetes Research Center, Harvard Medical School. Boston, MA. Jan. – Dec. 2014
  • Elected as the Canadian Representative on the (North American) Obesity Society Council. 2012-2015
  • Elected to the Board of Governors, Canadian Obesity Network, 2012-
  • Canadian Society for Nutritional Sciences Centrum Award, 2003
  • Laura and Arthur Colwin Endowed Summer Research Fellowship, and HB Steinbach Fellowship in Physiology, Marine Biological Laboratory, Woods Hole, Massachusetts. 2002.
  • Premier's Research Excellence Award, 2000.
  • Canadian Foundation for Innovation Researcher, New Opportunities Award, 1998.
  • John Charles Polanyi Prize - Physiology and Medicine. 1995.
  • Research Associateship, Girton College, University of Cambridge. 1992.
  • Natural Sciences and Engineering Research Council Postdoctoral Fellowship, 1991-3. 

Selected Publications

  • Neoma T Boardman*, Baher Migally*, Chantal Pileggi*, Gaganvir S Parmar*, Jian Ying Xuan*, Keir Menzies and Mary-Ellen Harper (2020) Glutaredoxin-2 and Sirtuin-3 deficiencies impair cardiac mitochondrial energetics but their effects are not additive. BBA: Molecular Basis of Disease. In Press.
  • Robert Dent, Ruth McPherson and Mary-Ellen Harper (2020) Factors Affecting Weight Loss Variability in Obesity. Metabolism Clinical and Experimental. In Press.
  • Chantal Pileggi*, Gaganvir Parmar*, and Mary-Ellen Harper (2020) The Lifecycle of Skeletal Muscle Mitochondria in Obesity. Obesity Reviews. In Press.
  • David A Patten*, Shawn McGuirk, Ujval Anilkumar, Ghadi Antoun*, Karan Gandhi*, Gaganvir Parmar*, Mohamed Ariff Iqbal, Jacob Wong, Richard B Richardson, Julie St-Pierre, Ruth S Slack, Mary-Ellen Harper. Altered mitochondrial fusion drives defensive glutathione synthesis in cells able to switch to glycolytic ATP production. BBA - Molecular Cell Research. In press. 
  • Luke Kennedy, Jagdeep Sanhu, Mary-Ellen Harper and Miroslava Cuperlovic-Culf. (2020) Role of Glutathione in Cancer: From Mechanisms to Therapies  Biomolecules. In press.
  • Mary-Ellen Harper and Mary Elizabeth Patti. (2020) Metabolic Terminology: What’s in a name? Nature Metabolism. 2(6):476-477.
  • Majid Nikpay, Paulina Lau, Sebastien Soubeyrand, Katey Whytlock, Kaitlyn Beecher, Chantal Pileggi*, Sujoy Ghosh, Mary-Ellen Harper, Robert Dent, and Ruth McPherson (2020) SGCG rs679482 associates with weight loss success in response to an intensively supervised outpatient program.  Diabetes. 69(9):2017-2026.
  • David A. Patten*, Mary-Ellen Harper and Neoma Boardman* (2020) Harnessing the protective role of OPA1 in diabetic cardiomyopathy. Acta Physiologica (Oxford). 229(1):e13466.
  • Zeina Salloum, Eric Lehoux, Mary-Ellen Harper and Isabelle Catelas. (2020) Effects of Cobalt and Chromium Ions on Glycolytic Flux and the Stabilization of Hypoxia-Inducible factor-1α in Macrophages in Vitro. J Orthop Res. In Press.
  • Fiona McMurray*, Megan MacFarlane*, Kijoo Kim*, David A. Patten*, Lan Wei-LaPierre, Morgan D. Fullerton, and Mary-Ellen Harper (2019). Maternal diet induced obesity alters muscle mitochondrial function in offspring without changing insulin sensitivity. FASEB J. 33 (12), 13515-13526.
  • Dmitry Grapov, Oliver Fiehn, Caitlin Campbell, Carol Chandler, Dustin Burnett, Elaine Souza, Gretchen Casazza, Nancy Keim, John Newman, Gary Hunter, Jose Fernandez, W.Timothy Garvey, Charles Hoppel, Mary-Ellen Harper, and Sean H. Adams. (2019) Exercise plasma metabolomics and xenometabolomics in obese, sedentary, insulin-resistant women: impact of a fitness and weight loss intervention. Am J Physiol: Endo Met. 317 (6), E999-E1014.              
  • David A. Patten*, Mathieu Ouelet, David S. Allan, Marc Germain, Stephen Baird, Mary-Ellen Harper+ and Richard B. Richardson+(2019). Mitochondrial adaptation in human mesenchymal stem cells following ionizing radiation.  FASEB J. 33 (8), 9263-9278 +Co-senior authors.
  • Rajaa Sebaa*, Jeff Johnson, Chantal Pileggi*, Michaela Norgren*, Jian Xuan*, Yuka Sai, Qiang Tong, Irena Krystkowiak, Emma Bondy-Chorney, Norman Davey, Nevan Krogan, Michael Downey+ and Mary-Ellen Harper+ (2019). SIRT3 controls brown fat thermogenesis by deacetylation regulation of pathways upstream of UCP1. Molecular Metabolism. 25:35-49 + Co-senior authors.
  • Melanie Villanueva, Connor Michie, Georges N Kanaan*, Ghazaleh Rafatian, Pushpinder Kanda, Bin Ye, Wenbin Liang, Mary-Ellen Harper and Darryl R Davis (2019). Glyoxalase 1 Prevents Chronic Hyperglycemia Induced Heart-Explant Derived Cell Dysfunction. Theranostics. 9(19):5720-5730.
  • Skye McBride*, Lan Wei-LaPierre, Fiona McMurray*, Megan MacFarlane*, Xing Qiu, David A. Patten, Robert T. Dirksen RT, Mary-Ellen Harper (2019). Skeletal muscle mitoflashes, pH, and the role of uncoupling protein-3. Arch Biochem Biophys. 663:239-248.
  • Majid Nikpay, Kaitlyn Beehler, Armand Valsesia, Jorg Hager, Mary-Ellen Harper, Robert Dent, and Ruth McPherson (2019). Genome-wide identification of circulating-miRNA expression quantitative trait loci reveals the role of several miRNAs in the regulation of cardiometabolic phenotypes. Cardiovascular Research. 115(11):1629-1645.
  • Lucien Nadeau, David Patten*, Audrey Caron, Léa Garneau, Marc Foretz, Pascal Haddad, Barbara G Andersen, Quinn LeBris, Mary-Ellen Harper, and Céline Aguer (2019). IL-15 improves skeletal muscle oxidative metabolism and glucose uptake in association with increased respiratory chain supercomplex formation and AMPK pathway activation. BBA General Subjects. 1863(2):395-407.
  • Georges Kanaan*, David Patten*, Calum Redpath and Mary-Ellen Harper (2019). Atrial fibrillation is associated with impaired atrial mitochondrial energetics and supercomplex formation in type 2 diabetes.  Canadian Journal of Diabetes. 43(1):67-75.
  • Zeina Salloum, Eric Lehoux, Mary-Ellen Harper and Isabelle Catalas (2018). Effects of cobalt and chromium ions on oxidative stress and cellular energetics in macrophages in vitro. Journal of Orthopaedic Research. 36(12):3178-3187.
  • Abi Rajkumar*, Awa Liaghati*, Jessica Chan, Gilles Lamothe, Robert Dent, Éric Doucet, Remi Rabasa-Lhoret, Denis Prud’homme, Mary-Ellen Harper** and Frédérique Tesson** (2018). Influence of ACSL5 genotype on fatty acid oxidation and mitochondrial bioenergetics -an in vitro, ex vivo and in vivo analysis. Metabolism Clinical and Experimental. 83:271-279. **Co-senior authors.
  • A. Brianne Thrush*, Ghadi Antoun*, Majid Nikpay, Jean-François Mauger, David Patten*, Brittany L. Beauchamp*, Paulina Lau, Éric Doucet, Pascal Imbeault, Robert Boushel, Jorg Hager, Armand Valsesia, Ruth Slack, Osama Y. Al-Dirbashi, Robert Dent**, Ruth McPherson** and Mary-Ellen Harper. (2018) Diet-resistant obesity is characterized by a distinct plasma proteomic signature and impaired muscle fiber metabolism, Int J Obesity. 42(3):353-362 (** co-senior authors).
  • Georges N. Kanaan*, Bianca Ichim*, Lara Gharibeh, Wael Maharsy, David Patten*, Jian Ying Xuan*, Arkadiy Reunov, Philip Marshall, John Veinot, Keir Menzies, Mona Nemer and Mary-Ellen Harper (2018). Glutaredoxin-2 Controls Cardiac Mitochondrial Dynamics and Energetics in Mice, and Protects Against Human Cardiac Pathologies. Redox Biol. 14:509-521.
  • Georges N. Kanaan* and Mary-Ellen Harper (2017) Cellular redox dysfunction in the development of cardiovascular diseases. BBA: General Subjects. 1861: 2822-9.
  • Ghadi Antoun*, Majid Nikpay, Ruth McPherson, Mary-Ellen Harper, and Robert Dent. (2018) Is type 2 diabetes associated with impaired capacity for weight loss? Can J Diabetes. 42(3):313-16.
  • Céline Aguer*, Brian Piccolo, Oliver Fiehn, Sean Adams and Mary-Ellen Harper (2017) A novel amino acid and metabolomics signature in mice overexpressing muscle uncoupling protein 3. FASEB J. 31(2):814-27.
  • Sparks LM, Redman LM, Conley KE, Harper ME, Yi F, Hodges A, Eroshkin A, Costford SR, Gabriel ME, Shook C, Cornnell HH, Ravussin E, Smith SR. (2017) Effects of 12 Months of Caloric Restriction on Muscle Mitochondrial Function in Healthy Individuals. J Clin Endocrinol Metab. 102(1):111-21
  • Mary-Ellen Harper (2016) Drugs and bugs: Turning on the heat through UCP1 and UCP3   J. Physiol. 594(24):7151-2.
  • Fiona McMurray*, David A. Patten* and Mary-Ellen Harper (2016) Reactive oxygen species and oxidative stress in obesity – Recent Findings and Empirical Approaches. Obesity. 24(11):2301-10.
  • Denis P. Blondin, Amani Daoud, Taryn Taylor, Hans C. Tingelstad, Véronic Bézaire*, Denis Richard, André C. Carpentier, Albert W. Taylor, Mary-Ellen Harper, Céline Aguer*, François Haman. (2016) Four-week cold acclimation in adult humans shifts uncoupling thermogenesis from skeletal muscles to BAT. J Physiol. 595(6):2099-113.
  • Sparks LM, Redman LM, Conley KE, Harper ME, Hodges A, Eroshkin A, Costford SR, Gabriel ME, Yi F, Shook C, Cornnell HH, Ravussin E, Smith SR. (2016) Differences in mitochondrial coupling reveal a novel signature of mitohormesis in muscle of healthy individuals. J Clin Endocrinol Metab. 102(1):111-21.
  • Abi Rajkumar*, Gilles Lamothe, Pierette Bolongo, Mary-Ellen Harper, Kristi Adamo, Eric Doucet, Remi Rabasa-Lhoret, Denis Prud'homme, Frederique Tesson. (2016) Acyl-CoA synthetase long-chain 5 genotype is associated with body composition changes in response to lifestyle interventions in postmenopausal women with overweight and obesity: a genetic association study on cohorts Montréal-Ottawa New Emerging Team, and Complications Associated with Obesity. BMC Med Genet.17(1):56
  • Kyle Scott, Maria Benkhalti Jandu, Nicholas D. Calvert, Mathieu Paquette, Li Zhen, Mary-Ellen Harper, Osama Y. Al-Dirbashi, and Jean-Marc Renaud. (2016) KATP channel deficiency in mouse FDB causes an impairment of energy metabolism during fatigue. Am. J. Physiol: Cell. 311(4):C559-C571.
  • L. Marcadier, Jean Michaud, Osama Y. Al-Dirbashi, Jeremy Schwartzentruber, Chandree L. Beaulieu, Sherri L. Katz, FORGE Canada Consortium, Jacek Majewski, Dennis E. Bulman, Michael T. Geraghty, Mary-Ellen Harper, Pranesh Chakraborty , Matthew A. Lines (2016) Severe Neonatal Presentation of Mitochondrial Citrate Carrier (SLC25A1) Deficiency. J. Inher. Metab. Diseases 30:73-9.
  • Mireille Khacho, Alysen Clark, Devon S. Svoboda, Joelle Azzi, Jason G. MacLaurin, Cynthia Meghaizel, Hiromi Sesaki, Diane C. Lagace, Marc Germain, Mary-Ellen Harper, David S. Park, Ruth S. Slack. (2016) Mitochondrial dynamics impacts stem cell identity and fate decisions by regulating a nuclear transcriptional program. Cell Stem Cell. 19(2):232-47.
  • Richard B Richardson and Mary-Ellen Harper. (2016) Mitochondrial stress controls the radiosensitivity of the oxygen effect: Implications for radiotherapy. Oncotarget. 7(16):21469-83.
  • Brittany Beauchamp* and Mary-Ellen Harper. (2016) In utero undernutrition programs skeletal and cardiac muscle metabolism.  Frontiers in Physiology, 6:401. doi: 10.3389/fphys.2015.00401. PMID: 26779032
  • Michael A. Kennedy, Tia C. Moffat, Kenneth Gable, Karolina Niewola-Staszkowska, Anne Johnston, Corey Nislow, Linda J. Harris, Robbie Loewith, Mary-Ellen Harper, Teresa Dunn, Steffany Bennett and Kristin Baetz. (2016)  A signaling lipid associated with Alzheimer’s disease causes mitochondrial dysfunction. Scientific Reports. 6:19332. doi: 10.1038/srep19332.
  • Ghadi Antoun*, Skye McBride*, Jason R. Vanstone, Turaya Naas, Jean Michaud, Hugh McMillan, Stephanie Redpath, Dennis Bulman, Jason Brophy, FORGE Canada Consortium, Kym M. Boycott, David Dyment, Martin Holcik, Alex Mackenzie, Mary-Ellen Harper§, and Matthew A. Lines§ (2016)  Detailed Clinical and Bioenergetic Characterization of Mitochondrial Encephalopathy, Cardiomyopathy, and Immunodeficiency due to FBXL4 deficiency. Journal of Inherited Metabolic Diseases. (Co-senior authors). 27:1-9.
  • Mirna Azar, Majid Nikpay, Mary-Ellen Harper, Ruth McPherson, and Robert Dent. (2016) Can response to dietary restriction predict weight loss after Roux-en-Y Gastroplasty?  Obesity.  24(4):805-11.
  • Hussein Daoud, Fiona McMurray*, Andrea Yu, Stephanie Luco, Jason Vanstone, Olga Jarinova, Nancy Carson, Kym M Boycott, Christopher Schofield, Mary-Ellen Harper, David A Dyment, Christine M Armour. (2016) Identification of a Pathogenic FTO Mutation by Next-Generation Sequencing in a Newborn with Growth Retardation and Developmental Delay. Journal of Medical Genetics. 53(3):200-7.
  • Mirna Azar, Majid Nikpay, Mary-Ellen Harper, Ruth McPherson, and Robert Dent. (2015) Adverse Effects of Beta-Blocker Therapy on Weight Loss in Response to a Controlled Dietary Regimen. Can. J. Cardiol. 32(10): 1246.e21–1246.
  • Ghadi Antoun*, Fiona McMurray*, A Brianne Thrush*, David A Patten, Alyssa Christine Peixoto*, Ruth S Slack, Ruth McPherson, Robert Dent, and Mary-Ellen Harper. (2015) Impaired Mitochondrial Oxidative Phosphorylation and Supercomplex Assembly in Rectus Abdominis of Diabetic Obese Individuals. Diabetologia. 58(12):2861-6.
  • Jason Vanstone, Amanda Smith, Skye McBride*, Turaya Naas, Martin Holcik, Ghadi Antoun, Mary-Ellen Harper, Jean Michaud, Erick Sell, Pranesh Chakraborty, Martine Tetreault, Jacek Majewski, Stephen Baird, Kym Boycott, David Dyment, and Alex MacKenzie and Matthew Lines*. (2016) DNM1L-related mitochondrial fission defect presenting as refractory epilepsy.  Eur. J. Human Genetics 24(7): 1084-8
  • Denuja Karunakaran, Laura Richards, Michele Geoffrion, Danyk Barrette, Ryan Gotfrit, Mary-Ellen Harper, and Katey Rayner. (2015) Therapeutic Inhibition of miR-33 Promotes Fatty Acid Oxidation but Does Not Ameliorate Metabolic Dysfunction in Diet-Induced Obesity. Arteriosclerosis, Thrombosis, and Vascular Biology. 35(12):2536-43.
  • Denuja Karunakaran, A. Brianne Thrush*, MA Nguyen, L Richards, Michelle Geoffrion, R Singaravelu, E Ramphos, P Shangari, Michelle Ouimet, John P Pezacki,  Katherine J Moore, L Perisic, L Maegdefessel, U Hedin, Mary-Ellen Harper, Katey J Rayner. (2015) Macrophage Mitochondrial Energy Status Regulates Cholesterol Efflux and is Enhanced by Anti-miR33 in Atherosclerosis. Circ Res. 117(3):266-78.
  • Brittany Beauchamp*, A. Brianne Thrush*, Jessica Quizi*, Ghadi Antoun*, Nathan McIntosh*, Osama Y. Al-Dirbashi, Mary-Elizabeth Patti, and Mary-Ellen Harper. (2015) Undernutrition during pregnancy in mice leads to dysfunctional cardiac muscle respiration in adult offspring. Biosci Rep. Apr 10;35(3). pii: e00200.
  • Céline Aguer*, Colin S. McCoin, Trina A. Knotts, A. Brianne Thrush*, Kikumi Ono-Moore, Ruth McPherson, Robert Dent, Daniel H. Hwang, Sean H. Adams3, and Mary-Ellen Harper. (2015) Acylcarnitines: potential implications for skeletal muscle insulin resistance. FASEB J. 29(1):336-45.

Fields of Interest

  • Mitochondrial energetics
  • Uncoupling proteins
  • Reactive oxygen species
  • Glutathione redox
  • Oxidative stress
  • Metabolic disease
  • Obesity
  • Diabetes
  • Biochemistry
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