18 results on '"Guertin, M"'
Search Results
2. [OP.5A.03] NOVEL STRATEGIES TO IMPROVE THE MANAGEMENT OF ALBUMINURIA IN HYPERTENSIVE DIABETIC PATIENTS.
- Author
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Hamet, P., Guertin, M.-R., Dumas, P., Tahir, R., Sylvestre, M.-P., Kaczorowski, J., Kushnarev, M., Santucci, L., Corbeil, G., Long, C., and Tremblay, J.
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- 2017
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3. A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy
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Cadrin-Tourigny, J. (Julia), Bosman, L.P. (Laurens P.), Nozza, A. (Anna), Wang, W. (Weijia), Tadros, R. (Rafik), Bhonsale, A. (Aditya), Bourfiss, M. (Mimount), Fortier, A. (Annik), Lie, ØH. (Øyvind H), Saguner, A.M. (Ardan M.), Svensson, A. (Anneli), Andorin, A. (Antoine), Tichnell, C. (Crystal), Murray, B. (Brittney), Zeppenfeld, K. (Katja), Berg, M.P. (Maarten) van den, Asselbergs, F.W. (Folkert), Wilde, A.A.M. (Arthur), Krahn, A.D. (Andrew D.), Talajic, M. (Mario), Rivard, L. (Lena), Chelko, S. (Stephen), Zimmerman, S.L. (Stefan), Kamel, M.S. (Mohamed), Crosson, J.E. (Jane E.), Judge, D.P. (Daniel), Yap, S.-C. (Sing-Chien), Heijden, J.F. (Jeroen) van der, Tandri, H. (Harikrishna), Jongbloed, J.D.H. (Jan), Guertin, M.-C. (Marie-Claude), Tintelen, J.P. (Peter) van, Platonov, P.G. (Pyotr G.), Duru, F. (Firat), Haugaa, K.H. (Kristina H.), Khairy, P. (Paul), Hauer, R.N.W. (Richard), Calkins, H. (Hugh), Riele, A.S. (Anneline) te, James, C.A. (Cynthia), Cadrin-Tourigny, J. (Julia), Bosman, L.P. (Laurens P.), Nozza, A. (Anna), Wang, W. (Weijia), Tadros, R. (Rafik), Bhonsale, A. (Aditya), Bourfiss, M. (Mimount), Fortier, A. (Annik), Lie, ØH. (Øyvind H), Saguner, A.M. (Ardan M.), Svensson, A. (Anneli), Andorin, A. (Antoine), Tichnell, C. (Crystal), Murray, B. (Brittney), Zeppenfeld, K. (Katja), Berg, M.P. (Maarten) van den, Asselbergs, F.W. (Folkert), Wilde, A.A.M. (Arthur), Krahn, A.D. (Andrew D.), Talajic, M. (Mario), Rivard, L. (Lena), Chelko, S. (Stephen), Zimmerman, S.L. (Stefan), Kamel, M.S. (Mohamed), Crosson, J.E. (Jane E.), Judge, D.P. (Daniel), Yap, S.-C. (Sing-Chien), Heijden, J.F. (Jeroen) van der, Tandri, H. (Harikrishna), Jongbloed, J.D.H. (Jan), Guertin, M.-C. (Marie-Claude), Tintelen, J.P. (Peter) van, Platonov, P.G. (Pyotr G.), Duru, F. (Firat), Haugaa, K.H. (Kristina H.), Khairy, P. (Paul), Hauer, R.N.W. (Richard), Calkins, H. (Hugh), Riele, A.S. (Anneline) te, and James, C.A. (Cynthia)
- Abstract
AIMS: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. METHODS AND RESULTS: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.6% reduction of ICD placements with the same proportion of protected patients (P < 0.001). CONCLUSION: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).
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- 2019
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4. ANXIOUSHEART: THE MEETING POINT OF CARDIAC AND ANXIOUS DISEASES
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Dyrda, K., primary, Brouillette, J., additional, Long, V., additional, and Guertin, M., additional
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- 2018
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5. CAN AMBULATORY ELECTROCARDIOGRAPHIC (HOLTER) TESTING ACCURATELY DIFFERENTIATE PATIENTS AT HIGHER VERSUS LOWER RISK OF DEATH AFTER MYOCARDIAL INFRACTION?
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Exner, D., primary, Kavanagh, K., additional, Hruczkowski, T., additional, Hersi, A., additional, Thibault, B., additional, Philippon, F., additional, Yee, R., additional, Guertin, M., additional, Tang, A., additional, and Huikuri, H., additional
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- 2017
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6. Evaluation of an e-Learning Training in Brief Motivational Interviewing (MOTIV@Coeur) for Cardiovascular Care Nurses: A Single Group Pre-Post Pilot Study
- Author
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Fontaine, G., primary, Cossette, S., additional, Heppell, S., additional, Boyer, L., additional, Simard, M.-J., additional, Tanguay, J.-F., additional, and Guertin, M.-C., additional
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- 2016
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7. High resolution X-ray structure of the N-terminal truncated form (residues 1-11) of Mycobacterium tuberculosis HbN
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Pesce, A., primary, Bustamante, J.P., additional, Bidon-Chanal, A., additional, Boechi, L., additional, Estrin, D.A., additional, Luque, F.J., additional, Sebilo, A., additional, Guertin, M., additional, Bolognesi, M., additional, Ascenzi, P., additional, and Nardini, M., additional
- Published
- 2015
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8. Characteristics affecting survival after locally advanced colorectal cancer in Quebec.
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Perron, L., Daigle, J. M., Vandal, N., Guertin, M. H., and Brisson, J.
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COLON cancer treatment ,CANCER-related mortality ,ELECTIVE surgery ,MEDICAL records - Abstract
Background We estimated the relations of sociodemographic, organizational, disease, and treatment variables with the risk of death from colorectal cancer (CRC) in a Quebec population-based sample of patients with locally advanced CRC (LACRC) who underwent tumour resection with curative intent. Methods Information from medical records and administrative databases was obtained for a random sample of 633 patients surgically treated for stages II-III rectal and stage III colon cancer and declared to the Quebec cancer registry in 1998 and 2003. We measured personal, disease, and clinical management characteristics, relative survival, and through multivariate modelling, relative excess rate (RER) of death. Results The relative 5- and 10-year survivals in this cohort were 67.7% [95% confidence interval (CI): 65.8% to 69.6%] and 61.2% (95% CI: 58.3% to 64.0%) respectively. Stage T4, stage N2, and emergency rather than elective surgery affected 18%, 24% and 10% of patients respectively. Those disease progression characteristics each independently increased the RER of death by factors of 2 to almost 5. Grade, vascular invasion, and tumour location were also significantly associated with the RER for death. Receiving guideline-adherent treatment was associated with a 60% reduction in the RER for death (0.41; 95% CI: 0.28 to 0.61), an effect that was consistent across age groups. Clear margins (proximal-distal, radial) and clinical trial enrolment were each associated with a nonsignificant 50% reduction in the RER. Of patients less than 70 years of age and 70 years of age and older, 81.3% and 42.0% respectively received guideline-adherent treatment. Conclusions This study is the first Quebec population-based examination of patients with LACRC and their management, outcomes, and outcome determinants. The results can help in planning CRC control strategies at a population level. [ABSTRACT FROM AUTHOR]
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- 2015
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9. The N-terminal pre-A region ofMycobacterium tuberculosis2/2HbN promotes NO-dioxygenase activity
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Darío A. Estrin, Anne Sebilo, Martino Bolognesi, Alessandra Pesce, Francisco J. Luque, Marco Nardini, Leonardo Boechi, Michel Guertin, Juan Pablo Bustamante, Paolo Ascenzi, Axel Bidon-Chanal, Pesce, A, Bustamante, Jp, Bidon Chanal, A, Boechi, L, Estrin, Da, Luque, Fj, Sebilo, A, Guertin, M, Bolognesi, M, Ascenzi, Paolo, and Nardini, M.
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0301 basic medicine ,Protein Conformation ,globin dynamics ,Stereochemistry ,Dimer ,heme/ligand tunneling ,Heme ,Molecular Dynamics Simulation ,Crystallography, X-Ray ,Nitric Oxide ,Biochemistry ,Dioxygenases ,03 medical and health sciences ,chemistry.chemical_compound ,Protein structure ,Bacterial Proteins ,Peroxynitrous Acid ,truncated hemoglobins ,NO dioxygenase ,2/2 hemoglobin ,Molecular Biology ,2/2 HEMOGLOBINS ,Ligand ,Otras Ciencias Químicas ,Ciencias Químicas ,Oxygen transport ,Mycobacterium tuberculosis ,Cell Biology ,computer.file_format ,Protein Data Bank ,2/2 hemoglobins ,Kinetics ,Peroxynitrous acid ,030104 developmental biology ,chemistry ,Mutation ,Protein Multimerization ,computer ,GLOBIN DYNAMICS ,CIENCIAS NATURALES Y EXACTAS ,Peroxynitrite ,globin dynamic - Abstract
A unique defense mechanisms by which Mycobacterium tuberculosis protects itself from nitrosative stress is based on the O2-dependent NO-dioxygenase (NOD) activity of truncated hemoglobin 2/2HbN (Mt2/2HbN). The NOD activity largely depends on the efficiency of ligand migration to the heme cavity through a two-tunnel (long and short) system; recently, it was also correlated with the presence at the Mt2/2HbN N-terminus of a short pre-A region, not conserved in most 2/2HbNs, whose deletion results in a drastic reduction of NO scavenging. In the present study, we report the crystal structure of Mt2/2HbN-ΔpreA, lacking the pre-A region, at a resolution of 1.53 Å. We show that removal of the pre-A region results in long range effects on the protein C-terminus, promoting the assembly of a stable dimer, both in the crystals and in solution. In the Mt2/2HbN-ΔpreA dimer, access of heme ligands to the short tunnel is hindered. Molecular dynamics simulations show that the long tunnel branch is the only accessible pathway for O2-ligand migration to/from the heme, and that the gating residue Phe(62)E15 partly restricts the diameter of the tunnel. Accordingly, kinetic measurements indicate that the kon value for peroxynitrite isomerization by Mt2/2HbN-ΔpreA-Fe(III) is four-fold lower relative to the full-length protein, and that NO scavenging by Mt2/2HbN-ΔpreA-Fe(II)-O2 is reduced by 35-fold. Therefore, we speculate that Mt2/2HbN evolved to host the pre-A region as a mechanism for preventing dimerization, thus reinforcing the survival of the microorganism against the reactive nitrosative stress in macrophages. Database Coordinates and structure factors have been deposited in the Protein Data Bank under accession number 5AB8. Removal of the pre-A region in M. tuberculosis 2/2HbN (Mt2/2HbN-ΔpreA) results in dimerization and in a reduced access to the heme pocket. Kinetic measurements indicate a 4-fold decrease in kon for peroxynitrite isomerization and a 35-fold decrease in NO-scavenging relative to full-length Mt2/2HbN. Thus, the pre-A region might be involved in reinforcing survival of the microorganism against nitrosative stress in macrophages. Fil: Pesce, Alessandra. Università degli Studi di Genova; Italia Fil: Bustamante, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; Argentina Fil: Bidon Chanal, Axel. Universidad de Barcelona; España Fil: Boechi, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; Argentina Fil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; Argentina Fil: Luque, Francisco Javier. Universidad de Barcelona; España Fil: Sebilo, Anne. Laval University; Canadá Fil: Guertin, Michel. Laval University; Canadá Fil: Bolognesi, Martino. Universidad de Milan; Italia Fil: Ascenzi, Paolo. Università di Roma; Italia Fil: Nardini, Marco. Universidad de Milan; Italia
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- 2015
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10. Jonathan B. Wittenberg (1923-2023).
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Ascenzi P, Bolognesi M, Guertin M, and Moens L
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- 2023
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11. Thirteen toxicology tidbits for the emergency clinician.
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Koutsogiannis Z and Guertin M
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- 2023
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12. Soft Tissue Sarcomas in Octogenarian Patients: Are Treatment Options and Oncological Outcomes Different? A SEER Retrospective Study.
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Guertin MP, Lee Y, Stewart SJ, Ramirez J, Nguyen A, Paraliticci G, and Pretell-Mazzini JA
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- Aged, 80 and over, Humans, Retrospective Studies, Octogenarians, Neoplasm Staging, Sarcoma epidemiology, Sarcoma therapy, Soft Tissue Neoplasms
- Abstract
Aims: As the US population continues to age, oncological strategies and outcomes for soft tissue sarcomas (STSs) should continue to be examined for varying age groups. The aim of this study was analyse and compare treatment strategies and oncological outcomes for octogenarian patients with STSs., Materials and Methods: Data from the Surveillance, Epidemiology and End Results (SEER) national database were used. Varying treatment modalities were studied when utilised for specific tumour staging with respect to the eighth edition of the American Joint Committee on Cancer., Results: In total, 24 666 patients were included for analysis, where 3341 (14%) were 80 years old or older. The octogenarian group was diagnosed with more advanced disease (stages II-IV), relative to their younger counterparts (85% versus 75%, P < 0.001). However, a smaller proportion of the older patients underwent surgical resection (74% versus 86%, P < 0.001). Likewise, the octogenarians received less chemotherapy (4% versus 21%, P < 0.001) and radiotherapy (29% versus 42%, P = 0.010). Surgical resection and chemotherapy significantly improved overall survival for those older patients with stage II STS, whereas surgical resection and radiotherapy improved mortality in this cohort with both stage III and IV STS. Overall survival at 1 and 5 years of follow-up was lower within the octogenarian group compared with the younger group (1 year: 68% versus 88%, P < 0.001 and 5 years: 7% versus 58%, P < 0.001)., Conclusions: Octogenarian patients, in most cases, are diagnosed with stage III or metastatic disease. Surgical resection of the primary tumour was beneficial in both age cohorts, with radiotherapy correlating to better overall survival when used in those patients with higher stage STS. Chemotherapy was associated with better mortality in the younger cohort with respect to tumour stage. The octogenarian overall survival at 1 and 5 years was lower than for younger patients., (Copyright © 2023 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)
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- 2023
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13. Responsible Return to Essential and Non-Essential Surgery During the COVID-19 Pandemic.
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Poulose BK, Phieffer LS, Mayerson J, Like D, Forrest LA, Rahmanian A, Bellamy B, Guertin M, and Pawlik TM
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- COVID-19 Testing, Humans, Ohio epidemiology, SARS-CoV-2, COVID-19, Pandemics
- Abstract
Non-essential surgery had largely been suspended during the COVID-19 Pandemic. Enormous amounts of resources were utilized to shift surgical practices to a "disaster footing" with most elective surgeons assuming new roles to offset the anticipated burden from surgical and medical personnel delivering acute care. As the number of COVID-19-infected patients began to plateau in the state of Ohio, a four-phase "Responsible Return to Surgery" approach was adopted in concert with the Ohio Department of Health and the Ohio Hospital Association. This approach was adopted understanding that a simple return to the status quo prior to the COVID-19 pandemic might be harmful to patients, providers, and staff. The discrete phases undertaken at our quaternary care institution for a responsible return to non-essential surgery are outlined with the goal of ensuring timely care, minimizing community transmission, and preserving personal protective equipment. Operationalizing these phases relied upon the widespread use of telehealth, systematic COVID-19 testing, and real-time monitoring of hospital and personal protective equipment resources.
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- 2021
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14. Ambulatory Surgery Center Medical Director: Visionary Leader.
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Guertin M, Heard J, and Del Rosario T
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- Ambulatory Surgical Procedures mortality, Emergency Medical Services, Humans, Organizational Culture, Patient Safety, Ambulatory Care Facilities organization & administration, Leadership, Physician Executives
- Abstract
The ambulatory surgery center medical director is a physician leader who recognizes the need to develop a culture that encourages communication and empowerment of employees and professional staff, leading to engagement that optimize care through patient selection, safety and satisfaction requires vision and guidance from the medical director and is central to success of the ASC. Innovative thinking further improves patient care and long-term success by leveraging advances in technology and sustainable practices., (Copyright © 2019 Elsevier Inc. All rights reserved.)
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- 2019
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15. Implementing a web-based introductory bioinformatics course for non-bioinformaticians that incorporates practical exercises.
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Vincent AT, Bourbonnais Y, Brouard JS, Deveau H, Droit A, Gagné SM, Guertin M, Lemieux C, Rathier L, Charette SJ, and Lagüe P
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- Humans, Software, Students, Universities, Computational Biology education, Internet, Teaching
- Abstract
A recent scientific discipline, bioinformatics, defined as using informatics for the study of biological problems, is now a requirement for the study of biological sciences. Bioinformatics has become such a powerful and popular discipline that several academic institutions have created programs in this field, allowing students to become specialized. However, biology students who are not involved in a bioinformatics program also need a solid toolbox of bioinformatics software and skills. Therefore, we have developed a completely online bioinformatics course for non-bioinformaticians, entitled "BIF-1901 Introduction à la bio-informatique et à ses outils (Introduction to bioinformatics and bioinformatics tools)," given by the Department of Biochemistry, Microbiology, and Bioinformatics of Université Laval (Quebec City, Canada). This course requires neither a bioinformatics background nor specific skills in informatics. The underlying main goal was to produce a completely online up-to-date bioinformatics course, including practical exercises, with an intuitive pedagogical framework. The course, BIF-1901, was conceived to cover the three fundamental aspects of bioinformatics: (1) informatics, (2) biological sequence analysis, and (3) structural bioinformatics. This article discusses the content of the modules, the evaluations, the pedagogical framework, and the challenges inherent to a multidisciplinary, fully online course. © 2017 by The International Union of Biochemistry and Molecular Biology, 46(1):31-38, 2018., (© 2017 The International Union of Biochemistry and Molecular Biology.)
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- 2018
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16. Mechanism of the Nitric Oxide Dioxygenase Reaction of Mycobacterium tuberculosis Hemoglobin N.
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Carabet LA, Guertin M, Lagüe P, and Lamoureux G
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- Hemoglobins, Abnormal chemistry, Hydrogen Bonding, Molecular Dynamics Simulation, Mycobacterium tuberculosis metabolism, Oxygenases chemistry, Quantum Theory, Thermodynamics, Hemoglobins, Abnormal metabolism, Mycobacterium tuberculosis chemistry, Oxygenases metabolism
- Abstract
Many globins convert
• NO to innocuous NO3 - through their nitric oxide dioxygenase (NOD) activity. Mycobacterium tuberculosis fights the oxidative and nitrosative stress imposed by its host (the toxic effects of O2 •- and• NO species and their OONO- and• NO2 derivatives) through the action of truncated hemoglobin N (trHbN), which catalyzes the NOD reaction with one of the highest rates among globins. The general NOD mechanism comprises the following steps: binding of O2 to the heme, diffusion of• NO into the heme pocket and formation of peroxynitrite (OONO- ), isomerization of OONO- , and release of NO3 - . Using quantum mechanics/molecular mechanics free-energy calculations, we show that the NOD reaction in trHbN follows a mechanism in which heme-bound OONO- undergoes homolytic cleavage to give FeIV ═O2 - and the• NO2 radical but that these potentially harmful intermediates are short-lived and caged by the heme pocket residues. In particular, the simulations show that Tyr33(B10) side chain is shielded from FeIV ═O2 - and• NO2 (and protected from irreversible oxidation and nitration) by forming stable hydrogen bonds with Gln58(E11) side chain and Leu54(E7) backbone. Aromatic residues Phe46(CD1), Phe32(B9), and Tyr33(B10) promote NO3 - dissociation via C-H···O bonding and provide stabilizing interactions for the anion along its egress route.- Published
- 2017
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17. The Application of Proteomics to Traumatic Brain and Spinal Cord Injuries.
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Sarkis GA, Mangaonkar MD, Moghieb A, Lelling B, Guertin M, Yadikar H, Yang Z, Kobeissy F, and Wang KK
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- Animals, Biomarkers, Comorbidity, Disease Models, Animal, Humans, Mass Spectrometry, Brain metabolism, Brain Injuries metabolism, Proteomics, Spinal Cord Injuries metabolism
- Abstract
Traumatic brain injury (TBI) and traumatic spinal cord injury (SCI), collectively termed neurotrauma, are two parallel neurological conditions that can cause long-lasting neurological impairment and other comorbidities in patients, while at the same time, can create a high burden to society. To date, there are still no FDA-approved therapeutic interventions for either TBI or SCI. Recent advances in proteomic technologies, including tandem mass spectrometry, as well as imaging mass spectrometry, have enabled new approaches to study the differential proteome in TBI and SCI with the use of either animal disease models and/or biosamples from clinical observational studies. Thus, the applications of state-of-the-art proteomic method hold promises in shedding light on identifying clinically useful neurotrauma "biomarkers" and/or in identifying distinct and, otherwise, unobvious systems pathways or "key drivers" that can be further exploited as new therapeutic intervention targets.
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- 2017
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18. Molecular model of hemoglobin N from Mycobacterium tuberculosis bound to lipid bilayers: a combined spectroscopic and computational study.
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Rhéault JF, Gagné È, Guertin M, Lamoureux G, Auger M, and Lagüe P
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- Amino Acid Sequence, Aspartic Acid chemistry, Bacterial Proteins metabolism, Cardiolipins chemistry, Cardiolipins metabolism, Circular Dichroism, Conserved Sequence, Databases, Protein, Lipid Bilayers metabolism, Molecular Dynamics Simulation, Nuclear Magnetic Resonance, Biomolecular, Oxygenases metabolism, Phosphatidylcholines chemistry, Phosphatidylcholines metabolism, Phosphatidylethanolamines chemistry, Phosphatidylethanolamines metabolism, Protein Conformation, Spectroscopy, Fourier Transform Infrared, Static Electricity, Truncated Hemoglobins metabolism, Bacterial Proteins chemistry, Lipid Bilayers chemistry, Models, Molecular, Mycobacterium tuberculosis enzymology, Oxygenases chemistry, Truncated Hemoglobins chemistry
- Abstract
A singular aspect of the 2-on-2 hemoglobin structures of groups I and II is the presence of tunnels linking the protein surface to the distal heme pocket, supporting the storage and the diffusion of small apolar ligands to/from the buried active site. As the solubility of apolar ligands is greater in biological membranes than in solution, the association of these proteins with biological membranes may improve the efficiency of ligand capture. As very little is known on this subject, we have investigated the interactions between hemoglobin N (HbN), a group I 2-on-2 hemoglobin from the pathogenic Mycobacterium tuberculosis (Mtb), and biological membranes using both experimental techniques and MD simulations. HbN has a potent nitric oxide dioxygenase activity (HbN-Fe²⁺-O₂ + •NO + H₂O → HbN-Fe³⁺-OH₂ + NO₃⁻) that is thought to protect the aerobic respiration of Mtb from inhibition by •NO. Three different membrane compositions were chosen for the studies, representative of the mycobacterial plasma membrane and the mammalian cell membranes. Both the experimental and the modeling results agreed with each other and allow for a detailed molecular description of HbN in association with membranes of different compositions. The results indicated that HbN is a peripheral protein, and the association with the membranes occurred via the pre-A, G, and H helices. In addition, HbN would be allowed to modulate the binding to the membranes via electrostatic interactions between the lipid membranes and the Asp100 residue. In its membrane-bound form the short tunnel of HbN is oriented toward the membrane interior and the other tunnels point toward the solvent. Such protein orientation would facilitate the uptake of nonpolar substrates from the membrane and the release of products to the solvent. It is interesting to note that the pre-A, G, and H helices are conserved among HbN from a few other Mycobacteria.
- Published
- 2015
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