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Toward a Shared-Care Model of Relapsing-Remitting Multiple Sclerosis: Role of the Primary Care Practitioner
- Jiwon Oh, Marie-Sarah Gagné-Brosseau, Melanie Guenette, Catherine Larochelle, François Lemieux, Suresh Menon, Sarah A. Morrow, Laurence Poliquin-Lasnier, Chantal Roy-Hewitson, Carolina Rush, Anne-Marie Trudelle, Paul S. Giacomini
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- Journal:
- Canadian Journal of Neurological Sciences / Volume 45 / Issue 3 / May 2018
- Published online by Cambridge University Press:
- 14 May 2018, pp. 304-312
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The objective of this study was to develop a shared-care model to enable primary-care physicians to participate more fully in meeting the complex, multidisciplinary healthcare needs of patients with multiple sclerosis (MS). Design: The design consisted of development of consensus recommendations and a shared-care algorithm. Participants: A working group of 11 Canadian neurologists involved in the management of patients with MS were included in this study. Main message: The clinical management of patients with multiple sclerosis is increasing in complexity as new disease-modifying therapies (DMTs) become available, and ongoing safety monitoring is required. A shared-care model that includes primary care physicians is needed. Primary care physicians can assist in the early detection of MS of individuals presenting with neurological symptoms. Additional key roles for family physicians are health promotion, symptom management, and safety and relapse monitoring of DMT-treated patients. General principles of health promotion include counseling MS patients on maintaining a healthy lifestyle; performing standard screening measures; and identifying and treating comorbidities. Of particular importance are depression and anxiety, which occur in >20% of MS patients. Standard work-ups and treatments are needed for common MS-related symptoms, such as fatigue, pain, bladder dysfunction, sexual dysfunction, spasticity, and sleep disorders. Ongoing safety monitoring is required for patients receiving specific DMTs. Multiple sclerosis medications are generally contraindicated during pregnancy, and patients should be counseled to practice effective contraception. Conclusions: Multiple sclerosis is a complex, disabling illness, which, similar to other chronic diseases, requires ongoing multidisciplinary care to meet the evolving needs of patients throughout the clinical course. Family physicians can play an invaluable role in maintaining general health, managing MS-related symptoms and comorbidities, monitoring for treatment-related adverse effects and MS relapses, and coordinating allied health services to ensure continuity of care to meet the complex and evolving needs of MS patients through the disease course. RÉSUMÉ:Élaborer un modèle de soins partagés dans les cas de sclérose en plaques récurrente-rémittente.Objectif: Élaborer un modèle de soins partagés afin de permettre aux médecins de première ligne de mieux répondre aux besoins complexes et multidisciplinaires de patients atteints de la sclérose en plaques (SP). Conception : Recommandations résultant d’un consensus et élaboration d’un algorithme en matière de soins partagés. Participants : Un groupe de travail formé de onze neurologues canadiens impliqués dans la prise en charge de patients atteints de la SP. Message-clé : La prise en charge clinique de patients atteints de la SP est de plus en plus complexe dans la mesure où des médicaments modificateurs de l’évolution de la maladie (MMSP) deviennent accessibles et où un suivi permanent en matière de sécurité est nécessaire. Soulignons aussi qu’un modèle de soins partagés incluant les médecins de première ligne est nécessaire. Ces professionnels peuvent permettre un dépistage plus rapide de la SP chez des individus présentant des symptômes neurologiques. Ils peuvent aussi jouer un rôle de premier plan en matière de promotion de la santé, de soulagement des symptômes et de suivi de patients traités avec des MMSP en ce qui a trait à leur sécurité et à de possibles rechutes. Parmi les principes généraux de promotion de la santé, on peut inclure les suivants : offrir aux patients atteints de la SP des conseils leur permettant de maintenir de saines habitudes de vie ; adopter des mesures de dépistage standards ; identifier et traiter les comorbidités. À cet égard, l’anxiété et la dépression sont d’une importance particulière et sont fréquemment signalées (> 20 %) chez les patients atteints de SP. Des démarches d’investigation et des traitements standards sont nécessaires dans le cas des symptômes courants reliés à la SP, par exemple de la fatigue, des douleurs, une dysfonction vésicale, des dysfonctions sexuelles, de la spasticité et des troubles du sommeil. On l’a dit, un suivi permanent s’impose dans le cas de patients bénéficiant d’un traitement spécifique avec des MMSP. Les médicaments associés à la SP sont généralement contre-indiqués durant la grossesse de sorte qu’on devrait conseiller aux patients d’adopter des méthodes de contraception efficaces. Conclusions : La SP est une maladie complexe et invalidante qui, à l’instar d’autres maladies chroniques, exige des soins multidisciplinaires continus afin de répondre, en lien avec un tableau clinique précis, aux besoins en constante évolution des patients. Les médecins de première ligne peuvent jouer un rôle irremplaçable à plusieurs égards : dans le maintien d’une bonne santé ; le suivi et le soulagement des symptômes et des comorbidités reliés à la SP ; le suivi des rechutes et des effets indésirables associés aux traitements. N’oublions pas non plus la coordination des services paramédicaux afin d’assurer, durant l’évolution de la SP, une continuité des soins répondant aux besoins complexes et en constante évolution des patients atteints de cette maladie.
2 - Sea Ice Physics and Modelling
- Edited by Tom Carrieres, Mark Buehner, Jean-Franҫois Lemieux, Leif Toudal Pedersen, Technical University of Denmark, Lyngby
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- Sea Ice Analysis and Forecasting
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- 12 October 2017
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- 05 October 2017, pp 1-9
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Summary
To forecast the evolution of the sea ice cover in a particular region over a certain period of time, an automated prediction system must have a sea ice model. To produce these forecasts, a sea ice model requires information about the initial sea ice conditions and the atmospheric and oceanic forcing that largely govern the evolution of sea ice. The goal of this chapter is to describe how dynamics and thermodynamics processes are represented in large-scale continuum-based sea ice models. The physical processes presented include the transfer of momentum at the ice interfaces, sea ice rheology, transport, ridging, lateral melt and vertical growth and melt. This chapter also introduces how the equations for dynamics and thermodynamics are typically implemented and solved numerically. Recent model developements such as wave-ice interactions, salt dynamics and melt pond modelling are also discussed.
7 - Current Ice Services and Their Expected Evolution
- Edited by Tom Carrieres, Mark Buehner, Jean-Franҫois Lemieux, Leif Toudal Pedersen, Technical University of Denmark, Lyngby
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- Sea Ice Analysis and Forecasting
- Published online:
- 12 October 2017
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- 05 October 2017, pp 174-199
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Techniques employed at NIIS are well established but remain a largely manual process that has benefited from the greatly improved availability of satellite imagery. A number of external factors will affect the evolution of ice services over the coming years including greatly increased volumes of satellite SAR imagery, increasing client demands and improving guidance from sea ice APS. The use of APS output should evolve from providing supporting information to becoming the backbone of an expanded suite of ice information products. This will allow ice anallysts to focus on areas where they may have the most effective impact while also enabling clients to access much more diverse information that is better suited to their individual needs.
The whey fermentation product malleable protein matrix decreases TAG concentrations in patients with the metabolic syndrome: a randomised placebo-controlled trial
- Ioanna Gouni-Berthold, Dominik M. Schulte, Wilhelm Krone, Jean-François Lapointe, Pierre Lemieux, Hans-Georg Predel, Heiner K. Berthold
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- Journal:
- British Journal of Nutrition / Volume 107 / Issue 11 / 14 June 2012
- Published online by Cambridge University Press:
- 14 October 2011, pp. 1694-1706
- Print publication:
- 14 June 2012
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Animal and human studies suggest that a malleable protein matrix (MPM) from whey decreases plasma lipid concentrations and may positively influence other components of the metabolic syndrome such as glucose metabolism and blood pressure (BP). The primary objective of this double-blind, multi-centre trial was to investigate the effects of a low-fat yoghurt supplemented with whey MPM on fasting TAG concentrations in patients with the metabolic syndrome. A total of 197 patients were randomised to receive MPM or a matching placebo yoghurt identical in protein content (15 g/d). Patients were treated during 3 months with two daily servings of 150 g yoghurt each to compare changes from baseline in efficacy variables. MPM treatment resulted in a significantly larger reduction of TAG concentrations in comparison to placebo (relative change − 16 %, P = 0·004). The difference was even more pronounced in subjects with elevated fasting TAG ( ≥ 200 mg/dl) at baseline ( − 18 %, P = 0·005). The relative treatment difference in fasting plasma glucose was − 7·1 mg/dl (P = 0·089). This effect was also more pronounced in subjects with impaired fasting glucose at baseline ( − 11 mg/dl, P = 0·03). In patients with hypertension, the relative treatment difference in systolic BP reached − 5·9 mmHg (P = 0·054). The relative treatment difference in body weight was − 1·7 kg (P = 0·015). The most common adverse events were gastrointestinal in nature. Conclusions from the present study are that consumption of a low-fat yoghurt supplemented with whey MPM twice a day over 3 months significantly reduces fasting TAG concentrations in patients with the metabolic syndrome and improves multiple other cardiovascular risk factors.
Introducing patients' and the public's perspectives to health technology assessment: A systematic review of international experiences
- Marie-Pierre Gagnon, Marie Desmartis, Dolorès Lepage-Savary, Johanne Gagnon, Michèle St-Pierre, Marc Rhainds, Renald Lemieux, Francois-Pierre Gauvin, Hugo Pollender, France Légaré
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- Journal:
- International Journal of Technology Assessment in Health Care / Volume 27 / Issue 1 / January 2011
- Published online by Cambridge University Press:
- 25 January 2011, pp. 31-42
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Objectives: The aim of this study was to review international experiences of patient or public involvement in the field of health technology assessment (HTA).
Methods: A systematic review of the scientific literature was conducted. A literature search was performed across nine databases. Other literature was identified through citation tracking, government websites (HTA agencies), and Internet search engines. Characteristics of the studies, description of the activities related to patient or public involvement, impact of these activities on the HTA process, and factors facilitating or limiting involvement were abstracted independently by two reviewers.
Results: A total of 1,441 potentially relevant papers were identified by the main search strategy. Among these, seventeen papers met the inclusion criteria; other search strategies identified seven additional documents. The findings reveal that patient or public involvement in HTA activities was reported in two domains, research and HTA process. In the research domain, patients are consulted to gather evidence about their perspectives, experiences, or preferences about a health technology. These perspectives could add key dimensions to the evaluation of health technologies that might otherwise be overlooked. In the domain of the HTA process, patients or public representatives participate in different stages of this process: prioritization, evidence assessment, or dissemination of findings.
Conclusions: There are few published examples of experiences involving patients and the public in HTA. These examples show that patients' or the public's perspectives could add important dimensions to the evaluation of health technologies. However, there is a need to develop more systematic approaches to considering patients' and the public's perspectives in HTA.
Contributors
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- By Rose Teteki Abbey, K. C. Abraham, David Tuesday Adamo, LeRoy H. Aden, Efrain Agosto, Victor Aguilan, Gillian T. W. Ahlgren, Charanjit Kaur AjitSingh, Dorothy B E A Akoto, Giuseppe Alberigo, Daniel E. Albrecht, Ruth Albrecht, Daniel O. Aleshire, Urs Altermatt, Anand Amaladass, Michael Amaladoss, James N. Amanze, Lesley G. Anderson, Thomas C. Anderson, Victor Anderson, Hope S. Antone, María Pilar Aquino, Paula Arai, Victorio Araya Guillén, S. Wesley Ariarajah, Ellen T. Armour, Brett Gregory Armstrong, Atsuhiro Asano, Naim Stifan Ateek, Mahmoud Ayoub, John Alembillah Azumah, Mercedes L. García Bachmann, Irena Backus, J. Wayne Baker, Mieke Bal, Lewis V. Baldwin, William Barbieri, António Barbosa da Silva, David Basinger, Bolaji Olukemi Bateye, Oswald Bayer, Daniel H. Bays, Rosalie Beck, Nancy Elizabeth Bedford, Guy-Thomas Bedouelle, Chorbishop Seely Beggiani, Wolfgang Behringer, Christopher M. Bellitto, Byard Bennett, Harold V. Bennett, Teresa Berger, Miguel A. Bernad, Henley Bernard, Alan E. Bernstein, Jon L. Berquist, Johannes Beutler, Ana María Bidegain, Matthew P. Binkewicz, Jennifer Bird, Joseph Blenkinsopp, Dmytro Bondarenko, Paulo Bonfatti, Riet en Pim Bons-Storm, Jessica A. Boon, Marcus J. Borg, Mark Bosco, Peter C. Bouteneff, François Bovon, William D. Bowman, Paul S. Boyer, David Brakke, Richard E. Brantley, Marcus Braybrooke, Ian Breward, Ênio José da Costa Brito, Jewel Spears Brooker, Johannes Brosseder, Nicholas Canfield Read Brown, Robert F. Brown, Pamela K. Brubaker, Walter Brueggemann, Bishop Colin O. Buchanan, Stanley M. Burgess, Amy Nelson Burnett, J. Patout Burns, David B. Burrell, David Buttrick, James P. Byrd, Lavinia Byrne, Gerado Caetano, Marcos Caldas, Alkiviadis Calivas, William J. Callahan, Salvatore Calomino, Euan K. Cameron, William S. Campbell, Marcelo Ayres Camurça, Daniel F. Caner, Paul E. Capetz, Carlos F. Cardoza-Orlandi, Patrick W. Carey, Barbara Carvill, Hal Cauthron, Subhadra Mitra Channa, Mark D. Chapman, James H. Charlesworth, Kenneth R. Chase, Chen Zemin, Luciano Chianeque, Philip Chia Phin Yin, Francisca H. Chimhanda, Daniel Chiquete, John T. Chirban, Soobin Choi, Robert Choquette, Mita Choudhury, Gerald Christianson, John Chryssavgis, Sejong Chun, Esther Chung-Kim, Charles M. A. Clark, Elizabeth A. Clark, Sathianathan Clarke, Fred Cloud, John B. Cobb, W. Owen Cole, John A Coleman, John J. Collins, Sylvia Collins-Mayo, Paul K. Conkin, Beth A. Conklin, Sean Connolly, Demetrios J. Constantelos, Michael A. Conway, Paula M. Cooey, Austin Cooper, Michael L. Cooper-White, Pamela Cooper-White, L. William Countryman, Sérgio Coutinho, Pamela Couture, Shannon Craigo-Snell, James L. Crenshaw, David Crowner, Humberto Horacio Cucchetti, Lawrence S. Cunningham, Elizabeth Mason Currier, Emmanuel Cutrone, Mary L. Daniel, David D. Daniels, Robert Darden, Rolf Darge, Isaiah Dau, Jeffry C. Davis, Jane Dawson, Valentin Dedji, John W. de Gruchy, Paul DeHart, Wendy J. Deichmann Edwards, Miguel A. De La Torre, George E. Demacopoulos, Thomas de Mayo, Leah DeVun, Beatriz de Vasconcellos Dias, Dennis C. Dickerson, John M. Dillon, Luis Miguel Donatello, Igor Dorfmann-Lazarev, Susanna Drake, Jonathan A. Draper, N. Dreher Martin, Otto Dreydoppel, Angelyn Dries, A. J. Droge, Francis X. D'Sa, Marilyn Dunn, Nicole Wilkinson Duran, Rifaat Ebied, Mark J. Edwards, William H. Edwards, Leonard H. Ehrlich, Nancy L. Eiesland, Martin Elbel, J. Harold Ellens, Stephen Ellingson, Marvin M. Ellison, Robert Ellsberg, Jean Bethke Elshtain, Eldon Jay Epp, Peter C. Erb, Tassilo Erhardt, Maria Erling, Noel Leo Erskine, Gillian R. Evans, Virginia Fabella, Michael A. Fahey, Edward Farley, Margaret A. Farley, Wendy Farley, Robert Fastiggi, Seena Fazel, Duncan S. Ferguson, Helwar Figueroa, Paul Corby Finney, Kyriaki Karidoyanes FitzGerald, Thomas E. FitzGerald, John R. Fitzmier, Marie Therese Flanagan, Sabina Flanagan, Claude Flipo, Ronald B. Flowers, Carole Fontaine, David Ford, Mary Ford, Stephanie A. Ford, Jim Forest, William Franke, Robert M. Franklin, Ruth Franzén, Edward H. Friedman, Samuel Frouisou, Lorelei F. Fuchs, Jojo M. Fung, Inger Furseth, Richard R. Gaillardetz, Brandon Gallaher, China Galland, Mark Galli, Ismael García, Tharscisse Gatwa, Jean-Marie Gaudeul, Luis María Gavilanes del Castillo, Pavel L. Gavrilyuk, Volney P. Gay, Metropolitan Athanasios Geevargis, Kondothra M. George, Mary Gerhart, Simon Gikandi, Maurice Gilbert, Michael J. Gillgannon, Verónica Giménez Beliveau, Terryl Givens, Beth Glazier-McDonald, Philip Gleason, Menghun Goh, Brian Golding, Bishop Hilario M. Gomez, Michelle A. Gonzalez, Donald K. Gorrell, Roy Gottfried, Tamara Grdzelidze, Joel B. Green, Niels Henrik Gregersen, Cristina Grenholm, Herbert Griffiths, Eric W. Gritsch, Erich S. Gruen, Christoffer H. Grundmann, Paul H. Gundani, Jon P. Gunnemann, Petre Guran, Vidar L. Haanes, Jeremiah M. Hackett, Getatchew Haile, Douglas John Hall, Nicholas Hammond, Daphne Hampson, Jehu J. Hanciles, Barry Hankins, Jennifer Haraguchi, Stanley S. Harakas, Anthony John Harding, Conrad L. Harkins, J. William Harmless, Marjory Harper, Amir Harrak, Joel F. Harrington, Mark W. Harris, Susan Ashbrook Harvey, Van A. Harvey, R. Chris Hassel, Jione Havea, Daniel Hawk, Diana L. Hayes, Leslie Hayes, Priscilla Hayner, S. Mark Heim, Simo Heininen, Richard P. Heitzenrater, Eila Helander, David Hempton, Scott H. Hendrix, Jan-Olav Henriksen, Gina Hens-Piazza, Carter Heyward, Nicholas J. Higham, David Hilliard, Norman A. Hjelm, Peter C. Hodgson, Arthur Holder, M. Jan Holton, Dwight N. Hopkins, Ronnie Po-chia Hsia, Po-Ho Huang, James Hudnut-Beumler, Jennifer S. Hughes, Leonard M. Hummel, Mary E. Hunt, Laennec Hurbon, Mark Hutchinson, Susan E. Hylen, Mary Beth Ingham, H. Larry Ingle, Dale T. Irvin, Jon Isaak, Paul John Isaak, Ada María Isasi-Díaz, Hans Raun Iversen, Margaret C. Jacob, Arthur James, Maria Jansdotter-Samuelsson, David Jasper, Werner G. Jeanrond, Renée Jeffery, David Lyle Jeffrey, Theodore W. Jennings, David H. Jensen, Robin Margaret Jensen, David Jobling, Dale A. Johnson, Elizabeth A. Johnson, Maxwell E. Johnson, Sarah Johnson, Mark D. Johnston, F. Stanley Jones, James William Jones, John R. Jones, Alissa Jones Nelson, Inge Jonsson, Jan Joosten, Elizabeth Judd, Mulambya Peggy Kabonde, Robert Kaggwa, Sylvester Kahakwa, Isaac Kalimi, Ogbu U. Kalu, Eunice Kamaara, Wayne C. Kannaday, Musimbi Kanyoro, Veli-Matti Kärkkäinen, Frank Kaufmann, Léon Nguapitshi Kayongo, Richard Kearney, Alice A. Keefe, Ralph Keen, Catherine Keller, Anthony J. Kelly, Karen Kennelly, Kathi Lynn Kern, Fergus Kerr, Edward Kessler, George Kilcourse, Heup Young Kim, Kim Sung-Hae, Kim Yong-Bock, Kim Yung Suk, Richard King, Thomas M. King, Robert M. Kingdon, Ross Kinsler, Hans G. Kippenberg, Cheryl A. Kirk-Duggan, Clifton Kirkpatrick, Leonid Kishkovsky, Nadieszda Kizenko, Jeffrey Klaiber, Hans-Josef Klauck, Sidney Knight, Samuel Kobia, Robert Kolb, Karla Ann Koll, Heikki Kotila, Donald Kraybill, Philip D. W. Krey, Yves Krumenacker, Jeffrey Kah-Jin Kuan, Simanga R. Kumalo, Peter Kuzmic, Simon Shui-Man Kwan, Kwok Pui-lan, André LaCocque, Stephen E. Lahey, John Tsz Pang Lai, Emiel Lamberts, Armando Lampe, Craig Lampe, Beverly J. Lanzetta, Eve LaPlante, Lizette Larson-Miller, Ariel Bybee Laughton, Leonard Lawlor, Bentley Layton, Robin A. Leaver, Karen Lebacqz, Archie Chi Chung Lee, Marilyn J. Legge, Hervé LeGrand, D. L. LeMahieu, Raymond Lemieux, Bill J. Leonard, Ellen M. Leonard, Outi Leppä, Jean Lesaulnier, Nantawan Boonprasat Lewis, Henrietta Leyser, Alexei Lidov, Bernard Lightman, Paul Chang-Ha Lim, Carter Lindberg, Mark R. Lindsay, James R. Linville, James C. Livingston, Ann Loades, David Loades, Jean-Claude Loba-Mkole, Lo Lung Kwong, Wati Longchar, Eleazar López, David W. Lotz, Andrew Louth, Robin W. Lovin, William Luis, Frank D. Macchia, Diarmaid N. J. MacCulloch, Kirk R. MacGregor, Marjory A. MacLean, Donald MacLeod, Tomas S. Maddela, Inge Mager, Laurenti Magesa, David G. Maillu, Fortunato Mallimaci, Philip Mamalakis, Kä Mana, Ukachukwu Chris Manus, Herbert Robinson Marbury, Reuel Norman Marigza, Jacqueline Mariña, Antti Marjanen, Luiz C. L. Marques, Madipoane Masenya (ngwan'a Mphahlele), Caleb J. D. Maskell, Steve Mason, Thomas Massaro, Fernando Matamoros Ponce, András Máté-Tóth, Odair Pedroso Mateus, Dinis Matsolo, Fumitaka Matsuoka, John D'Arcy May, Yelena Mazour-Matusevich, Theodore Mbazumutima, John S. McClure, Christian McConnell, Lee Martin McDonald, Gary B. McGee, Thomas McGowan, Alister E. McGrath, Richard J. McGregor, John A. McGuckin, Maud Burnett McInerney, Elsie Anne McKee, Mary B. McKinley, James F. McMillan, Ernan McMullin, Kathleen E. McVey, M. Douglas Meeks, Monica Jyotsna Melanchthon, Ilie Melniciuc-Puica, Everett Mendoza, Raymond A. Mentzer, William W. Menzies, Ina Merdjanova, Franziska Metzger, Constant J. Mews, Marvin Meyer, Carol Meyers, Vasile Mihoc, Gunner Bjerg Mikkelsen, Maria Inêz de Castro Millen, Clyde Lee Miller, Bonnie J. Miller-McLemore, Alexander Mirkovic, Paul Misner, Nozomu Miyahira, R. W. L. Moberly, Gerald Moede, Aloo Osotsi Mojola, Sunanda Mongia, Rebeca Montemayor, James Moore, Roger E. Moore, Craig E. Morrison O.Carm, Jeffry H. Morrison, Keith Morrison, Wilson J. Moses, Tefetso Henry Mothibe, Mokgethi Motlhabi, Fulata Moyo, Henry Mugabe, Jesse Ndwiga Kanyua Mugambi, Peggy Mulambya-Kabonde, Robert Bruce Mullin, Pamela Mullins Reaves, Saskia Murk Jansen, Heleen L. Murre-Van den Berg, Augustine Musopole, Isaac M. T. Mwase, Philomena Mwaura, Cecilia Nahnfeldt, Anne Nasimiyu Wasike, Carmiña Navia Velasco, Thulani Ndlazi, Alexander Negrov, James B. Nelson, David G. Newcombe, Carol Newsom, Helen J. Nicholson, George W. E. Nickelsburg, Tatyana Nikolskaya, Damayanthi M. A. Niles, Bertil Nilsson, Nyambura Njoroge, Fidelis Nkomazana, Mary Beth Norton, Christian Nottmeier, Sonene Nyawo, Anthère Nzabatsinda, Edward T. Oakes, Gerald O'Collins, Daniel O'Connell, David W. Odell-Scott, Mercy Amba Oduyoye, Kathleen O'Grady, Oyeronke Olajubu, Thomas O'Loughlin, Dennis T. Olson, J. Steven O'Malley, Cephas N. Omenyo, Muriel Orevillo-Montenegro, César Augusto Ornellas Ramos, Agbonkhianmeghe E. Orobator, Kenan B. Osborne, Carolyn Osiek, Javier Otaola Montagne, Douglas F. Ottati, Anna May Say Pa, Irina Paert, Jerry G. Pankhurst, Aristotle Papanikolaou, Samuele F. Pardini, Stefano Parenti, Peter Paris, Sung Bae Park, Cristián G. Parker, Raquel Pastor, Joseph Pathrapankal, Daniel Patte, W. Brown Patterson, Clive Pearson, Keith F. Pecklers, Nancy Cardoso Pereira, David Horace Perkins, Pheme Perkins, Edward N. Peters, Rebecca Todd Peters, Bishop Yeznik Petrossian, Raymond Pfister, Peter C. Phan, Isabel Apawo Phiri, William S. F. Pickering, Derrick G. Pitard, William Elvis Plata, Zlatko Plese, John Plummer, James Newton Poling, Ronald Popivchak, Andrew Porter, Ute Possekel, James M. Powell, Enos Das Pradhan, Devadasan Premnath, Jaime Adrían Prieto Valladares, Anne Primavesi, Randall Prior, María Alicia Puente Lutteroth, Eduardo Guzmão Quadros, Albert Rabil, Laurent William Ramambason, Apolonio M. Ranche, Vololona Randriamanantena Andriamitandrina, Lawrence R. Rast, Paul L. Redditt, Adele Reinhartz, Rolf Rendtorff, Pål Repstad, James N. Rhodes, John K. Riches, Joerg Rieger, Sharon H. Ringe, Sandra Rios, Tyler Roberts, David M. Robinson, James M. Robinson, Joanne Maguire Robinson, Richard A. H. Robinson, Roy R. Robson, Jack B. Rogers, Maria Roginska, Sidney Rooy, Rev. Garnett Roper, Maria José Fontelas Rosado-Nunes, Andrew C. Ross, Stefan Rossbach, François Rossier, John D. Roth, John K. Roth, Phillip Rothwell, Richard E. Rubenstein, Rosemary Radford Ruether, Markku Ruotsila, John E. Rybolt, Risto Saarinen, John Saillant, Juan Sanchez, Wagner Lopes Sanchez, Hugo N. Santos, Gerhard Sauter, Gloria L. Schaab, Sandra M. Schneiders, Quentin J. Schultze, Fernando F. Segovia, Turid Karlsen Seim, Carsten Selch Jensen, Alan P. F. Sell, Frank C. Senn, Kent Davis Sensenig, Damían Setton, Bal Krishna Sharma, Carolyn J. Sharp, Thomas Sheehan, N. Gerald Shenk, Christian Sheppard, Charles Sherlock, Tabona Shoko, Walter B. Shurden, Marguerite Shuster, B. Mark Sietsema, Batara Sihombing, Neil Silberman, Clodomiro Siller, Samuel Silva-Gotay, Heikki Silvet, John K. Simmons, Hagith Sivan, James C. Skedros, Abraham Smith, Ashley A. Smith, Ted A. Smith, Daud Soesilo, Pia Søltoft, Choan-Seng (C. S.) Song, Kathryn Spink, Bryan Spinks, Eric O. Springsted, Nicolas Standaert, Brian Stanley, Glen H. Stassen, Karel Steenbrink, Stephen J. Stein, Andrea Sterk, Gregory E. Sterling, Columba Stewart, Jacques Stewart, Robert B. Stewart, Cynthia Stokes Brown, Ken Stone, Anne Stott, Elizabeth Stuart, Monya Stubbs, Marjorie Hewitt Suchocki, David Kwang-sun Suh, Scott W. Sunquist, Keith Suter, Douglas Sweeney, Charles H. Talbert, Shawqi N. Talia, Elsa Tamez, Joseph B. Tamney, Jonathan Y. Tan, Yak-Hwee Tan, Kathryn Tanner, Feiya Tao, Elizabeth S. Tapia, Aquiline Tarimo, Claire Taylor, Mark Lewis Taylor, Bishop Abba Samuel Wolde Tekestebirhan, Eugene TeSelle, M. Thomas Thangaraj, David R. Thomas, Andrew Thornley, Scott Thumma, Marcelo Timotheo da Costa, George E. “Tink” Tinker, Ola Tjørhom, Karen Jo Torjesen, Iain R. Torrance, Fernando Torres-Londoño, Archbishop Demetrios [Trakatellis], Marit Trelstad, Christine Trevett, Phyllis Trible, Johannes Tromp, Paul Turner, Robert G. Tuttle, Archbishop Desmond Tutu, Peter Tyler, Anders Tyrberg, Justin Ukpong, Javier Ulloa, Camillus Umoh, Kristi Upson-Saia, Martina Urban, Monica Uribe, Elochukwu Eugene Uzukwu, Richard Vaggione, Gabriel Vahanian, Paul Valliere, T. J. Van Bavel, Steven Vanderputten, Peter Van der Veer, Huub Van de Sandt, Louis Van Tongeren, Luke A. Veronis, Noel Villalba, Ramón Vinke, Tim Vivian, David Voas, Elena Volkova, Katharina von Kellenbach, Elina Vuola, Timothy Wadkins, Elaine M. Wainwright, Randi Jones Walker, Dewey D. Wallace, Jerry Walls, Michael J. Walsh, Philip Walters, Janet Walton, Jonathan L. Walton, Wang Xiaochao, Patricia A. Ward, David Harrington Watt, Herold D. Weiss, Laurence L. Welborn, Sharon D. Welch, Timothy Wengert, Traci C. West, Merold Westphal, David Wetherell, Barbara Wheeler, Carolinne White, Jean-Paul Wiest, Frans Wijsen, Terry L. Wilder, Felix Wilfred, Rebecca Wilkin, Daniel H. Williams, D. Newell Williams, Michael A. Williams, Vincent L. Wimbush, Gabriele Winkler, Anders Winroth, Lauri Emílio Wirth, James A. Wiseman, Ebba Witt-Brattström, Teofil Wojciechowski, John Wolffe, Kenman L. Wong, Wong Wai Ching, Linda Woodhead, Wendy M. Wright, Rose Wu, Keith E. Yandell, Gale A. Yee, Viktor Yelensky, Yeo Khiok-Khng, Gustav K. K. Yeung, Angela Yiu, Amos Yong, Yong Ting Jin, You Bin, Youhanna Nessim Youssef, Eliana Yunes, Robert Michael Zaller, Valarie H. Ziegler, Barbara Brown Zikmund, Joyce Ann Zimmerman, Aurora Zlotnik, Zhuo Xinping
- Edited by Daniel Patte, Vanderbilt University, Tennessee
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- The Cambridge Dictionary of Christianity
- Published online:
- 05 August 2012
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- 20 September 2010, pp xi-xliv
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Modeling active RNA structures using the intersection of conformational space: Application to the lead-activated ribozyme
- SÉBASTIEN LEMIEUX, PASCAL CHARTRAND, ROBERT CEDERGREN, FRANÇOIS MAJOR
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The Pb2+ cleavage of a specific phosphodiester bond in yeast tRNAPhe is the classical model of metal-assisted RNA catalysis. In vitro selection experiments have identified a tRNAPhe variant, the leadzyme, that is very active in cleavage by Pb2+. We present here a three-dimensional modeling protocol that was used to propose a structure for this ribozyme, and is based on the computation of the intersection of conformational space of sequence variants and the use of chemical modification data. Sequence and secondary structure data were used in a first round of computer modeling that allowed identification of conformations compatible with all known leadzyme variants. Common conformations were then tested experimentally by evaluating the activity of analogues containing modified nucleotides in the catalytic core. These experiments led to a new structural hypothesis that was tested in a second round of computer modeling. The resulting proposal for the active conformation of the leadzyme is consistent with all known structural data. The final model suggests an in-line SN2 attack mechanism and predicts two Pb2+ binding sites. The protocol presented here is generally applicable in modeling RNAs whenever the catalytic or binding activity of structural analogues is known.