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8. The Parkinson Progression Marker Initiative (PPMI)

Author

Marek, Kenneth, Jennings, Danna, Lasch, Shirley, Siderowf, Andrew, Tanner, Caroline, Simuni, Tanya, Coffey, Chris, Kieburtz, Karl, Flagg, Emily, Chowdhury, Sohini, Poewe, Werner, Mollenhauer, Brit, Klinik, Paracelsus-Elena, Sherer, Todd, Frasier, Mark, Meunier, Claire, Rudolph, Alice, Casaceli, Cindy, Seibyl, John, Mendick, Susan, Schuff, Norbert, Zhang, Ying, Toga, Arthur, Crawford, Karen, Ansbach, Alison, De Blasio, Pasquale, Piovella, Michele, Trojanowski, John, Shaw, Les, Singleton, Andrew, Hawkins, Keith, Eberling, Jamie, Brooks, Deborah, Russell, David, Leary, Laura, Factor, Stewart, Sommerfeld, Barbara, Hogarth, Penelope, Pighetti, Emily, Williams, Karen, Standaert, David, Guthrie, Stephanie, Hauser, Robert, Delgado, Holly, Jankovic, Joseph, Hunter, Christine, Stern, Matthew, Tran, Baochan, Leverenz, Jim, Baca, Marne, Frank, Sam, Thomas, Cathi-Ann, Richard, Irene, Deeley, Cheryl, Rees, Linda, Sprenger, Fabienne, Lang, Elisabeth, Shill, Holly, Obradov, Sanja, Fernandez, Hubert, Winters, Adrienna, Berg, Daniela, Gauss, Katharina, Galasko, Douglas, Fontaine, Deborah, Mari, Zoltan, Gerstenhaber, Melissa, Brooks, David, Malloy, Sophie, Barone, Paolo, Longo, Katia, Comery, Tom, Ravina, Bernard, Grachev, Igor, Gallagher, Kim, Collins, Michelle, Widnell, Katherine L., Ostrowizki, Suzanne, Fontoura, Paulo, Ho, Tony, Luthman, Johan, Brug, Marcel van der, Reith, Alastair D., and Taylor, Peggy

Published
2011
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10. The genetic architecture of the human cerebral cortex

Author

Grasby, Katrina L, Jahanshad, Neda, Shatokhina, Natalia, Mirza-Schreiber, Nazanin, Moreira, Jose C V, Mühleisen, Thomas W, Müller-Myhsok, Bertram, Najt, Pablo, Nakahara, Soichiro, Nho, Kwangsik, Olde Loohuis, Loes M, Orfanos, Dimitri Papadopoulos, Pearson, John F, Zsembik, Leo C P, Pitcher, Toni L, Pütz, Benno, Quidé, Yann, Ragothaman, Anjanibhargavi, Rashid, Faisal M, Reay, William R, Redlich, Ronny, Reinbold, Céline S, Repple, Jonathan, Richard, Geneviève, Thomopoulos, Sophia I, Riedel, Brandalyn C, Risacher, Shannon L, Rocha, Cristiane S, Mota, Nina Roth, Salminen, Lauren, Saremi, Arvin, Saykin, Andrew J, Schlag, Fenja, Schmaal, Lianne, Schofield, Peter R, Zhu, Alyssa H, Secolin, Rodrigo, Shapland, Chin Yang, Shen, Li, Shin, Jean, Shumskaya, Elena, Sønderby, Ida E, Sprooten, Emma, Tansey, Katherine E, Teumer, Alexander, Thalamuthu, Anbupalam, Strike, Lachlan T, Tordesillas-Gutiérrez, Diana, Turner, Jessica A, Uhlmann, Anne, Vallerga, Costanza Ludovica, van der Meer, Dennis, van Donkelaar, Marjolein M J, van Eijk, Liza, van Erp, Theo G M, van Haren, Neeltje E M, van Rooij, Daan, Agartz, Ingrid, van Tol, Marie-José, Veldink, Jan H, Verhoef, Ellen, Walton, Esther, Wang, Mingyuan, Wang, Yunpeng, Wardlaw, Joanna M, Wen, Wei, Westlye, Lars T, Whelan, Christopher D, Alhusaini, Saud, Witt, Stephanie H, Wittfeld, Katharina, Wolf, Christiane, Wolfers, Thomas, Wu, Jing Qin, Yasuda, Clarissa L, Zaremba, Dario, Zhang, Zuo, Zwiers, Marcel P, Artiges, Eric, Almeida, Marcio A A, Assareh, Amelia A, Ayesa-Arriola, Rosa, Belger, Aysenil, Brandt, Christine L, Brown, Gregory G, Cichon, Sven, Curran, Joanne E, Davies, Gareth E, Degenhardt, Franziska, Dennis, Michelle F, Alnæs, Dag, Dietsche, Bruno, Djurovic, Srdjan, Doherty, Colin P, Espiritu, Ryan, Garijo, Daniel, Gil, Yolanda, Gowland, Penny A, Green, Robert C, Häusler, Alexander N, Heindel, Walter, Amlien, Inge K, Ho, Beng-Choon, Hoffmann, Wolfgang U, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Jack, Clifford R, Jang, MiHyun, Jansen, Andreas, Kimbrel, Nathan A, Kolskår, Knut, Painter, Jodie N, Andersson, Micael, Koops, Sanne, Krug, Axel, Lim, Kelvin O, Luykx, Jurjen J, Mathalon, Daniel H, Mather, Karen A, Mattay, Venkata S, Matthews, Sarah, Mayoral Van Son, Jaqueline, McEwen, Sarah C, Ard, Tyler, Melle, Ingrid, Morris, Derek W, Mueller, Bryon A, Nauck, Matthias, Nordvik, Jan E, Nöthen, Markus M, O'Leary, Daniel S, Opel, Nils, Martinot, Marie-Laure Paillère, Pike, G Bruce, Armstrong, Nicola J, Preda, Adrian, Quinlan, Erin B, Rasser, Paul E, Ratnakar, Varun, Reppermund, Simone, Steen, Vidar M, Tooney, Paul A, Torres, Fábio R, Veltman, Dick J, Voyvodic, James T, Ashley-Koch, Allison, Whelan, Robert, White, Tonya, Yamamori, Hidenaga, Adams, Hieab H H, Bis, Joshua C, Debette, Stephanie, Decarli, Charles, Fornage, Myriam, Gudnason, Vilmundur, Hofer, Edith, Atkins, Joshua R, Ikram, M Arfan, Launer, Lenore, Longstreth, W. T., Lopez, Oscar L, Mazoyer, Bernard, Mosley, Thomas H, Roshchupkin, Gennady V, Satizabal, Claudia L, Schmidt, Reinhold, Seshadri, Sudha, Bernard, Manon, Yang, Qiong, Initiative, Alzheimer’s Disease Neuroimaging, Consortium, CHARGE, Consortium, EPIGEN, Consortium, IMAGEN, Consortium, SYS, Initiative, Parkinson’s Progression Markers, Alvim, Marina K M, Ames, David, Anderson, Tim J, Brouwer, Rachel M, Andreassen, Ole A, Arias-Vasquez, Alejandro, Bastin, Mark E, Baune, Bernhard T, Beckham, Jean C, Blangero, John, Boomsma, Dorret I, Brodaty, Henry, Brunner, Han G, Buckner, Randy L, Buimer, Elizabeth E L, Buitelaar, Jan K, Bustillo, Juan R, Cahn, Wiepke, Cairns, Murray J, Calhoun, Vince, Carr, Vaughan J, Caseras, Xavier, Caspers, Svenja, Cavalleri, Gianpiero L, Cendes, Fernando, Bülow, Robin, Corvin, Aiden, Crespo-Facorro, Benedicto, Dalrymple-Alford, John C, Dannlowski, Udo, de Geus, Eco J C, Deary, Ian J, Delanty, Norman, Depondt, Chantal, Desrivières, Sylvane, Donohoe, Gary, Bürger, Christian, Espeseth, Thomas, Fernández, Guillén, Fisher, Simon E, Flor, Herta, Forstner, Andreas J, Francks, Clyde, Franke, Barbara, Glahn, David C, Gollub, Randy L, Grabe, Hans J, Colodro-Conde, Lucía, Cannon, Dara M, Gruber, Oliver, Håberg, Asta K, Hariri, Ahmad R, Hartman, Catharina A, Hashimoto, Ryota, Heinz, Andreas, Henskens, Frans A, Hillegers, Manon H J, Hoekstra, Pieter J, Holmes, Avram J, Chakravarty, Mallar, Hong, L Elliot, Hopkins, William D, Hulshoff Pol, Hilleke E, Jernigan, Terry L, Jönsson, Erik G, Kahn, René S, Kennedy, Martin A, Kircher, Tilo T J, Kochunov, Peter, Kwok, John B J, Chen, Qiang, Le Hellard, Stephanie, Loughland, Carmel M, Martin, Nicholas G, Martinot, Jean-Luc, McDonald, Colm, McMahon, Katie L, Meyer-Lindenberg, Andreas, Michie, Patricia T, Morey, Rajendra A, Mowry, Bryan, Cheung, Joshua W, Nyberg, Lars, Oosterlaan, Jaap, Ophoff, Roel A, Pantelis, Christos, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W J H, Polderman, Tinca J C, Posthuma, Danielle, Rietschel, Marcella, Couvy-Duchesne, Baptiste, Roffman, Joshua L, Rowland, Laura M, Sachdev, Perminder S, Sämann, Philipp G, Schall, Ulrich, Schumann, Gunter, Scott, Rodney J, Sim, Kang, Sisodiya, Sanjay M, Smoller, Jordan W, Dale, Anders M, Sommer, Iris E, St Pourcain, Beate, Stein, Dan J, Toga, Arthur W, Trollor, Julian N, Van der Wee, Nic J A, van 't Ent, Dennis, Völzke, Henry, Walter, Henrik, Weber, Bernd, Dalvie, Shareefa, Weinberger, Daniel R, Wright, Margaret J, Zhou, Juan, Stein, Jason L, Thompson, Paul M, Medland, Sarah E, Consortium, Enhancing NeuroImaging Genetics through Meta-Analysis, Witte, A Veronica, Darin, Abigail, Fleisher, Adam, de Araujo, Tânia K, Pierce, Aimee, Mintz, Akiva, Lerner, Alan, Reith, Alastair D, Hofman, Albert, Espay, Alberto, Ihlenfeld, Albrecht, Ing, Alex, Iranzo, Alex, Beiser, Alexa S, de Zubicaray, Greig I, Norbash, Alexander, Barbot, Alexis, Rudolph, Alice, Portillo, Alicia, Chalker, Alison, Levey, Allan I, Rosen, Allyson, Smith, Amanda, Catafau, Ana, de Zwarte, Sonja M C, Ulysse, Anaztasia, Uitterlinden, André G, Becker, Andreas, Budson, Andrew E, Kertesz, Andrew, Siderowf, Andrew, Bralten, Janita, den Braber, Anouk, Singleton, Andrew, James, Angela, Oliver, Angela, Mishra, Aniket, Hake, Ann Marie, Burke, Anna, Sarrael, Antero, Porsteinsson, Anton P, Stringaris, Argyris, McCoy, Arita, Doan, Nhat Trung, Villringer, Arno, Lenahan, Art, Toga, Arthur, Bokde, Arun, Rawlins, Ashlee, Lamb, Ashley, Lee, Athena, Raj, Balebail Ashok, Tran, Baochan, Dohm, Katharina, Ruggeri, Barbara, Saba, Barbara, Lane, Barton, Yanez, Beatriz, Ances, Beau, Dunlop, Becky, Mudge, Benita, Ravina, Bernard, Ittermann, Bernd, Ehrlich, Stefan, van Noort, Betteke, Lind, Betty, Shah, Bina, Stefanovic, Bojana, Goldstein, Bonnie S, Bonakdarpour, Borna, Matthews, Brandy R, Borowski, Bret, Ott, Brian R, Reynolds, Brigid, Engelbrecht, Hannah-Ruth, Mollenhauer, Brit, Miller, Bruce L, Psaty, Bruce M, Spann, Bryan M, Sadowsky, Carl, Linder, Carly, Franz, Carol E, Tanner, Caroline, Kopil, Catherine, Thomas, Cathi-Ann, Erk, Susanne, Ward, Chad, Bernick, Charles, Smith, Charles D, DeCarli, Charles, Caspell, Chelsea, Deeley, Cheryl, Riordan, Cheryl, Mathis, Chet, Onyike, Chiadi, Heyn, Chris Chinthaka, Fan, Chun Chieh, Hosein, Chris, Leach, Christi, Bÿchel, Christian, Gigliotti, Christina, Hunter, Christine, Belden, Christine M, Tzourio, Christophe, Coffey, Christopher, van Dyck, Christopher H, Clark, Christopher M, Fedko, Iryna O, Wu, Chuang-Kuo, Albers, Colleen S, Chu, Congying, Brand, Connie, Isensee, Corinna, van Duijn, Cornelia M, Bishop, Courtney, Bodge, Courtney, Foley, Sonya F, Tatsuoka, Curtis, Casaceli, Cynthia, Carlsson, Cynthia M, Mathews, Dana, D'Agostino, Daniel, Silverman, Daniel H S, Marson, Daniel, Berg, Daniela, Harvey, Danielle, Jennings, Danna, Ford, Judith M, Wolk, David A, Goldstein, David B, Bachman, David, Brooks, David, Clark, David, Geldmacher, David, Hart, David, Holtzman, David, Jones, David, Hibar, Derrek P, Fukunaga, Masaki, Knopman, David, Hewitt, David L, Perry, David, Russell, David, Standaert, David, Winkfield, David, Green, Davis Robert C, Fontaine, Deborah, Miller, Delwyn D, Gessert, Devon, Garrett, Melanie E, Kerwin, Diana, Willeke, Diana, Drost, Dick, Papadopoulos, Dimitri, Rowe, Dominic, Simpson, Donna M, Muni, Donna, Galasko, Douglas, Scharre, Douglas W, Fillmer, Ariane, Ge, Tian, Bartha, Rob, Celmins, Dzintra, Zimmerman, Earl A, Teng, Edmond, Tolosa, Eduardo, Coleman, Edward, Zamrini, Edward, Mitsis, Effie, Finger, Elizabeth, Giddaluru, Sudheer, Oates, Elizabeth, Sosa, Elizabeth, Woo, Ellen, Rogalski, Emily, Lethbridge, Emma, Dooley, Eoin, Foster, Eric, Reiman, Eric M, Quinlan, Erin Burke, Goldman, Aaron L, Franklin, Erin, Heinzen, Erin L, Fletcher, Evan, Sprenger, Fabienne, Crivello, Fabrice, Biondo, Francesca, Parfitt, Francine, Hefti, Franz, Beyer, Frauke, Nees, Frauke, Green, Melissa J, Leonard, Gabriel, Robert, Gabriel, Thai, Gaby, Marshall, Gad A, Barker, Gareth, Conrad, Gary, Tremont, Geoffrey, Bartzokis, George, Groenewold, Nynke A, Hsiung, Ging-Yuek Robin, Malferrari, Giulia, Chiang, Gloria, Pearlson, Godfrey D, Liang, Grace, Jicha, Greg, Sorensen, Greg, Todd, Gretchen, Jimenez, Gustavo, Grotegerd, Dominik, Zare, Habil, Grabe, Hans Jörgen, Vanderswag, Helen, Schmidt, Helena, Venkov, Heli, Lemaitre, Hervé, Gurholt, Tiril P, Grossman, Hillel, Shill, Holly, Soares, Holly, Lin, Honghuang, Capote, Horacio, Bergman, Howard, Chertkow, Howard, Feldman, Howard, Fillit, Howard, Rosen, Howard J, Gutman, Boris A, Koleva, Hristina, Fernandez, Hubert, Garavan, Hugh, Shim, Hyungsub, Grachev, Igor D, Richard, Irene, Filippi, Irina, Rachinsky, Irina, Wurster, Isabel, Lind, Penelope A, Hansell, Narelle K, Mintzer, Jacobo, Ziolkowski, Jaimie, Brewer, James, Lah, James J, Leverenz, James, Becker, James T, Tetrud, James, Singleton-Garvin, Jamika, Egebjerg, Jan, Cellar, Janet S, Harris, Mathew A, Pentilla, Jani, Brosch, Jared R, Tinklenberg, Jared, Karlawish, Jason H, Meyer, Javier Villanueva, Himali, Jayandra J, Poline, Jean-Baptiste, Gunter, Jeff, Kaye, Jeffrey A, Harrison, Marc B, Dalley, Jeffrey, Burns, Jeffrey M, Petrella, Jeffrey R, Mule, Jennifer, Salazar, Jennifer, Rotter, Jerome I, Yesavage, Jerome, Cedarbaum, Jesse, Jiang, Jiyang, Haswell, Courtney C, Allard, Joanne, Lord, Joanne L, Hetelle, Joel, Kwok, John B, Brockington, John, Morris, John C, Hsiao, John, Morris, John, Olichney, John, Trojanowki, John Q, Hauser, Michael, Rogers, John, Seibyl, John, Yankey, Jon, Dubow, Jordan S, Jankovic, Joseph, Quinn, Joseph, Kass, Joseph S, Taylor, Joy L, Heidebrink, Judith L, Herms, Stefan, Trollor, Julian, Fröhner, Juliane, Anderson, Karen, Blank, Karen, Crawford, Karen, Smith, Karen Ekstam, Bell, Karen L, Williams, Karen, Kieburtz, Karl, Heslenfeld, Dirk J, Gauss, Katharina, Gloer, Katherine, Johnson, Kathleen, Tingus, Kathleen, DeMarco, Kathryn, Sink, Kaycee M, Hawkins, Keith A, Johnson, Keith A, Kantarci, Kejal, Ho, New Fei, Faber, Kelley, Harless, Kelly, Makino, Kelly M, Marek, Kenneth, Spicer, Kenneth, Shianna, Kevin, Chen, Kewei, Nam, Ki Won, Martin, Kim, Poki-Walker, Kim, Hoehn, David, Seppi, Klaus, Johnson, Kris, Fargher, Kristin, Lipowski, Kristine, Espay, Kristy, Womack, Kyle, Chahine, Lama, Flashman, Laura A, Daedelow, Laura, Hoffmann, Per, Leary, Laura, Beckett, Laurel, Honig, Lawrence S, Thal, Leon, Shaw, Leslie M, Kuller, Lew, Apostolova, Liana, Teodoro, Liberty, Rees, Linda, Pizzagalli, Fabrizio, Holleran, Laurena, Lewis, Lindsay, Hergesheimer, Lindsey, Silbert, Lisa C, Ravdin, Lisa, Taylor-Reinwald, Lisa, Uribe, Liz, Schneider, Lon S, Daiello, Lori A, Richer, Louis, Poustka, Luise, Hoogman, Martine, Pirpamer, Lukas, Mesulam, M Marcel, Ismail, M Saleem, Ranola, Madelaine, Korecka, Magdalena, Raichle, Marc, Seltzer, Marc, van der Brug, Marcel, Hottenga, Jouke-Jan, Mesulam, Marek-Marsel, Carrillo, Maria, Carroll, Maria, Knol, Maria J, Kataki, Maria, Greig-Custo, Maria T, Paillere, Marie-Laure, Albert, Marilyn, Love, Marissa Natelson, Ikeda, Masashi, Mintun, Mark A, Frasier, Mark, Logue, Mark, Minton, Mark, Loeffler, Markus, Scholz, Markus, Baca, Marne, Farlow, Martin R, Sadowski, Martin, Janowitz, Deborah, Creech, Mary L, Hynes, Mary L, Quiceno, Mary, Oakley, MaryAnn, Harris, Mat, Senjem, Matt, Bernstein, Matthew, Panizzon, Matthew S, Stern, Matthew, Becerra, Mauricio, Jansen, Iris E, Witbracht, Megan, Vernooij, Meike W, Brandabur, Melanie, Keltz, Melanie, Lamar, Melissa, Yang, Mia, Ahlijanian, Michael, Borrie, Michael, Neale, Michael C, Donohue, Michael, Jia, Tianye, Lyons, Michael J, Lin, Michael, Rapp, Michael, Smolka, Michael, Weiner, Michael W, Weiner, Michael, Figurski, Michal, Perron, Michel, Assaly, Michele, Luciano, Michelle, Jockwitz, Christiane, Rainka, Michelle, Dang, Mimi, Sheikh, Mohammed O, Ghanbari, Mohsen, Gaikwad, Mrunalini, Chowdhury, Munir, Trncic, Nadira, Amin, Najaf, Johnson, Nancy, Kanai, Ryota, Kowalksi, Nancy, Monahan, Nancy, Gillespie, Nathan A, Pacini, Nathaniel, Buckholtz, Neil, Kowall, Neil, Graff-Radford, Neill R, Fox, Nick, Pavese, Nicola, Karama, Sherif, Cairns, Nigel J, Schuff, Norbert, Foster, Norm, Relkin, Norman, Oyonumo, Ntekim E, Pomara, Nunzio, James, Olga, Ogunlana, Olu, Ching, Christopher R K, Kasperaviciute, Dalia, Carmichael, Owen, Doraiswamy, P Murali, Casalin, Paola, Barone, Paolo, Fatica, Parianne, Conrod, Patricia, Johnson, Patricia Lynn, Samuels, Patricia, Aisen, Paul, Malloy, Paul, Kaufmann, Tobias, Thompson, Paul, Ogrocki, Paula, Bezivin-Frere, Pauline, Maillard, Pauline, Fontoura, Paulo, Taylor, Peggy, Hogarth, Penelope, Gowland, Penny, Davies, Peter, Kelly, Sinead, Hardy, Peter, Snyder, Peter J, Snyder, Peter, Amouyel, Philippe, Muglia, Pierandrea, Tariot, Pierre, Lu, Po H, Varma, Pradeep, Vemuri, Prashanthi, Kikuchi, Masataka, Doody, Rachelle S, Carter, Raina, Shah, Raj C, Griffith, Randall, Yeh, Randy, Duara, Ranjan, Tarawneh, Rawan, James, Raymond, Turner, Raymond Scott, Klein, Marieke, Hernando, Raymundo, Silverstein, Rebecca, Sperling, Reisa A, Wilson, Renee, Carson, Richard E, Frank, Richard, El Khouli, Riham, Koeppe, Robert A, Santulli, Robert B, Knapp, Michael, Hauser, Robert, Umek, Robert, Radtke, Rodney, Killiany, Ronald, Petersen, Ronald, Rodriguez, Rosemarie, Miranda, Ruben, Knodt, Annchen R, Bruehl, Ruediger, Xia, Rui, Swerdlow, Russell H, Ottmann, Ruth, Millenet, Sabina, Borges-Neto, Salvador, Frank, Samuel, Black, Sandra, Weintraub, Sandra, Obradov, Sanja, Krämer, Bernd, Asthana, Sanjay, Vaishnavi, Sanjeev, Dolen, Sara, Mason, Sara S, Hohmann, Sarah, Kremen, Sarah, Miller, Sarah, Walter, Sarah, Herring, Scott, Neu, Scott, Lam, Max, Aydin, Semiha, Ahmad, Shahzad, Harlan, Sherry, Sirrel, Sherye A, Lasch, Shirley, Hu, Shu-Ching, Li, Shuo, Kittur, Smita, Chowdhury, Sohini, Lancaster, Thomas M, Pawluczyk, Sonia, Maingault, Sophie, Schneider, Stacy, Seiler, Stephan, Guthrie, Stephanie, Kielb, Stephanie, Reeder, Stephanie, Correia, Stephen, Pasternak, Stephen, McMahon, Mary Agnes B, Lee, Phil H, Salloway, Stephen, Johnson, Sterling, Williams, Steve, Chao, Steven, Arnold, Steven E, Paul, Steven, Potkin, Steven, Factor, Stewart, Isaacson, Stuart, Lett, Tristram A, Kim, Sungeun, Ainscough, Susan, Schultz, Susan K, Landau, Susan, Mendick, Susan, Rountree, Susan, Ostrowizki, Suzanne, Veillette, Suzanne, van der Lee, Sven J, Desrivieres, Sylvane, Lewis, Lindsay B, Lee, T-Y, Simuni, Tanya, Foroud, Tatiana, Foroud, Tatiana M, Wong, Terence Z, Villena, Teresa, Comery, Thomas, Obisesan, Thomas O, Lopes-Cendes, Iscia, Banaschewski, Tobias, Sherer, Todd, Montine, Tom, Paus, Tomáš, Robbins, Trevor, Bromberg, Uli, Völker, Uwe, Pavlik, Valory, Arnedo, Vanessa, Kiyasova, Vera, Bates, Vernice, Logovinsky, Veronika, Sossi, Vesna, Shibley, Victoria, Frouin, Vincent, Lee, Virginia, Poewe, Werner, Jagust, William, Brooks, William M, Macciardi, Fabio, Pavlosky, William, Potter, William, Kremen, William S, Longstreth, William T, Niessen, Wiro J, Jian, Xueqiu, Stern, Yaakov, Saba, Yasaman, Cabrera, Yuliana, Grimmer, Yvonne, Marquand, Andre F, Khachaturian, Zaven, Mari, Zoltan, Mathias, Samuel R, Melzer, Tracy R, Milaneschi, Yuri, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Movement Disorder (MD), Alzheimer’s Disease Neuroimaging Initiative, CHARGE Consortium, EPIGEN Consortium, IMAGEN Consortium, SYS Consortium, Parkinson’s Progression Markers Initiative, Stochastics, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, Science and Society, Cognitive Psychology, IBBA, APH - Personalized Medicine, Complex Trait Genetics, APH - Methodology, Clinical Neuropsychology, Sociology and Social Gerontology, Amsterdam Neuroscience - Complex Trait Genetics, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Klinische Genetica, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA Klinische Genetica (5), Neurology, Psychiatry, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), Human genetics, APH - Digital Health, Psychology, Precision Medicine Institute of Psychiatry, Child and Adolescent Psychiatry / Psychology, Radiology & Nuclear Medicine, Clinical Genetics, Epidemiology, Medical Informatics, Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Neurodegeneratives Diseases Institute (IMN-UMR CNRS 5293), Centre National de la Recherche Scientifique (CNRS), General Paediatrics, ARD - Amsterdam Reproduction and Development, Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), [SDV]Life Sciences [q-bio], LOCI, Genome-wide association study, Brain mapping, 0302 clinical medicine, Cognition, Cortex (anatomy), ComputingMilieux_MISCELLANEOUS, Cerebral Cortex, 0303 health sciences, Brain Mapping, Multidisciplinary, COMMON VARIANTS, Parkinson Disease, Organ Size, Central sulcus, Magnetic Resonance Imaging, medicine.anatomical_structure, Cerebral cortex, Neuroinformatics, EXPRESSION, endocrine system, central sulcus, SURFACE-AREA, Biology, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genetic variation, medicine, Attention deficit hyperactivity disorder, Humans, General, Gene, METAANALYSIS, 030304 developmental biology, Progenitor, CORTICAL SULCI, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Genetic variants, Genetic Variation, Attention Deficit Disorder with Hyperactivity, Genetic Loci, Genome-Wide Association Study, functional annotation, medicine.disease, Genetic architecture, 030104 developmental biology, Evolutionary biology, OBSERVER-INDEPENDENT CHARACTERIZATION, Multiple comparisons problem, ddc:320, genome-wide association, Neuroscience, 030217 neurology & neurosurgery
Abstract

Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working group., The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.

Published
2020
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11. 5-Substituted-N-pyridazinylbenzamides as potent and selective LRRK2 inhibitors: Improved brain unbound fraction enables efficacy

Author

Ding, Xiao, Stasi, Luigi Piero, Dai, Xuedong, Long, Kai, Peng, Cheng, Zhao, Baowei, Wang, Hailong, Sun, Changhui, Hu, Huan, Wan, Zehong, Jandu, Karamjit S., Philps, Oliver J., Chen, Yan, Wang, Lizhen, Liu, Qian, Edge, Colin, Li, Yi, Dong, Kelly, Guan, Xiaoming, Tattersall, F. David, Reith, Alastair D., and Ren, Feng

Published
2019
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19. Discovery of 5-substituent-N-arylbenzamide derivatives as potent, selective and orally bioavailable LRRK2 inhibitors

Author

Ding, Xiao, Dai, Xuedong, Long, Kai, Peng, Cheng, Andreotti, Daniele, Bamborough, Paul, Eatherton, Andrew J., Edge, Colin, Jandu, Karamjit S., Nichols, Paula L., Philps, Oliver J., Stasi, Luigi Piero, Wan, Zehong, Xiang, Jia-Ning, Dong, Kelly, Dossang, Pamela, Ho, Ming-Hsun, Li, Yi, Mensah, Lucy, Guan, Xiaoming, Reith, Alastair D., and Ren, Feng

Published
2017
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25. Diagnosis of Parkinson's disease on the basis of clinical and genetic classification: A population-based modelling study

Author

Nalls, Mike A, McLean, Cory Y, Hardy, John, Seppi, Klaus, Reiter, Eva, Shill, Holly, Fernandez, Hubert, Ahmed, Anwar, Berg, Daniela, Wurster, Isabel, Mari, Zoltan, Brooks, David, Pavese, Nicola, Gasser, Thomas, Barone, Paolo, Isaacson, Stuart, Espay, Alberto, Rowe, Dominic, Brandabur, Melanie, Tetrud, James, Liang, Grace, Marder, Karen, Corvol, Jean-Christophe, Martí Masso, Jose Felix, Brice, Alexis, Tolosa, Eduardo, Aasly, Jan O, Giladi, Nir, Stefanis, Leonidas, Leary, Laura, Riordan, Cheryl, Rees, Linda, Sommerfeld, Barbara, Wood-Siverio, Cathy, Portillo, Alicia, Price, T Ryan, Lenahan, Art, Williams, Karen, Guthrie, Stephanie, Rawlins, Ashlee, Harlan, Sherry, Hunter, Christine, Tran, Baochan, Darin, Abigail, Linder, Carly, Todd, Gretchen, Nicolas, Aude, Thomas, Cathi-Ann, James, Raymond, Deeley, Cheryl, Bishop, Courtney, Sprenger, Fabienne, Willeke, Diana, Obradov, Sanja, Mule, Jennifer, Monahan, Nancy, Gauss, Katharina, Keller, Margaux F, Comyns, Kathleen, Fontaine, Deborah, Gigliotti, Christina, McCoy, Arita, Dunlop, Becky, Shah, Bina, Ainscough, Susan, James, Angela, Silverstein, Rebecca, Espay, Kristy, Molony, Cliona, Ranola, Madelaine, Santana, Helen M, Ngono, Nelly, Rezola, Elisabet, Rolan, Delores Vilas, Waro, Bjorg, Mirlman, Anat, Stamelou, Maria, Comery, Thomas, Papapetropoulos, Spyros, Gibbs, J Raphael, Ravina, Bernard, Grachev, Igor D, Dubow, Jordan S, Ahlijanian, Michael, Soares, Holly, Ostrowizki, Suzanne, Fontoura, Paulo, Chalker, Alison, Hewitt, David L, van der Brug, Marcel, Chen-Plotkin, Alice, Reith, Alastair D, Taylor, Peggy, Egebjerg, Jan, Minton, Mark, Siderowf, Andrew, Muglia, Pierandrea, Umek, Robert, Catafau, Ana, Suh, Eunran, Rick, Jacqueline, Letson, Christopher, Fiandaca, Massimo S, Mapstone, Mark, Federoff, Howard J, Noyce, Alastair J, Morris, Huw, Van Deerlin, Vivianna M, Weintraub, Daniel, Zabetian, Cyrus, Hernandez, Dena G, Eberly, Shirley, Lesage, Suzanne, Mullins, Meghan, Conley, Emily Drabant, Northover, Carrie A M, Frasier, Mark, Marek, Ken, Day-Williams, Aaron G, Stone, David J, Ioannidis, John P A, Singleton, Andrew B, Hutten, Samantha J, investigators, Parkinson's Disease Biomarkers Program and Parkinson's Progression Marker Initiative, Bowman, Dubois, Dawson, Ted, Dewey, Richard, German, Dwight Charles, Huang, Xuemei, Petyuk, Vladislav, Scherzer, Clemens, Vaillancourt, David, Gwinn, Katrina, West, Andrew, Zhang, Jing, Marek, Kenneth, Jennings, Danna, Lasch, Shirley, Tanner, Caroline, Simuni, Tanya, Coffey, Christopher, Kieburtz, Karl, Wilson, Renee, Sutherland, Margaret, Poewe, Werner, Mollenhauer, Brit, Galasko, Douglas, Foroud, Tatiana, Sherer, Todd, Chowdhury, Sohini, Kopil, Catherine, Arnedo, Vanessa, Casaceli, Cynthia, Martinez, Maria, Seibyl, John, Mendick, Susan, Schuff, Norbert, Caspell, Chelsea, Uribe, Liz, Foster, Eric, Gloer, Katherine, Yankey, Jon, Toga, Arthur, Crawford, Karen, Heutink, Peter, Smith, Danielle Elise, Casalin, Paola, Malferrari, Giulia, Trojanowski, John, Shaw, Les, Singleton, Andrew, Halter, Cheryl, Russell, David, Factor, Stewart, Hogarth, Penelope, Williams, Nigel M, Standaert, David, Hauser, Robert, Jankovic, Joseph, Stern, Matthew, Chahine, Lama, Hu, Shu-Ching, Frank, Samuel, Trenkwalder, Claudia, Oertel, Wolfgang, and Richard, Irene

Subjects
Male, Aging, Parkinson's disease, Genome-wide association study, Disease, Neurodegenerative, Cohort Studies, genetics [Parkinson Disease], Models, 2.1 Biological and endogenous factors, Family history, Aetiology, education.field_of_study, screening and diagnosis, Parkinson's Disease, Aged, Disease Progression, Female, Humans, Middle Aged, Parkinson Disease, Prodromal Symptoms, Models, Statistical, Neurology (clinical), Statistical, Detection, Cohort, Neurological, Biomarker (medicine), diagnosis [Parkinson Disease], Cohort study, 4.2 Evaluation of markers and technologies, medicine.medical_specialty, Population, Clinical Sciences, Parkinson's Disease Biomarkers Program and Parkinson's Progression Marker Initiative investigators, Article, Clinical Research, Internal medicine, medicine, ddc:610, education, Neurology & Neurosurgery, business.industry, Prevention, Neurosciences, medicine.disease, Brain Disorders, 4.1 Discovery and preclinical testing of markers and technologies, Good Health and Well Being, Physical therapy, business
Abstract

Summary Background Accurate diagnosis and early detection of complex diseases, such as Parkinson's disease, has the potential to be of great benefit for researchers and clinical practice. We aimed to create a non-invasive, accurate classification model for the diagnosis of Parkinson's disease, which could serve as a basis for future disease prediction studies in longitudinal cohorts. Methods We developed a model for disease classification using data from the Parkinson's Progression Marker Initiative (PPMI) study for 367 patients with Parkinson's disease and phenotypically typical imaging data and 165 controls without neurological disease. Olfactory function, genetic risk, family history of Parkinson's disease, age, and gender were algorithmically selected by stepwise logistic regression as significant contributors to our classifying model. We then tested the model with data from 825 patients with Parkinson's disease and 261 controls from five independent cohorts with varying recruitment strategies and designs: the Parkinson's Disease Biomarkers Program (PDBP), the Parkinson's Associated Risk Study (PARS), 23andMe, the Longitudinal and Biomarker Study in PD (LABS-PD), and the Morris K Udall Parkinson's Disease Research Center of Excellence cohort (Penn-Udall). Additionally, we used our model to investigate patients who had imaging scans without evidence of dopaminergic deficit (SWEDD). Findings In the population from PPMI, our initial model correctly distinguished patients with Parkinson's disease from controls at an area under the curve (AUC) of 0·923 (95% CI 0·900–0·946) with high sensitivity (0·834, 95% CI 0·711–0·883) and specificity (0·903, 95% CI 0·824–0·946) at its optimum AUC threshold (0·655). All Hosmer-Lemeshow simulations suggested that when parsed into random subgroups, the subgroup data matched that of the overall cohort. External validation showed good classification of Parkinson's disease, with AUCs of 0·894 (95% CI 0·867–0·921) in the PDBP cohort, 0·998 (0·992–1·000) in PARS, 0·955 (no 95% CI available) in 23andMe, 0·929 (0·896–0·962) in LABS-PD, and 0·939 (0·891–0·986) in the Penn-Udall cohort. Four of 17 SWEDD participants who our model classified as having Parkinson's disease converted to Parkinson's disease within 1 year, whereas only one of 38 SWEDD participants who were not classified as having Parkinson's disease underwent conversion (test of proportions, p=0·003). Interpretation Our model provides a potential new approach to distinguish participants with Parkinson's disease from controls. If the model can also identify individuals with prodromal or preclinical Parkinson's disease in prospective cohorts, it could facilitate identification of biomarkers and interventions. Funding National Institute on Aging, National Institute of Neurological Disorders and Stroke, and the Michael J Fox Foundation.

Published
2015
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26. Correlates of excessive daytime sleepiness in de novo Parkinson's disease: A case control study

Author

Simuni, Tanya, Caspell Garcia, Chelsea, Coffey, Christopher, Chahine, Lama M., Lasch, Shirley, Oertel, Wolfgang H., Mayer, Geert, Högl, Birgit, Postuma, Ron, Videnovic, Aleksandar, Amara, Amy Willis, Marek, Ken, Russell, David, Factor, Stewart, Hogarth, Penelope, Standaert, David, Hauser, Robert, Jankovic, Joseph, Stern, Matthew, Chahine, Lama, Leverenz, James, Frank, Samuel, Richard, Irene, Seppi, Klaus, Shill, Holly, Fernandez, Hubert, Berg, Daniela, Wurster, Isabel, Galasko, Douglas, Mari, Zoltan, Brooks, David, Pavese, Nicola, Barone, Paolo, Isaacson, Stuart, Espay, Alberto, Rowe, Dominic, Brandabur, Melanie, Tetrud, James, Liang, Grace, Iranzo, Alex, Tolosa, Eduardo, Leary, Laura, Riordan, Cheryl, Rees, Linda, Portillo, Alicia, Lenahan, Art, Williams, Karen, Guthrie, Stephanie, Rawlins, Ashlee, Harlan, Sherry, Hunter, Christine, Tran, Baochan, Darin, Abigail, Linder, Carly, Baca, Marne, Venkov, Heli, Thomas, Cathi Ann, James, Raymond, Deeley, Cheryl, Bishop, Courtney, Sprenger, Fabienne, Willeke, Diana, Obradov, Sanja, Mule, Jennifer, Monahan, Nancy, Gauss, Katharina, Fontaine, Deborah, Gigliotti, Christina, Arita McCoy, Null, Dunlop, Becky, Shah, Bina, Ainscough, Susan, James, Angela, Silverstein, Rebecca, Espay, Kristy, Ranola, Madelaine, Trenkwalder, Claudia, Reith, Alastair D., Struyk, Arie, Boeve, Bradley, Harvey, Brian, Comella, Cindy, Tattersall, David, Kelly, Madeline, Foldvary, Nancy, Caspell, Chelsea, Uribe, Liz, Foster, Eric, Gloer, Katherine, Yankey, Jon, Kieburtz, Karl, Wilson, Renee, Rudolph, Alice, Casaceli, Cynthia, Todd Sherer, Null, Chowdhury, Sohini, Frasier, Mark, Kopil, Catherine, Arnedo, Vanessa, Schuff, Norbert, Casalin, Paola, Malferrari, Giulia, Trojanowski, John, Shaw, Les, Singleton, Andrew, and Hawkins, Keith A.

Subjects
Aged, 80 and over, Adult, Male, Daytime somnolence, Parkinson's disease, Parkinson Disease, Comorbidity, Disorders of Excessive Somnolence, Middle Aged, Article, Neurology, Case-Control Studies, Biomarkers, Aged, Female, Humans, Neurology (clinical), 80 and over
Abstract

This study was undertaken to determine the frequency and correlates of excessive daytime sleepiness in de novo, untreated Parkinson's disease (PD) patients compared with the matched healthy controls.Data were obtained from the Parkinson's Progression Markers Initiative, an international study of de novo, untreated PD patients and healthy controls. At baseline, participants were assessed with a wide range of motor and nonmotor scales, including the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Excessive daytime sleepiness was assessed based on the Epworth Sleepiness scale (ESS), with a cutoff of 10.Four hundred twenty-three PD subjects and 196 healthy controls were recruited into the study. Mean ESS (min, max) score was 5.8 (0, 20) for the PD subjects and 5.6 (0, 19) for healthy controls (P = 0.54). Sixty-six (15.6%) PD subjects and 24 (12%) healthy controls had ESS of at least 10 (P = 0.28). No difference was seen in demographic characteristics, age of onset, disease duration, PD subtype, cognitive status, or utilization of sedatives between the PD sleepiness-positive versus the negative group. The sleepiness-positive group had higher MDS-UPDRS Part I and II but not III scores, and higher depression and autonomic dysfunction scores. Sleepiness was associated with a marginal reduction of A-beta (P = 0.05) but not alpha-synuclein spinal fluid levels in PD.This largest case control study demonstrates no difference in prevalence of excessive sleepiness in subjects with de novo untreated PD compared with healthy controls. The only clinical correlates of sleepiness were mood and autonomic dysfunction. Ongoing longitudinal analyses will be essential to further examine clinical and biological correlates of sleepiness in PD and specifically the role of dopaminergic therapy.

Published
2015

27. Phos-tag analysis of Rab10 phosphorylation by LRRK2: a powerful assay for assessing kinase function and inhibitors

Author

Ito, Genta, primary, Katsemonova, Kristina, additional, Tonelli, Francesca, additional, Lis, Pawel, additional, Baptista, Marco A.S., additional, Shpiro, Natalia, additional, Duddy, Graham, additional, Wilson, Steve, additional, Ho, Philip Wing-Lok, additional, Ho, Shu-Leong, additional, Reith, Alastair D., additional, and Alessi, Dario R., additional

Published
2016
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29. Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases

Author

Steger, Martin, primary, Tonelli, Francesca, additional, Ito, Genta, additional, Davies, Paul, additional, Trost, Matthias, additional, Vetter, Melanie, additional, Wachter, Stefanie, additional, Lorentzen, Esben, additional, Duddy, Graham, additional, Wilson, Stephen, additional, Baptista, Marco AS, additional, Fiske, Brian K, additional, Fell, Matthew J, additional, Morrow, John A, additional, Reith, Alastair D, additional, Alessi, Dario R, additional, and Mann, Matthias, additional

Published
2016
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30. Author response: Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases

Author

Steger, Martin, primary, Tonelli, Francesca, additional, Ito, Genta, additional, Davies, Paul, additional, Trost, Matthias, additional, Vetter, Melanie, additional, Wachter, Stefanie, additional, Lorentzen, Esben, additional, Duddy, Graham, additional, Wilson, Stephen, additional, Baptista, Marco AS, additional, Fiske, Brian K, additional, Fell, Matthew J, additional, Morrow, John A, additional, Reith, Alastair D, additional, Alessi, Dario R, additional, and Mann, Matthias, additional

Published
2016
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37. The identification of potent and selective imidazole-based inhibitors of B-Raf kinase

Author

Takle, Andrew K., primary, Brown, Murray J.B., additional, Davies, Susannah, additional, Dean, David K., additional, Francis, Gerraint, additional, Gaiba, Alessandra, additional, Hird, Alex W., additional, King, Frank D., additional, Lovell, Peter J., additional, Naylor, Antoinette, additional, Reith, Alastair D., additional, Steadman, Jon G., additional, and Wilson, David M., additional

Published
2006
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39. Isolation and Characterization of "Orphan-RTK" Ligands Using an Integrated Biosensor Approach.

Author

Reith, Alastair D. and Lackmann, Martin

Abstract

The interest in biosensor-based ligand isolation strategies is to a large extent, a result of fundamental changes in the way novel proteins are isolated and characterized. Advances in genetic screening techniques have led to the identification of novel protein families with little knowledge of function or physiological context (1,2) and a rapidly increasing number of these so-called "orphan proteins" calls for complementary strategies to elucidate their structure and function. Over the past few years, different approaches have been developed to isolate ligands solely on the basis of their affinity for a particular orphan receptor. These include expression cloning strategies to detect cell-membrane bound ligands with tagged receptor extracellular domain (ECD) fusion proteins (3-6) and cell rescue assays to detect soluble ligands (7-9). BIAcore technology has been applied to search for suitable ligand sources of orphan receptors (10-12), but is also well suited to integrated use within a "classical" purification scheme (13,14) and has been exploited as an affinity detector to facilitate the isolation of orphan proteins (15,16). The advantages of this technology include a fast, robot-driven assay that is unaffected by sample toxicity, and the ability to assess specificity and kinetics of the observed interaction even in relatively crude samples, thus minimizing the risk of false positives. [ABSTRACT FROM AUTHOR]

Published
2001
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40. Cloning and Characterization of RTK Ligands Using Receptor-Alkaline Phosphatase Fusion Proteins.

Author

Reith, Alastair D., Cheng, Hwai-Jong, and Flanagan, John G.

Abstract

Receptor tyrosine kinases (RTKs) bind to their ligands with high affinity and specificity. Soluble receptor approaches exploit these biological properties to make affinity probes that can be used to detect or to purify the cognate ligands (1,2). In many respects, these soluble receptor reagents resemble antibodies, and they can be used in almost all the same types of procedure. They can also have important advantages over antibodies. They can be used to identify and clone previously unknown ligands of orphan receptors (1-9). They can be produced much more quickly than antibodies. Also, because they exploit natural receptor-ligand interactions, they can give information not available with antibodies, for example permitting quantitative characterization of ligandreceptor binding interactions (1,2,10), or allowing the simultaneous detection of multiple cross-reacting ligands in an embryo (5,11,12). [ABSTRACT FROM AUTHOR]

Published
2001
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41. Analysis of SH2 Domain - Phosphopeptide Interactions by Isothermal Titration Calorimetry and Surface Plasmon Resonance.

Author

Reith, Alastair D., Panayotou, George, and Ladbury, John

Abstract

The interaction of activated growth factor receptors with signaling molecules has attracted enormous attention in the last few years because of the central role these processes play in growth differentiation and proliferation control in cells. The importance of src homology (SH)2 domains in mediating these interactions through binding to specific tyrosine phosphorylation sites on activated receptors has been well established. However, the complexity of intracel-lular signaling, and the apparent redundancy in some systems, has necessitated the development of assays for quantifying these interactions accurately. These in vitro studies have benefited from the linear nature of SH2 domain ligands, i.e., the ability of small synthetic phosphopeptides corresponding to receptor autophosphorylation sites to mimic, in most cases, the specificity and binding properties of the intact receptor. Several assays have been developed employing radioactive peptides or indirect detection of SH2 domains by immunological methods. These assays can determine, with varying degrees of accuracy, the equilibrium dissociation constant, KD (or binding constant, KB = 1/KD) for an interaction, thus providing quantification of its strength. However, additional information about the kinetic rates and thermodynamics can provide a better characterization. Correlated with high-resolution structural detail, these data can provide insight into the balance of bonds that have been made or broken, whether the molecules have undergone conformational change on interacting, or whether water has been released from the binding surface on formation of the complex. Information of this nature can add a further level of detail, helping to address issues such as the specificity of an interaction and the structural-thermodynamic relationship associated with forming the complex, all of which are factors that might be important when attempting pharmaceutical intervention. The use of isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR) biosensors has provided a great deal of information on these issues. [ABSTRACT FROM AUTHOR]

Published
2001
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42. cDNA Expression Cloning and Characterization of Phosphorylation Dependent Protein Interactors Using the Yeast Tribrid System.

Author

Reith, Alastair D., Volpers, Christoph, Lubinus, Manuel, Osborne, Mark A., and Kochan, Jarema P.

Abstract

The yeast two-hybrid system has been utilized by many laboratories in the characterization of protein-protein interactions that occur in eukaryotic and prokaryotic cell systems. In addition, the two-hybrid system has been used to isolate and characterize novel interacting proteins to aid in the understanding of biochemical signaling pathways for various receptors and enzymes. The interacting components are fused to inert components of the transcriptional apparatus. One of the components is fused to a DNA-binding domain and is generally referred to as the "bait." The second protein is fused to a transcriptional activation domain and is referred to as the "fish" or the "prey." When there is an association between the "bait" and the "prey," the DNA-binding domain and the transcriptional-activation domain are brought into close proximity to activate the transcription of the reporter gene. [ABSTRACT FROM AUTHOR]

Published
2001
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43. Identification of Receptor Tyrosine Kinase Associating Proteins Using the Yeast Two-Hybrid System.

Author

Reith, Alastair D. and Prigent, Sally A.

Abstract

Protein-protein interactions form the basis of most signal transduction pathways. In the case of pathways initiated by receptor tyrosine kinases (RTKs), phosphotyrosine residues present on the cytoplasmic domain of the activated receptor form docking sites for adaptor molecules and enzymes containing src homology (SH)2 and phosphotyrosine binding (PTB) domains (1). Association of these signaling components initiates cascades of interactions and reactions that determine the cell's response to the stimulus. Because these initial interactions are responsible for the biological properties of different receptors, there has been considerable interest in identifying potential binding proteins with a view to understanding the molecular basis of signaling diversity. [ABSTRACT FROM AUTHOR]

Published
2001
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44. Identification of Receptor Tyrosine Kinase (RTK) Substrates by the Cloning of ReceptorTargets (CORT) Strategy.

Author

Reith, Alastair D. and Daly, Roger J.

Abstract

Activation of receptor tyrosine kinases (RTXs) leads to autophosphorylation of the intracellular region of the receptor on specific tyrosine residues, thus creating binding sites for a variety of signaling proteins (1). These interactions are mediated by protein modules such as src homology (SH)2 and phosphotyrosine binding (PTB) domains, which target specific tyrosine phosphorylated peptide sequences (2). This chapter describes how the physical association of an RTK with particular substrates can be exploited in an expression cloning procedure and novel receptor targets identified. [ABSTRACT FROM AUTHOR]

Published
2001
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45. Purification of Tyrosine-Phosphorylated Proteins by Immunoaffinity Chromatography and Direct Cloning of Their cDNAs from Bacterial Expression Libraries.

Author

Reith, Alastair D., Di Fiore, Pier Paolo, and Fazioli, Francesca

Abstract

Growth factor receptors endowed with intrinsic tyrosine-kinase activity (receptor tyrosine kinases, RTKs) are capable of intracellular signal transduction through their ability to autophosphorylate and to phosphorylate cellular proteins, globally referred to as substrates (refs. 1-3 and references therein). [ABSTRACT FROM AUTHOR]

Published
2001
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46. Detection of Phosphorylation-Dependent Interactions by Far-Western Gel Overlay.

Author

Reith, Alastair D., Burnham, Mary Rose, DeBerry, Regina, and Bouton, Amy H.

Abstract

The far Western gel overlay assay is a highly sensitive tool for the detection of direct protein-protein interactions. The ability to distinguish direct associations between two proteins makes this technique ideal not only for identifying potential binding partners of a protein, but also for characterizing interaction domains and binding sites. The assay relies on the ability of the protein of interest to interact with target proteins that have been immobilized on nitrocelulose filters. Potential interactions can be monitored under various types of conditions by manipulation of the protein that is used as the probe. Such manipulations may include mutagenesis, or protein modifications such as phosphorylation. Detection of phosphorylation-dependent interactions is particularly relevant in light of the fact that many signaling proteins are modified by phosphorylation, which in turn affects activity, localization, and most importantly, the ability to form protein complexes (seerefs. 1-4). We describe here the standard protocol for the far-Western gel overlay assay, with modifications that enable the detection of phosphorylation-dependent protein interactions. This technique has been used successfully by our laboratory, as well as others to identify potential phosphorylation-dependent interactions between a number of signaling proteins (5-7). [ABSTRACT FROM AUTHOR]

Published
2001
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47. Analysis of Protein Kinase Subcellular Localization by Visualization of GFP Fusion Proteins.

Author

Reith, Alastair D., Zirngibl, Ralph A., and Greer, Peter

Abstract

The green fluorescent protein (GFP) from the jellyfish Aequorea victoria is fast becoming the marker of choice for protein localization and gene expression studies. The rapid rise in popularity stems from several advantages over traditional markers such as β-galactosidase and alkaline phosphatase, which typically require the addition of exogenous substrates for detection. The unique intrinsic spectral properties of GFP allow it to be directly visualized in fixed or live cells by fluorescence microscopy without the addition of cofactors or exogenous substrates (1-8). [ABSTRACT FROM AUTHOR]

Published
2001
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48. Cloning and Expression of Recombinant HEXA-HIS Tagged ZAP-70 Using the Baculovirus System.

Author

Reith, Alastair D., Purton, Tracey, Wilkinson, Sandra, and Murray, Edward J.

Abstract

The activation of T cells results in both tyrosine and serine/threonine phos-phorylations of a number of substrates within minutes of T-cell receptor (TCR) ligation (1,2). The phosphorylation of the immunoreceptor tyrosine-based activation motifs (ITAMs) on the (ξ-chain within the TCR complex act as binding sites for the N-terminal SH2 domains of ZAP-70 (3). This relocation brings ZAP-70 proximal to the CD4-associated p56lck kinase, which activates the kinase activity of ZAP-70 by phosphorylation at Y493 (4). The activated ZAP-70 is then able to transduce a signal via an as yet uncharacterized cascade, which may involve SLP-76 (5), vav (6) PLC-Γ( (7) p120/130 (8) and LAT (9). The major role of ZAP-70 in T-cell signal transduction has been highlighted in ZAP-70 deficient patients who suffer severe combined immunodeficiency disease (SCID) like symptoms (10). [ABSTRACT FROM AUTHOR]

Published
2001
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49. Protein Histidine Kinase.

Author

Reith, Alastair D., Matthews, Harry R., and Chan, Karina

Abstract

Protein phosphorylation on histidine occurs in a large number of processes in prokaryotes and in an unknown number of processes in eukaryotes. The functions of protein phosphohistidine in prokaryotes are much more clearly understood (1,2. The methods presented here have been developed for the study of protein histidine phosphorylation in eukaryotes where phosphohistidine is found as an intermediate in some enzyme reactions and may also be involved in signaling mechanisms (3). In prokaryotes, two types of protein phosphorylation on histidine have been characterized in detail. The first, historically, is the phosphoenolpyruvate-sugar phosphotransferase system (4,5). In this system, phosphohistidine acts as a phosphate donor and the initial phosphate donor is phosphoenolpyruvate, so this is not a protein kinase system. The second prokaryotic system is the twocomponent regulatory system (1,2). The core of this system comprises three protein domains, which may or may not be on different polypeptides. The first domain is the protein kinase domain, the second is the histidine substrate for this kinase and the third contains an aspartate residue that removes the phosphate from phosphohistidine. Genes homologous to those of the two-component system have been identified in lower eukaryotes (1,6,7). [ABSTRACT FROM AUTHOR]

Published
2001
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50. Cyclin-Dependent Kinases and Cyclin-Dependent Kinase Inhibitors.

Author

Reith, Alastair D. and Brooks, Gavin

Abstract

Normal cellular proliferation is under the tight control of both positive and negative regulators that determine whether a particular cell can progress through the cell cycle (seerefs. 1-3 for reviews). This carefully ordered progression of the mammalian cell cycle is controlled by the sequential formation, activation, and deactivation of specific cell cycle-regulatory molecules (Fig. 1) that exist as a series of complexes consisting of a catalytic kinase subunit (known as the cyclin-dependent kinase or CDK) and a regulatory cyclin subunit. These cyclin:CDK complexes form part of the positive regulatory machinery that drives the cell through the cycle. Most cyclin mRNAs and proteins show a dramatic fluctuation in their expression during the cell cycle. For example,G1/s cyclin, cyclin, cyclin E is unstable, peaks during lateG1 and disappears rapidly thereafter, whereas cyclins A and B accumulate transiently at the onset of S phase and in late G2 respectively, followed by their rapid degradation (1,2). In contrast, expression of the various CDK molecules remains relatively constant throughout the cell cycle. [ABSTRACT FROM AUTHOR]

Published
2001
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