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3. The Drosophila hep pathway mediates Lrrk2-induced neurodegeneration

Author

Yang, Dejun, Thomas, Joseph M., Li, Tianxia, Lee, Youngseok, Liu, Zhaohui, and Smith, Wanli W.

Subjects
Drosophila -- Health aspects, Parkinson disease -- Genetic aspects, RNA interference -- Health aspects, Gene mutation -- Health aspects, Biological sciences
Abstract

Although the pathogenesis of Parkinson's disease (PD) remains unclear, mutations in leucine-rich repeat kinase 2 (Lrrk2) are among the major causes of familial PD. Most of these mutations disrupt Lrrk2 kinase and (or) GTPase domain function, resulting in neuronal degeneration. However, the signal pathways underlying Lrrk2-induced neuronal degeneration are not fully understood. There is an expanding body of evidence that suggests a link between Lrrk2 function and MAP kinase (MAPK) cascades. To further investigate this link in vivo, genetic RNAi screens of the MAPK pathways were performed in a Drosophila model to identify genetic modifier(s) that can suppress G2019S-Lrrk2-induced PD-like phenotypes. The results revealed that the knockdown of hemipterous (hep, or JNKK) increased fly survival time, improved locomotor function, and reduced loss of dopaminergic neurons in G2019S-Lrrk2 transgenic flies. Expression of the dominant-negative allele of JNK (JNK-DN), a kinase that is downstream of hep in G2019S-Lrrk2 transgenic flies, elicited a similar effect. Moreover, treatment with the JNK inhibitor SP600125 partially reversed the G2019S-Lrrk2-induced loss of dopaminergic neurons. These results indicate that the hep pathway plays an important role in Lrrk2-linked Parkinsonism in flies. These studies provide new insights into the molecular mechanisms underlying Lrrk2-linked PD pathogenesis and aid in identifying potential therapeutic targets. Key words: Lrrk2, Parkinson's disease, JNK, neuronal degeneration, hep, dopamine neuron, Drosophila model. Meme si la pathogenese de la maladie de Parkinson (MP) demeure floue, des mutations de la proteine Lrrk2 (leucine riche repeat kinase 2) sont parmi les principales causes de la MP hereditaire. La plupart de ces mutations dereglent la fonction des domaines kinase ou GTPase de Lrrk2, resultant en une degeneration neuronale. Toutefois, les voies de signalisation qui sous-tendent la degeneration neuronale induite par Lrrk2 ne sont pas completement comprises. Ilyadeplus en plus de donnees qui suggerent qu'il existe un lien entre la fonction de Lrrk2 et les cascades des MAP kinases (MAPK). Afin d'approfondir ce lien in vivo, des criblages genetiques des voies des MAPK a l'aide d'ARNi ont ete realises chez la drosophile afin d'identifier les modificateurs genetiques qui peuvent supprimer les phenotypes de type parkinsonien induits par G2019S-Lrrk2. Les resultats ont revele que le knockdown de hemipterous (hep ou JNKK) accroissait la duree de vie des mouches, ameliorait la fonction locomotrice et reduisait la perte de neurones dopaminergiques chez les mouches transgeniques G2019S-Lrrk2. L'expression de l'allele dominant negatif de JNK (JNK-DN), une kinase qui agit en aval de hep chez les mouches transgeniques G2019S-Lrrk2, provoquait un effet similaire. De plus, un traitement avec l'inhibiteur de JNK SP600125 renversait partiellement la perte de neurones dopaminergiques induite par G2019S-Lrrk2. Ces resultats indiquent que la voie de hep joue un role important dans le parkinsonisme lie a Lrrk2 chez les mouches. Ces etudes apportent un eclairage nouveau sur les mecanismes moleculaires qui sous-tendent la pathogenese de la MP liee a Lrrk2 et contribuent a identifier des cibles therapeutiques potentielles. [Traduit par la Redaction] Mots-cles : Lrrk2, maladie de Parkinson, JNK, degeneration neuronale, hep, neurone a dopamine, modele de la drosophile., Introduction Parkinson's disease (PD) is one of the most common neurodegenerative disorders and is characterized by the selective loss of dopaminergic neurons and the presence of Lewy bodies. The clinical [...]

Published
2018
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20. Integrative phenotypic and genomic analyses reveal strain-dependent responses to acute ozone exposure and their associations with airway macrophage transcriptional activity

Author

Tovar, Adelaide, primary, Crouse, Wesley L., additional, Smith, Gregory J., additional, Thomas, Joseph M., additional, Keith, Benjamin P., additional, McFadden, Kathryn M., additional, Moran, Timothy P., additional, Furey, Terrence S., additional, and Kelada, Samir N. P., additional

Published
2021
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21. List of Contributors

Author

Abad, Juan-Carlos, primary, Abelson, Mark B, additional, Abramson, David H, additional, Acquadro, Martin A, additional, Adamis, Anthony P, additional, Adams, Wesley H, additional, Afshari, Natalie A, additional, Ai, Everett, additional, Aiello, Lloyd M, additional, Aiello, Lloyd P, additional, Akduman, Levent, additional, Albano, Marissa L, additional, Albert, Daniel M., additional, Alexandrou, Terry J, additional, Alfonso, Eduardo C, additional, Alié, Jorge L, additional, Alizadeh, Hassan, additional, Al Jadaan, Ibrahim A, additional, Al-Jastaneiah, Sabah, additional, Allen, Calliope E, additional, Allen, David, additional, Allen, Robert C, additional, Alm, Albert, additional, Al-Swailem, Samar, additional, Alt, Abigail K, additional, Altaweel, Michael M, additional, Anderson, Russell, additional, Andreoli, Christopher M, additional, Androudi, Sofia, additional, Ang, Leonard PK, additional, Anzaar, Fahd, additional, Apple, David J, additional, Arrigg, Claudia A, additional, Artal, Pablo, additional, Asbell, Penny, additional, Asdourian, George K, additional, Atebara, Neal, additional, Atmaca-Sonmez, Pelin, additional, Audo, Isabelle, additional, Auffarth, Gerd U, additional, Avery, Robin K, additional, Azar, Dimitri T, additional, Baker, Ann S, additional, Balles, Mark, additional, Barnes, Scott D, additional, Barnett, Donald M, additional, Barney, Neal P, additional, Barouch, Fina C, additional, Bartley, George B, additional, Barton, Jason JS, additional, Behlau, Irmgard, additional, Belda, Jose I, additional, Bennett, Jeffrey L, additional, Bennett, Timothy J, additional, Berdy, Gregg J, additional, Bernardino, Carlo Roberto, additional, Bernardino, Vitaliano, additional, Berson, Eliot L, additional, Bharadwaj, Amitabh, additional, Bhisitkul, Robert, additional, Bhui, Ravinder D, additional, Bilyk, Jurij, additional, Biousse, Valérie, additional, Bird, Alan C, additional, Blair, Norman Paul, additional, Blodi, Barbara A, additional, Blumenkranz, Mark S, additional, Boldt, H Culver, additional, Borchert, Mark S, additional, Borrillo, Luigi, additional, Borodic, Gary E, additional, Boruchoff, S Arthur, additional, Bose, Swaraj, additional, Boulton, Michael E, additional, Bowman, RW, additional, Bradley, Elizabeth A, additional, Brazitikos, Periklis D, additional, Breeze, Robert, additional, Bressler, Neil M, additional, Bressler, Susan B, additional, Brini, Alfred, additional, Budenz, Donald L, additional, Buffenn, Angela N, additional, Burk, Scott E, additional, Butrus, Salim, additional, Callanan, David, additional, Cameron, J Douglas, additional, Cantor, Louis B, additional, Cantore, William A, additional, Cantu-Dibildox, Jorge, additional, Casas, Victoria, additional, Casper, Miriam, additional, Casten, Robin J, additional, Catoira, Yara P, additional, Cavallerano, Jerry, additional, Chai, Samantha J, additional, Chalita, Maria R, additional, Chamberlain, Sherman M, additional, Chan, Audrey S, additional, Chan, Chi-Chao, additional, Chan, Paul, additional, Chapin, Matthew J, additional, Chapman, Karen L, additional, Chen, Eric, additional, Chen, Joe, additional, Chen, Julie A, additional, Chen, Teresa C, additional, Chen, Zhou, additional, Chévez-Barrios, Patricia, additional, Chew, Emily Y, additional, Chiang, Mark, additional, Chodosh, James, additional, Chong, Eva-Marie, additional, Chun, Denise, additional, Chylack, Leo T, additional, Ciardella, Antonio P, additional, Civan, Mortimer, additional, Clamen, Liane, additional, Clark, John I, additional, Cockerham, Glenn, additional, Cohen, Andre, additional, Cohen, Elisabeth J, additional, Colby, Kathryn A, additional, Coleman, Anne L, additional, Coleman, Hanna R, additional, Colin, Joseph, additional, Collier, J Michael, additional, Comer, Grant M, additional, Conlon, M Ronan, additional, Cooper, Kim E, additional, Corbett, James J, additional, Coma, Miguel C, additional, Cyrlin, Marshall N, additional, Dagi, Linda R, additional, Dahlgren, Matthew A, additional, Daley, Timothy J, additional, Da Mata, Andrea P, additional, Damato, Bertil, additional, D'Amico, Donald J, additional, Dana, Reza, additional, Danan-Husson, Aude, additional, Danesh-Meyer, Helen B, additional, Danis, Ronald P, additional, Darlington, Jason K, additional, Davidson, Stefanie L, additional, Davis, Janet L, additional, Davis, Elizabeth A, additional, de la Cruz, Jose J, additional, de la Garza, Adam G, additional, DeAngelis, Margaret M, additional, DeMartelaere, Sheri L, additional, Demer, Joseph L, additional, Dhaliwal, Avninder, additional, Dieckert, J Paul, additional, Do, Diana V, additional, Doane, Marshall G, additional, Dodds, Christopher, additional, Dohlman, Claes H, additional, Donati, Guy, additional, Donnenfeld, Eric D, additional, Drack, Arlene, additional, Dryja, Thaddeus P, additional, Dueker, David, additional, Duker, Jay S, additional, Dunbar, Jennifer A, additional, Dunn, James P, additional, Dupps, William J, additional, Durand, Marlene L, additional, Dutton, Jonathan J, additional, Eandi, Chiara M, additional, Edward, Deepak P, additional, Egan, Robert A, additional, Eichenbaum, David A, additional, Eklund, Susan E, additional, Engle, Elizabeth C, additional, Erickson, Kristine, additional, Esmaeli, Bita, additional, Fay, Aaron, additional, Feiner, Leonard, additional, Fekrat, Sharon, additional, Ferris, Frederick L, additional, Fine, Howard F, additional, Fletcher, Donald C, additional, Flikier, Paul, additional, Floyd, Richard P, additional, Flynn, Harry W, additional, Fong, Donald S, additional, Font, Ramon L, additional, Forbes, Brian JR, additional, Foroozan, Rod, additional, Foster, Bradley S, additional, Foster, C Stephen, additional, Foster, Jill A, additional, Foulks, Gary N, additional, Fountain, Tamara R, additional, Fox, Gregory M, additional, Freddo, Thomas F, additional, Freedman, Sharon F, additional, Freund, K Bailey, additional, Friberg, Thomas R, additional, Friedman, Alan H, additional, Friedman, David, additional, Friedman, Deborah I, additional, Friedman, Ephraim, additional, Fu, Arthur D, additional, Fulton, Anne B, additional, Galal, Ahmed, additional, Galetta, Steven, additional, Gallardo, Mark, additional, Gallie, Brenda, additional, Garner, Alec, additional, Garrity, James A, additional, Gatinel, Damien, additional, Gedde, Steven J, additional, Geist, Craig E, additional, Gerber, Steve, additional, Ghanem, Ramon C, additional, Gieser, Jon P, additional, Gilmore, Michael S, additional, Gimbel, Howard V, additional, Gipson, Ilene K, additional, Glover, Tyrone, additional, Goldberg, Robert A, additional, Goldenfeld, Mordechai, additional, Goldstein, Scott M, additional, Gomi, Cintia F, additional, Gong, Haiyan, additional, Gonzales, John A, additional, Goosey, John, additional, Gottlieb, Justin L, additional, Gould, Joshua, additional, Gragoudas, Evangelos S, additional, Granet, David B, additional, Greaney, Michael J, additional, Green, Daniel G, additional, Grehn, Franz, additional, Greiner, Jack V, additional, Greven, Craig M, additional, Griepentrog, Gregory J, additional, Groenewald, Carl, additional, Grosskreutz, Cynthia L, additional, Grover, Lori Latowski, additional, Gullapalli, Vamsi K, additional, Gulur, Padma, additional, Gunther, Jonathan, additional, Gupta, Manish, additional, Gupta, Mayank, additional, Guyer, David R, additional, Haivala, Darin R, additional, Haller, Julia A, additional, Halmagyi, GM, additional, Halperin, Lawrence S, additional, Hamdi, Islam M, additional, Hamilton, Steven R, additional, Hammersmith, Kristin M, additional, Han, Dennis P, additional, Hansen, Ronald M, additional, Harbour, J William, additional, Hariprasad, Seenu M, additional, Harissi-Dagher, Mona, additional, Hassan, Shirin E., additional, Hatton, Mark P, additional, Hawley, Pamela, additional, Hayashida, Yasutaka, additional, Heckenlively, John R, additional, Hedges, Thomas R, additional, Heggie, Alfred D, additional, Heher, Katrinka L, additional, Heier, Jeffrey S, additional, Hejtmancik, J Fielding, additional, Henderson, Bonnie A, additional, Hersh, Peter S, additional, Hidayat, Ahmed A, additional, Higginbotham, Eva Juliet, additional, Hirose, Tatsuo, additional, Ho, Allen C, additional, Ho, ThucAnh T, additional, Hogan, R Nick, additional, Holck, David E, additional, Holekamp, Nancy M, additional, Hovland, Peter G, additional, Hsu, Thomas C, additional, Hsu, William C, additional, Huang, Andrew JW, additional, Hughes, Mark S, additional, Hui, Jennifer, additional, Hunter, David G, additional, Huryn, Laryssa A, additional, Husain, Deeba, additional, Hyndiuk, Robert A, additional, Ip, Michael, additional, Jacobs, Brian J, additional, Jakobiec, Frederick A, additional, Jampol, Lee M, additional, Jensen, Harold G, additional, Ji, Fei, additional, Johnson, David L, additional, Johnson, Douglas H, additional, Johnson, Mark W, additional, Johnson, R Paul, additional, Johnson, Robert N, additional, Joos, Karen M, additional, Joyce, Nancy C, additional, Jumper, J Michael, additional, Jurkunas, Ula V., additional, Kahana, Alon, additional, Kahook, Malik Y, additional, Kanner, Elliott, additional, Kalwerisky, Kevin, additional, Kaplan, Henry J, additional, Karatza, Ekaterini C, additional, Kardon, Randy, additional, Katowitz, James A, additional, Katowitz, William R, additional, Kazlas, Melanie, additional, Keefe, Kelly S, additional, Kelley, Lara, additional, Kent, Charles J, additional, Kenyon, Kenneth R, additional, Khan, Bilal F, additional, Khan, Jemshed A, additional, Khan, Naheed W, additional, Khaw, Peng Tee, additional, Kherani, Femida, additional, Kim, Eva C, additional, Kim, Hee Joon, additional, Kim, Ivana K, additional, Kim, Jonathan W, additional, Kim, Rosa Y, additional, Kim, Stella K, additional, Kim, Tae-Im, additional, Klais, Christina M, additional, Klapper, Stephen R, additional, Klein, Barbara EK, additional, Kleinmann, Guy, additional, Klink, Thomas, additional, Klisovic, Dino D, additional, Klyce, Stephen D, additional, Kocaturk, Tolga, additional, Kohnen, Thomas, additional, Kojima, Takeshi, additional, Koller, Tobias, additional, Kostick, David A, additional, Kraut, Joel A, additional, Krishnan, Chandrasekharan, additional, Krueger, Ronald R, additional, Krug, Joseph H, additional, Krupsky, Sara, additional, Kuchtey, Rachel W, additional, Kurban, Ramsay S, additional, Kurz, Paul A, additional, Kuszak, JR, additional, Kwon, Young H, additional, Labbe, Thad A, additional, Lam, Deborah L, additional, Lamkin, Jeffrey C, additional, Lamping, Kathleen A, additional, Lane, Anne Marie, additional, Lane, Katherine A, additional, Lane, Keith J, additional, Lass, Jonathan H, additional, Lawrence, Mary G, additional, Lee, Andrew G, additional, Lee, Carol M, additional, Lee, Michael S, additional, Lee, Paul P, additional, Lee, William B, additional, Leibovitch, Igal, additional, Lemke, Bradley N, additional, Lemley, Craig A, additional, Leonardi, Andrea, additional, Lessell, Simmons, additional, Levin, Leonard A, additional, Levy-Clarke, Grace A, additional, Lew, Julie C, additional, Lewis, Craig, additional, Li, Wei, additional, Lim, Laurence S, additional, Lim, Lyndell L, additional, Lim, Wee-Kiak, additional, Liu, Grant T, additional, Loewenstein, John I, additional, Lott, McGregor N, additional, Lowry, Jonathan C, additional, Lyon, David B, additional, Lytle, Robert E, additional, MacCumber, Mathew, additional, Mackool, Bonnie T, additional, Madiwale, Nalini A, additional, Mah, Francis, additional, Mainster, Martin A, additional, Manning, Michael H, additional, Mansberger, Steven L, additional, Marc, Robert E, additional, Marchong, Mellone, additional, Marcus, Dennis M, additional, Mares, Julie A, additional, Marr, Brian P, additional, Martinez, Carlos E, additional, Massof, Robert W, additional, Matsumoto, Yukihiro, additional, Mattox, Cynthia, additional, Maus, Marlon, additional, McCabe, Cathleen M, additional, McCormick, Steven A, additional, McCrakken, Michael, additional, McCulley, James P, additional, McDermott, John A, additional, McDonald, H Richard, additional, McDonald, Marguerite B, additional, McDonnell, Peter J, additional, McGillivray, Robert, additional, McKeown, Craig A, additional, McLaughlin, James, additional, McMullen, W Wynn, additional, Melamed, Shlomo, additional, Meligonis, George, additional, Mendrinos, Efstratios, additional, Meyer, Dale R, additional, Meyerle, Catherine B, additional, Mieler, William F, additional, Migliori, Michael, additional, Mihm, Martin C, additional, Miller, Darlene, additional, Miller, David, additional, Miller, Joan W, additional, Miller, Neil R, additional, Mills, David M, additional, Mills, Monte D, additional, Milman, Tatyana, additional, Mogk, Lylas, additional, Mogk, Marja, additional, Monés, Jordi, additional, Montes-Micó, Robert, additional, Morse, Christie L, additional, Morton, Asa D, additional, Moskowitz, Anne, additional, Mukai, Shizuo, additional, Murphree, A Linn, additional, Murphy, Robert P, additional, Murray, Timothy G, additional, Murray, Philip I, additional, Nagao, Karina, additional, Neitz, Jay, additional, Neitz, Maureen, additional, Netland, Peter A, additional, Neufeld, Arthur H, additional, Newman, Nancy J, additional, Ng, Eugene WM, additional, Nguyen, Quan Dong, additional, Niederkorn, Jerry Y, additional, Noecker, Robert J, additional, Nussenblatt, Robert B, additional, O'Brien, Joan M, additional, O'Brien, Paul D, additional, O'Brien, Terrence P, additional, O'Day, Denis, additional, Olk, R Joseph, additional, Olsen, Karl R, additional, Onal, Sumru, additional, Ooi, Yen Hoong, additional, Opremcak, E Mitchel, additional, Ousler, George, additional, Ozment, Randall R, additional, Packer, Samuel, additional, Palmer, Millicent L, additional, Papaliodis, George N, additional, Park, DJ John, additional, Parke, David W, additional, Parsa, Cameron F, additional, Parsons, M Andrew, additional, Pasquale, Louis R, additional, Patel, Neha N, additional, Patel, Sayjal J, additional, Patrianakos, Thomas D, additional, Patrinely, James R, additional, Pavan-Langston, Deborah, additional, Peli, Eli, additional, Pepin, Susan M, additional, Perez, Victor L, additional, Pérez-Santonja, Juan J, additional, Perfect, John R, additional, Perry, Henry D, additional, Piatigorsky, Joram, additional, Pieramici, Dante, additional, Pierce, Eric A, additional, Pineda, Roberto, additional, Pless, Misha L, additional, Pomeranz, Howard D, additional, Pournaras, Constantin J, additional, Power, William, additional, Prakash, Manvi, additional, Prasad, Anita G, additional, Purvin, Valerie, additional, Quillen, David A, additional, Quinn, Graham E, additional, Rabena, Melvin D, additional, Rae, James L, additional, Raizman, Michael B, additional, Randazzo, Alessandro, additional, Rao, Narsing A, additional, Rapuano, Christopher J, additional, Reeves, Sherman W, additional, Regillo, Carl D, additional, Reichel, Elias, additional, Reinke, Martin H, additional, Rhee, Douglas, additional, Richter, Claudia U, additional, Rizzo, Joseph F, additional, Robb, Richard M, additional, Roden, Anja C, additional, Rodgers, I Rand, additional, Rodrigues, Merlyn M, additional, Ron, Yonina, additional, Rose, Geoffrey E, additional, Rosen, Emanuel S, additional, Rosenbaum, James T, additional, Rosenthal, Perry, additional, Rouse, Strutha C, additional, Rovner, Barry W, additional, Rozanowska, Malgorzata, additional, Rubin, Michael P, additional, Rubin, Peter AD, additional, Rumelt, Shimon, additional, Rustgi, Anil K, additional, Rutar, Tina, additional, Ruttum, Mark S, additional, Rutzen, Allan R, additional, Ryan, Edward T, additional, Sadun, Alfredo A, additional, Sahel, José-Alain, additional, Saligan, Leorey, additional, Salim, Sarwat, additional, Salmon, John F, additional, Salomão, Diva R, additional, Sami, David, additional, Sandberg, Michael A, additional, Sangwan, Virender S, additional, Saornil, Maria A, additional, Sassani, Joseph W, additional, Sayegh, Rony R, additional, Schachat, Andrew P, additional, Schell, Wiley A, additional, Schefler, Amy C, additional, Scheufele, Tina, additional, Schiedler, Vivian, additional, Schneider, Gretchen, additional, Schroeder, Alison, additional, Schuchard, Ronald A, additional, Schuman, Joel S, additional, Schwab, Ivan R, additional, Scott, Adrienne, additional, Scott, Ingrid U, additional, Sears, Marvin L, additional, Seddon, Johanna M, additional, Seiler, Theo, additional, Selkin, Robert P, additional, Semba, Richard D, additional, Serbanescu, Irina, additional, Sexton, Briar, additional, Shaarawy, Tarek M, additional, Shah, Peter, additional, Shapiro, Aron, additional, Sharma, Savitri, additional, Shein, Jean, additional, Shetlar, Debra J, additional, Shields, M Bruce, additional, Shields, Carol L, additional, Shields, Jerry A, additional, Shingleton, Bradford J, additional, Shore, John W, additional, Shuba, Lesya M, additional, Simon, Guy J Ben, additional, Simmons, Richard J, additional, Simpson, Michael, additional, Singh, Arun D, additional, Singh, Omah S, additional, Sisley, Karen, additional, Sit, Arthur J, additional, Smerdon, David, additional, Smiddy, William E, additional, Smith, Ronald E, additional, Smith, Terry J, additional, Snebold, Neal G, additional, Sobrin, Lucia, additional, Sorenson, John A, additional, Soukiasian, Sarkis H, additional, Spaeth, George L, additional, Spaide, Richard F, additional, Srivastava, Monika, additional, Srivastava, Sunil K, additional, Stangos, Alexandros N, additional, Starck, Tomy, additional, Stark, Walter J, additional, Stein, Joshua D, additional, Steinert, Roger F, additional, Strauss, Leon, additional, Streeten, Barbara W, additional, Streilein, J Wayne, additional, Strong, James D, additional, Sugino, Ilene K, additional, Suhler, Eric B, additional, Sullivan, Timothy J, additional, Sun, Jennifer K, additional, Sunness, Janet S, additional, Sutula, Francis C, additional, Syed, Nasreen A, additional, Ta, Christopher N, additional, Takei, Hidehiro, additional, Talamo, Jonathan H, additional, Tamesis, Richard R, additional, Tamhankar, Madhura, additional, Tarbet, Kristen J, additional, Tarver-Carr, Michelle, additional, Terry, Mark A, additional, Thomas, Joseph M, additional, Thompson, Vance, additional, Thorne, Jennifer E, additional, Thurtell, Matthew J, additional, Tingey, David P, additional, To, King W, additional, Tobaigy, Faisal M, additional, Tolentino, Michael J, additional, Tong, Melissa G, additional, Torkildsen, Gail, additional, Toth, Cynthia A, additional, Traboulsi, Elias I, additional, Trucksis, Michele, additional, Tsai, James C, additional, Tsai, Julie H, additional, Tse, David T, additional, Tseng, Scheffer CG, additional, Tu, Elmer Y, additional, Udell, Ira J, additional, Valenzuela, Alejandra A, additional, Van Gelder, Russell N, additional, Van Stavern, Gregory P, additional, Vander Veen, Deborah K, additional, Vavvas, Demetrios, additional, Verity, David H, additional, Vinciguerra, Paolo, additional, Vinger, Paul F, additional, Volpe, Nicholas J, additional, Wackernagel, Werner, additional, Wadhwa, Sonal Desai, additional, Wagoner, Michael D, additional, Waheed, Nadia K, additional, Walton, David S, additional, Wand, Martin, additional, Wang, Jie Jin, additional, Warden, Scott M, additional, Webb, Lennox, additional, Weber, David, additional, Wee, Daniel, additional, Westerfeld, Corey B, additional, Westfall, Christopher T, additional, Whitcup, Scott M, additional, White, Valerie A, additional, White, William L, additional, Wickens, Jason, additional, Wiggs, Janey L, additional, Wilensky, Jacob T, additional, Wilkinson, Charles P, additional, Williams, Patrick D, additional, Wilson, David J, additional, Wilson, M Roy, additional, Wilson, Steven E, additional, Winokur, Jules, additional, Wirostko, William J, additional, Wollstein, Gadi, additional, Wong, Albert Chak Ming, additional, Wong, Tien Y, additional, Woog, John J, additional, Wride, Michael, additional, Wu, Carolyn S, additional, WuDunn, Darrell, additional, Yang, Jean, additional, Yannuzzi, Lawrence A, additional, Yaremchuk, Michael J, additional, Yeatts, R Patrick, additional, Yee, Richard W, additional, Yeh, Steven, additional, Young, Lucy HY, additional, Yu, Jenny Y, additional, Yue, Beatrice YJT, additional, Zacks, Charles M, additional, Zagelbaum, Bruce M, additional, Zamani, Maryam, additional, Zarbin, Marco, additional, Zografos, Leonidas, additional, and Zoumalan, Christopher I, additional

Published
2008
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27. Kinetics for the reactions of H30+ (H20)n with CH3SOCH3

Author

Thomas, Joseph M. and Viggiano, A.A.

Subjects
Dimethyl sulfoxide -- Research, Ions -- Research, Chemical reaction, Rate of -- Research, Chemicals, plastics and rubber industries
Abstract

The rate constants and product branching functions for the proton hydrate clusters H3O+(H20)n (n = 0-4), reacting with dimethyl sulfoxide were measured. The reactions were studied over the temperature range 198-298 K. The instability of large clusters at higher temperatures only permitted their study at low temperatures. All reactions were fast, approaching the collisional limit. The small clusters were slightly slower than the collision limit especially at 298 K.

Published
1999

28. Transcriptional Profiling of the Murine Airway Response to Acute Ozone Exposure.

Author

Tovar, Adelaide, Smith, Gregory J, Thomas, Joseph M, Crouse, Wesley L, Harkema, Jack R, and Kelada, Samir N P

Subjects
OZONE, GENE expression, EXTRACELLULAR matrix, CELL proliferation, PERMEABILITY, TIGHT junctions
Abstract

Ambient ozone (O3) exposure has serious consequences on respiratory health, including airway inflammation and injury. Decades of research have yielded thorough descriptions of these outcomes; however, less is known about the molecular processes that drive them. The aim of this study was to further describe the cellular and molecular responses to O3 exposure in murine airways, with a particular focus on transcriptional responses in 2 critical pulmonary tissue compartments: conducting airways (CA) and airway macrophages (AM). After exposing adult, female C57BL/6J mice to filtered air, 1 or 2 ppm O3, we assessed hallmark responses including airway inflammation (cell counts and cytokine secretion) and injury (epithelial permeability), followed by gene expression profiling of CA and AM by RNA-seq. As expected, we observed concentration-dependent increases in airway inflammation and injury. Conducting airways and AM both exhibited changes in gene expression to both 1 and 2 ppm O3 that were largely compartment-specific. In CA, genes associated with epithelial barrier function, detoxification processes, and cellular proliferation were altered, while O3 affected genes involved in innate immune signaling, cytokine production, and extracellular matrix remodeling in AM. Further, CA and AM also exhibited notable differences in concentration–response expression patterns for large numbers of genes. Overall, our study has described transcriptional responses to acute O3 exposure, revealing both shared and unique gene expression patterns across multiple concentrations of O3 and in 2 important O3-responsive tissues. These profiles provide broad mechanistic insight into pulmonary O3 toxicity, and reveal a variety of targets for focused follow-up studies. [ABSTRACT FROM AUTHOR]

Published
2020
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33. Rotational analysis of the nonthermal NO(A 2Σ+, v’=0) distribution observed in the N2(A 3Σ+u, v’=0)+NO(X 2Π, v‘=0) energy transfer reaction.

Author

Thomas, Joseph M. and Katayama, Daniel H.

Subjects
*ENERGY transfer, *NITRIC oxide, *PHOTOELECTRICITY
Abstract

A rapidly pumped discharge-flow reactor was constructed to characterize the N2(A 3Σ+u,v’)+NO(X 2Π, v‘=0) energy transfer (ET) reaction. Emission spectra of the NO γ bands from the product NO A 2Σ state formed in the title reaction were collected with a 2.2 m vacuum-ultraviolet spectrograph monochromator utilizing both photographic and photoelectric techniques. The rotational structure of the γ bands resulting from the title reaction is resolved with a spectral resolution of Δλ∼0.1 Å. The product NO(A,v’) emission spectra were measured as a function of total pressure (∼0.8≤pTOTAL≤∼3.0 Torr) and initial N2(A,v’) population distribution at 298 K. The product NO(A,v’,N’) rotational distributions yield temperatures much higher than room temperature (>1600 K) and are discussed in detail. Vibrational level specific bimolecular rate constants kv’ ’s for the N2(A,4≤v’≤6)+NO reaction were measured using N2(B 3Πg–A 3Σ+u) laser-excited fluorescence detection with a fixed reaction time. The kv’ ’s are (9.5±1.0), (11.3±1.2), and (11.2±1.1)×10-11 cm3 molecule-1 s-1 for v’=4, 5, and 6, respectively. A comparison with previous measurements is presented. [ABSTRACT FROM AUTHOR]

Published
1991
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34. Rate constants for electronic quenching of N2(A 3Σ+u, v=0–6) by O2, NO, CO, N2O, and C2H4.

Author

Thomas, Joseph M., Kaufman, Frederick, and Golde, Michael F.

Subjects
*FLUORESCENCE, *VIBRATION (Mechanics), *QUANTUM theory, *ENERGY transfer
Abstract

Rate constants for the title reactions have been measured using the discharge-flow technique, with N2(B 3Πg –A 3Σ+u) laser-excited fluorescence detection. C2H4 is an efficient quencher and exhibits little dependence of rate constant on vibrational quantum number v in N2(A). The rate constants for NO, O2, and N2O increase with v at low v, but are nearly independent of v for v≥3. CO shows a very strong dependence, with a peak in the rate constant at v=2 and a trough at v=5. These are the first data for the reactions of N2(A, v=2–6) with N2O. The other data are compared with previous measurements and discussed in terms of models of electronic-to-electronic energy transfer. [ABSTRACT FROM AUTHOR]

Published
1987
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37. The Drosophilahep pathway mediates Lrrk2-induced neurodegeneration.

Author

Yang, Dejun, Thomas, Joseph M., Li, Tianxia, Lee, Youngseok, Liu, Zhaohui, and Smith, Wanli W.

Subjects
PARKINSON'S disease, NEURODEGENERATION, BRAIN diseases, DARDARIN, DOPAMINERGIC neurons, DROSOPHILA
Abstract

Copyright of Biochemistry & Cell Biology is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2018
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38. Major Amputations for Extremity Soft-Tissue Sarcoma.

Author

Smith, Henry G., Thomas, Joseph M., Smith, Myles J.F., Hayes, Andrew J., and Strauss, Dirk C.

Abstract

Introduction: With modern techniques facilitating limb conservation, amputation for extremity soft-tissue sarcoma (ESTS) is now rare. We sought to determine the indications and outcomes following major amputation for ESTS and whether amputation is prognostic of oncological outcomes in primary disease. Patients and Methods: Patients undergoing major amputations for ESTS from 2004 to 2014 were identified from electronic patient records. Results: The amputation rate in primary localized disease was 4.1%. Overall, 69 patients were identified, including 23 (33.3%) amputations for primary localized disease, 36 (52.2%) amputations for recurrent disease, and 10 (14.5%) amputations for metastatic disease. The local recurrence rate for localized disease at 3 years was 10.4%. Three-year overall survival (OS) was 50.3% following curative amputation, with a median survival of 41 months, and median OS following palliative amputation was 6 months. In the context of primary, localized disease, patients undergoing amputation had a greater proportion of high-grade tumors (69.6% vs. 41.1%; p = 0.009) of greater size (median 16.0 vs. 9.0 cm; p = 0.003) when compared with patients undergoing limb-conserving surgery. The rates of systemic relapse and disease-specific survival were poorer following amputation compared with limb-conserving surgery, however mode of surgery (amputation vs. limb conservation) was only prognostic for OS. Conclusions: Amputation maintains an important role in ESTS and achieves durable local control in those unsuitable for limb-conserving surgery. Survival following amputation in the presence of metastatic disease is poor and should be reserved for patients with significant symptoms. [ABSTRACT FROM AUTHOR]

Published
2018
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40. Correction: Novel Role for Surfactant Protein A in Gastrointestinal Graft-versus-Host Disease

Author

Gowdy, Kymberly M., primary, Cardona, Diana M., additional, Nugent, Julia L., additional, Giamberardino, Charles, additional, Thomas, Joseph M., additional, Mukherjee, Sambudho, additional, Martinu, Tereza, additional, Foster, W. Michael, additional, Plevy, Scott E., additional, Pastva, Amy M., additional, Wright, Jo Rae, additional, and Palmer, Scott M., additional

Published
2013
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42. Novel Role for Surfactant Protein A in Gastrointestinal Graft-versus-Host Disease

Author

Gowdy, Kymberly M., primary, Cardona, Diana M., additional, Nugent, Julia L., additional, Giamberardino, Charles, additional, Thomas, Joseph M., additional, Mukherjee, Sambudho, additional, Martinu, Tereza, additional, Foster, W. Michael, additional, Plevy, Scott E., additional, Pastva, Amy M., additional, Wright, Jo Rae, additional, and Palmer, Scott M., additional

Published
2012
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48. Characterization of UV Emissions Resulting from Electronic Energy Transfer in Atmospheric Molecules

Author

ORION INTERNATIONAL TECHNOLOGIES INC ALBUQUERQUE NM, Dentamaro, Anthony V., Thomas, Joseph M., ORION INTERNATIONAL TECHNOLOGIES INC ALBUQUERQUE NM, Dentamaro, Anthony V., and Thomas, Joseph M.

Abstract

State-specific experiments were performed which studied collision induced electronic transitions (CIET) in a diatomic molecule. These optical-optical double resonance (OODR) experiments employed a resonance enhanced multiphoton ionization (REMPI) technique for purposes of detection. A strong dependence on Franck-Condon factor (FCF) and small energy gap, as well as a propensity for conservation of rotational angular momentum have become trademarks of our CIET experiments. Present theoretical models of these processes are not able to fully reproduce the observed results, thus making it impoflant to perform experiments which consider a wide range of energy gaps and FCF. The volume of our data has led to the development of an empirical branching ratio model which appears to be quite accurate and useful in predicting deactivation rate constants for CIET in various diatomic molecules. These results have been incorporated into a model of atmospheric Lyman-Birge-Hopfield (LBH) emissions.

Published
1997

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