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1. Annual (2023) taxonomic update of RNA-directed RNA polymerase-encoding negative-sense RNA viruses (realm Riboviria: kingdom Orthornavirae: phylum Negarnaviricota)

Author: National Institute of Allergy and Infectious Diseases (US), Antiviral Countermeasures Development Center (US), Department of Agriculture (US), Department of the Army (US), Department of Health and Human Services (US), US Department of Homeland Security, Federal Government of the United States, Kuhn, Jens H. [0000-0002-7800-6045], Abe, Junya [0000-0003-3627-7071], Adkins, Scott [0000-0003-0095-8414], Alkhovsky, Sergey V. [0000-0001-6913-5841], Avsic-Zupanc, Tatjana [0000-0001-6243-0688], Ayllón, María A. [0000-0001-7893-6106], Bahl, Justin [0000-0001-7572-4300], Balkema-Buschmann, A. [0000-0001-7613-9592], Ballinger, Matthew J. [0000-0001-7453-8725], Bejerman, Nicolas [0000-0002-7851-3506], Biedenkopf, Nadine [0000-0002-6061-8019], Blair, Carol D.[0000-0002-2803-0354], Blasdell, Kim R.[0000-0003-2121-0376], Bradfute, Steven B.[0000-0002-1985-751X], Briese, Thomas [0000-0002-4819-8963], Buchholz, Ursula J. [0000-0002-2329-3198], Buchmeier, Michael J.[0000-0002-2387-9287], Bukreyev, Alexander [0000-0002-0342-4824], Burt, Felicity [0000-0002-7238-7799], Büttner, Carmen [0000-0002-2086-2594], Calisher, Charles H. [0000-0003-0213-294X], Cao, Mengji [0000-0003-0396-262X], Casas, Inmaculada [0000-0003-1840-1198], Chandran, Kartik [0000-0003-0232-7077], Charrel, Rémi N.[0000-0002-7675-8251], Chaturvedi, Krishna Kumar [0000-0002-6529-5466], Crane, Anya [0000-0002-2060-2469], De Swart, Rik L.[0000-0003-3599-8969], Debat, Humberto [0000-0003-3056-3739], Dheilly, Nolwenn M.[0000-0002-3675-5013], Di Paola, Nicholas [0000-0002-9694-3913], Di Serio, Francesco [0000-0003-2822-704X], Dietzgen, Ralf G.[0000-0002-7772-2250], Digiaro, Michele [0009-0006-3089-3606], Drexler, J. Felix [0000-0002-3509-0232], Duprex, W. Paul [0000-0003-1716-6376], Elbeaino, Toufic [0000-0003-2211-7907], Ergünay, Koray [0000-0001-5422-1982], Feng, Guozhong [0000-0002-9489-9322], Fooks, Anthony R.[0000-0002-3243-6154], Formenty, Pierre B.H.[0000-0002-9482-5411], Freitas-Astúa, Juliana [0000-0002-0506-6880], Gago-Zachert, Selma [0000-0002-1084-2119], García, María Laura [0000-0001-6468-6943], Garrison, Aura R.[0000-0003-3034-6400], Gaskin, Thomas R. [0000-0002-5644-4431], Gouy de Bellocq, Joelle [0000-0001-5831-6284], Griffiths, Anthony [0000-0001-5435-8364], Groschup, M. H.[0000-0003-0215-185X], Günther, Stephan [0000-0002-6562-0230], Hayashi, Kazusa [0009-0002-9395-0066], Hepojoki, Jussi [0000-0001-5699-214X], Higgins, Colleen M. [0000-0001-9016-2940], Horie, Masayuki [0000-0003-4682-7698], Hughes, Holly R.[0000-0003-1380-8263], Hyndman, Timothy [0000-0002-7047-5023], Jiāng, Dàohóng [0000-0002-3862-7461], Jonson, Gilda B.[0000-0003-0097-8634], Junglen, Sandra [0000-0002-3799-6011], Klempa, B.[0000-0002-6931-1224], Klingström, Jonas [0000-0001-9076-1441], Kondō, Hideki [0000-0001-9220-5350], Koonin, Eugene V. [0000-0003-3943-8299], Krupovic, Mart [0000-0001-5486-0098], Kurath, Gael [0000-0003-3294-560X], Laenen, Lies [0000-0001-9118-8608], Li, Jianrong [0000-0002-7130-1084], Lukashevich, Igor S.[0000-0001-6523-5116], MacDiarmid, Robin M.[0000-0002-7057-2018], Maes, Piet [0000-0002-4571-5232], Marklewitz, Marco [0000-0003-1828-8770], Marshall, Sergio H.[0000-0003-0438-8252], Marzano, Shin-Yi L. [0000-0003-0548-3761], Mühlberger, Elke [0000-0003-3547-9376], Nabeshima, Tomoyuki [0000-0002-6570-096X], Naidu, Rayapati [0000-0002-7273-5116], Natsuaki, Tomohide [0000-0003-1823-7308], Navarro, José A. [0000-0002-0536-6074], Neriya, Yutaro [0000-0002-1385-0050], Netesov, Sergey V. [0000-0002-7786-2464], Neumann, Gabriele [0000-0001-7054-1775], Nowotny, N. [0000-0002-3548-571X], Ochoa-Corona, Francisco M. [0000-0002-4112-8209], Pallás, Vicente [0000-0003-4954-989X], Papa, Anna [0000-0002-6643-3322], Paraskevopoulou, Sofia [0000-0003-2608-2596], Parrish, Colin R. [0000-0002-1836-6655], Pauvolid-Corrêa, Alex [0000-0002-6924-157X], Pawęska, Janusz T. [0000-0001-8776-7519], Pérez, Daniel R. [0000-0002-6569-5689], Pfaff, Florian [0000-0003-0178-6183], Plemper, Richard K. [0000-0003-2034-2107], Postler, Thomas S. [0000-0002-3558-9084], Rabbidge, Lee O. [0009-0001-7962-4881], Radoshitzky, Sheli R. [0000-0001-8976-8056], Ramos-González, Pedro L. [0000-0002-9640-6587], Rehanek, Marius [0000-0002-5710-5060], Resende, Renato O. [0000-0003-3852-1576], Romanowski, Víctor [0000-0001-6378-7929], Rubbenstroth, Dennis [0000-0002-8209-6274], Rubino, Luisa [0000-0002-2073-2415], Runstadler, Jonathan A. [0000-0002-6747-7765], Sabanadzovic, Sead [0000-0002-2995-2633], Salvato, Maria S. [0000-0002-3357-5391], Sasaya, Takahide [0000-0002-5020-9377], Schwemmle, Martin [0000-0002-2972-6855], Shi, Mang [0000-0002-6154-4437], Shimomoto, Yoshifumi [0000-0002-0796-7068], Kavi Sidharthan, Venkidusamy [0000-0003-1561-549X], Sironi, Manuela [0000-0002-2267-5266], Smither, Sophie [0000-0002-7835-3581], Spann, Kirsten [0000-0003-0567-8382], Spengler, Jessica R. [0000-0002-5383-0513], Stenglein, Mark D. [0000-0002-0993-813X], Takada, Ayato [0000-0003-2464-6642], Takeyama, Sawana [0009-0000-3771-5999], Tesh, Robert B. [0000-0002-9226-397X], Thornburg, Natalie J. [0000-0003-3523-3616], Tischler, Nicole D. [0000-0002-4578-4780], Tomitaka, Yasuhiro [0000-0002-6914-4016], Tomonaga, Keizō [0000-0003-0405-7103], Tordo, Noël [0000-0001-5873-059X], Tu, Changchun [0000-0002-8134-7502], Turina, Massimo [0000-0002-9659-9470], Tzanetakis, Ioannis E. [0000-0002-5970-1763], Vaira, Anna Maria [0000-0003-2526-4419], Van den Hoogen, Bernadette [0000-0003-1996-8559], Vanmechelen, Bert [0000-0002-8350-4356], Verbeek, Martin [0000-0002-8973-3803], Von Bargen, Susanne [0000-0001-8321-1572], Wada, Jiro [0000-0001-9846-0846], Wahl, Victoria [0000-0002-6588-4308], Walker, Peter J. [0000-0003-1851-642X], Waltzek, Thomas B. [0000-0001-6383-5978], Whitfield, Anna E. [0000-0002-3538-015X], Wolf, Yuri I. [0000-0002-0247-8708], Xylogianni, Evanthia [0009-0001-8768-0939], Yanagisawa, Hironobu [0000-0002-6729-466X], Ye, Gongyin [0000-0003-4937-8867], Yuan, Zhiming [0000-0002-3234-9616], Zerbini, F. Murilo [0000-0001-8617-0200], Okland, Arnfinn Lodden [0000-0003-3062-4386], Kuhn, Jens H., Abe, Junya, Adkins, Scott, Alkhovsky, Sergey V., Avsic-Zupanc, Tatjana, Ayllón, María A., Bahl, Justin, Balkema-Buschmann, A., Ballinger, Matthew J., Kumar Baranwal, Virendra, Beer, Martin, Bejerman, Nicolas, Bergeron, Éric, Biedenkopf, Nadine, Blair, Carol D., Blasdell, Kim R., Blouin, Arnaud G., Bradfute, Steven B., Briese, Thomas, Brown, Paul A., Buchholz, Ursula J., Buchmeier, Michael J., Bukreyev, Alexander, Burt, Felicity, Büttner, Carmen, Calisher, Charles H., Cao, Mengji, Casas, Inmaculada, Chandran, Kartik, Charrel, Rémi N., Chaturvedi, Krishna Kumar, Chooi, Kar Mun, Crane, Anya, Dal Bó, Elena, de la Torre, J. C., de Souza, William Marciel, De Swart, Rik L., Debat, Humberto, Dheilly, Nolwenn M., Di Paola, Nicholas, Di Serio, Francesco, Dietzgen, Ralf G., Digiaro, Michele, Drexler, J. Felix, Duprex, W. Paul, Dürrwald, Ralf, Easton, Andrew J., Elbeaino, Toufic, Ergünay, Koray, Feng, Guozhong, Firth, Andrew E., Fooks, Anthony R., Formenty, Pierre B.H., Freitas-Astúa, Juliana, Gago-Zachert, Selma, García, María Laura, García-Sastre, Adolfo, Garrison, Aura R., Gaskin, Thomas R., Gong, Wenjie, Gonzalez, Jean-Paul J., Gouy de Bellocq, Joelle, Griffiths, Anthony, Groschup, M. H., Günther, Ines, Günther, Stephan, Hammond, John, Hasegawa, Yusuke, Hayashi, Kazusa, Hepojoki, Jussi, Higgins, Colleen M., Hongo, Seiji, Horie, Masayuki, Hughes, Holly R., Hume, Adam J., Hyndman, Timothy, Ikeda, Kenichi, Jiāng, Dàohóng, Jonson, Gilda B., Junglen, Sandra, Klempa, B., Klingström, Jonas, Kondō, Hideki, Koonin, Eugene V., Krupovic, Mart, Kubota, Kenji, Kurath, Gael, Laenen, Lies, Lambert, Amy J., Li, Jianrong, Li, Jun-Min, Liu, Ran, Lukashevich, Igor S., MacDiarmid, Robin M, Maes, Piet, Marklewitz, Marco, Marshall, Sergio H., Marzano, Shin-Yi L., McCauley, John W., Mirazimi, Ali, Mühlberger, Elke, Nabeshima, Tomoyuki, Naidu, Rayapati, Natsuaki, Tomohide, Navarro, Beatriz, Navarro, José A., Neriya, Yutaro, Netesov, Sergey V., Neumann, Gabriele, Nowotny, N., Nunes, Márcio R.T., Ochoa-Corona, Francisco M., Okada, Tomoyuki, Palacios, Gustavo, Pallás, Vicente, Papa, Anna, Paraskevopoulou, Sofia, Parrish, Colin R., Pauvolid-Corrêa, Alex, Pawęska, Janusz T., Pérez, Daniel R., Pfaff, Florian, Plemper, Richard K., Postler, Thomas S., Rabbidge, Lee O., Radoshitzky, Sheli R., Ramos-González, Pedro L., Rehanek, Marius, Resende, Renato O., Reyes, Carina A., Rodrigues, Thaís C.S., Romanowski, Víctor, Rubbenstroth, Dennis, Rubino, Luisa, Runstadler, Jonathan A., Sabanadzovic, Sead, Sadiq, Sabrina, Salvato, Maria S., Sasaya, Takahide, Schwemmle, Martin, Sharpe, Stephen R., Shi, Mang, Shimomoto, Yoshifumi, Kavi Sidharthan, Venkidusamy, Sironi, Manuela, Smither, Sophie, Song, Jin-Won, Spann, Kirsten, Spengler, Jessica R., Stenglein, Mark D., Takada, Ayato, Takeyama, Sawana, Tatara, Akio, Tesh, Robert B., Thornburg, Natalie J., Tian, Xin, Tischler, Nicole D., Tomitaka, Yasuhiro, Tomonaga, Keizō, Tordo, Noël, Tu, Changchun, Turina, Massimo, Tzanetakis, Ioannis E., Vaira, Anna Maria, Van den Hoogen, Bernadette, Vanmechelen, Bert, Vasilakis, Nikos, Verbeek, Martin, Von Bargen, Susanne, Wada, Jiro, Wahl, Victoria, Walker, Peter J., Waltzek, Thomas B., Whitfield, Anna E., Wolf, Yuri I., Xia, Han, Xylogianni, Evanthia, Yanagisawa, Hironobu, Yano, Kazutaka, Ye, Gongyin, Yuan, Zhiming, Zerbini, F. Murilo, Zhang, Guilin, Zhang, Song, Zhang, Yong-Zhen, Zhao, Lu, Okland, Arnfinn Lodden, National Institute of Allergy and Infectious Diseases (US), Antiviral Countermeasures Development Center (US), Department of Agriculture (US), Department of the Army (US), Department of Health and Human Services (US), US Department of Homeland Security, Federal Government of the United States, Kuhn, Jens H. [0000-0002-7800-6045], Abe, Junya [0000-0003-3627-7071], Adkins, Scott [0000-0003-0095-8414], Alkhovsky, Sergey V. [0000-0001-6913-5841], Avsic-Zupanc, Tatjana [0000-0001-6243-0688], Ayllón, María A. [0000-0001-7893-6106], Bahl, Justin [0000-0001-7572-4300], Balkema-Buschmann, A. [0000-0001-7613-9592], Ballinger, Matthew J. [0000-0001-7453-8725], Bejerman, Nicolas [0000-0002-7851-3506], Biedenkopf, Nadine [0000-0002-6061-8019], Blair, Carol D.[0000-0002-2803-0354], Blasdell, Kim R.[0000-0003-2121-0376], Bradfute, Steven B.[0000-0002-1985-751X], Briese, Thomas [0000-0002-4819-8963], Buchholz, Ursula J. [0000-0002-2329-3198], Buchmeier, Michael J.[0000-0002-2387-9287], Bukreyev, Alexander [0000-0002-0342-4824], Burt, Felicity [0000-0002-7238-7799], Büttner, Carmen [0000-0002-2086-2594], Calisher, Charles H. [0000-0003-0213-294X], Cao, Mengji [0000-0003-0396-262X], Casas, Inmaculada [0000-0003-1840-1198], Chandran, Kartik [0000-0003-0232-7077], Charrel, Rémi N.[0000-0002-7675-8251], Chaturvedi, Krishna Kumar [0000-0002-6529-5466], Crane, Anya [0000-0002-2060-2469], De Swart, Rik L.[0000-0003-3599-8969], Debat, Humberto [0000-0003-3056-3739], Dheilly, Nolwenn M.[0000-0002-3675-5013], Di Paola, Nicholas [0000-0002-9694-3913], Di Serio, Francesco [0000-0003-2822-704X], Dietzgen, Ralf G.[0000-0002-7772-2250], Digiaro, Michele [0009-0006-3089-3606], Drexler, J. Felix [0000-0002-3509-0232], Duprex, W. Paul [0000-0003-1716-6376], Elbeaino, Toufic [0000-0003-2211-7907], Ergünay, Koray [0000-0001-5422-1982], Feng, Guozhong [0000-0002-9489-9322], Fooks, Anthony R.[0000-0002-3243-6154], Formenty, Pierre B.H.[0000-0002-9482-5411], Freitas-Astúa, Juliana [0000-0002-0506-6880], Gago-Zachert, Selma [0000-0002-1084-2119], García, María Laura [0000-0001-6468-6943], Garrison, Aura R.[0000-0003-3034-6400], Gaskin, Thomas R. [0000-0002-5644-4431], Gouy de Bellocq, Joelle [0000-0001-5831-6284], Griffiths, Anthony [0000-0001-5435-8364], Groschup, M. H.[0000-0003-0215-185X], Günther, Stephan [0000-0002-6562-0230], Hayashi, Kazusa [0009-0002-9395-0066], Hepojoki, Jussi [0000-0001-5699-214X], Higgins, Colleen M. [0000-0001-9016-2940], Horie, Masayuki [0000-0003-4682-7698], Hughes, Holly R.[0000-0003-1380-8263], Hyndman, Timothy [0000-0002-7047-5023], Jiāng, Dàohóng [0000-0002-3862-7461], Jonson, Gilda B.[0000-0003-0097-8634], Junglen, Sandra [0000-0002-3799-6011], Klempa, B.[0000-0002-6931-1224], Klingström, Jonas [0000-0001-9076-1441], Kondō, Hideki [0000-0001-9220-5350], Koonin, Eugene V. [0000-0003-3943-8299], Krupovic, Mart [0000-0001-5486-0098], Kurath, Gael [0000-0003-3294-560X], Laenen, Lies [0000-0001-9118-8608], Li, Jianrong [0000-0002-7130-1084], Lukashevich, Igor S.[0000-0001-6523-5116], MacDiarmid, Robin M.[0000-0002-7057-2018], Maes, Piet [0000-0002-4571-5232], Marklewitz, Marco [0000-0003-1828-8770], Marshall, Sergio H.[0000-0003-0438-8252], Marzano, Shin-Yi L. [0000-0003-0548-3761], Mühlberger, Elke [0000-0003-3547-9376], Nabeshima, Tomoyuki [0000-0002-6570-096X], Naidu, Rayapati [0000-0002-7273-5116], Natsuaki, Tomohide [0000-0003-1823-7308], Navarro, José A. [0000-0002-0536-6074], Neriya, Yutaro [0000-0002-1385-0050], Netesov, Sergey V. [0000-0002-7786-2464], Neumann, Gabriele [0000-0001-7054-1775], Nowotny, N. [0000-0002-3548-571X], Ochoa-Corona, Francisco M. [0000-0002-4112-8209], Pallás, Vicente [0000-0003-4954-989X], Papa, Anna [0000-0002-6643-3322], Paraskevopoulou, Sofia [0000-0003-2608-2596], Parrish, Colin R. [0000-0002-1836-6655], Pauvolid-Corrêa, Alex [0000-0002-6924-157X], Pawęska, Janusz T. [0000-0001-8776-7519], Pérez, Daniel R. [0000-0002-6569-5689], Pfaff, Florian [0000-0003-0178-6183], Plemper, Richard K. [0000-0003-2034-2107], Postler, Thomas S. [0000-0002-3558-9084], Rabbidge, Lee O. [0009-0001-7962-4881], Radoshitzky, Sheli R. [0000-0001-8976-8056], Ramos-González, Pedro L. [0000-0002-9640-6587], Rehanek, Marius [0000-0002-5710-5060], Resende, Renato O. [0000-0003-3852-1576], Romanowski, Víctor [0000-0001-6378-7929], Rubbenstroth, Dennis [0000-0002-8209-6274], Rubino, Luisa [0000-0002-2073-2415], Runstadler, Jonathan A. [0000-0002-6747-7765], Sabanadzovic, Sead [0000-0002-2995-2633], Salvato, Maria S. [0000-0002-3357-5391], Sasaya, Takahide [0000-0002-5020-9377], Schwemmle, Martin [0000-0002-2972-6855], Shi, Mang [0000-0002-6154-4437], Shimomoto, Yoshifumi [0000-0002-0796-7068], Kavi Sidharthan, Venkidusamy [0000-0003-1561-549X], Sironi, Manuela [0000-0002-2267-5266], Smither, Sophie [0000-0002-7835-3581], Spann, Kirsten [0000-0003-0567-8382], Spengler, Jessica R. [0000-0002-5383-0513], Stenglein, Mark D. [0000-0002-0993-813X], Takada, Ayato [0000-0003-2464-6642], Takeyama, Sawana [0009-0000-3771-5999], Tesh, Robert B. [0000-0002-9226-397X], Thornburg, Natalie J. [0000-0003-3523-3616], Tischler, Nicole D. [0000-0002-4578-4780], Tomitaka, Yasuhiro [0000-0002-6914-4016], Tomonaga, Keizō [0000-0003-0405-7103], Tordo, Noël [0000-0001-5873-059X], Tu, Changchun [0000-0002-8134-7502], Turina, Massimo [0000-0002-9659-9470], Tzanetakis, Ioannis E. [0000-0002-5970-1763], Vaira, Anna Maria [0000-0003-2526-4419], Van den Hoogen, Bernadette [0000-0003-1996-8559], Vanmechelen, Bert [0000-0002-8350-4356], Verbeek, Martin [0000-0002-8973-3803], Von Bargen, Susanne [0000-0001-8321-1572], Wada, Jiro [0000-0001-9846-0846], Wahl, Victoria [0000-0002-6588-4308], Walker, Peter J. [0000-0003-1851-642X], Waltzek, Thomas B. [0000-0001-6383-5978], Whitfield, Anna E. [0000-0002-3538-015X], Wolf, Yuri I. [0000-0002-0247-8708], Xylogianni, Evanthia [0009-0001-8768-0939], Yanagisawa, Hironobu [0000-0002-6729-466X], Ye, Gongyin [0000-0003-4937-8867], Yuan, Zhiming [0000-0002-3234-9616], Zerbini, F. Murilo [0000-0001-8617-0200], Okland, Arnfinn Lodden [0000-0003-3062-4386], Kuhn, Jens H., Abe, Junya, Adkins, Scott, Alkhovsky, Sergey V., Avsic-Zupanc, Tatjana, Ayllón, María A., Bahl, Justin, Balkema-Buschmann, A., Ballinger, Matthew J., Kumar Baranwal, Virendra, Beer, Martin, Bejerman, Nicolas, Bergeron, Éric, Biedenkopf, Nadine, Blair, Carol D., Blasdell, Kim R., Blouin, Arnaud G., Bradfute, Steven B., Briese, Thomas, Brown, Paul A., Buchholz, Ursula J., Buchmeier, Michael J., Bukreyev, Alexander, Burt, Felicity, Büttner, Carmen, Calisher, Charles H., Cao, Mengji, Casas, Inmaculada, Chandran, Kartik, Charrel, Rémi N., Chaturvedi, Krishna Kumar, Chooi, Kar Mun, Crane, Anya, Dal Bó, Elena, de la Torre, J. C., de Souza, William Marciel, De Swart, Rik L., Debat, Humberto, Dheilly, Nolwenn M., Di Paola, Nicholas, Di Serio, Francesco, Dietzgen, Ralf G., Digiaro, Michele, Drexler, J. Felix, Duprex, W. Paul, Dürrwald, Ralf, Easton, Andrew J., Elbeaino, Toufic, Ergünay, Koray, Feng, Guozhong, Firth, Andrew E., Fooks, Anthony R., Formenty, Pierre B.H., Freitas-Astúa, Juliana, Gago-Zachert, Selma, García, María Laura, García-Sastre, Adolfo, Garrison, Aura R., Gaskin, Thomas R., Gong, Wenjie, Gonzalez, Jean-Paul J., Gouy de Bellocq, Joelle, Griffiths, Anthony, Groschup, M. H., Günther, Ines, Günther, Stephan, Hammond, John, Hasegawa, Yusuke, Hayashi, Kazusa, Hepojoki, Jussi, Higgins, Colleen M., Hongo, Seiji, Horie, Masayuki, Hughes, Holly R., Hume, Adam J., Hyndman, Timothy, Ikeda, Kenichi, Jiāng, Dàohóng, Jonson, Gilda B., Junglen, Sandra, Klempa, B., Klingström, Jonas, Kondō, Hideki, Koonin, Eugene V., Krupovic, Mart, Kubota, Kenji, Kurath, Gael, Laenen, Lies, Lambert, Amy J., Li, Jianrong, Li, Jun-Min, Liu, Ran, Lukashevich, Igor S., MacDiarmid, Robin M, Maes, Piet, Marklewitz, Marco, Marshall, Sergio H., Marzano, Shin-Yi L., McCauley, John W., Mirazimi, Ali, Mühlberger, Elke, Nabeshima, Tomoyuki, Naidu, Rayapati, Natsuaki, Tomohide, Navarro, Beatriz, Navarro, José A., Neriya, Yutaro, Netesov, Sergey V., Neumann, Gabriele, Nowotny, N., Nunes, Márcio R.T., Ochoa-Corona, Francisco M., Okada, Tomoyuki, Palacios, Gustavo, Pallás, Vicente, Papa, Anna, Paraskevopoulou, Sofia, Parrish, Colin R., Pauvolid-Corrêa, Alex, Pawęska, Janusz T., Pérez, Daniel R., Pfaff, Florian, Plemper, Richard K., Postler, Thomas S., Rabbidge, Lee O., Radoshitzky, Sheli R., Ramos-González, Pedro L., Rehanek, Marius, Resende, Renato O., Reyes, Carina A., Rodrigues, Thaís C.S., Romanowski, Víctor, Rubbenstroth, Dennis, Rubino, Luisa, Runstadler, Jonathan A., Sabanadzovic, Sead, Sadiq, Sabrina, Salvato, Maria S., Sasaya, Takahide, Schwemmle, Martin, Sharpe, Stephen R., Shi, Mang, Shimomoto, Yoshifumi, Kavi Sidharthan, Venkidusamy, Sironi, Manuela, Smither, Sophie, Song, Jin-Won, Spann, Kirsten, Spengler, Jessica R., Stenglein, Mark D., Takada, Ayato, Takeyama, Sawana, Tatara, Akio, Tesh, Robert B., Thornburg, Natalie J., Tian, Xin, Tischler, Nicole D., Tomitaka, Yasuhiro, Tomonaga, Keizō, Tordo, Noël, Tu, Changchun, Turina, Massimo, Tzanetakis, Ioannis E., Vaira, Anna Maria, Van den Hoogen, Bernadette, Vanmechelen, Bert, Vasilakis, Nikos, Verbeek, Martin, Von Bargen, Susanne, Wada, Jiro, Wahl, Victoria, Walker, Peter J., Waltzek, Thomas B., Whitfield, Anna E., Wolf, Yuri I., Xia, Han, Xylogianni, Evanthia, Yanagisawa, Hironobu, Yano, Kazutaka, Ye, Gongyin, Yuan, Zhiming, Zerbini, F. Murilo, Zhang, Guilin, Zhang, Song, Zhang, Yong-Zhen, Zhao, Lu, and Okland, Arnfinn Lodden
Abstract: In April 2023, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by one new family, 14 new genera, and 140 new species. Two genera and 538 species were renamed. One species was moved, and four were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.
Published: 2023

2. Defining the causes of sporadic Parkinson’s disease in the global Parkinson’s genetics program (GP2)

Author: National Institute on Aging (US), National Institutes of Health (US), Aligning Science Against Parkinson's, Parkinson Research Foundation, Department of Health and Human Services (US), Towns, Clodagh, Richer, Madeleine, Jasaityte, Simona, Stafford, Eleanor J., Joubert, Julie, Antar, Tarek, Martínez-Carrasco, Alejandro, Makarious, Mary B., Casey, Bradford, Vitale, Dan, Levine, Kristin, Leonard, Hampton, Pantazis, Caroline B., Screven, Laurel A., Hernández, Dena G., Wegel, Claire E., Solle, Justin, Nalls, Mike A., Blauwendraat, Cornelis, Singleton, Andrew B., Tan, Manuela M. X., Iwaki, Hirotaka, Morris, Huw, Global Parkinson’s Genetics Program (GP2), Periñán, María Teresa, National Institute on Aging (US), National Institutes of Health (US), Aligning Science Against Parkinson's, Parkinson Research Foundation, Department of Health and Human Services (US), Towns, Clodagh, Richer, Madeleine, Jasaityte, Simona, Stafford, Eleanor J., Joubert, Julie, Antar, Tarek, Martínez-Carrasco, Alejandro, Makarious, Mary B., Casey, Bradford, Vitale, Dan, Levine, Kristin, Leonard, Hampton, Pantazis, Caroline B., Screven, Laurel A., Hernández, Dena G., Wegel, Claire E., Solle, Justin, Nalls, Mike A., Blauwendraat, Cornelis, Singleton, Andrew B., Tan, Manuela M. X., Iwaki, Hirotaka, Morris, Huw, Global Parkinson’s Genetics Program (GP2), and Periñán, María Teresa
Abstract: The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia.
Published: 2023

3. Mutation L319Q in the PB1 Polymerase Subunit Improves Attenuation of a Candidate Live-Attenuated Influenza A Virus Vaccine

Author: New York Influenza Center of Excellence, National Institute of Allergy and Infectious Diseases (US), Department of Health and Human Services (US), Centers of Excellence for Influenza Research and Surveillance (US), Department of Defense (US), Center for Research for Influenza Pathogenesis (US), Ministerio de Ciencia e Innovación (España), Icahn School of Medicine at Mount Sinai, Nogales, Aitor [0000-0002-2424-7900], Lowen, Anice C. [0000-0002-9829-112X], Chiem, Kevin [0000-0002-3892-5944], García-Sastre, Adolfo [0000-0002-6551-1827], Albrecht, Randy A. [0000-0003-4008-503X], Dewhurst, Stephen [0000-0001-7729-7920], Nogales, Aitor, Steel, John, Liu, Wen-Chun, Lowen, Anice C., Rodriguez, Laura, Chiem, Kevin, Cox, Andrew, García-Sastre, Adolfo, Albrecht, Randy A., Dewhurst, Stephen, Martínez-Sobrido, Luis, New York Influenza Center of Excellence, National Institute of Allergy and Infectious Diseases (US), Department of Health and Human Services (US), Centers of Excellence for Influenza Research and Surveillance (US), Department of Defense (US), Center for Research for Influenza Pathogenesis (US), Ministerio de Ciencia e Innovación (España), Icahn School of Medicine at Mount Sinai, Nogales, Aitor [0000-0002-2424-7900], Lowen, Anice C. [0000-0002-9829-112X], Chiem, Kevin [0000-0002-3892-5944], García-Sastre, Adolfo [0000-0002-6551-1827], Albrecht, Randy A. [0000-0003-4008-503X], Dewhurst, Stephen [0000-0001-7729-7920], Nogales, Aitor, Steel, John, Liu, Wen-Chun, Lowen, Anice C., Rodriguez, Laura, Chiem, Kevin, Cox, Andrew, García-Sastre, Adolfo, Albrecht, Randy A., Dewhurst, Stephen, and Martínez-Sobrido, Luis
Abstract: Influenza A viruses (IAV) remain emerging threats to human public health. Live-attenuated influenza vaccines (LAIV) are one of the most effective prophylactic options to prevent disease caused by influenza infections. However, licensed LAIV remain restricted for use in 2- to 49-year-old healthy and nonpregnant people. Therefore, development of LAIV with increased safety, immunogenicity, and protective efficacy is highly desired. The U.S.-licensed LAIV is based on the master donor virus (MDV) A/Ann Arbor/6/60 H2N2 backbone, which was generated by adaptation of the virus to growth at low temperatures. Introducing the genetic signature of the U.S. MDV into the backbone of other IAV strains resulted in varying levels of attenuation. While the U.S. MDV mutations conferred an attenuated phenotype to other IAV strains, the same amino acid changes did not significantly attenuate the pandemic A/California/04/09 H1N1 (pH1N1) strain. To attenuate pH1N1, we replaced the conserved leucine at position 319 with glutamine (L319Q) in PB1 and analyzed the in vitro and in vivo properties of pH1N1 viruses containing either PB1 L319Q alone or in combination with the U.S. MDV mutations using two animal models of influenza infection and transmission, ferrets and guinea pigs. Our results demonstrated that L319Q substitution in the pH1N1 PB1 alone or in combination with the mutations of the U.S. MDV resulted in reduced pathogenicity (ferrets) and transmission (guinea pigs), and an enhanced temperature sensitive phenotype. These results demonstrate the feasibility of generating an attenuated MDV based on the backbone of a contemporary pH1N1 IAV strain. IMPORTANCE Vaccination represents the most effective strategy to reduce the impact of seasonal IAV infections. Although LAIV are superior in inducing protection and sterilizing immunity, they are not recommended for many individuals who are at high risk for severe disease. Thus, development of safer and more effective LAIV are needed. A concer
Published: 2022

4. El exómero: conexión entre la secreción polarizada y el estrés iónico

Author: Ministerio de Economía, Industria y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Junta de Castilla y León, Universidad de Salamanca, University of Toledo, Department of Health and Human Services (US), Moscoso-Romero, Esteban, Moro, Sandra, Poddar, Abhishek, Mulet-Salort, José Miguel, Pérez, Pilar, Chen, Qian, Valdivieso, María Henar, Ministerio de Economía, Industria y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Junta de Castilla y León, Universidad de Salamanca, University of Toledo, Department of Health and Human Services (US), Moscoso-Romero, Esteban, Moro, Sandra, Poddar, Abhishek, Mulet-Salort, José Miguel, Pérez, Pilar, Chen, Qian, and Valdivieso, María Henar
Abstract: El exómero es un complejo proteico que facilita el transporte de vesículas desde la red trans del Golgi (TGN) hasta la membrana plasmática (MP). En Saccharomyces cerevisiae su ausencia causa la retención de un conjunto específico de proteínas cargo en este orgánulo. El exómero de Schizosaccharomyces pombe está compuesto por Cfr1 y Bch1. Los mutantes cfr1¿ y bch1¿ son sensibles a estrés iónico pero no osmótico. Además, la actividad ATPasa en la MP es mayor en un mutante del exómero, lo que sugiere una hiperpolarización de la membrana. Además, en respuesta a estrés por K+, los niveles de Ca2+ intracelular aumentan significativamente más en cfr1¿ que en el silvestre. Los análisis por microscopía muestran una morfología endosomal defectuosa en los mutantes. Esto va acompañado de un incremento de los niveles intracelulares del exportador de K+ Cta3 y el canal de Ca2+ Pck2, que están parcialmente acumulados en el endosoma prevacuolar. Aun así, estos transportadores iónicos llegan a la membrana en los sitios de crecimiento polarizado, lo que demuestra que su transporte desde el TGN ocurre en ausencia del exómero. En los momentos posteriores a su expresión génica en presencia de KCl, la localización polarizada de Cta3 y Pkd2 en la membrana está alterada en los mutantes, de manera que su distribución es asimétrica y subapical. Finalmente, el uso de sondas fluorescentes sugiere que en los mutantes hay una distribución defectuosa de algunos lípidos de la MP en presencia de KCl. Por tanto, el exómero participa en muchos procesos celulares que están alterados en respuesta a estrés por K+. Estos resultados apoyan la idea de que el exómero juega un papel general en el mantenimiento del TGN, la secreción polarizada, y la respuesta a estrés que no está necesariamente relacionado con una función como adaptador de cargo.
Published: 2022

5. A Broad and Potent H1-Specific Human Monoclonal Antibody Produced in Plants Prevents Influenza Virus Infection and Transmission in Guinea Pigs

Author: New York Influenza Center of Excellence, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Department of Health and Human Services (US), Centers of Excellence for Influenza Research and Surveillance (US), University of Rochester, Piepenbrink, Michael [0000-0001-7517-6412], Nogales, Aitor [0000-0002-2424-7900], Shuen, Michael [0000-0002-5223-412X], Meyers, Ashley J. [0000-0001-6427-472X], Martínez-Sobrido, Luis [0000-0001-7084-0804], Kobie, James J. [0000-0001-8069-0272], Park, Jun-Gyu, Ye, Chengjin, Piepenbrink, Michael, Nogales, Aitor, Wang, Haifeng, Shuen, Michael, Meyers, Ashley J., Martínez-Sobrido, Luis, Kobie, James J., New York Influenza Center of Excellence, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Department of Health and Human Services (US), Centers of Excellence for Influenza Research and Surveillance (US), University of Rochester, Piepenbrink, Michael [0000-0001-7517-6412], Nogales, Aitor [0000-0002-2424-7900], Shuen, Michael [0000-0002-5223-412X], Meyers, Ashley J. [0000-0001-6427-472X], Martínez-Sobrido, Luis [0000-0001-7084-0804], Kobie, James J. [0000-0001-8069-0272], Park, Jun-Gyu, Ye, Chengjin, Piepenbrink, Michael, Nogales, Aitor, Wang, Haifeng, Shuen, Michael, Meyers, Ashley J., Martínez-Sobrido, Luis, and Kobie, James J.
Abstract: Although seasonal influenza vaccines block most predominant influenza types and subtypes, humans still remain vulnerable to waves of seasonal and new potential pandemic influenza viruses for which no immunity may exist because of viral antigenic drift and/or shift. Previously, we described a human monoclonal antibody (hMAb), KPF1, which was produced in human embryonic kidney 293T cells (KPF1-HEK) with broad and potent neutralizing activity against H1N1 influenza A viruses (IAV) in vitro, and prophylactic and therapeutic activities in vivo. In this study, we produced hMAb KPF1 in tobacco plants (KPF1-Antx) and demonstrated how the plant-produced KPF1-Antx hMAb possesses similar biological activity compared with the mammalian-produced KPF1-HEK hMAb. KPF1-Antx hMAb showed broad binding to recombinant HA proteins and H1N1 IAV, including A/California/04/2009 (pH1N1) in vitro, which was comparable to that observed with KPF1-HEK hMAb. Importantly, prophylactic administration of KPF1-Antx hMAb to guinea pigs prevented pH1N1 infection and transmission in both prophylactic and therapeutic experiments, substantiating its clinical potential to prevent and treat H1N1 infections. Collectively, this study demonstrated, for the first time, a plant-produced influenza hMAb with in vitro and in vivo activity against influenza virus. Because of the many advantages of plant-produced hMAbs, such as rapid batch production, low cost, and the absence of mammalian cell products, they represent an alternative strategy for the production of immunotherapeutics for the treatment of influenza viral infections, including emerging seasonal and/or pandemic strains.
Published: 2020

6. Game-Theoretical Modeling of Interviral Conflicts Mediated by Mini-CRISPR Arrays

Author: Department of Health and Human Services (US), Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Iranzo, Jaime [0000-0002-4538-7726], Faure, Guilhem [0000-0001-9537-2277], Wolf, Yuri I. [0000-0002-0247-8708], Koonin, Eugene V. [0000-0003-3943-8299], Iranzo, Jaime, Faure, Guilhem, Wolf, Yuri I., Koonin, Eugene V., Department of Health and Human Services (US), Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Iranzo, Jaime [0000-0002-4538-7726], Faure, Guilhem [0000-0001-9537-2277], Wolf, Yuri I. [0000-0002-0247-8708], Koonin, Eugene V. [0000-0003-3943-8299], Iranzo, Jaime, Faure, Guilhem, Wolf, Yuri I., and Koonin, Eugene V.
Abstract: All cellular organisms coevolve with multiple viruses, so that both virus-host and intervirus conflicts are major factors of evolution. Accordingly, hosts evolve multiple, elaborate defense systems and viruses respond by evolving means of antidefense. Although less thoroughly characterized, several dedicated mechanisms of intervirus competition have been described as well. Recently, the genomes of some bacterial and archaeal viruses have been shown to harbor CRISPR mini-arrays that typically contain a single spacer targeting a closely related virus. The involvement of mini-arrays in an intervirus conflict has been experimentally demonstrated for a pair of archaeal viruses. We model the evolution of virus-encoded CRISPR mini-arrays using a game theoretical approach. Analysis of the model reveals multiple equilibria that include mutual targeting, unidirectional targeting, no targeting, cyclic polymorphism, and bistability. The choice between these evolutionary regimes depends on the model parameters including the coinfection frequency, differential productivity of the conflicting viruses, and the fitness cost of mini-arrays. At high coinfection frequencies, the model becomes a version of the Prisoner's dilemma in which defection, i.e., mutual targeting between the competing viruses, is the winning strategy.
Published: 2020

7. Proteomic Analysis of Methanonatronarchaeum thermophilum AMET1, a Representative of a Putative New Class of Euryarchaeota, “Methanonatronarchaeia”

Author: Ministry of Education, Culture and Science (The Netherlands), Department of Health and Human Services (US), CSIC - Centro Nacional de Biotecnología (CNB), Ministerio de Economía, Industria y Competitividad (España), European Commission, Instituto de Salud Carlos III, Ferrer, Manuel, Sorokin, Dimitry Y., Wolf, Yuri I., Ciordia, Sergio, Mena, M. Carmen, Bargiela, Rafael, Koonin, Eugene V., Makarova, Kira S., Ministry of Education, Culture and Science (The Netherlands), Department of Health and Human Services (US), CSIC - Centro Nacional de Biotecnología (CNB), Ministerio de Economía, Industria y Competitividad (España), European Commission, Instituto de Salud Carlos III, Ferrer, Manuel, Sorokin, Dimitry Y., Wolf, Yuri I., Ciordia, Sergio, Mena, M. Carmen, Bargiela, Rafael, Koonin, Eugene V., and Makarova, Kira S.
Abstract: The recently discovered Methanonatronarchaeia are extremely halophilic and moderately thermophilic methyl-reducing methanogens representing a novel class-level lineage in the phylum Euryarchaeota related to the class Halobacteria. Here we present a detailed analysis of 1D-nano liquid chromatography–electrospray ionization tandem mass spectrometry data obtained for “Methanonatronarchaeum thermophilum” AMET1 grown in different physiological conditions, including variation of the growth temperature and substrates. Analysis of these data allows us to refine the current understanding of the key biosynthetic pathways of this triple extremophilic methanogenic euryarchaeon and identify proteins that are likely to be involved in its response to growth condition changes.
Published: 2018

8. Modulation of innate immune responses by the influenza A NS1 and PA-X proteins

Author: National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Department of Health and Human Services (US), Department of Defense (US), University of Rochester, Comunidad de Madrid, Nogales, Aitor, Martínez-Sobrido, Luis, Topham, David J., DeDiego, Marta L., National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Department of Health and Human Services (US), Department of Defense (US), University of Rochester, Comunidad de Madrid, Nogales, Aitor, Martínez-Sobrido, Luis, Topham, David J., and DeDiego, Marta L.
Abstract: Influenza A viruses (IAV) can infect a broad range of animal hosts, including humans. In humans, IAV causes seasonal annual epidemics and occasional pandemics, representing a serious public health and economic problem, which is most effectively prevented through vaccination. The defense mechanisms that the host innate immune system provides restrict IAV replication and infection. Consequently, to successfully replicate in interferon (IFN)-competent systems, IAV has to counteract host antiviral activities, mainly the production of IFN and the activities of IFN-induced host proteins that inhibit virus replication. The IAV multifunctional proteins PA-X and NS1 are virulence factors that modulate the innate immune response and virus pathogenicity. Notably, these two viral proteins have synergistic effects in the inhibition of host protein synthesis in infected cells, although using different mechanisms of action. Moreover, the control of innate immune responses by the IAV NS1 and PA-X proteins is subject to a balance that can determine virus pathogenesis and fitness, and recent evidence shows co-evolution of these proteins in seasonal viruses, indicating that they should be monitored for enhanced virulence. Importantly, inhibition of host gene expression by the influenza NS1 and/or PA-X proteins could be explored to develop improved live-attenuated influenza vaccines (LAIV) by modulating the ability of the virus to counteract antiviral host responses. Likewise, both viral proteins represent a reasonable target for the development of new antivirals for the control of IAV infections. In this review, we summarize the role of IAV NS1 and PA-X in controlling the antiviral response during viral infection.
Published: 2018

9. Functional Evolution of the 2009 Pandemic H1N1 Influenza Virus NS1 and PA in Humans

Author: National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Department of Health and Human Services (US), University of Rochester, Comunidad de Madrid, Nogales, Aitor, Martínez-Sobrido, Luis, Chiem, Kevin, Topham, David J., DeDiego, Marta L., National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Department of Health and Human Services (US), University of Rochester, Comunidad de Madrid, Nogales, Aitor, Martínez-Sobrido, Luis, Chiem, Kevin, Topham, David J., and DeDiego, Marta L.
Abstract: In 2009, a pandemic H1N1 influenza A virus (IAV) (pH1N1) emerged in the human population from swine causing a pandemic. Importantly, this virus is still circulating in humans seasonally. To analyze the evolution of pH1N1 in humans, we sequenced viral genes encoding proteins inhibiting general gene expression (nonstructural protein 1 [NS1] and PA-X) from circulating seasonal viruses and compared them to the viruses isolated at the origin of the pandemic. Recent pH1N1 viruses contain amino acid changes in the NS1 protein (E55K, L90I, I123V, E125D, K131E, and N205S), as previously described (A. M. Clark, A. Nogales, L. Martinez-Sobrido, D. J. Topham, and M. L. DeDiego, J Virol 91:e00721-17, 2017, https://doi.org/10.1128/JVI.00721-17), and amino acid changes in the PA-X protein (V100I, N204S, R221Q, and L229S). These amino acid differences between early and more recent pH1N1 isolates are responsible for increased NS1-mediated inhibition of host gene expression and decreased PA-X-mediated shutoff, including innate immune response genes. In addition, currently circulating pH1N1 viruses have acquired amino acid changes in the PA protein (V100I, P224S, N321K, I330V, and R362K). A recombinant pH1N1 virus containing PA, PA-X, and NS1 genes from currently circulating viruses is fitter in replication in cultured cells and in mice and is slightly more pathogenic than the original ancestor pH1N1 virus. These results demonstrate the need to monitor the evolution of pH1N1 in humans for mutations in the viral genome that could result in enhanced virulence. Importantly, these results further support our previous findings suggesting that inhibition of global gene expression mediated by NS1 and PA-X proteins is subject to a balance which can determine virus pathogenesis and fitness.
Published: 2018

10. Genomic insights into the Ixodes scapularis tick vector of Lyme disease

Author: National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Department of Health and Human Services (US), Australian Research Council, Ministerio de Ciencia e Innovación (España), National Science Foundation (US), Xunta de Galicia, European Commission, Department of Agriculture (US), Texas AgriLife Research, European Research Council, Swiss National Science Foundation, Boehringer Ingelheim Fonds, Fundação para a Ciência e a Tecnologia (Portugal), Lundbeck Foundation, Gulia-Nuss, Monika, Nuss, Andrew B., Meyer, Jason M., Sonenshine, Daniel E., Roe, R. Michael, Waterhouse, Robert M., Sattelle, David B., Fuente, José de la, Ribeiro, Jose M., Megy, Karine, Thimmapuram, Jyothi, Miller, Jason R., Walenz, Brian P., Koren, Sergey, Hostetler, Jessica B., Thiagarajan, Mathangi, Joardar, Vinita S., Hannick, Linda I., Bidwell, Shelby, Hammond, Martin P., Young, Sarah, Zeng, Qiandong, Abrudan, Jenica L., Almeida, Francisca C., Ayllón, Nieves, Bhide, Ketaki, Bissinger, Brooke W., Bonzón-Kulichenko, Elena, Buckingham, Steven D., Caffrey, Daniel R., Caimano, Melissa J., Croset, Vincent, Driscoll, Timothy, Gilbert, Don, Gillespie, Joseph J., Giraldo-Calderón, Gloria I., Grabowski, Jeffrey M., Jiang, David, Khalil, Sayed M .S., Kim, Donghun, Kocan, Katherine M., Koči, Juraj, Kuhn, Richard J., Kurtti, Timothy J., Lees, Kristin, Lang, Emma G., Kennedy, Ryan C., Kwon, Hyeogsun, Perera, Rushika, Qi, Yumin, Radolf, Justin D., Sakamoto, Joyce M., Sánchez-Gracia, Alejandro, Severo, Maiara S., Silverman, Neal, Šimo, Ladislav, Tojo, Marta, Tornador, Cristian, Van Zee, Janice P., Vázquez, Jesús, Vieira, Filipe G., Villar, Margarita, Wespiser, Adam R., Yang, Yunlong, Zhu, Jiwei, Arensburger, Peter, Pietrantonio, Patricia V., Barker, Stephen C., Shao, Renfu, Zdobnov, Evgeny M., Hauser, Frank, Grimmelikhuijzen, Cornelis J. P., Park, Yoonseong, Rozas, Julio, Benton, Richard, Pedra, Joao H. F., Nelson, David R., Unger, Maria F., Tubio, Jose M. C., Tu, Zhijian, Robertson, Hugh M., Shumway, Martin, Sutton, Granger, Wortman, Jennifer R., Lawson, Daniel, Wikel, Stephen K., Nene, Vishvanath M., Fraser, Claire M., Collins, Frank H., Birren, Bruce, Nelson, Karen E., Caler, Elisabet, Hill, Catherine A., National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Department of Health and Human Services (US), Australian Research Council, Ministerio de Ciencia e Innovación (España), National Science Foundation (US), Xunta de Galicia, European Commission, Department of Agriculture (US), Texas AgriLife Research, European Research Council, Swiss National Science Foundation, Boehringer Ingelheim Fonds, Fundação para a Ciência e a Tecnologia (Portugal), Lundbeck Foundation, Gulia-Nuss, Monika, Nuss, Andrew B., Meyer, Jason M., Sonenshine, Daniel E., Roe, R. Michael, Waterhouse, Robert M., Sattelle, David B., Fuente, José de la, Ribeiro, Jose M., Megy, Karine, Thimmapuram, Jyothi, Miller, Jason R., Walenz, Brian P., Koren, Sergey, Hostetler, Jessica B., Thiagarajan, Mathangi, Joardar, Vinita S., Hannick, Linda I., Bidwell, Shelby, Hammond, Martin P., Young, Sarah, Zeng, Qiandong, Abrudan, Jenica L., Almeida, Francisca C., Ayllón, Nieves, Bhide, Ketaki, Bissinger, Brooke W., Bonzón-Kulichenko, Elena, Buckingham, Steven D., Caffrey, Daniel R., Caimano, Melissa J., Croset, Vincent, Driscoll, Timothy, Gilbert, Don, Gillespie, Joseph J., Giraldo-Calderón, Gloria I., Grabowski, Jeffrey M., Jiang, David, Khalil, Sayed M .S., Kim, Donghun, Kocan, Katherine M., Koči, Juraj, Kuhn, Richard J., Kurtti, Timothy J., Lees, Kristin, Lang, Emma G., Kennedy, Ryan C., Kwon, Hyeogsun, Perera, Rushika, Qi, Yumin, Radolf, Justin D., Sakamoto, Joyce M., Sánchez-Gracia, Alejandro, Severo, Maiara S., Silverman, Neal, Šimo, Ladislav, Tojo, Marta, Tornador, Cristian, Van Zee, Janice P., Vázquez, Jesús, Vieira, Filipe G., Villar, Margarita, Wespiser, Adam R., Yang, Yunlong, Zhu, Jiwei, Arensburger, Peter, Pietrantonio, Patricia V., Barker, Stephen C., Shao, Renfu, Zdobnov, Evgeny M., Hauser, Frank, Grimmelikhuijzen, Cornelis J. P., Park, Yoonseong, Rozas, Julio, Benton, Richard, Pedra, Joao H. F., Nelson, David R., Unger, Maria F., Tubio, Jose M. C., Tu, Zhijian, Robertson, Hugh M., Shumway, Martin, Sutton, Granger, Wortman, Jennifer R., Lawson, Daniel, Wikel, Stephen K., Nene, Vishvanath M., Fraser, Claire M., Collins, Frank H., Birren, Bruce, Nelson, Karen E., Caler, Elisabet, and Hill, Catherine A.
Abstract: Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing ∼57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick–host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host ‘questing’, prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival. We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent.
Published: 2016

11. Tick genome assembled: new opportunities for research on tick-host-pathogen interactions

Author: National Institute of Allergy and Infectious Diseases (US), Department of Health and Human Services (US), Fuente, José de la, Waterhouse, Robert M., Sonenshine, Daniel E., Roe, R. Michael, Ribeiro, Jose M., Sattelle, David B., Hill, Catherine A., National Institute of Allergy and Infectious Diseases (US), Department of Health and Human Services (US), Fuente, José de la, Waterhouse, Robert M., Sonenshine, Daniel E., Roe, R. Michael, Ribeiro, Jose M., Sattelle, David B., and Hill, Catherine A.
Abstract: As tick-borne diseases are on the rise, an international effort resulted in the sequence and assembly of the first genome of a tick vector. This result promotes research on comparative, functional and evolutionary genomics and the study of tick-host-pathogen interactions to improve human, animal and ecosystem health on a global scale.
Published: 2016

12. Inevitability of Genetic Parasites

Author: Department of Health and Human Services (US), National Library of Medicine (US), Iranzo, Jaime, Puigbò, Pere, Lobkovsky, Alexander E., Wolf, Yuri I., Koonin, Eugene V., Department of Health and Human Services (US), National Library of Medicine (US), Iranzo, Jaime, Puigbò, Pere, Lobkovsky, Alexander E., Wolf, Yuri I., and Koonin, Eugene V.
Abstract: Almost all cellular life forms are hosts to diverse genetic parasites with various levels of autonomy including plasmids, transposons and viruses. Theoretical modeling of the evolution of primordial replicators indicates that parasites (cheaters) necessarily evolve in such systems and can be kept at bay primarily via compartmentalization. Given the (near) ubiquity, abundance and diversity of genetic parasites, the question becomes pertinent: are such parasites intrinsic to life? At least in prokaryotes, the persistence of parasites is linked to the rate of horizontal gene transfer (HGT). We mathematically derive the threshold value of the minimal transfer rate required for selfish element persistence, depending on the element duplication and loss rates as well as the cost to the host. Estimation of the characteristic gene duplication, loss and transfer rates for transposons, plasmids and virus-related elements in multiple groups of diverse bacteria and archaea indicates that most of these rates are compatible with the long term persistence of parasites. Notably, a small but non-zero rate of HGT is also required for the persistence of non-parasitic genes. We hypothesize that cells cannot tune their horizontal transfer rates to be below the threshold required for parasite persistence without experiencing highly detrimental side-effects. As a lower boundary to the minimum DNA transfer rate that a cell can withstand, we consider the process of genome degradation and mutational meltdown of populations through Muller’s ratchet. A numerical assessment of this hypothesis suggests that microbial populations cannot purge parasites while escaping Muller’s ratchet. Thus, genetic parasites appear to be virtually inevitable in cellular organisms.
Published: 2016

13. The Double-Stranded DNA Virosphere as a Modular Hierarchical Network of Gene Sharing

Author: Department of Health and Human Services (US), Iranzo, Jaime, Krupovic, Mart, Koonin, Eugene V., Department of Health and Human Services (US), Iranzo, Jaime, Krupovic, Mart, and Koonin, Eugene V.
Abstract: Virus genomes are prone to extensive gene loss, gain, and exchange and share no universal genes. Therefore, in a broad-scale study of virus evolution, gene and genome network analyses can complement traditional phylogenetics. We performed an exhaustive comparative analysis of the genomes of double-stranded DNA (dsDNA) viruses by using the bipartite network approach and found a robust hierarchical modularity in the dsDNA virosphere. Bipartite networks consist of two classes of nodes, with nodes in one class, in this case genomes, being connected via nodes of the second class, in this case genes. Such a network can be partitioned into modules that combine nodes from both classes. The bipartite network of dsDNA viruses includes 19 modules that form 5 major and 3 minor supermodules. Of these modules, 11 include tailed bacteriophages, reflecting the diversity of this largest group of viruses. The module analysis quantitatively validates and refines previously proposed nontrivial evolutionary relationships. An expansive supermodule combines the large and giant viruses of the putative order “Megavirales” with diverse moderate-sized viruses and related mobile elements. All viruses in this supermodule share a distinct morphogenetic tool kit with a double jelly roll major capsid protein. Herpesviruses and tailed bacteriophages comprise another supermodule, held together by a distinct set of morphogenetic proteins centered on the HK97-like major capsid protein. Together, these two supermodules cover the great majority of currently known dsDNA viruses. We formally identify a set of 14 viral hallmark genes that comprise the hubs of the network and account for most of the intermodule connections.
Published: 2016

14. Competition among networks highlights the power of the weak

Author: Ministerio de Economía y Competitividad (España), Department of Health and Human Services (US), National Library of Medicine (US), Iranzo, Jaime, Buldú, Javier M., Aguirre, Jacobo, Ministerio de Economía y Competitividad (España), Department of Health and Human Services (US), National Library of Medicine (US), Iranzo, Jaime, Buldú, Javier M., and Aguirre, Jacobo
Abstract: The unpreventable connections between real networked systems have recently called for an examination of percolation, diffusion or synchronization phenomena in multilayer networks. Here we use network science and game theory to explore interactions in networks-of-networks and model these as a game for gaining importance. We propose a viewpoint where networks choose the connection strategies, in contrast with classical approaches where nodes are the active players. Specifically, we investigate how creating paths between networks leads to different Nash equilibria that determine their structural and dynamical properties. In a wide variety of cases, selecting adequate connections leads to a cooperative solution that allows weak networks to overcome the strongest opponent. Counterintuitively, each weak network can induce a global transition to such cooperative configuration regardless of the actions of the strongest network. This power of the weak reveals a critical dominance of the underdogs in the fate of networks-of-networks.
Published: 2016

15. Cyr61 as mediator of Src signaling in triple negative breast cancer cells

Author: Ministerio de Economía y Competitividad (España), Department of Health and Human Services (US), Sánchez-Bailón, María Pilar, Calcabrini, Annarica, Mayoral-Varo, Víctor, Pérez-Losada, J., Ciordia, Sergio, Albar, Juan Pablo, Martín-Pérez, Jorge, Ministerio de Economía y Competitividad (España), Department of Health and Human Services (US), Sánchez-Bailón, María Pilar, Calcabrini, Annarica, Mayoral-Varo, Víctor, Pérez-Losada, J., Ciordia, Sergio, Albar, Juan Pablo, and Martín-Pérez, Jorge
Abstract: SFKs are involved in tumorigenesis and metastasis. Here we analyzed c-Src contribution to initial steps of metastasis by tetracycline-dependent expression of a specific shRNA-c-Src, which suppressed c-Src mRNA and protein levels in metastatic MDA-MB-231 cells. c-Src suppression did not alter cell proliferation or survival, but it significantly reduced anchorage-independent growth. Concomitantly with diminished tyrosine-phosphorylation/activation of Fak, caveolin-1, paxillin and p130CAS, c-Src depletion also inhibited cellular migration, invasion and transendothelial migration. Quantitative proteomic analyses of the secretome showed that Cyr61 levels, which were detected in the exosomal fraction, were diminished upon shRNA-c-Src expression. In contrast, Cyr61 expression was unaltered inside cells. Cyr61 partially colocalized with cis-Golgi gp74 marker and with exosomal marker CD63, but c-Src depletion did not alter their cellular distribution. In SUM159PT cells, transient c-Src suppression also reduced secreted exosomal Cyr61 levels. Furthermore, conditional expression of a c-Src dominant negative mutant (SrcDN, c-Src-K295M/Y527F) in MDA-MB-231 and in SUM159PT diminished secreted Cyr61 as well. Cyr61 transient suppression in MDA-MB-231 inhibited invasion and transendothelial migration. Finally, in both MDA-MB-231 and SUM159PT, a neutralizing Cyr61 antibody restrained migration. Collectively, these results suggest that c-Src regulates secreted proteins, including the exosomal Cyr61, which are involved in modulating the metastatic potential of triple negative breast cancer cells.
Published: 2015

16. Antiviral immunity via RIG-I-mediated recognition of RNA bearing 5'-diphosphates

Author: Cancer Research UK, European Research Council, Fondation Bettencourt Schueller, Department of Health and Human Services (US), Vanderbilt University, Fundación Ramón Areces, German Research Foundation, German Center for Infection Research, Goubau, Delphine, Fujimura, Tsutomu, Reis e Sousa, Caetano, Cancer Research UK, European Research Council, Fondation Bettencourt Schueller, Department of Health and Human Services (US), Vanderbilt University, Fundación Ramón Areces, German Research Foundation, German Center for Infection Research, Goubau, Delphine, Fujimura, Tsutomu, and Reis e Sousa, Caetano
Abstract: Mammalian cells possess mechanisms to detect and defend themselves from invading viruses. In the cytosol, the RIG-I-like receptors (RLRs), RIG-I (retinoic acid-inducible gene I; encoded by DDX58) and MDA5 (melanoma differentiation-associated gene 5; encoded by IFIH1) sense atypical RNAs associated with virus infection. Detection triggers a signalling cascade via the adaptor MAVS that culminates in the production of type I interferons (IFN-¿ and ß; hereafter IFN), which are key antiviral cytokines. RIG-I and MDA5 are activated by distinct viral RNA structures and much evidence indicates that RIG-I responds to RNAs bearing a triphosphate (ppp) moiety in conjunction with a blunt-ended, base-paired region at the 5'-end (reviewed in refs 1, 2, 3). Here we show that RIG-I also mediates antiviral responses to RNAs bearing 5'-diphosphates (5'pp). Genomes from mammalian reoviruses with 5'pp termini, 5'pp-RNA isolated from yeast L-A virus, and base-paired 5'pp-RNAs made by in vitro transcription or chemical synthesis, all bind to RIG-I and serve as RIG-I agonists. Furthermore, a RIG-I-dependent response to 5'pp-RNA is essential for controlling reovirus infection in cultured cells and in mice. Thus, the minimal determinant for RIG-I recognition is a base-paired RNA with 5'pp. Such RNAs are found in some viruses but not in uninfected cells, indicating that recognition of 5'pp-RNA, like that of 5'ppp-RNA, acts as a powerful means of self/non-self discrimination by the innate immune system.
Published: 2014

17. Catecholamine/serotonin interactions. Systems thinking for brain function and disease

Author: Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red Salud Mental (España), Centre National de la Recherche Scientifique (France), Université de Bordeaux, Ministerio de Economía y Competitividad (España), Generalitat de Catalunya, Société Française de Physiologie, European Commission, Department of Health and Human Services (US), Hensler, Julie G., Artigas, Francesc, Bortolozzi, Analía, Daws, Lynette C., De Deurwaerdère, Phillippe, Milan, Léa, Navailles, Sylvia, Koek, Wouter, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red Salud Mental (España), Centre National de la Recherche Scientifique (France), Université de Bordeaux, Ministerio de Economía y Competitividad (España), Generalitat de Catalunya, Société Française de Physiologie, European Commission, Department of Health and Human Services (US), Hensler, Julie G., Artigas, Francesc, Bortolozzi, Analía, Daws, Lynette C., De Deurwaerdère, Phillippe, Milan, Léa, Navailles, Sylvia, and Koek, Wouter
Abstract: This chapter brings together the work of several leading laboratories, each an outstanding example of integrative approaches to complex diseases of the central nervous system. Cognitive dysfunction and negative symptoms associated with schizophrenia are believed to result from hypofunction of the mesocortical dopaminergic projections to prefrontal cortex (PFC). Noradrenergic targets for the augmentation of dopaminergic function in PFC show promise to improve cognitive deficits as well as negative symptoms. Serotonergic targets for the modulation of mesocortical dopaminergic neurotransmission include 5-HT2A and 5-HT1A receptors. The hallmark of Parkinson's disease is the destruction of nigrostriatal dopaminergic neurons. l-DOPA, a metabolic precursor of dopamine, is the standard of treatment. However, the ectopic release of dopamine (DA) from serotonin neurons and the clearance of extracellular DA by the norepinephrine transporter in areas enriched with noradrenergic terminals contribute to extracellular DA produced by l-DOPA and offer opportunities to improve l-DOPA therapy. The high-affinity transporters for monoamines are the primary targets for antidepressant drugs. However, many patients experience suboptimal therapeutic benefit or fail to respond to treatment. Organic cation transporters and plasma membrane monoamine transporter serve an important function in regulating monoamine neurotransmission and hold potential utility as targets for the development of therapeutic drugs. Improved therapeutic approaches will arise from not only understanding how monoamines influence one another within the central nervous system as an integrated whole but also addressing the pathophysiology of specific core symptoms or distinct syndromal dimensions (cognitive impairment, motor slowing, and negative affect) regardless of disease classification, for example, psychotic, affective, and neurodegenerative. © 2013 Elsevier Inc.
Published: 2013

18. Effect of cold stress (4ºC) and combined cold Stress-starvation on Campylobacter jejuni adherence to Caco-2 epithelial cells

Author: National Institutes of Health (US), Department of Health and Human Services (US), Kwarteng-Siaw, Miriam, Mingo, Elisa, Carrascosa, Alfonso V., Martínez-Rodríguez, Adolfo J., National Institutes of Health (US), Department of Health and Human Services (US), Kwarteng-Siaw, Miriam, Mingo, Elisa, Carrascosa, Alfonso V., and Martínez-Rodríguez, Adolfo J.
Published: 2013

19. Evolutionary Dynamics of the Prokaryotic Adaptive Immunity System CRISPR-Cas in an Explicit Ecological Context

Author: Comunidad de Madrid, Ministerio de Ciencia e Innovación (España), Department of Health and Human Services (US), National Library of Medicine (US), Iranzo, Jaime, Lobkovsky, Alexander E., Wolf, Yuri I., Koonin, Eugene V., Comunidad de Madrid, Ministerio de Ciencia e Innovación (España), Department of Health and Human Services (US), National Library of Medicine (US), Iranzo, Jaime, Lobkovsky, Alexander E., Wolf, Yuri I., and Koonin, Eugene V.
Abstract: A stochastic, agent-based mathematical model of the coevolution of the archaeal and bacterial adaptive immunity system, CRISPR-Cas, and lytic viruses shows that CRISPR-Cas immunity can stabilize the virus-host coexistence rather than leading to the extinction of the virus. In the model, CRISPR-Cas immunity does not specifically promote viral diversity, presumably because the selection pressure on each single proto-spacer is too weak. However, the overall virus diversity in the presence of CRISPR-Cas grows due to the increase of the host and, accordingly, the virus population size. Above a threshold value of total viral diversity, which is proportional to the viral mutation rate and population size, the CRISPR-Cas system becomes ineffective and is lost due to the associated fitness cost. Our previous modeling study has suggested that the ubiquity of CRISPR-Cas in hyperthermophiles, which contrasts its comparative low prevalence in mesophiles, is due to lower rates of mutation fixation in thermal habitats. The present findings offer a complementary, simpler perspective on this contrast through the larger population sizes of mesophiles compared to hyperthermophiles, because of which CRISPR-Cas can become ineffective in mesophiles. The efficacy of CRISPR-Cas sharply increases with the number of proto-spacers per viral genome, potentially explaining the low information content of the proto-spacer-associated motif (PAM) that is required for spacer acquisition by CRISPR-Cas because a higher specificity would restrict the number of spacers available to CRISPR-Cas, thus hampering immunity. The very existence of the PAM might reflect the tradeoff between the requirement of diverse spacers for efficient immunity and avoidance of autoimmunity.
Published: 2013

20. Blocking Effects of Human Tau on Squid Giant Synapse Transmission and Its Prevention by T-817 MA

Author: Department of Health and Human Services (US), Fundação de Amparo à Pesquisa do Estado de São Paulo, National Institute for Health Research (UK), Moreno, Herman, Choi, Soonwook, Yu, Eunah, Brusco, Janaina, Ávila, Jesús, Moreira, Jorge E., Sugimori, Mutsuyuki, Llinás, Rodolfo R., Department of Health and Human Services (US), Fundação de Amparo à Pesquisa do Estado de São Paulo, National Institute for Health Research (UK), Moreno, Herman, Choi, Soonwook, Yu, Eunah, Brusco, Janaina, Ávila, Jesús, Moreira, Jorge E., Sugimori, Mutsuyuki, and Llinás, Rodolfo R.
Abstract: Filamentous tau inclusions are hallmarks of Alzheimer’s disease and related neurodegenerative tauopathies, but the molecular mechanisms involved in tau-mediated changes in neuronal function and their possible effects on synaptic transmission are unknown. We have evaluated the effects of human tau protein injected directly into the presynaptic terminal axon of the squid giant synapse, which affords functional, structural, and biochemical analysis of its action on the synaptic release process. Indeed, we have found that at physiological concentration recombinant human tau (h-tau42) becomes phosphorylated, produces a rapid synaptic transmission block, and induces the formation of clusters of aggregated synaptic vesicles in the vicinity of the active zone. Presynaptic voltage clamp recordings demonstrate that h-tau42 does not modify the presynaptic calcium current amplitude or kinetics. Analysis of synaptic noise at the post-synaptic axon following presynaptic h-tau42 microinjection revealed an initial phase of increase spontaneous transmitter release followed by a marked reduction in noise. Finally, systemic administration of T-817MA, a proposed neuro-protective agent, rescued tau-induced synaptic abnormalities. Our results show novel mechanisms of h-tau42 mediated synaptic transmission failure and identify a potential therapeutic agent to treat tau-related neurotoxicity
Published: 2011

21. Characterization of a Natural Mutator Variant of Human DNA Polymerase l which Promotes Chromosomal Instability by Compromising NHEJ

Author: Ministerio de Ciencia y Tecnología (España), Comunidad de Madrid, Ligue Nationale contre le Cancer (France), National Institutes of Health (US), National Institute of Environmental Health Sciences (US), Department of Health and Human Services (US), Ministerio de Educación y Ciencia (España), Fundación Ramón Areces, Terrados, Gloria, Gapp, Jean-Pascal, Canitrot, Yvan, García, Miguel Ángel, Bebenek, Katarzyna, Kirchhoff, Tomas, Villanueva, Alberto, Boudsocq, François, Bergoglio, Valerie, Cazaux, Christophe, Kunkel, Thomas A., Hoffmann, Jean-Sebastien, Blanco, Luis, Ministerio de Ciencia y Tecnología (España), Comunidad de Madrid, Ligue Nationale contre le Cancer (France), National Institutes of Health (US), National Institute of Environmental Health Sciences (US), Department of Health and Human Services (US), Ministerio de Educación y Ciencia (España), Fundación Ramón Areces, Terrados, Gloria, Gapp, Jean-Pascal, Canitrot, Yvan, García, Miguel Ángel, Bebenek, Katarzyna, Kirchhoff, Tomas, Villanueva, Alberto, Boudsocq, François, Bergoglio, Valerie, Cazaux, Christophe, Kunkel, Thomas A., Hoffmann, Jean-Sebastien, and Blanco, Luis
Abstract: Background: DNA polymerase lambda (Poll) is a DNA repair polymerase, which likely plays a role in base excision repair (BER) and in non-homologous end joining (NHEJ) of DNA double-strand breaks (DSB). Principal Findings: Here, we described a novel natural allelic variant of human Poll (hPoll) characterized by a single nucleotide polymorphism (SNP), C/T variation in the first base of codon 438, resulting in the amino acid change Arg to Trp. In vitro enzyme activity assays of the purified W438 Poll variant revealed that it retained both DNA polymerization and deoxyribose phosphate (dRP) lyase activities, but had reduced base substitution fidelity. Ectopic expression of the W438 hPoll variant in mammalian cells increases mutation frequency, affects the DSB repair NHEJ pathway, and generates chromosome aberrations. All these phenotypes are dependent upon the catalytic activity of the W438 hPoll. Conclusions: The expression of a cancer-related natural variant of one specialized DNA polymerase can be associated to generic instability at the cromosomal level, probably due a defective NHEJ. These results establish that chromosomal aberrations can result from mutations in specialized DNA repair polymerases.
Published: 2009

22. El exómero: conexión entre la secreción polarizada y el estrés iónico

Author: Moscoso, Esteban, Moro, Sandra, Poddar, Abhishek, Mulet-Salort, José Miguel, Pérez, Pilar, Chen, Qian, Valdivieso, María Henar, Ministerio de Economía, Industria y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Junta de Castilla y León, Universidad de Salamanca, University of Toledo, and Department of Health and Human Services (US)
Abstract: Poster del trabajo presentado en el XV Congreso Nacional de Micología, celebrado en Valencia del 7 al 9 de septiembre de 2022, El exómero es un complejo proteico que facilita el transporte de vesículas desde la red trans del Golgi (TGN) hasta la membrana plasmática (MP). En Saccharomyces cerevisiae su ausencia causa la retención de un conjunto específico de proteínas cargo en este orgánulo. El exómero de Schizosaccharomyces pombe está compuesto por Cfr1 y Bch1. Los mutantes cfr1¿ y bch1¿ son sensibles a estrés iónico pero no osmótico. Además, la actividad ATPasa en la MP es mayor en un mutante del exómero, lo que sugiere una hiperpolarización de la membrana. Además, en respuesta a estrés por K+, los niveles de Ca2+ intracelular aumentan significativamente más en cfr1¿ que en el silvestre. Los análisis por microscopía muestran una morfología endosomal defectuosa en los mutantes. Esto va acompañado de un incremento de los niveles intracelulares del exportador de K+ Cta3 y el canal de Ca2+ Pck2, que están parcialmente acumulados en el endosoma prevacuolar. Aun así, estos transportadores iónicos llegan a la membrana en los sitios de crecimiento polarizado, lo que demuestra que su transporte desde el TGN ocurre en ausencia del exómero. En los momentos posteriores a su expresión génica en presencia de KCl, la localización polarizada de Cta3 y Pkd2 en la membrana está alterada en los mutantes, de manera que su distribución es asimétrica y subapical. Finalmente, el uso de sondas fluorescentes sugiere que en los mutantes hay una distribución defectuosa de algunos lípidos de la MP en presencia de KCl. Por tanto, el exómero participa en muchos procesos celulares que están alterados en respuesta a estrés por K+. Estos resultados apoyan la idea de que el exómero juega un papel general en el mantenimiento del TGN, la secreción polarizada, y la respuesta a estrés que no está necesariamente relacionado con una función como adaptador de cargo., Este trabajo ha sido posible gracias al apoyo del Ministerio de Economía, Industria y Competitividad/Ciencia, Investigación y Universidades/ programa European Regional Development Fund—FEDER—(BFU2017-84508-P y PID2020-115111GB-I00 a M-HV y PGC2018-098924-B-I00 a PP), y de la Junta de Castilla y Leon/programa FEDER (CSI150P20 a PP, y Escalera de Excelencia CLU-2017-03/14-20 al IBFG). SM disfrutó de becas de la Universidad de Salamanca y el Ministerio de Educación, y EMR disfrutó de una beca de la Junta de Castilla y León. Las becas de la Agencia Española de Investigación (AEI) PID2019-104054 GB-I00 y RTC-2017-6468-2-AR financiaron a JM. QC y AP fueron financiados por la “University of Toledo start up fund” y una beca del “National Institute of Health” (R15GM134496).
Published: 2022

23. Mutation L319Q in the PB1 Polymerase Subunit Improves Attenuation of a Candidate Live-Attenuated Influenza A Virus Vaccine

Author: Aitor Nogales, John Steel, Wen-Chun Liu, Anice C. Lowen, Laura Rodriguez, Kevin Chiem, Andrew Cox, Adolfo García-Sastre, Randy A. Albrecht, Stephen Dewhurst, Luis Martínez-Sobrido, New York Influenza Center of Excellence, National Institute of Allergy and Infectious Diseases (US), Department of Health and Human Services (US), Centers of Excellence for Influenza Research and Surveillance (US), Department of Defense (US), Center for Research on Influenza Pathogenesis, Ministerio de Ciencia e Innovación (España), Icahn School of Medicine at Mount Sinai, Nogales, Aitor [0000-0002-2424-7900], Lowen, Anice C [0000-0002-9829-112X], Chiem, Kevin [0000-0002-3892-5944], García-Sastre, Adolfo [0000-0002-6551-1827], Albrecht, Randy A [0000-0003-4008-503X], Dewhurst, Stephen [0000-0001-7729-7920], Nogales, Aitor, Lowen, Anice C, Chiem, Kevin, García-Sastre, Adolfo, Albrecht, Randy A, and Dewhurst, Stephen
Subjects: Microbiology (medical), Physiology, Guinea Pigs, Vaccines, Attenuated, Viral Proteins, Influenza A Virus, H1N1 Subtype, Orthomyxoviridae Infections, Protection efficacy, Influenza, Human, Genetics, Transmission, Animals, Humans, Vaccines, General Immunology and Microbiology, Ecology, Ferrets, Cell Biology, Master donor virus, Temperature sensitive, Infectious Diseases, Attenuated, Cold-adapted, Live-attenuated influenza vaccines, Influenza A virus, Influenza Vaccines, Mutation, Guinea pigs
Abstract: 15 Pág. Centro de Investigación en Sanidad Animal (CISA), Influenza A viruses (IAV) remain emerging threats to human public health. Live-attenuated influenza vaccines (LAIV) are one of the most effective prophylactic options to prevent disease caused by influenza infections. However, licensed LAIV remain restricted for use in 2- to 49-year-old healthy and nonpregnant people. Therefore, development of LAIV with increased safety, immunogenicity, and protective efficacy is highly desired. The U.S.-licensed LAIV is based on the master donor virus (MDV) A/Ann Arbor/6/60 H2N2 backbone, which was generated by adaptation of the virus to growth at low temperatures. Introducing the genetic signature of the U.S. MDV into the backbone of other IAV strains resulted in varying levels of attenuation. While the U.S. MDV mutations conferred an attenuated phenotype to other IAV strains, the same amino acid changes did not significantly attenuate the pandemic A/California/04/09 H1N1 (pH1N1) strain. To attenuate pH1N1, we replaced the conserved leucine at position 319 with glutamine (L319Q) in PB1 and analyzed the in vitro and in vivo properties of pH1N1 viruses containing either PB1 L319Q alone or in combination with the U.S. MDV mutations using two animal models of influenza infection and transmission, ferrets and guinea pigs. Our results demonstrated that L319Q substitution in the pH1N1 PB1 alone or in combination with the mutations of the U.S. MDV resulted in reduced pathogenicity (ferrets) and transmission (guinea pigs), and an enhanced temperature sensitive phenotype. These results demonstrate the feasibility of generating an attenuated MDV based on the backbone of a contemporary pH1N1 IAV strain. IMPORTANCE Vaccination represents the most effective strategy to reduce the impact of seasonal IAV infections. Although LAIV are superior in inducing protection and sterilizing immunity, they are not recommended for many individuals who are at high risk for severe disease. Thus, development of safer and more effective LAIV are needed. A concern with the current MDV used to generate the U.S.-licensed LAIV is that it is based on a virus isolated in 1960. Moreover, mutations that confer the temperature-sensitive, cold-adapted, and attenuated phenotype of the U.S. MDV resulted in low level of attenuation in the contemporary pandemic A/California/04/09 H1N1 (pH1N1). Here, we show that introduction of PB1 L319Q substitution, alone or in combination with the U.S. MDV mutations, resulted in pH1N1 attenuation. These findings support the development of a novel LAIV MDV based on a contemporary pH1N1 strain as a medical countermeasure against currently circulating H1N1 IAV., This research was partially funded by the New York Influenza Center of Excellence (NYICE) (HHSN 272201400005C), and Emory-UGA (HHSN 272201400004C), members of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services, Centers of Excellence for Influenza Research and Surveillance (CEIRS) network. The work was also supported by grants W81XWH-18-1-0460-PRMRP-DA (to L.M.-S.) and W81XWH-17-1-0168 (to S.D.) from the Department of Defense (DoD) Peer Reviewed Medical Research Program (PRMRP), as well as NIH R01 AI145332-01 (to L.M.-S.). This research was also partly funded by NIAID grant P01AI097092, by CEIRR (Center for Research on Influenza Pathogenesis and Transmission), a NIAID funded Center of Excellence for Influenza Research and Response (CEIRR, contract # 75N93021C00014) and by the Collaborative Influenza Vaccine Innovation Centers NIAID contract 75N93019C00051 to AG-S. A.N. received a “Ramon y Cajal” Incorporation grant (RYC-2017) from the Spanish Ministry of Science, Innovation. Finally, A.C. received support from NIH grants T32GM068411 and T32GM007356. Use of the Zeiss AxioImager.Z2 microscope and image analysis was performed at the Microscopy CoRE at the Icahn School of Medicine at Mount Sinai.
Published: 2022

24. A cholinergic neuroskeletal interface promotes bone formation during postnatal growth and exercise

Author: Stephen Gadomski, Claire Fielding, Andrés García-García, Claudia Korn, Chrysa Kapeni, Sadaf Ashraf, Javier Villadiego, Raquel del Toro, Olivia Domingues, Jeremy N. Skepper, Tatiana Michel, Jacques Zimmer, Regine Sendtner, Scott Dillon, Kenneth E.S. Poole, Gill Holdsworth, Michael Sendtner, Juan J. Toledo-Aral, Cosimo De Bari, Andrew W. McCaskie, Pamela G. Robey, Simón Méndez-Ferrer, National Institutes of Health (US), Gates Cambridge Scholarships, Fundación Ramón Areces, Fundación 'la Caixa', European Commission, German Research Foundation, Federal Ministry of Education and Research (Germany), Instituto de Salud Carlos III, Junta de Andalucía, Versus Arthritis, National Institute of Dental and Craniofacial Research (US), Department of Health and Human Services (US), NIHR Biomedical Research Centre (UK), MRC Cambridge Stem Cell Institute, National Health Institute Blood and Transplant (UK), Wellcome Trust, Cancer Research UK, Poole, Kenneth [0000-0003-4546-7352], McCaskie, Andrew [0000-0001-6476-0832], and Apollo - University of Cambridge Repository
Subjects: anabolic, Glial Cell Line-Derived Neurotrophic Factor Receptors, Anabolic, osteocyte, Cholinergic Agents, Development, bone, cholinergic, Osteogenesis, Genetics, Bone, development, Exercise, Cholinergic, exercise, autonomic, Interleukin-6, Neuroskeletal, Osteocyte, Cell Biology, Skeletal, sympathetic, skeletal, neuroskeletal, Autonomic, Cholinergic Fibers, Molecular Medicine, Sympathetic
Abstract: The autonomic nervous system is a master regulator of homeostatic processes and stress responses. Sympathetic noradrenergic nerve fibers decrease bone mass, but the role of cholinergic signaling in bone has remained largely unknown. Here, we describe that early postnatally, a subset of sympathetic nerve fibers undergoes an interleukin-6 (IL-6)-induced cholinergic switch upon contacting the bone. A neurotrophic dependency mediated through GDNF-family receptor-α2 (GFRα2) and its ligand, neurturin (NRTN), is established between sympathetic cholinergic fibers and bone-embedded osteocytes, which require cholinergic innervation for their survival and connectivity. Bone-lining osteoprogenitors amplify and propagate cholinergic signals in the bone marrow (BM). Moderate exercise augments trabecular bone partly through an IL-6-dependent expansion of sympathetic cholinergic nerve fibers. Consequently, loss of cholinergic skeletal innervation reduces osteocyte survival and function, causing osteopenia and impaired skeletal adaptation to moderate exercise. These results uncover a cholinergic neuro-osteocyte interface that regulates skeletogenesis and skeletal turnover through bone-anabolic effects., S.G. was supported by the NIH-OXCAM Program and the Gates Cambridge Trust. A.G.G. received fellowships from Ramón Areces and La Caixa Foundations. C.K. was supported by Marie Curie Career Integration grant H2020-MSCA-IF-2015-70841. M.S. and R.S. were supported by DFG, Se 697/7-1 and BMBF through the EnergI consortium TP6. J.V. and J.J.T.-A. were supported by Instituto de Salud Carlos III (PI12/02574), Junta de Andalucia (P12-CTS-2739), and, together with S.M.-F., by Red TerCel (ISCIII-Spanish Cell Therapy Network). S.A. and C.D.B. were supported by Versus Arthritis grant 21156. A.W.M. received funding from Versus Arthritis (21156). P.G.R. and S.G. were supported by the DIR, NIDCR, a part of the IRP, NIH, and DHHS (1ZIADE000380). K.E.S.P. acknowledges the support of the Cambridge NIHR Biomedical Research Centre. This work was supported by core support grants from MRC to the Cambridge Stem Cell Institute; National Health Service Blood and Transplant (United Kingdom), European Union’s Horizon 2020 research (ERC-2014-CoG-648765), MRC-AMED grant MR/V005421/1, and a Programme Foundation Award (C61367/A26670) from Cancer Research UK to S.M.-F. This research was funded in part by the Wellcome Trust (203151/Z/16/Z).
Published: 2022

25. Generation and Characterization of Single-Cycle Infectious Canine Influenza A Virus (sciCIV) and Its Use as Vaccine Platform

Author: Aitor Nogales, Kevin Chiem, Michael Breen, Marta L. DeDiego, Colin R. Parrish, Luis Martínez-Sobrido, New York Influenza Center of Excellence, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Department of Health and Human Services (US), Centers of Excellence for Influenza Research and Surveillance (US), Ministerio de Ciencia, Innovación y Universidades (España), Nogales, Aitor, Chiem, Kevin, DeDiego, Marta L., Parrish, Colin R, Martínez-Sobrido, Luis, Nogales, Aitor [0000-0002-2424-7900], Chiem, Kevin [0000-0002-3892-5944], DeDiego, Marta L. [0000-0002-7888-7372], Parrish, Colin R [0000-0002-1836-6655], and Martínez-Sobrido, Luis [0000-0001-7084-0804]
Subjects: Single-cycle infectious influenza A virus, Viral vectors, Reverse genetics, Influenza vaccine, Single-cycle influenza virus, Canine influenza virus, Reporter virus, Green fluorescent protein, Humoral response, Reporter gene, Influenza HA-expressing MDCK cells (MDCK-HA)
Abstract: 227-256 pp, Influenza A viruses (IAVs) infect a broad range of hosts, including multiple avian and mammalian species. The frequent emergence of novel IAV strains in different hosts, including in humans, results in the need for vigilance and ongoing development of new approaches to fighting or prevent those infections. Canine influenza is a contagious respiratory disease in dogs caused by two subtypes of IAV, the equine-origin H3N8 canine influenza virus (CIV), and the avian-origin H3N2 CIV. A novel approach to influenza vaccination involves single-cycle infectious influenza A viruses (sciIAVs), which are defective for an essential viral gene. They are propagated in complementing cell lines which provide the missing gene in trans. As sciIAV cannot complete their replication cycle in regular cells they are limited to a single round of viral replication. Because of their safety profile and ability to express foreign antigens inside infected cells, sciIAVs have served both as live-attenuated vaccines and as vaccine vectors for the expression of heterologous antigens. Here, we describe experimental procedures for the generation of a single-cycle infectious CIV (sciCIV), where the viral hemagglutinin (HA) gene was exchanged for the gene for green fluorescent protein (GFP). Complementation of the viral HA protein is provided in trans by stable HA-expressing cell lines. Methods for the in vitro characterization of HA deficient but GFP-expressing sciCIV (sciCIV ΔHA/GFP) are described, as well as its use as a potential vaccine., This research was partially funded by the New York Influenza Center of Excellence (NYICE), a member of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services, Centers of Excellence for Influenza Research and Surveillance (CEIRS) contract No. HHSN272201400005C (NYICE). This research was partially funded by a “Ramon y Cajal” Incorporation grant (RYC-2017) from the Spanish Ministry of Science, Innovation and Universities to A.N.
Published: 2022
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26. Novel Functions of IFI44L as a Feedback Regulator of Host Antiviral Responses

Author: Luis Martinez-Sobrido, David J. Topham, Marta L. DeDiego, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Department of Health and Human Services (US), University of Rochester, and Comunidad de Madrid
Subjects: IKK kinase activity, Immunology, Sequence Homology, Cellular Response to Infection, Interferon-induced protein, IKKβ kinase activity, Biology, Virus Replication, Antiviral Agents, Microbiology, Signaling transduction, Virus, Proinflammatory cytokine, Tacrolimus Binding Proteins, Interferon, Neoplasms, Virology, Influenza, Human, Tumor Cells, Cultured, medicine, Humans, IκBα phosphorylation, Amino Acid Sequence, IRF-3 phosphorylation, Phosphorylation, Feedback, Physiological, Innate immunity, Type I and III interferon responses, Innate immune system, Kinase, Tumor Suppressor Proteins, NF-kappa B, Antiviral responses, Orthomyxoviridae, IFI44L, Immunity, Innate, I-kappa B Kinase, Cell biology, IκBα, FKBP5, IKKε kinase activity, Insect Science, Interferons, Signal Transduction, Interferon regulatory factors, medicine.drug
Abstract: We describe a novel function for the interferon (IFN)-induced protein 44-like (IFI44L) gene in negatively modulating innate immune responses induced after virus infections. Furthermore, we show that decreasing IFI44L expression impairs virus production and that IFI44L expression negatively modulates the antiviral state induced by an analog of double-stranded RNA (dsRNA) or by IFN treatment. The mechanism likely involves the interaction of IFI44L with cellular FK506-binding protein 5 (FKBP5), which in turn interacts with kinases essential for type I and III IFN responses, such as inhibitor of nuclear factor kappa B (IκB) kinase alpha (IKKα), IKKβ, and IKKε. Consequently, binding of IFI44L to FKBP5 decreased interferon regulatory factor 3 (IRF-3)-mediated and nuclear factor kappa-B (NF-κB) inhibitor (IκBα)-mediated phosphorylation by IKKε and IKKβ, respectively. According to these results, IFI44L is a good target for treatment of diseases associated with excessive IFN levels and/or proinflammatory responses and for reduction of viral replication., This project was funded with federal funds from the National Institute of Allergy andInfectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services, under CEIRS contract HHSN272201400005C to D.J.T.; through a University of Rochester Research Award to M.L.D.; and with funds from Comunidad de Madrid, Madrid, Spain (reference 2017-T1/BMD-5155), to M.L.D.
Published: 2019
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27. Proteomic analysis of methanonatronarchaeum thermophilum AMET1, a representative of a putative new class of euryarchaeota, 'methanonatronarchaeia'

Author: María Carmen Mena, Kira S. Makarova, Yuri I. Wolf, Dimitry Y. Sorokin, Rafael Bargiela, Sergio Ciordia, Eugene V. Koonin, Manuel Ferrer, Ministry of Education, Culture and Science (The Netherlands), Department of Health and Human Services (US), CSIC - Centro Nacional de Biotecnología (CNB), Ministerio de Economía, Industria y Competitividad (España), European Commission, and Instituto de Salud Carlos III
Subjects: 0301 basic medicine, Proteomics, lcsh:QH426-470, Halophiles, Lineage (evolution), Genomics, Computational biology, Tandem mass spectrometry, Methanogenesis, Class Halobacteria, Article, 03 medical and health sciences, Genetics, proteomics, methanogenesis, halophiles, Methanonatronarchaeia, genomics, Genetics (clinical), biology, Chemistry, Thermophile, biology.organism_classification, Halophile, lcsh:Genetics, 030104 developmental biology, Euryarchaeota
Abstract: The recently discovered Methanonatronarchaeia are extremely halophilic and moderately thermophilic methyl-reducing methanogens representing a novel class-level lineage in the phylum Euryarchaeota related to the class Halobacteria. Here we present a detailed analysis of 1D-nano liquid chromatography–electrospray ionization tandem mass spectrometry data obtained for “Methanonatronarchaeum thermophilum” AMET1 grown in different physiological conditions, including variation of the growth temperature and substrates. Analysis of these data allows us to refine the current understanding of the key biosynthetic pathways of this triple extremophilic methanogenic euryarchaeon and identify proteins that are likely to be involved in its response to growth condition changes., D.Y.S. was supported by Gravitation-SIAM Program (grant 24002002, Dutch Ministry of Education and Science) and by RFBR (grant 16-04-00035). K.S.M., Y.I.W. and E.V.K. are supported by the intramural program of the U.S. Department of Health and Human Services (to the National Library of Medicine). The proteomic analysis was performed in the Proteomics Facility of The Spanish National Centre for Biotechnology (CNB-CSIC) that belongs to ProteoRed, PRB2-ISCIII, supported by grant PT13/0001. This project has received funding from the European Union’s Horizon 2020 research and innovation program [Blue Growth: Unlocking the potential of Seas and Oceans] under grant agreement No [634486]. This work was further funded by grants BIO2014-54494-R, BIO2017-85522-R, PCIN-2014-107 (within the ERA NET-IB2 program), PCIN-2017-078 (within the ERA-MarineBiotech program) from the Spanish Ministry of Economy, Industry and Competitiveness and grant AC17/00022 from the Instituto de Salud Carlos III (within the ERA TRANSCAN-2 program).
Published: 2018

28. 50 years of the International Committee on Taxonomy of Viruses: progress and prospects

Author: Stuart G. Siddell, Robert L. Harrison, Max L. Nibert, Andrew M. Q. King, Andrew J. Davison, Hélène Sanfaçon, Mart Krupovic, Sead Sabanadzovic, Arvind Varsani, Balázs Harrach, Nick J. Knowles, Andrew M. Kropinski, Francisco Murilo Zerbini, Michael J. Adams, Elliot J. Lefkowitz, B. Douglas Smith, Jens H. Kuhn, Richard J. Orton, Alexander E. Gorbalenya, Arcady Mushegian, Peter Simmonds, University of Hertfordshire [Hatfield] (UH), University of Alabama at Birmingham [ Birmingham] (UAB), The Pirbright Institute, Biotechnology and Biological Sciences Research Council (BBSRC), Hungarian Academy of Sciences (MTA), United States Department of Agriculture (USDA), University of Guelph, Biologie Moléculaire du Gène chez les Extrêmophiles (BMGE), Institut Pasteur [Paris] (IP), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), National Science Foundation [Arlington] (NSF), Harvard Medical School [Boston] (HMS), Mississippi State University [Mississippi], Agriculture and Agri-Food (AAFC), University of Bristol [Bristol], University of Oxford, Arizona State University [Tempe] (ASU), Universidade Federal de Viçosa = Federal University of Viçosa (UFV), University of Glasgow, University of Edinburgh, Leiden University Medical Center (LUMC), Universiteit Leiden, Lomonosov Moscow State University (MSU), The ICTV is supported by Grants from IUMS, the American Society of Virology and the Microbiology Society, and by a Grant from the Wellcome Trust (WT108418AIA) to P.S., A.J.D. and S.G.S. The involvement of J.H.K. was supported in part through Battelle Memorial Institute’s prime contract with the US National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272200700016I. A subcontractor to Battelle Memorial Institute who performed this work is J.H.K., an employee of Tunnell Government Services, Inc. The involvement of A.R.M. was supported in part by the National Science Foundation Individual Research and Development program. The views and conclusions contained in this document are those of the authors and should not be interpreted as necessarily representing the official policies, either expressed or implied, of the US Department of Health and Human Services, US National Science Foundation, or of the institutions and companies affiliated with the authors., The authors are the current ICTV EC Members together with two researchers (R.J.O., D.B.S.) supported by the Wellcome Trust grant detailed below. We gladly acknowledge the dedicated, voluntary efforts of hundreds of virologists based in various parts of the world over the entire period of the existence of the ICTV. The work of the organisation through its EC and Study Groups has always depended upon that contribution and will continue to do so., Institute for Animal Health, the Pirbright Institute, Institut Pasteur [Paris], Agriculture and Agri-Food [Ottawa] (AAFC), University of Oxford [Oxford], and Universidade Federal de Vicosa (UFV)
Subjects: 0301 basic medicine, Societies, Scientific, Rabies, [SDV]Life Sciences [q-bio], 030106 microbiology, Library science, Biology, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, History, 21st Century, Executive committee, MESH: Viruses, 03 medical and health sciences, Virology, Virus discovery, MESH: Phylogeny, Virus classification, Phylogeny, Virus species, Computational Biology, General Medicine, History, 20th Century, 3. Good health, MESH: Societies, Scientific, 030104 developmental biology, Viruses, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Online report, MESH: History, 20th Century, Metagenomics, MESH: Metagenomics, MESH: History, 21st Century, MESH: Computational Biology
Abstract: International audience; We mark the 50th anniversary of the International Committee on Taxonomy of Viruses (ICTV) by presenting a brief history of the organization since its foundation, showing how it has adapted to advancements in our knowledge of virus diversity and the methods used to characterize it. We also outline recent developments, supported by a grant from the Wellcome Trust (UK), that are facilitating substantial changes in the operations of the ICTV and promoting dialogue with the virology community. These developments will generate improved online resources, including a freely available and regularly updated ICTV Virus Taxonomy Report. They also include a series of meetings between the ICTV and the broader community focused on some of the major challenges facing virus taxonomy, with the outcomes helping to inform the future policy and practice of the ICTV.
Published: 2017
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29. Antiviral immunity via RIG-I-mediated recognition of RNA bearing 5′-diphosphates

Author: Tsutomu Fujimura, Christine Schuberth, Andrea J. Pruijssers, Jan Rehwinkel, Caetano Reis e Sousa, Delphine Goubau, Jason A. Iskarpatyoti, Martin Schlee, Gunther Hartmann, Thomas Zillinger, Terence S. Dermody, Annemarthe G. van der Veen, Safia Deddouche, Janos Ludwig, Marion Goldeck, Winfried Barchet, Cancer Research UK, European Research Council, Fondation Bettencourt Schueller, Department of Health and Human Services (US), Vanderbilt University, Fundación Ramón Areces, German Research Foundation, and German Center for Infection Research
Subjects: Male, viruses, Genome, Viral, Biology, Reoviridae, RIG-I-like receptor, Article, Virus, DEAD-box RNA Helicases, Mice, Sense (molecular biology), Animals, Base Pairing, Gene, Multidisciplinary, Innate immune system, Base Sequence, RIG-I, virus diseases, RNA, MDA5, biochemical phenomena, metabolism, and nutrition, Virology, Immunity, Innate, 3. Good health, Diphosphates, DEAD Box Protein 58, RNA, Viral, Female
Abstract: Mammalian cells possess mechanisms to detect and defend themselves from invading viruses. In the cytosol, the RIG-I-like receptors (RLRs), RIG-I (retinoic acid-inducible gene I; encoded by DDX58) and MDA5 (melanoma differentiation-associated gene 5; encoded by IFIH1) sense atypical RNAs associated with virus infection. Detection triggers a signalling cascade via the adaptor MAVS that culminates in the production of type I interferons (IFN-¿ and ß; hereafter IFN), which are key antiviral cytokines. RIG-I and MDA5 are activated by distinct viral RNA structures and much evidence indicates that RIG-I responds to RNAs bearing a triphosphate (ppp) moiety in conjunction with a blunt-ended, base-paired region at the 5'-end (reviewed in refs 1, 2, 3). Here we show that RIG-I also mediates antiviral responses to RNAs bearing 5'-diphosphates (5'pp). Genomes from mammalian reoviruses with 5'pp termini, 5'pp-RNA isolated from yeast L-A virus, and base-paired 5'pp-RNAs made by in vitro transcription or chemical synthesis, all bind to RIG-I and serve as RIG-I agonists. Furthermore, a RIG-I-dependent response to 5'pp-RNA is essential for controlling reovirus infection in cultured cells and in mice. Thus, the minimal determinant for RIG-I recognition is a base-paired RNA with 5'pp. Such RNAs are found in some viruses but not in uninfected cells, indicating that recognition of 5'pp-RNA, like that of 5'ppp-RNA, acts as a powerful means of self/non-self discrimination by the innate immune system., C.R.S., D.G., S.D. and A.G.V.V. are funded by Cancer Research UK, a prize from Fondation Bettencourt-Schueller, and a grant from the European Research Council (ERC Advanced Researcher Grant AdG-2010-268670). A.J.P. and T.S.D. are supported by Public Health Service award R37 AI038296 and the Elizabeth B. Lamb Center for Pediatric Research. T.F. is supported by the Fundación Ramón Areces. G.H., M.S. and W.B. are supported by the Deutsche Forschungsgemeinschaft (http://www.dfg.de; SFB670 to M.S., W.B. and G.H., DFG SCHL1930/1-1 to M.S., SFB704 to G.H. and W.B., SFB832 and KFO177 to G.H.). G.H. and M.S. are supported by the DFG Excellence Cluster ImmunoSensation. G.H. is supported by the German Center of Infectious Disease (DZIF).
Published: 2014
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30. Tick Genome Assembled: New Opportunities for Research on Tick-Host-Pathogen Interactions

Author: R. Michael Roe, Daniel E. Sonenshine, Robert M. Waterhouse, José M. C. Ribeiro, David B. Sattelle, José de la Fuente, Catherine A. Hill, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Waterhouse, Robert, National Institute of Allergy and Infectious Diseases (US), and Department of Health and Human Services (US)
Subjects: 0301 basic medicine, Proteomics, Microbiology (medical), Anaplasma, Evolution, 030231 tropical medicine, Immunology, Genome, Insect, lcsh:QR1-502, Genomics, Computational biology, Tick, Genome, Microbiology, lcsh:Microbiology, 03 medical and health sciences, 0302 clinical medicine, proteomics, parasitic diseases, evolution, genomics, Animals, Humans, ddc:576.5, Ecosystem health, biology, Ixodes, Host (biology), Ecology, Borrelia, Sequence Analysis, DNA, biology.organism_classification, bacterial infections and mycoses, tick, 030104 developmental biology, Infectious Diseases, Ixodes scapularis, Perspective, Host-Pathogen Interactions, Arachnid Vectors
Abstract: As tick-borne diseases are on the rise, an international effort resulted in the sequence and assembly of the first genome of a tick vector. This result promotes research on comparative, functional and evolutionary genomics and the study of tick-host-pathogen interactions to improve human, animal and ecosystem health on a global scale., National Institutes of Health (U.S.), National Institute of Allergy and Infectious Diseases (U.S.), United States. Dept. of Health and Human Services
Published: 2016

31. Nature Communications

Author: Adam R. Wespiser, Don Gilbert, Vincent Croset, Joseph J. Gillespie, Renfu Shao, Timothy J. Kurtti, Julio Rozas, Hugh M. Robertson, Stephen C. Barker, Karen E. Nelson, Ketaki Bhide, Yoonseong Park, Brooke W. Bissinger, Patricia V. Pietrantonio, Joao H. F. Pedra, Janice P. Van Zee, Peter Arensburger, Hyeogsun Kwon, Timothy P. Driscoll, Daniel Lawson, Ryan C. Kennedy, Emma G. Lang, David Jiang, Jessica B. Hostetler, Jesús Vázquez, Zhijian Jake Tu, José de la Fuente, Bruce W. Birren, Juraj Koči, David R. Nelson, Catherine A. Hill, Brian P. Walenz, Frank Hauser, Cornelis J. P. Grimmelikhuijzen, Mathangi Thiagarajan, Andrew B. Nuss, Richard Benton, Linda Hannick, Kristin Lees, Stephen K. Wikel, Daniel R. Caffrey, Evgeny M. Zdobnov, Jason R. Miller, Elisabet Caler, Melissa J. Caimano, José M. C. Ribeiro, Jeffrey M. Grabowski, Elena Bonzón-Kulichenko, Monika Gulia-Nuss, Marta Tojo, Daniel E. Sonenshine, Joyce M. Sakamoto, Rushika Perera, Sergey Koren, R. Michael Roe, Nieves Ayllón, Qiandong Zeng, Jyothi Thimmapuram, Katherine M. Kocan, Jenica L. Abrudan, Gloria I. Giraldo-Calderón, Margarita Villar, David B. Sattelle, Alejandro Sánchez-Gracia, Francisca C. Almeida, Donghun Kim, Granger G. Sutton, Richard J. Kuhn, Maiara S. Severo, Sayed M.S. Khalil, Jiwei Zhu, Cristian Tornador, Shelby L. Bidwell, Vinita Joardar, Jose M. C. Tubio, Robert M. Waterhouse, Justin D. Radolf, Martin Hammond, Sarah Young, Steven D. Buckingham, Frank H. Collins, Yumin Qi, Ladislav Šimo, Maria F. Unger, Jason M. Meyer, Karyn Megy, Neal S. Silverman, Filipe G. Vieira, Martin Shumway, Jennifer R. Wortman, Claire M. Fraser, Yunlong Yang, Vishvanath Nene, Waterhouse, Robert, Zdobnov, Evgeny, University of Nevada, Partenaires INRAE, Department of Entomology, Michigan State University [East Lansing], Michigan State University System-Michigan State University System, Department Biotechnology, University of São Paulo (USP), Department of Biological Sciences, The Open University [Milton Keynes] (OU), North Carolina State University, Center for High Performance Simulation and Department of Chemical and Biomolecular Engineering, Department of Genetic Medicine and Development, Université de Genève (UNIGE), Broad Institute of Harvard and MIT, Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL), Massachusetts Institute of Technology (MIT), University College of London [London] (UCL), SaBio, Instituto de Investigación en Recursos Cinegéticos (IREC), Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University [Stillwater], National Institute of Allergy and Infectious Deseases (NIAID), University of Cambridge [UK] (CAM), VectorBase, Purdue University, J. Craig Venter Institute [La Jolla, USA] (JCVI), University of Notre Dame [Indiana] (UND), Universitat Autònoma de Barcelona (UAB), Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS), University of Connecticut (UCONN), Virginia Polytechnic Institute and State University [Blacksburg], Department of Biology, Indiana University [Bloomington], Indiana University System-Indiana University System, Department of Biochemistry [Blacksburg], Virginia Tech [Blacksburg], Agricultural Research Center, Texas A&M University System, Minnesota State University, University of Manchester [Manchester], Department of Bioengineering and Therapeutic Sciences, University of California [San Francisco] (UCSF), University of California-University of California, Pennsylvania State University (Penn State), Penn State System-Penn State System, University of California [Riverside] (UCR), University of California, Universidade de Santiago de Compostela [Spain] (USC ), Department of Experimental and Health Sciences, Universitat Pompeu Fabra [Barcelona] (UPF), University of Barcelona, California State Polytechnic University [Pomona] (CAL POLY POMONA), University of Queensland [Brisbane], University of the Sunshine Coast (USC), University of Copenhagen = Københavns Universitet (KU), University of Tennessee, Universidade de Vigo, Cancer Genome Project, The Wellcome Trust Sanger Institute [Cambridge], University of Illinois, University of Illinois System, Quinnipiac University, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services (NIAID, NIH, DHHS) [N01-AI30071, HHSN272200900007C, HHSN266200400001C, 5R01GM77117-5], NIH-NIAID [HHSN266200400039C, HHSN272200900039C], Australian Research Council [DP120100240], Ministerio de Ciencia e Innovacion of Spain [BFU2007-6292, BFU2010-15484, BIO2009-07990, BIO2012-37926], NIH [1R01AI090062, 1R21AI096268, HHSN272200900040C, R01AI017828, R01AI043006], NSF [IOS-0949194], Xunta de Galicia of Spain [10PXIB918057PR], EU FP7 ANTIGONE [278976], USDA-NRI/CREES [2008-35302-18820], Texas AgriLife Research Vector Biology grant, European Research Council Starting Independent, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Biochemistry, Fralin Life Sciences Institute, NIH - National Institute of Allergy and Infectious Diseases (NIAID) (Estados Unidos), National Institutes of Health (Estados Unidos), Australian Research Council, Ministerio de Ciencia e Innovación (España), United States of Department of Health & Human Services, National Science Foundation (Estados Unidos), Xunta de Galicia (España), Unión Europea. Comisión Europea, United States Department of Agriculture. National Institute of Food and Agriculture, Texas AgriLife Research, European Research Council, Swiss National Science Foundation, Fundação para a Ciência e a Tecnologia (Portugal), Lundbeck Foundation, Broad Genomics Platform, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Department of Health and Human Services (US), National Science Foundation (US), Xunta de Galicia, European Commission, Department of Agriculture (US), Boehringer Ingelheim Fonds, Gulia-Nuss, Monika, and Fundação para a Ciência e Tecnologia (Portugal)
Subjects: 0301 basic medicine, beetle tribolium-castaneum, Langat virus, [SDV]Life Sciences [q-bio], General Physics and Astronomy, PROTEIN, CATTLE TICK, Xenopus laevis, Lyme disease, anaplasma-phagocytophilum infection, Lyme Disease/transmission, ddc:576.5, BEETLE TRIBOLIUM-CASTANEUM, Genetics, Lyme Disease, Genome, Multidisciplinary, biology, Ecology, cattle tick, evolutionary analyses, CHEMOSENSORY RECEPTORS, Babesiosis, Genomics, drosophila, 3. Good health, Ixodes/genetics, DROSOPHILA, Ixodes scapularis, LIFE-STYLE, chemosensory receptors, Anaplasma phagocytophilum, life-style, Human granulocytic anaplasmosis, boophilus-microplus, united-states, protein, Science, Ligand-Gated Ion Channels/genetics, UNITED-STATES, Tick, ANAPLASMA-PHAGOCYTOPHILUM INFECTION, Article, General Biochemistry, Genetics and Molecular Biology, Arachnid Vectors/genetics, 03 medical and health sciences, BOOPHILUS-MICROPLUS, parasitic diseases, medicine, Animals, Ixodes, Gene Expression Profiling, General Chemistry, Ligand-Gated Ion Channels, Genome/genetics, Oocytes, biology.organism_classification, medicine.disease, bacterial infections and mycoses, EVOLUTIONARY ANALYSES, 030104 developmental biology, Arachnid Vectors
Abstract: Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing ∼57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick–host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host ‘questing’, prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival. We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent., This project has been funded in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services (NIAID, NIH, DHHS) under contract numbers N01-AI30071, HHSN272200900007C, HHSN266200400001C and 5R01GM77117-5. Its contents are solely the responsibility of the authors and do not represent the official views of the NIH. Additional grants and contracts supporting work described in this manuscript were from the NIH-NIAID (HHSN266200400039C and HHSN272200900039C) to F.H.C., and a subcontract under HHSN272200900039C to C.A.H. and J.M.M., the Australian Research Council Discovery Project (DP120100240) to S.C.B. and R.S., the Ministerio de Ciencia e Innovación of Spain (BFU2007–6292; BFU2010–15484) to J.R., BIO2009–07990 and BIO2012–37926 to J.V. NIH-1R01AI090062 to Y.P., L.S., and J.K., NIH 1R21AI096268 and NSF IOS-0949194 to R.M.R., the Xunta de Galicia of Spain (10PXIB918057PR) to J.M.C.T. and M.T., BFU2011–23896 and EU FP7 ANTIGONE (278976) to J.F., the USDA-NRI/CREES (2008-35302-18820) and Texas AgriLife Research Vector Biology grant to P.V.P. and European Research Council Starting Independent Researcher Grant (205202) to R.B., J.M.R was supported by the intramural program of the NIAID, R.M.W. by a Marie Curie International Outgoing Fellowship PIOF-GA-2011–303312, E.M.Z. by Swiss National Science Foundation awards 31003A-125350 and 31003A-143936, J.M.G. by an NIH-NCATS award TL1 TR000162 and NSF Graduate Research Fellowship (DGE 1333468), V.C. by a Boehringer Ingelheim Ph.D. Fellowship, F.G.V. by a Fundação para a Ciência e a Tecnologia, Portugal fellowship (SFRH/BD/22360/2005), C.J.P.G. and F.H. by The Lundbeck Foundation (Denmark), and J.J.G. by NIH awards HHSN272200900040C, R01AI017828 and R01AI043006. Support from the Broad Genomics Platform is gratefully acknowledged.
Published: 2016
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32. Cyr61 as mediator of Src signaling in triple negative breast cancer cells

Author: María Pilar Sánchez-Bailón, Víctor Mayoral-Varo, Annarica Calcabrini, Jorge Martín-Pérez, Agnese Molinari, Kay Uwe Wagner, Sergio Ciordia, Juan Pablo Albar, Jesús Pérez Losada, Ministerio de Economía y Competitividad (España), and Department of Health and Human Services (US)
Subjects: Proteomics, c-Src, Triple Negative Breast Neoplasms, medicine.disease_cause, migration, CSK Tyrosine-Protein Kinase, Cell Movement, Cell Line, Tumor, medicine, Biomarkers, Tumor, Humans, RNA, Messenger, Paxillin, Cell Proliferation, biology, Cell growth, Cell migration, invasion, Cell biology, src-Family Kinases, Oncology, CYR61, triple negative breast cancer, biology.protein, Cancer research, Phosphorylation, Female, Cyr61, Signal transduction, Carcinogenesis, Proto-oncogene tyrosine-protein kinase Src, Cysteine-Rich Protein 61, Signal Transduction, Research Paper
Abstract: This work is licensed under a Creative Commons Attribution 3.0 License.-- et al., SFKs are involved in tumorigenesis and metastasis. Here we analyzed c-Src contribution to initial steps of metastasis by tetracycline-dependent expression of a specific shRNA-c-Src, which suppressed c-Src mRNA and protein levels in metastatic MDA-MB-231 cells. c-Src suppression did not alter cell proliferation or survival, but it significantly reduced anchorage-independent growth. Concomitantly with diminished tyrosine-phosphorylation/activation of Fak, caveolin-1, paxillin and p130CAS, c-Src depletion also inhibited cellular migration, invasion and transendothelial migration. Quantitative proteomic analyses of the secretome showed that Cyr61 levels, which were detected in the exosomal fraction, were diminished upon shRNA-c-Src expression. In contrast, Cyr61 expression was unaltered inside cells. Cyr61 partially colocalized with cis-Golgi gp74 marker and with exosomal marker CD63, but c-Src depletion did not alter their cellular distribution. In SUM159PT cells, transient c-Src suppression also reduced secreted exosomal Cyr61 levels. Furthermore, conditional expression of a c-Src dominant negative mutant (SrcDN, c-Src-K295M/Y527F) in MDA-MB-231 and in SUM159PT diminished secreted Cyr61 as well. Cyr61 transient suppression in MDA-MB-231 inhibited invasion and transendothelial migration. Finally, in both MDA-MB-231 and SUM159PT, a neutralizing Cyr61 antibody restrained migration. Collectively, these results suggest that c-Src regulates secreted proteins, including the exosomal Cyr61, which are involved in modulating the metastatic potential of triple negative breast cancer cells., MP. S-B. was supported by a FPI fellowship from Ministerio de Economía y Competitividad. JM-P is a member of GEICAM and of IdPAZ. This work was supported by SAF2009–09254 and SAF2012–38048 from Ministerio de Economía y Competitividad, Spain. KUW is supported, in part, by the Public Health Service grants CA117930.
Published: 2014

33. Distinct roles of cell wall biogenesis in yeast morphogenesis as revealed by multivariate analysis of high-dimensional morphometric data

Author: Hiroki Okada, Yoshikazu Ohya, James B. Konopka, Shinsuke Ohnuki, Cesar Roncero, Ministry of Education, Culture, Sports, Science and Technology (Japan), Japan Society for the Promotion of Science, Comisión Interministerial de Ciencia y Tecnología, CICYT (España), and Department of Health and Human Services (US)
Subjects: Antifungal Agents, Cell, Saccharomyces cerevisiae, Biosynthesis and Biodegradation, Morphogenesis, Biology, Cell morphology, Cell wall, Fungal Proteins, 03 medical and health sciences, chemistry.chemical_compound, Echinocandins, Echinocandin B, Cell Wall, medicine, Molecular Biology, Cell Shape, 030304 developmental biology, Chitin Synthase, 0303 health sciences, 030306 microbiology, Tunicamycin, Cell Biology, Chitin synthase, Articles, biology.organism_classification, 3. Good health, Cell biology, carbohydrates (lipids), medicine.anatomical_structure, Aminoglycosides, Biochemistry, chemistry, Mutation, biology.protein, Software
Abstract: This article is under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License., The cell wall of budding yeast is a rigid structure composed of multiple components. To thoroughly understand its involvement in morphogenesis, we used the image analysis software CalMorph to quantitatively analyze cell morphology after treatment with drugs that inhibit different processes during cell wall synthesis. Cells treated with cell wall-affecting drugs exhibited broader necks and increased morphological variation. Tunicamycin, which inhibits the initial step of N-glycosylation of cell wall mannoproteins, induced morphologies similar to those of strains defective in α-mannosylation. The chitin synthase inhibitor nikkomycin Z induced morphological changes similar to those of mutants defective in chitin transglycosylase, possibly due to the critical role of chitin in anchoring the β-glucan network. To define the mode of action of echinocandin B, a 1,3-β-glucan synthase inhibitor, we compared the morphology it induced with mutants of Fks1 that contains the catalytic domain for 1,3-β-glucan synthesis. Echinocandin B exerted morphological effects similar to those observed in some fks1 mutants, with defects in cell polarity and reduced glucan synthesis activity, suggesting that echinocandin B affects not only 1,3-β-glucan synthesis, but also another functional domain. Thus our multivariate analyses reveal discrete functions of cell wall components and increase our understanding of the pharmacology of antifungal drugs. © 2014 Authors., This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (21310127 and 24370002 to Y.O.), a grant from the Comisión Interministerial de Ciencia y Tecnología, Spain (BFU2010-18632 to C.R.), and a Public Health Service grant from the National Institute of Allergy and Infectious Diseases (AI-47837 to J.B.K.). H.O. and S.O. were Research Fellows of the Japan Society for the Promotion of Science.
Published: 2014

34. Effect of cold stress (4ºC) and combined cold Stress-starvation on Campylobacter jejuni adherence to Caco-2 epithelial cells

Author: Kwarteng-Siaw, Miriam, Mingo, Elisa, Carrascosa, Alfonso V., Martínez-Rodríguez, Adolfo J., National Institutes of Health (US), and Department of Health and Human Services (US)
Abstract: Trabajo presentado al Annual Biomedical Research Conference for Minority Students celebrada en Nashville (US) del 13 al 16 de noviembre de 2013., This research was funded by the Old Westbury Neurosciece International Program (OWNIP) through an MHIRT grant from the NIMHD (MD001429).
Published: 2013

35. Catecholamine/serotonin interactions. Systems thinking for brain function and disease

Author: Hensler, Julie G, Artigas, Francesc, Bortolozzi, Analía, Daws, Lynette C, de Deurwaerdère, Philippe, Milan, Léa, Navailles, Sylvia, Koek, Wouter, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red Salud Mental (España), Centre National de la Recherche Scientifique (France), Université de Bordeaux, Ministerio de Economía y Competitividad (España), Generalitat de Catalunya, Société Française de Physiologie, European Commission, Department of Health and Human Services (US), and De Deurwaerdere, Philippe
Subjects: Serotonin, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Organic cation transporter, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Schizophrenia, Parkinson’s disease, l-DOPA, Plasma membrane monoamine transporter
Abstract: This chapter brings together the work of several leading laboratories, each an outstanding example of integrative approaches to complex diseases of the central nervous system. Cognitive dysfunction and negative symptoms associated with schizophrenia are believed to result from hypofunction of the mesocortical dopaminergic projections to prefrontal cortex (PFC). Noradrenergic targets for the augmentation of dopaminergic function in PFC show promise to improve cognitive deficits as well as negative symptoms. Serotonergic targets for the modulation of mesocortical dopaminergic neurotransmission include 5-HT2A and 5-HT1A receptors. The hallmark of Parkinson's disease is the destruction of nigrostriatal dopaminergic neurons. l-DOPA, a metabolic precursor of dopamine, is the standard of treatment. However, the ectopic release of dopamine (DA) from serotonin neurons and the clearance of extracellular DA by the norepinephrine transporter in areas enriched with noradrenergic terminals contribute to extracellular DA produced by l-DOPA and offer opportunities to improve l-DOPA therapy. The high-affinity transporters for monoamines are the primary targets for antidepressant drugs. However, many patients experience suboptimal therapeutic benefit or fail to respond to treatment. Organic cation transporters and plasma membrane monoamine transporter serve an important function in regulating monoamine neurotransmission and hold potential utility as targets for the development of therapeutic drugs. Improved therapeutic approaches will arise from not only understanding how monoamines influence one another within the central nervous system as an integrated whole but also addressing the pathophysiology of specific core symptoms or distinct syndromal dimensions (cognitive impairment, motor slowing, and negative affect) regardless of disease classification, for example, psychotic, affective, and neurodegenerative. © 2013 Elsevier Inc., This research was supported by grants Instituto de Salud Carlos III PI10/00290 cofinanced by FEDER, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM, P91C) (to AB), and SAF 2012-35183 from the Ministerio de Economía y Competitividad (to FA). Structural funds of the Catalan Government (grant 2009SGR220) are also acknowledged. AB is supported by the Researcher Stabilization Program of the Health Department of the Generalitat de Catalunya. This work was supported by grants from “Centre National de la Recherche Scientifique,” the University of Bordeaux, the “Fondation de France,” the “Société française de Physiologie,” and the European community (COST action CM 1103) (PD). This work was supported in part from USPHS grants R01-MH064489 (LCD), R01-MH093320 (LCD & WK), and NARSAD (LCD).
Published: 2013

36. Cooperative stabilization of microtubule dynamics by EB1 and CLIP-170 involves displacement of stably bound P i at microtubule ends

Author: Rubén M. Buey, Cristina Manatschal, Herbert P. Miller, Michel O. Steinmetz, Saša Bjelić, Leslie Wilson, Manu Lopus, Consejo Superior de Investigaciones Científicas (España), European Commission, Swiss National Science Foundation, and Department of Health and Human Services (US)
Subjects: Binding Sites, Microtubule dynamics, Binding protein, fungi, macromolecular substances, Biology, Biochemistry, Microtubules, Cell biology, Neoplasm Proteins, Microtubule, Cytoplasm, Tubulin, Humans, Displacement (orthopedic surgery), Guanosine Triphosphate, Linker, Microtubule-Associated Proteins
Abstract: End binding protein 1 (EB1) and cytoplasmic linker protein of 170 kDa (CLIP-170) are two well-studied microtubule plus-end-tracking proteins (+TIPs) that target growing microtubule plus ends in the form of comet tails and regulate microtubule dynamics. However, the mechanism by which they regulate microtubule dynamics is not well understood. Using full-length EB1 and a minimal functional fragment of CLIP-170 (ClipCG12), we found that EB1 and CLIP-170 cooperatively regulate microtubule dynamic instability at concentrations below which neither protein is effective. By use of small-angle X-ray scattering and analytical ultracentrifugation, we found that ClipCG12 adopts a largely extended conformation with two noninteracting CAP-Gly domains and that it formed a complex in solution with EB1. Using a reconstituted steady-state mammalian microtubule system, we found that at a low concentration of 250 nM, neither EB1 nor ClipCG12 individually modulated plus-end dynamic instability. Higher concentrations (up to 2 μM) of the two proteins individually did modulate dynamic instability, perhaps by a combination of effects at the tips and along the microtubule lengths. However, when low concentrations (250 nM) of EB1 and ClipCG12 were present together, the mixture modulated dynamic instability considerably. Using a pulsing strategy with [γ 32P]GTP, we further found that unlike EB1 or ClipCG12 alone, the EB1-ClipCG12 mixture partially depleted the microtubule ends of stably bound 32P i. Together, our results suggest that EB1 and ClipCG12 act cooperatively to regulate microtubule dynamics. They further indicate that stabilization of microtubule plus ends by the EB1-ClipCG12 mixture may involve modification of an aspect of the stabilizing cap., Supported by USPHS NS13560 (L.W.), by a FEBS Fellowship, Juan de la Cierva postdoctoral contracts, and a Marie Curie Career Integration Grant EB-SxIP: 293831 (R.M.B), and by grants from the Swiss National Science Foundation (M.O.S.).
Published: 2012

37. Blocking Effects of Human Tau on Squid Giant Synapse Transmission and Its Prevention by T-817 MA

Author: Eunah Yu, Jesús Avila, Rodolfo R. Llinás, Janaína Brusco, Herman Moreno, Jorge E. Moreira, Soon-Wook Choi, Mutsuyuki Sugimori, Department of Health and Human Services (US), Fundação de Amparo à Pesquisa do Estado de São Paulo, and National Institute for Health Research (UK)
Subjects: Squid giant synapse, Hyperphosphorylation, neuro-protective agent, Altzheimer’s disease, Neural facilitation, Neurodegenerative, Neurotransmission, Synaptic vesicle, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, synaptic vesicles, Synaptic augmentation, synaptic transmission, human tau, Synaptic transmission, Active zone, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Original Research, 030304 developmental biology, 0303 health sciences, Chemistry, Synaptic pharmacology, tauopathies, Altzheimer's disease, Cell Biology, Human tau, hyperphosphorylation, 3. Good health, Synaptic fatigue, Tauopathies, neurodegenerative, Synaptic Vesicles, Neuro-protective agent, Neuroscience, 030217 neurology & neurosurgery
Abstract: Filamentous tau inclusions are hallmarks of Alzheimer’s disease and related neurodegenerative tauopathies, but the molecular mechanisms involved in tau-mediated changes in neuronal function and their possible effects on synaptic transmission are unknown. We have evaluated the effects of human tau protein injected directly into the presynaptic terminal axon of the squid giant synapse, which affords functional, structural, and biochemical analysis of its action on the synaptic release process. Indeed, we have found that at physiological concentration recombinant human tau (h-tau42) becomes phosphorylated, produces a rapid synaptic transmission block, and induces the formation of clusters of aggregated synaptic vesicles in the vicinity of the active zone. Presynaptic voltage clamp recordings demonstrate that h-tau42 does not modify the presynaptic calcium current amplitude or kinetics. Analysis of synaptic noise at the post-synaptic axon following presynaptic h-tau42 microinjection revealed an initial phase of increase spontaneous transmitter release followed by a marked reduction in noise. Finally, systemic administration of T-817MA, a proposed neuro-protective agent, rescued tau-induced synaptic abnormalities. Our results show novel mechanisms of h-tau42 mediated synaptic transmission failure and identify a potential therapeutic agent to treat tau-related neurotoxicity, Grant sponsors: NIH AG027476 to Herman Moreno; NS13742/ NS/NINDS/NIH HHS to RLl; FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo, Brasil) projects 2009/01571-6 and CinAPSe 05/56447-7 to Jorge E. Moreira.
Published: 2011
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38. Characterization of a natural mutator variant of human DNA polymerase lambda which promotes chromosomal instability by compromising NHEJ

Author: François Boudsocq, Miguel Garcia-Diaz, Tomas Kirchhoff, Thomas A. Kunkel, Jean-Pascal Capp, Gloria Terrados, Jean-Sébastien Hoffmann, Yvan Canitrot, Luis Blanco, Valérie Bergoglio, Alberto Villanueva, Katarzyna Bebenek, Christophe Cazaux, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences [Durham] (NIEHS-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Department of Environmental Medicine, New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-NYU Cancer Institute, Translational Research Laboratory, Catalan Institute of Oncology-Bellvitge Institute for Biomedical Research, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ministerio de Ciencia y Tecnología (España), Comunidad de Madrid, Ligue Nationale contre le Cancer (France), National Institutes of Health (US), National Institute of Environmental Health Sciences (US), Department of Health and Human Services (US), Ministerio de Educación y Ciencia (España), and Fundación Ramón Areces
Subjects: DNA Repair, DNA repair, DNA polymerase, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, lcsh:Medicine, DNA polymerase beta, Arginine, Polymorphism, Single Nucleotide, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Chromosome instability, Chromosomal Instability, Humans, DNA Breaks, Double-Stranded, Amino Acids, lcsh:Science, Codon, Molecular Biology, Polymerase, ComputingMilieux_MISCELLANEOUS, DNA Polymerase beta, 030304 developmental biology, Genetics, DNA Polymerase Lambda, Chromosome Aberrations, 0303 health sciences, Multidisciplinary, Molecular Biology/DNA Repair, ComputingMilieux_THECOMPUTINGPROFESSION, biology, lcsh:R, Tryptophan, DNA, DNA polymerase lambda, 3. Good health, Chromosomal instability, Non-homologous end joining, DNA-Binding Proteins, DNA Repair Enzymes, chemistry, 030220 oncology & carcinogenesis, Mutation, biology.protein, lcsh:Q, Research Article
Abstract: PLoS ONE 4(10): e7290., Background: DNA polymerase lambda (Poll) is a DNA repair polymerase, which likely plays a role in base excision repair (BER) and in non-homologous end joining (NHEJ) of DNA double-strand breaks (DSB). Principal Findings: Here, we described a novel natural allelic variant of human Poll (hPoll) characterized by a single nucleotide polymorphism (SNP), C/T variation in the first base of codon 438, resulting in the amino acid change Arg to Trp. In vitro enzyme activity assays of the purified W438 Poll variant revealed that it retained both DNA polymerization and deoxyribose phosphate (dRP) lyase activities, but had reduced base substitution fidelity. Ectopic expression of the W438 hPoll variant in mammalian cells increases mutation frequency, affects the DSB repair NHEJ pathway, and generates chromosome aberrations. All these phenotypes are dependent upon the catalytic activity of the W438 hPoll. Conclusions: The expression of a cancer-related natural variant of one specialized DNA polymerase can be associated to generic instability at the cromosomal level, probably due a defective NHEJ. These results establish that chromosomal aberrations can result from mutations in specialized DNA repair polymerases., This work was supported by Ministerio de Ciencia y Tecnologia Grants BFU2006-14390/BMC, CONSOLIDER CSD2007-00015 and Comunidad Autonoma de Madrid Grants P2006/BIO-0306 to L.B., by INCa ‘‘Checkpol’’, ARC, and ‘‘Ligue contre le Cancer (Region Midi-Pyrenees)’’ to J-S.H., by the Division of Intramural Research, NIEHS, NIH, DHHS to T.A.K., by SAF2002-02265 to A.V., and by an institutional grant to Centro de Biologia Molecular ‘‘Severo Ochoa’’ from Fundacion Ramon Areces. G.T. was recipient of a fellowship from the Ministerio de Educacion y Ciencia. A.V. is an Investigator of the Ramon y Cajal Program
Published: 2009
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39. Regulatory control of DNA end resection by Sae2 phosphorylation.

Author: Cannavo E, Johnson D, Andres SN, Kissling VM, Reinert JK, Garcia V, Erie DA, Hess D, Thomä NH, Enchev RI, Peter M, Williams RS, Neale MJ, and Cejka P
Subjects: Cell Cycle, DNA End-Joining Repair physiology, DNA, Fungal metabolism, DNA-Binding Proteins genetics, Endodeoxyribonucleases metabolism, Endonucleases chemistry, Endonucleases genetics, Exodeoxyribonucleases metabolism, Meiosis genetics, Multiprotein Complexes chemistry, Multiprotein Complexes metabolism, Phosphorylation, Protein Binding, Protein Multimerization, Saccharomyces cerevisiae enzymology, Saccharomyces cerevisiae metabolism, Saccharomyces cerevisiae Proteins chemistry, Saccharomyces cerevisiae Proteins genetics, DNA Breaks, Double-Stranded, DNA-Binding Proteins metabolism, Endonucleases metabolism, Recombinational DNA Repair physiology, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins metabolism
Abstract: DNA end resection plays a critical function in DNA double-strand break repair pathway choice. Resected DNA ends are refractory to end-joining mechanisms and are instead channeled to homology-directed repair. Using biochemical, genetic, and imaging methods, we show that phosphorylation of Saccharomyces cerevisiae Sae2 controls its capacity to promote the Mre11-Rad50-Xrs2 (MRX) nuclease to initiate resection of blocked DNA ends by at least two distinct mechanisms. First, DNA damage and cell cycle-dependent phosphorylation leads to Sae2 tetramerization. Second, and independently, phosphorylation of the conserved C-terminal domain of Sae2 is a prerequisite for its physical interaction with Rad50, which is also crucial to promote the MRX endonuclease. The lack of this interaction explains the phenotype of rad50S mutants defective in the processing of Spo11-bound DNA ends during meiotic recombination. Our results define how phosphorylation controls the initiation of DNA end resection and therefore the choice between the key DNA double-strand break repair mechanisms.
Published: 2018
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40. Population-based cancer screening programmes in low-income and middle-income countries: regional consultation of the International Cancer Screening Network in India.

Author: Sivaram S, Majumdar G, Perin D, Nessa A, Broeders M, Lynge E, Saraiya M, Segnan N, Sankaranarayanan R, Rajaraman P, Trimble E, Taplin S, Rath GK, and Mehrotra R
Subjects: Denmark, Female, Humans, Income, India, Male, Needs Assessment, Neoplasms epidemiology, Netherlands, Population Surveillance, Program Development, Program Evaluation, Referral and Consultation, Early Detection of Cancer methods, International Cooperation, Mass Screening organization & administration, Neoplasms prevention & control, Poverty
Abstract: The reductions in cancer morbidity and mortality afforded by population-based cancer screening programmes have led many low-income and middle-income countries to consider the implementation of national screening programmes in the public sector. Screening at the population level, when planned and organised, can greatly benefit the population, whilst disorganised screening can increase costs and reduce benefits. The International Cancer Screening Network (ICSN) was created to share lessons, experience, and evidence regarding cancer screening in countries with organised screening programmes. Organised screening programmes provide screening to an identifiable target population and use multidisciplinary delivery teams, coordinated clinical oversight committees, and regular review by a multidisciplinary evaluation board to maximise benefit to the target population. In this Series paper, we report outcomes of the first regional consultation of the ICSN held in Agartala, India (Sept 5-7, 2016), which included discussions from cancer screening programmes from Denmark, the Netherlands, USA, and Bangladesh. We outline six essential elements of population-based cancer screening programmes, and share recommendations from the meeting that policy makers might want to consider before implementation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
Published: 2018
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41. Challenges and Opportunities of Nontraditional Approaches to Treating Bacterial Infections.

Author: Tse BN, Adalja AA, Houchens C, Larsen J, Inglesby TV, and Hatchett R
Subjects: Antibodies, Monoclonal therapeutic use, Drug Resistance, Bacterial, Fecal Microbiota Transplantation, Humans, Immunologic Factors therapeutic use, Microbiota, Phage Therapy, Therapeutics methods, Therapeutics trends, Bacterial Infections therapy
Abstract: Due to increasing rates of antimicrobial-resistant infections and the current inadequacy of the antibiotic pipeline, there is increasing interest in nontraditional approaches to antibacterial therapies. We define "traditional" agents as small-molecule agents that directly target bacterial components to exert a bacteriostatic or bactericidal effect, and "nontraditional approaches" as antimicrobial therapeutics that work through other means (ie, not a small molecule and/or utilizes a nontraditional target). Due to their atypical features, such therapies may be less susceptible to the emergence of resistance than traditional antibiotics. They include approaches such as monoclonal antibodies, virulence disruptors, immunomodulators, phage therapies, microbiome-based therapies, antibiotic potentiators, and antisense approaches. This article discusses both the developmental and regulatory advantages and challenges associated with each of these technologies. By identifying existing regulatory and developmental gaps, we hope to provide a sense of where focusing resources may provide the greatest impact on successful product development., (Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)
Published: 2017
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42. Surgeon General's Report on Alcohol, Drugs, and Health.

Author: Murthy VH
Subjects: Alcoholism complications, Alcoholism epidemiology, Alcoholism prevention & control, Brain, Drug Overdose complications, Drug Overdose epidemiology, Drug Overdose prevention & control, Health Services Accessibility, Humans, Research Report, Reward, Substance-Related Disorders complications, Substance-Related Disorders prevention & control, United States epidemiology, Substance-Related Disorders epidemiology, United States Public Health Service
Published: 2017
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43. Mammalian gastrointestinal tract parameters modulating the integrity, surface properties, and absorption of food-relevant nanomaterials.

Author: Bellmann S, Carlander D, Fasano A, Momcilovic D, Scimeca JA, Waldman WJ, Gombau L, Tsytsikova L, Canady R, Pereira DI, and Lefebvre DE
Subjects: Animals, Humans, Surface Properties, Food, Gastrointestinal Tract physiology, Intestinal Absorption, Mammals physiology, Nanostructures chemistry
Abstract: Many natural chemicals in food are in the nanometer size range, and the selective uptake of nutrients with nanoscale dimensions by the gastrointestinal (GI) tract is a normal physiological process. Novel engineered nanomaterials (NMs) can bring various benefits to food, e.g., enhancing nutrition. Assessing potential risks requires an understanding of the stability of these entities in the GI lumen, and an understanding of whether or not they can be absorbed and thus become systemically available. Data are emerging on the mammalian in vivo absorption of engineered NMs composed of chemicals with a range of properties, including metal, mineral, biochemical macromolecules, and lipid-based entities. In vitro and in silico fluid incubation data has also provided some evidence of changes in particle stability, aggregation, and surface properties following interaction with luminal factors present in the GI tract. The variables include physical forces, osmotic concentration, pH, digestive enzymes, other food, and endogenous biochemicals, and commensal microbes. Further research is required to fill remaining data gaps on the effects of these parameters on NM integrity, physicochemical properties, and GI absorption. Knowledge of the most influential luminal parameters will be essential when developing models of the GI tract to quantify the percent absorption of food-relevant engineered NMs for risk assessment., (© 2015 The Authors. WIREs Nanomedicine and Nanobiotechnology published by Wiley Periodicals, Inc.)
Published: 2015
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44. Can primary care physician-driven community programs address the obesity epidemic among high-risk populations?

Author: Benjamin RM, Yanovski SZ, and Simons-Morton DG
Subjects: Female, Humans, Black or African American psychology, Behavior Therapy methods, Obesity prevention & control, Weight Gain physiology
Published: 2013
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45. Surveillance of transmitted HIV drug resistance using matched plasma and dried blood spot specimens from voluntary counseling and testing sites in Ho Chi Minh City, Vietnam, 2007-2008.

Author: Duc NB, Hien BT, Wagar N, Tram TH, Giang le T, Yang C, Wolfe MI, Hien NT, and Tuan NA
Subjects: Ambulatory Care Facilities, Dried Blood Spot Testing, Drug Resistance, Viral, Genotyping Techniques, HIV drug effects, HIV genetics, HIV Infections transmission, HIV Infections virology, Humans, Population Surveillance, Vietnam epidemiology, Voluntary Programs, Young Adult, Anti-Retroviral Agents pharmacology, Blood Chemical Analysis methods, HIV classification, HIV Infections blood, HIV Infections epidemiology
Abstract: During 2007-2008, surveillance of transmitted human immunodeficiency virus (HIV) drug resistance (TDR) was performed following World Health Organization guidance among clients with newly diagnosed HIV infection attending voluntary counseling and testing (VCT) sites in Ho Chi Minh City (HCMC), Vietnam. Moderate (5%-15%) TDR to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) was observed among VCT clients aged 18-21 years. Follow-up surveillance of TDR in HCMC and other geographic regions of Vietnam is warranted. Data generated will guide the national HIV drug resistance surveillance strategy and support selection of current and future first-line antiretroviral therapy and HIV prevention programs.
Published: 2012
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46. Demographic and immune correlates of human herpesvirus 8 seropositivity in Malawi, Africa.

Author: DeSantis SM, Pau CP, Archibald LK, Nwanyanwu OC, Kazembe PN, Dobbie H, Jarvis WR, and Jason J
Subjects: AIDS-Related Opportunistic Infections virology, Adolescent, Adult, Child, Child, Preschool, Cytokines blood, Female, Flow Cytometry, HIV Infections complications, HIV Infections virology, Hospitalization, Humans, Infant, Malawi epidemiology, Male, Middle Aged, Sarcoma, Kaposi virology, Seroepidemiologic Studies, AIDS-Related Opportunistic Infections epidemiology, Antibodies, Viral blood, Demography, HIV Infections epidemiology, Herpesvirus 8, Human immunology, Sarcoma, Kaposi epidemiology
Abstract: Background: In the USA, human herpesvirus 8 (HHV-8) is associated with Kaposi's sarcoma (KS) and HIV infection. We examined HHV-8 seroprevalence in a Malawian cohort, and assessed its relationship with HIV, KS, demographic characteristics, and immune findings., Methods: In 1997 and 1998, blood samples were obtained from 272 hospitalized Malawian patients, for whom demographic information was obtained, and 24 healthy volunteers without demographic data. We used enzyme immunoassays to assess seroprevalence and antibody titers to peptide antigens derived from HHV-8 K8.1 and ORF65-encoded proteins. Intracellular cytokines and cell surface antigens were assessed with four-color flow cytometry. Data were analyzed using non-parametric univariate and regression analytic techniques., Results: The rates of HHV-8 seroprevalence to either or both HHV-8 peptides were 67% for the patients and 54% for the healthy volunteers. Seroprevalence increased with patients' age (P<0.001) but was not associated with HIV status, percentage of lymphocytes expressing CD4, or KS (n=10). Seropositive females had lower antibody titers to both peptides than did males (medians: 455 versus 1361 for K8.1, P<0.001; and 268 versus 405 for ORF65, P=0.044). For the healthy volunteers, the percentage of CD8+ cells producing IFN-gamma after stimulation was significantly lower in ORF65-specific antibody-positive persons (medians: 24% versus 57%, P=0.008)., Conclusions: In Malawi, HHV-8 is endemic and is not associated with HIV infection or HIV severity. Seroprevalence rates increase in childhood, and, most steeply in adolescence. Titers are higher in seropositive males than in sero-positive females. The immune effects of HHV-8 in healthy adults are consistent with chronic inhibition of type 1 cytotoxic T-cell responsiveness, independent of HIV status.
Published: 2002
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47. Injury among cavers: results of a preliminary national survey.

Author: Ashford DA, Knutson RS, and Sacks JJ
Subjects: Adult, Athletic Injuries prevention & control, Female, Head Protective Devices, Humans, Hypothermia etiology, Hypothermia prevention & control, Male, Middle Aged, Protective Clothing, Risk Factors, Athletic Injuries epidemiology
Abstract: Background: To estimate the frequency of and risk factors for caving-associated injuries., Methods: A standardized questionnaire covering demographics, caving exposure, and injury history was distributed to all members of the National Speleological Society by inclusion in the monthly newsletter., Results: Of 9,532 members sent a questionnaire, 301 responded (3.2%). Respondents had an average of 18 years of caving experience, and 37% had sustained one or more injuries while caving. Hypothermia was the most frequent injury, followed by fractures, animal bites, and concussions. The rate of injury was about 1 per 1,990 hours in a cave. Injury rates for females were about twice those of males; older persons and those with more than 5 years of caving experience seemed to have lower injury rates., Conclusions: Many caving injuries appear potentially preventable. Proper technique for safe climbing should be a part of exploration training. There is a need for proper belaying or rappelling for even short ascents or descents. Helmet use should be stressed, as should adequate protection from hypothermia.
Published: 1999

48. Summary of the NIOSH guidelines for air sampling and analytical method development and evaluation.

Author: Kennedy ER, Fischbach TJ, Song R, Eller PM, and Shulman SA
Subjects: Chemistry Techniques, Analytical methods, Humans, National Institute for Occupational Safety and Health, U.S., United States, Air Pollutants, Occupational analysis, Chemistry Techniques, Analytical standards, Occupational Health
Abstract: Suggested guidelines for the development and evaluation of sampling and analytical methods for industrial hygiene monitoring have recently been published in a NIOSH technical report. These guidelines are based in part on various published approaches for method development and evaluation and serve as an attempt at a more unified experimental approach. This paper presents some salient features of this unified approach for method development and evaluation. The basic goal of the approach is to determine if the method under study meets the criterion to produce a result that fell within 25% of the true value 95 times out of 100 on average, although other factors of method performance are evaluated. The experiments proposed for the evaluation of method performance include determination of analytical recovery from the sampler, sampler capacity, storage stability of samples and effect of environmental factors. Evaluation criteria for the experimental data and procedures for the calculation of method bias, precision and accuracy are also included.
Published: 1996
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49. Programmed cell death and mutation induction in AHH-1 human lymphoblastoid cells exposed to m-amsa.

Author: Morris SM, Domon OE, McGarrity LJ, Chen JJ, and Casciano DA
Subjects: Analysis of Variance, Apoptosis genetics, Apoptosis physiology, B-Lymphocytes drug effects, Cell Cycle drug effects, Cell Line, Transformed, Cell Separation, Cell Survival, DNA Damage, Flow Cytometry, Humans, Hypoxanthine Phosphoribosyltransferase genetics, Necrosis, Protein-Tyrosine Kinases genetics, Signal Transduction drug effects, Suppression, Genetic drug effects, Amsacrine toxicity, Apoptosis drug effects
Abstract: One role of programmed cell death (apoptosis) is the removal of cells with DNA damage from the population. Certain cells, however, are able to suppress the signals for apoptotic cell death and maintain viability. This suggests that the susceptibility of a cell to either undergo apoptosis or escape from the apoptotic death pathways may be an important factor in chemical mutagenesis. In order to provide insight into the role of apoptosis in the recovery of chemically induced mutants, AHH-1 cells were exposed to the chromosomal mutagen, m-amsa, and the percentage of cells undergoing apoptosis or necrosis quantified by flow cytometry. Logistic regression analysis revealed that the primary manner of cell death was by apoptosis. Two specific-locus mutations assays, the tk and the hprt, were utilized as markers for cells with DNA damage and that retained clonogenicity under conditions known to induce apoptosis. Analysis of variance indicated that the concentration-dependent increase in the mutant fraction at the tk locus was significant and the result of the recovery of clones with the slow-growth phenotype. Because this phenotype is thought to reflect chromosomal mutations, these results are consistent with the survival and clonogenicity of damaged cells. This suggests that the ability to recover mutant cells may be influenced by the suppression of or an escape from the apoptotic death pathways.
Published: 1995
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50. Haloperidol- and SCH23390-induced dopaminergic supersensitivities are not additive in the rat.

Author: Parashos SA, Barone P, Marin CA, Paraschos AJ, Kapitzoglou-Logothetis V, and Chase TN
Subjects: Animals, Drug Interactions, Male, Motor Activity drug effects, Rats, Rats, Inbred Strains, Stereotyped Behavior drug effects, Antipsychotic Agents pharmacology, Benzazepines pharmacology, Haloperidol pharmacology
Abstract: The effect of chronic D-1 and/or D-2 dopamine receptor blockade on apomorphine-induced behaviors was studied in rats treated for 21 days with the selective D-1 antagonist SCH23390, the predominantly D-2 antagonist haloperidol, and the combination of the two drugs at the same daily doses (0.1 and 1 mg/kg respectively). Apomorphine (0.3 mg/kg) 4 days following the last injection of the drugs increased (49-70%) stereotypic behavior in all animals as compared to saline-treated controls. Although the SCH23390-induced increase was lower than haloperidol-induced supersensitivity, stereotypies after combined administration of both drugs did not differ significantly from either, suggesting that the effects of the two drugs are not additive. Underlying receptor changes and modified D-1/D-2 receptor interactions may account for the participation of both receptor subtypes to the development of neuroleptic-induced dopaminergic supersensitivity.
Published: 1989
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