199 results on '"Beddoe T"'
Search Results
52. Oxidoreductase NmDsbA3 from Neisseria meningitidis
- Author
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Vivian, J.P., primary, Scoullar, J., additional, Robertson, A.L., additional, Bottomley, S.P., additional, Horne, J., additional, Chin, Y., additional, Velkov, T., additional, Wielens, J., additional, Thompson, P.E., additional, Piek, S., additional, Byres, E., additional, Beddoe, T., additional, Wilce, M.C.J., additional, Kahler, C., additional, Rossjohn, J., additional, and Scanlon, M.J., additional
- Published
- 2008
- Full Text
- View/download PDF
53. The human non-classical major histocompatibility complex molecule HLA-E
- Author
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Hoare, H.L., primary, Sullivan, L.C., additional, Ely, L.K., additional, Beddoe, T., additional, Henderson, K.N., additional, Lin, J., additional, Clements, C.S., additional, Reid, H.H., additional, Brooks, A.G., additional, and Rossjohn, J., additional
- Published
- 2008
- Full Text
- View/download PDF
54. Human CD94/NKG2A in complex with HLA-E
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Petrie, E.J., primary, Clements, C.S., additional, Lin, J., additional, Sullivan, L.C., additional, Johnson, D., additional, Huyton, T., additional, Heroux, A., additional, Hoare, H.L., additional, Beddoe, T., additional, Reid, H.H., additional, Wilce, M.C.J., additional, Brooks, A.G., additional, and Rossjohn, J., additional
- Published
- 2008
- Full Text
- View/download PDF
55. Crystal structure of the A-subunit of the AB5 toxin from E. coli
- Author
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Paton, A.W., primary, Beddoe, T., additional, Thorpe, C.M., additional, Whisstock, J.C., additional, Wilce, M.C.J., additional, Rossjohn, J., additional, Talbot, U.M., additional, and Paton, J.C., additional
- Published
- 2006
- Full Text
- View/download PDF
56. The 2.0 angstroms crystal structure of a pocilloporin at pH 3.5: the structural basis for the linkage between color transition and halide binding
- Author
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Wilmann, P.G., primary, Battad, J., additional, Beddoe, T., additional, Olsen, S., additional, Smith, S.C., additional, Dove, S., additional, Devenish, R.J., additional, Rossjohn, J., additional, and Prescott, M., additional
- Published
- 2006
- Full Text
- View/download PDF
57. Crystal Structure of SB27 TCR in complex with HLA-B*3508-13mer peptide
- Author
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Tynan, F.E., primary, Burrows, S.R., additional, Buckle, A.M., additional, Clements, C.S., additional, Borg, N.A., additional, Miles, J.J., additional, Beddoe, T., additional, Whisstock, J.C., additional, Wilce, M.C., additional, Silins, S.L., additional, Burrows, J.M., additional, Kjer-Nielsen, L., additional, Konstenko, L., additional, Purcell, A.W., additional, McCluskey, J., additional, and Rossjohn, J., additional
- Published
- 2005
- Full Text
- View/download PDF
58. Structural Investigations of GFP-like proteins
- Author
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Wilmann, P. G., primary, Petersen, J., additional, Beddoe, T., additional, Devenish, R. J., additional, Prescott, M., additional, and Rossjohn, J., additional
- Published
- 2005
- Full Text
- View/download PDF
59. Conformational switch in polymorphic H-2K molecules containing an HSV peptide
- Author
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Webb, A.I., primary, Borg, N.A., additional, Dunstone, M.A., additional, Kjer-Nielsen, L., additional, Beddoe, T., additional, McCluskey, J., additional, Carbone, F.R., additional, Bottomley, S.P., additional, Purcell, A.W., additional, and Rossjohn, J., additional
- Published
- 2004
- Full Text
- View/download PDF
60. Crystal Structure of CD3gammaepsilon Heterodimer in Complex with OKT3 Fab Fragment
- Author
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Kjer-Nielsen, L., primary, Dunstone, M.A., additional, Kostenko, L., additional, Ely, L.K., additional, Beddoe, T., additional, Misfud, N.A., additional, Purcell, A.W., additional, Brooks, A.G., additional, McCluskey, J., additional, and Rossjohn, J., additional
- Published
- 2004
- Full Text
- View/download PDF
61. The 2.0 crystal structure of eqFP611, a far-red fluorescent protein from the sea anemone Entacmaea quadricolor
- Author
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Petersen, J., primary, Wilmann, P.G., additional, Beddoe, T., additional, Oakley, A.J., additional, Devenish, R.J., additional, Prescott, M., additional, and Rossjohn, J., additional
- Published
- 2003
- Full Text
- View/download PDF
62. The crystal structure of an autoantigen in multiple sclerosis
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Clements, C.S., primary, Reid, H.H., additional, Beddoe, T., additional, Tynan, F.E., additional, Perugini, M.A., additional, Johns, T.G., additional, Bernard, C.C., additional, and Rossjohn, J., additional
- Published
- 2003
- Full Text
- View/download PDF
63. Crystal structure of Coral pigment
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Prescott, M., primary, Ling, M., additional, Beddoe, T., additional, Oakley, A.J., additional, Dove, S., additional, Hoegh-Guldberg, O., additional, Devenish, R.J., additional, and Rossjohn, J., additional
- Published
- 2003
- Full Text
- View/download PDF
64. The protein encoded by the MFT1 gene is a targeting factor for mitochondrial precursor proteins, and not a core ribosomal protein
- Author
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Beilharz, T., Beddoe, T., Landl, K., Cartwright, P., and Lithgow, T.
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- 1997
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65. A new mode of recognition: an entropically favoured T-cell receptor
- Author
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Ely, Lk, Beddoe, T., Matthews, Jm, Kjer-Nielsen, L., Mccluskey, J., and Jamie Rossjohn
66. Large expert-curated database for benchmarking document similarity detection in biomedical literature search
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Zeineb, Zian, Brown, Peter, Tan, Aik-Choon, El-Esawi, Mohamed A., Liehr, Thomas, Blanck, Oliver, Gladue, Douglas P., Almeida, Gabriel M. F., Cernava, Tomislav, Sorzano, Carlos O., Yeung, Andy W. K., Engel, Michael S., Chandrasekaran, Arun Richard, Muth, Thilo, Staege, Martin S., Daulatabad, Swapna V., Widera, Darius, Zhang, Junpeng, Meule, Adrian, Honjo, Ken, Pourret, Olivier, Yin, Cong-Cong, Zhang, Zhongheng, Cascella, Marco, Flegel, Willy A., Goodyear, Carl S., Raaij, Mark J. van, Bukowy-Bieryllo, Zuzanna, Campana, Luca G., Kurniawan, Nicholas A., Lalaouna, David, Hüttner, Felix J., Ammerman, Brooke A., Ehret, Felix, Cobine, Paul A., Tan, Ene-Choo, Han, Hyemin, Xia, Wenfeng, McCrum, Christopher, Dings, Ruud P. M., Marinello, Francesco, Nilsson, Henrik, Nixon, Brett, Voskarides, Konstantinos, Yang, Long, Costa, Vincent D., Bengtsson-Palme, Johan, Bradshaw, William, Grimm, Dominik G., Kumar, Nitin, Martis, Elvis, Prieto, Daniel, Sabnis, Sandeep C., Amer, Said E. D. R., Liew, Alan W. C., Perco, Paul, Rahimi, Farid, Riva, Giuseppe, Zhang, Chongxing, Devkota, Hari P., Ogami, Koichi, Basharat, Zarrin, Fierz, Walter, Siebers, Robert, Tan, Kok-Hian, Boehme, Karen A., Brenneisen, Peter, Brown, James A. L., Dalrymple, Brian P., Harvey, David J., Ng, Grace, Werten, Sebastiaan, Bleackley, Mark, Dai, Zhanwu, Dhariwal, Raman, Gelfer, Yael, Hartmann, Marcus D., Miotla, Pawel, Tamaian, Radu, Govender, Pragashnie, Gurney-Champion, Oliver J., Kauppila, Joonas H., Zhang, Xiaolei, Echeverría, Natalia, Subhash, Santhilal, Sallmon, Hannes, Tofani, Marco, Bae, Taeok, Bosch, Oliver, Cuív, Páraic O., Danchin, Antoine, Diouf, Barthelemy, Eerola, Tuomas, Evangelou, Evangelos, Filipp, Fabian V., Klump, Hannes, Kurgan, Lukasz, Smith, Simon S., Terrier, Olivier, Tuttle, Neil, Ascher, David B., Janga, Sarath C., Schulte, Leon N., Becker, Daniel, Browngardt, Christopher, Bush, Stephen J., Gaullier, Guillaume, Ide, Kazuki, Meseko, Clement, Werner, Gijsbert D. A., Zaucha, Jan, Al-Farha, Abd A., Greenwald, Noah F., Popoola, Segun I., Rahman, Md Shaifur, Xu, Jialin, Yang, Sunny Y., Hiroi, Noboru, Alper, Ozgul M., Baker, Chris I., Bitzer, Michael, Chacko, George, Debrabant, Birgit, Dixon, Ray, Forano, Evelyne, Gilliham, Matthew, Kelly, Sarah, Klempnauer, Karl-Heinz, Lidbury, Brett A., Lin, Michael Z., Lynch, Iseult, Ma, Wujun, Maibach, Edward W., Mather, Diane E., Nandakumar, Kutty S., Ohgami, Robert S., Parchi, Piero, Tressoldi, Patrizio, Xue, Yu, Armitage, Charles, Barraud, Pierre, Chatzitheochari, Stella, Coelho, Luis P., Diao, Jiajie, Doxey, Andrew C., Hu, Pingzhao, Kaiser, Stefan, Mitchell, Kate M., Salama, Mohamed F., Shabalin, Ivan G., Song, Haijun, Stevanovic, Dejan, Yadollahpour, Ali, Zeng, Erliang, Zinke, Katharina, Alimba, C. G., Beyene, Tariku J., Cao, Zehong, Chan, Sherwin S., Gatchell, Michael, Kleppe, Andreas, Piotrowski, Marcin, Torga, Gonzalo, Woldesemayat, Adugna A., Cosacak, Mehmet I., Haston, Scott, Ross, Stephanie A., Williams, Richard, Wong, Alvin, Abramowitz, Matthew K., Effiong, Andem, Lee, Senhong, Abid, Muhammad Bilal, Agarabi, Cyrus, Alaux, Cedric, Albrecht, Dirk R., Atkins, Gerald J., Beck, Charles R., Bonvin, A. M. J. J., Bourke, Emer, Brand, Thomas, Braun, Ralf J., Bull, James A., Cardoso, Pedro, Carter, Dee, Delahay, Robin M., Ducommun, Bernard, Duijf, Pascal H. G., Epp, Trevor, Eskelinen, Eeva-Liisa, Fallah, Mazyar, Farber, Debora B., Fernandez-Triana, Jose, Feyerabend, Frank, Florio, Tullio, Friebe, Michael, Furuta, Saori, Gabrielsen, Mads, Gruber, Jens, Grybos, Malgorzata, Han, Qian, Heinrich, Michael, Helanterä, Heikki, Huber, Michael, Jeltsch, Albert, Jiang, Fan, Josse, Claire, Jurman, Giuseppe, Kamiya, Haruyuki, Keersmaecker, Kim de, Kristiansson, Erik, Leeuw, Frank-Erik de, Li, Jiuyong, Liang, Shide, Lopez-Escamez, Jose A., Lopez-Ruiz, Francisco J., Marchbank, Kevin J., Marschalek, Rolf, Martín, Carmen S., Miele, Adriana E., Montagutelli, Xavier, Morcillo, Esteban, Nicoletti, Rosario, Niehof, Monika, O’Toole, Ronan, Ohtomo, Toshihiko, Oster, Henrik, Palma, Jose-Alberto, Paterson, Russell, Peifer, Mark, Portilla, Maribel, Portillo, M. C., Pritchard, Antonia L., Pusch, Stefan, Raghava, Gajendra P. S., Roberts, Nicola J., Ross, Kehinde, Schuele, Birgitt, Sergeant, Kjell, Shen, Jun, Stella, Alessandro, Sukocheva, Olga, Uversky, Vladimir N., Vanneste, Sven, Villet, Martin H., Viveiros, Miguel, Vorholt, Julia A., Weinstock, Christof, Yamato, Masayuki, Zabetakis, Ioannis, Zhao, Xin, Ziegler, Andreas, Aizat, Wan M., Atlas, Lauren, Bridges, Kristina M., Chakraborty, Sayan, Deschodt, Mieke, Domingues, Helena S., Esfahlani, Shabnam S., Falk, Sebastian, Guisado, J. L., Kane, Nolan C., Kueberuwa, Gray, Lau, Colleen L., Liang, Dai, Liu, Enwu, Luu, Andreas M., Ma, Chuang, Ma, Lisong, Moyer, Robert, Norris, Adam D., Panthee, Suresh, Parsons, Jerod R., Peng, Yousong, Pinto, Inês Mendes, Reschke, Cristina R., Sillanpää, Elina, Stewart, Christopher J., Uhle, Florian, Yang, Hui, Zhou, Kai, Zhu, Shu, Ashry, Mohamed, Bergsland, Niels, Berthold, Maximilian, Chen, Chang-Er, Colella, Vito, Cuypers, Maarten, Eskew, Evan A., Fan, Xiao, Gajda, Maksymilian, Gonzálezlez-Prendes, Rayner, Goodin, Amie, Graham, Emily B., Groen, Ewout J. N., Gutiérrez-Sacristán, Alba, Habes, Mohamad, Heffler, Enrico, Higginbottom, Daniel B., Janzen, Thijs, Jayaraman, Jayakumar, Jibb, Lindsay A., Jongen, Stefan, Kinyanjui, Timothy, Koleva-Kolarova, Rositsa G., Li, Zhixiu, Liu, Yu-Peng, Lund, Bjarte A., Lussier, Alexandre A., Ma, Liping, Mier, Pablo, Moore, Matthew D., Nagler, Katja, Orme, Mark W., Pearson, James A., Prajapati, Anilkumar S., Saito, Yu, Tröder, Simon E., Uchendu, Florence, Verloh, Niklas, Voutchkova, Denitza D., Abu-Zaid, Ahmed, Bakkach, Joaira, Baumert, Philipp, Dono, Marcos, Hanson, Jack, Herbelet, Sandrine, Hobbs, Emma, Kulkarni, Ameya, Kumar, Narendra, Liu, Siqi, Loft, Nikolai D., Reddan, Tristan, Senghore, Thomas, Vindin, Howard, Xu, Haotian, Bannon, Ross, Chen, Branson, Cheung, Johnny T. K., Cooper, Jeffrey, Esnakula, Ashwini K., Feghali, Karine A., Ghelardi, Emilia, Gnasso, Agostino, Horbar, Jeffrey, Lai, Hei M., Li, Jian, Ma, Lan, Ma, Ruiyan, Pan, Zihang, Peres, Marco A., Pranata, Raymond, Seow, Esmond, Sydes, Matthew, Testoni, Ines, Westermair, Anna L., Yang, Yongliang, Afnan, Masoud, Albiol, Joan, Albuquerque, Lucia G., Amiya, Eisuke, Amorim, Rogerio M., An, Qianli, Andersen, Stig U., Aplin, John D., Argyropoulos, Christos, Asmann, Yan W., Assaeed, Abdulaziz M., Atanasov, Atanas G., Atchison, David A., Avery, Simon V., Avillach, Paul, Baade, Peter D., Backman, Lars, Badie, Christophe, Baldi, Alfonso, Ball, Elizabeth, Bardot, Olivier, Barnett, Adrian G., Basner, Mathias, Batra, Jyotsna, Bazanova, O. M., Beale, Andrew, Beddoe, Travis, Bell, Melanie L., Berezikov, Eugene, Berners-Price, Sue, Bernhardt, Peter, Berry, Edward, Bessa, Theolis B., Billington, Craig, Birch, John, Blakely, Randy D., Blaskovich, Mark A. T., Blum, Robert, Boelaert, Marleen, Bogdanos, Dimitrios, Bosch, Carles, Bourgoin, Thierry, Bouvard, Daniel, Boykin, Laura M., Bradley, Graeme, Braun, Daniel, Brownlie, Jeremy, Brühl, Albert, Burt, Austin, Butler, Lisa M., Byrareddy, Siddappa N., Byrne, Hugh J., Cabantous, Stephanie, Calatayud, Sara, Candal, Eva, Carlson, Kimberly, Casillas, Sònia, Castelvetro, Valter, Caswell, Patrick T., Cavalli, Giacomo, Cerovsky, Vaclav, Chagoyen, Monica, Chen, Chang-Shi, Chen, Dong F., Chen, Hao, Chen, Hui, Chen, Jui-Tung, Chen, Yinglong, Cheng, Changxiu, Cheng, Jianlin, Chinapaw, Mai, Chinopoulos, Christos, Cho, William C. S., Chong, Lillian, Chowdhury, Debashish, Chwalibog, Andre, Ciresi, A., Cockcroft, Shamshad, Conesa, Ana, Cook, Penny A., Cooper, David N., Coqueret, Olivier, Corea, Enoka M., Costa, Elisio, Coupland, Carol, Crawford, Stephanie Y., Cruz, Aparecido D., Cui, Huijuan, Cui, Qiang, Culver, David C., D’Angiulli, Amedeo, Dahms, Tanya E. S., Daigle, France, Dalgleish, Raymond, Danielsen, Håvard E., Darras, Sébastien, Davidson, Sean M., Day, David A., Degirmenci, Volkan, Demaison, Luc, Devriendt, Koenraad, Ding, Jiandong, Dogan, Yunus, Dong, X. C., Donner, Claudio F., Dressick, Walter, Drevon, Christian A., Duan, Huiling, Ducho, Christian, Dumaz, Nicolas, Dwarakanath, Bilikere S., Ebell, Mark H., Eisenhardt, Steffen, Elkum, Naser, Engel, Nadja, Erickson, Timothy B., Fairhead, Michael, Faville, Marty J., Fejzo, Marlena S., Festa, Fernanda, Feteira, Antonio, Flood-Page, Patrick, Forsayeth, John, Fox, Simon A., Franks, Steven J., Frentiu, Francesca D., Frilander, Mikko J., Fu, Xinmiao, Fujita, Satoshi, Galea, Ian, Galluzzi, Luca, Gani, Federica, Ganpule, Arvind P., García-Alix, Antonio, Gedye, Kristene, Giordano, Maurizio, Giunta, Cecilia, Gleeson, Paul A., Goarant, Cyrille, Gong, Haipeng, Gora, Diop, Gough, Michael J., Goyal, Ravinder, Graham, Kathryn E., Grande-Pérez, Ana, Graves, Patricia M., Greidanus, Harm, Grice, Darren, Grunau, Christoph, Gumulya, Yosephine, Guo, Yabin, Gurevich, Vsevolod V., Gusev, Oleg, Hacker, Elke, Hage, Steffen R., Hagen, Guy, Hahn, Steven, Haller, Dagmar M., Hammerschmidt, Sven, Han, Jianwei, Han, Renzhi, Handfield, Martin, Hapuarachchi, Hapuarachchige C., Harder, Timm, Hardingham, Jennifer E., Heck, Michelle, Heers, Marcel, Hew, Khe F., Higuchi, Yohei, Hilaire, Cynthia St, Hilton, Rachel, Hodzic, Enisa, Hone, Andrew, Hongoh, Yuichi, Hu, Guoku, Huber, Heinz P., Hueso, Luis E., Huirne, Judith, Hurt, Lisa, Idborg, Helena, Ikeo, Kazuho, Ingley, Evan, Jakeman, Philip M., Jensen, Arne, Jia, Hong, Jia, Husen, Jia, Shuqin, Jiang, Jianping, Jiang, Xingyu, Jin, Yi, Jo, Daehyun, Johnson, Andrew M., Johnston, Marie, Jonscher, Karen R., Jorens, Philippe G., Jorgensen, Jens O. L., Joubert, Johan W., Jung, Sin-Ho, Junior, Antonio M., Kahan, Thomas, Kamboj, Sunjeev K., Kang, Yong-Kook, Karamanos, Yannis, Karp, Natasha A., Kelly, Ryan, Kenna, Ralph, Kennedy, Jonathan, Kersten, Birgit, Khalaf, Roy A., Khalid, Javaria M., Khatlani, T., Khider, Tarig, Kijanka, Gregor S., King, Sarah R. B., Kluz, Tomasz, Knox, Paul, Kobayashi, Tatsuya, Koch, Karl-Wilhelm, Kohonen-Corish, Maija R. J., Kong, Xiangpeng, Konkle-Parker, Deborah, Korpela, Kalevi M., Kostrikis, Leondios G., Kraiczy, Peter, Kratz, Harald, Krause, Günter, Krebsbach, Paul H., Kristensen, Søren R., Kumari, Prerna, Kunimatsu, Akira, Kurdak, Hatice, Kwon, Young D., Lachat, Carl, Lagisz, Malgorzata, Laky, Brenda, Lammerding, Jan, Lange, Matthias, Larrosa, Mar, Laslett, Andrew L., LeClair, Elizabeth E., Lee, Kyung-Woo, Lee, Ming-Yih, Lee, Moon-Soo, Li, Genyuan, Li, Jiansheng, Lieb, Klaus, Lim, Yau Y., Lindsey, Merry L., Line, Paul-Dag, Liu, Dengcai, Liu, Fengbin, Liu, Haiyan, Liu, Hongde, Lloyd, Vett K., Lo, Te-Wen, Locci, Emanuela, Loidl, Josef, Lorenzen, Johan, Lorkowski, Stefan, Lovell, Nigel H., Lu, Hua, Lu, Wei, Lu, Zhiyong, Luengo, Gustavo S., Lundh, Lars-Gunnar, Lysy, Philippe A., Mabb, Angela, Mack, Heather G., Mackey, David A., Mahdavi, S. R., Maher, Pamela, Maher, Toby, Maity, Sankar N., Malgrange, Brigitte, Mamoulakis, Charalampos, Mangoni, Arduino A., Manke, Thomas, Manstead, Antony S. R., Mantalaris, Athanasios, Marsal, Jan, Marschall, Hanns-Ulrich, Martin, Francis L., Martinez-Raga, Jose, Martinez-Salas, Encarnacion, Mathieu, Daniel, Matsui, Yoichi, Maza, Elie, McCutcheon, James E., McKay, Gareth J., McMillan, Brian, McMillan, Nigel, Meads, Catherine, Medina, Loreta, Merrick, B. Alex, Metzger, Dennis W., Meunier, Frederic A., Michaelis, Martin, Micheau, Olivier, Mihara, Hisaaki, Mintz, Eric M., Mizukami, Takuo, Moalic, Yann, Mohapatra, D. P., Monteiro, Antonia, Montes, Matthieu, Moran, John V., Morozov, Sergey Y., Mort, Matthew, Murai, Noriyuki, Murphy, Denis J., Murphy, Susan K., Murray, Shauna A., Naganawa, Shinji, Nammi, Srinivas, Nasios, Grigorios, Natoli, Roman M., Nguyen, Frederique, Nicol, Christine, Nieuwerburgh, Filip van, Nilsen, Erlend B., Nobile, Clarissa J., O’Mahony, Margaret, Ohlsson, Sophie, Olatunbosun, Oluremi, Olofsson, Per, Ortiz, Alberto, Ostrikov, Kostya, Otto, Siegmar, Outeiro, Tiago F., Ouyang, Songying, Paganoni, Sabrina, Page, Andrew, Palm, Christoph, Paradies, Yin, Parsons, Michael H., Parsons, Nick, Pascal, Pigny, Paul, Elisabeth, Peckham, Michelle, Pedemonte, Nicoletta, Pellizzon, Michael A., Petrelli, M., Pichugin, Alexander, Pinto, Carlos J. C., Plevris, John N., Pollesello, Piero, Polz, Martin, Ponti, Giovanna, Porcelli, Piero, Prince, Martin, Quinn, Gwendolyn P., Quinn, Terence J., Ramula, Satu, Rappsilber, Juri, Rehfeldt, Florian, Reiling, Jan H., Remacle, Claire, Rezaei, Mohsen, Riddick, Eric W., Ritter, Uwe, Roach, Neil W., Roberts, David D., Robles, Guillermo, Rodrigues, Tiago, Rodriguez, Cesar, Roislien, Jo, Roobol, Monique J., Rowe, J. Alexandra, Ruepp, Andreas, Ruitenbeek, Jan van, Rust, Petra, Saad, Sonia, Sack, George H., Santos, Manuela, Saudemont, Aurore, Sava, Gianni, Schrading, Simone, Schramm, Alexander, Schreiber, Martin, Schuler, Sidney, Schymkowitz, Joost, Sczyrba, Alexander, Seib, Kate L., Shi, Han-Ping, Shimada, Tomohiro, Shin, Jeon-Soo, Shortt, Colette, Silveyra, Patricia, Skinner, Debra, Small, Ian, Smeets, Paul A. M., So, Po-Wah, Solano, Francisco, Sonenshine, Daniel E., Song, Jiangning, Southall, Tony, Speakman, John R., Srinivasan, Mandyam V., Stabile, Laura P., Stasiak, Andrzej, Steadman, Kathryn J., Stein, Nils, Stephens, Andrew W., Stewart, Douglas I., Stine, Keith, Storlazzi, Curt, Stoynova, Nataliya V., Strzalka, Wojciech, Suarez, Oscar M., Sultana, Taranum, Sumant, Anirudha V., Summers, Mathew J., Sun, Gang, Tacon, Paul, Tanaka, Kozo, Tang, Haixu, Tanino, Yoshinori, Targett-Adams, Paul, Tayebi, Mourad, Tayyem, Reema, Tebbe, Christoph C., Telfer, Evelyn E., Tempel, Wolfram, Teodorczyk-Injeyan, Julita A., Thijs, Gert, Thorne, Sally, Thrift, Amanda G., Tiffon, Celine, Tinnefeld, Philip, Tjahjono, Daryono H., Tolle, Fabrice, Toth, Ervin, Tredici, Andria L. del, Tsapas, Apostolos, Tsirigotis, Konstantinos, Turak, Ayse, Tzotzos, George, Udo, Edet E., Utsumi, Toshiaki, Vaidyanathan, Subramanian, Vaillant, Michel, Valsesia, Armand, Vandenbroucke, Roosmarijn E., Veiga, Feliciano H., Vendrell, Marc, Vesk, Peter A., Vickers, Paul, Victor, Victor M., Villemur, Richard, Vohl, Marie-Claude, Voolstra, Christian R., Vuillemin, Anne, Wakelin, Steven, Waldron, Levi, Walsh, Laurence J., Wang, Amanda Y., Wang, Fuan, Wang, Yun, Watanabe, Yoichi, Weigert, Andreas, Wen, Jet-Chau, Wham, Carol, White, Ethan P., Wiener, Jan, Wilharm, Gottfried, Wilkinson, Simon, Willmann, Raffaella, Wilson, Coralie, Wirth, Brunhilde, Wojan, Timothy R., Wolff, Mathieu, Wong, Bryan M., Wu, Tzu-Wei, Wuerbel, Hanno, Xiao, Xiangshu, Xu, Dong, Xu, J. W., Xu, Jianping, Xue, Bin, Yalcin, Suayib, Yan, Hong, Yang, En-Cheng, Yang, Shiqi, Yang, Wei, Ye, Yuzhen, Ye, Zhi-Qiang, Yli-Kauhaluoma, Jari, Yoneyama, Hiroshi, Yu, Ying, Yuan, Guo-Cheng, Yuh, Chiou-Hwa, Zaccolo, Manuela, Zeng, Chen, Zevnik, Branko, Zhang, Chi, Zhang, Li, Zhang, Yingkai, Zhang, Yusen, Zhang, Zhiyong, Zhang, Zhong-Yin, Zhao, Yuan, Zhou, Min, Zuberbier, Torsten, Aanei, Carmen M., Ahmad, Rafi, Al-Lawama, Manar, Alanio, Alexandre, Allardyce, Judith, Alonso-Caneiro, David, Atack, John M., Baier, Dirk, Bansal, Abhisheka, Benezeth, Yannick, Berbesque, Colette, Berrevoet, Frederik, Biedermann, Peter H. W., Bijleveld, Erik, Bittner, Florian, Blombach, Fabian, Bos, Wouter van den, Boudreau, Shellie A., Bramoweth, Adam D., Braubach, Oliver, Cai, Yufeng, Campbell, Matthew, Cao, Zanxia, Catry, Thibault, Chen, Xin, Cheng, Shuiqin, Chung, Hee-Jung, Chávez-Fumagalli, Miguel A., Conway, Aaron, Costa, Bruno M., Cyr, Normand, Dean, Lorraine T., Denzel, Martin S., Dlamini, S. V., Dudley, Kevin J., Dufies, Maeva, Ecke, Thorsten, Eckweiler, Denitsa, Eixarch, Elisenda, El-Adawy, Hosny, Emmrich, Julius V., Eustace, Alex J., Falter-Wagner, Christine M., Fuss, Johannes, Gao, Jianzhao, Gill, Martin R., Gloyn, Liz, Goggs, Robert, Govinden, Usha, Greene, Garrett, Greiff, Victor, Grundle, D. S., Grüneberg, Patrick, Gumede, Nicksy, Haore, Gbaguidi, Harrison, Pille, Hoenner, Xavier, Hojsgaard, Diego, Hori, Hikaru, Ikonomopoulou, Maria P., Jeurissen, Patrick, Johnson, Daniel M., Kabra, Dhiraj, Kamagata, Koji, Karmakar, Chandan, Kasian, Olga, Kaye, Linda K., Khan, Murad M., Kim, Yong-Min, Kish, J. 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P., Takeuchi, Hisashi, Tanadini-Lang, S., Tang, Fei, Tao, Wanyin, Theron, G., Tian, Chang F., Tian, Yu-Shi, Tuttle, Lisa M., Valenti, Anna, Verlot, Pierre, Walker, Mirella, Wang, Jun, Welter, Danielle, Winslade, Matthew, Wu, Dalei, Wu, Yi-Rui, Xiao, Han, Xu, Beisi, Xu, Juan, Xu, Ziyue, Yang, Dongdong, Yang, Mingjun, Yankilevich, Patricio, You, Yuyi, Yu, Chenglong, Zhan, Jian, Zhang, Gong, Zhang, Kai, Zhang, Tuo, Zhang, Yi, Zhao, Guoyan, Zhao, Jing, Zhou, Xiaofan, Zhu, Zhenxing, Ajani, Penelope A., Anazodo, Udunna C., Bagloee, Saeed A., Bail, Kasia, Bar, Ido, Bathelt, Joe, Benkeser, David, Bernier, Meghan L., Blanchard, Adam M., Boakye, Dominic W., Bonatsos, Vasileios, Boon, Michele H., Bouboulis, George, Bromfield, Elizabeth, Brown, Joshua, Bul, Kim C. 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A., Lin, Li, Ling, Tong, Liu, Yuchen, Liu, Zhonghua, Lu, Yao, Lum, Fok M., Luo, Hang, Machhi, Jatin, Macleod, Angus, Macwan, Isaac, Madala, Hanumantha R., Madani, Nima, Maio, Nicola de, Makowiecki, Kalina, Mallinson, Daniel J., Margelyte, Ruta, Maria, Caracausi, Markonis, Y., Marsili, Luca, Mavoa, Suzanne, McWilliams, Lorna, Megersa, Moa, Mendes, Caetano S. M., Menichetti, Julia, Mercieca-Bebber, Rebecca, Miller, Jack J., Minde, David-Paul M., Minges, Alexander, Mishra, Eleanor, Mishra, Virendra R., Moores, Carly, Morrice, Nicola, Moskalensky, Alexander E., Navarin, Nicolò, Negera, Edessa, Nolet, Philippe, Nordberg, Ana, Nordén, Rickard, Nowicki, Jessica P., Olova, Nelly, Olszewski, Paweł, Onzima, Robert, Pan, Chih-Long, Park, Charny, Park, Dong Ik, Park, Seyoung, Patil, Chandrashekhar D., Pedro, Sansoa A., Perry, Samuel R., Peter, Jessica, Peterson, Brent M., Pezzuolo, Andrea, Pozdnyakov, Ilya, Qian, Siyu, Qin, Lei, Rafe, Ali, Raote, Ishier, Raza, Ali, Rebl, Henrike, Refai, Osama, Regan, Tim, Richa, Tambi, Richardson, Mark F., Robinson, K. R., Rossoni, Luca, Rouet, Romain, Safaei, Soroush, Schneeberger, Pierre H. H., Schwotzer, Daniela, Sebastian, Agata, Selinski, Jennifer, Seltmann, Stefanie, Sha, Feng, Shalev, Nir, Shang, Jin-Long, Singer, Josef, Singh, Mandeep, Smith, Taylor, Solomon-Moore, Emma, Song, Lijuan, Soraggi, Samuele, Stanley, Ryan, Steckhan, Nico, Strobl, Frederic, Subissi, Lorenzo, Supriyanto, Irwan, Surve, Chinmay R., Suzuki, Tomo, Syme, Caitlin, Sörelius, Karl, Tang, Young, Tantawy, Marwa, Tennakoon, Sumudu, Teseo, Serafino, Toelzer, Christine, Tomov, Nikola, Tovar, Miguel, Tran, Linh, Tripathi, Sushil, Tuladhar, Anil M., Ukubuiwe, Azubuike C., Ung, Carolina O. L., Valgepea, Kaspar, Vatanparast, Hamid, Vidal, Arnau, Wang, Fang, Wang, Qing, Watari, Ricky, Webster, Rebecca, Webster, Ruth, Wei, Junnian, Wibowo, David, Wingenbach, Tanja S. H., Xavier, Rose M., Xiao, Shumin, Xiong, Peng, Xu, Shicai, Xu, Shilin, Yao, Ruifeng, Yao, Wen, Yin, Qinan, Yu, Yongbo, Zaitsu, Masayoshi, Zhan, Xiao-Yong, Zhang, Jilei, Zhang, Rongqiang, Zhang, Wei, Zhang, Xianglilan, Zheng, Shan, Zhou, Bailing, Zhou, Xiaoyan, Ahmad, Haroon, Akinwumi, Sayo A., Albery, Gregory F., Alhowimel, Ahmed, Ali, Junaid, Alshehri, Mansour, Alsuhaibani, Mohammed, Anikin, Andrey, Azubuike, Samuel O., Bach-Mortensen, Anders, Baltiansky, Lior, Bartas, Martin, Belachew, Kiflemariam Y., Bhardwaj, Vivek, Binder, Karin, Bland, Nicholas S., Boah, Michael, Bullen, Benjamin, Calabrò, Giovanna E., Callahan, Tiffany J., Cao, Bing, Chalmers, Kelsey, Chang, Wei, Che, Zhengping, Chen, Andrew T. Y., Chen, Haimin, Chen, Huaming, Chen, Youning, Chen, Zhao, Choi, YoungRok, Chowdhury, Mohiuddin A. K., Christensen, Martin R., Cooke, Robert S. 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M., Tang, Jun, Testa, Jean, Tian, Zhiqi, Tingting, Qian, Verheijen, Geert P., Vickstrom, Casey, Wang, Teng, Wang, Xiaomin, Wang, Zhenxing, Wei, Pan, Wilson, Alex, Wyart, Yassine, Abdul-Amir, Yousefzadeh, Abbas, Zare, Asma, Zeng, Zhen, Zhang, Chengrong, Zhang, Haowen, Zhang, Linxing, Zhang, Tongchuan, Zhang, Weijia, Zhang, Zhe, Zhou, Jianyu, Zhu, Dongjie, Adamo, Vincenzo, Adeyemo, Adebolajo A., Aggelidou, Maria, Al-Owaifeer, Adi M., Al-Riyami, Arwa Z., Alzghari, Saeed K., Andersen, Vibeke, Angus, Kathryn, Asaduzzaman, Muhammad, Asady, Hadi, Ato, Dai, Bai, Xiaoyong, Baines, Rebecca L., Ballantyne, Maghan, Ban, Bo, Beck, Jill, Ben-Nafa, Walid, Black, Emma, Blancher, Antoine, Blankstein, Ron, Bodagh, Neil, Borges, Paulo A. 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S., Kiyani, Musa, Klein, Reinhild, Kovesi, Tom, Kraschnewski, Jennifer L., Kumar, Addanki P., Labutin, Dmitry, Lazo-Langner, Alejandro, Leclercq, Guy, Li, Maoteng, Li, Qingchun, Li, Tangliang, Li, Yongzhe, Liao, Wei-Ting, Liao, Zheng-yin, Lin, Jessica, Lizer, J., Lobreglio, Giambattista, Lowies, Cher, Lu, Cheng, Majeed, Haroon, Martin, Adam, Martinez-Sobrido, Luis, Meresh, Edwin, Middelveen, Marianne, Mohebbi, Alireza, Mota, Jorge, Mozaheb, Zahra, Muyaya, Ley, Nandhakumar, Amar, Ng, Sheryl H. X., Obeidat, Monther, Oh, Deog-Hwan, Owais, Mohammed, Pace-Asciak, Pia, Panwar, Ajay, Park, Caroline, Patterson, Chris, Penagos-Tabaree, Felipe, Pianosi, Paolo T., Pinzi, Valentina, Pridans, Clare, Psaroulaki, Anna, Pujala, Ravi Kumar, Pulido-Arjona, Leonardo, Qi, Peng-Fei, Rahman, Proton, Rai, Nayanjot K., Rassaf, Tienush, Refardt, Julie, Ricciardi, Walter, Riess, Olaf, Rovas, Alexandros, Sacks, Frank M., Saleh, Sherif, Sampson, Christopher, Schmutz, Axel, Sepanski, Robert, Sharma, Neeraj, Singh, Manisha, Spearman, Paul, Subramaniapillai, Mehala, Swali, Ritu, Tan, Cher M., Tellechea, Juan I., Thomas, Lisa-Marie, Tong, Xin, Vavvas, Demetrios G., Veys, Ralf, Vitriol, Veronica, Wang, Horng-Dar, Wang, Jinhui, Wang, Jiucun, Waugh, Jason, Webb, S. A., Williams, Brendan A., Workman, Alan D., Xiang, Tingxiu, Xie, Li-Xin, Xu, Jun, Xu, Taosheng, Yang, Chongjun, Yoon, Jihoon G., Yuan, Christina M., Zaritsky, Arno, Zhang, Yao, Zhao, Haochen, Zuckerman, Hannah, Lyu, Ran, Pullan, Wayne, Zhou, Yaoqi, Gobet, Angélique, Sadoine, Margaux L., Ontwikkelingspsychologie (Psychologie, FMG), British Lung Foundation, Brown, P, Zhou, Y, Tan, A, El-Esawi, M, Liehr, T, Blanck, O, Gladue, D, Almeida, G, Cernava, T, Sorzano, C, Yeung, A, Engel, M, Chandrasekaran, A, Muth, T, Staege, M, Daulatabad, S, Widera, D, Zhang, J, Meule, A, Honjo, K, Pourret, O, Yin, C, Zhang, Z, Cascella, M, Flegel, W, Goodyear, C, van Raaij, M, Bukowy-Bieryllo, Z, Campana, L, Kurniawan, N, Lalaouna, D, Huttner, F, Ammerman, B, Ehret, F, Cobine, P, Tan, E, Han, H, Xia, W, Mccrum, C, Dings, R, Marinello, F, Nilsson, H, Nixon, B, Voskarides, K, Yang, L, Costa, V, Bengtsson-Palme, J, Bradshaw, W, Grimm, D, Kumar, N, Martis, E, Prieto, D, Sabnis, S, Amer, S, Liew, A, Perco, P, 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- Subjects
Technology and Engineering ,SCIENTIFIC SEARCH ,Expert-curated database ,Biokemia, solu- ja molekyylibiologia - Biochemistry, cell and molecular biology ,Databases ,RElevant LIterature SearcH consortium ,Medicine and Health Sciences ,Biomedical research ,benchmarking ,Biology ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) ,Settore MED/42 - IGIENE GENERALE E APPLICATA ,database ,Computer. Automation ,Science & Technology ,0804 Data Format ,relisch ,Scientific research in health sciences ,Mathematics and Statistics ,litearture search ,relisch , database ,biomedical research ,Biomedical literature ,Original Article ,RELISH ,Mathematical & Computational Biology ,RECOMMENDER-SYSTEMS ,Life Sciences & Biomedicine ,Mathematics ,0807 Library and Information Studies - Abstract
Made available in DSpace on 2020-12-11T01:57:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-10-29 Griffith University Gowonda HPC Cluster Queensland Cyber Infrastructure Foundation Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research. Griffith Univ, Sch Informat & Commun Technol, Gold Coast, Qld 4222, Australia Griffith Univ, Inst Glyc, Gold Coast, Qld 4222, Australia Univ Colorado, Dept Med Med Oncol, Anschutz Med Campus, Denver, CO USA Tanta Univ, Fac Sci, Bot Dept, Tanta, Egypt Friedrich Schiller Univ, Jena Univ Hosp, Inst Human Genet, Jena, Germany Univ Med Ctr Schleswig Holstein, Dept Radiat Oncol, Campus Kiel, Kiel, Germany ARS, USDA, Plum Isl Anim Dis Ctr, Greenport, NY 11944 USA Univ Jyvaskyla, Dept Biol & Environm Sci, Jyvaskyla, Finland Graz Univ Technol, Inst Environm Biotechnol, Graz, Austria CSIC, CNB, Natl Biotechnol Ctr, Dept Macromol Struct, Madrid, Spain Univ Hong Kong, Fac Dent, Oral & Maxillofacial Radiol Appl Oral Sci & Commu, Hong Kong, Peoples R China Univ Kansas, Div Entomol, Biodivers Inst, Lawrence, KS 66045 USA SUNY Albany, RNA Inst, Albany, NY 12222 USA Robert Koch Inst, Dept Methods Dev & Res Infrastruct, Berlin, Germany Martin Luther Univ Halle Wittenberg, Dept Surg & Conservat Pediat & Adolescent Med, Halle, Germany Indiana Univ Purdue Univ, IU Sch Informat & Comp, Dept BioHlth Informat, Indianapolis, IN 46202 USA Univ Reading, Sch Pharm Stem Cell Biol & Regenerat Med, Reading, Berks, England Dali Univ, Sch Engn, Dali City, Yunnan, Peoples R China Univ Hosp Munich LMU, Dept Psychiat & Psychotherapy, Munich, Germany Univ Tsukuba, Fac Life & Environm Sci, Ibaraki, Japan UniLaSalle, Aghyle, Beauvais, France Henry Ford Hlth Syst, Dept Immunol, Detroit, MI USA Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Emergency, Hangzhou 310016, Zhejiang, Peoples R China Ist Nazl Tumori Fdn Pascale IRCCS, Anesthesia & Pain Med, Naples, Italy NIH, Dept Transfus Med, Bethesda, MD USA Univ Glasgow, Inst Infect Immun & Inflammat, Glasgow, Lanark, Scotland Polish Acad Sci, Inst Human Genet, Poznan, Poland Univ Padua, Dept Surg Oncol & Gastroenterol DISCOG, Padua, Italy Eindhoven Univ Technol, Biomed Engn, Eindhoven, Netherlands Univ Strasbourg, IBMC, Strasbourg, France Heidelberg Univ, Dept Gen Visceral & Transplantat Surg, Heidelberg, Germany Univ Notre Dame, Psychol, Notre Dame, IN 46556 USA Harvard Med Sch, Massachusetts Gen Hosp, Radiol & Pathol, Boston, MA 02115 USA Auburn Univ, Dept Biol Sci, Auburn, AL 36849 USA KK Womens & Childrens Hosp, KK Res Ctr, Singapore, Singapore Univ Alabama, Educ Psychol, Tuscaloosa, AL USA UCL, Wellcome EPSRC Ctr Intervent & Surg Sci, London, England Maastricht Univ, Dept Nutr & Movement Sci, Maastricht, Netherlands Univ Arkansas Med Sci, Dept Radiat Oncol, Little Rock, AR 72205 USA Univ Padua, Dept Land Environm Agr & Forestry, Padua, Italy Univ Gothenburg, Dept Biol & Environm Sci, Gothenburg, Sweden Univ Newcastle, Prior Res Ctr Reprod Sci, Callaghan, NSW, Australia Univ Cyprus, Med Sch, Nicosia, Cyprus Shandong Agr Univ, Coll Plant Protect, Agr Big Data Res Ctr, Tai An, Shandong, Peoples R China NIMH, Neuropsychol Lab, Bldg 9, Bethesda, MD 20892 USA Univ Wisconsin, Wisconsin Inst Discovery, Madison, WI USA Univ Oxford, Struct Genom Consortium, Oxford, England Weihenstephan Triesdorf Univ Appl Sci, TUM Campus Straubing Biotechnol & Sustainabil, Bioinformat, Straubing, Germany Univ Michigan, Cardiovasc Res, Ann Arbor, MI 48109 USA Bombay Coll Pharm, Pharmaceut Chem, Mumbai, Maharashtra, India Inst Invest Biol Clemente Estable, Dev Neurobiol, Montevideo, Uruguay Gem Hosp & Res Ctr, Surg Gastroenterol & HPB Surg, Coimbatore, Tamil Nadu, India Kafr El Sheikh Univ, Fac Sci, Dept Zool, Kafr Al Sheikh, Egypt Med Univ Innsbruck, Dept Internal Med 4, Innsbruck, Austria Australian Natl Univ, Div Biomed Sci & Biochem, Canberra, ACT, Australia Univ Cattolica Sacro Cuore, Appl Technol Neuropsychol Lab, Milan, Italy Shandong Inst Parasit Dis, Med Entomol, Jinan, Shandong, Peoples R China Kumamoto Univ, Sch Pharm, Kumamoto, Japan Nagoya City Univ, Grad Sch Pharmaceut Sci, Dept Biol Chem, Nagoya, Aichi, Japan Univ Karachi, ICCBS, PCMD, Jamil ur Rahman Ctr Genome Res, Karachi 75270, Pakistan Labormed Zentrum Dr Risch, Vaduz, Liechtenstein Univ Otago, Med, Dunedin, New Zealand KK Womens & Childrens Hosp, Maternal Fetal Med, Singapore, Singapore Albert Ludwigs Univ Freiburg, GERN Tissue Replacement Regenerat & Neogenesis, Dept Orthoped & Trauma Surg, Med Ctr,Fac Med, Freiburg, Germany Heinrich Heine Univ, Inst Biochem & Mol Biol, Dusseldorf, Germany Natl Univ Ireland Galway, Surg, Galway, Ireland Univ Western Australia, Inst Agr, Perth, WA, Australia Univ Oxford, Nuffield Dept Med, Oxford, England SingHlth Polyclin, Punggol Polyclin, Singapore, Singapore Med Univ Innsbruck, Bioctr, Div Biol Chem, Innsbruck, Austria La Trobe Univ, La Trobe Inst Mol Sci, Biochem & Genet, Melbourne, Vic, Australia Univ Bordeaux, INRA, Bordeaux, France Agr & Agri Food Canada, Lethbridge Res & Dev Ctr, Lethbridge, AB, Canada St George Hosp, Trauma & Orthopaed, London, England Max Planck Inst Dev Biol, Dept Prot Evolut, Tubingen, Germany Med Univ Lublin, Dept Gynaecol 2, Lublin, Poland ICIT, ICSI Analyt Natl Res & Dev, Ramnicu Valcea, VL, Romania Univ KwaZulu Natal, Occupat Therapy, Westville Campus, Durban, South Africa Inst Canc Res, Joint Dept Phys, London, England Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden Wenzhou Med Univ, Affiliated Hosp 2, Orthopaed, Wenzhou, Zhejiang, Peoples R China Univ Republica, Fac Ciencias, Ctr Invest Nucl, Lab Virol Mol, Montevideo, Uruguay Univ Gothenburg, Dept Med Biochem & Cell Biol, Gothenburg, Sweden Charite Med Univ Berlin, Pediat Cardiol, Berlin, Germany Bambino Gesu Pediat Hosp, Dept Neurosci & Neurorehabil, Neurorehabil Unit, Rome, Italy Indiana Univ Sch Med Northwest, Microbiol & Immunol, Gary, IN USA Univ Regensburg, Dept Behav & Mol Neurobiol, Regensburg, Germany Univ Queensland, Diamantina Inst, Brisbane, Qld, Australia Translat Res Inst, Brisbane, Qld, Australia Univ Hong Kong, Sch Biomed Sci, Hong Kong, Peoples R China St Jude Childrens Res Hosp, Pharmaceut Sci Dept, 332 N Lauderdale St, Memphis, TN 38105 USA Univ Durham, Mus, Durham, England Univ Ioannina, Med Sch, Dept Hyg & Epidemiol, Ioannina, Greece Tech Univ Munich, Sch Life Sci Weihenstephan, Maximus von Imhof Forum 3, D-85354 Freising Weihenstephan, Germany Univ Hosp Essen, Inst Transfus Med, Essen, Germany Virginia Commonwealth Univ, Comp Sci, Richmond, VA USA Univ Queensland, Inst Social Sci Res, Brisbane, Qld, Australia Univ Lyon, Ctr Int Rech Infectiol, Lyon, France Griffith Univ, Sch Allied Hlth Sci, Gold Coast, Qld, Australia Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic, Australia Indiana Univ Purdue Univ, Dept Biohlth Informat, Sch Informat & Comp, Indianapolis, IN 46202 USA Philipps Univ Marburg, Inst Lung Res, Marburg, Germany Indiana Univ, Dept Biol, Bloomington, IN USA Univ Florida, Oral Biol, Gainesville, FL USA Univ Colorado, Dept Biochem, Boulder, CO 80309 USA Kyoto Univ, Ctr Promot Interdisciplinary Educ & Res, Kyoto, Japan Friedrich Loeffler Inst, Inst Virus Diagnost, Greifswald, Germany Univ Oxford, Dept Zool, Oxford, England Tech Univ Munich, Dept Bioinformat, Munich, Germany Univ Adelaide, Sch Anim & Vet Sci, Adelaide, SA, Australia Stanford Univ, Canc Biol, Palo Alto, CA 94304 USA Covenant Univ, Dept Elect & Informat Engn, Ota, Nigeria Heinrich Heine Univ, Inst Stem Cell Res & Regenerat Med, Dusseldorf, Germany Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC, Canada Albert Einstein Coll Med, Psychiat, New York, NY USA Akdeniz Univ, Med Biol & Genet, Antalya, Turkey NIMH, NIH, Bethesda, MD 20892 USA Med Univ Hosp, Internal Med 1, Tubingen, Germany NET ESolut, Netelabs, Mclean, VA USA Univ Southern Denmark, Inst Publ Hlth, Odense, Denmark John Innes Ctr, Mol Microbiol, Norwich, Norfolk, England Univ Adelaide, Waite Res Precinct, Australian Res Council, Ctr Excellence Plant Energy Biol, Adelaide, SA, Australia Univ Cambridge, Cambridge Inst Publ Hlth, Cambridge, England Univ Munster, Inst Biochem, Munster, Germany Australian Natl Univ, Natl Ctr Epidemiol & Populat Hlth RSPH, Canberra, ACT, Australia Stanford Univ, Neurobiol & Bioengn, Palo Alto, CA 94304 USA Univ Birmingham, Geog Earth & Environm Sci, Birmingham, W Midlands, England Murdoch Univ, Sch Vet & Life Sci, Perth, WA, Australia George Mason Univ, Ctr Climate Change Commun, Fairfax, VA 22030 USA Univ Adelaide, Sch Agr Food & Wine, Adelaide, SA, Australia Southern Med Univ, Sch Pharmaceut Sci, Guangzhou, Guangdong, Peoples R China Stanford Univ, Pathol, Palo Alto, CA 94304 USA Univ Bologna, Dept Expt Diagnost & Specialty Med, Bologna, Italy Univ Padua, Dept Gen Psychol, Padua, Italy Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Dept Bioinformat & Syst Biol, Key Lab Mol Biophys,Minist Educ, Wuhan, Hubei, Peoples R China Huazhong Univ Sci & Technol, Collaborat Innovat Ctr Biomed Engn, Wuhan, Hubei, Peoples R China Queensland Univ Technol, Sch Biomed Sci, Brisbane, Qld, Australia French Natl Ctr Sci Res, CNRS, Inst Biol Physicochim, Paris, France Univ Warwick, Dept Sociol, Coventry, W Midlands, England European Mol Biol Lab, Struct & Computat Biol, Heidelberg, Germany Univ Cincinnati, Coll Med, Canc Biol, Cincinnati, OH USA Univ Waterloo, Biol, Waterloo, ON, Canada Sorbonne Univ, CNRS, Integrat Biol Marine Models LBI2M, SBR, Roscoff, France Univ Manitoba, Biochem & Med Genet, Winnipeg, MB, Canada Max Planck Inst Solid State Res, Ultrafast Solid State Spect, Stuttgart, Germany Imperial Coll London, Sch Publ Hlth, Dept Infect Dis Epidemiol, London, England Mansoura Univ, Fac Vet Med, Biochem, Mansoura, Egypt Univ Virginia, Mol Physiol & Biol Phys, Charlottesville, VA USA China Univ Geosci, State Key Lab Biogeol & Environm Geol, Wuhan, Hubei, Peoples R China Clin Neurol & Psychiat Children & Youth, Child Psychiat, Belgrade, Serbia Ahvaz Jundishapur Univ Med Sci, Med Phys, Ahwaz, Iran Univ Iowa City, Coll Dent, Div Biostat & Computat Biol, Dept Prevent & Community Dent, Iowa City, IA USA Univ Iowa City, Coll Dent, Div Biostat & Computat Biol, Dept Biomed Engn, Iowa City, IA USA Univ Iowa City, Coll Dent, Div Biostat & Computat Biol, Dept Biostat, Iowa City, IA USA Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany Univ Ibadan, Dept Zool, Ibadan, Nigeria Kansas State Univ, Coll Vet Med, Manhattan, KS 66506 USA Univ Tasmania, Sch Technol Environm & Design, Discipline ICT, Hobart, Tas, Australia Childrens Mercy Hosp, Radiol, Kansas City, MO 64108 USA Stockholm Univ, Dept Phys, Stockholm, Sweden Oslo Univ Hosp, Inst Canc Genet & Informat, Oslo, Norway CSIRO, CSIRO Mfg, Pullenvale, Qld, Australia Johns Hopkins Sch Med, Urol, Baltimore, MD USA Univ South Africa, Life & Consumer Sci, Johannesburg, South Africa German Ctr Neurodegenerat Dis, Mech Induced Plast Brain, Bonn, Germany UCL, Inst Child Hlth, Dev Biol & Canc, London, England Simon Fraser Univ, Biomed Physiol & Kinesiol, Burnaby, BC, Canada Univ Manchester, Ctr Hlth Informat, Manchester, Lancs, England Univ Queensland, Sch Human Movement & Nutr Sci, Brisbane, Qld, Australia Albert Einstein Coll Med, Dept Med, New York, NY USA Georgetown Univ, Kennedy Inst Eth, Washington, DC 20057 USA Dermatol Skin & Canc Fdn, Carlton, Vic, Australia Med Coll Wisconsin, Div Hematol, Milwaukee, WI 53226 USA Med Coll Wisconsin, Div Oncol, Milwaukee, WI 53226 USA Med Coll Wisconsin, Div Infect Dis, Milwaukee, WI 53226 USA US FDA, Off Biotechnol Prod, Washington, DC 20204 USA Worcester Polytech Inst, Biomed Engn, Worcester, MA 01609 USA Univ Adelaide, Ctr Orthopaed & Trauma Res, Adelaide, SA, Australia Publ Hlth England, Natl Infect Serv, Bristol, Avon, England Univ Utrecht, Fac Sci Chem, Utrecht, Netherlands Natl Univ Ireland Galway, Pathol, Galway, Ireland Imperial Coll London, NHLI, London, England Danube Private Univ, Neurodegenerat, Krems Donau, Austria Imperial Coll London, Dept Chem, London, England Univ Helsinki, Finnish Museum Nat Hist, Helsinki, Finland Univ Sydney, Sch Life & Environm Sci, Sydney, NSW, Australia Univ Nottingham, Nottingham Digest Dis Ctr, Nottingham, England Univ Toulouse, CNRS, ITAV, USR3505, Toulouse, France ASCR, Inst Mol Genet, CZ Openscreen, Prague, Czech Republic Univ Turku, Inst Biomed, Turku, Finland York Univ, Sch Kinesiol & Hlth Sci, Toronto, ON, Canada Univ Calif Los Angeles, Stein Eye Inst, Ophthalmol, Los Angeles, CA USA Agr & Agri Food Canada, Ottawa Res & Dev Ctr, Ottawa, ON, Canada Helmholtz Zentrum Geesthacht, Mat Design & Characterizat, Geesthacht, Germany Unvers Genova, Internal Med, Genoa, Italy Otto von Guericke Univ, Intelligent Catheter INKS, Magdeburg, Germany Univ Toledo, Canc Biol, 2801 W Bancroft St,Hlth Sci Campus, Toledo, OH 43606 USA CRUK Beatson Inst, Struct Biol, Glasgow, Lanark, Scotland Leibniz Inst Primate Res, Med RNA Biol, Gottingen, Germany Univ Limoges, PEIRENE, EA 7500, Limoges, France Hainan Univ, Vet Med, Haikou, Hainan, Peoples R China UCL, Sch Pharam, Pharmacognosy & Phytotherapy, London, England Univ Oulu, Ecol & Genet Res Unit, Oulu, Finland Rhein Westfal TH Aachen, Inst Biochem & Mol Immunol, Aachen, Germany Univ Stuttgart, Inst Biochem & Tech Biochem, Stuttgart, Germany Peking Univ, Shenzhen Grad Sch, Sch Chem Biol & Biotechnol, Shenzhen, Peoples R China GIGA Res Inst, Med Oncol, Liege, Belgium CHULiege, Liege, Belgium Fdn Bruno Kessler, MPBA, Trento, Italy Hokkaido Univ, Grad Sch Med, Dept Neurobiol, Sapporo, Hokkaido, Japan Univ Leuven, Oncol, Leuven, Belgium Chalmers Univ Technol, Dept Math Sci, Gothenburg, Sweden Radboud Univ Nijmegen, Med Ctr, Dept Neurol, Nijmegen, Netherlands Univ South Australia, Sch Informat Technol & Math Sci, Adelaide, SA, Australia Bio Thera Solut Ltd, Dept Computat Biol, Guangzhou, Guangdong, Peoples R China Inst Invest Biosanitario Granada IBS, Otolaryngol, Granada, Spain Curtin Univ, Sch Mol & Life Sci, Perth, WA, Australia Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England Goethe Univ, Biol DCAL, Inst Pharm, Frankfurt, Germany Univ Lyon, ICBMS, UMR 5246, Lyon, France Inst Pasteur, Dept Genomes & Genet, Paris, France Univ Valencia, Pharmacol, Valencia, Spain Council Agr Res & Econ, Res Ctr Olive Citrus & Tree Fruit, Caserta, Italy Fraunhofer Inst Toxicol & Expt Med ITEM, Preclin Pharmacol & Vitro Toxicol, Hannover, Germany Univ Tasmania, Sch Med, Hobart, Tas, Australia Chugai Pharmaceut Co Ltd, Oncol Lifecycle Management Dept, Tokyo, Japan Univ Lubeck, Inst Neurobiol, Lubeck, Germany NYU, Sch Med, Neurol, New York, NY USA Univ Putra Malaysia, Dept Plant Pathol, Seri Kembangan, Malaysia Univ N Carolina, Biol, Chapel Hill, NC 27515 USA Univ Southampton, Fac Hlth Sci, Southampton, Hants, England Univ Highlands & Islands, Genet & Immunol Res Grp, Inverness, Scotland Heidelberg Univ, Inst Pathol, Heidelberg, Germany Indraprastha Inst Informat Technol, Dept Computat Biol, New Delhi, India Glasgow Caledonian Univ, Sch Hlth & Life Sci, Glasgow, Lanark, Scotland Liverpool John Moores Univ, Pharm & Biomol Sci, Liverpool, Merseyside, England Parkinsons Inst & Clin Ctr, Basic Res, Sunnyvale, CA USA Luxembourg Inst Sci & Technol, Environm Res & Innovat, Luxembourg, Luxembourg Univ Wollongong, Sch Comp & Informat Technol, Wollongong, NSW, Australia Univ Bari Aldo Moro, Dept Biomed Sci & Human Oncol, Bari, Italy Flinders Univ S Australia, Coll Nursing & Hlth Sci, Adelaide, SA, Australia Univ S Florida, Mol Med, Tampa, FL USA Univ Texas Dallas, Behav & Brain Sci, Richardson, TX 75083 USA Rhodes Univ, Zool & Entomol, Grahamstown, South Africa Univ Nova Lisboa, Inst Higiene & Med Trop, Lisbon, Portugal Swiss Fed Inst Technol, Inst Microbiol, Zurich, Switzerland Inst Ulm, German Red Cross Blood Serv, Immunohaematol, Ulm, Germany Tokyo Womens Med Univ, Inst Adv Biomed Engn & Sci, Tokyo, Japan Univ Limerick, Biol Sci, Limerick, Ireland McGill Univ, Dept Anim Sci, Montreal, PQ, Canada StatSol, Lubeck, Germany Univ KwaZulu Natal, Sch Math Stat & Comp Sci, Pietermaritzburg, South Africa Univ Kebangsaan Malaysia, Inst Syst Biol INBIOSIS, Bangi, Malaysia NIH, Natl Ctr Complementary & Integrat Hlth, Bldg 10, Bethesda, MD 20892 USA Univ Kansas, Med Ctr, Family Med Res Div, Kansas City, KS 66103 USA ASTAR, Inst Mol & Cell Biol, Multimodal Mol Biol, Singapore, Singapore Univ Leuven, Dept Chron Dis Metab & Ageing, Leuven, Belgium Int Iberian Nanotechnol Lab INL, Braga, Portugal Anglia Ruskin, Comp & Technol, Cambridge, England Max Planck Inst Biochem, Struct Cell Biol, Planegg, Germany Univ Seville, Dept Comp Architecture & Technol, Seville, Spain Univ Colorado, EBIO, Boulder, CO 80309 USA Univ Manchester, Canc Sci, Manchester, Lancs, England Australian Natl Univ, Res Sch Populat Hlth, Canberra, ACT, Australia Singapore MIT Alliance Res & Technol, Biosyst, Singapore, Singapore Australian Catholic Univ, Mary MacKillop Inst Hlth Res, Musculoskeletal Hlth & Ageing Res Program, Melbourne, Vic, Australia Ruhr Univ Bochum, Gen Surg, St Josef Hosp, Bochum, Germany Northwest A&F Univ, Coll Life Sci, Xianyang, Shaanxi, Peoples R China Australian Natl Univ, Res Sch Biol, Div Plant Sci, Canberra, ACT, Australia Battelle Mem Inst, Clin & Nonclin Res, Columbus, OH USA Southern Methodist Univ, Biol Sci, Dallas, TX 75275 USA Teikyo Univ, Inst Med Mycol, Tokyo, Japan Tempus Labs, Bioinformat, Chicago, IL USA Hunan Univ, Coll Biol, Changsha, Hunan, Peoples R China Inst Cochin, Dept Infect Immun & Inflammat, Paris, France Royal Coll Surgeons Ireland, FutureNeuro Res Ctr Physiol & Med Phys, Dublin, Ireland Univ Jyvaskyla, Gerontol Res Ctr, Jyvaskyla, Finland Heidelberg Univ, Dept Anesthesiol, Heidelberg, Germany Penn State Univ, Biol, University Pk, PA 16802 USA Chinese Acad Sci, Inst Microbiol, State Key Lab Microbial Resources, Beijing, Peoples R China Univ Sci & Technol China, Sch Life Sci, Hefei, Anhui, Peoples R China Michigan State Univ, Anim Sci, E Lansing, MI 48824 USA SUNY Buffalo, Jacobs Sch Med & Biomed Sci, Dept Neurol, Buffalo Neuroimaging Anal Ctr, New York, NY USA Univ Rostock, Inst Biol Sci, Rostock, Germany South China Normal Univ, Sch Environm, Environm Res Inst, Guangzhou, Guangdong, Peoples R China Univ Bari, Dept Vet Med, Bari, Italy Radboud Univ Nijmegen, Med Ctr, Primary & Community Care, Nijmegen, Netherlands EcoHlth Alliance, New York, NY USA Mayo Clin, Cardiovasc Dept, Rochester, MN USA Med Univ Silesia, Sch Med Katowice, Dept Epidemiol, Katowice, Poland Univ Lleida, Anim Sci, Lleida, Spain Univ Florida, Coll Pharm, Pharmaceut Outcomes & Policy, Gainesville, FL USA Pacific Northwest Natl Lab, Earth & Biol Sci Directorate, Richland, WA 99352 USA Univ Edinburgh, Ctr Discovery Brain Sci, Edinburgh, Midlothian, Scotland Harvard Med Sch, Dept Biomed Informat, Boston, MA 02115 USA Univ Penn, Radiol, Philadelphia, PA 19104 USA Humanitas Univ & Res Hosp, Asthma & Allergy Unit, Biomed Sci Personalized Med, Rozzano, Italy Australian Natl Univ, Dept Quantum Sci, Canberra, ACT, Australia Carl von Ossietzky Univ Oldenburg, Ecol Genom, Oldenburg, Germany Int Med Univ, Paediat Dent & Orthodont, Kuala Lumpur, Malaysia Univ Ottawa, Sch Nursing, Ottawa, ON, Canada Maastricht Univ, Dept Educ Support, Maastricht, Netherlands Univ Manchester, Math, Manchester, Lancs, England Kings Coll London, Fac Life Sci & Med, Sch Populat Hlth Sci, London, England Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld, Australia Harbin Med Univ, Publ Hlth Sch, Epidemiol, Harbin, Heilongjiang, Peoples R China UiT Arctic Univ Norway, Dept Chem, Tromso, Norway Cornell Univ, Biol Stat & Computat Biol, Ithaca, NY USA East China Normal Univ, Sch Ecol & Environm Sci, Shanghai Key Lab Urban Ecol Proc & Ecorestorat, Shanghai, Peoples R China Johannes Gutenberg Univ Mainz, Fac Biol, Mainz, Germany Univ Massachusetts, Food Sci, Amherst, MA 01003 USA Max Planck Inst Terr Microbiol, Complex Adapt Traits Res Grp, Marburg, Germany NIHR Biomed Res Ctr Resp, Ctr Exercise & Rehabil Sci, Leicester, Leics, England Yale Univ, Dept Internal Med, Sect Endocrinol, New Haven, CT USA Sardar Patel Univ, Dept Biosci, Anand, Gujarat, India Univ Tokyo, Dept Appl Phys, Tokyo, Japan Univ Cologne, Vivo Res Facil ivRF, Cologne Excellence Cluster Cellular Stress Respon, Cologne, Germany Natl Open Univ Nigeria, Dept Publ Hlth Sci, Lagos, Nigeria Univ Hosp Regensburg, Dept Radiol, Regensburg, Germany Natl Univ Singapore, Geog, Singapore, Singapore Alfaisal Univ, Coll Med, Riyadh, Saudi Arabia Abdelmalek Essaadi Univ, Fac Sci & Techn Tangier, Biomed Genom & Oncogenet Res Lab, Tetouan, Morocco Tech Univ Munich, Fac Sport & Hlth Sci, Exercise Biol Grp, Munich, Germany Univ Santiago de Compostela, Dept Psicoloxia Social Basica & Metodoloxia, Galiza, Spain Griffith Univ, Signal Proc Lab, Brisbane, Qld, Australia Univ Ghent, Dept Neurol, Ghent, Belgium Ghent Univ Hosp, Ghent, Belgium Univ Ghent, Fac Vet Med, Merelbeke, Belgium Albert Einstein Coll Med, Inst Clin & Translat Res, New York, NY USA Anglia Ruskin Univ, Fac Med Sci, Cambridge, England Peking Univ, Coll Chem & Mol Engn, Beijing, Peoples R China Herlev & Gentofte Hosp, Dept Dermatol & Allergy, Hellerup, Denmark Lady Cilento Childrens 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Univ Adelaide, ARCPOH, Adelaide, SA, Australia Pelita Harapan Univ, Fac Med, Cardiol & Vasc Med, Tangerang, Indonesia Inst Mental Hlth, Res Div, Singapore, Singapore UCL, MRC Clin Trials Unit, London, England Univ Padua, Dept Philosophy Sociol Educ & Appl Psychol FISPPA, Padua, Italy Univ Lubeck, Dept Psychiat & Psychotherapy, Lubeck, Germany Dalian Univ Technol, Ctr Mol Med, Dalian, Liaoning, Peoples R China Tianjin United Family Healthcare, Reprod Med, Tianjin, Peoples R China Univ Autonoma Barcelona, Dept Engn Quim Biol & Ambiental, Barcelona, Spain Sao Paulo State Univ UNESP, Dept Anim Sci, Sao Paulo, Brazil Helmholtz Zentrum Munchen, Inst Computat Biol, Canc Syst Biol, Ingolstadter Land Str 1, D-85764 Munich, Germany Univ Tokyo, Dept Cardiovasc Med, Tokyo, Japan Sao Paulo State Univ, Vet Clin, Sao Paulo, Brazil Zhejiang Univ, Inst Biotechnol, Hangzhou, Zhejiang, Peoples R China Aarhus Univ, Dept Mol Biol & Genet, Aarhus, Denmark Univ Manchester, St Marys Hosp, Maternal & Fetal Hlth, Manchester, Lancs, England Univ New Mexico, Internal Med, Albuquerque, NM 87131 USA Mayo Clin, Div Biomed Stat & Informat, Jacksonville, FL 32224 USA King Saud Univ, Plant Prod, Riyadh, Saudi Arabia Polish Acad Sci, Inst Genet & Anim Breeding, Dept Mol Biol, Warsaw, Poland Queensland Univ Technol, Optometry & Vis Sci, Brisbane, Qld, Australia Univ Nottingham, Sch Life Sci, Nottingham, England Canc Council Queensland, Canc Res Ctr, Brisbane, Qld, Australia Umea Univ, Dept Chem, Umea, Sweden Publ Hlth England, Ctr Radiat Chem & Environm Hazards, Bristol, Avon, England Univ Campania L Vanvitelli, DISTABIF, Caserta, Italy Bartshealth, Obstet & Gyanecol, London, England Univ Clermont Auvergne, GReD Lab, Clermont Ferrand, France INRA Abeilles & Environm, Avignon, France Queensland Univ Technol, Sch Publ Hlth & Social Work, Brisbane, Qld, Australia Univ Penn, Psychiat, Philadelphia, PA 19104 USA Novosibirsk State Univ, Res Inst Physiol & Basic Med, Novosibirsk, Russia UCL, Dept Chem, London, England La Trobe Univ, Anim Plant & Soil Sci, Melbourne, Vic, Australia Univ Arizona, Epidemiol & Biostat, Tucson, AZ USA Univ Groningen, Univ Med Ctr Groningen, ERIBA, Groningen, Netherlands Univ Gothenburg, Inst Clin Sci, Dept Radiat Phys, Gothenburg, Sweden SUNY Upstate Med Univ, Biochem & Mol Biol, Syracuse, NY 13210 USA Fundacao Oswaldo Cruz, Ctr Pesquisas Goncalo Moniz, Salvador, Bahia, Brazil Inst Environm Sci & Res ESR, Food Water & Environm Microbiol, Christchurch, New Zealand Univ Otago, Food Sci, Dunedin, New Zealand Florida Atlantic Univ, Biomed Sci, Boca Raton, FL 33431 USA Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia Univ Hosp Wurzburg, Inst Clin Neurobiol, Wurzburg, Germany Inst Trop Med, Publ Hlth, Antwerp, Belgium Univ Thessaly, Sch Hlth Sci, Fac Med, Dept Rheumatol & Clin Immunol, Larisa, Greece Univ Basel, UZB Univ Ctr Dent Med, Dept Orthodont & Pediat Dent, Basel, Switzerland Sorbonne Univ, Museum Natl Hist Nat, Inst Systemat Evolut Biodiversite ISYEB, MNHN,CNRS,UMR 7205,EPHE, Paris, France CNRS, Inst Adv Biosci, Paris, France Univ Western Australia, Sch Mol Sci, Perth, WA, Australia Univ Ft Hare, Biochem & Microbiol, Alice, South Africa Univ Tubingen, Phys, Tubingen, Germany Griffith Univ, Sch Environm & Sci, Brisbane, Qld, Australia Philosoph Theol Hsch Vallendar, Stat & Standardised Methods, Vallendar, Germany Imperial Coll London, Life Sci, London, England Univ Adelaide, Adelaide Med Sch, Adelaide, SA, Australia Univ Nebraska Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE USA Technol Univ Dublin, FOCAS Res Inst, Dublin, Ireland INSERM, Natl Inst Hlth & Med Res, Canc Res Ctr Toulouse, Paris, France Univ Santiago de Compostela, Dept Bioloxia Func, Grp BRAINSHARK, Galiza, Spain Univ Nebraska, Biol, Kearney, NE USA Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona, Spain Univ Pisa, Chem & Ind Chem, Pisa, Italy Univ Manchester, Wellcome Trust Ctr Cell Matrix Res, Manchester, Lancs, England Univ Montpellier, CNRS, Inst Human Genet, Montpellier, France Czech Acad Sci, Inst Organ Chem & Biochem, Prague, Czech Republic CSIC, Natl Ctr Biotechnol CNB, Computat Syst Biol Grp, Madrid, Spain Natl Cheng Kung Univ, Dept Biochem & Mol Biol, Tainan, Taiwan Harvard Med Sch, Schepens Eye Res Inst, Ophthalmol, Boston, MA 02115 USA Lanzhou Univ, Hosp 2, Dept Gen Surg, Lanzhou, Gansu, Peoples R China Univ Technol Sydney, Sch Life Sci, Sydney, NSW, Australia JT Chen Clin, Gynecol, Tokyo, Japan Univ Western Australia, Sch Agr & Environm, Perth, WA, Australia Beijing Normal Univ, Fac Geog Sci, Beijing, Peoples R China Univ Missouri, Elect Engn & Comp Sci, Columbia, MO USA Vrije Univ Amsterdam Med Ctr, Amsterdam Publ Hlth Res Inst, Dept Publ & Occupat Hlth, Amsterdam, Netherlands Semmelweis Univ, Med Biochem, Budapest, Hungary Queen Elizabeth Hosp, Dept Clin Oncol, Hong Kong, Peoples R China Univ Pittsburgh, Chem, Pittsburgh, PA USA GB Pant Inst Post Grad Med Educ & Res, Neurol, New Delhi, India Univ Copenhagen, Vet & Anim Sci, Copenhagen, Denmark Univ Palermo, Biomed Dept Internal & Specialist Med DIBIMIS, Sect Endocrinol, Palermo, Italy UCL, NPP, London, England Univ Florida, Microbiol & Cell Sci, Gainesville, FL USA Univ Salford, Sch Hlth Sci, Manchester, Lancs, England Cardiff Univ, Inst Med Genet, Cardiff, S Glam, Wales INSERM, ICO Canc Ctr, Angers, France Univ Colombo, Fac Med, Microbiol, Colombo, Sri Lanka Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing, Peoples R China Univ Porto, Fac Pharm, Porto, Portugal Univ Nottingham, Div Primary Care, Nottingham, England Univ Illinois, Pharm Syst Outcomes & Policy, Chicago, IL USA Pontificia Univ Catolica Goias, Escola Ciencias Agr & Biol, Goiania, Go, Brazil China Japan Friendship Hosp, Dept Oncol, Beijing, Peoples R China Boston Univ, Chem, Boston, MA 02215 USA Amer Univ, Environm Sci, Washington, DC 20016 USA Carleton Univ, Neurosci, Ottawa, ON, Canada Univ Regina, Chem & Biochem, Regina, SK, Canada Univ Montreal, Microbiolgy, Montreal, PQ, Canada Univ Leicester, Dept Genet & Genome Biol, Leicester, Leics, England Univ Queensland, Sch Agr & Food Sci, Gatton, Qld, Australia CNRS, BIOM, Paris, France UCL, Hatter Cardiovasc Inst, London, England Flinders Univ S Australia, Sci & Engn, Adelaide, SA, Australia Univ Warwick, Engn, Coventry, W Midlands, England Katholieke Univ Leuven, Ctr Human Genet, Leuven, Belgium Fudan Univ, Dept Macromol Sci, Shanghai, Peoples R China Dokuz Eylul Univ, Biol Educ, Izmir, Turkey Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA Mondo Med, Pulm Dis, Borgomanero, Italy US Naval, Res Lab, Ctr Bio Mol Sci & Engn, Washington, DC USA Univ Oslo, Inst Basic Med Sci, Dept Nutr, Oslo, Norway Peking Univ, Dept Mech & Engn Sci, Beijing, Peoples R China Saarland Univ, Dept Pharm Pharmaceut & Med Chem, Saarbrucken, Germany INSERM, Natl Inst Hlth & Med Res, Skin Res Inst, Paris, France Shanghai Proton & Heavy Ion Ctr, Res & Dev, Shanghai, Peoples R China Univ Georgia, Epidemiol, Athens, GA 30602 USA Univ Freiburg, Med Ctr, Dept Plast & Hand Surg, Freiburg, Germany Sidra Med, Res, Doha, Qatar Rostock Univ, Med Ctr, Dept Oral Maxillofacial & Plast Surg, Rostock, Germany Harvard Med Sch, Brigham & Womens Hosp, Emergency Med, Boston, MA 02115 USA AgResearch, Forage Sci, Palmerston North, New Zealand Univ Calif Los Angeles, Med, Los Angeles, CA USA Arizona State Univ, Biodesign Inst, Virginia G Piper Ctr Personalized Diagnost, Tempe, AZ USA Sheffield Hallam Univ, Res Inst, Mat & Engn, Sheffield, S Yorkshire, England Aneurin Bevan Univ Healthboard, Resp Med, Newport, Shrops, England Univ Calif San Francisco, Neurol Surg, San Francisco, CA 94143 USA Univ Western Australia, UWA Dent Sch, Perth, WA, Australia Fordham Univ, Biol Sci, Bronx, NY 10458 USA Univ Helsinki, Inst Biotechnol, Helsinki, Finland Fujian Normal Univ, Coll Life Sci, Fuzhou, Fujian, Peoples R China Univ Fukui, Dept Frontier Fiber Technol & Sci, Fukui, Japan Univ Southampton, Fac Med, Clin & Expt Sci, Southampton, Hants, England Univ Urbino, Dept Biomol Sci, Urbino, Italy Osped San Luigi, Allergol Unit, Turin, Italy Muljibhai Patel Urol Hosp, Dept Urol, Nadiad, Gujarat, India Univ Granada, Stratig & Paleontol, Granada, Spain Massey Univ, Sch Vet Sci, Auckland, New Zealand CNR, High Performance Comp & Networking Inst, Naples, Italy Univ Childrens Hosp Zurich, Div Metab, Zurich, Switzerland Univ Childrens Hosp Zurich, Childrens Res Ctr, Zurich, Switzerland Univ Melbourne, Biochem & Mol Biol, Parkville, Vic, Australia Inst Pasteur, Leptospirosis Res & Expertise Unit, Noumea, New Caledonia Tsinghua Univ, Sch Life Sci, Beijing, Peoples R China Cheikh Anta Diop Univ UCAD, Sci Fac, Biol Anim Dept, Dakar, Senegal Providence Portland Med Ctr, Earle A Chiles Res Inst, Portland, OR USA Agr & Agri Food Canada, Lacombe Res & Dev Ctr, Lacombe, AB, Canada Alberta Innovates, Performance Management & Evaluat, Edmonton, AB, Canada Univ Malaga, CSIC, Inst Hortofruticultura Subtrop Mediterranea La Ma, IHSM,UMA, Malaga, Spain James Cook Univ, Coll Publ Hlth Med & Vet Sci, Cairns, Qld, Australia European Commiss, Joint Res Ctr, Ispra, Italy Univ Montpellier, Montpellier, France CSIRO, Floreat, WA, Australia Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangzhou, Guangdong, Peoples R China Vanderbilt Univ, Pharmacol, 221 Kirkland Hall, Nashville, TN 37235 USA RIKEN, KFU RIKEN Translat Genom Unit, Yokohama, Kanagawa, Japan Univ Tubingen, Neurobiol Vocal Commun, Tubingen, Germany Univ Colorado, UCCS Ctr Biofrontiers Inst, Colorado Springs, CO 80907 USA Fred Hutchinson Canc Ctr, Div Basic Sci, Seattle, WA USA Univ Geneva, Fac Med, Primary Care Unit, Geneva, Switzerland Ernst Moritz Arndt Univ Greifswald, Dept Mol Genet & Infect Biol, Greifswald, Germany East China Univ Sci & Technol, Dept Fine Chem, Shanghai, Peoples R China Ohio State Univ, Surg, Columbus, OH 43210 USA Oragenics, R&D, Tampa, FL USA Natl Environm Agcy, Environm Hlth Inst, Singapore, Singapore Friedrich Loeffler Inst, Inst Diagnost Virol, Greifswald, Germany Queen Elizabeth Hosp, Oncol, Woodville, SA, Australia USDA, Emerging Pests & Pathogens Res Unit, Ithaca, NY USA Univ Freiburg, Med Ctr, Dept Neurosurg, Epilepsy Ctr, Freiburg, Germany Univ Hong Kong, Fac Educ, Informat & Technol Studies, Hong Kong, Peoples R China Univ Tokyo, Grad Sch Agr & life Sci, Agr & Environm Biol, Tokyo, Japan Univ Pittsburgh, Dept Med, Pittsburgh Heart Lung & Blood Vasc Med Inst, Pittsburgh, PA USA Guys & St Thomas NHS Fdn Trust, Directorate Transplant Renal & Urol, London, England Univ Sarajevo, Clin Ctr, Clin Heart Blood Vessel & Rheumat Dis, Sarajevo, Bosnia & Herceg Univ Kent, Sch Math Stat & Actuarial Sci, Canterbury, Kent, England Tokyo Inst Technol, Dept Life Sci & Technol, Tokyo, Japan Univ Appl Sci Munich, Laser Ctr Dept Appl Sci & Mechatron, Munich, Germany CIC NanoGUNE, Nanodevices, San Sebastian, Spain Vrije Univ Amsterdam Med Ctr, Gynaecol, Amsterdam, Netherlands Cardiff Univ, Med Sch, Div Populat Med, Cardiff, S Glam, Wales Karolinska Inst, Dept Med, Solna, Sweden Natl Inst Genet, Ctr Informat Biol, Mishima, Shizuoka, Japan Murdoch Univ, Harry Perkins Inst Med Res, Perth, WA, Australia Univ Limerick, Phys Educ & Sport Sci, Limerick, Ireland Ruhr Univ Bochum, Campus Clin Gynecol, Univ Str, Bochum, Germany Southwest Med Univ, Sch Publ Hlth, Epidemiol & Biostat, Luzhou, Sichuan, Peoples R China Beijing Canc Hosp, Minist Educ Beijing, Key Lab Carcinogenesis & Translat Res, Ctr Mol Diagnost, Beijing, Peoples R China Chinese Acad Sci, Chengdu Inst Biol, Herpetol Dept, Chengdu, Sichuan, Peoples R China Key Lab Nano Biol Effects & Safety, Beijing, Peoples R China NIBR, PK Sci, Basel, Switzerland Daejeon St Marys Hosp, Pain Ctr, Daejeon, South Korea Univ Western Ontario, Sch Hlth Studies, London, ON, Canada Univ Aberdeen, Hlth Psychol Grp, Aberdeen, Scotland Univ Colorado, Anesthesiol, Anschutz Med Campus, Boulder, CO 80309 USA Univ Antwerp, UZA Antwerp Univ Hosp, Crit 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Res Ctr, Stem Cell & Regenerat Med, Riyadh, Saudi Arabia Univ Bahri, Ind Pulp & Paper, Khartoum, Sudan Univ Queensland, Mater Med Res Inst, Mater Res Inst, Brisbane, Qld, Australia Colorado State Univ, NREL, Ft Collins, CO 80523 USA Rzeszow Univ Hosp, Ob Gyn Dept, Rzeszow, Poland Univ Leeds, Fac Biol Sci, Leeds, W Yorkshire, England Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA Carl von Ossietzky Univ Oldenburg, Neurosci, Oldenburg, Germany UNSW, St George & Sutherland Clin Sch, Microbiome Res Ctr, Sydney, NSW, Australia NYU, Sch Med, Dept Biochem, New York, NY 10016 USA NYU, Sch Med, Dept Mol Pharmacol, New York, NY USA Univ Mississippi, Med Ctr, Med Infect Dis, Jackson, MS 39216 USA Tampere Univ, Fac Social Sci Psychol, Tampere, Finland Univ Cyprus, Dept Biol Sci, Nicosia, Cyprus Goethe Univ, Inst Med Microbiol & Infect Control, Frankfurt, Germany Charite Med Univ Berlin, Inst Radiol, Berlin, Germany Univ Cologne, Univ Hosp Cologne, Internal Med 1, Cologne, Germany Univ Calif Los Angeles, Sch Dent, Sect Periodont, Los Angeles, CA 90024 USA Aalborg Univ Hosp, Dept Clin Biochem, Aalborg, Denmark Manipal Acad Higher Educ, Pharm Practice, Manipal, Karnataka, India Univ Tokyo, Inst Med Sci, Dept Radiol, Tokyo, Japan Cukurova Univ, Family Med, Fac Med, Adana, Turkey Catholic Univ Korea, Coll Med, Dept Humanities & Social Med, Seoul, South Korea Univ Ghent, Food Technol Safety & Hlth, Ghent, Belgium UNSW Sydney, Sch Biol Earth & Environm Sci BEES, Sydney, NSW, Australia St Vincent Shoulder & Sports Clin, Res Unit, Vienna, Austria Cornell Univ, Biomed Engn, Ithaca, NY USA Leibniz Inst Plant Genet & Crop Plant Res IPK, Res Grp Bioinformat & Informat Technol, Gatersleben, Germany Univ Europea Madrid, Sch Doctoral Studies, Madrid, Spain CSIRO Mfg, Biomed Mfg, Melbourne, Vic, Australia Depaul Univ, Biol Sci, Chicago, IL 60604 USA Konkuk Univ, Dept Anim Sci & Technol, Seoul, South Korea Chang Gung Univ, Grad Inst Med Mechatron, Taoyuan, Taiwan Korea Univ, Coll Med, Psychiat, Seoul, South Korea Princeton Univ, Chem, Princeton, NJ 08544 USA Henan Univ Chinese Med, Henan Key Lab Chinese Med Resp Dis, Zhengzhou, Henan, Peoples R China Univ Med Ctr Mainz, Dept Psychiat & Psychotherapy, Mainz, Germany Monash Univ Malaysia, Sch Sci, Selangor, Malaysia Univ Mississippi, Med Ctr, Physiol & Biophys, Jackson, MS 39216 USA Univ Oslo, Dept Transplantat Med, Oslo, Norway Sichuan Agr Univ, Triticeae Res Inst, Yaan, Sichuan, Peoples R China Guangzhou Univ Chinese Med, Gastroenterol, Guangzhou, Guangdong, Peoples R China Southeast Univ, Sch Biol Sci & Med Engn, Suzhou, Jiangsu, Peoples R China Mt Allison Univ, Biol, Sackville, NB, Canada Ithaca Coll, Biol, Ithaca, NY 14850 USA Univ Cagliari, Dept Med Sci & Publ Hlth, Monserrato, Italy Univ Vienna, Chromosome Biol, Vienna, Austria Univ Zurich, Nephrol, Zurich, Switzerland Friedrich Schiller Univ, Inst Nutr Sci, Jena, Germany UNSW Sydney, Grad Sch Biomed Engn, Sydney, NSW, Australia Tulane Univ, Sch Med, Biochem & Mol Biol, 1430 Tulane Ave, New Orleans, LA 70112 USA NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA NIH, NCBI, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA LOreal Res & Innovat, Aulnay Sous Bois, France Lund Univ, Dept Psychol, Malmo, Sweden Catholic Univ Louvain, Inst Rech Expt & Clin, Brussels, Belgium Georgia State Univ, Neurosci Inst, Atlanta, GA 30303 USA Univ Melbourne, Ophthalmol, Surg, Parkville, Vic, Australia Univ Western Australia, Ctr Ophthalmol & Visual Sci, Perth, WA, Australia Iran Univ Med Sci, Med Phys, Fac Med, Tehran, Iran Salk Inst Biol Studies, Cellular Neurobiol, La Jolla, CA USA Imperial Coll London, Fibrosis Res Grp, London, England Univ Texas MD Anderson Canc Ctr, Genitourinary Med Oncol, Houston, TX 77030 USA Univ Liege, GIGA Neurosci, Liege, Belgium Univ Crete, Sch Med, Urol, Iraklion, Greece Flinders Univ S Australia, Flinders Med Ctr, Dept Clin Pharmacol, Adelaide, SA, Australia Max Planck Inst Immunobiol & Epigenet, Bioinformat, Breisgau, Germany Cardiff Univ, Sch Psychol, Cardiff, S Glam, Wales Imperial Coll London, Chem Engn, London, England Lund Univ, Skane Univ Hosp, Clin Sci, Malmo, Sweden Sahlgrens Acad, Inst Clin Sci, Dept Mol & Clin Med, Gothenburg, Sweden Univ Cent Lancashire, Sch Pharm & Biomed Sci, Preston, Lancs, England Hosp Univ Doctor Peset, Psychiat & Clin Psychol, Valencia, Spain Ctr Biol Mol Severo Ochoa, Genome Dynam & Funct, Madrid, Spain Unvivers Hosp Lille, Dept Intens Care, Lille, France Kansai Med Univ, Surg, Osaka, Japan Univ Toulouse, Inst Natl Polytech Toulouse, Ecole Natl Super Agron Toulouse, Lab Genom & Biotechnol Fruit, Toulouse, France UiT Arctic Univ Norway, Inst Psychol, Tromsto, Norway Queens Univ, Ctr Publ Hlth, Belfast, Antrim, North Ireland Univ Manchester, Ctr Primary Care & Hlth Serv Res, Manchester, Lancs, England Griffith Univ, Menzies Hlth Inst, Gold Coast, Qld, Australia Anglia Ruskin Univ, FHSCE, Cambridge, England Univ Lleida, Dept Expt Med, Lleida, Spain NIEHS, Biomol Screening Branch, Div Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA Albany Med Coll, Immunol & Microbial Dis, Albany, NY 12208 USA Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia Univ Kent, Sch Biosci, Canterbury, Kent, England Univ Bourgogne Franche Comte, INSERM, LNC, UMR 1231, Besancon, France Ritsumeikan Univ, Coll Life Sci, Dept Biotechnol, Shiga, Japan Kent State Univ, Biol Sci, Kent, OH 44242 USA Natl Inst Infect Dis, Dept Safety Res Blood & Biol Prod, Tokyo, Japan European Inst Marine Studies, Lab Microbiol Extreme Environm, Plouzane, France Univ Iowa, Dept Pharmacol, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA Natl Univ Singapore, Biol Sci, Singapore, Singapore Conservatoire Natl Arts & Metiers, Lab GBA, EA4627, Paris, France Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA Lomonosov Moscow State Univ, Belozersky Inst Physicochem Biol, Moscow, Russia Jikei Univ, Sch Med, Dept Mol Biol, Tokyo, Japan Univ South Wales, Genom & Computat Biol, Treforest, Wales Duke Univ, Med Ctr, Obstet & Gynecol, Durham, NC USA Univ Technol Sydney, Climate Change Cluster, Sydney, NSW, Australia Nagoya Univ, Grad Sch Med, Dept Radiol, Nagoya, Aichi, Japan Western Sydney Univ, Sch Sci & Hlth, Sydney, NSW, Australia TEI Epirus, Dept Speech & Language Therapy, Ioannina, Greece Indiana Univ Purdue Univ, Orthopaed Surg, Indianapolis, IN 46202 USA Oniris, Vet Pathol, Nantes, France Royal Vet Coll, Pathobiol & Populat Sci, Hatfield, Herts, England Univ Ghent, Lab Pharmaceut Biotechnol, Ghent, Belgium Norwegian Inst Nat Res, Terr Ecol, Trondheim, Norway Univ Calif Merced, Mol & Cell Biol, Merced, CA USA Univ Dublin, Trinity Coll Dublin, Sch Engn, Ctr Transport Res, Dublin, Ireland Lund Univ, Inst Clin Sci, Nephrol, Malmo, Sweden Univ Birmingham, Mech Engn, Birmingham, W Midlands, England Lund Univ, Inst Clin Sci, OB GYN, Lund, Sweden Fdn Jimenez Diaz Hosp, Nephrol & Hypertens, Madrid, Spain Queensland Univ Technol, Sch Chem Phys & Mech Engn, Brisbane, Qld, Australia Otto von Guericke Univ, Psychol, Magdeburg, Germany Univ Med Ctr Gottingen, Dept Expt Neurodegenerat, Gottingen, Germany Harvard Med Sch, Spaulding Rehabil Hosp, Phys Med & Rehabil, Boston, MA 02115 USA Quadram Inst Biosci, Sci Operat, Norwich, Norfolk, England Ostbayer Tech Hsch Regensburg OTH Regensburg, Regensburg Med Image Comp ReMIC, Regensburg, Germany Deakin Univ, Fac Arts & Educ, Melbourne, Vic, Australia Univ Warwick, Warwick Med Sch, Coventry, W Midlands, England INSERM, Natl Inst Hlth & Med Res, Biochem & Mol Biol, Paris, France Univ Liege, Tax Inst, Liege, Belgium Univ Leeds, Sch Mol & Cellular Biol, Leeds, W Yorkshire, England IRCCS Ist Giannina Gaslini, UOC Genet Med, Genoa, Italy Res Diets Inc, Sci, New Brunswick, NJ USA Univ Perugia, Dept Phys & Geol, Perugia, Italy Walter Reed Natl Mil Med Ctr, Cellular Immunol, Bethesda, MD USA Univ Fed Santa Catarina, Biol Sci Ctr, Microbiol Immunol & Parasitol Dept, Florianopolis, SC, Brazil Univ Edinburgh, Royal Infirm, Ctr Liver & Digest Disorders, Edinburgh, Midlothian, Scotland Orion Pharma, Crit Care Proprietary Prod Div, Espoo, Finland MIT, Dept Civil & Environm Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA Univ Turin, Dept Vet Sci, Turin, Italy Univ G dAnnunzio, Dept Psychol Hlth & Territorial Sci, Chieti, Italy NYU, Sch Med, OB GYN, New York, NY USA Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland Univ Turku, Dept Biol, Turku, Finland Tech Univ Berlin, Bioanalyt, Berlin, Germany Univ Goettingen, Inst Phys Biophys 3, Gottingen, Germany Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Translat Res Adv Therapeut & Innovat Oncol TRACTI, Houston, TX 77030 USA Univ Liege, Life Sci, Liege, Belgium Tarbiat Modares Univ, Fac Med Sci, Dept Toxicol, Tehran, Iran ARS, USDA, Stoneville, MS USA Univ Regensburg, RCI Regensburg Ctr Intervent Immunol, Regensburg, Germany Univ Nottingham, Sch Psychol, Nottingham, England NIH, Pathol Lab, Bethesda, MD 20892 USA Univ Carlos III Madrid, Elect Engn, Madrid, Spain Inst Med Mol, Chem Biol, Lisbon, Portugal Univ Costa Rica, CIET, San Jose, Costa Rica Univ Stavanger, Fac Hlth Sci, Stavanger, Norway Erasmus MC, Urol, Rotterdam, Netherlands Univ Edinburgh, Sch Biol Sci, Edinburgh, Midlothian, Scotland German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Bioinformat & Syst Biol IBIS, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany Leiden Univ, Huygens Kamerlingh Onnes Lab, Leiden, Netherlands Univ Vienna, Nutr Sci, Vienna, Austria Kolling Inst Med Res, Med, St Leonards, NSW, Australia Johns Hopkins Sch Med, Biol Chem, Baltimore, MD USA Univ Montreal, Med Nutr & Microbiome Lab, Montreal, PQ, Canada GlaxoSmithKline, Cell & Gene Therapy, Stevenage, Herts, England Univ Trieste, Life Sci, Trieste, Italy Rhein Westfal TH Aachen, Dept Radiol, Aachen, Germany Univ Duisburg Essen, Univ Hosp Essen, West German Canc Ctr, Dept Med Oncol, Essen, Germany Med Univ Vienna, Obstet & Gynecol, Vienna, Austria FHI 360, Social & Behav Hlth Sci Div, Washington, DC USA KU Leuven VIB, Switch Lab, Leuven, Belgium Bielefeld Univ, Fac Technol, Bielefeld, Germany Capital Med Univ, Beijing Shijitan Hosp, Dept Clin Nutr, Dept Gastrointestinal Surg, Beijing, Peoples R China Meiji Univ, Dept Agr Chem, Kawasaki, Japan Yonsei Univ, Coll Med, Microbiol, Seoul, South Korea Johnson & Johnson EAME, Maidenhead, Berks, England Penn State Coll Med, Pediat, Hershey, PA USA Univ N Carolina, Dept Social Med, Chapel Hill, NC 27515 USA Univ Western Australia, ARC CoE Plant Energy Biol, Perth, WA, Australia Wageningen Univ, Div Human Nutr & Hlth, Wageningen, Netherlands Kings Coll London, Dept Neuroimaging, London, England Univ Murcia, Biochem & Mol Biol, Murcia, Spain Old Dominion Univ, Dept Biol Sci, Norfolk, VA 23529 USA Monash Univ, Biochem & Mol Biol, Melbourne, Vic, Australia Chinese Acad Sci, Inst Genet & Dev Biol, Beijing, Peoples R China Univ Pittsburgh, Pharmacol & Chem Biol, Pittsburgh, PA USA Univ Lausanne, Ctr Integrat Genom, Lausanne, Switzerland Univ Queensland, Sch Pharm, Brisbane, Qld, Australia Leibniz Inst Plant Genet & Crop Plant Res IPK Gat, Genebank, Gatersleben, Germany Piramal Imaging, Res & Dev, Berlin, Germany Univ Leeds, Civil Engn, Leeds, W Yorkshire, England Univ Missouri, Chem & Biochem, St Louis, MO 63121 USA US Geol Survey, Coastal & Marine Geol Program, Pacific Coastal & Marine Sci Ctr, Santa Cruz, CA USA Ajinomoto Genet Res Inst, Moscow, Russia Jagiellonian Univ, Fac Biochem Biophys & Biotechnol, Dept Plant Biotechnol, Krakow, Poland Univ Puerto Rico, Engn Sci & Mat, Mayaguez, PR USA Univ Regina, Dept Chem & Biochem, Regina, SK, Canada Argonne Natl Lab, Ctr Nanoscale Mat, 9700 S Cass Ave, Argonne, IL 60439 USA Univ Sunshine Coast, Sunshine Coast Mind & Neurosci Thompson Inst, Sippy Downs, Qld, Australia Chinese Peoples Liberat Army Gen Hosp, Dept Gastroenterol & Hepatol, Beijing, Peoples R China Griffith Univ, Griffith Ctr Social & Cultural Res, Gold Coast, Qld, Australia Tohoku Univ, Inst Dev Aging Canc, Dept Mol Oncol, Sendai, Miyagi, Japan Indiana Univ, Comp Sci, Bloomington, IN USA Fukushima Med Univ, Sch Med, Dept Pulm Med, Fukushima, Japan MEDIVIR AB, Biol, Huddinge, Sweden Western Sydney Univ, Neuroimmunol, Sydney, NSW, Australia Univ Jordan, Nutr & Food Technol, Amman, Jordan Thunen Inst Forest Genet, Fed Res Ctr Rura Areas Forestry & Fisheries, Inst Biodivers, Grosshansdorf, Germany Univ Edinburgh, Inst Cell Biol, Edinburgh, Midlothian, Scotland Univ Edinburgh, Ctr Integrat Physiol, Edinburgh, Midlothian, Scotland Univ Toronto, Struct Genom Consortium, Toronto, ON, Canada Canadian Mem Chiropract Coll, Grad Educ & Res, Toronto, ON, Canada Agilent Technol, R&D, Leuven, Belgium Univ British Columbia, Sch Nursing, Vancouver, BC, Canada Monash Univ, Monash Hlth, Sch Clin Sci, Stroke & Ageing Res,Dept Med, Melbourne, Vic, Australia French Natl Canc Inst, Innovat, Transfer, Biol, Boulogne, France Ludwig Maximilians Univ Munchen, Phys Chem, NanoBioSci, Munich, Germany Bandung Inst Technol, Sch Pharm, Med Chem, Bandung, Indonesia Univ Luxembourg, Life Sci Res Unit, Luxembourg, Luxembourg Lund Univ, Skane Univ Hosp, Dept Gastroenterol, Malmo, Sweden Millennium Hlth, Translat Genet, San Diego, CA USA Aristotle Univ Thessaloniki, Med Dept 2, Clin Res & Evidence Based Med Unit, Thessaloniki, Greece Jan Kochanowski Univ Humanities & Sci, Piotrkow Trybunalski Branch, Dept Psychol, Kielce, Poland McMaster Univ, Engn Phys, Hamilton, ON, Canada Marche Polytech Univ, Dept Agr Food & Environm Sci, Ancona, Italy Kuwait Univ, Fac Med, Microbiol, Kuwait, Kuwait Fujita Hlth Univ, Dept Breast Surg, Toyoake, Aich, Japan North West Reg Spinal Injuries Ctr, Spinal Injuries Ctr, Southport, Merseyside, England Luxembourg Inst Hlth, Competence Ctr Methodol & Stat, Luxembourg, Luxembourg Nestle Inst Hlth Sci SA, Metab Hlth, Ecublens, Vaud, Switzerland Ctr Inflammat Res VIB, Ghent, Belgium Univ Ghent, Dept Biomed Mol Biol, Ghent, Belgium Univ Lisbon, Inst Educ, Curriculo Formacao Prof & Tecnol, Lisbon, Portugal Univ Edinburgh, Ctr Inflammat Res, Edinburgh, Midlothian, Scotland Univ Melbourne, Sch BioSci, Parkville, Vic, Australia Northumbria Univ, Comp & Informat Sci, Newcastle Upon Tyne, Tyne & Wear, England Univ Valencia, Endocrinol, Valencia, Spain INRS, Inst Armand Frappier, Laval, PQ, Canada Univ Laval, INAF, Sch Nutr, Quebec City, PQ, Canada Univ Konstanz, Dept Biol, Constance, Germany Univ Cote dAzur, LAMHESS, Nice, France Scion, Syst Ecol, Christchurch, New Zealand CUNY, Grad Sch Publ Hlth & Hlth Policy, Epidemiol & Biostat, New York, NY 10021 USA Univ Queensland, Sch Dent, Brisbane, Qld, Australia George Inst Global Hlth, Renal & Metab Div, Sydney, NSW, Australia Wuhan Univ, Coll Chem & Mol Sci, Wuhan, Hubei, Peoples R China Griffith Univ, Sch Environm & Sci, Gold Coast, Qld, Australia Univ Minnesota, Radiat Oncol, Minneapolis, MN USA Goethe Univ, Fac Med, Frankfurt, Germany Natl Yunlin Univ Sci & Technol, Dept & Grad Sch Safety & Environm Engn, Touliu, Yunlin, Taiwan Massey Univ, Sch Sport Exercise & Nutr, Auckland, New Zealand Univ Florida, Wildlife Ecol & Conservat, Gainesville, FL USA Bournemouth Univ, Dept Psychol, Poole, Dorset, England Robert Koch Inst, Project Grp P2, Berlin, Germany Univ Edinburgh, MRC Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland Univ Basel, Biozentrum, Basel, Switzerland Univ Wollongong, Sch Med, Wollongong, NSW, Australia Univ Cologne, Inst Human Genet, Cologne, Germany Rural Econ Branch, Econ Res Serv, Washington, DC USA Uivers Bordeaux, CNRS, Inst Neurosci Cognit & Integrat Aquitaine, Bordeaux, France Univ Calif Riverside, Dept Chem & Environm Engn, Riverside, CA 92521 USA Univ Calif Riverside, Mat Sci & Engn Program, Riverside, CA 92521 USA Mackay Med Coll, Dept Med, New Taipei, Taiwan Univ Bern, Div Anim Welf, Bern, Switzerland Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Med Sci, Shanghai, Peoples R China McMaster Univ, Biol, Hamilton, ON, Canada Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL USA Hacettepe Univ, Inst Canc, Med Oncol, Ankara, Turkey City Univ Hong Kong, Dept Elect Engn, Hong Kong, Peoples R China Natl Taiwan Univ, Dept Entomol, Taipei, Taiwan Chinese Acad Agr Sci, Inst Environm & Sustainable Dev Agr, Ecol Secur, Beijing, Peoples R China Florida State Univ, Inst Mol Biophys, Chem & Biochem, Tallahassee, FL USA Peking Univ, Shenzhen Grad Sch, State Key Lab Chem Oncogen, Lab Computat Chem & Drug Design, Shenzhen, Peoples R China Univ Helsinki, Fac Pharm, Div Pharmaceut Chem & Technol, Drug Res Program, Helsinki, Finland Tohoku Univ, Microbial Biotechnol, Sendai, Miyagi, Japan Tianjin Med Univ, Sch Basical Med Sci, Dept Pharmacol, Tianjin, Peoples R China Dana Farber Canc Inst, Biostat & Computat Biol, Boston, MA 02115 USA Natl Hlth Res Inst, Inst Mol & Genom Med, Zhunan, Taiwan 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Informat Engn, Xiangtan, Hunan, Peoples R China Univ Hlth Network, Mood Disorders & Psychopharmacol, Toronto, ON, Canada Sao Paulo State Univ UNESP, Dept Anim Sci, Sao Paulo, Brazil Sao Paulo State Univ, Vet Clin, Sao Paulo, Brazil
- Published
- 2019
67. Enhancement of loop-mediated isothermal amplification (LAMP) with guanidine hydrochloride for the detection of Streptococcus equi subspecies equi (Strangles).
- Author
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Knox A and Beddoe T
- Subjects
- Horses, Animals, Sensitivity and Specificity, Streptococcus equi genetics, Streptococcus equi isolation & purification, Reproducibility of Results, DNA, Bacterial genetics, Limit of Detection, Streptococcus, Nucleic Acid Amplification Techniques methods, Nucleic Acid Amplification Techniques veterinary, Horse Diseases diagnosis, Horse Diseases microbiology, Molecular Diagnostic Techniques methods, Streptococcal Infections veterinary, Streptococcal Infections diagnosis, Streptococcal Infections microbiology, Guanidine
- Abstract
Streptococcus equi subspecies equi , commonly referred to as "strangles", poses a significant biosecurity challenge across equine farms worldwide. The continuous prevalence and highly transmissibility of strangles necessitates a rapid and accurate diagnostic procedure. However, current "gold-standard" techniques, such as cultures and quantitative polymerase chain reaction (qPCR), are unreliable or inaccessible, and require lengthy periods between sample collection and results. Moreover, the lack of a standardized detection protocol can lead to variations in results. This study aimed to develop a reproducible and field-deployable diagnostic assay to detect strangles in real-time. Utilising the rapid technique loop-mediated isothermal amplification (LAMP), we developed an assay targeting a conserved region of the S. equi- specific M gene (SeM). Additionally, we optimised our assay with guanidine hydrochloride (GuHCl) to enhance the assay's performance and detection capabilities. The Str-LAMP was able to detect S. equi within 13 minutes and 20 seconds for both synthetic DNA and clinical isolates, with a limit of detection (LOD) of 53 copies/µl. Our assay demonstrated high repeatability with the inter-coefficient of variation ranging from 0.17% to 3.93%. Furthermore, the clinical sensitivity and specificity was calculated at 91.3% and 93.3%, respectively, with a correct classification rate of 91.8%. The implementation of this newly developed strangles assay can be employed as an efficient aid for in-field surveillance programs. The assay's reproducibility can allow for equine managers to undertake routine self-surveillance on their properties, without the requirement of specialised training. The Str-LAMP assay has the potential to be a valuable tool to help mitigate potential strangles outbreaks., Competing Interests: Travis Beddoe is an Academic Editor for PeerJ., (©2024 Knox and Beddoe.)
- Published
- 2024
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68. Evaluation of LAMP for Fasciola hepatica detection from faecal samples of experimentally and naturally infected cattle.
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Bari T, Al Mamun MA, Toet H, Rathinasamy V, Larkins JA, Beddoe T, Spithill TW, Piedrafita D, and Greenhill AR
- Subjects
- Sheep, Cattle, Animals, Humans, Enzyme-Linked Immunosorbent Assay veterinary, Feces, DNA, Sensitivity and Specificity, Fasciola hepatica genetics, Sheep Diseases diagnosis, Fascioliasis diagnosis, Fascioliasis veterinary, Cattle Diseases diagnosis
- Abstract
Fasciola hepatica causes liver fluke disease in production animals and humans worldwide. Faecal egg counts (FEC) are the most common diagnostic tool for the diagnosis of liver fluke disease. However, FEC has low sensitivity and is often unreliable for the detection of patent infection. In this study, loop-mediated isothermal amplification (LAMP) was optimised and evaluated for the detection of Fasciola hepatica infection, with the aim of increased sensitivity and making it suitable for on-farm application. LAMP was initially conducted under laboratory conditions, optimised to enable visual detection using calcein dye. DNA extraction based on bead-beating was developed to enable on-farm application. LAMP results were compared to FEC and polymerase chain reaction (PCR). Under laboratory conditions, LAMP was conducted using two incubation methods: a conventional PCR thermocycler and a field-deployable LAMP instrument. When compared to a 'rigorous' FEC protocol consisting of multiple counts using a comparatively large volume of faeces and with infection confirmed post-mortem, LAMP was highly sensitive and specific (using silica membrane DNA extraction sensitivity 88 %, specificity 100 %; using sieving and beat-beating DNA extraction sensitivity 98.9 %, specificity 100 %). When applied on-farm, LAMP was compared to conventional FEC, which suggested high sensitivity but low specificity (sensitivity 97 %, specificity 37.5 %). However, further analysis, comparing field LAMP results to laboratory PCR, suggested that the low specificity was likely the outcome of the inability of conventional FEC to detect all true F. hepatica positive samples. Based on the high sensitivity and specificity of LAMP compared to a 'rigorous' FEC protocol and its ability to be used in field settings, the study demonstrates the potential of LAMP for diagnosing F. hepatica infection in agriculture., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tanjina Bari reports financial support was provided by Australian Government Department of Education., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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69. Current and Future Advances in the Detection and Surveillance of Biosecurity-Relevant Equine Bacterial Diseases Using Loop-Mediated Isothermal Amplification (LAMP).
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Knox A, Zerna G, and Beddoe T
- Abstract
Horses play an important role throughout the world, whether for work, culture, or leisure, providing an ever-growing significant contribution to the economy. The increase in importation and movement of horses, both nationally and internationally, has inevitably allowed for the global equine industry to grow. Subsequently, however, the potential for transmission of fatal equine bacterial diseases has also escalated, and devasting outbreaks continue to occur. To prevent such events, disease surveillance and diagnosis must be heightened throughout the industry. Current common, or "gold-standard" techniques, have shown to be inadequate at times, thus requiring newer technology to impede outbreaks. Loop-mediated isothermal amplification (LAMP) has proven to be a reliable, rapid, and accessible tool in both diagnostics and surveillance. This review will discuss equine bacterial diseases of biosecurity relevance and their current diagnostic approaches, as well as their respective LAMP assay developments. Additionally, we will provide insight regarding newer technology and advancements associated with this technique and their potential use for the outlined diseases.
- Published
- 2023
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70. Transcription Factor Dynamics in Cross-Regulation of Plant Hormone Signaling Pathways.
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Yin L, Zander M, Huang SC, Xie M, Song L, Saldierna Guzmán JP, Hann E, Shanbhag BK, Ng S, Jain S, Janssen BJ, Clark NM, Walley JW, Beddoe T, Bar-Joseph Z, Lewsey MG, and Ecker JR
- Abstract
Cross-regulation between hormone signaling pathways is indispensable for plant growth and development. However, the molecular mechanisms by which multiple hormones interact and co-ordinate activity need to be understood. Here, we generated a cross-regulation network explaining how hormone signals are integrated from multiple pathways in etiolated Arabidopsis ( Arabidopsis thaliana ) seedlings. To do so we comprehensively characterized transcription factor activity during plant hormone responses and reconstructed dynamic transcriptional regulatory models for six hormones; abscisic acid, brassinosteroid, ethylene, jasmonic acid, salicylic acid and strigolactone/karrikin. These models incorporated target data for hundreds of transcription factors and thousands of protein-protein interactions. Each hormone recruited different combinations of transcription factors, a subset of which were shared between hormones. Hub target genes existed within hormone transcriptional networks, exhibiting transcription factor activity themselves. In addition, a group of MITOGEN-ACTIVATED PROTEIN KINASES (MPKs) were identified as potential key points of cross-regulation between multiple hormones. Accordingly, the loss of function of one of these (MPK6) disrupted the global proteome, phosphoproteome and transcriptome during hormone responses. Lastly, we determined that all hormones drive substantial alternative splicing that has distinct effects on the transcriptome compared with differential gene expression, acting in early hormone responses. These results provide a comprehensive understanding of the common features of plant transcriptional regulatory pathways and how cross-regulation between hormones acts upon gene expression.
- Published
- 2023
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71. Simple and practical sialoglycan encoding system reveals vast diversity in nature and identifies a universal sialoglycan-recognizing probe derived from AB5 toxin B subunits.
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Sasmal A, Khan N, Khedri Z, Kellman BP, Srivastava S, Verhagen A, Yu H, Bruntse AB, Diaz S, Varki N, Beddoe T, Paton AW, Paton JC, Chen X, Lewis NE, and Varki A
- Subjects
- Salmonella typhi chemistry, Sialic Acids, Polysaccharides, Cholera Toxin, Escherichia coli, Bacterial Toxins chemistry
- Abstract
Vertebrate sialic acids (Sias) display much diversity in modifications, linkages, and underlying glycans. Slide microarrays allow high-throughput explorations of sialoglycan-protein interactions. A microarray presenting ~150 structurally defined sialyltrisaccharides with various Sias linkages and modifications still poses challenges in planning, data sorting, visualization, and analysis. To address these issues, we devised a simple 9-digit code for sialyltrisaccharides with terminal Sias and underlying two monosaccharides assigned from the nonreducing end, with 3 digits assigning a monosaccharide, its modifications, and linkage. Calculations based on the encoding system reveal >113,000 likely linear sialyltrisaccharides in nature. Notably, a biantennary N-glycan with 2 terminal sialyltrisaccharides could thus have >1010 potential combinations and a triantennary N-glycan with 3 terminal sequences, >1015 potential combinations. While all possibilities likely do not exist in nature, sialoglycans encode enormous diversity. While glycomic approaches are used to probe such diverse sialomes, naturally occurring bacterial AB5 toxin B subunits are simpler tools to track the dynamic sialome in biological systems. Sialoglycan microarray was utilized to compare sialoglycan-recognizing bacterial toxin B subunits. Unlike the poor correlation between B subunits and species phylogeny, there is stronger correlation with Sia-epitope preferences. Further supporting this pattern, we report a B subunit (YenB) from Yersinia enterocolitica (broad host range) recognizing almost all sialoglycans in the microarray, including 4-O-acetylated-Sias not recognized by a Yersinia pestis orthologue (YpeB). Differential Sia-binding patterns were also observed with phylogenetically related B subunits from Escherichia coli (SubB), Salmonella Typhi (PltB), Salmonella Typhimurium (ArtB), extra-intestinal E.coli (EcPltB), Vibrio cholera (CtxB), and cholera family homologue of E. coli (EcxB)., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2022
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72. Heterologous production of Cannabis sativa-derived specialised metabolites of medicinal significance - Insights into engineering strategies.
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Wiles D, Shanbhag BK, O'Brien M, Doblin MS, Bacic A, and Beddoe T
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- Flavonoids metabolism, Metabolic Engineering methods, Terpenes metabolism, Cannabinoids metabolism, Cannabis genetics, Cannabis metabolism
- Abstract
Cannabis sativa L. has been known for at least 2000 years as a source of important, medically significant specialised metabolites and several bio-active molecules have been enriched from multiple chemotypes. However, due to the many levels of complexity in both the commercial cultivation of cannabis and extraction of its specialised metabolites, several heterologous production approaches are being pursued in parallel. In this review, we outline the recent achievements in engineering strategies used for heterologous production of cannabinoids, terpenes and flavonoids along with their strength and weakness. We provide an overview of the specialised metabolism pathway in C. sativa and a comprehensive list of the specialised metabolites produced along with their medicinal significance. We highlight cannabinoid-like molecules produced by other species. We discuss the key biosynthetic enzymes and their heterologous production using various hosts such as microbial and eukaryotic systems. A brief discussion on complementary production strategies using co-culturing and cell-free systems is described. Various approaches to optimise specialised metabolite production through co-expression, enzyme engineering and pathway engineering are discussed. We derive insights from recent advances in metabolic engineering of hosts with improved precursor supply and suggest their application for the production of C. sativa speciality metabolites. We present a collation of non-conventional hosts with speciality traits that can improve the feasibility of commercial heterologous production of cannabis-based specialised metabolites. We provide a perspective of emerging research in synthetic biology, allied analytical techniques and plant heterologous platforms as focus areas for heterologous production of cannabis specialised metabolites in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2022
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73. Environmental detection of Fasciola hepatica by loop-mediated isothermal amplification.
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Tran L, Toet H, and Beddoe T
- Subjects
- Animals, Humans, Triclabendazole, DNA, Water, Fasciola hepatica genetics, Anthelmintics therapeutic use
- Abstract
Fasciola hepatica , commonly referred to as liver flukes, is a substantial zoonotic parasitic disease of humans and livestock globally. While infection is readily controlled by anthelmintics, namely triclabendazole, the heavy reliance on triclabendazole has resulted in drug resistance appearing worldwide. Due to drug resistance, it is imperative to adopt an integrated parasite management program to preserve the efficacy of currently available anthelmintics. A integrated liver fluke management plan would benefit from a simple rapid, field-deployable diagnostic for detection of F. hepatica in environment and the host. Therefore, a rapid DNA test using loop-mediated isothermal amplification was developed and optimised for the detection of F. hepatica from faecal and water samples to enable the detection of parasites both within the host and from the environment. The assay presented here is fast, with amplification in ≤20 min, and highly sensitive, with a detection limit of 5 × 10
-4 ng/µL. The workflow presented here provides a time to result of ≤60 min without requiring a commercial kit for the extraction of DNA from faecal and water samples, and pending further validation from field-samples, could potentially be used to enable real-time decision making to mitigate parasite prevalence on a farming property and with no requirement for sample transportation., Competing Interests: Travis Beddoe received funding from Cooperative Research Centre Project (CRC-P) awarded to Geneworks and La Trobe University, however, funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., (© 2022 Tran et al.)- Published
- 2022
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74. Development of molecular detection methods of Bovicola ovis from sheep fleece.
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Tran L, Rawlin GT, and Beddoe T
- Subjects
- Animals, Australia, Sheep, Wool parasitology, Insecticides, Ischnocera, Lice Infestations diagnosis, Lice Infestations epidemiology, Lice Infestations veterinary, Phthiraptera, Sheep Diseases parasitology
- Abstract
The sheep body louse (Bovicola ovis) commonly referred to as sheep lice are small chewing ectoparasites of sheep. Infection results in significant economic costs to the Australian sheep industry due to reduced wool quality caused by chronic itching from sheep rubbing and biting fleece. Treatment relies on use of insecticides; however, resistance has developed against pyrethroid and other insect growth regulator lousicides. There is urgent need to develop cost-effective lice management to reduce the use of insecticides, with the application of insecticidal treatments only applied when an infestation is detected. However, the current detection method relies on fleece parting for detection of B. ovis which is highly dependent on the skill of the inspector, the number of sheep examined, and the prevalence and severity of the infestation. To improve B. ovis detection, a highly sensitive (5 × 10
-8 ng/μL) and specific multiplex quantitative PCR which simultaneously detects sheep lice and sheep DNA was developed. In addition, a B. ovis loop-mediated isothermal amplification (LAMP) assay was developed for field use. The B. ovis LAMP (Bov-LAMP) assay was optimized to reliably detect B. ovis from wool samples down to 5 × 10-6 ng/μL, with time to positive (Tp ) < 10 min. Both assays demonstrate high sensitivity and specificity, enabling rapid identification of B. ovis DNA from sheep fleece samples and have the capacity to be used for ongoing management and surveillance of B. ovis in Australian sheep flocks., (© 2022. The Author(s).)- Published
- 2022
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75. Sialoglycan-binding patterns of bacterial AB 5 toxin B subunits correlate with host range and toxicity, indicating evolution independent of A subunits.
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Khan N, Sasmal A, Khedri Z, Secrest P, Verhagen A, Srivastava S, Varki N, Chen X, Yu H, Beddoe T, Paton AW, Paton JC, and Varki A
- Subjects
- Animals, Evolution, Molecular, Mammals metabolism, N-Acetylneuraminic Acid metabolism, Phylogeny, Plague microbiology, Protein Binding, Protein Subunits metabolism, Yersinia pestis metabolism, Bacteria classification, Bacteria metabolism, Bacterial Toxins metabolism, Bacterial Toxins toxicity, Host Specificity, Polysaccharides metabolism
- Abstract
Many pathogenic bacteria secrete AB
5 toxins that can be virulence factors. Cytotoxic A subunits are delivered to the cytosol following B subunit binding to specific host cell surface glycans. Some B subunits are not associated with A subunits, for example, YpeB of Yersinia pestis, the etiologic agent of plague. Plague cannot be eradicated because of Y. pestis' adaptability to numerous hosts. We previously showed selective binding of other B5 pentamers to a sialoglycan microarray, with sialic acid (Sia) preferences corresponding to those prominently expressed by various hosts, for example, N-acetylneuraminic acid (Neu5Ac; prominent in humans) or N-glycolylneuraminic acid (Neu5Gc; prominent in ruminant mammals and rodents). Here, we report that A subunit phylogeny evolved independently of B subunits and suggest a future B subunit nomenclature based on bacterial species names. We also found via phylogenetic analysis of B subunits, which bind Sias, that homologous molecules show poor correlation with species phylogeny. These data indicate ongoing lateral gene transfers between species, including mixing of A and B subunits. Consistent with much broader host range of Y. pestis, we show that YpeB recognizes all mammalian Sia types, except for 4-O-acetylated ones. Notably, YpeB alone causes dose-dependent cytotoxicity, which is abolished by a mutation (Y77F) eliminating Sia recognition, suggesting that cell proliferation and death are promoted via lectin-like crosslinking of cell surface sialoglycoconjugates. These findings help explain the host range of Y. pestis and could be important for pathogenesis. Overall, our data indicate ongoing rapid evolution of both host Sias and pathogen toxin-binding properties., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
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76. Crystal structures of pertussis toxin with NAD + and analogs provide structural insights into the mechanism of its cytosolic ADP-ribosylation activity.
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Sakari M, Tran MT, Rossjohn J, Pulliainen AT, Beddoe T, and Littler DR
- Subjects
- ADP-Ribosylation, Adenosine Diphosphate Ribose metabolism, Bordetella pertussis, Cytosol metabolism, NAD metabolism, Pertussis Toxin chemistry, Virulence Factors, Bordetella chemistry
- Abstract
Bordetella pertussis is the causative agent of whooping cough, a highly contagious respiratory disease. Pertussis toxin (PT), a major virulence factor secreted by B. pertussis, is an AB5-type protein complex topologically related to cholera toxin. The PT protein complex is internalized by host cells and follows a retrograde trafficking route to the endoplasmic reticulum, where it subsequently dissociates. The released enzymatic S1 subunit is then translocated from the endoplasmic reticulum into the cytosol and subsequently ADP-ribosylates the inhibitory alpha-subunits (Gαi) of heterotrimeric G proteins, thus promoting dysregulation of G protein-coupled receptor signaling. However, the mechanistic details of the ADP-ribosylation activity of PT are not well understood. Here, we describe crystal structures of the S1 subunit in complex with nicotinamide adenine dinucleotide (NAD+), with NAD+ hydrolysis products ADP-ribose and nicotinamide, with NAD+ analog PJ34, and with a novel NAD+ analog formed upon S1 subunit crystallization with 3-amino benzamide and NAD+, which we name benzamide amino adenine dinucleotide. These crystal structures provide unprecedented insights into pre- and post-NAD+ hydrolysis steps of the ADP-ribosyltransferase activity of PT. We propose that these data may aid in rational drug design approaches and further development of PT-specific small-molecule inhibitors., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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77. OZITX, a pertussis toxin-like protein for occluding inhibitory G protein signalling including Gα z .
- Author
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Keen AC, Pedersen MH, Lemel L, Scott DJ, Canals M, Littler DR, Beddoe T, Ono Y, Shi L, Inoue A, Javitch JA, and Lane JR
- Subjects
- Pertussis Toxin pharmacology, Receptors, G-Protein-Coupled metabolism, Signal Transduction, GTP-Binding Protein alpha Subunits, Gi-Go genetics, Heterotrimeric GTP-Binding Proteins genetics, Heterotrimeric GTP-Binding Proteins metabolism
- Abstract
Heterotrimeric G proteins are the main signalling effectors for G protein-coupled receptors. Understanding the distinct functions of different G proteins is key to understanding how their signalling modulates physiological responses. Pertussis toxin, a bacterial AB
5 toxin, inhibits Gαi/o G proteins and has proven useful for interrogating inhibitory G protein signalling. Pertussis toxin, however, does not inhibit one member of the inhibitory G protein family, Gαz . The role of Gαz signalling has been neglected largely due to a lack of inhibitors. Recently, the identification of another Pertussis-like AB5 toxin was described. Here we show that this toxin, that we call OZITX, specifically inhibits Gαi/o and Gαz G proteins and that expression of the catalytic S1 subunit is sufficient for this inhibition. We identify mutations that render Gα subunits insensitive to the toxin that, in combination with the toxin, can be used to interrogate the signalling of each inhibitory Gα G protein., (© 2022. The Author(s).)- Published
- 2022
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78. The Role of Anti-Viral Effector Molecules in Mollusc Hemolymph.
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Watson A, Agius J, Ackerly D, Beddoe T, and Helbig K
- Subjects
- Animals, Australia, Hemocytes metabolism, Immunity, Innate, Invertebrates, Mollusca metabolism, Antiviral Agents metabolism, Hemolymph
- Abstract
Molluscs are major contributors to the international and Australian aquaculture industries, however, their immune systems remain poorly understood due to limited access to draft genomes and evidence of divergences from model organisms. As invertebrates, molluscs lack adaptive immune systems or 'memory', and rely solely on innate immunity for antimicrobial defence. Hemolymph, the circulatory fluid of invertebrates, contains hemocytes which secrete effector molecules with immune regulatory functions. Interactions between mollusc effector molecules and bacterial and fungal pathogens have been well documented, however, there is limited knowledge of their roles against viruses, which cause high mortality and significant production losses in these species. Of the major effector molecules, only the direct acting protein dicer-2 and the antimicrobial peptides (AMPs) hemocyanin and myticin-C have shown antiviral activity. A better understanding of these effector molecules may allow for the manipulation of mollusc proteomes to enhance antiviral and overall antimicrobial defence to prevent future outbreaks and minimize economic outbreaks. Moreover, effector molecule research may yield the description and production of novel antimicrobial treatments for a broad host range of animal species.
- Published
- 2022
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79. Bovine Natural Antibody Relationships to Specific Antibodies and Fasciola hepatica Burdens after Experimental Infection and Vaccination with Glutathione S -Transferase.
- Author
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Zerna G, Cameron TC, Toet H, Spithill TW, and Beddoe T
- Abstract
Fasciola hepatica is the causative agent of fasciolosis, a significant parasitic disease occurring worldwide. Despite ongoing efforts, there is still no vaccine to control liver fluke infections in livestock. Recently, it has been suggested that natural antibodies (NAbs) can amplify specific antibodies (SpAb) and have a direct killing effect, but it is unknown if this phenomenon occurs during parasitic helminth infection or targeted vaccination. NAbs are antibodies produced by the innate immune system, capable of binding antigens without prior exposure. This study explores the role of bovine NAbs, using the exogenous glycoprotein keyhole limpet hemocyanin (KLH), in response to F. hepatica infection and SpAb production after infection and vaccination. The cattle's NAbs were differently influenced by parasite infection and vaccination, with an increase in KLH-binding IgG and IgM levels after infection and reduced KLH-binding IgM levels following vaccination. Underlying NAbs reacting to KLH showed no correlations to the final fluke burdens after experimental infection or vaccination. However, NAbs reacting to whole-worm extract (WWE) prior to infection were positively correlated to increased fluke burdens within the infected bovine host. Furthermore, after infection, the specific IgG reacting to WWE was positively reflected by the underlying NAb IgG response. Following subcutaneous vaccination with F. hepatica native glutathione S -transferase (GST), there was a non-significant 33% reduction in fluke burden. Vaccinated animals with higher underlying NAbs had a higher induction of vaccine-induced SpAbs, with trends observed between KLH-binding IgM and anti-GST IgG and IgM. Our findings provide a platform to allow further investigation to determine if NAb levels could mirror fluke-SpAb production for exploitation in a combined selective breeding and vaccination program. Additionally, this work suggests that liver fluke could possibly evade the host's immune system by utilising surface-bound IgM NAbs.
- Published
- 2022
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80. The Biomolecules Journal Club: Highlights on Recent Papers-1.
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Rabanal F, Johnson MS, Alaimo A, Bolanos-Garcia VM, and Beddoe T
- Subjects
- Animals, Humans, Periodicals as Topic, Anti-Bacterial Agents
- Abstract
We are glad to share with you our first Journal Club and to highlight some of the most interesting papers published recently [...].
- Published
- 2022
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81. Evaluation of the Role of Galectins in Parasite Immunity.
- Author
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Swan J, Sakthivel D, Beddoe T, Stear M, Piedrafita D, and Preston S
- Subjects
- Animals, Sheep, Staining and Labeling, Fasciola hepatica immunology, Fascioliasis immunology, Fascioliasis veterinary, Galectins genetics, Galectins physiology, Haemonchiasis immunology, Haemonchiasis veterinary, Haemonchus immunology, Sheep Diseases immunology, Sheep Diseases parasitology
- Abstract
Galectin-11 (LGALS-11) and galectin-14 (LGALS-14) are ruminant specific galectins, first reported in sheep. Although their roles in parasite immunity are still being elucidated, it appears that they influence protection against parasites. In gastrointestinal infections with the nematode Haemonchus contortus, both galectin-11 and galectin-14 appear to be protective. However, in a chronic infection of liver fluke, Fasciola hepatica, these galectins may aid parasite survival. To unravel the structural, functional, and ligand profile of galectin-11 and galectin-14, recombinant production of these proteins is vital. Here we present the recombinant production of soluble galectin-11 and galectin-14 from domestic sheep for in vitro and structural biology studies. These methods include parasite cultivation and infection, galectin staining of host and parasite tissue, surface staining of parasites with recombinant galectins, pull-down assays to identify endogenous galectin binding proteins, and in vitro assays to monitor the effect of galectins on parasite development., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2022
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82. Development of a loop-mediated isothermal amplification assay for detection of Austropeplea tomentosa from environmental water samples.
- Author
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Tran L, Rathinasamy VA, and Beddoe T
- Abstract
Lymnaeid snails are key intermediate hosts for the development and survival of Fasciola spp., the causative agent of Fascioliasis which are economically important parasites infecting humans and livestock globally. The current control method for treating Fascioliasis is heavily reliant on anthelmintic drugs, particularly Triclabendazole (TCBZ) which has resulted in drug-resistant parasites and poses significant risk as there are no long-term efficacious alternatives available. Sustainable control measures at the farm level could include both parasite and snail control will play an important role in Fasciola spp. control and reduce the reliance on anthelmintic drugs. Implementation of such sustainable control measures requires effective identification of snails on the property however Lymnaeid snails are small and difficult to physically locate. Snail identification using an environmental DNA approach is a recent approach in which physically locating snails are not required. Austropeplea tomentosa, is the primary intermediate snail host for F. hepatica transmission in South-East Australia and we present an in-field loop-mediated isothermal amplification and water filtering method for the detection of A. tomentosa eDNA from water samples to improve current surveillance methods. This methodology is highly sensitive with a detection limit of 5 × 10
- 6 ng/μL, detected in < 20 minutes, with cumulative sample preparation and amplification time under 1 hour. This proposed workflow could assist in monitoring areas to determine the risk of Fascioliasis infection and implement strategies to manage snail populations to ultimately reduce the risk of infection for humans and livestock., Supplementary Information: The online version contains supplementary material available at 10.1186/s44149-022-00061-9., Competing Interests: Competing interestsThe authors declare no conflict of interest in the present study. The funding sources had no part in study design and conceptualization, collection, analysis, or interpretation of data, writing the manuscript, or in the decision to publish results., (© The Author(s) 2022.)- Published
- 2022
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83. Evaluation of Immunogenicity and Efficacy of Fasciola hepatica Tetraspanin 2 (TSP2) Fused to E. coli Heat-Labile Enterotoxin B Subunit LTB Adjuvant Following Intranasal Vaccination of Cattle.
- Author
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Zerna G, Rathinasamy VA, Toet H, Anderson G, Dempster R, Spithill TW, and Beddoe T
- Abstract
Fasciolosis, caused by the liver flukes Fasciola hepatica and F. gigantica, is an economically important and globally distributed zoonotic disease. Liver fluke infections in livestock cause significant losses in production and are of particular concern to regions where drug resistance is emerging. Antigens of the F. hepatica surface tegument represent promising vaccine candidates for controlling this disease. Tetraspanins are integral tegumental antigens that have shown partial protection as vaccine candidates against other trematode species. The Escherichia coli heat-labile enterotoxin's B subunit (LTB) is a potent mucosal adjuvant capable of inducing an immune response to fused antigens. This study investigates the potential of F. hepatica tetraspanin 2 extracellular loop 2 (rFhTSP2) as a protective vaccine antigen and determines if fusion of FhTSP2 to LTB can enhance protection in cattle. Cattle were immunised subcutaneously with rFhTSP2 mixed in the Freund's adjuvant and intranasally with rLTB-FhTSP2 in saline, accounting for equal molar ratios of tetraspanin in both groups. Vaccination with rFhTSP2 stimulated a strong specific serum IgG response, whereas there was no significant serum IgG response following rLTB-FhTSP2 intranasal vaccination. There was no substantial antigen specific serum IgA generated in all groups across the trial. Contrastingly, after the fluke challenge, a rise in antigen specific saliva IgA was observed in both vaccination groups on Day 42, with the rLTB-FhTSP2 vaccination group showing significant mucosal IgA production at Day 84. However, neither vaccine group showed a significant reduction of fluke burden nor faecal egg output. These results suggest that intranasal vaccination with rLTB-FhTSP2 does elicit a humoral mucosal response but further work is needed to evaluate if mucosal delivery of liver fluke antigens fused to LTB is a viable vaccine strategy.
- Published
- 2021
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84. Teladorsagia Circumcincta Galectin-Mucosal Interactome in Sheep.
- Author
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Hafidi NN, Swan J, Faou P, Lowe R, Rajapaksha H, Cairns C, Stear M, and Beddoe T
- Abstract
Teladorsagia circumcincta is the most important gastrointestinal parasite in the livestock industry in temperate regions around the world, causing great economic losses. The infective third-stage larvae (L3) of Teladorsagia circumcincta secrete a large number of excretory-secretory (E/S) molecules, some of which are likely to play critical roles in modulating the host immune response. One of the most abundant E/S molecules is a protein termed Tci-gal-1, which has similarity to mammalian galectins. Galectins are a family of carbohydrate-binding molecules, with characteristic domain organisation and affinity for β-galactosids that mediate a variety of important cellular functions including inflammation and immune responses. To understand the role of Tci-gal-1 at the host-parasite interface, we used a proteomics pull-down approach to identify Tc-gal-1 interacting proteins from sheep abomasal scrapes and whole tissue. A total of 135 unique proteins were identified from whole abomasal tissue samples, while 89 proteins were isolated from abomasal scrape samples. Of these proteins, 63 were present in both samples. Many of the host proteins identified, such as trefoil factors and mucin-like proteins, play critical roles in the host response. The identification of Tci-gal-1 binding partners provides new insights on host-parasite interactions and could lead to the development of new control strategies.
- Published
- 2021
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85. Analysis of daily variation in the release of faecal eggs and coproantigen of Fasciola hepatica in naturally infected dairy cattle and the impact on diagnostic test sensitivity.
- Author
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Kelley JM, Stevenson MA, Rathinasamy V, Rawlin G, Beddoe T, and Spithill TW
- Subjects
- Animals, Cattle, Diagnostic Tests, Routine statistics & numerical data, Feces, Female, Parasite Egg Count veterinary, Antigens, Helminth metabolism, Cattle Diseases diagnosis, Cattle Diseases parasitology, Enzyme-Linked Immunosorbent Assay standards, Enzyme-Linked Immunosorbent Assay veterinary, Fasciola hepatica, Fascioliasis diagnosis, Fascioliasis veterinary
- Abstract
The liver fluke, Fasciola hepatica (F. hepatica) is a widespread parasite infection in dairy cattle in Victoria, South-eastern Australia. Robust diagnosis of fluke infection is needed in dairy cattle to identify sub-clinical infections which often go unnoticed, causing significant production losses. We tested the coproantigen ELISA (cELISA) and the FlukeFinder faecal egg count kit® on naturally infected cows in a fluke endemic region of Victoria. The aim of the study was to investigate the variation in the release of coproantigens and eggs into faeces over a 5-day period, at the morning (AM) and afternoon (PM) milkings, and to assess the impact of the timing of faecal sample collection on diagnostic test sensitivity. Ten cows were enrolled into the study based on positive F. hepatica faecal egg counts (LFEC) and faecal samples from the ten cows were collected twice daily, at the 7-9 AM and 4-6 PM milking, for five consecutive days. At the conclusion of the sampling period, the cows were euthanized and F. hepatica burden determined at necropsy. A moderate negative correlation between cow age and cELISA optical density (OD) was observed using data from all samples (R -0.63; 95 % CI -0.68 to -0.57). Over the 5-day sampling period, we observed within-animal variation between days for both the cELISA OD (2.6-8.9 fold) and LFEC (5-16 fold), with more variation in values observed in the PM samples for both tests. The correlation with total fluke burden was higher in the AM sampling using both the cELISA and LFEC (R 0.64 and 0.78, respectively). The sensitivity was 100 % for the cELISA using various cut offs from the literature (0.014 OD, 0.030 OD, and 1.3 % or 1.6 % of the positive control). The sensitivity of the FlukeFinder kit® (based on 588 faecal samples and not accounting for lack of independence in the data) was 88 % (95 % CI 85 %-90 %). Seventy one false negatives were recorded from the 588 LFEC tests all of which were observed in the cows with fluke burdens <14 flukes; 42 of the 71 false negative LFECs occurred in one individual cow which had the lowest burden of nine flukes. In dairy cows, the cut-off for production losses due to fasciolosis is estimated at> 10 fluke. Both the cELISA and the LFEC identified all cows that had burdens equal to or greater than this cut-off. Five of the ten cows also exhibited relatively high paramphistome egg counts., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2021
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86. Isothermal Nucleic Acid Amplification Technologies for the Detection of Equine Viral Pathogens.
- Author
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Knox A and Beddoe T
- Abstract
The global equine industry provides significant economic contributions worldwide, producing approximately USD $300 billion annually. However, with the continuous national and international movement and importation of horses, there is an ongoing threat of a viral outbreak causing large epidemics and subsequent significant economic losses. Additionally, horses serve as a host for several zoonotic diseases that could cause significant human health problems. The ability to rapidly diagnose equine viral diseases early could lead to better management, treatment, and biosecurity strategies. Current serological and molecular methods cannot be field-deployable and are not suitable for resource-poor laboratories due to the requirement of expensive equipment and trained personnel. Recently, isothermal nucleic acid amplification technologies, such as loop-mediated isothermal amplification (LAMP) and insulated isothermal polymerase chain reaction (iiPCR), have been developed to be utilized in-field, and provide rapid results within an hour. We will review current isothermal diagnostic techniques available to diagnose equine viruses of biosecurity and zoonotic concern and provide insight into their potential for in-field deployment.
- Published
- 2021
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87. Current Status for Controlling the Overlooked Caprine Fasciolosis.
- Author
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Zerna G, Spithill TW, and Beddoe T
- Abstract
The disease fasciolosis is caused by the liver flukes Fasciola hepatica and F. gigantica , which infect a wide range of mammals and production livestock, including goats. These flatworm parasites are globally distributed and predicted to cost the livestock industry a now conservative USD 3 billion per year in treatment and lowered on-farm productivity. Infection poses a risk to animal welfare and results in lowered fertility rates and reduced production yields of meat, milk and wool. This zoonotic disease is estimated to infect over 600 million animals and up to 2.4 million humans. Current and future control is threatened with the global emergence of flukes resistant to anthelmintics. Drug resistance calls for immediate on-farm parasite management to ensure treatments are effective and re-infection rates are kept low, while a sustainable long-term control method, such as a vaccine, is being developed. Despite the recent expansion of the goat industry, particularly in developing countries, there are limited studies on goat-focused vaccine control studies and the effectiveness of drug treatments. There is a requirement to collate caprine-specific fasciolosis knowledge. This review will present the current status of liver fluke caprine infections and potential control methods for application in goat farming.
- Published
- 2021
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88. Fasciola hepatica Control Practices on a Sample of Dairy Farms in Victoria, Australia.
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Kelley JM, Rawlin G, Beddoe T, Stevenson M, and Spithill TW
- Abstract
In Australia, little is known about the strategies used by farmers to control Fasciola hepatica ( F. hepatica ) infection in dairy cattle. Triclabendazole-resistant F. hepatica have recently been found on several dairy and beef properties in Australia. It is difficult to draw conclusions about how widespread resistance is in Australian dairy cattle because we have little information about flukicide usage, drug resistance testing, and alternative flukicide usage on-farm. The study objectives were to determine how dairy farmers are currently controlling F. hepatica and to identify knowledge gaps where F. hepatica control strategies need to be communicated to farmers to improve management. The survey was distributed online or by hard copy and 36 dairy farmers completed the survey. There were 34 questions including closed, open-ended, multicheck box, demographic, and text questions. Descriptive statistics were used to quantify each response. The survey results showed high use of clorsulon, limited rotation of flukicides, and limited use of diagnostic tests to inform treatment options and timing. There was poor adherence to best management practice in determining the dose of flukicides administered to cattle, with farmers often relying on estimating body weights or average body weights, suggesting that underdosing of animals is likely to be prevalent. Most respondents in this study did not isolate and quarantine treated and newly returned or purchased animals before joining them with the main herd. The research identified four knowledge gaps where communication needs to be enhanced to improve control of F. hepatica : diagnostic testing to inform flukicide use, rotation of flukicide actives, flukicide administration, and increased testing of replacement animals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kelley, Rawlin, Beddoe, Stevenson and Spithill.)
- Published
- 2021
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89. Current Status of Loop-Mediated Isothermal Amplification Technologies for the Detection of Honey Bee Pathogens.
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Cameron TC, Wiles D, and Beddoe T
- Abstract
Approximately one-third of the typical human Western diet depends upon pollination for production, and honey bees ( Apis mellifera ) are the primary pollinators of numerous food crops, including fruits, nuts, vegetables, and oilseeds. Regional large scale losses of managed honey bee populations have increased significantly during the last decade. In particular, asymptomatic infection of honey bees with viruses and bacterial pathogens are quite common, and co-pathogenic interaction with other pathogens have led to more severe and frequent colony losses. Other multiple environmental stress factors, including agrochemical exposure, lack of quality forage, and reduced habitat, have all contributed to the considerable negative impact upon bee health. The ability to accurately diagnose diseases early could likely lead to better management and treatment strategies. While many molecular diagnostic tests such as real-time PCR and MALDI-TOF mass spectrometry have been developed to detect honey bee pathogens, they are not field-deployable and thus cannot support local apiary husbandry decision-making for disease control. Here we review the field-deployable technology termed loop-mediated isothermal amplification (LAMP) and its application to diagnose honey bee infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cameron, Wiles and Beddoe.)
- Published
- 2021
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90. Towards understanding the liver fluke transmission dynamics on farms: Detection of liver fluke transmitting snail and liver fluke-specific environmental DNA in water samples from an irrigated dairy farm in Southeast Australia.
- Author
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Rathinasamy V, Tran L, Swan J, Kelley J, Hosking C, Williamson G, Knowles M, Elliott T, Rawlin G, Spithill TW, and Beddoe T
- Subjects
- Animals, Cattle, DNA, Environmental genetics, Dairying, Fascioliasis transmission, Cattle Diseases parasitology, Cattle Diseases transmission, DNA, Environmental analysis, Fasciola hepatica genetics, Fascioliasis veterinary, Snails parasitology, Water parasitology
- Abstract
Livestock production around the world is impacted by liver fluke (Fasciola spp.) infection resulting in serious economic losses to the beef, dairy and sheep industries with significant losses of about $90 million per annum in Australia. Triclabendazole (TCBZ) is the most effective anthelmintic treatment available to control liver fluke infections; however, the widespread emergence of TCBZ resistance in livestock threatens liver fluke control. Alternative control measures to lower exposure of livestock to liver fluke infection would help to preserve the usefulness of current anthelmintic treatments. Environmental DNA (eDNA) based identification of liver fluke and the intermediate snail host in the water bodies is a robust method to assess the risk of liver fluke infection on farms. In this study, we used a multiplex quantitative PCR assay of water samples to detect and quantify eDNA of Fasciola hepatica (F. hepatica) and Austropeplea tomentosa (A. tomentosa), a crucial intermediate snail host for liver fluke transmission in South-east Australia. Water samples were collected from an irrigation channel for a period of 7 months in 2016 (February, March, May, September, October, November and December) at a dairy farm located at Maffra, Victoria, South-east Australia. Using an effective eDNA extraction method, the multiplex qPCR assay allows for the independent but simultaneous detection of eDNA released from liver fluke life stages and snails using specific primers and a probe targeting the ITS-2 region of the liver fluke and snail, respectively, with minimal inhibition from contaminants in field collected water samples. The sensitivity of this assay to detect eDNA of liver fluke and snails was observed to be 14 fg and 50 fg, respectively, in the presence of field collected water samples. Differential levels of liver fluke and snail specific eDNA in water were observed at the time points analysed in this study. The successful detection of eDNA specific to liver fluke and snails from the field collected water samples provides a precedent for the use of this method as a monitoring tool to determine the prevalence of liver fluke and liver fluke-transmitting snails in irrigation regions. Further, this method has the enormous potential to allow an assessment of the liver fluke transmission zones on farms and to inform the application of effective control strategies., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2021
- Full Text
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91. Air sampling for detection of infectious laryngotracheitis (ILT) in commercial poultry flocks.
- Author
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Brown L, Premaratna D, Segal Y, and Beddoe T
- Subjects
- Animals, Australia epidemiology, Chickens, Poultry, Herpesviridae Infections diagnosis, Herpesviridae Infections veterinary, Poultry Diseases diagnosis, Viral Vaccines
- Abstract
Objective: Infectious laryngotracheitis (ILT) is an acute and highly contagious viral respiratory disease of poultry, caused by gallid herpesvirus 1 (ILTV), which causes significant economic losses. Due to recent outbreaks of ILT in Australia, it has been proposed that ILT could be transmitted between poultry sheds by airborne transmission; however, there has never been direct detection of ILTV from air samples. We aimed to optimize a sampling system for the detection of airborne ILTV in poultry sheds., Results: Poultry farms with a known outbreaks of ILT were used for detection of airborne ILTV. Infected chickens were verified by detection of ILTV nucleic acid in feather shafts with all farms being positive. Using a liquid cyclonic impinging device, it was found that recovery and detection of airborne ILTV was possible in alkaline PEG buffer. Additional sampling was performed at different heights to determine the presence of ILTV in the air. In farm 3, all three air samples at both heights were positive for ILTV while at farm 2 only one sample at 45 cm was positive. We envisaged in the future air sampling will be able to detect and track potential transmission of ILTV both inside and outside of the poultry shed.
- Published
- 2020
- Full Text
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92. Characterization of a profilin-like protein from Fasciola hepatica .
- Author
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Wilkie J, Cameron TC, and Beddoe T
- Abstract
Fasciola hepatica is the causative agent of fasciolosis, an important disease of humans and livestock around the world. There is an urgent requirement for novel treatments for F. hepatica due to increasing reports of drug resistance appearing around the world. The outer body covering of F. hepatica is referred to as the tegument membrane which is of crucial importance for the modulation of the host response and parasite survival; therefore, tegument proteins may represent novel drug or vaccine targets. Previous studies have identified a profilin-like protein in the tegument of F. hepatica . Profilin is a regulatory component of the actin cytoskeleton in all eukaryotic cells, and in some protozoan parasites, profilin has been shown to drive a potent IL-12 response. This study characterized the identified profilin form F. hepatica (termed Fh Profilin) for the first time. Recombinant expression of Fh Profilin resulted in a protein approximately 14 kDa in size which was determined to be dimeric like other profilins isolated from a range of eukaryotic organisms. Fh Profilin was shown to bind poly-L-proline (pLp) and sequester actin monomers which is characteristic of the profilin family; however, there was no binding of Fh Profilin to phosphatidylinositol lipids. Despite Fh Profilin being a component of the tegument, it was shown not to generate an immune response in experimentally infected sheep or cattle., Competing Interests: The authors declare that they have no competing interests., (© 2020 Wilkie et al.)
- Published
- 2020
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93. Molecular characterisation and vaccine efficacy of two novel developmentally regulated surface tegument proteins of Fasciola hepatica.
- Author
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McCusker P, Toet H, Rathinasamy V, Young N, Beddoe T, Anderson G, Dempster R, McVeigh P, McCammick E, Wells D, Mousley A, Marks NJ, Maule AG, and Spithill TW
- Subjects
- Amino Acid Sequence, Animals, Cattle, Cattle Diseases immunology, Fascioliasis immunology, Female, Glycoproteins chemistry, Glycoproteins genetics, Glycoproteins immunology, Helminth Proteins chemistry, Male, Membrane Proteins chemistry, Membrane Proteins genetics, Membrane Proteins immunology, Phylogeny, Rats, Rats, Sprague-Dawley, Sequence Alignment, Sheep, Sheep Diseases immunology, Sheep, Domestic, Fasciola hepatica genetics, Fasciola hepatica immunology, Fascioliasis veterinary, Gene Expression Regulation immunology, Helminth Proteins genetics, Helminth Proteins immunology, Vaccines immunology
- Abstract
The surface tegument of Fasciola hepatica is a crucial tissue due to its key role at the host-parasite interface. We characterised three novel proteins, termed Fhteg1, Fhteg5 and Fhteg8, that are found in the tegument membrane fraction of adult F. hepatica. Bioinformatic analysis of proteomic datasets identified Fhteg5 and Fhteg8 as tegumental glycoproteins and revealed that Fhteg1, Fhteg5 and Fhteg8 are associated with exosomes of adult F. hepatica. Fhteg1, Fhteg5 and Fhteg8 appear to be related to uncharacterised sequences in F. gigantica, Fasciolopsis buski, Echinostoma caproni, Clonorchis sinensis, Opisthorchis viverrini, Schistosoma japonicum and S. mansoni, although F. hepatica appears to have expanded this family. Fhteg1 and Fhteg5 were characterised in detail. The Fhteg1 and Fhteg5 gene transcripts each demonstrate significant upregulation in juvenile fluke 2-4 days post-excystment, with transcript levels maintained during development over 3 weeks in vitro. RNAseq data showed that both Fhtegs are expressed in the adult life stage, although the transcript levels were about 8 fold lower than those in juveniles (3 week post infection). Using immunocytochemistry, Fhteg1 and Fhteg5 were each shown to be expressed in cells adjacent to the muscle layer as well as on the surface of 1 week old juveniles, whilst Fhteg5 was also present in cells at the base of the pharynx. RNAi mediated knockdown of Fhteg1 and Fhteg5 transcripts in 4-10 day old juveniles had no effect on parasite survival, movement or growth in vitro. Although no IgG responses were observed for Fhteg1 or Fhteg5 during infection in sheep and cattle, both proteins elicited a low IgG response in a proportion of infected rats. Rats vaccinated with Fhteg1 and Fhteg5 showed good IgG responses to both proteins and a mean 48.2 % reduction in worm burden following parasite challenge. Although vaccination of cattle with both proteins induced a range of IgG responses, no protection was observed against parasite challenge. This is the first study to provide insights into the molecular properties of two novel, developmentally regulated surface tegument proteins in F. hepatica., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
94. The oligomeric assembly of galectin-11 is critical for anti-parasitic activity in sheep (Ovis aries).
- Author
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Sakthivel D, Preston S, Gasser RB, Costa TPSD, Hernandez JN, Shahine A, Shakif-Azam MD, Lock P, Rossjohn J, Perugini MA, González JF, Meeusen E, Piedrafita D, and Beddoe T
- Subjects
- Amino Acid Sequence, Animals, Models, Molecular, Parasitic Diseases, Animal drug therapy, Parasitic Diseases, Animal parasitology, Parasitic Sensitivity Tests, Protein Conformation, Sheep, Sheep, Domestic, Structure-Activity Relationship, Antiparasitic Agents chemistry, Antiparasitic Agents pharmacology, Galectins chemistry, Galectins pharmacology, Protein Multimerization
- Abstract
Galectins are a family of glycan-binding molecules with a characteristic affinity for ß-D-glycosides that mediate a variety of important cellular functions, including immune and inflammatory responses. Galectin-11 (LGALS-11) has been recently identified as a mediator induced specifically in animals against gastrointestinal nematodes and can interfere with parasite growth and development. Here, we report that at least two natural genetic variants of LGALS-11 exist in sheep, and demonstrate fundamental differences in anti-parasitic activity, correlated with their ability to dimerise. This study improves our understanding of the role of galectins in the host immune and inflammatory responses against parasitic nematodes and provides a basis for genetic studies toward selective breeding of animals for resistance to parasites.
- Published
- 2020
- Full Text
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95. The Consequences of Stigma for Knowledge Production: Sheep Producers' Attitudes to Footrot Diagnostics and Control in Australia.
- Author
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Best N, Menéndez R, Rawlin G, Suter R, Rodoni B, and Beddoe T
- Abstract
In Australia, there is documented confusion from producers around the clinical disease of footrot, and anecdotally, knowledge of what tools are available for the diagnosis and management of footrot. When discussing footrot with producers, the authors noted a hesitation to discuss, with denial often expressed. The disease can be debilitating, both on the sheep's welfare and the producer's well-being, as it is a very difficult disease to manage and eradicate. Gaining an understanding of producer perceptions of the disease may help ensure any future actions for management and control are in-line with those identified by producers. A combination of a web-based, and manually distributed surveys of 45 sheep producers was conducted. This included closed- and open-ended questions, multi check box, and Likert scales. Responses were quantified by descriptive statistics and a thematic analysis conducted of short answers. The results of this survey indicate satisfaction with footrot diagnostics is low, while satisfaction with control methods is high. There was also a poor general understanding of footrot as a disease, and a general distrust in peers when it comes to correct management of footrot. This research addresses a gap in the literature about how sociological conditions affect diagnosis and control of footrot disease. It provides three main recommendations-simplifying the diagnostic message, encouraging a culture of trust among sheep producers and increasing governmental support-as a way to tackle this problem., (Copyright © 2020 Best, Menéndez, Rawlin, Suter, Rodoni and Beddoe.)
- Published
- 2020
- Full Text
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96. Determination of the prevalence and intensity of Fasciola hepatica infection in dairy cattle from six irrigation regions of Victoria, South-eastern Australia, further identifying significant triclabendazole resistance on three properties.
- Author
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Kelley JM, Rathinasamy V, Elliott TP, Rawlin G, Beddoe T, Stevenson MA, and Spithill TW
- Subjects
- Animals, Antiplatyhelmintic Agents pharmacology, Cattle, Dairying, Fascioliasis drug therapy, Fascioliasis prevention & control, Fascioliasis veterinary, Prevalence, Triclabendazole pharmacology, Victoria epidemiology, Cattle Diseases epidemiology, Cattle Diseases parasitology, Drug Resistance, Fasciola hepatica drug effects
- Abstract
Fasciola hepatica (liver fluke) is a widespread parasite infection of livestock in Victoria, South-eastern Australia, where high rainfall and a mild climate is suitable for the main intermediate host Austropeplea tomentosa. The aims of this study were to quantify the prevalence and intensity of F. hepatica in dairy cattle in the irrigated dairy regions of Victoria and determine if triclabendazole resistance was present in infected herds. Cattle in 83 herds from the following six irrigation regions were tested for F. hepatica: Macalister Irrigation District (MID), Upper Murray (UM), Murray Valley (MV), Central Goulburn (CG), Torrumbarry (TIA) and Loddon Valley (LV). Twenty cattle from each herd were tested using the F. hepatica faecal egg count (FEC) as well as the coproantigen ELISA (cELISA). The mean individual animal true prevalence of F. hepatica across all regions was 39 % (95 % credible interval [CrI] 27%-51%) by FEC and 39 % (95 % CrI 27%-50%) by cELISA with the highest true prevalence (75-80 %) found in the MID. Our results show that 46 % of the herds that took part in this study were likely to experience fluke-associated production losses, based on observations that herd productivity is impaired when the true within-herd prevalence is > 25 %. Using the FEC and cELISA reduction tests, triclabendazole resistance was assessed on 3 herds in total (2 from the 83 in the study; and 1 separate herd that did not take part in the prevalence study) and resistance was confirmed in all 3 herds. This study has confirmed that F. hepatica is endemic in several dairy regions in Victoria: triclabendazole resistance may be contributing to the high prevalence in some herds. From our analysis, we estimate that the state-wide economic loss associated with fasciolosis is in the order of AUD 129 million (range AUD 38-193 million) per year or about AUD 50,000 (range AUD 15,000-75,000) per herd per year., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2020
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97. Crocodilepox Virus Evolutionary Genomics Supports Observed Poxvirus Infection Dynamics on Saltwater Crocodile ( Crocodylus porosus ).
- Author
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Sarker S, Isberg SR, Moran JL, Araujo R, Elliott N, Melville L, Beddoe T, and Helbig KJ
- Subjects
- Amino Acid Sequence, Animal Diseases epidemiology, Animals, Australia, Phylogeny, Prevalence, Recombination, Genetic, Alligators and Crocodiles virology, Animal Diseases virology, Chordopoxvirinae classification, Chordopoxvirinae genetics, Evolution, Molecular, Genome, Viral, Genomics methods, Poxviridae Infections veterinary
- Abstract
Saltwater crocodilepox virus (SwCRV), belonging to the genus Crocodylidpoxvirus , are large DNA viruses posing an economic risk to Australian saltwater crocodile ( Crocodylus porosus ) farms by extending production times. Although poxvirus-like particles and sequences have been confirmed, their infection dynamics, inter-farm genetic variability and evolutionary relationships remain largely unknown. In this study, a poxvirus infection dynamics study was conducted on two C. porosus farms. One farm (Farm 2) showed twice the infection rate, and more concerningly, an increase in the number of early- to late-stage poxvirus lesions as crocodiles approached harvest size, reflecting the extended production periods observed on this farm. To determine if there was a genetic basis for this difference, 14 complete SwCRV genomes were isolated from lesions sourced from five Australian farms. They encompassed all the conserved genes when compared to the two previously reported SwCRV genomes and fell within three major clades. Farm 2's SwCRV sequences were distributed across all three clades, highlighting the likely mode of inter-farm transmission. Twenty-four recombination events were detected, with one recombination event resulting in consistent fragmentation of the P4c gene in the majority of the Farm 2 SwCRV isolates. Further investigation into the evolution of poxvirus infection in farmed crocodiles may offer valuable insights in evolution of this viral family and afford the opportunity to obtain crucial information into natural viral selection processes in an in vivo setting., Competing Interests: The authors declare no conflict of interest.
- Published
- 2019
- Full Text
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98. Proteomic identification of galectin-11 and -14 ligands from Fasciola hepatica.
- Author
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Swan J, Sakthivel D, Cameron TC, Faou P, Downs R, Rajapaksha H, Piedrafita D, and Beddoe T
- Subjects
- Animals, Antigens, Helminth isolation & purification, Helminth Proteins isolation & purification, Ligands, Mass Spectrometry, Protein Binding, Proteomics, Antigens, Helminth analysis, Fasciola hepatica growth & development, Galectins metabolism, Helminth Proteins analysis, Host-Parasite Interactions, Protein Interaction Mapping, Sheep
- Abstract
Fasciola hepatica is a globally distributed zoonotic trematode that causes fasciolosis in livestock, wildlife, ruminants and humans. Fasciolosis causes a significant economic impact on the agricultural sector and affects human health. Due to the increasing prevalence of triclabendazole resistance in F. hepatica, alternative treatment methods are required. Many protein antigens have been trialled as vaccine candidates with low success, however, the tegument of F. hepatica is highly glycosylated and the parasite-derived glycoconjugate molecules have been identified as an important mediator in host-parasite interactions and as prime targets for the host immune system. Galectin-11 (LGALS-11) and galectin-14 (LGALS-14) are two ruminant-specific glycan-binding proteins, showing upregulation in the bile duct of sheep infected with F. hepatica, which are believed to mediate host-parasite interaction and innate immunity against internal parasites. For the first known time, this study presents the ligand profile of whole worm and tegument extracts of F. hepatica that interacted with immobilised LGALS-11 and LGALS-14. LGALS-14 interacted with a total of 255 F. hepatica proteins. The protein which had the greatest interaction was identified as an uncharacterised protein which contained a C-type lectin domain. Many of the other proteins identified were previously trialled vaccine candidates including glutathione S-transferase, paramyosin, cathepsin L, cathepsin B, fatty acid binding protein and leucine aminopeptidase. In comparison to LGALS-14, LGALS-11 interacted with only 49 F. hepatica proteins and it appears to have a much smaller number of binding partners in F. hepatica. This is, to our knowledge, the first time host-specific lectins have been used for the enrichment of F. hepatica glycoproteins and this study has identified a number of glycoproteins that play critical roles in host-parasite interactions which have the potential to be novel vaccine candidates., (Copyright © 2019 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2019
- Full Text
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99. Evaluation of loop-mediated isothermal amplification (LAMP) assay for detection of aprV2 positive Dichelobacter nodosus in-field by secondary users.
- Author
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Best N, Rodoni B, Rawlin G, and Beddoe T
- Subjects
- Animal Technicians standards, Animals, Dichelobacter nodosus physiology, Foot Rot microbiology, Gram-Negative Bacterial Infections diagnosis, Gram-Negative Bacterial Infections microbiology, Reproducibility of Results, Sensitivity and Specificity, Sheep, Sheep Diseases microbiology, South Australia, Animal Technicians statistics & numerical data, Bacterial Proteins genetics, Dichelobacter nodosus genetics, Foot Rot diagnosis, Gram-Negative Bacterial Infections veterinary, Nucleic Acid Amplification Techniques methods, Serine Endopeptidases genetics, Sheep Diseases diagnosis
- Abstract
Objective: Dichelobacter nodosus is the primary aetiological agent of footrot in sheep. Ovine footrot causes considerable economic losses and substantial animal welfare issues in the Australian sheep industry. Current methods for detecting D. nodosus are difficult, laborious and time-consuming. Recently, we developed a robust LAMP assay (VDN LAMP) that was able to identify aprV2 positive D. nodosus in-field. A major advantage of LAMP technology is the ability of the assay to be performed by non-specialists with minimal training. We aimed to assess the performance of the VDN LAMP in-field in comparison to a laboratory-based aprV2/aprB2 rtPCR when used by secondary users after training by the authors., Results: Two animal health officers (termed secondary users) from Department of Primary Industries and Regions, South Australia (PIRSA) were trained in the use of VDN LAMP, before carrying out in-field testing on several locations in South Australia. The performance of VDN LAMP assay by secondary user 1 was shown to successfully detect 73.91% (n = 53) aprV2 positive samples, while secondary user 2 detected 37.93% (n = 30) aprV2 positive samples. Overall, the ability to identify virulent D. nodosus by VDN LAMP by secondary users was mixed for various reasons, however, this could be rectified by additional training and commercial production of the LAMP kits to increase stability. We envisaged in the future VDN LAMP will able to be used by non-specialists to aid control programs.
- Published
- 2019
- Full Text
- View/download PDF
100. Optimization of a Loop Mediated Isothermal Amplification (LAMP) Assay for In-Field Detection of Dichelobacter nodosus With aprV2 (VDN LAMP) in Victorian Sheep Flocks.
- Author
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Best N, Rawlin G, Suter R, Rodoni B, and Beddoe T
- Abstract
Dichelobacter nodosus is the primary etiological agent of footrot in sheep and has a variety of virulence factors. Of these, AprV2, an extracellular protease, has been shown to be capable of causing severe or "virulent" disease symptoms under the right conditions. Due to this, a loop-mediated isothermal amplification (LAMP) assay for the detection of aprV2 -positive D. nodosus (VDN LAMP) was developed and evaluated for field use. A sample of 19 sheep flocks (309 sheep) in Victoria, Australia, were tested to determine the optimum conditions for in-field VDN LAMP assay use and sampling, for detecting aprV2- positive D. nodosus infected sheep. VDN LAMP performance was compared to a validated rtPCR that detects aprV2 and the benign strain counterpart, aprB2 , using biologically duplicate samples to determine sensitivity and specificity. Flocks were sampled either in winter-spring (moist) or early summer (dry) conditions and had a range of clinical expressions of the disease ovine footrot. Variables considered for optimizing field performance were: sample collection method, sample preparation, clinical expression of disease, and nature of the feet when sampled (moist vs. dry, clean vs. soiled). The test was found to perform best when sheep were sampled with moist, clean feet, using a dry swab with the sample prepared in alkaline polyethylene glycol, pH 13.0, as the collection buffer. A sensitivity of 89% and specificity of 97% was seen when used in-field under these conditions, when compared to aprV2 detection by rtPCR, with "very good" agreement to rtPCR results. This study shows the VDN LAMP test is easy to use in-field to identify the presence of aprV2- positive D. nodosus in sheep flocks.
- Published
- 2019
- Full Text
- View/download PDF
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