Author: "Sonenshine DE" - Searchworks@Jio Institute Digital Library Search Results

197 results on '"Sonenshine DE"'

1. Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Author: Brown, P, Tan, A-C, El-Esawi, MA, Liehr, T, Blanck, O, Gladue, DP, Almeida, GMF, Cernava, T, Sorzano, CO, Yeung, AWK, Engel, MS, Chandrasekaran, AR, Muth, T, Staege, MS, Daulatabad, SV, Widera, D, Zhang, J, Meule, A, Honjo, K, Pourret, O, Yin, C-C, Zhang, Z, Cascella, M, Flegel, WA, Goodyear, CS, van Raaij, MJ, Bukowy-Bieryllo, Z, Campana, LG, Kurniawan, NA, Lalaouna, D, Huttner, FJ, Ammerman, BA, Ehret, F, Cobine, PA, Tan, E-C, Han, H, Xia, W, McCrum, C, Dings, RPM, Marinello, F, Nilsson, H, Nixon, B, Voskarides, K, Yang, L, Costa, VD, Bengtsson-Palme, J, Bradshaw, W, Grimm, DG, Kumar, N, Martis, E, Prieto, D, Sabnis, SC, Amer, SEDR, Liew, AWC, Perco, P, Rahimi, F, Riva, G, Zhang, C, Devkota, HP, Ogami, K, Basharat, Z, Fierz, W, Siebers, R, Tan, K-H, Boehme, KA, Brenneisen, P, Brown, JAL, Dalrymple, BP, Harvey, DJ, Ng, G, Werten, S, Bleackley, M, Dai, Z, Dhariwal, R, Gelfer, Y, Hartmann, MD, Miotla, P, Tamaian, R, Govender, P, Gurney-Champion, OJ, Kauppila, JH, Zhang, X, Echeverria, N, Subhash, S, Sallmon, H, Tofani, M, Bae, T, Bosch, O, Cuiv, PO, Danchin, A, Diouf, B, Eerola, T, Evangelou, E, Filipp, FV, Klump, H, Kurgan, L, Smith, SS, Terrier, O, Tuttle, N, Ascher, DB, Janga, SC, Schulte, LN, Becker, D, Browngardt, C, Bush, SJ, Gaullier, G, Ide, K, Meseko, C, Werner, GDA, Zaucha, J, Al-Farha, AA, Greenwald, NF, Popoola, SI, Rahman, MS, Xu, J, Yang, SY, Hiroi, N, Alper, OM, Baker, CI, Bitzer, M, Chacko, G, Debrabant, B, Dixon, R, Forano, E, Gilliham, M, Kelly, S, Klempnauer, K-H, Lidbury, BA, Lin, MZ, Lynch, I, Ma, W, Maibach, EW, Mather, DE, Nandakumar, KS, Ohgami, RS, Parchi, P, Tressoldi, P, Xue, Y, Armitage, C, Barraud, P, Chatzitheochari, S, Coelho, LP, Diao, J, Doxey, AC, Gobet, A, Hu, P, Kaiser, S, Mitchell, KM, Salama, MF, Shabalin, IG, Song, H, Stevanovic, D, Yadollahpour, A, Zeng, E, Zinke, K, Alimba, CG, Beyene, TJ, Cao, Z, Chan, SS, Gatchell, M, Kleppe, A, Piotrowski, M, Torga, G, Woldesemayat, AA, Cosacak, MI, Haston, S, Ross, SA, Williams, R, Wong, A, Abramowitz, MK, Effiong, A, Lee, S, Abid, MB, Agarabi, C, Alaux, C, Albrecht, DR, Atkins, GJ, Beck, CR, Bonvin, AMJJ, Bourke, E, Brand, T, Braun, RJ, Bull, JA, Cardoso, P, Carter, D, Delahay, RM, Ducommun, B, Duijf, PHG, Epp, T, Eskelinen, E-L, Fallah, M, Farber, DB, Fernandez-Triana, J, Feyerabend, F, Florio, T, Friebe, M, Furuta, S, Gabrielsen, M, Gruber, J, Grybos, M, Han, Q, Heinrich, M, Helantera, H, Huber, M, Jeltsch, A, Jiang, F, Josse, C, Jurman, G, Kamiya, H, de Keersmaecker, K, Kristiansson, E, de Leeuw, F-E, Li, J, Liang, S, Lopez-Escamez, JA, Lopez-Ruiz, FJ, Marchbank, KJ, Marschalek, R, Martin, CS, Miele, AE, Montagutelli, X, Morcillo, E, Nicoletti, R, Niehof, M, O'Toole, R, Ohtomo, T, Oster, H, Palma, J-A, Paterson, R, Peifer, M, Portilla, M, Portillo, MC, Pritchard, AL, Pusch, S, Raghava, GPS, Roberts, NJ, Ross, K, Schuele, B, Sergeant, K, Shen, J, Stella, A, Sukocheva, O, Uversky, VN, Vanneste, S, Villet, MH, Viveiros, M, Vorholt, JA, Weinstock, C, Yamato, M, Zabetakis, I, Zhao, X, Ziegler, A, Aizat, WM, Atlas, L, Bridges, KM, Chakraborty, S, Deschodt, M, Domingues, HS, Esfahlani, SS, Falk, S, Guisado, JL, Kane, NC, Kueberuwa, G, Lau, CL, Liang, D, Liu, E, Luu, AM, Ma, C, Ma, L, Moyer, R, Norris, AD, Panthee, S, Parsons, JR, Peng, Y, Pinto, IM, Reschke, CR, Sillanpaa, E, Stewart, CJ, Uhle, F, Yang, H, Zhou, K, Zhu, S, Ashry, M, Bergsland, N, Berthold, M, Chen, C-E, Colella, V, Cuypers, M, Eskew, EA, Fan, X, Gajda, M, Gonzalezlez-Prendes, R, Goodin, A, Graham, EB, Groen, EJN, Gutierrez-Sacristan, A, Habes, M, Heffler, E, Higginbottom, DB, Janzen, T, Jayaraman, J, Jibb, LA, Jongen, S, Kinyanjui, T, Koleva-Kolarova, RG, Li, Z, Liu, Y-P, Lund, BA, Lussier, AA, Mier, P, Moore, MD, Nagler, K, Orme, MW, Pearson, JA, Prajapati, AS, Saito, Y, Troder, SE, Uchendu, F, Verloh, N, Voutchkova, DD, Abu-Zaid, A, Bakkach, J, Baumert, P, Dono, M, Hanson, J, Herbelet, S, Hobbs, E, Kulkarni, A, Liu, S, Loft, ND, Reddan, T, Senghore, T, Vindin, H, Xu, H, Bannon, R, Chen, B, Cheung, JTK, Cooper, J, Esnakul, AK, Feghali, KA, Ghelardi, E, Gnasso, A, Horbar, J, Lai, HM, Ma, R, Pan, Z, Peres, MA, Pranata, R, Seow, E, Sydes, M, Testoni, I, Westermair, AL, Yang, Y, Afnan, M, Albiol, J, Albuquerque, LG, Amiya, E, Amorim, RM, An, Q, Andersen, SU, Aplin, JD, Argyropoulos, C, Asmann, YW, Assaeed, AM, Atanasov, AG, Atchison, DA, Avery, SV, Avillach, P, Baade, PD, Backman, L, Badie, C, Baldi, A, Ball, E, Bardot, O, Barnett, AG, Basner, M, Batra, J, Bazanova, OM, Beale, A, Beddoe, T, Bell, ML, Berezikov, E, Berners-Price, S, Bernhardt, P, Berry, E, Bessa, TB, Billington, C, Birch, J, Blakely, RD, Blaskovich, MAT, Blum, R, Boelaert, M, Bogdanos, D, Bosch, C, Bourgoin, T, Bouvard, D, Boykin, LM, Bradley, G, Braun, D, Brownlie, J, Bruhl, A, Burt, A, Butler, LM, Byrareddy, SN, Byrne, HJ, Cabantous, S, Calatayud, S, Candal, E, Carlson, K, Casillas, S, Castelvetro, V, Caswell, PT, Cavalli, G, Cerovsky, V, Chagoyen, M, Chen, C-S, Chen, DF, Chen, H, Chen, J-T, Chen, Y, Cheng, C, Cheng, J, Chinapaw, M, Chinopoulos, C, Cho, WCS, Chong, L, Chowdhury, D, Chwalibog, A, Ciresi, A, Cockcroft, S, Conesa, A, Cook, PA, Cooper, DN, Coqueret, O, Corea, EM, Costa, E, Coupland, C, Crawford, SY, Cruz, AD, Cui, H, Cui, Q, Culver, DC, D'Angiulli, A, Dahms, TES, Daigle, F, Dalgleish, R, Danielsen, HE, Darras, S, Davidson, SM, Day, DA, Degirmenci, V, Demaison, L, Devriendt, K, Ding, J, Dogan, Y, Dong, XC, Donner, CF, Dressick, W, Drevon, CA, Duan, H, Ducho, C, Dumaz, N, Dwarakanath, BS, Ebell, MH, Eisenhardt, S, Elkum, N, Engel, N, Erickson, TB, Fairhead, M, Faville, MJ, Fejzo, MS, Festa, F, Feteira, A, Flood-Page, P, Forsayeth, J, Fox, SA, Franks, SJ, Frentiu, FD, Frilander, MJ, Fu, X, Fujita, S, Galea, I, Galluzzi, L, Gani, F, Ganpule, AP, Garcia-Alix, A, Gedye, K, Giordano, M, Giunta, C, Gleeson, PA, Goarant, C, Gong, H, Gora, D, Gough, MJ, Goyal, R, Graham, KE, Grande-Perez, A, Graves, PM, Greidanus, H, Grice, D, Grunau, C, Gumulya, Y, Guo, Y, Gurevich, VV, Gusev, O, Hacker, E, Hage, SR, Hagen, G, Hahn, S, Haller, DM, Hammerschmidt, S, Han, J, Han, R, Handfield, M, Hapuarachchi, HC, Harder, T, Hardingham, JE, Heck, M, Heers, M, Hew, KF, Higuchi, Y, St Hilaire, C, Hilton, R, Hodzic, E, Hone, A, Hongoh, Y, Hu, G, Huber, HP, Hueso, LE, Huirne, J, Hurt, L, Idborg, H, Ikeo, K, Ingley, E, Jakeman, PM, Jensen, A, Jia, H, Jia, S, Jiang, J, Jiang, X, Jin, Y, Jo, D, Johnson, AM, Johnston, M, Jonscher, KR, Jorens, PG, Jorgensen, JOL, Joubert, JW, Jung, S-H, Junior, AM, Kahan, T, Kamboj, SK, Kang, Y-K, Karamanos, Y, Karp, NA, Kelly, R, Kenna, R, Kennedy, J, Kersten, B, Khalaf, RA, Khalid, JM, Khatlani, T, Khider, T, Kijanka, GS, King, SRB, Kluz, T, Knox, P, Kobayashi, T, Koch, K-W, Kohonen-Corish, MRJ, Kong, X, Konkle-Parker, D, Korpela, KM, Kostrikis, LG, Kraiczy, P, Kratz, H, Krause, G, Krebsbach, PH, Kristensen, SR, Kumari, P, Kunimatsu, A, Kurdak, H, Kwon, YD, Lachat, C, Lagisz, M, Laky, B, Lammerding, J, Lange, M, Larrosa, M, Laslett, AL, LeClair, EE, Lee, K-W, Lee, M-Y, Lee, M-S, Li, G, Lieb, K, Lim, YY, Lindsey, ML, Line, P-D, Liu, D, Liu, F, Liu, H, Lloyd, VK, Lo, T-W, Locci, E, Loidl, J, Lorenzen, J, Lorkowski, S, Lovell, NH, Lu, H, Lu, W, Lu, Z, Luengo, GS, Lundh, L-G, Lysy, PA, Mabb, A, Mack, HG, Mackey, DA, Mahdavi, SR, Maher, P, Maher, T, Maity, SN, Malgrange, B, Mamoulakis, C, Mangoni, AA, Manke, T, Manstead, ASR, Mantalaris, A, Marsal, J, Marschall, H-U, Martin, FL, Martinez-Raga, J, Martinez-Salas, E, Mathieu, D, Matsui, Y, Maza, E, McCutcheon, JE, Mckay, GJ, McMillan, B, McMillan, N, Meads, C, Medina, L, Merrick, BA, Metzger, DW, Meunier, FA, Michaelis, M, Micheau, O, Mihara, H, Mintz, EM, Mizukami, T, Moalic, Y, Mohapatra, DP, Monteiro, A, Montes, M, Moran, JV, Morozov, SY, Mort, M, Murai, N, Murphy, DJ, Murphy, SK, Murray, SA, Naganawa, S, Nammi, S, Nasios, G, Natoli, RM, Nguyen, F, Nicol, C, van Nieuwerburgh, F, Nilsen, EB, Nobile, CJ, O'Mahony, M, Ohlsson, S, Olatunbosun, O, Olofsson, P, Ortiz, A, Ostrikov, K, Otto, S, Outeiro, TF, Ouyang, S, Paganoni, S, Page, A, Palm, C, Paradies, Y, Parsons, MH, Parsons, N, Pascal, P, Paul, E, Peckham, M, Pedemonte, N, Pellizzon, MA, Petrelli, M, Pichugin, A, Pinto, CJC, Plevris, JN, Pollesello, P, Polz, M, Ponti, G, Porcelli, P, Prince, M, Quinn, GP, Quinn, TJ, Ramula, S, Rappsilber, J, Rehfeldt, F, Reiling, JH, Remacle, C, Rezaei, M, Riddick, EW, Ritter, U, Roach, NW, Roberts, DD, Robles, G, Rodrigues, T, Rodriguez, C, Roislien, J, Roobol, MJ, Rowe, JA, Ruepp, A, van Ruitenbeek, J, Rust, P, Saad, S, Sack, GH, Santos, M, Saudemont, A, Sava, G, Schrading, S, Schramm, A, Schreiber, M, Schuler, S, Schymkowitz, J, Sczyrba, A, Seib, KL, Shi, H-P, Shimada, T, Shin, J-S, Shortt, C, Silveyra, P, Skinner, D, Small, I, Smeets, PAM, So, P-W, Solano, F, Sonenshine, DE, Song, J, Southall, T, Speakman, JR, Srinivasan, MV, Stabile, LP, Stasiak, A, Steadman, KJ, Stein, N, Stephens, AW, Stewart, DI, Stine, K, Storlazzi, C, Stoynova, NV, Strzalka, W, Suarez, OM, Sultana, T, Sumant, AV, Summers, MJ, Sun, G, Tacon, P, Tanaka, K, Tang, H, Tanino, Y, Targett-Adams, P, Tayebi, M, Tayyem, R, Tebbe, CC, Telfer, EE, Tempel, W, Teodorczyk-Injeyan, JA, Thijs, G, Thorne, S, Thrift, AG, Tiffon, C, Tinnefeld, P, Tjahjono, DH, Tolle, F, Toth, E, del Tredici, AL, Tsapas, A, Tsirigotis, K, Turak, A, Tzotzos, G, Udo, EE, Utsumi, T, Vaidyanathan, S, Vaillant, M, Valsesia, A, Vandenbroucke, RE, Veiga, FH, Vendrell, M, Vesk, PA, Vickers, P, Victor, VM, Villemur, R, Vohl, M-C, Voolstra, CR, Vuillemin, A, Wakelin, S, Waldron, L, Walsh, LJ, Wang, AY, Wang, F, Wang, Y, Watanabe, Y, Weigert, A, Wen, J-C, Wham, C, White, EP, Wiener, J, Wilharm, G, Wilkinson, S, Willmann, R, Wilson, C, Wirth, B, Wojan, TR, Wolff, M, Wong, BM, Wu, T-W, Wuerbel, H, Xiao, X, Xu, D, Xu, JW, Xue, B, Yalcin, S, Yan, H, Yang, E-C, Yang, S, Yang, W, Ye, Y, Ye, Z-Q, Yli-Kauhaluoma, J, Yoneyama, H, Yu, Y, Yuan, G-C, Yuh, C-H, Zaccolo, M, Zeng, C, Zevnik, B, Zhang, L, Zhang, Y, Zhang, Z-Y, Zhao, Y, Zhou, M, Zuberbier, T, Aanei, CM, Ahmad, R, Al-Lawama, M, Alanio, A, Allardyce, J, Alonso-Caneiro, D, Atack, JM, Baier, D, Bansal, A, Benezeth, Y, Berbesque, C, Berrevoet, F, Biedermann, PHW, Bijleveld, E, Bittner, F, Blombach, F, Van den Bos, W, Boudreau, SA, Bramoweth, AD, Braubach, O, Cai, Y, Campbell, M, Catry, T, Chen, X, Cheng, S, Chung, H-J, Chavez-Fumagalli, MA, Conway, A, Costa, BM, Cyr, N, Dean, LT, Denzel, MS, Dlamini, SV, Dudley, KJ, Dufies, M, Ecke, T, Eckweiler, D, Eixarch, E, El-Adawy, H, Emmrich, JV, Eustace, AJ, Falter-Wagner, CM, Fuss, J, Gao, J, Gill, MR, Gloyn, L, Goggs, R, Govinden, U, Greene, G, Greiff, V, Grundle, DS, Gruneberg, P, Gumede, N, Haore, G, Harrison, P, Hoenner, X, Hojsgaard, D, Hori, H, Ikonomopoulou, MP, Jeurissen, P, Johnson, DM, Kabra, D, Kamagata, K, Karmakar, C, Kasian, O, Kaye, LK, Khan, MM, Kim, Y-M, Kish, JK, Kobold, S, Kohanbash, G, Kohls, G, Kugler, J-M, Kumar, G, Lacy-Colson, J, Latif, A, Lauschke, VM, Li, B, Lim, CJ, Liu, X, Lu, J-J, Lu, Q, Mahavadi, P, Marzocchi, U, McGarrigle, CA, van Meerten, T, Min, R, Moal, I, Molari, M, Molleman, L, Mondal, SR, Van de Mortel, T, Moss, WN, Moultos, OA, Mukherjee, M, Nakayama, K, Narayan, E, Navaratnarajah, Neumann, P-A, Nie, J, Nie, Y, Niemeyer, F, Fiona, Nwaiwu, O, Oldenmenger, WH, Olumayede, E, Ou, J, Pallebage-Gamarallage, M, Pearce, SP, Pelkonen, T, Pelleri, MC, Pereira, JL, Pheko, M, Pinto, KA, Piovesan, A, Pluess, M, Podolsky, IM, Prescott, J, Qi, D, Qi, X, Raikou, VD, Ranft, A, Rhodes, J, Rotge, J-Y, Rowe, AD, Saggar, M, Schuon, RA, Shahid, S, Shalchyan, V, Shirvalkar, P, Shiryayev, O, Singh, J, Smout, MJ, Soares, A, Song, C, Srivastava, K, Srivastava, RK, Sun, J, Szabo, A, Szymanski, W, Tai, CNP, Takeuchi, H, Tanadini-Lang, S, Tang, F, Tao, W, Theron, G, Tian, CF, Tian, Y-S, Tuttle, LM, Valenti, A, Verlot, P, Walker, M, Wang, J, Welter, D, Winslade, M, Wu, D, Wu, Y-R, Xiao, H, Xu, B, Xu, Z, Yang, D, Yang, M, Yankilevich, P, You, Y, Yu, C, Zhan, J, Zhang, G, Zhang, K, Zhang, T, Zhao, G, Zhao, J, Zhou, X, Zhu, Z, Ajani, PA, Anazodo, UC, Bagloee, SA, Bail, K, Bar, I, Bathelt, J, Benkeser, D, Bernier, ML, Blanchard, AM, Boakye, DW, Bonatsos, V, Boon, MH, Bouboulis, G, Bromfield, E, Brown, J, Bul, KCM, Burton, KJ, Butkowski, EG, Carroll, G, Chao, F, Charrier, EE, Chen, Y-C, Chenguang, Choi, JR, Christoffersen, T, Comel, JC, Cosse, C, Cui, Y, van Dessel, P, Dhaval, Diodato, D, Duffey, M, Dutt, A, Egea, LG, El-Said, M, Faye, M, Fernandez-Fernandez, B, Foley, KG, Founou, LL, Fu, F, Gadelkareem, RA, Galimov, E, Garip, G, Gemmill, A, Gouil, Q, Grey, J, Gridneva, Z, Grothe, MJ, Grebert, T, Guerrero, F, Guignard, L, Haenssgen, MJ, Hasler, D, Holgate, JY, Huang, A, Hulse-Kemp, AM, Jean-Quartier, C, Jeon, S-M, Jia, Y, Jutzeler, C, Kalatzis, P, Karim, M, Karsay, K, Keitel, A, Kempe, A, Keown, JR, Khoo, CM, Khwaja, N, Kievit, RA, Kosanic, A, Koutoukidis, DA, Kramer, P, Kumar, D, Kirag, N, Lanza, G, Le, TD, Leem, JW, Leightley, D, Leite, A, Lercher, L, Li, Y, Lim, R, Lima, LRA, Lin, L, Ling, T, Liu, Y, Liu, Z, Lu, Y, Lum, FM, Luo, H, Machhi, J, Macleod, A, Macwan, I, Madala, HR, Madani, N, de Maio, N, Makowiecki, K, Mallinson, DJ, Margelyte, R, Maria, C, Markonis, Y, Marsili, L, Mavoa, S, McWilliams, L, Megersa, M, Mendes, CSM, Menichetti, J, Mercieca-Bebber, R, Miller, JJ, Minde, D-PM, Minges, A, Mishra, E, Mishra, VR, Moores, C, Morrice, N, Moskalensky, AE, Navarin, N, Negera, E, Nolet, P, Nordberg, A, Norden, R, Nowicki, JP, Olova, N, Olszewski, P, Onzima, R, Pan, C-L, Park, C, Park, DI, Park, S, Patil, CD, Pedro, SA, Perry, SR, Peter, J, Peterson, BM, Pezzuolo, A, Pozdnyakov, I, Qian, S, Qin, L, Rafe, A, Raote, I, Raza, A, Rebl, H, Refai, O, Regan, T, Richa, T, Richardson, MF, Robinson, KR, Rossoni, L, Rouet, R, Safaei, S, Schneeberger, PHH, Schwotzer, D, Sebastian, A, Selinski, J, Seltmann, S, Sha, F, Shalev, N, Shang, J-L, Singer, J, Singh, M, Smith, T, Solomon-Moore, E, Song, L, Soraggi, S, Stanley, R, Steckhan, N, Strobl, F, Subissi, L, Supriyanto, I, Surve, CR, Suzuki, T, Syme, C, Sorelius, K, Tang, Y, Tantawy, M, Tennakoon, S, Teseo, S, Toelzer, C, Tomov, N, Tovar, M, Tran, L, Tripathi, S, Tuladhar, AM, Ukubuiwe, AC, Ung, COL, Valgepea, K, Vatanparast, H, Vidal, A, Wang, Q, Watari, R, Webster, R, Wei, J, Wibowo, D, Wingenbach, TSH, Xavier, RM, Xiao, S, Xiong, P, Xu, S, Yao, R, Yao, W, Yin, Q, Zaitsu, M, Zeineb, Z, Zhan, X-Y, Zhang, R, Zhang, W, Zheng, S, Zhou, B, Ahmad, H, Akinwumi, SA, Albery, GF, Alhowimel, A, Ali, J, Alshehri, M, Alsuhaibani, M, Anikin, A, Azubuike, SO, Bach-Mortensen, A, Baltiansky, L, Bartas, M, Belachew, KY, Bhardwaj, V, Binder, K, Bland, NS, Boah, M, Bullen, B, Calabro, GE, Callahan, TJ, Cao, B, Chalmers, K, Chang, W, Che, Z, Chen, ATY, Chen, Z, Choi, Y, Chowdhury, MAK, Christensen, MR, Cooke, RSC, Cottini, M, Covington, NV, Cunningham, C, Delarocque, J, Devos, L, Dhar, AR, Ding, K-F, Dong, K, Dong, Z, Dreyer, N, Ekstrand, C, Fardet, T, Feleke, BE, Feurer, T, Freitas, 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and Zhou, Y
Published: 2019

2. Overview: Ticks as vectors of pathogens that cause disease in humans and animals

Author: José M. Venzal, Sonenshine De, Katherine M. Kocan, Agustín Estrada-Peña, and de la Fuente J
Subjects: biology, Borrelia, Zoology, Vertebrate, Rickettsia Infections, Disease, Disease Vectors, Tick, bacterial infections and mycoses, biology.organism_classification, Tick Infestations, Ticks, biology.animal, parasitic diseases, Animals, Humans, Helminths, Protozoa, Acari, Borrelia Infections, Ixodidae
Abstract: This article belongs to the Special Issue Biology of ticks., Ticks (Acari: Ixodidae) transmit a wide variety of pathogens to vertebrates including viruses, bacteria, protozoa and helminthes. Tick-borne pathogens are believed to be responsible for more than 100,000 cases of illness in humans throughout the world. Ticks are considered to be second worldwide to mosquitoes as vectors of human diseases, but they are the most important vectors of disease-causing pathogens in domestic and wild animals. Infection and development of pathogens in both tick and vertebrate hosts are mediated by molecular mechanisms at the tick-pathogen interface. These mechanisms, involving traits of both ticks and pathogens, include the evolution of common and species-specific characteristics. The molecular characterization of the tick-pathogen interface is rapidly advancing and providing new avenues for the development of novel control strategies for both tick infestations and their associated pathogens.
Published: 2008

3. A Contribution to the Ecology of Ticks Infesting Wild Birds and Rabbits in the Virginia-North Carolina Piedmont (Acarina: Ixodidae)1

Author: Sonenshine De and Stout Ij
Subjects: Larva, Sparrow, General Veterinary, biology, Ecology, Tick, biology.organism_classification, Infectious Diseases, Insect Science, biology.animal, Parasitology, Nymph, Junco, Ixodidae, Bobwhite quail, Haemaphysalis leporispalustris
Abstract: Host-parasite relationships and seasonal dynamics of 3 species of ticks infesting birds or rabbits or both at 2 localities in the Piedmont area of Virginia and North Carolina are described. Cottontail rabbits represented the dominant host for the immatures of Haemaphysalis leporispalustris (Packard) and Ixodes dentatus Marx in Virginia, where both rabbits and birds were examined. Bobwhite quail were almost as important as rabbits as hosts for immatures of H. leporispalustris , but not for immatures of I. dentatus. Other important bird hosts for the immatures of these 2 tick species included members of the Fringillidae, Mimidae, Troglodytidae, Turdidae, and Parulidae. Ixodes brunneus Koch was found primarily on the Slate-colored Junco, Cardinal, and White-throated Sparrow between November and April. Tick burdens on birds at the 2 Piedmont localities were similar, but were substantially lower than the burdens reported in other areas of the United States. Host-seeking activity by immatures of the 2 bird-rabbit ticks was bimodal, with peak activity in late summer or fall (dominant period) and again in winter or early spring. In the fall, host-seeking activity by I. dentatus immatures occurred 1 or 2 months later than host seeking by immatures of H. leporispalustris.
Published: 1970

4. Large expert-curated database for benchmarking document similarity detection in biomedical literature search

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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. 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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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Univ, Univ Exeter, Hillingdon Hosp NHS Fdn Trust, Natl & Kapodistrian Univ Athens, Lausanne Univ Hosp, Queens Univ Belfast, Cold Spring Harbor Lab, Hosp Clin Porto Alegre, Univ Paris 05, Indian Inst Adv Res, Bambino Ges Childrens Res Hosp, Univ Cadiz, Mansoura Univ Hosp, Ctr Expertise & Biol Diagnost Cameroon, Swiss Fed Labs Mat Sci & Technol, Assiut Univ, Univ Derby, SUNY Stony Brook, Walter & Eliza Hall Inst Med Res, Janelia Res Campus, USDA ARS, Med Univ Graz, Ajou Univ, Univ Dundee, Tech Univ Dresden, Natl Univ Hlth Syst, Univ Canterbury, Univ Hosp Southern Denmark, Baylor Coll Med, Adnan Menderes Univ Aydin, Oasi Res Inst IRCCS, LSHTM, Leibniz Univ Hannover, Xi An Jiao Tong Univ, Shenzhen Univ, Cent South Univ, Univ Bridgeport, Texas Tech Univ, Univ Montana, NHLBI, Cleveland Clin, NARO, Eduardo Mondlane Univ, RAS, Beijing Inst Technol, Univ Hlth Network, Univ Bath, Fisheries & Oceans Canada, Queensland Govt, Uppsala Univ, Childrens Canc Hosp, Leibniz Inst Nat Prod Res & Infect Biol, Duy Tan Univ, Henan Agr Univ, Beijing Inst Microbiol & Epidemiol, Minist Hlth, Prince Sattam Bin Abdulaziz Univ, Univ Auckland, Osped Niguarda Ca Granda, Univ Vet Med, Univ Saskatchewan, Univ Coimbra, South Cent High Specialty Hosp, Wageningen Bioveterinary Res, Guangdong Second Prov Gen Hosp, Hiroshima Univ, Univ Iceland, Kathmandu Univ, Fraunhofer MEVIS, Univ Tehran Med Sci, Univ Messina, AO Papardo Hosp Messina, Univ Stirling, Saveh Univ Med Sci, Gakujutsu Shien Co Ltd, Univ Plymouth, CHU Toulouse, Azorean Biodivers Grp, Univ Acores, Univ Malawi, Bioself Commun, Ahmadu Bello Univ, Dalhousie Univ, VisMederi Srl, Amer Univ Beirut, Mechnikov Res Inst Vaccines & Sera, Vreden Russian Res Inst Traumatol & Orthopaed, Hangzhou Ctr Dis Control & Prevent, Kaohsiung Med Univ, Zoetis, Aintree Univ Hosp NHS Fdn Trust, Wrightington Hosp, Loyola Univ, Atkins Vet Serv, Kangwon Natl Univ, Kakatiya Med Coll, Univ Antioquia, IISER, Univ Rosario, Univ Hosp Basel, Univ Hosp Munster, Univ Kentucky, Univ Calif Irvine, Univ Hosp Leuven, Chongqing Med Univ, Childrens Hosp Kings Daughters, China Three Gorges Univ, and Xiangtan Univ
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. 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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 Univ Oxford, Physiol Anat & Genet, Oxford, England George Washington Univ, Phys, Washington, DC USA Univ Nebraska, Sch Biol Sci, Lincoln, NE USA Toronto Gen Hosp, Res Inst, Dept Lab Med & Pathobiol, Toronto, ON, Canada Univ Texas Dallas, Biol Sci, Richardson, TX 75083 USA NYU, Dept Chem, New York, NY USA Shandong Univ, Sch Math & Stat, Jinan, Shandong, Peoples R China Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei, Anhui, Peoples R China Purdue Univ, Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA NIBSC, Adv Therapies, Ridge, Herts, England Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Pulm & Crit Care Med, Shanghai, Peoples R China Charite Med Univ Berlin, Dermatol & Allergy, Berlin, Germany Univ Hosp St Etienne, Hematol, St Etienne, France Inland Norway Univ Appl Sci, Inst Biotechnol, Elverum, Norway Univ Jordan, Pediat, Amman, Jordan Inst Pasteur, Mol Mycol Unit, Paris, France Cardiff Univ, Sch Med, Inst Psychol Med & Clin Neurosci, Med Res Council Ctr Neuropsychiat Genet & Genom, Cardiff, S Glam, Wales Zurich Univ Appl Sci, Social Work, Zurich, Switzerland Jawaharlal Nehru Univ, Sch Life Sci, New Delhi, India Univ Burgundy Franche Comte, LE2I, Dijon, France Univ Roehampton, Life Sci, London, England Ghent Univ Hosp, Gen & HPB Surg, Ghent, Belgium Univ Wurzburg, Insect Fungus Symbiosis Lab, Wurzburg, Germany Radboud Univ Nijmegen, Behav Sci Inst, Nijmegen, Netherlands Fraunhofer WKI, Applicat Ctr HOFZET, Hannover, Germany UCL, Struct & Mol Biol, London, England Univ Amsterdam, Dev Psychol, Amsterdam, Netherlands Aalborg Univ, Hlth Sci & Technol, CNAP, SMI, Aalborg, Denmark VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA Cedars Sinai Med Ctr, Neurosurg, Los Angeles, CA 90048 USA Sun Yat Sen Univ, Sch Data & Comp Sci, Guangzhou, Guangdong, Peoples R China Dezhou Univ, Shandong Prov Key Lab Biophys, Guangzhou, Guangdong, Peoples R China Maison Teledetection, Inst Rech Dev, UMR Espace DEv, Montpellier, France Xiamen Univ, Sch Life Sci, Xiamen, Fujian, Peoples R China Nanjing Univ, Sch Med, Jinling Hosp, Natl Clin Res Ctr Kidney Dis,Dept Med Imaging, Nanjing, Jiangsu, Peoples R China Univ Kent, Sch Social Policy Sociol & Social Res, Canterbury, Kent, England Univ Fed Minas Gerais, Infect Dis & Trop Med, Belo Horizonte, MG, Brazil Univ Minho, Sch Med, Life & Hlth Sci Res Inst ICVS, Braga, Portugal Univ Montreal, Biochim & Med Mol, Montreal, PQ, Canada Johns Hopkins Bloomberg Sch Publ Hlth, Epidemiol, Baltimore, MD USA Max Planck Inst Biol Ageing, Metab & Genet Regulat Ageing, Cologne, Germany Univ Swaziland, Hlth Sci, Kwaluseni, Eswatini Queensland Univ Technol, Inst Future Environm, Brisbane, Qld, Australia Ctr Sci Monaco, Dept Biol Med, Monaco, Monaco HELIOS Hosp, Urol, Bad Saarow Pieskow, Germany Tech Univ Carolo Wilhelmina Braunschweig, Inst Microbiol, Braunschweig, Germany Univ Barcelona, Barcelona Ctr Maternal Fetal & Neonatal Med, Fetal i D Fetal Med Res Ctr, IDIBAPS BCNatal,Hosp Clin, Barcelona, Spain Univ Barcelona, Hosp St Joan de Deu, Barcelona, Spain Friedrich Loeffler Inst, Inst Bacterial Infect & Zoonoses, Jena, Germany Charite Med Univ Berlin, Neurol, Berlin, Germany Dublin City Univ, Natl Inst Cellular Biotechnol, Mol Therapeut Canc Ireland, Dublin, Ireland Schoen Clin Roseneck, Prien Am Chiemsee, Germany Univ Med Ctr Hamburg Eppendorf, Inst Sex Res & Forens Psychiat, Hamburg, Germany Nankai Univ, Sch Math Sci, Tianjin, Peoples R China Nankai Univ, LPMC, Tianjin, Peoples R China Univ Oxford, Oncol, Oxford, England Royal Holloway Univ London, Class, Egham, Surrey, England Cornell Univ, Clin Sci, Ithaca, NY USA Univ KwaZulu Natal, Pharmaceut Chem, Westville Campus, Durban, South Africa Royal Coll Surgeons Ireland, Med, Dublin, Ireland Univ Oslo, Dept Immunol, Oslo, Norway Bermuda Inst Ocean Sci, Marine Nitrogen Cycling Lab, St Georges, Bermuda Kanazawa Univ, Inst Liberal Arts & Sci, Kanazawa, Ishikawa, Japan World Hlth Org Reg Off Africa, Brazzaville, Rep Congo Univ Hosp BesanCon, Infect Control Dept, Besancon, France Galapagos NV, Clin Dev, Mechelen, Belgium Univ Tasmania, Integrated Marine Observing Syst, Hobart, Tas, Australia Georg August Univ Gottingen, Albrecht von Haller Inst Plant Sci, Dept Systemat Biodivers & Evolut Plants, Gottingen, Germany Univ Occupat & Environm Hlth, Dept Psychiat, Fukuoka, Fukuoka, Japan IMDEA Food, Program Precis Nutr & Aging, Madrid, Spain Radboud Univ Nijmegen, Med Sch, IQHealthcare, Nijmegen, Netherlands Maastricht Univ, Dept Cardiovasc Surg, Maastricht, Netherlands German Diabet Ctr, Inst Clin Biochem & Pathobiochem, Dusseldorf, Germany Juntendo Univ, Grad Sch Med, Dept Radiol, Tokyo, Japan Deakin Univ, Sch Informat Technol, Melbourne, Vic, Australia Max Planck Inst Eusenforschung, Dept Interface Chem & Surface Sci, Dusseldorf, Germany Edge Hill Univ, Dept Psychol, Ormskirk, England Aga Khan Univ, Psychiat, Karachi, Pakistan KRIBB, Korean Bioinformat Ctr, Seoul, South Korea Cardinal Hlth Specialty Solut, Hlth Econ & Outcomes Res, Dallas, TX USA Klinikum Univ Munchen, Div Clin Pharmacol, Munich, Germany Univ Pittsburgh, Neurol Surg, Pittsburgh, PA USA Rhein Westfal TH Aachen, Dept Child & Adolescent Psychiat Psychosomat & Ps, Aachen, Germany Univ Copenhagen, Inst Mol & Cellular Biol, Copenhagen, Denmark St Jude Childrens Res Hosp, Struct Biol, 332 N Lauderdale St, Memphis, TN 38105 USA Royal Shrewsbury Hosp, Colorectal Surg, Shrewsbury, Salop, England Univ Nottingham, Fac Med & Hlth Sci, Nottingham, England Karolinska Inst, Dept Physiol & Pharmacol, Solna, Sweden Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Electroanalyt Chem, Jilin, Jilin, Peoples R China Univ British Columbia, Pediat, Vancouver, BC, Canada Chinese Acad Agr Sci, State Key Lab Cotton Biol, Res Base Anyang Inst Technol, Cotton Germplasm Resources,Inst Cotton Res, Beijing, Peoples R China Chinese Univ Hong Kong, Anaesthesia & Intens Care, Hong Kong, Peoples R China Univ Macau, ICMS, Zhuhai, Guangdong, Peoples R China North China Elect Power Univ, Sch Renewable Energy, Beijing, Peoples R China Justus Liegbig Univ, Dept Internal Med, Giessen, Germany Aarhus Univ, Biosci, Aarhus, Denmark Univ Dublin, Trinity Coll Dublin, Irish Longitudinal Study Ageing TILDA, Dublin, Ireland Univ Groningen, Univ Med Ctr Groningen, Hematol, Groningen, Netherlands Vrije Univ Amsterdam Med Ctr, Child Neurol, Amsterdam, Netherlands EBI, EMBL, Cambridge, England Max Planck Inst Marine Microbiol, HGF MPG Joint Res Grp Deep Sea Ecol & Technol, Bremen, Germany Max Planck Inst Human Dev, Ctr Adapt Rat, Berlin, Germany King Faisal Univ, Math, Al Hufuf, Saudi Arabia Griffith Univ, Sch Nursing & Midwifery, Gold Coast, Qld, Australia Iowa State Univ, Roy J Carver Dept Biochemsitry Biophys & Mol Biol, Ames, IA USA Delft Univ Technol, Fac Mech Maritime & Mat Engn, Engn Thermodynam Proc & Energy Dept, Leeghwaterstr 39, NL-2628 CB Delft, Netherlands Univ Nebraska Med Ctr, Coll Allied Hlth Profess, Cytotechnol Educ, Omaha, NE USA Shinko Mem Hosp, Dept Cardiovasc Med, Kobe, Hyogo, Japan Imperial Coll London, Mat, London, England Tech Univ Munich, Dept Surg, Munich, Germany Chinese Acad Agr Sci, Res Inst Pomol, Minist Agr, Lab Qual & Safety Risk Assessment Fruit Xingcheng, Shenyang, Liaoning, Peoples R China James Madison Univ, Commun Sci & Disorders, Harrisonburg, VA 22807 USA Univ Hosp Ulm, Inst Orthopaed Res & Biomech, Ulm, Germany Univ Essex, Sch Hlth & Social Care, Colchester, Essex, England Alpha Altis, Res Serv, Nottingham, England Erasmus MC, Med Oncol, Rotterdam, Netherlands Fed Univ Oye, Dept Ind Chem, Ekiti, Nigeria Duke Univ, Med Ctr, Cell Biol, Durham, NC USA Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England Univ Manchester, Canc Res UK Manchester Inst, Manchester, Lancs, England Helsinki Univ Hosp, Childrens Hosp, Helsinki, Finland Univ Aveiro, CESAM Ctr Environm & Marine Studies, Dept Biol, Aveiro, Portugal Univ Botswana, Psychol, Gaborone, Botswana Univ Fed Bahia, Nursing Sch, Salvador, BA, Brazil Queen Mary Univ London, Biol & Expt Psychol, London, England Natl Univ Pharm, Med Chem Dept, Kharkov, Ukraine Univ Bolton, Dept Educ & Psychol, Bolton, England La Trobe Univ, Dept Chem & Phys, Melbourne, Vic, Australia Gen Hosp Northern Theater Command, Dept Gastroenterol, Shenyang, Liaoning, Peoples R China Doctors Hosp, Dept Nephrol, Athens, Greece Univ Hosp Essen, Pediat 3, Essen, Germany Imperial Coll London, Infect Dis Epidemiol, London, England Sorbonne Univ, Dept Psychiat, Paris, France UNSW Sydney, Educ, Sydney, NSW, Australia Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA Hannover Med Sch, Clin Laryngol Rhinol & Otol, Hannover, Germany Curtin Univ, Ctr Aboriginal Studies, Perth, WA, Australia Iran Univ Sci & Technol, Biomed Engn Dept, Tehran, Iran Univ Calif San Francisco, Anesthesiol, San Francisco, CA 94143 USA Khalifa Univ Sci & Technol, Mech Engn, Abu Dhabi, U Arab Emirates Univ Florida, Hort Sci, Gainesville, FL USA James Cook Univ, Australian Inst Trop Hlth & Med, Ctr Biodiscovery & Mol Dev Therapeut, Cairns, Qld, Australia Univ Porto, Fac Med, CINTESIS, Porto, Portugal Shaoxing Peoples Hosp, Med Res Ctr, Shaoxing, Zhejiang, Peoples R China NIH, Dept Transfus Med, Bethesda, MD 20892 USA AIIMS, Dept Biotechnol, New Delhi, India Univ Ottawa, Biochem Microbiol & Immunol, Ottawa, ON, Canada Univ Oslo, Inst Clin Med, Div Mental Hlth & Addict, Oslo, Norway Univ Groningen, Univ Med Ctr Groningen, Dept Radiol, Groningen, Netherlands Univ Hong Kong, Sch Nursing, Hong Kong, Peoples R China Tokyo Med Univ, Ibaraki Med Ctr, Urol, Tokyo, Japan Univ Hosp Zurich, Dept Radiat Oncol, Zurich, Switzerland Univ Maryland, Inst Human Virol, Div Immunotherapy, Baltimore, MD 21201 USA Univ Maryland, Dept Surg, Baltimore, MD 21201 USA Stellenbosch Univ, Fac Med & Hlth Sci, Div Mol Biol & Human Genet, Stellenbosch, South Africa China Agr Univ, Coll Biol Sci, Beijing, Peoples R China Osaka Univ, Grad Sch Pharmaceut Sci, Suita, Osaka, Japan Univ Washington, Biochem, Seattle, WA 98195 USA Natl Res Council Italy, Inst Biosci & BioResources, Naples, Italy Univ Lyon, Phys, Lyon, France Univ Basel, Fac Psychol, Ctr Social Psychol, Basel, Switzerland Queen Mary Univ London, Barts Canc Inst, Ctr Mol Oncol, London, England EBI, EMBL, Samples Phenotypes & Ontol Team, Cambridge, England Charles Sturt Univ, Fac Arts & Educ, Bathurst, NSW, Australia Shandong Univ, Helmholtz Inst Biotechnol, Sch Life Sci, State Key Lab Microbial Technol, Jinan, Shandong, Peoples R China Shantou Univ, Dept Biol, Shantou, Guangdong, Peoples R China Shanxi Univ, Inst Biomed Sci, Taiyuan, Shanxi, Peoples R China St Jude Childrens Res Hosp, Computat Biol, 332 N Lauderdale St, Memphis, TN 38105 USA Harbin Med Univ, Coll Bioinformat Sci & Technol, Harbin, Heilongjiang, Peoples R China NIH, Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA Georgia Inst Technol, Dept Biol Sci, Atlanta, GA 30332 USA XtalPi Inc, Cambridge, MA USA Consejo Nacl Invest Cient & Tecn, Partner Inst Max Planck Soc, Inst Invest Biomed Buenos Aires IBioBA, Bioinformat, Buenos Aires, DF, Argentina Univ Sydney, Save Sight Inst, Sydney, NSW, Australia Univ South Australia, Canc Res Inst, Australian Ctr Precis Hlth, Adelaide, SA, Australia Jinan Univ, Inst Life & Hlth Engn, Guangdong Higher Educ Inst, Key Lab Funct Prot Res, Guangzhou, Guangdong, Peoples R China Univ Texas Hlth Sci Ctr Houston, Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA Weill Cornell Med, Dept Microbiol & Immunol, New York, NY USA Guangdong Inst Appl Biol Resources, Biotechnol Lab, Guangzhou, Guangdong, Peoples R China Shandong Normal Univ, Coll Life Sci, Jinan, Shandong, Peoples R China Shandong Univ, Life Sci Dept, Jinan, Shandong, Peoples R China South China Agr Univ, Integrat Microbiol Res Ctr, Guangzhou, Guangdong, Peoples R China Liaoning Acad Agr Sci, Crop Mol Improving Lab, Shenyang, Liaoning, Peoples R China Lawson Hlth Res Inst, Med Biophys, London, ON, Canada Univ Melbourne, Infrastruct Engn, Parkville, Vic, Australia Univ Canberra, Fac Hlth, Canberra, ACT, Australia Univ Cambridge, MRC Cognit & Brain Sci Unit, Cambridge, England Emory Univ, Biostat & Bioinformat, Atlanta, GA 30322 USA Johns Hopkins Sch Med, Anesthesiol & Crit Care Med, Baltimore, MD USA Nottingham Trent Univ, Sch Anim Rural & Environm Sci, Nottingham, England Univ Exeter, Biosci, Exeter, Devon, England Hillingdon Hosp NHS Fdn Trust, London, England Univ Glasgow, MRC CSO Social & Publ Hlth Sci Unit, Glasgow, Lanark, Scotland Natl & Kapodistrian Univ Athens, Evaggelismos Athens Hosp, ICU, Athens, Greece Univ Newcastle, Biol Sci, Callaghan, NSW, Australia Coventry Univ, Fac Hlth & Life Sci, Ctr Innovat Res Life Course, Coventry, W Midlands, England Lausanne Univ Hosp, Serv Endocrinol Diabet & Metab, Lausanne, Switzerland Charles Sturt Univ, Sch Community Hlth, Bathurst, NSW, Australia Queens Univ Belfast, Inst Global Food Secur, Belfast, Antrim, North Ireland Natl Univ Singapore, Inst Policy Studies, Singapore, Singapore Univ Penn, Intitute Med & Engn, Philadelphia, PA 19104 USA Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA Univ Michigan, EECS, Ann Arbor, MI 48109 USA Univ British Columbia, Ctr Blood Res, Vancouver, BC, Canada UiT Arctic Univ Norway, Dept Hlth & Care Sci, Fac Hlth Sci, Tromso, Norway Hosp Clin Porto Alegre, Physiotherapy, Porto Alegre, RS, Brazil Univ Paris 05, Med Sch, Paris, France Chinese Acad Agr Sci, Inst Crop Sci, Natl Key Facil Crop Gene Resources & Genet Improv, Beijing, Peoples R China Univ Ghent, Expt Clin & Hlth Psychol, Ghent, Belgium Indian Inst Adv Res, Bioinformat & Struct Biol, Gandhinagar, Gujart, India Bambino Ges Childrens Res Hosp, Lab Mol Med, Rome, Italy Heidelberg Univ, Ctr Infect Dis Parasitol, Heidelberg, Germany Stanford Univ, Elect Engn, Palo Alto, CA 94304 USA Univ Cadiz, Biol, Andalucia, Spain Mansoura Univ Hosp, Gen Surg, Mansoura, Egypt Inst Pasteur, Virol Pole, Dakar, Senegal Cardiff Univ, Div Canc & Genet, Cardiff, S Glam, Wales Ctr Expertise & Biol Diagnost Cameroon, Food Safety & Environm Microbiol, Yaounde, Cameroon Swiss Fed Labs Mat Sci & Technol, Lab Thin Films & Photovolta, Dubendorf, Switzerland Assiut Univ, Assiut Urol & Nephrol Hosp, Fac Med, Assiut, Egypt UCL, GEE, London, England UCL, IHA, London, England Univ Derby, Univ Derby Online Learning, Derby, England SUNY Stony Brook, Family Populat & Prevent Med, Stony Brook, NY 11794 USA Walter & Eliza Hall Inst Med Res, Mol Med Div, Melbourne, Vic, Australia Newcastle Univ, Northern Inst Canc Res, Newcastle Upon Tyne, Tyne & Wear, England German Ctr Neurodegenerat Dis, Clin Dementia Res, Bonn, Germany Sorbonne Univ, CNRS, UMR 7144, Stn Biol, Paris, France Univ Barcelona, Odontoestomatol, Barcelona, Spain Janelia Res Campus, Comp Sci, Ashburn, VA USA Univ Oxford, Ctr Trop Med & Global Hlth, Oxford, England Univ Bern, ARTORG Ctr Biomed Engn Res, Bern, Switzerland Australian Natl Univ, Eccles Inst Neurosci, John Curtain Sch Med Res, Canberra, ACT, Australia John Innes Ctr, Metab Biol, Norwich, Norfolk, England USDA ARS, Genom & Bioinformat Res Unit, Raleigh, NC 27695 USA Med Univ Graz, Inst Med Informat Stat & Documentat, Holzinger Grp, Graz, Austria Ajou Univ, Pharm, Suwon, South Korea City Univ Hong Kong, Sch Energy & Environm, Hong Kong, Peoples R China Univ British Columbia, Sch Kinseiol, Vancouver, BC, Canada Univ Copenhagen, Marine Biol Sect, Dept Biol, Copenhagen, Denmark Univ Vienna, Dept Commun, Vienna, Austria Univ Dundee, Sch Social Sci, Dundee, Scotland Tech Univ Dresden, Inst Bot, Dresden, Germany Univ Oxford, Div Struct Biol, Oxford, England Natl Univ Hlth Syst, Med, Singapore, Singapore Univ Canterbury, Sch Biol Sci, Christchurch, New Zealand Univ Hosp Southern Denmark, Focused Res Unit Mol Diagnost & Clin Res, Odense, Denmark Univ Oxford, Primary Care Hlth Sci, Oxford, England Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA Adnan Menderes Univ Aydin, Fac Nursing, Dept Publ Hlth Nursing, Aydin, Turkey Oasi Res Inst IRCCS, Dept Neurol IC, Troina, Italy Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA Kings Coll London, Kings Ctr Mil Hlth Res, London, England LSHTM, Dept Infect Dis Epidemiol, London, England Leibniz Univ Hannover, BMWZ Organ Chem, Hannover, Germany Xi An Jiao Tong Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Xian, Shaanxi, Peoples R China Univ South Australia, Sch Pharm & Med Sci, Adelaide, SA, Australia Univ Fed Santa Catarina, Dept Phys Educ, Florianopolis, SC, Brazil Southern Med Univ, Nanfang Hosp, Dept Oncol, Guangzhou, Guangdong, Peoples R China Stanford Univ, Hansen Expt Phys Lab, Palo Alto, CA 94304 USA Shenzhen Univ, Affiliated Hosp 1, Shenzhen Peoples Hosp 2, Inst Translat Med, Shenzhen, Guangdong, Peoples R China Univ Hong Kong, Dept Stat & Actuarial Sci, Hong Kong, Peoples R China UCL, Dept Mech Engn, London, England ASTAR, Singapore Immunol Network, Lab Microbial Immun, Singapore, Singapore Cent South Univ, State Key Lab Powder Met, Changsha, Hunan, Peoples R China Univ Aberdeen, Inst Appl Hlth Sci, Aberdeen, Scotland Univ Bridgeport, Biomed Engn, Bridgeport, CT 06601 USA Texas Tech Univ, Hlth Sci Ctr, Pharmaceut Sci, Lubbock, TX 79430 USA Univ Montana, Ecosyst & Conservat Sci, Missoula, MT 59812 USA Univ Goettingen, Dept Syst Neurosci, Gottingen, Germany NHLBI, Lab Syst Genet, Bldg 10, Bethesda, MD 20892 USA Cleveland Clin, Lou Ruvo Ctr Brain Hlth, Imaging, Las Vegas, NV USA Flinders Univ S Australia, Coll Nursing & Hlth Sci, Nutr & Dietet, Adelaide, SA, Australia Univ Padua, Dept Math, Padua, Italy Lund Univ, Fac Law, Lund, Sweden Univ Gothenburg, Dept Microbiol & Immunol, Gothenburg, Sweden NARO, Kachwekano Zardi, Entebbe, Uganda Natl Yunlin Univ Sci & Technol, Bachelor Program Interdisciplinary Studies, Touliu, Yunlin, Taiwan Aarhus Univ, Dept Biomed, Danish Res Inst Translat Neurosci DANDRITE, Aarhus, Denmark Eduardo Mondlane Univ, Math & Comp Sci, Maputo, Mozambique Univ Bern, Dept Old Age Psychiat & Psychotherapy, Bern, Switzerland RAS, Inst Cytol, Lab Cytol Unicellular Organisms, St Petersburg, Russia Beijing Inst Technol, Sch Chem & Chem Engn, Beijing, Peoples R China Univ Queensland, Queensland Alliance Agr & Food Innovat, Brisbane, Qld, Australia Fraunhofer Inst Toxicol & Expt Med ITEM, Inhalat Toxicol, Hannover, Germany Univ Hong Kong, Publ Hlth, Hong Kong, Peoples R China Univ Hlth Network, Anesthesia & Pain Med, Toronto, ON, Canada Univ Toronto, Toronto, ON, Canada Univ Bath, Dept Hlth, Bath, Avon, England Univ Copenhagen, Computat & RNA Biol, Copenhagen, Denmark Fisheries & Oceans Canada, Bedford Inst Oceanog, Dartmouth, NS, Canada Goethe Univ, CEF MC, BMLS, Phys Biol, Frankfurt, Germany Albert Einstein Coll Med, Anat & Struct Biol, New York, NY USA Queensland Govt, Dept Environm & Sci, Brisbane, Qld, Australia Uppsala Univ, Vasc Surg Sect, Dept Surg Sci, Uppsala, Sweden Childrens Canc Hosp, Res, Cairo, Egypt Leibniz Inst Nat Prod Res & Infect Biol, Bio Pilot Plant, Jena, Germany Duy Tan Univ, Inst Res & Dev, Da Nang, Vietnam Univ Helsinki, Helsinki Inst Life Sci HiLIFE, Helsinki, Finland Univ Queensland, Australian Inst Bioengn & Nanotechnol, Brisbane, Qld, Australia George Inst Global Hlth, Sydney, NSW, Australia Griffith Univ, Griffith Inst Drug Discovery, Brisbane, Qld, Australia Dezhou Univ, Coll Phys & Elect Informat, Shandong Prov Key Lab Biophys, Dezhou, Peoples R China Henan Agr Univ, Coll Life Sci, Zhengzhou, Henan, Peoples R China Univ Tokyo, Publ Hlth, Tokyo, Japan Sun Yat Sen Univ, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China Univ Illinois, Dept Med, Chicago, IL USA Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, Beijing, Peoples R China Minist Hlth, Key Lab Neonatal Dis, Shanghai, Peoples R China Covenant Univ, Dept Phys, Ota, Nigeria Prince Sattam Bin Abdulaziz Univ, Dept Phys Therapy & Hlth Rehabil, Al Kharj, Saudi Arabia Lund Univ, Cognit Sci, Malmo, Sweden Natl Open Univ Nigeria, Dept Publ & Environm Hlth, Abuja, Nigeria Peking Univ, Sch Publ Hlth, Dept Lab Sci & Technol, Beijing, Peoples R China Univ Sydney, Sch Publ Hlth, Menzies Ctr Hlth Policy, Sydney, NSW, Australia Univ Auckland, Dept Elect & Comp Engn, Auckland, New Zealand Beijing Univ Chinese Med, Res Ctr TCM Informat Engn, Beijing, Peoples R China Osped Niguarda Ca Granda, Cardiac Surg, Milan, Italy Univ Vet Med, Clin Horses, Hannover, Germany Harbin Med Univ, Lab Med Genet, Harbin, Heilongjiang, Peoples R China Univ Saskatchewan, Dept Psychol, Saskatoon, SK, Canada Univ Coimbra, Ctr Studies Geog & Spatial Planning CEGOT, Coimbra, Portugal Univ Groningen, Univ Med Ctr Groningen, Epidemiol, Groningen, Netherlands South Cent High Specialty Hosp, Dept Neurol & Neurosurg, Pemex, Mexico Shandong Agr Univ, Coll Informat Sci & Engn, Tai An, Shandong, Peoples R China Curtin Univ, Natl Drug Res Inst, Perth, WA, Australia Wageningen Bioveterinary Res, Bacteriol & Epidemiol, Lelystad, Netherlands Guangdong Second Prov Gen Hosp, Dept Rheumatol & Immunol, Guangzhou, Guangdong, Peoples R China Erasmus MC, Biomed Rngineering, Rotterdam, Netherlands Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Hiroshima, Japan Univ Iceland, Sch Hlth Sci, Reykjavik, Iceland Ohio State Univ, Mat Sci & Engn, Columbus, OH 43210 USA Kathmandu Univ, Sch Med Sci, Dept Physiotherapy, Dhulikhel, Nepal Univ Queensland, Sch Biomed Sci, Brisbane, Qld, Australia Fraunhofer MEVIS, Image Guided Therapies, Bremen, Germany Natl Univ Hlth Syst, Haematol Oncol, Singapore, Singapore Sun Yat Sen Univ, Canc Ctr, Breast Oncol, Guangzhou, Guangdong, Peoples R China Med Coll Wisconsin, Pharmacol & Toxicol, Wauwatosa, WI USA Queensland Univ Technol, Sci & Engn Fac, Sch Chem Phys & Mech Engn, Brisbane, Qld, Australia Univ Turin, Dept Mol Biotechnol & Hlth Sci, Turin, Italy Univ Tehran Med Sci, Sch Rehabil, Physiotherapy Dept, Tehran, Iran Univ Helsinki, Dept Forest Sci, Helsinki, Finland Univ Messina, Human Pathol, Messina, Italy AO Papardo Hosp Messina, Messina, Italy Univ Ibadan, Coll Med, Inst Child Hlth, Ibadan, Nigeria King Faisal Univ, Coll Med, Fac Ophthalmol, Al Hasa, Saudi Arabia Univ Stirling, Inst Social Mkt, Stirling, Scotland Saveh Univ Med Sci, Social Determinants Hlth Res Ctr, Saveh, Iran Gakujutsu Shien Co Ltd, Tokyo, Japan Chinese Acad Sci, Inst Geochem, Guiyang, Guizhou, Peoples R China Univ Plymouth, Med Sch, Plymouth, Devon, England CHU Toulouse, Immunol, Toulouse, France Azorean Biodivers Grp, Ctr Ecol Evolut & Environm Changes, Azores, Portugal Univ Acores, Azores, Portugal RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan Peking Univ, Sch Publ Hlth, Dept Global Hlth, Beijing, Peoples R China Chang Gung Univ, Chang Gung Mem Hosp, Dept Neurol, Linkou Med Ctr, Taoyuan, Taiwan Chang Gung Univ, Coll Med, Taoyuan, Taiwan Univ Malawi, Coll Med, Biomed Sci Dept, Blantyre, Malawi Univ Malawi, Coll Med, Pharm Dept, Blantyre, Malawi Bioself Commun, Biocurat, Marseille, France Peking Univ, Hosp 3, Dept Neurol, Beijing, Peoples R China Ahmadu Bello Univ, Fac Basic Clin Sci, Coll Hlth Sci, Dept Pathol, Zaria, Nigeria Dalhousie Univ, Dept Anesthesia Pain Management & Perioperat Med, Halifax, NS, Canada VisMederi Srl, Siena, Italy UCL, Canc Res UK, London, England UCL, UCL Canc Trials Ctr, London, England Univ Ottawa, Family Med, Ottawa, ON, Canada China Agr Univ, Coll Engn, Beijing, Peoples R China Leiden Univ, Leiden Acad Ctr Drug Res, Div Drug Discovery & Safety, Leiden, Netherlands Sun Yat Sen Univ, Affiliated Hosp 1, Dept Intervent Radiol, Guangzhou, Guangdong, Peoples R China Amer Univ Beirut, Med Ctr, Infect Dis, Beirut, Lebanon Sheffield Hallam Univ, Dept Social Work Social Care & Community Studies, Sheffield, S Yorkshire, England Mechnikov Res Inst Vaccines & Sera, Viral Hepatitis, Moscow, Russia Univ Ottawa, Pediat, Ottawa, ON, Canada Vreden Russian Res Inst Traumatol & Orthopaed, Dept Wound Infect Treatment & Prevent, St Petersburg, Russia Hangzhou Ctr Dis Control & Prevent, Dept TB Control & Prevent, Hangzhou, Zhejiang, Peoples R China Kaohsiung Med Univ, Dept Biotechnol, Kaohsiung, Taiwan Zoetis, Diagnost, Kalamazoo, MI USA Aintree Univ Hosp NHS Fdn Trust, Head & Neck Oncol Res, Liverpool, Merseyside, England Wrightington Hosp, Trauma & Orthopaed, Manchester, Lancs, England Loyola Univ, Med Ctr, Dept Psychiat, 2160 S 1st Ave, Maywood, IL 60153 USA Atkins Vet Serv, Microbiol, Calgary, AB, Canada Univ Porto, FADEUP, CIAFEL, Porto, Portugal Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore Kangwon Natl Univ, Coll Biotechnol & Biosci, Dept Food Sci & Biotechnol, Chunchon, South Korea Kakatiya Med Coll, Internal Med, Warangal, Telangana, India Univ Antioquia, Vet Med Sch, CIBAV Res Grp, Medellin, Colombia IISER, Dept Phys, Soft & Act Matter Grp, Tirupati 517507, Andhra Pradesh, India Univ Rosario, Sch Med & Hlth, Ctr Studies Phys Activ Measurements, Bogota, Colombia Univ Hosp Essen, Cardiol & Vasc Med, Essen, Germany Univ Hosp Basel, Endocrinol, Basel, Switzerland Univ Tubingen, Inst Med Genet & Appl Genom, Tubingen, Germany Univ Hosp Munster, Div Gen Internal Med Nephrol & Rheumatolog, Dept Med D, Munster, Germany Univ Kentucky, Dept Nephrol, Lexington, KY USA Univ Freiburg, Dept Anaesthesiol & Crit Care, Med Ctr, Freiburg, Germany Univ Calif Irvine, Dept Med, Orange, CA 92668 USA Univ Hosp Leuven, Dept Urol, Leuven, Belgium Chinese Acad Sci, Coll Life Sci, Beijing, Peoples R China Univ Florida, Orthopaed & Rehabil, Gainesville, FL USA Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Mol Oncol & Epigenet, Chongqing, Peoples R China Tsinghua Univ, Dept Chem Engn, Beijing, Peoples R China Yonsei Univ, Coll Med, Dept Pharmacol, Seoul, South Korea Childrens Hosp Kings Daughters, Eastern Virginia Med Sch, Dept Pediat, Norfolk, VA USA China Three Gorges Univ, Coll Sci, Dept Math, Yichang, Peoples R China Xiangtan Univ, Coll 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

5. Anti-tick vaccine candidate subolesin is important for blood feeding and innate immune gene expression in soft ticks.

Author: Nandy K, Tamakloe C, Sonenshine DE, Sultana H, and Neelakanta G
Subjects: Animals, Gene Expression, Immunity, Innate, Argasidae, Ornithodoros genetics, Vaccines genetics, Cystatins genetics
Abstract: Subolesin is a conserved molecule in both hard and soft ticks and is considered as an effective candidate molecule for the development of anti-tick vaccine. Previous studies have reported the role of subolesin in blood feeding, reproduction, development, and gene expression in hard ticks. However, studies addressing the role of subolesin in soft ticks are limited. In this study, we report that subolesin is not only important in soft tick Ornithodoros turicata americanus blood feeding but also in the regulation of innate immune gene expression in these ticks. We identified and characterized several putative innate immune genes including Toll, Lysozyme precursor (Lp), fibrinogen-domain containing protein (FDP), cystatin and ML-domain containing protein (MLD) in O. turicata americanus ticks. Quantitative real-time polymerase chain reaction analysis revealed the expression of these genes in both O. turicata americanus salivary glands and midgut and in all developmental stages of these soft ticks. Significantly increased expression of fdp was noted in salivary glands and midgut upon O. turicata americanus blood feeding. Furthermore, RNAi-mediated knockdown of O. turicata americanus subolesin expression affected blood feeding and innate immune gene expression in these ticks. Significant downregulation of toll, lp, fdp, cystatin, and mld transcripts was evident in sub-dsRNA-treated ticks when compared to the levels noted in mock-dsRNA-treated control. Collectively, our study not only reports identification and characterization of various innate immune genes in O. turicata americanus ticks but also provides evidence on the role of subolesin in blood feeding and innate immune gene expression in these medically important ticks., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Nandy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Published: 2023
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6. Identification of a rickettsial endosymbiont in a soft tick Ornithodoros turicata americanus.

Author: Liu L, Sonenshine DE, Sultana H, and Neelakanta G
Subjects: Animals, RNA, Ribosomal, 16S genetics, Phylogeny, Senegal, Argasidae genetics, Ornithodoros genetics
Abstract: Bacterial endosymbionts are abundantly found in both hard and soft ticks. Occidentia massiliensis, a rickettsial endosymbiont, was first identified in the soft tick Ornithodoros sonrai collected from Senegal and later was identified in a hard tick Africaniella transversale. In this study, we noted the presence of Occidentia species, designated as Occidentia-like species, in a soft tick O. turicata americanus. Sequencing and phylogenetic analyses of the two genetic markers, 16S rRNA and groEL confirmed the presence of Occidentia-like species in O. turicata americanus ticks. The Occidentia-like species was noted to be present in all developmental stages of O. turicata americanus and in different tick tissues including ovaries, synganglion, guts and salivary gland. The levels of Occidentia-like species 16S rRNA transcripts were noted to be significantly higher in ovaries than in a gut tissue. In addition, Occidentia-like species groEL expression was noted to be significantly higher in tick synganglion than in ovaries and gut tissues. Furthermore, levels of Occidentia-like species 16S rRNA transcripts increased significantly upon O. turicata americanus blood feeding. Taken together, our study not only shows that Occidentia-like species is present in O. turicata americanus but also suggests that this bacterium may play a role in tick-bacteria interactions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Published: 2022
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7. Tick transmission of Borrelia burgdorferi to the murine host is not influenced by environmentally acquired midgut microbiota.

Author: Narasimhan S, Rajeevan N, Graham M, Wu MJ, DePonte K, Marion S, Masson O, O'Neal AJ, Pedra JHF, Sonenshine DE, and Fikrig E
Subjects: Animals, Mammals, Mice, Nymph microbiology, Borrelia burgdorferi genetics, Ixodes microbiology, Lyme Disease microbiology, Microbiota
Abstract: Background: Ixodes scapularis is the predominant tick vector of Borrelia burgdorferi, the agent of Lyme disease, in the USA. Molecular interactions between the tick and B. burgdorferi orchestrate the migration of spirochetes from the midgut to the salivary glands-critical steps that precede transmission to the vertebrate host. Over the last decade, research efforts have invoked a potential role for the tick microbiome in modulating tick-pathogen interactions., Results: Using multiple strategies to perturb the microbiome composition of B. burgdorferi-infected nymphal ticks, we observe that changes in the microbiome composition do not significantly influence B. burgdorferi migration from the midgut, invasion of salivary glands, or transmission to the murine host. We also show that within 24 and 48 h of the onset of tick feeding, B. burgdorferi spirochetes are within the peritrophic matrix and epithelial cells of the midgut in preparation for exit from the midgut., Conclusions: This study highlights two aspects of tick-spirochete interactions: (1) environmental bacteria associated with the tick do not influence spirochete transmission to the mammalian host and (2) the spirochete may utilize an intracellular exit route during migration from the midgut to the salivary glands, a strategy that may allow the spirochete to distance itself from microbiota in the midgut lumen effectively. This may explain in part, the inability of environment-acquired midgut microbiota to significantly influence spirochete transmission. Unraveling a molecular understanding of this exit strategy will be critical to gain new insights into the biology of the spirochete and the tick. Video Abstract., (© 2022. The Author(s).)
Published: 2022
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8. Editorial: Tick Saliva: Secret to Blood Feeding Success.

Author: Sonenshine DE, Nuttall PA, and Narasimhan S
Abstract: 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.
Published: 2022
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9. Microbiomes of Blood-Feeding Arthropods: Genes Coding for Essential Nutrients and Relation to Vector Fitness and Pathogenic Infections. A Review.

Author: Sonenshine DE and Stewart PE
Abstract: Background: Blood-feeding arthropods support a diverse array of symbiotic microbes, some of which facilitate host growth and development whereas others are detrimental to vector-borne pathogens. We found a common core constituency among the microbiota of 16 different arthropod blood-sucking disease vectors, including Bacillaceae , Rickettsiaceae , Anaplasmataceae , Sphingomonadaceae , Enterobacteriaceae , Pseudomonadaceae , Moraxellaceae and Staphylococcaceae . By comparing 21 genomes of common bacterial symbionts in blood-feeding vectors versus non-blooding insects, we found that certain enteric bacteria benefit their hosts by upregulating numerous genes coding for essential nutrients. Bacteria of blood-sucking vectors expressed significantly more genes ( p < 0.001) coding for these essential nutrients than those of non-blooding insects. Moreover, compared to endosymbionts, the genomes of enteric bacteria also contained significantly more genes ( p < 0.001) that code for the synthesis of essential amino acids and proteins that detoxify reactive oxygen species. In contrast, microbes in non-blood-feeding insects expressed few gene families coding for these nutrient categories. We also discuss specific midgut bacteria essential for the normal development of pathogens (e.g., Leishmania ) versus others that were detrimental (e.g., bacterial toxins in mosquitoes lethal to Plasmodium spp.).
Published: 2021
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10. Tick extracellular vesicles enable arthropod feeding and promote distinct outcomes of bacterial infection.

Author: Oliva Chávez AS, Wang X, Marnin L, Archer NK, Hammond HL, Carroll EEM, Shaw DK, Tully BG, Buskirk AD, Ford SL, Butler LR, Shahi P, Morozova K, Clement CC, Lawres L, Neal AJO, Mamoun CB, Mason KL, Hobbs BE, Scoles GA, Barry EM, Sonenshine DE, Pal U, Valenzuela JG, Sztein MB, Pasetti MF, Levin ML, Kotsyfakis M, Jay SM, Huntley JF, Miller LS, Santambrogio L, and Pedra JHF
Subjects: Anaplasma phagocytophilum pathogenicity, Animals, Arthropods metabolism, Arthropods microbiology, Arthropods physiology, Cell Line, Dermacentor metabolism, Dermacentor microbiology, Dermacentor physiology, Extracellular Vesicles ultrastructure, Francisella tularensis pathogenicity, Gene Ontology, Humans, Inflammation immunology, Inflammation metabolism, Inflammation parasitology, Intravital Microscopy, Ixodes metabolism, Ixodes microbiology, Ixodes physiology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Microscopy, Electron, Transmission, Proteomics, R-SNARE Proteins metabolism, Skin immunology, Skin microbiology, T-Lymphocytes metabolism, Tandem Mass Spectrometry, Vesicle-Associated Membrane Protein 2 metabolism, Bacterial Infections immunology, Bacterial Infections metabolism, Extracellular Vesicles metabolism, Skin parasitology, Ticks metabolism, Ticks microbiology
Abstract: Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans and other animals. Here, we reveal that pathogen spreading from arthropods to the mammalian host is multifaceted. Extracellular vesicles from Ixodes scapularis enable tick feeding and promote infection of the mildly virulent rickettsial agent Anaplasma phagocytophilum through the SNARE proteins Vamp33 and Synaptobrevin 2 and dendritic epidermal T cells. However, extracellular vesicles from the tick Dermacentor andersoni mitigate microbial spreading caused by the lethal pathogen Francisella tularensis. Collectively, we establish that tick extracellular vesicles foster distinct outcomes of bacterial infection and assist in vector feeding by acting on skin immunity. Thus, the biology of arthropods should be taken into consideration when developing strategies to control vector-borne diseases.
Published: 2021
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11. Tick Ecdysteroid Hormone, Global Microbiota/ Rickettsia Signaling in the Ovary versus Carcass during Vitellogenesis in Part-Fed (Virgin) American Dog Ticks, Dermacentor variabilis .

Author: Ponnusamy L, Sutton H, Mitchell RD 3rd, Sonenshine DE, Apperson CS, and Roe RM
Abstract: The transovarial transmission of tick-borne bacterial pathogens is an important mechanism for their maintenance in natural populations and transmission, causing disease in humans and animals. The mechanism for this transmission and the possible role of tick hormones facilitating this process have never been studied. Injections of physiological levels of the tick hormone, 20-hydroxyecdysone (20E), into part-fed (virgin) adult females of the American dog tick, Dermacentor variabilis , attached to the host caused a reduction in density of Rickettsia montanensis in the carcass and an increase in the ovaries compared to buffer-injected controls. This injection initiates yolk protein synthesis and uptake by the eggs but has no effect on blood feeding. Francisella sp. and R. montanensis were the predominant bacteria based on the proportionality in the carcass and ovary. The total bacteria load increased in the carcass and ovaries, and bacteria in the genus Pseudomonas increased in the carcass after the 20E injection. The mechanism of how the Rickettsia species respond to changes in tick hormonal regulation needs further investigation. Multiple possible mechanisms for the proliferation of R. montanensis in the ovaries are proposed.
Published: 2021
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12. Antibodies against EGF-like domains in Ixodes scapularis BM86 orthologs impact tick feeding and survival of Borrelia burgdorferi.

Author: Koči J, Bista S, Chirania P, Yang X, Kitsou C, Rana VS, Yas OB, Sonenshine DE, and Pal U
Subjects: Animals, Mice, Antibodies immunology, Arthropod Proteins immunology, Borrelia burgdorferi immunology, Feeding Behavior, Ixodes immunology, Lyme Disease immunology
Abstract: Ixodes scapularis ticks transmit multiple pathogens, including Borrelia burgdorferi sensu stricto, and encode many proteins harboring epidermal growth factor (EGF)-like domains. We show that I. scapularis produces multiple orthologs for Bm86, a widely studied tick gut protein considered as a target of an anti-tick vaccine, herein termed as Is86. We show that Is86 antigens feature at least three identifiable regions harboring EGF-like domains (termed as EGF-1, EGF-2, and EGF-3) and are differentially upregulated during B. burgdorferi infection. Although the RNA interference-mediated knockdown of Is86 genes did not show any influences on tick engorgement or B. burgdorferi sensu stricto persistence, the immunization of murine hosts with specific recombinant EGF antigens marginally reduced spirochete loads in the skin, in addition to affecting tick blood meal engorgement and molting. However, given the borderline impact of EGF immunization on tick engorgement and pathogen survival in the vector, it is unlikely that these antigens, at least in their current forms, could be developed as potential vaccines. Further investigations of the biological significance of Is86 (and other tick antigens) would enrich our knowledge of the intricate biology of ticks, including their interactions with resident pathogens, and contribute to the development of anti-tick measures to combat tick-borne illnesses.
Published: 2021
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13. Epigenetic Regulation of Tick Biology and Vectorial Capacity.

Author: De S, Kitsou C, Sonenshine DE, Pedra JHF, Fikrig E, Kassis JA, and Pal U
Subjects: Animals, Arthropod Vectors classification, Arthropod Vectors genetics, Humans, Tick-Borne Diseases genetics, Tick-Borne Diseases transmission, Ticks microbiology, Ticks parasitology, Ticks virology, Arthropod Vectors growth & development, Disease Transmission, Infectious, Epigenesis, Genetic, Host-Pathogen Interactions, Tick-Borne Diseases epidemiology, Ticks physiology
Abstract: Ticks exist across diverse environments and transmit numerous pathogens. Due to their long and unique life cycles, these arthropods likely evolved robust epigenetic mechanisms that provide sustainable responses and buffers against extreme environmental conditions. Herein, we highlight how the study of the epigenetic basis of tick biology and vectorial capacity will enrich our knowledge of tick-borne infections., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
Published: 2021
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14. Varroa destructor mites vector and transmit pathogenic honey bee viruses acquired from an artificial diet.

Author: Posada-Florez F, Ryabov EV, Heerman MC, Chen Y, Evans JD, Sonenshine DE, and Cook SC
Subjects: Animals, Animal Diseases genetics, Animal Diseases metabolism, Animal Diseases transmission, Animal Feed virology, Bees metabolism, Bees parasitology, Bees virology, RNA Viruses classification, RNA Viruses genetics, RNA Viruses metabolism, Varroidae virology, Virus Diseases genetics, Virus Diseases metabolism, Virus Diseases transmission
Abstract: The ectoparasitic mite Varroa destructor is one of the most destructive pests of the honey bee (Apis mellifera) and the primary biotic cause of colony collapse in many regions of the world. These mites inflict physical injury on their honey bee hosts from feeding on host hemolymph and fat body cells/cellular components, and serve as the vector for deadly honey bee viruses, including Deformed wing virus (DWV) and the related Varroa destructor virus-1 (VDV-1) (i.e., DWV-like viruses). Studies focused on elucidating the dynamics of Varroa-mediated vectoring and transmission of DWV-like viruses may be confounded by viruses present in ingested host tissues or the mites themselves. Here we describe a system that includes an artificial diet free of insect tissue-derived components for maintaining Varroa mites for in vitro experimentation. Using this system, together with the novel engineered cDNA clone-derived genetically tagged VDV-1 and wild-type DWV, we demonstrated for the first time that Varroa mites provided an artificial diet supplemented with engineered viruses for 36 hours could acquire and transmit sufficient numbers of virus particles to establish an infection in virus-naïve hosts. While the in vitro system described herein provides for only up to five days of mite survival, precluding study of the long-term impacts of viruses on mite health, the system allows for extensive insights into the dynamics of Varroa-mediated vectoring and transmission of honey bee viruses., Competing Interests: The authors have declared that no competing interests exist.
Published: 2020
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15. Heme Oxygenase-1 Induction by Blood-Feeding Arthropods Controls Skin Inflammation and Promotes Disease Tolerance.

Author: DeSouza-Vieira T, Iniguez E, Serafim TD, de Castro W, Karmakar S, Disotuar MM, Cecilio P, Lacsina JR, Meneses C, Nagata BM, Cardoso S, Sonenshine DE, Moore IN, Borges VM, Dey R, Soares MP, Nakhasi HL, Oliveira F, Valenzuela JG, and Kamhawi S
Subjects: Animals, Arthropods, Culicidae, Dermatitis pathology, Female, Insect Bites and Stings pathology, Leishmania, Leishmaniasis enzymology, Mice, Mice, Inbred C57BL, Dermatitis enzymology, Heme Oxygenase-1 biosynthesis, Insect Bites and Stings enzymology, Vector Borne Diseases enzymology, Vector Borne Diseases pathology
Abstract: Hematophagous vectors lacerate host skin and capillaries to acquire a blood meal, resulting in leakage of red blood cells (RBCs) and inflammation. Here, we show that heme oxygenase-1 (HO-1), a pleiotropic cytoprotective isoenzyme that mitigates heme-mediated tissue damage, is induced after bites of sand flies, mosquitoes, and ticks. Further, we demonstrate that erythrophagocytosis by macrophages, including a skin-residing CD163 + CD91 + professional iron-recycling subpopulation, produces HO-1 after bites. Importantly, we establish that global deletion or transient inhibition of HO-1 in mice increases inflammation and pathology following Leishmania-infected sand fly bites without affecting parasite number, whereas CO, an end product of the HO-1 enzymatic reaction, suppresses skin inflammation. This indicates that HO-1 induction by blood-feeding sand flies promotes tolerance to Leishmania infection. Collectively, our data demonstrate that HO-1 induction through erythrophagocytosis is a universal mechanism that regulates skin inflammation following blood feeding by arthropods, thus promoting early-stage disease tolerance to vector-borne pathogens., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
Published: 2020
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16. Three-dimensional reconstruction of the feeding apparatus of the tick Ixodes ricinus (Acari: Ixodidae): a new insight into the mechanism of blood-feeding.

Author: Vancová M, Bílý T, Šimo L, Touš J, Horodyský P, Růžek D, Novobilský A, Salát J, Strnad M, Sonenshine DE, Grubhoffer L, and Nebesářová J
Subjects: Animals, Female, Imaging, Three-Dimensional, Mice, Microscopy, Electron, Scanning, Mouth parasitology, Nymph parasitology, Feeding Behavior, Ixodes anatomy & histology, Mouth anatomy & histology, Nymph anatomy & histology, Salivation, Tick Infestations parasitology
Abstract: The different components of the mouthparts of hard ticks (Ixodidae) enable these parasites to penetrate host skin, secrete saliva, embed, and suck blood. Moreover, the tick's mouthparts represent a key route for saliva-assisted pathogen transmission as well as pathogen acquisition from blood meal during the tick feeding process. Much has been learned about the basic anatomy of the tick's mouthparts and in the broad outlines of how they function in previous studies. However, the precise mechanics of these functions are little understood. Here, we propose for the first time an animated model of the orchestration of the tick mouthparts and associated structures during blood meal acquisition and salivation. These two actions are known to alternate during tick engorgement. Specifically, our attention has been paid to the mechanism underlining the blood meal uptake into the pharynx through the mouth and how ticks prevent mixing the uptaken blood with secreted saliva. We animated function of muscles attached to the salivarium and their possible opening /closing of the salivarium, with a plausible explanation of the movement of saliva within the salivarium and massive outpouring of saliva.
Published: 2020
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17. Insights into the feeding behaviors and biomechanics of Varroa destructor mites on honey bee pupae using electropenetrography and histology.

Author: Li AY, Cook SC, Sonenshine DE, Posada-Florez F, Noble NII, Mowery J, Gulbronson CJ, and Bauchan GR
Subjects: Animals, Biomechanical Phenomena, Electrophysiological Phenomena, Female, Microspheres, Pharynx innervation, Pharynx physiology, Pupa parasitology, Bees parasitology, Feeding Behavior physiology, Varroidae physiology
Abstract: Feeding behaviors and biomechanics of female Varroa destructor mites are revealed from AC-DC electropenetrography (EPG) recordings of mites feeding from Apis mellifera honey bee pupae and histology of mite internal ingestion apparatus. EPG signals characteristic of arthropod suction feeding (ingestion) were identified for mites that fed on pupae during overnight recordings. Ingestion by these mites was confirmed afterwards by observing internally fluorescent microbeads previously injected into their hosts. Micrographs of internal ingestion apparatus illustrate the connection between a gnathosomal tube and a pharyngeal lumen, which is surrounded by alternating dilator and constrictor muscles. Inspection of EPG signals showed the muscularized mite pharyngeal pump operates at a mean repetition rate of 4.5 cycles/s to ingest host fluids. Separate feeding events observed for mites numbered between 23 and 33 over approximately 16 h of recording, with each event lasting ~10 s. Feeding events were each separated by ~2 min. Consecutive feeding events separated by either locomotion or prolonged periods of quiescence were grouped into feeding bouts, which ranged in number from one to six. Statistical analyses of EPG data revealed that feeding events were prolonged for mites having lower pharyngeal pump frequencies, and mites having prolonged feeding events went unfed for significantly more time between feeding events. These results suggest that mites may adjust behaviors to meet limitations of their feeding apparatus to acquire similar amounts of food. Data reported here help to provide a more robust view of Varroa mite feeding than those previously reported and are both reminiscent of, as well as distinct from, some other acarines and fluid-feeding insects., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Published: 2019
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18. Vitellogenin Receptor as a Target for Tick Control: A Mini-Review.

Author: Mitchell RD 3rd, Sonenshine DE, and Pérez de León AA
Abstract: While much effort has been put into understanding vitellogenesis in insects and other organisms, much less is known of this process in ticks. There are several steps that facilitate yolk formation in developing oocytes of which the vitellogenin receptor (VgR) is a key component. The tick VgR binds vitellogenin (Vg) circulating in the hemolymph to initiate receptor-mediated endocytosis and its transformation into vitellin (Vn). The conversion of Vg into Vn, the final form of the yolk protein, occurs inside oocytes of the female tick ovary. Vn is critical to tick embryos since it serves as the nutritional source for their development, survival, and reproduction. Recent studies also suggest that pathogenic microbes, i.e., Babesia spp., that rely on ticks for propagation and dissemination likely "hitchhike" onto Vg molecules as they enter developing oocytes through the VgR. Suppressing VgR messenger RNA synthesis via RNA interference (RNAi) completely blocked Babesia spp. transmission into developing tick oocytes, thereby inhibiting vertical transmission of these pathogenic microbes from female to eggs. To date, VgRs from only four tick species, Dermacentor variabilis , Rhipicephalus microplus , Amblyomma hebraeum , and Haemaphysalis longicornis , have been fully sequenced and characterized. In contrast, many more VgRs have been described in various insect species. VgR is a critical component in egg formation and maturation that can serve as a precise target for tick control. However, additional research will help identify unique residues within the receptor that are specific to ticks or other arthropod disease vectors while avoiding cross-reactivity with non-target species. Detailed knowledge of the molecular structure and functional role of tick VgRs will enable development of novel vaccines to control ticks and tick-borne diseases.
Published: 2019
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19. Insights into the metabolism and behaviour of Varroa destructor mites from analysis of their waste excretions.

Author: Posada-Florez F, Sonenshine DE, Egekwu NI, Rice C, Lupitskyy R, and Cook SC
Subjects: Animals, Bees parasitology, Entomology methods, Feces chemistry, Female, Maryland, Varroidae metabolism, Chromatography, High Pressure Liquid methods, Purines analysis, Tandem Mass Spectrometry methods, Varroidae physiology
Abstract: Varroa destructor mites (Acari: Varroidae) are harmful ectoparasites of Apis mellifera honey bees. Female foundresses of wax-capped pupal host cells and their daughters feed on host fluids from open wounds on the host's integument. Details of V. destructor mite nutrition are forthcoming, and little is known about the potential physical effects on hosts from mite feeding. Chemical analysis of waste excretions can infer details of animals' nutrition. Here, chemical analysis by high-performance liquid chromatography/mass spectrometry (HPLC-MS/MS) of mite excretions showed that the purine content of V. destructor waste consists of guanine with traces of hypoxanthine. Traces of uric acid and caffeine were also detected. Concentrations of guanine attenuated over time and excretions collected from senescing mites did not contain detectable guanine. Non-reproducing individual female mites maintained in vitro, housed in gelatin capsules and provided a honey bee pupa, deposited an average of nearly 18 excretions daily, mostly on the host's integument rather than on the capsule wall. The weight and volume of excretions suggest mites can consume nearly a microlitre of host fluids each day. Compounded over 10 days, this together with open wounds, could lead to substantial water loss and stress to developing pupae.
Published: 2019
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20. Argasid and ixodid systematics: Implications for soft tick evolution and systematics, with a new argasid species list.

Author: Mans BJ, Featherston J, Kvas M, Pillay KA, de Klerk DG, Pienaar R, de Castro MH, Schwan TG, Lopez JE, Teel P, Pérez de León AA, Sonenshine DE, Egekwu NI, Bakkes DK, Heyne H, Kanduma EG, Nyangiwe N, Bouattour A, and Latif AA
Subjects: Animals, Argas classification, Argas genetics, Argasidae genetics, Classification, DNA Barcoding, Taxonomic, DNA, Ribosomal chemistry, DNA, Ribosomal genetics, High-Throughput Nucleotide Sequencing, Ornithodoros classification, Ornithodoros genetics, Phylogeny, RNA, Ribosomal, 18S genetics, RNA, Ribosomal, 28S genetics, Sequence Analysis, DNA, Argasidae classification, Genetic Speciation, Genome, Mitochondrial genetics
Abstract: The systematics of the genera and subgenera within the soft tick family Argasidae is not adequately resolved. Different classification schemes, reflecting diverse schools of scientific thought that elevated or downgraded groups to genera or subgenera, have been proposed. In the most recent classification scheme, Argas and Ornithodoros are paraphyletic and the placement of various subgenera remains uncertain because molecular data are lacking. Thus, reclassification of the Argasidae is required. This will enable an understanding of soft tick systematics within an evolutionary context. This study addressed that knowledge gap using mitochondrial genome and nuclear (18S and 28S ribosomal RNA) sequence data for representatives of the subgenera Alectorobius, Argas, Chiropterargas, Ogadenus, Ornamentum, Ornithodoros, Navis (subgen. nov.), Pavlovskyella, Persicargas, Proknekalia, Reticulinasus and Secretargas, from the Afrotropical, Nearctic and Palearctic regions. Hard tick species (Ixodidae) and a new representative of Nuttalliella namaqua (Nuttalliellidae), were also sequenced with a total of 83 whole mitochondrial genomes, 18S rRNA and 28S rRNA genes generated. The study confirmed the utility of next-generation sequencing to retrieve systematic markers. Paraphyly of Argas and Ornithodoros was resolved by systematic analysis and a new species list is proposed. This corresponds broadly with the morphological cladistic analysis of Klompen and Oliver (1993). Estimation of divergence times using molecular dating allowed dissection of phylogeographic patterns for argasid evolution. The discovery of cryptic species in the subgenera Chiropterargas, Ogadenus and Ornithodoros, suggests that cryptic speciation is common within the Argasidae. Cryptic speciation has implications for past biological studies of soft ticks. These are discussed in particular for the Ornithodoros (Ornithodoros) moubata and Ornithodoros (Ornithodoros) savignyi groups., (Copyright © 2018 Elsevier GmbH. All rights reserved.)
Published: 2019
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21. Identification and characterization of a histamine-binding lipocalin-like molecule from the relapsing fever tick Ornithodoros turicata.

Author: Neelakanta G, Sultana H, Sonenshine DE, and Andersen JF
Subjects: Amino Acid Sequence, Animals, Arthropod Proteins chemistry, Arthropod Proteins metabolism, Base Sequence, Female, Gene Expression Profiling, Larva genetics, Larva growth & development, Larva metabolism, Lipocalins chemistry, Lipocalins metabolism, Nymph genetics, Nymph growth & development, Nymph metabolism, Ornithodoros growth & development, Ornithodoros metabolism, Phylogeny, Salivary Glands metabolism, Sequence Alignment, Arthropod Proteins genetics, Gene Expression, Histamine metabolism, Lipocalins genetics, Ornithodoros genetics
Abstract: Lipocalins are low molecular weight membrane transporters that are abundantly expressed in the salivary glands and other tissues of ticks. In this study, we identified a lipocalin-like molecule, designated as otlip, from the soft ticks Ornithodoros turicata, the vector for the relapsing fever causing spirochete Borrelia turicatae. We noted that the expression of otlip was developmentally regulated, with adult ticks expressing significantly higher levels in comparison to the larvae or nymphal ticks. Expression of otlip was evident in both fed and unfed O. turicata ticks, with significantly increased expression in the salivary glands in comparison to the midgut or ovary tissues. High conservation of the biogenic amine-binding motif was evident in the deduced primary amino acid sequence of Otlip. Protein modelling of Otlip revealed conservation of most of the residues involved in binding histamine or serotonin ligand. In vitro assays demonstrated binding of recombinant Otlip with histamine. Furthermore, prediction of post-translational modifications revealed that Otlip contained phosphorylation and myristoylation sites. Taken together, our study not only provides evidence for the presence of a lipocalin-like molecule in O. turicata ticks but also suggests a role for this molecule in the salivary glands of this medically important vector., (© 2017 The Royal Entomological Society.)
Published: 2018
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22. Range Expansion of Tick Disease Vectors in North America: Implications for Spread of Tick-Borne Disease.

Author: Sonenshine DE
Subjects: Animals, Animals, Wild, Geography, Medical, Humans, North America, Arachnid Vectors, Ixodidae, Tick-Borne Diseases epidemiology
Abstract: Ticks are the major vectors of most disease-causing agents to humans, companion animals and wildlife. Moreover, ticks transmit a greater variety of pathogenic agents than any other blood-feeding arthropod. Ticks have been expanding their geographic ranges in recent decades largely due to climate change. Furthermore, tick populations in many areas of their past and even newly established localities have increased in abundance. These dynamic changes present new and increasing severe public health threats to humans, livestock and companion animals in areas where they were previously unknown or were considered to be of minor importance. Here in this review, the geographic status of four representative tick species are discussed in relation to these public health concerns, namely, the American dog tick, Dermacentor variabilis , the lone star tick, Amblyomma americanum , the Gulf Coast Tick, Amblyomma maculatum and the black-legged tick, Ixodes scapularis . Both biotic and abiotic factors that may influence future range expansion and successful colony formation in new habitats are discussed., Competing Interests: The author declares no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.
Published: 2018
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23. Using an in vitro system for maintaining Varroa destructor mites on Apis mellifera pupae as hosts: studies of mite longevity and feeding behavior.

Author: Egekwu NI, Posada F, Sonenshine DE, and Cook S
Subjects: Animals, Bees growth & development, Feeding Behavior, Female, Longevity, Pupa growth & development, Pupa parasitology, Varroidae growth & development, Bees parasitology, Host-Parasite Interactions, Pest Control, Biological methods, Varroidae physiology
Abstract: Varroa destructor mites (varroa) are ectoparasites of Apis mellifera honey bees, and the damage they inflict on hosts is likely a causative factor of recent poor honey bee colony performance. Research has produced an arsenal of control agents against varroa mites, which have become resistant to many chemical means of their control, and other means have uncertain efficacy. Novel means of control will result from a thorough understanding of varroa physiology and behavior. However, robust knowledge of varroa biology is lacking; mites have very low survivability and reproduction away from their natural environment and host, and few tested protocols of maintaining mites in vitro are available as standardized methods for varroa research. Here, we describe the 'varroa maintenance system' (VMS), a tool for maintaining in vitro populations of varroa on its natural host, and present best practices for its use in varroa and host research. Additionally, we present results using the VMS from research of varroa and host longevity and varroa feeding behavior. Under these conditions, from two trials, mites lived an average of 12 and 14 days, respectively. For studies of feeding behavior, female mites inflicted wounds located on a wide range of sites on the host's integument, but preferred to feed from the host's abdomen and thorax. Originally in the phoretic-phase, female mites in VMS had limited reproduction, but positive instances give insights into the cues necessary for initiating reproduction. The VMS is a useful tool for laboratory studies requiring long-term survival of mites, or host-parasite interactions.
Published: 2018
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24. Ticks, Ixodes scapularis , Feed Repeatedly on White-Footed Mice despite Strong Inflammatory Response: An Expanding Paradigm for Understanding Tick-Host Interactions.

Author: Anderson JM, Moore IN, Nagata BM, Ribeiro JMC, Valenzuela JG, and Sonenshine DE
Abstract: Ticks transmit infectious agents including bacteria, viruses and protozoa. However, their transmission may be compromised by host resistance to repeated tick feeding. Increasing host resistance to repeated tick bites is well known in laboratory animals, including intense inflammation at the bite sites. However, it is not known whether this also occurs in wild rodents such as white-footed mice, Peromyscus leucopus , and other wildlife, or if it occurs at all. According to the "host immune incompetence" hypothesis, if these mice do not have a strong inflammatory response, they would not reject repeated tick bites by Ixodes scapularis . To test this hypothesis, histopathological studies were done comparing dermal inflammation in P. leucopus versus guinea pigs, Cavia porcellus , repeatedly infested with I. scapularis . In P. leucopus , the immune cell composition was like that seen in laboratory mouse models, with some differences. However, there was a broad sessile lesion with intact dermal architecture, likely enabling the ticks to continue feeding unimpeded. In contrast, in C. porcellus , there was a relatively similar mixed cellular profile, but there also was a large, leukocyte-filled cavitary lesion and scab-like hyperkeratotic changes to the epidermal layer, along with itching and apparent pain. Ticks attached to sensitized C. porcellus fed poorly or were dislodged, presumably due to the weakened anchoring of the tick's mouthparts cemented in the heavily inflamed and disintegrating dermal tissues. This is the first time that the architecture of the skin lesions has been recognized as a major factor in understanding tick-host tolerance versus tick bite rejection. These findings broadly strengthen previous work done on lab animal models but also help explain why I. scapularis can repeatedly parasitize white-footed mice, supporting the "immune evasion theory" but cannot repeatedly parasitize other, non-permissive hosts such as guinea pigs.
Published: 2017
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25. Microbial Invasion vs. Tick Immune Regulation.

Author: Sonenshine DE and Macaluso KR
Subjects: Anaplasma phagocytophilum immunology, Anaplasma phagocytophilum pathogenicity, Animals, Babesia microti immunology, Babesia microti pathogenicity, Borrelia burgdorferi immunology, Borrelia burgdorferi pathogenicity, Humans, Rickettsia rickettsii immunology, Rickettsia rickettsii pathogenicity, Host-Pathogen Interactions immunology, Immunity, Innate immunology, Tick-Borne Diseases immunology, Tick-Borne Diseases microbiology, Ticks immunology, Ticks microbiology
Abstract: Ticks transmit a greater variety of pathogenic agents that cause disease in humans and animals than any other haematophagous arthropod, including Lyme disease, Rocky Mountain spotted fever, human granulocytic anaplasmosis, babesiosis, tick-borne encephalitis, Crimean Congo haemorhagic fever, and many others (Gulia-Nuss et al., 2016). Although diverse explanations have been proposed to explain their remarkable vectorial capacity, among the most important are their blood feeding habit, their long term off-host survival, the diverse array of bioactive molecules that disrupt the host's natural hemostatic mechanisms, facilitate blood flow, pain inhibitors, and minimize inflammation to prevent immune rejection (Hajdušek et al., 2013). Moreover, the tick's unique intracellular digestive processes allow the midgut to provide a relatively permissive microenvironment for survival of invading microbes. Although tick-host-pathogen interactions have evolved over more than 300 million years (Barker and Murrell, 2008), few microbes have been able to overcome the tick's innate immune system, comprising both humoral and cellular processes that reject them. Similar to most eukaryotes, the signaling pathways that regulate the innate immune response, i.e., the Toll, IMD (Immunodeficiency) and JAK-STAT (Janus Kinase/ Signal Transducers and Activators of Transcription) also occur in ticks (Gulia-Nuss et al., 2016). Recognition of pathogen-associated molecular patterns (PAMPs) on the microbial surface triggers one or the other of these pathways. Consequently, ticks are able to mount an impressive array of humoral and cellular responses to microbial challenge, including anti-microbial peptides (AMPs), e.g., defensins, lysozymes, microplusins, etc., that directly kill, entrap or inhibit the invaders. Equally important are cellular processes, primarily phagocytosis, that capture, ingest, or encapsulate invading microbes, regulated by a primordial system of thioester-containing proteins, fibrinogen-related lectins and convertase factors (Hajdušek et al., 2013). Ticks also express reactive oxygen species (ROS) as well as glutathione-S-transferase, superoxide dismutase, heat shock proteins and even protease inhibitors that kill or inhibit microbes. Nevertheless, many tick-borne microorganisms are able to evade the tick's innate immune system and survive within the tick's body. The examples that follow describe some of the many different strategies that have evolved to enable ticks to transmit the agents of human and/or animal disease.
Published: 2017
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26. Infrared light detection by the haller's organ of adult american dog ticks, Dermacentor variabilis (Ixodida: Ixodidae).

Author: Mitchell RD 3rd, Zhu J, Carr AL, Dhammi A, Cave G, Sonenshine DE, and Roe RM
Subjects: Animals, Extremities, Phototaxis, Dermacentor physiology, Dermacentor ultrastructure, Infrared Rays
Abstract: The Haller's organ (HO), unique to ticks and mites, is found only on the first tarsus of the front pair of legs. The organ has an unusual morphology consisting of an anterior pit (AP) with protruding sensilla and a posterior capsule (Cp). The current thinking is that the HO's main function is chemosensation analogous to the insect antennae, but the functionality of its atypical structure (exclusive to the Acari) is unexplained. We provide the first evidence that the HO allows the American dog tick, Dermacentor variabilis, to respond to infrared (IR) light. Unfed D. variabilis adults with their HOs present were positively phototactic to IR. However, when the HOs were removed, no IR response was detected. Ticks in these experiments were also attracted to white light with and without the HOs, but were only positively phototactic to white light when the ocelli (primitive eyes) were unobstructed. Covering the eyes did not prevent IR attraction. A putative TRPA1 receptor was characterized from a D. variabilis-specific HO transcriptome we constructed. This receptor was homologous to transient receptor potential cation channel, subfamily A, member 1 (TRPA1) from the pit organ of the pit viper, python, and boa families of snakes, the only receptor identified so far for IR detection. HO scanning electron microscopy (SEM) studies in the American dog tick showed the AP and Cp but also novel structures not previously described; the potential role of these structures in IR detection is discussed. The ability of ticks to use IR for host finding is consistent with their obligatory hematophagy and has practical applications in tick trapping and the development of new repellents., (Copyright © 2017 Elsevier GmbH. All rights reserved.)
Published: 2017
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27. Tick Haller's Organ, a New Paradigm for Arthropod Olfaction: How Ticks Differ from Insects.

Author: Carr AL, Mitchell RD III, Dhammi A, Bissinger BW, Sonenshine DE, and Roe RM
Subjects: Amino Acid Sequence, Animals, Behavior, Animal, Insect Proteins chemistry, Insect Proteins genetics, Insect Proteins metabolism, Male, Phylogeny, RNA, Messenger genetics, RNA, Messenger metabolism, Sensory Receptor Cells metabolism, Sequence Analysis, RNA, Taste, Transcriptome genetics, Animal Structures anatomy & histology, Animal Structures physiology, Smell genetics, Ticks anatomy & histology, Ticks physiology
Abstract: Ticks are the vector of many human and animal diseases; and host detection is critical to this process. Ticks have a unique sensory structure located exclusively on the 1st pairs of legs; the fore-tarsal Haller's organ, not found in any other animals, presumed to function like the insect antennae in chemosensation but morphologically very different. The mechanism of tick chemoreception is unknown. Utilizing next-generation sequencing and comparative transcriptomics between the 1st and 4th legs (the latter without the Haller's organ), we characterized 1st leg specific and putative Haller's organ specific transcripts from adult American dog ticks, Dermacentor variabilis . The analysis suggested that the Haller's organ is involved in olfaction, not gustation. No known odorant binding proteins like those found in insects, chemosensory lipocalins or typical insect olfactory mechanisms were identified; with the transcriptomic data only supporting a possible olfactory G-protein coupled receptor (GPCR) signal cascade unique to the Haller's organ. Each component of the olfactory GPCR signal cascade was identified and characterized. The expression of GPCR, G αo and β-arrestin transcripts identified exclusively in the 1st leg transcriptome, and putatively Haller's organ specific, were examined in unfed and blood-fed adult female and male D. variabilis . Blood feeding to repletion in adult females down-regulated the expression of all three chemosensory transcripts in females but not in males; consistent with differences in post-feeding tick behavior between sexes and an expected reduced chemosensory function in females as they leave the host. Data are presented for the first time of the potential hormonal regulation of tick chemosensation; behavioral assays confirmed the role of the Haller's organ in N , N -diethyl-meta-toluamide (DEET) repellency but showed no role for the Haller's organ in host attachment. Further research is needed to understand the potential role of the GPCR cascade in olfaction., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in collection, analysis or interpretation of data; in writing of the manuscript and in the decision to publish the results.
Published: 2017
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28. Ticks elicit variable fibrinogenolytic activities upon feeding on hosts with different immune backgrounds.

Author: Vora A, Taank V, Dutta SM, Anderson JF, Fish D, Sonenshine DE, Catravas JD, Sultana H, and Neelakanta G
Subjects: Animals, Body Weight drug effects, Down-Regulation genetics, Gene Expression Regulation drug effects, HSP70 Heat-Shock Proteins genetics, HSP70 Heat-Shock Proteins metabolism, Immunocompetence drug effects, Ixodes drug effects, Matrix Metalloproteinases metabolism, Mice, SCID, Purine Nucleosides pharmacology, RNA, Messenger genetics, RNA, Messenger metabolism, Salivary Glands drug effects, Salivary Glands metabolism, Tissue Extracts metabolism, Up-Regulation genetics, Feeding Behavior drug effects, Fibrinogen metabolism, Fibrinolysis drug effects, Host-Parasite Interactions immunology, Ixodes physiology
Abstract: Ticks secrete several anti-hemostatic factors in their saliva to suppress the host innate and acquired immune defenses against infestations. Using Ixodes scapularis ticks and age-matched mice purchased from two independent commercial vendors with two different immune backgrounds as a model, we show that ticks fed on immunodeficient animals demonstrate decreased fibrinogenolytic activity in comparison to ticks fed on immunocompetent animals. Reduced levels of D-dimer (fibrin degradation product) were evident in ticks fed on immunodeficient animals in comparison to ticks fed on immunocompetent animals. Increased engorgement weights were noted for ticks fed on immunodeficient animals in comparison to ticks fed on immunocompetent animals. Furthermore, the LC-MS/MS and quantitative real-time-PCR analysis followed by inhibitor and antibody-blocking assays revealed that the arthropod HSP70-like molecule contributes to differential fibrinogenolysis during tick feeding. Collectively, these results not only indicate that ticks elicit variable fibrinogenolysis upon feeding on hosts with different immune backgrounds but also provide insights for the novel role of arthropod HSP70-like molecule in fibrinogenolysis during blood feeding.
Published: 2017
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29. An In Vitro Blood-Feeding Method Revealed Differential Borrelia turicatae (Spirochaetales: Spirochaetaceae) Gene Expression After Spirochete Acquisition and Colonization in the Soft Tick Ornithodoros turicata (Acari: Argasidae).

Author: Neelakanta G, Sultana H, Sonenshine DE, and Marconi RT
Subjects: Animals, Bacterial Proteins metabolism, Borrelia growth & development, Borrelia physiology, Feeding Behavior, Female, Humans, Male, Mice, Relapsing Fever blood, Spirochaetales genetics, Spirochaetales growth & development, Spirochaetales physiology, Bacterial Proteins genetics, Borrelia genetics, Ornithodoros microbiology, Ornithodoros physiology, Relapsing Fever microbiology
Abstract: In the Midwestern, Southwestern, and Southern part of the United States, the soft tick Ornithodoros turicata transmits the spirochete Borrelia turicatae, the causative agent of relapsing fever in humans. In this study, we report a simplified and an efficient method of in vitro feeding to evaluate O. turicata-B. turicatae interactions. Both nymphal and adult female ticks successfully acquired spirochetes upon in vitro feeding on the B. turicatae-infected blood. We also noted transstadial transmission of spirochetes to adult ticks that were molted from nymphs fed on B. turicatae-infected blood. A differential expression pattern for some of the B. turicatae genes was evident after acquisition and colonization of the vector. The levels of arthropod-associated lipoprotein Alp-mRNA were significantly upregulated and the mRNA levels of factor H binding protein FhbA and immunogenic protein BipA were significantly downregulated in the spirochetes after acquisition into ticks in comparison with spirochetes grown in culture medium. In addition, genes such as bta124 and bta116 were significantly upregulated in spirochetes in unfed ticks in comparison with the levels noted in spirochetes after acquisition. These findings represent an efficient in vitro blood-feeding method to study B. turicatae gene expression after acquisition and colonization in these ticks. In summary, we report that B. turicatae survive and develop in the tick host when acquired by in vitro feeding. We also report that B. turicatae genes are differentially expressed in ticks in comparison with the in vitro-grown cultures, indicating influence of tick environment on spirochete gene expression., (© The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Published: 2017
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30. Tick Genome Assembled: New Opportunities for Research on Tick-Host-Pathogen Interactions.

Author: de la Fuente J, Waterhouse RM, Sonenshine DE, Roe RM, Ribeiro JM, Sattelle DB, and Hill CA
Subjects: Animals, Arachnid Vectors pathogenicity, Host-Pathogen Interactions, Humans, Ixodes pathogenicity, Sequence Analysis, DNA, Arachnid Vectors genetics, Genome, Insect, Ixodes genetics
Abstract: As tick-borne diseases are on the rise, an international effort resulted in the sequence and assembly of the first genome of a tick vector. This result promotes research on comparative, functional and evolutionary genomics and the study of tick-host-pathogen interactions to improve human, animal and ecosystem health on a global scale.
Published: 2016
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31. Evidence of female sex pheromones and characterization of the cuticular lipids of unfed, adult male versus female blacklegged ticks, Ixodes scapularis.

Author: Carr AL, Sonenshine DE, Strider JB Jr, and Roe RM
Subjects: Animals, Female, Ixodes physiology, Male, Ixodes chemistry, Lipids analysis, Sex Attractants analysis
Abstract: Copulation in Ixodes scapularis involves physical contact between the male and female (on or off the host), male mounting of the female, insertion/maintenance of the male chelicerae in the female genital pore (initiates spermatophore production), and the transfer of the spermatophore by the male into the female genital pore. Bioassays determined that male mounting behavior/chelicerae insertion required direct contact with the female likely requiring non-volatile chemical cues with no evidence of a female volatile sex pheromone to attract males. Unfed virgin adult females and replete mated adult females elicited the highest rates of male chelicerae insertion with part fed virgin adult females exhibiting a much lower response. Whole body surface hexane extracts of unfed virgin adult females and males, separately analyzed by GC-MS, identified a number of novel tick surface associated compounds: fatty alcohols (1-hexadecanol and 1-heptanol), a fatty amide (erucylamid), aromatic hydrocarbons, a short chain alkene (1-heptene), and a carboxylic acid ester (5β-androstane). These compounds are discussed in terms of their potential role in female-male communication. The two most abundant fatty acid esters found were butyl palmitate and butyl stearate present in ratios that were sex specific. Only 6 n-saturated hydrocarbons were identified in I. scapularis ranging from 10 to 18 carbons.
Published: 2016
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32. Mevalonate-Farnesal Biosynthesis in Ticks: Comparative Synganglion Transcriptomics and a New Perspective.

Author: Zhu J, Khalil SM, Mitchell RD, Bissinger BW, Egekwu N, Sonenshine DE, and Roe RM
Subjects: Aedes enzymology, Amino Acid Sequence, Animals, Cholesterol biosynthesis, Farnesol metabolism, Female, Geranyltranstransferase chemistry, Geranyltranstransferase metabolism, Juvenile Hormones metabolism, Male, Methyltransferases chemistry, Methyltransferases metabolism, Mice, Models, Biological, Molecular Sequence Data, NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases chemistry, NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases metabolism, Phylogeny, Sequence Alignment, Biosynthetic Pathways, Corpora Allata metabolism, Farnesol analogs & derivatives, Mevalonic Acid metabolism, Ticks genetics, Ticks metabolism, Transcriptome genetics
Abstract: Juvenile hormone (JH) controls the growth, development, metamorphosis, and reproduction of insects. For many years, the general assumption has been that JH regulates tick and other acarine development and reproduction the same as in insects. Although researchers have not been able to find the common insect JHs in hard and soft tick species and JH applications appear to have no effect on tick development, it is difficult to prove the negative or to determine whether precursors to JH are made in ticks. The tick synganglion contains regions which are homologous to the corpora allata, the biosynthetic source for JH in insects. Next-gen sequencing of the tick synganglion transcriptome was conducted separately in adults of the American dog tick, Dermacentor variabilis, the deer tick, Ixodes scapularis, and the relapsing fever tick, Ornithodoros turicata as a new approach to determine whether ticks can make JH or a JH precursor. All of the enzymes that make up the mevalonate pathway from acetyl-CoA to farnesyl diphosphate (acetoacetyl-CoA thiolase, HMG-S, HMG-R, mevalonate kinase, phosphomevalonate kinase, diphosphomevalonate decarboxylase, and farnesyl diphosphate synthase) were found in at least one of the ticks studied but most were found in all three species. Sequence analysis of the last enzyme in the mevalonate pathway, farnesyl diphosphate synthase, demonstrated conservation of the seven prenyltransferase regions and the aspartate rich motifs within those regions typical of this enzyme. In the JH branch from farnesyl diphosphate to JH III, we found a putative farnesol oxidase used for the conversion of farnesol to farnesal in the synganglion transcriptome of I. scapularis and D. variabilis. Methyltransferases (MTs) that add a methyl group to farnesoic acid to make methyl farnesoate were present in all of the ticks studied with similarities as high as 36% at the amino acid level to insect JH acid methyltransferase (JHAMT). However, when the tick MTs were compared to the known insect JHAMTs from several insect species at the amino acid level, the former lacked the farnesoic acid binding motif typical in insects. The P450s shown in insects to add the C10,11 epoxide to methyl farnesoate, are in the CYP15 family; this family was absent in our tick transcriptomes and in the I. scapularis genome, the only tick genome available. These data suggest that ticks do not synthesize JH III but have the mevalonate pathway and may produce a JH III precursor.
Published: 2016
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33. Genomic insights into the Ixodes scapularis tick vector of Lyme disease.

Author: Gulia-Nuss M, Nuss AB, Meyer JM, Sonenshine DE, Roe RM, Waterhouse RM, Sattelle DB, de la Fuente J, Ribeiro JM, Megy K, Thimmapuram J, Miller JR, Walenz BP, Koren S, Hostetler JB, Thiagarajan M, Joardar VS, Hannick LI, Bidwell S, Hammond MP, Young S, Zeng Q, Abrudan JL, Almeida FC, Ayllón N, Bhide K, Bissinger BW, Bonzon-Kulichenko E, Buckingham SD, Caffrey DR, Caimano MJ, Croset V, Driscoll T, Gilbert D, Gillespie JJ, Giraldo-Calderón GI, Grabowski JM, Jiang D, Khalil SMS, Kim D, Kocan KM, Koči J, Kuhn RJ, Kurtti TJ, Lees K, Lang EG, Kennedy RC, Kwon H, Perera R, Qi Y, Radolf JD, Sakamoto JM, Sánchez-Gracia A, Severo MS, Silverman N, Šimo L, Tojo M, Tornador C, Van Zee JP, Vázquez J, Vieira FG, Villar M, Wespiser AR, Yang Y, Zhu J, Arensburger P, Pietrantonio PV, Barker SC, Shao R, Zdobnov EM, Hauser F, Grimmelikhuijzen CJP, Park Y, Rozas J, Benton R, Pedra JHF, Nelson DR, Unger MF, Tubio JMC, Tu Z, Robertson HM, Shumway M, Sutton G, Wortman JR, Lawson D, Wikel SK, Nene VM, Fraser CM, Collins FH, Birren B, Nelson KE, Caler E, and Hill CA
Subjects: Animals, Gene Expression Profiling, Genomics, Lyme Disease transmission, Oocytes, Xenopus laevis, Anaplasma phagocytophilum, Arachnid Vectors genetics, Genome genetics, Ixodes genetics, Ligand-Gated Ion Channels genetics
Abstract: Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing ∼57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick-host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host 'questing', prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival. We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent.
Published: 2016
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34. Comparison of synganglion neuropeptides, neuropeptide receptors and neurotransmitter receptors and their gene expression in response to feeding in Ixodes scapularis (Ixodidae) vs. Ornithodoros turicata (Argasidae).

Author: Egekwu N, Sonenshine DE, Garman H, Barshis DJ, Cox N, Bissinger BW, Zhu J, and M Roe R
Subjects: Animals, Diuresis, Feeding Behavior, Female, Ganglion Cysts metabolism, Gene Expression, Gene Ontology, Molting, Reproduction, Salivary Glands metabolism, Insect Proteins metabolism, Ixodes metabolism, Neuropeptides metabolism, Ornithodoros metabolism, Receptors, Neuropeptide metabolism
Abstract: Illumina GAII high-throughput sequencing was used to compare expressed genes for female synganglion neuropeptides, neuropeptide receptors and neurotransmitter receptors of the soft tick Ornithodoros turicata with the hard tick Ixodes scapularis. Gene ontology molecular level three mapping revealed no significant differences amongst the same categories represented in O. turicata and I. scapularis. Transcripts predicting 22 neuropeptides or their receptors in the O. turicata synganglion were similar to annotations for 23 neuropeptides or receptors previously identified from I scapularis, with minor exceptions. A transcript predicting ecdysis triggering hormone receptor was identified in O. turicata; transcripts encoding for proprotein convertase and glycoprotein B were identified in both species. Transcripts predicting the same neurotransmitter receptors were found in the synganglion of both species. Gene expression of the transcripts showed numerous differences in response to feeding. Major differences were observed in expression of genes believed important in regulating slow vs. rapid feeding, blood water elimination, cuticle synthesis plasticity and in signalling reproductive activity. Although the glutamate receptor was strongly upregulated in both species, the gamma aminobutyric acid receptor, which inhibits glutamate, was upregulated significantly only in I. scapularis. These differences are consistent with the slow vs. rapid action of the pharyngeal pump in the two species., (© 2016 The Royal Entomological Society.)
Published: 2016
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35. Rickettsia parkeri Transmission to Amblyomma americanum by Cofeeding with Amblyomma maculatum (Acari: Ixodidae) and Potential for Spillover.

Author: Wright CL, Sonenshine DE, Gaff HD, and Hynes WL
Subjects: Animals, Feeding Behavior, Female, Guinea Pigs, Ixodidae growth & development, Larva growth & development, Larva physiology, Larva virology, Male, Nymph growth & development, Nymph physiology, Nymph virology, Real-Time Polymerase Chain Reaction, Rickettsia Infections microbiology, Species Specificity, Virginia, Ixodidae microbiology, Ixodidae physiology, Rickettsia physiology, Rickettsia Infections transmission
Abstract: Amblyomma americanum (L.) is a human-biting ixodid tick distributed throughout much of the southeastern United States. Rickettsia parkeri is a member of the spotted fever group rickettsiae and causes a febrile illness in humans commonly referred to as "Tidewater spotted fever" or "R. parkeri rickettsiosis." Although the Gulf Coast tick, Amblyomma maculatum Koch, is the primary vector of R. parkeri, a small proportion of A. americanum have also been shown to harbor R. parkeri. The purpose of this investigation was to determine whether R. parkeri is spilling over into A. americanum in eastern Virginia and also to determine through laboratory experiments, whether A. americanum can acquire R. parkeri by cofeeding alongside infected ticks. Of 317 wild-caught, flat adult A. americanum tested from 29 counties and independent cities in coastal Virginia, a single female A. americanum was positive for R. parkeri, suggesting that R. parkeri is spilling over into this species, but at very low rates (<1.0%). Laboratory studies using guinea pigs indicated that nymphal A. americanum were able to acquire R. parkeri while feeding alongside infected A. maculatum and then transstadially maintain the infection. Nymphal A. americanum infected with Rickettsia amblyommii, however, were less likely to acquire R. parkeri, suggesting that infection with R. amblyommii may prevent R. parkeri from establishing infection in A. americanum., (© The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Published: 2015
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36. Experimental vertical transmission of Rickettsia parkeri in the Gulf Coast tick, Amblyomma maculatum.

Author: Wright CL, Gaff HD, Sonenshine DE, and Hynes WL
Subjects: Animals, Female, Larva microbiology, Larva physiology, Male, Molting, Nymph microbiology, Oviposition, Ovum microbiology, Rickettsia classification, Infectious Disease Transmission, Vertical, Ixodidae microbiology, Rickettsia physiology
Abstract: Rickettsia parkeri, an obligate intracellular bacterium, is a member of the spotted fever group of rickettsiae (SFGR), and is transmitted to humans and other animals by invertebrate vectors. In the United States, the primary vector of R. parkeri is the Gulf Coast tick, Amblyomma maculatum Koch. This study investigates the vertical transmission dynamics of R. parkeri within a field-derived, naturally infected colony of A. maculatum. Transovarial and transstadial transmission of the pathogen was observed over three generations, with transovarial transmission efficiency averaging 83.7% and transstadial transmission rates approaching 100%. Fitness costs were determined by comparing reproduction values of the R. parkeri-infected A. maculatum colony to values from a R. parkeri-free colony. No significant reproductive fitness costs to the host ticks were detected in the R. parkeri-infected A. maculatum colony. Significantly fewer engorged F1 nymphs and F2 larvae of the R. parkeri-free colony succeeded in molting, suggesting that there may be some advantage to survival conferred by R. parkeri. The results of this study indicate that R. parkeri is maintained in A. maculatum populations efficiently by transovarial and transstadial transmission without any noticeable effects on tick reproduction or survival., (Copyright © 2015 Elsevier GmbH. All rights reserved.)
Published: 2015
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37. TickBot: a novel robotic device for controlling tick populations in the natural environment.

Author: Gaff HD, White A, Leas K, Kelman P, Squire JC, Livingston DL, Sullivan GA, Baker EW, and Sonenshine DE
Subjects: Animals, Humans, Ixodidae drug effects, Robotics, Tick Control instrumentation, Virginia, Acaricides administration & dosage, Carbon Dioxide administration & dosage, Permethrin administration & dosage, Tick Control methods, Tick Infestations prevention & control, Tick-Borne Diseases prevention & control, Ticks drug effects
Abstract: A semi-autonomous 4-wheeled robot (TickBot) was fitted with a denim cloth treated with an acaricide (permethrin™) and tested for its ability to control ticks in a tick-infested natural environment in Portsmouth, Virginia. The robot's sensors detect a magnetic field signal from a guide wire encased in 80m polyethylene tubing, enabling the robot to follow the trails, open areas and other terrain where the tubing was located. To attract ticks to the treated area, CO2 was distributed through the same tubing, fitted with evenly spaced pores and flow control valves, which permitted uniform CO2 distribution. Tests were done to determine the optimum frequency for TickBot to traverse the wire-guided treatment site as well as the duration of operation that could be accomplished on a single battery charge. Prior to treatment, dragging was done to determine the natural abundance of ticks in the test site. Controls were done without CO2 and without permethrin. TickBot proved highly effective in reducing the overall tick densities to nearly zero with the treatment that included both carbon dioxide pretreatment and the permethrin treated cloth. Following a 60min traverse of the treatment areas, adult tick numbers, almost entirely Amblyomma americanum, was reduced to zero within 1h and remained at or near zero for 24h. Treatments without CO2 also showed reduction of ticks to near zero within 1h, but the populations were no different than the control sections at 4h. This study demonstrates the efficacy of TickBot as a tick control device to significantly reduce the risk of tick bites and disease transmission to humans and companion animals visiting a previously tick-infested natural environment. Continued deployment of TickBot for additional days or weeks can assure a relatively tick-safe environment for enjoyment by the public., (Copyright © 2014 Elsevier GmbH. All rights reserved.)
Published: 2015
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38. Identification and comparative analysis of subolesin/akirin ortholog from Ornithodoros turicata ticks.

Author: Sultana H, Patel U, Sonenshine DE, and Neelakanta G
Subjects: Amino Acid Sequence, Animals, Base Sequence, Evolution, Molecular, Female, Humans, Male, Ornithodoros genetics, Ornithodoros metabolism, Phylogeny, RNA, Messenger genetics, Sequence Alignment, Sequence Analysis, DNA, Ornithodoros immunology, Salivary Glands metabolism
Abstract: Background: Subolesin is an evolutionary conserved molecule in diverse arthropod species that play an important role in the regulation of genes involved in immune responses, blood digestion, reproduction and development. In this study, we have identified a subolesin ortholog from soft ticks Ornithodoros turicata, the vector of the relapsing fever spirochete in the United States., Methods: Uninfected fed or unfed O. turicata ticks were used throughout this study. The subolesin mRNA was amplified by reverse transcription polymerase chain reaction (RT-PCR) and sequenced. Quantitative-real time PCR (QRT-PCR) was performed to evaluate subolesin mRNA levels at different O. turicata developmental stages and from salivary glands and gut tissues. Bioinformatics and comparative analysis was performed to predict potential post-translational modifications in O. turicata subolesin amino-acid sequences., Results: Our study reveals that O. turicata subolesin gene expression is developmentally regulated, where; adult ticks expressed significantly higher levels in comparison to the larvae or nymphal ticks. Expression of subolesin was evident in both unfed and fed ticks and in the salivary glands and midgut tissues. The expression of subolesin transcripts varied in fed ticks with peak levels at day 14 post-feeding. Phylogenetic analysis revealed that O. turicata subolesin showed a high degree of sequence conservation with subolesin's from other soft and hard ticks. Bioinformatics and comparative analysis predicted that O. turicata subolesin carry three Protein kinase C and one Casein kinase II phosphorylation sites. However, no myristoylation or glycosylation sites were evident in the O. turicata subolesin sequence., Conclusion: Our study provides important insights in recognizing subolesin as a conserved potential candidate for the development of a broad-spectrum anti-vector vaccine to control not only ticks but also several other arthropods that transmit diseases to humans and animals.
Published: 2015
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39. Transcriptome of the female synganglion of the black-legged tick Ixodes scapularis (Acari: Ixodidae) with comparison between Illumina and 454 systems.

Author: Egekwu N, Sonenshine DE, Bissinger BW, and Roe RM
Subjects: Animals, Female, Ixodes metabolism, Neuropeptides genetics, Neuropeptides metabolism, Neurotransmitter Agents genetics, Neurotransmitter Agents metabolism, Polymerase Chain Reaction methods, Receptors, Neurotransmitter genetics, Receptors, Neurotransmitter metabolism, Ganglia, Invertebrate metabolism, Ixodes genetics, Transcriptome
Abstract: Illumina and 454 pyrosequencing were used to characterize genes from the synganglion of female Ixodes scapularis. GO term searching success for biological processes was similar for samples sequenced by both methods. However, for molecular processes, it was more successful for the Illumina samples than for 454 samples. Functional assignments of transcripts predicting neuropeptides, neuropeptide receptors, neurotransmitter receptors and other genes of interest was done, supported by strong e-values (<-6), and high consensus sequence alignments. Transcripts predicting 15 putative neuropeptide prepropeptides ((allatostatin, allatotropin, bursicon α, corticotropin releasing factor (CRF), CRF-binding protein, eclosion hormone, FMRFamide, glycoprotein A, insulin-like peptide, ion transport peptide, myoinhibitory peptide, inotocin ( = neurophysin-oxytocin), Neuropeptide F, sulfakinin and SIFamide)) and transcripts predicting receptors for 14 neuropeptides (allatostatin, calcitonin, cardioacceleratory peptide, corazonin, CRF, eclosion hormone, gonadotropin-releasing hormone/AKH-like, insulin-like peptide, neuropeptide F, proctolin, pyrokinin, SIFamide, sulfakinin and tachykinin) are reported. Similar to Dermacentor variabilis, we found transcripts matching pro-protein convertase, essential for converting neuropeptide hormones to their mature form. Additionally, transcripts predicting 6 neurotransmitter/neuromodulator receptors (acetylcholine, GABA, dopamine, glutamate, octopamine and serotonin) and 3 neurotransmitter transporters (GABA transporter, noradrenalin-norepinephrine transporter and Na+-neurotransmitter/symporter) are described. Further, we found transcripts predicting genes for pheromone odorant receptor, gustatory receptor, novel GPCR messages, ecdysone nuclear receptor, JH esterase binding protein, steroidogenic activating protein, chitin synthase, chitinase, and other genes of interest. Also found were transcripts predicting genes for spermatogenesis-associated protein, major sperm protein, spermidine oxidase and spermidine synthase, genes not normally expressed in the female CNS of other invertebrates. The diversity of messages predicting important genes identified in this study offers a valuable resource useful for understanding how the tick synganglion regulates important physiological functions.
Published: 2014
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40. The ToxAvapA toxin-antitoxin locus contributes to the survival of nontypeable Haemophilus influenzae during infection.

Author: Ren D, Kordis AA, Sonenshine DE, and Daines DA
Subjects: Animals, Bacterial Proteins genetics, Chinchilla, Coculture Techniques, Culture Media, Conditioned chemistry, Female, Haemophilus influenzae enzymology, Haemophilus influenzae growth & development, Humans, Ribonucleases metabolism, Survival Analysis, Antitoxins genetics, Genetic Loci, Haemophilus influenzae genetics, Haemophilus influenzae physiology, Toxins, Biological genetics
Abstract: Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen that is a common cause of acute and recurrent mucosal infections. One uncharacterized NTHi toxin-antitoxin (TA) module, NTHI1912-1913, is a host inhibition of growth (higBA) homologue. We hypothesized that this locus, which we designated toxAvapA, contributed to NTHi survival during infection. We deleted toxAvapA and determined that growth of the mutant in defined media was not different from the parent strain. We tested the mutant for persistence during long-term in vitro co-culture with primary human respiratory tissues, which revealed that the ΔtoxAvapA mutant was attenuated for survival. We then performed challenge studies using the chinchilla model of otitis media and determined that mutant survival was also reduced in vivo. Following purification, the toxin exhibited ribonuclease activity on RNA in vitro, while the antitoxin did not. A microarray comparison of the transcriptome revealed that the tryptophan biosynthetic regulon was significantly repressed in the mutant compared to the parent strain. HPLC studies of conditioned medium confirmed that there was no significant difference in the concentration of tryptophan remaining in the supernatant, indicating that the uptake of tryptophan by the mutant was not affected. We conclude that the role of the NTHi toxAvapA TA module in persistence following stress is multifactorial and includes effects on essential metabolic pathways.
Published: 2014
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41. The use of ivermectin to kill ixodes scapularis ticks feeding on humans.

Author: Sheele JM, Ford LR, Tse A, Chidester B, Byers PA, and Sonenshine DE
Subjects: Administration, Oral, Adult, Animals, Female, Humans, Ivermectin administration & dosage, Male, Mortality, Nymph drug effects, Young Adult, Ivermectin pharmacology, Ixodes drug effects
Abstract: Objective: The purpose of this study was to determine whether 400 µg/kg oral ivermectin is able to kill Ixodes scapularis nymphs and adult female ticks feeding on humans., Methods: Ten study subjects each wore 2 ostomy bags, the one containing 24 I scapularis nymphs, and the other containing 24 I scapularis adult females. Twenty-four hours after the ostomy bags were attached, study subjects received either 400 µg/kg ivermectin or placebo. Thirty hours after the ivermectin or placebo was consumed, the ticks were removed, and mortality determined in a double-blinded manner., Results: Eleven percent of the I scapularis nymphs attached in the ivermectin group compared with 17% in the placebo. Mortality for the I scapularis nymphs that attached at the time of removal was 55% in the ivermectin group and 47% in the placebo group. Mortality for the I scapularis nymphs 5 days after removal was 92% in the ivermectin group and 88% for the placebo. Three percent of the I scapularis adults attached in the ivermectin group compared with 9% in the placebo group. Mortality for I scapularis adults was 0% on day 3 and 33% on day 8 for both the ivermectin and placebo groups. There were statistically insignificant differences in the mortality rates between I scapularis nymphs and adults exposed to ivermectin or placebo., Conclusions: There were a high number of ticks that died in both groups but the data do not support our hypothesis that ivermectin can kill I scapularis. The study was not designed to determine whether it could prevent the transmission of tick-borne illness., (© 2014 Wilderness Medical Society Published by Wilderness Medical Society All rights reserved.)
Published: 2014
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42. Ticks and spotted fever group rickettsiae of southeastern Virginia.

Author: Nadolny RM, Wright CL, Sonenshine DE, Hynes WL, and Gaff HD
Subjects: Animals, Arachnid Vectors classification, DNA, Bacterial genetics, Humans, Male, Polymerase Chain Reaction, Population Surveillance, Rickettsia classification, Rickettsia genetics, Rickettsia Infections epidemiology, Rickettsia Infections microbiology, Ticks classification, Virginia epidemiology, Arachnid Vectors microbiology, Rickettsia isolation & purification, Ticks microbiology
Abstract: The incidence of tick-borne rickettsial disease in the southeastern United States has been rising steadily through the past decade, and the range expansions of tick species and tick-borne infectious agents, new and old, has resulted in an unprecedented mix of vectors and pathogens. The results of an ongoing 4-year surveillance project describe the relative abundance of questing tick populations in southeastern Virginia. Since 2009, more than 66,000 questing ticks of 7 species have been collected from vegetation in a variety of habitats, with Amblyomma americanum constituting over 95% of ticks collected. Other species represented included Ixodes scapularis, Dermacentor variabilis, Amblyomma maculatum, Ixodes affinis, Haemaphysalis leporispalustris, and Ixodes brunneus. We found that 26.9-54.9% of A. americanum ticks tested were positive for Rickettsia amblyommii, a non-pathogenic symbiont of this tick species. We also found no evidence of R. rickettsii in D. variabilis ticks, although they did show low infection rates of R. montanensis (1.5-2.0%). Rickettsia parkeri and Candidatus R. andeanae were found in 41.8-55.7% and 0-1.5% A. maculatum ticks, respectively. The rate of R. parkeri in A. maculatum ticks is among the highest in the literature and has increased in the 2 years since R. parkeri and A. maculatum were first reported in southeastern Virginia. We conclude that tick populations in southeastern Virginia have recently undergone dramatic changes in species and abundance and that these populations support a variety of rickettsial agents with the potential for increased risk to human health., (Copyright © 2013 Elsevier GmbH. All rights reserved.)
Published: 2014
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43. Gene expression of tissue-specific molecules in ex vivo Dermacentor variabilis (Acari: Ixodidae) during rickettsial exposure.

Author: Sunyakumthorn P, Petchampai N, Grasperge BJ, Kearney MT, Sonenshine DE, and Macaluso KR
Subjects: Animals, Aprotinin, Arthropod Proteins metabolism, Dermacentor immunology, Female, Glutathione Transferase genetics, Glutathione Transferase metabolism, Organ Specificity, Protease Inhibitors metabolism, Real-Time Polymerase Chain Reaction, Thymosin genetics, Thymosin metabolism, Arthropod Proteins genetics, Dermacentor genetics, Dermacentor microbiology, Gene Expression Regulation, Rickettsia physiology
Abstract: Ticks serve as both vectors and the reservoir hosts capable of transmitting spotted fever group Rickettsia by horizontal and vertical transmission. Persistent maintenance of Rickettsia species in tick populations is dependent on the specificity of the tick and Rickettsia relationship that limits vertical transmission of particular Rickettsia species, suggesting host-derived mechanisms of control. Tick-derived molecules are differentially expressed in a tissue-specific manner in response to rickettsial infection; however, little is known about tick response to specific rickettsial species. To test the hypothesis that tissue-specific tick-derived molecules are uniquely responsive to rickettsial infection, a bioassay to characterize the tick tissue-specific response to different rickettsial species was used. Whole organs of Dermacentor variabilis (Say) were exposed to either Rickettsia montanensis or Rickettsia amblyommii, two Rickettsia species common, or absent, in field-collected D. variabilis, respectively, for 1 and 12 h and harvested for quantitative real time-polymerase chain reaction assays of putative immune-like tick-derived factors. The results indicated that tick genes are differently expressed in a temporal and tissue-specific manner. Genes encoding glutathione S-transferase 1 (dvgst1) and Kunitz protease inhibitor (dvkpi) were highly expressed in midgut, and rickettsial exposure downregulated the expression of both genes. Two other genes encoding glutathione S-transferase 2 (dvgst2) and beta-thymosin (dvpbeta-thy) were highly expressed in ovary, with dvbeta-thy expression significantly downregulated in ovaries exposed to R. montanensis, but not R. amblyommii, at 12-h postexposure, suggesting a selective response. Deciphering the tissue-specific molecular interactions between tick and Rickettsia will enhance our understanding of the key mechanisms that mediate rickettsial infection in ticks.
Published: 2013
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44. Ivermectin causes Cimex lectularius (bedbug) morbidity and mortality.

Author: Sheele JM, Anderson JF, Tran TD, Teng YA, Byers PA, Ravi BS, and Sonenshine DE
Subjects: Adult, Animals, Female, Humans, Insecticides administration & dosage, Ivermectin administration & dosage, Male, Mice, Nymph drug effects, Young Adult, Bedbugs drug effects, Insect Bites and Stings prevention & control, Insecticides pharmacology, Ivermectin pharmacology
Abstract: Background: Bedbug infestations are increasing across North America and Europe, with more people presenting to Emergency Departments for treatment. Physicians cannot provide substantive treatment for people affected by bedbugs., Study Objective: To determine if ivermectin, a relatively inexpensive and safe, long-acting oral anti-parasitic drug is able to cause bedbug morbidity and mortality., Methods: We evaluated the effects of ivermectin on bedbugs using an artificial feeding membrane and mice and humans. Bedbug morbidity, mortality, and nymph molting was recorded., Results: Using an artificial feeding membrane, bedbug mortality was 98% (n = 81) for 260 ng/mL ivermectin and 0% for 0 ng/mL ivermectin (control; n = 90) after 13 days. Mortality for bedbugs fed on mice injected with the human equivalent of 200 μg/kg ivermectin was 86% (n = 22), vs. 0% in the 0 μg/kg ivermectin (control; n = 21). Of the surviving nymphs, 0% exposed to ivermectin molted by day 75, vs. 80% in the control group by day 8. Bedbugs that fed once on human study subjects 3 h after consuming 200 μg/kg of oral ivermectin had a 63% (n = 24) 20-day mortality rate, vs. 8% (n = 24) in the control group. Of the surviving nymphs, 0% (n = 5) in the 3-h ivermectin group molted, vs. 80% (n = 10) of the control group., Conclusions: It may be possible that ivermectin could help eradicate, suppress, or prevent a bedbug infestation., (Copyright © 2013 Elsevier Inc. All rights reserved.)
Published: 2013
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45. Responses of Amblyomma americanum and Dermacentor variabilis to odorants that attract haematophagous insects.

Author: Carr AL, Roe RM, Arellano C, Sonenshine DE, Schal C, and Apperson CS
Subjects: Animals, Dermacentor drug effects, Dermacentor physiology, Feeding Behavior drug effects, Insect Control, Species Specificity, Ixodidae drug effects, Ixodidae physiology, Pheromones pharmacology
Abstract: Carbon dioxide (CO(2) ), 1-octen-3-ol, acetone, ammonium hydroxide, L-lactic-acid, dimethyl trisulphide and isobutyric acid were tested as attractants for two tick species, Amblyomma americanum and Dermacentor variabilis (Acari: Ixodidae), in dose-response bioassays using Y-tube olfactometers. Only CO(2) , acetone, 1-octen-3-ol and ammonium hydroxide elicited significant preferences from adult A. americanum, and only CO(2) was attractive to adult D. variabilis. Acetone, 1-octen-3-ol and ammonium hydroxide were separately evaluated at three doses against CO(2) (from dry ice) at a field site supporting a natural population of A. americanum nymphs and adults. Carbon dioxide consistently attracted the highest number of host-seeking ticks. However, for the first time, acetone, 1-octen-3-ol and ammonium hydroxide were shown to attract high numbers of A. americanum. Further research is needed to determine the utility of these semiochemicals as attractants in tick surveillance and area-wide management programmes., (© 2012 The Royal Entomological Society.)
Published: 2013
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46. Initial assessment of the ability of ivermectin to kill Ixodes scapularis and Dermacentor variabilis ticks feeding on humans.

Author: Sheele JM, Byers PA, and Sonenshine DE
Subjects: Adult, Animals, Antiparasitic Agents administration & dosage, Arachnid Vectors, Humans, Ivermectin administration & dosage, Tick Infestations drug therapy, Tick Infestations prevention & control, Tick-Borne Diseases drug therapy, Tick-Borne Diseases prevention & control, Antiparasitic Agents pharmacology, Dermacentor drug effects, Ivermectin pharmacology, Ixodes drug effects
Abstract: Objective: The purpose of this study was to determine Ixodes scapularis and Dermacentor variabilis tick mortality when fed on humans who have consumed 400 μg/kg oral ivermectin., Methods: Six study subjects, 3 in each group, were randomly assigned to receive either 400 μg/kg ivermectin or placebo in a blinded manner. After consuming either ivermectin or placebo, each study subject had 2 colostomy bags attached to his or her abdomen. One of the colostomy bags contained 7 I scapularis nymphs and 7 adults. The other colostomy bag contained 7 D variabilis nymphs and 7 adults. Tick mortality was recorded over the next 24 hours., Results: Fifty-five percent (6 of 11) of the attached I scapularis nymphs exposed to ivermectin had morbidity (3 of 11) or died (3 of 11), compared with 0% morbidity and mortality in the 2 I scapularis nymphs that attached in the placebo group. No I scapularis adults or D variabilis nymphs attached to feed. Among D variabilis adults that attached to feed, there was a 0% mortality rate for both the placebo group (0 of 6) and the ivermectin group (0 of 8)., Conclusions: We demonstrate a novel method to confine ticks to human subjects to study tick-borne diseases. While there was a trend toward I scapularis morbidity and mortality in the ivermectin arm, the low number of ticks that attached in the placebo group limited our analysis. Most ticks began feeding in the last 12 hours of the experiment, significantly limiting their exposure to ivermectin. Ivermectin does not cause early death in D variabilis adults., (Copyright © 2013 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)
Published: 2013
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47. Molecular characterization and tissue-specific gene expression of Dermacentor variabilis α-catenin in response to rickettsial infection.

Author: Sunyakumthorn P, Petchampai N, Kearney MT, Sonenshine DE, and Macaluso KR
Subjects: Amino Acid Sequence, Animals, Arthropod Proteins genetics, Arthropod Vectors genetics, Dermacentor genetics, Dermacentor microbiology, Feeding Behavior, Female, Gene Expression, Molecular Sequence Data, RNA, Messenger metabolism, Rickettsia Infections transmission, Sequence Analysis, DNA, alpha Catenin genetics, Arthropod Proteins metabolism, Arthropod Vectors metabolism, Dermacentor metabolism, Rickettsia physiology, alpha Catenin metabolism
Abstract: Alpha catenin is a cytoskeleton protein that acts as a regulator of actin rearrangement by forming an E-cadherin adhesion complex. In Dermacentor variabilis, a putative α-catenin (Dvα-catenin) was previously identified as differentially regulated in ovaries of ticks chronically infected with Rickettsia montanensis. To begin characterizing the role(s) of Dvα-catenin during rickettsial infection, the full-length Dvα-catenin cDNA was cloned and analysed. Comparative sequence analysis demonstrates a 3069-bp cDNA with a 2718-bp open reading frame with a sequence similar to Ixodes scapularisα-catenin. A portion of Dvα-catenin is homologous to the vinculin-conserved domain containing a putative actin-binding region and β-catenin-binding and -dimerization regions. Quantitative reverse-transcription PCR analysis demonstrated that Dvα-catenin is predominantly expressed in tick ovaries and is responsive to tick feeding. The tissue-specific gene expression analysis of ticks exposed to Rickettsia demonstrates that Dvα-catenin expression was significantly downregulated 12 h after exposure to R. montanensis, but not in Rickettsia amblyommii-exposed ovaries, compared with Rickettsia-unexposed ticks. Studying tick-derived molecules associated with rickettsial infection will provide a better understanding of the transmission dynamics of tick-borne rickettsial diseases., (© 2012 The Authors. Insect Molecular Biology © 2012 The Royal Entomological Society.)
Published: 2012
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48. In vitro propagation of Candidatus Rickettsia andeanae isolated from Amblyomma maculatum.

Author: Luce-Fedrow A, Wright C, Gaff HD, Sonenshine DE, Hynes WL, and Richards AL
Subjects: Animals, Argentina, Cell Culture Techniques methods, Peru, Rickettsia classification, Rickettsia genetics, United States, Bacteriological Techniques methods, Ixodidae microbiology, Rickettsia growth & development, Rickettsia isolation & purification
Abstract: Candidatus Rickettsia andeanae was identified during an investigation of a febrile outbreak in northwestern Peru (2002). DNA sequencing from two ticks (Amblyomma maculatum, Ixodes boliviensis) collected during the investigation revealed a novel Rickettsia agent with similarity to the spotted fever group rickettsiae. Since then, Candidatus R. andeanae has been detected in A. maculatum ticks collected in the southeastern and southcentral United States, Argentina, and Peru. To date, Candidatus R. andeanae has not been successfully cultivated in the laboratory. We present evidence for the continuous cultivation in three cell lines of Candidatus R. andeanae isolated from an A. maculatum tick (Portsmouth, Virginia)., (Published 2011. This article is a U.S. Government work and is in the public domain in the USA.)
Published: 2012
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49. Ixodes affinis (Acari: Ixodidae) in southeastern Virginia and implications for the spread of Borrelia burgdorferi, the agent of Lyme disease.

Author: Nadolny RM, Wright CL, Hynes WL, Sonenshine DE, and Gaff HD
Subjects: Animals, Demography, Disease Reservoirs, Humans, Ixodes classification, Lyme Disease microbiology, Virginia, Arachnid Vectors, Borrelia burgdorferi pathogenicity, Ixodes microbiology, Lyme Disease transmission
Published: 2011
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50. Synganglion transcriptome and developmental global gene expression in adult females of the American dog tick, Dermacentor variabilis (Acari: Ixodidae).

Author: Bissinger BW, Donohue KV, Khalil SM, Grozinger CM, Sonenshine DE, Zhu J, and Roe RM
Subjects: Acetylcholine metabolism, Acetylcholinesterase chemistry, Acetylcholinesterase metabolism, Amino Acid Sequence, Animals, Central Nervous System growth & development, Central Nervous System metabolism, Dermacentor genetics, Dermacentor growth & development, Feeding Behavior, Female, Gene Expression Profiling, Molecular Sequence Data, Neurotransmitter Transport Proteins genetics, Neurotransmitter Transport Proteins metabolism, Oligonucleotide Array Sequence Analysis, Polymerase Chain Reaction, Receptors, GABA chemistry, Receptors, GABA metabolism, Receptors, Neurotransmitter genetics, Receptors, Neurotransmitter metabolism, Receptors, Nicotinic chemistry, Receptors, Nicotinic metabolism, Receptors, Steroid metabolism, Sexual Behavior, Animal, Dermacentor metabolism, Hormones metabolism, Neuropeptides metabolism, Neurotransmitter Agents metabolism
Abstract: 454 Pyrosequencing was used to characterize the expressed genes from the synganglion and associated neurosecretory organs of unfed and partially fed virgin and mated replete females of the American dog tick, Dermacentor variabilis. A total of 14,881 contiguous sequences (contigs) was assembled, with an average size of 229 bp. Gene ontology terms for Level 2 biological processes were assigned to 4366 contigs. Seven acetylcholinesterases, a muscarinic acetylcholine (ACh) receptor, two nicotinic ACh receptor β-subunits, two ACh unc-18 regulators, two dopamine receptors, two gamma aminobutyric acid (GABA) receptors, two GABA transporters, two norepinephrine transporters and an octopamine receptor are described. Microarrays were conducted to examine global gene expression and quantitative real-time polymerase chain reaction was used to verify expression of selected neuropeptides. Hierarchical clustering of all differentially expressed transcripts grouped part-fed and replete ticks as being more similar in terms of differentially expressed genes with unfed ticks as the outgroup. Nine putative neuropeptides (allatostatin, bursicon-β, preprocorazonin, glycoprotein hormone α, insulin-like peptide, three orcokinins, preprosulphakinin) and a gonadotropin releasing hormone receptor were differentially expressed, and their developmental expression and role in reproduction was investigated. The presence of eclosion hormone, corazonin and bursicon in the synganglion, which in insects regulate behaviour and cuticle development associated with moulting, suggest that this system may be used in ticks to regulate blood feeding, cuticle expansion and development related to female reproduction; adult ticks do not moult., (© 2011 The Authors. Insect Molecular Biology © 2011 The Royal Entomological Society.)
Published: 2011
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