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1. Tangential Microfiltration of blackberry (Rubus adenotrichus Schltdl.) juice sweetened with stevia (Stevia rebaudiana Bertoni)

Author

César González T., Fabrice Vaillant B., and María Soledad Tapia G.

Subjects
conservation, drink, filtration, formulation, membrane, sweetener, Agriculture, Agriculture (General), S1-972
Abstract

The modern consumer values those components that can promote their well-being and help them reduce the risk of diseases the use of steviolglucosides as a sweetener in the formulation of foods is promising. The study evaluated the tangential microfiltration for clarification and conservation of blackberry juice sweetened with dried leaves of stevia. Two ceramic membranes were evaluated. The tests were performed at 35°C in concentration mode at a constant transmembrane pressure and tangential velocity. The formulation of the juice was defined through sensory evaluation tests. Volume, flow permeate, temperature, and pressure input and output were registered. The results of the variables analyzed in the process, as well as the physicochemical characterization of clarified juice, helped define the operating conditions for draw two formulations of microfiltrated juice, sweetened with stevia or sucrose, and thus evaluate the effectiveness of microfiltration as a conservation treatment. Aciduric microorganisms were quantified; molds and yeasts were carried out in the generated pasteurized samples stored at five different temperatures (5, 20, 30, 37, and 45°C). The recovery permeate juice obtained was 84.62%. The permeate Flow (Jp), exhibited higher values at 40L/hm2. Also, the concentration of stevioside and rebaudioside A in the retentate increased with advancing ultrafiltration. A significant variation in color, turbidity, and soluble solids, was observed, unlike the pH. Also, its chemical and microbiological stability is confirmed that allows you to preserve quality during 27 days of storage.

Published
2019
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2. A phase II study of bevacizumab and erlotinib after radiation and temozolomide in MGMT unmethylated GBM patients

Author

Raizer, J. J., Giglio, P., Hu, J., Groves, M., Merrell, R., Conrad, C., Phuphanich, S., Puduvalli, V. K., Loghin, M., Paleologos, N., Yuan, Y., Liu, D., Rademaker, A., Yung, W. K., Vaillant, B., Rudnick, J., Chamberlain, M., Vick, N., Grimm, S., Tremont-Lukats, I. W., De Groot, J., Aldape, K., Gilbert, M. R., and Brain Tumor Trials Collaborative

Published
2016
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3. Tangential Microfiltration of blackberry (Rubus adenotrichus Schltdl.) juice sweetened with stevia (Stevia rebaudiana Bertoni).

Author

González T., César, Vaillant B., Fabrice, and Tapia G., María Soledad

Subjects
STEVIA rebaudiana, MICROFILTRATION, RUBUS, BLACKBERRIES, CHEMICAL stability, SWEETENERS, FRUIT juices
Abstract

Copyright of Revista de Ciencias Agricolas is the property of University of Narino, Faculty of Agricultural Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2019
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5. STEM CELLS

Author

Joshi, K., primary, Gupta, S., additional, Mazumder, S., additional, Okemoto, Y., additional, Angenieux, B., additional, Kornblum, H., additional, Nakano, I., additional, Synowitz, M., additional, Kumar, J., additional, Petrosino, S., additional, Imperatore, R., additional, Smith, E., additional, Wendt, P., additional, Erdmann, B., additional, Nuber, U., additional, Matiash, V., additional, Chirasani, S., additional, Cristino, L., additional, DiMarzo, V., additional, Kettenmann, H., additional, Glass, R., additional, Soroceanu, L., additional, Matlaf, L., additional, Cobbs, C., additional, Kim, Y.-W., additional, Kim, S. H., additional, Kwon, C., additional, Han, D.-y., additional, Kim, E. H., additional, Chang, J. H., additional, Liu, J.-L., additional, Kim, Y. H., additional, Kim, S., additional, Long, P. M., additional, Viapiano, M. S., additional, Jaworski, D. M., additional, Kanemura, Y., additional, Shofuda, T., additional, Kanematsu, D., additional, Matsumoto, Y., additional, Yamamoto, A., additional, Nonaka, M., additional, Moriuchi, S., additional, Nakajima, S., additional, Suemizu, H., additional, Nakamura, M., additional, Okada, Y., additional, Okano, H., additional, Yamasaki, M., additional, Price, R. L., additional, Song, J., additional, Bingmer, K., additional, Zimmerman, P., additional, Rivera, A., additional, Yi, J.-Y., additional, Cook, C., additional, Chiocca, E. A., additional, Kwon, C.-H., additional, Kang, S.-G., additional, Shin, H.-D., additional, Mok, H.-S., additional, Park, N.-R., additional, Sim, J. K., additional, Shin, H. J., additional, Park, Y. K., additional, Jeun, S. S., additional, Hong, Y.-K., additional, Lang, F. F., additional, McKenzie, B. A., additional, Zemp, F. J., additional, Lun, X., additional, Narendran, A., additional, McFadden, G., additional, Kurz, E., additional, Forsyth, P., additional, Talsma, C. E., additional, Flack, C. G., additional, Zhu, T., additional, He, X., additional, Soules, M., additional, Heth, J. A., additional, Muraszko, K., additional, Fan, X., additional, Chen, L., additional, Guerrero-Cazares, H., additional, Noiman, L., additional, Smith, C., additional, Beltran, N., additional, Levchenko, A., additional, Quinones-Hinojosa, A., additional, Peruzzi, P., additional, Godlewski, J., additional, Lawler, S. E., additional, Sarkar, S., additional, Doring, A., additional, Wang, X., additional, Kelly, J., additional, Hader, W., additional, Dunn, J. F., additional, Kinniburgh, D., additional, Robbins, S., additional, Cairncross, G., additional, Weiss, S., additional, Yong, V. W., additional, Vollmann-Zwerenz, A., additional, Velez-Char, N., additional, Jachnik, B., additional, Ramm, P., additional, Leukel, P., additional, Bogdahn, U., additional, Hau, P., additional, Kim, S.-H., additional, Lee, M. K., additional, Chwae, Y.-J., additional, Yoo, B. C., additional, Kim, K.-H., additional, Kristoffersen, K., additional, Stockhausen, M.- T., additional, Poulsen, H. S., additional, Kaluzova, M., additional, Machaidze, R., additional, Wankhede, M., additional, Hadjipanayis, C. G., additional, Romane, A. M., additional, Sim, F. J., additional, Wang, S., additional, Chandler-Militello, D., additional, Li, X., additional, Al Fanek, Y., additional, Walter, K., additional, Johnson, M., additional, Achanta, P., additional, Goldman, S. A., additional, Shinojima, N., additional, Hossain, A., additional, Takezaki, T., additional, Gumin, J., additional, Gao, F., additional, Nwajei, F., additional, Cheung, V., additional, Figueroa, J., additional, Pellegatta, S., additional, Orzan, F., additional, Anghileri, E., additional, Guzzetti, S., additional, Porrati, P., additional, Eoli, M., additional, Finocchiaro, G., additional, Fu, J., additional, Koul, D., additional, Yao, J., additional, Gumin, J. G., additional, Sulman, E., additional, Lang, F., additional, Aldape, K. K., additional, Colman, H., additional, Yung, A. W., additional, Aldape, K., additional, Alonso, M. M., additional, Manterola, L., additional, urquiza, L., additional, Cortes-Santiago, N., additional, Diez-Valle, R., additional, Tejada-Solis, S., additional, Garcia-foncillas, J., additional, Fueyo, J., additional, Gomez-Manzano, C., additional, Nguyen, S., additional, Stechishin, O., additional, Luchman, A., additional, Lathia, J. D., additional, Gallagher, J., additional, Li, M., additional, Myers, J., additional, Hjelmeland, A., additional, Huang, A., additional, Rich, J., additional, Bhat, K., additional, Vaillant, B., additional, Balasubramaniyan, V., additional, Ezhilarasan, R., additional, Hitomi, M., additional, Gadani, S., additional, Adkins, J., additional, Vasanji, A., additional, Wu, Q., additional, Soeda, A., additional, McLendon, R., additional, Chenn, A., additional, Park, D., additional, Weinstein, J. N., additional, Alfred Yung, W. K., additional, Zagzag, D., additional, Esencay, M., additional, Klopsis, D., additional, Liu, M., additional, Narayana, A., additional, Parker, E., additional, Golfinos, J., additional, Clark, P. A., additional, Kandela, I. K., additional, Weichert, J. P., additional, Kuo, J. S., additional, Fouse, S. D., additional, Nagarajan, R. P., additional, Nakamura, J., additional, James, C. D., additional, Chang, S., additional, Costello, J. F., additional, Gong, X., additional, Kankar, G., additional, Di, K., additional, Reeves, A., additional, Linskey, M., additional, Bota, D. A., additional, Schmid, R. S., additional, Bash, R. E., additional, Vitucci, M., additional, Werneke, A. M., additional, Miller, C. R., additional, Kim, E., additional, Kim, M., additional, Kim, K., additional, Lee, J., additional, Du, F., additional, Li, P., additional, Wechsler-Reya, R., additional, and Yang, Z.-j., additional

Published
2011
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7. Stem Cells

Author

He, H., primary, Emmett, M. R., additional, Marshall, A. G., additional, Ji, Y., additional, Conrad, C. A., additional, Priebe, W., additional, Colman, H., additional, Lang, F. F., additional, Madden, T. L., additional, Kristoffersen, K., additional, Stockhausen, M.-T., additional, Poulsen, H. S., additional, Binder, Z. A., additional, Orr, B., additional, Lim, M., additional, Weingart, J. D., additional, Brem, H., additional, Olivi, A., additional, Riggins, G. J., additional, Gallia, G. L., additional, Litofsky, N. S., additional, Miller, D. C., additional, Rath, P., additional, Anthony, D. C., additional, Feng, Q., additional, Franklin, C., additional, Pei, L., additional, Free, A., additional, Kirk, M. D., additional, Shi, H., additional, Timmer, M., additional, Theiss, H., additional, Juerchott, K., additional, Ries, C., additional, Paron, I., additional, Franz, W., additional, Selbig, J., additional, Guo, K., additional, Tonn, J. C., additional, Schichor, C., additional, Zhou, Y.-H., additional, Hu, Y., additional, Pioli, P. D., additional, Rajneesh, K., additional, Limoli, C. L., additional, Yu, L., additional, Hess, K. R., additional, Linskey, M. E., additional, Faber, F., additional, Jaeger, D., additional, Thorsteinsdottir, J., additional, Albrecht, V., additional, Tonn, J.-C., additional, Price, R., additional, Song, J., additional, Zimmerman, P., additional, Duale, H., additional, Rivera, A., additional, Kaur, B., additional, Parada, L., additional, Cook, C., additional, Chiocca, E. A., additional, Kwon, C.-H., additional, Munoz, D. M., additional, Guha, A., additional, Estrada-Bernal, A., additional, Van Brocklyn, J. R., additional, Gu, C., additional, Mahasenan, K. V., additional, Joshi, K., additional, Gupta, S., additional, Mattson, A., additional, Li, C., additional, Nakano, I., additional, Chi, A. S., additional, Rheinbay, E., additional, Wakimoto, H., additional, Gillespie, S., additional, Kasif, S., additional, Rabkin, S. D., additional, Martuza, R. L., additional, Bernstein, B. E., additional, Skirboll, S. L., additional, Wurdak, H., additional, Zhu, S., additional, Romero, A., additional, Lorger, M., additional, Watson, J., additional, Chiang, C.-y., additional, Zhang, J., additional, Natu, V. S., additional, Lairson, L. L., additional, Walker, J. R., additional, Trussell, C. M., additional, Harsh, G. R., additional, Vogel, H., additional, Felding-Habermann, B., additional, Orth, A. P., additional, Miraglia, L. J., additional, Rines, D. R., additional, Schultz, P. G., additional, Hide, T., additional, Takezaki, T., additional, Nakamura, H., additional, Makino, K., additional, Kuratsu, J.-i., additional, Kondo, T., additional, Yao, J., additional, Kim, Y.-W., additional, Koul, D., additional, Almeida, J. S., additional, Weinstein, J. N., additional, Alfred Yung, W. K., additional, Miyazaki, T., additional, Chaudhury, A. R., additional, Wong, A. J., additional, Del Vecchio, C., additional, Mitra, S., additional, Han, S.-Y., additional, Holgado-Madruga, M., additional, Gupta, P., additional, Golebiewska, A., additional, Brons, N. H., additional, Bjerkvig, R., additional, Niclou, S. P., additional, Ramm, P., additional, Vollmann-Zwerenz, A., additional, Beier, C., additional, Aigner, L., additional, Bogdahn, U., additional, Kalbitzer, H. R., additional, Hau, P., additional, Sanzey, M., additional, Vallar, L., additional, Tamura, K., additional, Aoyagi, M., additional, Ando, N., additional, Ogishima, T., additional, Yamamoto, M., additional, Ohno, K., additional, Perin, A., additional, Fung, K. H., additional, Longatti, P., additional, Guiot, M.-C., additional, Del Maestro, R. F., additional, Rossi, S., additional, Stechishin, O., additional, Weiss, S., additional, Stifani, S., additional, Goodman, L., additional, Gao, F., additional, Gumin, J., additional, Ezhilarasan, R., additional, Love, P., additional, George, A., additional, Lang, F., additional, Aldape, K., additional, Sulman, E. P., additional, Soeda, A., additional, Lee, D.-H., additional, Shaffrey, M. E., additional, Oldfield, E. H., additional, Park, D. M., additional, Dietrich, J., additional, Han, R., additional, Noble, M., additional, Yang, M. Y., additional, Liu, X., additional, Madhankumar, A. B., additional, Sheehan, J., additional, Slagle-Webb, B., additional, Connor, J. R., additional, Fu, J., additional, Shen, R.-J., additional, Kaluzova, M., additional, Machaidze, R., additional, Nduom, E. N. K., additional, Burden, C. T., additional, Hadjipanayis, C. G., additional, Lei, L., additional, Sonabend, A., additional, Guarnieri, P., additional, Ludwig, T., additional, Rosenfeld, S., additional, Bruce, J., additional, Canoll, P., additional, Vaillant, B. D., additional, Bhat, K., additional, Balasubramaniyam, V., additional, Wang, S., additional, Sulman, E., additional, Goodman, L. D., additional, Love, P. N., additional, Soules, M., additional, Zhu, T., additional, Flack, C., additional, Talsma, C., additional, Hamm, L., additional, Muraszko, K., additional, Fan, X., additional, Matsuoka, Y., additional, Kawano, Y., additional, Kobayashi, D., additional, Kumagai, J., additional, Frank, R. T., additional, Najbauer, J., additional, Aboody, K. S., additional, Metz, M., additional, Garcia, E., additional, Aramburo, S., additional, Valenzuela, V., additional, Gutova, M., additional, Annala, A. J., additional, Barish, M., additional, Danks, M., additional, Kim, S. U., additional, Portnow, J., additional, Hofstetter, C., additional, Gursel, D., additional, Mubita, L., additional, Holland, E., additional, Boockvar, J., additional, Monje, M., additional, Freret, M., additional, Masek, M., additional, Edwards, M. S., additional, Fisher, P. G., additional, and Beachy, P., additional

Published
2010
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8. Cell Biology and Signaling

Author

Long, P. M., primary, Wesley, U. V., additional, Jaworski, D. M., additional, Rana, M., additional, Kiehl, T.-R., additional, So, K., additional, Gould, P., additional, Ajewung, N., additional, Kamnasaran, D., additional, Emmett, M. R., additional, Wang, X., additional, Marshall, A. G., additional, Ji, Y., additional, Fokt, I., additional, Skora, S., additional, Conrad, C. A., additional, Priebe, W., additional, Zhu, H., additional, Cao, X., additional, Keir, S., additional, Ali-Osman, F., additional, Lo, H.-W., additional, Da Fonseca, C. O., additional, Arun, V., additional, Wiley, J. C., additional, Kaur, H., additional, Guha, A., additional, Fenton, K., additional, Abdelwahab, M. G., additional, Stafford, P., additional, Rho, J. M., additional, Preul, M. C., additional, Scheck, A. C., additional, Brossier, N. M., additional, Carroll, S. L., additional, Gajadhar, A., additional, Mukherjee, J., additional, Wolf, A., additional, Hawkins, C., additional, Costa, P., additional, Cardoso, A. L. C., additional, de Almeida, L. P., additional, de Lima, M. C. P., additional, Canoll, P., additional, Bruce, J., additional, Lavon, I., additional, Granit, A., additional, Einstein, O., additional, Ben-Hur, T., additional, Siegal, T., additional, Pang, J. C., additional, Poon, W. S., additional, Zhou, L., additional, Ng, H.-K., additional, Rovin, R. A., additional, Lawrence, J. E., additional, Segula, J. J., additional, Winn, R. J., additional, Patil, S., additional, Burzynski, S. R., additional, Mrowczynski, E., additional, Grela, K., additional, Cheng, S., additional, Liu, K., additional, Feng, H., additional, Bacho, R., additional, Kazlauskas, A., additional, Smith, E. M., additional, Symes, K., additional, Hu, B., additional, Lee, C. Y., additional, Fotovati, A., additional, Dunn, S. E., additional, Proescholdt, M. A., additional, Storr, E.-M., additional, Lohmeier, A., additional, Brawanski, A., additional, Jarzynka, M. J., additional, Ravichandran, K. S., additional, Vuori, K., additional, Tang, C., additional, Nshikawa, R., additional, Johns, T. G., additional, Furnari, F. B., additional, Cavenee, W. K., additional, Zhong, J., additional, O'Neill, G. M., additional, Deleyrolle, L. P., additional, Rahman, M., additional, Dunbar, E. M., additional, Caldeira, M. A., additional, Reynolds, B. A., additional, Liu, X., additional, Yacyshyn, S., additional, Dasgupta, B., additional, Han, X., additional, Yang, X., additional, Wheeler, C. G., additional, Filippova, N., additional, Langford, C. P., additional, Ding, Q., additional, Fathallah, H. M., additional, Gillespie, G. Y., additional, Nabors, L. B., additional, Davidson, T. B., additional, Gortalum, F., additional, Ji, L., additional, Engell, K., additional, Sposto, R., additional, Asgharzadeh, S., additional, Erdreich-Epstein, A., additional, Lawn, S. O., additional, Weiss, S., additional, Senger, D., additional, Forsyth, P., additional, Latha, K., additional, Chumbalkar, V., additional, Li, M., additional, Gururaj, A., additional, Hwang, Y., additional, Maywald, R., additional, Dakeng, S., additional, Dao, L., additional, Baggerly, K., additional, Sawaya, R., additional, Aldape, K., additional, Cavenee, W., additional, Furnari, F., additional, Bogler, O., additional, Arumugam, J., additional, Sim, H., additional, Pineda, C. A., additional, Pan, Y., additional, Viapiano, M. S., additional, Van Schaick, J. A., additional, Akagi, K., additional, Burkett, S., additional, DiFabio, C., additional, Tuskan, R., additional, Walrath, J., additional, Reilly, K., additional, Dai, B., additional, Jing, Z., additional, Kang, S.-H., additional, Li, D., additional, Xie, K., additional, Huang, S., additional, Gong, X., additional, Vuong, Y., additional, Bota, D. A., additional, Stegh, A. H., additional, Inda, M.-d.-M., additional, Bonavia, R., additional, Mukasa, A., additional, Narita, Y., additional, Sah, D., additional, Vandenberg, S., additional, Brennan, C., additional, Johns, T., additional, Bachoo, R., additional, Hadwiger, P., additional, Tan, P., additional, DePinho, R., additional, Kusne, Y., additional, Meerson, A., additional, Rushing, E. J., additional, Yang, W., additional, McDonough, W., additional, Kislin, K., additional, Loftus, J. C., additional, Berens, M., additional, Lu, Z., additional, Ghosh, S., additional, Verma, A., additional, Zhou, H., additional, Chin, S., additional, Bruggers, C., additional, Kestle, J., additional, Khatua, S., additional, Broekman, M. L., additional, Maas, N. S., additional, Skog, J., additional, Breakefield, X. O., additional, Sena-Esteves, M., additional, de Vrij, J., additional, Lamfers, M., additional, Maas, N., additional, Dirven, C., additional, Esteves, M., additional, Broekman, M., additional, Chidambaram, A., additional, Dumur, C. I., additional, Graf, M., additional, Vanmeter, T. E., additional, Fillmore, H. L., additional, Broaddus, W. C., additional, Silber, J., additional, Ozawa, T., additional, Kastenhuber, E., additional, Djaballah, H., additional, Holland, E. C., additional, Huse, J. T., additional, Agnihotri, S., additional, Munoz, D., additional, Han, J. E., additional, Albesiano, E., additional, Pradilla, G., additional, Lim, M., additional, Alshami, J., additional, Sabau, C., additional, Seyed Sadr, M., additional, Anan, M., additional, Seyed Sadr, E., additional, Siu, V., additional, Del Maestro, R., additional, Trinh, G., additional, Le, P., additional, Petrecca, K., additional, Sonabend, A. M., additional, Soderquist, C., additional, Lei, L., additional, Guarnieri, P., additional, Leung, R., additional, Yun, J., additional, Sisti, J., additional, Castelli, M., additional, Bruce, S., additional, Bruce, R., additional, Ludwig, T., additional, Rosenfeld, S., additional, Bruce, J. N., additional, Phillips, J. J., additional, Huillard, E., additional, Polley, M.-Y., additional, Rosen, S. D., additional, Rowitch, D. H., additional, Werb, Z., additional, Sarkar, C., additional, Jha, P., additional, Pathak, P., additional, Suri, V., additional, Sharma, M. C., additional, Chattopadhyay, P., additional, Chosdol, K., additional, Suri, A., additional, Gupta, D., additional, Mahapatra, A. K., additional, Kapoor, G. S., additional, Zhan, Y., additional, Boockvar, J. A., additional, O'Rourke, D. M., additional, Kwatra, M. M., additional, Kim, J. W., additional, Park, C.-K., additional, Han, J. H., additional, Park, S. H., additional, Kim, S.-K., additional, Jung, H.-W., additional, Narayanan, R., additional, Levin, B. S., additional, Maeder, M. L., additional, Joung, J. K., additional, Nutt, C. L., additional, Louis, D. N., additional, Dudley, A., additional, Jayaram, P., additional, Pei, Z., additional, Shi, X., additional, Laterra, J., additional, Watkins, P. A., additional, Mawrin, C., additional, Rempel, S. A., additional, McClung, H. M., additional, McFarland, B. C., additional, Nozell, S. E., additional, Huszar, D., additional, Benveniste, E. N., additional, Burton, T., additional, Eisenstat, D. D., additional, Gibson, S. B., additional, Lukiw, W. J., additional, Cui, J. G., additional, Li, Y. Y., additional, Zhao, Y., additional, Culicchia, F., additional, See, W., additional, Pieper, R., additional, Luchman, A., additional, Stechishin, O., additional, Nguyen, S., additional, Kelly, J., additional, Blough, M., additional, Cairncross, G., additional, Shah, S. R., additional, Mohyeldin, A., additional, Adams, H., additional, Garzon-Muvdi, T., additional, Aprhys, C., additional, Quinones-Hinojosa, A., additional, Weeks, A. C., additional, Restrepo, A., additional, Ivanchuk, S., additional, Smith, C., additional, Rutka, J. T., additional, Sengupta, R., additional, Yang, L., additional, Burbassi, S., additional, Zhang, B., additional, Markant, S. L., additional, Yang, Z.-j., additional, Meucci, O., additional, Wechsler-Reya, R. J., additional, Rubin, J. B., additional, Wykosky, J., additional, Chin, L., additional, Auvergne, R. M., additional, Sim, F. J., additional, Wang, S., additional, Chandler-Militello, D., additional, Burch, J., additional, Li, X., additional, Bennet, A., additional, Mohile, N., additional, Pilcher, W., additional, Walter, K., additional, Johnson, M., additional, Achanta, P., additional, Natesan, S., additional, Goldman, S. A., additional, Beauchamp, A. S., additional, Gibo, D. M., additional, Debinski, W., additional, Jiang, H., additional, Martin, V., additional, Gomez-Manzano, C., additional, Johnson, D. G., additional, Alonso, M., additional, White, E. J., additional, Xu, J., additional, McDonnell, T., additional, Shinojima, N., additional, Fueyo, J., additional, Sandhya Rani, M. R., additional, Huang, P., additional, Prayson, R., additional, Hedayat, H., additional, Sloan, A. E., additional, Novacki, A., additional, Ahluwalia, M. S., additional, Tipps, R., additional, Gladson, C. L., additional, Liu, J.-L., additional, Mao, Z., additional, Yung, W. K. A., additional, Bhat, K., additional, Salazar, K., additional, Balasubramaniyan, V., additional, Vaillant, B., additional, Hollingsworth, F., additional, Gumin, J., additional, Diefes, K., additional, Patel, D., additional, Lang, F., additional, Colman, H., additional, Parsyan, A., additional, Shahbazian, D., additional, Alain, T., additional, Martineau, Y., additional, Petroulakis, E., additional, Larsson, O., additional, Gkogkas, C., additional, Topisirovic, I., additional, Mathonnet, G., additional, Tettweiler, G., additional, Hellen, C., additional, Pestova, T., additional, Svitkin, Y., additional, Sonenberg, N., additional, Zerrouqi, A., additional, Pyrzynska, B., additional, Van Meir, E., additional, Twitty, G. B., additional, Hong, S. W., additional, Lee, H. K., additional, Finniss, S., additional, Xiang, C., additional, Cazacu, S., additional, Brodie, C., additional, Ginn, K. F., additional, Wise, A., additional, Farassati, F., additional, Brown, C., additional, Barish, M., additional, deCarvalho, A. C., additional, Hasselbach, L., additional, Nelson, K., additional, Lemke, N., additional, Schultz, L., additional, Mikkelsen, T., additional, Onvani, S., additional, Kongkham, P., additional, Smith, C. A., additional, Bier, A., additional, Hershkovitz, H., additional, Kahana, S., additional, Decarvalho, A., additional, Massey, S. C., additional, and Swanson, K. R., additional

Published
2010
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24. An expanded safety/feasibility study of the EMulate Therapeutics Voyager™ System in patients with recurrent glioblastoma.

Author

Barkhoudarian G, Badruddoja M, Blondin N, Chowdhary S, Cobbs C, Duic JP, Flores JP, Fonkem E, McClay E, Nabors LB, Salacz M, Taylor L, Vaillant B, Gill J, and Kesari S

Subjects
Humans, Feasibility Studies, Neoplasm Recurrence, Local, Prospective Studies, Brain Neoplasms drug therapy, Glioblastoma drug therapy
Abstract

Aim: The EMulate Therapeutics Voyager™ is a simple, wearable, home-use device that uses an alternating electromagnetic field to alter biologic signaling within cells. Objective: To assess the safety/feasibility of the Voyager in the treatment of recurrent glioblastoma (rGBM). Methods: In this study, patients with rGBM were treated with Voyager as monotherapy or in combination with standard chemotherapy at the Investigator's discretion. Safety was assessed by incidence of adverse events associated with the Voyager. Patients were followed until death. Results: A total of 75 patients were enrolled and treated for at least one day with the Voyager (safety population). Device-related adverse events were uncommon and generally did not result in interruption or withdrawal from treatment. There were no serious adverse events associated with Voyager. A total of 60 patients were treated for at least one month (clinical utility population). The median progression-free survival (PFS) was 17 weeks (4.3 months) in the Voyager only group (n = 24) and 21 weeks (5.3 months) in the Voyager + concurrent therapy group (n = 36). The median overall survival (OS) was 7 months in the Voyager only group and 9 months in the Voyager + concurrent therapy group. In patients treated with Voyager + concurrent therapy, the median OS for patients enrolled with their 1st or 2nd recurrence (n = 26) was 10 months, while in patients enrolled with their 3rd or 4th recurrence (n = 10) OS was 7 months. Conclusion: The data support the safety and feasibility of the Voyager for the treatment of rGBM. Further prospective study of the device is warranted. Trial Registration Number: NCT02296580 (ClinicalTrials.gov).

Published
2023
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25. Phenotypic Plasticity of Invasive Edge Glioma Stem-like Cells in Response to Ionizing Radiation.

Author

Minata M, Audia A, Shi J, Lu S, Bernstock J, Pavlyukov MS, Das A, Kim SH, Shin YJ, Lee Y, Koo H, Snigdha K, Waghmare I, Guo X, Mohyeldin A, Gallego-Perez D, Wang J, Chen D, Cheng P, Mukheef F, Contreras M, Reyes JF, Vaillant B, Sulman EP, Cheng SY, Markert JM, Tannous BA, Lu X, Kango-Singh M, Lee LJ, Nam DH, Nakano I, and Bhat KP

Subjects
Glioma pathology, Humans, Adaptation, Physiological genetics, Glioma radiotherapy, Radiation, Ionizing
Abstract

Unresectable glioblastoma (GBM) cells in the invading tumor edge can act as seeds for recurrence. The molecular and phenotypic properties of these cells remain elusive. Here, we report that the invading edge and tumor core have two distinct types of glioma stem-like cells (GSCs) that resemble proneural (PN) and mesenchymal (MES) subtypes, respectively. Upon exposure to ionizing radiation (IR), GSCs, initially enriched for a CD133 + PN signature, transition to a CD109 + MES subtype in a C/EBP-β-dependent manner. Our gene expression analysis of paired cohorts of patients with primary and recurrent GBMs identified a CD133-to-CD109 shift in tumors with an MES recurrence. Patient-derived CD133 - /CD109 + cells are highly enriched with clonogenic, tumor-initiating, and radiation-resistant properties, and silencing CD109 significantly inhibits these phenotypes. We also report a conserved regulation of YAP/TAZ pathways by CD109 that could be a therapeutic target in GBM., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2019
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26. Aberrant mesenchymal differentiation of glioma stem-like cells: implications for therapeutic targeting.

Author

Balasubramaniyan V, Vaillant B, Wang S, Gumin J, Butalid ME, Sai K, Mukheef F, Kim SH, Boddeke HW, Lang F, Aldape K, Sulman EP, Bhat KP, and Colman H

Subjects
Animals, Apoptosis, Brain Neoplasms genetics, Brain Neoplasms metabolism, Cell Proliferation, Cell Transformation, Neoplastic metabolism, Gene Expression Regulation, Neoplastic, Glioma genetics, Glioma metabolism, Humans, Mesoderm metabolism, Mice, Mice, Nude, Neoplastic Stem Cells metabolism, RNA, Messenger genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, Brain Neoplasms pathology, Cell Differentiation, Cell Transformation, Neoplastic pathology, Glioma pathology, Mesoderm pathology, Neoplastic Stem Cells pathology
Abstract

Differentiation has been proposed as a therapeutic strategy for glioblastoma (GBM) in part due to observations of stem-like cells in GBM that have been shown to undergo terminal differentiation in response to growth factor withdrawal and BMP activation. However, the effects of long term exposure to serum culture conditions on glioma sphere cultures/glioma stem-like cells (GSCs) have not been examined. Here we show that GSCs retained both neurosphere formation and tumor initiation abilities after short or long term serum exposure. Under these conditions, GSCs expressed both neural lineage and stem cell markers, highlighting the aberrant pseudo-differentiation state. GSCs maintained under adherent serum cultured conditions continued to proliferate and initiate tumor formation with efficiencies similar to GSCs maintained under proliferating (neurosphere) conditions. Proneural (PN) GSCs under serum exposure showed an induction of mesenchymal (MES) gene expression signatures. Our data indicate that exposure to serum containing media result in aberrant differentiation (e.g. toward MES lineage) and activation of alternative oncogenic pathways in GSCs.

Published
2015
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27. Experimental validation of 5 in-silico predicted glioma biomarkers.

Author

Towner RA, Jensen RL, Vaillant B, Colman H, Saunders D, Giles CB, and Wren JD

Subjects
Brain metabolism, Brain Neoplasms metabolism, Brain Neoplasms pathology, Case-Control Studies, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Glioma pathology, Humans, Neoplasm Grading, Oligonucleotide Array Sequence Analysis, Prognosis, Algorithms, Biomarkers, Tumor metabolism, Calcium-Binding Proteins metabolism, Extracellular Matrix Proteins metabolism, Glioma metabolism, Membrane Proteins metabolism, Nerve Tissue Proteins metabolism
Abstract

Background: Glioblastoma multiforme (GBM) is a high-grade glioma with poor prognosis. Identification of new biomarkers specific to GBM could help in disease diagnosis. We have developed and validated a bioinformatics method to predict proteins likely to be suitable as glioma biomarkers via a global microarray meta-analysis to identify uncharacterized genes consistently coexpressed with known glioma-associated genes., Methods: A novel bioinformatics method was implemented called global microarray meta-analysis, using approximately 16,000 microarray experiments to identify uncharacterized genes consistently coexpressed with known glioma-associated genes. These novel biomarkers were validated as proteins highly expressed in human gliomas varying in tumor grades using immunohistochemistry. Glioma gene databases were used to assess delineation of expression of these markers in varying glioma grades and subtypes of GBM., Results: We have identified 5 potential biomarkers-spondin1, Plexin-B2, SLIT3, fibulin-1, and LINGO1-that were validated as proteins highly expressed on the surface of human gliomas using immunohistochemistry. Expression of spondin1, Plexin-B2, and SLIT3 was significantly higher (P < .01) in high-grade gliomas than in low-grade gliomas. These biomarkers were significant discriminators in grade IV gliomas compared with either grade III or II tumors and also distinguished between GBM subclasses., Conclusions: This study strongly suggests that this type of bioinformatics approach has high translational potential to rapidly discern which poorly characterized proteins may be of clinical relevance.

Published
2013
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28. Mesenchymal differentiation mediated by NF-κB promotes radiation resistance in glioblastoma.

Author

Bhat KPL, Balasubramaniyan V, Vaillant B, Ezhilarasan R, Hummelink K, Hollingsworth F, Wani K, Heathcock L, James JD, Goodman LD, Conroy S, Long L, Lelic N, Wang S, Gumin J, Raj D, Kodama Y, Raghunathan A, Olar A, Joshi K, Pelloski CE, Heimberger A, Kim SH, Cahill DP, Rao G, Den Dunnen WFA, Boddeke HWGM, Phillips HS, Nakano I, Lang FF, Colman H, Sulman EP, and Aldape K

Subjects
Animals, Basic Helix-Loop-Helix Transcription Factors genetics, Basic Helix-Loop-Helix Transcription Factors metabolism, Cell Differentiation genetics, Cluster Analysis, DNA Methylation, Disease Models, Animal, Epigenesis, Genetic, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Glioblastoma mortality, Humans, Hyaluronan Receptors genetics, Hyaluronan Receptors metabolism, Mice, Nerve Tissue Proteins genetics, Nerve Tissue Proteins metabolism, Oligodendrocyte Transcription Factor 2, Prognosis, Signal Transduction, Transcriptome, Tumor Necrosis Factor-alpha pharmacology, Xenograft Model Antitumor Assays, Glioblastoma genetics, Glioblastoma metabolism, NF-kappa B genetics, NF-kappa B metabolism, Radiation Tolerance genetics
Abstract

Despite extensive study, few therapeutic targets have been identified for glioblastoma (GBM). Here we show that patient-derived glioma sphere cultures (GSCs) that resemble either the proneural (PN) or mesenchymal (MES) transcriptomal subtypes differ significantly in their biological characteristics. Moreover, we found that a subset of the PN GSCs undergoes differentiation to a MES state in a TNF-α/NF-κB-dependent manner with an associated enrichment of CD44 subpopulations and radioresistant phenotypes. We present data to suggest that the tumor microenvironment cell types such as macrophages/microglia may play an integral role in this process. We further show that the MES signature, CD44 expression, and NF-κB activation correlate with poor radiation response and shorter survival in patients with GBM., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Published
2013
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29. ELTD1, a potential new biomarker for gliomas.

Author

Towner RA, Jensen RL, Colman H, Vaillant B, Smith N, Casteel R, Saunders D, Gillespie DL, Silasi-Mansat R, Lupu F, Giles CB, and Wren JD

Subjects
Adult, Animals, Blotting, Western, Brain Neoplasms genetics, Cell Line, Tumor, Coloring Agents, Computational Biology, Databases, Genetic, Female, Ferrocyanides, Gene Expression Regulation, Neoplastic genetics, Glioblastoma genetics, Humans, Immunohistochemistry, Magnetic Resonance Imaging, Male, Microarray Analysis, Neoplasm Transplantation, Nuclear Magnetic Resonance, Biomolecular, Rats, Rats, Inbred F344, Receptors, G-Protein-Coupled analysis, Biomarkers, Tumor analysis, Brain Neoplasms diagnosis, Brain Neoplasms metabolism, Glioblastoma diagnosis, Glioblastoma metabolism, Receptors, G-Protein-Coupled genetics
Abstract

Background: Glioblastoma multiforme (GBM), a high-grade glioma, is characterized by being diffuse, invasive, and highly angiogenic and has a very poor prognosis. Identification of new biomarkers could help in the further diagnosis of GBM., Objective: To identify ELTD1 (epidermal growth factor, latrophilin, and 7 transmembrane domain-containing protein 1 on chromosome 1) as a putative glioma-associated marker via a bioinformatic method., Methods: We used advanced data mining and a novel bioinformatics method to predict ELTD1 as a potential novel biomarker that is associated with gliomas. Validation was done with immunohistochemistry, which was used to detect levels of ELTD1 in human high-grade gliomas and rat F98 glioma tumors. In vivo levels of ELTD1 in rat F98 gliomas were assessed using molecular magnetic resonance imaging., Results: ELTD1 was found to be significantly higher (P = .03) in high-grade gliomas (50 patients) compared with low-grade gliomas (21 patients) and compared well with traditional immunohistochemistry markers including vascular endothelial growth factor, glucose transporter 1, carbonic anhydrase IX, and hypoxia-inducible factor 1α. ELTD1 gene expression indicates an association with grade, survival across grade, and an increase in the mesenchymal subtype. Significantly high (P < .001) in vivo levels of ELTD1 were additionally found in F98 tumors compared with normal brain tissue., Conclusion: Results of this study strongly suggests that associative analysis was able to accurately identify ELTD1 as a putative glioma-associated biomarker. The detection of ELTD1 was also validated in both rodent and human gliomas and may serve as an additional biomarker for gliomas in preclinical and clinical diagnosis of gliomas.

Published
2013
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30. Regulation of HGF expression by ΔEGFR-mediated c-Met activation in glioblastoma cells.

Author

Garnett J, Chumbalkar V, Vaillant B, Gururaj AE, Hill KS, Latha K, Yao J, Priebe W, Colman H, Elferink LA, and Bogler O

Subjects
Animals, Brain Neoplasms genetics, Brain Neoplasms pathology, Cell Transformation, Neoplastic genetics, Cell Transformation, Neoplastic metabolism, Cyanoacrylates metabolism, ErbB Receptors genetics, Glioblastoma genetics, Glioblastoma pathology, HEK293 Cells, Hepatocyte Growth Factor genetics, Hepatocyte Growth Factor metabolism, Humans, Mice, Mice, Nude, Phosphorylation genetics, Proto-Oncogene Proteins c-met genetics, Pyridines metabolism, RNA Interference, STAT3 Transcription Factor genetics, STAT3 Transcription Factor metabolism, Signal Transduction, Tumor Cells, Cultured, Brain Neoplasms metabolism, ErbB Receptors metabolism, Glioblastoma metabolism, Hepatocyte Growth Factor biosynthesis, Proto-Oncogene Proteins c-met metabolism
Abstract

The hepatocyte growth factor receptor (c-Met) and a constitutively active mutant of the epidermal growth factor receptor (ΔEGFR/EGFRvIII) are frequently overexpressed in glioblastoma (GBM) and promote tumorigenesis. The mechanisms underlying elevated hepatocyte growth factor (HGF) production in GBM are not understood. We found higher, coordinated mRNA expression levels of HGF and c-Met in mesenchymal (Mes) GBMs, a subtype associated with poor treatment response and shorter overall survival. In an HGF/c-Met-dependent GBM cell line, HGF expression declined upon silencing of c-Met using RNAi or by inhibiting its activity with SU11274. Silencing c-Met decreased anchorage-independent colony formation and increased the survival of mice bearing intracranial GBM xenografts. Consistent with these findings, c-Met activation by ΔEGFR also elevated HGF expression, and the inhibition of ΔEGFR with AG1478 reduced HGF levels. Interestingly, c-Met expression was required for ΔEGFR-mediated HGF production, anchorage-independent growth, and in vivo tumorigenicity, suggesting that these pathways are coupled. Using an unbiased mass spectrometry-based screen, we show that signal transducer and activator of transcription 3 (STAT3) Y705 is a downstream target of c-Met signaling. Suppression of STAT3 phosphorylation with WP1193 reduced HGF expression in ΔEGFR-expressing GBM cells, whereas constitutively active STAT3 partially rescued HGF expression and colony formation in c-Met knockdown cells expressing ΔEGFR. These results suggest that the c-Met/HGF signaling axis is enhanced by ΔEGFR through increased STAT3-dependent HGF expression and that targeting c-Met in Mes GBMs may be an important strategy for therapy.

Published
2013
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31. A prognostic gene expression signature in infratentorial ependymoma.

Author

Wani K, Armstrong TS, Vera-Bolanos E, Raghunathan A, Ellison D, Gilbertson R, Vaillant B, Goldman S, Packer RJ, Fouladi M, Pollack I, Mikkelsen T, Prados M, Omuro A, Soffietti R, Ledoux A, Wilson C, Long L, Gilbert MR, and Aldape K

Subjects
Adolescent, Age Factors, Antigens, Neoplasm metabolism, Child, Cluster Analysis, DNA Topoisomerases, Type II metabolism, DNA-Binding Proteins metabolism, Databases, Genetic, Ependymoma diagnosis, Ependymoma genetics, Ependymoma metabolism, Female, Humans, Infratentorial Neoplasms diagnosis, Infratentorial Neoplasms genetics, Infratentorial Neoplasms metabolism, Longitudinal Studies, Male, Oligonucleotide Array Sequence Analysis, Prognosis, Reproducibility of Results, Sex Factors, Survival Analysis, Young Adult, Ependymoma physiopathology, Gene Expression Profiling methods, Gene Expression Regulation, Neoplastic physiology, Infratentorial Neoplasms physiopathology
Abstract

Patients with ependymoma exhibit a wide range of clinical outcomes that are currently unexplained by clinical or histological factors. Little is known regarding molecular biomarkers that could predict clinical behavior. Since recent data suggest that these tumors display biological characteristics according to their location (cerebral vs. infratentorial vs. spinal cord), rather than explore a broad spectrum of ependymoma, we focused on molecular alterations in ependymomas arising in the infratentorial compartment. Unsupervised clustering of available gene expression microarray data revealed two major subgroups of infratentorial ependymoma. Group 1 tumors over expressed genes that were associated with mesenchyme, Group 2 tumors showed no distinct gene ontologies. To assess the prognostic significance of these gene expression subgroups, real-time reverse transcriptase polymerase chain reaction assays were performed on genes defining the subgroups in a training set. This resulted in a 10-gene prognostic signature. Multivariate analysis showed that the 10-gene signature was an independent predictor of recurrence-free survival after adjusting for clinical factors. Evaluation of an external dataset describing subgroups of infratentorial ependymomas showed concordance of subgroup definition, including validation of the mesenchymal subclass. Importantly, the 10-gene signature was validated as a predictor of recurrence-free survival in this dataset. Taken together, the results indicate a link between clinical outcome and biologically identified subsets of infratentorial ependymoma and offer the potential for prognostic testing to estimate clinical aggressiveness in these tumors.

Published
2012
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32. Treatment of spinal cord tumors.

Author

Vaillant B and Loghin M

Abstract

Tumors associated with the spinal cord can have devastating effects on patient function and quality of life. Most of these tumors are from metastatic disease, usually to the epidural space. Less frequently, the tumors are intrinsic to the spinal cord itself (ie, primary tumor). Regardless of the etiology, spinal cord tumors often present first with progressive local or radicular pain, or both. Other symptoms include weakness, sensory changes, or sphincter dysfunction. The timeliness of diagnosis of spinal cord tumors and promptness of treatment are important, as they directly affect outcome. Dexamethasone, a corticosteroid, is used as a temporizing measure to improve or stabilize neurologic function until definitive treatment. For nonambulatory patients with epidural metastatic tumors, surgery followed by radiation therapy maximizes neurologic function and modestly lengthens survival. However, palliative radiotherapy alone is recommended for those with neurologic deficits lasting longer than 48 hours, survival prognosis less than 3 months, inability to tolerate surgery, multiple areas of compression, or radiosensitive tumors. An ambulatory patient with a stable spine should be considered for radiation treatment only. The role of chemotherapy for epidural metastatic tumors is not well established. For intramedullary metastases, the role of surgery and chemotherapy remains controversial and radiation is the mainstay. For low-grade or benign primary spinal cord tumors, resective surgery is of benefit and can be curative. For high-grade tumors, the benefit of resection is less clear, and radiotherapy and/or chemotherapy may be helpful. The use of chemotherapy for primary spinal cord tumors has rarely been assessed. Agents reported in the literature for treatment of spinal cord gliomas include temozolomide, irinotecan, cisplatin, and carboplatin. A multidisciplinary approach is often required to maximize the therapeutic and functional outcome of patients with metastatic and primary spinal cord tumors.

Published
2009
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34. Antineutrophil cytoplasmic antibody-associated active scleritis.

Author

Hoang LT, Lim LL, Vaillant B, Choi D, and Rosenbaum JT

Subjects
Adult, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Female, Fluorescent Antibody Technique, Indirect, Glucocorticoids therapeutic use, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Peroxidase, Prognosis, Radioimmunoassay, Retrospective Studies, Scleritis diagnostic imaging, Scleritis drug therapy, Serine Endopeptidases, Tomography, X-Ray Computed, Ultrasonography, Visual Acuity, Antibodies, Antineutrophil Cytoplasmic blood, Scleritis immunology
Abstract

Objective: To determine whether antineutrophil cytoplasmic antibody (ANCA) testing provides prognostic information in evaluating scleritis., Methods: Retrospective medical record review of patients evaluated at a tertiary care center from January 1, 1995, to June 30, 2006, was performed to compare clinical features, treatments, and associated systemic disease in patients who test positive for ANCA vs patients whose ANCA tests are negative., Results: Among 78 patients identified, 14 tested positive for ANCA. Patients with positive ANCA test results were more likely to have an associated systemic disorder (10 of 14 or 71%) than were patients who tested negative for ANCA (26 of 64 or 41%; P = .04), and the disorder was more likely to have been diagnosed as a result of scleritis work-up (2 of 10 or 20% vs 19 of 26 or 73%; P = .007). Patients with positive ANCA test results had significantly more ocular complications (21 of 14 or 86% vs 20 of 64 or 31%; P < .001), including keratopathy (5 of 14 or 36% vs 6 of 64 or 9%; P = .02), visual acuity of 20/50 or worse (8 of 14 or 57% vs 11 of 64 or 17%; P = .001), and vascular pannus (3 of 14 or 21% vs 1 of 64 or 2%; P = .02). Aggressive therapy, such as chronic systemic corticosteroids (9 of 14 or 64% vs 9 of 64 or 14%; P < .001) and alkylator therapy (8 of 14 or 57% vs 7 of 64 or 11%; P < .001), was more likely to be recommended for patients who tested positive for ANCA., Conclusions: A substantial subset of patients with scleritis are also positive for ANCA. These patients are more likely to have severe ocular disease and undiagnosed primary vasculitic disease, thereby requiring more aggressive therapy. An ANCA test may be useful in the evaluation and treatment of patients with scleritis.

Published
2008
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35. Regulation of hepatic fibrosis and extracellular matrix genes by the th response: new insight into the role of tissue inhibitors of matrix metalloproteinases.

Author

Vaillant B, Chiaramonte MG, Cheever AW, Soloway PD, and Wynn TA

Subjects
Animals, Cytokines biosynthesis, Interferon-gamma genetics, Interferon-gamma physiology, Interleukin-10 genetics, Interleukin-10 physiology, Kinetics, Liver enzymology, Liver pathology, Liver Cirrhosis enzymology, Liver Cirrhosis pathology, Matrix Metalloproteinases genetics, Mice, Mice, Inbred C57BL, Mice, Knockout, RNA, Messenger biosynthesis, Schistosomiasis mansoni enzymology, Schistosomiasis mansoni pathology, Tissue Inhibitor of Metalloproteinase-1 genetics, Tissue Inhibitor of Metalloproteinase-2 genetics, Transcriptional Activation, Liver Cirrhosis immunology, Matrix Metalloproteinases biosynthesis, Schistosomiasis mansoni immunology, Th2 Cells immunology, Tissue Inhibitor of Metalloproteinase-1 physiology, Tissue Inhibitor of Metalloproteinase-2 physiology
Abstract

Hepatic fibrosis is the hallmark of Schistosoma mansoni infection and often results in portal hypertension and bleeding from esophageal varices. The fibrotic process is highly dependent on type 2 cytokines, yet their role in the regulation of extracellular matrix remodeling genes remains largely unknown. Here, we examined the expression of matrix metalloproteases (MMP) -2, -3, -9, -12, and -13 and their inhibitors, tissue inhibitor of metalloproteases (TIMP) -1, -2, and -3, in the livers of infected mice and correlated their expression profiles with fibrosis and type 2 cytokine production. Expression of MMP-2, -3, -9, -12, and -13 and of TIMP-1 and -2 mRNA rapidly increased at the onset of egg laying in infected mice, while TIMP-3 was unchanged. Because TIMP are presumed to be important regulators of the extracellular matrix, and their expression correlated with the development of fibrosis, we studied their role in fibrogenesis by infecting TIMP-1- and TIMP-2-deficient mice. Strikingly, our data revealed no role for TIMP-1 or -2 in the fibrotic pathology induced by S. mansoni eggs. Because of these findings, we infected IL-10/IFN-gamma-deficient mice that develop an exaggerated fibrotic response to determine whether changes in type 2 cytokine dominance influence the pattern of MMP and TIMP expression. Fibrosis and type 2 cytokine production correlated with increased MMP-2/MMP-9 vs TIMP-1/TIMP-2 expression. These data, in addition to our knockout studies, demonstrate that TIMP-1/TIMP-2 play no essential role in fibrogenesis in schistosomiasis. Indeed, our findings suggest that inhibiting profibrotic cytokines or specific MMP may be a more effective strategy to ameliorate fibrotic pathology.

Published
2001
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36. The cloning by complementation of the pawn-A gene in Paramecium.

Author

Haynes WJ, Vaillant B, Preston RR, Saimi Y, and Kung C

Subjects
Alleles, Amino Acid Sequence, Animals, Base Sequence, Calcium metabolism, Calcium Channels genetics, Molecular Sequence Data, Mutation, Open Reading Frames genetics, Paramecium tetraurelia metabolism, Patch-Clamp Techniques, Sequence Analysis, DNA, Signal Transduction genetics, Transformation, Genetic, Cloning, Molecular methods, Genetic Complementation Test, Membrane Proteins genetics, Paramecium tetraurelia genetics, Protozoan Proteins
Abstract

The genetic dissection of a simple avoidance reaction behavior in Paramecium tetraurelia has shown that ion channels are a critical molecular element in signal transduction. Pawn mutants, for example, were originally selected for their inability to swim backward, a trait that has since been shown to result from the loss of a voltage-dependent calcium current. The several genes defined by this phenotype were anticipated to be difficult to clone since the 800-ploid somatic macronucleus of P. tetraurelia is a formidable obstacle to cloning by complementation. Nonetheless, when the macronucleus of a pawn mutant (pwA/pwA) was injected with total wild-type DNA or a fractional library of DNA, its clonal descendants all responded to stimuli like the wild type. By sorting a fractional library, we cloned and sequenced a 2.3-kb fragment that restores the Ca2+ current and excitability missing in pawn-A. Data from RNase protection assays, followed by the sequencing of mutant alleles and cDNA clones, established an open reading frame. The conceptually translated product suggests a novel protein that may be glycophosphatidylinositol anchored. We also discuss the general usefulness of this method in cloning other unknown DNA sequences from Paramecium that are functionally responsible for various mutant phenotypes.

Published
1998
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37. Random mutagenesis reveals a region important for gating of the yeast K+ channel Ykc1.

Author

Loukin SH, Vaillant B, Zhou XL, Spalding EP, Kung C, and Saimi Y

Subjects
Amino Acid Sequence, Animals, Fungal Proteins chemistry, Fungal Proteins genetics, Molecular Sequence Data, Oocytes, Patch-Clamp Techniques, Plasmids genetics, Potassium Channels chemistry, Potassium Channels genetics, Saccharomyces cerevisiae growth & development, Saccharomyces cerevisiae metabolism, Sequence Alignment, Sequence Analysis, DNA, Structure-Activity Relationship, Transfection, Xenopus, Fungal Proteins metabolism, Ion Channel Gating, Mutagenesis, Potassium Channels metabolism, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins
Abstract

YKC1 (TOK1, DUK1, YORK) encodes the outwardly rectifying K+ channel of the yeast plasma membrane. Non-targeted mutations of YKC1 were isolated by their ability to completely block proliferation when expressed in yeast. All such mutations examined occurred near the cytoplasmic ends of the transmembrane segments following either of the duplicated P loops, which we termed the 'post-P loop' (PP) regions. These PP mutations specifically caused marked defects in the 'C1' states, a set of interrelated closed states that Ykc1 enters and exits at rates of tens to hundreds of milliseconds. These results indicate that the Ykc1 PP region plays a role in determining closed state conformations and that non-targeted mutagenesis and microbial selection can be a valuable tool for probing structure-function relationships of ion channels.

Published
1997
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38. YKC1 encodes the depolarization-activated K+ channel in the plasma membrane of yeast.

Author

Zhou XL, Vaillant B, Loukin SH, Kung C, and Saimi Y

Subjects
Amino Acid Sequence, Animals, Base Sequence, Cell Membrane physiology, DNA Primers, Drosophila, Membrane Potentials, Molecular Sequence Data, Open Reading Frames, Patch-Clamp Techniques, Plasmids, Potassium Channels chemistry, Protein Structure, Secondary, Restriction Mapping, Sequence Homology, Amino Acid, Genes, Fungal, Potassium Channels genetics, Potassium Channels physiology, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae physiology
Abstract

Our previous patch-clamp studies showed that depolarization activates a K(+)-specific current in the plasma membrane of the budding yeast, Saccharomyces cerevisiae [Gustin et al. (1986) Science 233, 1195-1197]. The Yeast Genome Sequencing Project has now uncovered on the left arm of chromosome X an open reading frame (ORF) that predicts a 77-kDa protein reminiscent of a shaker-like alpha subunit with 6 membrane spans followed by a subunit with 2 spans. We found that deleting this ORF removes the yeast K+ current. Furnishing the ORF from plasmids restores or even greatly amplifies this current. These manipulations have no effects on the 40-pS mechanosensitive conductance also native to this membrane. Thus, this ORF, named YKC1 here, likely encodes a structure for the K(+)-specific channel of the yeast plasma membrane. This and other K+ channel subunits are compared and the possible uses of this gene in research are discussed. YKC1 has recently been shown by others to induce in frog oocytes a K+ current. Its activation is coupled to EK+ and its outward rectification depends on external divalent cations. We found the YKC1 channel in its native membrane activates at low voltages largely independent of EK+ and it remains so despite removal of divalents by chelation.

Published
1995
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39. [Ileo-anal anastomosis. Nursing care].

Author

Vaillant B and Vandenecke B

Subjects
Adult, Anal Canal surgery, Anastomosis, Surgical methods, Humans, Ileum surgery, Anastomosis, Surgical nursing
Published
1990

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