95 results on '"Trznadel M"'
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2. Formation and morphology of latex monolayers. Computer simulation studies
- Author
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Trznadel, M. and Slomkowski, S.
- Published
- 1996
- Full Text
- View/download PDF
3. Bisphenol A causes reproductive toxicity, decreases dnmt1 transcription, and reduces global DNA methylation in breeding zebrafish (Danio rerio)
- Author
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Laing, L. V., Viana, J., Dempster, E. L., Trznadel, M., Trunkfield, L. A., Uren Webster, T. M., van Aerle, R., Paull, G. C., Wilson, R. J., Mill, J., and Santos, E. M.
- Subjects
DNA (Cytosine-5-)-Methyltransferase 1 ,endocrine system ,plasticizers ,endocrine ,Air Pollutants, Occupational ,Epigenesis, Genetic ,Phenols ,vertebrate ,Animals ,waste ,DNA (Cytosine-5-)-Methyltransferases ,Estrogens, Non-Steroidal ,Benzhydryl Compounds ,Gonads ,Zebrafish ,teleost ,Genome ,urogenital system ,DNA Methylation ,Zebrafish Proteins ,Aquatic ,Liver ,Fertilization ,methylation ,hormones, hormone substitutes, and hormone antagonists ,Research Paper - Abstract
Bisphenol A (BPA) is a commercially important high production chemical widely used in epoxy resins and polycarbonate plastics, and is ubiquitous in the environment. Previous studies demonstrated that BPA activates estrogenic signaling pathways associated with adverse effects on reproduction in vertebrates and that exposure can induce epigenetic changes. We aimed to investigate the reproductive effects of BPA in a fish model and to document its mechanisms of toxicity. We exposed breeding groups of zebrafish (Danio rerio) to 0.01, 0.1, and 1 mg/L BPA for 15 d. We observed a significant increase in egg production, together with a reduced rate of fertilization in fish exposed to 1 mg/L BPA, associated with significant alterations in the transcription of genes involved in reproductive function and epigenetic processes in both liver and gonad tissue at concentrations representing hotspots of environmental contamination (0.1 mg/L) and above. Of note, we observed reduced expression of DNA methyltransferase 1 (dnmt1) at environmentally relevant concentrations of BPA, along with a significant reduction in global DNA methylation, in testes and ovaries following exposure to 1 mg/L BPA. Our findings demonstrate that BPA disrupts reproductive processes in zebrafish, likely via estrogenic mechanisms, and that environmentally relevant concentrations of BPA are associated with altered transcription of key enzymes involved in DNA methylation maintenance. These findings provide evidence of the mechanisms of action of BPA in a model vertebrate and advocate for its reduction in the environment.
- Published
- 2016
4. Two-Dimensional Latex Assemblies for Biosensors
- Author
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Slomkowski, S., primary, Kowalczyk, M., additional, Trznadel, M., additional, and Kryszewski, M., additional
- Published
- 1996
- Full Text
- View/download PDF
5. Use of anticoagulants and antiplatelet agents in stable outpatients with coronary artery disease and atrial fibrillation. International CLARIFY registry
- Author
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Fauchier, L., Greenlaw, N., Ferrari, R., Ford, I., Fox, K. M., Tardif, J. -C., Tendera, M., Steg, P. G., Sokn, F. J., Reid, C., Lang, I., Van den Branden, F., Cesar, L. M., Mattos, M. A., Nazar Luqman, H., Goudev, A., Dorian, P., Hu, D., Widimsky, P., Hassager, C., Danchin, N., Kaab, S., Vardas, P., Sulaiman, K. J., Al Mahmeed, W., Al Suwaidi, J., Al Rashdan, I., Abdulkader, F., Merkely, B., Kaul, U., Daly, K., Tavazzi, L., Jang, Y., Erglis, A., Laucevicius, A., Jamaluddin, A. N., Gamba, M. A., Tulevski, I. I., Stepinska, J., Morais, J., Macarie, C., Oganov, R., Shalnova, S., Al-Zaibag, M., Hou, M. K., Kamensky, G., Fras, Z., Kanic, V., Naidoo, D. P., Zamorano, J. L., Rickli, H., Jaussi, A., Sriratanasathavorn, C., Kalra, P., Lutai, M., Oleksandr, Nguyen, L. V., Henry, R., Ahuad Guerrero, A., Basara, M., Belcastro, F., Bertarini, J. A., Cazenave, C., Dreycopp, H., Egido, J., Estrella, J., Garofalo, D., Giordano, J., Lagioia, H., Lago, N., La Greca, R., Lema, L., Lopez Cabanillas, N., Luquez, H., Miller, C., Prada, E., Rodenas, P., Schena, R. G., Suarez, G., Tomatti, A., Colquhoun, D. M., Conradie, A., Cox, S., Cross, D., Fathi, R., Fitzgerald, B., Hamilton-Craig, I., Holt, G., Jayasinghe, S. R., Mai, N., Moolman, J., Motyer, R. A., Phillips, K., Rafter, A., Rahman, A., Rainbird, A., Scalia, G., Taylor, A., West, P., Alford, K., Amor, R., Astridge, P., Bastian, B., Bates, F., Doohan, M. M., Du Plooy, J., Ford, J. C., Kanagaratnam, L., Khoury, V., Parkin, R., Rogers, J., Sceats, G., Waldman, A., Wang, D., Wright, S., Ardill, J., Aylward, P., Beltrame, J. F., Bradley, J., Heddle, W., Joseph, M., Rajendran, S., Varughese, S., Brice, E., Hockings, B., Janssen, J., Kozlowski, A., O'Shea, J., Playford, D. A., Woollard, K., Ajani, A., Barron, G., Better, N., Chan, B., Chan, R., Cotroneo, J., Counsell, J. T., Eccleston, D. S., Forge, B. H. R., Hamer, A., Horrigan, M., Jelinek, V. M. J., Lew, R., O'Donnell, D., Panetta, F., Sebastian, M., Soward, A., Srivastava, P., Strathmore, N. F., Sylivris, S., Szto, G., Veth, V., Yip, T., Badr-Eslam, R., Kleemann, L., Steurer, G., Morz-Proszowski, B., Auhser, F., Teleky, U., Sepp, G., Beinhauer, A., Kero, D., Lavicka, C., Perger, T., Hadjiivanov, V., Feldner-Busztin, M., Mika, R., Filip, W., Mahr, A., Toplak, J., Millauer, M. G., Haralambus, P., Walcher, K., Karner, K. H., Ziak, E., Painsipp, P., Frank, U., Suntinger, A., Gritsch, W., Bode, G., Herrmann, R., Raffelsberger, R., Topf, H., Moser, E., Fochterle, J., Honsig, T., Mayr, K., Mayr, H., Kaserbacher, R., Dzien, A., Galehr, E., Felbermayer, M., Schwarz, R., Amini, R., Appeltants, H., Ballet, A., Bar, J. -P., Beckers, J., Bergen, J. -M., Berkenboom, G., Bernard, X., Bouvy, T., Briki, R., Claeys, M., Dascotte, Y., Davin, L., De Backer, T., De Keyser, F., De Meester, A., De Ridder, S., Dendale, P., Denef, K., Dhondt, E., Emonts, M., Geraedts, J. T. M., Goethals, M., Gregoire, J. -M., Haine, E., Herbots, T., Hoffer, E., Hutse, W. H. J., Kassab, A., Lafontaine, P., Lancellotti, P., Lefebvre, P., Lesseliers, H., Lozano, A., Maamar, R., Martinez, C., Noel, J. -F., Odent, G., Pasquet, A., Peperstraete, B., Purnode, P., Rogowsky, A., Rosseel, M., Salembier, J. -P., Surmont, P., Thermol, P., Vandeplas, A. M. F., Van de Walle, S., Vandergoten, P., Vanhauwaert, B. G., Vanneste, L., Vercammen, J., Verleyen, D., Vermander, D., Vervoort, G., Weytjens, C., Yanni, N., da Costa Pereira, A., Rocha de Lorenzo, A., Felice Castro Issa, A., Mahler Mioto, B., de Brito Vianna, C., Segre, C. A. W., Grupi, C. J., Okawabata, C., Favarato, D., Giusti Rossi, E., Fernandes, F., Pitella, F., Alvarez Ramires, F. J., Henpin Yue Cesena, F., Monteiro Ferreira, J. F., Junior, J. F., Tonet, L., Nastari, L., Machado Cesar, L., Gowdak, L. H., Matos, M. A., Moretti, M., Morgado, P. C., Vicente Amato, R., Tadeu Munhoz, R., Coimbra, S. R., Luqman, H. N., Yakovova, S., Mantcheva, M., Mincheva, V., Baurenski, L., Karastanev, K., Yordanova, V., Peneva, Y., Bailey, A., Wong, P., Fagan, M., Sabe-Affaki, G., Villasenor, F. M., Belisle, P., Son, W. K., Manyari, D. E., Giacomantonio, N., Lubelsky, B. J., Ezekiel, D., Leong, J. C. S., Grover, A., Vavougios, J., Pesant, Y., Kushner, A. M., Yeung, M. M. M., Vertes, G. E., Nasser-Sharif, F. J., Abdulla, A. H. K., Spensieri, D., Roy, A., Nguyen, T. T., Leclair, M., Morra, P., Everton Biglow, C., Baril, J. F., Lai, K., Wong, D. S., Martinho, V., Antoniadis, G. A., Searles, G. R., Rouse, D., Brisson, G., King Wong, S., Collette, R. S., M. S. C., Ho, Constance, C., Gendreau, R., Kellam, G. W., Cieza Lara, T. A., Boyrazian, H. A., Shamsuzzaman, M., Spink, D. R., Wong, A. P. T., Grewal, R. S., Che, C., Janes, J., Hechtenthal, N., Czarnecka, M., Saulnier, D., Levesque, G., Clavette, P. F., Kennedy, D. R., Kokis, A., Orenstein-Lyall, T. L., Shekhar Pandey, A., Robb, J., Verret, G., Czarnecki, W., Tsui, W. W. H., Perreault, F., Chouinard, G., Lafrance, G., Fullerton, G. M., Lavoie, J. P., Le Bouthillier, P., Tran, Q. H., Rodriguez Marrero, I., Ramadan, F. B., Talbot, P., Fazil, M. A., Cha, J. Y. -M., Garg, S., Chehayeb, R., Roy, B., Chan, Y. K., Harlos, H. E., Matheson, H. B., Patel, R., Vaz, G. F., Bhatt, J. S., Liu, E., Ashton, T. H., Sullivan, H., Quinn, L. P., Yared, K., Gupta, A., Sullivan, B., Campbell, J., Pallie, S., Kim, H., Vizel, S., Savard, D., Cherry, J. M., Gold, J., Chiu, S., Brouillette, G., Singh, R. R., Varma, S., Belanger, A., Myburgh, J. L., Berlingieri, J., Nisker, W., Boutros, G., Bakbak, A. I., Healley, W., Lasalle, L., Liu, F., Tu, C., Lv, S., Liu, X., Gao, H., Li, H., Zhao, H., Cao, L., Zhao, S., Wang, Y., Wu, D., Gu, F., Pan, G., Liu, P., Wang, X., Jiang, H., Li, J., Wang, J., Zhang, L., Ke, Y., Li, D., Chen, G., Xue, H., Jin, Q., Dong, W., Chen, Y., Fu, Z., Hu, H., Liang, Q., Yang, X., Zhou, Z., Xu, Z., Shao, C., Zhang, H., Pei, H., Song, L., Yu, M., Guan, T., Tang, Y., Wu, Y., Yang, M., Ceng, Q., Chen, X., Lin, L., Peng, Y., Yan, X., Yao, E., Zheng, X., Chen, B., Chen, H., Chen, W., Wang, R., Zheng, Y., Tan, H., Zhou, S., Zhou, Y., Liu, Z., Lu, Q., Lai, L., Pan, J., Wang, L., Fu, Q., Peng, J., Du, N., Lv, Y., Miao, W., Wang, H., Pu, Y., Wang, T., Dong, M., Gong, L., Zhang, J., Chen, Z., Jiang, Q., Ma, F., Xu, W., Dai, M., Wu, J., Yu, X., Chen, C., Huo, Y., Sun, L., Gao, W., Li, Z., Hu, Y., Chen, M., Li, G., Xue, M., Yao, Y., Pan, X., Sang, Z., Zhao, G., Hang, J., Ma, S., Zhang, G., Zhou, G., Li, W., Zhu, B., Yu, B., Zhu, S., Mao, J., Xu, M., Liu, Q., Huang, Q., Xie, Y., Feng, L., Chen, F., Chen, L., Liu, Y., Pei, X., Sun, A., Tian, Z., Wang, W., Yang, H., Yu, A., Zhang, M., Zhang, C., Guan, X., Zhou, X., Li, Y., Xing, Y., Chen, K., Luo, L., Dong, S., Zhang, Y., Ai, F., Xiong, C., Yang, F., Yang, K., Yan, J., Zhu, M., Zhang, A., Shan, G., Chen, J., Guo, J., Wu, S., Li, L., Liu, R., Yang, Y., Gao, X., Du, Z., Liang, L., Zhao, Y., Qian, J., He, L., Xiong, L., Chen, P., Peng, C., Zhu, J., Liu, J., Xie, X., Jiang, F., Li, A., Yang, Q., Cong, H., Guo, Y., Ren, N., Xiao, J., Zhao, R., Jiang, J., Deng, X., Wang, S., Wu, K., Zhang, X., Du, W., Shuang, D., Wei, J., Yuan, C., Li, F., Ou, X., Ou, Y., Yu, G., Zhang, S., Gao, J., Qian, Z., Wu, G., Zheng, S., Xu, D., Xie, J., Ren, W., Yao, X., Cai, B., Lv, J., Dong, J., Deng, Z., Bozkova, J., Carda, J., Dedkova, S., Dufka, A., Fridrich, J., Hodac, T., Jirmar, R., Kadleckova, A., Karlicek, M., Krupicka, J., Kuchar, J., Lavicka, V., Leso, J., Lorenc, Z., Micko, M., Navratil, P., Petrova, I., Povolna, P., Raisova, L., Raska, P., Ravlyk, V., Schlesingerova, S., Smrckova, E., Sternthal, P., Stursova, H., Vymetal, P., Zaoral, L., Wiggers, P., Markenvard, J., Andersen, L. K., Frost, L., Refsgaard, J., Strange, S., Egstrup, K., Sykulski, R., Hildebrant, P., Haghfelt, T., Ege, M., Cattan, S., Adam-Blanpain, M., Adda, M., Aimouch, N., Ardouin, L., Assouline, S., Aumjaud, A., Barjhoux, C., Baroudi, R., Beaurain, C., Bennouna, M. A., Bernard, A., Bernardeau, C., Blanc, E., Blum-Decary, I., Bodur, G., Boesch, C., Bonal, J., Bonhomme, R., Bonnet, J. L., Bories, J., Bourachot, M. L., Brumelot, F., Brunehaut Petaut, M., Brunschwig, C., Buffet, P., Calmettes, P., Centa, I., Chartier, B., Chemin, P., Chometon, F., Cohen, J., Colin, R., Cottin, Y., Crespo, F., Dabboura, A., David, F., Dehayes, P., Dematteo, P., Dibon, O., Dodemant, P., Dormagen, V., Dreyfus, X., Dubois, J. M., Duclos, F., Ducoudre, M., Duprez, O., Durand, P., Durand, E., Egloff, P., Escande, M., Escourrou Berdou, M. C., Esna Ashari, G., Feldmann, I., Ferrieres, J., Foltzer, E., Fontanet, B., Garandeau, M., Garban, T., Geffroy, S., Gillet, T., Godart, S., Gosse, P., Gratia, P., Greiner, O., Gueusquin, A., Guiu, E., Guy, J. M., Haddad, S., Hennebelle, V., Honorat, S., Hourany, A., Hua, G., Jacquier, P., Jean, S., Jeremiasz, R., Kohler, P., Lacroix, A., Leandri, M., Lemiere, Y., Liautard, M., Loheac, P., Louchart, J. C., Magnus, P., Maheu, B., Malaterre, H. R., Manchet, G., Mantoux, J., Manzi, D., Marachli, M., Maroun, M., Meneveau, N., Messas, E., Mougeolle, J. L., Mouhat, T., Muller, J. J., Naisseh, M., Nocon, P., Onger, D., Ouguoujil, A., Ovize, M., Page, E., Pareathumby, K., Pleskof, A., Poinson, P., Pons, G., Pouderou, P., Poujois, J. N., Probst, V., Prunier, F., Prunier, L., Puel, V., Rechtman, D., Rennert, R., Rijavec, B., Riou, Y., Robert, J., Roche, C., Roul, G., Salaun, B., Saleh, B., Sandalian, A., Sander, M., Schenowitz, A., Silvestre, A., Soleille, H., Tabet, S., Tardy, M., Thomas-Richard, F., Truong, B., Varaldi, J., Vial, H., Walch, J. M., Wazana, M., Zeitouni, R., Audibert, H., Alizon, F., Amlaiky, A., Asplanato, M., Baranes, C., Bariaud, M., Bernasconi, F., Bousquet, P., Ceraulo, C., De Geeter, G., Donetti, J., Doucet, B., Doucet, J., Dutoya, T., Ennouchi, D., Fallacher, M. H., Fouquet, G., Fourchard, V., Gdalia, J., Grollier, G., Guerard, S., Jeannerat, P. A., Jobic, Y., Joulie, V., Jourdain, P., Jouve, V., Ketelers, R., Khaznadar, G., Kohan, P., Koujan, B., Lammens, B., Landragin, I., Le Moal, E., M'Bey, D., Maes, F., Maheas Morlet, S., Massabie, R., Meddah, D., Meriaux, F. X., Mestre-Fernandes, C., Meyssonnier, P., Migliore, M., Milewski, J., Millet, J. F., Mingam, S., Nazeyrollas, P., Paganelli, F., Pellerin, F., Petitjean, F., Pinzani, A., Pladys, A., Primot, P., Pucheu, A., Rahali, A., Ravoala, P., Rousson, D., Samama, P., Sardon, M., Silvestri, R., Soskin, P., Tabone, X., Tricot, C., Vaquette, B., Vogel, M., Weingrod, M., Aboyans, V., Amoretti, R., Aubry, J., Berthezene, P., Binet, D., Bonnaud, X., Bonnet, P., Bonny, A., Bouchaya, T., Boureux, C., Bourgeois, J. M., Brottier, L., Cavert, B., Cleron, S., Dechoux, E., Delhomme, C., Detienne, J. P., Dubs, J. P., Faudon, B., Fellous, F., Fressonnet, R., Garaud, Y., Garcia, D., Geneves, M., Gleizes, J. L., Guyetand, C., Hermellin, B., Iovescu, D., Kanner, J. P., Khanoyan, P., Leherissier, A., Maximovitch, A., Merian, B., Messali, P., Moreau, Y., Moyal, J., Payot, L., Petoin Peuch, L., Prevot, J. L., Raymond, P., Relange, D., Reymond, S., Robert, J. F., Rosenstein, H., Schneider, J., Schultz, R., Tanielian, P., Thoin, F., Thomas, L., Touzet, P., Steg, G., Amiel Oster Sauvinet, G., Baylac Domengetroy, F., Chamou, K., Etcheverry, B., Farges, J. L., Fraboulet, J. Y., Goralski, M., Janody, D., Mamez, B., Manlay, W., Paillard, F., Pelier, F., Petit, A., Skonieczny, M., Augarde, R., Fournier, J. B., Liandrat, S., Lim, P., Noury, A. I., Paris, D., Saade, M., Stordeur, J. M., Pornin, M., Galinier, M., Balice-Pasquinelli, M. A., Sosner, P., Yvorra, S., Delcoulx, E., Mouquet, F., Poulard, J. E., Sudre, A., Heno, P., Biausque, F., Guenoun, M., Attia, G., Pouwels, S., Carpentier, L., Verbrugge, E., Ziccarelli, C., Elkohen, M., Tricoire, J., Lang, P., Huttin, O., Altevogt, B. -M., Altmann, U., Baar, M., Berrisch-Rahmel, S., Birkenhagen, A., Blase, I., Blindt, R., Bosch, R., Brattstrom, A., Breuer, H. -H., Castrucci, M., Cicek-Hartvig, S., Cierpka, R., Claus, M., Deissner, M., Drexler, M., Eggeling, T., Eisele, G., Enayat, D., Frickel, S., Gessner, S., Giokoglu, K., Gmehling, J., Goss, F., Grooterhorst, P., Gysan, D. B., Haberl, R., Haerer, W., Hassler jun, N., Heinemann, S., Henschel, F., Hinrichsen, M., Hofer, W., Hofmeister, A., Hoh, G., Horstkotte, E., Jager, F., Jeserich, M., Keil, U., Killat, H., Kimmel, S., Kindel, M., Kindler, P., Kleta, S., Konemann, J., Konig, K., Krause-Allmendinger, H., Kronberg, K., Kruck, I., Mannl, V., Meinel, A., Mentz, G., Meyer-Michael, E., Mibach, F., Moller, S., Muth, S., Nelbock-Huber, E., Ohlmeyer, D., Ozkan-Rashed, Z., Paulus, C. -P., Perings, S., Placke, J., Raters, C., Reifart, N., Rink, A., Rybak, K., Salecker, I., Schermaul, K. -H., Schmidt, E., Schmitz, K. -H., Schon, N., Schroder, T., Sievers, B., Simon, M., Spengler, U., Speth-Nitschke, M., Stumpp, A., Szabo, S., Taggeselle, J., Tamm, A., Thelemann, A., Thelemann, C., Thummel, H., Unger, G., Utech, A., Volmar, J., Wauer, B., Wehr, G., Weinrich, L., Weinrich, R., Windstetter, U., Wirtz, J. H., Wittlich, N., Ziehn, P., Zundorf, P., Al Wahshi, Y., Singh, P. P., Narayan, A., Al Tamimi, F., Al Yazeedi, J., Ayche, M., Al Lawati, A., Al Dhanki, M., Salustri, A., Al Sousi, A., Salah, T., Tamimi, M. Y., Agrawal, A., Wassef, A., Baslaib, F., Al Radaideh, G., Yusufali, A., Bazargani, N., Akbar, M., Abdel Wahab, H., Abdel Malak, S., Ghaly, I., Al Ghool, S., Al Kandari, F., Haiba, M., Alanbaei, M., El Menyar, A., Gomaa, M. M., Khalifa, A., Garadah, T., Avgerinos, C., Gouli, O., Stergiou, D., Alexopoulos, I., Pappas, C., Petropoulos, I., Chatzioakim, G., Pontikakis, N., Priftis, C., Mpompoth, P., Bourazanis, I., Papathanasioy, A., Avlonitis, S., Zakopoulos, C., Koutsimpanis, G., Tsamopoulos, I., Christoforidis, C., Zachos, V., Kalaras, P., Karachaliou, M., Liatas, C., Pournaras, G., Theodorakis, G., Orestis, I., Panisois, K., Chalkiadakis, E., Arfaras, V., Melainis, Kolios, G., Boutsikos, P., Kotsalos, A., Mitropoulos, D., Samothrakitis, A., Svolis, K., Anastasiou, E., Gkinis, T., Dalampyras, P., Kalampalikis, A., Leontaridis, I., Gabriilidis, S., Konstantinidis, I., Plastiras, V., Tarenidis, P., Marozsan, I., Edes, I., Czuriga, I., Cziraki, A., Toth, K., Dongo, A., Turi, P., Forster, T., Borbola, J., Bachmann, B., Masszi, G., Orban, M., Gerges, G., Balogh, G., Bajcsi, E., Sereg, M., Dezsi, C. 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A., Sepulcri, F., Brunner, H., Schindler, J., Kraus, M., Gmur, W., Bouranasompop, C., Jiraroj-ungkun, W., Lapanun, W., Vivekaphirat, V., Panpunnung, S., Dutsadeevettakul, S., Tasneeyapant, S., Ngamjanyaporn, P., Apitamsuntorn, S., Tantisiriwat, W., Suithichaiyakul, T., Kuanprasert, S., Wongcharoen, W., Phrommintikul, A., Musigchai, C., Chantrarat, T., Uerojanaungkul, P., Apinyasawat, S., Tangcharoen, T., Lertnantakul, M., Wasuwat, A., Harinasuta, J., See, O., Chaithiraphan, V., Boonyasirinant, T., Boonyapisit, W., Kittipovanonth, M., Buakhamsri, A., Piyayotai, D., Hutayanon, P., Junejo, S., Aiyegbayo, O., Ancliff, H., Bradshaw, C., Cervenak, R., Choi, H., George, E., Gilmour, I., Gough, D., Idrissi-Sbai, A., Ingham, J., Al-Khalidi, B., Liston, A., Mackrell, J., Pattison, I., Ramachandran, R., Ray, N., Reddy, G., Sen, I., Shetty, K., Singh, L., Stanley, M., Wallace, A., Weatherhead, M., Gilbert, T., McCansh, G., Higgins, S., Killeen, C., Cromarty, I., Franklin, P., Pinch, E., Dhesi, A., Dernedde, C., Lawrence, M., Simper, H., Noble, M., Dalton, G., Stevens, L., Berry, P., Hand, C., Oliver, R., Jones, H., Sampson, P., Taylor, N., Grogono, R., Dalrymple, J., Martin, A., Thurston, S., Elsby, K., Vallis, M., Morrison, G., Lang, C., Watson, A., Thomson, A., Dougall, H., La Hay, B., Compson, L., McCracken, A., Calder, J., Weber, F., Richmond, D., Brownlie, R., Brown, G., MacCowan, H., Heap, A., Perry, M., Holden, L. A., Scott, G., Haldane, N., Hood, S., Cullen, I., Bell, J., McNaught, P., Sharif, M., Dunn, J., Hay, D., Ross, S., Shaw, R., Hay, L., Langridge, S., Burns, R., Crawford, L., Kennedy, A., Logan, D., McAlavey, P., Brown, M., Costello, P., McLaren, G., Potter, A., McPherson, J., Drijfhout, M., Finlayson, J., Troup, D., Woodall, A., Pearce, J., Williams, S., Parkar, W., Yusuf, A., Benett, I., Bishop, P., Thomas, H., Caldwell, I., Ormiston, P., Kwok, S., Kanumilli, N., Saul, P., Milligan, H., Wilkinson, I., Vance, A., Paul, N., Paul, C., Shaikh, I., Ellis, R., Vites, N., Steeds, R., Goodwin, D., Aftab, A., Banham, S., Chauhan, N., Grocutt, M. S., Gupte, A., Jordan, R., Jheeta, B. S., Ladha, K., Nazir, M., Pal, R., Patel, R. P., McManus, R., Singal, A., Saunders, P., Syed, A. B., Bahal, A., Dau, H., Walker, D. M., McNeilly, R., Bolidai, A., MacCarthy, N., Lawton, D., Vardhani, M., Sengupta, G., Kinloch, D., Howie, F., Serrano-Garcia, A., Paget, S. E., Till, R., Seal, P., Morrell, J., Maxwell, T., Singh, G., Warden, D., Elias, R., Dixon, C., Pandey, R. K., Challenor, V., Davies, S., Gibbs, M., Gillet, A., Goldie, C., Jarvis, I., Johnson, P., Malden, M., Moore, J., Morton, C., Nehrig, K., Sheringham, P., Wilson, G., Halcox, J., O'Connor, I., Ling, K., Edwards, D., Charles, H., Weatherup, A., Davies, E., Watkins, N., Morgan, D., Davies, R., Lindsay, A., Beacock, D., Balai, R., Kirmond, P., Brindle, P., Bundy, C., Cahill, T., Dayani, A., Eavis, P., Mohr, S., Hayne, S., Krasucki, C., Micheals, M., Orpen, I., Parker, I., Sewell, R., Sharp, D., Smith, A., Stevens, A., Upton, J., Victory, J., Wernham, C., Davis, R., Mays, C., Andrews, M., Takhar, J., Travill, C., Choudhury, P., Matta, W., Ihonor, A., O'Dong, C., Rahman, S., Singer, P., Gillam, S., Bath, P. S., Razzaq, N., O'Toole, O., Rowe, P., Williams, H., Allcock, A., Tucker, A., Sprott, V., Kyd, K., Cunliffe, G., Arden, C., Bateman, A., Kassianos, G., Sinclair, D., Turner, C., Jagathesan, R., Sattar, F., Ashford, A., Chukwu, A., Taylor, H., Pradhan, R., Rundell, T., Howlett, R., Bietzk, R., Myint, M., Partington, M., O'Reilly, F., Baverstock, M., Dixon, S., Tennekoon, M., Brand, N., Haimes, P., Keller, P., Whetstone, S., Kovyrshyna, O., Rogozhyna, V., Kiver, T., Vasylenko, V., Kucheryava, L., Salimova, S., Alekseenko, V., Gukov, O., Myhailiv, I., Kardashevskaya, L., Prikolota, O., Bashkirtcev, O., Andreev, E., Tkachenko, L., Mospan, M., Batushkin, V., Safonova, L., Ogorodnichuk, A., Pustovit, S., Romanov, S., Burlakova, L., Voloshko, Y., Lafarenko, V., Vlasuk, Z., Leshchuk, O., Chushak, S., Koval, V., Stasuk, O., Pogrebna, O., Kornienko, S., Tikhonova, S., Fesenko, T., Kuzmina, T., Ushakov, O., Vechtomova, N., Potapska, L., Illushechkin, I., Kryvenkova, E., Lysunets, O., Tsygankov, O., Bardachenko, L., Voloshyna, L., Ginzburg, V., Franskyavichene, L., Korotich, T., Vyshnevaya, N., Bilous, N., Kulinich, S., Kulik, V., Sadykova, I., Berezhna, T., Molotyagina, S., Pham, M. H., Pham, H. T., Khong, N. H., K. B., Do, T. B., Le, P. A., Do, T. C., Do, Nguyen, N. Q., Q. H., Do, K. C., Vu, Pham, N. H., Pham, T. H. T., M. C., Ta, Phan, D. P., Nguyen, T. T. H., Pham, T. T. N., T. L., To, V. T., Le, Dang, L., Bui, L., Pham, T. T. H., Phan, H. H., Bui, T. T. H., Tuong, T. V. A., Nguyen, T. P., Nguyen, T. H., Nguyen, B. K., D. B., Vu, Pham, N. S., T. Q., Do, Pham, T. S., Dang, V. D., D. T., Le, V. C., Do, Nguyen, T. K. L., Luong, H. D., Luu, T. Q., Pham, N. V., Huynh, T. K., N. T. H., Tu, Ngo, K. A., Nguyen, T. T. C., Ong, T. T. L., Doan, V. B., Kim, T. B., T. N., Vo, Tran, T. T. T., Nguyen, T. A., Tran, V. D., Nguyen, A. K., Tran, A. C., Ngo, M. H., N. H., Vu, I. T., Ly, Tran, N. P. H., Tran, L. U. P., Nguyen, T. N., Tran, T. H., Truong, P. H., Mai, T. L., Hoang, V. S., Bui, C. M. A., Dang, V. P., Truong, Q. B., M. P., Vo, Nguyen, V. T., Chau, N. H., T. T. H., Ta, Dinh, H. N., Tran, H., Nguyen, H. K. N., Chung, A., Chung, E., Martina-Hooi, B., Angela, R., Ramoutar, P., Fillet, R., Tilluckdharry, R., Dookie, T., Foster, E., Hart, C., Omardeen, F., Ramphall, S., Lalla, C., Cheng, J., Elliott, V., Falconer, H., Hurlock-Clarke, L., Ishmael, R., Lalljie, G., Lee, K., Liqui-Lung, A., Massay, R., Mohammed, H., Brown, C., Daniel, R., Didier, M., Salas, Z., CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), University of Glasgow, Maria Cecilia Hospital [Cotignola], Royal Brompton Hospital, Montreal Heart Institute Coordinating Centre (MHICC), Université de Montréal (UdeM), Medical University of Silesia (SUM), Université Paris Diderot - Paris 7 (UPD7), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Dorogoichenko, Aleksandra, Laucevičius, Aleksandras, Jurgaitienė, Rūta, Šlapikas, Rimvydas, Barauskienė, Gražina, Jankauskienė, Edita, Revienė, Sigita, Vaišvila, Tautvydas, Zaronskienė, Danutė, Šlapikienė, Ona Birutė, Kupstytė, Nora, Rinkūnienė, Egidija, Steponėnienė, Rima Vitalija, Kojelienė, Jūratė, Badarienė, Jolita, Dženkevičiūtė, Vilma, Sadauskienė, Eglė, Butkuvienė, Irena, Stankevičius, R., Paliulionienė, R., Snikytė, R., Mažutavičius, R., and CLARIFY Investigators
- Subjects
Male ,Genetics and Molecular Biology (all) ,Heart disease ,medicine.medical_treatment ,atrial fibrillation ,coronary ,anticoagulants ,patients ,atrial flutter ,lcsh:Medicine ,Coronary Artery Disease ,Practice Patterns ,030204 cardiovascular system & hematology ,Chest pain ,Biochemistry ,[SHS]Humanities and Social Sciences ,Cohort Studies ,Coronary artery disease ,Angina ,0302 clinical medicine ,Aged ,Anticoagulants ,Atrial Fibrillation ,Drug Therapy, Combination ,Female ,Guideline Adherence ,Humans ,Outpatients ,Platelet Aggregation Inhibitors ,Practice Patterns, Physicians' ,Registries ,Practice Patterns, Physicians'/statistics & numerical data ,030212 general & internal medicine ,Myocardial infarction ,lcsh:Science ,Stroke ,Anticoagulants/administration & dosage ,Multidisciplinary ,Medicine (all) ,Atrial fibrillation ,Guideline Adherence/statistics & numerical data ,3. Good health ,Combination ,Cardiology ,[SHS] Humanities and Social Sciences ,medicine.symptom ,Research Article ,medicine.medical_specialty ,Coronary Artery Disease/drug therapy ,Agricultural and Biological Sciences (all) ,Biochemistry, Genetics and Molecular Biology (all) ,NO ,03 medical and health sciences ,Drug Therapy ,Internal medicine ,medicine ,Platelet Aggregation Inhibitors/administration & dosage ,Physicians' ,Atrial Fibrillation/drug therapy ,business.industry ,lcsh:R ,Percutaneous coronary intervention ,Outpatients/statistics & numerical data ,medicine.disease ,lcsh:Q ,Human medicine ,business - Abstract
BACKGROUND: Few data are available regarding the use of antithrombotic strategies in coronary artery disease patients with atrial fibrillation (AF) in everyday practice. We sought to describe the prevalence of AF and its antithrombotic management in a contemporary population of patients with stable coronary artery disease.METHODS AND FINDINGS: CLARIFY is an international, prospective, longitudinal registry of outpatients with stable coronary artery disease, defined as prior (≥12 months) myocardial infarction, revascularization procedure, coronary stenosis >50%, or chest pain associated with evidence of myocardial ischemia. Overall, 33,428 patients were screened, of whom 32,954 had data available for analysis at baseline; of these 2,229 (6.7%) had a history of AF. Median (interquartile range) CHA2DS2-VASc score was 4 (3, 5). Oral anticoagulation alone was used in 25.7%, antiplatelet therapy alone in 52.8% (single 41.8%, dual 11.0%), and both in 21.5%. OAC use was independently associated with permanent AF (pCONCLUSIONS: In this contemporary cohort of patients with stable coronary artery disease and AF, most of whom are theoretical candidates for anticoagulation, oral anticoagulants were used in only 47.2%. Half of the patients received antiplatelet therapy alone and one-fifth received both antiplatelets and oral anticoagulants. Efforts are needed to improve adherence to guidelines in these patients.TRIAL REGISTRATION: ISRCTN registry of clinical trials: ISRCTN43070564.
- Published
- 2015
6. Insulator-Metal transition in Polyaniline induced by plasticizers
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Fedorko, P., Djurado, D., Trznadel, M., Dufour, B., Rannou, P., and Travers, J.P.
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- 2003
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7. Effect of solvent-dopant competition on the conductivity of polyaniline films
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Trznadel, M. and Rannou, P.
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- 1999
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8. Preliminary SANS studies of PANI-CSA films
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Terech, P., Trznadel, M., Rannou, P., Travers, J.P., Nechtschein, M., Legrand, J.F., and Djurado, D.
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- 1999
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9. Preparation and properties of fractionated regioregular poly(3-alkylthiophenes)
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Trznadel, M., Pron, A., and Zagorska, M.
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- 1999
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10. EPR study of regioregular poly(3-hexylthiophene)
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Trznadel, M., Chauvet, O., Lapkowski, M., and Pron, A.
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- 1999
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11. Bisphenol A causes reproductive toxicity, decreases dnmt1transcription, and reduces global DNA methylation in breeding zebrafish (Danio rerio)
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Laing, L. V., Viana, J., Dempster, E. L., Trznadel, M., Trunkfield, L. A., Uren Webster, T. M., van Aerle, R., Paull, G. C., Wilson, R. J., Mill, J., and Santos, E. M.
- Abstract
ABSTRACTBisphenol A (BPA) is a commercially important high production chemical widely used in epoxy resins and polycarbonate plastics, and is ubiquitous in the environment. Previous studies demonstrated that BPA activates estrogenic signaling pathways associated with adverse effects on reproduction in vertebrates and that exposure can induce epigenetic changes. We aimed to investigate the reproductive effects of BPA in a fish model and to document its mechanisms of toxicity. We exposed breeding groups of zebrafish (Danio rerio) to 0.01, 0.1, and 1 mg/L BPA for 15 d. We observed a significant increase in egg production, together with a reduced rate of fertilization in fish exposed to 1 mg/L BPA, associated with significant alterations in the transcription of genes involved in reproductive function and epigenetic processes in both liver and gonad tissue at concentrations representing hotspots of environmental contamination (0.1 mg/L) and above. Of note, we observed reduced expression of DNA methyltransferase 1 (dnmt1) at environmentally relevant concentrations of BPA, along with a significant reduction in global DNA methylation, in testes and ovaries following exposure to 1 mg/L BPA. Our findings demonstrate that BPA disrupts reproductive processes in zebrafish, likely via estrogenic mechanisms, and that environmentally relevant concentrations of BPA are associated with altered transcription of key enzymes involved in DNA methylation maintenance. These findings provide evidence of the mechanisms of action of BPA in a model vertebrate and advocate for its reduction in the environment.
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- 2016
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12. Fractionated regioregular poly(3-hexylthiophene). Spectroscopic and electrochemical studies
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Trznadel, M., primary
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- 1998
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13. Electrical characterization of diodes based on regioregular poly(3-hexylthiophene)
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Barta, P., primary, Sanetra, J., additional, Gryboś, P., additional, Nizioł, S., additional, and Trznadel, M., additional
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- 1998
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14. Optical studies of regioregular poly(3-octylthiophene)s under pressure
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Kaniowski, T., primary, Nizioł, S., additional, Sanetra, J., additional, Trznadel, M., additional, and Proń, A., additional
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- 1998
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15. X-ray diffraction and optical studies of fractionalized regioregular poly(3-hexylthiophene)
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Kaniowski, T., primary, Łużny, W., additional, Nizioł, S., additional, Sanetra, J., additional, and Trznadel, M., additional
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- 1998
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16. Spectroscopic studies of regioregular poly(3-decylthiophene)
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Louarn, G., primary, Trznadel, M., additional, Zagorska, M., additional, Lapkowski, M., additional, Pron, Adam, additional, Buisson, J.P., additional, and Lefrant, S., additional
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- 1997
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17. X-ray diffraction study of regioregular poly(3-alkylthiophenes)
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Łużny, W., primary, Trznadel, M., additional, and Proń, A., additional
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- 1996
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18. Oriented PP–PS composites obtained by polymerization of styrene inside oriented PP matrices. II. Shrinkage behavior and mechanical properties
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Trznadel, M., primary, Pluta, M., additional, and Kryszewski, M., additional
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- 1993
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19. Oriented PP-PS composites obtained by polymerization of styrene inside oriented PP matrices. I. Dispersion of PS and the composites' orientation
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Trznadel, M., primary, Pluta, M., additional, and Kryszewski, M., additional
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- 1993
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20. Solubilisation and Plastification of Polyaniline in the Protonated State
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Laska, J., primary, Trznadel, M., additional, and Pron, A., additional
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- 1993
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21. Structure of iPP‐PS composites with specific dispersion of PS component
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Kryszewski, M., primary, Pluta, M., additional, Trznadel, M., additional, and Milczarek, P., additional
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- 1992
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22. Thermal Shrinkage Of Oriented Polymers
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Trznadel, M., primary and Kryszewski, M., additional
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- 1992
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23. Diffusion and subsequent polymerization of styrene in oriented polypropylene matrix
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Trznadel, M., primary, Milczarek, P., additional, and Kryszewski, M., additional
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- 1991
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24. The influence internal stress relaxation on the induction effect of shrinkage in oriented polycarbonate.
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Trznadel, M.
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- 1989
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25. Effect of Molecular Weight on Spectroscopic and Spectroelectrochemical Properties of Regioregular Poly(3-hexylthiophene)
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Trznadel, M., Pron, A., Zagorska, M., Chrzaszcz, R., and Pielichowski, J.
- Abstract
Using experimentally established sequence of extractions, we were able to fractionate regioregular poly(3-hexylthiophene) (R-P3HT) into four fractions differing significantly in their molecular weight (M
n ) and exhibiting low polydispersity coefficients. 1H NMR analysis of low molecular fractions enabled us to propose the dominant chain termination mechanisms and identify the sources of regioregularity defects. In particular, it turned out that the presence of small amounts of undesired isomer of 2-bromo-3-hexylthiophene, namely, 2-bromo-4-hexylthiophene, strongly influences the molecular weight and to a much lesser extent the regioregularity of the polymer obtained via Grignard type polycondensation. In the reaction with the growing chain, 2-bromo-4-hexylthiophene either causes its termination, lowering in this manner the molecular weight of the resulting polymer, or introduces regioregularity defects of TT−HH (TT = tail to tail; HH = head to head) type. The average conjugation length in R-P3HT increases with the increase of Mn as manifested by a bathochromic shift of the λmax and the appearance of the vibrational structure in the UV−vis−near-IR spectra of the fractions of higher molecular weight. This conclusion is supported by FTIR data. The onset of the oxidative doping of R-P3HT shifts to lower potentials with the increase of the molecular weight as evidenced by cyclic voltammetry and UV−vis−near-IR spectroelectrochemistry.- Published
- 1998
26. Thermally stimulated shrinkage forces in oriented polymers: 1. Temperature dependence
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Pakula, T., primary and Trznadel, M., additional
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- 1985
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27. Thermally stimulated shrinkage forces in oriented polymers: 2. Time dependence
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Trznadel, M., primary, Pakula, T., additional, and Kryszewski, M., additional
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- 1985
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28. Shrinkage and related relaxation of internal stresses in oriented glassy polymers
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Trznadel, M., primary and Kryszewski, M., additional
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- 1988
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29. Thermally stimulated shrinkage forces in oriented polymers: Induction time
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Trznadel, M., primary
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- 1986
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30. The influence of internal stresses on viscoelastic and thermal properties of oriented and aged glassy polymers
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Trznadel, M., primary, Pakuła, T., additional, and Kryszewski, M., additional
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- 1988
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31. Elevated temperature exacerbates pharmaceutical-induced oxidative stress in zebrafish (Danio rerio) larvae.
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Boreham R, Ball JS, Hetheridge M, Owen S, Trznadel M, and Tyler CR
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- Animals, Climate Change, Hot Temperature adverse effects, Acetaminophen toxicity, Diclofenac toxicity, Temperature, Zebrafish physiology, Oxidative Stress, Water Pollutants, Chemical toxicity, Larva drug effects
- Abstract
There is growing evidence that rising global temperatures resulting from climate change may exacerbate the toxic effect of pollutants and heterotherms, including fish, in which homestatic mechanisms are directly influenced by environmental temperature will be most affected. Pharmaceuticals discharged into the environment are potentially harmful to wildlife as many of their drug targets are conserved across divergent phyla. Oxidative stress (OS) is a major mechanism by which many pharmaceutical contaminants can induce toxicity but this has received little consideration in the context of effects in wildlife. Further, these mechanisms are relatively poorly understood, particularly regarding multiple stressor interactions. We used transgenic TG(EpRE:mCherry) zebrafish, developed in our laboratory for detecting OS, as our experimental model. We show that the oxidative effects of high concentrations of pharmaceuticals from three different therapeutic classes (paracetamol, diclofenac and doxorubicin) are increased at temperatures elevated by 2-5 °C above those for zebrafish standard husbandry and relevant to their current natural environment (and predicted under the IPCC 2023 scenarios for intermediate to very high greenhouse gas emissions). These OS responses were primarily seen in the pronephros, liver, and gastrointestinal tract. The increase in OS at the increased water temperature may have resulted from the elevated temperature acting as a direct additive physiological stressor to the OS imposed by the drugs and/or via the temperature increasing the chemicals oxidative effect. For paracetamol, it appeared that the elevated responses at the higher temperature of 33 °C were in part due to an increase in uptake of the drug. Our data illustrate that risk assessments for chemicals inducing OS in fish (and likely other heterotherms) should consider the influence of temperature to ensure environmental protection in future environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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32. Exposure effects of synthetic glucocorticoid drugs on skeletal developmental and immune cell function in zebrafish.
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Hamilton CM, Winter MJ, Ball JS, Trznadel M, Margiotta-Casaluci L, Owen SF, and Tyler CR
- Abstract
Synthetic glucocorticoids (GCs) are used to treat a wide range of human health conditions and as such are frequently detected in the aquatic environment. This, together with the highly conserved nature of the glucocorticoid system across vertebrates means that the potential for biological effects of GCs in fish is relatively high. Here, we found that exposure of zebrafish (Danio rerio) to environmentally relevant concentrations of 4 of the most widely used synthetic GCs (beclomethasone dipropionate, budesonide, fluticasone propionate, and prednisolone), from 0 to 4 days post fertilisation (dpf), resulted in no effects on embryo-larval development or bone and cartilage formation. However, after exposure to equivalents of human therapeutic plasma levels, developmental abnormalities were observed that included pericardial oedema, blood pooling and alterations in jaw cartilage. Furthermore, using a double transgenic zebrafish osteoblast and chondrocyte reporter line, exposure up to 10 dpf resulted in alterations to lower jaw cartilage and bone development for all compounds at, and above, human therapeutic plasma concentrations. In the case of beclomethasone dipropionate, a reduction in lower jaw intercranial distance was observed at the environmentally relevant concentration of 0.1 μg/L. Using further transgenic reporter lines with fluorescently tagged neutrophils and macrophages, we also show exposure of embryo-larvae (0-4 dpf) to the GCs tested resulted in altered immune cell migration, but only at relatively high exposure concentrations. Collectively, our findings show GC exposure impacts embryo-larval zebrafish development, immune function, and skeletal formation, but predominantly at concentrations greater than those currently reported for the aquatic environment. Despite this, however, it is suggested that studies with longer exposure times, and to mixtures of multiple GCs (many GCs act via the same mechanism of action) are warranted before we can confidently assert that these commonly detected contaminants do not pose a risk to fish in the wild., Competing Interests: Declaration of competing interest CH was in receipt of a scholarship (awarded to CRT, MJW and LM-C) co-funded by AstraZeneca. SFO is an employee and share holder of AstraZeneca, a biopharmaceutical company with an interest in the discovery, development and commercialisation of prescription medicines including glucocorticoids., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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33. Phylogenomic diversity of archigregarine apicomplexans.
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Lax G, Park E, Na I, Jacko-Reynolds V, Kwong WK, House CSE, Trznadel M, Wakeman K, Leander BS, and Keeling P
- Subjects
- Animals, Transcriptome, Genetic Variation, Phylogeny, Apicomplexa genetics, Apicomplexa classification
- Abstract
Gregarines are a large and diverse subgroup of Apicomplexa, a lineage of obligate animal symbionts including pathogens such as Plasmodium , the malaria parasite. Unlike Plasmodium , however, gregarines are poorly studied, despite the fact that as early-branching apicomplexans they are crucial to our understanding of the origin and evolution of all apicomplexans and their parasitic lifestyle. Exemplifying this, the earliest branch of gregarines, the archigregarines, are particularly poorly studied: around 80 species have been described from marine invertebrates, but almost all of them were assigned to a single genus, Selenidium . Most are known only from light micrographs and largely unresolved rDNA phylogenies, where they exhibit a great deal of sequence variation, and fall into four subclades. To resolve the relationships within archigregarines, we sequenced 12 single-cell transcriptomes from species representing all four known subclades, as well as one blastogregarine (which frequently branch with Selenidium ). A 190-gene phylogenomic tree confirmed four maximally supported individual clades of archigregarines and blastogregarines. These clades are discrete and distantly related, and also correlate with host identity. We propose the establishment of three novel genera of archigregarines to reflect their phylogenetic diversity and host range, and nine novel species isolated from a range of marine invertebrates.
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- 2024
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34. Biological variability hampers the use of skeletal staining methods in zebrafish embryo developmental toxicity assays.
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Hoyberghs J, Ball J, Trznadel M, Beekhuijzen M, Burbank M, Wilhelmi P, Muriana A, Powles-Glover N, Letamendia A, and Van Cruchten S
- Subjects
- Animals, Staining and Labeling, Bone and Bones drug effects, Bone and Bones abnormalities, Embryonic Development drug effects, Fluoresceins toxicity, Anthraquinones toxicity, Zebrafish embryology, Teratogens toxicity, Embryo, Nonmammalian drug effects, Toxicity Tests methods
- Abstract
Zebrafish embryo assays are used by pharmaceutical and chemical companies as new approach methodologies (NAMs) in developmental toxicity screening. Despite an overall high concordance of zebrafish embryo assays with in vivo mammalian studies, false negative and false positive results have been reported. False negative results in risk assessment models are of particular concern for human safety, as developmental anomalies may be missed. Interestingly, for several chemicals and drugs that were reported to be false negative in zebrafish, skeletal findings were noted in the in vivo studies. As the number of skeletal endpoints assessed in zebrafish is very limited compared to the in vivo mammalian studies, the aim of this study was to investigate whether the sensitivity could be increased by including a skeletal staining method. Three staining methods were tested on zebrafish embryos that were exposed to four teratogens that caused skeletal anomalies in rats and/or rabbits and were false negative in zebrafish embryo assays. These methods included a fixed alizarin red-alcian blue staining, a calcein staining, and a live alizarin red staining. The results showed a high variability in staining intensity of larvae exposed to mammalian skeletal teratogens, as well as variability between control larvae originating from the same clutch of zebrafish. Hence, biological variability in (onset of) bone development in zebrafish hampers the detection of (subtle) treatment-related bone effects that are not picked-up by gross morphology. In conclusion, the used skeletal staining methods did not increase the sensitivity of zebrafish embryo developmental toxicity assays., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Steven Van Cruchten reports financial support was provided by University of Antwerp. Jonathan Ball reports financial support and equipment, drugs, or supplies were provided by University of Exeter. Steven Van Cruchten is Associate Editor for Reproductive Toxicology and Guest Editor for the Special Issue on NAMs for DART testing If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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35. Exposure Effects of Environmentally Relevant Concentrations of the Tricyclic Antidepressant Amitriptyline in Early Life Stage Zebrafish.
- Author
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Gould SL, Winter MJ, Trznadel M, Lange A, Hamilton CM, Boreham RJ, Hetheridge MJ, Young A, Norton WHJ, and Tyler CR
- Abstract
Antidepressants are one of the most globally prescribed classes of pharmaceuticals, and drug target conservation across phyla means that nontarget organisms may be at risk from the effects of exposure. Here, we address the knowledge gap for the effects of chronic exposure (28 days) to the tricyclic antidepressant amitriptyline (AMI) on fish, including for concentrations with environmental relevance, using zebrafish ( Danio rerio ) as our experimental model. AMI was found to bioconcentrate in zebrafish, was readily transformed to its major active metabolite nortriptyline, and induced a pharmacological effect (downregulation of the gene encoding the serotonin transporter; slc6a4a ) at environmentally relevant concentrations (0.03 μg/L and above). Exposures to AMI at higher concentrations accelerated the hatch rate and reduced locomotor activity, the latter of which was abolished after a 14 day period of depuration. The lack of any response on the features of physiology and behavior we measured at concentrations found in the environment would indicate that AMI poses a relatively low level of risk to fish populations. The pseudopersistence and likely presence of multiple drugs acting via the same mechanism of action, however, together with a global trend for increased prescription rates, mean that this risk may be underestimated using current ecotoxicological assessment paradigms.
- Published
- 2024
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36. Parallel functional reduction in the mitochondria of apicomplexan parasites.
- Author
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Keeling PJ, Mtawali M, Trznadel M, Livingston SJ, and Wakeman KC
- Subjects
- Biological Evolution, Apicomplexa genetics, Apicomplexa physiology, Apicomplexa classification, Mitochondria genetics
- Abstract
Extreme functional reduction of mitochondria has taken place in parallel in many distantly related lineages of eukaryotes, leading to a number of recurring metabolic states with variously lost electron transport chain (ETC) complexes, loss of the tricarboxylic acid (TCA) cycle, and/or loss of the mitochondrial genome. The resulting mitochondria-related organelles (MROs) are generally structurally reduced and in the most extreme cases barely recognizable features of the cell with no role in energy metabolism whatsoever (e.g., mitosomes, which generally only make iron-sulfur clusters). Recently, a wide diversity of MROs were discovered to be hiding in plain sight: in gregarine apicomplexans. This diverse group of invertebrate parasites has been known and observed for centuries, but until recent applications of culture-free genomics, their mitochondria were unremarkable. The genomics, however, showed that mitochondrial function has reduced in parallel in multiple gregarine lineages to several different endpoints, including the most reduced mitosomes. Here we review this remarkable case of parallel evolution of MROs, and some of the interesting questions this work raises., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)
- Published
- 2024
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37. Coral-infecting parasites in cold marine ecosystems.
- Author
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Trznadel M, Holt CC, Livingston SJ, Kwong WK, and Keeling PJ
- Subjects
- Animals, Apicomplexa physiology, Apicomplexa genetics, Apicomplexa classification, Symbiosis, Cold Temperature, Dinoflagellida physiology, Dinoflagellida genetics, Host-Parasite Interactions, Anthozoa parasitology, Coral Reefs
- Abstract
Coral reefs are a biodiversity hotspot,
1 , 2 and the association between coral and intracellular dinoflagellates is a model for endosymbiosis.3 , 4 Recently, corals and related anthozoans have also been found to harbor another kind of endosymbiont, apicomplexans called corallicolids.5 Apicomplexans are a diverse lineage of obligate intracellular parasites6 that include human pathogens such as the malaria parasite, Plasmodium.7 Global environmental sequencing shows corallicolids are tightly associated with tropical and subtropical reef environments,5 , 8 , 9 where they infect diverse corals across a range of depths in many reef systems, and correlate with host mortality during bleaching events.10 All of this points to corallicolids being ecologically significant to coral reefs, but it is also possible they are even more widely distributed because most environmental sampling is biased against parasites that maintain a tight association with their hosts throughout their life cycle. We tested the global distribution of corallicolids using a more direct approach, by specifically targeting potential anthozoan host animals from cold/temperate marine waters outside the coral reef context. We found that corallicolids are in fact common in such hosts, in some cases at high frequency, and that they infect the same tissue as parasites from topical coral reefs. Parasite phylogeny suggests corallicolids move between hosts and habitats relatively frequently, but that biogeography is more conserved. Overall, these results greatly expand the range of corallicolids beyond coral reefs, suggesting they are globally distributed parasites of marine anthozoans, which also illustrates significant blind spots that result from strategies commonly used to sample microbial biodiversity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)- Published
- 2024
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38. New Parabasalia symbionts Snyderella spp. and Daimonympha gen. nov. from South American Rugitermes termites and the parallel evolution of a cell with a rotating "head".
- Author
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Hehenberger E, Boscaro V, James ER, Hirakawa Y, Trznadel M, Mtawali M, Fiorito R, Del Campo J, Karnkowska A, Kolisko M, Irwin NAT, Mathur V, Scheffrahn RH, and Keeling PJ
- Subjects
- Animals, Phylogeny, South America, Parabasalidea, Isoptera
- Abstract
Most Parabasalia are symbionts in the hindgut of "lower" (non-Termitidae) termites, where they widely vary in morphology and degree of morphological complexity. Large and complex cells in the class Cristamonadea evolved by replicating a fundamental unit, the karyomastigont, in various ways. We describe here four new species of Calonymphidae (Cristamonadea) from Rugitermes hosts, assigned to the genus Snyderella based on diagnostic features (including the karyomastigont pattern) and molecular phylogeny. We also report a new genus of Calonymphidae, Daimonympha, from Rugitermes laticollis. Daimonympha's morphology does not match that of any known Parabasalia, and its SSU rRNA gene sequence corroborates this distinction. Daimonympha does however share a puzzling feature with a few previously described, but distantly related, Cristamonadea: a rapid, smooth, and continuous rotation of the anterior end of the cell, including the many karyomastigont nuclei. The function of this rotatory movement, the cellular mechanisms enabling it, and the way the cell deals with the consequent cell membrane shear, are all unknown. "Rotating wheel" structures are famously rare in biology, with prokaryotic flagella being the main exception; these mysterious spinning cells found only among Parabasalia are another, far less understood, example., (© 2023 The Authors. Journal of Eukaryotic Microbiology published by Wiley Periodicals LLC on behalf of International Society of Protistologists.)
- Published
- 2023
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39. Contrasting outcomes of genome reduction in mikrocytids and microsporidians.
- Author
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Žárský V, Karnkowska A, Boscaro V, Trznadel M, Whelan TA, Hiltunen-Thorén M, Onut-Brännström I, Abbott CL, Fast NM, Burki F, and Keeling PJ
- Subjects
- Phylogeny, Evolution, Molecular, Genome, Introns, Eukaryota genetics, Microsporidia genetics
- Abstract
Background: Intracellular symbionts often undergo genome reduction, losing both coding and non-coding DNA in a process that ultimately produces small, gene-dense genomes with few genes. Among eukaryotes, an extreme example is found in microsporidians, which are anaerobic, obligate intracellular parasites related to fungi that have the smallest nuclear genomes known (except for the relic nucleomorphs of some secondary plastids). Mikrocytids are superficially similar to microsporidians: they are also small, reduced, obligate parasites; however, as they belong to a very different branch of the tree of eukaryotes, the rhizarians, such similarities must have evolved in parallel. Since little genomic data are available from mikrocytids, we assembled a draft genome of the type species, Mikrocytos mackini, and compared the genomic architecture and content of microsporidians and mikrocytids to identify common characteristics of reduction and possible convergent evolution., Results: At the coarsest level, the genome of M. mackini does not exhibit signs of extreme genome reduction; at 49.7 Mbp with 14,372 genes, the assembly is much larger and gene-rich than those of microsporidians. However, much of the genomic sequence and most (8075) of the protein-coding genes code for transposons, and may not contribute much of functional relevance to the parasite. Indeed, the energy and carbon metabolism of M. mackini share several similarities with those of microsporidians. Overall, the predicted proteome involved in cellular functions is quite reduced and gene sequences are extremely divergent. Microsporidians and mikrocytids also share highly reduced spliceosomes that have retained a strikingly similar subset of proteins despite having reduced independently. In contrast, the spliceosomal introns in mikrocytids are very different from those of microsporidians in that they are numerous, conserved in sequence, and constrained to an exceptionally narrow size range (all 16 or 17 nucleotides long) at the shortest extreme of known intron lengths., Conclusions: Nuclear genome reduction has taken place many times and has proceeded along different routes in different lineages. Mikrocytids show a mix of similarities and differences with other extreme cases, including uncoupling the actual size of a genome with its functional reduction., (© 2023. The Author(s).)
- Published
- 2023
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40. Functional brain imaging in larval zebrafish for characterising the effects of seizurogenic compounds acting via a range of pharmacological mechanisms.
- Author
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Winter MJ, Pinion J, Tochwin A, Takesono A, Ball JS, Grabowski P, Metz J, Trznadel M, Tse K, Redfern WS, Hetheridge MJ, Goodfellow M, Randall AD, and Tyler CR
- Subjects
- Animals, Functional Neuroimaging, Larva, Seizures chemically induced, Seizures drug therapy, Brain diagnostic imaging, Zebrafish
- Abstract
Background and Purpose: Functional brain imaging using genetically encoded Ca
2+ sensors in larval zebrafish is being developed for studying seizures and epilepsy as a more ethical alternative to rodent models. Despite this, few data have been generated on pharmacological mechanisms of action other than GABAA antagonism. Assessing larval responsiveness across multiple mechanisms is vital to test the translational power of this approach, as well as assessing its validity for detecting unwanted drug-induced seizures and testing antiepileptic drug efficacy., Experimental Approach: Using light-sheet imaging, we systematically analysed the responsiveness of 4 days post fertilisation (dpf; which are not considered protected under European animal experiment legislation) transgenic larval zebrafish to treatment with 57 compounds spanning more than 12 drug classes with a link to seizure generation in mammals, alongside eight compounds with no such link., Key Results: We show 4dpf zebrafish are responsive to a wide range of mechanisms implicated in seizure generation, with cerebellar circuitry activated regardless of the initiating pharmacology. Analysis of functional connectivity revealed compounds targeting cholinergic and monoaminergic reuptake, in particular, showed phenotypic consistency broadly mapping onto what is known about neurotransmitter-specific circuitry in the larval zebrafish brain. Many seizure-associated compounds also exhibited altered whole brain functional connectivity compared with controls., Conclusions and Implications: This work represents a significant step forward in understanding the translational power of 4dpf larval zebrafish for use in neuropharmacological studies and for studying the events driving transition from small-scale pharmacological activation of local circuits, to the large network-wide abnormal synchronous activity associated with seizures., (© 2021 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)- Published
- 2021
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41. Hypoxia modifies the response to flutamide and linuron in male three-spined stickleback (Gasterosteus aculeatus).
- Author
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Fitzgerald JA, Trznadel M, Katsiadaki I, and Santos EM
- Subjects
- Animals, Flutamide, Hypoxia, Linuron, Male, Smegmamorpha, Water Pollutants, Chemical
- Abstract
Hypoxia is a major stressor in aquatic environments and it is frequently linked with excess nutrients resulting from sewage effluent discharges and agricultural runoff, which often also contain complex mixtures of chemicals. Despite this, interactions between hypoxia and chemical toxicity are poorly understood. We exposed male three-spined stickleback during the onset of sexual maturation to a model anti-androgen (flutamide; 250 μg/L) and a pesticide with anti-androgenic activity (linuron; 250 μg/L), under either 97% or 56% air saturation (AS). We assessed the effects of each chemical, alone and in combination with reduced oxygen concentration, by measuring the transcription of spiggin in the kidney, as a marker of androgen signalling, and 11 genes in the liver involved in some of the molecular pathways hypothesised to be affected by the exposures. Spiggin transcription was strongly inhibited by flutamide under both AS conditions. In contrast, for linuron, a strong inhibition of spiggin was observed under 97% AS, but this effect was supressed under reduced air saturation, likely due to interactions between the hypoxia inducible factor and the aryl hydrocarbon receptor (AhR) pathways. In the liver, hypoxia inducible factor 1α was induced following exposure to both flutamide and linuron, however this was independent of the level of air saturation. This work illustrates the potential for interactions between hypoxia and pollutants with endocrine or AhR agonist activity to occur, with implications for risk assessment and management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)
- Published
- 2020
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42. Variability in cyanobacteria sensitivity to antibiotics and implications for environmental risk assessment.
- Author
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Le Page G, Gunnarsson L, Trznadel M, Wedgwood KCA, Baudrot V, Snape J, and Tyler CR
- Subjects
- Anti-Bacterial Agents analysis, Cyanobacteria drug effects, Environmental Monitoring, Risk Assessment, Water Pollutants, Chemical analysis, Anti-Bacterial Agents toxicity, Cyanobacteria physiology, Water Pollutants, Chemical toxicity
- Abstract
Once released into the environment antibiotics can kill or inhibit the growth of bacteria, and in turn potentially have effects on bacterial community structure and ecosystem function. Environmental risk assessment (ERA) seeks to establish protection limits to minimise chemical impacts on the environment, but recent evidence suggests that the current regulatory approaches for ERA for antibiotics may not be adequate for protecting bacteria that have fundamental roles in ecosystem function. In this study we assess the differences in interspecies sensitivity of eight species of cyanobacteria to seven antibiotics (cefazolin, cefotaxime, ampicillin, sufamethazine, sulfadiazine, azithromycin and erythromycin) with three different modes of action. We found that variability in the sensitivity to these antibiotics between species was dependent on the mode of action and varied by up to 70 times for β-lactams. Probabilistic analysis using species sensitivity distributions suggest that the current predicted no effect concentration PNEC for the antibiotics may be either over or under protective of cyanobacteria dependent on the species on which it is based and the mode of action of the antibiotic; the PNECs derived for the macrolide antibiotics were over protective but PNECs for β-lactams were generally under protective. For some geographical locations we identify a significant risk to cyanobacteria populations based upon measured environmental concentrations of selected antibiotics. We conclude that protection limits, as determined according to current regulatory guidance, may not always be protective and might be better derived using SSDs and that including toxicity data for a wider range of (cyano-) bacteria would improve confidence for the ERA of antibiotics., (Copyright © 2019. Published by Elsevier B.V.)
- Published
- 2019
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43. New insights into organ-specific oxidative stress mechanisms using a novel biosensor zebrafish.
- Author
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Mourabit S, Fitzgerald JA, Ellis RP, Takesono A, Porteus CS, Trznadel M, Metz J, Winter MJ, Kudoh T, and Tyler CR
- Subjects
- Animals, Animals, Genetically Modified, Antioxidant Response Elements genetics, Antioxidants, Biomarkers, Gene Expression Regulation drug effects, Humans, Reactive Oxygen Species, Water Pollutants, Chemical chemistry, Zebrafish genetics, Antioxidant Response Elements physiology, Biosensing Techniques, Oxidative Stress physiology, Water Pollutants, Chemical toxicity, Zebrafish metabolism
- Abstract
Background: Reactive oxygen species (ROS) arise as a result from, and are essential in, numerous cellular processes. ROS, however, are highly reactive and if left unneutralised by endogenous antioxidant systems, can result in extensive cellular damage and/or pathogenesis. In addition, exposure to a wide range of environmental stressors can also result in surplus ROS production leading to oxidative stress (OS) and downstream tissue toxicity., Objectives: Our aim was to produce a stable transgenic zebrafish line, unrestricted by tissue-specific gene regulation, which was capable of providing a whole organismal, real-time read-out of tissue-specific OS following exposure to a wide range of OS-inducing environmental contaminants and conditions. This model could, therefore, serve as a sensitive and specific mechanistic in vivo biomarker for all environmental conditions that result in OS., Methods: To achieve this aim, we exploited the pivotal role of the electrophile response element (EpRE) as a globally-acting master regulator of the cellular response to OS. To test tissue specificity and quantitative capacity, we selected a range of chemical contaminants known to induce OS in specific organs or tissues, and assessed dose-responsiveness in each using microscopic measures of mCherry fluorescence intensity., Results: We produced the first stable transgenic zebrafish line Tg (3EpRE:hsp70:mCherry) with high sensitivity for the detection of cellular RedOx imbalances, in vivo in near-real time. We applied this new model to quantify OS after exposure to a range of environmental conditions with high resolution and provided quantification both of compound- and tissue-specific ROS-induced toxicity., Discussion: Our model has an extremely diverse range of potential applications not only for biomonitoring of toxicants in aqueous environments, but also in biomedicine for identifying ROS-mediated mechanisms involved in the progression of a number of important human diseases, including cancer., (Copyright © 2019. Published by Elsevier Ltd.)
- Published
- 2019
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44. Cardiovascular Effects and Molecular Mechanisms of Bisphenol A and Its Metabolite MBP in Zebrafish.
- Author
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Brown AR, Green JM, Moreman J, Gunnarsson LM, Mourabit S, Ball J, Winter MJ, Trznadel M, Correia A, Hacker C, Perry A, Wood ME, Hetheridge MJ, Currie RA, and Tyler CR
- Subjects
- Animals, Child, Estrogens, Humans, Phenols, Benzhydryl Compounds, Zebrafish
- Abstract
The plastic monomer bisphenol A (BPA) is one of the highest production volume chemicals in the world and is frequently detected in wildlife and humans, particularly children. BPA has been associated with numerous adverse health outcomes relating to its estrogenic and other hormonal properties, but direct causal links are unclear in humans and animal models. Here we simulated measured (1×) and predicted worst-case (10× ) maximum fetal exposures for BPA, or equivalent concentrations of its metabolite MBP, using fluorescent reporter embryo-larval zebrafish, capable of quantifying Estrogen Response Element (ERE) activation throughout the body. Heart valves were primary sites for ERE activation by BPA and MBP, and transcriptomic analysis of microdissected heart tissues showed that both chemicals targeted several molecular pathways constituting biomarkers for calcific aortic valve disease (CAVD), including extra-cellular matrix (ECM) alteration. ECM collagen deficiency and impact on heart valve structural integrity were confirmed by histopathology for high-level MBP exposure, and structural defects (abnormal curvature) of the atrio-ventricular valves corresponded with impaired cardiovascular function (reduced ventricular beat rate and blood flow). Our results are the first to demonstrate plausible mechanistic links between ERE activation in the heart valves by BPA's reactive metabolite MBP and the development of valvular-cardiovascular disease states.
- Published
- 2019
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45. Spheroid Size Does not Impact Metabolism of the β-blocker Propranolol in 3D Intestinal Fish Model.
- Author
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Langan LM, Owen SF, Trznadel M, Dodd NJF, Jackson SK, Purcell WM, and Jha AN
- Abstract
Compared to two-dimensional (2D) cell culture, cellular aggregates or spheroids (3D) offer a more appropriate alternative in vitro system where individual cell-cell communication and micro-environment more closely represent the in vivo organ; yet we understand little of the physiological conditions at this scale. The relationship between spheroid size and oxygen microenvironment, an important factor influencing the metabolic capacity of cells, was first established using the fish intestine derived RTgutGC cell line. Subsequently, pharmaceutical metabolism (Propranolol), as determined by high performance liquid chromatography, in this intestinal model was examined as a function of spheroid size. Co-efficient of variation between spheroid size was below 12% using the gyratory platform method, with the least variation observed in the highest cell seeding density. The viable, high oxygen micro-environment of the outer rim of the spheroid, as determined by electron paramagnetic resonance (EPR) oximetry, decreased over time, and the hypoxic zone increased as a function of spheroid size. Despite a trend of higher metabolism in smaller spheroids, the formation of micro-environments (quiescent, hypoxic or anoxic) did not significantly affect metabolism or function of an environmentally relevant pharmaceutical in this spheroid model.
- Published
- 2018
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46. Estrogenic Mechanisms and Cardiac Responses Following Early Life Exposure to Bisphenol A (BPA) and Its Metabolite 4-Methyl-2,4-bis( p-hydroxyphenyl)pent-1-ene (MBP) in Zebrafish.
- Author
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Moreman J, Takesono A, Trznadel M, Winter MJ, Perry A, Wood ME, Rogers NJ, Kudoh T, and Tyler CR
- Subjects
- Animals, Estrogens, Humans, Phenols, Benzhydryl Compounds, Zebrafish
- Abstract
Environmental exposure to Bisphenol A (BPA) has been associated with a range of adverse health effects, including on the cardiovascular system in humans. Lack of agreement on its mechanism(s) of action likely stem from comparisons between in vivo and in vitro test systems and potential multiple effects pathways. In rodents, in vivo, metabolic activation of BPA produces 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), which is reported to be up to 1000 times more potent as an estrogen than BPA. We investigated the estrogenic effects and estrogen receptor signaling pathway(s) of BPA and MBP following early life exposure using a transgenic, estrogen responsive (ERE-TG) zebrafish and a targeted morpholino approach to knockdown the three fish estrogen receptor (ER) subtypes. The functional consequences of BPA exposure on the cardiovascular system of zebrafish larvae were also examined. The heart atrioventricular valves and the bulbus arteriosus were primary target tissues for both BPA and MBP in the ERE-TG zebrafish, and MBP was approximately 1000-fold more potent than BPA as an estrogen in these tissues. Estrogen receptor knockdown with morpholinos indicated that the estrogenic responses in the heart for both BPA and MBP were mediated via an estrogen receptor 1 (esr1) dependent pathway. At the highest BPA concentration tested (2500 μg/L), alterations in the atrial:ventricular beat ratio indicated a functional impact on the heart of 5 days post fertilization (dpf) larvae, and there was also a significantly reduced heart rate in these larvae at 14 dpf. Our findings indicate that some of the reported adverse effects on heart function associated with BPA exposure (in mammals) may act through an estrogenic mechanism, but that fish are unlikely to be susceptible to adverse effects on heart development for environmentally relevant exposures.
- Published
- 2018
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47. Early life exposure to ethinylestradiol enhances subsequent responses to environmental estrogens measured in a novel transgenic zebrafish.
- Author
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Green JM, Lange A, Scott A, Trznadel M, Wai HA, Takesono A, Brown AR, Owen SF, Kudoh T, and Tyler CR
- Subjects
- Animals, Animals, Genetically Modified metabolism, Benzhydryl Compounds metabolism, Estrogens adverse effects, Estrogens metabolism, Estrogens physiology, Ethinyl Estradiol metabolism, Genistein metabolism, Phenols metabolism, Water Pollutants, Chemical adverse effects, Zebrafish metabolism, Environmental Exposure adverse effects, Ethinyl Estradiol adverse effects, Zebrafish growth & development
- Abstract
Estrogen plays fundamental roles in a range of developmental processes and exposure to estrogen mimicking chemicals has been associated with various adverse health effects in both wildlife and human populations. Estrogenic chemicals are found commonly as mixtures in the environment and can have additive effects, however risk analysis is typically conducted for single-chemicals with little, or no, consideration given for an animal's exposure history. Here we developed a transgenic zebrafish with a photoconvertable fluorophore (Kaede, green to red on UV light exposure) in a skin pigment-free mutant element (ERE)-Kaede-Casper model and applied it to quantify tissue-specific fluorescence biosensor responses for combinations of estrogen exposures during early life using fluorescence microscopy and image analysis. We identify windows of tissue-specific sensitivity to ethinylestradiol (EE2) for exposure during early-life (0-5 dpf) and illustrate that exposure to estrogen (EE2) during 0-48 hpf enhances responsiveness (sensitivity) to different environmental estrogens (EE2, genistein and bisphenol A) for subsequent exposures during development. Our findings illustrate the importance of an organism's stage of development and estrogen exposure history for assessments on, and possible health risks associated with, estrogen exposure.
- Published
- 2018
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48. Acute Toxicity, Teratogenic, and Estrogenic Effects of Bisphenol A and Its Alternative Replacements Bisphenol S, Bisphenol F, and Bisphenol AF in Zebrafish Embryo-Larvae.
- Author
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Moreman J, Lee O, Trznadel M, David A, Kudoh T, and Tyler CR
- Subjects
- Animals, Estrogens, Humans, Larva, Zebrafish, Benzhydryl Compounds toxicity, Phenols toxicity, Sulfones toxicity, Teratogens toxicity
- Abstract
Bisphenol A (BPA), a chemical incorporated into plastics and resins, has estrogenic activity and is associated with adverse health effects in humans and wildlife. Similarly structured BPA analogues are widely used but far less is known about their potential toxicity or estrogenic activity in vivo. We undertook the first comprehensive analysis on the toxicity and teratogenic effects of the bisphenols BPA, BPS, BPF, and BPAF in zebrafish embryo-larvae and an assessment on their estrogenic mechanisms in an estrogen-responsive transgenic fish Tg(ERE:Gal4ff)(UAS:GFP). The rank order for toxicity was BPAF > BPA > BPF > BPS. Developmental deformities for larval exposures included cardiac edema, spinal malformation, and craniofacial deformities and there were distinct differences in the effects and potencies between the different bisphenol chemicals. These effects, however, occurred only at concentrations between 1.0 and 200 mg/L which exceed those in most environments. All bisphenol compounds induced estrogenic responses in Tg(ERE:Gal4ff)(UAS:GFP) zebrafish that were inhibited by coexposure with ICI 182 780, demonstrating an estrogen receptor dependent mechanism. Target tissues included the heart, liver, somite muscle, fins, and corpuscles of Stannius. The rank order for estrogenicity was BPAF > BPA = BPF > BPS. Bioconcentration factors were 4.5, 17.8, 5.3, and 0.067 for exposure concentrations of 1.0, 1.0, 0.10, and 50 mg/L for BPA, BPF, BPAF, and BPS, respectively. We thus show that these BPA alternatives induce similar toxic and estrogenic effects to BPA and that BPAF is more potent than BPA, further highlighting health concerns regarding the use of BPA alternatives.
- Published
- 2017
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49. High-Content and Semi-Automated Quantification of Responses to Estrogenic Chemicals Using a Novel Translucent Transgenic Zebrafish.
- Author
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Green JM, Metz J, Lee O, Trznadel M, Takesono A, Brown AR, Owen SF, Kudoh T, and Tyler CR
- Subjects
- Animals, Estrogens metabolism, Estrone metabolism, Zebrafish Proteins genetics, Animals, Genetically Modified, Zebrafish metabolism
- Abstract
Rapid embryogenesis, together with genetic similarities with mammals, and the desire to reduce mammalian testing, are major incentives for using the zebrafish model in chemical screening and testing. Transgenic zebrafish, engineered for identifying target gene expression through expression of fluorophores, have considerable potential for both high-content and high-throughput testing of chemicals for endocrine activity. Here we generated an estrogen responsive transgenic zebrafish model in a pigment-free "Casper" phenotype, facilitating identification of target tissues and quantification of these responses in whole intact fish. Using the ERE-GFP-Casper model we show chemical type and concentration dependence for green fluorescent protein (GFP) induction and both spatial and temporal responses for different environmental estrogens tested. We also developed a semiautomated (ArrayScan) imaging and image analysis system that we applied to quantify whole body fluorescence responses for a range of different estrogenic chemicals in the new transgenic zebrafish model. The zebrafish model developed provides a sensitive and highly integrative system for identifying estrogenic chemicals, their target tissues and effect concentrations for exposures in real time and across different life stages. It thus has application for chemical screening to better direct health effects analysis of environmental estrogens and for investigating the functional roles of estrogens in vertebrates.
- Published
- 2016
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50. Novel insights into CB1 cannabinoid receptor signaling: a key interaction identified between the extracellular-3 loop and transmembrane helix 2.
- Author
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Marcu J, Shore DM, Kapur A, Trznadel M, Makriyannis A, Reggio PH, and Abood ME
- Subjects
- Amino Acid Sequence, Benzoxazines pharmacology, Binding, Competitive drug effects, Cell Line, Cyclohexanols pharmacology, Energy Metabolism drug effects, Guanosine 5'-O-(3-Thiotriphosphate) metabolism, Humans, Immunosuppressive Agents pharmacology, Models, Chemical, Molecular Sequence Data, Morpholines pharmacology, Mutagenesis, Site-Directed, Naphthalenes pharmacology, Piperidines metabolism, Protein Conformation, Protein Structure, Secondary, Pyrazoles metabolism, Radioligand Assay, Receptor, Cannabinoid, CB1 agonists, Receptor, Cannabinoid, CB1 antagonists & inhibitors, Rimonabant, Signal Transduction drug effects, Receptor, Cannabinoid, CB1 drug effects
- Abstract
Activation of the cannabinoid CB1 receptor (CB1) is modulated by aspartate residue D2.63(176) in transmembrane helix (TMH) 2. Interestingly, D2.63 does not affect the affinity for ligand binding at the CB1 receptor. Studies in class A G protein-coupled receptors have suggested an ionic interaction between residues of TMH2 and 7. In this report, modeling studies identified residue K373 in the extracellular-3 (EC-3) loop in charged interactions with D2.63. We investigated this possibility by performing reciprocal mutations and biochemical studies. D2.63(176)A, K373A, D2.63(176)A-K373A, and the reciprocal mutant with the interacting residues juxtaposed D2.63(176)K-K373D were characterized using radioligand binding and guanosine 5'-3-O-(thio)triphosphate functional assays. None of the mutations resulted in a significant change in the binding affinity of N-(piperidiny-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A) or (-)-3cis -[2-hydroxyl-4-(1,1-dimethyl-heptyl)phenyl]-trans-4-[3-hydroxyl-propyl] cyclohexan-1-ol (CP55,940). Modeling studies indicated that binding-site interactions and energies of interaction for CP55,940 were similar between wild-type and mutant receptors. However, the signaling of CP55,940, and (R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]-pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthalenyl)-methanone mesylate (WIN55,212-2) was impaired at the D2.63(176)A-K373A and the single-alanine mutants. In contrast, the reciprocal D2.63(176)K-K373D mutant regained function for both CP55,940 and WIN55,212-2. Computational results indicate that the D2.63(176)-K373 ionic interaction strongly influences the conformation(s) of the EC-3 loop, providing a structure-based rationale for the importance of the EC-3 loop to signal transduction in CB1. The putative ionic interaction results in the EC-3 loop pulling over the top (extracellular side) of the receptor; this EC-3 loop conformation may serve protective and mechanistic roles. These results suggest that the ionic interaction between D2.63(176) and K373 is important for CB1 signal transduction.
- Published
- 2013
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