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1. miR135a administration ameliorates brain ischemic damage by preventing TRPM7 activation during brain ischemia.

Author

Cepparulo, P., Brancaccio, P., Sirabella, R., Anzilotti, S., Guida, N., Laudati, G., Valsecchi, V., Vinciguerra, A., Viscardi, V., D'Esposito, L., Formisano, L., Annunziato, L., Pignataro, G., and Cuomo, O.

Subjects
CEREBRAL ischemia, BRAIN damage, ARTERIAL occlusions, CEREBRAL arteries, THERAPEUTICS
Abstract

Background: miRNA‐based strategies have recently emerged as a promising therapeutic approach in several neurodegenerative diseases. Unregulated cation influx is implicated in several cellular mechanisms underlying neural cell death during ischemia. The brain constitutively active isoform of transient receptor potential melastatin 7 (TRPM7) represents a glutamate excitotoxicity‐independent pathway that significantly contributes to the pathological Ca2+ overload during ischemia. Aims: In the light of these premises, inhibition of TRPM7 may be a reasonable strategy to reduce ischemic injury. Since TRPM7 is a putative target of miRNA135a, the aim of the present paper was to evaluate the role played by miRNA135a in cerebral ischemia. Therefore, the specific objectives of the present paper were: (1) to evaluate miR135a expression in temporoparietal cortex of ischemic rats; (2) to investigate the effect of the intracerebroventricular (icv) infusion of miR135a on ischemic damage and neurological functions; and (3) to verify whether miR135a effects may be mediated by an alteration of TRPM7 expression. Methods: miR135a expression was evaluated by RT‐ PCR and FISH assay in temporoparietal cortex of ischemic rats. Ischemic volume and neurological functions were determined in rats subjected to transient middle cerebral artery occlusion (tMCAo) after miR135a intracerebroventricular perfusion. Target analysis was performed by Western blot. Results: Our results demonstrated that, in brain cortex, 72 h after ischemia, miR135a expression increased, while TRPM7 expression was parallelly downregulated. Interestingly, miR135a icv perfusion strongly ameliorated the ischemic damage and improved neurological functions, and downregulated TRPM7 protein levels. Conclusions: The early prevention of TRPM7 activation is protective during brain ischemia. [ABSTRACT FROM AUTHOR]

Published
2024
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2. miR135a administration ameliorates brain ischemic damage by preventing TRPM7 activation during brain ischemia

Author

Cepparulo, P., primary, Brancaccio, P., additional, Sirabella, R., additional, Anzilotti, S., additional, Guida, N., additional, Laudati, G., additional, Valsecchi, V., additional, Vinciguerra, A., additional, Viscardi, V., additional, D'Esposito, L., additional, Formisano, L., additional, Annunziato, L., additional, Pignataro, G., additional, and Cuomo, O., additional

Published
2023
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8. Regulated assembly of a supramolecular centrosome scaffold in vitro

Author

Woodruff, J. B., primary, Wueseke, O., additional, Viscardi, V., additional, Mahamid, J., additional, Ochoa, S. D., additional, Bunkenborg, J., additional, Widlund, P. O., additional, Pozniakovsky, A., additional, Zanin, E., additional, Bahmanyar, S., additional, Zinke, A., additional, Hong, S. H., additional, Decker, M., additional, Baumeister, W., additional, Andersen, J. S., additional, Oegema, K., additional, and Hyman, A. A., additional

Published
2015
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9. Occurrence of polychlorobiphenyls in buffalo mozzarella cheese from Campania (Italy)

Author

Cirillo, T, Viscardi, V, Farina, A, Fasano, E, Del Prete, U, and Amodio Cocchieri, R

Abstract

Buffalo milk and mozzarella cheese produced in the Caserta and Salerno areas in Campania region have been investigated on the presence and the levels of polychlorobiphenyls (PCBs). Seven congeners, six non dioxin-like (NDL-PCBs nos. 28, 52, 101, 138, 153 and 180) and one dioxin-like (DL-PCB n. 118), were detected. PCBs were found at detectable levels in the 83% of the buffalo milk and in the 100% of the mozzarella cheese samples from Caserta; in those from Salerno the prevalence of contamination was 77% for milk and 73% for mozzarellas, respectively. The NDL-PCB content of mozzarellas collected in Caserta was significantly higher than that found in those from Salerno. The more diffuse congeners were PCB 28, 138 and 153 both in milk and in mozzarella cheese; PCB 118 contributed to the total PCB content for the 7% in milk and 2-3% in mozzarella cheese. On the basis of the Italian annual average consumption the contribution of mozzarella to the daily dietary intake of NDL-PCB can vary between 0.41 and 21.33 ng kg-1 bw, median value of 3.66 ng kg-1 bw. The levels of contamination in milk and dairies analyzed are similar or quite lower than those found in other European countries., Journal of Preventive Medicine and Hygiene, Vol 49, No 4 (2008)

Published
2008
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10. Acquacoltura in Italia, un modello integrato di verifica di qualità del prodotto

Author

DE GIUSTI, M, AMODIO COCCHIERI, R, DE VITO, Elisabetta, Grasso, G. M., Ortaggi, G, Reali, D, Ricciardi, G, ROMANO SPICA, V, GRUPPO COLLABORATORE TUFI D, BOCCIA A., Fuscoletti, M, DEL CIMMUTO, A, Cirillo, T, Viscardi, V, Langiano, Elisa, Lanni, L, Torosantucci, L, Fanelli, I, Giuliano, A, Pinto, B, Garritano, S, Boccia, S, Orsini, M, and Marinelli, L.

Subjects
Acquacoltura, Microbiologia, Policlorobifenili (PCB), EDC, OGM
Published
2007

11. Acquacoltura in Italia, un modello integrato di verifica di qualità del prodotto

Author

DE GIUSTI, Maria, AMODIO COCCHIERI, R., DE VITO, E., Grasso, G. M., Ortaggi, G., Reali, D., Ricciardi, G., ROMANO SPICA, V., Boccia, Antonio, Tufi, Daniela, Fuscoletti, M., DEL CIMMUTO, Angela, Cirillo, T., Viscardi, V., Langiano, E., Lanni, L., Torosantucci, L., Fanelli, L., Giuliano, A., Pinto, B., Garritano, S., Boccia, S., Orsini, M., and Marinelli, L.

Subjects
Acquacoltura, Microbiologia, OGM, Policlorobifenili, EDC
Published
2007

13. Abstracts

Author

Barthelemy, O., primary, Silvain, J., additional, Brieger, D., additional, Bellemain-Appaix, A., additional, Cayla, G., additional, Beygui, F., additional, Lancar, R., additional, Collet, J. P., additional, Mercadier, A., additional, Montalescot, G., additional, Cha, K. S., additional, Nam, Y. H., additional, Kim, J. H., additional, Park, S. Y., additional, Park, T. H., additional, Kim, M. H., additional, Kim, Y. D., additional, Lee, H. C., additional, Ahn, M. S., additional, Hong, T. J., additional, Blanco, R., additional, Blanco, F., additional, Szarfer, J., additional, Garcia Escudero, A., additional, Gigena, G., additional, Gagliardi, J., additional, Rodriguez, A., additional, Sarmiento, R., additional, Affatatto, S., additional, Riccitelli, M., additional, Petris, A., additional, Datcu, M. D., additional, Pop, C., additional, Radoi, M., additional, Arsenescu-Georgescu, C., additional, Petrescu, I., additional, Petrescu, L., additional, Serban, L., additional, Nechita, E., additional, Tatu-Chitoiu, G., additional, Dorobantu, M., additional, Benedek, I., additional, Craiu, E., additional, Sinescu, C., additional, Ionescu, D. D., additional, Ginghina, C., additional, Minescu, B., additional, Izzo, A., additional, Mantovani, P., additional, Tomasi, L., additional, Dall'oglio, L., additional, Bonatti, S., additional, Rosiello, R., additional, Romano, M., additional, Agostini, F., additional, Zanini, R., additional, Zhao, Z. Y., additional, Wu, Y. J., additional, Li, J. J., additional, Yany, Y. J., additional, Qian, H. Y., additional, Tang, Y. D., additional, Timoteo, A. T., additional, Toste, A., additional, Lousinha, A., additional, Ramos, R., additional, Oliveira, J. A., additional, Ferreira, M. L., additional, Ferreira, R. C., additional, Cabades, C., additional, Diez Gil, J. L., additional, Aguar, P., additional, Sanmiguel, D., additional, Lopez-March, A., additional, Marmol, R., additional, Guerra, L., additional, Girbes, V., additional, Ferrando, J., additional, Rincon De Arellano, A., additional, Patricio, L., additional, Blondal, M., additional, Ainla, T., additional, Marandi, T., additional, Eha, J., additional, Oliveira, M. M., additional, Silva, M. N., additional, Cunha, P. S., additional, Feliciano, J., additional, Silva, S., additional, Kanovsky, J., additional, Kala, P., additional, Parenica, J., additional, Poloczek, M., additional, Prymusova, K., additional, Kubkova, L., additional, Spinar, J., additional, Olinic, D., additional, Homorodean, C., additional, Ober, M., additional, Olinic, M., additional, Andrioaia, C., additional, Condac, A., additional, Masmoudi, M., additional, Berdaoui, B., additional, Labidi, S., additional, Tapia Ballesteros, C., additional, Hernandez Luis, C., additional, Sandin, M. G., additional, Vegas, J. M., additional, Andion, R., additional, Martinez, N., additional, Gonzalez, I. A., additional, Alvarado, M., additional, Amat, I. J., additional, San Roman, J. A., additional, Garcia Gonzalez, M. J., additional, Arroyo Ucar, E., additional, Hernandez Garcia, C., additional, Dorta Martin, M., additional, Marrero Rodriguez, F., additional, Dragu, R., additional, Kapeliovich, M., additional, Hammerman, H., additional, Silva, D., additional, Cortez-Dias, N., additional, Jorge, C., additional, Silva Marques, J., additional, Carilho Ferreira, P., additional, Robalo Martins, S., additional, Almeida Ribeiro, M., additional, Calisto, C., additional, Fiuza, M., additional, Lopes, M. G., additional, Milicevic, P., additional, Panic, M., additional, Stankovic, I., additional, Milicevic, D., additional, Kalezic, T., additional, Kafedzic, S., additional, Ilic, I., additional, Cerovic, M., additional, Putnikovic, B., additional, Neskovic, A., additional, Rott, D., additional, Leibowitz, D., additional, Monhart, Z., additional, Reissigova, J., additional, Grunfeldova, H., additional, Jansky, P., additional, Valente, B., additional, Villanueva Benito, I., additional, Solla, I., additional, Paredes, E., additional, Diaz Castro, O., additional, Calvo, F., additional, Baz, J. A., additional, Iniguez, A., additional, Aleksova, A., additional, Gerloni, R., additional, Belfiore, R., additional, Carriere, C., additional, Barbati, G., additional, Fabris, E., additional, Possa, F., additional, Nait, D., additional, Milo, M., additional, Sinagra, G., additional, Marques, N., additional, Mimoso, J., additional, Gomes, V., additional, Agra Bermejo, R. M., additional, Emad Abu Assi, E. A. A., additional, Sergio Raposeiras Roubin, S. R. R., additional, Pilar Cabanas Grandio, P. C. G., additional, Carlos Pena Gil, C. P. G., additional, Jose Maria Garcia Acuna, J. M. G. A., additional, Jose Ramon Gonzalez Juanatey, J. R. G. J., additional, Daly, M. J., additional, Scott, P., additional, Owens, C. G., additional, Tomlin, A., additional, Smith, B., additional, Adgey, A. A. J., additional, Alvarez-Contreras, L. R., additional, Juarez, U., additional, Altamirano, A., additional, Arias, A., additional, Alvarez-San Gabriel, A., additional, Gonzalez-Pacheco, H., additional, Martinez-Sanchez, C., additional, Rahnavardi, M., additional, Keshtkar-Jahromi, M., additional, Vakili, H., additional, Gholamin, S., additional, Razavi, S. M., additional, Gilis-Januszewski, T., additional, Mellwig, K.- P., additional, Wiemer, M., additional, Gilis-Januszewski, J., additional, Peterschroeder, A., additional, Koerfer, J., additional, Horstkotte, D., additional, Vrsalovic, M., additional, Getaldic, B., additional, Vrkic, N., additional, Pintaric, H., additional, Khan, S., additional, Wasan, B., additional, Moretti, L., additional, Grossi, P., additional, Silenzi, S., additional, Testa, M., additional, Candelori, L., additional, Clementi, L. N., additional, Forlini, M., additional, Lando, L., additional, Pezzuoli, M. L., additional, Corradetti, P., additional, Leurent, G., additional, Pennec, P. Y., additional, Filippi, E., additional, Moquet, B., additional, Hacot, J. P., additional, Druelles, P., additional, Rialan, A., additional, Rouault, G., additional, Coudert, I., additional, Le Breton, H., additional, Gevaert, S., additional, Tromp, F., additional, Vandecasteele, E., additional, De Somer, F., additional, Van Belleghem, Y., additional, Bouchez, S., additional, Martens, F., additional, Herck, I., additional, De Pauw, M., additional, Ludka, O., additional, Sepsi, M., additional, Miklik, R., additional, Dusek, L., additional, Tomcikova, D., additional, Garcia-Acuna, J. M., additional, Aguiar-Souto, P., additional, Raposeiras Roubin, S., additional, Agra-Bermejo, R., additional, Jacquet, M., additional, Abu-Assi, E., additional, Gonzalez-Juanatey, J. R., additional, Ibatov, A., additional, Labrova, R., additional, Karlik, R., additional, Lokaj, P., additional, She, Q., additional, Deng, S. B., additional, Huang, S. H., additional, Gu, L. J., additional, Rong, J. I. A. N., additional, Wu, Z. K., additional, Li, Y., additional, Zhang, J., additional, Parascan, L., additional, Campanile, A., additional, Spinelli, L., additional, Santulli, G., additional, Ciccarelli, M., additional, De Gennaro, S., additional, Assante Di Panzillo, E., additional, Trimarco, B., additional, Iaccarino, G., additional, Bobescu, E., additional, Datcu, G., additional, Dobreanu, D., additional, Doka, B., additional, Charniot, J.- C., additional, Cosson, C., additional, Albertini, J. P., additional, Bittar, R., additional, Giral, P., additional, Cherfils, C., additional, Guillerm, E., additional, Bonnefont-Rousselot, D., additional, Rusali, A., additional, Cojocaru, L., additional, Parepa, I., additional, Koizumi, T., additional, Iida, S., additional, Sato, J., additional, Kikutani, T., additional, Muramatsu, T., additional, Nishimura, S., additional, Komiyama, N., additional, Lee, W. P., additional, Ong, B. B., additional, Haralambos, K., additional, Townsend, D., additional, Rees, J. A. E., additional, Williams, E. J., additional, Halcox, J. P., additional, Mcdowell, I., additional, Damjanovic, M., additional, Koracevic, G., additional, Djordjevic-Radojkovic, D., additional, Pavlovic, M., additional, Krstic, N., additional, Ciric-Zdravkovic, S., additional, Stojkovic, A., additional, Perisic, Z., additional, Apostolovic, S., additional, Faustino, A., additional, Seca, L., additional, Barra, S., additional, Caetano, F., additional, Providencia, R., additional, Silva, J., additional, Gomes, P., additional, Costa, G., additional, Costa, M., additional, Leitao-Marques, A., additional, Volkova, A. L., additional, Arutyunov, G. P., additional, Bylova, N. A., additional, Dayter, I. I., additional, Jao, Y. T. F. N., additional, Fang, C. C., additional, Chen, Y., additional, Yu, C. L., additional, Wang, S. P., additional, Valencia, J., additional, Perez-Berbel, P., additional, Ruiz-Nodar, J. M., additional, Pineda, J., additional, Bordes, P., additional, Quintanilla, M., additional, Mainar, V., additional, Sogorb, F., additional, Santos, N., additional, Serrao, M., additional, Cafe, H., additional, Silva, B., additional, Oliveira, R., additional, Caires, G., additional, Drumond, A., additional, Araujo, J., additional, Providencia, R. A., additional, Gomes, P. L., additional, Pais, J. R., additional, Mota, P., additional, Leitao-Marques, A. M., additional, Farhan, S., additional, Jarai, R., additional, Tentzeris, I., additional, Vogel, B., additional, Freynhofer, M. K., additional, Wojta, J., additional, Huber, K., additional, Poli, M., additional, Trambaiolo, P., additional, Corsi, F., additional, De Luca, M., additional, Mustilli, M., additional, Lukic, V., additional, Simonetti, M., additional, Ferraiuolo, G., additional, Lettino, M., additional, Casella, G., additional, Conte, M. R., additional, De Luca, L., additional, Geraci, G., additional, Ceravolo, R., additional, Pani, A., additional, Fradella, G., additional, Schratter, A., additional, Thiele, H., additional, Klemm, T., additional, Demmin, K., additional, Lehmann, D., additional, Mende, M., additional, Schuler, G., additional, Pittl, U., additional, Chernova, A., additional, Nikulina, S. U., additional, Naruke, T., additional, Inomata, T., additional, Yanagisawa, T., additional, Maekawa, E., additional, Mizutani, T., additional, Shinagawa, H., additional, Nishii, M., additional, Takeuchi, I., additional, Takehana, H., additional, Izumi, T., additional, Paulo, C., additional, Mascarenhas, J., additional, Patacho, M., additional, Pimenta, J., additional, Bettencourt, P., additional, Nardai, S., additional, Szabo, G. Y., additional, Berta, B., additional, Edes, I., additional, Merkely, B., additional, Delgado Silva, J., additional, Baptista, R., additional, Faria, R., additional, Trigo, J., additional, Gago, P., additional, Gheorghe, G., additional, Nanea, I. T., additional, Cristea, A., additional, Almarichi, S., additional, Martins, H., additional, Saraiva, F., additional, Jorge, E., additional, Mendes, P. L., additional, Monteiro, P., additional, Costa, S., additional, Franco, F., additional, Providencia, L. A., additional, Nanea, T., additional, Gheorghe, G. S., additional, Visan, S., additional, Paun, N., additional, Gaber, R., additional, Delewi, R., additional, Nijveldt, R., additional, De Bruin, H. A., additional, Hirsch, A., additional, Van Der Laan, A., additional, Bouma, B. J., additional, Tijssen, J. P. G., additional, Van Rossum, A. C., additional, Zijlstra, F., additional, Piek, J. J., additional, Rus, H., additional, Donea, M., additional, Ciurea, C., additional, Ifteni, G., additional, Casolo, G., additional, Chioccioli, M., additional, Magnacca, M., additional, Del Meglio, J., additional, Comella, A., additional, Baratto, M., additional, Lera, J., additional, Salvadori, L., additional, Tessa, C., additional, Vignali, C., additional, Keca, Z., additional, Momcilov Popin, T., additional, Panic, G., additional, White, R., additional, Mateen, F., additional, Weaver, A., additional, Agmon, Y., additional, Okisheva, E., additional, Tsaregorodtsev, D., additional, Sulimov, V., additional, Amat Santos, I. J., additional, Hernandez, C., additional, Tapia, C., additional, Campo, A., additional, Fredman, D., additional, Svensson, L., additional, Rosenqvist, M., additional, Tadel-Kocjancic, S., additional, Radsel, P., additional, Knafelj, R., additional, Gorjup, V., additional, Noc, M., additional, Zima, E., additional, Jenei, Z. S., additional, Kovacs, E., additional, Osztheimer, I., additional, Molnar, L., additional, Horvath, A., additional, Becker, D., additional, Geller, L., additional, Maggi, R., additional, Furukawa, T., additional, Viscardi, V., additional, Brignole, M., additional, Leal, S. R. N., additional, Dores, H., additional, Rosario, I., additional, Monge, J., additional, Carvalho, M. J., additional, Arroja, I., additional, Leitao, A., additional, Fonseca, C., additional, Aleixo, A., additional, Silva, A., additional, Keuleers, S., additional, Herijgers, P., additional, Herregods, M. C., additional, Budts, W., additional, Dubois, C., additional, Meuris, B., additional, Verhamme, P., additional, Flameng, W., additional, Van De Werf, F., additional, Adriaenssens, T., additional, Badran, H., additional, Elnoamany, M., additional, Lolah, T., additional, Olariu, C., additional, Macarie, C., additional, Mollik, M. A. H., additional, Hassan, A. I., additional, Paul, T. K., additional, Haque, M. Z., additional, Jahan, R., additional, Rahmatullah, M., additional, Khatun, M. A., additional, Rahman, M. T., additional, Chowdhury, M. H., additional, Bustamante Munguira, J., additional, Tamayo, E., additional, Garcia-Cuenca, I., additional, Bustamante, E., additional, Gualis, J., additional, Gomez-Martinez, M. L., additional, Florez, S., additional, Gomez-Herreras, J. I., additional, Ramirez Rodriguez, R., additional, Ramirez Rodriguez, A. M., additional, Garcia-Bello, M. A., additional, Hernadez Ortega, E., additional, Caballero Dorta, E., additional, Garcia Quintana, A., additional, Piro Mastraccio, V., additional, Medina Fernandez Aceytuno, A., additional, Assanelli, E., additional, De Metrio, M., additional, Rubino, M., additional, Lauri, G., additional, Cabiati, A., additional, Campodonico, J., additional, Grazi, M., additional, Moltrasio, M., additional, Marana, I., additional, Marenzi, G., additional, Lovlien, M., additional, Schei, B., additional, Picon-Heras, R., additional, Acebal, C., additional, Garcia Rubira, J. C., additional, Vivas Balcones, D., additional, Nunez-Gil, I., additional, Ruiz-Mateos, B., additional, Ibanez, B., additional, Fernandez-Ortiz, A., additional, Vintila, V. D., additional, Enescu, O. A., additional, Stoicescu, C. I., additional, Udroiu, C., additional, Cinteza, M., additional, Tatu - Chitoiu, G., additional, Vinereanu, D., additional, Fresco, C., additional, De Biasio, M., additional, Muser, D., additional, Sappa, R., additional, Morocutti, G., additional, Bernardi, G., additional, Proclemer, A., additional, Fontanella, B., additional, Affatato, A., additional, Ciccarese, C., additional, Sacchini, M., additional, Volpini, M., additional, Bianchetti, F., additional, Verzura, G., additional, Dei Cas, L., additional, Pudil, R., additional, Blaha, V., additional, Vojacek, J., additional, Paraskevaidis, I., additional, Ikonomidis, I., additional, Parissis, J., additional, Papadopoulos, C., additional, Stasinos, V., additional, Bistola, V., additional, Anastasiou-Nana, M., additional, Shochat, M., additional, Shotan, A., additional, Kazatsker, M., additional, Gurovich, V., additional, Asif, A., additional, Noiman, E., additional, Levy, Y., additional, Blondhaim, D., additional, Rabinovich, P., additional, Meisel, S., additional, Petrovic, S., additional, Glasnovic, J., additional, Tomasevic, M., additional, Sakac, D., additional, Obradovic, S., additional, Londono Sanchez, O., additional, Pacreu, S., additional, Torres, L., additional, Mihaylov, G., additional, Shaban, G. M., additional, Trendafilova, E., additional, Krasteva, V., additional, Mudrov, T. S., additional, Didon, J. P., additional, Panageas, V., additional, Vlachos, N., additional, Pernat, A., additional, Radan, I., additional, Mozina, H., additional, Pepi, P., additional, Cionini, F., additional, Baccaglioni, N., additional, Viertel, A., additional, Havers, J., additional, Ballard, G., additional, Groenefeld, G., additional, Branco, L. M., additional, Ferreira, L., additional, Fiarresga, A., additional, Lettieri, L., additional, Reggiani, A., additional, Juarez Prera, R., additional, Blanco Palacios, G., additional, Martin, A.- C., additional, Manzo Silberman, S., additional, Chaib, A., additional, Varenne, O., additional, Allouch, P., additional, Salengro, E., additional, Jegou, A., additional, Margot, O., additional, Spaulding, C., additional, Diego, A., additional, De Miguel, A., additional, Cuellas, C., additional, Fraile, E., additional, Martin, J., additional, Vega, B., additional, Bangueses, R., additional, Fernandez-Vazquez, F., additional, Perez De Prado, A., additional, Leal, S., additional, Correia, M. J., additional, Monge, J. C., additional, Abecasis, J., additional, Garcia-Garcia, C., additional, Subirana, I., additional, Sala, J., additional, Bruguera, J., additional, Valle, V., additional, Sanz, G., additional, Fiol, M., additional, Aros, F., additional, Marrugat, J., additional, Elosua, R., additional, Barra, S. N. C., additional, Leitao Marques, A., additional, Yang, Y. J., additional, Xu, B., additional, Song, G. Y., additional, G, R. L., additional, Aleksic, A., additional, Serpytis, P., additional, Rucinskas, K., additional, Kalinauskas, A., additional, Karvelyte, N., additional, Santos De Sousa, C. I., additional, Ferreira, S., additional, Calaca, J., additional, Lousada, N., additional, Palma Reis, R., additional, Gualandro, D. M., additional, Seguro, L. F. B. C., additional, Braga, F. G. M., additional, Silvestre, O. M., additional, Lage, R. L., additional, Fabri, J., additional, Oliveira, M. T., additional, Urbano Moral, J. A., additional, Torres Llergo, J., additional, Solanilla Rodriguez, R., additional, Sanchez Gonzalez, A., additional, Martinez Martinez, A., additional, Den Uil, C. A., additional, Lagrand, W. K., additional, Van Der Ent, M., additional, Jewbali, L. S. D., additional, Cheng, J. M., additional, Spronk, P. E., additional, Simoons, M. L., additional, Mornos, C., additional, Dragulescu, D., additional, Ionac, A., additional, Guardado, J., additional, Azevedo, O., additional, Fernandes, M., additional, Canario-Almeida, F., additional, Sanfins, V., additional, Pereira, A., additional, Almeida, J., additional, Kaplunova, V. U., additional, Belenkov, Y. N., additional, Privalova, E. V., additional, Fomin, A. A., additional, Suvorov, A. Y., additional, Goodkova, A., additional, Rubakova, M. G., additional, Kuznetsova, I. A., additional, Semernin, E. N., additional, Keshavarzi, F., additional, Kojuri, J., additional, Mikhailov, V. M., additional, Vezhenkova, I. V., additional, Goodkova, A. Y. A., additional, Pavlovic, I., additional, Schwarz, M., additional, Jakl, G., additional, Smetana, P., additional, Perkmann, T., additional, Mayr, A., additional, Mair, J., additional, Klug, G., additional, Schocke, M., additional, Trieb, T., additional, Jaschke, W., additional, Pachinger, O., additional, Metzler, B., additional, Bronze Carvalho, L., additional, Azevedo, J., additional, Andrade, M. L., additional, Relvas, M. J., additional, Coucello, J., additional, Morais, G., additional, Seabra, M., additional, Afamefule, F., additional, Luaces Mendez, M., additional, Teijeiro-Mestre, R., additional, Nunez-Gil, I. J., additional, Leco-Gil, N., additional, Madronal-Cerezo, E., additional, Zannin, I., additional, Ruiz, J., additional, Orynchak, M. A., additional, Vakalyuk, I. I., additional, Vakalyuk, I. 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Published
2010
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19. Telomeres and DNA damage checkpoints

Author

Hugo Cartagena-Lirola, Michela Clerici, Valeria Viscardi, Maria Pia Longhese, Viscardi, V, Clerici, M, Cartagena Lirola, H, and Longhese, M

Subjects
DNA Replication, DNA re-replication, DNA Repair, DNA repair, DNA damage, BIO/18 - GENETICA, Biology, Biochemistry, Genomic Instability, chemistry.chemical_compound, Telomere Homeostasis, Humans, Mec1, CHEK1, Telomerase, Genetics, Checkpoint, Tel1, General Medicine, Telomere, G2-M DNA damage checkpoint, chemistry, DNA mismatch repair, biological phenomena, cell phenomena, and immunity, DNA, DNA Damage
Abstract

In all eukaryotic organisms, interruptions in duplex DNA molecules elicit a DNA damage response, which includes activation of DNA repair machineries and surveillance mechanisms, known as DNA damage checkpoints. Telomeres and double-strand breaks (DSBs) share the common feature of being physical ends of chromosomes. However, unlike DSBs, telomeres do not activate the DNA damage checkpoints and are usually protected from end-to-end fusions and other processing events that normally promote repair of DNA breaks. This indicates that they are shielded from being recognized and processed as DSBs. On the other hand, chromosome ends resemble damaged DNA, as several factors required for DNA repair and checkpoint networks play important roles in telomere length maintenance. Due to the critical role of both DNA damage checkpoints and telomere homeostasis in maintaining genetic stability and in counteracting cancer development, the knowledge of their interconnections is essential for our understanding of these key cellular controls.

Published
2005

20. The Mec1p and Tel1p checkpoint kinases allow humanized yeast to tolerate chronic telomere dysfunctions by suppressing telomere fusions

Author

Maria Pia Longhese, Enea Gino Di Domenico, Cristina Auriche, Fiorentina Ascenzioni, Valeria Viscardi, Eric Gilson, di Domenico, E, Auriche, C, Viscardi, V, Longhese, M, Gilson, E, and Ascenzioni, F

Subjects
Checkpoints, Genome instability, Saccharomyces cerevisiae Proteins, Yeast, Telomere, Telomere fusion, Checkpoints, TEL1, MEC1, BIO/18 - GENETICA, Saccharomyces cerevisiae, Biology, Protein Serine-Threonine Kinases, Biochemistry, Genomic Instability, chemistry.chemical_compound, Humans, MEC1, Molecular Biology, Gene, Telomere fusion, Telomere-binding protein, Microbial Viability, Base Sequence, Checkpoint, Kinase, TEL1, Intracellular Signaling Peptides and Proteins, Cell Biology, G2-M DNA damage checkpoint, Cell cycle, Telomere, Molecular biology, Yeast, DNA-Binding Proteins, chemistry, Chromosomes, Fungal, DNA, DNA Damage
Abstract

In this work we report that budding yeasts carrying human-type telomeric repeats at their chromosome termini show a chronic activation of the Rad53-dependent DNA damage checkpoint pathway and a G2/M cell cycle delay. Furthermore, in the absence of either TEL1/ATM or MEC1/ATR genes, which encodes phosphatidylinositol 3-kinase-related kinases (PIKKs), we detected telomere fusions, whose appearance correlates with a reduced cell viability and a high rate of genome instability. Based on sequence analysis, telomere fusions occurred primarily between ultrashort telomeres. Microcolony formation assays argue against the possibility that fusion-containing cells are eliminated by PIKK-dependent signalling. These findings reveal that humanized telomeres in yeast cells are sensed as a chronically damaged DNA but do not greatly impair cell viability as long as the cells have a functional DNA damage checkpoint.

Published
2008

21. MRX-dependent DNA Damage Response to Short Telomeres

Author

Valeria Viscardi, Giovanna Lucchini, Diego Bonetti, Maria Pia Longhese, Hugo Cartagena-Lirola, Viscardi, V, Bonetti, D, Cartagena Lirola, H, Lucchini, G, and Longhese, M

Subjects
double-strand break, Saccharomyces cerevisiae Proteins, Base pair, DNA damage, Saccharomyces cerevisiae, BIO/18 - GENETICA, Models, Biological, MRX, Molecular Biology, biology, Tel1, Chromosome, Cell Biology, Articles, G2-M DNA damage checkpoint, Telomere, biology.organism_classification, Molecular biology, Transport protein, Cell biology, Protein Transport, MRX complex, Multiprotein Complexes, checkpoints, DNA Damage
Abstract

Telomere structure allows cells to distinguish the natural chromosome ends from double-strand breaks (DSBs). However, DNA damage response proteins are intimately involved in telomere metabolism, suggesting that functional telomeres may be recognized as DNA damage during a time window. Here we show by two different systems that short telomeres are recognized as DSBs during the time of their replication, because they induce a transient MRX-dependent DNA damage checkpoint response during their prolonged elongation. The MRX complex, which is recruited at telomeres under these conditions, dissociates from telomeres concomitantly with checkpoint switch off when telomeres reach a new equilibrium length. We also show that MRX recruitment to telomeres is sufficient to activate the checkpoint independently of telomere elongation. We propose that MRX can signal checkpoint activation by binding to short telomeres only when they become competent for elongation. Because full-length telomeres are refractory to MRX binding and the shortest telomeres are elongated of only a few base pairs per generation, this limitation may prevent unscheduled checkpoint activation during an unperturbed S phase.

Published
2007

22. The functions of budding yeast Sae2 in the DNA damage response require Mec1- and Tel1-dependent phosphorylation

Author

Valeria Viscardi, Giovanna Lucchini, Hugo Cartagena-Lirola, Maria Pia Longhese, Enrico Baroni, Baroni, E, Viscardi, V, Cartagena Lirola, H, Lucchini, G, and Longhese, M

Subjects
Spo11, Cell cycle checkpoint, Saccharomyces cerevisiae Proteins, DNA Repair, DNA repair, DNA damage, Ultraviolet Rays, Genes, Fungal, Molecular Sequence Data, BIO/18 - GENETICA, Saccharomyces cerevisiae, Protein Serine-Threonine Kinases, Fungal Proteins, Bleomycin, checkpoint, Mec1, CHEK1, Amino Acid Sequence, DNA, Fungal, Molecular Biology, Sae2, Alleles, biology, Base Sequence, phosphorylation, Cell Cycle, Tel1, DNA replication, Intracellular Signaling Peptides and Proteins, Cell Biology, G2-M DNA damage checkpoint, Endonucleases, Molecular biology, DNA Dynamics and Chromosome Structure, MRX complex, Amino Acid Substitution, biology.protein, Mutagenesis, Site-Directed, DNA Damage, Signal Transduction
Abstract

Genetic inheritance requires exceptional genetic stability over many generations of cells and organisms. To ensure that cells pass accurate copies of their genomes on to the next generation, evolution has overlaid the core cell cycle machinery with a series of surveillance pathways, termed checkpoints, that provide the cells with the capacity to survive genotoxic insults. These protective mechanisms are signal transduction pathways specialized in detecting abnormal DNA structures and in coordinating cell cycle progression with DNA repair. Their activation leads to cell cycle progression delay and concomitant activation of DNA repair pathways, thus preventing replication or segregation of damaged DNA molecules. The keystone of the DNA damage checkpoint is a protein kinase family related to phosphoinositide 3-kinase, among which are Saccharomyces cerevisiae Mec1 (48, 61, 90) and Tel1 (26, 52), Schizosaccharomyces pombe Rad3 (5), Drosophila melanogaster Mei-41 (29), and mammalian ATR (5) and ATM (72). These protein kinases respond to various stresses by phosphorylating key proteins, thus regulating numerous processes, depending on the spectra of their substrates (for reviews, see references 1 and 75). In particular, S. cerevisiae Mec1 and S. pombe Rad3, more closely related to human ATR, are the prototype transducers of the DNA damage and replication stress signals; they respond to UV damage, double-strand breaks (DSBs), and stalled replication forks. Conversely, yeast Tel1, similar to human ATM, is likely involved only in the response to DSBs (for reviews, see references 57 and 75). Tel1 and Mec1 also contribute to telomere length maintenance. In fact, TEL1 deletion causes marked telomere shortening in yeast (26, 52), and mec1 tel1 cells show more-dramatic telomere shortening than each single mutant, similar to that seen in cells lacking active telomerase (67). The absence of Tel1 does not affect either telomerase catalytic activity or binding to telomeric DNA of the Cdc13 protein, which mediates telomerase action (9, 83). However, when telomerase is artificially targeted to telomeres, their lengthening is at least as effective in mec1 tel1 as in wild-type cells, suggesting that Mec1 and Tel1 may act by recruiting to telomeres either telomerase or telomerase-activating factors (83). One characteristic of ATR-related proteins is their need for an accessory protein. Mec1 physically interacts with the checkpoint protein Ddc2 (also called Lcd1 or Pie1) (60, 69, 89), functionally related to Rad26 and ATRIP, which bind S. pombe Rad3 and human ATR, respectively (12, 20). Although the Mec1-Ddc2 complex plays a key role in the DNA damage checkpoint, full Mec1-dependent activation of downstream targets requires other factors, such as the Ddc1/Rad17/Mec3 and Rad24/Rfc2 to -5 complexes (for a review, see reference 42), presumed to be structure-specific DNA damage sensors based on their similarities to the proliferating cell nuclear antigen (PCNA) and its accessory factor replication factor C (RFC), respectively (7, 25, 46, 79). Once DNA perturbations are sensed, checkpoint signals are propagated through the protein kinases Chk1 and Rad53, which also undergo phosphorylation in response to DNA damage in a Mec1-dependent manner (70, 71). While Rad53 is required for proper response to DNA damage in all the cell cycle phases, Chk1 contributes only to the activation of the G2/M checkpoint in a Rad53-independent way (71). The DNA damage-sensing functions are then linked with the downstream effectors through DNA damage-specific or S-phase-specific mediators. In particular, while Rad9 is required to activate Rad53 in response to DNA damage by acting as a scaffold protein upon which Rad53 may autophosphorylate and self-activate (24, 73), Mrc1 seems to act as the Rad9 counterpart in activating Rad53 in response to DNA replication blocks (2, 58). Whereas human ATM plays a key role in responding to DSBs in human cells, S. cerevisiae Tel1 has only a secondary role in the DNA damage response. In fact, Tel1, which is primarily involved in telomere metabolism, seems to respond to unprocessed DSBs by controlling a checkpoint that becomes apparent only in the absence of Mec1, and converges with the canonical Mec1 pathway on the effector kinase Rad53 (84). A trimeric complex, known as MRN (Mre11-Rad50-Nbs1) in mammals and MRX (Mre11-Rad50-Xrs2) in S. cerevisiae, is a substrate for the ATM/Tel1 kinase. In fact, mammalian Mre11 and Nbs1 are phosphorylated in response to DNA damage, and their phosphorylation depends on ATM (21, 22, 39, 91, 93). This response is evolutionarily conserved, as DNA damage also stimulates Tel1-dependent phosphorylation of the S. cerevisiae Mre11 and Xrs2 proteins (15, 27). In both yeast and humans, this complex plays multiple roles in chromosome metabolism and DNA repair. It has been implicated in telomere maintenance, regulation of DNA replication, nonhomologous end joining, and meiotic DSB formation or resection (for reviews, see references 16, 62, and 86). Moreover, it may control DSB processing during mitotic homologous recombination, thus amplifying the checkpoint signal and stimulating the Mec1/Tel1 kinases (84). Finally, the MRX complex is involved in the S. cerevisiae checkpoint response as part of the DNA damage-sensing apparatus, since mre11Δ, rad50Δ, and xrs2Δ yeast cells are defective in S-phase checkpoint activation in response to DSB-inducing agents and hydroxyurea (HU) (15, 27). Some processes involving the MRX complex also require the SAE2/COM1 gene, whose loss-of-function alleles were originally identified together with the rad50s and mre11s separation-of-function alleles in a search for mutants whose meiotic products died if DSBs were made but could survive when meiotic recombination and reductional chromosome segregation were prevented by mutations inactivating the SPO11 gene (49, 65). The topoisomerase II-like Spo11 protein is necessary for the creation of meiotic DSBs, which are subjected to rapid resection of their 5′ strand termini, yielding molecules with 3′ single-stranded tails, presumably used to form strand exchange products during recombination (62). While the MRX complex participates in both the formation and the processing of DSBs at meiotic recombination hot spots, the Sae2 protein seems to participate only in DSB processing. In fact, in contrast to mrx-null alleles, which are unable to initiate meiotic DSBs, both sae2Δ and the rad50s and mre11s separation-of-function alleles were shown to allow SPO11-mediated DSB formation, but not single-strand endonucleolytic removal of Spo11 from the DNA ends, thus uncoupling cleavage of DNA strands from subsequent exonucleolytic resection (34). Since the MRX complex has nuclease activity, the lack of Sae2 might directly modify its in vivo nuclease function, and the rad50s allele might affect its ability to interact with Sae2, as previously suggested (66). Although Sae2, as well as the MRX complex, is dispensable for some mitotic homologous recombination processes requiring Rad52 and Rad51 (6, 32, 47, 82), several observations indicate that Sae2 may also have mitotic functions. (i) sae2Δ cells have been shown to be hypersensitive to the alkylating agent methyl methanesulfonate (MMS), and the fidelity of mitotic DSB repair in these cells has been shown to be affected (49, 66). (ii) Sae2, along with MRX, is also required for repair of mitotic hairpin-capped DSBs induced by inverted Alu sequences, indicating that Sae2 may participate in making protected DNA ends accessible to resection in mitotic cells also (40). (iii) A lack of Sae2 enhances Tel1-mediated Rad53 phosphorylation after DNA damage, and this enhancement requires the MRX complex, suggesting that sae2Δ cells may accumulate DNA lesions specifically sensed by the Tel1/MRX-dependent checkpoint (84). (iv) High levels of Sae2 not only cause telomere lengthening in a Tel1-dependent manner, but also accelerate the rebalancing of telomere length when sudden telomere elongation is induced by TEL1 overexpression, suggesting a role for Sae2 in unprotected telomeric end processing (87). We now show that the functions of Sae2 in DNA repair and recombination require the checkpoint pathway that responds to DNA damage during the mitotic cell cycle. Sae2, whose lack delays the recovery from checkpoint-mediated cell cycle arrest, undergoes Mec1- and Tel1-dependent phosphorylation both periodically during the unperturbed cell cycle and in response to DNA damage independently of cell cycle progression. Site-directed mutagenesis of the favored ATM/ATR phosphorylation sites indicates that they are essential not only for DNA damage-induced Sae2 phosphorylation but also for Sae2 functions in vivo.

Published
2004

23. Sudden telomere lengthening triggers a Rad53-dependent checkpoint in Saccharomyces cerevisiae

Author

Valeria Viscardi, M. Romano, Maria Pia Longhese, Giovanna Lucchini, Enrico Baroni, Viscardi, V, Baroni, E, Romano, M, Lucchini, G, and Longhese, M

Subjects
Telomerase, Cell cycle checkpoint, Saccharomyces cerevisiae Proteins, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Telomere-Binding Proteins, S. cerevisiae, Cell Cycle Proteins, BIO/18 - GENETICA, Protein Serine-Threonine Kinases, MRX, Fungal Proteins, checkpoint, Molecular Biology, Telomere-binding protein, Fungal protein, biology, Cell Cycle, Tel1, Intracellular Signaling Peptides and Proteins, Cell Biology, Articles, G2-M DNA damage checkpoint, Cell cycle, Telomere, biology.organism_classification, Endonucleases, Molecular biology, Genes, cdc, Checkpoint Kinase 2, Rad53, Mutation, DNA Damage
Abstract

Telomeres are specialized functional complexes that ensure chromosome stability by protecting chromosome ends from fusions and degradation and avoiding chromosomal termini from being sensed as DNA breaks. Budding yeast Tel1 is required both for telomere metabolism and for a Rad53-dependent checkpoint responding to unprocessed double-strand breaks. We show that overexpression of a GAL1-TEL1 fusion causes transient telomere lengthening and activation of a Rad53-dependent G2/M checkpoint in cells whose telomeres are short due to the lack of either Tel1 or Yku70. Sudden telomere elongation and checkpoint-mediated cell cycle arrest are also triggered in wild-type cells by overproducing a protein fusion between the telomeric binding protein Cdc13 and the telomerase-associated protein Est1. Checkpoint activation by GAL1-TEL1 requires ongoing telomere elongation. In fact, it is turned off concomitantly with telomeres reaching a new stable length and is partially suppressed by deletion of the telomerase EST2 gene. Moreover, both telomere length rebalancing and checkpoint inactivation under galactose-induced conditions are accelerated by high levels of either the Sae2 protein, involved in double-strand breaks processing, or the negative telomere length regulator Rif2. These data suggest that sudden telomere lengthening elicits a checkpoint response that inhibits the G2/M transition.

Published
2003

24. Systemic administration of blood-derived exosomes induced by remote ischemic post-conditioning, by delivering a specific cluster of miRNAs, ameliorates ischemic damage and neurological function.

Author

Cuomo O, Anzilotti S, Brancaccio P, Cepparulo P, Lombardi G, Viscardi V, Vinciguerra A, Annunziato L, and Pignataro G

Abstract

MicroRNAs, contained in exosomes or freely circulating in the plasma, might play a pivotal role in the infarct-sparing effect exerted by r emote limb ischemic postconditioning (RLIP). The aims of the present study were: (1) To evaluate the effect of pure exosomes isolated from plasma of animals subjected to RLIP systemically administered to ischemic rats; (2) To finely dissect exosomes content in terms of miRNAs; (3) To select those regulatory miRNAs specifically expressed in protective exosomes and to identify molecular pathways involved in their neurobeneficial effects. Circulating exosomes were isolated from blood of animals exposed to RLIP and administered to animals exposed to tMCAO by intracerebroventricular, intraperitoneal or intranasal routes. Exosomal miRNA signature was evaluated by microarray and FISH analysis. Plasmatic exosomes isolated from plasma of RLIP rats attenuated cerebral ischemia reperfusion injury and improved neurological functions until 3 days after ischemia induction. Interestingly, miR-702-3p and miR-423-5p seem to be mainly involved in exosome protective action by modulating NOD1 and NLRP3, two key triggers of neuroinflammation and neuronal death. Collectively, the results of the present work demonstrated that plasma-released exosomes after RLIP may transfer a neuroprotective signal to the brain of ischemic animals, thus representing a potentially translatable therapeutic strategy in stroke., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Published
2024
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25. Protective effects of functional Nano-Selenium supplementation on spleen injury through regulation of p38 MAPK and NF-κB protein expression.

Author

Xiang R, Xiao X, Liu J, Guo Z, He H, Wang X, Wen X, Angelo V, and Han J

Subjects
Humans, Rats, Animals, p38 Mitogen-Activated Protein Kinases metabolism, Spleen metabolism, Interleukin-6, Rats, Sprague-Dawley, Dietary Supplements, NF-kappa B metabolism, Selenium therapeutic use, Selenium pharmacology
Abstract

Selenium (Se) is a trace element necessary for humans to maintain normal physiological activities, and Se deficiency may lead to splenic injury, while Se supplementation can alleviate splenic injury. However, the mechanism is unclear. In this study, we constructed a Se deficiency animal model by feeding Sprague-Dawley (SD) rats with low Se feed. Meanwhile, we observed the repairing effect of Se supplementation on splenic injury with two doses of novel nano-selenium (Nano-Se) supplement by gavage. We measured the Se content in the spleens of the rats by atomic fluorescence spectroscopy (AFS) method and combined the results of hematoxylin-eosin (HE) and Masson staining to observe the splenic injury, comprehensively evaluating the construction of the animal model of low selenium-induced splenic injury. We measured the mRNA and protein expression levels of p38 mitogen-activated protein kinase (p38 MAPK), nuclear factor kappa-B (NF-κB), and interleukin-6 (IL-6) in the spleen by Real-time quantitative polymerase chain reaction (qPCR), western blot (WB), and immunohistochemistry (IHC). We found that the Se deficiency group exhibited lower Se content, splenic fibrosis, and high expression of p38 MAPK, NF-κB, and IL-6 compared to the normal group. The Se supplement groups exhibited higher Se content, attenuated splenic injury, and down-regulated expression of p38 MAPK, NF-κB, and IL-6 relative to the Se deficiency group. This study suggests that Se deficiency leads to splenic injury in rats, and Se supplementation may attenuate splenic injury by inhibiting the expression of p38 MAPK, NF-κB and IL-6., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Published
2024
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26. Performance Evaluation of a Dengue IgG Rapid Diagnostic Test Designed to Determine Dengue Serostatus as Part of Prevaccination Screening.

Author

Liberal V, Forrat R, Zhang C, Pan C, Bonaparte M, Yin W, Zheng L, Viscardi V, Wu Y, Ataman-Önal Y, Savarino S, and Chen C

Subjects
Antibodies, Viral, Diagnostic Tests, Routine, Double-Blind Method, Humans, Immunoglobulin G, Retrospective Studies, Dengue diagnosis, Dengue prevention & control, Dengue Vaccines therapeutic use
Abstract

The World Health Organization has recommended prevaccination screening for prior dengue infection as the preferred approach prior to vaccination with the dengue vaccine CYD-TDV. These screening tests need to be highly specific and sensitive, and deliverable at the point-of-care. We evaluate here the sensitivity and specificity of the newly developed OnSite Dengue IgG rapid diagnostic test (RDT). A retrospective double-blind study of the sensitivity and specificity of the OnSite Dengue IgG RDT was performed using a sample panel consisting of archived serum specimens collected during CYD-TDV clinical trials in Latin American and Asia, with the reference serostatus for each sample determined by an algorithm using measured dengue PRNT 90 , PRNT 50 , and NS1 IgG ELISA. An additional panel of dengue seronegative samples positive for other flaviviruses and infections was used to assess cross-reactivity. Samples were included from 579 participants; 346 in the specificity panel and 233 in the sensitivity panel. The OnSite dengue IgG RDT exhibited a specificity of 98.0% (95% CI = 95.9 to 99.2) and sensitivity of 95.3% (95% CI = 91.7 to 97.6). The sensitivity for samples exhibiting a multitypic immune profile (PRNT 90 -positive to >1 dengue serotype) was 98.8% while for monotypic immune samples (PRNT 90 -positive to a single dengue serotype) it was 88.1%. The OnSite dengue IgG RDT showed minimal to no cross-reactivity to related flaviviruses. These findings support the use of the OnSite dengue IgG RDT to determine dengue serostatus in CYD-TDV prevaccination screening. IMPORTANCE Dengue remains a significant public health issue, with over 5.2 million cases reported to the World Health Organization (WHO) in 2019. The tetravalent dengue vaccine (CYD-TDV) is currently licensed for use in those aged ≥9 years; however, vaccinees with no previous exposure to dengue experience an increased risk of hospitalized and severe dengue upon subsequent heterotypic infection. Consequently, WHO recommends screening for prior dengue infection before vaccination. Screening tests for previous infection need to be highly specific and sensitive, and deliverable at the point-of-care. High sensitivity ensures that the largest number of individuals with previous infection can be identified and vaccinated, while high specificity prevents the inadvertent vaccination of those without previous infection. This study of the OnSite Dengue IgG Rapid Test, which was explicitly developed to meet this need, found that it had both high specificity (98.0% [95% CI = 95.9 to 99.2]) and sensitivity (95.3% [95% CI = 91.7 to 97.6]).

Published
2022
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27. Exploring How Self-care Language Is Used for Adults With Type 2 Diabetes in the Canadian and American Literature.

Author

Viscardi V, Alliston P, and Sherifali D

Subjects
Adult, Canada epidemiology, Health Personnel, Humans, Language, United States, Diabetes Mellitus, Type 2 therapy, Self Care
Abstract

Barbara Riegel's theory of self-care has been used to create a Self-Care of Heart Failure Index, which has been adapted by researchers into a Self-Care of Diabetes Inventory (SCODI) for individuals living with type 2 diabetes mellitus (T2DM). The SCODI measures how an individual is currently caring for their T2DM to identify areas in need of health-care provider support. The SCODI tool appears to have widespread international dissemination, but it is unknown how the SCODI or Riegel's concept of self-care are being utilized in the Canadian or American diabetes literature. In this critical review we seek to determine how the concept of self-care, including Riegel's concept of self-care, and the SCODI are being utilized in the Canadian and American diabetes literature for adults with T2DM. Critical review methodology was used to identify publications that had an adult T2DM population and self-care language. All included studies (n=11) were assessed using the Strengthening the Reporting of Observational Studies in Epidemiology statement and Joanna Briggs Institute critical appraisal checklist to determine methodologic quality. Included studies were of medium to high quality and often did not define or measure self-care. When studies measured self-care, they utilized the Summary of Diabetes Self-Care Activities (SDSCA) more often (46%) than the SCODI (18%). Future research should collaborate with the international community to set a clear definition of self-care and create a theory-driven approach to self-care for T2DM as well as consider understanding the differences and similarities between the SDSCA and SCODI tools., (Copyright © 2021 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Published
2022
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28. A Milk-Fat Based Diet Increases Metastasis in the MMTV-PyMT Mouse Model of Breast Cancer.

Author

Velazquez FN, Viscardi V, Montemage J, Zhang L, Trocchia C, Delamont MM, Ahmad R, Hannun YA, Obeid LM, and Snider AJ

Subjects
Animal Feed, Animals, Antigens, Polyomavirus Transforming, Breast Neoplasms genetics, Breast Neoplasms metabolism, Female, Lung Neoplasms genetics, Lung Neoplasms metabolism, Mammary Tumor Virus, Mouse genetics, Olive Oil toxicity, Risk Assessment, Risk Factors, Tumor Burden, Tumor Necrosis Factor-alpha metabolism, Breast Neoplasms pathology, Diet, High-Fat adverse effects, Dietary Fats toxicity, Fatty Acids toxicity, Lung Neoplasms secondary, Milk toxicity
Abstract

A high-fat diet (HFD) and obesity are risk factors for many diseases including breast cancer. This is particularly important with close to 40% of the current adult population being overweight or obese. Previous studies have implicated that Mediterranean diets (MDs) partially protect against breast cancer. However, to date, the links between diet and breast cancer progression are not well defined. Therefore, to begin to define and assess this, we used an isocaloric control diet (CD) and two HFDs enriched with either olive oil (OOBD, high in oleate, and unsaturated fatty acid in MDs) or a milk fat-based diet (MFBD, high in palmitate and myristate, saturated fatty acids in Western diets) in a mammary polyomavirus middle T antigen mouse model (MMTV-PyMT) of breast cancer. Our data demonstrate that neither MFBD or OOBD altered the growth of primary tumors in the MMTV-PyMT mice. The examination of lung metastases revealed that OOBD mice exhibited fewer surface nodules and smaller metastases when compared to MFBD and CD mice. These data suggest that different fatty acids found in different sources of HFDs may alter breast cancer metastasis.

Published
2021
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29. Loss of sphingosine kinase 1 increases lung metastases in the MMTV-PyMT mouse model of breast cancer.

Author

Velazquez FN, Zhang L, Viscardi V, Trocchia C, Hannun YA, Obeid LM, and Snider AJ

Subjects
Animals, Carcinogenesis, Disease Models, Animal, Female, Gene Expression Regulation, Neoplastic, Mice, Mice, Knockout, Lung Neoplasms secondary, Mammary Neoplasms, Experimental metabolism, Phosphotransferases (Alcohol Group Acceptor) physiology, Retroviridae Infections metabolism, Tumor Virus Infections metabolism
Abstract

Breast cancer is a very heterogeneous disease, and ~30% of breast cancer patients succumb to metastasis, highlighting the need to understand the mechanisms of breast cancer progression in order to identify new molecular targets for treatment. Sphingosine kinase 1 (SK1) has been shown to be upregulated in patients with breast cancer, and several studies have suggested its involvement in breast cancer progression and/or metastasis, mostly based on cell studies. In this work we evaluated the role of SK1 in breast cancer development and metastasis using a transgenic breast cancer model, mouse mammary tumor virus-polyoma middle tumor-antigen (MMTV-PyMT), that closely resembles the characteristics and evolution of human breast cancer. The results show that SK1 deficiency does not alter tumor latency or growth, but significantly increases the number of metastatic lung nodules and the average metastasis size in the lung of MMTV-PyMT mice. Additionally, analysis of Kaplan-Meier plotter of human disease shows that high SK1 mRNA expression can be associated with a better prognosis for breast cancer patients. These results suggest a metastasis-suppressing function for SK1 in the MMTV-PyMT model of breast cancer, and that its role in regulating human breast cancer progression and metastasis may be dependent on the breast cancer type., Competing Interests: The authors have declared that no competing interests exist.

Published
2021
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31. Detection of Neorickettsia risticii, the agent of Potomac horse fever, in horses from Rio de Janeiro, Brazil.

Author

Paulino PG, Almosny N, Oliveira R, Viscardi V, Müller A, Guimarães A, Baldani C, da Silva C, Peckle M, Massard C, and Santos H

Subjects
Animals, Brazil, DNA, Ribosomal genetics, Neorickettsia risticii isolation & purification, RNA, Bacterial genetics, RNA, Ribosomal, 16S genetics, Anaplasmataceae Infections diagnosis, Anaplasmataceae Infections genetics, Anaplasmataceae Infections microbiology, Anaplasmataceae Infections veterinary, DNA, Bacterial genetics, Horse Diseases diagnosis, Horse Diseases genetics, Horse Diseases microbiology, Horses, Neorickettsia risticii genetics, Phylogeny
Abstract

This study aims to report the presence of Neorickettsia risticii DNA in blood samples from naturally infected horses in Rio de Janeiro, provide clinicopathological findings related to the infection, and report the phylogenetic diversity of the 16S rDNA of N. risticii in order to evaluate its heterogeneity. Real-time quantitative polymerase chain reaction (qPCR) was performed to investigate the presence of N. risticii in samples collected from horses (n = 187). Five positive samples were found in the molecular screening. Hypoalbuminemia and high levels of creatine kinase and lactate dehydrogenase were the predominant findings in the biochemical analysis. The sequences were similar to those of N. risticii. Phylogenetic analysis revealed genotype segregation based on the geographical distribution in the N. risticii sequence clade. Dendrograms constructed with five hypervariable regions revealed that V4 distinguished Neorickettsia at the species level and produced a phylogeny that best represented the phylogeny obtained with the complete 16S rDNA sequence. This is the first report of N. risticii DNA in the blood of Brazilian horses based on sequences deposited in GenBank. Further studies are necessary to clarify the epidemiological chain of this vector-borne parasite in order to determine and establish appropriate preventive measures in the equine trading market.

Published
2020
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32. Alkaline phosphatase activity in airway fluid obtained by tracheal wash from adult horses.

Author

Viscardi V, Jorge ML, Silva KM, Sad EP, Fonseca AB, Alencar NX, and Lessa DA

Subjects
Animals, Bronchoalveolar Lavage Fluid, Horses, Male, Respiratory Tract Diseases enzymology, Alkaline Phosphatase metabolism, Respiratory Tract Diseases veterinary, Trachea enzymology
Abstract

Background: Collection of fluid from the lower respiratory tract (LRT) plays an important role in both the pathophysiological investigation and diagnosis of respiratory tract disease. Enzymes such as ALP are, among others, indicators of cell damage or death, type II pneumocyte proliferation, and neutrophil invasion, and have been useful as biomarkers of respiratory disease in other species., Objectives: The purpose of this study was to determine and compare tracheal wash (TW) ALP activity in healthy horses and horses with LRT inflammation (LRTI) determined by TW cytology profile., Methods: Tracheal washes were collected from asymptomatic adult geldings to measure ALP activity. The horses were allocated to the healthy group or the group with LRT inflammation based on differential leukocyte counts of TW preparations. Horses with > 20% neutrophils and > 1% eosinophils were allocated to the LRTI group, the horses with < 20% neutrophils and < 1% eosinophils were the controls., Results: Tracheal wash ALP activity, measured using a semiautomatic chemistry analyzer, was statistically significantly higher in 18 horses with LRTI (18.9 ± 11.2 × 10(3) U/L) than in healthy horses (10.3 ± 5.9 × 10(3) U/L) (P = .021)., Conclusions: Determining tracheal wash ALP activity is a simple, inexpensive and safe technique that can be used to facilitate the early diagnosis of equine respiratory disease, since it is higher in asymptomatic adult horses with a TW cytology profile consistent with LRT inflammation than in healthy adult horses with a normal TW cytology profile., (© 2016 American Society for Veterinary Clinical Pathology.)

Published
2016
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33. Evaluating the Effect of a Diabetes Health Coach in Individuals with Type 2 Diabetes.

Author

Sherifali D, Viscardi V, Bai JW, and Ali RM

Subjects
Combined Modality Therapy trends, Diabetes Complications prevention & control, Diabetes Mellitus, Type 2 blood, Glycated Hemoglobin analysis, Health Promotion trends, Humans, Patient Education as Topic trends, Randomized Controlled Trials as Topic, Self Care trends, Workforce, Behavior Therapy trends, Diabetes Mellitus, Type 2 therapy, Evidence-Based Medicine, Hyperglycemia prevention & control, Patient Compliance, Precision Medicine trends
Abstract

Objectives: Diabetes health coaching has not been adequately assessed in individuals with type 2 diabetes. The objective of this review was to synthesize the evidence of health coaching for individuals with diabetes to determine the effects of coaching on diabetes control, specifically on glycated hemoglobin (A1C) levels., Methods: The EMBASE, MEDLINE, CINAHL, PsychINFO and Cochrane Central Register of Controlled Trials databases were searched from inception to January 2015. Reference lists from important publications were also reviewed. At least 2 evaluators independently screened and extracted data from eligible studies., Results: A total of 8 trials met the selection criteria, which included 724 adult participants; 353 participants were randomized to a diabetes health coaching intervention, and 371 were randomized to usual care. The pooled effect of diabetes health coaching overall was a statistically significant reduction of A1C levels by 0.32 (95% CI, -0.50 to -0.15). Longer diabetes health coaching exposure (>6 months) resulted in a 0.57% reduction in A1C levels (95% CI, -0.76 to -0.38), compared to shorter diabetes health coaching exposure (≤6 months) (-0.23%; 95% CI, -0.37 to -0.09). Across all studies, diabetes health coaching consisted of goal setting, knowledge acquisition, individualized care and frequent follow up., Conclusions: Diabetes health coaching has an emerging role in healthcare that facilitates self-care, behaviour change and offers frequent follow up and support. This review finds that health coaching for those with diabetes is an effective intervention for improving glycemic control, which may be of greater benefit when offered in addition to existing diabetes care., (Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Published
2016
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34. Centrosomes. Regulated assembly of a supramolecular centrosome scaffold in vitro.

Author

Woodruff JB, Wueseke O, Viscardi V, Mahamid J, Ochoa SD, Bunkenborg J, Widlund PO, Pozniakovsky A, Zanin E, Bahmanyar S, Zinke A, Hong SH, Decker M, Baumeister W, Andersen JS, Oegema K, and Hyman AA

Subjects
Animals, Caenorhabditis elegans Proteins chemistry, Caenorhabditis elegans Proteins genetics, Cell Cycle Proteins chemistry, Cell Cycle Proteins genetics, Centrosome diagnostic imaging, Metabolic Networks and Pathways, Phosphorylation, Polymerization, Protein Binding, Protein Structure, Tertiary, Ultrasonography, Polo-Like Kinase 1, Caenorhabditis elegans genetics, Caenorhabditis elegans metabolism, Caenorhabditis elegans Proteins metabolism, Cell Cycle Proteins metabolism, Centrosome metabolism, Protein Serine-Threonine Kinases metabolism, Proto-Oncogene Proteins metabolism
Abstract

The centrosome organizes microtubule arrays within animal cells and comprises two centrioles surrounded by an amorphous protein mass called the pericentriolar material (PCM). Despite the importance of centrosomes as microtubule-organizing centers, the mechanism and regulation of PCM assembly are not well understood. In Caenorhabditis elegans, PCM assembly requires the coiled-coil protein SPD-5. We found that recombinant SPD-5 could polymerize to form micrometer-sized porous networks in vitro. Network assembly was accelerated by two conserved regulators that control PCM assembly in vivo, Polo-like kinase-1 and SPD-2/Cep192. Only the assembled SPD-5 networks, and not unassembled SPD-5 protein, functioned as a scaffold for other PCM proteins. Thus, PCM size and binding capacity emerge from the regulated polymerization of one coiled-coil protein to form a porous network., (Copyright © 2015, American Association for the Advancement of Science.)

Published
2015
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35. Rare case of optic pathway glioma with extensive intra-ocular involvement in a child with neurofibromatosis type 1.

Author

Gupta V, Sabri K, Whelan KF, and Viscardi V

Subjects
Antineoplastic Agents, Phytogenic therapeutic use, Child, Preschool, Female, Humans, Magnetic Resonance Imaging, Neurofibromatosis 1 drug therapy, Neurofibromatosis 1 genetics, Neurofibromin 1 genetics, Optic Disk pathology, Optic Nerve Glioma drug therapy, Optic Nerve Glioma genetics, Optic Nerve Neoplasms drug therapy, Optic Nerve Neoplasms genetics, Point Mutation, Subretinal Fluid, Vinblastine therapeutic use, Visual Acuity physiology, Neurofibromatosis 1 pathology, Optic Nerve Glioma pathology, Optic Nerve Neoplasms pathology
Abstract

We present a case of a 3-year-old girl with a positive family history of neurofibromatosis type-1 (NF1) presented with best corrected visual acuity of 20/40 in the right eye and <20/400 in the left eye. External ocular examination revealed left eye proptosis of 3 mm, grade II left relative afferent pupillary defect and full range of ocular motility with no strabismus. Slit lamp examination revealed iris lisch nodules bilaterally. Dilated fundus examination of the right eye was normal. Left eye disclosed a large mass extending from the optic nerve head, with associated subretinal fluid. There was neovascularization at the optic disc as well as a superior retinal hemorrhage. Computed tomography of brain/orbits showed an enlarged left optic nerve with a large mass at the optic nerve head, with no evidence of calcification. In addition, a large left optic pathway glioma (OPG), multiple hamartomas within the brain and a smaller low-grade right OPG was also reported. The remarkable feature of our case is the rare intraocular optic nerve involvement of the OPG. Early and regular ophthalmological assessment of all NF1 suspect/confirmed cases is of paramount importance in order to detect OPG early, resulting in timely intervention and salvage of vision.

Published
2015
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36. The Caenorhabditis elegans pericentriolar material components SPD-2 and SPD-5 are monomeric in the cytoplasm before incorporation into the PCM matrix.

Author

Wueseke O, Bunkenborg J, Hein MY, Zinke A, Viscardi V, Woodruff JB, Oegema K, Mann M, Andersen JS, and Hyman AA

Subjects
Animals, Caenorhabditis elegans genetics, Caenorhabditis elegans Proteins genetics, Cell Cycle Proteins genetics, Centrioles metabolism, Microtubule-Organizing Center metabolism, Microtubules metabolism, Multiprotein Complexes metabolism, Protein Serine-Threonine Kinases genetics, Protein Serine-Threonine Kinases metabolism, RNA Interference, RNA, Small Interfering, Caenorhabditis elegans cytology, Caenorhabditis elegans Proteins metabolism, Cell Cycle Proteins metabolism, Centrosome metabolism, Cytoplasm metabolism
Abstract

Centrosomes are the main microtubule-organizing centers in animal cells. Centrosomes consist of a pair of centrioles surrounded by a matrix of pericentriolar material (PCM) that assembles from cytoplasmic components. In Caenorhabditis elegans embryos, interactions between the coiled-coil proteins SPD-5 and SPD-2 and the kinase PLK-1 are critical for PCM assembly. However, it is not known whether these interactions promote the formation of cytoplasmic complexes that are added to the PCM or whether the components interact only during incorporation into the PCM matrix. Here we address this problem by using a combination of live-cell fluorescence correlation spectroscopy, mass spectrometry, and hydrodynamic techniques to investigate the native state of PCM components in the cytoplasm. We show that SPD-2 is monomeric, and neither SPD-2 nor SPD-5 exists in complex with PLK-1. SPD-5 exists mostly as a monomer but also forms complexes with the PP2A-regulatory proteins RSA-1 and RSA-2, which are required for microtubule organization at centrosomes. These results suggest that the interactions between SPD-2, SPD-5, and PLK-1 do not result in formation of cytoplasmic complexes, but instead occur in the context of PCM assembly., (© 2014 Wueseke et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)

Published
2014
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37. Structure of the C. elegans ZYG-1 cryptic polo box suggests a conserved mechanism for centriolar docking of Plk4 kinases.

Author

Shimanovskaya E, Viscardi V, Lesigang J, Lettman MM, Qiao R, Svergun DI, Round A, Oegema K, and Dong G

Subjects
Amino Acid Sequence, Animals, Caenorhabditis elegans Proteins genetics, Centrioles metabolism, Dimerization, Molecular Sequence Data, Protein Binding, Protein Kinases genetics, Protein Structure, Tertiary, Species Specificity, Structure-Activity Relationship, Caenorhabditis elegans genetics, Caenorhabditis elegans Proteins chemistry, Caenorhabditis elegans Proteins metabolism, Centrioles physiology, Models, Molecular, Protein Kinases chemistry, Protein Kinases metabolism, Protein Serine-Threonine Kinases metabolism
Abstract

Plk4 family kinases control centriole assembly. Plk4s target mother centrioles through an interaction between their cryptic polo box (CPB) and acidic regions in the centriolar receptors SPD-2/Cep192 and/or Asterless/Cep152. Here, we report a crystal structure for the CPB of C. elegans ZYG-1, which forms a Z-shaped dimer containing an intermolecular β sheet with an extended basic surface patch. Biochemical and in vivo analysis revealed that electrostatic interactions dock the ZYG-1 CPB basic patch onto the SPD-2-derived acidic region to promote ZYG-1 targeting and new centriole assembly. Analysis of a different crystal form of the Drosophila Plk4 (DmPlk4) CPB suggests that it also forms a Z-shaped dimer. Comparison of the ZYG-1 and DmPlk4 CPBs revealed structural changes in the ZYG-1 CPB that confer selectivity for binding SPD-2 over Asterless-derived acidic regions. Overall, our findings suggest a conserved mechanism for centriolar docking of Plk4 homologs that initiate daughter centriole assembly., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Published
2014
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38. Direct binding of SAS-6 to ZYG-1 recruits SAS-6 to the mother centriole for cartwheel assembly.

Author

Lettman MM, Wong YL, Viscardi V, Niessen S, Chen SH, Shiau AK, Zhou H, Desai A, and Oegema K

Subjects
Amino Acid Sequence, Animals, Animals, Genetically Modified embryology, Animals, Genetically Modified genetics, Animals, Genetically Modified metabolism, Caenorhabditis elegans embryology, Caenorhabditis elegans genetics, Caenorhabditis elegans Proteins genetics, Cell Cycle Proteins genetics, Centrioles genetics, Conserved Sequence, Embryo, Nonmammalian metabolism, Enzyme Activation, Male, Molecular Sequence Data, Multiprotein Complexes genetics, Multiprotein Complexes metabolism, Mutation, Phosphorylation, Protein Binding, Protein Interaction Mapping, Protein Kinases genetics, Protein Multimerization, RNA Interference, Transgenes, Caenorhabditis elegans metabolism, Caenorhabditis elegans Proteins metabolism, Cell Cycle Proteins metabolism, Centrioles metabolism, Protein Kinases metabolism
Abstract

Assembly of SAS-6 dimers to form the centriolar cartwheel requires the ZYG-1/Plk4 kinase. Here, we show that ZYG-1 recruits SAS-6 to the mother centriole independently of its kinase activity; kinase activity is subsequently required for cartwheel assembly. We identify a direct interaction between ZYG-1 and the SAS-6 coiled coil that explains its kinase activity-independent function in SAS-6 recruitment. Perturbing this interaction, or the interaction between an adjacent segment of the SAS-6 coiled coil and SAS-5, prevented SAS-6 recruitment and cartwheel assembly. SAS-6 mutants with alanine substitutions in a previously described ZYG-1 target site or in 37 other residues, either phosphorylated by ZYG-1 in vitro or conserved in closely related nematodes, all supported cartwheel assembly. We propose that ZYG-1 binding to the SAS-6 coiled coil recruits the SAS-6-SAS-5 complex to the mother centriole, where a ZYG-1 kinase activity-dependent step, whose target is unlikely to be SAS-6, triggers cartwheel assembly., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Published
2013
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39. Food safety at home: knowledge and practices of consumers.

Author

Langiano E, Ferrara M, Lanni L, Viscardi V, Abbatecola AM, and De Vito E

Abstract

AIM: To define food safety and risk perception of foodborne diseases in the private home setting and identify specific behaviours during food purchase, storage and preparation in a large survey study. SUBJECT AND METHODS: A large sample of individuals (n = 1,000) living in the area of Cassino, Italy, volunteered to participate in the study. All participants were randomly recruited and underwent a questionnaire-based interview at their home regarding food-safety measures. Logistic regression analyses were used to test for correlations between demographic characteristics and knowledge/behaviours of food diseases. Risks of hazardous practices in the home were calculated according to educational, physical, occupational and marital status. All analyses were performed using the EPIINFO 3.5 statistical program. RESULTS: Our data showed that there was an insufficient amount of knowledge regarding foodborne diseases and pathogens. In most families, we found that there was a lack of correct adherence to food hygiene, mainly due to errors during both food preparation and storage. There was a higher risk for food safety errors in families with children, older persons and pregnant women. CONCLUSION: Our findings confirm that the home environment represents an important site for the spread of pathogens responsible for foodborne diseases. In order to adopt good hygiene practices in the home setting, consumers need to be informed about safety procedures of domestic food handling, storage and preparation.

Published
2012
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40. Survey of lead, cadmium, mercury and arsenic in seafood purchased in Campania, Italy.

Author

Cirillo T, Fasano E, Viscardi V, Arnese A, and Amodio-Cocchieri R

Subjects
Animals, Aquaculture, Bivalvia, Cephalopoda, Diet, European Union, Fishes, Frozen Foods analysis, Humans, Italy, Maximum Allowable Concentration, Species Specificity, Arsenic analysis, Cadmium analysis, Food Contamination analysis, Lead analysis, Mercury analysis, Seafood analysis
Abstract

Lead, cadmium, mercury and arsenic were surveyed in fresh catch, farmed and frozen marine fish, cephalopods and mussels marketed in Campania (Italy), and the population's weekly intake from seafood was assessed. A total of 162 specimens of fish and cephalopods and 30 pools of mussels were analyzed. Pb levels in fresh catch species ranged between <20 and 689 ng/g; in farmed from <20 to 438 ng/g and in frozen from <20 to 541 ng/g. Cd values ranged in fresh catch seafood from <0.8 to 19.8 ng/g; in farmed from <0.8 to 42.3 ng/g; in frozen from <0.8 to 93.1. Hg levels ranged 8-339 ng/g in wild seafood; <5-226 ng/g in farmed and <5-313 ng/g in frozen. In fresh catch seafood, As values ranged <10-231 ng/g; in farmed from 12-310 ng/g and in frozen 12-272 ng/g. Cd and Hg concentrations were below the EU limits in all species; two samples of farmed European seabass and two frozen samples exceeded EU limits for Pb. The median weekly dietary intake could affect the provisional tolerable weekly intake (PTWI) of Pb by 2% (range 0.5-16.5%), Cd PTWI by 0.9% (range 0.1-8.0%), Hg PTWI by 9.6% (range 0.6-41.0%) and the As PTWI by 3.6% (range 0.4-12.5%). Considering the upper values in the ranges, seafood represents a non-negligible contribution to Pb weekly intake (16.5%), but mainly to the weekly intake of Hg (41.0%) for high seafood consumers and those consuming the most contaminated species.

Published
2010
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41. The Mec1p and Tel1p checkpoint kinases allow humanized yeast to tolerate chronic telomere dysfunctions by suppressing telomere fusions.

Author

di Domenico EG, Auriche C, Viscardi V, Longhese MP, Gilson E, and Ascenzioni F

Subjects
Base Sequence, Chromosomes, Fungal metabolism, DNA Damage, DNA-Binding Proteins, Genomic Instability, Humans, Microbial Viability, Saccharomyces cerevisiae cytology, Intracellular Signaling Peptides and Proteins metabolism, Protein Serine-Threonine Kinases metabolism, Saccharomyces cerevisiae enzymology, Saccharomyces cerevisiae Proteins metabolism, Telomere enzymology, Telomere pathology
Abstract

In this work we report that budding yeasts carrying human-type telomeric repeats at their chromosome termini show a chronic activation of the Rad53-dependent DNA damage checkpoint pathway and a G2/M cell cycle delay. Furthermore, in the absence of either TEL1/ATM or MEC1/ATR genes, which encodes phosphatidylinositol 3-kinase-related kinases (PIKKs), we detected telomere fusions, whose appearance correlates with a reduced cell viability and a high rate of genome instability. Based on sequence analysis, telomere fusions occurred primarily between ultrashort telomeres. Microcolony formation assays argue against the possibility that fusion-containing cells are eliminated by PIKK-dependent signalling. These findings reveal that humanized telomeres in yeast cells are sensed as a chronically damaged DNA but do not greatly impair cell viability as long as the cells have a functional DNA damage checkpoint.

Published
2009
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42. Occurrence of polychlorobiphenyls in buffalo mozzarella cheese from Campania (Italy).

Author

Cirillo T, Viscardi V, Farina A, Fasano E, Del Prete U, and Amodio Cocchieri R

Subjects
Analysis of Variance, Animals, Buffaloes, Italy, Cheese analysis, Dioxins analysis, Environmental Pollutants analysis, Food Contamination analysis, Milk chemistry, Polychlorinated Biphenyls analysis
Abstract

Buffalo milk and mozzarella cheese produced in the Caserta and Salerno areas in Campania region have been investigated on the presence and the levels of polychlorobiphenyls (PCBs). Seven congeners, six non dioxin-like (NDL-PCBs nos. 28, 52, 101, 138, 153 and 180) and one dioxin-like (DL-PCB n. 118), were detected. PCBs were found at detectable levels in the 83% of the buffalo milk and in the 100% of the mozzarella cheese samples from Caserta; in those from Salerno the prevalence of contamination was 77% for milk and 73% for mozzarellas, respectively. The NDL-PCB content of mozzarellas collected in Caserta was significantly higher than that found in those from Salerno. The more diffuse congeners were PCB 28, 138 and 153 both in milk and in mozzarella cheese; PCB 118 contributed to the total PCB content for the 7% in milk and 2-3% in mozzarella cheese. On the basis of the Italian annual average consumption the contribution of mozzarella to the daily dietary intake of NDL-PCB can vary between 0.41 and 21.33 ng kg(-1) bw, median value of 3.66 ng kg(-1) bw. The levels of contamination in milk and dairies analyzed are similar or quite lower than those found in other European countries.

Published
2008

43. MRX-dependent DNA damage response to short telomeres.

Author

Viscardi V, Bonetti D, Cartagena-Lirola H, Lucchini G, and Longhese MP

Subjects
Models, Biological, Protein Transport, Telomere genetics, DNA Damage, Multiprotein Complexes metabolism, Saccharomyces cerevisiae metabolism, Saccharomyces cerevisiae Proteins metabolism, Telomere metabolism
Abstract

Telomere structure allows cells to distinguish the natural chromosome ends from double-strand breaks (DSBs). However, DNA damage response proteins are intimately involved in telomere metabolism, suggesting that functional telomeres may be recognized as DNA damage during a time window. Here we show by two different systems that short telomeres are recognized as DSBs during the time of their replication, because they induce a transient MRX-dependent DNA damage checkpoint response during their prolonged elongation. The MRX complex, which is recruited at telomeres under these conditions, dissociates from telomeres concomitantly with checkpoint switch off when telomeres reach a new equilibrium length. We also show that MRX recruitment to telomeres is sufficient to activate the checkpoint independently of telomere elongation. We propose that MRX can signal checkpoint activation by binding to short telomeres only when they become competent for elongation. Because full-length telomeres are refractory to MRX binding and the shortest telomeres are elongated of only a few base pairs per generation, this limitation may prevent unscheduled checkpoint activation during an unperturbed S phase.

Published
2007
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44. Budding Yeast Sae2 is an In Vivo Target of the Mec1 and Tel1 Checkpoint Kinases During Meiosis.

Author

Cartagena-Lirola H, Guerini I, Viscardi V, Lucchini G, and Longhese MP

Subjects
Cell Cycle Proteins metabolism, Cell Cycle Proteins physiology, DNA Repair, Endonucleases, Fungal Proteins physiology, Intracellular Signaling Peptides and Proteins, Phosphorylation, Protein Serine-Threonine Kinases, Recombination, Genetic, Saccharomyces cerevisiae Proteins physiology, Fungal Proteins metabolism, Meiosis, Saccharomyces cerevisiae Proteins metabolism
Abstract

DNA double-strand breaks (DSBs) are introduced into the genome to initiate meiotic recombination. Their accurate repair is monitored by the meiotic recombination checkpoint that prevents nuclear division until completion of meiotic DSB repair. We show that the Saccharomyces cerevisiae Sae2 protein, known to be involved in processing meiotic DSBs, is phosphorylated periodically during the meiotic cycle. Sae2 phosphorylation occurs at the onset of premeiotic S phase, is maximal at the time of meiotic DSB generation and decreases when DSBs are repaired by homologous recombination. Hyperactivation of the meiotic recombination checkpoint caused by the failure to repair DSBs results in accumulation and persistence of phosphorylated Sae2, indicating a possible link between checkpoint activation and meiosis-induced Sae2 phosphorylation. Accordingly, Sae2 phosphorylation depends on the checkpoint kinases Mec1 and Tel1, whose simultaneous deletion also impairs meiotic DSB repair. Moreover, replacing with alanines the Sae2 serine and threonine residues belonging to Mec1/Tel1-dependent putative phosphorylation sites impairs not only Sae2 phosphorylation during meiosis, but also meiotic DSB repair. Thus, checkpoint-mediated phosphorylation of Sae2 is important to support its meiotic recombination functions.

Published
2006
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45. Telomeres and DNA damage checkpoints.

Author

Viscardi V, Clerici M, Cartagena-Lirola H, and Longhese MP

Subjects
DNA Repair, DNA Replication, Genomic Instability, Humans, Telomere metabolism, DNA Damage, Telomerase metabolism, Telomere chemistry
Abstract

In all eukaryotic organisms, interruptions in duplex DNA molecules elicit a DNA damage response, which includes activation of DNA repair machineries and surveillance mechanisms, known as DNA damage checkpoints. Telomeres and double-strand breaks (DSBs) share the common feature of being physical ends of chromosomes. However, unlike DSBs, telomeres do not activate the DNA damage checkpoints and are usually protected from end-to-end fusions and other processing events that normally promote repair of DNA breaks. This indicates that they are shielded from being recognized and processed as DSBs. On the other hand, chromosome ends resemble damaged DNA, as several factors required for DNA repair and checkpoint networks play important roles in telomere length maintenance. Due to the critical role of both DNA damage checkpoints and telomere homeostasis in maintaining genetic stability and in counteracting cancer development, the knowledge of their interconnections is essential for our understanding of these key cellular controls.

Published
2005
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46. The functions of budding yeast Sae2 in the DNA damage response require Mec1- and Tel1-dependent phosphorylation.

Author

Baroni E, Viscardi V, Cartagena-Lirola H, Lucchini G, and Longhese MP

Subjects
Alleles, Amino Acid Sequence, Amino Acid Substitution, Base Sequence, Bleomycin pharmacology, Cell Cycle, DNA Repair, DNA, Fungal genetics, Endonucleases, Fungal Proteins genetics, Genes, Fungal, Intracellular Signaling Peptides and Proteins, Molecular Sequence Data, Mutagenesis, Site-Directed, Phosphorylation, Protein Serine-Threonine Kinases, Saccharomyces cerevisiae cytology, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins genetics, Signal Transduction, Ultraviolet Rays, DNA Damage, Fungal Proteins metabolism, Saccharomyces cerevisiae metabolism, Saccharomyces cerevisiae Proteins metabolism
Abstract

DNA damage checkpoint pathways sense DNA lesions and transduce the signals into appropriate biological responses, including cell cycle arrest, induction of transcriptional programs, and modification or activation of repair factors. Here we show that the Saccharomyces cerevisiae Sae2 protein, known to be involved in processing meiotic and mitotic double-strand breaks, is required for proper recovery from checkpoint-mediated cell cycle arrest after DNA damage and is phosphorylated periodically during the unperturbed cell cycle and in response to DNA damage. Both cell cycle- and DNA damage-dependent Sae2 phosphorylation requires the main checkpoint kinase, Mec1, and the upstream components of its pathway, Ddc1, Rad17, Rad24, and Mec3. Another pathway, involving Tel1 and the MRX complex, is also required for full DNA damage-induced Sae2 phosphorylation, that is instead independent of the downstream checkpoint transducers Rad53 and Chk1, as well as of their mediators Rad9 and Mrc1. Mutations altering all the favored ATM/ATR phosphorylation sites of Sae2 not only abolish its in vivo phosphorylation after DNA damage but also cause hypersensitivity to methyl methanesulfonate treatment, synthetic lethality with RAD27 deletion, and decreased rates of mitotic recombination between inverted Alu repeats, suggesting that checkpoint-mediated phosphorylation of Sae2 is important to support its repair and recombination functions.

Published
2004
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47. Sudden telomere lengthening triggers a Rad53-dependent checkpoint in Saccharomyces cerevisiae.

Author

Viscardi V, Baroni E, Romano M, Lucchini G, and Longhese MP

Subjects
Cell Cycle genetics, Checkpoint Kinase 2, DNA Damage physiology, Endonucleases, Genes, cdc, Intracellular Signaling Peptides and Proteins, Mutation genetics, Recombinant Fusion Proteins metabolism, Saccharomyces cerevisiae cytology, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins metabolism, Telomerase metabolism, Telomere enzymology, Telomere-Binding Proteins metabolism, Cell Cycle Proteins, Fungal Proteins metabolism, Protein Serine-Threonine Kinases metabolism, Saccharomyces cerevisiae metabolism, Telomere genetics
Abstract

Telomeres are specialized functional complexes that ensure chromosome stability by protecting chromosome ends from fusions and degradation and avoiding chromosomal termini from being sensed as DNA breaks. Budding yeast Tel1 is required both for telomere metabolism and for a Rad53-dependent checkpoint responding to unprocessed double-strand breaks. We show that overexpression of a GAL1-TEL1 fusion causes transient telomere lengthening and activation of a Rad53-dependent G2/M checkpoint in cells whose telomeres are short due to the lack of either Tel1 or Yku70. Sudden telomere elongation and checkpoint-mediated cell cycle arrest are also triggered in wild-type cells by overproducing a protein fusion between the telomeric binding protein Cdc13 and the telomerase-associated protein Est1. Checkpoint activation by GAL1-TEL1 requires ongoing telomere elongation. In fact, it is turned off concomitantly with telomeres reaching a new stable length and is partially suppressed by deletion of the telomerase EST2 gene. Moreover, both telomere length rebalancing and checkpoint inactivation under galactose-induced conditions are accelerated by high levels of either the Sae2 protein, involved in double-strand breaks processing, or the negative telomere length regulator Rif2. These data suggest that sudden telomere lengthening elicits a checkpoint response that inhibits the G2/M transition.

Published
2003
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