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6. Supplementary Figure 5 from RNAi-Mediated Silencing of Myc Transcription Inhibits Stem-like Cell Maintenance and Tumorigenicity in Prostate Cancer

Author

Carlo V. Catapano, Giuseppina M. Carbone, Manuela Sarti, Sandra Pinton, Stefano Di Marco, Sara Napoli, Ramon Garcia-Escudero, Domenico Albino, Anastasia Malek, and Gianluca Civenni

Abstract

PDF file - 38K, PC3 cells cultured in sphere forming conditions (bulk) and sorted subpopulations (CD44+/CD24- and CD44+/CD24+) were transfected with Myc13-Cy3 siRNA and the intracellular level of Cy3-labeled siRNA was determined after 4 h by flow cytometry.

Published
2023
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7. Supplementary Figure 6 from RNAi-Mediated Silencing of Myc Transcription Inhibits Stem-like Cell Maintenance and Tumorigenicity in Prostate Cancer

Author

Carlo V. Catapano, Giuseppina M. Carbone, Manuela Sarti, Sandra Pinton, Stefano Di Marco, Sara Napoli, Ramon Garcia-Escudero, Domenico Albino, Anastasia Malek, and Gianluca Civenni

Abstract

PDF file - 22K, Expression of Myc in normal prostate epithelial cells (PrECs) and ESE3kd-PrECs determined by qRT-PCR.

Published
2023
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9. Supplementary Figure 4 from RNAi-Mediated Silencing of Myc Transcription Inhibits Stem-like Cell Maintenance and Tumorigenicity in Prostate Cancer

Author

Carlo V. Catapano, Giuseppina M. Carbone, Manuela Sarti, Sandra Pinton, Stefano Di Marco, Sara Napoli, Ramon Garcia-Escudero, Domenico Albino, Anastasia Malek, and Gianluca Civenni

Abstract

PDF file - 28K, Expression of the cell surface markers CD44 and CD24 determined by qRT-PCR in PC3 and DU145 cells grown in adherent or sphere forming conditions.

Published
2023
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10. Supplementary Figure 7 from RNAi-Mediated Silencing of Myc Transcription Inhibits Stem-like Cell Maintenance and Tumorigenicity in Prostate Cancer

Author

Carlo V. Catapano, Giuseppina M. Carbone, Manuela Sarti, Sandra Pinton, Stefano Di Marco, Sara Napoli, Ramon Garcia-Escudero, Domenico Albino, Anastasia Malek, and Gianluca Civenni

Abstract

PDF file - 100K, Normal prostate epithelial cells (PrECs) were transfected with GL3 and Myc13 siRNA in 12-well plates and counted w/ Neubauer haemocytometer chamber over 9-day period.

Published
2023
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11. Initial Invasive or Conservative Strategy for Stable Coronary Disease

Author

Maron D. J., Hochman J. S., Reynolds H. R., Bangalore S., O'Brien S. M., Boden W. E., Chaitman B. R., Senior R., Lopez-Sendon J., Alexander K. P., Lopes R. D., Shaw L. J., Berger J. S., Newman J. D., Sidhu M. S., Goodman S. G., Ruzyllo W., Gosselin G., Maggioni A. P., White H. D., Bhargava B., Min J. K., John Mancini G. B., Berman D. S., Picard M. H., Kwong R. Y., Ali Z. A., Mark D. B., Spertus J. A., Krishnan M. N., Elghamaz A., Moorthy N., Hueb W. A., Demkow M., Mavromatis K., Bockeria O., Peteiro J., Miller T. D., Szwed H., Doerr R., Keltai M., Selvanayagam J. B., Gabriel Steg P., Held C., Kohsaka S., Mavromichalis S., Kirby R., Jeffries N. O., Harrell F. E., Rockhold F. W., Broderick S., Bruce Ferguson T., Williams D. O., Harrington R. A., Stone G. W., Rosenberg Y, ISCHEMIA Research Group: Joseph Ricci, A Tello Montoliu, A I Robero Aniorte, Abbey Mulder, Abhay A Laddu, Abhinav Goyal, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Abraham Oomman, Adam J Jaskowiak, Adam Kolodziej, Adam Witkowski, Adnan Hameed, Adriana Anesini, Afshan Hussain, Agne Juceviciene, Agne Urboniene, Agnes Jakal, Agnieszka Szramowska, Ahmad Khairuddin, Ahmed Abdel-Latif, Ahmed Adel, Ahmed Aljzeeri, Ahmed Kamal, Ahmed Talaat, Aimee Mann, Aira Contreras, Ajit Kumar, V K Kumar, Akemi Furukawa, Akshay Bagai, Akvile Smigelskaite, Alain Furber, Alain Rheault, Alaine Melanie Loehr, Alan Rosen, Albert Varga, Albertina Qelaj, Alberto Barioli, Aldo Russo, Alec Moorman, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alena Kuleshova, Alessandro Sionis, Alexander A Sirker, Alexander M Chernyavskiy, Alexandra Craft, Alexandra Vazquez, Alexandre Ciappina Hueb, Alexandre S Colafranseschi, Alexandre Schaan de Quadros, Alexandre Tognon, Ali Alghamdi, Alice Manica Muller, Aline Nogueira Rabaça, Aline Peixoto Deiro, Alison Hallam, Allegra Stone, Allison Schley, Almudena Castro, Alvaro Rabelo Ales, Amanda Germann, Amanda O'Malley, Amar Uxa, Amarachi Ojajuni, Amarino C Oliveira Jr, Amber B Hull, Ambuj Roy, Amer Zarka, Amir Janmohamed, Ammani Brown, Ammy Malinay, Amparo Martinez Monzonis, Amy J Richards, Amy Iskandrian, Amy Ollinger, Ana D Djordjevic-Dikic, Ana Fernández Martínez, Ana Gomes Almeida, Ana Paula Batista, Ana Rita Francisco, Ana S Mladenovic, Ana Santana, Anam Siddiqui, Anastasia M Kuzmina-Krutetskaya, Andras Vertes, Andre S Sousa, Andre Gabriel, André Schmidt, Andrea M Lundeen, Andrea Bartykowszki, Andrea Lorimer, Andrea Mortara, Andrea Pascual, Andreia Coelho, Andreia Rocha, Andrés García-Rincón, Andrew G Howarth, Andrew J Moriarty, Andrew Docherty, Andrew Starovoytov, Andrew Zurick, Andrzej Łabyk, Andrzej Swiatkowski, Andy Lam, Anelise Kawakami, Angela Hoye, Angela Kim, Angelique Smit, Angelo Nobre, Anil V Shah, Anja Ljubez, Anjali Anand, Ankush Sachdeva, Ann Greenberg, Ann Luyten, Ann Ostrander, Anna Di Donato, Anna Cichocka-Radwan, Anna Fojt, Anna Plachcinska, Anna Proietti, Anna Teresinska, Anne Marie Webb, Anne Cartwright, Anne Heath, Anne Mackin, Anong Amaritakomol, Anong Chaiyasri, Anoop Chauhan, Anoop Mathew, Anthony Gemignani, Anto Luigi Andres, Antonia Vega, Antonietta Hansen, Antonino Ginel Iglesias, Antonio Carlos Carvalho, Antonio Di Chiara, Antonio Serra Peñaranda, Antonio Carvalho, Antonio Colombo, Antonio Fiarresga, Anupama Rao, Aquiles Valdespino-Estrada, Araceli Boan, Areef Ishani, Ariel Diaz, Arijit Ghosh, Arintaya Prommintikul, Arline Roberts, Arnold H Seto, Arnold P Good, Arshed Quyyumi, Arthur J Labovitz, Arthur Kerner, Arturo S Campos-Santaolalla, Arunima Misra, Ashok Mukherjee, Ashok Seth, Ashraf Seedhom, Asim N Cheema, Asker Ahmed, Atul Mathur, Atul Verma, Audrey W Leong, Axel Åkerblom, Axelle Fuentes, Aynun Naher, Badhma Valaiyapathi, Baljeet Kaur, Bandula Guruge, Barbara Brzezińska, Barbara Nardi, Bartosz Czarniak, Bebek Singh, Begoña Igual, Bela Merkely, Belen Cid Alvarez, Benjamin J Spooner, Benjamin J W Chow, Benjamin Cheong, Benoy N Shah, Bernard de Bruyne, Bernardas Valecka, Bernhard Jäger, Beth A Archer, Beth Abramson, Beth Jorgenson, Bethany Harvey, Betsy O'Neal, Bev Atkinson, Bev Bozek, Bevin Lang, Bijulal Sasidharan, Bin Yang, Bin Zhang, Binoy Mannekkattukudy Kurian, Bjoern Goebel, Bob Hu, Bogdan A Popescu, Bogdan Crnokrak, Bolin Zhu, Bonnie J Kirby, Brandi D Zimbelman, Brandy Starks, Branko D Beleslin, Brenda Hart, Brian P Shapiro, Brian McCandless, Brianna Wisniewski, Brigham R Smith, Brooks Mirrer, Bruce McManus, Bruce Rutkin, Bruna Edilena Paulino, Bruna Maria Ascoli, Bryn Smith, Byron J Allen, C Michael Gibson, C Noel Bairey Merz, Calin Pop, Cameron Hague, Camila Thais de Ormundo, Candace Gopaul, Candice P Edillo, Carísi A Polanczyk, Carita Krannila, Carla Vicente, Carl-Éric Gagné, Carlo Briguori, Carlos Peña Gil, Carlos Alvarez, Carly Ohmart, Carmen C Beladan, Carmen Ginghina, Carol M Kartje, Caroline Alsweiler, Caroline Brown, Caroline Callison, Caroline Pinheiro, Caroline Rodgers, Caroline Spindler, Carolyn Corbett, Carrie Drum, Casey Riedberger, Catherine Bone, Catherine Fleming, Catherine Gordon, Catherine Jahrsdorfer, Catherine Lemay, Catherine Weick, Cathrine Patten, Cecilia Goletto, Cezary Kepka, Chandini Suvarna, Chang Xu, Chantale Mercure, Charle A Viljoen, Charlene Wiyarand, Charles Jia-Yin Hou, Charles Y Lui, Charles Cannan, Charles Cornet, Charlotte Pirro, Chataroon Rimsukcharoenchai, Chen Wang, Cheng-Ting Tsai, Chen-Yen Chien, Cheryl A Allardyce, Chester M Hedgepeth, Chetan Patel, Chiara Attanasio, Chih-Hsuan Yen, Chi-Ming Chow, Ching Min Er, Ching-Ching Ong, Cholenahally Nanjappa Manjunath, Chris Beck, Chris Buller, Christel Vassaliere, Christian Hamm, Christiano Caldeira, Christie Ballantyne, Christina Björklund, Christine R Hinton, Christine Bergeron, Christine Masson, Christine Roraff, Christine Shelley, Christophe Laure, Christophe Thuaire, Christopher Kinsey, Christopher McFarren, Christopher Spizzieri, Christopher Travill, Chun-Chieh Liu, Chung-Lieh Hung, Chunguang Li, Chun-Ho Yun, Chunli Xia, Ciarra Heard, Cidney Schultz, Clare Venn-Edmonds, Claudia P Hochberg, Claudia Wegmayr, Claudia Cortés, Claudia Escobar, Cláudia Freixo, Claudio T Mesquita, Clemens T Kadalie, Colin Berry, Constance Philander, Corine Thobois, Costantino Costantini, Courtney Page, Craig Atkinson, Craig Barr, Craig Paterson, Cristina Bare, Cynthia Baumann, Cynthia Burman, Dalisa Espinosa, Damien Collison, Dan Deleanu, Dan Elian, Dan Gao, Dana Oliver, Daniel P Vezina, Daniel O'Rourke, Daniele Komar, Danielle Schade, Darrel P Francis, Dastan Malaev, David A Bull, David E Winchester, David P Faxon, David Booth, David Cohen, David DeMets, David Foo, David Schlichting, David Taggart, David Waters, David Wohns, Davis Vo, Dawid Teodorczyk, Dawn Shelstad, Dawn Turnbull, Dayuan Li, Dean Kereiakes, Deborah O'Neill, Deborah Yip, Debra K Johnson, Debra Dees, Deepak L Bhatt, Deepika Gopal, Deepti Kumar, Deirdre Mattina, Deirdre Murphy, Delano R Small, Delsa K Rose, Dengke Jiang, Denis Carl Phaneuf, Denise Braganza, Denise Fine, Derek Cyr, Desiree Tobin, Diana Cukali, Diana Parra, Diane Camara, Diane Minshall Liu, Diego Adrián Vences, Diego Franca de Cunha, Dimitrios Stournaras, Dipti Patel, Dongze Li, Donna Exley, Dorit Grahl, Dragana Stanojevic, Duarte Cacela, Dwayne S G Conway, E Pinar Bermudez, Eapen Punnoose, Edgar L Tay, Edgar Karanjah, Edoardo Verna, Eduardo Hernandez-Rangel, Edward D Nicol, Edward O McFalls, Edward T Martin, Edyta Kaczmarska, Ekaterina I Lubinskaya, Elena A Demchenko, Elena Refoyo Salicio, Eli Feen, Elihú Durán-Cortés, Elisabeth M Janzen, Elise L Hannemann, Elise van Dongen, Elissa Restelli Piloto, Eliza Kaplan, Elizabeta Srbinovska Kostovska, Elizabeth Capasso-Gulve, Elizabeth Congdon, Elizabeth Ferguson, Elizaveta V Zbyshevskaya, Ellen Magedanz, Ellie Fridell, Ellis W Lader, Elvin Kedhi, Emanuela Racca, Emilie Tachot, Emily DeRosa, Encarnación Alonso-Álvarez, Eric Nicollet, Eric Peterson, Erick Alexánderson Rosas, Erick Donato Morales, Erin Orvis, Ermina Moga, Estelle Montpetit, Estevao Figueiredo, Eugene Passamani, Eugenia Nikolsky, Eunice Yeoh, Evgeniy I Kretov, Ewa Szczerba, Ewelina Wojtala, Expedito Eustáquio Ribeiro Silva, F Marin Ortuño, Fabio R Farias, Fabio Fimiani, Fabrizio Rolfo, Fa-Chang Yu, Fadi Hage, Fadi Matar, Fahim Haider Jafary, Fang Feng, Fang Liu, Fatima Ranjbaran, Fatima Rodriguez, Fausto J Pinto, Fauzia Rashid, Federica Ramani, Fei Wang, Fernanda Igansi, Filipa Silva, Filippo Ottani, Fiona Haines, Firas Al Solaiman, Flávia Egydio, Flavio Lyra, Florian Egger, Fran Farquharson, Frances Laube, Francesc Carreras Costa, Francesca de Micco, Francesca Bianchini, Francesca Pezzetta, Francesca Pietrucci, Francesco Orso, Francesco Pisano, Francis Burt, Francisca Patuleia Figueiras, Francisco Fernandez-Aviles, Francois Pierre Mongeon, Frans Van de Werf, Franziska Guenther, Fraser N Witherow, Fred Mohr, Frederico Dall'Orto, Fumiyuki Otsuka, G De La Morena, G Karthikeyan, Gabor Dekany, Gabor Kerecsen, Gabriel Galeote, Gabriel Grossmann, Gabriel Vorobiof, Gabriela Sanchez de Souza, Gabriela Guzman, Gabriela Zeballos, Gabriele Gabrielli, Gabriele Jakl-Kotauschek, Gail A Shammas, Gail Brandt, Gang Chen, Gary E Lane, Gary J Luckasen, Gautam Sharma, Gelmina Mikolaitiene, Gennie Yee, Georg Nickenig, George E Revtyak, George J Juang, Gerald Fletcher, Gerald Leonard, Gerard Patrick Devlin, Gerard Esposito, Gergely Ágoston, Gervasio Lamas, Geza Fontos, Ghada Mikhail, Gia Cobb, Gian Piero Perna, Gianpiero Leone, Giles Roditi, Gilles Barone-Rochette, Girish Mishra, Giuseppe Tarantini, Glenda Wong, Glenn S Hamroff, Glenn Rayos, Gong Cheng, Gonzalo Barge-Caballero, Goran Davidović, Goran Stankovic, Gordana Stevanovic, Grace Jingyan Wang, Grace M Young, Graceanne Wayser, Graciela Scaro, Graham S Hillis, Graham Wong, Grazyna Anna Szulczyk, Gregor Simonis, Gregory Kumkumian, Gretchen Ann Peichel, Grzegorz Gajos, Gudrun Steinmaurer, Guilherme G Rucatti, Guilherme Portugal, Guilhermina Cantinho Lopes, Guillem Pons Lladó, Gunnar Frostfelt, Gurpreet S Wander, Gurpreet Gulati, Gustavo Pucci, Hafidz Abd Hadi, Haibo Zhang, Haitao Wang, Halina Marciniak, Han Chen, Hanan Kerr, Hani Najm, Hanna Douglas, Hannah Phillips, Hao Dai, Haojian Dong, Haqeel Jamil, Harikrishnan Sivadasanpillai, Harry Suryapranata, Hassan Reda, Hayley Pomeroy, Heather Barrentine, Heather Golden, Heather Hurlburt, Heidi Wilson, Helen C Tucker, Helene Abergel, Hemalata Siddaram, Hermine Osseni, Herwig Schuchlenz, Hesong Zeng, Hicham Skali, Hilda Solomon, Hollie Horton, Holly Hetrick, Holly Little, Holly Park, Hongjie Chi, Hossam Mahrous, Howard A Levite, Hristo Pejkov, Huajun Li, Hugo Bloise-Adames, Hugo Marques, Hui Zhong, Hui-Min Zhang, Humayrah Hashim, Hung-I Yeh, Hussien El Fishawy, Ian Webb, Iftikhar Kullo, Igor O Grazhdankin, Ihab Hamzeh, Ikraam Hassan, Ikuko Ueda, Ileana L Pina, Ilona Tamasauskiene, Ilse Bouwhuis, Imran Arif, Ina Wenzelburger, Inês Zimbarra Cabrita, Ines Rodrigues, Inga H Robbins, Inga Soveri, Ingela Schnittger, Iqbal Karimullah, Ira M Dauber, Iram Rehman, Irena Peovska Mitevska, Irene Marthe Lang, Irina Subbotina, Irma Kalibataite-Rutkauskiene, Irni Yusnida, Isabel Estela Carvajal, Isabella C Palazzo, Isabelle Hogan, Isabelle Roy, Ishba Syed, Ishita Tejani, Ivan A Naryshkin, Ivana Jankovic, Iwona Niedzwiecka, J David Knight, Jacek Kusmierek, Jackie M White, Jackie Chow, Jacob Udell, Jacqueline E Tamis-Holland, Jacqueline Fannon, Jacquelyn A Quin, Jacquelyn Do, Jaekyeong Heo, Jakub Maksym, James E Davies, James H O'Keefe Jr, James J Jang, James Cha, James Harrison, James Hirsch, James Stafford, James Tatoulis, Jamie Rankin, Jan Henzel, Jan Orga, Jana Tancredi, Janaina Oliveira, Jane Burton, Jane Eckstein, Jane Marucci, Janet P Knight, Janet Blount, Janet Halliday, Janetta Kourzenkova, Janitha Raj, Jan-Malte Sinning, Jaqueline Pozzibon, Jaroslaw Drozdz, Jaroslaw Karwowski, Jason D Glover, Jason Loh Kwok, Jason T Call, Jason Linefsky, Jassira Gomes, Jati Anumpa, Javier J Garcia, Javier Courtis, Jay Meisner, K Jayakumar, Jayne Scales, Jean E Denaro, Jean Michel Juliard, Jean Ho, Jeanette K Stansborough, Jean-Michel Juliard, Jeanne Russo, Jeannette J M Schoep, Jeet Thambyrajah, Jeff Leimberger, Jeffery A Breall, Jeffrey A Kohn, Jeffrey C Milliken, Jeffrey Anderson, Jeffrey Blume, Jeffrey Kanters, Jeffrey Lorin, Jeffrey Moses, Jelena J Stepanovic, Jelena Celutkiene, Jelena Djokic, Jelena Stojkovic, Jenne M Jose, Jenne Manchery, Jennifer A Mull, Jennifer H Czerniak, Jennifer L Stanford, Jennifer Gillis, Jennifer Horst, Jennifer Isaacs, Jennifer Langdon, Jennifer Thomson, Jennifer Tomfohr, Jennifer White, Jen-Yuan Kuo, Jeremy Rautureau, Jerome Fleg, Jessica Berg, Jessica Rodriguez, Jessica Waldron, Jhina Patro, Jia Li, Jiajia Mao, Jiamin Liu, Jian'an Wang, Jianhua Li, Jianxin Zhang, Jie Qi, Jihyun Lyo, Jill Marcus, Jim Blankenship, Jing Zhang, Jingjing Liu, Jing-Yao Fan, Jiun-Yi Li, Jiwan Pradhan, Jiyan Chen, J M Rivera Caravaca, Jo Evans, Joan Garcia Picart, Joan Hecht, Joanna Jaroch, Joanna Zalewska, Joanne Kelly, Joanne Taaffe, João Reynaldo Abbud, João V Vitola, Joaquín V Peñafiel, Jocelyne Benatar, Jody Bindeman, Joe Sabik, Joel Klitch, Johann Christopher, Johannes Aspberg, John D Friedman, John F Beltrame, John F Heitner, John Joseph Graham, John R Davies, John Doan, John Kotter, John Kurian, John Mukai, John Pownall, Jolanta Sobolewska, Jon Kobashigawa, Jonathan L Goldberg, Jonathan W Bazeley, Jonathan Byrne, Jonathan Himmelfarb, Jonathan Leipsic, Jonean Thorsen, Jorge F Trejo Gutierrez, Jorge Escobedo, Jorik Timmer, José A Ortega-Ramírez, José Antonio Marin-Neto, Jose D Salas, Jose Enrique Castillo, Jose Francisco Saraiva, José J Cuenca-Castillo, Jose L Diez, José Luis Narro Villanueva, José Luiz da Vieira, José M Flores-Palacios, Jose Ramon Gonzalez, Jose Seijas Amigo, Jose Fragata, Josep Maria Padró, Josheph F X McGarvey Jr, Joseph Hannan, Joseph Sacco, Joseph Sweeny, Joseph Wiesel, Josephine D Abraham, Joshua P Loh, Joy Burkhardt, Joyce R White, Joyce Riestenberg-Smith, Judit Sebo, Judith L Meadows, Judith Wright, Judy Mae Foltz, Judy Hung, Judy Otis, Juergen Stumpf, Jui-Peng Tsai, Julia S Dionne, Julia de Aveiro Morata, Julie Bunke, Julie Morrow, Julio César Figal, Jun Fujita, Jun Jiang, Junhua Li, Junqing Yang, Juntima Euathrongchit, Jyotsna Garg, K Manjula Rani, K Preethi, Kaatje Goetschalckx, Kai Eggers, Kamalakar Surineni, Kanae Hirase, T R Kapilamoorthy, Karen Calfas, Karen Gratrix, Karen Hallett, Karen Hultberg, Karen Nugent, Karen Petrosyan, Karen Swan, Karolina Kryczka, Karolina Wojtczak-Soska, Karolina Wojtera, Karsten Lenk, Karthik Ramasamy, Katarzyna Łuczak, Katarzyna Malinowska, Kate Pointon, Kate Robb, Katherine Martin, Kathleen Claes, Kathryn Carruthers, Kathy E Siegel, Katia Drouin, Katie Fowler-Lehman, Kavita Rawat, Kay Rowe, Keiichi Fukuda, Keith A A Fox, Ken Mahaffey, Kendra Unterbrink, Kenneth Giedd, Kerrie Van Loo, Kerry Lee, Kerstin Bonin, Kevin R Bainey, Kevin T Harley, Kevin Anstrom, Kevin Chan, Kevin Croce, Kevin Landolfo, Kevin Marzo, Keyur Patel, Khaled Abdul-Nour, Khaled Alfakih, Khaled Dajani, Khaled Ziada, Khaula Baloch, Khrystyna Kushniriuk, Kian-Keong Poh, Kim F Ireland, Kim Holland, Kimberly Ann Byrne, Kimberly E Halverson, Kimberly Elmore, Kimberly Miller-Cox, Kiran Reddy, Kirsten J Quiles, Kirsty Abercrombie, Klaus Matschke, Konrad Szymczyk, Koo Hui Chan, Kotiboinna Preethi, Kozhaya Sokhon, Krissada Meemuk, Kristian Thygesen, Kristin M Salmi, Kristin Newby, Kristina Wippler, Kristine Arges, Kristine Teoh, Krystal Etherington, Krystyna Łoboz-Grudzień, Krzysztof W Reczuch, Krzysztof Bury, Krzysztof Drzymalski, Krzysztof Kukuła, Kuo-Tzu Sung, Kurt Huber, Ladda Douangvila, Lance Sullenberger, Larissa Miranda Trama, Laszlone Matics, Laura Drew, Laura Flint, Laura Keinaite, Laura Sarti, Laurel Kolakaluri, Lawrence M Phillips, Lawrence Friedman, Lawrence Phillips, Lazar Velicki, Leah Howell, Leandro C Maranan, Leanne Cox, Ledjalem Daba, Lei Zhang, Lekshmi Dharmarajan, Leo Bockeria, Leonardo Pizzol Caetano, Leonardo Bridi, Leonid L Bershtein, Leszek Sokalski, Li Hai Yan, Li Li, Lia Nijmeijer, Lidia Sousa, Lihong Xu, Lihua Zhang, Lili Zhang, Lilia Schiavi, Lilian Mazza Barbosa, Lillian L Khor, Lina Felix-Stern, Linda L Hall, Linda M Hollenweger, Linda Arcand, Linda Davidson-Ray, Linda Schwarz, Lindsey N Sikora, Lingping Chi, Lino Patricio, Liping Zhang, Lisa Chaytor, Lisa Hatch, Lisa McCloy, Lisa Wong, Liselotte Persson, Lixin Jiang, Liz Low, Ljiljana Pupic, Loïc Bière, Lorenzo Monti, Lori Christensen, Lori Pritchard, Loriane Black, Lori-Ann Desimone, Lori-Ann Larmand, Lorraine McGregor, Louise Morby, Louise Thomson, Luc Harvey, Luciana de Pádua Baptista, Lucilla Garcia, Ludivine Eliahou, Ludmila Helmer, Luis F Smidt, Luis Bernanrdes, Luis Guzman, Luiz A Carvalho, Luyang Xiong, Lynette L Teo, Lynn M Neeson, Lynne Winstanley, M Barbara Srichai-Parsia, M Quintana Giner, M Sowjanya Reddy, M Valdés Chávarri, M Grazia Rossi, Maarten Simoons, Maayan Konigstein, Maciej Lesiak, Maciej Olsowka, Mafalda Selas, Magalie Corfias, Magdalena Madero Rovalo, Magdalena Łanocha, Magdalena Miller, Magdalena Misztal-Teodorczyk, Magdalena Rantinella, Magdy Abdelhamid, Magnolia Jimenez, Mahboob Alam, Mahevamma Mylarappa, Mahfouz El Shahawy, Mahmoud Mohamed, Mahmud Al-Bustami, Majo X Joseph, Malgorzata Frach, Małgorzta Celińska-Spodar, Malte Helm, Manas Chacko, Mandy Murphy, Manitha Vinod, Manjula Rani, Manu Dhawan, Manuela Mombelli, Marcel Weber, Marcello Galvani, Marcelo Jamus Rodrigues, Marcia F Dubin, Marcia F Werner Bayer, Marcin Szkopiak, Marco Antonio Monsalve, Marco Bizzaro Santos, Marco Magnoni, Marco Marini, Marco Sicuro, Marco Zenati, Marcos Valério Coimbra Resende, Marek Roik, Margalit Bentzvi, Margaret Gilsenan, Margaret Iraola, Margot C Quinn, Maria A Alfonso, Maria Antonieta Pereira Moraes, María Dolores Martínez-Ruíz, María Fernanda Canales, Maria Inês Caetano, Maria P Corral, Maria Pérez García, Maria Victoria Actis, Maria Aguirre, Maria Andreasson, Maria Aprile, Maria Colton, Maria Eugenia Martin, Maria Lasala, Maria Lorenzo, Maria Posada, Maria Shier, Maria Thottam, Mariana V Furtado, Mariana Yumi Okada, Marianna D A Dracoulakis, Marianne De Andrade, Mariano Rubio, Marie Essermark, Marielle Scherrer-Crosbie, Marija T Petrovic, Marija Zdravkovic, Marilyn Black, Marina Garcia, Mario J Garcia, Mariola Szulik, Marisa Orgera, Mark A de Belder, Mark Harbinson, Mark Hyun, Mark Peterson, Mark Xavier, Marlowe Mosley, Marta Capinha, Marta Marcinkiewicz-Siemion, Marta Swiderek, Martha Meyer, Martina Ceseri, Martina Tricoli, Marvin Kronenberg, Mary Williams, Mary Ann Champagne, Mary Colleen Rogge, Mary R Soltau, Mary Streif, Massimo Villella, Massoud Leesar, Matei Claudia, Mateusz Solecki, Matías Nicolás Mungo, Matthew Wall Jr, Matthew Budoff, Matthew Jezior, Matthew Luckie, Matthias Friedrich, Mauren P Haeffner, Maximilian Tscharre, Max-Paul Winter, Mayana Almeida, Mayil S Krishnam, Mayuri Patel, Meenakshi Mishra, Megan Manocchia, Meghana Kakade, Melanie J Munro, Melissa D Chaplin, Melissa LeFevre, Mervyn Andiapen, Michael A Gibson, Michael B Rubens, Michael C Turner, Michael D Shapiro, Michael W Lee, Michael Berlowitz, Michael Davidson, Michael Mack, Michael McDaniel, Michael Mumma, Michal Wlodarczyk, Michel G Khouri, Michel S Slama, Michele Rawlins, Michelle M Bonner, Michelle M Seib, Michelle Chang, Michelle Crowder, Michelle Dixon, Michelle Mayon, Michelle McEvoy, Michelle Yee, Miguel M Fernandes, Miguel Nobre Menezes, Miguel Souto Bayarri, Miguel Barrero, Mikhail T Torosoff, Milan R Dobric, Milan Dobric, Milica Nikola Dekleva, Milind Avdhoot Gadkari, Millie Gomez, Min Tun Kyaw, Miriam Brooks, Miroslav Stevo Martinovic, Mitchel B Lustre, Mohammad Tariq Vakani, Mohammad El-Hajjar, Mohammed Al-Amoodi, Mohammed Hussain, Mohammed Saleem, Moisés Blanco-Calvo, Moisés Jiménez-Santos, Mona Bhatia, Monica Rosca, Monika Laukyte, Montserrat Gracida Blanca, Montserrat Vila Perales, Mouaz H Al-Mallah, Moysés de Oliveira Filho, Mpiko Ntsekhe, Muhamed Saric, Mulei Chen, Myriam Brousseau, Myrthes Emy Takiuti, Nada Cemerlic-Adjic, Nadia Asif, Nadia Gakou, Nafisa Hussain, Nana O Katamadze, Nancy L Clapp, Nancy Aedy, Nandita Nataraj, Nanette K Wenger, Naomi Uchida, Nasrul Ismail, Natalia S Oliveira, Natalia de Carvalho Maffei, Natalie Spitzer, Natasha C Putnam, Naved Aslam, Neamat Mowafy, Neeraj Pandit, Neeraj Parakh, Nevena Garcevic, Ngaire Meadows, Nhi N Tran, Nicholas Danchin, Nicki Lakeman, Nicola Johnston, Nicolas W Shammas, Nicole Saint Vrestil, Nicole Deming, Nier Zhong, Niket Patel, Nikola N Boskovic, Nikolaos Karogiannis, Nikos Werner, Nina Johnston, Ning Zhang, Ning Zhou, Niree Hindoyan, Nirmal Kumar, Nitika Chadha, Nitish Naik, Nodira Aripova, Noloyiso Mtana, Nona A Eskelson, Noor Syamira 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Vincent Setang, C P Vineeth, Virginai Pubull Nuñez, Virginia Fernández-Figares, Vitor Gomes, Viviana Gabriel, Viviane Dos Santos, Viviane Almeida, Vlad A Iliescu, Vladan Mudrenovic, Vladimir Dzavik, Vojislav L Giga, Walter Enrique Mogrovejo, Wan Xian Chan, Wanda C Marfori, Wanda Parker, Warangkana Mekara, Wassim Nona, Wayne Old, Wayne Pennachi, Weerachai Nawarawong, Wei Chen, Wei Su, Weibing Xing, Wei-Ren Lan, Wenda Crawford, Wendy L Stewart, Wendy Drewes, Wenhua Lin, William B Abernethy, William D Salerno, William F Fearon, William Vergoni, William Weintraub, Winnie C Sia, Wlodzimierz J Musial, Xacobe Flores-Ríos, Xavier Garcia-Moll Marimon, Xi Su, Xiang Ma, Xiangqiong Gu, Xiao Wang, Xiaomei Li, Xiaowei Yao, Xin Fu, Xin Su, Xin Zeng, Xinchun Yang, Xiuhong Li, Xuehua Fang, Xutong Wang, Yaming Geng, Yan Yan, Yanek Pépin-Dubois, Yanfu Wang, Yang Wang, Yanmeng Tian, Yaping Huang, Yechen Han, Yesenia Zambrano, Yi-Hsuan Yang, Ying Tung Sia, Yining Yang, Yitong Ma, Yolayfi Peralta, Yongjian Wu, Yu Kunwu, Yu Zhao, Yudong Peng, Yueh-Hung Lin, Yulan Zhao, Yumei Dong, Yunhai Zhao, Yutthaphan Wannasopha, Yvonne Taul, Zakir Sahul, Zalina Kudzoeva, Zbigniew Kalarus, Zeljko Z Markovic, Zhen Huang, Zheng Ji, Zhenyu Liu, Zhou Yue, Zhulin Zhang, Zhuxi Li, Zile Singh Meharwal, Ziliang Bai, Zixiang Yu, Zohra Huda, Zoltan Davidovits

Subjects
Male, Cardiac Catheterization, Computed Tomography Angiography, medicine.medical_treatment, Myocardial Ischemia, Coronary Disease, Coronary Artery Disease, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Coronary Angiography, ISCHEMIA Research Group, law.invention, Angina, Coronary artery disease, 0302 clinical medicine, Randomized controlled trial, law, Cardiovascular Disease, Myocardial Revascularization, 030212 general & internal medicine, Coronary Artery Bypass, 11 Medical and Health Sciences, Cardiac catheterization, General Medicine, Middle Aged, humanities, Cardiovascular Diseases, Cardiology, Female, Human, medicine.medical_specialty, Ischemia, Article, 03 medical and health sciences, Geriatric cardiology, Percutaneous Coronary Intervention, General & Internal Medicine, Internal medicine, medicine, Humans, Angina, Unstable, Aged, business.industry, Coronary Artery Bypa, Percutaneous coronary intervention, Bayes Theorem, medicine.disease, Heart failure, Quality of Life, business
Abstract

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

Published
2020
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12. Xylem anatomy and hydraulic traits in Vitis grafted cuttings in view of their impact on the young grapevine decline

Author

Enrico Battiston, Sara Falsini, Alessio Giovannelli, Silvia Schiff, Corrado Tani, Roberta Panaiia, Alessio Papini, Stefano Di Marco, and Laura Mugnai

Subjects
Plant Science
Abstract

Grapevine grafting is an essential practice in viticulture and over the years, various bench grafting techniques have been developed to mechanize the nursery process and to increase the yield in number of viable cuttings. Bench grafting is a fundamental nursery practice that can potentially affect the quality of propagation material also in young decline associated to grapevine trunk diseases and has been recently reported to influence leaf symptoms development associated with diseases of Esca complex. The study aimed to investigate how three bench grafting methods [i.e., (i) Omega graft as mechanical technique, (ii) Whip and Tongue graft as manual technique and (iii) Full Cleft graft as semi-mechanical technique] can influence these phenomena. Specifically, the different methods were compared for their effect on the anatomical development of the grafting point and the functionality of the xylem, also considering two factors: the grapevine cultivar (Cabernet Sauvignon, Glera and Teroldego) and the scion/rootstock diameter (thin and large). Observations by light microscopy on the anatomical evolution and measurements on the xylem morphology and hydraulic traits were correlated with the grafting methods and the investigated varieties. The anatomical observations revealed that the mechanical (Omega) and semi-mechanical (Full Cleft) grafting methods have a faster callusing response while the manual technique (Whip and Tongue) has a slower but greater vascularization of the differentiated callus. Significant differences between cultivars and/or grafting types were also detected in necrotic area on the grafted tissues. Statistical analysis of the grapevine vessels suggested differences in xylem parameters between cultivars, while grafting type had no significant effects. On the other hand, the grafting type significantly affected the intrinsic growth rate. The study confirms the potential incidence of lesions and dysfunctionalities correlated with the grafting method applied, which can potentially induce grafted vine declines in vineyards due to the necrotic area detected on the grafted tissues.

Published
2022
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13. P3HT-GRAPHENE DEVICE FOR THE RESTORATION OF VISUAL PROPERTIES IN A RAT MODEL OF RETINITIS PIGMENTOSA

Author

Simona Francia, Stefano Di Marco, Mattia L. DiFrancesco, Davide V. Ferrari, Dmytro Shmal, Alessio Cavalli, Grazia Pertile, Marcella Attanasio, José Fernando Maya‐Vetencourt, Giovanni Manfredi, Guglielmo Lanzani, Fabio Benfenati, and Elisabetta Colombo

Subjects
Mechanics of Materials, General Materials Science, Industrial and Manufacturing Engineering
Abstract

Retinal degeneration is one of the prevalent causes of blindness worldwide, for which no effective treatment has yet been identified. Inorganic photovoltaic devices have been investigated for visual restoration in advanced stage Retinitis pigmentosa (RP), although lack of implant flexibility and foreign-object reactions have limited their application. Organic photoactive retinal prostheses may overcome these limitations, being biomimetic and tissue friendly. Inspired by organic photovoltaic strategies involving graphene, a hybrid retinal prosthesis was recently engineered consisting of a dual poly-3-hexylthiophene (P3HT) and graphene layer onto a flexible substrate. Here, this hybrid prosthesis was subretinally implanted in vivo in 5-month-old Royal College of Surgeons (RCS) rats, a rodent model of RP. Implanted dystrophic rats restored visual performances at both subcortical and cortical levels in response to light stimuli, in the absence of marked inflammatory responses. Moreover, the analysis of the physical-mechanical properties after prolonged permanence in the eye showed excellent biocompatibility and robustness of the device. Overall, the results demonstrate that graphene-enhanced organic photovoltaic devices can be suitably employed for the rescue of retinal dystrophies and supports the translation of the organic strategy into the medical practice.TABLE OF CONTENTSInspired by organic photovoltaic, a hybrid retinal prosthesis consisting of poly-3-hexylthiophene (P3HT) and graphene on a flexible substrate was subretinally implanted in vivo in Royal College of Surgeons (RCS) rats, a model of Retinitis pigmentosa. Implanted dystrophic rats restored visual performances at both subcortical and cortical levels in response to light stimuli, in the absence of marked inflammatory responses.

Published
2022
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14. Xylem anatomy and hydraulic traits in

Author

Enrico, Battiston, Sara, Falsini, Alessio, Giovannelli, Silvia, Schiff, Corrado, Tani, Roberta, Panaiia, Alessio, Papini, Stefano, Di Marco, and Laura, Mugnai

Abstract

Grapevine grafting is an essential practice in viticulture and over the years, various bench grafting techniques have been developed to mechanize the nursery process and to increase the yield in number of viable cuttings. Bench grafting is a fundamental nursery practice that can potentially affect the quality of propagation material also in young decline associated to grapevine trunk diseases and has been recently reported to influence leaf symptoms development associated with diseases of Esca complex. The study aimed to investigate how three bench grafting methods [i.e., (i) Omega graft as mechanical technique, (ii) Whip and Tongue graft as manual technique and (iii) Full Cleft graft as semi-mechanical technique] can influence these phenomena. Specifically, the different methods were compared for their effect on the anatomical development of the grafting point and the functionality of the xylem, also considering two factors: the grapevine cultivar (Cabernet Sauvignon, Glera and Teroldego) and the scion/rootstock diameter (thin and large). Observations by light microscopy on the anatomical evolution and measurements on the xylem morphology and hydraulic traits were correlated with the grafting methods and the investigated varieties. The anatomical observations revealed that the mechanical (Omega) and semi-mechanical (Full Cleft) grafting methods have a faster callusing response while the manual technique (Whip and Tongue) has a slower but greater vascularization of the differentiated callus. Significant differences between cultivars and/or grafting types were also detected in necrotic area on the grafted tissues. Statistical analysis of the grapevine vessels suggested differences in xylem parameters between cultivars, while grafting type had no significant effects. On the other hand, the grafting type significantly affected the intrinsic growth rate. The study confirms the potential incidence of lesions and dysfunctionalities correlated with the grafting method applied, which can potentially induce grafted vine declines in vineyards due to the necrotic area detected on the grafted tissues.

Published
2022

15. Single-cell-resolution map of human retinal pigment epithelium helps discover subpopulations with differential disease sensitivity

Author

Davide Ortolan, Ruchi Sharma, Andrei Volkov, Arvydas Maminishkis, Nathan A. Hotaling, Laryssa A. Huryn, Catherine Cukras, Stefano Di Marco, Silvia Bisti, and Kapil Bharti

Subjects
Multidisciplinary, Retinal Diseases, Artificial Intelligence, Humans, Macula Lutea, Retinal Pigment Epithelium
Abstract

Regional phenotypic and functional differences in the retinal pigment epithelium (RPE) monolayer have been suggested to account for regional susceptibility in ocular diseases such as age-related macular degeneration (AMD), late-onset retinal degeneration (L-ORD), and choroideremia (CHM). However, a comprehensive description of human topographical RPE diversity is not yet available, thus limiting the understanding of regional RPE diversity and degenerative disease sensitivity in the eye. To develop a complete morphometric RPE map of the human eye, artificial intelligence–based software was trained to recognize, segment, and analyze RPE borders. Five statistically different, concentric RPE subpopulations (P1 to P5) were identified using cell area as a parameter, including a subpopulation (P4) with cell area comparable to that of macular cells in the far periphery of the eye. This work provides a complete reference map of human RPE subpopulations and their location in the eye. In addition, the analysis of cadaver non-AMD and AMD eyes and ultra-widefield fundus images of patients revealed differential vulnerability of the five RPE subpopulations to different retinal diseases.

Published
2022

16. Modulation of neuronal firing: what role can nanotechnology play?

Author

Valentina Castagnola, Elisabetta Colombo, Fabio Benfenati, José Fernando Maya-Vetencourt, Stefano Di Marco, Mattia L. DiFrancesco, Guglielmo Lanzani, and Giovanni Manfredi

Subjects
Neurons, 0303 health sciences, Materials science, nanoelectrodes, Neuronal firing, Biomedical Engineering, Medicine (miscellaneous), Bioengineering, 02 engineering and technology, Development, 021001 nanoscience & nanotechnology, 03 medical and health sciences, nanomaterials, neural stimulation, Modulation, Neural stimulation, Nanotechnology, General Materials Science, 0210 nano-technology, Neuroscience, 030304 developmental biology
Published
2020
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17. First Description of Non-Enzymatic Radical-Generating Mechanisms Adopted by Fomitiporia mediterranea: An Unexplored Pathway of the White Rot Agent of the Esca Complex of Diseases

Author

Samuele Moretti, Mary-Lorène Goddard, Alessandro Puca, Jacques Lalevée, Stefano Di Marco, Laura Mugnai, Eric Gelhaye, Barry Goodell, Christophe Bertsch, and Sibylle Farine

Subjects
Microbiology (medical), Fmed, CMF, phenolates, ferric iron, •OH, grapevine, GTDs, Plant Science, Ecology, Evolution, Behavior and Systematics
Abstract

Fomitiporia mediterranea (Fmed) is the primary Basidiomycota species causing white rot in European vineyards affected by the Esca complex of diseases (ECD). In the last few years, an increasing number of studies have highlighted the importance of reconsidering the role of Fmed in ECD etiology, justifying an increase in research interest related to Fmed’s biomolecular pathogenetic mechanisms. In the context of the current re-evaluation of the binary distinction (brown vs. white rot) between biomolecular decay pathways induced by Basidiomycota species, our research aims to investigate the potential for non-enzymatic mechanisms adopted by Fmed, which is typically described as a white rot fungus. Our results demonstrate how, in liquid culture reproducing nutrient restriction conditions often found in wood, Fmed can produce low molecular weight compounds, the hallmark of the non-enzymatic “chelator-mediated Fenton” (CMF) reaction, originally described for brown rot fungi. CMF reactions can redox cycle with ferric iron, generating hydrogen peroxide and ferrous iron, necessary reactants leading to hydroxyl radical (•OH) production. These observations led to the conclusion that a non-enzymatic radical-generating CMF-like mechanism may be utilized by Fmed, potentially together with an enzymatic pool, to contribute to degrading wood constituents; moreover, indicating significant variability between strains.

Published
2023
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19. Activity of

Author

Stefano, Di Marco, Elisa Giorgia, Metruccio, Samuele, Moretti, Marco, Nocentini, Giuseppe, Carella, Andrea, Pacetti, Enrico, Battiston, Fabio, Osti, and Laura, Mugnai

Abstract

Grapevine trunk diseases are widespread in all grape-growing countries. The diseases included in the Esca complex of diseases are particularly common in European vineyards. Their distinctive foliar symptoms are well known to be associated not only with losses in quantity, as with all grapevine wood diseases, but also with losses in the quality of the crop. Protection of pruning wounds is known to reduce infections in artificial inoculations and, to some extent, reduce the external leaf symptoms. The application of biological control agents in the field is typically started at the first appearance of symptoms. In this article, the two strains belonging to two different species

Published
2021

20. Innovative Delivery of Cu(II) Ions by a Nanostructured Hydroxyapatite: Potential Application in Planta to Enhance the Sustainable Control of Plasmopara viticola

Author

Laura Mugnai, Livio Antonielli, Florence Fontaine, Enrico Battiston, Stefano Di Marco, Résistance Induite et Bioprotection des Plantes - EA 4707 (RIBP), Université de Reims Champagne-Ardenne (URCA)-SFR Condorcet, and Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0106 biological sciences, biology, [SDV]Life Sciences [q-bio], Plant Science, biology.organism_classification, 01 natural sciences, 010602 entomology, Horticulture, Plasmopara viticola, Downy mildew, Viticulture, Vitis vinifera, Agronomy and Crop Science, ComputingMilieux_MISCELLANEOUS, 010606 plant biology & botany
Abstract

Downy mildew caused by Plasmopara viticola is probably the most serious disease affecting grapevine (Vitis vinifera), and it is capable of causing consistent yield losses. In organic viticulture, the only acceptable and effective means to control the disease is by applications of copper-based fungicides. However, the use of copper in agriculture is expected to be further restricted by European countries because of its critical ecotoxicological and phytotoxicological profile. Research on ways to reduce the effective amounts of copper by developing innovative formulations as well as optimization of the distribution and persistence of copper-based pesticides for downy mildew control seems to be a promising approach. This research investigated the delivery properties of biomimetic synthetic hydroxyapatite (HA) to enhance the biological activity of Cu(II) ions. To this aim, four Cu(II) compounds were formulated with the innovative HA component and applied in an in vitro antifungal assay against Botrytis cinerea, a common grapevine pathogen suitable for in vitro activity tests, and finally, in in planta efficacy assays against P. viticola under greenhouse conditions. The in vitro results highlighted a different inhibition activity for each Cu(II) compound and indicated a different interaction between the cupric compounds and HA, potentially related to different delivery mechanisms of Cu(II) from HA. Under greenhouse conditions, additional findings on the biological activity of the applied formulations were gained, especially on the efficacy of various concentrations of HA in the formulations, the influence of dose variation of the formulation and the treatment efficiency, and the persistence under rain-washing effect. This study revealed promising findings on the formulation based on the HA particles and the soluble Cu(II) compound, which resulted in reduced disease severity and incidence in all of the experimental conditions, including the lower Cu(II) dosage and the rain-washing effect. This suggests that coformulation of the three insoluble Cu(II) compounds with HA might significantly enhance the adsorption and release of Cu(II) ions by HA particles.

Published
2019
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21. The Timecourses of Functional, Morphological, and Molecular Changes Triggered by Light Exposure in Sprague-Dawley Rat Retinas

Author

James Ashley, Silvia Bisti, Stefano Di Marco, Serena Riccitelli, and Mattia Di Paolo

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, Time Factors, Light, QH301-705.5, Article, Retina, functional analysis, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, In vivo, Glial Fibrillary Acidic Protein, medicine, Electroretinography, Animals, Biology (General), Fibroblast, early detection, Pathological, remodeling, Glial fibrillary acidic protein, biology, Neurodegeneration, Retinal Degeneration, neurodegeneration, Retinal, General Medicine, light damage, medicine.disease, Rats, 030104 developmental biology, medicine.anatomical_structure, chemistry, Gliosis, Gene Expression Regulation, 030221 ophthalmology & optometry, biology.protein, Fibroblast Growth Factor 2, sense organs, medicine.symptom
Abstract

Retinal neurodegeneration can impair visual perception at different levels, involving not only photoreceptors, which are the most metabolically active cells, but also the inner retina. Compensatory mechanisms may hide the first signs of these impairments and reduce the likelihood of receiving timely treatments. Therefore, it is essential to characterize the early critical steps in the neurodegenerative progression to design adequate therapies. This paper describes and correlates early morphological and biochemical changes in the degenerating retina with in vivo functional analysis of retinal activity and investigates the progression of neurodegenerative stages for up to 7 months. For these purposes, Sprague–Dawley rats were exposed to 1000 lux light either for different durations (12 h to 24 h) and examined seven days afterward (7d) or for a fixed duration (24 h) and monitored at various time points following the exposure (up to 210d). Flash electroretinogram (fERG) recordings were correlated with morphological and histological analyses to evaluate outer and inner retinal disruptions, gliosis, trophic factor release, and microglial activation. Twelve hours or fifteen hours of exposure to constant light led to a severe retinal dysfunction with only minor morphological changes. Therefore, early pathological signs might be hidden by compensatory mechanisms that silence retinal dysfunction, accounting for the discrepancy between photoreceptor loss and retinal functional output. The long-term analysis showed a transient functional recovery, maximum at 45 days, despite a progressive loss of photoreceptors and coincident increases in glial fibrillary acidic protein (GFAP) and basic fibroblast growth factor-2 (bFGF-2) expression. Interestingly, the progression of the disease presented different patterns in the dorsal and ventral retina. The information acquired gives us the potential to develop a specific diagnostic tool to monitor the disease’s progression and treatment efficacy.

Published
2021

22. Biocompatibility of a Conjugated Polymer Retinal Prosthesis in the Domestic Pig

Author

José Fernando Maya-Vetencourt, Stefano Di Marco, Maurizio Mete, Mattia Di Paolo, Domenico Ventrella, Francesca Barone, Alberto Elmi, Giovanni Manfredi, Andrea Desii, Walter G. Sannita, Silvia Bisti, Guglielmo Lanzani, Grazia Pertile, Maria Laura Bacci, Fabio Benfenati, Maya-Vetencourt, José Fernando, Di Marco, Stefano, Mete, Maurizio, Di Paolo, Mattia, Ventrella, Domenico, Barone, Francesca, Elmi, Alberto, Manfredi, Giovanni, Desii, Andrea, Sannita, Walter G., Bisti, Silvia, Lanzani, Guglielmo, Pertile, Grazia, Bacci, Maria Laura, and Benfenati, Fabio

Subjects
etinal degeneration, retinitis pigmentosa, biomedical pig, retinal prosthesis, conjugated polymers, 0301 basic medicine, Retinal degeneration, Proliferative vitreoretinopathy, Histology, genetic structures, Biocompatibility, lcsh:Biotechnology, retinal prosthesis, Biomedical Engineering, Bioengineering, 02 engineering and technology, 03 medical and health sciences, chemistry.chemical_compound, In vivo, lcsh:TP248.13-248.65, retinitis pigmentosa, Retinitis pigmentosa, medicine, conjugated polymers, Outer nuclear layer, Original Research, Retina, biomedical pig, retinal degeneration, Chemistry, Bioengineering and Biotechnology, Retinal, 021001 nanoscience & nanotechnology, medicine.disease, eye diseases, 030104 developmental biology, medicine.anatomical_structure, sense organs, 0210 nano-technology, Biomedical engineering, Biotechnology
Abstract

The progressive degeneration of retinal photoreceptors is one of the most significant causes of blindness in humans. Conjugated polymers represent an attractive solution to the field of retinal prostheses, and a multi-layer fully organic prosthesis implanted subretinally in dystrophic Royal College of Surgeons (RCS) rats was able to rescue visual functions. As a step toward human translation, we report here the fabrication and in vivo testing of a similar device engineered to adapt to the human-like size of the eye of the domestic pig, an excellent animal paradigm to test therapeutic strategies for photoreceptors degeneration. The active conjugated polymers were layered onto two distinct passive substrates, namely electro-spun silk fibroin (ESF) and polyethylene terephthalate (PET). Naive pigs were implanted subretinally with the active device in one eye, while the contralateral eye was sham implanted with substrate only. Retinal morphology and functionality were assessed before and after surgery by means of in vivo optical coherence tomography and full-field electroretinogram (ff-ERG) analysis. After the sacrifice, the retina morphology and inflammatory markers were analyzed by immunohistochemistry of the excised retinas. Surprisingly, ESF-based prostheses caused a proliferative vitreoretinopathy with disappearance of the ff-ERG b-wave in the implanted eyes. In contrast, PET-based active devices did not evoke significant inflammatory responses. As expected, the subretinal implantation of both PET only and the PET-based prosthesis locally decreased the thickness of the outer nuclear layer due to local photoreceptor loss. However, while the implantation of the PET only substrate decreased the ff-ERG b-wave amplitude with respect to the pre-implant ERG, the eyes implanted with the active device fully preserved the ERG responses, indicating an active compensation of the surgery-induced photoreceptor loss. Our findings highlight the possibility of developing a new generation of conjugated polymer/PET-based prosthetic devices that are highly biocompatible and potentially suitable for subretinal implantation in patients suffering from degenerative blindness.

Published
2020

23. Saffron Shifts the Degenerative and Inflammatory Phenotype in Photoreceptor Degeneration

Author

Benedetto Falsini, Marco Piccardi, Mattia Di Paolo, Stefano Di Marco, Silvia Bisti, and Maria Anna Maggi

Subjects
chemistry.chemical_classification, Reactive oxygen species, genetic structures, Neurodegeneration, Retinal, Biology, Macular degeneration, medicine.disease, Photoreceptor degeneration, Phenotype, eye diseases, chemistry.chemical_compound, chemistry, Visual function, medicine, Neuroscience
Abstract

Photoreceptor neurodegenerative processes are induced by a variety of factors: genetic mutations, environmental stresses, aging, and a combination of them. The final outcome is photoreceptors malfunction and eventually death leading to progressive deterioration of visual function. At present, there is no cure for most retinal diseases. Recently, saffron has become an interesting candidate to cope with morphological and functional consequences of retinal neurodegeneration. Data obtained in both animal models and clinical trials in age-related macular degeneration and Stargardt patients provided evidence that saffron treatment reduces photoreceptor death, slows down the progression of neuroinflammatory processes, and eventually improves and maintains visual function. The ways of action are complex and not limited to reducing reactive oxygen species production. In fact, saffron treatment is also able to activate many genes. In addition, the chemical composition of saffron's components (mainly the ratio between different crocins) is a critical factor in defining the efficacy of treatment.

Published
2020
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24. Factors Involved on Tiger-Stripe Foliar Symptom Expression of Esca of Grapevine

Author

Mirella Bellocci, Elisa Giorgia Metruccio, Michele Pisante, Giuseppe Cillo, Stefano Di Marco, Francesco Calzarano, and Giancarlo Pagnani

Subjects
0106 biological sciences, 0301 basic medicine, Vine, grapevine, esca complex, wood disease control, leaf symptoms, Plant Science, engineering.material, Biology, 01 natural sciences, Vineyard, Asymptomatic, Article, Normalized Difference Vegetation Index, Fruit set, 03 medical and health sciences, Yield (wine), medicine, Ecology, Evolution, Behavior and Systematics, Ecology, Botany, food and beverages, Horticulture, 030104 developmental biology, QK1-989, Shoot, engineering, Fertilizer, medicine.symptom, 010606 plant biology & botany
Abstract

Esca of grapevine causes yield losses correlated with incidence and severity symptom expression. Factors associated with leaf symptom mechanisms are yet to be fully clarified. Therefore, in 2019 and 2020, macro and microelement analyses and leaf reflectance measurements were carried out on leaves at different growth stages in a vineyard located in Abruzzo, central Italy. Surveys were carried out on leaves of both never leaf-symptomatic vines and different categories of diseased vine shoots. Never leaf-symptomatic and diseased vines were also treated with a fertilizer mixture that proved to be able to limit the symptom expression. Results showed that untreated asymptomatic diseased vines had high calcium contents for most of the vegetative season. On the contrary, treated asymptomatic diseased vines showed higher contents of calcium, magnesium, and sodium, at berries pea-sized, before the onset of symptoms. These vines had better physiological efficiency showing higher water index (WI), normalized difference vegetation index (NDVI), and green normalized difference vegetation index (GNDVI) values, compared to untreated asymptomatic vines, at fruit set. Results confirmed the strong response of the plant to symptom expression development and the possibility of limiting this response with calcium and magnesium applications carried out before the symptom onset.

Published
2021
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25. Retinal Neurodegeneration: Correlation between Nutraceutical Treatment and Animal Model

Author

Eugenia Piragine, Claudia Gargini, Silvia Bisti, Mattia Di Paolo, Francesca Corsi, Stefano Di Marco, and Ilaria Piano

Subjects
Male, Retinal degeneration, Aging, Nutraceutical compounds, Oxidative stress, Preventative therapy, Animals, Dietary Supplements, Flavanones, Mice, Mice, Inbred C57BL, Neurodegenerative Diseases, Plant Extracts, Rats, Rats, Inbred F344, Retinal Diseases, Retinal Neurons, Crocus, Genetic enhancement, lcsh:TX341-641, Gene mutation, Inbred C57BL, Bioinformatics, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Animal model, Nutraceutical, Medicine, Inbred F344, Nutrition and Dietetics, business.industry, Neurodegeneration, Retinal, medicine.disease, Clinical trial, chemistry, 030221 ophthalmology & optometry, business, lcsh:Nutrition. Foods and food supply, 030217 neurology & neurosurgery, Food Science
Abstract

Retinal diseases can be induced by a variety of factors, including gene mutations, environmental stresses and dysmetabolic processes. The result is a progressive deterioration of visual function, which sometimes leads to blindness. Many treatments are under investigation, though results are still mostly unsatisfactory and restricted to specific pathologies, particularly in the case of gene therapy. The majority of treatments have been tested in animal models, but very few have progressed to human clinical trials. A relevant approach is to study the relation between the type of treatments and the degenerative characteristics of the animal model to better understand the effectiveness of each therapy. Here we compare the results obtained from different animal models treated with natural compounds (saffron and naringenin) to anticipate the potentiality of a single treatment in different pathologies.

Published
2021
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26. List of Contributors

Author

Mir Ajaz Akram, Rajendra Awasthi, Hamid A. Bakshi, K. Hüsnü Can Başer, Sabeeha Bashir, Silvia Bisti, Mohammad Hossein Boskabady, Nathalie Chahine, Ramez Chahine, Neerupma Dhiman, Benedetto Falsini, Tahereh Farkhondeh, Hakkim L. Faruck, Homa Fatma, Zahra Gholamnezhad, Vahideh Ghorani, Gamze Guclu, Mortaza Hajyzadeh, Ruqaya Jabeen, Riffat John, Parisa Pourali Kahriz, Prachi Kaushik, Hasim Kelebek, Mohammad Afsar Khan, Harsha Kharkwal, Khalid Mahmood Khawar, Mohammad Reza Khazdair, Müberra Koşar, G.T. Kulkarni, Hariom Kumar, Maria Anna Maggi, Stefano Di Marco, Arghavan Memarzia, Roohi Mirza, Amin Mokhtari-Zaer, Dhondup Namgyal, Tanveer Naved, Fatih Olmez, Mattia Di Paolo, Marco Piccardi, Nikolaos Pitsikas, Shaista Qadir, Saeideh Saadat, Saeed Samarghandian, Ercument Osman Sarihan, Maryam Sarwat, Serkan Selli, Archana Sharma, Bhupesh Sharma, Muzafar Ahmad Sheikh, Hifzur R. Siddique, Sajida Sumaiya, Murtaza M. Tambuwala, Sangilimuthu Alagar Yadav, and Mehmet Ugur Yildirim

Published
2019
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28. Functionalization of a nanostructured hydroxyapatite with Cu(II) compounds as a pesticide: in situ transmission electron microscopy and environmental scanning electron microscopy observations of treated Vitis vinifera L. leaves

Author

Maria C Salvatici, Laura Mugnai, Enrico Battiston, Alessandro Lavacchi, Stefano Di Marco, and Antonietta Gatti

Subjects
Materials science, Biocompatibility, Nanoparticle, Metal Nanoparticles, 02 engineering and technology, 010501 environmental sciences, Toxicology, 01 natural sciences, law.invention, Hydroxyapatite, Dynamic light scattering, Microscopy, Electron, Transmission, X-Ray Diffraction, law, Microscopy, Vitis, Environmental scanning electron microscope, Cu, 0105 earth and related environmental sciences, Plant Diseases, General Medicine, 021001 nanoscience & nanotechnology, Dynamic Light Scattering, Fungicides, Industrial, Pesticide, Plant Leaves, Durapatite, Oomycetes, Transmission electron microscopy, Insect Science, Drug delivery, Microscopy, Electron, Scanning, Surface modification, Electron microscope, 0210 nano-technology, Agronomy and Crop Science, Copper, Nuclear chemistry
Abstract

Background The present study evaluated a biocompatible material for plant protection with the aim of reducing the amount of active substance applied. We used a synthetic hydroxyapatite (HA) that has been studied extensively as a consequence of its bioactivity and biocompatibility. An aggregation between HA nanoparticles and four Cu(II) compounds applied to Vitis vinifera L. leaves as a pesticide was studied. Formulations were characterized by X-ray diffraction (XRD), dynamic light scattering (DLS) and electron microscopy and applied in planta to verify particle aggregation and efficiency in controlling the pathogen Plasmopara viticola. Results The XRD patterns showed different crystalline phases dependig on the Cu(II) compound formulated with HA particles, DLS showed that nanostructured particles are stable as aggregates out of the nanometer range and, in all formulations, transmission electron microscopy (TEM) and environmental scanning electron microscopy (ESEM) microscopy showed large aggregates which were partially nanostructured and were recognized as stable in their micrometric dimensions. Such particles did not show phytotoxic effects after their application in planta. Conclusion A formulation based on HA and a soluble Cu(II) compound showed promising results in the control of the fungal pathogen, confirming the potential role of HA as an innovative delivery system of Cu(II) ions. The present work indicates the possibility of improving the biological activity of a bioactive substance by modifying its structure through an achievable formulation with a biocompatible material. © 2018 Society of Chemical Industry.

Published
2017
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29. A promoter-proximal transcript targeted by genetic polymorphism controls E-cadherin silencing in human cancers

Author

Gabriele Varani, Giuseppina Pisignano, Abhishek Mitra, Carlo V. Catapano, Marco Magistri, Sarah N. Mapelli, Claudia Enriquez, Sara Napoli, Sara Allegrini, Giovanna Chiorino, Gioacchino D'Ambrosio, Chiara Pastori, Gianluca Civenni, Domenico Albino, Stefano Di Marco, Maurizia Mello-Grand, Ramón García-Escudero, and Giuseppina M. Carbone

Subjects
Male, 0301 basic medicine, Science, General Physics and Astronomy, Biology, Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, Epigenesis, Genetic, 03 medical and health sciences, Antigens, CD, Neoplasms, microRNA, Humans, Gene silencing, Genes, Tumor Suppressor, Gene Silencing, Epigenetics, Eukaryotic Initiation Factors, Allele, Promoter Regions, Genetic, Alleles, Genetics, Argonaute Proteins/genetics, Cadherins/genetics, Cell Differentiation, Eukaryotic Initiation Factors/genetics, Gene Expression Regulation, Neoplastic, Methyltransferases/genetics, Mutagenesis, Site-Directed, Neoplasms/genetics, Nucleic Acid Conformation, Polymorphism, Genetic, Prostatic Neoplasms/genetics, Prostatic Neoplasms/metabolism, Repressor Proteins/genetics, Multidisciplinary, Prostatic Neoplasms, Promoter, Methyltransferases, General Chemistry, Argonaute, Cadherins, Non-coding RNA, 3. Good health, Chromatin, Repressor Proteins, 030104 developmental biology, Argonaute Proteins
Abstract

Long noncoding RNAs are emerging players in the epigenetic machinery with key roles in development and diseases. Here we uncover a complex network comprising a promoter-associated noncoding RNA (paRNA), microRNA and epigenetic regulators that controls transcription of the tumour suppressor E-cadherin in epithelial cancers. E-cadherin silencing relies on the formation of a complex between the paRNA and microRNA-guided Argonaute 1 that, together, recruit SUV39H1 and induce repressive chromatin modifications in the gene promoter. A single nucleotide polymorphism (rs16260) linked to increased cancer risk alters the secondary structure of the paRNA, with the risk allele facilitating the assembly of the microRNA-guided Argonaute 1 complex and gene silencing. Collectively, these data demonstrate the role of a paRNA in E-cadherin regulation and the impact of a noncoding genetic variant on its function. Deregulation of paRNA-based epigenetic networks may contribute to cancer and other diseases making them promising targets for drug discovery., Promoter-proximal transcripts have been proposed to act as cis-acting elements regulating transcription. Here, the authors provide evidence that a promoter-proximal RNA, in combination with other epigenetic regulators, controls transcription of E-cadherin in epithelial cancers.

Published
2017
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30. Antioxidant Saffron and Central Retinal Function in ABCA4-Related Stargardt Macular Dystrophy

Author

Dario Marangoni, Antonello Fadda, Benedetto Falsini, Adriano Magli, Francesco Martelli, Matteo Bertelli, Angelo Maria Minnella, Stefano Di Marco, Silvia Bisti, and Marco Piccardi

Subjects
Male, Photoreceptors, 0301 basic medicine, Time Factors, Visual acuity, genetic structures, Crocetin, Visual Acuity, Administration, Oral, ABCA4, Pilot Projects, Gene mutation, Antioxidants, chemistry.chemical_compound, 0302 clinical medicine, Stargardt Disease, Prospective Studies, ABCA4 gene mutation, Child, Cross-Over Studies, Nutrition and Dietetics, biology, Settore MED/30 - MALATTIE APPARATO VISIVO, Brief Report, Middle Aged, Neuroprotection, Saffron, Phenotype, Treatment Outcome, medicine.anatomical_structure, Focal electroretinogram, Administration, Female, medicine.symptom, lcsh:Nutrition. Foods and food supply, Oral, Adult, medicine.medical_specialty, Adolescent, Personalized medicine, Retinal function, lcsh:TX341-641, Placebo, Retina, Young Adult, 03 medical and health sciences, Double-Blind Method, Ophthalmology, Electroretinography, medicine, Humans, Genetic Predisposition to Disease, Aged, business.industry, Retinal, Crocus, medicine.disease, Stargardt disease, Oxidative Stress, 030104 developmental biology, chemistry, Dietary Supplements, Mutation, 030221 ophthalmology & optometry, biology.protein, ATP-Binding Cassette Transporters, business, Food Science
Abstract

Retinal oxidative damage, associated with an ATP-binding cassette, sub-family A, member 4, also known as ABCA4 gene mutation, has been implicated as a major underlying mechanism for Stargardt disease/fundus flavimaculatus (STG/FF). Recent findings indicate that saffron carotenoid constituents crocins and crocetin may counteract retinal oxidative damage, inflammation and protect retinal cells from apoptosis. This pilot study aimed to evaluate central retinal function following saffron supplementation in STG/FF patients carrying ABCA4 mutations. Methods: in a randomized, double-blind, placebo-controlled study (clinicaltrials.gov: NCT01278277), 31 patients with ABCA4-related STG/FF and a visual acuity >0.25 were randomly assigned to assume oral saffron (20 mg) or placebo over a six month period and then reverted to P or S for a further six month period. Full ophthalmic examinations, as well as central 18° focal electroretinogram (fERG) recordings, were performed at baseline and after six months of either saffron or placebo. The fERG fundamental harmonic component was isolated by Fourier analysis. Main outcome measures were fERG amplitude (in µV) and phase (in degrees). The secondary outcome measure was visual acuity. Results: supplement was well tolerated by all patients throughout follow-up. After saffron, fERG amplitude was unchanged; after placebo, amplitude tended to decrease from baseline (mean change: −0.18 log µV, p < 0.05). Reverting the treatments, amplitude did not change significantly. fERG phase and visual acuity were unchanged throughout follow-up. Conclusions: short-term saffron supplementation was well tolerated and had no detrimental effects on the electroretinographic responses of the central retina and visual acuity. The current findings warrant further long-term clinical trials to assess the efficacy of saffron supplementation in slowing down the progression of central retinal dysfunction in ABCA4-related STG/FF.

Published
2019
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31. Fluorescent light induces neurodegeneration in the rodent nigrostriatal system but near infrared LED light does not

Author

Rita Maccarone, Stefano Di Marco, Ilaria Pietrantoni, Claudia Mattei, Mattia Di Paolo, Annamaria Capozzo, Stefania Romeo, Giovanni Corsini, Luca Lozzi, Roberto Maggio, Francesca Vaglini, Mario Rossi, Serena Riccitelli, Gabriella Aloisi, Flora Vitale, C Pardini, Irene Fasciani, Marta Capannolo, Cristina Viaggi, and Eugenio Scarnati

Subjects
0301 basic medicine, Male, Parkinson's disease, Light, Infrared Rays, Dopamine, Substantia nigra, Striatum, Biology, Receptors, Dopamine, 03 medical and health sciences, Basal (phylogenetics), Mice, 0302 clinical medicine, Fluorescent light, medicine, Animals, Viability assay, Molecular Biology, Dopamine neuron, 5-HT receptor, Neurons, Neuroscience (all), LED light, General Neuroscience, Dopaminergic Neurons, Neurodegeneration, Neurodegenerative Diseases, Firing pattern, Light pollution, Developmental Biology, Neurology (clinical), medicine.disease, Mice, Inbred C57BL, Substantia Nigra, 030104 developmental biology, nervous system, Biophysics, Neuroscience, 030217 neurology & neurosurgery, medicine.drug
Abstract

We investigated the effects of continuous artificial light exposure on the mouse substantia nigra (SN). A three month exposure of C57Bl/6J mice to white fluorescent light induced a 30% reduction in dopamine (DA) neurons in SN compared to controls, accompanied by a decrease of DA and its metabolites in the striatum. After six months of exposure, neurodegeneration progressed slightly, but the level of DA returned to the basal level, while the metabolites increased with respect to the control. Three month exposure to near infrared LED light (∼710nm) did not alter DA neurons in SN, nor did it decrease DA and its metabolites in the striatum. Furthermore mesencephalic cell viability, as tested by [3H]DA uptake, did not change. Finally, we observed that 710nm LED light, locally conveyed in the rat SN, could modulate the firing activity of extracellular-recorded DA neurons. These data suggest that light can be detrimental or beneficial to DA neurons in SN, depending on the source and wavelength.

Published
2017

32. Foliar Symptom Expression of Wood Decay in Actinidia deliciosa in Relation to Environmental Factors

Author

Stefano Di Marco and Fabio Osti

Subjects
Actinidia deliciosa, Phenology, Incidence (epidemiology), Environmental factor, food and beverages, Actinidiaceae, Plant Science, Biology, biology.organism_classification, medicine.disease_cause, Vineyard, Horticulture, Botany, Shoot, Management methods, medicine, Agronomy and Crop Science
Abstract

Di Marco, S., and Osti, F. 2008. Foliar symptom expression of wood decay in Actinidia deliciosa in relation to environmental factors. Plant Dis. 92:1150-1157. Kiwifruit vines (Actinidia deliciosa var. deliciosa) have recently been affected by a new form of decay caused by several fungi that produce different types of wood deterioration in the trunk and cordons. Surveys were conducted over a period of 5 years to investigate epidemiological aspects of the disease in a typical Italian growing area (Emilia-Romagna), where kiwifruit is widely cultivated and where the disease was noted for the first time. The disease was widespread over the kiwifruit growing area surveyed, and its incidence increased over the course of the survey. No relationship was found between vineyard soil characteristics or management methods and the annual incidence of symptomatic vines. Foliar symptoms did not consistently express every season even on obviously infected vines. The time of appearance and the development of the disease were correlated with plant phenology and temperature. In particular, from June to August, temperature seemed to affect the annual incidence of the disease in terms of both symptomatic shoots and symptomatic vines. The aspects in common between the decay of kiwifruit and esca of grapevine could be hypothesized and are discussed.

Published
2008
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33. A computational model of cell culture dynamics: the role of connectivity and synaptic receptors in the appearance of synchronized bursting events

Author

Hayder Amin, Thierry Nieus, Stefano Di Marco, Luca Berdondini, and Davide Lonardoni

Subjects
0303 health sciences, Artificial neural network, Computer science, General Neuroscience, Information processing, AMPA receptor, Network dynamics, 03 medical and health sciences, Cellular and Molecular Neuroscience, Bursting, 0302 clinical medicine, Order (biology), Poster Presentation, Neuroscience, 030217 neurology & neurosurgery, Biological network, Cultured neuronal network, 030304 developmental biology
Abstract

How an ensemble of neurons wires together to form a functional unit is a fundamental problem in neuroscience. The architecture of neuronal wiring, in fact, determines how neurons communicate and may be important for information processing performed by neuronal networks. However current knowledge is mainly limited to networks consisting of a small number of neurons, while the topological structure of biological networks remains still unknown. Primary neuronal cultures represent an ideal preparation to investigate the basic principles of network dynamics. At the mature stage, they display network-wide synchronous bursting events (SBEs) sharing similar spatiotemporal patterns of firing [1]. Interestingly, high-density MEA recordings have shown that SBEs actually correspond to propagating activities through the network. Typically, the simulated SBEs originated from a few and specific sites as in experiments [2], but the nature and the role of such events is still under debate. In order to investigate the determinants of such dynamics, we developed a computational model that mimics the main features of the recordings obtained by a high density multi-electrode-array device (4096 electrodes inter-spaced by 20um, [3]). With only a few topological constraints, the model expressed realistic SBEs along time that can be well clustered into only a few groups differing for their ignition sites and propagation directions, similarly to what it is observed experimentally. Furthermore, we used the model together with experimental datasets to investigate the effects of synaptic blockers of the AMPA, NMDA and GABA synapses on the network activity. In particular, we showed that NMDA receptors can be among the principal mechanisms involved in triggering a sequence of SBEs, a firing regime that is typically observed in for mature neuronal cultures. Such regime is characterized by a principal SBE recruiting a great percentage of neurons and followed by a sequence of several weaker SBEs interleaved by hundreds of milliseconds. Altogether, the results obtained with our neural network computational model show that this model can replicate most of the salient firing properties observed experimentally in cultured neuronal networks and that it can serve for exploring the properties of signals and responses observed in neuronal networks properties.

Published
2015
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34. Rank Order Coding: a Retinal Information Decoding Strategy Revealed by Large-Scale Multielectrode Array Retinal Recordings

Author

Geoffrey, Portelli, John M, Barrett, Gerrit, Hilgen, Timothée, Masquelier, Alessandro, Maccione, Stefano, Di Marco, Luca, Berdondini, Pierre, Kornprobst, and Evelyne, Sernagor

Subjects
Retinal Ganglion Cells, retina, Time Factors, multielectrode array, Action Potentials, Datasets as Topic, Signal Processing, Computer-Assisted, New Research, rank order coding, ganglion cells, Mice, Inbred C57BL, population coding, Animals, Sensory and Motor Systems, Microelectrodes, Photic Stimulation, Vision, Ocular
Abstract

Visual Abstract, How a population of retinal ganglion cells (RGCs) encodes the visual scene remains an open question. Going beyond individual RGC coding strategies, results in salamander suggest that the relative latencies of a RGC pair encode spatial information. Thus, a population code based on this concerted spiking could be a powerful mechanism to transmit visual information rapidly and efficiently., How a population of retinal ganglion cells (RGCs) encodes the visual scene remains an open question. Going beyond individual RGC coding strategies, results in salamander suggest that the relative latencies of a RGC pair encode spatial information. Thus, a population code based on this concerted spiking could be a powerful mechanism to transmit visual information rapidly and efficiently. Here, we tested this hypothesis in mouse by recording simultaneous light-evoked responses from hundreds of RGCs, at pan-retinal level, using a new generation of large-scale, high-density multielectrode array consisting of 4096 electrodes. Interestingly, we did not find any RGCs exhibiting a clear latency tuning to the stimuli, suggesting that in mouse, individual RGC pairs may not provide sufficient information. We show that a significant amount of information is encoded synergistically in the concerted spiking of large RGC populations. Thus, the RGC population response described with relative activities, or ranks, provides more relevant information than classical independent spike count- or latency- based codes. In particular, we report for the first time that when considering the relative activities across the whole population, the wave of first stimulus-evoked spikes is an accurate indicator of stimulus content. We show that this coding strategy coexists with classical neural codes, and that it is more efficient and faster. Overall, these novel observations suggest that already at the level of the retina, concerted spiking provides a reliable and fast strategy to rapidly transmit new visual scenes.

Published
2015

35. High-density MEA recordings unveil the dynamics of bursting events in Cell Cultures

Author

Alessandro Maccione, Hayder Amin, Thierry Nieus, Luca Berdondini, Stefano Di Marco, and Davide Lonardoni

Subjects
Cells, Cell Culture Techniques, Biomedical Engineering, Action Potentials, High density, Health Informatics, Biology, Hippocampus, Bursting, Biological neural network, Electrode array, Animals, Collective dynamics, Cells, Cultured, Neurons, Cultured, Microelectrodes, Nerve Net, Rats, Signal Processing, 1707, food and beverages, Microelectrode, Electrode, Neuroscience, Biomedical engineering
Abstract

High density multielectrode arrays (MEAs) based on CMOS technology (CMOS-MEAs) can simultaneously record extracellular spiking activity in neuronal cultures from 4096 closely spaced microelectrodes. This allows for a finer investigation of neuronal network activity compared to conventional MEAs with a few tens of electrodes. However, the sensing properties of these devices differ. To highlight this aspect, here we investigate and discuss the differences observed when quantifying spontaneous synchronized bursting events (SBEs) in datasets acquired with conventional MEAs and high-density MEAs from comparable hippocampal cultures. We found that datasets acquired with high-density MEAs exhibit collective dynamics similar to conventional arrays, but are characterized by a higher percentage of random spikes, i.e. spikes that are not part of a burst, most probably resulting from the larger recording capability. Additionally, the percentage of electrodes that record a burst is remarkably small on high-density MEAs compared to what can be observed on conventional MEAs and SBEs appear to be propagating in time across the electrode array, by involving shorter sequences of spikes per electrode. Overall, these results highlight a lower level of network synchronization involved in SBEs compared to what has been debated for several decades based on conventional MEA recordings from cell cultures.

Published
2015
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36. Microelectronics, bioinformatics and neurocomputation for massive neuronal recordings in brain circuits with large scale multielectrode array probes

Author

Alessandro Maccione, Gian Nicola Angotzi, Luca Berdondini, Stefano Di Marco, Stefano Zordan, Mauro Gandolfo, Hayder Amin, and Thierry Nieus

Subjects
CMOS-MEAs, Computer science, Data analysis, Neurocomputation, Action Potentials, Neuroimaging, Bioinformatics, Multiplexing, Big data, Electrode array, Microelectronics, Animals, Signal conditioning, Electrophysiology, Neuroscience (all), Neurons, Artificial neural network, business.industry, General Neuroscience, Brain, Computational Biology, Multielectrode array, Electric Stimulation, CMOS, Semiconductors, Temporal resolution, business, Microelectrodes
Abstract

Deciphering neural network function in health and disease requires recording from many active neurons simultaneously. Developing approaches to increase their numbers is a major neurotechnological challenge. Parallel to recent advances in optical Ca(2+) imaging, an emerging approach consists in adopting complementary-metal-oxide-semiconductor (CMOS) technology to realize MultiElectrode Array (MEA) devices. By implementing signal conditioning and multiplexing circuits, these devices allow nowadays to record from several thousands of single neurons at sub-millisecond temporal resolution. At the same time, these recordings generate very large data streams which become challenging to analyze. Here, at first we shortly review the major approaches developed for data management and analysis for conventional, low-resolution MEAs. We highlight how conventional computational tools cannot be easily up-scaled to very large electrode array recordings, and custom bioinformatics tools are an emerging need in this field. We then introduce a novel approach adapted for the acquisition, compression and analysis of extracellular signals acquired simultaneously from 4096 electrodes with CMOS MEAs. Finally, as a case study, we describe how this novel large scale recording platform was used to record and analyze extracellular spikes from the ganglion cell layer in the wholemount retina at pan-retinal scale following patterned light stimulation.

Published
2015

37. A scalable high performance client/server framework to manage and analyze high dimensional datasets recorded by 4096 CMOS-MEAs

Author

Stefano Di Marco, Alessandro Maccione, Stefano Zordan, Thierry Nieus, Matteo Zanotto, Luca Berdondini, and Hayder Amin

Subjects
Client–server model, CMOS, Computer architecture, Artificial Intelligence, Hardware_GENERAL, Neurotechnology, Computer science, Mechanical Engineering, Scalability, High dimensional, Analysis tools
Abstract

Large scale CMOS-MEAs are an emerging neurotechnology enabling extracellular recordings in-vitro and in-vivo with thousand's electrodes simultaneously. This is on the way to provide the unprecedented capability of acquiring signals from several thousands of single-units, thus opening novel perspectives for electrophysiology, but also novel challenges for analysis and management of large datasets. Here, we propose an analysis platform designed for managing unprecedentedly large datasets of electrical recordings acquired with a 4096-electrode array platform. Furthermore it provides a computational framework to facilitate the development and integration of new analysis tools exploiting high-resolution electrical recordings.

Published
2015
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38. Loggerhead turtle(Caretta caretta)by catches on long‐lines: The importance of olfactory stimuli

Author

Stefano Di Marco, Emilio Balletto, Susanna Piovano, Cristina Giacoma, Alberto Dominici, and Alvise Zannetti

Subjects
Scomber, biology, Swordfish, Fishing, Captivity, biology.organism_classification, law.invention, Predation, Fishery, Sea turtle, law, Animal Science and Zoology, Gladius, Turtle (robot)
Abstract

In order to reduce sea turtle by‐catches on surface drifting long‐lines during professional swordfish (Xiphias gladius) fishing, the relevance of olfactory stimuli in eliciting predation by loggerhead sea turtles (Caretta caretta) was investigated. Choice experiments were run in captivity. Squid‐shaped plastic lures having or lacking scomber odour were presented to 27 specimens (22 immatures and 5 adults). The turtles’ behavioural responses highlighted the importance of chemical clues in eliciting approaching and biting behaviours. This study was carried out within the framework of the EU‐Life Project ‘Urgent conservation measures for C. caretta in the Pelagie islands’ (LIFE 99 NAT/IT/006271).

Published
2004
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39. Recurrently connected and localized neuronal communities initiate coordinated spontaneous activity in neuronal networks

Author

Thierry Nieus, Alessandro Maccione, Davide Lonardoni, Luca Berdondini, Hayder Amin, and Stefano Di Marco

Subjects
0301 basic medicine, Physiology, Action Potentials, Hippocampus, Infographics, Biochemistry, 0302 clinical medicine, Models, Animal Cells, Medicine and Health Sciences, lcsh:QH301-705.5, Cells, Cultured, Neurons, Cultured, Ecology, Simulation and Modeling, Neurochemistry, Neurotransmitters, Multielectrode array, Electrophysiology, Computational Theory and Mathematics, Modeling and Simulation, Neurological, Cellular Types, Graphs, Network Analysis, Research Article, Network analysis, medicine.drug, Computer and Information Sciences, Neural Networks, Evolution, Cells, Models, Neurological, Neurophysiology, AMPA receptor, Biology, Cellular level, Network Motifs, Research and Analysis Methods, Membrane Potential, gamma-Aminobutyric acid, 03 medical and health sciences, Cellular and Molecular Neuroscience, Behavior and Systematics, Genetics, medicine, Animals, Molecular Biology, Ecology, Evolution, Behavior and Systematics, business.industry, Mechanism (biology), Data Visualization, Computational Biology, Biology and Life Sciences, Cell Biology, Gamma-Aminobutyric Acid, Nerve Net, Rats, 030104 developmental biology, lcsh:Biology (General), nervous system, Cellular Neuroscience, Artificial intelligence, business, Neuroscience, 030217 neurology & neurosurgery
Abstract

Developing neuronal systems intrinsically generate coordinated spontaneous activity that propagates by involving a large number of synchronously firing neurons. In vivo, waves of spikes transiently characterize the activity of developing brain circuits and are fundamental for activity-dependent circuit formation. In vitro, coordinated spontaneous spiking activity, or network bursts (NBs), interleaved within periods of asynchronous spikes emerge during the development of 2D and 3D neuronal cultures. Several studies have investigated this type of activity and its dynamics, but how a neuronal system generates these coordinated events remains unclear. Here, we investigate at a cellular level the generation of network bursts in spontaneously active neuronal cultures by exploiting high-resolution multielectrode array recordings and computational network modelling. Our analysis reveals that NBs are generated in specialized regions of the network (functional neuronal communities) that feature neuronal links with high cross-correlation peak values, sub-millisecond lags and that share very similar structural connectivity motifs providing recurrent interactions. We show that the particular properties of these local structures enable locally amplifying spontaneous asynchronous spikes and that this mechanism can lead to the initiation of NBs. Through the analysis of simulated and experimental data, we also show that AMPA currents drive the coordinated activity, while NMDA and GABA currents are only involved in shaping the dynamics of NBs. Overall, our results suggest that the presence of functional neuronal communities with recurrent local connections allows a neuronal system to generate spontaneous coordinated spiking activity events. As suggested by the rules used for implementing our computational model, such functional communities might naturally emerge during network development by following simple constraints on distance-based connectivity., Author summary Coordinated spontaneous spiking activity is fundamental for the normal formation of brain circuits during development. However, how ensembles of neurons generate these events remains unclear. To address this question, in the present study, we investigated the network properties that might be required to a neuronal system for the generation of these spontaneous waves of spikes. We performed our study on spontaneously active neuronal cell cultures using high-resolution electrical recordings and a computational network model developed to reproduce our experimental data both quantitatively and qualitatively. Through the analysis of both experimental and simulated data, we found that network bursts are initiated in regions of the network, or “functional communities”, characterized by particular local connectivity properties. We also found that these regions can amplify the background asynchronous spiking activity preceding a network burst and, in this way, can give rise to coordinated spiking events. As a whole, our results suggest the presence of functional communities of neurons in a developing neuronal system that might naturally emerge by following simple constraints on distance-based connectivity. These regions are most likely required for the generation of the spontaneous coordinated activity that can drive activity-dependent circuit formation.

Published
2017
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40. RECQ5 Helicase Cooperates with MUS81 Endonuclease in Processing Stalled Replication Forks at Common Fragile Sites during Mitosis

Author

Zdenka Hasanova, Pavel Janscak, Kalpana Surendranath, Radhakrishnan Kanagaraj, Ian D. Hickson, Nagaraja Chappidi, Hana Sedlackova, Stefano Di Marco, Jana Langhoff, Veronika Altmannova, Stefano Ferrari, Lumir Krejci, Shruti Menon, Daniela Hühn, Victoria Marini, Rahul Bhowmick, University of Zurich, and Janscak, Pavel

Subjects
0301 basic medicine, Time Factors, DNA Repair, DNA damage, DNA repair, Mitosis, Replication Origin, 610 Medicine & health, Biology, Transfection, 1307 Cell Biology, Chromosome segregation, 03 medical and health sciences, Control of chromosome duplication, Chromosomal Instability, Chromosome Segregation, CDC2 Protein Kinase, 1312 Molecular Biology, Humans, Phosphorylation, Molecular Biology, Binding Sites, Endodeoxyribonucleases, RecQ Helicases, Chromosome Fragile Sites, Chromosomal fragile site, 10061 Institute of Molecular Cancer Research, Helicase, DNA, Cell Biology, Endonucleases, MUS81, Molecular biology, Cyclin-Dependent Kinases, DNA-Binding Proteins, enzymes and coenzymes (carbohydrates), HEK293 Cells, 030104 developmental biology, biology.protein, 570 Life sciences, biology, Origin recognition complex, RNA Interference, Rad51 Recombinase, DNA Damage, HeLa Cells, Protein Binding
Abstract

The MUS81-EME1 endonuclease cleaves late replication intermediates at common fragile sites (CFSs) during early mitosis to trigger DNA-repair synthesis that ensures faithful chromosome segregation. Here, we show that these DNA transactions are promoted by RECQ5 DNA helicase in a manner dependent on its Ser727 phosphorylation by CDK1. Upon replication stress, RECQ5 associates with CFSs in early mitosis through its physical interaction with MUS81 and promotes MUS81-dependent mitotic DNA synthesis. RECQ5 depletion or mutational inactivation of its ATP-binding site, RAD51-interacting domain, or phosphorylation site causes excessive binding of RAD51 to CFS loci and impairs CFS expression. This leads to defective chromosome segregation and accumulation of CFS-associated DNA damage in G1 cells. Biochemically, RECQ5 alleviates the inhibitory effect of RAD51 on 3'-flap DNA cleavage by MUS81-EME1 through its RAD51 filament disruption activity. These data suggest that RECQ5 removes RAD51 filaments stabilizing stalled replication forks at CFSs and hence facilitates CFS cleavage by MUS81-EME1.

Published
2017
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41. RNAi-mediated silencing of Myc transcription inhibits stem-like cell maintenance and tumorigenicity in prostate cancer

Author

Giuseppina M. Carbone, Sandra Pinton, Carlo V. Catapano, Anastasia Malek, Sara Napoli, Manuela Sarti, Stefano Di Marco, Gianluca Civenni, Domenico Albino, and Ramón García-Escudero

Subjects
Oncology, Male, Cancer Research, medicine.medical_specialty, Transcription, Genetic, Cell, Genes, myc, Biology, Prostate cancer, Mice, RNA interference, Transcription (biology), Internal medicine, medicine, Tumor Cells, Cultured, Gene silencing, Animals, Humans, RNA, Small Interfering, Gene, Transcription factor, Cellular Senescence, Cell Proliferation, Regulation of gene expression, Carcinoma, Prostatic Neoplasms, medicine.disease, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Cell Transformation, Neoplastic, Cancer research, Neoplastic Stem Cells, RNA Interference
Abstract

Several studies link disease progression, recurrence, and treatment failures to the cancer stem-like cell (CSC) subpopulation within the heterogeneous tumor cell population. Myc is a transcription factor having a central function in stem cell biology and in human cancers. Hence, Myc represents an attractive target to develop CSC-specific therapies. Recent findings suggest that Myc transcription can be silenced using an RNA interference (RNAi)–based strategy that targets noncoding promoter-associated RNA (paRNA) overlapping the transcription start site. In this study, we investigated the effects of silencing Myc transcription on prostate CSC in cell culture and xenograft models of human prostate cancer. Treatment with an effective promoter-targeting siRNA reduced the fraction of CSCs, leading to reduced self-renewal, tumor-initiating, and metastatic capability. Combined analysis of stem-like cells and senescence markers indicated that Myc silencing triggered a phenotypic shift and senescence in the CSC subpopulation. Notably, systemic delivery of the promoter-targeting siRNA in the xenograft model produced a striking suppression in the development of prostate tumors. Our results support a pivotal role for Myc in CSC maintenance and show that Myc targeting via RNAi-based transcriptional silencing can trigger CSC senescence and loss of their tumor-initiating capability. More generally, our findings demonstrate the efficacy of RNAi-based transcriptional strategies and the potential to target regulatory noncoding paRNAs for therapeutic applications. Cancer Res; 73(22); 6816–27. ©2013 AACR.

Published
2013

42. Modulation of Type-1 and Type-2 Cannabinoid Receptors by Saffron in a Rat Model of Retinal Neurodegeneration

Author

Darin Zerti, Stefano Di Marco, Natalia Battista, Rita Maccarone, Mauro Maccarrone, Silvia Bisti, Cinzia Rapino, and Monia Di Tommaso

Subjects
Genetics and Molecular Biology (all), Photoreceptors, 0301 basic medicine, Retinal degeneration, Sensory Receptors, Cannabinoid receptor, Light, medicine.medical_treatment, Protein Expression, ved/biology.organism_classification_rank.species, lcsh:Medicine, Social Sciences, Apoptosis, Medicine (all), Biochemistry, Genetics and Molecular Biology (all), Agricultural and Biological Sciences (all), Pharmacology, Biochemistry, Receptor, Cannabinoid, CB2, chemistry.chemical_compound, Mathematical and Statistical Techniques, 0302 clinical medicine, Receptor, Cannabinoid, CB1, Animal Cells, Crocus sativus, Medicine and Health Sciences, Psychology, Enzyme-Linked Immunoassays, lcsh:Science, Neurons, Multidisciplinary, Cell Death, Retinal Degeneration, Protein Transport, Neuroprotective Agents, medicine.anatomical_structure, Cell Processes, Physical Sciences, Sensory Perception, lipids (amino acids, peptides, and proteins), Anatomy, Cellular Types, Statistics (Mathematics), Research Article, Signal Transduction, Ocular Anatomy, Research and Analysis Methods, Neuroprotection, Retina, 03 medical and health sciences, Ocular System, Gene Expression and Vector Techniques, medicine, Animals, Photoreceptor Cells, Statistical Methods, Immunoassays, Molecular Biology Techniques, Outer nuclear layer, Immunohistochemistry Techniques, Molecular Biology, Analysis of Variance, Molecular Biology Assays and Analysis Techniques, Plant Extracts, ved/biology, lcsh:R, Biology and Life Sciences, Afferent Neurons, Retinal, Cell Biology, Crocus, medicine.disease, Rats, Histochemistry and Cytochemistry Techniques, 030104 developmental biology, Gene Expression Regulation, chemistry, Cellular Neuroscience, Dietary Supplements, Immunologic Techniques, Eyes, Cannabinoid receptor antagonist, lcsh:Q, Cannabinoid, Head, Mathematics, 030217 neurology & neurosurgery, Endocannabinoids, Neuroscience
Abstract

Experimental studies demonstrated that saffron (Crocus sativus) given as a dietary supplement counteracts the effects of bright continuous light (BCL) exposure in the albino rat retina, preserving both morphology and function and probably acting as a regulator of programmed cell death [1]. The purpose of this study was to ascertain whether the neuroprotective effect of saffron on rat retina exposed to BCL is associated with a modulation of the endocannabinoid system (ECS). To this aim, we used eight experimental groups of Sprague-Dawley rats, of which six were exposed to BCL for 24 hours. Following retinal function evaluation, retinas were quickly removed for biochemical and morphological analyses. Rats were either saffron-prefed or intravitreally injected with selective type-1 (CB1) or type-2 (CB2) cannabinoid receptor antagonists before BCL. Prefeeding and intravitreally injections were combined in two experimental groups before BCL. BCL exposure led to enhanced gene and protein expression of retinal CB1 and CB2 without affecting the other ECS elements. This effect of BCL on CB1 and CB2 was reversed by saffron treatment. Selective CB1 and CB2 antagonists reduced photoreceptor death, preserved morphology and visual function of retina, and mitigated the outer nuclear layer (ONL) damage due to BCL. Of interest, CB2-dependent neuroprotection was more pronounced than that conferred by CB1. These data suggest that BCL modulates only distinct ECS elements like CB1 and CB2, and that saffron and cannabinoid receptors could share the same mechanism in order to afford retinal protection.

Published
2016
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43. Effects of GIK (glucose-insulin-potassium) on stress-induced myocardial ischaemia

Author

Beatrice Boldrini, Stefano Di Marco, Umberto Conti, Ele Ferrannini, Andrea Natali, Cecilia Morgantini, and Gabriella Marcucci

Subjects
Blood Glucose, Male, medicine.medical_specialty, medicine.medical_treatment, Myocardial Ischemia, Ischemia, Scintigraphy, Contractility, Stress, Physiological, Internal medicine, medicine, Humans, Insulin, cardiovascular diseases, Myocardial infarction, Radionuclide Imaging, Cardioplegic Solutions, Saline, Aged, Exercise Tolerance, medicine.diagnostic_test, Vascular disease, business.industry, General Medicine, Middle Aged, medicine.disease, Myocardial Contraction, Dipyridamole, Glucose, Exercise Test, Potassium, Cardiology, Female, business, Perfusion, Echocardiography, Stress, medicine.drug
Abstract

Despite the evidence in experimental animal models that insulin, or GIK (glucose–insulin–potassium), improves left ventricular function and perfusion during both acute and chronic ischaemia, clinical studies have generated conflicting results. We tested the hypothesis that pretreatment with GIK attenuates the vascular and functional effects of stress-induced myocardial ischaemia in humans. Twenty-two patients with evidence of inducible myocardial ischaemia were enrolled; 11 patients with normal ventricular function underwent two dipyridamole echocardiography tests, and 11 with regional contractility defects from previous myocardial infarction were submitted to two ECG exercise tests combined with 201Tl myocardial perfusion scintigraphy; the tests were preceded by 60 min of either normal saline or an isoglycaemic GIK infusion. On a stress echocardiogram, a 30% reduction in the severity of ischaemia was observed. On ECG ergometry, GIK infusion slightly increased the time to ischaemia (+0.6 min, P =0.07); however, the higher workload (+8%, P =0.07) was achieved at a similar rate–pressure plateau. On scintigraphy, an increase in ischaemic segments (+48%, P

Published
2010

44. Permanent functional reorganization of retinal circuits induced by early long-term visual deprivation

Author

Dario A. Protti, Silvia Bisti, Stefano Di Marco, and Vincent A. Nguyen

Subjects
Retinal Ganglion Cells, Visual perception, Patch-Clamp Techniques, Time Factors, genetic structures, Light, Action Potentials, Sensory system, Biology, Neurotransmission, Inhibitory postsynaptic potential, Retinal ganglion, Retina, chemistry.chemical_compound, Animals, Rats, Long-Evans, Visual Pathways, Vision, Ocular, Neuronal Plasticity, General Neuroscience, Electric Conductivity, Retinal, Neural Inhibition, Articles, Darkness, Synaptic Potentials, Rats, chemistry, Animals, Newborn, Receptive field, Excitatory postsynaptic potential, Sensory Deprivation, Neuroscience, Photic Stimulation
Abstract

Early sensory experience shapes the functional and anatomical connectivity of neuronal networks. Light deprivation alters synaptic transmission and modifies light response properties in the visual system, from retinal circuits to higher visual centers. These effects are more pronounced during a critical period in juvenile life and are mostly reversed by restoring normal light conditions. Here we show that complete light deprivation, from birth to periods beyond the critical period, permanently modifies the receptive field properties of retinal ganglion cells. Visual deprivation reduced both the strength of light responses in ganglion cells and their receptive field size. Light deprivation produced an imbalance in the ratio of inhibitory to excitatory inputs, with a shift toward larger inhibitory conductances. Ganglion cell receptive fields in visually deprived animals showed a spatial mismatch of inhibitory and excitatory inputs and inhibitory inputs were highly scattered over the receptive field. These results indicate that visual experience early in life is critical for the refinement of retinal circuits and for appropriate signaling of the spatiotemporal properties of visual stimuli, thus influencing the response properties of neurons in higher visual centers and their processing of visual information.

Published
2009

45. [Rehabilitation program in patients with moderate-to-severe intermittent claudication: immediate results and one year follow-up]

Author

Massimo Bulckaen, Luciana Lacopetti, Franco Giuntoli, William Vergoni, Duccio Rossini, Stefano Di Marco, and Roberto Giovannetti

Subjects
Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Side effect, medicine.medical_treatment, Vasodilator Agents, lcsh:Medicine, Propionil-L-Carnitine, Prostaglandin-E1, Carnitine, medicine, Humans, Treadmill, Alprostadil, Aged, Retrospective Studies, Rehabilitation, exercise, business.industry, lcsh:R, Retrospective cohort study, Exercise therapy, Intermittent Claudication, Middle Aged, Intermittent claudication, Exercise Therapy, peripheral vessels, Vitamin B Complex, rehabilitation, Physical therapy, Observational study, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, Claudication, business
Abstract

Background: Physical training is believed the primary treatment of claudication symptoms. Although exercise therapy is self-effective, some drugs improving functional capacity have additive effects. TASC (Trans Atlantic Society Consensus) considers Propionil-L-Carnitine (PLC) and prostaglandin-E1 (PGE1) as poorly studied drugs with potential benefits in improving claudication. This retrospective, observational study was performed to compare the efficacy of PGE1 and PLC, and to evaluate both the immediate results of an intensive, short-course rehabilitation program and the outcome at one year follow-up. Methods: Twenty-five patients with severe-moderate claudication were selected. All patients were subjected to an intensive, supervised exercise program for 4 weeks in combination with either PGE1 (10 patients) or PLC (15 patients). Drugs were infused i.v. before every exercise session: 60 μg PGE1 within 2 hours and 600 mg PLC within 10 minutes. Patients were trained with the same supervised treadmill walking-exercise program. At the end of the rehabilitation period, patients were instructed to keep walking (advised home exercise). Initial claudication distance (ICD) and absolute claudication distance (ACD) were evaluated during a constant treadmill test (3 km/hour speed, 10% grade) at entry, after 4 weeks and at one year follow-up. A patient was considered as no-responder if his/her improvement in ACD was

Published
2007

46. Applications of Trichoderma to prevent Phaeomoniella chlamydospora infections in organic nurseries

Author

STEFANO DI MARCO and FABIO OSTI

Subjects
fungi, technology, industry, and agriculture, food and beverages
Abstract

In order to prevent or reduce infection in grapevine nurseries, greenhouse and nursery trials were carried out to evaluate the effects of Trichoderma harzianum (Rootshield®) on the morpho-physiological characteristics of grapevine and on Phaeomoniella chlamydospora artificially inoculated on potted cuttings. The long-distance activity of Trichoderma against Botrytis cinerea was also examined. The study was performed in a commercial nursery where plants were grown organically. Results greatly depended on the vine-growth stage at which Trichoderma was applied. Treatment at rooting was the most effective, whilst callusing-box application or treatments at both rooting and callusing gave inconsistent but generally negative results. Treatment at rooting further improved the quantitative and qualitative characteristics of the root system, and increased the percentage of certifiable vines produced. Moreover, Trichoderma application also reduced the necrotic area caused by B. cinerea inoculated on the leaves collected from Trichoderma-treated plants and the extent of necrosis of P. chlamydospora-inoculated cuttings. This reduction in necrosis was significantly higher 15 months after inoculation. On the other hand, Trichoderma increased vine mortality at the end of the growing season compared with untreated plants. On the whole, only when it was applied at rooting did Trichoderma produce positive effects on the morpho-phisiological characteristics of grapevine and increased its tolerance to stress-related diseases, such as forms of esca found in the nursery.

Published
2007

47. Abstract 3307: Transcriptional silencing of c-Myc by promoter-directed siRNA efficiently target prostate cancer stem cells

Author

Giuseppina M. Carbone, Anastasia Malek, Domenico Albino, Stefano Di Marco, Sandra Pinton, Carlo V. Catapano, Manuela Sarti, and Gianluca Civenni

Subjects
Cancer Research, biology, CD44, Cancer, medicine.disease, medicine.disease_cause, Metastasis, Prostate cancer, Oncology, Cancer stem cell, medicine, Cancer research, biology.protein, Gene silencing, Stem cell, Carcinogenesis
Abstract

Prostate cancer is the most frequent epithelial cancer in elderly men in Western countries. Depending on the stage, prostate cancer treatment requires surgery, hormone therapy, radio- and chemo-therapy. c-MYC is a transcription factor activated by mitogenic signaling pathways and playing a central function in stem cell biology. Over-activity of c-Myc plays a central role in tumorigenesis by affecting cell proliferation, metabolic adaptation and survival. Amplification of c-MYC is one of the most common genetic alterations occurring in cancer genomes. c-Myc expression is significantly elevated in invasive prostate adenocarcinomas compared to benign prostatic hyperplasia and normal prostate tissue. Particularly, c-Myc is highly expressed in prostate cancer cells having the CD44+/CD24- phenotype, which is described as a hallmark of cancer progenitor/stem cells (CSCs). Importantly, several studies link therapy resistance and disease progression to the CSC subpopulation within the highly heterogeneous cellular composition of the tumor. CSCs are likely the tumor initiating population that produces metastasis and disease recurrence. These lines of evidence suggest a central role of c-Myc in the maintenance of CSC compartment in human tumors and justify c-Myc as a therapeutic target. Previously, we showed that the c-Myc gene could be silenced with small interfering RNAs (siRNA) targeting its promoter. Interestingly, single transfection with myc targeting siRNA (myc-siRNA) induced long lasting effects on cell proliferation and clonogenicity, indicative of a persistent loss of proliferative and clonogenic potential. In this study, we investigated the effects of transcriptional silencing of c-Myc on the CSC subpopulation in human prostate cancer cell lines in vitro and in vivo. We found that treatment with myc-siRNA significantly reduced the fraction of CSCs defined by expression of stem cell surface markers CD44 and CD24, in vitro sphere forming ability and self-renewal. Furthermore, combined analysis of senescence and cell surface markers showed that senescence occurred prevalently in the CD44+/CD24- cell subpopulation leading to its depletion, and reduced self renewal capability, in vivo tumorigenicity and metastatic potential. Moreover, repeated intraperitoneal administration of myc-siRNA over a 4-week period reduced tumor growth in a xenogeneic prostate cancer model. These results are consistent with the role of c-Myc in the maintenance of the CSC subpopulation in human prostate tumors and suggest that c-Myc downregulation induces an irreversible loss of clonogenic and tumor-initiating capability linked to the induction of cell senescence in CSCs. Our findings show also that an RNAi-based transcriptional therapy directed to genes directly involved in the maintenance of the cancer stem cells could be an efficient approach to block progression and relapse of prostate cancer. Citation Format: Gianluca Civenni, Anastasia Malek, Domenico Albino, Manuela Sarti, Sandra Pinton, Stefano Di Marco, Giuseppina M. Carbone, Carlo V. Catapano. Transcriptional silencing of c-Myc by promoter-directed siRNA efficiently target prostate cancer stem cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3307. doi:10.1158/1538-7445.AM2013-3307

Published
2013
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48. CURRENT PRESENTATION AND MANAGEMENT OF 7148 PATIENTS WITH ATRIAL FIBRILLATION IN INTERNAL MEDICINE AND CARDIOLOGY UNITS: THE ATA-AF SURVEY

Author

Domenico Panuccio, Donata Lucci, Giovanni Mathieu, Fabrizio Colombo, Carlo Nozzoli, Antonella Valerio, Stefano Di Marco, Giuseppe Di Pasquale, Gualberto Gussoni, and Giorgio Vescovo

Subjects
medicine.medical_specialty, business.industry, Internal medicine, Internal Medicine, medicine, Cardiology, Atrial fibrillation, Presentation (obstetrics), Intensive care medicine, business, medicine.disease
Published
2011
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50. Characterization of a Polymer-Based, Fully Organic Prosthesis for Implantation into the Subretinal Space of the Rat

Author

Guglielmo Lanzani, Silvia Bisti, Andrea Desii, Fabio Di Fonzo, Mattia Di Paolo, Lucia Laudato, Mattia Bramini, José Fernando Maya-Vetencourt, Rita Maccarone, Maria Rosa Antognazza, Diego Ghezzi, Ilaria Donelli, Angela Russo, Giuliano Freddi, Grazia Pertile, Fabio Benfenati, Stefano Di Marco, Maurizio Mete, and Michele Cilli

Subjects
0301 basic medicine, Materials science, Biocompatibility, medicine.medical_treatment, retinal prosthesis, Biomedical Engineering, Pharmaceutical Science, Fibroin, Biocompatible Materials, 02 engineering and technology, Prosthesis, Retina, Biomaterials, Experimental, 03 medical and health sciences, biocompatibility, Implants, Experimental, Materials Testing, medicine, conjugated polymers, Animals, Implants, RCS rats, silk fibroin, Rats, chemistry.chemical_classification, Biocompatibility, Conjugated polymers, RCS rats, Retinal prosthesis, Silk fibroin, Biomedical Engineering, Biomaterials, 3003, Polymer, 021001 nanoscience & nanotechnology, Biocompatible material, 030104 developmental biology, medicine.anatomical_structure, chemistry, Retinal Prosthesis, 0210 nano-technology, Retinal Dystrophies, Biomedical engineering
Abstract

Replacement strategies arise as promising approaches in case of inherited retinal dystrophies leading to blindness. A fully organic retinal prosthesis made of conjugated polymers layered onto a silk fibroin substrate is engineered. First, the biophysical and surface properties are characterized; then, the long-term biocompatibility is assessed after implantation of the organic device in the subretinal space of 3-months-old rats for a period of five months. The results indicate a good stability of the subretinal implants over time, with preservation of the physical properties of the polymeric layer and a tight contact with the outer retina. Immunoinflammatory markers detect only a modest tissue reaction to the surgical insult and the foreign body that peaks shortly after surgery and progressively decreases with time to normal levels at five months after implantation. Importantly, the integrity of the polymeric layer in direct contact with the retinal tissue is preserved after five months of implantation. The recovery of the foreign-body tissue reaction is also associated with a normal b-wave in the electroretinographic response. The results demonstrate that the device implanted in nondystrophic eyes is well tolerated, highly biocompatible, and suitable as retinal prosthesis in case of photoreceptor degeneration.

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