Author: "Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP)" / Topic: humans - Searchworks@Jio Institute Digital Library Search Results

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1. Muc5ac gastric mucin glycosylation is shaped by FUT2 activity and functionally impacts Helicobacter pylori binding

Author: Jeanna Bugaytsova, Thomas Borén, Joana Gomes, Celso A. Reis, Emmanuel Maes, Anna Shevtsova, Yannick Rossez, Catherine Robbe-Masselot, Ana Magalhães, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Umeå University, CNRS, Université de Lille, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, Instituto de Patologia e Imunologia Molecular da Universidade do Porto [IPATIMUP], Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF], Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF], Université de Lille-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), and Instituto de Investigação e Inovação em Saúde
Subjects: 0301 basic medicine, Glycosylation, Helicobacter pylori/metabolism, Mucus/metabolism, Mucin 5AC, Bacterial Adhesion, chemistry.chemical_compound, 0302 clinical medicine, fluids and secretions, Helicobacter, Fucosylation, Gastric Mucosa/metabolism, Mice, Knockout, Infections/microbiology, Multidisciplinary, Fucosyltransferases/genetics, respiratory system, Fucosyltransferases, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Helicobacter pylori/physiology, Protein Binding, Biology, Article, Microbiology in the medical area, Microbiology, Helicobacter Infections, Glycocalyx, 03 medical and health sciences, Lewis Blood Group Antigens, Polysaccharides, Mikrobiologi inom det medicinska området, Gastric mucosa, medicine, Animals, Humans, Polysaccharides/metabolism, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Adhesins, Bacterial, Mucin 5AC/metabolism, Cancer och onkologi, Helicobacter pylori, Gastric Mucins, Mucin, biology.organism_classification, Mucus, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Lewis Blood-Group System/metabolism, Helicobacter Infections/metabolism, Mice, Inbred C57BL, 030104 developmental biology, chemistry, Gastric Mucosa, Cancer and Oncology, Gastric Mucins/metabolism, Fucosyltransferases/metabolism, Adhesins, Bacterial/metabolism
Abstract: The gastrointestinal tract is lined by a thick and complex layer of mucus that protects the mucosal epithelium from biochemical and mechanical aggressions. This mucus barrier confers protection against pathogens but also serves as a binding site that supports a sheltered niche of microbial adherence. The carcinogenic bacteria Helicobacter pylori colonize the stomach through binding to host glycans present in the glycocalyx of epithelial cells and extracellular mucus. The secreted MUC5AC mucin is the main component of the gastric mucus layer, and BabA-mediated binding of H. pylori to MUC5AC confers increased risk for overt disease. In this study we unraveled the O-glycosylation profile of Muc5ac from glycoengineered mice models lacking the FUT2 enzyme and therefore mimicking a non-secretor human phenotype. Our results demonstrated that the FUT2 determines the O-glycosylation pattern of Muc5ac, with Fut2 knock-out leading to a marked decrease in a1,2-fucosylated structures and increased expression of the terminal type 1 glycan structure Lewis-a. Importantly, for the first time, we structurally validated the expression of Lewis-a in murine gastric mucosa. Finally, we demonstrated that loss of mucin FUT2-mediated fucosylation impairs gastric mucosal binding of H. pylori BabA adhesin, which is a recognized feature of pathogenicity. The authors thank Nuno Mendes for excellent technical support at the animal facility of IPATIMUP, University of Porto; Dr. Jacques Bara from the U-673 INSERM, CNRS, Paris, France for providing the PM7, 45M1 and 7LE antibodies; Dr Ingemar Carlstedt, University of Lund, Sweden for providing LUM6-3 and LUM5-1 antibodies and Dr. Ola Söderberg from the Uppsala Universitet, Sweden for support with the PLA experiments. This work was financed by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274) and the projects with the references FCOMP-01-0124-FEDER 028188 and FCOMP-01-0124-FEDER041276 (EXPL/CTM-BIO/0762/2013, PTDC/BBB-EBI/0786/2012 and PTDC/BBB-EBI/0567/2014). The authors acknowledge the support by Gastric Glyco Explorer Initial Training Network (Seventh Framework Programme GastricGlycoExplorer project, grant number 316929). AM received an individual grant (SFRH/BPD/75871/2011) from FCT, POPH (Programa Operacional Potencial Humano) and FSE (Fundo Social Europeu) and acknowledges EMBO for a Short-Term Fellowship (EMBO ASTF 330-212). The resources provided by the Consortium for Functional Glycomics were funded by NIGMS-GM62116. TB is supported by grants from Vetenskapsrådet/VR, Cancerfonden, and the J.C. Kempe and Seth M. Kempe Memorial Foundation and this work was in part performed within the Umeå Centre for Microbial Research (UCMR), and the Biochemical Imaging Center Umeå (BICU).
Published: 2016
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2. NOS1 mutations cause hypogonadotropic hypogonadism with sensory and cognitive deficits that can be reversed in infantile mice

Author: Konstantina Chachlaki, Andrea Messina, Virginia Delli, Valerie Leysen, Csilla Maurnyi, Chieko Huber, Gaëtan Ternier, Katalin Skrapits, Georgios Papadakis, Sonal Shruti, Maria Kapanidou, Xu Cheng, James Acierno, Jesse Rademaker, Sowmyalakshmi Rasika, Richard Quinton, Marek Niedziela, Dagmar L’Allemand, Duarte Pignatelli, Mirjam Dirlewander, Mariarosaria Lang-Muritano, Patrick Kempf, Sophie Catteau-Jonard, Nicolas J. Niederländer, Philippe Ciofi, Manuel Tena-Sempere, John Garthwaite, Laurent Storme, Paul Avan, Erik Hrabovszky, Alan Carleton, Federico Santoni, Paolo Giacobini, Nelly Pitteloud, Vincent Prevot, CHU Lille, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), FHU 1,000 Days for Health [Lille], Université de Lille, Université de Lausanne = University of Lausanne (UNIL), National and Kapodistrian University of Athens (NKUA), Lausanne University Hospital, Institute of Experimental Medicine [Budapest] (KOKI), Hungarian Academy of Sciences (MTA), Université de Genève = University of Geneva (UNIGE), Oxford Brookes University, Newcastle University [Newcastle], Poznan University of Medical Sciences [Poland] (PUMS), University of Applied Sciences of Eastern Switzerland (FHO), Universidade do Porto = University of Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Geneva University Hospitals and Geneva University, University Children’s Hospital Zurich, Bern University Hospital [Berne] (Inselspital), University of Bern, Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidad de Córdoba = University of Córdoba [Córdoba], Instituto Maimonides de Investigación Biomédica de Cordoba (IMIBIC), Universidad de Córdoba = University of Córdoba [Córdoba]-Hospital Universitario Reina Sofía, Instituto de Salud Carlos III [Madrid] (ISC), University College of London [London] (UCL), Wolfson Institute for Biomedical Research (WIBR), Université de Clermont-Ferrand, ANR-17-CE16-0015,GRAND,Vieillissement et démence: un rôle hormonal?(2017), and Prevot, Vincent
Subjects: Hypogonadism, General Medicine, Nitric Oxide Synthase Type I, Nitric Oxide, Animals, Cognition, Gonadotropin-Releasing Hormone/genetics, Gonadotropin-Releasing Hormone/metabolism, Humans, Hypogonadism/complications, Hypogonadism/congenital, Hypogonadism/genetics, Mice, Mutant Proteins, Mutation/genetics, Nitric Oxide Synthase Type I/genetics, Nitrites, Gonadotropin-Releasing Hormone, Mutation, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 610 Medicine & health
Abstract: The nitric oxide (NO) signaling pathway in hypothalamic neurons plays a key role in the regulation of the secretion of gonadotropin-releasing hormone (GnRH), which is crucial for reproduction. We hypothesized that a disruption of neuronal NO synthase (NOS1) activity underlies some forms of hypogonadotropic hypogonadism. Whole-exome sequencing was performed on a cohort of 341 probands with congenital hypogonadotropic hypogonadism to identify ultrarare variants in NOS1 . The activity of the identified NOS1 mutant proteins was assessed by their ability to promote nitrite and cGMP production in vitro. In addition, physiological and pharmacological characterization was carried out in a Nos1 -deficient mouse model. We identified five heterozygous NOS1 loss-of-function mutations in six probands with congenital hypogonadotropic hypogonadism (2%), who displayed additional phenotypes including anosmia, hearing loss, and intellectual disability. NOS1 was found to be transiently expressed by GnRH neurons in the nose of both humans and mice, and Nos1 deficiency in mice resulted in dose-dependent defects in sexual maturation as well as in olfaction, hearing, and cognition. The pharmacological inhibition of NO production in postnatal mice revealed a critical time window during which Nos1 activity shaped minipuberty and sexual maturation. Inhaled NO treatment at minipuberty rescued both reproductive and behavioral phenotypes in Nos1 -deficient mice. In summary, lack of NOS1 activity led to GnRH deficiency associated with sensory and intellectual comorbidities in humans and mice. NO treatment during minipuberty reversed deficits in sexual maturation, olfaction, and cognition in Nos1 mutant mice, suggesting a potential therapy for humans with NO deficiency.
Published: 2022
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3. A global metagenomic map of urban microbiomes and antimicrobial resistance

Author: Nadine Farhat, Tomoki Takeda, Astred Castro, Ken McGrath, Khaliun Sanchir, Iman Hajirasouliha, Eunice So, Laraib Zafar, Diana N. Nunes, Harun Mustafa, Amy Zhang, Priscilla Lisboa, Christian Schori, Marisano James, Jasna Chalangal, Sebastien Halary, Shahryar Rana, Yunmi Lee, Oli Schacher, Liliana Godoy, David A. Coil, Phanthira Pugdeethosal, Michelle D. Williams, German Marchandon, Angela Cantillo, Naoya Takahashi, Christopher Mozsary, Juana Gonzalez, Patrick K. H. Lee, Gerardo de Lamotte, Alessandro Robertiello, Steven Du, Fabienne Velter, Stefan G. Stark, Miguel Carbajo, Vincent Matthys, David A. Westfall, Julia Boeri, Irène Mauricette Mendy, Jonathan Cedillo, Francesco Oteri, Robert W. Crawford, Takayuki Ito, Tina Wunderlin, Maureen Muscat, David Paez-Espino, Carmen Urgiles, Aida Nesimi, Steffen Schaaf, Adan Ramirez-Rojas, Kunihiko Miyake, Christopher E. Mason, Anais Cardenas, Sharah Islam, Diego Benítez, Melissa Pool Pizzi, Kianna Ciaramella, Ciro Borrelli, Riham Islam, Dorottya Nagy-Szakal, Abd-Manaaf Bakere, Ait-hamlat Adel, Olha Lakhneko, Badamnyambuu Iderzorig, Ana Valeria Castro, Adam Phillips, Robert A. Petit, Flavia Corsi, Romain Conte, Krista Ryon, Soojin Jang, Joseph Benson, Fernanda de Souza Gomes Kehdy, Cindy Wang, Nicole Mathews, Jenn-Wei Chen, Rachel Paras, Paulina Pastuszek, Abigail Lyons, Paul Roldán, Muntaha Munia, Pierre Nicolas, Cassie L. Ettinger, Kyrylo Pyrshev, Katterinne N. Mendez, Eduardo Castro-Nallar, Valeriia Dotsenko, Michelle Tuz, Krizzy Mallari, Eileen Png, Yuya Sonohara, Tanja Miketic, Stéphane Delmas, Shu Zhang, Masaki Sato, Yuanting Zheng, Jifeng Zhu, Roland Häusler, Lucie Bittner, Savlatjon Rahmatulloev, Jonathan Foox, Bruno D'Alessandro, Alketa Plaku, Faisal Alquaddoomi, Yang Zhang, Kern Rei Chng, Juliana Lago, Allaeddine Chettouh, Tamera Henry, Houtan Noushmehr, Tranette Gregory, Sara Abdul Majid, Frank J. Kelly, Benjamin Pulatov, Laurie Casalot, Takema Kajita, Lennard Epping, Thais Fernanda Bartelli, Eftar Moniruzzaman, Renee Vivancos-Koopman, Thirumalaisamy P. Velavan, Tracy W. Liu, Yelyzaveta Tymoshenko, Alma Plaku, Nika Gurianova, Ambar Mendez, Anna Tomaselli, Sonia Dorado, Donato Giovannelli, Hira Choudhry, Synti Ng, Sheelta S. Kumar, Jennifer Q. Lu, Weijun Liang, Ellen Koag, Dennis Gankin, Maria João Amorim, Gwenola Simon, Kiyoshi Suganuma, Mikhail Karasikov, Christos A. Ouzounis, Madelyn May, Eran Elhaik, Stephan Ossowski, Kevin Bolzli, Matthew Arthur, Yuya Oto, Jananan Pathmanathan, Salah Mahmoud, Kou Takahashi, Brunna Marques, Kelly French, Felipe Sepúlveda, Shusei Yoshikawa, Paulo Thiago de Souza Santos, Andrew N. Gray, Juliana S Bernardes, Felipe Segato, Björn Brindefalk, George C. Yeh, Jhovana L. Velasco Flores, Jill Sullivan, Silva Baburyan, Denisse Flores, Russell Y. Neches, Sabrina Persaud, Rasheena Wright, Takumi Togashi, Verónica Antelo, Nao Kato, Skye Felice, Tatjana Mustac, Daisy Donnellan, Katerine Carrillo, Anna Litskevitch, Catalina García, Sota Ito, Naya Eady, Andrew Wan, Irene Meng, Sophie Guasco, Danilo Ercolini, Francesca De Filippis, Vincent Lemaire, Luice Fan, Lothar H. Wieler, Mariia Rybak, Jorge Sanchez, Jonathan S. Gootenberg, Itsuki Tomita, Maritza S Mosella, Laura Garcia, Natalka Makogon, Daisy Cheung, Hitler Francois Vasquez Arevalo, Freddy Asenjo, Gabriela P. Branco, Erika Cifuentes, Chloé Dequeker, Aspassia D. Chatziefthimiou, Alexis Terrero, Roy Meoded, Isabelle de Oliveira Moraes, Shaleni K. Singh, Orgil-Erdene Molomjamts, Karishma Miah, Laurent David, Wolfgang Haehr, Dao Phuong Giang, Romain Lannes, Prashanthi Ratnanandan, Ryota Yamanaka, Riccardo Vicedomini, Sadaf Ayaz, Oluwatosin M. Osuolale, Laura E. Vann, Gregory Chem, Andrea Gonzalez, Aszia Burrell, Ariel Chernomoretz, Sakura Ishizuka, Michelle Rivera, Avigdor Nosrati, Michelle B. Chen, Juliette Auvinet, Nils Ordioni, Tomoro Warashina, Guillaume Blanc, Tomislav Ivankovic, Christina Black, Lauren E. Hittle, David Hess-Homeier, Michael Kozhar, Hamood Suliman, Karobi Moitra, Saher Rahiel, Spyridon Gkotzis, Jenny Arevalo, Shaikh B. Iqbal, Beth Mutai, Mohammed Mohsin, Scott Tighe, Sylvie Collin, Yoshitaka Saito, Wayne Menary, Youping Deng, Lucy Lee, Esmeralda Jiminez, Ayuki Watanabe, Nikos C. Kyrpides, Natasha Mohan, Angelika Pupiec, Dedan Githae, Simone Cawthorne, Jonathan A. Eisen, Tomoki Iwashiro, Chiaki Homma, Thomas Saw Aung, Laura Molina, Marcus H. Y. Leung, Ophélie Da Silva, Yan Ling Wong, Hosna Noorzi, Mario Moreno, Alina Butova, Leming Shi, Brian W. Wong, Sarah S. Jackson, Moses Lin, Annabelle Meagher, Pujita Das, Catherine Burke, Mitsuki Ota, Maria Domenica Moccia, Nicolas Sprinsky, Catherine E. Pugh, David C. Green, Fazlina Fauzi, Erdenetsetseg Batdelger, Annie Geiger, Valeria Ventorino, Tolulope Oluwadare, Delisia Cuebas, Catalina Truong, Leonardo Posada, Michael Angelov, Tathiane M. Malta, Amanda Ng, Francesca Nadalin, Arya Hawkins-Zafarnia, Yuh Shiwa, Athena Mitsios, Milton Ozório Moraes, Manolo Laiola, Kalyn Ali, Jaden J.A. Hastings, Ikuto Saito, Maheen Shakil, Chisato Suzuki, Elena M. Vayndorf, Hubert Rehrauer, Ajay Menon, Kaitlan Russell, Aliyah Shari, Rebecca Smith, Gregorio Iraola, Max Priestman, Alan Briones, Silver A. Wolf, Camila Gonzalez-Poblete, Eleonora De Lazzari, Shirley Chiu, Michelle Ki, Irene Hoxie, Marianne Jaubert, Ayantu Jinfessa, Ryan J. King, Nghiem Xuan Hoan, Jalia Bynoe, Jacob Friedman, Aneisa Ramcharan, Pablo Fresia, Cristina Muñoz, Muhammad Afaq, Anyi Tang, Médine Benchouaia, Isabella Kuniko T. Takenaka, Anastasia Chasapi, Areeg Naeem, Hannah Benisty, Cecilia N. Cossio, Nathalie Hüsser, Mahfuza Sabina, Thais S. Sabedot, JoAnn Jacobs, Camila P. E. de Souza, Manuela Oliveira, Jean-Pierre Bouly, Mariko Usui, Wilson Miranda, Natalia Marciniak, Hiram Caballero, Samuel Weekes, Alexandra B. Graf, Emily Leong, Tatyana Nikolayeva, Dominique Thomas, Charlotte Greselle, Cecilia Salazar, Sreya Ray Chaudhuri, Kevin Becher, Sandra Roth, Ryusei Miura, Kari Oline Bøifot, Dimitri Manoir, Oliver Toth, Chandrima Bhattacharya, Manuel Perez, Isha Lamba, Takafumi Tsurumaki, Timothy D. Read, Anna-Lena M. Schinke, Ryan Sankar, Le Huu Song, Narasimha Rao Nedunuri, Emmanuel Dias-Neto, Ana Flávia Costa, Adiell Melamed, Christelle Desnues, Natalie R. Davidson, Aaron E. Darling, Hyung Jun Kim, Josephine Galipon, Jacqueline Orrego, Dimitar Vassilev, Michael Huber, Nur Hazlin Hazrin-Chong, Gaston H. Gonnet, Kaymisha Knights, Osman U. Sezerman, Dmitry Meleshko, Eunice Thambiraja, Jingcheng Yang, Aubin Fleiss, Gloria Nguyen, Katelyn Jackson, Nuria Aventin, Stephanie L. Hyland, Andrea Hässig, Catharine Aquino, Simona Lysakova, Israel O. Osuolale, Kasia Sluzek, Rania Siam, Alina Frolova, Samuel Hernandez, Yui Him Lo, Bazartseren Boldgiv, Ben Young, Maryna Korshevniuk, Majelia Ampadu, Yuk Man Tang, Amanda L. Muehlbauer, Sade Thomas, Gabriel Figueroa, Alexis Rivera, Lisbeth Pineda, Alexandra Dutan, Jennifer M. Tran, Chris K. Deng, Vedbar S. Khadka, Paola Florez de Sessions, Elizabeth Humphries, Hugues Richard, Hiba Naveed, Nora C. Toussaint, Mahshid Khavari, Maria del Mar Vivanco Ruiz, Antonin Thiébaut, Nicolás Rascovan, Marius Dybwad, Orhan Özcan, Lawrence Kwong, David Danko, Shaira Khan, Andrea Tassinari, Silvia Beurmann, Tsoi Ying Lai, Nanami Kubota, Tieliu Shi, Diana Chicas, Evan E. Afshin, Hirokazu Yano, Jonas Krebs, Mayuko Nakagawa, Hyun Jung Lee, Irene González Navarrete, Rachid Ounit, Lucia E. Alvarado-Arnez, Masaki Nasu, Allison Chan, Harilanto Andrianjakarivony, Jennifer Amachee, Mahdi Taye, Wan Chiew Ng, Kathryn O’Brien, Shino Ishikawa, Tristan Bitard-Feildel, Sora Takagi, Felix Hartkopf, Niamh B. O’Hara, Marcos A. S. Fonseca, Subhamitra Pakrashi, Amrit Kaur, Eva Hell, Patricia Vera-Wolf, Naimah Munim, Luiza Ferreira de Araújo, Mizuki Igarashi, Brianna Pompa-Hogan, Alessandra Carbone, Anne-Sophie Benoiston, Eric Helfrich, Michael A. Suarez-Villamil, Omar O. Abudayyeh, Natasha Abdullah, Jaime J. Fuentes, Juan Carlos Forero, Tetiana Yeskova, Denis Bertrand, Sambhawa Priya, Denisse Maldonado, Agier Nicolas, Ana Valeria B Castro, Starr Chatziefthimiou, André Kahles, Aaishah Francis, Fernanda Arredondo, Emilio Tarcitano, Irvind Buttar, Alex Alexiev, Jennifer Molinet, Sarah Shalaby, Itunu A. Oluwadare, Jason Sperry, Katrin Bakhl, Ana M. Cañas, Sofia Ahsanuddin, Miar Elaskandrany, Elodie Laine, Sven Bönigk, Johannes Werner, Stephen Eduard Boja Ruiz, Gargi Dayama, Paulina Buczansla, Brandon Valentine, Bharath Prithiviraj, Toni Bode, Stas Zubenko, Jake Cohen, Guilllaume Jospin, Zulena Saravi, Per O. Ljungdahl, Inderjit Kaur, Mauricio Moldes, Giuseppe KoLoMonaco, Denise Syndercombe Court, Sonia Bouchard, Sonia Losim, Sookwon Moon, Heba Shaaban, Suraj Patel, Sibo Zhu, Sarh Aly, Arif Asyraf Md Supie, LaShonda Dorsey, Juan Guerra, François Baudon, Rantimi A. Olawoyin, Alexia Bordigoni, Iqra Faiz, Mathilde Garcia, Gabriella Mason-Buck, María Gabriela Portilla, Niranjan Nagarajan, Fumie Takahara, Nancy Merino, Watson Andrew, Gina Kim, Yuma Sato, Hyenah Shim, Marie-Laure Jerier, Affifah Saadah Ahmad Kassim, Katerina Kuchin, Daniel Butler, Paweł P. Łabaj, Nadezhda Kobko-Litskevitch, Emmanuel F. Mongodin, Yuto Togashi, Paula Rodríguez, Pilar Lopez Hernandez, Xiaoqing Chen, Maria A. Sierra, Olga Nikolayeva, Manon Loubens, Colleen Conger, Hikaru Shirahata, Chenhao Li, Timothy Donahoe, Youngja Park, Lucia Elena Alvarado Arnez, Salama Chaker, Francisco Chavez, Alessandra Breschi, Jorge L. Sanchez, Kaung Myat San, Nayra Aguilar Rojas, Marcos Abraao, Kai Sasaki, Bryan Nazario, Olena Yemets, Klas I. Udekwu, Lynn M. Schriml, Anisia Peters, Aliaksei Holik, Mark Hernandez, Emile Faure, Malay Bhattacharyya, Josef W. Moser, Núria Andreu Somavilla, María Mercedes Zambrano, Kannan Rajendran, Gabriela E. Albuquerque, Tao Qing, Kazutoshi Tsuda, Ymke De Jong, Princess Osma, Mayra Arauco Livia, Javier Quilez Oliete, Carl Chrispin, Hyun Woo Joo, Ingrid Lafontaine, Nala An, Seisuke Sato, Felipe Segato Dezem, Andrew Maltez Thomas, Alexandre Desert, Xiao Wen Cai, O. Osuolale, Jun Wu, Coral Pardo-Esté, Courtney Robinson, Yuri Matsuzaki, Marina Nieto-Caballero, Cem Meydan, Ralph Schlapbach, Mark Menor, Sofia Castro, Rachel Kwong, Brittany Blyther, Olexandr Lykhenko, Jason R. Schriml, Christian Brion, Jenessa Orpilla, Juan A. Ugalde, Elsy Mankah Ngwa, Álvaro Aranguren, Lauren Mak, Matías Giménez, Ashanti Narce, Torsten Semmler, Stefan I. Tsonev, Abdollahi Nika, Katherine E. Dahlhausen, Monika Devi, Gunnar Rätsch, Oasima Muner, Carla Bello, Muhammad Al-Fath Amran, Anyelic Rosario, Melissa Ortega, Andrea Patrignani, Ante Peros, Elias McComb, Ryo Sato, Ireen Alam, Clara N. Dias, Soma Tanaka, Dayana Calderon, Ran Blekhman, Mathilde Mignotte, Alicia Boyd, Jochen Hecht, Thomas Neff, Xinzhao Tong, Josue Alicea, Kiara Olmeda, Sonia Marinovic, Carme Arnan, Kohei Ito, Samantha L. Goldman, Marianna S. Serpa, Renee Richer, Kaisei Sato, Jordana M. Silva, Akash Keluth Chavan, Sangwan Kim, Laís Pereira Ferreira, Sophie Vacant, Nowshin Sayara, Haruo Suzuki, Madeline Leahy, Juan C. Severyn, Sierra Vincent, Masaru Tomita, Maliha Mamun, Lucinda B. Davenport, Gabriella Oken, Dagmara Lewandowska, Gustavo Adolfo Malca Salas, Andrii Kuklin, Tyler Wong, Charlie Feigin, Eric Minwei Liu, Sonia L. Ghose, Daniela Bezdan, Antonietta La Storia, Juan P. Escalera-Antezana, Nuno Rufino de Sousa, Samuel M. Gerner, Weill Cornell Medicine [New York], Icahn School of Medicine at Mount Sinai [New York] (MSSM), Genome Institute of Singapore (GIS), Centre for Genomic Regulation [Barcelona] (CRG), Universitat Pompeu Fabra [Barcelona] (UPF)-Centro Nacional de Analisis Genomico [Barcelona] (CNAG), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Lawrence Berkeley National Laboratory [Berkeley] (LBNL), AUTRES, Massachusetts Institute of Technology (MIT), Indian Statistical Institute [Kolkata], University of Minnesota System, Universidad Andrés Bello [Santiago] (UNAB), California State University [Sacramento], University of Naples Federico II, University of Hawaii, Institut méditerranéen d'océanologie (MIO), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Toulon (UTLN), Medical Genomics Group, University College of London [London] (UCL)-UCL Cancer Institute, Norwegian Defence Research Establishment (FFI), Lund University [Lund], Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine, University of Vienna [Vienna], King‘s College London, University of Colorado [Boulder], Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur Korea - Institut Pasteur de Corée, Fudan University [Shanghai], City University of Hong Kong [Hong Kong] (CUHK), Stockholm University, University of Maryland School of Medicine, University of Maryland System, Fundação Oswaldo Cruz (FIOCRUZ), University of São Paulo (USP), Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Barcelona Institute of Science and Technology (BIST), Elizade University, Acibadem Mehmet Ali Aydınlar University, Paléogénomique microbienne - Microbial paleogenomics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Robert Koch Institute [Berlin] (RKI), East China Normal University [Shangaï] (ECNU), Cairo University, Vietnamese-German Center for Medical Research, Keio University, Université du Vermont, Universidad del Desarrollo, University of Sofia, University of Alaska [Fairbanks] (UAF), Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Corporación Corpogen-Research Center, Biologie Computationnelle et Quantitative = Laboratory of Computational and Quantitative Biology (LCQB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Weill Cornell Medicine [Cornell University], Cornell University [New York], University of Naples Federico II = Università degli studi di Napoli Federico II, Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Universidade de São Paulo = University of São Paulo (USP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Софийски университет = Sofia University, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidad Andrés Bello - UNAB (CHILE), Acibadem University Dspace, Danko, D., Bezdan, D., Afshin, E. E., Ahsanuddin, S., Bhattacharya, C., Butler, D. J., Chng, K. R., Donnellan, D., Hecht, J., Jackson, K., Kuchin, K., Karasikov, M., Lyons, A., Mak, L., Meleshko, D., Mustafa, H., Mutai, B., Neches, R. Y., Ng, A., Nikolayeva, O., Nikolayeva, T., Png, E., Ryon, K. A., Sanchez, J. L., Shaaban, H., Sierra, M. A., Thomas, D., Young, B., Abudayyeh, O. O., Alicea, J., Bhattacharyya, M., Blekhman, R., Castro-Nallar, E., Canas, A. M., Chatziefthimiou, A. D., Crawford, R. W., De Filippis, F., Deng, Y., Desnues, C., Dias-Neto, E., Dybwad, M., Elhaik, E., Ercolini, D., Frolova, A., Gankin, D., Gootenberg, J. S., Graf, A. B., Green, D. C., Hajirasouliha, I., Hastings, J. J. A., Hernandez, M., Iraola, G., Jang, S., Kahles, A., Kelly, F. J., Knights, K., Kyrpides, N. C., Labaj, P. P., Lee, P. K. H., Leung, M. H. Y., Ljungdahl, P. O., Mason-Buck, G., Mcgrath, K., Meydan, C., Mongodin, E. F., Moraes, M. O., Nagarajan, N., Nieto-Caballero, M., Noushmehr, H., Oliveira, M., Ossowski, S., Osuolale, O. O., Ozcan, O., Paez-Espino, D., Rascovan, N., Richard, H., Ratsch, G., Schriml, L. M., Semmler, T., Sezerman, O. U., Shi, L., Shi, T., Siam, R., Song, L. H., Suzuki, H., Court, D. S., Tighe, S. W., Tong, X., Udekwu, K. I., Ugalde, J. A., Valentine, B., Vassilev, D. I., Vayndorf, E. M., Velavan, T. P., Wu, J., Zambrano, M. M., Zhu, J., Zhu, S., Mason, C. E., Abdullah, N., Abraao, M., Adel, A. -H., Afaq, M., Al-Quaddoomi, F. S., Alam, I., Albuquerque, G. E., Alexiev, A., Ali, K., Alvarado-Arnez, L. E., Aly, S., Amachee, J., Amorim, M. G., Ampadu, M., Amran, M. A. -F., An, N., Andrew, W., Andrianjakarivony, H., Angelov, M., Antelo, V., Aquino, C., Aranguren, A., Araujo, L. F., Vasquez Arevalo, H. F., Arevalo, J., Arnan, C., Alvarado Arnez, L. E., Arredondo, F., Arthur, M., Asenjo, F., Aung, T. S., Auvinet, J., Aventin, N., Ayaz, S., Baburyan, S., Bakere, A. -M., Bakhl, K., Bartelli, T. F., Batdelger, E., Baudon, F., Becher, K., Bello, C., Benchouaia, M., Benisty, H., Benoiston, A. -S., Benson, J., Benitez, D., Bernardes, J., Bertrand, D., Beurmann, S., Bitard-Feildel, T., Bittner, L., Black, C., Blanc, G., Blyther, B., Bode, T., Boeri, J., Boldgiv, B., Bolzli, K., Bordigoni, A., Borrelli, C., Bouchard, S., Bouly, J. -P., Boyd, A., Branco, G. P., Breschi, A., Brindefalk, B., Brion, C., Briones, A., Buczansla, P., Burke, C. M., Burrell, A., Butova, A., Buttar, I., Bynoe, J., Bonigk, S., Boifot, K. O., Caballero, H., Cai, X. W., Calderon, D., Cantillo, A., Carbajo, M., Carbone, A., Cardenas, A., Carrillo, K., Casalot, L., Castro, S., Castro, A. V., Castro, A., Castro, A. V. B., Cawthorne, S., Cedillo, J., Chaker, S., Chalangal, J., Chan, A., Chasapi, A. I., Chatziefthimiou, S., Chaudhuri, S. R., Chavan, A. K., Chavez, F., Chem, G., Chen, X., Chen, M., Chen, J. -W., Chernomoretz, A., Chettouh, A., Cheung, D., Chicas, D., Chiu, S., Choudhry, H., Chrispin, C., Ciaramella, K., Cifuentes, E., Cohen, J., Coil, D. A., Collin, S., Conger, C., Conte, R., Corsi, F., Cossio, C. N., Costa, A. F., Cuebas, D., D'Alessandro, B., Dahlhausen, K. E., Darling, A. E., Das, P., Davenport, L. B., David, L., Davidson, N. R., Dayama, G., Delmas, S., Deng, C. K., Dequeker, C., Desert, A., Devi, M., Dezem, F. S., Dias, C. N., Donahoe, T. R., Dorado, S., Dorsey, L., Dotsenko, V., Du, S., Dutan, A., Eady, N., Eisen, J. A., Elaskandrany, M., Epping, L., Escalera-Antezana, J. P., Ettinger, C. L., Faiz, I., Fan, L., Farhat, N., Faure, E., Fauzi, F., Feigin, C., Felice, S., Ferreira, L. P., Figueroa, G., Fleiss, A., Flores, D., Velasco Flores, J. L., Fonseca, M. A. S., Foox, J., Forero, J. C., Francis, A., French, K., Fresia, P., Friedman, J., Fuentes, J. J., Galipon, J., Garcia, M., Garcia, L., Garcia, C., Geiger, A., Gerner, S. M., Ghose, S. L., Giang, D. P., Gimenez, M., Giovannelli, D., Githae, D., Gkotzis, S., Godoy, L., Goldman, S., Gonnet, G. H., Gonzalez, J., Gonzalez, A., Gonzalez-Poblete, C., Gray, A., Gregory, T., Greselle, C., Guasco, S., Guerra, J., Gurianova, N., Haehr, W., Halary, S., Hartkopf, F., Hawkins-Zafarnia, A., Hazrin-Chong, N. H., Helfrich, E., Hell, E., Henry, T., Hernandez, S., Hernandez, P. L., Hess-Homeier, D., Hittle, L. E., Hoan, N. X., Holik, A., Homma, C., Hoxie, I., Huber, M., Humphries, E., Hyland, S., Hassig, A., Hausler, R., Husser, N., Petit, R. A., Iderzorig, B., Igarashi, M., Iqbal, S. B., Ishikawa, S., Ishizuka, S., Islam, S., Islam, R., Ito, K., Ito, S., Ito, T., Ivankovic, T., Iwashiro, T., Jackson, S., Jacobs, J., James, M., Jaubert, M., Jerier, M. -L., Jiminez, E., Jinfessa, A., De Jong, Y., Joo, H. W., Jospin, G., Kajita, T., Ahmad Kassim, A. S., Kato, N., Kaur, A., Kaur, I., de Souza Gomes Kehdy, F., Khadka, V. S., Khan, S., Khavari, M., Ki, M., Kim, G., Kim, H. J., Kim, S., King, R. J., Kolomonaco, G., Koag, E., Kobko-Litskevitch, N., Korshevniuk, M., Kozhar, M., Krebs, J., Kubota, N., Kuklin, A., Kumar, S. S., Kwong, R., Kwong, L., Lafontaine, I., Lago, J., Lai, T. Y., Laine, E., Laiola, M., Lakhneko, O., Lamba, I., de Lamotte, G., Lannes, R., De Lazzari, E., Leahy, M., Lee, H., Lee, Y., Lee, L., Lemaire, V., Leong, E., Lewandowska, D., Li, C., Liang, W., Lin, M., Lisboa, P., Litskevitch, A., Liu, E. M., Liu, T., Livia, M. A., Lo, Y. H., Losim, S., Loubens, M., Lu, J., Lykhenko, O., Lysakova, S., Mahmoud, S., Majid, S. A., Makogon, N., Maldonado, D., Mallari, K., Malta, T. M., Mamun, M., Manoir, D., Marchandon, G., Marciniak, N., Marinovic, S., Marques, B., Mathews, N., Matsuzaki, Y., Matthys, V., May, M., Mccomb, E., Meagher, A., Melamed, A., Menary, W., Mendez, K. N., Mendez, A., Mendy, I. M., Meng, I., Menon, A., Menor, M., Meoded, R., Merino, N., Miah, K., Mignotte, M., Miketic, T., Miranda, W., Mitsios, A., Miura, R., Miyake, K., Moccia, M. D., Mohan, N., Mohsin, M., Moitra, K., Moldes, M., Molina, L., Molinet, J., Molomjamts, O. -E., Moniruzzaman, E., Moon, S., de Oliveira Moraes, I., Moreno, M., Mosella, M. S., Moser, J. W., Mozsary, C., Muehlbauer, A. L., Muner, O., Munia, M., Munim, N., Muscat, M., Mustac, T., Munoz, C., Nadalin, F., Naeem, A., Nagy-Szakal, D., Nakagawa, M., Narce, A., Nasu, M., Navarrete, I. G., Naveed, H., Nazario, B., Nedunuri, N. R., Neff, T., Nesimi, A., Ng, W. C., Ng, S., Nguyen, G., Ngwa, E., Nicolas, A., Nicolas, P., Nika, A., Noorzi, H., Nosrati, A., Nunes, D. N., O'Brien, K., O'Hara, N. B., Oken, G., Olawoyin, R. A., Oliete, J. Q., Olmeda, K., Oluwadare, T., Oluwadare, I. A., Ordioni, N., Orpilla, J., Orrego, J., Ortega, M., Osma, P., Osuolale, I. O., Osuolale, O. M., Ota, M., Oteri, F., Oto, Y., Ounit, R., Ouzounis, C. A., Pakrashi, S., Paras, R., Pardo-Este, C., Park, Y. -J., Pastuszek, P., Patel, S., Pathmanathan, J., Patrignani, A., Perez, M., Peros, A., Persaud, S., Peters, A., Phillips, A., Pineda, L., Pizzi, M. P., Plaku, A., Pompa-Hogan, B., Portilla, M. G., Posada, L., Priestman, M., Prithiviraj, B., Priya, S., Pugdeethosal, P., Pugh, C. E., Pulatov, B., Pupiec, A., Pyrshev, K., Qing, T., Rahiel, S., Rahmatulloev, S., Rajendran, K., Ramcharan, A., Ramirez-Rojas, A., Rana, S., Ratnanandan, P., Read, T. D., Rehrauer, H., Richer, R., Rivera, A., Rivera, M., Robertiello, A., Robinson, C., Rodriguez, P., Rojas, N. A., Roldan, P., Rosario, A., Roth, S., Ruiz, M., Boja Ruiz, S. E., Russell, K., Rybak, M., Sabedot, T. S., Sabina, M., Saito, I., Saito, Y., Malca Salas, G. A., Salazar, C., San, K. M., Sanchez, J., Sanchir, K., Sankar, R., de Souza Santos, P. T., Saravi, Z., Sasaki, K., Sato, Y., Sato, M., Sato, S., Sato, R., Sato, K., Sayara, N., Schaaf, S., Schacher, O., Schinke, A. -L. M., Schlapbach, R., Schori, C., Schriml, J. R., Segato, F., Sepulveda, F., Serpa, M. S., De Sessions, P. F., Severyn, J. C., Shakil, M., Shalaby, S., Shari, A., Shim, H., Shirahata, H., Shiwa, Y., Da Silva, O., Silva, J. M., Simon, G., Singh, S. K., Sluzek, K., Smith, R., So, E., Andreu Somavilla, N., Sonohara, Y., Rufino de Sousa, N., Souza, C., Sperry, J., Sprinsky, N., Stark, S. G., La Storia, A., Suganuma, K., Suliman, H., Sullivan, J., Supie, A. A. M., Suzuki, C., Takagi, S., Takahara, F., Takahashi, N., Takahashi, K., Takeda, T., Takenaka, I. K., Tanaka, S., Tang, A., Man Tang, Y., Tarcitano, E., Tassinari, A., Taye, M., Terrero, A., Thambiraja, E., Thiebaut, A., Thomas, S., Thomas, A. M., Togashi, Y., Togashi, T., Tomaselli, A., Tomita, M., Tomita, I., Toth, O., Toussaint, N. C., Tran, J. M., Truong, C., Tsonev, S. I., Tsuda, K., Tsurumaki, T., Tuz, M., Tymoshenko, Y., Urgiles, C., Usui, M., Vacant, S., Vann, L. E., Velter, F., Ventorino, V., Vera-Wolf, P., Vicedomini, R., Suarez-Villamil, M. A., Vincent, S., Vivancos-Koopman, R., Wan, A., Wang, C., Warashina, T., Watanabe, A., Weekes, S., Werner, J., Westfall, D., Wieler, L. H., Williams, M., Wolf, S. A., Wong, B., Wong, Y. L., Wong, T., Wright, R., Wunderlin, T., Yamanaka, R., Yang, J., Yano, H., Yeh, G. C., Yemets, O., Yeskova, T., Yoshikawa, S., Zafar, L., Zhang, Y., Zhang, S., Zhang, A., Zheng, Y., and Zubenko, S.
Subjects: Urban Population, Drug Resistance, Sequence assembly, Microbiologia, microbiome, global health, computer.software_genre, Medical and Health Sciences, shotgun sequencing, BGC, 0302 clinical medicine, Databases, Genetic, 11. Sustainability, Global health, AMR, 11 Medical and Health Sciences, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, built environment, metagenome, antimicrobial resistance, NGS, de novo assembly, biology, Shotgun sequencing, Microbiota, built Environment, Bacterial, Biodiversity, Biological Sciences, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infection, Biotechnology, Geospatial analysis, [SDV.BID]Life Sciences [q-bio]/Biodiversity, Article, General Biochemistry, Genetics and Molecular Biology, Databases, 03 medical and health sciences, Antibiotic resistance, Genetic, Drug Resistance, Bacterial, International MetaSUB Consortium, Genetics, Humans, Microbiome, 030304 developmental biology, Human Genome, 06 Biological Sciences, 15. Life on land, biology.organism_classification, Resistènica als medicaments antiinfecciosos, SAÚDE PÚBLICA, Genòmica, 13. Climate action, Evolutionary biology, Metagenomics, Antimicrobial Resistance, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, computer, 030217 neurology & neurosurgery, Archaea, Developmental Biology
Abstract: Summary We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities., Graphical abstract, Highlights • Cities possess a consistent “core” set of non-human microbes • Urban microbiomes echo important features of cities and city-life • Antimicrobial resistance genes are widespread in cities • Cities contain many novel bacterial and viral species, This systematic, worldwide catalog of urban microbiomes represents a metagenomic atlas important for understanding the ecology, virulence, and antibiotic resistance of city-specific microbial communities.
Published: 2021
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4. In Silico Logical Modelling to Uncover Cooperative Interactions in Cancer

Author: Claudine Chaouiya, Gianluca Selvaggio, Florence Janody, Microsoft Research, University of Trento [Trento], Computational and Systems Biology [Trento] (COSBI), Microsoft Research-University of Trento [Trento], Institut de Mathématiques de Marseille (I2M), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), and Universidade do Porto = University of Porto
Subjects: cooperative oncogenesis, Epithelial-Mesenchymal Transition, Computer science, Carcinogenesis, Logic, QH301-705.5, In silico, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, Computational biology, Review, Models, Biological, Catalysis, Inorganic Chemistry, 03 medical and health sciences, 0302 clinical medicine, Multidisciplinary approach, Neoplasms, medicine, Tumor Microenvironment, Animals, Humans, Logical data model, Computer Simulation, Physical and Theoretical Chemistry, Biology (General), Molecular Biology, QD1-999, Spectroscopy, 030304 developmental biology, 0303 health sciences, Computational model, Organic Chemistry, epithelium to mesenchymal transition, Cancer, General Medicine, medicine.disease, Computer Science Applications, Chemistry, Gain of function, 030220 oncology & carcinogenesis, logical computational model, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], tumour microenvironment, signalling pathways, Logical modelling
Abstract: The multistep development of cancer involves the cooperation between multiple molecular lesions, as well as complex interactions between cancer cells and the surrounding tumour microenvironment. The search for these synergistic interactions using experimental models made tremendous contributions to our understanding of oncogenesis. Yet, these approaches remain labour intensive and challenging. To tackle such a hurdle, an integrative, multidisciplinary effort is required. In this article, we highlight the use of logical computational models combined to experimental validations as an effective approach to identify cooperative mechanisms and therapeutic strategies in the context of cancer biology. In silico models overcome limitations of reductionist approaches by capturing tumour complexity, and by generating powerful testable hypotheses. We review representative examples of logical models reported in the literature and their validation. We then provide further analyses of our logical model of Epithelium to Mesenchymal Transition (EMT), searching for additional cooperative interactions involving inputs from the tumour microenvironment and gain of function mutations in NOTCH.
Published: 2021

5. COVID-19 infection in adult patients with hematological malignancies:a European Hematology Association Survey (EPICOVIDEHA)

Author: Pagano, Livio, Salmanton-García, Jon, Marchesi, Francesco, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Verga, Luisa, Víšek, Benjamin, Ilhan, Osman, Nadali, Gianpaolo, Weinbergerová, Barbora, Córdoba-Mascuñano, Raúl, Marchetti, Monia, Collins, Graham P., Farina, Francesca, Cattaneo, Chiara, Cabirta, Alba, Gomes-Silva, Maria, Itri, Federico, van Doesum, Jaap, Ledoux, Marie-Pierre, Čerňan, Martin, Jakšić, Ozren, Duarte, Rafael F., Magliano, Gabriele, Omrani, Ali S., Fracchiolla, Nicola S., Kulasekararaj, Austin, Valković, Toni, Poulsen, Christian Bjørn, Machado, Marina, Glenthøj, Andreas, Stoma, Igor, Ráčil, Zdeněk, Piukovics, Klára, Navrátil, Milan, Emarah, Ziad, Sili, Uluhan, Maertens, Johan, Blennow, Ola, Bergantim, Rui, García-Vidal, Carolina, Prezioso, Lucia, Guidetti, Anna, del Principe, Maria Ilaria, Popova, Marina, de Jonge, Nick, Ormazabal-Vélez, Irati, Fernández, Noemí, Falces-Romero, Iker, Cuccaro, Annarosa, Meers, Stef, Buquicchio, Caterina, Antić, Darko, Al-Khabori, Murtadha, García-Sanz, Ramón, Biernat, Monika M., Tisi, Maria Chiara, Sal, Ertan, Rahimli, Laman, Čolović, Natasa, Schönlein, Martin, Calbacho, Maria, Tascini, Carlo, Miranda-Castillo, Carolina, Khanna, Nina, Méndez, Gustavo-Adolfo, Petzer, Verena, Novák, Jan, Besson, Caroline, Duléry, Rémy, Lamure, Sylvain, Nucci, Marcio, Zambrotta, Giovanni, Žák, Pavel, Seval, Guldane Cengiz, Bonuomo, Valentina, Mayer, Jiří, López-García, Alberto, Sacchi, Maria Vittoria, Booth, Stephen, Ciceri, Fabio, Oberti, Margherita, Salvini, Marco, Izuzquiza, Macarena, Nunes-Rodrigues, Raquel, Ammatuna, Emanuele, Obr, Aleš, Herbrecht, Raoul, Núñez-Martín-Buitrago, Lucía, Mancini, Valentina, Shwaylia, Hawraa, Sciumè, Mariarita, Essame, Jenna, Nygaard, Marietta, Batinić, Josip, Gonzaga, Yung, Regalado-Artamendi, Isabel, Karlsson, Linda Katharina, Shapetska, Maryia, Hanakova, Michaela, El-Ashwah, Shaimaa, Borbényi, Zita, Çolak, Gökçe Melis, Nordlander, Anna, Dragonetti, Giulia, Maraglino, Alessio Maria Edoardo, Rinaldi, Amelia, De Ramón-Sánchez, Cristina, Cornely, Oliver A., Finizio, Olimpia, Fazzi, Rita, Sapienza, Giuseppe, Chauchet, Adrien, Van Praet, Jens, Prattes, Juergen, Dargenio, Michelina, Rossi, Cédric, Shirinova, Ayten, Malak, Sandra, Tafuri, Agostino, Ommen, Hans-Beier, Bologna, Serge, Khedr, Reham Abdelaziz, Choquet, Sylvain, Joly, Bertrand, Ceesay, M. Mansour, Philippe, Laure, Kho, Chi Shan, Desole, Maximilian, Tsirigotis, Panagiotis, Otašević, Vladimir, Borducchi, Davimar M. M., Antoniadou, Anastasia, Gaziev, Javid, Almaslamani, Muna A., García-Poutón, Nicole, Paterno, Giovangiacinto, Torres-López, Andrea, Tarantini, Giuseppe, Mellinghoff, Sibylle, Gräfe, Stefanie, Börschel, Niklas, Passweg, Jakob, Merelli, Maria, Barać, Aleksandra, Wolf, Dominik, Shaikh, Mohammad Usman, Thiéblemont, Catherine, Bernard, Sophie, Funke, Vaneuza Araújo Moreira, Daguindau, Etienne, Khostelidi, Sofya, Nucci, Fabio Moore, Martín-González, Juan-Alberto, Landau, Marianne, Soussain, Carole, Laureana, Cécile, Lacombe, Karine, Kohn, Milena, Aliyeva, Gunay, Piedimonte, Monica, Fouquet, Guillemette, Rêgo, Mayara, Hoell-Neugebauer, Baerbel, Cartron, Guillaume, Pinto, Fernando, Alburquerque, Ana Munhoz, Passos, Juliana, Yilmaz, Asu Fergun, Redondo-Izal, Ana-Margarita, Altuntaş, Fevzi, Heath, Christopher, Kolditz, Martin, Schalk, Enrico, Guolo, Fabio, Karthaus, Meinolf, Della Pepa, Roberta, Vinh, Donald, Noël, Nicolas, Deau Fischer, Bénédicte, Drenou, Bernard, Mitra, Maria Enza, Meletiadis, Joseph, Bilgin, Yavuz M., Jindra, Pavel, Espigado, Ildefonso, Drgoňa, Ľuboš, Serris, Alexandra, Di Blasi, Roberta, Ali, Natasha, EPICOVIDEHA working group, [missing], Pagano, Livio, Salmanton-Garcia, Jon, Marchesi, Francesco, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Verga, Luisa, Visek, Benjamin, Ilhan, Osman, Nadali, Gianpaolo, Weinbergerova, Barbora, Cordoba-Mascunano, Raul, Marchetti, Monia, Collins, Graham P., Farina, Francesca, Cattaneo, Chiara, Cabirta, Alba, Gomes-Silva, Maria, Itri, Federico, van Doesum, Jaap, Ledoux, Marie-Pierre, Cernan, Martin, Jaksic, Ozren, Duarte, Rafael F., Magliano, Gabriele, Omrani, Ali S., Fracchiolla, Nicola S., Kulasekararaj, Austin, Valkovic, Toni, Poulsen, Christian Bjorn, Machado, Marina, Glenthoj, Andreas, Stoma, Igor, Racil, Zdenek, Piukovics, Klara, Navratil, Milan, Emarah, Ziad, Sili, Uluhan, Maertens, Johan, Blennow, Ola, Bergantim, Rui, Garcia-Vidal, Carolina, Prezioso, Lucia, Guidetti, Anna, del Principe, Maria Ilaria, Popova, Marina, de Jonge, Nick, Ormazabal-Velez, Irati, Fernandez, Noemi, Falces-Romero, Iker, Cuccaro, Annarosa, Meers, Stef, Buquicchio, Caterina, Antic, Darko, Al-Khabori, Murtadha, Garcia-Sanz, Ramon, Biernat, Monika M., Tisi, Maria Chiara, Sal, Ertan, Rahimli, Laman, Colovic, Natasa, Schonlein, Martin, Calbacho, Maria, Tascini, Carlo, Miranda-Castillo, Carolina, Khanna, Nina, Mendez, Gustavo-Adolfo, Petzer, Verena, Novak, Jan, Besson, Caroline, Dulery, Remy, Lamure, Sylvain, Nucci, Marcio, Zambrotta, Giovanni, Zak, Pavel, Seval, Guldane Cengiz, Bonuomo, Valentina, Mayer, Jiri, Lopez-Garcia, Alberto, Sacchi, Maria Vittoria, Booth, Stephen, Ciceri, Fabio, Oberti, Margherita, Salvini, Marco, Izuzquiza, Macarena, Nunes-Rodrigues, Raquel, Ammatuna, Emanuele, Obr, Ales, Herbrecht, Raoul, Nunez-Martin-Buitrago, Lucia, Mancini, Valentina, Shwaylia, Hawraa, Sciume, Mariarita, Essame, Jenna, Nygaard, Marietta, Batinic, Josip, Gonzaga, Yung, Regalado-Artamendi, Isabel, Karlsson, Linda Katharina, Shapetska, Maryia, Hanakova, Michaela, El-Ashwah, Shaimaa, Borbenyi, Zita, Colak, Gokce Melis, Nordlander, Anna, Dragonetti, Giulia, Maraglino, Alessio Maria Edoardo, Rinaldi, Amelia, De Ramon-Sanchez, Cristina, Cornely, Oliver A., Pagano, L., Salmanton-Garcia, J., Marchesi, F., Busca, A., Corradini, P., Hoenigl, M., Klimko, N., Koehler, P., Pagliuca, A., Passamonti, F., Verga, L., Visek, B., Ilhan, O., Nadali, G., Weinbergerova, B., Cordoba-Mascunano, R., Marchetti, M., Collins, G. P., Farina, F., Cattaneo, C., Cabirta, A., Gomes-Silva, M., Itri, F., van Doesum, J., Ledoux, M. -P., Cernan, M., Jaksic, O., Duarte, R. F., Magliano, G., Omrani, A. S., Fracchiolla, N. S., Kulasekararaj, A., Valkovic, T., Poulsen, C. B., Machado, M., Glenthoj, A., Stoma, I., Racil, Z., Piukovics, K., Navratil, M., Emarah, Z., Sili, U., Maertens, J., Blennow, O., Bergantim, R., Garcia-Vidal, C., Prezioso, L., Guidetti, A., del Principe, M. I., Popova, M., de Jonge, N., Ormazabal-Velez, I., Fernandez, N., Falces-Romero, I., Cuccaro, A., Meers, S., Buquicchio, C., Antic, D., Al-Khabori, M., Garcia-Sanz, R., Biernat, M. M., Tisi, M. C., Sal, E., Rahimli, L., Colovic, N., Schonlein, M., Calbacho, M., Tascini, C., Miranda-Castillo, C., Khanna, N., Mendez, G. -A., Petzer, V., Novak, J., Besson, C., Dulery, R., Lamure, S., Nucci, M., Zambrotta, G., Zak, P., Seval, G. C., Bonuomo, V., Mayer, J., Lopez-Garcia, A., Sacchi, M. V., Booth, S., Ciceri, F., Oberti, M., Salvini, M., Izuzquiza, M., Nunes-Rodrigues, R., Ammatuna, E., Obr, A., Herbrecht, R., Nunez-Martin-Buitrago, L., Mancini, V., Shwaylia, H., Sciume, M., Essame, J., Nygaard, M., Batinic, J., Gonzaga, Y., Regalado-Artamendi, I., Karlsson, L. K., Shapetska, M., Hanakova, M., El-Ashwah, S., Borbenyi, Z., Colak, G. M., Nordlander, A., Dragonetti, G., Maraglino, A. M. E., Rinaldi, A., De Ramon-Sanchez, C., Cornely, O. A., Finizio, O., Fazzi, R., Sapienza, G., Chauchet, A., Van Praet, J., Prattes, J., Dargenio, M., Rossi, C., Shirinova, A., Malak, S., Tafuri, A., Ommen, H. -B., Bologna, S., Khedr, R. A., Choquet, S., Joly, B., Ceesay, M. M., Philippe, L., Kho, C. S., Desole, M., Tsirigotis, P., Otasevic, V., Borducchi, D. M. M., Antoniadou, A., Gaziev, J., Almaslamani, M. A., Garcia-Pouton, N., Paterno, G., Torres-Lopez, A., Tarantini, G., Mellinghoff, S., Grafe, S., Borschel, N., Passweg, J., Merelli, M., Barac, A., Wolf, D., Shaikh, M. U., Thieblemont, C., Bernard, S., Funke, V. A. M., Daguindau, E., Khostelidi, S., Nucci, F. M., Martin-Gonzalez, J. -A., Landau, M., Soussain, C., Laureana, C., Lacombe, K., Kohn, M., Aliyeva, G., Piedimonte, M., Fouquet, G., Rego, M., Hoell-Neugebauer, B., Cartron, G., Pinto, F., Alburquerque, A. M., Passos, J., Yilmaz, A. F., Redondo-Izal, A. -M., Altuntas, F., Heath, C., Kolditz, M., Schalk, E., Guolo, F., Karthaus, M., Della Pepa, R., Vinh, D., Noel, N., Deau Fischer, B., Drenou, B., Mitra, M. E., Meletiadis, J., Bilgin, Y. M., Jindra, P., Espigado, I., Drgona, L., Serris, A., Di Blasi, R., Ali, N., Stem Cell Aging Leukemia and Lymphoma (SALL), Salvy-Córdoba, Nathalie, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), University Hospital of Cologne [Cologne], Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, IFO - Istituto Nazionale Tumori Regina Elena [Roma] (IRE), Città della Salute e della Scienza University-Hospital, IRCCS Istituto Nazionale dei Tumori [Milano], University of California [San Diego] (UC San Diego), University of California (UC), Medical University of Graz, Odessa National I.I.Mechnikov University, Faculty of Medicine [Cologne], University Hospital of Cologne [Cologne]-University of Cologne, King's College Hospital (KCH), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), Dipartimento di Medicina e Chirurgia = School of Medicine and Surgery [Monza], Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Faculty of Medicine in Hradec Kralove [Republique Tchèque], Charles University [Prague] (CU), Ankara University School of Medicine [Turkey], Azienda Ospedaliera Universitaria Integrata of Verona, Masaryk University [Brno] (MUNI), Fundación Jiménez Díaz, Fundacion Jimenez Diaz [Madrid] (FJD), Ospedale SS Antonio e Biagio e Cesare Arrigo, Churchill Hospital Oxford Centre for Haematology, IRCCS San Raffaele Scientific Institute [Milan, Italie], ASST Spedali Civili of Brescia, Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], Universitat Autònoma de Barcelona (UAB), Instituto Português de Oncologia de Lisboa Francisco Gentil, Ospedale San Luigi Gonzaga, University Medical Center Groningen [Groningen] (UMCG), Institut de Cancérologie de Strasbourg Europe (ICANS), Palacky University Olomouc, Zagreb School of Medicine [Zagreb, Croatia] (Dubrava University Hospital), University of Zagreb, Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain], ASST Great Metropolitan Niguarda / ASST Grande Ospedale Metropolitano Niguarda [Milan, Italia], Hamad Medical Corporation [Doha, Qatar], Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Rijeka, Croatian Cooperative Group for Hematological Diseases (CROHEM), Zealand University Hospital [Roskilde, Denmark], Hospital General Universitario 'Gregorio Marañón' [Madrid], Department of Clinical Microbiology [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Homieĺ State Medical University (GSMU), Institute of Hematology and Blood Transfusion [Prague, Czech Republic], University of Szeged [Szeged], University Hospital Ostrava, Mansoura University [Egypt], Marmara University [Kadıköy - İstanbul], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Karolinska University Hospital [Stockholm], Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto = University of Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Hospital de São João [Porto], Faculdade de Medicina da Universidade do Porto (FMUP), Clinic Barcelona Hospital Universitari, Department of Public Health and Cell Biology, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy, Pavlov First Saint Petersburg State Medical University [St. Petersburg], Vrije Universiteit Medical Centre (VUMC), Vrije Universiteit Amsterdam [Amsterdam] (VU), Complejo Hospitalario de Navarra, Hospital Universitario Marqués de Valdecilla [Santander], La Paz University Hospital, Azienda Usl Toscana centro [Firenze], AZ Klina, Clinical Center of Serbia (KCS), University of Belgrade [Belgrade], Sultan Qaboos University Hospital, Partenaires INRAE, Hospital Universitario de Salamanca, Servicio de Haematologia, Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), University of Wrocław [Poland] (UWr), San Bortolo Hospital, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hospital Universitario 12 de Octubre [Madrid], Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Universidad Rey Juan Carlos [Madrid] (URJC), University of Basel (Unibas), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), University Hospital Kralovské Vinohrady, Centre Hospitalier de Versailles André Mignot (CHV), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département Hématologie biologique [CHRU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Universidade Federal do Estado do Rio de Janeiro (UNIRIO), San Gerardo Hospital of Monza, Oxford NIHR Biomedical Research Centre, IRCCS Ospedale San Raffaele [Milan, Italy], Assi Sette Llaghi Varese, Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto (IPO Porto), University Hospital Olomouc [Czech Republic], ASST Grande Ospedale Metropolitano Niguarda, University Hospital Centre Zagreb, Instituto Nacional do Câncer, Copenhagen University Hospital, Republican Scientific and Practical Center (RSPC) for organ and Tissue Transplantation, Minsk, Republican Scientific and Practical Center (RSPC) for Organ and Transplantation, German Centre for Infection Research (DZIF), Gilead Sciences, Pagano, Livio [0000-0001-8287-928X], Salmanton-García, Jon [0000-0002-6766-8297], Marchesi, Francesco [0000-0001-6353-2272], Busca, Alessandro [0000-0001-5361-5613], Corradini, Paolo [0000-0002-9186-1353], Hoenigl, Martin [0000-0002-1653-2824], Klimko, Nikolay [0000-0001-6095-7531], Koehler, Philipp [0000-0002-7386-7495], Pagliuca, Antonio [0000-0003-2519-0333], Passamonti, Francesco [0000-0001-8068-5289], Verga, Luisa [0000-0003-1142-8435], Víšek, Benjamin [0000-0001-8268-452X], Ilhan, Osman [0000-0003-1665-372X], Weinbergerová, Barbora [0000-0001-6460-2471], Córdoba, Raúl [0000-0002-7654-8836], Marchetti, Monia [0000-0001-7615-0572], Farina, Francesca [0000-0002-5124-6970], Cattaneo, Chiara [0000-0003-0031-3237], Cabirta, Alba [0000-0001-7198-8894], Gomes-Silva, Maria [0000-0002-6993-2450], Itri, Federico [0000-0002-3532-5281], Doesum, Jaap van [0000-0003-0214-3219], Ledoux, Marie-Pierre [0000-0002-3261-3616], Čerňan, Martin [0000-0003-2345-1229], Jakšić, Ozren [0000-0003-4026-285X], Magliano, Gabriel [0000-0002-9129-1530], Omrani, Ali S. [0000-0001-5309-6358], Fracchiolla, Nicola S. [0000-0002-8982-8079], Kulasekararaj, Austin G. [0000-0003-3180-3570], Valković, Toni [0000-0001-6083-8815], Poulsen, Christian Bjørn [0000-0001-9785-1378], Machado, Marina [0000-0002-8370-2248], Glenthøj, Andrea [0000-0003-2082-0738], Stoma, Igor [0000-0003-0483-7329], Ráčil, Zdeněk [0000-0003-3511-4596], Piukovics, Klára [0000-0003-4480-3131], Emarah, Ziad [0000-0003-0622-2598], Sili, Uluhan [0000-0002-9939-9298], Maertens, Johan [0000-0003-4257-5980], Bergantim, Rui [0000-0002-7811-9509], García-Vidal, Carolina [0000-0002-8915-0683], Prezioso, Lucia [0000-0003-1660-4960], Principe, Maria Ilaria del [0000-0002-3958-0669], Popova, Marina [0000-0001-8536-5495], Jonge, Nick de [0000-0002-9901-0887], Ormazabal-Vélez, Irati [0000-0003-1141-5546], Falces-Romero, Iker [0000-0001-5888-7706], Cuccaro, Annarosa [0000-0002-0237-1839], Meers, Stef [0000-0003-1754-2175], Buquicchio, Caterina [0000-0002-3683-5953], Antić, Darko [0000-0002-2608-1342], Al-Khabori, Murtadha [0000-0002-2937-8838], García-Sanz, Ramón [0000-0003-4120-2787], Biernat, Monika [0000-0003-3161-3398], Tisi, Maria Chiara [0000-0001-8231-6700], Sal, Ertan [0000-0003-2761-2675], Rahimli, Laman [0000-0003-2266-445X], Schönlein, Martin [0000-0002-1010-0975], Calbacho, María [0000-0001-8106-4863], Tascini, Carlo [0000-0001-9625-6024], Miranda-Castillo, Carolina [0000-0001-8763-9576], Khanna, Nina [0000-0002-2642-419X], Méndez, Gustavo-Adolfo [0000-0003-0514-7004], Petzer, Verena [0000-0002-9205-1440], Besson, Caroline [0000-0003-4364-7173], Duléry, Rémy [0000-0002-5024-1713], Lamure, Sylvain [0000-0001-5980-305X], Nucci, Marcio [0000-0003-4867-0014], Zambrotta, Giovanni [0000-0002-8612-2994], Žák, Pavel [0000-0003-4465-5343], Cengiz Seval, Guldane [0000-0001-9433-2054], Bonuomo, Valentina [0000-0001-6491-8337], Mayer, Jiří [0000-0003-0567-9887], López-García, Alberto [0000-0002-5354-5261], Sacchi, Maria Vittoria [0000-0001-8133-3357], Booth, Stephen [0000-0003-2687-0234], Ciceri, Fabio [0000-0003-0873-0123], Nunes-Rodrigues, Raquel [0000-0002-8347-4281], Ammatuna, Emanuele [0000-0001-8247-4901], Obr, Aleš [0000-0002-6758-3074], Herbrecht, Raoul [0000-0002-9381-4876], Shwaylia, Hawraa [0000-0002-4098-6092], Sciumè, Mariarita [0000-0001-7958-4966], Essame, Jenna [0000-0003-0926-5577], Batinić, Josip [0000-0001-5595-9911], Gonzaga, Yung [0000-0003-1416-2118], Regalado-Artamendi, Isabel [0000-0002-9673-9015], Karlsson, Linda Katharina [0000-0003-3317-7550], Shapetska, Maryia [0000-0002-1223-9161], El-Ashwah, Shaimaa [0000-0003-2210-1534], Çolak, Gökçe Melis [0000-0002-7662-7454], Dragonetti, Giulia [0000-0003-1775-6333], Rinaldi, Amelia [0000-0002-8211-5076], Ramón, Cristina de [0000-0002-8167-6410], Cornely, Oliver A. [0000-0001-9599-3137], Institut Català de la Salut, [Pagano L] Hematology, Fondazione Policlinico Universitario Agostino Gemelli - IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy. Università Cattolica del Sacro Cuore, Rome, Italy. [Salmanton-García J] Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Excellence Center for Medical Mycology (ECMM), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. Cologne Excellence Cluster On Cellular Stress Responses in Aging Associated Diseases (CECAD), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. [Marchesi F] Hematology and Stem Cell Transplant Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy. [Busca A] Stem Cell Transplant Center, AOU Citta’ Della Salute E Della Scienza, Turin, Italy. [Corradini P] University of Milan and Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy. [Hoenigl M] Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, San Diego, CA, USA. Clinical and Translational Fungal Working Group, University of California San Diego, La Jolla, CA, USA. Section of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical University of Graz, Graz, Austria. [Cabirta A, Izuzquiza M] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, Hematology, Salmanton-García, Jon, Klimko, Nikolay, Víšek, Benjamin, Weinbergerová, Barbora, Córdoba, Raúl, Doesum, Jaap van, Čerňan, Martin, Jakšić, Ozren, Magliano, Gabriel, Kulasekararaj, Austin G., Valković, Toni, Poulsen, Christian Bjørn, Glenthøj, Andrea, Ráčil, Zdeněk, Piukovics, Klára, García-Vidal, Carolina, Principe, Maria Ilaria del, Jonge, Nick de, Ormazabal-Vélez, Irati, Antić, Darko, García-Sanz, Ramón, Biernat, Monika, Schönlein, Martin, Calbacho, María, Méndez, Gustavo-Adolfo, Duléry, Rémy, Žák, Pavel, Cengiz Seval, Guldane, Mayer, Jiří, López-García, Alberto, Obr, Aleš, Sciumè, Mariarita, Batinić, Josip, Çolak, Gökçe Melis, Ramón, Cristina de, and Universidad de Sevilla. Departamento de Medicina
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, Cancer Research, MESH: Registries, Epidemiology, MESH: Hospitalization, Hematological malignancies, Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores], MESH: Aged, 80 and over, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, Malalties - Factors de risc, Risk of mortality, Medicine and Health Sciences, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], 80 and over, Medicine, MESH: COVID-19, Registries, Sang - Malalties - Complicacions, RC254-282, Cause of death, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Interna medicina, MESH: Aged, Aged, 80 and over, Hematology, MESH: Middle Aged, Mortality rate, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Myeloid leukemia, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, CANCER, Europe, Hospitalization, Intensive Care Units, Oncology, MESH: Young Adult, Hematologic Neoplasms, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Infektologija, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, COVID-19, EHA, Pandemic, Aged, Humans, SARS-CoV-2, Young Adult, técnicas de investigación::métodos epidemiológicos::estadística como asunto::probabilidad::riesgo::factores de riesgo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], [SDV.CAN] Life Sciences [q-bio]/Cancer, Intensive care, Internal medicine, Diseases of the blood and blood-forming organs, MESH: SARS-CoV-2, neoplasias::neoplasias por localización::neoplasias hematológicas [ENFERMEDADES], Molecular Biology, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Internal Medicine, pandemic, hematological malignancies, epidemiology, MESH: Humans, Science & Technology, business.industry, Myelodysplastic syndromes, Research, MESH: Adult, Neoplasms::Neoplasms by Site::Hematologic Neoplasms [DISEASES], medicine.disease, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Infectology, Settore MED/15, MESH: Male, Settore MED/15 - MALATTIE DEL SANGUE, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, COVID-19 (Malaltia) - Diagnòstic, MESH: Intensive Care Units, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], MESH: Europe, RC633-647.5, business, MESH: Female, Other subheadings::Other subheadings::/complications [Other subheadings], MESH: Hematologic Neoplasms
Abstract: Background Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value, EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).
Published: 2021
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6. Orally administrated chitosan microspheres bind Helicobacter pylori and decrease gastric infection in mice

Author: M. Cristina L. Martins, André F. Maia, Ricardo Silva-Carvalho, Lia M. Costa, Catarina L. Seabra, Fátima Gärtner, Celso A. Reis, Pedro Oliveira, Inês C. Gonçalves, Susana Junqueira-Neto, Ana Magalhães, Bernardo Antunes, Joana Gomes, Paulo Costa, Eliette Touati, Patrícia C. Henriques, Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Instituto de Engenharia Biomédica [Porto, Portugal] (INEB), Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Instituto de Biologia Molecular e Celular - institute for molecular and cell biology [Porto, Portugal] (IBMC), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Faculdade de Medicina da Universidade do Porto (FMUP), Pathogenèse de Helicobacter / Helicobacter Pathogenesis, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Pharmaceutical Technology Laboratory [Porto], Faculdade de Farmácia da Universidade do Porto (FFUP), Universidade do Porto-Universidade do Porto, This work was financed by PTDC/CTM-BIO/4043/2014 and by Portuguese funds from FCT UID/BIM/04293/2019, UID/Multi/04378/2019, EXPL/CTM-BIO/0762/2013 and by L'OrealPortugal/FCT/UNESCO. Authors wish to thank FCT for Inês C. Gonçalves research position (IF/01479/2015), Patricia C. Henriques PhD grant (SFRH/BD/120154/2016) and Catarina L. Seabra PhD grant (SFRH/BD/89001/2012)., and The authors acknowledge the support of i3S Scientific Platforms, namely the Bioimaging Center for Biomaterials and Regenerative Therapies (b.IMAGE), and the BioSciences Screening for the imaging data acquisition using equipment maintained by the platforms, both members of the PPBI (PPBI-POCI-01-0145-feder-022122), and CCGEN and Paula Magalhães, for the help during the PCR analysis.
Subjects: Bacteria adhesion, 0206 medical engineering, Biomedical Engineering, Mucoadhesion, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 02 engineering and technology, Microparticles, Biochemistry, Microbiology, Helicobacter Infections, Biomaterials, Mice, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, In vivo, medicine, Gastric mucosa, Animals, Humans, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, Molecular Biology, Gastric Infection, Gastrointestinal tract, Chitosan, biology, Helicobacter pylori, business.industry, Stomach, General Medicine, 021001 nanoscience & nanotechnology, biology.organism_classification, 020601 biomedical engineering, Mucus, Microspheres, 3. Good health, Mice, Inbred C57BL, medicine.anatomical_structure, Gastric Mucosa, 0210 nano-technology, business, Ex vivo, Biotechnology
Abstract: International audience; Persistent Helicobacter pylori (H. pylori) infection is related to 90% of gastric cancers. With bacterial resistance rising and treatment inefficiency affecting 15% of the patients, alternative treatments urge. Chitosan microspheres (ChMics) have been proposed as an H. pylori-binding system. This work evaluates ChMics biocompatibility, mucopenetration and capacity to treat H. pylori infection in mice after oral administration. ChMics of different size (XL, ∼120 µm and XS, ∼40 µm) and degree of acetylation (6% and 16%) were developed and revealed to be able to adhere both human and mouse-adapted H. pylori strains without cytotoxicity towards human gastric cells. Ex vivo studies showed that smaller (XS) microspheres penetrate further within the gastric foveolae, suggesting their ability to reach deeply adherent bacteria. In vivo assays showed 88% reduction of infection when H. pylori-infected mice (C57BL/6) were treated with more mucoadhesive XL6 and XS6 ChMics. Overall, ChMics clearly demonstrate ability to reduce H. pylori gastric infection in mice, with chitosan degree of acetylation being a dominant factor over microspheres' size on H. pylori removal efficiency. These results evidence the strong potential of this strategy as an antibiotic-free approach to fight H. pylori infection, where microspheres are orally administered, bind H. pylori in the stomach, and remove them through the gastrointestinal tract. STATEMENT OF SIGNIFICANCE: Approximately 90% of gastric cancers are caused by the carcinogenic agent Helicobacter pylori, which infects >50% of the world population. Bacterial resistance, reduced antibiotic bioavailability, and the intricate distribution of bacteria in mucus and within gastric foveolae hamper the success of most strategies to fight H. pylori. We demonstrate that an antibiotic-free therapy based on bare chitosan microspheres that bind and remove H. pylori from stomach can achieve 88% reduction of infection from H. pylori-infected mice. Changing size and mucoadhesive properties, microspheres can reach different areas of gastric mucosa: smaller and less mucoadhesive can penetrate deeper into the foveolae. This promising, simple and inexpensive strategy paves the way for a faster bench-to-bedside transition, therefore holding great potential for clinical application.
Published: 2019
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7. Population genetics-informed meta-analysis in seven genes associated with risk to dengue fever disease

Author: Anavaj Sakuntabhai, Luísa Pereira, Verónica Fernandes, María G. Guzmán, Beatriz Sierra, Isabelle Casademont, Nourdin Harich, Bruno Cavadas, Marisa Oliveira, Lotfi Cherni, Nicole Pedro, Farida Alshamali, Fanny Koeth, Diana P. Saraiva, Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Dubai Police General Headquarters, Université Chouaib Doukkali (UCD), Université de Tunis El Manar (UTM), Université de Monastir - University of Monastir (UM), Pedro Kouri Institute of Tropical Medicine, Génomique évolutive, modélisation et santé (CNRS-UMR2000), Faculdade de Medicina da Universidade do Porto (FMUP), The research leading to these results has received funding from the European Commission Seventh Framework Programme [FP7/2007-2013] for the DENFREE project under Grant Agreement no. 282378. MO has a PhD grant from FCT (The Portuguese Foundation for Science and Technology - SFRH/BD/95626/2013). IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT, FEDER and COMPETE (PEst-C/SAU/LA0003/2013)., European Project: 282378,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,DENFREE(2012), Universidade do Porto = University of Porto, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Génomique évolutive, modélisation et santé (GEMS)
Subjects: Genetic Markers, 0301 basic medicine, Microbiology (medical), Candidate gene, Genotype, Population, Population genetics, Disease, Biology, Polymorphism, Single Nucleotide, Microbiology, Worldwide diversity, Dengue fever, Dengue, 03 medical and health sciences, Genetic drift, Dengue disease, Genetics, medicine, Humans, Genetic Predisposition to Disease, education, Global risk, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Genetic association, education.field_of_study, Odds ratio, East Asian and Latin American cohorts, medicine.disease, 3. Good health, Meta-analysis, 030104 developmental biology, Infectious Diseases, Gene Expression Regulation, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Demography
Abstract: International audience; Population genetics theory predicted that rare frequent markers would be the main contributors for heritability of complex diseases, but meta-analyses of genome-wide association studies are revealing otherwise common markers, present in all population groups, as the identified candidate genes. In this work, we applied a population-genetics informed meta-analysis to 10 markers located in seven genes said to be associated with dengue fever disease. Seven markers (in PLCE1, CD32, CD209, OAS1 and OAS3 genes) have high-frequency and the other three (in MICB and TNFA genes) have intermediate frequency. Most of these markers have high discriminatory power between population groups, but their frequencies follow the rules of genetic drift, and seem to have not been under strong selective pressure. There was a good agreement in directional consistency across trans-ethnic association signals, in East Asian and Latin American cohorts, with heterogeneity generated by randomness between studies and especially by low sample sizes. This led to confirm the following significant associations: with DF, odds ratio of 0.67 for TNFA-rs1800629-A; with DHF, 0.82 for CD32-rs1801274-G; with DSS, 0.55 for OAS3-rs2285933-G, 0.80 for PLCE1-rs2274223-G and 1.32 for MICB-rs3132468-C. The overall genetic risks confirmed sub-Saharan African populations and descendants as the best protected against the severer forms of the disease, while Southeast and Northeast Asians are the least protected ones. European and close neighbours are the best protected against dengue fever, while, again, Southeast and Northeast Asians are the least protected ones. These risk scores provide important predictive information for the largely na\"ive European and North American regions, as well as for Africa where misdiagnosis with other hemorrhagic diseases is of concern.
Published: 2018
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8. Latin Americans show wide-spread Converso ancestry and imprint of local Native ancestry on physical appearance

Author: Juan C. Chacon-Duque, Hugo Villamil-Ramírez, Giovanni Poletti, Samuel Canizales-Quinteros, Mirsha Quinto-Sánchez, Maria Cátira Bortolini, Maria-Laura Parolin, Macarena Fuentes-Guajardo, Francisco Rothhammer, Rolando González-José, Valeria Villegas, Francisco Mauro Salzano, Javier Mendoza-Revilla, Verónica Gomes, Caio Cesar Silva de Cerqueira, Cheryl A. Winkler, José R. Sandoval, Carla Gallo, Elena Llop, Rosenda I. Peñaloza-Espinosa, Vanessa Granja, Daniel Corach, Lavinia Schuler-Faccini, Yali Xue, Garrett Hellenthal, Mercedes Villena, Virginia Ramallo, Victor Acuña-Alonzo, Gabriel Bedoya, Paola Everardo Martínez, Karla Sandoval, Andres Ruiz-Linares, David J. Balding, Claudio M. Bravi, Pedro Moral, Jean-Michel Dugoujon, Tábita Hünemeier, António Amorim, Malena Hurtado, Kaustubh Adhikari, René Vasquez, Julio Molina, Leonor Gusmão, Ramiro Barrantes, Carlos Resende, Jorge Gómez-Valdés, Alberto Salazar-Granara, Héctor Rangel-Villalobos, William Klitz, Rodrigo Barquera, Molecular Genetics Laboratory, Escuela Nacional de Antropologia y Historia, Departamento de Genética, Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS)-Instituto de Biociencias, Instituto Boliviano de Biologıa de la Altura, Universidad Autonoma Tomas Frias, Facultad de Medicina & Instituto de Alta Investigacion, Universidad de Tarapaca-Universidade de Chile, School of Human Evolution and Social Change, Arizona State University [Tempe] (ASU), Instituto Multidisciplinario de Biología Celular [La Plata] (IMBICE), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Universidad Nacional de la Plata [Argentine] (UNLP)-Comisión de Investigaciones Científicas [Buenos Aires] (CIC), Centro de Investigaciones Biomédicas de Guatemala, Servicio de Huellas Digitales Genéticas [Buenos Aires], Facultad de Farmacia y Bioquímica [Buenos Aires] (FFYB), Universidad de Buenos Aires [Buenos Aires] (UBA)-Universidad de Buenos Aires [Buenos Aires] (UBA), Escuela de Biologia, Universidad Nacional de Costa Rica, Population Genetics, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Universidade de Lisboa (ULISBOA), Human Evolution, The Wellcome Trust Sanger Institute [Cambridge], Anthropologie Moléculaire et Imagerie de Synthèse (AMIS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), University of Barcelona, Unit of Molecular Biology and Genomic Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Laboratorio de Genética Molecular, Universidad de Antioquia = University of Antioquia [Medellín, Colombia], University College of London [London] (UCL), Dept of Genetics, Evolution and Environment [London] (UCL-GEE), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Instituto de Investigação e Inovação em Saúde, Universidade de Lisboa = University of Lisbon (ULISBOA), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: haplotype, Latin Americans, Biología, [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, purl.org/pe-repo/ocde/ford#1.03.00 [https], Human physical appearance, Colonialism, migration, CONVERSO JEWS, purl.org/becyt/ford/1 [https], Genética y Herencia, 0302 clinical medicine, genetics, Nose / anatomy & histology, East mediterranean, lcsh:Science, 0303 health sciences, Genealogy, Geography, Indians, South American / genetics, American Indian, Genetic structure, CIENCIAS NATURALES Y EXACTAS, Latin americans, Science, purl.org/pe-repo/ocde/ford#1.06.03 [https], Human Migration, Nose, Article, Ciencias Biológicas, 03 medical and health sciences, Indians, North American / genetics, parasitic diseases, Humans, human, purl.org/becyt/ford/1.6 [https], Mexico, Historical record, 030304 developmental biology, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Indians, South American, ANCESTRY INFORMATIVE, Environmental adaptation, South America, Converso jews, LATIN AMERICANS, Haplotypes, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Ancestry informative, purl.org/pe-repo/ocde/ford#1.04.00 [https], Indians, North American, lcsh:Q, 030217 neurology & neurosurgery, anatomy and histology
Abstract: Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly to the intermixing (admixture) of Native Americans, Europeans and Sub-Saharan Africans. Using novel haplotype-based methods, here we infer sub-continental ancestry in over 6,500 Latin Americans and evaluate the impact of regional ancestry variation on physical appearance. We find that Native American ancestry components in Latin Americans correspond geographically to the present-day genetic structure of Native groups, and that sources of non-Native ancestry, and admixture timings, match documented migratory flows. We also detect South/East Mediterranean ancestry across Latin America, probably stemming mostly from the clandestine colonial migration of Christian converts of non-European origin (Conversos). Furthermore, we find that ancestry related to highland (Central Andean) versus lowland (Mapuche) Natives is associated with variation in facial features, particularly nose morphology, and detect significant differences in allele frequencies between these groups at loci previously associated with nose morphology in this sample., Latin Americans trace their ancestry to the admixture of Native Americans, Europeans and Sub-Saharan Africans. Here, the authors develop a novel haplotype-based approach and analyse over 6,500 Latin Americans to infer the geographically-detailed genetic structure of this population.
Published: 2018
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9. Evidence-Based Clinical Use of Nanoscale Extracellular Vesicles in Nanomedicine

Author: Guillaume van Niel, Carla Oliveira, Roberto Furlan, Ihsan Gursel, Anabela Cordeiro da Silva, Edit I. Buzás, Samir El Andaloussi, Eva Rohde, Alicia Llorente, Hernando A. del Portillo, Graça Raposo, Bernd Giebel, An Hendrix, Maja Kosanović, Lorraine O'Driscoll, Natasa Zarovni, Apolonija Bedina Zavec, Stefano Fais, Bertrand Kaeffer, Giovanni Camussi, Gabriella Pocsfalvi, María Yáñez-Mó, Irina Nazarenko, Tanja Ficko Trček, Marei Sammar, Lawrence Rajendran, Marjo Yliperttula, Antonio Marcilla, Francesc E. Borràs, Marilena E. Lekka, Joana Carvalho, Georg Lipps, Pia Siljander, Veronika Kralj-Iglič, Francesco Cappello, M. Helena Vasconcelos, Mariantonia Logozzi, Istituto Superiore di Sanità, Trinity College Dublin, Hospital Germans Trias I Pujol, Department of Genetics, Cell- and Immunobiology, Semmelweis University, Universita di Torino, Università degli Studi di Palermo, Institute of Molecular Pathology and Immunology, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Institute for Molecular and Cell Biology, University of Porto Medical School, Hospital Clínic de Barcelona, Karolinska Institutet [Stockholm], University of Oxford [Oxford], Lek Pharmaceuticals d.d., a Sandoz Company, San Raffaele Scientific Institute, Ghent University Hospital, Bilkent University [Ankara], University of Ljubljana, Physiologie des Adaptations Nutritionnelles (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), University of Belgrade, University of Ioannina, University of Applied Sciences and Arts Northwestern Switzerland (HES-SO), Universitat de València (UV), ORT Braude College, Partenaires INRAE, Oslo University Hospital [Oslo], University of Freiburg [Freiburg], Universidade do Porto, Consiglio Nazionale delle Ricerche (CNR), Universität Zürich [Zürich] = University of Zurich (UZH), Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris], Paracelsus Medical University, University of Salzburg, University of Helsinki, Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, P-4200135 Oporto, Portugal, Univ Porto IPATIMUP, Inst Invest & Inovacao Saude i3S, P-4200135 Oporto, Portugal, Hospital Sta Cristina, Exosomics Siena SpA, National Institute of Chemistry, Institute for Transfusion Medicine, University Hospital Essen, Universität Duisburg-Essen [Essen], Fais, S., O'Driscoll, L., Borras, F., Buzas, E., Camussi, G., Cappello, F., Carvalho, J., Cordeiro Da Silva, A., Del Portillo, H., El Andaloussi, S., Ficko Trček, T., Furlan, R., Hendrix, A., Gursel, I., Kralj-Iglic, V., Kaeffer, B., Kosanovic, M., Lekka, M., Lipps, G., Logozzi, M., Marcilla, A., Sammar, M., Llorente, A., Nazarenko, I., Oliveira, C., Pocsfalvi, G., Rajendran, L., Raposo, G., Rohde, E., Siljander, P., Van Niel, G., Vasconcelos, M., Yáñez-Mó, M., Yliperttula, M., Zarovni, N., Zavec, A., and Giebel, B.
Subjects: 0301 basic medicine, Medical nanotechnology, Physiology, Medizin, General Physics and Astronomy, xxx xxx, Cell Communication, Exosomes, Regenerative medicine, Theranostic Nanomedicine, Membrane microparticle, Engineering (all), Drug Delivery Systems, Pathophysiological, Cell-Derived Microparticles, Caveolae, Diagnosis, General Materials Science, Lipid raft, Phospholipids, Clinical Trials as Topic, Phospholipid membrane, Vesicle, General Engineering, Science and Technology, Materials Science (all), Physics and Astronomy (all), 3. Good health, Cell biology, Intercellular communications, Clinical trial (topic), Nanomedicine, Drug delivery, [SDV.IMM]Life Sciences [q-bio]/Immunology, Human, Endosome, Drug delivery system, Nanotechnology, Biology, Program diagnostics, 03 medical and health sciences, Extracellular Vesicles, Animals, Humans, Therapeutic agents, Settore BIO/16 - Anatomia Umana, Animal, Recent researches, Microvesicles, Cell membranes, Exosome, 030104 developmental biology, International cooperation, Membrane microdomains
Abstract: collaboration au projet H2020 European Cooperation in Science and Technology (COST) program European Network on Microvesicles and Exosomes in Health and Disease (ME-HAD); International audience; Recent research has demonstrated that all body fluids assessed contain substantial amounts of vesicles that range in size from 30 to 1000 nm and that are surrounded by phospholipid membranes containing different membrane microdomains such as lipid rafts and caveolae. The most prominent representatives of these so-called extracellular vesicles (EVs) are nanosized exosomes (70-150 nm), which are derivatives of the endosomal system, and microvesicles (100-1000 nm), which are produced by outward budding of the plasma membrane. Nanosized EVs are released by almost all cell types and mediate targeted intercellular communication under physiological and pathophysiological conditions. Containing cell-type specific signatures, EVs have been proposed as biomarkers in a variety of diseases. Furthermore, according to their physical functions, EVs of selected cell types have been used as therapeutic agents in immune therapy, vaccination trials, regenerative medicine, and drug delivery. Undoubtedly, the rapidly emerging field of basic and applied EV research will significantly influence the biomedicinal landscape in the future. In this Perspective, we, a network of European scientists from clinical, academic, and industry settings collaborating through the H2020 European Cooperation in Science and Technology (COST) program European Network on Microvesicles and.Exosomes in Health and Disease (ME-HAD), demonstrate the high potential of nanosized EVs for both diagnostic and therapeutic (i.e., theranostic) areas of nanomedicine.
Published: 2016
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10. Helicobacter pylori Activates Matrix Metalloproteinase 10 in Gastric Epithelial Cells via EGFR and ERK-mediated Pathways

Author: Dionyssios N. Sgouras, Manuel A. S. Santos, Rui M. Ferreira, Ceu Figueiredo, Ioanna S. Sougleri, Ines Pinto-Ribeiro, Maria José Oliveira, Angela M. Costa, Laura Carreto, Fátima Carneiro, Marina S. Leite, Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Laboratoire de microbiologie médicale = Laboratory of Medical Microbiology [Athènes], Institut Pasteur Hellénique, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Instituto de Engenharia Biomédica (INEB), Faculdade de Medicina da Universidade do Porto (FMUP), Universidade de Aveiro, Hospital de São João [Porto], This work was supported by the European Regional Development Fund (FEDER)–Portugal (through Programa Operacional Factores de Competitividade–COMPETE), Fundação para a Ciência e a Tecnologia (project PTDC/BIA-MIC/116890/2010 and fellowships SFRH/BPD/109446/2015 [to A. M. C.], SFRH/BPD/84084/2012 [to R. M. F.], SFHRH/BD/110803/2015 [to I. P.-R.], and SFRH/BPD/110065/2015 [to M. L.]), the Hellenic Society of Gastrointestinal Oncology and Experimental Research Center–ELPEN (scholarship to I. S. S.), and the InfeNeutra project, KRIPIS National Strategic Reference Framework, Ministry of Culture and Education of Greece (ESPA 2007–2013, MIS 450598 to I. S. S.)., We thank Armando Castro, Manuel Moutinho, and Armindo Pereira (Department of Pathology, CHSJ) for technical support., European Project: 116890,FCT::,PTDC/2010,PTDC/BIA-MIC/116890/2010(2012), and Universidade do Porto = University of Porto
Subjects: 0301 basic medicine, MAPK/ERK pathway, Male, Small interfering RNA, MAP Kinase Kinase 4, MESH: Helicobacter pylori/pathogenicity, MESH: Gastric Mucosa/microbiology, Receptor tyrosine kinase, Invasion, Immunology and Allergy, MESH: ErbB Receptors/metabolism, MESH: Middle Aged, biology, Kinase, Middle Aged, invasion, CagA, ErbB Receptors, MESH: Gastric Mucosa/enzymology, Infectious Diseases, medicine.anatomical_structure, Female, MMP-10, MESH: Bacterial Proteins/metabolism, Proto-oncogene tyrosine-protein kinase Src, MESH: Antigens, Bacterial/metabolism, MESH: Enzyme Activation, MESH: Cell Line, Tumor, MAP Kinase Signaling System, Virulence Factors, EGFR, Cell Line, 03 medical and health sciences, Bacterial Proteins, Matrix Metalloproteinase 10, Cell Line, Tumor, Gastric mucosa, medicine, MESH: MAP Kinase Signaling System, Humans, MESH: MAP Kinase Kinase 4/metabolism, Antigens, Bacterial, MESH: Humans, Helicobacter pylori, MESH: Virulence Factors/metabolism, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, biology.organism_classification, bacterial infections and mycoses, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, digestive system diseases, MESH: Male, MESH: Cell Line, Enzyme Activation, 030104 developmental biology, Gastric Mucosa, Immunology, Cancer research, biology.protein, MESH: Matrix Metalloproteinase 10/metabolism, MESH: Female
Abstract: International audience; Helicobacter pylori colonizes the human stomach and increases the risk for peptic ulcer disease and gastric carcinoma. H. pylori upregulates the expression and activity of several matrix metalloproteinases (MMPs) in cell lines and in the gastric mucosa. The aim of this study was to explore the mechanisms leading to upregulation of MMP10 in gastric epithelial cells induced by H. pylori. Infection of gastric cells with H. pylori led to an increase in levels of MMP-10 messenger RNA, protein secretion, and activity. cagA knockout mutants or CagA phosphorylation-defective mutants failed to increase MMP10 expression. These results were confirmed in infection experiments with clinical isolates with known cagA status and in human gastric biopsy specimens. Treatment of cells with chemical inhibitors of the receptor tyrosine kinase EGFR and the kinase Src abrogated H. pylori-induced MMP10 expression. Inhibitors of ERK1/2 and JNK kinases abolished and significantly decreased H. pylori-induced MMP10 expression, respectively, whereas inhibition of the kinase p38 had no effect. Finally, inhibition of MMP10 expression by small interfering RNA led to a decrease in the gastric cell-invasive phenotype mediated by the infection. In conclusion, CagA-positive H. pylori strains stimulate MMP10 expression. MMP-10 modulation occurs via EGFR activation in a process that involves Src, ERK, and JNK pathways. MMP-10 may be implicated in H. pylori-mediated extracellular matrix remodeling.
Published: 2015
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11. OCT-1 is over-expressed in intestinal metaplasia and intestinal gastric carcinomas and binds to, but does not transactivate, CDX2 in gastric cells

Author: Isabelle Van Seuningen, Patrícia Mesquita, José Domingues de Almeida, Elisabete Silva, Nuno Mendes, Raquel Almeida, Filipe Santos-Silva, Leonor David, Celso A. Reis, Michal Shoshkes, Faculdade de Medicina, VAN SEUNINGEN, ISABELLE, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Mucines Epitheliales : du Gene a la Fonction, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, and Universidade do Porto
Subjects: genetic structures, [SDV]Life Sciences [q-bio], Chronic gastritis, Electrophoretic Mobility Shift Assay, Biology, Transfection, Pathology and Forensic Medicine, 03 medical and health sciences, Transactivation, 0302 clinical medicine, Stomach Neoplasms, Tumor Cells, Cultured, medicine, Gastric mucosa, Humans, CDX2 Transcription Factor, Promoter Regions, Genetic, CDX2, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Homeodomain Proteins, Ciências da Saúde, Metaplasia, 0303 health sciences, Expression vector, Stomach, Transdifferentiation, Health sciences, Intestinal metaplasia, medicine.disease, eye diseases, digestive system diseases, Neoplasm Proteins, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Gastric Mucosa, Gastritis, 030220 oncology & carcinogenesis, Chronic Disease, embryonic structures, Trans-Activators, Cancer research, sense organs, Precancerous Conditions, Octamer Transcription Factor-1
Abstract: Intestinal metaplasia (IM) is a preneoplastic lesion of the stomach in which there is transdifferentiation of the gastric mucosa to an intestinal phenotype. The caudal-related homeobox gene CDX2 encodes an intestine-specific transcription factor crucial for the regulation of proliferation and differentiation of intestinal cells. In addition, CDX2 is involved in the induction of IM in the stomach. The aim of this study was to access the putative involvement of OCT-1 in the induction of CDX2 expression de novo in gastric mucosa leading to the onset of IM. OCT-1 protein expression was evaluated by immunohistochemistry in 31 biopsies with chronic gastritis, 15 biopsies with foci of IM and adjacent gastric mucosa and 42 gastric carcinomas. Furthermore, we evaluated OCT-1 binding by electrophoretic mobility shift assay and activation of the CDX2 promoter by co-transfecting a CDX2 promoter/reporter construct with an OCT-1 expression vector in two gastric carcinoma cell lines, GP220 and MKN45. Our results show that OCT-1 is expressed in chronic gastritis, particularly when it is adjacent to IM and is expressed in 87% of IM foci. Furthermore, 74% of the gastric carcinomas were positive for OCT-1 and a strong association was observed between OCT-1 expression and intestinal-type carcinoma. We identified that OCT-1 binds to the CDX2 promoter, although we could not see a transactivation effect in gastric carcinoma cell lines. In conclusion, we observed increased OCT-1 expression in IM and in intestinal gastric carcinomas and identified the capacity of OCT-1 to bind to the CDX2 promoter, although we could not demonstrate a direct effect of OCT-1 in the transactivation of CDX2. Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Published: 2005
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12. Gastric cancer: Basic aspects

Author: Silvia Molina-Castro, Ceu Figueiredo, Joana Pereira-Marques, José Carlos Machado, Christine Varon, Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidad de Costa Rica (UCR), Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto = University of Porto, and Varon, Christine
Subjects: 0301 basic medicine, Carcinogenesis, [SDV]Life Sciences [q-bio], DNMT3B, gastric cancer stem cells, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, Stomach Neoplasms, microRNA, Genetic predisposition, medicine, Humans, Gene silencing, Epigenetics, Cell Proliferation, marker, biology, digestive, oral, and skin physiology, Gastroenterology, Cancer, General Medicine, Helicobacter pylori, biology.organism_classification, medicine.disease, digestive system diseases, microRNAs, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Infectious Diseases, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, immune checkpoint inhibition, PDX1, molecular classification, Signal Transduction
Abstract: International audience; Gastric cancer is one of the most incident and deadliest malignancies in the world. Gastric cancer is a heterogeneous disease and the end point of a long and multistep process, which results from the stepwise accumulation of numerous (epi)genetic alterations, leading to dysregulation of oncogenic and tumor suppressor pathways. Gastric cancer stem cells have emerged as fundamental players in cancer development and as contributors to gastric cancer heterogeneity. For this special issue, we will report last year's update on the gastric cancer molecular classification, and in particular address the gastric cancer groups who could benefit from immune checkpoint therapy. We will also review the latest advances on gastric cancer stem cells, their properties as gastric cancer markers and therapeutic targets, and associated signaling pathways. The understanding of the molecular basis underlying gastric cancer heterogeneity and of the role played by gastric cancer stem cells in cancer development and heterogeneity is of major significance, not only for identifying novel targets for cancer prevention and treatment, but also for clinical management and patient stratification for targeted therapies.
Published: 2017
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13. Key elements of the BMP/SMAD pathway co-localize with CDX2 in intestinal metaplasia and regulate CDX2 expression in human gastric cell lines

Author: I. Van Seuningen, Rutger J. Jacobs, Vânia Camilo, G. R. van den Brink, Leonor David, Rita Barros, Nuno Mendes, Bruno Pereira, Isabelle Duluc, Paula Paulo, Filipe Santos-Silva, Raquel Almeida, Jean-Noël Freund, Maria Azevedo, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), De l'homéostasie tissulaire au cancer et à l'inflammation, Institut National de la Santé et de la Recherche Médicale (INSERM), Leiden University Medical Center (LUMC), Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, Mucines Epitheliales : du Gene a la Fonction, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, VAN SEUNINGEN, ISABELLE, Universidade do Porto, and Gastroenterology and Hepatology
Subjects: Pathology, medicine.medical_specialty, Chromatin Immunoprecipitation, animal structures, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Blotting, Western, Bone Morphogenetic Protein 2, SMAD, Bone Morphogenetic Protein 4, Biology, Bone morphogenetic protein, Pathology and Forensic Medicine, Smad1 Protein, 03 medical and health sciences, 0302 clinical medicine, Stomach Neoplasms, Transforming Growth Factor beta, Cell Line, Tumor, medicine, Humans, CDX2 Transcription Factor, RNA, Small Interfering, CDX2, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Smad4 Protein, Regulation of gene expression, Homeodomain Proteins, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, Growth factor, Carcinoma, Intestinal metaplasia, medicine.disease, Immunohistochemistry, BMPR1A, digestive system diseases, 3. Good health, [SDV] Life Sciences [q-bio], Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, embryonic structures, Bone Morphogenetic Proteins, Cancer research, Ectopic expression, RNA Interference
Abstract: Helicobacter pylori infection induces intestinal metaplasia of the stomach, a preneoplastic lesion associated with an increased risk for gastric cancer development. Intestinal metaplasia is induced by the intestine-specific transcription factor CDX2 but the mechanisms responsible for this ectopic expression have never been described. We hypothesized that the BMP/SMAD pathway has a role in CDX2 regulation, in this context, for the following reasons: (1) the BMP pathway is crucial for normal intestinal differentiation and (2) there is an influx of BMP2 and BMP4-producing cells to the stomach upon Helicobacter pylori infection. We evaluated the expression of key elements of the BMP pathway in human stomach specimens with IM. Growth factor treatments, with BMP2 and BMP4, were performed in cultured cells and a knock-down experiment of SMAD4 was done using RNAi. We showed overexpression in IM of BMP2/4, BMPR1A, and SMAD4 in 56% of IM foci, and pSMAD1/5/8 in 100% of IM foci as compared to adjacent mucosa. In vitro, treatment of AGS cells with BMP2 and BMP4 increased endogenous CDX2 expression as well as the intestinal differentiation markers MUC2 and LI-cadherin. On the other hand, SMAD4 knock-down led to decreased endogenous CDX2, MUC2, and LI-cadherin in AGS. Treatment of the SMAD4 knock-down cells had no influence on CDX2 expression as opposed to wild-type cells. A 9.3 kb CDX2 promoter could be transactivated by SMAD4 and SMAD1 in a cell-dependent manner. In conclusion, we identified for the first time that the BMP pathway is active in intestinal metaplasia and that BMP2 and BMP4 regulate CDX2 expression and promote intestinal differentiation through the canonical signal transducers.
Published: 2008
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13 results on '"Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP)"'

1. Muc5ac gastric mucin glycosylation is shaped by FUT2 activity and functionally impacts Helicobacter pylori binding

2. NOS1 mutations cause hypogonadotropic hypogonadism with sensory and cognitive deficits that can be reversed in infantile mice

3. A global metagenomic map of urban microbiomes and antimicrobial resistance

4. In Silico Logical Modelling to Uncover Cooperative Interactions in Cancer

5. COVID-19 infection in adult patients with hematological malignancies:a European Hematology Association Survey (EPICOVIDEHA)

6. Orally administrated chitosan microspheres bind Helicobacter pylori and decrease gastric infection in mice

7. Population genetics-informed meta-analysis in seven genes associated with risk to dengue fever disease

8. Latin Americans show wide-spread Converso ancestry and imprint of local Native ancestry on physical appearance

9. Evidence-Based Clinical Use of Nanoscale Extracellular Vesicles in Nanomedicine

10. Helicobacter pylori Activates Matrix Metalloproteinase 10 in Gastric Epithelial Cells via EGFR and ERK-mediated Pathways

11. OCT-1 is over-expressed in intestinal metaplasia and intestinal gastric carcinomas and binds to, but does not transactivate, CDX2 in gastric cells

12. Gastric cancer: Basic aspects

13. Key elements of the BMP/SMAD pathway co-localize with CDX2 in intestinal metaplasia and regulate CDX2 expression in human gastric cell lines

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