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3. Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms

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Barbara Wanjiru Citarella, Christiana Kartsonaki, Elsa D. Ibáñez-Prada, Bronner P. Gonçalves, Joaquin Baruch, Martina Escher, Mark G. Pritchard, Jia Wei, Fred Philippy, Andrew Dagens, Matthew Hall, James Lee, Demetrios James Kutsogiannis, Evert-Jan Wils, Marília Andreia Fernandes, Bharath Kumar Tirupakuzhi Vijayaraghavan, Prasan Kumar Panda, Ignacio Martin-Loeches, Shinichiro Ohshimo, Arie Zainul Fatoni, Peter Horby, Jake Dunning, Jordi Rello, Laura Merson, Amanda Rojek, Michel Vaillant, Piero Olliaro, Luis Felipe Reyes, S.A. Moharam, Sabriya Abdalasalam, Alaa Abdalfattah Abdalhadi, Naana Reyam Abdalla, Walaa Abdalla, Almthani Hamza Abdalrheem, Ashraf Abdalsalam, Saedah Abdeewi, Esraa Hassan Abdelgaum, Mohamed Abdelhalim, Mohammed Abdelkabir, Israa Abdelrahman, Sheryl Ann Abdukahil, Lamees Adil Abdulbaqi, Salaheddin Abdulhamid, Widyan Abdulhamid, Nurul Najmee Abdulkadir, Eman Abdulwahed, Rawad Abdunabi, Ryuzo Abe, Laurent Abel, Ahmed Mohammed Abodina, Amal Abrous, Lara Absil, Kamal Abu Jabal, Nashat Abu Salah, Abdurraouf Abusalama, Tareg Abdallah Abuzaid, Subhash Acharya, Andrew Acker, Elisabeth Adam, Safia Adem, Manuella Ademnou, Francisca Adewhajah, Diana Adrião, Anthony Afum-Adjei Awuah, Melvin Agbogbatey, Saleh Al Ageel, Aya Mustafa Ahmed, Musaab Mohammed Ahmed, Shakeel Ahmed, Zainab Ahmed Alaraji, Abdulrahman Ahmed Elhefnawy Enan, Reham Abdelhamid Ahmed Khalil, Ali Mostafa Ahmed Mohamed Abdelaziz, Kate Ainscough, Eka Airlangga, Tharwat Aisa, Ali Aisha, Bugila Aisha, Ali Ait Hssain, Younes Ait Tamlihat, Takako Akimoto, Ernita Akmal, Chika Akwani, Eman Al Qasim, Ahmed Alajeeli, Ahmed Alali, Razi Alalqam, Aliya Mohammed Alameen, Mohammed Al-Aquily, Zinah A. Alaraji, Khalid Albakry, Safa Albatni, Angela Alberti, Osama Aldabbourosama, Tala Al-dabbous, Amer Aldhalia, Abdulkarim Aldoukali, Senthilkumar Alegesan, Marta Alessi, Beatrice Alex, Kévin Alexandre, Abdulrahman Al-Fares, Asil Alflite, Huda Alfoudri, Qamrah Alhadad, Hoda Salem Alhaddad, Maali Khalid Mohamed Abdalla Alhasan, Ahmad Nabil Alhouri, Hasan Alhouri, Adam Ali, Imran Ali, Maha TagElser Mohammed Ali, Syed Ali Abbas, Yomna Ali Abdelghafar, Naseem Ali Sheikh, Kazali Enagnon Alidjnou, Mahmoud Aljadi, Sarah Aljamal, Mohammed Alkahlout, Akram Alkaseek, Qabas Alkhafajee, Clotilde Allavena, Nathalie Allou, Lana Almasri, Abdulrahman Almjersah, Raja Ahmed Alqandouz, Walaa Alrfaea, Moayad Alrifaee, Rawan Alsaadi, Yousef Al-Saba'a, Entisar Alshareea, Eslam Alshenawy, Aneela Altaf, João Melo Alves, João Alves, Rita Alves, Joana Alves Cabrita, Maria Amaral, Amro Essam Amer, Nur Amira, Amos Amoako Adusei, John Amuasi, Roberto Andini, Claire Andrejak, Andrea Angheben, François Angoulvant, Sophia Ankrah, Séverine Ansart, Sivanesen Anthonidass, Massimo Antonelli, Carlos Alexandre Antunes de Brito, Ardiyan Apriyana, Yaseen Arabi, Irene Aragao, Francisco Arancibia, Carolline Araujo, Antonio Arcadipane, Patrick Archambault, Lukas Arenz, Jean-Benoît Arlet, Christel Arnold-Day, Lovkesh Arora, Rakesh Arora, Elise Artaud-Macari, Diptesh Aryal, Angel Asensio, Elizabeth A. Ashley, Muhammad Ashraf, Muhammad Sheharyar Ashraf, Abir Ben Ashur, Franklin Asiedu-Bekoe, Namra Asif, Mohammad Asim, Grace Assi, Jean Baptiste Assie, Amirul Asyraf, Fouda Atangana, Ahmed Atia, Minahel Atif, Asia Atif Abdelrhman Abdallahrs, Anika Atique, Moad Atlowly, AM Udara Lakshan Attanyake, Johann Auchabie, Hugues Aumaitre, Adrien Auvet, Abdelmalek Awad Ali Mohammed, Eyvind W. Axelsen, Ared Ayad, Ahmed Ayman Hassan Helmi, Laurène Azemar, Mohammed Azizeldin, Cecile Azoulay, Hakeem Babatunde, Benjamin Bach, Delphine Bachelet, Claudine Badr, Roar Bævre-Jensen, Nadia Baig, John Kenneth Baillie, J Kevin Baird, Erica Bak, Agamemnon Bakakos, Nazreen Abu Bakar, Hibah Bileid Bakeer, Ashraf Bakri, Andriy Bal, Mohanaprasanth Balakrishnan, Irene Bandoh, Firouzé Bani-Sadr, Renata Barbalho, Nicholas Yuri Barbosa, Wendy S. Barclay, Saef Umar Barnett, Michaela Barnikel, Helena Barrasa, Cleide Barrigoto, Marie Bartoli, Joaquín Baruch, Romain Basmaci, Muhammad Fadhli Hassin Basri, AbdAlkarim Batool, Denise Battaglini, Jules Bauer, Diego Fernando Bautista Rincon, Denisse Bazan Dow, Abigail Beane, Alexandra Bedossa, Ker Hong Bee, Husna Begum, Sylvie Behilill, Albertus Beishuizen, Aleksandr Beljantsev, David Bellemare, Anna Beltrame, Beatriz Amorim Beltrão, Marine Beluze, Nicolas Benech, Lionel Eric Benjiman, Suzanne Bennett, Luís Bento, Jan-Erik Berdal, Lamis Berdeweel, Delphine Bergeaud, Hazel Bergin, Giulia Bertoli, Lorenzo Bertolino, Simon Bessis, Sybille Bevilcaqua, Karine Bezulier, Amar Bhatt, Krishna Bhavsar, Isabella Bianchi, Claudia Bianco, Sandra Bichoka, Farah Nadiah Bidin, Felwa Bin Humaid, Mohd Nazlin Bin Kamarudin, Muhannud Binnawara, Zeno Bisoffi, Patrick Biston, Laurent Bitker, Mustapha Bittaye, Jonathan Bitton, Pablo Blanco-Schweizer, Catherine Blier, Frank Bloos, Mathieu Blot, Filomena Boccia, Laetitia Bodenes, Debby Bogaert, Anne-Hélène Boivin, Ariel Bolanga, Isabela Bolaños, Pierre-Adrien Bolze, François Bompart, Aurelius Bonifasius, Joe Bonney, Diogo Borges, Raphaël Borie, Hans Martin Bosse, Elisabeth Botelho-Nevers, Lila Bouadma, Olivier Bouchaud, Sabelline Bouchez, Damien Bouhour, Kévin Bouiller, Laurence Bouillet, Camile Bouisse, Latsaniphone Bountthasavong, Anne-Sophie Boureau, John Bourke, Maude Bouscambert, Aurore Bousquet, Marielle Boyer-Besseyre, Maria Boylan, Fernando Augusto Bozza, Axelle Braconnier, Cynthia Braga, Timo Brandenburger, Filipa Brás Monteiro, Luca Brazzi, Dorothy Breen, Patrick Breen, David Brewster, Kathy Brickell, Tessa Broadley, Helen Brotherton, Alex Browne, Nicolas Brozzi, Sonja Hjellegjerde Brunvoll, Marjolein Brusse-Keizer, Petra Bryda, Nina Buchtele, Polina Bugaeva, Marielle Buisson, Danilo Buonsenso, Erlina Burhan, Donald Buri, Aidan Burrell, Ingrid G. Bustos, Denis Butnaru, André Cabie, Susana Cabral, Joana Cabrita, Eder Caceres, Cyril Cadoz, Rui Caetano Garcês, Kate Calligy, Jose Andres Calvache, João Camões, Valentine Campana, Paul Campbell, Josie Campisi, Cecilia Canepa, Mireia Cantero, Janice Caoili, Pauline Caraux-Paz, Sheila Cárcel, Filipa Cardoso, Filipe Cardoso, Nelson Cardoso, Sofia Cardoso, Simone Carelli, Nicolas Carlier, Thierry Carmoi, Gayle Carney, Inês Carqueja, Marie-Christine Carret, François Martin Carrier, Ida Carroll, Gail Carson, Maire-Laure Casanova, Mariana Cascão, Siobhan Casey, José Casimiro, Bailey Cassandra, Silvia Castañeda, Nidyanara Castanheira, Guylaine Castor-Alexandre, Ivo Castro, Ana Catarino, François-Xavier Catherine, Paolo Cattaneo, Roberta Cavalin, Giulio Giovanni Cavalli, Alexandros Cavayas, Adrian Ceccato, Masaneh Ceesay, Shelby Cerkovnik, Minerva Cervantes-Gonzalez, Muge Cevik, Anissa Chair, Catherine Chakveatze, Adrienne Chan, Meera Chand, Jean-Marc Chapplain, Charlotte Charpentier, Julie Chas, Muhammad Mobin Chaudry, Jonathan Samuel Chávez Iñiguez, Anjellica Chen, Yih-Sharng Chen, Léo Chenard, Matthew Pellan Cheng, Antoine Cheret, Thibault Chiarabini, Julian Chica, Suresh Kumar Chidambaram, Leong Chin Tho, Catherine Chirouze, Davide Chiumello, Sung-Min Cho, Bernard Cholley, Danoy Chommanam, Marie-Charlotte Chopin, Yock Ping Chow, Ting Soo Chow, Nathaniel Christy, Hiu Jian Chua, Jonathan Chua, Jose Pedro Cidade, José Miguel Cisneros Herreros, Anna Ciullo, Jennifer Clarke, Rolando Claure-Del Granado, Sara Clohisey, Cassidy Codan, Caitriona Cody, Jennifer Coles, Megan Coles, Gwenhaël Colin, Michael Collins, Pamela Combs, Jennifer Connolly, Marie Connor, Anne Conrad, Elaine Conway, Graham S. Cooke, Hugues Cordel, Amanda Corley, Sabine Cornelis, Alexander Daniel Cornet, Arianne Joy Corpuz, Andrea Cortegiani, Grégory Corvaisier, Camille Couffignal, Sandrine Couffin-Cadiergues, Roxane Courtois, Stéphanie Cousse, Juthaporn Cowan, Rachel Cregan, Gloria Crowl, Jonathan Crump, Claudina Cruz, Marc Csete, Ailbhe Cullen, Matthew Cummings, Gerard Curley, Elodie Curlier, Colleen Curran, Paula Custodio, Ana da Silva Filipe, Charlene Da Silveira, Al-Awwab Dabaliz, John Arne Dahl, Darren Dahly, Umberto D'Alessandro, Peter Daley, Zaina Dalloul, Heidi Dalton, Jo Dalton, Seamus Daly, Juliana Damas, Joycelyn Dame, Cammandji Damien, Nick Daneman, Jorge Dantas, Frédérick D'Aragon, Gillian de Loughry, Diego de Mendoza, Etienne De Montmollin, Rafael Freitas de Oliveira França, Ana Isabel de Pinho Oliveira, Rosanna De Rosa, Cristina De Rose, Thushan de Silva, Peter de Vries, Jillian Deacon, David Dean, Alexa Debard, Bianca DeBenedictis, Marie-Pierre Debray, Nathalie DeCastro, William Dechert, Romain Decours, Eve Defous, Isabelle Delacroix, Alexandre Delamou, Eric Delaveuve, Karen Delavigne, Nathalie M. Delfos, Ionna Deligiannis, Andrea Dell'Amore, Christelle Delmas, Pierre Delobel, Corine Delsing, Elisa Demonchy, Emmanuelle Denis, Dominique Deplanque, Pieter Depuydt, Diane Descamps, Mathilde Desvallées, Santi Dewayanti, Pathik Dhangar, Alpha Diallo, Souleymane Taran Diallo, Sylvain Diamantis, André Dias, Fernanda Dias Da Silva, Rodrigo Diaz, Juan Jose Diaz, Priscila Diaz, Bakary K. Dibba, Kévin Didier, Jean-Luc Diehl, Wim Dieperink, Jérôme Dimet, Vincent Dinot, Fara Diop, Alphonsine Diouf, Yael Dishon, Cedric Djadda, Félix Djossou, Annemarie B. Docherty, Helen Doherty, Arjen M. Dondorp, Christl A. Donnelly, Yoann Donohue, Sean Donohue, Peter Doran, Céline Dorival, Eric D'Ortenzio, Yash Doshi, Phouvieng Douangdala, James Joshua Douglas, Renee Douma, Nathalie Dournon, Joanne Downey, Mark Downing, Thomas Drake, Aoife Driscoll, Ibrahim Kwaku Duah, Claudio Duarte Fonseca, Vincent Dubee, François Dubos, Audrey Dubot-Pérès, Alexandre Ducancelle, Toni Duculan, Susanne Dudman, Abhijit Duggal, Paul Dunand, Mathilde Duplaix, Emanuele Durante-Mangoni, Lucian Durham, III, Bertrand Dussol, Juliette Duthoit, Xavier Duval, Anne Margarita Dyrhol-Riise, Sim Choon Ean, Ada Ebo, Marco Echeverria-Villalobos, Michael Edelstein, Siobhan Egan, Linn Margrete Eggesbø, Khadeja Ehzaz, Carla Eira, Mohammed El Sanharawi, Marwan El Sayed, Mohammed Elabid, Mohamed Bashir Elagili, Subbarao Elapavaluru, Mohammad Elbahnasawy, Sohail Elboshra, Brigitte Elharrar, Jacobien Ellerbroek, Merete Ellingjord-Dale, Hamida ELMagrahi, Mohammad Muatasm Elmubark, Loubna Elotmani, Lauren Eloundou, Philippine Eloy, Basma Elshaikhy, Tarek Elshazly, Wafa Elsokni, Aml Ahmed Eltayeb, Iqbal Elyazar, Zarief Kamel Emad, Hussein Embarek, Isabelle Enderle, Tomoyuki Endo, Gervais Eneli, Chan Chee Eng, Ilka Engelmann, Vincent Enouf, Olivier Epaulard, Haneen Esaadi, Mariano Esperatti, Hélène Esperou, Catarina Espírito Santo, Marina Esposito-Farese, Rachel Essaka, Lorinda Essuman, João Estevão, Manuel Etienne, Anna Greti Everding, Mirjam Evers, Isabelle Fabre, Marc Fabre, Ismaila Fadera, Asgad Osman Abdalla Fadlalla, Amna Faheem, Arabella Fahy, Cameron J. Fairfield, Zul Fakar, Komal Fareed, Pedro Faria, Ahmed Farooq, Hanan Fateena, Mohamed Fathi, Salem Fatima, Karine Faure, Raphaël Favory, Mohamed Fayed, Niamh Feely, Jorge Fernandes, Susana Fernandes, François-Xavier Ferrand, Eglantine Ferrand Devouge, Joana Ferrão, Mário Ferraz, Benigno Ferreira, Isabel Ferreira, Bernardo Ferreira, Sílvia Ferreira, Nicolas Ferriere, Céline Ficko, Claudia Figueiredo-Mello, William Finlayson, Thomas Flament, Tom Fletcher, Aline-Marie Florence, Letizia Lucia Florio, Brigid Flynn, Deirdre Flynn, Jean Foley, Victor Fomin, Tatiana Fonseca, Patricia Fontela, Karen Forrest, Simon Forsyth, Denise Foster, Giuseppe Foti, Berline Fotso, Erwan Fourn, Robert A. Fowler, Marianne Fraher, Diego Franch-Llasat, Christophe Fraser, John F. Fraser, Marcela Vieira Freire, Ana Freitas Ribeiro, Craig French, Caren Friedrich, Ricardo Fritz, Stéphanie Fry, Nora Fuentes, Masahiro Fukuda, G. Argin, Valérie Gaborieau, Rostane Gaci, Massimo Gagliardi, Jean-Charles Gagnard, Amandine Gagneux-Brunon, Abdou Gai, Sérgio Gaião, Linda Gail Skeie, Adham Mohamed Galal Mohamed Ramadan, Phil Gallagher, Carrol Gamble, Yasmin Gani, Arthur Garan, Rebekha Garcia, Julia Garcia-Diaz, Esteban Garcia-Gallo, Navya Garimella, Denis Garot, Valérie Garrait, Basanta Gauli, Anatoliy Gavrylov, Alexandre Gaymard, Johannes Gebauer, Eva Geraud, Louis Gerbaud Morlaes, Nuno Germano, Malak Ghemmeid, Praveen Kumar Ghisulal, Jade Ghosn, Marco Giani, Tristan Gigante, Elaine Gilroy, Guillermo Giordano, Michelle Girvan, Valérie Gissot, Gezy Giwangkancana, Daniel Glikman, Petr Glybochko, Eric Gnall, Geraldine Goco, François Goehringer, Siri Goepel, Jean-Christophe Goffard, Jin Yi Goh, Brigitta Golács, Jonathan Golob, Kyle Gomez, Joan Gómez-Junyent, Marie Gominet, Alicia Gonzalez, Patricia Gordon, Isabelle Gorenne, Laure Goubert, Cécile Goujard, Tiphaine Goulenok, Margarite Grable, Jeronimo Graf, Edward Wilson Grandin, Pascal Granier, Giacomo Grasselli, Lorenzo Grazioli, Christopher A. Green, Courtney Greene, William Greenhalf, Segolène Greffe, Domenico Luca Grieco, Matthew Griffee, Fiona Griffiths, Ioana Grigoras, Albert Groenendijk, Fassou Mathias Grovogui, Heidi Gruner, Yusing Gu, Jérémie Guedj, Martin Guego, Anne-Marie Guerguerian, Daniela Guerreiro, Romain Guery, Anne Guillaumot, Laurent Guilleminault, Maisa Guimarães de Castro, Thomas Guimard, Marieke Haalboom, Daniel Haber, Ali Hachemi, Abdurrahman Haddud, Nadir Hadri, Wael Hafez, Fakhir Raza Haidri, Fatima Mhd Rida Hajij, Sheeba Hakak, Adam Hall, Sophie Halpin, Shaher Hamdan, Abdelhafeez Hamdi, Jawad Hameed, Ansley Hamer, Raph L. Hamers, Rebecca Hamidfar, Bato Hammarström, Naomi Hammond, Terese Hammond, Lim Yuen Han, Matly Hanan, Rashan Haniffa, Kok Wei Hao, Hayley Hardwick, Ewen M. Harrison, Janet Harrison, Samuel Bernard Ekow Harrison, Alan Hartman, Sulieman Hasan, Mohammad Ali Nabil Hasan, Mohd Shahnaz Hasan, Junaid Hashmi, Madiha Hashmi, Amoni Hassan, Ebtisam Hassanin, Muhammad Hayat, Ailbhe Hayes, Leanne Hays, Jan Heerman, Lars Heggelund, Ahmed Helmi, Ross Hendry, Martina Hennessy, Aquiles Rodrigo Henriquez-Trujillo, Maxime Hentzien, Diana Hernandez, Andrew Hershey, Liv Hesstvedt, Astarini Hidayah, Eibhlin Higgins, Rupert Higgins, Samuel Hinton, Hiroaki Hiraiwa, Haider Hirkani, Hikombo Hitoto, Antonia Ho, Yi Bin Ho, Alexandre Hoctin, Isabelle Hoffmann, Wei Han Hoh, Oscar Hoiting, Rebecca Holt, Jan Cato Holter, Juan Pablo Horcajada, Ikram Houas, Mabrouka Houderi, Catherine L. Hough, Stuart Houltham, Jimmy Ming-Yang Hsu, Jean-Sébastien Hulot, Abby Hurd, Iqbal Hussain, Aliae Mohamed Hussein, Mahmood Hussein, Fatima Ibrahim, Bashir Ibran, Samreen Ijaz, M. Arfan Ikram, Carlos Cañada Illana, Patrick Imbert, Muhammad Imran Ansari, Rana Imran Sikander, Hugo Inácio, Carmen Infante Dominguez, Yun Sii Ing, Mariachiara Ippolito, Vera Irawany, Sarah Isgett, Tiago Isidoro, Nadiah Ismail, Margaux Isnard, Mette Stausland Istre, Junji Itai, Daniel Ivulich, Danielle Jaafar, Salma Jaafoura, Hamza Jaber, Julien Jabot, Clare Jackson, Abubacarr Jagne, Stéphane Jaureguiberry, Denise Jaworsky, Florence Jego, Anilawati Mat Jelani, Synne Jenum, Ruth Jimbo-Sotomayor, Ong Yiaw Joe, Ruth Noemí Jorge García, Silje Bakken Jørgensen, Cédric Joseph, Mark Joseph, Swosti Joshi, Mercé Jourdain, Philippe Jouvet, Anna Jung, Hanna Jung, Dafsah Juzar, Ouifiya Kafif, Florentia Kaguelidou, Neerusha Kaisbain, Thavamany Kaleesvran, Sabina Kali, Karl Trygve Kalleberg, Smaragdi Kalomoiri, Muhammad Aisar Ayadi Kamaluddin, Armand Saloun Kamano, Zul Amali Che Kamaruddin, Nadiah Kamarudin, Kavita Kamineni, Darshana Hewa Kandamby, Kong Yeow Kang, Darakhshan Kanwal, Dyah Kanyawati, Mohamed Karghul, Pratap Karpayah, Todd Karsies, Daisuke Kasugai, Kevin Katz, Christy Kay, Lamees Kayyali, Seán Keating, Pulak Kedia, Andrea Kelly, Aoife Kelly, Claire Kelly, Niamh Kelly, Sadie Kelly, Yvelynne Kelly, Maeve Kelsey, Kalynn Kennon, Sommay Keomany, Maeve Kernan, Younes Kerroumi, Sharma Keshav, Shams Khail, Sarah Khaled, Imrana Khalid, Antoine Khalil, Irfan Khan, Quratul Ain Khan, Sushil Khanal, Abid Khatak, Krish Kherajani, Michelle E. Kho, Denisa Khoo, Ryan Khoo, Saye Khoo, Muhammad Nasir Khoso, Amin Khuwaja, Khor How Kiat, Yuri Kida, Peter Kiiza, Beathe Kiland Granerud, Anders Benjamin Kildal, Jae Burm Kim, Antoine Kimmoun, Detlef Kindgen-Milles, Nobuya Kitamura, Eyrun Floerecke Kjetland Kjetland, Paul Klenerman, Rob Klont, Gry Kloumann Bekken, Stephen R. Knight, Robin Kobbe, Paa Kobina Forson, Chamira Kodippily, Malte Kohns Vasconcelos, Sabin Koirala, Mamoru Komatsu, Franklina Korkor Abebrese, Volkan Korten, Stephanie Kouba, Mohamed Lamine Kourouma, Karifa Kourouma, Arsène Kpangon, Karolina Krawczyk, Ali Kredan, Vinothini Krishnan, Sudhir Krishnan, Oksana Kruglova, Anneli Krund, Pei Xuan Kuan, Ashok Kumar, Deepali Kumar, Ganesh Kumar, Mukesh Kumar, Dinesh Kuriakose, Ethan Kurtzman, Demetrios Kutsogiannis, Galyna Kutsyna, Ama Kwakyewaa Bedu-Addo, Sylvie Kwedi, Konstantinos Kyriakoulis, Marie Lachatre, Marie Lacoste, John G. Laffey, Nadhem Lafhej, Marie Lagrange, Fabrice Laine, Olivier Lairez, Sanjay Lakhey, Marc Lambert, François Lamontagne, Marie Langelot-Richard, Vincent Langlois, Eka Yudha Lantang, Marina Lanza, Cédric Laouénan, Samira Laribi, Delphine Lariviere, Stéphane Lasry, Sakshi Lath, Naveed Latif, Youssef Latifeh, Odile Launay, Didier Laureillard, Yoan Lavie-Badie, Andy Law, Cassie Lawrence, Teresa Lawrence, Minh Le, Clément Le Bihan, Cyril Le Bris, Georges Le Falher, Lucie Le Fevre, Quentin Le Hingrat, Marion Le Maréchal, Soizic Le Mestre, Gwenaël Le Moal, Vincent Le Moing, Hervé Le Nagard, Ema Leal, Marta Leal Santos, Biing Horng Lee, Heng Gee Lee, Su Hwan Lee, Jennifer Lee, Todd C. Lee, Yi Lin Lee, Gary Leeming, Bénédicte Lefebvre, Laurent Lefebvre, Benjamin Lefèvre, Sylvie LeGac, Merili-Helen Lehiste, Jean-Daniel Lelievre, François Lellouche, Adrien Lemaignen, Véronique Lemee, Anthony Lemeur, Gretchen Lemmink, Ha Sha Lene, Jenny Lennon, Rafael León, Marc Leone, Tanel Lepik, Quentin Lepiller, François-Xavier Lescure, Olivier Lesens, Mathieu Lesouhaitier, Amy Lester-Grant, Andrew Letizia, Sophie Letrou, Bruno Levy, Yves Levy, Claire Levy-Marchal, Katarzyna Lewandowska, Erwan L'Her, Gianluigi Li Bassi, Janet Liang, Ali Liaquat, Geoffrey Liegeon, Kah Chuan Lim, Wei Shen Lim, Chantre Lima, Bruno Lina, Lim Lina, Andreas Lind, Maja Katherine Lingad, Guillaume Lingas, Sylvie Lion-Daolio, Keibun Liu, Marine Livrozet, Patricia Lizotte, Antonio Loforte, Navy Lolong, Leong Chee Loon, Diogo Lopes, Dalia Lopez-Colon, Anthony L. Loschner, Paul Loubet, Bouchra Loufti, Guillame Louis, Silvia Lourenco, Lara Lovelace-Macon, Lee Lee Low, Marije Lowik, Jia Shyi Loy, Jean Christophe Lucet, Carlos M. Luna, Olguta Lungu, Miles Lunn, Liem Luong, Nestor Luque, Dominique Luton, Olavi Maasikas, Moïse Machado, Sara Machado, Gabriel Macheda, Mustafa Magzoub, Rafael Mahieu, Sophie Mahy, Ana Raquel Maia, Lars S. Maier, Oumou Maiga Ascofare, Mylène Maillet, Thomas Maitre, Nimisha Abdul Majeed, Maximilian Malfertheiner, Nadia Malik, Paddy Mallon, Fernando Maltez, Denis Malvy, Victoria Manda, Laurent Mandelbrot, Frank Manetta, Julie Mankikian, Edmund Manning, Aldric Manuel, Veronika Maráczi, Ceila Maria Sant′Ana Malaque, Flávio Marino, Samuel Markowicz, Ana Marques, Catherine Marquis, Laura Marsh, Brian Marsh, Megan Marshal, John Marshall, Celina Turchi Martelli, Dori-Ann Martin, Emily Martin, Guillaume Martin-Blondel, Alessandra Martinelli, F. Eduardo Martinez, Martin Martinot, Alejandro Martín-Quiros, Ana Martins, João Martins, Nuno Martins, Caroline Martins Rego, Gennaro Martucci, Olga Martynenko, Eva Miranda Marwali, Marsilla Marzukie, David Maslove, Sabina Mason, Sobia Masood, Fatma Masoud, Moise Massoma, Palmer Masumbe, Mohd Basri Mat Nor, Moshe Matan, Henrique Mateus Fernandes, Meghena Mathew, Christina Mathew, Mathieu Mattei, Laurence Maulin, Juergen May, Javier Maynar, Mayfong Mayxay, Thierry Mazzoni, Lisa Mc Sweeney, Colin McArthur, Naina McCann, Peter McCanny, Aine McCarthy, Anne McCarthy, Colin McCloskey, Rachael McConnochie, Sherry McDermott, Sarah E. McDonald, Aine McElroy, Samuel McElwee, Natalie McEvoy, Allison McGeer, Kenneth A. McLean, Paul McNally, Bairbre McNicholas, Edel Meaney, Cécile Mear-Passard, Maggie Mechlin, Nastia Medombou, Omar Mehkri, Ferruccio Mele, Luis Melo, Kashif Ali Memon, João João Mendes, Ogechukwu Menkiti, Kusum Menon, France Mentré, Alexander J. Mentzer, Emmanuelle Mercier, Noémie Mercier, Antoine Merckx, Mayka Mergeay-Fabre, Blake Mergler, António Mesquita, Roberta Meta, Osama Metwally, Agnès Meybeck, Dan Meyer, Alison M. Meynert, Vanina Meysonnier, Mehdi Mezidi, Céline Michelanglei, Isabelle Michelet, Efstathia Mihelis, Vladislav Mihnovit, Duha Milad Abdullah, Jennene Miller, Hugo Miranda-Maldonado, Nor Arisah Misnan, Nik Nur Eliza Mohamed, Nouralsabah Mohamed, Tahira Jamal Mohamed, Alaa Mohamed Ads, Ahmed Reda Mohamed Elsayed Abdelhalim, Libya Mohammed, Shrouk Fawze Mohammed Mostafa, Manahil Omer Abdelrahman Mohammedahmed, Omer Abdullah Mohammedelhassan, Asma Moin, Walaa Mokhtar, Elena Molinos, Brenda Molloy, Mary Mone, Agostinho Monteiro, Claudia Montes, Giorgia Montrucchio, Sarah Moore, Shona C. Moore, Lina Morales Cely, Marwa Morgom, Lucia Moro, Catherine Motherway, Ana Motos, Hugo Mouquet, Clara Mouton Perrot, Julien Moyet, Suleiman Haitham Mualla, Mohamed Muftah, Aisha Kalsoom Mufti, Ng Yong Muh, Mo'nes Muhaisen, Dzawani Muhamad, Jimmy Mullaert, Fredrik Müller, Karl Erik Müller, Daniel Munblit, Syed Muneeb Ali, Nadeem Munir, Laveena Munshi, Aisling Murphy, Patrick Murray, Marlène Murris, Srinivas Murthy, Himed Musaab, Alamin Mustafa, Mus'ab Mustafa, Dana Mustafa, Himasha Muvindi, Dimitra Melia Myrodia, Farah Nadia Mohd-Hanafiah, Behzad Nadjm, Dave Nagpal, Alex Nagrebetsky, Blanka Nagybányai-Nagy, Herwin Nanda Boudoin, Mangala Narasimhan, Nageswaran Narayanan, Prashant Nasa, Rashid Nasim Khan, Ahmad Nasrallah, Adel Gerges Nassif Metri, Alasdair Nazerali-Maitland, Nadège Neant, Holger Neb, Nikita Nekliudov, Matthew Nelder, Erni Nelwan, Raul Neto, Emily Neumann, Wing Yiu Ng, Pauline Yeung Ng, Anthony Nghi, Duc Nguyen, Orna Ni Choileain, Niamh Ni Leathlobhair, Nerissa Niba, Alistair D. Nichol, Prompak Nitayavardhana, Stephanie Nonas, Nurul Amani Mohd Noordin, Nurul Faten Izzati Norharizam, Anita North, Alessandra Notari, Mahdad Noursadeghi, Adam Nowinski, Saad Nseir, Leonard Numfor, Nurnaningsih Nurnaningsih, Dwi Utomo Nusantara, Elsa Nyamankolly, Anders Benteson Nygaard, Fionnuala O. Brien, Annmarie O. Callaghan, Annmarie O'Callaghan, Giovanna Occhipinti, Derbrenn OConnor, Max O'Donnell, Lawrence Ofori-Boadu, Tawnya Ogston, Takayuki Ogura, Tak-Hyuk Oh, Sophie O'Halloran, Katie O'Hearn, Sally-Ann Ohene, João Oliveira, Larissa Oliveira, Piero L. Olliaro, Cinderella Omar Rageh Elnaggar, Alsarrah Ali Mohammed Omer, Pierre Ondobo, David S.Y. Ong, Jee Yan Ong, Wilna Oosthuyzen, Anne Opavsky, Peter Openshaw, Saijad Orakzai, Claudia Milena Orozco-Chamorro, Jamel Ortoleva, Mohamed Osama Elsayed Soliman, Javier Osatnik, Linda O'Shea, Miriam O'Sullivan, Eman Othman, Siti Zubaidah Othman, Nadia Ouamara, Rachida Ouissa, Micheal Owusu, Ama Akyampomaa Owusu-Asare, Eric Oziol, Maïder Pagadoy, Justine Pages, Amanda Palacios, Massimo Palmarini, Giovanna Panarello, Hem Paneru, Lai Hui Pang, Mauro Panigada, Nathalie Pansu, Aurélie Papadopoulos, Rachael Parke, Melissa Parker, Jérémie Pasquier, Bruno Pastene, Fabian Patauner, Drashti Patel, Mohan Dass Pathmanathan, Luís Patrão, Patricia Patricio, Lisa Patterson, Rajyabardhan Pattnaik, Christelle Paul, Mical Paul, Jorge Paulos, William A. Paxton, Jean-François Payen, Sandra L. Peake, Kalaiarasu Peariasamy, Giles J. Peek, Florent Peelman, Nathan Peiffer-Smadja, Vincent Peigne, Mare Pejkovska, Paolo Pelosi, Ithan D. Peltan, Rui Pereira, Daniel Perez, Thomas Perpoint, Antonio Pesenti, Vincent Pestre, Lenka Petrou, Michele Petrovic, Ventzislava Petrov-Sanchez, Frank Olav Pettersen, Gilles Peytavin, Richard Odame Philips, Ooyanong Phonemixay, Soulichanya Phoutthavong, Michael Piagnerelli, Walter Picard, Olivier Picone, Maria de Piero, Djura Piersma, Carlos Pimentel, Raquel Pinto, Catarina Pires, Lionel Piroth, Ayodhia Pitaloka, Chiara Piubelli, Riinu Pius, Simone Piva, Laurent Plantier, Hon Shen Png, Julien Poissy, Ryadh Pokeerbux, Sergio Poli, Georgios Pollakis, Diane Ponscarme, Diego Bastos Porto, Andra-Maris Post, Douwe F. Postma, Pedro Povoa, Diana Póvoas, Jeff Powis, Sofia Prapa, Viladeth Praphasiri, Sébastien Preau, Christian Prebensen, Jean-Charles Preiser, Anton Prinssen, Gamage Dona Dilanthi Priyadarshani, Lucia Proença, Sravya Pudota, Bambang Pujo Semedi, Mathew Pulicken, Peter Puplampu, Gregory Purcell, Luisa Quesada, Vilmaris Quinones-Cardona, Else Quist-Paulsen, Mohammed Quraishi, Fadi Qutishat, Maia Rabaa, Christian Rabaud, Ebenezer Rabindrarajan, Aldo Rafael, Marie Rafiq, Abdelrahman Ragab, Mutia Rahardjani, Arslan Rahat Ullah, Ahmad Kashfi Haji Ab Rahman, Rozanah Abd Rahman, Fernando Rainieri, Giri Shan Rajahram, Pratheema Ramachandran, Nagarajan Ramakrishnan, José Ramalho, Ahmad Afiq Ramli, Blandine Rammaert, Grazielle Viana Ramos, Asim Rana, Rajavardhan Rangappa, Ritika Ranjan, Christophe Rapp, Aasiyah Rashan, Thalha Rashan, Ghulam Rasheed, Menaldi Rasmin, Indrek Rätsep, Cornelius Rau, Tharmini Ravi, Ali Raza, Andre Real, Stanislas Rebaudet, Sarah Redl, Brenda Reeve, Attaur Rehman, Muhammad Osama Rehman Khalid, Dag Henrik Reikvam, Renato Reis, Jonathan Remppis, Martine Remy, Hongru Ren, Hanna Renk, Anne-Sophie Resseguier, Matthieu Revest, Oleksa Rewa, Maria Ines Ribeiro, Antonia Ricchiuto, David Richardson, Denise Richardson, Laurent Richier, Siti Nurul Atikah Ahmad Ridzuan, Ana L. Rios, Asgar Rishu, Patrick Rispal, Karine Risso, Maria Angelica Rivera Nuñez, Chiara Robba, André Roberto, Stephanie Roberts, Charles Roberts, David L. Robertson, Olivier Robineau, Anna Roca, Ferran Roche-Campo, Paola Rodari, Simão Rodeia, Bernhard Roessler, Claire Roger, Pierre-Marie Roger, Roberto Roncon-Albuquerque, Jr., Mélanie Roriz, Manuel Rosa-Calatrava, Michael Rose, Dorothea Rosenberger, Andrea Rossanese, Matteo Rossetti, Patrick Rossignol, Carine Roy, Benoît Roze, Desy Rusmawatiningtyas, Clark D. Russell, Maeve Ryan, Steffi Ryckaert, Aleksander Rygh Holten, Isabela Saba, Sairah Sadaf, Musharaf Sadat, Valla Sahraei, Abdurraouf Said, Nadia Saidani, Pranya Sakiyalak, Fodé Bangaly Sako, Moamen Salah, Ali Alaa Salah Eldin Mohamed Abbas, Nawal Salahuddin, Leonardo Salazar, Jodat Saleem, Mohammed Saleh Alyasiri, Talat Ahmed Abu Salem, Gabriele Sales, Charlotte Salmon Gandonniere, Hélène Salvator, Dana Samardali, Shaden Samardali, Yehia Samir Shaaban Aly Orabi, Emely Sanchez, Olivier Sanchez, Kizy Sanchez de Oliveira, Angel Sanchez-Miralles, Vanessa Sancho-Shimizu, Gyan Sandhu, Zulfiqar Sandhu, Pierre-François Sandrine, Oana Săndulescu, Marlene Santos, Shirley Sarfo-Mensah, Bruno Sarmento Banheiro, Iam Claire E. Sarmiento, Benjamine Sarton, Ankana Satya, Sree Satyapriya, Rumaisah Satyawati, Egle Saviciute, Yen Tsen Saw, Justin Schaffer, Tjard Schermer, Arnaud Scherpereel, Marion Schneider, János Schnur, Stephan Schroll, Michael Schwameis, Gary Schwartz, Janet T. Scott, James Scott-Brown, Nicholas Sedillot, Tamara Seitz, Jaganathan Selvanayagam, Mageswari Selvarajoo, Malcolm G. Semple, Rasidah Bt Senian, Eric Senneville, Claudia Sepulveda, Filipa Sequeira, Tânia Sequeira, Ary Serpa Neto, Ellen Shadowitz, Syamin Asyraf Shahidan, Hamza Shahla, Laila Shalabi, Haitam Shames, Anuraj Shankar, Shaikh Sharjeel, Pratima Sharma, Catherine A. Shaw, Victoria Shaw, John Robert Sheenan, Dr. Rajesh Mohan Shetty, Rohan Shetty, Mohiuddin Shiekh, Nobuaki Shime, Keiki Shimizu, Sally Shrapnel, Shubha Kalyan Shrestha, Pramesh Sundar Shrestha, Hoi Ping Shum, Nassima Si Mohammed, Ng Yong Siang, Moses Siaw-Frimpong, Jeanne Sibiude, Bountoy Sibounheuang, Nidhal Siddig, Atif Siddiqui, Maqsood Ahmed Siddiqui, Louise Sigfrid, Fatoumata Sillah, Piret Sillaots, Catarina Silva, Maria Joao Silva, Rogério Silva, Benedict Sim Lim Heng, Wai Ching Sin, Dario Sinatti, Mahendra Singh, Punam Singh, Pompini Agustina Sitompul, Karisha Sivam, Vegard Skogen, Sue Smith, Benjamin Smood, Coilin Smyth, Morgane Snacken, Dominic So, Tze Vee Soh, Lene Bergendal Solberg, Joshua Solomon, Tom Solomon, Emily Somers, Agnès Sommet, Myung Jin Song, Rima Song, Tae Song, Jack Song Chia, Arne Søraas, Albert Sotto, Edouard Soum, Ana Chora Sousa, Marta Sousa, Maria Sousa Uva, Vicente Souza-Dantas, Mamadou Saliou Sow, Alexandra Sperry, Elisabetta Spinuzza, B. P. Sanka Ruwan Sri Darshana, Shiranee Sriskandan, Sarah Stabler, Thomas Staudinger, Stephanie-Susanne Stecher, Trude Steinsvik, Ymkje Stienstra, Birgitte Stiksrud, Eva Stolz, Amy Stone, Anca Streinu-Cercel, Adrian Streinu-Cercel, Geoff Strong, Ami Stuart, David Stuart, Richa Su, Decy Subekti, Gabriel Suen, Jacky Y. Suen, Prasanth Sukumar, Asfia Sultana, Charlotte Summers, Dubravka Supic, Deepashankari Suppiah, Magdalena Surovcová, Atie Suwarti, Andrey Svistunov, Sarah Syahrin, Augustina Sylverken, Konstantinos Syrigos, Jaques Sztajnbok, Konstanty Szuldrzynski, Shirin Tabrizi, Fabio S. Taccone, Lysa Tagherset, Shahdattul Mawarni Taib, Sara Taleb, Cheikh Talla, Jelmer Talsma, Renaud Tamisier, Maria Lawrensia Tampubolon, Kim Keat Tan, Yan Chyi Tan, Hiroyuki Tanaka, Taku Tanaka, Hayato Taniguchi, Huda Taqdees, Arshad Taqi, Coralie Tardivon, Yousef Tarek Kamal Mostafa, Ali Tarhabat, Pierre Tattevin, M Azhari Taufik, Hassan Tawfik, Tze Yuan Tee, João Teixeira, Sofia Tejada, Marie-Capucine Tellier, Sze Kye Teoh, Vanessa Teotonio, François Téoulé, Olivier Terrier, Nicolas Terzi, Hubert Tessier-Grenier, Adrian Tey, Alif Adlan Mohd Thabit, Anand Thakur, Zhang Duan Tham, Suvintheran Thangavelu, Elmi Theron, Vincent Thibault, Simon-Djamel Thiberville, Benoît Thill, Jananee Thirumanickam, Niamh Thompson, Shaun Thompson, Emma C. Thomson, David Thomson, Mathew Thorpe, Surain Raaj Thanga Thurai, Ryan S. Thwaites, Paul Tierney, Vadim Tieroshyn, Peter S. Timashev, Jean-François Timsit, Noémie Tissot, Fiona Toal, Jordan Zhien Yang Toh, Maria Toki, Kristian Tonby, Sia Loong Tonnii, Marta Torre, Antoni Torres, Margarida Torres, Rosario Maria Torres Santos-Olmo, Hernando Torres-Zevallos, Aboubacar Tounkara, Michael Towers, Fodé Amara Traoré, Tony Trapani, Cécile Tromeur, Ioannis Trontzas, Tiffany Trouillon, Jeanne Truong, Christelle Tual, Sarah Tubiana, Helen Tuite, Alexis F. Turgeon, Jean-Marie Turmel, Lance C.W. Turtle, Anders Tveita, Pawel Twardowski, Makoto Uchiyama, PG Ishara Udayanga, Andrew Udy, Roman Ullrich, Alberto Uribe, Asad Usman, Effua Usuf, Timothy M. Uyeki, Cristinava Vajdovics, Piero Valentini, Luís Val-Flores, Stijn Van de Velde, Marcel van den Berge, Machteld van der Feltz, Job van der Palen, Paul van der Valk, Nicky Van Der Vekens, Peter Van der Voort, Sylvie Van Der Werf, Laura van Gulik, Jarne Van Hattem, Carolien van Netten, Ilonka van Veen, Noémie Vanel, Henk Vanoverschelde, Michael Varrone, Shoban Raj Vasudayan, Charline Vauchy, Pavan Kumar Vecham, Shaminee Veeran, Aurélie Veislinger, Sebastian Vencken, Sara Ventura, Annelies Verbon, José Ernesto Vidal, César Vieira, Deepak Vijayan, Judit Villar, Pierre-Marc Villeneuve, Andrea Villoldo, Gayatri Vishwanathan, Benoit Visseaux, Hannah Visser, Chiara Vitiello, Manivanh Vongsouvath, Harald Vonkeman, Fanny Vuotto, Suhaila Abdul Wahab, Noor Hidayu Wahab, Nadirah Abdul Wahid, Marina Wainstein, Laura Walsh, Wan Fadzlina Wan Muhd Shukeri, Chih-Hsien Wang, Steve Webb, Katharina Weil, Tan Pei Wen, Hassi Wesam, Sanne Wesselius, T. Eoin West, Murray Wham, Bryan Whelan, Nicole White, Paul Henri Wicky, Aurélie Wiedemann, Surya Otto Wijaya, Keith Wille, Sue Willems, Bailey Williams, Patricia J. Williams, Virginie Williams, Jessica Wittman, Calvin Wong, Xin Ci Wong, Yew Sing Wong, Teck Fung Wong, Natalie Wright, Lim Saio Xian, Ioannis Xynogalas, Siti Rohani Binti Mohd Yakop, Masaki Yamazaki, Elizabeth Yarad, Yazdan Yazdanpanah, Nicholas Yee Liang Hing, Abdelrahman Yehia Mahmoud Abdelaal, Cécile Yelnik, Chian Hui Yeoh, Stephanie Yerkovich, Touxiong Yiaye, Toshiki Yokoyama, Hodane Yonis, Obada Yousif, Saptadi Yuliarto, Akram Zaaqoq, Marion Zabbe, Gustavo E. Zabert, Kai Zacharowski, Masliza Zahid, Maram Zahran, Nor Zaila Binti Zaidan, Maria Zambon, Miguel Zambrano, Alberto Zanella, Nurul Zaynah, Hiba Zayyad, Alexander Zoufaly, and David Zucman

Subjects
COVID-19, Non-respiratory symptoms, Respiratory symptoms, Risk factors, Mortality, Science (General), Q1-390, Social sciences (General), H1-99
Abstract

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83–0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.

Published
2024
Full Text
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7. Method claim madness: finding infringement when steps of a patented method are practiced abroad.

Author

Valla, S. Maurice

Subjects
Exterritoriality -- Laws, regulations and rules, Patent infringement -- Laws, regulations and rules, Government regulation, Patent Code of 1952 (35 U.S.C. 271)
Abstract

It has long been understood that US patents are limited in their territorial reach. Nearly 100 years ago, the US Supreme Court noted that "the right conferred by a patent [...]

Published
2006

9. The presence of N-terminal secretion signal sequences leads to strong stimulation of the total expression levels of three tested medically important proteins during high-cell-density cultivations of Escherichia coli

Author

Sletta, H., Hakvag, S., Vee Aune, T.E., Tondervik, A., Nedal, A., Aune, R., Evensen, G., Valla, S., Ellingsen, T.E., and Brautaset, T.

Subjects
Escherichia coli -- Genetic aspects, Escherichia coli -- Physiological aspects, Granulocytes -- Research, Biological sciences
Abstract

The use of the pJB658-based expression system to produce granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-[alpha]2b (IFN-[alpha]2b), and single-chain antibody variable fragment (scFv-phOx) both intracellularly lacking signal sequences and through secretion with signal sequences during high-cell-density cultivation is described.

Published
2007

10. Broad-host-range plasmid pJB658 can be used for industrial-level production of a secreted host-toxic single-chain antibody fragment in Escherichia coli

Author

Sletta, H., Aune, R., Nedal, A., Ellingsen, T.E., Aune, T.E.V., Valla, S., Hellebust, H., Hkvag, S., and Brautaset, T.

Subjects
Plasmids -- Research, Host-bacteria relationships -- Research, Escherichia coli -- Research, Biological sciences
Abstract

The unique properties of plasmid pJB658 are utilized to express a host-toxic antibody fragment, scFv-phOx, in high-cell-density cultivation of Escherichia coli. The findings indicate that soluble hapten 2-phenyloxazol-5-one could be produced to a high volumetric yield in high-cell-density cultures of Escherichia coli.

Published
2004

12. Paediatric COVID-19 mortality: a database analysis of the impact of health resource disparity

Author

Nick Daneman, John Marshall, Vinod Kumar, Aasiyah Rashan, Jérôme Dimet, Sylvain Diamantis, John F Fraser, Dominique Deplanque, Anne Conrad, François Lellouche, Heidi Gruner, Detlef Kindgen-Milles, Agnes Meybeck, Maxime Hentzien, Clotilde Allavena, André Cabié, Firouzé Bani-Sadr, Patrick Rossignol, Arjen M Dondorp, Rashan Haniffa, Harald Vonkeman, Lionel Piroth, Mathieu Blot, Yaseen Arabi, Marie-Pierre Debray, François Angoulvant, Marc Leone, Maria Zambon, Florentia Kaguelidou, Marc Lambert, Olivier Lairez, Tom Solomon, Carrol Gamble, Laura Marsh, David Richardson, Christiana Kartsonaki, Philippe Jouvet, Asgar Rishu, Eman Al Qasim, Rachael Parke, Srinivas Murthy, Alistair Nichol, Calum Semple, Colin McArthur, Gail Carson, Jake Dunning, Laura Merson, Peter Horby, David Maslove, Nadia Malik, Stephen R Knight, Annelies Verbon, Oana Sândulescu, Patrick Archambault, Paul McNally, Marlene Murris, Aurore Bousquet, Kenneth A McLean, Hugues Cordel, Marc Fabre, Laurence Bouillet, Melissa Parker, Xavier Duval, Amanda Corley, James Lee, Kusum Menon, Christian Rabaud, Paul Klenerman, Jean-François Timsit, Jennifer Lee, Nicolas Terzi, Saad Nseir, Gwenhaël Colin, Steve Webb, Kalynn Kennon, Caroline Mudara, Diana Hernández, Yazdan Yazdanpanah, Elias Iosifidis, Emmanuel Roilides, Yi Lin Lee, Pieter Depuydt, Jean-François Payen, Ana Martins, Samreen Ijaz, Meera Chand, Wei Shen Lim, Bruno Levy, Eric D'ortenzio, Jean-Charles Preiser, Pierre Delobel, Claudia Figueiredo-Mello, Jaques Sztajnbok, Ana Freitas Ribeiro, Tiphaine Goulenok, Bronner P Gonçalves, Arnaud Scherpereel, Chloe Donohue, Carlo Giaquinto, Karolina Nowicka, Adrien Auvet, Debby Bogaert, Elisabeth Botelho-Nevers, Amandine Gagneux-Brunon, Merce Jourdain, Anne McCarthy, Todd C Lee, António Mesquita, Sue Smith, Jia Wei, Jenny Lennon, Antoine Khalil, Nathalie Pansu, Victor Fomin, Audrey Barrelet, Christophe Fraser, Daniel Munblit, Robert A Fowler, William Greenhalf, François-Xavier Lescure, Nicolas Carlier, Saye Khoo, Riinu Pius, Lisa Norman, Louise Sigfrid, Sophie Halpin, Clare Jackson, Antonia Ho, Andrew Dagens, Thomas Flament, Julie Mankikian, Romain Basmaci, Peter Openshaw, Mary Copland, Brenda Reeve, William Dechert, Patricia Lizotte, Felwa Bin Humaid, Tom Fletcher, Adrien Lemaignen, Pierre Tattevin, Christelle Delmas, Hélène Espérou, Claire Lévy-Marchal, Olivier Picone, Jeanne Sibiude, Cecile Yelnik, Olivia V Swann, Michelle Girvan, Piero L Olliaro, Beatrice Alex, Benjamin Bach, Alexander J Mentzer, Mahdad Noursadeghi, Shona C Moore, Massimo Palmarini, Georgios Pollakis, Vanessa Sancho-Shimizu, Shiranee Sriskandan, David Stuart, Charlotte Summers, Ryan S Thwaites, Hayley Hardwick, Wilna Oosthuyzen, Fiona Griffiths, Jo Dalton, Egle Saviciute, Stephanie Roberts, Janet Harrison, Marie Connor, Gary Leeming, Ross Hendry, Victoria Shaw, Jade Ghosn, Lucille Blumberg, Nicolas Benech, James Scott-Brown, Odile Launay, Todd Karsies, Yoan Lavie-Badie, Minh Le, Elise Artaud-Macari, Mylène Maillet, Huda Alfoudri, Djura Piersma, Didier Laureillard, Graham S. Cooke, Nicholas Sedillot, Anne-Sophie Boureau, Tony Trapani, Laurent Abel, Samuel Hinton, Sally Shrapnel, Heidi Dalton, Guillaume Martin-Blondel, Valérie Garrait, Isabelle Delacroix, Samantha Lissauer, Malte Kohns Vasconcelos, Oleksa Rewa, Erlina Burhan, Sara Machado, Jean-Benoît Arlet, Raphaël Borie, Kévin Bouiller, Vincent Langlois, Mélanie Roriz, Mical Paul, Vincent Dubée, Erwan L'her, Michael Rose, Luis Felipe Reyes, Anna Beltrame, Stéphanie Fry, Andrew Udy, Laurent Plantier, Jean-Christophe Goffard, Denis Malvy, Nina Jamieson, Irfan Khan, François Dubos, Jean-Sébastien Hulot, Paola Rodari, Paul Campbell, Abigail Beane, Cécile Tromeur, Paul Loubet, Marina Esposito-Farèse, France Mentré, Valérie Gaborieau, Anne-Marie Guerguerian, Cécile Goujard, Vincent Thibault, Rodrigo Díaz, Patricia Gordon, Sadie Kelly, Bertrand Dussol, Simon Forsyth, Marion Schneider, Nathalie Gault, Marielle Buisson, Yves Levy, Prasan Kumar Panda, Marjolein Brusse-Keizer, Carine Roy, Walter Picard, Tom Drake, Paul Tierney, Olivier Sanchez, Antoine Kimmoun, David Thomson, Nathan Peiffer-Smadja, Julien Poissy, Lila Bouadma, Bruno Lina, Maude Bouscambert, Alexandre Gaymard, Gilles Peytavin, Jeremie Guedj, Claire Andrejak, Cedric Laouenan, Anissa Chair, Samira Laribi, Marie-Capucine Tellier, Sandrine Couffin-Cadiergues, Soizic Le Mestre, Ventzislava Petrov-Sanchez, Alpha Diallo, NoéMie Mercier, Sarah Tubiana, Marion Noret, Oriane Puechal, Caroline Semaille, Patrick Imbert, Jonathan Remppis, Emmanuelle Mercier, Rui Pereira, Sylvie Van Der Werf, Waasila Jassat, Arsene Kpangon, Dominique Luton, Sophie Mahy, Pierre-Adrien Bolze, Sarah Moore, Adrienne Chan, Raphael Favory, Daniel Mathieu, Andrea Angheben, Andrea Rossanese, Matthew Hall, Johann Auchabie, Mohammed Quraishi, Katharina Weil, Hanna Renk, Hans Martin Bosse, Christophe Rapp, Vincent Peigne, Tae Song, Dewi Guellec, Mark G. Pritchard, Adrian Streinu-Cercel, Christl A Donnelly, François Goehringer, Elodie Curlier, Catherine Chirouze, Stéphane Jaureguiberry, Ary Serpa Neto, Jose Andres Calvache, Laurent Bitker, Hodane Yonis, Neerusha Kaisbain, Coline Jaud-Fischer, Laurent Mandelbrot, Jérémie Pasquier, Juliette Patrier, Gianluigi Li Bassi, Sheryl Ann Abdukahil, Jia Shyi Loy, Filipe Cardoso, Diptesh Aryal, Polina Bugaeva, Evert-Jan Wils, Stephanie Yerkovich, Julie Chas, Thushan de Silva, Ruth Lyons, Murray Wham, Sara Clohisey, Seán Keating, Thibault Chiarabini, Agnes Sommet, Hugues Aumaître, Sylvie LeGac, Sarah E McDonald, Jeanne Truong, Camille Couffignal, Anne-Hélène Boivin, Timo Brandenburger, Diane Descamps, Tala Al-Dabbous, Mark Joseph, Hwa Jin Cho, Desy Rusmawatiningtyas, Muhammad Rayhan, Christel Arnold-Day, Navy Lolong, Ernita Akmal, Menaldi Rasmin, Daniel Marino, Neurinda Permata Kusumastuti, Stéphane Lasry, Amanda Rojek, Sebastien Preau, Jean-Marie Turmel, Nowneet Kumar Bhat, Cynthia Braga, Pavan Kumar Vecham, Benoit Thill, Karine Faure, Denis Garot, Grégory Corvaisier, Elsa Nyamankolly, Joshua Solomon, Emma Clarke, Patricia Fontela, Eva Geraud, Eva Miranda Marwali, Aria Kekalih, Saptadi Yuliarto, Dyah Kanya Wati, Ivy Cerelia Valerie, Maureen Masha, Jolanta Popielska, Anca Streinu-Cercel, Mohan Dass Pathmanathan, Barbara Wanjiru Citarella, Heidi Jean Dalton, Nurul Najmee Abdulkadir, Lara Absil, Subhash Acharya, Diana Adrião, Younes Ait Tamlihat, Kévin Alexandre, Kazali Enagnon Alidjnou, Nathalie Allou, Rita Alves, Joana Alves Cabrita, Maria Amaral, Nur Amira, Phoebe Ampaw, Séverine Ansart, Sivanesen Anthonidass, Carlos Alexandre Brito, Ardiyan Apriyana, Carolline Araujo, Muhammad Ashraf, Jean Baptiste Assie, Amirul Asyraf, Anika Atique, AM Udara Attanyake, Laurène Azemar, Cecile Azoulay, Delphine Bachelet, Claudine Badr, J. Kenneth Baillie, Nazreen Abu Bakar, Mohanaprasanth Balakrishnan, Valeria Balan, Renata Barbalho, Wendy S. Barclay, Saef Umar Barnett, Marie Bartoli, Joaquín Baruch, Muhammad Fadhli Basri, Jules Bauer, Diego Fernando Rincon, Alexandra Bedossa, Ker Hong Bee, Husna Begum, Sylvie Behilill, Albertus Beishuizen, Marine Beluze, Lionel Eric Benjiman, Dehbia Benkerrou, Delphine Bergeaud, José Luis Sobrino, Giulia Bertoli, Simon Bessis, Sybille Bevilcaqua, Karine Bezulier, Krishna Bhavsar, Farah Nadiah Bidin, Mohd Nazlin Kamarudin, François Bissuel, Jonathan Bitton, Laetitia Bodenes, Isabela Bolaños, François Bompart, Diogo Borges, Olivier Bouchaud, Sabelline Bouchez, Dounia Bouhmani, Damien Bouhour, Camile Bouisse, Jason Bouziotis, Bianca Boxma, Marielle Boyer-Besseyre, Fernando Augusto Bozza, Axelle Braconnier, Kathy Brickell, Aidan Burrell, Ingrid G Bustos, Denis Butnaru, Eder Caceres, Cyril Cadoz, Rui Caetano Garcês, Valentine Campana, Pauline Caraux-Paz, Chiara Simona Cardellino, Sofia Cardoso, Filipa Cardoso, Thierry Carmoi, Marie-Christine Carret, François Martin Carrier, Maire-Laure Casanova, Mariana Cascão, José Casimiro, Nidyanara Castanheira, Guylaine Castor-Alexandre, François-Xavier Catherine, Paolo Cattaneo, Roberta Cavalin, Minerva Cervantes-Gonzalez, Catherine Chakveatze, Christelle Chantalat Auger, Jean-Marc Chapplain, Anjellica Chen, Matthew Pellan Cheng, Antoine Cheret, Julian Chica, Suresh Kumar Chidambaram, Leong Chin Tho, Bernard Cholley, Marie-Charlotte Chopin, Ting Soo Chow, Hiu Jian Chua, Jonathan Chua, Alexandra Coelho, Megan Coles, Pamela Combs, Sabine Cornelis, Alexander Daniel Cornet, Arianne Joy Corpuz, Emma Costigan, Roxane Courtois, Stéphanie Cousse, Rachel Cregan, Sabine Croonen, Claudina Cruz, Juan Luis Bermúdez, Jaime Cruz Rojo, Paula Custodio, Ana Silva Filipe, Charlene Da Silveira, Juliana Damas, Corinne Daniel, Emmanuelle A Dankwa, Jorge Dantas, Etienne De Montmollin, Rafael Freitas França, Peter de Vries, Jillian Deacon, Alexa Debard, Nathalie DeCastro, Lauren Deconninck, Romain Decours, Eve Defous, Eric Delaveuve, Karen Delavigne, Corine Delsing, Elisa Demonchy, Emmanuelle Denis, Mathilde Desvallées, Santi Dewayanti, Pathik Dhanger, André Dias, Kévin Didier, Jean-Luc Diehl, Wim Dieperink, Vincent Dinot, Fara Diop, Alphonsine Diouf, Yael Dishon, Félix Djossou, Annemarie B. Docherty, Maria Donnelly, Céline Dorival, James Joshua Douglas, Nathalie Dournon, Murray Dryden, Claudio Duarte Fonseca, Alexandre Ducancelle, Paul Dunand, Sim Choon Ean, Mohammed El Sanharawi, Brigitte Elharrar, Philippine Eloy, Isabelle Enderle, Chan Chee Eng, Ilka Engelmann, Vincent Enouf, Olivier Epaulard, Martina Escher, Catarina Espírito Santo, João Estevão, Manuel Etienne, Nadia Ettalhaoui, Mirjam Evers, Isabelle Fabre, Amna Faheem, Arabella Fahy, Cameron J. Fairfield, Pedro Faria, Ahmed Farooq, Hanan Fateena, Jorge Fernandes, Marília Andreia Fernandes, François-Xavier Ferrand, Eglantine Ferrand Devouge, Joana Ferrão, Mário Ferraz, Bernardo Ferreira, Nicolas Ferriere, Céline Ficko, Clara Flateau, Tatiana Fonseca, Erwan Fourn, Robert A. Fowler, Marcela Vieira Freire, Rostane Gaci, Jean-Charles Gagnard, Yasmin Gani, Noelia García Barrio, Esteban Garcia-Gallo, Louis Gerbaud Morlaes, Nuno Germano, Jess Gibson, Tristan Gigante, Morgane Gilg, Guillermo Giordano, Valérie Gissot, Daniel Glikman, Petr Glybochko, Geraldine Goco, Siri Goepel, Jin Yi Goh, Marie Gominet, Bronner P. Gonçalves, Isabelle Gorenne, Laure Goubert, Pascal Granier, Christopher A. Green, Courtney Greene, Segolène Greffe, Albert Groenendijk, Anja Grosse Lordemann, Yusing Gu, Martin Guego, Daniela Guerreiro, Romain Guery, Anne Guillaumot, Laurent Guilleminault, Thomas Guimard, Marieke Haalboom, Daniel Haber, Hannah Habraken, Ali Hachemi, Nadir Hadri, Fakhir Haidri, Ansley Hamer, Rebecca Hamidfar, Lim Yuen Han, Kok Wei Hao, Ewen M. Harrison, Lars Heggelund, Astarini Hidayah, Rupert Higgins, Hikombo Hitoto, Yi Bin Ho, Alexandre Hoctin, Isabelle Hoffmann, Wei Han Hoh, Ikram Houas, Catherine L. Hough, Jimmy Ming-Yang Hsu, Arfan Ikram, Hajnal-Gabriela Illes, Hugo Inácio, Yun Sii Ing, Sarah Isgett, Tiago Isidoro, Nadiah Ismail, Margaux Isnard, Danielle Jaafar, Salma Jaafoura, Julien Jabot, Pierre Jaquet, Florence Jego, Anilawati Mat Jelani, Ong Yiaw Joe, Cédric Joseph, Swosti Joshi, Dafsah Juzar, Ouifiya Kafif, Thavamany Kaleesvran, Sabina Kali, Muhammad Aisar Kamaluddin, Zul Amali Kamaruddin, Nadiah Kamarudin, Kong Yeow Kang, Pratap Karpayah, Anant Kataria, Kevin Katz, Yvelynne Kelly, Younes Kerroumi, Sharma Keshav, Coralie Khan, Quratul Ain Khan, Sushil Khanal, Abid Khatak, Ryan Khoo, Denisa Khoo, Khor How Kiat, Peter Kiiza, Rob Klont, Gry Kloumann Bekken, Robin Kobbe, Chamira Kodippily, Vinothini Krishnan, Ganesh Kumar, Bharath Kumar Vijayaraghavan, Demetrios Kutsogiannis, Marie Lachatre, Marie Lacoste, Marie Lagrange, Fabrice Laine, Antonio Lalueza, Marie Langelot-Richard, Marina Lanza, Delphine Lariviere, Andy Law, Teresa Lawrence, Clément Le Bihan, Cyril Le Bris, Georges Le Falher, Lucie Le Fevre, Quentin Le Hingrat, Marion Le Maréchal, Gwenaël Le Moal, Vincent Le Moing, Hervé Le Nagard, Paul Le Turnier, Ema Leal, Marta Leal Santos, Heng Gee Lee, Biing Horng Lee, Laurent Lefebvre, Bénédicte Lefebvre, Benjamin Lefèvre, Jean-Daniel Lelievre, Véronique Lemee, Anthony Lemeur, Ha Sha Lene, Quentin Lepiller, Olivier Lesens, Mathieu Lesouhaitier, Geoffrey Liegeon, Kah Chuan Lim, Lim Lina, Guillaume Lingas, Sylvie Lion-Daolio, Marine Livrozet, Leong Chee Loon, Diogo Lopes, Anthony L. Loschner, Bouchra Loufti, Guillame Louis, Lee Lee Low, Marije Lowik, Jean Christophe Lucet, Carlos Lumbreras Bermejo, Liem Luong, Oryane Mabiala, Moïse Machado, Gabriel Macheda, Hashmi Madiha, Guillermo Maestro de la Calle, Rafael Mahieu, Thomas Maitre, Fernando Maltez, Victoria Manda, Jose M. Mandei, Edmund Manning, Aldric Manuel, Ceila Sant'Ana Malaque, Samuel Markowicz, Celina Turchi Martelli, Martin Martinot, Caroline Martins Rego, Marsilla Marzukie, Sabina Mason, Sobia Masood, Basri Mat Nor, Moshe Matan, Mathieu Mattei, Romans Matulevics, Laurence Maulin, Thierry Mazzoni, Cécile Mear-Passard, Ogechukwu Menkiti, Antoine Merckx, Mayka Mergeay-Fabre, Alison M. Meynert, Vanina Meysonnier, Amina Meziane, Mehdi Mezidi, Céline Michelanglei, Isabelle Michelet, Nor Arisah Misnan, Tahira Jamal Mohamed, Nik Nur Mohamed, Asma Moin, Agostinho Monteiro, Claudia Montes, Lina Morales Cely, Lucia Moro, Hugo Mouquet Ben Morton, Clara Mouton Perrot, Julien Moyet, Ng Yong Muh, Dzawani Muhamad, Jimmy Mullaert, Karl Erik Müller, Himed Musaab, Himasha Muvindi, Gugapriyaa Muyandy, Nadège Neant, Nikita Nekliudov, Raul Neto, Anthony Nghi, Duc Nguyen, Nurul Amani Noordin, Nurul Faten Norharizam, Nurnaningsih Nurnaningsih, Annmarie O'Callaghan, Katie O'Hearn, Agnieszka Oldakowska, Piero L. Olliaro, David S.Y. Ong, Jee Yan Ong, Saijad Orakzai, Claudia Milena Orozco-Chamorro, Linda O'Shea, Siti Zubaidah Othman, Nadia Ouamara, Rachida Ouissa, Eric Oziol, Justine Pages Maïder Pagadoy, Lai Hui Pang, Aurélie Papadopoulos, Bruno Pastene, Christelle Paul, Jorge Paulos, William A. Paxton, Kalaiarasu Peariasamy, Miguel Pedrera Jiménez, Florent Peelman, Ithan D. Peltan, Daniel Perez, Thomas Perpoint, Vincent Pestre, Michele Petrovic, Scott Pharand, Carola Pierobon, Carlos Pimentel, Raquel Pinto, Catarina Pires, Isabelle Pironneau, Hon Shen Png, Ryadh Pokeerbux, Maria Pokorska-Spiewak, Diane Ponscarme, Douwe F. Postma, Diana Póvoas, Gamage Dona Priyadarshani, Vilmaris Quinones-Cardona, Víctor Quirós González, Marie Rafiq, Rozanah Abd Rahman, Ahmad Kashfi Rahman, Giri Shan Rajahram, Nagarajan Ramakrishnan, José Ramalho, Ahmad Afiq Ramli, Blandine Rammaert, Grazielle Viana Ramos, Thalha Rashan, Cornelius Rau, Tharmini Ravi, Stanislas Rebaudet, Sarah Redl, Attaur Rehman, Martine Remy, Hongru Ren, Anne-Sophie Resseguier, Matthieu Revest, Laurent Richier, Siti Nurul Ridzuan, Ana L Rios, Patrick Rispal, Karine Risso, David L. Robertson, Olivier Robineau, Pierre-Marie Roger, Juliette Romaru, Manuel Rosa-Calatrava, Bénédicte Rossignol, Stella Rousset, Benoît Roze, Clark D. Russell, Musharaf Sadat, Valla Sahraei, Maximilien Saint-Gilles, Stéphane Sallaberry, Charlotte Salmon Gandonniere, Hélène Salvator, Zulfiqar Sandhu, Pierre-François Sandrine, Shirley Sarfo-Mensah, Benjamine Sarton, Parthena Savvidou, Yen Tsen Saw, Janet T. Scott, Jaganathan Selvanayagam, Mageswari Selvarajoo, Malcolm G. Semple, Rasidah Bt Senian, Eric Senneville, Tânia Sequeira, Pablo Serrano Balazote, Ellen Shadowitz, Syamin Asyraf Shahidan, Mohammad Shamsah, Shaikh Sharjeel, Catherine A. Shaw, Ashraf Sheharyar, Mohiuddin Shiekh, Nassima Si Mohammed, Ng Yong Siang, Benedict Sim Heng, Karisha Sivam, Morgane Snacken, Tze Vee Soh, Rima Song, Azlan Mat Soom, Albert Sotto, B. P Edouard Soum, Sanka Sri Darshana, Sarah Stabler, Ymkje Stienstra, Jacky Y. Suen, Deepashankari Suppiah, Andrey Svistunov, Sarah Syahrin, Shirin Tabrizi, Fabio S. Taccone, Lysa Tagherset, Shahdattul Mawarni Taib, Ewa Talarek, Kim Keat Tan, Yan Chyi Tan, Coralie Tardivon, M Azhari Taufik, Richard S. Tedder, Tze Yuan Tee, João Teixeira, Sze Kye Teoh, François Téoulé, Olivier Terrier, Hubert Tessier-Grenier, Alif Adlan Thabit, Zhang Duan Tham, Suvintheran Thangavelu, Simon-Djamel Thiberville, Jananee Thirumanickam, Emma C. Thomson, Surain Raaj Thurai, Peter S Timashev, Noémie Tissot, Jordan Zhien Toh, Sia Loong Tonnii, Marta Torre, Margarida Torres, Théo Treoux, Tiffany Trouillon, Christelle Tual, Lance C.W. Turtle, PG Ishara Udayanga, Timothy M. Uyeki, Luís Val-Flores, Amélie Valran, Marcel van den Berge, Job van der Palen, Paul van der Valk, Peter Van der Voort, Jarne Van Hattem, Carolien van Netten, Ilonka van Veen, Noémie Vanel, Shoban Raj Vasudayan, Charline Vauchy, Shaminee Veeran, Aurélie Veislinger, James Vickers, José Ernesto Vidal, César Vieira, Benoit Visseaux, Fanny Vuotto, Noor Hidayu Wahab, Suhaila Abdul Wahab, Nadirah Abdul Wahid, Tan Pei Wen, Sanne Wesselius, Nicole White, Paul Henri Wicky, Aurélie Wiedemann, Calvin Wong, Xin Ci Wong, Yew Sing Wong, Teck Fung Wong, Gan Ee Xian, Lim Saio Xian, Kuan Pei Xuan, Siti Rohani Yakop, Nicholas Yee Hing, Chian Hui Yeoh, Obada Yousif, Marion Zabbe, Masliza Zahid, Maram Zahran, Nor Zaila Zaidan, Konrad Zawadka, Nurul Zaynah, Hiba Zayyad, and David Zucman

Subjects
Pediatrics, RJ1-570
Abstract

Background The impact of the COVID-19 pandemic on paediatric populations varied between high-income countries (HICs) versus low-income to middle-income countries (LMICs). We sought to investigate differences in paediatric clinical outcomes and identify factors contributing to disparity between countries.Methods The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) COVID-19 database was queried to include children under 19 years of age admitted to hospital from January 2020 to April 2021 with suspected or confirmed COVID-19 diagnosis. Univariate and multivariable analysis of contributing factors for mortality were assessed by country group (HICs vs LMICs) as defined by the World Bank criteria.Results A total of 12 860 children (3819 from 21 HICs and 9041 from 15 LMICs) participated in this study. Of these, 8961 were laboratory-confirmed and 3899 suspected COVID-19 cases. About 52% of LMICs children were black, and more than 40% were infants and adolescent. Overall in-hospital mortality rate (95% CI) was 3.3% [=(3.0% to 3.6%), higher in LMICs than HICs (4.0% (3.6% to 4.4%) and 1.7% (1.3% to 2.1%), respectively). There were significant differences between country income groups in intervention profile, with higher use of antibiotics, antivirals, corticosteroids, prone positioning, high flow nasal cannula, non-invasive and invasive mechanical ventilation in HICs. Out of the 439 mechanically ventilated children, mortality occurred in 106 (24.1%) subjects, which was higher in LMICs than HICs (89 (43.6%) vs 17 (7.2%) respectively). Pre-existing infectious comorbidities (tuberculosis and HIV) and some complications (bacterial pneumonia, acute respiratory distress syndrome and myocarditis) were significantly higher in LMICs compared with HICs. On multivariable analysis, LMIC as country income group was associated with increased risk of mortality (adjusted HR 4.73 (3.16 to 7.10)).Conclusion Mortality and morbidities were higher in LMICs than HICs, and it may be attributable to differences in patient demographics, complications and access to supportive and treatment modalities.

Published
2022
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13. IP Provisions Of The TPP May Not Satisfy The Pharmaceutical Industry

Author

Valla, S. Maurice

Subjects
Intellectual property law -- Interpretation and construction, Trade agreements -- Laws, regulations and rules, Pharmaceutical industry -- Laws, regulations and rules, Government regulation, Business, international
Abstract

On October 5, 2015, agreement was reached on the text for the Trans-Pacific Partnership (TPP) trade agreement. The 12 signatories (United States, Canada, Mexico, Australia, New Zealand, Japan, Malaysia, Vietnam, [...]

Published
2015

14. What Constitutes Patentable Subject Matter In Biotechnology?

Author

Valla, S. Maurice

Subjects
Sequenom Inc. -- Cases, Patents -- Cases, Biotechnology industries -- Cases, Patent law -- Analysis, Company legal issue, Patent/copyright issue, Business, international
Abstract

With its recent (June 12, 2015) decision in Ariosa v. Sequenom, the Court of Appeals for the Federal Circuit affirmed the Northern District of California's broad interpretation of the U.S. [...]

Published
2015

15. Meeting report: 1st international functional metagenomics workshop may 7-8, 2012, St. Jacobs, Ontario, Canada

Author

Engel, K., Ashby, D., Brady, S., Cowan, D., Doemer, J., Edwards, E., Fiebig, K., Martens, E., Mccormac, D., Mead, D., Miyazaki, K., Moreno-Hagelsieb, G., O'Gara, Fergal, Reid, A., Rose, D., Simonet, P., Sjöling, S., Smalla, K., Streit, W., Tedman-Jones, J., Valla, S., Wellington, E., Wu, C., Liles, M., Neufeld, J., Sessitsch, A., Charles, T., Engel, K., Ashby, D., Brady, S., Cowan, D., Doemer, J., Edwards, E., Fiebig, K., Martens, E., Mccormac, D., Mead, D., Miyazaki, K., Moreno-Hagelsieb, G., O'Gara, Fergal, Reid, A., Rose, D., Simonet, P., Sjöling, S., Smalla, K., Streit, W., Tedman-Jones, J., Valla, S., Wellington, E., Wu, C., Liles, M., Neufeld, J., Sessitsch, A., and Charles, T.

Abstract

This report summarizes the events of the 1st International Functional Metagenomics Work-shop. The workshop was held on May 7 and 8, 2012, in St. Jacobs, Ontario, Canada and was focused on building an international functional metagenomics community, exploring strate-gic research areas, and identifying opportunities for future collaboration and funding. The workshop was initiated by researchers at the University of Waterloo with support from the Ontario Genomics Institute (OGI), Natural Sciences and Engineering Research Council of Canada (NSERC) and the University of Waterloo.

Published
2013

18. Poly(ethylene-co-butylene)-b-(styrene-ran-maleic anhydride)2 Compatibilizers via Nitroxide Mediated Radical Polymerization

Author

Lessard, B., primary, Aumand-Bourque, C., additional, Chaudury, R., additional, Gomez, D., additional, Haroon, A., additional, Ibrahimian, N., additional, Mackay, S., additional, Noel, M.-C., additional, Patel, R., additional, Sitaram, S., additional, Valla, S., additional, White, B., additional, and Maric, M., additional

Published
2011
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32. Poly(ethylene-co-butylene)-b-(styrene-ran-maleic anhydride)2Compatibilizers via Nitroxide Mediated Radical Polymerization

Author

Lessard, B., Aumand-Bourque, C., Chaudury, R., Gomez, D., Haroon, A., Ibrahimian, N., Mackay, S., Noel, M.-C., Patel, R., Sitaram, S., Valla, S., White, B., and Maric, M.

Abstract

Telechelic poly(ethylene-ran-butylene) initiator terminated with [tert-butyl[1-(diethoxyphosphoryl)-2,2-dimethylpropyl]amino] nitroxide groups (PEB-(SG1)2) was used to initiate the controlled radical copolymerization of maleic anhydride (MA) and styrene (ST). The ST/MA copolymerizations were performed in 1,4-dioxane at 110°C and resulted in PEB-b-P(ST-ran-MA)2triblock copolymers with relatively narrow molecular weight distributions (M¯m/M¯n˜1.5). Gel permeation chromatography (GPC) indicated that the initiator used was ˜93% efficient. The resulting copolymers were then blended as 20 wt.% dispersions in nylon 6 (PA6) at 230°C. With as little as 10 mol.% of MA in the feed to make the PEB-b-P(ST-ran-MA)2, blends were deemed dynamically compatibilized based on the reduced particle size. All of the PEB-b-P(ST-ran-MA)2/PA6 blends resulted in a minor phase particle size D¯vs=0.1µm while the PEB-b-P(ST)/PA6 blend had D¯vs=1.15µm (i.e. no MA in the copolymer). Tensile testing revealed yield stresses and strains decreased steadily from pure PA6 to non-reactive PEB-b-P(ST)2/PA6 to PEB-b-P(ST-ran-MA)2/PA6. However, no difference in tensile properties was observed between PEB-b-P(ST-ran-MA)2/PA6 samples made from PEB-b-P(ST-ran-MA)2copolymer of varying MA content.

Published
2011
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33. The catalytic activities of the bifunctional Azotobacter vinelandii mannuronan C-5-epimerase and alginate lyase AlgE7 probably originate from the same active site in the enzyme.

Author

Svanem, B I, Strand, W I, Ertesvag, H, Skjåk-Braek, G, Hartmann, M, Barbeyron, T, and Valla, S

Abstract

The Azotobacter vinelandii genome encodes a family of seven secreted Ca(2+)-dependent epimerases (AlgE1--7) catalyzing the polymer level epimerization of beta-D-mannuronic acid (M) to alpha-L-guluronic acid (G) in the commercially important polysaccharide alginate. AlgE1--7 are composed of two types of protein modules, A and R, and the A-modules have previously been found to be sufficient for epimerization. AlgE7 is both an epimerase and an alginase, and here we show that the lyase activity is Ca(2+)-dependent and also responds similarly to the epimerases in the presence of other divalent cations. The AlgE7 lyase degraded M-rich alginates and a relatively G-rich alginate from the brown algae Macrocystis pyrifera most effectively, producing oligomers of 4 (mannuronan) to 7 units. The sequences cleaved were mainly G/MM and/or G/GM. Since G-moieties dominated at the reducing ends even when mannuronan was used as substrate, the AlgE7 epimerase probably stimulates the lyase pathway, indicating a complex interplay between the two activities. A truncated form of AlgE1 (AlgE1-1) was converted to a combined epimerase and lyase by replacing the 5'-798 base pairs in the algE1-1 gene with the corresponding A-module-encoding DNA sequence from algE7. Furthermore, substitution of an aspartic acid residue at position 152 with glycine in AlgE7A eliminated almost all of both the lyase and epimerase activities. Epimerization and lyase activity are believed to be mechanistically related, and the results reported here strongly support this hypothesis by suggesting that the same enzymatic site can catalyze both reactions.

Published
2001
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36. The recombinant Azotobacter vinelandii mannuronan C-5-epimerase AlgE4 epimerizes alginate by a nonrandom attack mechanism.

Author

Høidal, H K, Ertesvåg, H, Skjåk-Braek, G, Stokke, B T, and Valla, S

Abstract

The Ca2+-dependent mannuronan C-5-epimerase AlgE4 is a representative of a family of Azotobacter vinelandii enzymes catalyzing the polymer level epimerization of beta-D-mannuronic acid (M) to alpha-L-guluronic acid (G) in the commercially important polysaccharide alginate. The reaction product of recombinantly produced AlgE4 is predominantly characterized by an alternating sequence distribution of the M and G residues (MG blocks). AlgE4 was purified after intracellular overexpression in Escherichia coli, and the activity was shown to be optimal at pH values between 6.5 and 7.0, in the presence of 1-3 mM Ca2+, and at temperatures near 37 degrees C. Sr2+ was found to substitute reasonably well for Ca2+ in activation, whereas Zn2+ strongly inhibited the activity. During epimerization of alginate, the fraction of GMG blocks increased linearly as a function of the total fraction of G residues and comparably much faster than that of MMG blocks. These experimental data could not be accounted for by a random attack mechanism, suggesting that the enzyme either slides along the alginate chain during catalysis or recognizes a pre-existing G residue as a preferred substrate in its consecutive attacks.

Published
1999

38. In vitro transcription in E. coli crude lysates prepared on cellophane discs.

Author

Valla, S and Lindqvist, B H

Abstract

An in vitro RNA-synthesizing system consisting of gently lysed E. coli cells on cellophane discs is described. The system has been optimalized with respect to total RNA synthesis. Under certain standard conditions DNA dependent RNA polymerase (EC 2.7.7.6) is responsible for the majority of the RNA synthesis. The extensive rifampicin sensitivity of the synthesis indicates that most of the transcripts are initiated in vitro. The RNA synthesizing system described here has been developed with the aim of studying phage transcription in vitro. We show here that lysates of a P4 infected P2 lysogen support initiation and propagation of transcription from the P2 prophage.

Published
1978
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39. The Azotobacter vinelandii mannuronan C-5-epimerase AlgE1 consists of two separate catalytic domains.

Author

Ertesvåg, H, Høidal, H K, Skjåk-Braek, G, and Valla, S

Abstract

The Azotobacter vinelandii enzyme AlgE1 is a member of a family of secreted mannuronan C-5-epimerases. These enzymes convert beta-D-mannuronic acid residues (M) to alpha-L-guluronic acid residues (G) at the polymer level in the industrially important polysaccharide alginate, leading to altered physical and immunological properties of the polymer. The reaction product of AlgE1 was found to be a mixture of blocks of continuous G residues (G-blocks) and blocks containing alternating M and G residues (MG-blocks). The enzyme is dependent on Ca2+ for activity, and only Sr2+ of those tested was able to replace Ca2+. Zn2+ blocked the activity even at low concentrations. algE1 has been divided into two parts based on the modular type of structure previously reported to be a characteristic of the secreted epimerases, and each part has been expressed in Escherichia coli. These experiments showed that AlgE1 contains two catalytic domains, AlgE1-1, which introduces both G-blocks and MG-blocks, and AlgE1-2, which only introduces MG-blocks. AlgE1-1 has a much lower specific activity than both AlgE1-2 and AlgE1. However, the two halves of AlgE1 seem to cooperate in such a way that they contribute approximately equally to the overall epimerization reaction.

Published
1998

40. Conjugative transfer of the naturally occurring plasmids of Acetobacter xylinum by IncP-plasmid-mediated mobilization

Author

Valla, S, Coucheron, D H, and Kjosbakken, J

Abstract

Broad-host-range plasmids and cloning vectors were conjugatively transferred to Acetobacter xylinum. One of the plasmids, RP4::Mu cts61, was used for the insertion of Tn1 into the 16-, 44-, and 64-kilobase-pair plasmids of A. xylinum. The Tn1-labeled plasmids could be mobilized by a helper plasmid. Many of the Tn1 insertions affected the copy number of the plasmids.

Published
1986
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43. Strong stimulation of recombinant protein production in Escherichia coli by combining stimulatory control elements in an expression cassette

Author

Zwick Friederike, Lale Rahmi, and Valla Svein

Subjects
Recombinant, XylS/Pm, UTR, Gene expression, Promoter, Mutant, Escherichia coli, Microbiology, QR1-502
Abstract

Abstract Background The XylS/Pm expression system has been used to produce recombinant proteins at industrial levels in Escherichia coli. Activation of transcription from the Pm promoter takes place in the presence of benzoic acid or derivatives of it. Previous mutagenesis studies resulted in identification of several variants of the expression control elements xylS (X), Pm (P) and the 5'-untranslated region (U) that individually gave rise to strongly stimulated expression. The goal of this study was to test if combination of such stimulatory mutations in the same expression vectors would lead to further increase of expression levels. Results We combined X, P and U variants that were originally identified due to their ability to strongly stimulate expression of the reporter gene bla (resistance to penicillin). Combination of optimized elements stimulated bla expression up to 75-fold (X, P and U combined) relative to the wild-type system, while accumulated transcript levels increased about 50-fold. This is much more than for the elements individually. We also tested combination of the variant elements on two other and unrelated genes, celB (encoding phosphoglucomutase) and the human growth factor gene gm-csf. Protein production from these genes is much more efficient than from bla in the wild-type system, but expression was still significantly stimulated by the combination of X, P and U variants, although not to the same extent as for bla. We also integrated a single copy of the expression cassette with each gene into the E. coli chromosome and found that the expression level from this single copy was higher for bla than for the wild-type plasmid system, while it was lower for celB and gm-csf. Conclusion Our results show that combination of stimulatory expression control elements can be used to further increase production of different proteins in E. coli. For one reporter gene (bla) this allowed for more protein production from a single gene copy integrated on the chromosome, compared to the wild-type plasmid system. The approach described here should in principle be applicable for improvement of any expression cassette.

Published
2012
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45. β-Catenin is reduced in membranes of human prolactinoma cells and it is inhibited by temozolomide in prolactin secreting tumor models.

Author

Demarchi G, Valla S, Perrone S, Chimento A, Bonadeo N, Vitale DL, Spinelli FM, Cervio A, Sevlever G, Alaniz L, Berner S, and Cristina C

Subjects
Animals, Cyclin D1, Humans, Mice, Models, Theoretical, Prolactin metabolism, Prolactin therapeutic use, Temozolomide pharmacology, Temozolomide therapeutic use, beta Catenin, Pituitary Neoplasms pathology, Prolactinoma drug therapy, Prolactinoma metabolism, Prolactinoma pathology
Abstract

Introduction: Prolactinomas are the most frequent pituitary tumor subtype. Despite most of them respond to medical treatment, a proportion are resistant and become a challenge in clinical management. Wnt/β-Catenin pathway has been implicated in several cancers including pituitary tumors and other sellar region malignancies. Interestingly, Wnt/β-Catenin inhibition augments the cytotoxicity of the chemotherapeutic agent Temozolomide (TMZ) in different cancers. TMZ is now being implemented as rescue therapy for aggressive pituitary adenoma treatment. However, the molecular mechanisms associated with TMZ action in pituitary tumors remain unclear., Objectives: Our aims in the present study were to evaluate differential β-Catenin expression in human resistant prolactinomas and Wnt/β-Catenin signaling activation and involvement in Prolactin (PRL) secreting experimental models treated with TMZ., Results: We first evaluated by immunohistochemistry β-Catenin localization in human resistant prolactinomas in which we demonstrated reduced membrane β-Catenin in prolactinoma cells compared to normal pituitaries, independently of the Ki-67 proliferation indexes. In turn, in vivo 15 mg/kg of orally administered TMZ markedly reduced PRL production and increased prolactinoma cell apoptosis in mice bearing xenografted prolactinomas. Intratumoral β-Catenin strongly correlated with Prl and Cyclin D1, and importantly, TMZ downregulated both β-Catenin and Cyclin D1, supporting their significance in prolactinoma growth and as candidates of therapeutic targets. When tested in vitro, TMZ directly reduced MMQ cell viability, increased apoptosis and produced G2/M cell cycle arrest. Remarkably, β-Catenin activation and VEGF secretion were inhibited by TMZ in vitro., Conclusions: We concluded that dopamine resistant prolactinomas undergo a β-Catenin relocalization in relation to normal pituitaries and that TMZ restrains experimental prolactinoma tumorigenicity by reducing PRL production and β-Catenin activation. Together, our findings contribute to the understanding of Wnt/β-Catenin implication in prolactinoma maintenance and TMZ therapy, opening the opportunity of new treatment strategies for aggressive and resistant pituitary tumors.

Published
2022
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46. Syndecan-1 Depletion Has a Differential Impact on Hyaluronic Acid Metabolism and Tumor Cell Behavior in Luminal and Triple-Negative Breast Cancer Cells.

Author

Valla S, Hassan N, Vitale DL, Madanes D, Spinelli FM, Teixeira FCOB, Greve B, Espinoza-Sánchez NA, Cristina C, Alaniz L, and Götte M

Subjects
Apoptosis drug effects, Apoptosis genetics, CD24 Antigen genetics, CD24 Antigen metabolism, Cell Cycle drug effects, Cell Cycle genetics, Cell Line, Tumor, Databases, Factual, Female, Glycocalyx chemistry, Glycocalyx drug effects, Humans, Hyaluronan Receptors genetics, Hyaluronan Receptors metabolism, Hyaluronan Synthases genetics, Hyaluronan Synthases metabolism, Hyaluronic Acid pharmacology, Kruppel-Like Factor 4, Kruppel-Like Transcription Factors genetics, Kruppel-Like Transcription Factors metabolism, MCF-7 Cells, MicroRNAs genetics, MicroRNAs metabolism, Mitogen-Activated Protein Kinase 1 genetics, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 genetics, Mitogen-Activated Protein Kinase 3 metabolism, PTEN Phosphohydrolase genetics, PTEN Phosphohydrolase metabolism, Protein Binding, Proto-Oncogene Proteins c-akt genetics, Proto-Oncogene Proteins c-akt metabolism, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, RNA-Binding Proteins genetics, RNA-Binding Proteins metabolism, Survival Analysis, Syndecan-1 antagonists & inhibitors, Syndecan-1 metabolism, Triple Negative Breast Neoplasms metabolism, Triple Negative Breast Neoplasms mortality, Triple Negative Breast Neoplasms pathology, Gene Expression Regulation, Neoplastic, Glycocalyx metabolism, Hyaluronic Acid metabolism, Syndecan-1 genetics, Triple Negative Breast Neoplasms genetics, Wnt Signaling Pathway genetics
Abstract

Glycosaminoglycans (GAGs) and proteoglycans (PGs) are major components of the glycocalyx. The secreted GAG and CD44 ligand hyaluronic acid (HA), and the cell surface PG syndecan-1 (Sdc-1) modulate the expression and activity of cytokines, chemokines, growth factors, and adhesion molecules, acting as critical regulators of tumor cell behavior. Here, we studied the effect of Sdc-1 siRNA depletion and HA treatment on hallmark processes of cancer in breast cancer cell lines of different levels of aggressiveness. We analyzed HA synthesis, and parameters relevant to tumor progression, including the stem cell phenotype, Wnt signaling constituents, cell cycle progression and apoptosis, and angiogenic markers in luminal MCF-7 and triple-negative MDA-MB-231 cells. Sdc-1 knockdown enhanced HAS-2 synthesis and HA binding in MCF-7, but not in MDA-MB-231 cells. Sdc-1-depleted MDA-MB-231 cells showed a reduced CD24-/CD44+ population. Furthermore, Sdc-1 depletion was associated with survival signals in both cell lines, affecting cell cycle progression and apoptosis evasion. These changes were linked to the altered expression of KLF4, MSI2, and miR-10b and differential changes in Erk, Akt, and PTEN signaling. We conclude that Sdc-1 knockdown differentially affects HA metabolism in luminal and triple-negative breast cancer model cell lines and impacts the stem phenotype, cell survival, and angiogenic factors.

Published
2021
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47. Evaluation of a Lyophilized CRISPR-Cas12 Assay for a Sensitive, Specific, and Rapid Detection of SARS-CoV-2.

Author

Curti LA, Primost I, Valla S, Ibañez Alegre D, Olguin Perglione C, Repizo GD, Lara J, Parcerisa I, Palacios A, Llases ME, Rinflerch A, Barrios M, Pereyra Bonnet F, Gimenez CA, and Marcone DN

Subjects
COVID-19 virology, Clustered Regularly Interspaced Short Palindromic Repeats, Humans, Molecular Diagnostic Techniques, Nasopharynx virology, RNA, Viral genetics, SARS-CoV-2 classification, SARS-CoV-2 genetics, SARS-CoV-2 isolation & purification, Sensitivity and Specificity, COVID-19 diagnosis, COVID-19 Testing methods
Abstract

We evaluated a lyophilized CRISPR-Cas12 assay for SARS-CoV-2 detection (Lyo-CRISPR SARS-CoV-2 kit) based on reverse transcription, isothermal amplification, and CRISPR-Cas12 reaction. From a total of 210 RNA samples extracted from nasopharyngeal swabs using spin columns, the Lyo-CRISPR SARS-CoV-2 kit detected 105/105 (100%; 95% confidence interval (CI): 96.55-100) positive samples and 104/105 (99.05%; 95% CI: 94.81-99.97) negative samples that were previously tested using commercial RT-qPCR. The estimated overall Kappa index was 0.991, reflecting an almost perfect concordance level between the two diagnostic tests. An initial validation test was also performed on 30 nasopharyngeal samples collected in lysis buffer, in which the Lyo-CRISPR SARS-CoV-2 kit detected 20/21 (95.24%; 95% CI: 76.18-99.88) positive samples and 9/9 (100%; 95% CI: 66.37-100) negative samples. The estimated Kappa index was 0.923, indicating a strong concordance between the test procedures. The Lyo-CRISPR SARS-CoV-2 kit was suitable for detecting a wide range of RT-qPCR-positive samples (cycle threshold range: 11.45-36.90) and dilutions of heat-inactivated virus (range: 2.5-100 copies/µL); no cross-reaction was observed with the other respiratory pathogens tested. We demonstrated that the performance of the Lyo-CRISPR SARS-CoV-2 kit was similar to that of commercial RT-qPCR, as the former was highly sensitive and specific, timesaving (1.5 h), inexpensive, and did not require sophisticated equipment. The use of this kit would reduce the time taken for diagnosis and facilitate molecular diagnosis in low-resource laboratories.

Published
2021
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48. Identification of Regulatory Genes and Metabolic Processes Important for Alginate Biosynthesis in Azotobacter vinelandii by Screening of a Transposon Insertion Mutant Library.

Author

Mærk M, Jakobsen ØM, Sletta H, Klinkenberg G, Tøndervik A, Ellingsen TE, Valla S, and Ertesvåg H

Abstract

Azotobacter vinelandii produces the biopolymer alginate, which has a wide range of industrial and pharmaceutical applications. A random transposon insertion mutant library was constructed from A. vinelandii ATCC12518Tc in order to identify genes and pathways affecting alginate biosynthesis, and about 4,000 mutant strains were screened for altered alginate production. One mutant, containing a mucA disruption, displayed an elevated alginate production level, and several mutants with decreased or abolished alginate production were identified. The regulatory proteins AlgW and AmrZ seem to be required for alginate production in A. vinelandii , similarly to Pseudomonas aeruginosa . An algB mutation did however not affect alginate yield in A. vinelandii although its P. aeruginosa homolog is needed for full alginate production. Inactivation of the fructose phosphoenolpyruvate phosphotransferase system protein FruA resulted in a mutant that did not produce alginate when cultivated in media containing various carbon sources, indicating that this system could have a role in regulation of alginate biosynthesis. Furthermore, impaired or abolished alginate production was observed for strains with disruptions of genes involved in peptidoglycan biosynthesis/recycling and biosynthesis of purines, isoprenoids, TCA cycle intermediates, and various vitamins, suggesting that sufficient access to some of these compounds is important for alginate production. This hypothesis was verified by showing that addition of thiamine, succinate or a mixture of lysine, methionine and diaminopimelate increases alginate yield in the non-mutagenized strain. These results might be used in development of optimized alginate production media or in genetic engineering of A. vinelandii strains for alginate bioproduction., (Copyright © 2020 Mærk, Jakobsen, Sletta, Klinkenberg, Tøndervik, Ellingsen, Valla and Ertesvåg.)

Published
2020
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50. New insights into Pseudomonas fluorescens alginate biosynthesis relevant for the establishment of an efficient production process for microbial alginates.

Author

Maleki S, Mærk M, Hrudikova R, Valla S, and Ertesvåg H

Subjects
Alginates, Biosynthetic Pathways genetics, Biotechnology, Genes, Bacterial, Glucose metabolism, Glucosephosphate Dehydrogenase antagonists & inhibitors, Glucosephosphate Dehydrogenase metabolism, Glucuronic Acid biosynthesis, Hexuronic Acids, Immunohistochemistry, Industrial Microbiology, Pseudomonas fluorescens genetics, Pseudomonas fluorescens ultrastructure, Stress, Physiological, Pseudomonas fluorescens metabolism
Abstract

Alginate denotes a family of linear polysaccharides with a wide range of industrial and pharmaceutical applications. Presently, all commercially available alginates are manufactured from brown algae. However, bacterial alginates have advantages with regard to compositional homogeneity and reproducibility. In order to be able to design bacterial strains that are better suited for industrial alginate production, defining limiting factors for alginate biosynthesis is of vital importance. Our group has been studying alginate biosynthesis in Pseudomonas fluorescens using several complementary approaches. Alginate is synthesised and transported out of the cell by a multiprotein complex spanning from the inner to the outer membrane. We have developed an immunogold labelling procedure in which the porin AlgE, as a part of this alginate factory, could be detected by transmission electron microscopy. No time-dependent correlation between the number of such factories on the cell surface and alginate production level was found in alginate-producing strains. Alginate biosynthesis competes with the central carbon metabolism for the key metabolite fructose 6-phosphate. In P. fluorescens, glucose, fructose and glycerol, are metabolised via the Entner-Doudoroff and pentose phosphate pathways. Mutational analysis revealed that disruption of the glucose 6-phosphate dehydrogenase gene zwf-1 resulted in increased alginate production when glycerol was used as carbon source. Furthermore, alginate-producing P. fluorescens strains cultivated on glucose experience acid stress due to the simultaneous production of alginate and gluconate. The combined results from our studies strongly indicate that the availability of fructose 6-phosphate and energy requires more attention in further research aimed at the development of an optimised alginate production process., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Published
2017
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