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1. Gene family expansions and transcriptome signatures uncover fungal adaptations to wood decay.

Author

Hage, Hayat, Miyauchi, Shingo, Virágh, Máté, Drula, Elodie, Min, Byoungnam, Chaduli, Delphine, Navarro, David, Favel, Anne, Norest, Manon, Lesage-Meessen, Laurence, Bálint, Balázs, Merényi, Zsolt, de Eugenio, Laura, Morin, Emmanuelle, Martínez, Angel T, Baldrian, Petr, Štursová, Martina, Martínez, María Jesús, Novotny, Cenek, Magnuson, Jon K, Spatafora, Joey W, Maurice, Sundy, Pangilinan, Jasmyn, Andreopoulos, Willian, LaButti, Kurt, Hundley, Hope, Na, Hyunsoo, Kuo, Alan, Barry, Kerrie, Lipzen, Anna, Henrissat, Bernard, Riley, Robert, Ahrendt, Steven, Nagy, László G, Grigoriev, Igor V, Martin, Francis, and Rosso, Marie-Noëlle

Subjects
Genetics, Biotechnology, Human Genome, Microbiology, Evolutionary Biology
Abstract

Because they comprise some of the most efficient wood-decayers, Polyporales fungi impact carbon cycling in forest environment. Despite continuous discoveries on the enzymatic machinery involved in wood decomposition, the vision on their evolutionary adaptation to wood decay and genome diversity remains incomplete. We combined the genome sequence information from 50 Polyporales species, including 26 newly sequenced genomes and sought for genomic and functional adaptations to wood decay through the analysis of genome composition and transcriptome responses to different carbon sources. The genomes of Polyporales from different phylogenetic clades showed poor conservation in macrosynteny, indicative of genome rearrangements. We observed different gene family expansion/contraction histories for plant cell wall degrading enzymes in core polyporoids and phlebioids and captured expansions for genes involved in signalling and regulation in the lineages of white rotters. Furthermore, we identified conserved cupredoxins, thaumatin-like proteins and lytic polysaccharide monooxygenases with a yet uncharacterized appended module as new candidate players in wood decomposition. Given the current need for enzymatic toolkits dedicated to the transformation of renewable carbon sources, the observed genomic diversity among Polyporales strengthens the relevance of mining Polyporales biodiversity to understand the molecular mechanisms of wood decay.

Published
2021

2. Fungal Enzymes for Saccharification of Gamma‐Valerolactone‐Pretreated White Birch Wood: Optimization of the Production of Talaromyces amestolkiae Cellulolytic Cocktail.

Author

de Eugenio, Laura I., de la Torre, Isabel, de Salas, Felipe, Vila, Francisco, Alonso, David, Prieto, Alicia, and Martínez, María Jesús

Subjects
*FUNGAL enzymes, *CELLULOSIC ethanol, *ISOELECTRIC focusing, *NATURAL resources, *WOOD, *LIGNOCELLULOSE, *CELLULASE
Abstract

Lignocellulosic biomass, the most abundant natural resource on earth, can be used for cellulosic ethanol production but requires a pretreatment to improve enzyme access to the polymeric sugars while obtaining value from the other components. γ‐Valerolactone (GVL) is a promising candidate for biomass pretreatment since it is renewable and bio‐based. In the present work, the effect of a pretreatment based on GVL on the enzymatic saccharification of white birch was evaluated at a laboratory scale and the importance of the washing procedure for the subsequent saccharification was demonstrated. Both the saccharification yield and the production of cellulosic ethanol were higher using a noncommercial enzyme crude from Talaromyces amestolkiae than with the commercial cocktail Cellic CTec2 from Novozymes. Furthermore, the production of extracellular cellulases by T. amestolkiae has been optimized in 2 L bioreactors, with improvements ranging from 40% to 75%. Finally, it was corroborated by isoelectric focus that optimization of cellulase secretion by T. amestolkiae did not affect the pattern production of the main β‐glucosidases and endoglucanases secreted by this fungus. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Association of Time of Day With Outcomes Among Patients Triaged for a Suspected Severe Stroke in Nonurban Catalonia

Author

García-Tornel, Álvaro, Flores, Alan, Terceño, Mikel, Cardona, Pedro, Amaro, Sergi, Gomis, Meritxell, Zaragoza, Josep, Krupinski, Jerzy, Gómez-Choco, Manuel, Mas, Natalia, Cocho, Dolores, Catena, Esther, Purroy, Francesc, Deck, Matias, Rubiera, Marta, Pagola, Jorge, Rodriguez-Luna, David, Juega, Jesús, Rodríguez-Villatoro, Noelia, Molina, Carlos A., Soro, Cristina, Jimenez, Xavier, Salvat-Plana, Mercè, Dávalos, Antoni, Jovin, Tudor G, Abilleira, Sonia, Pérez de la Ossa, Natalia, Ribó, Marc, Sanjuan, Estela, Santana, Katherine, Maisterra, Olga, Santamarina, Estevo, Muchada, Marian, Boned, Sandra, Franco, Antonio Palasi, Gadea, Marta Olivé, Deck, Matías, Requena, Manuel, Sala, Victoria, Muñoz, Lucía, Millán, Mónica, López-Cancio, Elena, Dorado, Laura, Hernández-Pérez, María, Ciurans, Jordi, Samaniego, Daniela, Canento, Tamara, Martin, Lorena, Planas, Anna, Broto, Joaquin, Sorrentino, Agustín, Paré, Martí, Zhu, Nuole, Garrido, Alicia, Grau, Laia, Crespo, Ane Miren, Presas, Silvia, Almendrote, Miriam, Ramos, Alba, Lucente, Giuseppe, Ispierto, Lourdes, Lozano, Manuel, Becerra, Juan Luis, Jiménez, Marta, Rolán, Dolores Vilas, Guanyabens, Nicolas, Sanchez-Ojanguren, Josep, Martínez-Piñeiro, Alicia, Forcén, Sara, Gea, Mireia, Álvarez, Marta, Ramos, Anna, Lizarbe, Manuel Domínguez, Guerra, Rubio, Bragado, Irene, Arbex, Andrea, Rodríguez, Luis, Bustamante, Alejandro, Portela, Pere Cardona, García, Helena Quesada, Rodríguez, Blanca Lara, Cayuela, Nuria, Miró, Julia, Marzal, Clara, Paipa, Andrés, Campoy, Sergio, Núñez, Ana, Arroyo, Pablo, Besora, Sarah, Adell, Vanessa, Campdelacreu, Jaume, Martí, Montse Alemany, González, Belén, Vila, Laura Bau, Crespo, Marta Fiter, Berbel, Anna, Urbaneja, Ma. Cristina Villaescusa, Guillen, Núria, Vidal, Nuria, Santamaria, Patricia Valentina Vérez, Navarro, Diego Herrero, Simó, Marta, Falip, Mercedes, Matas, Elisabeth, Ochoa, Neus Mongay, Gifreu, Ariadna, Muñoz, Albert, Romero, Lucía, Portell, Eduard, Perez, Guillermo Hernández, Esteve, F. Ruiz, Teixidor, Silvia, Talavera, Augusto Salazar, Gómez, Roser, Nuin, Xabier Urra, Vargas, Martha, Chamorro, Ángel, Llull, Laura, Renú, Arturo, Rudilosso, Salvatore, del Valle, Raquel Sánchez, Ariño, Helena, Solà, Nuria, la Puma, Delón, Gil, Francisco, Gómez, Juan Bernardo, Matos, Nuria, Falgàs, Neus, Borrego, Sergi, Sánchez, Almudena, Balasa, Mircea, Montejo, Carmen, Guasp, Mar, Reyes, David, Cervilla, Pablo Sánchez, Contador, Jose Miguel, Monge, Victor Augusto Vera, Ramos, Oscar, Rodríguez, Alejandro, Campello, Ana Rodríguez, Ballester, Gemma Romeral, Trujillano, Mireia Llop, Steinhauer, Eva Giralt, Godia, Elisa Cuadrado, Santiago, Angel Javier Ois, Conde, Jordi Jimenez, Fábregas, Joan Martí, Guisado, Daniel, Prats, Luís, Camps, Pol, Delgado, Raquel, Domeño, Alejandro Martínez, Marín, Rebeca, Cànovas, David, Estela, Jordi, Ros, Marta, Aranceta, Sonsoles, Espinosa, Jordi, Rubio, Marta, Lafuente, Cristina, Barrachina, Oriol, Anguita, Alicia, Reverter, Anna, García, Carmen, Sansa, Gemma, Hervas, Mariona, Crosas, Monica, Delgado, Tania, Folch, Dra Sonia Huertas, Gamito, Gemma Muñoz, Alvarez, Josep Trenado, Subirana, Teresa, Molina, Jessica, Besora, Sarah, Romero, Laura Comes, Valls, Gemma Guardia, Jover, Miriam, Sotova, Javier Joaquín, García Sánchez, Sonia Mª, Valenzuela, Sebastian, Mengual, Juan José, Font, M. Àngels, Gómez Ruiz, Mª Isabel, Zubizarreta, Irati, González, Susana Fernández, Gubieras, Laura, Cobos, Carmen E., Romo, Luis Mena, Caballol, Nuria, Cano, Luis, Leal, Joaquín Serena, Blas, Yolanda Silva, Trigo, Irene Bragado, Viturro, Saima Bashir, Albiñana, Laura Pardo, Garrido, Montserrat Reina, Cazcarra, Carla Marco, Uscamaita, Karol Enrique, Márquez, Fabian, Coll, Cristina, Villlas, Mar Irida Lloret, Vila, Berta Solano, Perna, Berta Alemany, Domínguezl, Daniel López, de Lera, Mercedes, Foraster, Anna Cots, Monge, Victor Augusto Vera, Bojaryn, Urszula, Benabdelhak, Ikram, Capdevila, Gerard Mauri, Montesinos, Jordi Sanahuja, Vázquez, Daniel, Hervás, José Vicente, González, Cristina, Quílez, Alejandro, Pascual, Mikel Vicente, Ruiz, María, Riba, Yolanda, Villar, M. Pilar Gil, García, Cristina, Roig, Xavier Ustrell, Mora, Mònica Baldrich, Guinjoan, Anna Pellisé, Borras, Judit, Martínez, Alba Mañé, Marés, Rafael, Viñas i Gaya, Jaume, Seró, Laia, Rodríguez, Paula, Castilho, Gislaine, Ortega, Angela Monterde, Reverté, Silvia, Baiges, Joan Josep, Ozaeta, Gisela Martín, Escalante, Sonia, Belloch, Patricia Esteve, Payo, Iago, Salvado, Júlia Saura, Soler Insa, Josep M, Vilamala, Ester Tio, Navarro, Josep Abos, Tabuenca, Héctor Cruz, Sánchez, Tamara Canento, Ros, Marta, Matos, Nuria, Roldán, Elisabet, Rubiol, Elsa Puiggrós, Franquet, Elisabet, Fuentes, Lidia, Donaire, Javier, Martí, Elena, Giménez, Laura, Vázquez, Junior Gil, Ambrós, Eloisa Nieto Clara Gris, Rodríguez, Puri, Oletta, José Félix, Mellado, Pilar Pons, Gómez, Bárbara, Raileau, Vergilin, Pardina, Oscar, Mercadal, Jordi, López-Diéguez, María, Pérez, Pilar, Gabarró, Lourdes, Orriols, María, Molina, José Carlos, Canet, Joan Josep, Roca, Mireia, Álvaro, Muriel, Boneu, Francesc, Giménez, Georgina, Albà, Jaume, Gibert, Francesc, Garcia, Jéssica, Barragan, Patricia, Jurado, Gustavo, Pascual_Medicina Interna, Vanesa, Ortega, Josep Sabaté, Solano, Joan Amaurys Martínez, Fernández, Víctor, Torres, Mónica, Alvaredo, Ana Belén Montero, Parejo, Laura Redondo, Aragonés, Josep Maria, Bullón, Anna, Loste, Cora, González, Paula, Bejarano, Neker, Sanchez, Francisco, Lucchetti, Gianni, Pla, Xavier, Gimeno, Dr Javier, Reynaga, Esteban, Barcons, Montse, Celedón, Gabriel, Ortiz, Juan, Anastasovski, Dr Goran, Mascaró, Dr Oscar, de los Ríos, Dr Javier Diez, Feliu, Meritxell, Ribera, Anna, Ruiz, Cristhian, Corominas, Gerard, Nunes, Dra Daniella, Roca, Claudia, Latorre, Nadina, Yataco, Lizbeth, Cruz, Maricelys, Blanco, Nerea, Castejón, Santiago, Sunyer, Claustre Pont, Garcia, Jordi Espinosa, Martin, Rodrigo Paz, de Luis Sanchez, Albert, Vivas, Dolores Espinosa, Molina, Juan Valencia, Palome, Planels, Chaume, Laia Tomas, Vilella, Ares Villagrasa, Bustamante, Marco, Boltes, Anunciación, Rodríguez, Fernando, Arrieta, Itziar, Molist, Jordi Ciurans, Andreu, Barnés, Soler, Ernest Palomeras, Buscà, Nicolau Guanyabens, López, Manuel Daza, Farreres, Jordi Bigas, Ruiz, Virginia Casado, Batiste, Desiree Muriana, Sanz Cartagena, Mª Pilar, de Vega, Eulalia Cabot, Real, Josep Bassa, Roman, Hector Pelaez, Socolich, César, Alonso Camp, Josep Mª, Orgaz, Antonio Tomás Cano, Fossas Felip, Mª Pilar, Morón, Nicolás, Bacca, Sandra, Molina, Mauricio, Casarramona, Francesc, Elias, Lorena, Bukaei, Muhammad Zidane, Gutierrez, Jose Antonio Martos, Escuin, Judith Lopez, Olaizola, Cristina, Vargas, Yolexis López, Oyonarte, Juan Jiménez, Soultana, Rashida, Golpe, Eduardo Sanjurjo, Salvador, Esther, Vila, Guillem, Serrano, Marcos, Claverol, Matilde Nuria López, Lamolla, Marian, Amate, Miquel, Rodriguez, Adriana, Romero, Ruth, del Carpio, Montgomery, Hernandez, Ana Isabel, Martín, Julián, Rosas, M Carmen, Nogueroles, Antonio, Encarnación, Sorilandy, Robles, Augusto, Herrera, Jose Antonio, Gavilán, Roger, Mameghani, Toghrol, Araujo, Gastón, Morales, M.Angeles Garrido, Segui, Enric Ramon Albert, Climent, Eva Fernandez, Pujol, Francesc Paris, Seira, Mireia Judit Garrofé, Pía, Lucía Gómez, Nuñez, Fernando Salleres, Peñalver, Cristina Aguar, Lopes, Cristina Vaz, Tasa, Elisenda Ribera, Vilchez, Carmen Repullo, Zambrana, Modesto Sánchez, Ribas, Beatriu Suescun, Panés, Inés Vilà, Planavila, Montserrat Vila, Lorenzo, Alicia Vaqueiro, Guixes, Meritxell Sabartés, Medina, Jorge, Sambrano, David, Zamarreño, Javi, Pirela, Carmen, Vélez, Paola, Cajamarca, Luis, Pérez, Honey, Martínez, Yarles, Gonçalves, Jesus Alexander, Regordosa, Carles, Mormeneo, Claudia, Griu, Laura, Colina, Maria Francia, Farik, Enric, Duch, Dolors Carrión, Badenas, Carles, Bernal, Oscar, Agramunt, Núria, Morales, Shyrlei, Reynoso, Victoria, Guerrero, Miguel, Cid, Primitivo Romera, Folqué, Mònica, Pedroza, Claudia, Hachem, Adnan, Martínez, Íñigo Soteras, García, Xavier Verdera, Amorós, Mercè López, Subirós, Xavier Costa, Benet, Marta Cufí, Van Eendenburg, Cecile, Osuna, Teresa, Santos, Dra Gina, Pallisera, Dra Mireia, Oliva, Dr Lluís Gonzalo, Sanchez, Dra Gemma, Basurto, Dr Xavier, Vivoda, Dr Ludgi, Van der Kleyn, Dr Richard, Robles, Dra Laura, Barranco, Ana Cabanelas, Almendros, Mª Cruz, Oliveras, Marc Pérez, Álvarez, Amelia Fernández, Rybyeva, Maria, Viñas, Antoni, Barcons, Maria, Tavera, Joaquim Danès Alberto, Burbano, Pablo, López, Cintie, Cruz, David, Bisbe, Paula, Fernández, Nora, Palacio, Juan Carlos, Fraiz, Eduardo, Aguiló, Oriol, Amorodjo, Rollmy, Velázquez, John, Sánchez, Elena, Español, Jaume, Perez de Celis, Judit, Coll, Anna, Díaz, Glòria, Vergés i Sala, Margarida, Casas Capdevila, Mª Ángels, Ferrini, Yosmairy Yoselin, Gorriz, Aitor, Navarro, Diego-Javier Cucurell, Velásquez, Dulce, Pla Soler, Jaume, González, Josep, Higuera, Julian David, Cuellar, Lina, Miniello, Liza Margarita, Pujol, Lluis, Cracan, Sorin, Vives, Mora, Angela, M, Lopez, Lopez, Molist, Montse Gorchs, Anna, Delofeu, Muñoz, Silvia Solà, Yolanda, Ferreres, Pujalte, Carol, Marín, Elisabeth Téllez, Casas, Yolanda Font, Luque, Sara Hernández, Sendra, Joaquim Mejias, Valero, Francesca Mellado, Escala, Campos, De Lacanal, Galup, Diaz, Lopez, Paramio, Castillo, Estopà, Català, Moreda, Español, Majo, Calafell, Almeida, Carballo, Naval, Castro, Elena, M, Ruiz, Cregut, Lluis, Pere, Font, Deulofeu, Sanjuan, Fabregat, Pere, Joan, Gorchs, Fontquerni, Bellés, Forés, Antoni, Joan, Herrera, Gomez, Carlos, Juan, Prades, Hijazo, Torvisco, Itzaina, Rovira, Marti, Gonzalez, Obiols, Cavero, Olive, Gil, Querol, Soledad, M, Rodriguez, Rico, Sambernardo, Rios, Molina, Ropero, Ramon, Jose, Valero, Sanchez, Arevalo, Santos, Jose, Maria, Garcia, Soto, Angeles, Maria, Escribano, Tebar, Garcia, Torres, José, Pedro, Carrion, Verdes, Isabel, M, Lopez, Verge, Jose, Juan, Canela, Lopez, Angeles, M, Guarque, Lucas, Alvarez, Morales, Arnulfo, Jorge, Fornieles, Morell, Gomez, Subirats, Teresa, Maria, Masa, Miquel, Torello, Lopez, Val, Mercedes, Maria, Reyes, Palmero, Manuel, Juan, Forne, Rodriguez, Turiel, Ruana, Gonzalez, Sanchez, Gornals, Sebastia, Rico, Abrio, Falip, Albert Gual, Oliveros, Aznar, Perotti, Brugues, Molinero, Calvet, Franco, Catells, Medina, Corrales, Miro, Daroca, Marquez, Duran, Pradas, Feliu, Casanova, Figueras, Tortajada, Garcia, Gallego, Grajera, del Mar, Azahara, Arroyo, Las, de Jesus, Dulcenombre, Sanz, Laserreta, Vidal, Llambrich, Corral, Monllao, de la Cruz, Morales, Blanco, Moreno, Orgaz, Orejuela, Suazo, Piñana, Minguillon, Pons, Gómez, Rodríguez, Carlos, José, Pereira, Rodriguez, Porcel, Anna, Sedo, Villar, Sevil, Lopez, Sierra, Romero, Torres, Calveres, Anna, Trepat, Arnella, Ventura, Gil, Acera, Teresa, M, Vico, Biesot, Galea, Castro, Maria, Rosa, Chafer, Escorcia, Antonio, Juan, Moreda, Español, Faure, Gil, Luque, Hernandez, Delgado, Jimenez, Gay, Mallafre, Angel, M., Sanzo, Olivares, Fondevila, Pubill, Fort, Sabate, Agámez, Segovia, Carlos, Antonio, Longaretti, Turata, Hernandez, Valle, Guixens, Trayner, Valor, Aguilar, Alvarez, Aguirre, Naval, Alastrue, Baquero, Alferez, Marne, Alonso, Orozco, Aloy, Colino, Alvarez, Peñuela, Alvarez, Cirilo, Ameller, Vanessa, Maria, Guerrero, Andujar, Remedios, Estefania, Sillero, Auladell, Sorbet, Azcarate, Genesca, Basany, Barduena, Benavent, Tudela, Benito, Pardo, Blanch, Pla, Boluda, Gonzalez, Bonilla, Serramalera, Bru, Andreu, Burnat, Calvo-Rayo, Caballero, Casellas, Calvo, Mombiela, Camps, Bresme, Cano, Fernandez, Carcelen, Solà, Caro, Matavacas, Casasas, Bolado, Castanedo, Cortina, Cerdeña, Jane, Abella, Borrego, Laia Collado, Orri, Colom, Vilanova, Comellas, Sole, Conillera, Torres, Cots, Estepa, Cuchi, de Sostoa Graell, Marc, del Rio Lopez, Laura, Compte, Delgado, Bueno, Diaz, Maneiro, Diaz, Lucia, Andrea, Palau, Domenech, Carme, M., Carasso, Duran, Javier, Pablo, Marquez, Duran, Abidi, El, Martin, Escoda, Casanovas, Esteve, Perez, Fernandez, Quintero, Ferre, Escobar, Flores, Abad, Fontcuberta, del Valle, Fortes, del Valle, Fortes, Luisa, Mª, Quesada, Franco, Maria, Sara, Romero, Franco, Teresa, Maria, Francisco, Gallego, Gala, Gamiz, Castañeda, Garcia, Rodriguez, Garcia, Gemma, Casajuana, Arroyo, Gomez, Girbau, Gomez, Fernandez, Gonzalez, Gonzalez, Gonzalez, Gonzalez, Gonzalez, Lopez, Gonzalez, Obeso, Gual, Blanco, Guerrero, Roca, Guillemas, Eudaldo, Guillermo, Hernandez, Sebastia, Covas, Homar, Alvarez, Hostench, Royo, Huerta, Barcelo, Ibañez, Cruz, Izquiero, Etxetxikia, Jaione Urdangarin, Gimenez, Juárez, Alami, Khlifi, Gasco, Laparra, Moreales, Lara, Arroyo, Las, de Jesus, Dulcenombre, Medina, Lasaosa, Lourdes, Maria, Cava, Lazaro, Berrar, Leon, Maturana, López, Ramirez, Lopez, Romero, López, Marco, Lorente, Martin, Lorenzo, Casals, Lozano, Nicola, Lujan, Diaz, Madrid, Antonio, Jose, Morales, Maria Teresa Peris, Clemente, Marti, Castaño, Martinez, Natanael, David, Gamez, Martinez, Gonzalez, Martinez, Quesada, Martinez, de la Cabeza, Maria, Fusté, Marzà, Lasheras, Melendo, Mestre, Miralles, Pastalle, Montserrat Puig, Vidal, Montserrate, Mellado, Mora, Ponce, Morales, Fornieles, Morell, Cabre, Morera, Vivet, Morera, Souza, Mundi, Quiles, Muñoz, Rosa, Navea, Iglesias, Neira, Asuncion, M, Manrique, Nuñez, Pilar, Mª, Martinez, Obiols, Reig, Pallares, Torres, Partegas, Berengueras, Pascual, Gamez, Perez, Oset, Perez, Restrepo, Perez, Alejandra, Maria, Yeste, Planas, Mangado, Planells, Minguillon, Pons, Carbonell, Puertas, Blanco, Quinteiro, Benavente, Rebollar, Fernandez, Recasens, Gomez, Reyes, del Carmen, Maria, Pou, Roca, Ferrer, Rodriguez, Franco, Rodriguez, Fuertes, Rodriguez, Muñoz, Rodriguez, Navarro, Rodriguez, Iniesta, Roig, Gracia, Romero, Brunet, Rovira, de Eugenio, Rovira, Baena, Rubio, Llorens, Ruiz, Llamazares, Sala, Alaez, San Juan, Segura, Sanchez, Soldevilla, Santasusana, Salmeron, Sanz, Perez, Segura, Balcells, Serra, Dumitras, Sorina, Montoya, Teixidor, Vicente, Tena, Salinas, Tierno, Ines, Ester, Testa, Toledo, Figueras, Tomàs, Ruperez, Tomas, Garcia-Penche, Torrano, Esparza, Torres, Blanco, Vazquez, De la Paz, Vazquez, Gil, Vazquez, Gonzalez, Vazquez, Meler, Vidal, Cots, Vilalta, Jimenez, Vilches, Jose, Maria, Fernandez, Visser, Gavin, Viu, Vives, Vives, Jimenez, Carmona, Jose, Francisco, Vilches, Galobardes, Gomez, Gonzalez, Manzanera, Jodar, Cortes, Marimon, Orive, Marrodan, Bosch, Martin, Jose, Maria, Lopez, Martorell, Roca, Millares, Jesus, M, Guri, Miralles, Hernandez, Muliterno, Oliva, Muñoz, Pujol, Pons, Conde, Postius, Arruñada, Prieto, Antonio, Jose, Mathé, Quintana, Mata, Rosell, Alvarez, Aguirre, Alvarez, Alvarin, Flores, Arrufat, Pago, Bañuelos, Andreu, Burnat, Vilar, Campo, Hidalgo, Cardus, Gil, Castello, Gloria, Maria, Montsesinos, Castrillo, Estopà, Català, Garces, Clave, Sanroma, Comes, Sequi, Descalzo, Ricol, Errando, Campillo, Escudero, del Mar, Maria, Alvarez, Fernandez, Gomez, Fernandez, Perez, Fernandez, Espinosa, Franch, Graells, Freixes, Plaza, Garcia, Gallego, Garcia-Marron, Simancas, Hernandez, Covas, Homar, Royo, Huerta, Armas, Jaraba, Ramos, Jimenez, Canela, Lopez, Angeles, M, Lopez, Lopez, Oganissian, Lopez, Romero, Madrona, Rosa, M, Millan, Martinez, Morón, Martínez, Encinas, Merchan, Fornieles, Morell, Jimenez, Moreno, Rico, Muñoz, Rodriguez, Navarro, Ibañez, Nogales, Maria, Rita, Viera, Novillo, Torrabadella, Parella, Alba, Mari, Villar, Pera, Montserrat, Carla, Carbonell, Puertas, Miralles, Rabella, Trilles, Ramis, Ortiz, Ribera, Fuertes, Rodriguez, Gonzalez, Sanchez, Perez, Sastre, Perez, Segura, Borrega, Soro, Garcia, Soto, Angeles, Maria, Fores, Tapia, Bernad, Tellez, Alvarez, Trenado, Moreda, Español, Martin, Felix, Perez, Herrero, Manzanera, Jodar, Fuster, Lanau, Gomariz, Lopez, Orive, Marrodan, Bosch, Martin, Jose, Maria, Guri, Miralles, Oliva, Muñoz, Lozano, Pardo, Pujol, Pons, Altimiras, Quintana, Lopez, Ventosa, Damian, Almodovar, Colino, Alvarez, Monterroso, Alvarez, Comas, Arambudo, Garzon, Boullon, Capella, Burgos, Garcia, Campuzano, Del Mar, Maria, Olivas, Capdevila, Fernandez, Carcelen, Solà, Caro, Marti, Carre, Isabel, Clara, Bacaicoa, Carretero, Gil, Castello, Gloria, Maria, Montsesinos, Castrillo, Calderon, Cazorla, Osuna, Chacon, Planas, Cortes, Olio, Cortit, Estany, Delhomme, Carasso, Duran, Javier, Pablo, Campillo, Escudero, del Mar, Maria, Martinez, Fructuos, Lopez, Garcia, Luis, Pascual, Plaza, Garcia, Vallve, Genis Amill, Arroyo, Gomez, Girbau, Gomez, Muñoz, Gonzalez, Ventura, Hernaez, Covas, Homar, Gimenez, Lavernia, Rojo, Martin, Medina, Martínez, Millan, Martinez, Barrera, Mayol, Pi, Mercader, Dalmau, Merino, Campodarbe, Miguel, Pastalle, Montserrat Puig, de la Cruz, Morales, Fornieles, Morell, Sanchez, Moreno, Javier, Francisco, Reig, Pallares, Torrabadella, Parella, Alba, Mari, Barrameda, Penela, Ajenjo, Prieto, Benavente, Rebollar, Pareja, Rodriguez, Piñar, Rodríguez, Javier, Francisco, Tello, Rodriguez, Pereda, Romero, Saborido, Sainz, Martin, Santacana, Martinez, Santos, Chavez, Sierra, Testa, Toledo, Figueras, Tomàs, Garcia, Torres, José, Pedro, Torres, Turbau, Domenech, Vicente, Esteo, Villena, Pertegaz, Vives, Gonzalez, Baena, Pont, Bagaria, Sanchez, Beltran, Alarcon, Bonet, Ballescà, Borch, Clanchet, Buhils, Garcia, Closa, Carril, Colomina, Sanchez, Cristina Fernandez, Toledo, Edurne Judith Fernandez, Rodriguez, Espases, Resa, Espert, Xavier, F, Sol, Fernández, Lugo, Gonzalez, Llesera, Gracia, Lendinez, Herrada, Liesa, Juliench, Alicia, Sandra, Ortega, Lopez, Yuste, Lopez, Villanueva, Lozano, Soto, Lucia Sola, Castellano, Madrid, Cano, Megias, Jesus, Daniel, Ponce, Montasell, Sospedra, Montesinos, Martinez, Moya, Herrera, Muñoz, Isabel, M, Fernandez, Ocaña, Jose, Maria, Bernal, Palau, Sole, Perez, Carbonell, Ramon, Lop, Ribas, López, Rubio, Lopez, Rueda, Castaño, Sabat, Lara, Sabata, Ramírez, Salmerón, Gornals, Sebastia, Creus, Serra, Dalmau, Serrano, Mainero, Sumasi, Gabriel, Gonzalo, Masa, Torello, Primo, Valencia, Muñoz, Ana Maria Viñuales, Roig, Josep, and Hidalgo, Verònica

Published
2023
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5. Expression and Characterization of Two α-l-Arabinofuranosidases from Talaromyces amestolkiae: Role of These Enzymes in Biomass Valorization

Author

Juan A. Méndez-Líter, Laura I. de Eugenio, Manuel Nieto-Domínguez, Alicia Prieto, and María Jesús Martínez

Subjects
glycoside hydrolases, hemicellulose, GH62, biodegradation, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

α-l-arabinofuranosidases are glycosyl hydrolases that catalyze the break between α-l-arabinofuranosyl substituents or between α-l-arabinofuranosides and xylose from xylan or xylooligosaccharide backbones. While they belong to several glycosyl hydrolase (GH) families, there are only 24 characterized GH62 arabinofuranosidases, making them a small and underrepresented group, with many of their features remaining unknown. Aside from their applications in the food industry, arabinofuranosidases can also aid in the processing of complex lignocellulosic materials, where cellulose, hemicelluloses, and lignin are closely linked. These materials can be fully converted into sugar monomers to produce secondary products like second-generation bioethanol. Alternatively, they can be partially hydrolyzed to release xylooligosaccharides, which have prebiotic properties. While endoxylanases and β-xylosidases are also necessary to fully break down the xylose backbone from xylan, these enzymes are limited when it comes to branched polysaccharides. In this article, two new GH62 α-l-arabinofuranosidases from Talaromyces amestolkiae (named ARA1 and ARA-2) have been heterologously expressed and characterized. ARA-1 is more sensitive to changes in pH and temperature, whereas ARA-2 is a robust enzyme with wide pH and temperature tolerance. Both enzymes preferentially act on arabinoxylan over arabinan, although ARA-1 has twice the catalytic efficiency of ARA-2 on this substrate. The production of xylooligosaccharides from arabinoxylan catalyzed by a T. amestolkiae endoxylanase was significantly increased upon pretreatment of the polysaccharide with ARA-1 or ARA-2, with the highest synergism values reported to date. Finally, both enzymes (ARA-1 or ARA-2 and endoxylanase) were successfully applied to enhance saccharification by combining them with a β-xylosidase already characterized from the same fungus.

Published
2023
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7. Fungal–Lactobacteria Consortia and Enzymatic Catalysis for Polylactic Acid Production

Author

Laura I. de Eugenio, Carlos Murguiondo, Sandra Galea-Outon, Alicia Prieto, and Jorge Barriuso

Subjects
bioplastic, starch, lignocellulosic biomass, L. plantarum, biofilm, Biology (General), QH301-705.5
Abstract

Polylactic acid (PLA) is the main biobased plastic manufactured on an industrial scale. This polymer is synthetized by chemical methods, and there is a strong demand for the implementation of clean technologies. This work focuses on the microbial fermentation of agro-industrial waste rich in starch for the production of lactic acid (LA) in a consolidated bioprocess, followed by the enzymatic synthesis of PLA. Lactic acid bacteria (LAB) and the fungus Rhizopus oryzae were evaluated as natural LA producers in pure cultures or in fungal–lactobacteria co-cultures formed by an LAB and a fungus selected for its metabolic capacity to degrade starch and to form consortia with LAB. Microbial interaction was analyzed by scanning electron microscopy and biofilm production was quantified. The results show that the fungus Talaromyces amestolkiae and Lactiplantibacillus plantarum M9MG6-B2 establish a cooperative relationship to exploit the sugars from polysaccharides provided as carbon sources. Addition of the quorum sensing molecule dodecanol induced LA metabolism of the consortium and resulted in improved cooperation, producing 99% of the maximum theoretical yield of LA production from glucose and 65% from starch. Finally, l-PLA oligomers (up to 19-LA units) and polymers (greater than 5 kDa) were synthetized by LA polycondensation and enzymatic ring-opening polymerization catalyzed by the non-commercial lipase OPEr, naturally produced by the fungus Ophiostoma piceae.

Published
2023
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10. Thioglycoligase derived from fungal GH3 β-xylosidase is a multi-glycoligase with broad acceptor tolerance

Author

Manuel Nieto-Domínguez, Beatriz Fernández de Toro, Laura I. de Eugenio, Andrés G. Santana, Lara Bejarano-Muñoz, Zach Armstrong, Juan Antonio Méndez-Líter, Juan Luis Asensio, Alicia Prieto, Stephen G. Withers, Francisco Javier Cañada, and María Jesús Martínez

Subjects
Science
Abstract

Thioglycoligases have proved useful for bonding carbohydrates to non-sugar acceptors, however, the scope of these biocatalysts is usually limited. Here, the authors engineer a xylosidase into a thioglycoligase with the ability to form O-, N-, S- and Se- glycosides together with sugar esters and phosphoesters.

Published
2020
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11. A glucotolerant β-glucosidase from the fungus Talaromyces amestolkiae and its conversion into a glycosynthase for glycosylation of phenolic compounds

Author

Juan Antonio Méndez-Líter, Manuel Nieto-Domínguez, Beatriz Fernández de Toro, Andrés González Santana, Alicia Prieto, Juan Luis Asensio, Francisco Javier Cañada, Laura Isabel de Eugenio, and María Jesús Martínez

Subjects
Transglycosylation, Glycosynthases, Glycoside hydrolases, Phenolic compounds, Microbiology, QR1-502
Abstract

Abstract Background The interest for finding novel β-glucosidases that can improve the yields to produce second-generation (2G) biofuels is still very high. One of the most desired features for these enzymes is glucose tolerance, which enables their optimal activity under high-glucose concentrations. Besides, there is an additional focus of attention on finding novel enzymatic alternatives for glycoside synthesis, for which a mutated version of glycosidases, named glycosynthases, has gained much interest in recent years. Results In this work, a glucotolerant β-glucosidase (BGL-1) from the ascomycete fungus Talaromyces amestolkiae has been heterologously expressed in Pichia pastoris, purified, and characterized. The enzyme showed good efficiency on p-nitrophenyl glucopyranoside (pNPG) (K m = 3.36 ± 0.7 mM, k cat = 898.31 s−1), but its activity on cellooligosaccharides, the natural substrates of these enzymes, was much lower, which could limit its exploitation in lignocellulose degradation applications. Interestingly, when examining the substrate specificity of BGL-1, it showed to be more active on sophorose, the β-1,2 disaccharide of glucose, than on cellobiose. Besides, the transglycosylation profile of BGL-1 was examined, and, for expanding its synthetic capacities, it was converted into a glycosynthase. The mutant enzyme, named BGL-1-E521G, was able to use α-d-glucosyl-fluoride as donor in glycosylation reactions, and synthesized glucosylated derivatives of different pNP-sugars in a regioselective manner, as well as of some phenolic compounds of industrial interest, such as epigallocatechin gallate (EGCG). Conclusions In this work, we report the characterization of a novel glucotolerant 1,2-β-glucosidase, which also has a considerable activity on 1,4-β-glucosyl bonds, that has been cloned in P. pastoris, produced, purified and characterized. In addition, the enzyme was converted into an efficient glycosynthase, able to transfer glucose molecules to a diversity of acceptors for obtaining compounds of interest. The remarkable capacities of BGL-1 and its glycosynthase mutant, both in hydrolysis and synthesis, suggest that it could be an interesting tool for biotechnological applications.

Published
2020
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12. Synthesis and Characterization of a Novel Resveratrol Xylobioside Obtained Using a Mutagenic Variant of a GH10 Endoxylanase

Author

Ana Pozo-Rodríguez, Juan A. Méndez-Líter, Rocío García-Villalba, David Beltrán, Eva Calviño, Andrés G. Santana, Laura I. de Eugenio, Francisco Javier Cañada, Alicia Prieto, Jorge Barriuso, Francisco A. Tomás-Barberán, and María Jesús Martínez

Subjects
antioxidants, colonic fermentation, fungal enzyme, glycoconjugates, glycoside hydrolases, glycosynthase, Therapeutics. Pharmacology, RM1-950
Abstract

Resveratrol is a natural polyphenol with antioxidant activity and numerous health benefits. However, in vivo application of this compound is still a challenge due to its poor aqueous solubility and rapid metabolism, which leads to an extremely low bioavailability in the target tissues. In this work, rXynSOS-E236G glycosynthase, designed from a GH10 endoxylanase of the fungus Talaromyces amestolkiae, was used to glycosylate resveratrol by using xylobiosyl-fluoride as a sugar donor. The major product from this reaction was identified by NMR as 3-O-ꞵ-d-xylobiosyl resveratrol, together with other glycosides produced in a lower amount as 4′-O-ꞵ-d-xylobiosyl resveratrol and 3-O-ꞵ-d-xylotetraosyl resveratrol. The application of response surface methodology made it possible to optimize the reaction, producing 35% of 3-O-ꞵ-d-xylobiosyl resveratrol. Since other minor glycosides are obtained in addition to this compound, the transformation of the phenolic substrate amounted to 70%. Xylobiosylation decreased the antioxidant capacity of resveratrol by 2.21-fold, but, in return, produced a staggering 4,866-fold improvement in solubility, facilitating the delivery of large amounts of the molecule and its transit to the colon. A preliminary study has also shown that the colonic microbiota is capable of releasing resveratrol from 3-O-ꞵ-d-xylobiosyl resveratrol. These results support the potential of mutagenic variants of glycosyl hydrolases to synthesize highly soluble resveratrol glycosides, which could, in turn, improve the bioavailability and bioactive properties of this polyphenol.

Published
2022
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13. Incidence and characteristics of uncommon dementia subtypes: Results from 10 years of clinical surveillance by the Registry of Dementia of Girona

Author

Alemany, Berta, Coll, Cristina, Cots, Anna, Hernández, Marta, Gich, Jordi, López-Pousa, Secundino, Lozano, Manuela, Molins, Albert, Pericot-Nierga, Immaculada, Ramió-Torrentà, Lluís, Robles, René, Salavedra, Judit, Serena, Joaquín, Silva, Yolanda, Solano, Berta, Terceño, Mikel, Estrada, Antoni Turon, Vilalta-Franch, Joan, Alsina, Elisabet, Belchí, Olga, de Eugenio, Rosa, Hernández, Erélido, Flaqué, Margarita, Carmona, Olga, Cullell, Marta, Osuna, Teresa, Fernández, M<ce:sup loc='post">a</ce:sup> del Mar, Van Eendenburg, Cecile, Bisbe, Josep, Linares, Marta, Daniel, Fabian Marquez, Vallmajó, Natalia, Perkal, Héctor, Viñas, Marta, Casas, Isabel, Turbau, Josefa, Cuy, Josep M<ce:sup loc='post">a</ce:sup>, Manzano, Anna, Roig, Anna Maria, Coromina, Joan, Soto, Mònica Palacios, Calvó-Perxas, Laia, Turon-Estrada, Antoni, Turró-Garriga, Oriol, and Garre-Olmo, Josep

Published
2019
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14. Exploiting xylan as sugar donor for the synthesis of an antiproliferative xyloside using an enzyme cascade

Author

Manuel Nieto-Domínguez, José Alberto Martínez-Fernández, Beatriz Fernández de Toro, Juan A. Méndez-Líter, Francisco Javier Cañada, Alicia Prieto, Laura I. de Eugenio, and María Jesús Martínez

Subjects
Endoxylanase, β-Xylosidase, Response surface methodology, Transxylosylation, Antiproliferative, Microbiology, QR1-502
Abstract

Abstract Background Currently, industrial societies are seeking for green alternatives to conventional chemical synthesis. This demand has merged with the efforts to convert lignocellulosic biomass into value-added products. In this context, xylan, as one of main components of lignocellulose, has emerged as a raw material with high potential for advancing towards a sustainable economy. Results In this study, the recombinant endoxylanase rXynM from the ascomycete Talaromyces amestolkiae has been heterologously expressed in Pichia pastoris and used as one of the catalysts of an enzyme cascade developed to synthesize the antiproliferative 2-(6-hydroxynaphthyl) β-d-xylopyranoside, by transglycosylation of 2,6-dihydroxynaphthalene. The approach combines the use of two fungal xylanolytic enzymes, rXynM and the β-xylosidase rBxTW1 from the same fungus, with the cost-effective substrate xylan. The reaction conditions for the cascade were optimized by a Central Composite Design. Maximal productions of 0.59 and 0.38 g/L were reached using beechwood xylan and birchwood xylan, respectively. For comparison, xylans from other sources were tested in the same reaction, suggesting that a specific optimization is required for each xylan variety. The results obtained using this enzyme cascade and xylan were similar or better to those previously reported for a single catalyst and xylobiose, an expensive sugar donor. Conclusions Beechwood and birchwood xylan, two polysaccharides easily available from biomass, were used in a novel enzyme cascade to synthetize an antiproliferative agent. The approach represents a green alternative to the conventional chemical synthesis of 2-(6-hydroxynaphthyl) β-d-xylopyranoside using a cost-effective substrate. The work highlights the role of xylan as a raw material for producing value-added products and the potential of fungal xylanolytic enzymes in the biomass conversion.

Published
2019
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15. Survival, effect measures, and impact numbers after dementia diagnosis: a matched cohort study

Author

Garre-Olmo J, Ponjoan A, Inoriza JM, Blanch J, Sánchez-Pérez I, Cubí R, de Eugenio R, Turró-Garriga O, and Vilalta-Franch J

Subjects
epidemiology, diagnosis, dementia, mortality, Infectious and parasitic diseases, RC109-216
Abstract

Josep Garre-Olmo,1–3 Anna Ponjoan,1,4–5 José Maria Inoriza,6,7 Jordi Blanch,4 Inma Sánchez-Pérez,6 Rafel Cubí,4 Rosa de Eugenio,7 Oriol Turró-Garriga,1,2 Joan Vilalta-Franch On behalf of the Registry of Dementia of Girona Study Group (ReDeGi Study Group)11Research Group on Ageing, Disability and Health, Girona Biomedical Research Institute (IDIBGI), Catalonia, Spain; 2Registry of Dementia of Girona, Health Assistance Institute, Catalonia, Spain; 3Department of Medical Sciences, School of Medicine, University of Girona, Catalonia, Spain; 4Vascular Health Research Group (ISV-Girona), Foundation University Institute for Primary Health Care Research Jordi Gol I Gurina, Catalonia, Spain; 5Autonomous University of Barcelona, Catalonia, Spain; 6Research Group on Health Services and Health Outcomes (GRESSIRES), Integrated Health Services Baix Empordà (SSIBE), Catalonia, Spain; 7Hospital de Palamós, Integrated Health Services Baix Empordà (SSIBE), Catalonia, SpainBackground: Knowledge on survival after diagnosis is important for all stakeholders. We aimed to estimate the survival and life expectancy after a dementia diagnosis, and to quantify the impact of dementia subtypes on mortality.Methods: Retrospective matched cohort study using a linkage between a dementia-specific registry and two primary care electronic medical records databases. Between 1 January 2007 and 31 December 2015 there were 5,156 subjects aged 60 years and over registered by the Registry of Dementia of Girona and matched to 15,468 age-sex and comorbidity individuals without dementia attended by general practitioners in the province of Girona (Catalonia, Spain).Results: The median survival was 5.2 years (95% CI 5.0 to 5.4), the median life expectancy was 74.7 years (95% CI 71.9 to 76.5), and there were differences by gender. The mortality rate was 127.1 per 1,000 person-years (95% CI 121.6 to 132.7), and the hazard ratio for mortality in persons with dementia ranged between 1.63 (95% CI 1.52 to 1.76) for Alzheimer’s disease and 2.52 (95% CI 1.90 to 3.35) for Parkinson-plus syndromes. There was one death per year attributable to dementia for every 18.6 persons with dementia, and for every 2.4 persons with dementia who die, one death was attributable to dementia.Conclusion: The prognosis after dementia diagnosis is conditioned by demographic and clinical features. Although survival is larger for women, they also experience a higher number of years of life lost. Parkinson-plus syndromes and dementia due to multiple etiologies are among the most malignant subtypes regarding mortality.Keywords: epidemiology, diagnosis, dementia, mortality

Published
2019

16. Transglycosylation products generated by Talaromyces amestolkiae GH3 β-glucosidases: effect of hydroxytyrosol, vanillin and its glucosides on breast cancer cells

Author

Juan Antonio Méndez-Líter, Isabel Tundidor, Manuel Nieto-Domínguez, Beatriz Fernández de Toro, Andrés González Santana, Laura Isabel de Eugenio, Alicia Prieto, Juan Luis Asensio, Francisco Javier Cañada, Cristina Sánchez, and María Jesús Martínez

Subjects
Transglycosylation, β-Glucosidases, Glycosyl hydrolases, Hydroxytyrosol, Vanillin, Glucosides, Microbiology, QR1-502
Abstract

Abstract Background Transglycosylation represents one of the most promising approaches for obtaining novel glycosides, and plant phenols and polyphenols are emerging as one of the best targets for creating new molecules with enhanced capacities. These compounds can be found in diet and exhibit a wide range of bioactivities, such as antioxidant, antihypertensive, antitumor, neuroprotective and anti-inflammatory, and the eco-friendly synthesis of glycosides from these molecules can be a suitable alternative for increasing their health benefits. Results Transglycosylation experiments were carried out using different GH3 β-glucosidases from the fungus Talaromyces amestolkiae. After a first screening with a wide variety of potential transglycosylation acceptors, mono-glucosylated derivatives of hydroxytyrosol, vanillin alcohol, 4-hydroxybenzyl alcohol, and hydroquinone were detected. The reaction products were analyzed by thin-layer chromatography, high-pressure liquid chromatography, and mass spectrometry. Hydroxytyrosol and vanillyl alcohol were selected as the best options for transglycosylation optimization, with a final conversion yield of 13.8 and 19% of hydroxytyrosol and vanillin glucosides, respectively. NMR analysis confirmed the structures of these compounds. The evaluation of the biological effect of these glucosides using models of breast cancer cells, showed an enhancement in the anti-proliferative capacity of the vanillin derivative, and an improved safety profile of both glucosides. Conclusions GH3 β-glucosidases from T. amestolkiae expressed in P. pastoris were able to transglycosylate a wide variety of acceptors. Between them, phenolic molecules like hydroxytyrosol, vanillin alcohol, 4-hydroxybenzyl alcohol, and hydroquinone were the most suitable for its interesting biological properties. The glycosides of hydroxytyrosol and vanillin were tested, and they improved the biological activities of the original aglycons on breast cancer cells.

Published
2019
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17. Glycosylation of Epigallocatechin Gallate by Engineered Glycoside Hydrolases from Talaromyces amestolkiae: Potential Antiproliferative and Neuroprotective Effect of These Molecules

Author

Juan A. Méndez-Líter, Ana Pozo-Rodríguez, Enrique Madruga, María Rubert, Andrés G. Santana, Laura I. de Eugenio, Cristina Sánchez, Ana Martínez, Alicia Prieto, and María Jesús Martínez

Subjects
fungal enzymes, glycoconjugates, polyphenol, glucose, sophorose, xylose, Therapeutics. Pharmacology, RM1-950
Abstract

Glycoside hydrolases (GHs) are enzymes that hydrolyze glycosidic bonds, but some of them can also catalyze the synthesis of glycosides by transglycosylation. However, the yields of this reaction are generally low since the glycosides formed end up being hydrolyzed by these same enzymes. For this reason, mutagenic variants with null or drastically reduced hydrolytic activity have been developed, thus enhancing their synthetic ability. Two mutagenic variants, a glycosynthase engineered from a β-glucosidase (BGL-1-E521G) and a thioglycoligase from a β-xylosidase (BxTW1-E495A), both from the ascomycete Talaromyces amestolkiae, were used to synthesize three novel epigallocatechin gallate (EGCG) glycosides. EGCG is a phenolic compound from green tea known for its antioxidant effects and therapeutic benefits, whose glycosylation could increase its bioavailability and improve its bioactive properties. The glycosynthase BGL-1-E521G produced a β-glucoside and a β-sophoroside of EGCG, while the thioglycoligase BxTW1-E495A formed the β-xyloside of EGCG. Glycosylation occurred in the 5″ and 4″ positions of EGCG, respectively. In this work, the reaction conditions for glycosides’ production were optimized, achieving around 90% conversion of EGCG with BGL-1-E521G and 60% with BxTW1-E495A. The glycosylation of EGCG caused a slight loss of its antioxidant capacity but notably increased its solubility (between 23 and 44 times) and, in the case of glucoside, also improved its thermal stability. All three glycosides showed better antiproliferative properties on breast adenocarcinoma cell line MDA-MB-231 than EGCG, and the glucosylated and sophorylated derivatives induced higher neuroprotection, increasing the viability of SH-S5Y5 neurons exposed to okadaic acid.

Published
2022
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18. Association of Time of Day With Outcomes Among Patients Triaged for a Suspected Severe Stroke in Nonurban Catalonia

Author

Álvaro García-Tornel, Alan Flores, Mikel Terceño, Pedro Cardona, Sergi Amaro, Meritxell Gomis, Josep Zaragoza, Jerzy Krupinski, Manuel Gómez-Choco, Natalia Mas, Dolores Cocho, Esther Catena, Francesc Purroy, Matias Deck, Marta Rubiera, Jorge Pagola, David Rodriguez-Luna, Jesús Juega, Noelia Rodríguez-Villatoro, Carlos A. Molina, Cristina Soro, Xavier Jimenez, Mercè Salvat-Plana, Antoni Dávalos, Tudor G Jovin, Sonia Abilleira, Natalia Pérez de la Ossa, Marc Ribó, Estela Sanjuan, Katherine Santana, Olga Maisterra, Estevo Santamarina, Marian Muchada, Sandra Boned, Antonio Palasi Franco, Marta Olivé Gadea, Matías Deck, Manuel Requena, Victoria Sala, Lucía Muñoz, Mónica Millán, Elena López-Cancio, Laura Dorado, María Hernández-Pérez, Jordi Ciurans, Daniela Samaniego, Tamara Canento, Lorena Martin, Anna Planas, Joaquin Broto, Agustín Sorrentino, Martí Paré, Nuole Zhu, Alicia Garrido, Laia Grau, Ane Miren Crespo, Silvia Presas, Miriam Almendrote, Alba Ramos, Giuseppe Lucente, Lourdes Ispierto, Manuel Lozano, Juan Luis Becerra, Marta Jiménez, Dolores Vilas Rolán, Nicolas Guanyabens, Josep Sanchez-Ojanguren, Alicia Martínez-Piñeiro, Sara Forcén, Mireia Gea, Marta Álvarez, Anna Ramos, Manuel Domínguez Lizarbe, Rubio Guerra, Irene Bragado, Andrea Arbex, Luis Rodríguez, Alejandro Bustamante, Pere Cardona Portela, Helena Quesada García, Blanca Lara Rodríguez, Nuria Cayuela, Julia Miró, Clara Marzal, Andrés Paipa, Sergio Campoy, Ana Núñez, Pablo Arroyo, Sarah Besora, Vanessa Adell, Jaume Campdelacreu, Montse Alemany Martí, Belén González, Laura Bau Vila, Marta Fiter Crespo, Anna Berbel, Ma. Cristina Villaescusa Urbaneja, Núria Guillen, Nuria Vidal, Patricia Valentina Vérez Santamaria, Diego Herrero Navarro, Marta Simó, Mercedes Falip, Elisabeth Matas, Neus Mongay Ochoa, Ariadna Gifreu, Albert Muñoz, Lucía Romero, Eduard Portell, Guillermo Hernández Perez, F. Ruiz Esteve, Silvia Teixidor, Augusto Salazar Talavera, Roser Gómez, Xabier Urra Nuin, Martha Vargas, Ángel Chamorro, Laura Llull, Arturo Renú, Salvatore Rudilosso, Raquel Sánchez del Valle, Helena Ariño, Nuria Solà, Delón la Puma, Francisco Gil, Juan Bernardo Gómez, Nuria Matos, Neus Falgàs, Sergi Borrego, Almudena Sánchez, Mircea Balasa, Carmen Montejo, Mar Guasp, David Reyes, Pablo Sánchez Cervilla, Jose Miguel Contador, Victor Augusto Vera Monge, Oscar Ramos, Alejandro Rodríguez, Ana Rodríguez Campello, Gemma Romeral Ballester, Mireia Llop Trujillano, Eva Giralt Steinhauer, Elisa Cuadrado Godia, Angel Javier Ois Santiago, Jordi Jimenez Conde, Joan Martí Fábregas, Daniel Guisado, Luís Prats, Pol Camps, Raquel Delgado, Alejandro Martínez Domeño, Rebeca Marín, David Cànovas, Jordi Estela, Marta Ros, Sonsoles Aranceta, Jordi Espinosa, Marta Rubio, Cristina Lafuente, Oriol Barrachina, Alicia Anguita, Anna Reverter, Carmen García, Gemma Sansa, Mariona Hervas, Monica Crosas, Tania Delgado, Dra Sonia Huertas Folch, Gemma Muñoz Gamito, Josep Trenado Alvarez, Teresa Subirana, Jessica Molina, Laura Comes Romero, Gemma Guardia Valls, Miriam Jover, Javier Joaquín Sotova, Sonia Mª García Sánchez, Sebastian Valenzuela, Juan José Mengual, M. Àngels Font, Mª Isabel Gómez Ruiz, Irati Zubizarreta, Susana Fernández González, Laura Gubieras, Carmen E. Cobos, Luis Mena Romo, Nuria Caballol, Luis Cano, Joaquín Serena Leal, Yolanda Silva Blas, Irene Bragado Trigo, Saima Bashir Viturro, Laura Pardo Albiñana, Montserrat Reina Garrido, Carla Marco Cazcarra, Karol Enrique Uscamaita, Fabian Márquez, Cristina Coll, Mar Irida Lloret Villlas, Berta Solano Vila, Berta Alemany Perna, Daniel López Domínguezl, Mercedes de Lera, Anna Cots Foraster, Urszula Bojaryn, Ikram Benabdelhak, Gerard Mauri Capdevila, Jordi Sanahuja Montesinos, Daniel Vázquez, José Vicente Hervás, Cristina González, Alejandro Quílez, Mikel Vicente Pascual, María Ruiz, Yolanda Riba, M. Pilar Gil Villar, Cristina García, Xavier Ustrell Roig, Mònica Baldrich Mora, Anna Pellisé Guinjoan, Judit Borras, Alba Mañé Martínez, Rafael Marés, Jaume Viñas i Gaya, Laia Seró, Paula Rodríguez, Gislaine Castilho, Angela Monterde Ortega, Silvia Reverté, Joan Josep Baiges, Gisela Martín Ozaeta, Sonia Escalante, Patricia Esteve Belloch, Iago Payo, Júlia Saura Salvado, Josep M Soler Insa, Ester Tio Vilamala, Josep Abos Navarro, Héctor Cruz Tabuenca, Tamara Canento Sánchez, Elisabet Roldán, Elsa Puiggrós Rubiol, Elisabet Franquet, Lidia Fuentes, Javier Donaire, Elena Martí, Laura Giménez, Junior Gil Vázquez, Eloisa Nieto Clara Gris Ambrós, Puri Rodríguez, José Félix Oletta, Pilar Pons Mellado, Bárbara Gómez, Vergilin Raileau, Oscar Pardina, Jordi Mercadal, María López-Diéguez, Pilar Pérez, Lourdes Gabarró, María Orriols, José Carlos Molina, Joan Josep Canet, Mireia Roca, Muriel Álvaro, Francesc Boneu, Georgina Giménez, Jaume Albà, Francesc Gibert, Jéssica Garcia, Patricia Barragan, Gustavo Jurado, Vanesa Pascual_Medicina Interna, Josep Sabaté Ortega, Joan Amaurys Martínez Solano, Víctor Fernández, Mónica Torres, Ana Belén Montero Alvaredo, Laura Redondo Parejo, Josep Maria Aragonés, Anna Bullón, Cora Loste, Paula González, Neker Bejarano, Francisco Sanchez, Gianni Lucchetti, Xavier Pla, Dr Javier Gimeno, Esteban Reynaga, Montse Barcons, Gabriel Celedón, Juan Ortiz, Dr Goran Anastasovski, Dr Oscar Mascaró, Dr Javier Diez de los Ríos, Meritxell Feliu, Anna Ribera, Cristhian Ruiz, Gerard Corominas, Dra Daniella Nunes, Claudia Roca, Nadina Latorre, Lizbeth Yataco, Maricelys Cruz, Nerea Blanco, Santiago Castejón, Claustre Pont Sunyer, Jordi Espinosa Garcia, Rodrigo Paz Martin, Albert de Luis Sanchez, Dolores Espinosa Vivas, Juan Valencia Molina, Planels Palome, Laia Tomas Chaume, Ares Villagrasa Vilella, Marco Bustamante, Anunciación Boltes, Fernando Rodríguez, Itziar Arrieta, Jordi Ciurans Molist, Barnés Andreu, Ernest Palomeras Soler, Nicolau Guanyabens Buscà, Manuel Daza López, Jordi Bigas Farreres, Virginia Casado Ruiz, Desiree Muriana Batiste, Mª Pilar Sanz Cartagena, Eulalia Cabot de Vega, Josep Bassa Real, Hector Pelaez Roman, César Socolich, Josep Mª Alonso Camp, Antonio Tomás Cano Orgaz, Mª Pilar Fossas Felip, Nicolás Morón, Sandra Bacca, Mauricio Molina, Francesc Casarramona, Lorena Elias, Muhammad Zidane Bukaei, Jose Antonio Martos Gutierrez, Judith Lopez Escuin, Cristina Olaizola, Yolexis López Vargas, Juan Jiménez Oyonarte, Rashida Soultana, Eduardo Sanjurjo Golpe, Esther Salvador, Guillem Vila, Marcos Serrano, Matilde Nuria López Claverol, Marian Lamolla, Miquel Amate, Adriana Rodriguez, Ruth Romero, Montgomery del Carpio, Ana Isabel Hernandez, Julián Martín, M Carmen Rosas, Antonio Nogueroles, Sorilandy Encarnación, Augusto Robles, Jose Antonio Herrera, Roger Gavilán, Toghrol Mameghani, Gastón Araujo, M.Angeles Garrido Morales, Enric Ramon Albert Segui, Eva Fernandez Climent, Francesc Paris Pujol, Mireia Judit Garrofé Seira, Lucía Gómez Pía, Fernando Salleres Nuñez, Cristina Aguar Peñalver, Cristina Vaz Lopes, Elisenda Ribera Tasa, Carmen Repullo Vilchez, Modesto Sánchez Zambrana, Beatriu Suescun Ribas, Inés Vilà Panés, Montserrat Vila Planavila, Alicia Vaqueiro Lorenzo, Meritxell Sabartés Guixes, Jorge Medina, David Sambrano, Javi Zamarreño, Carmen Pirela, Paola Vélez, Luis Cajamarca, Honey Pérez, Yarles Martínez, Jesus Alexander Gonçalves, Carles Regordosa, Claudia Mormeneo, Laura Griu, Maria Francia Colina, Enric Farik, Dolors Carrión Duch, Carles Badenas, Oscar Bernal, Núria Agramunt, Shyrlei Morales, Victoria Reynoso, Miguel Guerrero, Primitivo Romera Cid, Mònica Folqué, Claudia Pedroza, Adnan Hachem, Íñigo Soteras Martínez, Xavier Verdera García, Mercè López Amorós, Xavier Costa Subirós, Marta Cufí Benet, Cecile Van Eendenburg, Teresa Osuna, Dra Gina Santos, Dra Mireia Pallisera, Dr Lluís Gonzalo Oliva, Dra Gemma Sanchez, Dr Xavier Basurto, Dr Ludgi Vivoda, Dr Richard Van der Kleyn, Dra Laura Robles, Ana Cabanelas Barranco, Mª Cruz Almendros, Marc Pérez Oliveras, Amelia Fernández Álvarez, Maria Rybyeva, Antoni Viñas, Maria Barcons, Joaquim Danès Alberto Tavera, Pablo Burbano, Cintie López, David Cruz, Paula Bisbe, Nora Fernández, Juan Carlos Palacio, Eduardo Fraiz, Oriol Aguiló, Rollmy Amorodjo, John Velázquez, Elena Sánchez, Jaume Español, Judit Perez de Celis, Anna Coll, Glòria Díaz, Margarida Vergés i Sala, Mª Ángels Casas Capdevila, Yosmairy Yoselin Ferrini, Aitor Gorriz, Diego-Javier Cucurell Navarro, Dulce Velásquez, Jaume Pla Soler, Josep González, Julian David Higuera, Lina Cuellar, Liza Margarita Miniello, Lluis Pujol, Sorin Cracan, Mora Vives, M Angela, Lopez Lopez, Montse Gorchs Molist, Delofeu Anna, Silvia Solà Muñoz, Ferreres Yolanda, Carol Pujalte, Elisabeth Téllez Marín, Yolanda Font Casas, Sara Hernández Luque, Joaquim Mejias Sendra, Francesca Mellado Valero, Campos Escala, Galup De Lacanal, Lopez Diaz, Castillo Paramio, Català Estopà, Español Moreda, Calafell Majo, Carballo Almeida, Castro Naval, M Elena, Cregut Ruiz, Pere Lluis, Deulofeu Font, Fabregat Sanjuan, Joan Pere, Fontquerni Gorchs, Forés Bellés, Joan Antoni, Gomez Herrera, Juan Carlos, Hijazo Prades, Itzaina Torvisco, Marti Rovira, Obiols Gonzalez, Olive Cavero, Querol Gil, M Soledad, Rico Rodriguez, Rios Sambernardo, Ropero Molina, Jose Ramon, Sanchez Valero, Santos Arevalo, Maria Jose, Soto Garcia, Maria Angeles, Tebar Escribano, Torres Garcia, Pedro José, Verdes Carrion, M Isabel, Verge Lopez, Juan Jose, Lopez Canela, M Angeles, Lucas Guarque, Morales Alvarez, Jorge Arnulfo, Morell Fornieles, Subirats Gomez, Maria Teresa, Torello Masa, Miquel, Val Lopez, Maria Mercedes, Palmero Reyes, Juan Manuel, Rodriguez Forne, Ruana Turiel, Sanchez Gonzalez, Sebastia Gornals, Abrio Rico, Albert Gual Falip, Aznar Oliveros, Brugues Perotti, Calvet Molinero, Catells Franco, Corrales Medina, Daroca Miro, Duran Marquez, Feliu Pradas, Figueras Casanova, Garcia Tortajada, Grajera Gallego, Azahara del Mar, Las Arroyo, Dulcenombre de Jesus, Laserreta Sanz, Llambrich Vidal, Monllao Corral, Morales de la Cruz, Moreno Blanco, Orejuela Orgaz, Piñana Suazo, Pons Minguillon, Rodríguez Gómez, José Carlos, Rodriguez Pereira, Sedo Porcel, Anna, Sevil Villar, Sierra Lopez, Torres Romero, Trepat Calveres, Anna, Ventura Arnella, Acera Gil, M Teresa, Biesot Vico, Castro Galea, Rosa Maria, Escorcia Chafer, Juan Antonio, Gil Faure, Hernandez Luque, Jimenez Delgado, Mallafre Gay, M. Angel, Olivares Sanzo, Pubill Fondevila, Sabate Fort, Segovia Agámez, Antonio Carlos, Turata Longaretti, Valle Hernandez, Trayner Guixens, Aguilar Valor, Aguirre Alvarez, Alastrue Naval, Alferez Baquero, Alonso Marne, Aloy Orozco, Alvarez Colino, Alvarez Peñuela, Ameller Cirilo, Maria Vanessa, Andujar Guerrero, Estefania Remedios, Auladell Sillero, Azcarate Sorbet, Basany Genesca, Benavent Barduena, Benito Tudela, Blanch Pardo, Boluda Pla, Bonilla Gonzalez, Bru Serramalera, Burnat Andreu, Caballero Calvo-Rayo, Calvo Casellas, Camps Mombiela, Cano Bresme, Carcelen Fernandez, Caro Solà, Casasas Matavacas, Castanedo Bolado, Cerdeña Cortina, Abella Jane, Laia Collado Borrego, Colom Orri, Comellas Vilanova, Conillera Sole, Cots Torres, Cuchi Estepa, Marc de Sostoa Graell, Laura del Rio Lopez, Delgado Compte, Diaz Bueno, Diaz Maneiro, Andrea Lucia, Domenech Palau, M. Carme, Duran Carasso, Pablo Javier, El Abidi, Escoda Martin, Esteve Casanovas, Fernandez Perez, Ferre Quintero, Flores Escobar, Fontcuberta Abad, Fortes del Valle, Mª Luisa, Franco Quesada, Sara Maria, Franco Romero, Gallego Francisco, Gamiz Gala, Garcia Castañeda, Garcia Rodriguez, Casajuana Gemma, Gomez Arroyo, Gomez Girbau, Gonzalez Fernandez, Gonzalez Gonzalez, Gonzalez Lopez, Gual Obeso, Guerrero Blanco, Guillemas Roca, Guillermo Eudaldo, Sebastia Hernandez, Homar Covas, Hostench Alvarez, Huerta Royo, Ibañez Barcelo, Izquiero Cruz, Jaione Urdangarin Etxetxikia, Juárez Gimenez, Khlifi Alami, Laparra Gasco, Lara Moreales, Lasaosa Medina, Maria Lourdes, Lazaro Cava, Leon Berrar, López Maturana, Lopez Ramirez, López Romero, Lorente Marco, Lorenzo Martin, Lozano Casals, Lujan Nicola, Madrid Diaz, Jose Antonio, Maria Teresa Peris Morales, Marti Clemente, Martinez Castaño, David Natanael, Martinez Gamez, Martinez Gonzalez, Martinez Quesada, Maria de la Cabeza, Marzà Fusté, Melendo Lasheras, Miralles Mestre, Montserrat Puig Pastalle, Montserrate Vidal, Mora Mellado, Morales Ponce, Morera Cabre, Morera Vivet, Mundi Souza, Muñoz Quiles, Navea Rosa, Neira Iglesias, M Asuncion, Nuñez Manrique, Mª Pilar, Obiols Martinez, Pallares Reig, Partegas Torres, Pascual Berengueras, Perez Gamez, Perez Oset, Perez Restrepo, Maria Alejandra, Planas Yeste, Planells Mangado, Puertas Carbonell, Quinteiro Blanco, Rebollar Benavente, Recasens Fernandez, Reyes Gomez, Maria del Carmen, Roca Pou, Rodriguez Ferrer, Rodriguez Franco, Rodriguez Fuertes, Rodriguez Muñoz, Rodriguez Navarro, Roig Iniesta, Romero Gracia, Rovira Brunet, Rovira de Eugenio, Rubio Baena, Ruiz Llorens, Sala Llamazares, San Juan Alaez, Sanchez Segura, Santasusana Soldevilla, Sanz Salmeron, Segura Perez, Serra Balcells, Sorina Dumitras, Teixidor Montoya, Tena Vicente, Tierno Salinas, Ester Ines, Toledo Testa, Tomàs Figueras, Tomas Ruperez, Torrano Garcia-Penche, Torres Esparza, Vazquez Blanco, Vazquez De la Paz, Vazquez Gil, Vazquez Gonzalez, Vidal Meler, Vilalta Cots, Vilches Jimenez, Visser Fernandez, Viu Gavin, Vives Vives, Carmona Jimenez, Francisco Jose, Galobardes Vilches, Gonzalez Gomez, Jodar Manzanera, Marimon Cortes, Marrodan Orive, Martin Bosch, Martorell Lopez, Millares Roca, M Jesus, Miralles Guri, Muliterno Hernandez, Muñoz Oliva, Pons Pujol, Postius Conde, Prieto Arruñada, Quintana Mathé, Rosell Mata, Alvarin Alvarez, Arrufat Flores, Bañuelos Pago, Campo Vilar, Cardus Hidalgo, Castello Gil, Maria Gloria, Castrillo Montsesinos, Clave Garces, Comes Sanroma, Descalzo Sequi, Errando Ricol, Escudero Campillo, Maria del Mar, Fernandez Alvarez, Fernandez Gomez, Franch Espinosa, Freixes Graells, Garcia Plaza, Garcia-Marron Gallego, Hernandez Simancas, Jaraba Armas, Jimenez Ramos, Lopez Oganissian, Madrona Romero, M Rosa, Martinez Millan, Martínez Morón, Merchan Encinas, Moreno Jimenez, Muñoz Rico, Navarro Rodriguez, Nogales Ibañez, Rita Maria, Novillo Viera, Parella Torrabadella, Mari Alba, Pera Villar, Carla Montserrat, Rabella Miralles, Ramis Trilles, Ribera Ortiz, Sastre Perez, Soro Borrega, Tapia Fores, Tellez Bernad, Trenado Alvarez, Felix Martin, Herrero Perez, Lanau Fuster, Lopez Gomariz, Pardo Lozano, Quintana Altimiras, Ventosa Lopez, Almodovar Damian, Alvarez Monterroso, Arambudo Comas, Boullon Garzon, Burgos Capella, Campuzano Garcia, Maria Del Mar, Capdevila Olivas, Carre Marti, Clara Isabel, Carretero Bacaicoa, Cazorla Calderon, Chacon Osuna, Cortes Planas, Cortit Olio, Delhomme Estany, Fructuos Martinez, Garcia Lopez, Pascual Luis, Genis Amill Vallve, Gonzalez Muñoz, Hernaez Ventura, Lavernia Gimenez, Martin Rojo, Martínez Medina, Mayol Barrera, Mercader Pi, Merino Dalmau, Miguel Campodarbe, Moreno Sanchez, Francisco Javier, Penela Barrameda, Prieto Ajenjo, Rodriguez Pareja, Rodríguez Piñar, Rodriguez Tello, Romero Pereda, Sainz Saborido, Santacana Martin, Santos Martinez, Sierra Chavez, Turbau Torres, Vicente Domenech, Villena Esteo, Vives Pertegaz, Baena Gonzalez, Bagaria Pont, Beltran Sanchez, Bonet Alarcon, Borch Ballescà, Buhils Clanchet, Closa Garcia, Colomina Carril, Cristina Fernandez Sanchez, Edurne Judith Fernandez Toledo, Espases Rodriguez, Espert Resa, F Xavier, Fernández Sol, Gonzalez Lugo, Gracia Llesera, Herrada Lendinez, Juliench Liesa, Sandra Alicia, Lopez Ortega, Lopez Yuste, Lozano Villanueva, Lucia Sola Soto, Madrid Castellano, Megias Cano, Daniel Jesus, Montasell Ponce, Montesinos Sospedra, Moya Martinez, Muñoz Herrera, Ocaña Fernandez, Palau Bernal, Perez Sole, Ramon Carbonell, Ribas Lop, Rubio López, Rueda Lopez, Sabat Castaño, Sabata Lara, Salmerón Ramírez, Serra Creus, Serrano Dalmau, Sumasi Mainero, Gonzalo Gabriel, Torello Masa, Valencia Primo, Ana Maria Viñuales Muñoz, Josep Roig, and Verònica Hidalgo

Subjects
Advanced and Specialized Nursing, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract

Background: We aim to assess whether time of day modified the treatment effect in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion Trial), a cluster-randomized trial that did not demonstrate the benefit of direct transportation to a thrombectomy-capable center versus nearest local stroke center for patients with a suspected large vessel stroke triaged in nonurban Catalonia between March 2017 and June 2020. Methods: We performed a post hoc analysis of RACECAT to evaluate if the association between initial transport routing and functional outcome differed according to trial enrollment time: daytime (8:00 am –8:59 pm ) and nighttime (9:00 pm –7:59 am ). Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with ischemic stroke. Subgroup analyses according to stroke subtype were evaluated. Results: We included 949 patients with an ischemic stroke, of whom 258 patients(27%) were enrolled during nighttime. Among patients enrolled during nighttime, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days (adjusted common odds ratio [acOR], 1.620 [95% CI, 1.020–2.551]); no significant difference between trial groups was present during daytime (acOR, 0.890 [95% CI, 0.680–1.163]; P interaction =0.014). Influence of nighttime on the treatment effect was only evident in patients with large vessel occlusion(daytime, acOR 0.766 [95% CI, 0.548–1.072]; nighttime, acOR, 1.785 [95% CI, 1.024–3.112] ; P interaction P interaction >0.1 for all comparisons). We observed longer delays in alteplase administration, interhospital transfers, and mechanical thrombectomy initiation during nighttime in patients allocated to local stroke centers. Conclusions: Among patients evaluated during nighttime for a suspected acute severe stroke in non-urban areas of Catalonia, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days. This association was only evident in patients with confirmed large vessel occlusion on vascular imaging. Time delays in alteplase administration and interhospital transfers might mediate the observed differences in clinical outcome. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02795962.

Published
2023

19. Workflows and Outcomes in Patients With Suspected Large Vessel Occlusion Stroke Triaged in Urban and Nonurban Areas

Author

Alvaro Garcia-Tornel, Monica Millan, Marta Rubiera, Alejandro Bustamante, Manuel Requena, Laura Dorado, Marta Olivé-Gadea, Xavier Jiménez, Angels Soto, Marisol Querol, Maria Hernández-Pérez, Meritxell Gomis, Pere Cardona, Xabier Urra, Francesc Purroy, Yolanda Silva, Xavier Ustrell, Patricia Esteve, Mercè Salvat-Plana, Miquel Gallofré, Carlos Molina, Antoni Dávalos, Tudor Jovin, Sonia Abilleira, Marc Ribo, Natalia Pérez de la Ossa, Marc Ribó Jacobi, Estela Sanjuan, Katherine Santana, Noelia Rodríguez, Jorge Pagola, David Rodriguez-Luna, Olga Maisterra, Estevo Santamarina, Marian Muchada, Jesús Juega, Sandra Boned, Antonio Palasi Franco, Álvaro García -Tornel, Matías Deck, Victoria Sala, Lucía Muñoz, Mónica Millán, Elena López-Cancio, María Hernández-Pérez, Jordi Ciurans, Daniela Samaniego, Tamara Canento, Lorena Martin, Anna Planas, Joaquin Broto, Agustín Sorrentino, Martí Paré, Nuole Zhu, Alicia Garrido, Laia Grau, Ane Miren Crespo, Silvia Presas, Miriam Almendrote, Alba Ramos, Giuseppe Lucente, Lourdes Ispierto, Manuel Lozano, Juan Luis Becerra, Marta Jiménez, Dolores Vilas Rolán, Nicolas Guanyabens, Josep Sanchez-Ojanguren, Alicia Martínez-Piñeiro, Sara Forcén, Mireia Gea, Marta Álvarez, Anna Ramos, Manuel Domínguez Lizarbe, Sara, Rubio Guerra, Irene Bragado, Andrea Arbex, Luis Rodríguez, Pere Cardona Portela, Helena Quesada García, Blanca Lara Rodríguez, Nuria Cayuela, Julia Miró, Clara Marzal, Andrés Paipa, Sergio Campoy, Ana Núñez, Pablo Arroyo, Sarah Besora, Vanessa Adell, Jaume Campdelacreu, Montse Alemany Martí, Belén González, Laura Bau Vila, Marta Fiter Crespo, Anna Berbel, Ma. Cristina Villaescusa Urbaneja, Núria Guillen, Nuria Vidal, Patricia Valentina Vérez Santamaria, Diego Herrero Navarro, Marta Simó, Mercedes Falip, Elisabeth Matas, Neus Mongay Ochoa, Ariadna Gifreu, Albert Muñoz, Lucía Romero, Eduard Portell, Guillermo Hernández Perez, F. Ruiz Esteve, Silvia Teixidor, Augusto Salazar Talavera, Roser Gómez, Xabier Urra Nuin, Martha Vargas, Ángel Chamorro, Sergio Amaro, Laura Llull, Arturo Renú, Salvatore Rudilosso, Raquel Sánchez del Valle, Helena Ariño, Nuria Solà, Delón la Puma, Francisco Gil, Juan Bernardo Gómez, Nuria Matos, Neus Falgàs, Sergi Borrego, Almudena Sánchez, Mircea Balasa, Carmen Montejo, Mar Guasp, David Reyes, Pablo Sánchez Cervilla, Jose Miguel Contador, Victor Augusto Vera Monge, Oscar Ramos, Alejandro Rodríguez, Ana Rodríguez Campello, Gemma Romeral Ballester, Mireia Llop Trujillano, Eva Giralt Steinhauer, Elisa Cuadrado Godia, Angel Javier Ois Santiago, Jordi Jimenez Conde, Joan Martí Fábregas, Daniel Guisado, Luís Prats, Pol Camps, Raquel Delgado, Alejandro Martínez Domeño, Rebeca Marín, David Cànovas, Jordi Estela, Marta Ros, Sonsoles Aranceta, Jordi Espinosa, Marta Rubio, Cristina Lafuente, Oriol Barrachina, Alicia Anguita, Anna Reverter, Carmen García, Gemma Sansa, Mariona Hervas, Monica Crosas, Tania Delgado, Jerzy Krupinski, Sonia Huertas Folch, Gemma Muñoz Gamito, Josep Trenado Alvarez, Teresa Subirana, Jessica Molina, Laura Comes Romero, Gemma Guardia Valls, Miriam Jover, Javier Joaquín Sotova, Sonia Mª García Sánchez, Sebastian Valenzuela (intensivista), Manuel Gómez-Choco, Juan José Mengual, M. Àngels Font, Mª Isabel Gómez Ruiz, Irati Zubizarreta, Susana Fernández González, Laura Gubieras, Carmen E. Cobos, Luis Mena Romo, Nuria Caballol, Luis Cano, Joaquín Serena Leal, Mikel Terceño Izarra, Irene Bragado Trigo, Saima Bashir Viturro, Laura Pardo Albiñana, Montserrat Reina Garrido, Carla Marco Cazcarra, Karol Enrique Uscamaita, Fabian Márquez, Cristina Coll, Mar Irida Lloret Villlas, Berta Solano Vila, Berta Alemany Perna, Daniel López Domínguezl, Mercedes de Lera, Anna Cots Foraster, Urszula Bojaryn, Ikram Benabdelhak, Gerard Mauri Capdevila, Jordi Sanahuja Montesinos, Daniel Vázquez, José Vicente Hervás, Cristina González, Alejandro Quílez, Mikel Vicente Pascual, María Ruiz, Yolanda Riba, M. Pilar Gil Villar, Cristina García, Xavier Ustrell Roig, Mònica Baldrich Mora, Anna Pellisé Guinjoan, Judit Borras, Alba Mañé Martínez, Rafael Marés, Jaume Viñas i Gaya, Laia Seró, Alan Flores, Paula Rodríguez, Gislaine Castilho, Angela Monterde Ortega, Silvia Reverté, Josep Zaragoza, Joan Josep Baiges, Gisela Martín Ozaeta, Sonia Escalante, Iago Payo, Júlia Saura Salvado, Natalia Mas Sala, Josep M Soler Insa, Ester Tio Vilamala, Josep Abos Navarro, Héctor Cruz Tabuenca, Tamara Canento Sánchez, Elisabet Roldán, Elsa Puiggrós Rubiol, Elisabet Franquet, Lidia Fuentes, Javier Donaire, Elena Martí, Laura Giménez, Junior Gil Vázquez, Eloisa Nieto Clara Gris Ambrós, Puri Rodríguez, José Félix Oletta, Pilar Pons Mellado, Catena, Bárbara Gómez, Vergilin Raileau, Esther Catena Ruíz, Oscar Pardina, Jordi Mercadal, María López-Diéguez, Pilar Pérez, Lourdes Gabarró, María Orriols, Joan Josep Canet, Mireia Roca, Muriel Álvaro, Francesc Boneu, Georgina Giménez, Jaume Albà, Francesc Gibert, Jéssica Garcia, Patricia Barragan, Gustavo Jurado, Josep Sabaté Ortega, Joan Amaurys Martínez Solano, Víctor Fernández, Mónica Torres, Ana Belén Montero Alvaredo, Laura Redondo Parejo, Josep Maria Aragonés, Anna Bullón, Cora Loste, Paula González, Neker Bejarano, Francisco Sanchez, Gianni Lucchetti, Xavier Pla, Javier Gimeno, Esteban Reynaga, Montse Barcons, Gabriel Celedón, Juan Ortiz, Goran Anastasovski, Oscar Mascaró, Javier Diez de los Ríos, Meritxell Feliu, Anna Ribera, Cristhian Ruiz, Gerard Corominas, Daniella Nunes, Claudia Roca, Nadina Latorre, Lizbeth Yataco, Maricelys Cruz, Nerea Blanco, Santiago Castejón, Dolores Cocho Calderón, Claustre Pont Sunyer, Jordi Espinosa Garcia, Rodrigo Paz Martin, Albert de Luis Sanchez, Dolores Espinosa Vivas, Juan Valencia Molina, Gemma, Planels Palome, Laia Tomas Chaume, Ares Villagrasa Vilella, Marco Bustamante, Anunciación Boltes, Fernando Rodríguez, Itziar Arrieta, Jordi Ciurans Molist, Barnés Andreu, Ernest Palomeras Soler, Nicolau Guanyabens Buscà, Manuel Daza López, Jordi Bigas Farreres, Virginia Casado Ruiz, Desiree Muriana Batiste, Mª Pilar Sanz Cartagena, Eulalia Cabot de Vega, Josep Bassa Real, Hector Pelaez Roman, César Socolich, Josep Mª Alonso Camp, Antonio Tomás Cano Orgaz, Mª Pilar Fossas Felip, Nicolás Morón, Sandra Bacca, Mauricio Molina, Francesc Casarramona, Lorena Elias, Muhammad Zidane Bukaei, Jose Antonio Martos Gutierrez, Judith Lopez Escuin, Cristina Olaizola, Yolexis López Vargas, Juan Jiménez Oyonarte, Rashida Soultana, Eduardo Sanjurjo Golpe, Esther Salvador, Guillem Vila, Marcos Serrano, Matilde Nuria López Claverol, Marian Lamolla, Miquel Amate, Adriana Rodriguez, Ruth Romero, Montgomery del Carpio, Ana Isabel Hernandez, Julián Martín, M Carmen Rosas, Antonio Nogueroles, Sorilandy Encarnación, Augusto Robles, Jose Antonio Herrera, Roger Gavilán, Toghrol Mameghani, Gastón Araujo, M.Angeles Garrido Morales, Enric Ramon Albert Segui, Eva Fernandez Climent, Francesc Paris Pujol, Mireia Judit Garrofé Seira, Lucía Gómez Pía, Fernando Salleres Nuñez, Cristina Aguar Peñalver, Cristina Vaz Lopes, Elisenda Ribera Tasa, Carmen Repullo Vilchez, Modesto Sánchez Zambrana, Beatriu Suescun Ribas, Inés Vilà Panés, Montserrat Vila Planavila, Alicia Vaqueiro Lorenzo, Meritxell Sabartés Guixes, Jorge Medina, David Sambrano, Javi Zamarreño, Carmen Pirela, Paola Vélez, Luis Cajamarca, Honey Pérez, Yarles Martínez, Jesus Alexander Gonçalves, Carles Regordosa, Claudia Mormeneo, Laura Griu, Maria Francia Colina, Enric Farik, Dolors Carrión Duch, Carles Badenas, Oscar Bernal, Núria Agramunt, Shyrlei Morales, Victoria Reynoso, Miguel Guerrero, Primitivo Romera Cid, Mònica Folqué, Claudia Pedroza, Adnan Hachem, Íñigo Soteras Martínez, Xavier Verdera García, Mercè López Amorós, Xavier Costa Subirós, Marta Cufí Benet, Cecile Van Eendenburg, Teresa Osuna, Dra Gina Santos, Mireia Pallisera, Lluís Gonzalo Oliva, Gemma Sanchez, Xavier Basurto, Ludgi Vivoda, Richard Van der Kleyn, Laura Robles, Ana Cabanelas Barranco, Mª Cruz Almendros, Marc Pérez Oliveras, Amelia Fernández Álvarez, Maria Rybyeva, Antoni Viñas, Maria Barcons, Joaquim Danès Alberto Tavera, Pablo Burbano, Cintie López, David Cruz, Paula Bisbe, Nora Fernández, Juan Carlos Palacio, Eduardo Fraiz, Oriol Aguiló, Rollmy Amorodjo, John Velázquez, Elena Sánchez, Jaume Español, Judit Perez de Celis, Anna Coll, Glòria Díaz, Margarida Vergés i Sala, Mª Ángels Casas Capdevila, Yosmairy Yoselin Ferrini, Aitor Gorriz, Diego-Javier Cucurell Navarro, Dulce Velásquez, Jaume Pla Soler, Josep González, Julian David Higuera, Lina Cuellar, Liza Margarita Miniello, Lluis Pujol, Sorin Cracan, Mora Vives, M Angela, Lopez Lopez, null Anabel, Montse Gorchs Molist, Delofeu Anna, Silvia Solà Muñoz, Ferreres Yolanda, Carol Pujalte, Elisabeth Téllez Marín, Yolanda Font Casas, Sara Hernández Luque, Joaquim Mejias Sendra, Francesca Mellado Valero, Campos Escala, Galup De Lacanal, Lopez Diaz, Castillo Paramio, Català Estopà, Español Moreda, Calafell Majo, Carballo Almeida, Castro Naval, M Elena, Cregut Ruiz, Pere Lluis, Deulofeu Font, Fabregat Sanjuan, Joan Pere, Fontquerni Gorchs, Forés Bellés, Joan Antoni, Gomez Herrera, Juan Carlos, Hijazo Prades, Itzaina Torvisco, Marti Rovira, Obiols Gonzalez, Olive Cavero, Querol Gil, M Soledad, Rico Rodriguez, Rios Sambernardo, Ropero Molina, Jose Ramon, Sanchez Valero, Santos Arevalo, Maria Jose, Soto Garcia, Maria Angeles, Tebar Escribano, Torres Garcia, Pedro José, Verdes Carrion, M Isabel, Verge Lopez, Juan Jose, Lopez Canela, M Angeles, Lucas Guarque, Morales Alvarez, Jorge Arnulfo, Morell Fornieles, Subirats Gomez, Maria Teresa, Torello Masa, Val Lopez, Maria Mercedes, Palmero Reyes, Juan Manuel, Rodriguez Forne, Ruana Turiel, Sanchez Gonzalez, Sebastia Gornals, Abrio Rico, Albert Gual Falip, Aznar Oliveros, Brugues Perotti, Calvet Molinero, Catells Franco, Corrales Medina, Daroca Miro, Duran Marquez, Feliu Pradas, Figueras Casanova, Garcia Tortajada, Grajera Gallego, Azahara del Mar, Las Arroyo, Dulcenombre de Jesus, Laserreta Sanz, Llambrich Vidal, Monllao Corral, Morales de la Cruz, Moreno Blanco, Orejuela Orgaz, Piñana Suazo, Pons Minguillon, Rodríguez Gómez, José Carlos, Rodriguez Pereira, Sedo Porcel, Sevil Villar, Sierra Lopez, Torres Romero, Trepat Calveres, Ventura Arnella, Acera Gil, M Teresa, Biesot Vico, Castro Galea, Rosa Maria, Escorcia Chafer, Juan Antonio, Gil Faure, Hernandez Luque, Jimenez Delgado, Mallafre Gay, M. Angel, Olivares Sanzo, Pubill Fondevila, Sabate Fort, Segovia Agámez, Antonio Carlos, Turata Longaretti, Valle Hernandez, Trayner Guixens, Aguilar Valor, Aguirre Alvarez, Alastrue Naval, Alferez Baquero, Alonso Marne, Cristina, Aloy Orozco, Alvarez Colino, Alvarez Peñuela, Ameller Cirilo, Maria Vanessa, Andujar Guerrero, Estefania Remedios, Auladell Sillero, Azcarate Sorbet, Basany Genesca, Benavent Barduena, Benito Tudela, Blanch Pardo, Boluda Pla, Bonilla Gonzalez, Bru Serramalera, Burnat Andreu, Caballero Calvo-Rayo, Calvo Casellas, Camps Mombiela, Cano Bresme, Carcelen Fernandez, Caro Solà, Casasas Matavacas, Castanedo Bolado, Cerdeña Cortina, Abella Jane, Laia Collado Borrego, Colom Orri, Comellas Vilanova, Conillera Sole, Cots Torres, Cuchi Estepa, de Sostoa Graell, del Rio Lopez, Delgado Compte, Diaz Bueno, Diaz Maneiro, Andrea Lucia, Domenech Palau, M. Carme, Duran Carasso, Pablo Javier, El Abidi, Escoda Martin, Esteve Casanovas, Fernandez Perez, Ferre Quintero, Flores Escobar, Fontcuberta Abad, Fortes del Valle, Mª Luisa, Franco Quesada, Sara Maria, Franco Romero, Gallego Francisco, Gamiz Gala, Alicia, Garcia Castañeda, Garcia Rodriguez, Casajuana Gemma, Gomez Arroyo, Gomez Girbau, Gonzalez Fernandez, Gonzalez Gonzalez, Gonzalez Lopez, Gual Obeso, Guerrero Blanco, Guillemas Roca, Guillermo Eudaldo, Hernandez Sebastia, Homar Covas, Hostench Alvarez, Huerta Royo, Ibañez Barcelo, Izquiero Cruz, Jaione Urdangarin Etxetxikia, Juárez Gimenez, Khlifi Alami, Laparra Gasco, Lara Moreales, Lasaosa Medina, Maria Lourdes, Lazaro Cava, Leon Berrar, López Maturana, Lopez Ramirez, López Romero, Lorente Marco, Lorenzo Martin, Lozano Casals, Lujan Nicola, Madrid Diaz, Jose Antonio, Maria Teresa Peris Morales, Marti Clemente, Martinez Castaño, David Natanael, Martinez Gamez, Martinez Gonzalez, Martinez Quesada, Maria de la Cabeza, Marzà Fusté, Mireia, M Conillera, Melendo Lasheras, Miralles Mestre, Montserrat Puig Pastalle, Montserrate Vidal, Mora Mellado, Morales Ponce, Morera Cabre, Morera Vivet, Mundi Souza, Muñoz Quiles, Navea Rosa, Neira Iglesias, M Asuncion, Nuñez Manrique, Mª Pilar, Obiols Martinez, Pallares Reig, Partegas Torres, Pascual Berengueras, Perez Gamez, Perez Oset, Perez Restrepo, Maria Alejandra, Planas Yeste, Planells Mangado, Puertas Carbonell, Quinteiro Blanco, Rebollar Benavente, Recasens Fernandez, Reyes Gomez, Maria del Carmen, Roca Pou, Rodriguez Ferrer, Rodriguez Franco, Rodriguez Fuertes, Rodriguez Muñoz, Rodriguez Navarro, Roig Iniesta, Romero Gracia, Rovira Brunet, Rovira de Eugenio, Rubio Baena, Ruiz Llorens, Sala Llamazares, San Juan Alaez, Sanchez Segura, Santasusana Soldevilla, Sanz Salmeron, Segura Perez, Serra Balcells, Sorina Dumitras, Teixidor Montoya, Tena Vicente, Tierno Salinas, Ester Ines, Toledo Testa, Tomàs Figueras, Tomas Ruperez, Torrano Garcia-Penche, Torres Esparza, Florenc Uku, Vazquez Blanco, Vazquez De la Paz, Vazquez Gil, Vazquez Gonzalez, Vidal Meler, Vilalta Cots, Vilches Jimenez, Visser Fernandez, Viu Gavin, Vives Vives, Carmona Jimenez, Francisco Jose, Galobardes Vilches, Gonzalez Gomez, Jodar Manzanera, Marimon Cortes, Marrodan Orive, Martin Bosch, Martorell Lopez, Millares Roca, M Jesus, Miralles Guri, Muliterno Hernandez, Muñoz Oliva, Pons Pujol, Postius Conde, Prieto Arruñada, Quintana Mathé, Rosell Mata, Alvarin Alvarez, Arrufat Flores, Bañuelos Pago, Campo Vilar, Cardus Hidalgo, Castello Gil, Maria Gloria, Castrillo Montsesinos, Clave Garces, Comes Sanroma, Descalzo Sequi, Errando Ricol, Escudero Campillo, Maria del Mar, Fernandez Alvarez, Fernandez Gomez, Franch Espinosa, Freixes Graells, Garcia Plaza, Garcia-Marron Gallego, Hernandez Simancas, Jaraba Armas, Jimenez Ramos, Lopez Oganissian, Madrona Romero, M Rosa, Martinez Millan, Martínez Morón, Merchan Encinas, Moreno Jimenez, Muñoz Rico, Navarro Rodriguez, Nogales Ibañez, Rita Maria, Novillo Viera, Parella Torrabadella, Mari Alba, Pera Villar, Carla Montserrat, Rabella Miralles, Ramis Trilles, Ribera Ortiz, Sastre Perez, Soro Borrega, Tapia Fores, Tellez Bernad, Trenado Alvarez, Felix Martin, Herrero Perez, Lanau Fuster, Lopez Gomariz, Pardo Lozano, Quintana Altimiras, Ventosa Lopez, Almodovar Damian, Alvarez Monterroso, Arambudo Comas, Boullon Garzon, Burgos Capella, Campuzano Garcia, Maria Del Mar, Capdevila Olivas, Carre Marti, Clara Isabel, Carretero Bacaicoa, Cazorla Calderon, Chacon Osuna, Cortes Planas, Cortit Olio, Delhomme Estany, Fructuos Martinez, Garcia Lopez, Pascual Luis, Genis Amill Vallve, Gonzalez Muñoz, Hernaez Ventura, Lavernia Gimenez, Martin Rojo, Martínez Medina, Mayol Barrera, Mercader Pi, Merino Dalmau, Miguel Campodarbe, Moreno Sanchez, Francisco Javier, Alba Mari, Penela Barrameda, Prieto Ajenjo, Rodriguez Pareja, Rodríguez Piñar, Javier Francisco, Rodriguez Tello, Romero Pereda, Sainz Saborido, Santacana Martin, Santos Martinez, Sierra Chavez, Turbau Torres, Vicente Domenech, Villena Esteo, Vives Pertegaz, Baena Gonzalez, Bagaria Pont, Beltran Sanchez, Bonet Alarcon, Borch Ballescà, Buhils Clanchet, Closa Garcia, Colomina Carril, Cristina Fernandez Sanchez, Fernandez Toledo Edurne Judith, Espases Rodriguez, Espert Resa, F Xavier, Fernández Sol, Gonzalez Lugo, Gracia Llesera, Herrada Lendinez, Juliench Liesa, Sandra Alicia, Lopez Ortega, Lopez Yuste, Lozano Villanueva, Lucia Sola Soto, Madrid Castellano, Megias Cano, Daniel Jesus, Montasell Ponce, Montesinos Sospedra, Moya Martinez, Muñoz Herrera, Ocaña Fernandez, Palau Bernal, Perez Sole, Ramon Carbonell, Ribas Lop, Rubio López, Rueda Lopez, Sabat Castaño, Sabata Lara, Salmerón Ramírez, Serra Creus, Serrano Dalmau, Sumasi Mainero, Gonzalo Gabriel, Valencia Primo, Ana Maria Viñuales Muñoz, Josep Roig, and Verònica Hidalgo.

Subjects
Stroke, Advanced and Specialized Nursing, Treatment Outcome, Endovascular Procedures, Humans, Neurology (clinical), Cardiology and Cardiovascular Medicine, Brain Ischemia, Ischemic Stroke, Thrombectomy, Workflow
Abstract

Background: We aim to compare the outcome of patients from urban areas, where the referral center is able to perform thrombectomy, with patients from nonurban areas enrolled in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion). Methods: Patients with suspected large vessel occlusion stroke, as evaluated by a Rapid Arterial Occlusion Evaluation score of ≥5, from urban catchment areas of thrombectomy-capable centers during RACECAT trial enrollment period were included in the Stroke Code Registry of Catalonia. Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with an ischemic stroke. Secondary outcomes included mortality at 90 days, rate of thrombolysis and thrombectomy, time from onset to thrombolysis, and thrombectomy initiation. Propensity score matching was used to assemble a cohort of patients with similar characteristics. Results: The analysis included 1369 patients from nonurban areas and 2502 patients from urban areas. We matched 920 patients with an ischemic stroke from urban areas and nonurban areas based on their propensity scores. Patients with ischemic stroke from nonurban areas had higher degrees of disability at 90 days (median [interquartle range] modified Rankin Scale score, 3 [2–5] versus 3 [1–5], common odds ratio, 1.25 [95% CI, 1.06–1.48]); the observed average effect was only significant in patients with large vessel stroke (common odds ratio, 1.36 [95% CI, 1.08–1.65]). Mortality rate was similar between groups(odds ratio, 1.02 [95% CI, 0.81–1.28]). Patients from nonurban areas had higher odds of receiving thrombolysis (odds ratio, 1.36 [95% CI, 1.16–1.67]), lower odds of receiving thrombectomy(odds ratio, 0.61 [95% CI, 0.51–0.75]), and longer time from stroke onset to thrombolysis (mean difference 38 minutes [95% CI, 25–52]) and thrombectomy(mean difference 66 minutes [95% CI, 37–95]). Conclusions: In Catalonia, Spain, patients with large vessel occlusion stroke triaged in nonurban areas had worse neurological outcomes than patients from urban areas, where the referral center was able to perform thrombectomy. Interventions aimed at improving organizational practices and the development of thrombectomy capabilities in centers located in remote areas should be pursued. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02795962.

Published
2022

20. A Fungal Versatile GH10 Endoxylanase and Its Glycosynthase Variant: Synthesis of Xylooligosaccharides and Glycosides of Bioactive Phenolic Compounds

Author

Ana Pozo-Rodríguez, Juan A. Méndez-Líter, Laura I. de Eugenio, Manuel Nieto-Domínguez, Eva Calviño, Francisco Javier Cañada, Andrés G. Santana, Jaime Díez, Juan L. Asensio, Jorge Barriuso, Alicia Prieto, and María Jesús Martínez

Subjects
antioxidants, fungal enzyme, glycosylation, hydrolysis, oligosaccharides, protein engineering, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

The study of endoxylanases as catalysts to valorize hemicellulosic residues and to obtain glycosides with improved properties is a topic of great industrial interest. In this work, a GH10 β-1,4-endoxylanase (XynSOS), from the ascomycetous fungus Talaromyces amestolkiae, has been heterologously produced in Pichia pastoris, purified, and characterized. rXynSOS is a highly glycosylated monomeric enzyme of 53 kDa that contains a functional CBM1 domain and shows its optimal activity on azurine cross-linked (AZCL)–beechwood xylan at 70 °C and pH 5. Substrate specificity and kinetic studies confirmed its versatility and high affinity for beechwood xylan and wheat arabinoxylan. Moreover, rXynSOS was capable of transglycosylating phenolic compounds, although with low efficiencies. For expanding its synthetic capacity, a glycosynthase variant of rXynSOS was developed by directed mutagenesis, replacing its nucleophile catalytic residue E236 by a glycine (rXynSOS-E236G). This novel glycosynthase was able to synthesize β-1,4-xylooligosaccharides (XOS) of different lengths (four, six, eight, and ten xylose units), which are known to be emerging prebiotics. rXynSOS-E236G was also much more active than the native enzyme in the glycosylation of a broad range of phenolic compounds with antioxidant properties. The interesting capabilities of rXynSOS and its glycosynthase variant make them promising tools for biotechnological applications.

Published
2022
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21. Modelos 3D derivados de fotogrametría terrestre para la estimación de variables de inventario forestal

Author

A. de Eugenio, A. Fernández-Landa, and S. Merino-de-Miguel

Subjects
árbol, fotogrametría, diámetro, cubicación, volumen maderable, Geography (General), G1-922
Abstract

La gestión eficiente de las masas forestales necesita de la medición de árboles individuales de manera precisa. A partir de dichas mediciones se elaboran ecuaciones y modelos que posteriormente pueden aplicarse a ejemplares de similares características, con el objetivo de estimar variables derivadas como el volumen maderable. De manera tradicional, la obtención de dichas mediciones requería el apeo de ejemplares. En este trabajo se evalúa una nueva metodología de medición, basada en la reconstrucción de modelos 3D de árboles mediante métodos fotogramétricos terrestres. Dentro del MUP (Monte de Utilidad Pública) n°39 (Madrid) se seleccionaron 4 parcelas, en cada una de las cuales se midieron y fotografiaron 5 pies. Para la medición se emplearon: forcípula, dendrómetro Criterion RD1000 e hipsómetro Vertex III. Las imágenes se tomaron con una cámara no métrica Canon IXUS 85 IS. A partir de las imágenes se construyeron modelos tridimensionales usando el software VisualSFM (Structure from Motion). Sobre esos modelos se realizaron posteriormente medidas por medio del software Meshlab. La evaluación se realiza a través de la comparación de los diámetros medidos en los modelos 3D con los obtenidos por medio de otra metodología de medición ya validada (usando el dendrómetro láser Criterion RD1000). No se encontraron diferencias significativas entre las mediciones realizadas con Criterion y las realizadas sobre el modelo 3D. La cubicación de árboles en pie por medio de métodos fotogramétricos es una alternativa fiable con potencial de desarrollo en los próximos años.

Published
2018
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22. The β-glucosidase secreted by Talaromyces amestolkiae under carbon starvation: a versatile catalyst for biofuel production from plant and algal biomass

Author

Juan Antonio Méndez-Líter, Laura Isabel de Eugenio, Alicia Prieto, and María Jesús Martínez

Subjects
Fungi, Glycosyl hydrolases, Saccharification, Laminarinase, Biofuels, Carbon starvation, Fuel, TP315-360, Biotechnology, TP248.13-248.65
Abstract

Abstract Background In the last years, the most outstanding trend for obtaining high added-value components and second-generation (2G) biofuels consisted on exploitation of plant biomass. But recently, 3G biofuels, based in algae biomass, have emerged as a great alternative for production of energy. Results In this work, a versatile β-glucosidase from the ascomycete fungus Talaromyces amestolkiae has been purified, characterized, and heterologously expressed. The synthesis of this β-glucosidase (BGL-3) was not induced by cellulose, and the presence of a specific carbon source is not required for its production, which is uncommon for β-glucosidases. BGL-3, which was obtained from a basal medium with glucose as carbon source, was profusely secreted under carbon starvation conditions, which was corroborated by qRT-PCR assays. BGL-3 was purified from T. amestolkiae cultures in one step, and biochemically characterized. The enzyme showed high thermal stability, and very high efficiency on pNPG (K m of 0.14 mM and V max of 381.1 U/mg), cellobiose (K m of 0.48 mM and V max of 447.1 U/mg), and other cello-oligosaccharides. Surprisingly, it also showed remarkable ability to hydrolyze laminarin, a β-1,3-glucan present in algae. The recombinant enzyme, obtained in the yeast Pichia pastoris, exhibited kinetic and physicochemical properties similar to those found for the native protein. Enzyme efficiency was examined in wheat straw saccharification processes, in which BGL-3 worked better supplementing Celluclast 1.5L than the commercial cellulase cocktail N-50010. Besides, BGL-3 hydrolyzed laminarin more efficiently than a commercial laminarinase. Conclusions A very efficient 1,4-β-glucosidase, which also showed activity over 1,3-β-glucose bonds, has been produced, purified, and characterized. This is the first report of such versatility in a 1,4-β-glucosidase. The application of this enzyme for saccharification of wheat straw and laminarin and its comparison with commercial enzymes suggest that it could be an interesting tool for the production of 2G and 3G biofuels.

Published
2018
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23. Lytic Polysaccharide Monooxygenase from Talaromyces amestolkiae with an Enigmatic Linker-like Region: The Role of This Enzyme on Cellulose Saccharification

Author

Juan Antonio Méndez-Líter, Iván Ayuso-Fernández, Florian Csarman, Laura Isabel de Eugenio, Noa Míguez, Francisco J. Plou, Alicia Prieto, Roland Ludwig, and María Jesús Martínez

Subjects
LPMO, wheat straw, brewers spent grain, saccharification, AA9, oxidative biomass degradation, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

The first lytic polysaccharide monooxygenase (LPMO) detected in the genome of the widespread ascomycete Talaromyces amestolkiae (TamAA9A) has been successfully expressed in Pichia pastoris and characterized. Molecular modeling of TamAA9A showed a structure similar to those from other AA9 LPMOs. Although fungal LPMOs belonging to the genera Penicillium or Talaromyces have not been analyzed in terms of regioselectivity, phylogenetic analyses suggested C1/C4 oxidation which was confirmed by HPAEC. To ascertain the function of a C-terminal linker-like region present in the wild-type sequence of the LPMO, two variants of the wild-type enzyme, one without this sequence and one with an additional C-terminal carbohydrate binding domain (CBM), were designed. The three enzymes (native, without linker and chimeric variant with a CBM) were purified in two chromatographic steps and were thermostable and active in the presence of H2O2. The transition midpoint temperature of the wild-type LPMO (Tm = 67.7 °C) and its variant with only the catalytic domain (Tm = 67.6 °C) showed the highest thermostability, whereas the presence of a CBM reduced it (Tm = 57.8 °C) and indicates an adverse effect on the enzyme structure. Besides, the potential of the different T. amestolkiae LPMO variants for their application in the saccharification of cellulosic and lignocellulosic materials was corroborated.

Published
2021
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24. A novel, highly efficient β-glucosidase with a cellulose-binding domain: characterization and properties of native and recombinant proteins

Author

J. A. Méndez-Líter, J. Gil-Muñoz, M. Nieto-Domínguez, J. Barriuso, L. I. de Eugenio, and M. J. Martínez

Subjects
Fungi, Glycosyl hydrolases, Pichia pastoris, Carbohydrate binding modules, Saccharification, Brewers spent grain, Fuel, TP315-360, Biotechnology, TP248.13-248.65
Abstract

Abstract Background Cellulose, the most abundant biopolymer on earth, is an alternative for fossil fuels as a renewable feedstock for the production of second-generation biofuels and other chemicals. The discovery of novel, highly efficient β-glucosidases remains as one of the major bottlenecks for cellulose degradation. In this context, the ascomycete Talaromyces amestolkiae, isolated from cereal samples, has been studied as a promising source for these enzymes. Results BGL-2 is the major β-glucosidase secreted by this fungus in the presence of cellulosic inductors. This enzyme possesses a CBD (Cellulose Binding Domain), an unusual feature among this type of proteins. Besides, when growing on cellulose, the fungus produced two different bgl-2 mRNAs that were cloned and expressed in Pichia pastoris. A complete recombinant protein (BGL-2*) and its truncated form, lacking CBD (BGL-2T*), have been purified, characterized and compared with the native enzyme (BGL-2). The three BGL-2 forms studied are highly stable in a wide pH range, but BGL-2T* showed an improved thermal stability at 50 °C after 72 h. Using p-nitrophenyl-β-d-glucopyranoside as a substrate, the steady-state kinetic characterization of the three proteins showed a similar K m and k cat for BGL-2 and BGL-2*, while the truncated protein displayed a threefold higher value for k cat . All tested BGL-2 enzymes were as well highly efficient using cellobiose and other short oligosaccharides as a substrate. In view of biotechnological applications, the recombinant T. amestolkiae enzymes in saccharification of brewers’ spent grain were studied, being comparable to commercial β-glucosidase cocktails. Conclusion A new β-glucosidase from T. amestolkiae has been studied. The enzyme, containing a functional CBD, has been expressed in P. pastoris. The comparative analyses of the native protein and its recombinant forms, with and without CBD, suggest that they could be suitable tools for valorization of lignocellulosic biomass.

Published
2017
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29. Trends in the Prescription and Long-Term Utilization of Antidementia Drugs Among Patients with Alzheimer’s Disease in Spain: A Cohort Study Using the Registry of Dementias of Girona

Author

Calvó-Perxas, Laia, Turró-Garriga, Oriol, Vilalta-Franch, Joan, Lozano-Gallego, Manuela, de Eugenio, Rosa, Márquez, Fabián, Carmona, Olga, Gich, Jordi, Manzano, Anna, Viñas, Marta, Roig, Anna Mª, Garre-Olmo, Josep, Gich, Jordi, Molins, Albert, Ramió, Lluís, Serena, Joaquín, Silva, Yolanda, Terceño, Mikel, Robles, René, Hernández, Marta, Lozano, Manuela, Pericot, Immaculada, Vilalta-Franch, Joan, Estrada, Antoni Turon, Llinàs, Jordi, López-Pousa, Secundino, Solano, Berta, Terceño, Mikel, Alsina, Elisabet, de Eugenio, Rosa, Hernández, Erélido, Flaqué, Margarita, Carmona, Olga, Cullell, Marta, Osuna, Teresa, del Mar Fernández, Mª, Bisbe, Josep, Linares, Marta, Daniel, Fabian Marquez, Vallmajó, Natalia, Perkal, Héctor, Viñas, Marta, Casas, Isabel, Turbau, Josefa, Cuy, Josep Mª, Manzano, Anna, Roig, Anna Maria, Coromina, Joan, Soto, Mònica Palacios, and on behalf of the Registry of Dementias of Girona Study Group (ReDeGi Study Group)

Published
2017
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30. Production of a β-Glucosidase-Rich Cocktail from Talaromyces amestolkiae Using Raw Glycerol: Its Role for Lignocellulose Waste Valorization

Author

Juan A. Méndez-Líter, Laura I. de Eugenio, Neumara L. S. Hakalin, Alicia Prieto, and María Jesús Martínez

Subjects
biodiesel by-products, cellulases, fungi, hydrolases, wastes, Biology (General), QH301-705.5
Abstract

As β-glucosidases represent the major bottleneck for the industrial degradation of plant biomass, great efforts are being devoted to discover both novel and robust versions of these enzymes, as well as to develop efficient and inexpensive ways to produce them. In this work, raw glycerol from chemical production of biodiesel was tested as carbon source for the fungus Talaromyces amestolkiae with the aim of producing enzyme β-glucosidase-enriched cocktails. Approximately 11 U/mL β-glucosidase was detected in these cultures, constituting the major cellulolytic activity. Proteomic analysis showed BGL-3 as the most abundant protein and the main β-glucosidase. This crude enzyme was successfully used to supplement a basal commercial cellulolytic cocktail (Celluclast 1.5 L) for saccharification of pretreated wheat straw, corroborating that even hardly exploitable industrial wastes, such as glycerol, can be used as secondary raw materials to produce valuable enzymatic preparations in a framework of the circular economy.

Published
2021
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31. Marcos de deseo y violencia: el árabe como Otro en J. Butler y J. Massad

Author

Guillermo de Eugenio Pérez

Subjects
género, poscolonialismo, homosexualidad, árabe, violencia, marco, Philosophy (General), B1-5802
Abstract

El presente artículo propone una aportación al debate suscitado en torno al problema que plantean la violencia y la sexualidad (particularmente la homosexualidad) en la representación del otro, en este caso del árabe como Otro, partiendo en primer lugar de las consideración que hace Judith Butler sobre la noción de marco teórico y sus implicaciones políticas, éticas y estéticas. En un segundo momento confrontaremos este enfoque con las críticas planteadas por J. Massad al presunto orientalismo y etnocentrismo de ciertas corrientes reivindicativas de los derechos LGTB desde el punto de la especificidad cultural del mundo árabe y analizaremos la polémica suscitada por dichas críticas entre distintos interlocutores.

Published
2017
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32. Differential β-glucosidase expression as a function of carbon source availability in Talaromyces amestolkiae: a genomic and proteomic approach

Author

Laura I. de Eugenio, Juan A. Méndez-Líter, Manuel Nieto-Domínguez, Lola Alonso, Jesús Gil-Muñoz, Jorge Barriuso, Alicia Prieto, and María Jesús Martínez

Subjects
Fungi, Ascomycete, Glycosidase, Lignocellulosic biomass, Saccharification, Fuel, TP315-360, Biotechnology, TP248.13-248.65
Abstract

Abstract Background Genomic and proteomic analysis are potent tools for metabolic characterization of microorganisms. Although cellulose usually triggers cellulase production in cellulolytic fungi, the secretion of the different enzymes involved in polymer conversion is subjected to different factors, depending on growth conditions. These enzymes are key factors in biomass exploitation for second generation bioethanol production. Although highly effective commercial cocktails are available, they are usually deficient for β-glucosidase activity, and genera like Penicillium and Talaromyces are being explored for its production. Results This article presents the description of Talaromyces amestolkiae as a cellulase-producer fungus that secretes high levels of β-glucosidase. β-1,4-endoglucanase, exoglucanase, and β-glucosidase activities were quantified in the presence of different carbon sources. Although the two first activities were only induced with cellulosic substrates, β-glucosidase levels were similar in all carbon sources tested. Sequencing and analysis of the genome of this fungus revealed multiple genes encoding β-glucosidases. Extracellular proteome analysis showed different induction patterns. In all conditions assayed, glycosyl hydrolases were the most abundant proteins in the supernatants, albeit the ratio of the diverse enzymes from this family depended on the carbon source. At least two different β-glucosidases have been identified in this work: one is induced by cellulose and the other one is carbon source-independent. The crudes induced by Avicel and glucose were independently used as supplements for saccharification of slurry from acid-catalyzed steam-exploded wheat straw, obtaining the highest yields of fermentable glucose using crudes induced by cellulose. Conclusions The genome of T. amestolkiae contains several genes encoding β-glucosidases and the fungus secretes high levels of this activity, regardless of the carbon source availability, although its production is repressed by glucose. Two main different β-glucosidases have been identified from proteomic shotgun analysis. One of them is produced under different carbon sources, while the other is induced in cellulosic substrates and is a good supplement to Celluclast in saccharification of pretreated wheat straw.

Published
2017
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33. Creating the Pick’s disease International Consortium: Association study ofMAPTH2 haplotype with risk of Pick’s disease

Author

Valentino, Rebecca R, primary, Scotton, William J, additional, Roemer, Shanu F, additional, Lashley, Tammaryn, additional, Heckman, Michael G, additional, Shoai, Maryam, additional, Martinez-Carrasco, Alejandro, additional, Tamvaka, Nicole, additional, Walton, Ronald L, additional, Baker, Matthew C, additional, Macpherson, Hannah L, additional, Real, Raquel, additional, Soto-Beasley, Alexandra I, additional, Mok, Kin, additional, Revesz, Tamas, additional, Warner, Thomas T, additional, Jaunmuktane, Zane, additional, Boeve, Bradley F, additional, Christopher, Elizabeth A, additional, DeTure, Michael, additional, Duara, Ranjan, additional, Graff-Radford, Neill R, additional, Josephs, Keith A, additional, Knopman, David S, additional, Koga, Shunsuke, additional, Murray, Melissa E, additional, Lyons, Kelly E, additional, Pahwa, Rajesh, additional, Parisi, Joseph E, additional, Petersen, Ronald C, additional, Whitwell, Jennifer, additional, Grinberg, Lea T, additional, Miller, Bruce, additional, Schlereth, Athena, additional, Seeley, William W, additional, Spina, Salvatore, additional, Grossman, Murray, additional, Irwin, David J, additional, Lee, Edward B, additional, Suh, EunRan, additional, Trojanowski, John Q, additional, Van Deerlin, Vivianna M, additional, Wolk, David A, additional, Connors, Theresa R, additional, Dooley, Patrick M, additional, Frosch, Matthew P, additional, Oakley, Derek H, additional, Aldecoa, Iban, additional, Balasa, Mircea, additional, Gelpi, Ellen, additional, Borrego-Écija, Sergi, additional, de Eugenio Huélamo, Rosa Maria, additional, Gascon-Bayarri, Jordi, additional, Sánchez-Valle, Raquel, additional, Sanz-Cartagena, Pilar, additional, Piñol-Ripoll, Gerard, additional, Molina-Porcel, Laura, additional, Bigio, Eileen H, additional, Flanagan, Margaret E, additional, Gefen, Tamar, additional, Rogalski, Emily J, additional, Weintraub, Sandra, additional, Redding-Ochoa, Javier, additional, Chang, Koping, additional, Troncoso, Juan C, additional, Prokop, Stefan, additional, Newell, Kathy L, additional, Ghetti, Bernardino, additional, Jones, Matthew, additional, Richardson, Anna, additional, Robinson, Andrew C, additional, Roncaroli, Federico, additional, Snowden, Julie, additional, Allinson, Kieren, additional, Green, Oliver, additional, Rowe, James B, additional, Singh, Poonam, additional, Beach, Thomas G, additional, Serrano, Geidy E, additional, Flowers, Xena E, additional, Goldman, James E, additional, Heaps, Allison C, additional, Leskinen, Sandra P, additional, Teich, Andrew F, additional, Black, Sandra E, additional, Keith, Julia L, additional, Masellis, Mario, additional, Bodi, Istvan, additional, King, Andrew, additional, Sarraj, Safa-Al, additional, Troakes, Claire, additional, Halliday, Glenda M, additional, Hodges, John R, additional, Kril, Jillian J, additional, Kwok, John B, additional, Piguet, Olivier, additional, Gearing, Marla, additional, Arzberger, Thomas, additional, Roeber, Sigrun, additional, Attems, Johannes, additional, Morris, Christopher M, additional, Thomas, Alan J, additional, Evers, Bret M., additional, White, Charles L, additional, Mechawar, Naguib, additional, Sieben, Anne A, additional, Cras, Patrick P, additional, De Vil, Bart B, additional, De Deyn, Peter Paul P.P., additional, Duyckaerts, Charles, additional, Ber, Isabelle Le, additional, Seihean, Danielle, additional, Turbant-Leclere, Sabrina, additional, MacKenzie, Ian R, additional, McLean, Catriona, additional, Cykowski, Matthew D, additional, Ervin, John F, additional, Wang, Shih-Hsiu J, additional, Graff, Caroline, additional, Nennesmo, Inger, additional, Nagra, Rashed M, additional, Riehl, James, additional, Kovacs, Gabor G, additional, Giaccone, Giorgio, additional, Nacmias, Benedetta, additional, Neumann, Manuela, additional, Ang, Lee-Cyn, additional, Finger, Elizabeth C, additional, Blauwendraat, Cornelis, additional, Nalls, Mike A, additional, Singleton, Andrew B, additional, Vitale, Dan, additional, Cunha, Cristina, additional, Carvalho, Agostinho, additional, Wszolek, Zbigniew K, additional, Morris, Huw R, additional, Rademakers, Rosa, additional, Hardy, John A, additional, Dickson, Dennis W, additional, Rohrer, Jonathan D, additional, and Ross, Owen A, additional

Published
2023
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38. Creating the Pick’s disease International Consortium: Association study of MAPT H2 haplotype with risk of Pick’s disease

Author

Rebecca R Valentino, William J Scotton, Shanu F Roemer, Tammaryn Lashley, Michael G Heckman, Maryam Shoai, Alejandro Martinez-Carrasco, Nicole Tamvaka, Ronald L Walton, Matthew C Baker, Hannah L Macpherson, Raquel Real, Alexandra I Soto-Beasley, Kin Mok, Tamas Revesz, Thomas T Warner, Zane Jaunmuktane, Bradley F Boeve, Elizabeth A Christopher, Michael DeTure, Ranjan Duara, Neill R Graff-Radford, Keith A Josephs, David S Knopman, Shunsuke Koga, Melissa E Murray, Kelly E Lyons, Rajesh Pahwa, Joseph E Parisi, Ronald C Petersen, Jennifer Whitwell, Lea T Grinberg, Bruce Miller, Athena Schlereth, William W Seeley, Salvatore Spina, Murray Grossman, David J Irwin, Edward B Lee, EunRan Suh, John Q Trojanowski, Vivianna M Van Deerlin, David A Wolk, Theresa R Connors, Patrick M Dooley, Matthew P Frosch, Derek H Oakley, Iban Aldecoa, Mircea Balasa, Ellen Gelpi, Sergi Borrego-Écija, Rosa Maria de Eugenio Huélamo, Jordi Gascon-Bayarri, Raquel Sánchez-Valle, Pilar Sanz-Cartagena, Gerard Piñol-Ripoll, Laura Molina-Porcel, Eileen H Bigio, Margaret E Flanagan, Tamar Gefen, Emily J Rogalski, Sandra Weintraub, Javier Redding-Ochoa, Koping Chang, Juan C Troncoso, Stefan Prokop, Kathy L Newell, Bernardino Ghetti, Matthew Jones, Anna Richardson, Andrew C Robinson, Federico Roncaroli, Julie Snowden, Kieren Allinson, Oliver Green, James B Rowe, Poonam Singh, Thomas G Beach, Geidy E Serrano, Xena E Flowers, James E Goldman, Allison C Heaps, Sandra P Leskinen, Andrew F Teich, Sandra E Black, Julia L Keith, Mario Masellis, Istvan Bodi, Andrew King, Safa-Al Sarraj, Claire Troakes, Glenda M Halliday, John R Hodges, Jillian J Kril, John B Kwok, Olivier Piguet, Marla Gearing, Thomas Arzberger, Sigrun Roeber, Johannes Attems, Christopher M Morris, Alan J Thomas, Bret M. Evers, Charles L White, Naguib Mechawar, Anne A Sieben, Patrick P Cras, Bart B De Vil, Peter Paul P.P. De Deyn, Charles Duyckaerts, Isabelle Le Ber, Danielle Seihean, Sabrina Turbant-Leclere, Ian R MacKenzie, Catriona McLean, Matthew D Cykowski, John F Ervin, Shih-Hsiu J Wang, Caroline Graff, Inger Nennesmo, Rashed M Nagra, James Riehl, Gabor G Kovacs, Giorgio Giaccone, Benedetta Nacmias, Manuela Neumann, Lee-Cyn Ang, Elizabeth C Finger, Cornelis Blauwendraat, Mike A Nalls, Andrew B Singleton, Dan Vitale, Cristina Cunha, Agostinho Carvalho, Zbigniew K Wszolek, Huw R Morris, Rosa Rademakers, John A Hardy, Dennis W Dickson, Jonathan D Rohrer, and Owen A Ross

Subjects
Article
Abstract

BackgroundPick’s disease (PiD) is a rare and predominantly sporadic form of frontotemporal dementia that is classified as a primary tauopathy. PiD is pathologically defined by argyrophilic inclusion Pick bodies and ballooned neurons in the frontal and temporal brain lobes. PiD is characterised by the presence of Pick bodies which are formed from aggregated, hyperphosphorylated, 3-repeat tau proteins, encoded by theMAPTgene. TheMAPTH2 haplotype has consistently been associated with a decreased disease risk of the 4-repeat tauopathies of progressive supranuclear palsy and corticobasal degeneration, however its role in susceptibility to PiD is unclear. The primary aim of this study was to evaluate the association betweenMAPTH2 and risk of PiD.MethodsWe established the Pick’s disease International Consortium (PIC) and collected 338 (60.7% male) pathologically confirmed PiD brains from 39 sites worldwide. 1,312 neurologically healthy clinical controls were recruited from Mayo Clinic Jacksonville, FL (N=881) or Rochester, MN (N=431). For the primary analysis, subjects were directly genotyped forMAPTH1-H2 haplotype-defining variant rs8070723. In secondary analysis, we genotyped and constructed the six-variantMAPTH1 subhaplotypes (rs1467967, rs242557, rs3785883, rs2471738, rs8070723, and rs7521).FindingsOur primary analysis found that theMAPTH2 haplotype was associated with increased risk of PiD (OR: 1.35, 95% CI: 1.12-1.64 P=0.002). In secondary analysis involving H1 subhaplotypes, a protective association with PiD was observed for the H1f haplotype (0.0% vs. 1.2%, P=0.049), with a similar trend noted for H1b (OR: 0.76, 95% CI: 0.58-1.00, P=0.051). The 4-repeat tauopathy risk haplotypeMAPTH1c was not associated with PiD susceptibility (OR: 0.93, 95% CI: 0.70-1.25, P=0.65).InterpretationThe PIC represents the first opportunity to perform relatively large-scale studies to enhance our understanding of the pathobiology of PiD. This study demonstrates that in contrast to its protective role in 4R tauopathies, theMAPTH2 haplotype is associated with an increased risk of PiD. This finding is critical in directing isoform-related therapeutics for tauopathies.FundingSee funding section

Published
2023

39. Characterization of a Dye-Decolorizing Peroxidase from Irpex lacteus Expressed in Escherichia coli: An Enzyme with Wide Substrate Specificity Able to Transform Lignosulfonates

Author

Laura Isabel de Eugenio, Rosa Peces-Pérez, Dolores Linde, Alicia Prieto, Jorge Barriuso, Francisco Javier Ruiz-Dueñas, and María Jesús Martínez

Subjects
fungi, oxidoreductases, DyP, lignocellulosic biomass, lignin, Biology (General), QH301-705.5
Abstract

A dye-decolorizing peroxidase (DyP) from Irpex lacteus was cloned and heterologously expressed as inclusion bodies in Escherichia coli. The protein was purified in one chromatographic step after its in vitro activation. It was active on ABTS, 2,6-dimethoxyphenol (DMP), and anthraquinoid and azo dyes as reported for other fungal DyPs, but it was also able to oxidize Mn2+ (as manganese peroxidases and versatile peroxidases) and veratryl alcohol (VA) (as lignin peroxidases and versatile peroxidases). This corroborated that I. lacteus DyPs are the only enzymes able to oxidize high redox potential dyes, VA and Mn+2. Phylogenetic analysis grouped this enzyme with other type D-DyPs from basidiomycetes. In addition to its interest for dye decolorization, the results of the transformation of softwood and hardwood lignosulfonates suggest a putative biological role of this enzyme in the degradation of phenolic lignin.

Published
2021
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40. Optimization of β-1,4-Endoxylanase Production by an Aspergillus niger Strain Growing on Wheat Straw and Application in Xylooligosaccharides Production

Author

Zahra Azzouz, Azzeddine Bettache, Nawel Boucherba, Alicia Prieto, Maria Jesus Martinez, Said Benallaoua, and Laura Isabel de Eugenio

Subjects
fungi, enzymes, hemicellulose, xylan, wastes, hydrolysis, Organic chemistry, QD241-441
Abstract

Plant biomass constitutes the main source of renewable carbon on the planet. Its valorization has traditionally been focused on the use of cellulose, although hemicellulose is the second most abundant group of polysaccharides on Earth. The main enzymes involved in plant biomass degradation are glycosyl hydrolases, and filamentous fungi are good producers of these enzymes. In this study, a new strain of Aspergillus niger was used for hemicellulase production under solid-state fermentation using wheat straw as single-carbon source. Physicochemical parameters for the production of an endoxylanase were optimized by using a One-Factor-at-a-Time (OFAT) approach and response surface methodology (RSM). Maximum xylanase yield after RSM optimization was increased 3-fold, and 1.41- fold purification was achieved after ultrafiltration and ion-exchange chromatography, with about 6.2% yield. The highest activity of the purified xylanase was observed at 50 °C and pH 6. The enzyme displayed high thermal and pH stability, with more than 90% residual activity between pH 3.0–9.0 and between 30–40 °C, after 24 h of incubation, with half-lives of 30 min at 50 and 60 °C. The enzyme was mostly active against wheat arabinoxylan, and its kinetic parameters were analyzed (Km = 26.06 mg·mL−1 and Vmax = 5.647 U·mg−1). Wheat straw xylan hydrolysis with the purified β-1,4 endoxylanase showed that it was able to release xylooligosaccharides, making it suitable for different applications in food technology.

Published
2021
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43. Need for Strategic Environmental Assessment on the Bi-Oceanic Route in Mato Grosso do Sul.

Author

Fernandes Arguelho, Joelma, Furtado Loubet, Luciano, de Eugenio, Carmen, and Pereira Borges, Pedro

Subjects
ENVIRONMENTAL impact analysis, LITERATURE reviews, SUSTAINABLE development, TRANSPARENCY in government, SOCIAL impact
Abstract

Copyright of Interações is the property of Revista Interacoes and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2023
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45. Synthesis and Characterization of a Novel Resveratrol Xylobioside Obtained Using a Mutagenic Variant of a GH10 Endoxylanase

Author

Pozo-Rodríguez, Ana, primary, Méndez-Líter, Juan A., additional, García-Villalba, Rocío, additional, Beltrán, David, additional, Calviño, Eva, additional, Santana, Andrés G., additional, de Eugenio, Laura I., additional, Cañada, Francisco Javier, additional, Prieto, Alicia, additional, Barriuso, Jorge, additional, Tomás-Barberán, Francisco A., additional, and Martínez, María Jesús, additional

Published
2022
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47. El masoquismo ¿una enfermedad literaria?

Author

Guillermo de Eugenio Perez

Subjects
masochism, literature, disease, sexuality, perversion, sacher-masoch, krafft-ebing, Women. Feminism, HQ1101-2030.7
Abstract

The main idea of this paper resides in the conception of masochism as a cultural and literary phenomenon, since only in this way becomes possible to give an account of the complexity thatcharacterizes it and their functioning as a form of subjectivation. The issue of masochism, from the viewpoint of its psychological use, consists in its blurred status as clinical term ¿is it descriptive or explicative? In the first case ¿what doesit describes? Not only a behaviour or a reflex reaction to pain, since flagella-tion, as a purely physiological sexual stimulus is something different, called "algolagnia". Masochism constitutes a "disease" of imagination, since its main feature isto describe a fantasy, a literary scene. Sacher-Masoch's novel Venus im Furs became a referent for European maso-chists by exhibiting a voluptuousness linked to a paraphernalia of furs, dogs, horses, knifes and heels. These fantasies were not created, but re-appropriated by him; they were already present in the testimonies of the psychiatrist Krafft-Ebing's patients, in his work Psychopathia Sexualis. Havelock Ellis, Krafft-Ebing, Féré, Freud and Sabine Spielrein developed the idea of sadomasochism as double-sided explicative device, among others. Departing precisely from Sacher-Masoch's novel, the French phi-losopher Gilles Deleuze offered an interpretation of masochism as the oppositeof sadism. Masochism was therefore incompatible with sadism, and not its complementary form. If the analysis of literary language high-lights that the order of sadist literature is that of the institutionalization of abuse, the language of masochism is marked by the sign of the contract and the agreement.

Published
2015

49. Psychotropic Drugs in Patients With Alzheimer's Disease: A Longitudinal Study by the Registry of Dementias of Girona (ReDeGi) in Catalonia, Spain

Author

Castellanos, Mar, Batlle, David Genís, Gich, Jordi, Molins, Albert, Ramió, Lluís, Serena, Joaquín, Silva, Yolanda, Hernández, Marta, Lejarreta, Saioa, Lozano, Manuela, Pericot, Immaculada, Vilalta-Franch, Joan, Estrada, Antoni Turon, Turbau, Josefa, Llinàs, Jordi, López-Pousa, Secundino, Alsina, Elisabet, de Eugenio, Rosa, Hernández, Erélido, Flaqué, Margarita, Carmona, Olga, Cullell, Marta, Osuna, Teresa, Aguirregomozcorta, Maria, Fernández, M<ce:sup loc='post">a</ce:sup> del Mar, Bisbe, Josep, Linares, Marta, Daniel, Fabian Marquez, Vallmajó, Natalia, Espada, Fernando, Casadevall, Teresa, Perkal, Héctor, Viñas, Marta, Casas, Isabel, Cuy, Josep M<ce:sup loc='post">a</ce:sup>, Manzano, Anna, Roig, Anna Maria, Coromina, Joan, Soto, Mònica Palacios, Calvó-Perxas, Laia, Turró-Garriga, Oriol, Palacios, Mónica, Pericot-Nierga, Imma, and Garre-Olmo, Josep

Published
2014
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