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101. Interactive Reconciliation with Low-Density Parity-Check Codes

Author

Martinez-Mateo, Jesus, Elkouss, David, and Martin, Vicente

Subjects
Computer Science - Information Theory
Abstract

Efficient information reconciliation is crucial in several scenarios, being quantum key distribution a remarkable example. However, efficiency is not the only requirement for determining the quality of the information reconciliation process. In some of these scenarios we find other relevant parameters such as the interactivity or the adaptability to different channel statistics. We propose an interactive protocol for information reconciliation based on low-density parity-check codes. The coding rate is adapted in real time by using simultaneously puncturing and shortening strategies, allowing it to cover a predefined error rate range with just a single code. The efficiency of the information reconciliation process using the proposed protocol is considerably better than the efficiency of its non-interactive version.

Published
2010
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102. Rate Compatible Protocol for Information Reconciliation: An application to QKD

Author

Elkouss, David, Martinez-Mateo, Jesus, Lancho, Daniel, and Martin, Vicente

Subjects
Computer Science - Information Theory
Abstract

Information Reconciliation is a mechanism that allows to weed out the discrepancies between two correlated variables. It is an essential component in every key agreement protocol where the key has to be transmitted through a noisy channel. The typical case is in the satellite scenario described by Maurer in the early 90's. Recently the need has arisen in relation with Quantum Key Distribution (QKD) protocols, where it is very important not to reveal unnecessary information in order to maximize the shared key length. In this paper we present an information reconciliation protocol based on a rate compatible construction of Low Density Parity Check codes. Our protocol improves the efficiency of the reconciliation for the whole range of error rates in the discrete variable QKD context. Its adaptability together with its low interactivity makes it specially well suited for QKD reconciliation.

Published
2010
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103. Una aproximación al panorama actual del consumo de cannabis en España.

Author

Folgar, Manuel Isorna, Rivera, Francisca Fariña, Pastor, Francisco Salvador Pascual, Ares, Jaime Fraga, Almaraz-Gómez, Ana, Ecenarro, Fernando Alonso, Alonso-Molero, Jéssica, Ámez-Miranda, Ángela, Amezcua-Prieto, Carmen, Aonso-Diego, Gema, Horcajadas, Francisco Arias, Aso, Ester, Ayán, Carlos, Blázquez-Abellán, Gema, García, Julio B. Bobes, Rey, Fátima Braña, Castro, Millán Brea, Brime, Begoña, Putze, Guillermo Burillo, Carral, José María Cancela, Castaño, Yasmina, Cayuela-Fuentes, Pedro Simón, Senecal, Cristina Cerquella, Díaz, Benjamín Climent, Comes-Fayos, Javier, Conde, María Dolores Dapía, Delgado-Rodríguez, Miguel, Beloso, Rosa María Diaz, Duaso, María José, Garrido, José María Failde, Fernández-Villa, Tania, Álvarez, Leticia García, García-Hernández, Pedro Antonio, García-Portilla, Paz, Mancebo, Isabel Germán, Gervilla, Elena, Blanco, Leticia González, González-Javier, Francisca, González-Roz, Alba, González-Sala, Francisco, Herrera-Gutiérrez, Eva, Guerra, Joseba Huarte, Ceberio, Ania Irazoqui, Elso, Mikele Jauregui, Treviño, Luis Jiménez, Lila, Marisol, Llorens, Noelia, Morales, Agustín Llopis, Lozano-Polo, Adelaida, Mateos-Campo, Ramona, Martín, Vicente, Martínez-Ruiz, Virginia, Martínez-Sánchez, Ester, García, Mariví Mateo, Miranda, Isabel Menéndez, Miñarro, José, Escribà, Yoana Monzonís, Suarez-Varela, María Morales, Moya-Albiol, Luis, Vicente, Cristina Nuez, Ortiz-Moncada, Rocío, Requeijo, Miriam Otero, Pastor, Francisco Pascual, Santos, Pedro Manuel Pérez, Redondo-Martín, Susana, Boubeta, Antonio Rial, Losano, Gabriela M. Richard, Tutusaus, Xavier Roca, Rodríguez-Arias, Marta, de Fonseca, Fernando Rodriguez, Reinado, Carmen Rodríguez, Rivera, Paula Rodríguez, Romero-Martínez, Ángel, Sáiz, Pilar A., Sauco, Miguel Felipe Sánchez, Sarrate-Costa, Carolina, Secades-Villa, Roberto, Suárez, Carmen Solera, Valiente, Luis M. Uriarte, Valero-Juan, Luis Félix, Figueiredo, María José Vázquez, Díez, Rocío Villa, Villanueva-Blasco, Víctor José, Weidberg, Sara, Galán, Joseba Zabala, Folgar, Manuel Isorna, Rivera, Francisca Fariña, Pastor, Francisco Salvador Pascual, Ares, Jaime Fraga, Almaraz-Gómez, Ana, Ecenarro, Fernando Alonso, Alonso-Molero, Jéssica, Ámez-Miranda, Ángela, Amezcua-Prieto, Carmen, Aonso-Diego, Gema, Horcajadas, Francisco Arias, Aso, Ester, Ayán, Carlos, Blázquez-Abellán, Gema, García, Julio B. Bobes, Rey, Fátima Braña, Castro, Millán Brea, Brime, Begoña, Putze, Guillermo Burillo, Carral, José María Cancela, Castaño, Yasmina, Cayuela-Fuentes, Pedro Simón, Senecal, Cristina Cerquella, Díaz, Benjamín Climent, Comes-Fayos, Javier, Conde, María Dolores Dapía, Delgado-Rodríguez, Miguel, Beloso, Rosa María Diaz, Duaso, María José, Garrido, José María Failde, Fernández-Villa, Tania, Álvarez, Leticia García, García-Hernández, Pedro Antonio, García-Portilla, Paz, Mancebo, Isabel Germán, Gervilla, Elena, Blanco, Leticia González, González-Javier, Francisca, González-Roz, Alba, González-Sala, Francisco, Herrera-Gutiérrez, Eva, Guerra, Joseba Huarte, Ceberio, Ania Irazoqui, Elso, Mikele Jauregui, Treviño, Luis Jiménez, Lila, Marisol, Llorens, Noelia, Morales, Agustín Llopis, Lozano-Polo, Adelaida, Mateos-Campo, Ramona, Martín, Vicente, Martínez-Ruiz, Virginia, Martínez-Sánchez, Ester, García, Mariví Mateo, Miranda, Isabel Menéndez, Miñarro, José, Escribà, Yoana Monzonís, Suarez-Varela, María Morales, Moya-Albiol, Luis, Vicente, Cristina Nuez, Ortiz-Moncada, Rocío, Requeijo, Miriam Otero, Pastor, Francisco Pascual, Santos, Pedro Manuel Pérez, Redondo-Martín, Susana, Boubeta, Antonio Rial, Losano, Gabriela M. Richard, Tutusaus, Xavier Roca, Rodríguez-Arias, Marta, de Fonseca, Fernando Rodriguez, Reinado, Carmen Rodríguez, Rivera, Paula Rodríguez, Romero-Martínez, Ángel, Sáiz, Pilar A., Sauco, Miguel Felipe Sánchez, Sarrate-Costa, Carolina, Secades-Villa, Roberto, Suárez, Carmen Solera, Valiente, Luis M. Uriarte, Valero-Juan, Luis Félix, Figueiredo, María José Vázquez, Díez, Rocío Villa, Villanueva-Blasco, Víctor José, Weidberg, Sara, and Galán, Joseba Zabala

Published
2022

104. Reproductive factors, hormonal interventions, and gastric cancer risk in the Stomach cancer Pooling (StoP) Project

Author

Song, Minkyo, primary, Jayasekara, Harindra, additional, Pelucchi, Claudio, additional, Rabkin, Charles S., additional, Johnson, Kenneth C., additional, Hu, Jinfu, additional, Palli, Domenico, additional, Ferraroni, Monica, additional, Liao, Linda M., additional, Bonzi, Rossella, additional, Zaridze, David, additional, Maximovitch, Dmitry, additional, Aragonés, Nuria, additional, Martin, Vicente, additional, Castaño-Vinyals, Gemma, additional, Guevara, Marcela, additional, Tsugane, Shoichiro, additional, Hamada, Gerson Shigueaki, additional, Hidaka, Akihisa, additional, Negri, Eva, additional, Ward, Mary H., additional, Sinha, Rashmi, additional, Lagiou, Areti, additional, Lagiou, Pagona, additional, Boffetta, Paolo, additional, Curado, Maria Paula, additional, Lunet, Nuno, additional, Vioque, Jesus, additional, Zhang, Zuo-Feng, additional, La Vecchia, Carlo, additional, and Camargo, M. Constanza, additional

Published
2023
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106. TNFAIP3-interacting protein 1 polymorphisms and their association with symptomatic human respiratory syncytial virus infection and bronchiolitis in infants younger than one year from South Africa: A case-control study

Author

Martin-Vicente, María, primary, Mthiyane, Hloni, additional, Jiménez-Sousa, María A, additional, Subramoney, Kathleen, additional, Hellferscee, Orienka, additional, Wolter, Nicole, additional, Walaza, Sibongile, additional, Fernández-Rodríguez, Amanda, additional, Cohen, Cheryl, additional, von Gottberg, Anne, additional, Resino, Salvador, additional, Martínez, Isidoro, additional, and Treurnicht, Florette K, additional

Published
2023
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107. IgG antibody levels against the SARS-CoV-2 spike protein in mother–child dyads after COVID-19 vaccination

Author

Muñoz-Gómez, María José, primary, Martin-Vicente, María, additional, Vigil-Vazquez, Sara, additional, Carrasco, Itziar, additional, Lobo, Alicia Hernanz, additional, Mas, Vicente, additional, Vázquez, Mónica, additional, Manzanares, Angela, additional, Cano, Olga, additional, Zamora, Clara, additional, Alonso, Roberto, additional, Sepulveda-Crespo, Daniel, additional, Tarancon-Diez, Laura, additional, Muñoz-Fernández, María Ángeles, additional, Muñoz-Chapuli, Mar, additional, Resino, Salvador, additional, Navarro, Maria Luisa, additional, and Martinez, Isidoro, additional

Published
2023
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110. Differential requirements of protein geranylgeranylation for the virulence of human pathogenic fungi

Author

Ana Camila Oliveira Souza, Qusai Al Abdallah, Kaci DeJarnette, Adela Martin-Vicente, Ashley V. Nywening, Christian DeJarnette, Emily A. Sansevere, Wenbo Ge, Glen E. Palmer, and Jarrod R Fortwendel

Subjects
aspergillus fumigatus, candida albicans, prenylation, prenyltransferases, geranylgeranylation, geranylgeranyltransferase-i, protein localization, fungal virulence, Infectious and parasitic diseases, RC109-216
Abstract

Protein prenylation is a crucial post-translational modification largely mediated by two heterodimeric enzyme complexes, farnesyltransferase and geranylgeranyltransferase type-I (GGTase-I), each composed of a shared α-subunit and a unique β-subunit. GGTase-I enzymes are validated drug targets that contribute to virulence in Cryptococcus neoformans and to the yeast-to-hyphal transition in Candida albicans. Therefore, we sought to investigate the importance of the α-subunit, RamB, and the β-subunit, Cdc43, of the A. fumigatus GGTase-I complex to hyphal growth and virulence. Deletion of cdc43 resulted in impaired hyphal morphogenesis and thermo-sensitivity, which was exacerbated during growth in rich media. The Δcdc43 mutant also displayed hypersensitivity to cell wall stress agents and to cell wall synthesis inhibitors, suggesting alterations of cell wall biosynthesis or stress signaling. In support of this, analyses of cell wall content revealed decreased amounts of β-glucan in the Δcdc43 strain. Despite strong in vitro phenotypes, the Δcdc43 mutant was fully virulent in two models of murine invasive aspergillosis, similar to the control strain. We further found that a strain expressing the α-subunit gene, ramB, from a tetracycline-inducible promoter was inviable under non-inducing in vitro growth conditions and was virtually avirulent in both mouse models. Lastly, virulence studies using C. albicans strains with tetracycline-repressible RAM2 or CDC43 expression revealed reduced pathogenicity associated with downregulation of either gene in a murine model of disseminated infection. Together, these findings indicate a differential requirement for protein geranylgeranylation for fungal virulence, and further inform the selection of specific prenyltransferases as promising antifungal drug targets for each pathogen.

Published
2019
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111. Colorectal cancer, sun exposure and dietary vitamin D and calcium intake in the MCC-Spain study

Author

Vallès, Xavier, Alonso, M. Henar, López-Caleya, Juan Francisco, Díez-Obrero, Virginia, Dierssen-Sotos, Trinidad, Lope, Virginia, Molina-Barceló, Ana, Chirlaque, María Dolores, Jiménez-Moleón, José Juan, Fernández Tardón, Guillermo, Castilla, Jesús, Amiano, Pilar, Capelo, Rocío, Castaño-Vinyals, Gemma, Guinó, Elisabet, Molina de la Torre, Antonio José, Moreno-Iribas, Conchi, Pérez Gómez, Beatriz, Aragonés, Nuria, Llorca, Javier, Martín, Vicente, Kogevinas, Manolis, Pollán, Marina, and Moreno, Victor

Published
2018
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116. Whole-genome sequencing reveals highly specific gene targeting by in vitro assembled Cas9-ribonucleoprotein complexes in Aspergillus fumigatus

Author

Qusai Al Abdallah, Ana Camila Oliveira Souza, Adela Martin-Vicente, Wenbo Ge, and Jarrod R. Fortwendel

Subjects
Aspergillus fumigatus, CRISPR/Cas9, Genome editing, Off-target mutation, Biotechnology, TP248.13-248.65
Abstract

Abstract Background CRISPR/Cas9-based genome editing is quickly becoming a powerful tool within the field of fungal genetics. Adaptation of CRISPR/Cas9 systems are allowing for rapid and highly efficient gene targeting within fungi. We recently reported the adaptation of a simple CRISPR/Cas9 system for gene deletion that is effective across multiple genetic backgrounds of Aspergillus fumigatus. This system employs in vitro assembly of Cas9 ribonucleoproteins (RNPs) coupled with micro-homology repair templates for gene deletion. Although highly efficient at gene targeting in wild type genetic backgrounds of A. fumigatus, the potential for our system to produce unwanted off-target mutations has not been addressed. Results Next-generation Illumina sequencing was used to identify genome mutations among transformants isolated from standard (no Cas9) and Cas9-mediated integration of a hygromycin deletion cassette. Two different concentrations of Cas9 were utilized to examine the association of Cas9 concentration with total numbers and types of genomic mutations. For each of the three test groups (zero, low, and high Cas9), three transformants were sequenced and compared to the parent strain. Bioinformatics analyses revealed the average number of total mutations to be similar among all three test groups. A. fumigatus transformation using standard, non-Cas9-mediated methods resulted in an average of 373 ± 28 mutations. In comparison, transformation with in vitro assembled Cas9-RNPs using either high (1 µg/µl) or low (0.5 µg/µl) levels of Cas9 resulted in an average of 326 ± 19 and 395 ± 69 mutations, respectively. In all cases, the vast majority of mutations identified were intergenic. No correlation between the amount of Cas9 utilized for transformation and the overall number of mutations was found. Finally, the specific type of mutation introduced during the transformation process was not Cas9-dependent, as both single-nucleotide polymorphisms and insertion/deletion events were not significantly different between the experimental groups. Conclusions CRISPR/Cas9-based genome editing in A. fumigatus using in vitro assembled RNPs coupled with microhomology templates is a reliable method of gene targeting. This system is highly efficient and is not associated with increased off-target mutations caused by introduction of the Cas9 nuclease.

Published
2018
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117. Shift work and colorectal cancer risk in the MCC-Spain case–control study

Author

Papantoniou, Kyriaki, Castaño-Vinyals, Gemma, Espinosa, Ana, Turner, Michelle C, Alonso-Aguado, Maria Henar, Martin, Vicente, Aragonés, Nuria, Pérez-Gómez, Beatriz, Pozo, Benito Mirón, Gómez-Acebo, Inés, Ardanaz, Eva, Altzibar, Jone M, Peiro, Rosana, Tardon, Adonina, Lorca, José Andrés, Chirlaque, Maria Dolores, García-Palomo, Andrés, Jimenez-Moleon, Jose Juan, Dierssen, Trinidad, Ederra, Maria, Amiano, Pilar, Pollan, Marina, Moreno, Victor, and Kogevinas, Manolis

Published
2017

118. Identification of host endotypes using peripheral blood transcriptomics in a prospective cohort of patients with endocarditis

Author

Duarte-Herrera, Israel David, primary, Lopez-Martinez, Cecilia, additional, Rodriguez-Garcia, Raquel, additional, Parra, Diego, additional, Martin-Vicente, Paula, additional, Exojo-Ramirez, Sara, additional, Miravete-Lagunes, Karla, additional, Iglesias-Fraile, Lisardo, additional, Gonzalez-Iglesias, Marcelino, additional, Fernandez-Rodriguez, Margarita, additional, Carretero-Ledesma, Marta, additional, Lopez-Alonso, Ines, additional, Gomez, Juan, additional, Coto, Eliecer, additional, Fernandez, Javier, additional, Amado-Rodriguez, Laura, additional, and Albaiceta, Guillermo M, additional

Published
2023
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120. Helicobacter pylori serological biomarkers of gastric cancer risk in the MCC-Spain case-control Study

Author

Fernández de Larrea-Baz, Nerea, Pérez-Gómez, Beatriz, Michel, Angelika, Romero, Beatriz, Lope, Virginia, Pawlita, Michael, Fernández-Villa, Tania, Moreno, Victor, Martín, Vicente, Willhauck-Fleckenstein, Martina, López-Abente, Gonzalo, Castilla, Jesús, Fernández-Tardón, Guillermo, Dierssen-Sotos, Trinidad, Santibáñez, Miguel, Peiró, Rosana, Jiménez-Moleón, José Juan, Navarro, Carmen, Castaño-Vinyals, Gemma, Kogevinas, Manolis, Pollán, Marina, de Sanjosé, Silvia, del Campo, Rosa, Waterboer, Tim, and Aragonés, Nuria

Published
2017
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125. Antibody levels to <scp>SARS‐CoV</scp> ‐2 spike protein in mothers and children from delivery to six months later

Author

María Martin‐Vicente, Itziar Carrasco, María José Muñoz‐Gomez, Alicia Hernanz Lobo, Vicente Mas, Sara Vigil‐Vázquez, Mónica Vázquez, Angela Manzanares, Olga Cano, Roberto Alonso, Daniel Sepúlveda‐Crespo, Laura Tarancón‐Díez, María Ángeles Muñoz‐Fernández, Mar Muñoz‐Chapuli, Salvador Resino, Maria Luisa Navarro, and Isidoro Martinez

Subjects
Obstetrics and Gynecology
Abstract

Pregnant women are vulnerable to severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. Neutralizing antibodies against the SARS-CoV-2 spike (S) protein protect from severe disease. This study analyzes the antibody titers to SARS-CoV-2 S protein in pregnant women and their newborns at delivery, and six months later.We conducted a prospective study on pregnant women with confirmed SARS-CoV-2 infection and newborns. Antibody (IgG, IgM, and IgA) titers were determined using immunoassays in serum and milk samples. An angiotensin-converting enzyme 2 (ACE2) receptor-binding inhibition assay to the S protein was performed on the same serum and milk samples.At birth, antibodies to SARS-CoV-2 spike protein were detected in 81.9% of mothers' sera, 78.9% of cord blood samples, and 63.2% of milk samples. Symptomatic women had higher antibody titers (IgG, IgM, and IgA) than the asymptomatic ones (P 0.05). At six months postpartum, IgG levels decreased drastically in children's serum (P 0.001) but remained high in mothers' serum. Antibody titers correlated positively with its capacity to inhibit the ACE2-spike protein interaction at baseline in maternal sera (RHigh antibody levels against SARS-CoV-2 spike protein were found in most pregnant women. Due to the efficient transfer of IgG to cord blood and high IgA titers in breast milk, neonates may be passively immunized to SARS-CoV-2 infection. Our findings could guide newborn management and maternal vaccination policies.

Published
2022
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126. Consumption of aspartame and other artificial sweeteners and risk of cancer in the Spanish multicase‐control study (MCC‐Spain)

Author

Palomar‐Cros, Anna, primary, Straif, Kurt, additional, Romaguera, Dora, additional, Aragonés, Nuria, additional, Castaño‐Vinyals, Gemma, additional, Martin, Vicente, additional, Moreno, Victor, additional, Gómez‐Acebo, Inés, additional, Guevara, Marcela, additional, Aizpurua, Amaia, additional, Molina‐Barceló, Ana, additional, Jiménez‐Moleón, José‐Juan, additional, Tardón, Adonina, additional, Contreras‐Llanes, Manuel, additional, Marcos‐Gragera, Rafael, additional, Huerta, José Mª, additional, Pérez‐Gómez, Beatriz, additional, Espinosa, Ana, additional, Hernández‐Segura, Natalia, additional, Obón‐Santacana, Mireia, additional, Alonso‐Molero, Jessica, additional, Burgui, Rosana, additional, Amiano, Pilar, additional, Pinto‐Carbó, Marina, additional, Olmedo‐Requena, Rocio, additional, Fernández‐Tardón, Guillermo, additional, Santos‐Sánchez, Vanessa, additional, Fernández de Larrea‐Baz, Nerea, additional, Fernández‐Villa, Tania, additional, Casabonne, Delphine, additional, Dierssen‐Sotos, Trinidad, additional, Ardanaz, Eva, additional, Dorronsoro, Ane, additional, Pollán, Marina, additional, Kogevinas, Manolis, additional, and Lassale, Camille, additional

Published
2023
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129. Implementation of efficient surface discretisation algorithms adapted to geometric models specific to the footwear industry

Author

Universidad de Alicante. Departamento de Tecnología Informática y Computación, Calabuig-Barbero, Eduardo, Martinez-Martinez, German, Sanchez-Romero, Jose-Luis, Jimeno-Morenilla, Antonio, Lopez-Martin, Vicente, Mora, Higinio, Universidad de Alicante. Departamento de Tecnología Informática y Computación, Calabuig-Barbero, Eduardo, Martinez-Martinez, German, Sanchez-Romero, Jose-Luis, Jimeno-Morenilla, Antonio, Lopez-Martin, Vicente, and Mora, Higinio

Abstract

In 3D modelling, a surface mesh is a collection of vertices, edges, and faces that define the shape of a 3D object. The surface mesh is typically used to represent the outer surface of an object, as opposed to the internal structure. A surface mesh is usually defined as a polygon mesh, which is a collection of polygons (triangles or quadrilaterals are the most common) that are connected at their vertices. The vertices of the mesh define the shape of the object, and the edges and faces provide the topological information that describes how the vertices are connected. Surface meshes are often used in 3D modelling software to create 3D objects for animation, video games, and other purposes. Although triangular meshes are the most widely used in various fields, they have a series of disadvantages that quad meshes solve in most cases. This article presents a set of algorithms capable of generating quad meshes from any type of input triangular mesh, preserving the geometric characteristics of the initial model. This process is known as ‘remeshing’. The results obtained by these algorithms on a large number of models related to the footwear industry have been compared, as well as analysing the advantages and disadvantages of each one of them applied to geometric models commonly used in footwear industry.

Published
2023

134. GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19

Author

Pairo-Castineira, Erola, Rawlik, Konrad, Bretherick, Andrew D, Qi, Ting, Wu, Yang, Nassiri, Isar, McConkey, Glenn A, Zechner, Marie, Klaric, Lucija, Griffiths, Fiona, Oosthuyzen, Wilna, Kousathanas, Athanasios, Richmond, Anne, Millar, Jonathan, Russell, Clark D, Malinauskas, Tomas, Thwaites, Ryan, Morrice, Kirstie, Keating, Sean, Maslove, David, Nichol, Alistair, Semple, Malcolm G, Knight, Julian, Shankar-Hari, Manu, Summers, Charlotte, Hinds, Charles, Horby, Peter, Ling, Lowell, McAuley, Danny, Montgomery, Hugh, Openshaw, Peter J M, Begg, Colin, Walsh, Timothy, Tenesa, Albert, Flores, Carlos, Riancho, José A, Rojas-Martinez, Augusto, Lapunzina, Pablo, Yang, Jian, Ponting, Chris P, Wilson, James F, Vitart, Veronique, Abedalthagafi, Malak, Luchessi, Andre D, Parra, Esteban J, Cruz, Raquel, Carracedo, Angel, Fawkes, Angie, Murphy, Lee, Rowan, Kathy, Pereira, Alexandre C, Law, Andy, Fairfax, Benjamin, Hendry, Sara Clohisey, Baillie, J Kenneth, GenOMICC Investigators, SCOURGE Consortium, ISARICC Investigators, The 23andMe COVID-19 Team, Brochado-Kith, Oscar, Ceballos, Francisco C, Fernandez-Rodriguez, Amanda, Jimenez-Sousa, Maria Angeles, Martin-Vicente, Maria, Resino, Salvador, Virseda-Berdices, Ana, Meijome, Xose M, Instituto de Salud Carlos III, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Fundación Amancio Ortega, Banco Santander, Gobierno de Canarias (España), Fundación Canaria de Investigación Sanitaria, Centro de Supercomputación de Galicia, National Council for Scientific and Technological Development (Brasil), Sepsis Trust NZ, Wellcome Trust, Illumina (Reino Unido), Westlake Educational Foundation, British Heart Foundation, Biotechnology and Biological Sciences Research Council (Reino Unido), UK Research and Innovation, Medical Research Council (Reino Unido), LifeArc, and Department of Health and Social Care (Reino Unido)

Abstract

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A). GenOMICC was funded by Sepsis Research (the Fiona Elizabeth Agnew Trust), the Intensive Care Society, a Wellcome Trust Senior Research Fellowship (to J.K.B., 223164/Z/21/Z), the Department of Health and Social Care (DHSC), Illumina, LifeArc, the Medical Research Council, UKRI, a BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070 and BBS/E/D/30002275) and UKRI grants MC_PC_20004, MC_PC_19025, MC_PC_1905 and MRNO2995X/1. A.D.B. acknowledges funding from the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z), the Edinburgh Clinical Academic Track (ECAT) programme. This research is supported in part by the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant MC_PC_20029). Laboratory work was funded by a Wellcome Intermediate Clinical Fellowship to B.F. (201488/Z/16/Z). We acknowledge the staff at NHS Digital, Public Health England and the Intensive Care National Audit and Research Centre who provided clinical data on the participants; and the National Institute for Healthcare Research Clinical Research Network (NIHR CRN) and the Chief Scientist’s Office (Scotland), who facilitate recruitment into research studies in NHS hospitals, and to the global ISARIC and InFACT consortia. GenOMICC genotype controls were obtained using UK Biobank Resource under project 788 funded by Roslin Institute Strategic Programme Grants from the BBSRC (BBS/E/D/10002070 and BBS/E/D/30002275) and Health Data Research UK (HDR-9004 and HDR-9003). UK Biobank data were used in the GSMR analyses presented here under project 66982. The UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government, British Heart Foundation and Diabetes UK. The work of L.K. was supported by an RCUK Innovation Fellowship from the National Productivity Investment Fund (MR/R026408/1). J.Y. is supported by the Westlake Education Foundation. SCOURGE is funded by the Instituto de Salud Carlos III (COV20_00622 to A.C., PI20/00876 to C.F.), European Union (ERDF) ‘A way of making Europe’, Fundación Amancio Ortega, Banco de Santander (to A.C.), Cabildo Insular de Tenerife (CGIEU0000219140 ‘Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19’ to C.F.) and Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC20/57 to C.F.). We also acknowledge the contribution of the Centro National de Genotipado (CEGEN) and Centro de Supercomputación de Galicia (CESGA) for funding this project by providing supercomputing infrastructures. A.D.L. is a recipient of fellowships from the National Council for Scientific and Technological Development (CNPq)-Brazil (309173/2019-1 and 201527/2020-0). We thank the members of the Banco Nacional de ADN and the GRA@CE cohort group; and the research participants and employees of 23andMe for making this work possible. A full list of contributors who have provided data that were collated in the HGI project, including previous iterations, is available online (https://www.covid19hg.org/acknowledgements). Sí

Published
2023

136. Visualization of Large-Scale Neural Simulations

Author

Hernando, Juan B., Duelo, Carlos, Martin, Vicente, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, Grandinetti, Lucio, editor, Lippert, Thomas, editor, and Petkov, Nicolai, editor

Published
2014
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141. Visualizing knowledge and attitude factors related to influenza vaccination of physicians

Author

Alonso, Jordi, Baricot, Maretva, Caleró, Sebastian, Caylà, Joan, Lafuente, Sara, Rius, Cristina, Torner, Nuria, Diaz, José, Cenoz, Manuel García, Baz, Iván Martínez, Quintana, José María, González, Amaia Bilbao, Antón-Ladislao, Ane, García-Gutiérrez, Susana, Soldevila, Núria, González-Candelas, Fernando, Godoy, Pere, Castilla, Jesús, Mayoral, José María, Astray, Jenaro, Martín, Vicente, Tamames, Sonia, Toledo, Diana, Aguirre, Urko, and Domínguez, Angela

Published
2015
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142. Corrigendum to “Dissecting the genetic heterogeneity of gastric cancer”

Author

Hess, Timo, Maj, Carlo, Gehlen, Jan, Borisov, Oleg, Haas, Stephan L., Gockel, Ines, Vieth, Michael, Piessen, Guillaume, Alakus, Hakan, Vashist, Yogesh, Pereira, Carina, Knapp, Michael, Schüller, Vitalia, Quaas, Alexander, Grabsch, Heike I., Trautmann, Jessica, Malecka-Wojciesko, Ewa, Mokrowiecka, Anna, Speller, Jan, Mayr, Andreas, Schröder, Julia, Hillmer, Axel M., Heider, Dominik, Lordick, Florian, Pérez-Aísa, Ángeles, Campo, Rafael, Espinel, Jesús, Geijo, Fernando, Thomson, Concha, Bujanda, Luis, Sopeña, Federico, Lanas, Ángel, Pellisé, María, Pauligk, Claudia, Goetze, Thorsten Oliver, Zelck, Carolin, Reingruber, Julian, Hassanin, Emadeldin, Elbe, Peter, Alsabeah, Sandra, Lindblad, Mats, Nilsson, Magnus, Kreuser, Nicole, Thieme, René, Tavano, Francesca, Pastorino, Roberta, Arzani, Dario, Persiani, Roberto, Jung, Jin-On, Nienhüser, Henrik, Ott, Katja, Schumann, Ralf R., Kumpf, Oliver, Burock, Susen, Arndt, Volker, Jakubowska, Anna, Ławniczak, Małgorzta, Moreno, Victor, Martín, Vicente, Kogevinas, Manolis, Pollán, Marina, Dąbrowska, Justyna, Salas, Antonio, Cussenot, Olivier, Boland-Auge, Anne, Daian, Delphine, Deleuze, Jean-Francois, Salvi, Erika, Teder-Laving, Maris, Tomasello, Gianluca, Ratti, Margherita, Senti, Chiara, De Re, Valli, Steffan, Agostino, Hölscher, Arnulf H., Messerle, Katharina, Bruns, Christiane Josephine, Sīviņš, Armands, Bogdanova, Inga, Skieceviciene, Jurgita, Arstikyte, Justina, Moehler, Markus, Lang, Hauke, Grimminger, Peter P., Kruschewski, Martin, Vassos, Nikolaos, Schildberg, Claus, Lingohr, Philipp, Ridwelski, Karsten, Lippert, Hans, Fricker, Nadine, Krawitz, Peter, Hoffmann, Per, Nöthen, Markus M., Veits, Lothar, Izbicki, Jakob R., Mostowska, Adrianna, Martinón-Torres, Federico, Cusi, Daniele, Adolfsson, Rolf, Cancel-Tassin, Geraldine, Höblinger, Aksana, Rodermann, Ernst, Ludwig, Monika, Keller, Gisela, Metspalu, Andres, Brenner, Hermann, Heller, Joerg, Neef, Markus, Schepke, Michael, Dumoulin, Franz Ludwig, Hamann, Lutz, Cannizzaro, Renato, Ghidini, Michele, Plaßmann, Dominik, Geppert, Michael, Malfertheiner, Peter, Glehen, Olivier, Skoczylas, Tomasz, Majewski, Marek, Lubiński, Jan, Palmieri, Orazio, Boccia, Stefania, Latiano, Anna, Aragones, Nuria, Schmidt, Thomas, Dinis-Ribeiro, Mário, Medeiros, Rui, Al-Batran, Salah-Eddin, Leja, Mārcis, Kupcinskas, Juozas, García-González, María A., Venerito, Marino, and Schumacher, Johannes

Published
2023
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143. The stomach cancer pooling (StoP) project : study design and presentation

Author

Pelucchi, Claudio, Lunet, Nuno, Boccia, Stefania, Zhang, Zuo-Feng, Praud, Delphine, Boffetta, Paolo, Levi, Fabio, Matsuo, Keitaro, Ito, Hidemi, Hu, Jinfu, Johnson, Kenneth C., Ferraroni, Monica, Yu, Guo-Pei, Peleteiro, Bárbara, Malekzadeh, Reza, Derakhshan, Mohammad H., Ye, Weimin, Zaridze, David, Maximovitch, Dmitry, Aragonés, Nuria, Martín, Vicente, Pakseresht, Mohammadreza, Pourfarzi, Farhad, Bellavia, Andrea, Orsini, Nicola, Wolk, Alicja, Mu, Lina, Arzani, Dario, Kurtz, Robert C., Lagiou, Pagona, Trichopoulos, Dimitrios, Muscat, Joshua, La Vecchia, Carlo, and Negri, Eva

Published
2015

144. Overexpression of the Aspergillus fumigatus Small GTPase, RsrA, Promotes Polarity Establishment during Germination

Author

Adela Martin-Vicente, Ana C. O. Souza, Ashley V. Nywening, Wenbo Ge, and Jarrod R. Fortwendel

Subjects
Rsr1, Ras, Aspergillus fumigatus, polarity establishment, germination, Biology (General), QH301-705.5
Abstract

Cell polarization comprises highly controlled processes and occurs in most eukaryotic organisms. In yeast, the processes of budding, mating and filamentation require coordinated mechanisms leading to polarized growth. Filamentous fungi, such as Aspergillus fumigatus, are an extreme example of cell polarization, essential for both vegetative and pathogenic growth. A major regulator of polarized growth in yeast is the small GTPase Rsr1, which is essential for bud-site selection. Here, we show that deletion of the putative A. fumigatus ortholog, rsrA, causes only a modest reduction of growth rate and delay in germ tube emergence. In contrast, overexpression of rsrA results in a morphogenesis defect, characterized by a significant delay in polarity establishment followed by the establishment of multiple growth axes. This aberrant phenotype is reversed when rsrA expression levels are decreased, suggesting that correct regulation of RsrA activity is crucial for accurate patterning of polarity establishment. Despite this finding, deletion or overexpression of rsrA resulted in no changes of A. fumigatus virulence attributes in a mouse model of invasive aspergillosis. Additional mutational analyses revealed that RsrA cooperates genetically with the small GTPase, RasA, to support A. fumigatus viability.

Published
2020
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145. Repeated influenza vaccination for preventing severe and fatal influenza infection in older adults: a multicentre case-control study

Author

Casado, Itziar, Dominguez, Angela, Toledo, Diana, Chamorro, Judith, Astray, Jenaro, Egurrola, Mikel, Fernandez-Sierra, Maria Amelia, Martin, Vicente, Morales-Suarez-Varela, Maria, Godoy, Pere, and Castilla, Jesus

Subjects
Influenza vaccines -- Dosage and administration, Elderly -- Health aspects, Influenza -- Risk factors -- Drug therapy, Health
Abstract

BACKGROUND: The effectiveness of repeated vaccination for influenza to prevent severe cases remains unclear. We evaluated the effectiveness of influenza vaccination on preventing admissions to hospital for influenza and reducing disease severity. METHODS: We conducted a case-control study in 20 hospitals in Spain during the 2013/14 and 2014/15 influenza seasons. Community-dwelling adults aged 65 years or older who were admitted to hospital for laboratory-confirmed influenza were matched with inpatient controls by sex, age, hospital and admission date. The effectiveness of vaccination in the current and 3 previous seasons in preventing influenza was estimated for inpatients with nonsevere influenza and for those with severe influenza who were admitted to intensive care units (ICUs) or who died. RESULTS: We enrolled 130 inpatients with severe and 598 with nonsevere influenza who were matched to 333 and 1493 controls, respectively. Compared with patients who were unvaccinated in the current and 3 previous seasons, adjusted effectiveness of influenza vaccination in the current and any previous season was 31% (95% confidence interval [CI] 13%-46%) in preventing admission to hospital for nonsevere influenza, 74% (95% CI 42%-88%) in preventing admissions to ICU and 70% (95% CI 34%-87%) in preventing death. Vaccination in the current season only had no significant effect on cases of severe influenza. Among inpatients with influenza, vaccination in the current and any previous season reduced the risk of severe outcomes (adjusted odds ratio 0.45, 95% CI 0.26-0.76). INTERPRETATION: Among older adults, repeated vaccination for influenza was twice as effective in preventing severe influenza compared with nonsevere influenza in patients who were admitted to hospital, which is attributable to the combination of the number of admissions to hospital for influenza that were prevented and reduced disease severity. These results reinforce recommendations for annual vaccination for influenza in older adults., Seasonal influenza has a large effect on admissions to hospital and deaths among older adults. (1,2) Influenza vaccination is effective in preventing visits to primary health care and hospital admissions [...]

Published
2018
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148. C-terminus Proteolysis and Palmitoylation Cooperate for Optimal Plasma Membrane Localization of RasA in Aspergillus fumigatus

Author

Qusai Al Abdallah, Adela Martin-Vicente, Ana Camila Oliveira Souza, Wenbo Ge, and Jarrod R. Fortwendel

Subjects
Aspergillus, Ras, CAAX, prenylation, palmitoylation, cell wall, Microbiology, QR1-502
Abstract

RasA is a major regulator of fungal morphogenesis and virulence in Aspergillus fumigatus. The proper localization of RasA to the plasma membrane is essential for the formation of invasive hyphae during infection. In yeast, the localization of Ras2p to the plasma membrane is orchestrated by several post-translational modifications (PTM) at the C-terminal CAAX box that are thought to occur in sequential order. These PTMs include: (1) CAAX motif farnesylation by the farnesyltransferase complex composed of Ram1p and Ram2p; (2) proteolysis of the -AAX residues by Rce1p or Ste24p; (3) methylation of the remaining prenylated cysteine residue by Ste14p, and; (4) palmitoylation at a single conserved cysteine residue mediated by the Erf2p/Erf4p palmitoyltransferase. We previously reported that homologs of each RasA PTM enzyme are conserved in A. fumigatus. Additionally, we delineated a major role for protein farnesylation in A. fumigatus growth and virulence. In this work, we characterize the post-prenylation processing enzymes of RasA in A. fumigatus. The genes encoding the RasA post-prenylation enzymes were first deleted and examined for their roles in growth and regulation of RasA. Only when strains lacked cppB, the A. fumigatus homologue of yeast RCE1, there was a significant reduction in fungal growth and conidial germination. In addition, cppB-deletion mutants displayed hypersensitivity to the cell wall-perturbing agents Calcofluor White and Congo Red and the cell wall biosynthesis inhibitor Caspofungin. In contrast to the previously published data in yeast, the deletion of post-prenylation modifying enzymes did not alter the plasma membrane localization or activation of RasA. To delineate the molecular mechanisms underlying these differences, we investigated the interplay between dual-palmitoylation of the RasA hypervariable region and CAAX proteolysis for stabilization of RasA at the plasma membrane. Our data indicate that, in the absence of proper CAAX proteolysis, RasA accumulation at the plasma membrane is stabilized by dual palmitoyl groups on the dual cysteine residues. Therefore, we conclude CAAX proteolysis and dual-palmitoylation of the hypervariable region is important for maintaining a stable attachment association of RasA with the plasma membrane to support optimal fungal growth and development.

Published
2018
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150. Activismo digital de los movimientos sociales en Portugal y la pandemia Covid-19: el União de Mulheres Alternativa e Resposta y Casa do Brasil de Lisboa

Author

Maximiliano Martin Vicente, Ana Carolina Trindade, and Caroline Kraus Luvizotto

Subjects
Government, Informative content, Content analysis, Recent episode, Political science, Media studies, language, Public policy, Portuguese, Solidarity, language.human_language, Social movement
Abstract

La pandemia COVID-19 ha impuesto una nueva realidad a los movimientos sociales y la participación ciudadana, al prohibir y restringir las protestas sociales y las manifestaciones en las calles, acciones tradicionales de los movimientos sociales. En este escenario se revigora el ciberactivismo o activismo digital, que tiene en la información el principal eje para tomar decisiones. Este artículo analiza el papel de los movimientos sociales durante los primeros meses de la pandemia COVID-19 a partir del contenido informativo del activismo digital de los movimientos sociales portugueses: União de Mulheres Alternativa e Resposta - UMAR y Casa do Brasil de Lisboa - CBL. A partir de la revisión de la literatura y siguiendo los preceptos metodológicos del Análisis de Contenidos, los resultados obtenidos indican que tanto UMAR como CBL ejercieron, fundamentalmente, un activismo digital centrado en redes de solidaridad y de apoyo mutuo, algo que estaba ya establecido en la trayectoria de actuación de cada movimiento. Los movimientos sociales continuaron usando la información para crear y fortalecer lazos, protestar, construir y difundir conocimiento y monitorear las acciones gubernamentales y sus políticas públicas. El reciente episodio de la pandemia mostró que aún quedan muchos desafíos por superar, pero las perspectivas son muy prometedoras para el activismo digital.

Published
2021
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