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1. Conveni entre l'Ajuntament de Barcelona i la Fundació The Barcelona Institute of Science and Technology (BIST) per al desenvolupament del projecte Dones líders en ciència i tecnologia

Author: Ajuntament de Barcelona, Barcelona Institute of Science and Technology, Ajuntament de Barcelona, and Barcelona Institute of Science and Technology
Published: 2024

2. Protocol de col·laboració institucional per a l'impuls de la Ciutadella del Coneixement

Author: Ajuntament de Barcelona, Generalitat de Catalunya, Universitat Pompeu Fabra, Consejo Superior de Investigaciones Científicas (Espanya), Universitat de Barcelona, Universitat Autònoma de Barcelona, Barcelona Institute of Science and Technology, Ministerio de Ciencia e Innovación, Fundació Pasqual Maragall, Ministerio de Universidades, Ajuntament de Barcelona, Generalitat de Catalunya, Universitat Pompeu Fabra, Consejo Superior de Investigaciones Científicas (Espanya), Universitat de Barcelona, Universitat Autònoma de Barcelona, Barcelona Institute of Science and Technology, Ministerio de Ciencia e Innovación, Fundació Pasqual Maragall, and Ministerio de Universidades
Published: 2023

3. Solving unsolved rare neurological diseases-a Solve-RD viewpoint

Author: Schüle, Rebecca, Timmann, Dagmar, Erasmus, Corrie E., Reichbauer, Jennifer, Wayand, Melanie, Solve-RD-DITF-RND Baets Jonathan Balicza Peter Chinnery Patrick Dürr Alexandra Haack Tobias Hengel Holger Horvath Rita Houlden Henry Kamsteeg Erik-Jan Kamsteeg Christoph Lohmann Katja Macaya Alfons Marcé-Grau Anna Maver Ales Molnar Judit Münchau Alexander Peterlin Borut Riess Olaf Schöls Ludger European Reference Network for Rare Neurological Diseases, Tübingen, Germany Schüle Rebecca European Reference Network for Rare Neurological Diseases, Tübingen, Germany Stevanin Giovanni Synofzik Matthis European Reference Network for Rare Neurological Diseases, Tübingen, Germany Timmerman Vincent van de Warrenburg Bart Department of Neurology, Donders Centre for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands van Os Nienke Vandrovcova Jana Wayand Melanie German Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany Wilke Carlo German Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany, Baets, Jonathan, Balicza, Peter, Chinnery, Patrick, Dürr, Alexandra, Haack, Tobias, Hengel, Holger, Horvath, Rita, Houlden, Henry, Kamsteeg, Erik-Jan, Kamsteeg, Christoph, Lohmann, Katja, Macaya, Alfons, Marcé-Grau, Anna, Maver, Ales, Molnar, Judit, Münchau, Alexander, Peterlin, Borut, Riess, Olaf, Schöls, Ludger, Stevanin, Giovanni, Synofzik, Matthis, Timmerman, Vincent, van de Warrenburg, Bart, van Os, Nienke, Vandrovcova, Jana, Wilke, Carlo, Bevot, Andrea, Zuchner, Stephan, Beltran, Sergi, Laurie, Steven, Matalonga, Leslie, Graessner, Holm, The Solve-RD Consortium Graessner Holm Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany Zurek Birte Ellwanger Kornelia Ossowski Stephan Demidov German Sturm Marc Schulze-Hentrich Julia M. Heutink Peter Brunner Han Scheffer Hans Hoogerbrugge Nicoline Hoischen Alexander ’t Hoen Peter A. C. Vissers Lisenka E. L. M. Gilissen Christian Steyaert Wouter Sablauskas Karolis de Voer Richarda M. Janssen Erik de Boer Elke Steehouwer Marloes Yaldiz Burcu Kleefstra Tjitske Brookes Anthony J. Veal Colin Gibson Spencer Wadsley Marc Mehtarizadeh Mehdi Riaz Umar Warren Greg Dizjikan Farid Yavari Shorter Thomas Töpf Ana Straub Volker Bettolo Chiara Marini Specht Sabine Clayton-Smith Jill Banka Siddharth Alexander Elizabeth Jackson Adam Faivre Laurence Thauvin Christel Vitobello Antonio Denommé-Pichon Anne-Sophie Duffourd Yannis Tisserant Emilie Bruel Ange-Line Peyron Christine Pélissier Aurore Beltran Sergi Facultat de Biologia, Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona (UB), Barcelona, Spain Gut Ivo Glynne Laurie Steven CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain Piscia Davide Matalonga Leslie CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain Papakonstantinou Anastasios Bullich Gemma Corvo Alberto Garcia Carles Fernandez-Callejo Marcos Hernández Carles Picó Daniel Paramonov Ida Lochmüller Hanns Gumus Gulcin Bros-Facer Virginie Rath Ana Hanauer Marc Olry Annie Lagorce David Havrylenko Svitlana Izem Katia Rigour Fanny Durr Alexandra Davoine Claire-Sophie Guillot-Noel Léna Heinzmann Anna Coarelli Giulia Bonne Gisèle Evangelista Teresinha Allamand Valérie Nelson Isabelle Yaou Rabah Ben Metay Corinne Eymard Bruno Cohen Enzo Atalaia Antonio Stojkovic Tanya Macek Milan Jr. Turnovec Marek Thomasová Dana Kremliková Radka Pourová Franková Vera Havlovicová Markéta Kremlik Vlastimil Parkinson Helen Keane Thomas Spalding Dylan Senf Alexander Robinson Peter Danis Daniel Robert Glenn Costa Alessia Patch Christine Hanna Mike Houlden Henry Reilly Mary Vandrovcova Jana Muntoni Francesco Zaharieva Irina Sarkozy Anna de Jonghe Peter Nigro Vincenzo Banfi Sandro Torella Annalaura Musacchia Francesco Piluso Giulio Ferlini Alessandra Selvatici Rita Rossi Rachele Neri Marcella Aretz Stefan Spier Isabel Sommer Anna Katharina Peters Sophia Oliveira Carla Pelaez Jose Garcia Matos Ana Rita José Celina São Ferreira Marta Gullo Irene Fernandes Susana Garrido Luzia Ferreira Pedro Carneiro Fátima Swertz Morris A. Johansson Lennart van der Velde Joeri K. van der Vries Gerben Neerincx Pieter B. Roelofs-Prins Dieuwke Köhler Sebastian Metcalfe Alison Verloes Alain Drunat Séverine Rooryck Caroline Trimouille Aurelien Castello Raffaele Morleo Manuela Pinelli Michele Varavallo Alessandra De la Paz Manuel Posada Sánchez Eva Bermejo Martín Estrella López Delgado Beatriz Martínez de la Rosa F. Javier Alonso García Ciolfi Andrea Dallapiccola Bruno Pizzi Simone Radio Francesca Clementina Tartaglia Marco Renieri Alessandra Benetti Elisa Balicza Peter Molnar Maria Judit Maver Ales Peterlin Borut Münchau Alexander Lohmann Katja Herzog Rebecca Pauly Martje Macaya Alfons Marcé-Grau Anna Osorio Andres Nascimiento de Benito Daniel Natera Lochmüller Hanns Thompson Rachel Polavarapu Kiran Beeson David Cossins Judith Cruz Pedro M. Rodriguez Hackman Peter Johari Mridul Savarese Marco Udd Bjarne Horvath Rita Capella Gabriel Valle Laura Holinski-Feder Elke Laner Andreas Steinke-Lange Verena Schröck Evelin Rump Andreas, Zurek, Birte, Ellwanger, Kornelia, Ossowski, Stephan, Demidov, German, Sturm, Marc, Schulze-Hentrich, Julia M., Heutink, Peter, Brunner, Han, Scheffer, Hans, Hoogerbrugge, Nicoline, Hoischen, Alexander, ’t Hoen, Peter A. C., Vissers, Lisenka E. L. M., Gilissen, Christian, Steyaert, Wouter, Sablauskas, Karolis, de Voer, Richarda M., Janssen, Erik, de Boer, Elke, Steehouwer, Marloes, Yaldiz, Burcu, Kleefstra, Tjitske, Brookes, Anthony J., Veal, Colin, Gibson, Spencer, Wadsley, Marc, Mehtarizadeh, Mehdi, Riaz, Umar, Warren, Greg, Dizjikan, Farid Yavari, Shorter, Thomas, Töpf, Ana, Straub, Volker, Bettolo, Chiara Marini, Specht, Sabine, Clayton-Smith, Jill, Banka, Siddharth, Alexander, Elizabeth, Jackson, Adam, Faivre, Laurence, Thauvin, Christel, Vitobello, Antonio, Denommé-Pichon, Anne-Sophie, Duffourd, Yannis, Tisserant, Emilie, Bruel, Ange-Line, Peyron, Christine, Pélissier, Aurore, Gut, Ivo Glynne, Piscia, Davide, Papakonstantinou, Anastasios, Bullich, Gemma, Corvo, Alberto, Garcia, Carles, Fernandez-Callejo, Marcos, Hernández, Carles, Picó, Daniel, Paramonov, Ida, Lochmüller, Hanns, Gumus, Gulcin, Bros-Facer, Virginie, Rath, Ana, Hanauer, Marc, Olry, Annie, Lagorce, David, Havrylenko, Svitlana, Izem, Katia, Rigour, Fanny, Durr, Alexandra, Davoine, Claire-Sophie, Guillot-Noel, Léna, Heinzmann, Anna, Coarelli, Giulia, Bonne, Gisèle, Evangelista, Teresinha, Allamand, Valérie, Nelson, Isabelle, Yaou, Rabah Ben, Metay, Corinne, Eymard, Bruno, Cohen, Enzo, Atalaia, Antonio, Stojkovic, Tanya, Macek, Milan, Turnovec, Marek, Thomasová, Dana, Kremliková, Radka Pourová, Franková, Vera, Havlovicová, Markéta, Kremlik, Vlastimil, Parkinson, Helen, Keane, Thomas, Spalding, Dylan, Senf, Alexander, Robinson, Peter, Danis, Daniel, Robert, Glenn, Costa, Alessia, Patch, Christine, Hanna, Mike, Reilly, Mary, Muntoni, Francesco, Zaharieva, Irina, Sarkozy, Anna, de Jonghe, Peter, Nigro, Vincenzo, Banfi, Sandro, Torella, Annalaura, Musacchia, Francesco, Piluso, Giulio, Ferlini, Alessandra, Selvatici, Rita, Rossi, Rachele, Neri, Marcella, Aretz, Stefan, Spier, Isabel, Sommer, Anna Katharina, Peters, Sophia, Oliveira, Carla, Pelaez, Jose Garcia, Matos, Ana Rita, José, Celina São, Ferreira, Marta, Gullo, Irene, Fernandes, Susana, Garrido, Luzia, Ferreira, Pedro, Carneiro, Fátima, Swertz, Morris A., Johansson, Lennart, van der Velde, Joeri K., van der Vries, Gerben, Neerincx, Pieter B., Roelofs-Prins, Dieuwke, Köhler, Sebastian, Metcalfe, Alison, Verloes, Alain, Drunat, Séverine, Rooryck, Caroline, Trimouille, Aurelien, Castello, Raffaele, Morleo, Manuela, Pinelli, Michele, Varavallo, Alessandra, De la Paz, Manuel Posada, Sánchez, Eva Bermejo, Martín, Estrella López, Delgado, Beatriz Martínez, de la Rosa, F. Javier Alonso García, Ciolfi, Andrea, Dallapiccola, Bruno, Pizzi, Simone, Radio, Francesca Clementina, Tartaglia, Marco, Renieri, Alessandra, Benetti, Elisa, Molnar, Maria Judit, Herzog, Rebecca, Pauly, Martje, Osorio, Andres Nascimiento, de Benito, Daniel Natera, Thompson, Rachel, Polavarapu, Kiran, Beeson, David, Cossins, Judith, Cruz, Pedro M. Rodriguez, Hackman, Peter, Johari, Mridul, Savarese, Marco, Udd, Bjarne, Capella, Gabriel, Valle, Laura, Holinski-Feder, Elke, Laner, Andreas, Steinke-Lange, Verena, Schröck, Evelin, Rump, Andreas, Solve-RD-DITF-RND, Solve-RD Consortium, Schule, R., Timmann, D., Erasmus, C. E., Reichbauer, J., Wayand, M., van de Warrenburg, B., Schols, L., Wilke, C., Bevot, A., Zuchner, S., Beltran, S., Laurie, S., Matalonga, L., Graessner, H., Synofzik, M., Nigro, V., Banfi, S., Torella, A., Piluso, G., Medicum, University of Helsinki, Department of Medical and Clinical Genetics, Klinische Genetica, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA Klinische Genetica (5), Wilke, Carlo [0000-0002-7250-8597], Beltran, Sergi [0000-0002-2810-3445], Laurie, Steven [0000-0003-3913-5829], Graessner, Holm [0000-0001-9803-7183], Synofzik, Matthis [0000-0002-2280-7273], and Apollo - University of Cambridge Repository
Subjects: genetics [Rare Diseases], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Medizin, Datasets as Topic, 0302 clinical medicine, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], Medicine, Genetics (clinical), 0303 health sciences, methods [Genomics], Management science, Neurodevelopmental disorders, Neurodegenerative diseases, 030305 genetics & heredity, 1184 Genetics, developmental biology, physiology, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], Genomics, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], genetics [Nervous System Diseases], 3. Good health, Chemistry, Practice Guidelines as Topic, Malalties rares, pathology [Rare Diseases], methods [Genetic Testing], Movement disorders, Other Research Donders Center for Medical Neuroscience [Radboudumc 0], Socio-culturale, standards [Exome Sequencing], standards [Genetic Testing], pathology [Nervous System Diseases], 03 medical and health sciences, Rare Diseases, Viewpoint, Exome Sequencing, Genetics, Humans, Genetic Testing, ddc:610, Biology, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, Sistema nerviós -- Malalties, methods [Exome Sequencing], standards [Genomics], 3111 Biomedicine, Human medicine, Nervous System Diseases, business, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], 030217 neurology & neurosurgery
Abstract: Rare genetic neurological disorders (RND; ORPHA:71859) are a heterogeneous group of disorders comprising >1700 distinct genetic disease entities. However, genetic discoveries have not yet translated into dramatic increases of diagnostic yield and indeed rates of molecular genetic diagnoses have been stuck at about 30–50% across NGS modalities and RND phenotypes [1, 2]. Existence of yet unknown disease genes as well as shortcomings of commonly employed NGS technologies and analysis pipelines in detecting certain variant types are typically cited to explain the low diagnosis rates. To increase the diagnostic yield in RNDs - one of the four focus disease groups in Solve-RD - we follow two major approaches, that we will here present and exemplify: (i) systematic state-of the art re-analysis of large cohorts of unsolved whole-exome/genome sequencing (WES/WGS) RND datasets; and (ii) novel-omics approaches. Based on the way Solve-RD systematically organizes researchers’ expertise to channel this approach [3], the European Reference Network for Rare Neurological Diseases (ERN-RND) has established its own Data Interpretation Task Force (DITF) within SOLVE-RD, which is currently composed of clinical and genetic experts from 29 sites in 15 European countries. The Solve-RD project has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No. 779257. Data were analysed using the RD‐Connect Genome‐Phenome Analysis Platform, which received funding from EU projects RD‐Connect, Solve-RD and EJP-RD (Grant Numbers FP7 305444, H2020 779257, H2020 825575), Instituto de Salud Carlos III (Grant Numbers PT13/0001/0044, PT17/0009/0019; Instituto Nacional de Bioinformática, INB) and ELIXIR Implementation Studies. The study was further funded by the Federal Ministry of Education and Research, Germany, through the TreatHSP network (01GM1905 to RS and LS), the National Institute of Neurological Diseases and Stroke (R01NS072248 to SZ and RS), the European Joint Program on Rare Diseases-EJP-RD COFUND-EJP N° 825575 through funding for the PROSPAX consortium (441409627 to MS, RS and BvW). CW was supported by the PATE program of the Medical Faculty, University of Tübingen. CEE received support from the Dutch Princess Beatrix Muscle Fund and the Dutch Spieren voor Spieren Muscle fund. Authors on this paper are members of the European Reference Network for Rare Neurological Diseases (ERN-RND, Project ID 739510)
Published: 2021
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4. Quimiometria, imatges hiperespectrals i teixit vegetal: fem ús de tota la informació de les nostres dades?

Author: Adrián Gómez-Sánchez; Universitat de Barcelona, Mónica Marro; Barcelona Institute of Science and Technology (BIST). Institut de Ciències Fotòniques (ICFO), María Marsal; Barcelona Institute of Science and Technology (BIST). Institut de Ciències Fotòniques (ICFO), Pablo Loza-Álvarez; Barcelona Institute of Science and Technology (BIST). Institut de Ciències Fotòniques (ICFO), Anna de Juan; Universitat de Barcelona. Grup de Quimiometria, Adrián Gómez-Sánchez; Universitat de Barcelona, Mónica Marro; Barcelona Institute of Science and Technology (BIST). Institut de Ciències Fotòniques (ICFO), María Marsal; Barcelona Institute of Science and Technology (BIST). Institut de Ciències Fotòniques (ICFO), Pablo Loza-Álvarez; Barcelona Institute of Science and Technology (BIST). Institut de Ciències Fotòniques (ICFO), and Anna de Juan; Universitat de Barcelona. Grup de Quimiometria
Abstract: Descobrir quins compostos químics hi ha en un teixit biològic i on estan localitzats ens dona una informació crucial sobre la funcionalitat d’aquests compostos i del mateix teixit. Aquesta informació la proporcionen les tècniques d’imatgeria hiperespectral (HI), que associen la informació espectral a la posició dels píxels a la mostra. Aquestes tècniques, però, generen una gran quantitat de dades complexes que s’han de gestionar amb l’ús d’eines quimiomètriques, com ara el mètode de resolució multivariant de corbes per mínims quadrats alternats (MCR-ALS), per poder fer una interpretació correcta de la mesura. A més, la informació complementària proporcionada per les diferents plataformes espectroscòpiques d’imatgeria hiperespectral es pot combinar mitjançant estratègies de fusió d’imatges per ajudar a obtenir una descripció més completa del teixit en estudi. Aquest treball s’orienta a mostrar el potencial de la combinació de la imatgeria hiperespectral i la quimiometria per interpretar la informació associada als teixits biològics. Per il·lustrar-ho, es mostra l’estudi de diverses microseccions de fulles de planta d’arròs mitjançant les imatges Raman, de fluorescència i la seva fusió.Paraules clau: Imatgeria hiperespectral, fusió d’imatges, quimiometria, teixit vegetal., Discovering the nature and location of chemical compounds in a biological tissue provides crucial information about the functionality of the compounds and the tissue. This information is provided by hyperspectral imaging (HI) techniques, which associate spectral information with the pixel position in the sample. These techniques, however, generate a large amount of complex data that must be processed with chemometric tools, such as the Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) method, to enable a proper interpretation of the measurement. In addition, the complementary information provided by different spectroscopic hyperspectral imaging platforms can be combined using suitable image fusion strategies to obtain a more complete description of the biological tissue. This paper seeks to show the potential of the combination of hyperspectral imaging and chemometric tools to gather information associated with biological tissues. For this purpose, a study performed on several rice leaf and root microsections using Raman and fluorescence image fusion is described.Keywords: Hyperspectral imaging, image fusion, chemometrics, plant tissue.
Published: 2020

5. Photoinduced electron transfer in 5-bromouracil labeled DNA. A contrathermodynamic mechanism revisited by electron transfer theories.

Author: CupelliniCurrent address: Institute for Research in Biomedicine (IRB Barcelona) The Barcelona Institute of Science and Technology Baldiri Reixac 10 08028 Barcelona Spain., Lorenzo, Wityk, Paweł, Mennucci, Benedetta, and Rak, Janusz
Abstract: The understanding of the 5-bromouracil (BrU) based photosensitization mechanism of DNA damage is of large interest due to the potential applications in photodynamic therapy. Photoinduced electron transfer (ET) in BrU labeled duplexes comprising the 5′-GBrU or 5′-ABrU sequence showed that a much lower reactivity was found for the 5′-GBrU pattern. Since the ionization potential of G is lower than that of A, this sequence selectivity has been dubbed a contrathermodynamic one. In the current work, we employ the Marcus and Marcus–Levich–Jortner theory of ET in order to shed light on the observed effect. By using a combination of Density Functional Theory (DFT) and solvation continuum models, we calculated the electronic couplings, reorganization energies, and thermodynamic stimuli for electron transfer which enabled the rates of forward and back ET to be estimated for the two considered sequences. The calculated rates show that the photoreaction could not be efficient if the ET process proceeded within the considered dimers. Only after introducing additional adenines between G and BrU, which accelerates the forward and slows down the back ET, is a significant amount of photodamage expected. [ABSTRACT FROM AUTHOR]
Published: 2019
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6. Heat-controlled micropillar array device for microsystems technology.

Author: TorrasPresent address: Institute for Bioengineering of Catalonia (IBEC) Barcelona Institute of Science and Technology (BIST) Baldiri Reixac 10-12 E-08028 Barcelona Spain., Nária, Duque, Marcos, Camargo, Carlos J., Esteve, Jaume, and Sánchez-Ferrer, Antoni
Published: 2017
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7. Carm1-arginine methylation of the transcription factor C/EBPα regulates transdifferentiation velocity

Author: Torcal Garcia, Guillem, Kowenz-Leutz, Elisabeth, TIAN, TIAN, Klonizakis, Antonis, Lerner, Jonathan, de Andres-Aguayo, Luisa, Vila-Casadesús, Maria, Peiró, Sandra, Institut Català de la Salut, [Torcal Garcia G, Klonizakis A, De Andres-Aguayo L] Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Spain. [Kowenz-Leutz E] Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany. [Tian TV, Vila Casadesus M] Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Lerner J] Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States. [Peiro S] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Cell Physiological Phenomena::Cell Differentiation [PHENOMENA AND PROCESSES], Cell Physiological Phenomena::Cell Transdifferentiation [PHENOMENA AND PROCESSES], Cèl·lules B, fenómenos químicos::fenómenos bioquímicos::alquilación::metilación [FENÓMENOS Y PROCESOS], Chemical Phenomena::Biochemical Phenomena::Alkylation::Methylation [PHENOMENA AND PROCESSES], Diferenciació cel·lular, Ratolins, fenómenos fisiológicos celulares::transdiferenciación celular [FENÓMENOS Y PROCESOS], Metilació, Eukaryota::Animals::Chordata::Vertebrates::Mammals::Eutheria::Rodentia::Muridae::Murinae::Mice [ORGANISMS], Eukaryota::animales::Chordata::vertebrados::mamíferos::Eutheria::Rodentia::Muridae::Murinae::ratones [ORGANISMOS], fenómenos fisiológicos celulares::diferenciación celular [FENÓMENOS Y PROCESOS]
Abstract: Developmental biology; Gene regulation; Transcription factor Biologia del desenvolupament; Regulació gènica; Factor de transcripció Biología del desarrollo; Regulación génica; Factor de transcripción Here, we describe how the speed of C/EBPα-induced B cell to macrophage transdifferentiation (BMT) can be regulated, using both mouse and human models. The identification of a mutant of C/EBPα (C/EBPαR35A) that greatly accelerates BMT helped to illuminate the mechanism. Thus, incoming C/EBPα binds to PU.1, an obligate partner expressed in B cells, leading to the release of PU.1 from B cell enhancers, chromatin closing and silencing of the B cell program. Released PU.1 redistributes to macrophage enhancers newly occupied by C/EBPα, causing chromatin opening and activation of macrophage genes. All these steps are accelerated by C/EBPαR35A, initiated by its increased affinity for PU.1. Wild-type C/EBPα is methylated by Carm1 at arginine 35 and the enzyme’s perturbations modulate BMT velocity as predicted from the observations with the mutant. Increasing the proportion of unmethylated C/EBPα in granulocyte/macrophage progenitors by inhibiting Carm1 biases the cell’s differentiation toward macrophages, suggesting that cell fate decision velocity and lineage directionality are closely linked processes. TG was supported by the Center for Genomic Regulation, Barcelona, the Spanish Ministry of Economy, Industry and Competitiveness, (Plan Estatal PID2019-109354GB-100), AGAUR (SGR 006713) and the 4D-Genome European Research Council Synergy grant. KSZ was supported by the NIH grant R01GM36477. We have used ChatGPT to improve parts of the text.
Published: 2023

8. In Vitro Antibacterial Activity of Silver Nanoparticles Conjugated with Amikacin and Combined with Hyperthermia against Drug-Resistant and Biofilm-Producing Strains

Author: Marta Palau, Estela Muñoz, Muriel F. Gusta, Nieves Larrosa, Xavier Gomis, Joan Gilabert, Benito Almirante, Victor Puntes, Robert Texidó, Joan Gavaldà, Institut Català de la Salut, [Palau M, Almirante B, Gavaldà J] Laboratori de Resistència Microbiana, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Spanish Network for Research in Infectious Diseases (REIPI RD19/0016), Instituto de Salud Carlos III, Madrid, Spain. CIBERINFEC, ISCIII-CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain. [Muñoz E] Laboratori de Resistència Microbiana, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Freixanet Gusta M] Institut Català de Nanociència i Nanotecnologia (ICN2), CSIC, The Barcelona Institute of Science and Technology (BIST), Campus UAB, Bellaterra, Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. CIBER en Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN, Madrid, Spain. [Larrosa N] Spanish Network for Research in Infectious Diseases (REIPI RD19/0016), Instituto de Salud Carlos III, Madrid, Spain. CIBERINFEC, ISCIII-CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain. Servei de Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Gomis X] Laboratori de Resistència Microbiana, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. CIBERINFEC, ISCIII-CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain. [Gilabert J] Tractivus SL, Barcelona, Spain i Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. [Puntes V] Institut Català de Nanociència i Nanotecnologia (ICN2), CSIC, The Barcelona Institute of Science and Technology (BIST), Campus UAB, Bellaterra, Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. CIBER en Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN, Madrid, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Microbiology (medical), General Immunology and Microbiology, Ecology, Nanopartícules, Physiology, Technology, Industry, and Agriculture::Manufactured Materials::Nanostructures::Nanoparticles::Metal Nanoparticles [TECHNOLOGY, INDUSTRY, AND AGRICULTURE], terapéutica::hipertermia inducida [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Cell Biology, acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antibacterianos [COMPUESTOS QUÍMICOS Y DROGAS], tecnología, industria y agricultura::productos manufacturados::nanoestructuras::nanopartículas::nanopartículas metálicas [TECNOLOGÍA, INDUSTRIA Y AGRICULTURA], Infectious Diseases, Medicaments antiinfecciosos, Genetics, Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial Agents [CHEMICALS AND DRUGS], Therapeutics::Hyperthermia, Induced [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Calor - Efectes fisiològics
Abstract: Antibacterial activity; Biofilms; Silver nanoparticles Actividad antibacteriana; Biopelículas; Nanopartículas de plata Activitat antibacteriana; Biopel·lícules; Nanopartícules de plata In view of the current increase and spread of antimicrobial resistance (AMR), there is an urgent need to find new strategies to combat it. This study had two aims. First, we synthesized highly monodispersed silver nanoparticles (AgNPs) of approximately 17 nm, and we functionalized them with mercaptopoly(ethylene glycol) carboxylic acid (mPEG-COOH) and amikacin (AK). Second, we evaluated the antibacterial activity of this treatment (AgNPs_mPEG_AK) alone and in combination with hyperthermia against planktonic and biofilm-growing strains. AgNPs, AgNPs_mPEG, and AgNPs_mPEG_AK were characterized using a suite of spectroscopy and microscopy methods. Susceptibility to these treatments and AK was determined after 24 h and over time against 12 clinical multidrug-resistant (MDR)/extensively drug-resistant (XDR) isolates of Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The efficacy of the treatments alone and in combination with hyperthermia (1, 2, and 3 pulses at 41°C to 42°C for 15 min) was tested against the same planktonic strains using quantitative culture and against one P. aeruginosa strain growing on silicone disks using confocal laser scanning microscopy. The susceptibility studies showed that AgNPs_mPEG_AK was 10-fold more effective than AK alone, and bactericidal efficacy after 4, 8, 24, or 48 h was observed against 100% of the tested strains. The combination of AgNPs_mPEG_AK and hyperthermia eradicated 75% of the planktonic strains and exhibited significant reductions in biofilm formation by P. aeruginosa in comparison with the other treatments tested, except for AgNPs_mPEG_AK without hyperthermia. In conclusion, the combination of AgNPs_mPEG_AK and hyperthermia may be a promising therapy against MDR/XDR and biofilm-producing strains. IMPORTANCE Antimicrobial resistance (AMR) is one of the greatest public health challenges, accounting for 1.27 million deaths worldwide in 2019. Biofilms, a complex microbial community, directly contribute to increased AMR. Therefore, new strategies are urgently required to combat infections caused by AMR and biofilm-producing strains. Silver nanoparticles (AgNPs) exhibit antimicrobial activity and can be functionalized with antibiotics. Although AgNPs are very promising, their effectiveness in complex biological environments still falls below the concentrations at which AgNPs are stable in terms of aggregation. Thus, improving the antibacterial effectiveness of AgNPs by functionalizing them with antibiotics may be a significant change to consolidate AgNPs as an alternative to antibiotics. It has been reported that hyperthermia has a large effect on the growth of planktonic and biofilm-producing strains. Therefore, we propose a new strategy based on AgNPs functionalized with amikacin and combined with hyperthermia (41°C to 42°C) to treat AMR and biofilm-related infections. This study was supported by research grants from the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III (FIS 01162); la Marató TV3 (472/U/2018); the CaixaImpulse Program (Fundació LaCaixa); and the Spanish Network for Research in Infectious Diseases (REIPI RD19/0016).
Published: 2023

9. Exploiting endocytosis for transfection of mRNA for cytoplasmatic delivery using cationic gold nanoparticles

Author: Muriel F. Gustà, Michael J. Edel, Vivian A. Salazar, Belén Alvarez-Palomo, Manel Juan, Massimo Broggini, Giovanna Damia, Paolo Bigini, Alessandro Corbelli, Fabio Fiordaliso, Alexander Barbul, Rafi Korenstein, Neus G. Bastús, Víctor Puntes, Institut Català de la Salut, [Gustà MF] Institut Català de Nanociència i Nanotecnologia (ICN2), Consejo Superior de Investigaciones Científicas (CSIC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain. [Edel MJ] Hospital Clínic de Barcelona, Servei Immunologia-IDIBAPS, Barcelona, Spain. Unit of Anatomy and Embryology, Universitat Autònoma de Barcelona, Faculty of Medicine, Barcelona, Spain. University of Western Australia, Faculty of Medicine, Discipline of Medical Sciences and Genetics, School of Biomedical Sciences, Perth, WA, Australia. [Salazar VA] Institut Català de Nanociència i Nanotecnologia (ICN2), Consejo Superior de Investigaciones Científicas (CSIC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. [Alvarez-Palomo B] Banc de Sang i Teixits, Cell Therapy Service, Barcelona, Spain. [Juan M] Hospital Clínic de Barcelona, Servei Immunologia-IDIBAPS, Barcelona, Spain. [Broggini M] IRCCS‐Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy. [Puntes V] Institut Català de Nanociència i Nanotecnologia (ICN2), Consejo Superior de Investigaciones Científicas (CSIC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Nanopartícules, Immunology, Technology, Industry, and Agriculture::Manufactured Materials::Nanostructures::Nanoparticles::Metal Nanoparticles [TECHNOLOGY, INDUSTRY, AND AGRICULTURE], nucleótidos y nucleósidos de ácidos nucleicos::ácidos nucleicos::ARN::ARN mensajero [COMPUESTOS QUÍMICOS Y DROGAS], técnicas de investigación::técnicas genéticas::técnicas de transferencia génica::transfección [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], tecnología, industria y agricultura::productos manufacturados::nanoestructuras::nanopartículas::nanopartículas metálicas [TECNOLOGÍA, INDUSTRIA Y AGRICULTURA], Endocitosi, Transfecció, Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Messenger [CHEMICALS AND DRUGS], fenómenos fisiológicos celulares::endocitosis [FENÓMENOS Y PROCESOS], RNA, Immunology and Allergy, Cell Physiological Phenomena::Endocytosis [PHENOMENA AND PROCESSES], Investigative Techniques::Genetic Techniques::Gene Transfer Techniques::Transfection [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT]
Abstract: Gene therapeutics; Gold nanoparticles; Safety Terapia génica; Nanopartículas de oro; Seguridad Teràpia gènica; Nanopartícules d'or; Seguretat Introduction: Gene therapy holds promise to cure various diseases at the fundamental level. For that, efficient carriers are needed for successful gene delivery. Synthetic ‘non-viral’ vectors, as cationic polymers, are quickly gaining popularity as efficient vectors for transmitting genes. However, they suffer from high toxicity associated with the permeation and poration of the cell membrane. This toxic aspect can be eliminated by nanoconjugation. Still, results suggest that optimising the oligonucleotide complexation, ultimately determined by the size and charge of the nanovector, is not the only barrier to efficient gene delivery. Methods: We herein develop a comprehensive nanovector catalogue comprising different sizes of Au NPs functionalized with two different cationic molecules and further loaded with mRNA for its delivery inside the cell. Results and Discussion: Tested nanovectors showed safe and sustained transfection efficiencies over 7 days, where 50 nm Au NPs displayed the highest transfection rates. Remarkably, protein expression was increased when nanovector transfection was performed combined with chloroquine. Cytotoxicity and risk assessment demonstrated that nanovectors are safe, ascribed to lesser cellular damage due to their internalization and delivery via endocytosis. Obtained results may pave the way to design advanced and efficient gene therapies for safely transferring oligonucleotides. We acknowledge financial support from the Spanish Ministerio de Ciencia, Innovación y Universidades (MCIU) (RTI2018-099965-B-I00, AEI/FEDER,UE) proyectos de I+D+i de programación conjunta internacional MCIN/AEI (CONCORD, PCI2019-103436) cofunded by the European Union and Generalitat de Catalunya (2017-SGR-1431). ICN2 is supported by the Severo Ochoa program from Spanish MINECO (SEV-2017-0706) and is funded by the CERCA Programme/Generalitat de Catalunya.
Published: 2023
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10. Heterogeneous Rate Constant for Amorphous Silica Nanoparticle Adsorption on Phospholipid Monolayers

Author: Alex Vakurov, Rik Drummond-Brydson, Nicola William, Didem Sanver, Neus Bastús, Oscar H. Moriones, V. Puntes, Andrew L. Nelson, European Commission, Vakurov, Alex, Sanver, Didem, Bastús, Neus G., Moriones, Oscar Hernando, Institut Català de la Salut, [Vakurov A, Nelson AL] School of Chemistry, University of Leeds, Leeds LS2 9JT, U.K. [Drummond-Brydson R] School of Chemical and Process Engineering, University of Leeds, Leeds LS2 9JT, U.K. [William N] School of Chemistry, University of Leeds, Leeds LS2 9JT, U.K. Didem Sanver − Department of Food Engineering, Faculty of Engineering, Necmettin Erbakan University, Konya 42050, Turkey. [Sanver D] Department of Food Engineering, Faculty of Engineering, Necmettin Erbakan University, Konya 42050, Turkey. [Bastús N] Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC, The Barcelona Institute of Science and Technology, Barcelona 08193, Spain. [Moriones OH] Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC, The Barcelona Institute of Science and Technology, Barcelona 08193, Spain, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Puntes V] Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC, The Barcelona Institute of Science and Technology, Barcelona 08193, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. ICREA, Barcelona 08010, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Technology, Industry, and Agriculture::Manufactured Materials::Nanostructures::Nanoparticles [TECHNOLOGY, INDUSTRY, AND AGRICULTURE], Nanopartícules, Nanotecnologia, Surface Properties, Lipids::Membrane Lipids::Phospholipids [CHEMICALS AND DRUGS], Water, tecnología, industria y agricultura::productos manufacturados::nanoestructuras::nanopartículas [TECNOLOGÍA, INDUSTRIA Y AGRICULTURA], Silica, Surfaces and Interfaces, tecnología, industria y agricultura::tecnología::miniaturización::nanotecnología [TECNOLOGÍA, INDUSTRIA Y AGRICULTURA], Silicon Dioxide, Condensed Matter Physics, Technology, Industry, and Agriculture::Technology::Miniaturization::Nanotechnology [TECHNOLOGY, INDUSTRY, AND AGRICULTURE], Electrochemistry, Nanoparticles, General Materials Science, Colloids, Adsorption, Layers, lípidos::lípidos de membranas::fosfolípidos [COMPUESTOS QUÍMICOS Y DROGAS], Phospholipids, Spectroscopy, Fosfolípids
Abstract: The interaction of amorphous silica nanoparticles with phospholipid monolayers and bilayers has received a great deal of interest in recent years and is of importance for assessing potential cellular toxicity of such species, whether natural or synthesized for the purpose of nanomedical drug delivery and other applications. This present communication studies the rate of silica nanoparticle adsorption on to phospholipid monolayers in order to extract a heterogeneous rate constant from the data. This rate constant relates to the initial rate of growth of an adsorbed layer of nanoparticles as SiO2 on a unit area of the monolayer surface from unit concentration in dispersion. Experiments were carried out using the system of dioleoyl phosphatidylcholine (DOPC) monolayers deposited on Pt/Hg electrodes in a flow cell. Additional studies were carried out on the interaction of soluble silica with these layers. Results show that the rate constant is effectively constant with respect to silica nanoparticle size. This is interpreted as indicating that the interaction of hydrated SiO2 molecular species with phospholipid polar groups is the molecular initiating event (MIE) defined as the initial interaction of the silica particle surface with the phospholipid layer surface promoting the adsorption of silica nanoparticles on DOPC. The conclusion is consistent with the observed significant interaction of soluble SiO2 with the DOPC layer and the established properties of the silica–water interface., We acknowledge EU for supporting ENNSATOX GA No. 229244, HISENTS GA No. 685817, and SABYDOMA GA No 862296.
Published: 2022
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11. GEMC1 and MCIDAS interactions with SWI/SNF complexes regulate the multiciliated cell-specific transcriptional program

Author: Michael Lewis, Berta Terré, Philip A. Knobel, Tao Cheng, Hao Lu, Camille Stephan-Otto Attolini, Jordann Smak, Etienne Coyaud, Isabel Garcia-Cao, Shalu Sharma, Chithran Vineethakumari, Jessica Querol, Gabriel Gil-Gómez, Gabriele Piergiovanni, Vincenzo Costanzo, Sandra Peiró, Brian Raught, Haotian Zhao, Xavier Salvatella, Sudipto Roy, Moe R. Mahjoub, Travis H. Stracker, Institut Català de la Salut, [Lewis M, Attolini CSO] Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain. [Terré B] Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain. MRC Clinical Trials Unit at UCL, London, UK. [Knobel PA] Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain. CDR-Life AG, Zurich, Switzerland. [Cheng T] Washington University in St Louis, Departments of Medicine (Nephrology), Cell Biology and Physiology, St. Louis, MO, USA. [Lu H] Institute of Molecular and Cell Biology, Proteos, Singapore, Singapore. [Querol J] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Cancer Research, Cellular and Molecular Neuroscience, fenómenos genéticos::regulación de la expresión génica [FENÓMENOS Y PROCESOS], Cell Physiological Phenomena::Cell Differentiation [PHENOMENA AND PROCESSES], Immunology, Regulació genètica, Cell Biology, Diferenciació cel·lular, Genetic Phenomena::Gene Expression Regulation [PHENOMENA AND PROCESSES], fenómenos fisiológicos celulares::diferenciación celular [FENÓMENOS Y PROCESOS]
Abstract: Cell signalling; Transcription Señalización celular; Transcripción Senyalització cel·lular; Transcripció Multiciliated cells (MCCs) project dozens to hundreds of motile cilia from their apical surface to promote the movement of fluids or gametes in the mammalian brain, airway or reproductive organs. Differentiation of MCCs requires the sequential action of the Geminin family transcriptional activators, GEMC1 and MCIDAS, that both interact with E2F4/5-DP1. How these factors activate transcription and the extent to which they play redundant functions remains poorly understood. Here, we demonstrate that the transcriptional targets and proximal proteomes of GEMC1 and MCIDAS are highly similar. However, we identified distinct interactions with SWI/SNF subcomplexes; GEMC1 interacts primarily with the ARID1A containing BAF complex while MCIDAS interacts primarily with BRD9 containing ncBAF complexes. Treatment with a BRD9 inhibitor impaired MCIDAS-mediated activation of several target genes and compromised the MCC differentiation program in multiple cell based models. Our data suggest that the differential engagement of distinct SWI/SNF subcomplexes by GEMC1 and MCIDAS is required for MCC-specific transcriptional regulation and mediated by their distinct C-terminal domains. We thank F. Guillemot, C. Lynch, M. Serrano, and S. Brody for antibodies, F. Supek for cells and reagents, A. Holland and C. Jewett for DEUP1 antibody and expansion microscopy suggestions, J. St-Germain for data analysis, J. Lüders for help with expansion microscopy, T. Dantas for sharing unpublished data and support from the IRB Functional Genomics and Biostatistics/Bioinformatics, Protein Expression and Mass Spectrometry Core Facilities. ML and BT were funded by Severo Ochoa FPI fellowships from the Ministry of Science, Innovation and Universities (MCIU), PK by an Advanced Postdoc Mobility fellowship from the Swiss National Science Foundation and the Kurt and Senta Herrmann Foundation and I.G.C by an AECC fellowship. THS was funded by the MCIU (PGC2018-095616-B-I00/GINDATA) and by the NIH Intramural Research Program, National Cancer Institute, Center for Cancer Research. X.S. was supported by MINECO (PID2019-110198RB-I00) and the European Research Council (CONCERT, contract number 648201). IRB Barcelona is the recipient of institutional funding from FEDER and the Centres of Excellence Severo Ochoa award to IRB Barcelona from MINECO (Government of Spain). MRM was funded by the National Heart, Lung and Blood Institute of the NIH (R01-HL128370). VC was funded by the Associazione Italiana per la Ricerca sul Cancro (AIRC), the European Research Council (ERC) grant 614541 and the GiovanniArmenise foundation career development award to VC. SR was funded by a Singapore National Medical Research Council (NMRC) Open Fund-Individual Research Grant (OFIRG19nov-0037). HZ was supported by National Cancer Institute (R01 CA220551).
Published: 2023

12. The development of highly dense highly protected surfactant ionizable lipid RNA loaded nanoparticles

Author: González-Rioja, Ramon, Bastús, Neus G, Franco Puntes, Victor, Salazar, Vivian Angélica, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Generalitat de Catalunya, Institut Català de la Salut, [González-Rioja R, Salazar VA] Institut Català de Nanociència i Nanotecnologia (ICN2), Consejo Superior de Investigaciones Científicas (CSIC), The Barcelona Institute of Science and Technology (BIST), Universitat Autònoma de Barcelona, Bellaterra, Spain. [Bastús NG] Institut Català de Nanociència i Nanotecnologia (ICN2), Consejo Superior de Investigaciones Científicas (CSIC), The Barcelona Institute of Science and Technology (BIST), Universitat Autònoma de Barcelona, Bellaterra, Spain. Centro de Investigación Biomédica en Red (CIBER) en Bioingeniería, Biomateriales y Nanomedicina, Centro de Investigación Biomédica en Red en Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain. [Puntes V] Institut Català de Nanociència i Nanotecnologia (ICN2), Consejo Superior de Investigaciones Científicas (CSIC), The Barcelona Institute of Science and Technology (BIST), Universitat Autònoma de Barcelona, Bellaterra, Spain. Centro de Investigación Biomédica en Red (CIBER) en Bioingeniería, Biomateriales y Nanomedicina, Centro de Investigación Biomédica en Red en Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain. Grup de Recerca de Nanopartícules Farmacocinètiques, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Grup de Recerca de Malalties Infeccioses, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Technology, Industry, and Agriculture::Manufactured Materials::Nanostructures::Nanoparticles [TECHNOLOGY, INDUSTRY, AND AGRICULTURE], Drug delivery carriers, Biodistribution and clearance, Ionizable lipid nanoparticles, Nanopartícules, Pharmaceutical Preparations::Dosage Forms::Drug Carriers [CHEMICALS AND DRUGS], RNA-loading, Immunology, Medicaments - Modes d'administració, Immunology and Allergy, tecnología, industria y agricultura::productos manufacturados::nanoestructuras::nanopartículas [TECNOLOGÍA, INDUSTRIA Y AGRICULTURA], Pharmacokinetics, preparados farmacéuticos::formas farmacéuticas::portadores de fármacos [COMPUESTOS QUÍMICOS Y DROGAS]
Abstract: The long quest for efficient drug administration has been looking for a universal carrier that can precisely transport traditional drugs, new genomic and proteic therapeutic agents. Today, researchers have found conditions to overcome the two main drug delivery dilemmas. On the one side, the versatility of the vehicle to efficiently load, protect and transport the drug and then release it at the target place. On the other hand, the questions related to the degree of PEGylation which are needed to avoid nanoparticle (NP) aggregation and opsonization while preventing cellular uptake. The development of different kinds of lipidic drug delivery vehicles and particles has resulted in the development of ionizable lipid nanoparticles (iLNPs), which can overcome most of the typical drug delivery problems. Proof of their success is the late approval and massive administration as the prophylactic vaccine for SARS-CoV-2. These ILNPs are built by electrostatic aggregation of surfactants, the therapeutic agent, and lipids that self-segregate from an aqueous solution, forming nanoparticles stabilized with lipid polymers, such as PEG. These vehicles overcome previous limitations such as low loading and high toxicity, likely thanks to low charge at the working pH and reduced size, and their entry into the cells via endocytosis rather than membrane perforation or fusion, always associated with higher toxicity. We herein revise their primary features, synthetic methods to prepare and characterize them, pharmacokinetic (administration, distribution, metabolization and excretion) aspects, and biodistribution and fate. Owing to their advantages, iLNPs are potential drug delivery systems to improve the management of various diseases and widely available for clinical use., We acknowledge financial support from the Spanish Ministerio de Ciencia, Innovación y Universidades (MCIU) (RTI2018-099965- B-I00, AEI/FEDER,UE) proyectos de I+D+i de programación conjunta internacional MCIN/AEI (CONCORD, PCI2019- 103436) cofunded by the European Union and Generalitat de Catalunya (2017-SGR-1431). ICN2 is supported by the Severo Ochoa program from Spanish MINECO (SEV-2017-0706) and is funded by the CERCA Programme/Generalitat de Catalunya.
Published: 2023
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13. Comparison of cerebral metabolic rate of oxygen, blood flow, and bispectral index under general anesthesia

Author: Susanna Tagliabue, Claus Lindner, Ivette Chochron da Prat, Angela Sanchez-Guerrero, Isabel Serra, Michał Kacprzak, Federica Maruccia, Olga Martinez Silva, Udo M. Weigel, Miriam de Nadal, Maria A. Poca, Turgut Durduran, Institut Català de la Salut, [Tagliabue S, Lindner C] ICFO – Institut de Ciències Fotòniques, The Barcelona Institute of Science and Technology, Barcelona, Spain. [Chochron da Prat I, Martinez Silva O] Servei d’Anestesiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Sanchez-Guerrero A] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Unitat de Recerca en Neurotraumatologia i Neurocirurgia (UNINN), Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Serra I] Centre de Recerca Matemàtica, Bellaterra, Spain. Barcelona Supercomputing Center—Centre Nacional de Supercomputació, Spain. [Kacprzak M] ICFO – Institut de Ciències Fotòniques, The Barcelona Institute of Science and Technology, Barcelona, Spain. Nalecz Institute of Biocybernetics and Biomedical Engineering PAS, Warsaw, Poland. [Maruccia F] ICFO – Institut de Ciències Fotòniques, The Barcelona Institute of Science and Technology, Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Unitat de Recerca en Neurotraumatologia i Neurocirurgia (UNINN), Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [de Nadal M] Servei d’Anestesiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Poca MA] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Unitat de Recerca en Neurotraumatologia i Neurocirurgia (UNINN), Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Neurocirurgia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: técnicas de investigación::técnicas de química analítica::análisis espectral [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Time-resolved spectroscopy, Radiological and Ultrasound Technology, Propofol-induced anesthesia, Anestèsia, Sang - Circulació, Neuroscience (miscellaneous), anestesia y analgesia::anestesia::anestesia general [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Cerebral blood flow, Investigative Techniques::Chemistry Techniques, Analytical::Spectrum Analysis [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Cerebral physiological changes, Cerebral metabolic rate of oxygen, Anàlisi espectral, Anesthesia and Analgesia::Anesthesia::Anesthesia, General [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Circulatory and Respiratory Physiological Phenomena::Cardiovascular Physiological Phenomena::Blood Circulation::Cerebrovascular Circulation [PHENOMENA AND PROCESSES], Bispectral index, Near-infrared spectroscopy, Radiology, Nuclear Medicine and imaging, fenómenos fisiológicos respiratorios y circulatorios::fenómenos fisiológicos cardiovasculares::circulación sanguínea::circulación cerebrovascular [FENÓMENOS Y PROCESOS], Diffuse correlation spectroscopy, Diffuse optics
Abstract: Cerebral blood flow; Diffuse optics; Propofol-induced anesthesia Flujo sanguíneo cerebral; Óptica difusa; Anestesia inducida por propofol Flux sanguini cerebral; Òptica difusa; Anestèsia induïda per propofol Significance The optical measurement of cerebral oxygen metabolism was evaluated. Aim Compare optically derived cerebral signals to the electroencephalographic bispectral index (BIS) sensors to monitor propofol-induced anesthesia during surgery. Approach Relative cerebral metabolic rate of oxygen (rCMRO2) and blood flow (rCBF) were measured by time-resolved and diffuse correlation spectroscopies. Changes were tested against the relative BIS (rBIS) ones. The synchronism in the changes was also assessed by the R-Pearson correlation. Results In 23 measurements, optically derived signals showed significant changes in agreement with rBIS: during propofol induction, rBIS decreased by 67% [interquartile ranges (IQR) 62% to 71%], rCMRO2 by 33% (IQR 18% to 46%), and rCBF by 28% (IQR 10% to 37%). During recovery, a significant increase was observed for rBIS (48%, IQR 38% to 55%), rCMRO2 (29%, IQR 17% to 39%), and rCBF (30%, IQR 10% to 44%). The significance and direction of the changes subject-by-subject were tested: the coupling between the rBIS, rCMRO2, and rCBF was witnessed in the majority of the cases (14/18 and 12/18 for rCBF and 19/21 and 13/18 for rCMRO2 in the initial and final part, respectively). These changes were also correlated in time (R > 0.69 to R = 1, p-values < 0.05). Conclusions Optics can reliably monitor rCMRO2 in such conditions. This work received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 675332 (BitMap), No. 101016087 (VASCOVID) and No. 101017113 (TinyBRAINS), KidsBrainIT (ERA-NET NEURON), FEDER EC and LASERLAB-EUROPE V (EC H2020 no. 871124). It was also supported by Fundació CELLEX Barcelona, Fundació Mir-Puig the “Severo Ochoa” Programme for Centres of Excellence in R&D (SEV-2015-0522), the Obra social “la Caixa” Foundation (LlumMedBcn), Generalitat de Catalunya (CERCA, AGAUR-2017-SGR-1380, RIS3CAT-001-P-001682 CECH), la Fundació La Marató de TV3 (201724.31 and 201709.31), and by Agencia Estatal de Investigación (PHOTOMETABO, PID2019-106481RB-C31/10.13039/501100011033).
Published: 2023

14. Microfluidic-based dynamic BH3 profiling predicts anticancer treatment efficacy

Author: Albert Manzano-Muñoz, José Yeste, María A. Ortega, Fernando Martín, Anna López, Jordi Rosell, Sandra Castro, César Serrano, Josep Samitier, Javier Ramón-Azcón, Joan Montero, Institut Català de la Salut, [Manzano-Muñoz A] Nanobioengineering Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. [Yeste J, López A] Biosensors for Bioengineering Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. [Ortega MA] Biosensors for Bioengineering Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. Vitala Technologies, Barcelona, Spain. [Martín F] Nanobioengineering Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain. [Rosell J] Sarcoma Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Castro S] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Serrano C] Sarcoma Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Cancer Research, técnicas de investigación::reología::microfluídica [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Càncer - Tractament, Investigative Techniques::Rheology::Microfluidics [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Apoptosi, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Other subheadings::Other subheadings::/drug therapy [Other subheadings], fenómenos fisiológicos celulares::muerte celular::apoptosis [FENÓMENOS Y PROCESOS], Neoplasms [DISEASES], neoplasias [ENFERMEDADES], terapéutica::medicina de precisión [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Oncology, Medicaments - Eficàcia, Medicina personalitzada, Therapeutics::Precision Medicine [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Cell Physiological Phenomena::Cell Death::Apoptosis [PHENOMENA AND PROCESSES]
Abstract: Cancer therapy; Predictive markers; Translational research Terapia del cáncer; Marcadores predictivos; Investigación traslacional Teràpia del càncer; Marcadors predictius; Recerca translacional Precision medicine is starting to incorporate functional assays to evaluate anticancer agents on patient-isolated tissues or cells to select for the most effective. Among these new technologies, dynamic BH3 profiling (DBP) has emerged and extensively been used to predict treatment efficacy in different types of cancer. DBP uses synthetic BH3 peptides to measure early apoptotic events (‘priming’) and anticipate therapy-induced cell death leading to tumor elimination. This predictive functional assay presents multiple advantages but a critical limitation: the cell number requirement, that limits drug screening on patient samples, especially in solid tumors. To solve this problem, we developed an innovative microfluidic-based DBP (µDBP) device that overcomes tissue limitations on primary samples. We used microfluidic chips to generate a gradient of BIM BH3 peptide, compared it with the standard flow cytometry based DBP, and tested different anticancer treatments. We first examined this new technology’s predictive capacity using gastrointestinal stromal tumor (GIST) cell lines, by comparing imatinib sensitive and resistant cells, and we could detect differences in apoptotic priming and anticipate cytotoxicity. We then validated µDBP on a refractory GIST patient sample and identified that the combination of dactolisib and venetoclax increased apoptotic priming. In summary, this new technology could represent an important advance for precision medicine by providing a fast, easy-to-use and scalable microfluidic device to perform DBP in situ as a routine assay to identify the best treatment for cancer patients. Ramon y Cajal Programme, Ministerio de Economia y Competitividad grant RYC-2015–18357. (J.M.). Ministerio de Ciencia, Innovación y Universidades grant RTI2018-094533-A-I00 (J.M.). CELLEX foundation (J.M., A.M.). Beca Trienal Fundación Mari Paz Jiménez Casado (J.M.). European Research Council, grant ERC-StG-DAMOC 714317 (J.R.-A.). European Research Council, H2020 EU framework FET-open BLOC 863037 (J.R.-A.). Spanish Ministry of Economy and Competitiveness, “Severo Ochoa” Program for Centers of Excellence in R&D SEV-2020-2023 (J.R.-A.). Generalitat de Catalunya. CERCA Programme 2017-SGR-1079 (J.R.-A., J.S.). Fundación Bancaria “la Caixa”- Obra Social “la Caixa” (project IBEC-La Caixa Health Ageing) (J.R.-A.). Fero Foundation (C.S.). Networking Biomedical Research Center (CIBER). CIBER is an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, and the Instituto de Salud Carlos III (RD16/0006/0012), with the support of the European Regional Development Fund (J.S.).
Published: 2022
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15. Single and Multisite Graphene-Based Electroretinography Recording Electrodes: A Benchmarking Study

Author: Jose de la Cruz, Diep Nguyen, Xavi Illa, Jessica Bousquet, Antonio P. Pérez‐Marín, Elena del Corro, Serge Picaud, Jose A. Garrido, Clement Hebert, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Agence Nationale de la Recherche (France), Generalitat de Catalunya, Ministerio de Economía y Competitividad (España), Catalan Institute of Nanoscience and Nanotechnology (ICN2), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Barcelona Institute of Science and Technology (BIST), Barcelona Institute of Science and Technology (BIST), Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Instituto de Microelectrònica de Barcelona (IMB-CNM), Centro Nacional de Microelectronica [Spain] (CNM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), and Marazova, Katia
Subjects: [SDV] Life Sciences [q-bio], [SDV.GEN]Life Sciences [q-bio]/Genetics, MEA, Mechanics of Materials, ERG, [SDV]Life Sciences [q-bio], graphene, General Materials Science, [SDV.GEN] Life Sciences [q-bio]/Genetics, Industrial and Manufacturing Engineering, photoreceptor degeneration
Abstract: Electroretinography (ERG) is a clinical test employed to understand and diagnose many retinopathies. ERG is usually performed by placing a macroscopic ring gold wire electrode on the cornea while flashing light onto the eye to measure changes in the transretinal potential. However, macroscopic gold electrodes are severely limiting since they do not provide a flexible interface to contact the sensitive corneal tissue, making this technique highly uncomfortable for the patient. Another major drawback is the opacity of gold electrodes, which only allows them to record the ERG signal on the corneal periphery, preventing central ERG recordings. To overcome the limitations of metal-based macroscopic ERG electrodes, flexible electrodes are fabricated using graphene as a transparent, flexible, and sensitive material. The transparency of the graphene is exploited to fabricate microelectrode arrays (MEAs) that are able to perform multisite recording on the cornea. The graphene-based ERG electrodes are benchmarked against the widely used gold electrodes in a P23H rat model with photoreceptor degeneration. This study shows that the graphene-based ERG electrodes can faithfully record ERGs under a wide range of conditions (light intensity, stage of photoreceptor degeneration, etc.) while offering additional benefits for ERG recordings such as transparency and flexibility., J.d.l.C. and D.N. contributed equally to this work. This project received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement nos. 881603 (GrapheneCore3). This work was within the project FIS2017-85787-R funded by the “Ministerio de Ciencia, Innovación y Universidades” of Spain, the “Agencia Estatal de Investigación (AEI),” and the “Fondo Europeo de Desarrollo Regional (FEDER/UE).” Support was also provided by the French state funds managed by the Agence Nationale de la Recherche within the Programme Investissements d'Avenir, LABEX LIFESENSES (ANR-10-LABX-65) and IHU FOReSIGHT (ANR-18-IAHU-0001). The ICN2 is supported by the Severo Ochoa Centres of Excellence program, funded by the Spanish Research Agency (AEI, grant no. SEV-2017-0706), and by the CERCAProgram/Generalitat de Catalunya. E.d.C. acknowledges the Spanish MINECO Juan de la Cierva Fellowship JC-2015-25201. This work made use of the Spanish ICTS Network MICRONANOFABS partially supported by MICINN and the ICTS “NANBIOSIS,” more specifically by the Micro-NanoTechnology Unit of the CIBER in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) at the IMB-CNM. J.d.l.C. would like to thank Laura García for the work on the images and figures throughout the whole paper writing process. E.d.C acknowledges the grant RYC2019-027879-I financed by MCIN/AEI /10.13039/501100011033. The project leading to these results have received funding from “la Caixa” Foundation (ID 100010434), under the agreement LCF/PR/HR19/52160003. These activities are co-funded with 50% by the European Regional Development Fund under the framework of the ERFD Operative Programme for Catalunya 2014–2020 with the support of the Department de Recerca i Universitat (GraphCAT 001-P-001702).
Published: 2022
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16. A combination of molecular and clinical parameters provides a new strategy for high-grade serous ovarian cancer patient management

Author: Melissa Bradbury, Eva Borràs, Marta Vilar, Josep Castellví, José Luis Sánchez-Iglesias, Assumpció Pérez-Benavente, Antonio Gil-Moreno, Anna Santamaria, Eduard Sabidó, Institut Català de la Salut, [Bradbury M] Centre de Regulació Genòmica, Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. Universitat Pompeu Fabra, Barcelona, Spain. Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Ginecologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Borràs E, Sabidó E] Centre de Regulació Genòmica, Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. Universitat Pompeu Fabra, Barcelona, Spain. [Vilar M] Centre de Regulació Genòmica, Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Castellví J] Servei d’Anatomia Patològica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Sánchez-Iglesias JL, Pérez-Benavente A] Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Ginecologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Gil-Moreno A] Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Ginecologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain. [Santamaria A] Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Laboratori de Cicle Cel·lular i Càncer, Grup de Recerca Biomèdica en Urologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Proteomics, Ovarian Neoplasms, Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms [DISEASES], Marcadors tumorals, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], factores biológicos::biomarcadores::marcadores tumorales [COMPUESTOS QUÍMICOS Y DROGAS], Proteins, General Medicine, Ovaris - Càncer - Tractament, neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas [ENFERMEDADES], Other subheadings::Other subheadings::/drug therapy [Other subheadings], General Biochemistry, Genetics and Molecular Biology, Cystadenocarcinoma, Serous, Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma::Cystadenocarcinoma::Cystadenocarcinoma, Serous [DISEASES], Biomarkers, Tumor, Humans, Female, Biological Factors::Biomarkers::Biomarkers, Tumor [CHEMICALS AND DRUGS], neoplasias::neoplasias por tipo histológico::neoplasias glandulares y epiteliales::carcinoma::adenocarcinoma::cistoadenocarcinoma::cistoadenocarcinoma seroso [ENFERMEDADES]
Abstract: Biomarker; Prediction; Proteomics Biomarcador; Predicción; Proteómica Biomarcador; Predicció; Proteòmica Background High-grade serous carcinoma (HGSC) is the most common and deadly subtype of ovarian cancer. Although most patients will initially respond to first-line treatment with a combination of surgery and platinum-based chemotherapy, up to a quarter will be resistant to treatment. We aimed to identify a new strategy to improve HGSC patient management at the time of cancer diagnosis (HGSC-1LTR). Methods A total of 109 ready-available formalin-fixed paraffin-embedded HGSC tissues obtained at the time of HGSC diagnosis were selected for proteomic analysis. Clinical data, treatment approach and outcomes were collected for all patients. An initial discovery cohort (n = 21) were divided into chemoresistant and chemosensitive groups and evaluated using discovery mass-spectrometry (MS)-based proteomics. Proteins showing differential abundance between groups were verified in a verification cohort (n = 88) using targeted MS-based proteomics. A logistic regression model was used to select those proteins able to correctly classify patients into chemoresistant and chemosensitive. The classification performance of the protein and clinical data combinations were assessed through the generation of receiver operating characteristic (ROC) curves. Results Using the HGSC-1LTR strategy we have identified a molecular signature (TKT, LAMC1 and FUCO) that combined with ready available clinical data (patients’ age, menopausal status, serum CA125 levels, and treatment approach) is able to predict patient response to first-line treatment with an AUC: 0.82 (95% CI 0.72–0.92). Conclusions We have established a new strategy that combines molecular and clinical parameters to predict the response to first-line treatment in HGSC patients (HGSC-1LTR). This strategy can allow the identification of chemoresistance at the time of diagnosis providing the optimization of therapeutic decision making and the evaluation of alternative treatment strategies. Thus, advancing towards the improvement of patient outcome and the individualization of HGSC patients’ care. This work was supported by the PhD4MD collaborative research program between the Vall d’Hebron Research Institute (VHIR) and the Centre for Genomic Regulation (CRG). It has been supported by grants from the Instituto Carlos III (PI18/01017), the Miguel Servet Program (CPII18/00027) and the Ministerio de Economía y Competitividad y Fondos FEDER (RTC-2015-3821-1 to AS and CTQ2016-80364-P to ES). This project has also received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 823839 (EPIC-XS).The CRG/UPF Proteomics Unit is part of the Spanish Infrastructure for Omics Technologies (ICTS OmicsTech) and it is supported by “Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya” (2017SGR595 and 2017SGR1661). We also acknowledge support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme / Generalitat de Catalunya.
Published: 2022

17. Pathways Related to NLRP3 Inflammasome Activation Induced by Gold Nanorods

Author: Rob J. Vandebriel, Sylvie Remy, Jolanda P. Vermeulen, Evelien G. E. Hurkmans, Kirsten Kevenaar, Neus G. Bastús, Beatriz Pelaz, Mahmoud G. Soliman, Victor F. Puntes, Wolfgang J. Parak, Jeroen L. A. Pennings, Inge Nelissen, Institut Català de la Salut, [Vandebriel RJ, Vermeulen JP, Hurkmans EGE, Kevenaar K] Centre for Health Protection, National Institute for Public Health & the Environment, Bilthoven, The Netherlands. [Remy S] Health Unit, VITO NV, Mol, Belgium. [Bastús NG] Institut Català de Nanociència i Nanotecnologia (ICN2), Consejo Superior de Investigaciones Científicas (CSIC), The Barcelona Institute of Science and Technology (BIST), Universitat Autònoma de Barcelona, Bellaterra, Spain. [Puntes VF] Institut Català de Nanociència i Nanotecnologia (ICN2), Consejo Superior de Investigaciones Científicas (CSIC), The Barcelona Institute of Science and Technology (BIST), Universitat Autònoma de Barcelona, Bellaterra, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, and European Commission
Subjects: Macromolecular Substances::Multiprotein Complexes::Inflammasomes [CHEMICALS AND DRUGS], Inflammasomes, Technology, Industry, and Agriculture::Manufactured Materials::Nanostructures::Nanoparticles::Metal Nanoparticles [TECHNOLOGY, INDUSTRY, AND AGRICULTURE], oxidative phosphorylation, Metal Nanoparticles, Or, Nanorod, purinergic receptor, tecnología, industria y agricultura::productos manufacturados::nanoestructuras::nanotubos [TECNOLOGÍA, INDUSTRIA Y AGRICULTURA], Catalysis, tecnología, industria y agricultura::productos manufacturados::nanoestructuras::nanopartículas::nanopartículas metálicas [TECNOLOGÍA, INDUSTRIA Y AGRICULTURA], Inorganic Chemistry, NLRP3, NLR Family, Pyrin Domain-Containing 3 Protein, Humans, Oxidative phosphorylation, Physical and Theoretical Chemistry, paraoxonase-2, Molecular Biology, Nanosphere, Paraoxonase-2, Spectroscopy, Technology, Industry, and Agriculture::Manufactured Materials::Nanostructures::Nanotubes [TECHNOLOGY, INDUSTRY, AND AGRICULTURE], Inflammation, Nanotubes, sustancias macromoleculares::complejos multiproteicos::inflamasomas [COMPUESTOS QUÍMICOS Y DROGAS], Nanopartícules, integumentary system, Organic Chemistry, cholesterol, General Medicine, gold, nanorod, Computer Science Applications, nanosphere, Cholesterol, inflammation, nanostar, Gold, Nanotubs, Purinergic receptor, Nanostar
Abstract: The widespread and increasing use of engineered nanomaterials (ENM) increases the risk of human exposure, generating concern that ENM may provoke adverse health effects. In this respect, their physicochemical characteristics are critical. The immune system may respond to ENM through inflammatory reactions. The NLRP3 inflammasome responds to a wide range of ENM, and its activation is associated with various inflammatory diseases. Recently, anisotropic ENM have become of increasing interest, but knowledge of their effects on the immune system is still limited. The objective of the study was to compare the effects of gold ENM of different shapes on NLRP3 inflammasome activation and related signalling pathways. Differentiated THP-1 cells (wildtype, ASC-or NLRP3-deficient), were exposed to PEGylated gold nanorods, nanostars, and nanospheres, and, thus, also different surface chemistries, to assess NLRP3 inflammasome activation. Next, the exposed cells were subjected to gene expression analysis. Nanorods, but not nanostars or nanospheres, showed NLRP3 inflammasome activation. ASC-or NLRP3-deficient cells did not show this effect. Gene Set Enrichment Analysis revealed that gold nanorod-induced NLRP3 inflammasome activation was accompanied by downregulated sterol/cholesterol biosynthesis, oxidative phosphorylation, and purinergic receptor signalling. At the level of individual genes, downregulation of Paraoxonase-2, a protein that controls oxidative stress, was most notable. In conclusion, the shape and surface chemistry of gold nanoparticles determine NLRP3 inflammasome activation. Future studies should include particle uptake and intracellular localization., This research was funded by the EU FP7 project FutureNanoNeeds (GA N° 604602), RIVM, and VITO.
Published: 2022

18. Novel Dent disease 1 cellular models reveal biological processes underlying ClC-5 loss-of-function

Author: Mónica Durán, Carla Burballa, Gema Ariceta, Vivek Malhotra, Anna Meseguer, Gerard Cantero-Recasens, Cristian M. Butnaru, Eduard Sarró, Institut Català de la Salut, [Durán M, Cantero-Recasens G, Sarró E] CIBBIM Nanomedicina-Grup de Recerca en Fisiopatologia Renal, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Burballa C] CIBBIM Nanomedicina-Grup de Recerca en Fisiopatologia Renal, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, Spain. [Butnaru CM] Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, Spain. [Malhotra V] Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, Spain. Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain. [Ariceta G] CIBBIM Nanomedicina-Grup de Recerca en Fisiopatologia Renal, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Nefrologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Meseguer A] CIBBIM Nanomedicina-Grup de Recerca en Fisiopatologia Renal, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Red de Investigación Renal (REDINREN), Instituto de Salud Carlos III-FEDER, Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: AcademicSubjects/SCI01140, Cromosoma X - Anomalies, 0301 basic medicine, Adhesions, Endocytic cycle, Antiporter, Dent Disease, Cell motility, Kidney, enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades genéticas congénitas::enfermedades genéticas ligadas al cromosoma X::enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades genéticas congénitas::enfermedad de Dent [ENFERMEDADES], medicine.disease_cause, Epithelium, Kidney Tubules, Proximal, 0302 clinical medicine, X-linked inheritance, Homeostasis, Chronic, Cell proliferation, Genetics (clinical), Biological Phenomena, Mutation, Dent's disease, Molecular mass, Proximal, Organic acid transport, Genetic Diseases, X-Linked, Cell migration, Extracellular matrix, Ronyons - Malalties, General Medicine, Kidney tubules, Endocytosis, Gene expression profiling, Cell biology, Proteinuria, Nephrocalcinosis, Phenotype, Cell lines, General Article, Malalties congènites, Extracellular matrix organization, Anions, Organic genotype-phenotype associations, Kidney development, Hypercalciuria, Genetic Phenomena::Genetic Variation::Mutation [PHENOMENA AND PROCESSES], Kidney failure, Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Genetic Diseases, X-Linked::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Dent Disease [DISEASES], Biology, Nephrolithiasis, Cell Line, 03 medical and health sciences, Chloride Channels, Albumins, Genetics, medicine, Animals, Humans, Molecular Biology, Genetic Association Studies, fenómenos genéticos::variación genética::mutación [FENÓMENOS Y PROCESOS], urogenital system, medicine.disease, Anion homeostasis, 030104 developmental biology, Genes, Acids, 030217 neurology & neurosurgery
Abstract: Dent disease 1; Cellular models Enfermedad de Dent 1; Modelos celulares Malaltia de Dent 1; Models cel·lulars Dent disease 1 (DD1) is a rare X-linked renal proximal tubulopathy characterized by low molecular weight proteinuria and variable degree of hypercalciuria, nephrocalcinosis and/or nephrolithiasis, progressing to chronic kidney disease. Although mutations in the electrogenic Cl−/H+ antiporter ClC-5, which impair endocytic uptake in proximal tubule cells, cause the disease, there is poor genotype–phenotype correlation and their contribution to proximal tubule dysfunction remains unclear. To further discover the mechanisms linking ClC-5 loss-of-function to proximal tubule dysfunction, we have generated novel DD1 cellular models depleted of ClC-5 and carrying ClC-5 mutants p.(Val523del), p.(Glu527Asp) and p.(Ile524Lys) using the human proximal tubule-derived RPTEC/TERT1 cell line. Our DD1 cellular models exhibit impaired albumin endocytosis, increased substrate adhesion and decreased collective migration, correlating with a less differentiated epithelial phenotype. Despite sharing functional features, these DD1 cell models exhibit different gene expression profiles, being p.(Val523del) ClC-5 the mutation showing the largest differences. Gene set enrichment analysis pointed to kidney development, anion homeostasis, organic acid transport, extracellular matrix organization and cell-migration biological processes as the most likely involved in DD1 pathophysiology. In conclusion, our results revealed the pathways linking ClC-5 mutations with tubular dysfunction and, importantly, provide new cellular models to further study DD1 pathophysiology. This work was supported in part by Asdent Patients Association and grants from Ministerio de Ciencia e Innovación (SAF201459945-R and SAF201789989-R to A.M.), the Fundación Senefro (SEN2019 to A.M.) and Red de Investigación Renal REDinREN (12/0021/0013). A.M. group holds the Quality Mention from the Generalitat de Catalunya (2017 SGR).
Published: 2021
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19. TFIIIC as a Potential Epigenetic Modulator of Histone Acetylation in Human Stem Cells

Author: Marco Vezzoli, Lara Isabel de Llobet Cucalon, Chiara Di Vona, Marco Morselli, Barbara Montanini, Susana de la Luna, Martin Teichmann, Giorgio Dieci, Roberto Ferrari, Institut Català de la Salut, [Vezzoli M, Morselli M, Montanini B] Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy. [de Llobet Cucalon LI] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Di Vona C] Genome Biology Program, Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST) and Universitat Pompeu Fabra (UPF), Barcelona, Spain. CIBER of Rare Diseases (CIBERER), Barcelona, Spain. [de la Luna S] Genome Biology Program, Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST) and Universitat Pompeu Fabra (UPF), Barcelona, Spain. CIBER of Rare Diseases (CIBERER), Barcelona, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: fenómenos genéticos::regulación de la expresión génica::epigénesis genética [FENÓMENOS Y PROCESOS], células::células madre::células madre pluripotentes::células madre embrionarias::células madre embrionarias humanas [ANATOMÍA], Neurogenesis, Cells::Stem Cells::Pluripotent Stem Cells::Embryonic Stem Cells::Human Embryonic Stem Cells [ANATOMY], p300, Catalysis, Epigènesi, neoplasias [ENFERMEDADES], Inorganic Chemistry, Physical and Theoretical Chemistry, Molecular Biology, TFIIIC, Otros calificadores::/terapia [Otros calificadores], Spectroscopy, Cèl·lules mare embrionàries, Càncer - Tractament, Organic Chemistry, Acetylation, Other subheadings::/therapy [Other subheadings], General Medicine, H3K27ac, Computer Science Applications, Neoplasms [DISEASES], H3K18ac, Genetic Phenomena::Gene Expression Regulation::Epigenesis, Genetic [PHENOMENA AND PROCESSES], hESCs
Abstract: Acetylation; Neurogenesis Acetilación; Neurogénesis Acetilació; Neurogènesi Regulation of histone acetylation dictates patterns of gene expression and hence cell identity. Due to their clinical relevance in cancer biology, understanding how human embryonic stem cells (hESCs) regulate their genomic patterns of histone acetylation is critical, but it remains largely to be investigated. Here, we provide evidence that acetylation of histone H3 lysine-18 (H3K18ac) and lysine-27 (H3K27ac) is only partially established by p300 in stem cells, while it represents the main histone acetyltransferase (HAT) for these marks in somatic cells. Our analysis reveals that whereas p300 marginally associated with H3K18ac and H3K27ac in hESCs, it largely overlapped with these histone marks upon differentiation. Interestingly, we show that H3K18ac is found at “stemness” genes enriched in RNA polymerase III transcription factor C (TFIIIC) in hESCs, whilst lacking p300. Moreover, TFIIIC was also found in the vicinity of genes involved in neuronal biology, although devoid of H3K18ac. Our data suggest a more complex pattern of HATs responsible for histone acetylations in hESCs than previously considered, suggesting a putative role for H3K18ac and TFIIIC in regulating “stemness” genes as well as genes associated with neuronal differentiation of hESCs. The results break ground for possible new paradigms for genome acetylation in hESCs that could lead to new avenues for therapeutic intervention in cancer and developmental diseases. This work was supported by Bando Galileo 2022 (G22-142) to R.F. and M.T. The research is also supported by the AIRC IG Grant 27712-A to R.F. This work was also supported by the Spanish Ministry of Science and Innovation (PID2019-107185GB-I00) to S.d.l.L. The CRG acknowledge the support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the support of the CERCA Programme/Generalitat de Catalunya. This work was also supported by the Ligue Contre le Cancer, committees des Landes et de la Dordogne to M.T.
Published: 2023
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20. Nanoceria dissolution at acidic pH by breaking off the catalytic loop

Author: Dmitry Galyamin, Lena M. Ernst, Aina Fitó-Parera, Guillem Mira-Vidal, Neus G. Bastús, Neus Sabaté, Victor Puntes, European Research Council, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Generalitat de Catalunya, Universidad Autónoma de Barcelona, Institut Català de la Salut, [Galyamin D, Fitó-Parera A] Institut de Microelectrònica de Barcelona, IMB-CNM (CSIC). C/dels Til·lers, Campus Universitat Autònoma de Barcelona, Bellaterra, Spain. [Ernst LM] Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Mira-Vidal G, Bastús NG] Instiut Català de Nanociència I Nanotecnologia (ICN2), CSIC and The Barcelona Institute of Science and Technology (BIST). Campus UAB, Barcelona, Spain. [Sabaté N] Institut de Microelectrònica de Barcelona, IMB-CNM (CSIC). C/dels Til·lers, Campus Universitat Autònoma de Barcelona, Bellaterra, Spain. Institució Catalana de Recerca I Estudis Avançats (ICREA), Barcelona, Spain. [Puntes V] Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d'Hebron Hospital Universitari, Barcelona, Spain. Instiut Català de Nanociència I Nanotecnologia (ICN2), CSIC and The Barcelona Institute of Science and Technology (BIST). Campus UAB, Barcelona, Spain. Institució Catalana de Recerca I Estudis Avançats (ICREA), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Chemical Phenomena::Oxidation-Reduction [PHENOMENA AND PROCESSES], Technology, Industry, and Agriculture::Manufactured Materials::Nanostructures::Nanoparticles [TECHNOLOGY, INDUSTRY, AND AGRICULTURE], Nanopartícules, Farmacocinètica, Reacció d'oxidació-reducció, Physiological Phenomena::Pharmacological and Toxicological Phenomena::Pharmacokinetics [PHENOMENA AND PROCESSES], fenómenos químicos::oxidación-reducción [FENÓMENOS Y PROCESOS], fenómenos fisiológicos::fenómenos farmacológicos y toxicológicos::farmacocinética [FENÓMENOS Y PROCESOS], tecnología, industria y agricultura::productos manufacturados::nanoestructuras::nanopartículas [TECNOLOGÍA, INDUSTRIA Y AGRICULTURA], General Materials Science
Abstract: This manuscript proves the reproducibility and robustness of cerium oxide nanoparticles, nanoceria, employed as a chemical reagent with oxidizing capacity (as an electron sink) at acidic pH. Unlike nanoceria multi-enzyme-mimetic capabilities at neutral or high pH, nanoceria can behave as a stoichiometric reagent at low pH where insoluble Ce4+ ions transform into soluble Ce3+ in the nanocrystal that finally dissolves. This behaviour can be interpreted as enzyme-like when nanoceria is in excess with respect to the substrate. Under these conditions, the Ce3+/Ce4+ ratio in the NPs can easily be estimated by titration with ferrocyanide. This procedure could become a rapid assessment tool for evaluating nanoceria capacity in liquid environments., N. Sabaté would like to acknowledge the financial support received from ERC Consolidator Grant (SUPERCELL – GA.648518). N. G. B and V. P. acknowledge financial support from the Spanish Ministerio de Ciencia, Innovación y Universidades (MCIU) (RTI2018-099965-B-I00, AEI/FEDER,UE) proyectos de I + D + i de programación conjunta internacional MCIN/AEI (CONCORD, PCI2019-103436) cofunded by the European Union and Generalitat de Catalunya (2017-SGR-1431). ICN2 is supported by the Severo Ochoa program from Spanish MINECO (SEV-2017-0706) and is funded by the CERCA Programme/Generalitat de Catalunya. Dmitry Galyamin thanks the doctoral program “Electroquímica. Ciència i Tecnologia” of the Universitat Autònoma de Barcelona (UAB).
Published: 2022

21. The trophectoderm acts as a niche for the inner cell mass through C/EBPα-regulated IL-6 signaling

Author: Marcos Plana-Carmona, Gregoire Stik, Romain Bulteau, Carolina Segura-Morales, Noelia Alcázar, Chris D.R. Wyatt, Antonios Klonizakis, Luisa de Andrés-Aguayo, Maxime Gasnier, Tian V. Tian, Guillem Torcal Garcia, Maria Vila-Casadesús, Nicolas Plachta, Manuel Serrano, Mirko Francesconi, Thomas Graf, Institut Català de la Salut, [Plana-Carmona M, Stik G, Segura-Morales C] Gene Regulation, Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Spain. [Bulteau R] Laboratoire de Biologie et Modélisation de la Cellule, Université de Lyon, Lyon, France. [Alcázar N] Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Wyatt CDR] Gene Regulation, Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Spain. Department of Genetics, Evolution & Environment, University College London, London, UK. [Tian TV] Gene Regulation, Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Vila-Casadesús M] Gene Regulation, Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Embryology, factores biológicos::péptidos y proteínas de señalización intercelular::citocinas::interleucinas::interleucina-6 [COMPUESTOS QUÍMICOS Y DROGAS], INNER CELL MASS, Embryonic Development, Pre-implantation embryo development, Biochemistry, Morula, Interleucina-6, Genetics, CCAAT-Enhancer-Binding Protein-alpha, TRANSDIFFERENTIATION, Gene Regulation, Physiological Phenomena::Growth and Development::Morphogenesis::Embryonic and Fetal Development::Embryonic Development [PHENOMENA AND PROCESSES], Fisiologia cel·lular, Transdifferentiation, C/EBP transcription factor, Embriologia, Interleukin-6, somatic cell reprogramming, Cell Biology, Gene regulation, Blastocyst, pre-implantation embryo development, Biological Factors::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins::Interleukin-6 [CHEMICALS AND DRUGS], estructuras embrionarias::mórula [ANATOMÍA], Trophectoderm, IL-6 signaling, Inner cell mass, Embryonic Structures::Morula [ANATOMY], fenómenos fisiológicos::crecimiento y desarrollo::morfogénesis::desarrollo embrionario y fetal::desarrollo embrionario [FENÓMENOS Y PROCESOS], Somatic cell reprogramming, Developmental Biology
Abstract: Gene regulation; Somatic cell reprogramming; Trophectoderm Regulación de genes; Reprogramación de células somáticas; Trofoectodermo Regulació de gens; Reprogramació de cèl·lules somàtiques; Trofectoderma IL-6 has been shown to be required for somatic cell reprogramming into induced pluripotent stem cells (iPSCs). However, how Il6 expression is regulated and whether it plays a role during embryo development remains unknown. Here, we describe that IL-6 is necessary for C/EBPα-enhanced reprogramming of B cells into iPSCs but not for B cell to macrophage transdifferentiation. C/EBPα overexpression activates both Il6 and Il6ra genes in B cells and in PSCs. In embryo development, Cebpa is enriched in the trophectoderm of blastocysts together with Il6, while Il6ra is mostly expressed in the inner cell mass (ICM). In addition, Il6 expression in blastocysts requires Cebpa. Blastocysts secrete IL-6 and neutralization of the cytokine delays the morula to blastocyst transition. The observed requirement of C/EBPα-regulated IL-6 signaling for pluripotency during somatic cell reprogramming thus recapitulates a physiologic mechanism in which the trophectoderm acts as niche for the ICM through the secretion of IL-6. We thank C. Berenguer for help with B cell reprogramming and bone marrow collection; S. Nakagawa and B. Pernaute for advice on pre-implantation embryo culture and manipulation, and Kyle M. Loh for his valuable discussions; the flow cytometry and microscopy units of UPF-CRG for technical assistance; the CRG genomics core facility for sequencing and Graf laboratory members for critical discussions. Work in the laboratory of T.G. was supported by the Spanish Ministry of Economy, Industry and Competitiveness (Plan Estatal PID2019-109354GB-I00), the CRG, AGAUR (SGR 726), and a European Research Council Synergy grant (4D-Genome). M.P.-C. was supported by an FPI fellowship (BES-2016-076900). Work in the laboratory of M.S. was funded by the IRB and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund (SAF2017-82613-R), ERC (ERC-2014-AdG/669622), la Caixa Foundation, and Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement of Catalonia (Grup de Recerca consolidat 2017 SGR 282).
Published: 2022

22. BRCA1 mutations in high-grade serous ovarian cancer are associated with proteomic changes in DNA repair, splicing, transcription regulation and signaling

Author: Bradbury, Melissa, Castellvi, Josep, Méndez Fernández, Olga, Sanchez Iglesias, Jose Luis, Pérez-Benavente, Assumpció, Gil-Moreno, Antonio, Sabidó, Eduard, Santamaría, Anna, Borràs, Eva, Universitat Autònoma de Barcelona. Vall d'Hebron Institut de Recerca (VHIR), Institut Català de la Salut, [Bradbury M] Proteomics Unit, Centre de Regulació Genòmica, Barcelona Institute of Science and Technology (BIST), 08003 Barcelona, Spain. Universitat Pompeu Fabra, 08003 Barcelona, Spain. Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Ginecologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Borràs E, Sabidó E] Proteomics Unit, Centre de Regulació Genòmica, Barcelona Institute of Science and Technology (BIST), 08003 Barcelona, Spain. Universitat Pompeu Fabra, 08003 Barcelona, Spain. [Castellví J] Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Méndez O] Laboratori de Cicle Cel•lular i Càncer, Grup de Recerca Biomèdica en Urologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Sánchez-Iglesias JL, Pérez-Benavente A] Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Ginecologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Gil-Moreno A] Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Ginecologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain. [Santamaria A] Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Laboratori de Cicle Cel•lular i Càncer, Grup de Recerca Biomèdica en Urologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Ovarian Neoplasms, Proteomics, ADN - Reparació, Multidisciplinary, Genetic Phenomena::DNA Repair [PHENOMENA AND PROCESSES], DNA Repair, BRCA1 Protein, Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms [DISEASES], Mutació (Biologia), Genetic Phenomena::Genetic Variation::Mutation [PHENOMENA AND PROCESSES], neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas [ENFERMEDADES], Ovaris -- Càncer, fenómenos genéticos::reparación del ADN [FENÓMENOS Y PROCESOS], Cystadenocarcinoma, Serous, Genòmica, Ovaris - Càncer, Ovarian cancer, Mutation, Humans, Female, fenómenos genéticos::variación genética::mutación [FENÓMENOS Y PROCESOS], Genètica
Abstract: Ovarian cancer; Proteomics Cáncer de ovarios: Proteómica Càncer d'ovaris; Proteòmica Despite recent advances in the management of BRCA1 mutated high-grade serous ovarian cancer (HGSC), the physiology of these tumors remains poorly understood. Here we provide a comprehensive molecular understanding of the signaling processes that drive HGSC pathogenesis with the addition of valuable ubiquitination profiling, and their dependency on BRCA1 mutation-state directly in patient-derived tissues. Using a multilayered proteomic approach, we show the tight coordination between the ubiquitination and phosphorylation regulatory layers and their role in key cellular processes related to BRCA1-dependent HGSC pathogenesis. In addition, we identify key bridging proteins, kinase activity, and post-translational modifications responsible for molding distinct cancer phenotypes, thus providing new opportunities for therapeutic intervention, and ultimately advance towards a more personalized patient care. This work was supported by the PhD4MD collaborative research program between the Vall d’Hebron Research Institute (VHIR) and the Centre for Genomic Regulation (CRG). The CRG/UPF Proteomics Unit is part of the Spanish Infrastructure for Omics Technologies (ICTS OmicsTech) and it is a member of the ProteoRed PRB3 consortium which is supported by grant PT17/0019 of the PE I+D+i 2013-2016 from the Instituto de Salud Carlos III (ISCIII) and ERDF. We acknowledge support from the Spanish Ministry of Science, Innovation and Universities, (CTQ2016-80364-P and “Centro de Excelencia Severo Ochoa 2013-2017”, SEV-2012-0208), and “Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya” (2017SGR595 and 2017SGR1661). This project has also received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 823839 (EPIC-XS). It has also been supported by grants from the Instituto Carlos III (PI15/00238, PI18/01017, PI21/00977), the Miguel Servet Program (CP13/00158 and CPII18/00027) and the Ministerio de Economía y Competitividad y Fondos FEDER (RTC-2015-3821-1). The authors are grateful to the team members of the Proteomics Unit at the Centre for Genomic Regulation, the Biomedical Research Group in Gynecology at the Vall d’Hebron Institute, the Gynecological Oncology Unit at the Vall d’Hebron Hospital and the Biomedical Research Group in Urology at the Vall d’Hebron Institute for their assistance.
Published: 2022

23. Innate Memory Reprogramming by Gold Nanoparticles Depends on the Microbial Agents That Induce Memory

Author: Swartzwelter, Benjamin J., Michelini, Sara, Frauenlob, Tobias, Barbero, Francesco, Verde, Alessandro, De Luca, Anna Chiara, Franco Puntes, Victor, Institut Català de la Salut, [Swartzwelter BJ] Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Napoli, Italy. Department Biosciences, Paris Lodron University of Salzburg (PLUS), Salzburg, Austria. [Michelini S, Frauenlob T] Department Biosciences, Paris Lodron University of Salzburg (PLUS), Salzburg, Austria. [Barbero F] Institut Català de Nanociència i Nanotecnologia (ICN2), Consejo Superior de Investigaciones Científicas (CSIC) and The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. [Verde A, De Luca AC] Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Napoli, Italy. [Puntes V] Institut Català de Nanociència i Nanotecnologia (ICN2), Consejo Superior de Investigaciones Científicas (CSIC) and The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Institució Catalana de Recerca I Estudis Avançats (ICREA), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Otros calificadores::Otros calificadores::/administración & dosificación [Otros calificadores], Memòria - Efecte dels medicaments, Nanopartícules, Hemic and Immune Systems::Blood::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Hemic and Immune Systems::Hemic and Immune Systems::Hemic and Immune Systems::Hemic and Immune Systems::Monocytes [ANATOMY], Monòcits - Immunologia, Technology, Industry, and Agriculture::Manufactured Materials::Nanostructures::Nanoparticles::Metal Nanoparticles [TECHNOLOGY, INDUSTRY, AND AGRICULTURE], Other subheadings::Other subheadings::/administration & dosage [Other subheadings], sistemas sanguíneo e inmunológico::sangre::células sanguíneas::leucocitos::leucocitos mononucleares::sistemas sanguíneo e inmunológico::sistemas sanguíneo e inmunológico::sistemas sanguíneo e inmunológico::sistemas sanguíneo e inmunológico::monocitos [ANATOMÍA], Immune System Phenomena::Immunity::Adaptive Immunity::Immunologic Memory [PHENOMENA AND PROCESSES], fenómenos del sistema inmunitario::inmunidad::inmunidad adaptativa::memoria inmunológica [FENÓMENOS Y PROCESOS], tecnología, industria y agricultura::productos manufacturados::nanoestructuras::nanopartículas::nanopartículas metálicas [TECNOLOGÍA, INDUSTRIA Y AGRICULTURA]
Abstract: Inmunidad innata; Agentes microbianos; Nanopartículas Innate immunity; Microbial agents; Nanoparticles Immunitat innata; Agents microbians; Nanopartícules Innate immune memory, the ability of innate cells to react in a more protective way to secondary challenges, is induced by exposure to infectious and other exogeous and endogenous agents. Engineered nanoparticles are particulate exogenous agents that, as such, could trigger an inflammatory reaction in monocytes and macrophages and could therefore be also able to induce innate memory. Here, we have evaluated the capacity of engineered gold nanoparticles (AuNPs) to induce a memory response or to modulate the memory responses induced by microbial agents. Microbial agents used were in soluble vs. particulate form (MDP and the gram-positive bacteria Staphylococcus aureus; β-glucan and the β-glucan-producing fungi C. albicans), and as whole microrganisms that were either killed (S. aureus, C. albicans) or viable (the gram-negative bacteria Helicobacter pylori). The memory response was assessed in vitro, by exposing human primary monocytes from 2-7 individual donors to microbial agents with or without AuNPs (primary response), then resting them for 6 days to allow return to baseline, and eventually challenging them with LPS (secondary memory response). Primary and memory responses were tested as production of the innate/inflammatory cytokine TNFα and other inflammatory and anti-inflammatory factors. While inactive on the response induced by soluble microbial stimuli (muramyl dipeptide -MDP-, β-glucan), AuNPs partially reduced the primary response induced by whole microorganisms. AuNPs were also unable to directly induce a memory response but could modulate stimulus-induced memory in a circumscribed fashion, limited to some agents and some cytokines. Thus, the MDP-induced tolerance in terms of TNFα production was further exacerbated by co-priming with AuNPs, resulting in a less inflammatory memory response. Conversely, the H. pylori-induced tolerance was downregulated by AuNPs only relative to the anti-inflammatory cytokine IL-10, which would lead to an overall more inflammatory memory response. These effects of AuNPs may depend on a differential interaction/association between the reactive particle surfaces and the microbial components and agents, which may lead to a change in the exposure profiles. As a general observation, however, the donor-to-donor variability in memory response profiles and reactivity to AuNPs was substantial, suggesting that innate memory depends on the individual history of exposures. This work was supported by the EU Commission H2020 projects PANDORA (GA 671881) and ENDONANO (GA 812661), the Italian MIUR InterOmics Flagship projects MEMORAT and MAME, the Italian MIUR/PRIN-20173ZECCM, the Priority program ACBN (Allergy Cancer BioNano Research Centre) of the University of Salzburg, the Cancer Cluster Salzburg, the Research Grant from the University of Salzburg, and the Austrian Science Fund (FWF) Grant Nr. P 29941.
Published: 2021

24. A new BiofilmChip device for testing biofilm formation and antibiotic susceptibility

Author: Josep Samitier, María Teresa Martín-Gómez, Núria Blanco-Cabra, Betsy Verónica Arévalo-Jaimes, Maria Jose Lopez-Martinez, Eduard Torrents, Institut Català de la Salut, [Blanco-Cabra N, Arévalo-Jaimes BV] Bacterial Infections and Antimicrobial Therapies Group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. [López-Martínez MJ, Samitier J] Nanobioengineering Group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) Madrid, Spain. Department of Electronics and Biomedical Engineering, University of Barcelona, Barcelona, Spain. [Martin-Gómez MT] Servei de Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Torrents E] Bacterial Infections and Antimicrobial Therapies Group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. Microbiology Section, Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Staphylococcus aureus, medicine.drug_class, Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Microbiological Techniques::Bacteriological Techniques [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Microfluidics, Antibiotics, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Microbial Sensitivity Tests, Microbiologia - Tècnica, infecciones bacterianas y micosis::infecciones bacterianas [ENFERMEDADES], acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antibacterianos [COMPUESTOS QUÍMICOS Y DROGAS], Other subheadings::Other subheadings::/drug therapy [Other subheadings], Applied Microbiology and Biotechnology, Microbiology, Article, Microbial ecology, Antibiotic resistance, Anti-Infective Agents, medicine, Malalties bacterianes - Tractament, Humans, Medicaments antibacterians - Ús terapèutic, New device, Bacterial Infections and Mycoses::Bacterial Infections [DISEASES], Clinical microbiology, Electrical impedance spectroscopy, Bacteriological Techniques, diagnóstico::técnicas y procedimientos diagnósticos::técnicas de laboratorio clínico::técnicas microbiológicas::técnicas bacteriológicas [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Chemistry, QR100-130, Infectious-disease diagnostics, Biological techniques, Health care, Biofilm, Bacterial Infections, Mycobacterium tuberculosis, Drug susceptibility, Antimicrobial, Anti-Bacterial Agents, Homogeneous, Biofilms, Pseudomonas aeruginosa, Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial Agents [CHEMICALS AND DRUGS], Delivery of Health Care, Laboratories, Clinical, Biotechnology
Abstract: Biofilms; Microbiologia clínica; Diagnòstic de malalties infeccioses Biofilms; Microbiología clínica; Diagnóstico de enfermedades infecciosas Biofilms; Clinical microbiology; Infectious-disease diagnostics Currently, three major circumstances threaten the management of bacterial infections: increasing antimicrobial resistance, expansion of chronic biofilm-associated infections, and lack of an appropriate approach to treat them. To date, the development of accelerated drug susceptibility testing of biofilms and of new antibiofouling systems has not been achieved despite the availability of different methodologies. There is a need for easy-to-use methods of testing the antibiotic susceptibility of bacteria that form biofilms and for screening new possible antibiofilm strategies. Herein, we present a microfluidic platform with an integrated interdigitated sensor (BiofilmChip). This new device allows an irreversible and homogeneous attachment of bacterial cells of clinical origin, even directly from clinical specimens, and the biofilms grown can be monitored by confocal microscopy or electrical impedance spectroscopy. The device proved to be suitable to study polymicrobial communities, as well as to measure the effect of antimicrobials on biofilms without introducing disturbances due to manipulation, thus better mimicking real-life clinical situations. Our results demonstrate that BiofilmChip is a straightforward tool for antimicrobial biofilm susceptibility testing that could be easily implemented in routine clinical laboratories. We thank Prof. Tim Tolker-Nielsen from Costerton Biofilm Center, University of Copenhagen, for providing the P. aeruginosa MK171 strain. This work was supported in part through grants to ET from the Ministerio de Ciencia, Innovación y Universidades (BIO2015-63557-R and RTI2018-098573-B-100) (MINECO/FEDER), the Generalitat de Catalunya (2017 SGR1079 and CERCA program), and the Spanish Cystic Fibrosis Foundation and La Caixa Foundation. The authors want to acknowledge MicroFabSpace and the Microscopy Characterization Facility, Unit 7 of ICTS “NANBIOSIS” from CIBER-BBN at IBEC. This research was supported by the Networking Biomedical Research Center (CIBER), Spain. CIBER is an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, and the Instituto de Salud Carlos III (RD16/0006/0012), with the support of the European Regional Development Fund. This work was funded by the CERCA Programme and by the Commission for Universities and Research of the Department of Innovation, Universities, and Enterprise of the Generalitat de Catalunya (2017 SGR 1079). This work was developed in the context of AdvanceCat and Base3D with the support of ACCIÓ (Catalonia Trade and Investment; Generalitat de Catalunya) under the Catalonian ERDF operational program (European Regional Development Fund) 2014–2020. This work was funded by the Spanish Ministry of Economy and Competitiveness (MINECO) through the projects MINDS (Proyectos I+D Excelencia + FEDER): TEC2015-70104-P, CTQ2016-75870-P.
Published: 2021

25. Combining microfluidics with machine learning algorithms for RBC classification in rare hereditary hemolytic anemia

Author: Maria Jose Lopez-Martinez, Josep Samitier, Eugenio Martinelli, Begoña Álvarez-González, David Beneitez-Pastor, Davide Di Giuseppe, Valeria Rizzuto, Arianna Mencattini, Maria del Mar Mañú-Pereira, Institut Català de la Salut, [Rizzuto V] Josep Carreras Leukaemia Research Institute (IJC), 08916 Badalona, Spain. Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology BIST, 08028 Barcelona, Spain. Department of Medicine, University of Barcelona, 08036 Barcelona, Spain. [Mencattini A, Di Giuseppe D, Martinelli E] Department of Electronic Engineering, University of Rome Tor Vergata, 00133 Rome, Italy. University of Rome Tor Vergata, Interdisciplinary Center for Advanced Studies on Lab-on-Chip and Organ-on-Chip Applications (ICLOC), 00133 Rome, Italy. [Álvarez-González B] Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology BIST, 08028 Barcelona, Spain. Centro de Investigacion Biomedica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain. [Beneitez-Pastor D] Unitat de Trastorns de Glòbuls Vermells, Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Grup de Recerca Translacional en Càncer en la Infància i l’Adolescència, Línia de recerca de Trastorns d'Anèmia Rara, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. ERN-EuroBloodNet Member, 08035 Barcelona, Spain. [Mañú-Pereira MDM] Grup de Recerca Translacional en Càncer en la Infància i l’Adolescència, Línia de recerca de Trastorns d'Anèmia Rara, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. ERN-EuroBloodNet Member, 08035 Barcelona, Spain., and Vall d'Hebron Barcelona Hospital Campus
Subjects: técnicas de investigación::procedimientos analíticos con microchip::técnicas analíticas microfluídicas [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], 0301 basic medicine, Male, Erythrocytes, Computer science, Microfluidics, Anèmia, computer.software_genre, Settore ING-INF/07, Machine Learning, 0302 clinical medicine, Lab-On-A-Chip Devices, Image Processing, Computer-Assisted, Multidisciplinary, Intel·ligència artificial, Processament d'imatges, Anemia, Microfluidic Analytical Techniques, medicine.anatomical_structure, Hematies, 030220 oncology & carcinogenesis, Red pulp, Medicine, Female, Information Science::Computing Methodologies::Algorithms::Artificial Intelligence::Machine Learning [INFORMATION SCIENCE], Science, Anaemia, Machine learning, Hereditary Hemolytic Anemia, Anemia, Hemolytic, Congenital, Article, 03 medical and health sciences, Image processing, Anèmia hemolítica - Diagnòstic, Investigative Techniques::Microchip Analytical Procedures::Microfluidic Analytical Techniques [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Erythrocyte Deformability, medicine, In vitro study, Humans, enfermedades hematológicas y linfáticas::enfermedades hematológicas::anemia::anemia hemolítica::anemia hemolítica congénita [ENFERMEDADES], business.industry, Hemic and Lymphatic Diseases::Hematologic Diseases::Anemia::Anemia, Hemolytic::Anemia, Hemolytic, Congenital [DISEASES], Sickle cell disease, Microfluídica, Ciencias de la información::metodologías computacionales::algoritmos::inteligencia artificial::aprendizaje automático [CIENCIA DE LA INFORMACIÓN], 030104 developmental biology, Artificial intelligence, business, computer
Abstract: Anemia; Microfluídica; Enfermedad de células falciformes Anèmia; Microfluídica; Malaltia de cèl·lules falciformes Anaemia; Microfluidics; Sickle cell disease Combining microfluidics technology with machine learning represents an innovative approach to conduct massive quantitative cell behavior study and implement smart decision-making systems in support of clinical diagnostics. The spleen plays a key-role in rare hereditary hemolytic anemia (RHHA), being the organ responsible for the premature removal of defective red blood cells (RBCs). The goal is to adapt the physiological spleen filtering strategy for in vitro study and monitoring of blood diseases through RBCs shape analysis. Then, a microfluidic device mimicking the slits of the spleen red pulp area and video data analysis are combined for the characterization of RBCs in RHHA. This microfluidic unit is designed to evaluate RBC deformability by maintaining them fixed in planar orientation, allowing the visual inspection of RBC’s capacity to restore their original shape after crossing microconstrictions. Then, two cooperative learning approaches are used for the analysis: the majority voting scheme, in which the most voted label for all the cell images is the class assigned to the entire video; and the maximum sum of scores to decide the maximally scored class to assign. The proposed platform shows the capability to discriminate healthy controls and patients with an average efficiency of 91%, but also to distinguish between RHHA subtypes, with an efficiency of 82%. This work was supported by Networking Biomedical Research Center (CIBER), Spain. CIBER is an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, and the Instituto de Salud Carlos III (RD16/0006/0012), with the support of the European Regional Development Fund. This work was funded by the European Commission H2020-MSCA-ITN-2019, Grant Agreement N860436, “EVIDENCE” and by the CERCA Programme and by the Commission for Universities and Research of the Department of Innovation, Universities, and Enterprise of the Generalitat de Catalunya (2017 SGR 1079), it has been developed in the context of AdvanceCat with the support of ACCIÓ (Catalonia Trade and Investment; Generalitat de Catalunya) under the Catalonian ERDF operational program (European Regional Development Fund) 2014–2020.
Published: 2021

26. Proteomic Studies on the Management of High-Grade Serous Ovarian Cancer Patients: A Mini-Review

Author: Anna Santamaria, Assumpció Pérez-Benavente, Eduard Sabidó, Antonio Gil-Moreno, Melissa Bradbury, Eva Borràs, Institut Català de la Salut, [Bradbury M] Centre de Regulació Genòmica, Barcelona Institute of Science and Technology (BIST), Dr Aiguader 88, 08003 Barcelona, Spain. Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Dr Aiguader 88, 08003 Barcelona, Spain. Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Unitat d'Oncologia Ginecològica, Servei de Ginecologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Borràs E, Sabidó E] Centre de Regulació Genòmica, Barcelona Institute of Science and Technology (BIST), Dr Aiguader 88, 08003 Barcelona, Spain. Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Dr Aiguader 88, 08003 Barcelona, Spain. [Pérez-Benavente A] Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Unitat d'Oncologia Ginecològica, Servei de Ginecologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Gil-Moreno A] Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Unitat d'Oncologia Ginecològica, Servei de Ginecologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red (CIBERONC), Instituto de Salud Carlos III, Avenida de Monforte de Lemos 3-5, 28029 Madrid, Spain. [Santamaria A] Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Laboratori de Cicle Cel·lular i Càncer, Grup de Recerca Biomèdica en Urologia, Vall Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: 0301 basic medicine, Oncology, Proteomics, Cancer Research, medicine.medical_specialty, Ovaris - Càncer -Tractament, medicine.medical_treatment, Genomics, Disease, Review, Proteòmica, neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas [ENFERMEDADES], Ovaris -- Càncer, Mini review, 03 medical and health sciences, 0302 clinical medicine, proteomics, Natural Science Disciplines::Biological Science Disciplines::Biochemistry::Proteomics [DISCIPLINES AND OCCUPATIONS], Ovarian cancer, Internal medicine, medicine, Serous ovarian cancer, genomics, RC254-282, Otros calificadores::/terapia [Otros calificadores], mass spectrometry, Chemotherapy, Mass spectrometry, business.industry, Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms [DISEASES], disciplinas de las ciencias naturales::disciplinas de las ciencias biológicas::bioquímica::proteómica [DISCIPLINAS Y OCUPACIONES], Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Biomarker, Other subheadings::/therapy [Other subheadings], medicine.disease, 030104 developmental biology, ovarian cancer, 030220 oncology & carcinogenesis, Biomarker (medicine), biomarker, business, Cancer tissue, cancer tissue
Abstract: Teixit cancerígen; Càncer d'ovaris; Proteòmica Tejido canceroso; Cáncer de ovarios; Proteómica Cancer tissue; Ovarian cancer; Proteomics High-grade serous ovarian cancer (HGSC) remains the most common and deadly subtype of ovarian cancer. It is characterized by its late diagnosis and frequent relapse despite standardized treatment with cytoreductive surgery and platinum-based chemotherapy. The past decade has seen significant advances in the clinical management and molecular understanding of HGSC following the publication of the Cancer Genome Atlas (TCGA) researchers and the introduction of targeted therapies with anti-angiogenic drugs and poly(ADP-ribose) polymerase inhibitors in specific subgroups of patients. We provide a comprehensive review of HGSC, focusing on the most important molecular advances aimed at providing a better understanding of the disease and its response to treatment. We emphasize the role that proteomic technologies are now playing in these two aspects of the disease, through the identification of proteins and their post-translational modifications in ovarian cancer tumors. Finally, we highlight how the integration of proteomics with genomics, exemplified by the work performed by the Clinical Proteomic Tumor Analysis Consortium (CPTAC), can guide the development of new biomarkers and therapeutic targets. This work was supported by the PhD4MD collaborative research program between the Vall d’Hebron Research Institute (VHIR) and the Centre for Genomic Regulation (CRG). The CRG/UPF Proteomics Unit is part of the Spanish Infrastructure for Omics Technologies (ICTS OmicsTech) and it is a member of the ProteoRed PRB3 consortium which is supported by grant PT17/0019 of the PE I + D + i 2013–2016 from the Instituto de Salud Carlos III (ISCIII) and ERDF. We acknowledge support from the Spanish Ministry of Science and Innovation (CTQ2016-80364-P) and “Centro de Excelencia Severo Ochoa 2013–2017”, SEV-2012-0208; the “Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya” (2017SGR595 and 2017SGR1661), from the Instituto de Salud Carlos III (PI15/02238, PI18/01017, CPII18/00027) and from the Ministerio de Economia y Competitividad y Fondos FEDER (RTC-2015-3821). We also acknowledge the support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme/Generalitat de Catalunya.
Published: 2021

27. Hollow metal nanostructures for enhanced plasmonics: synthesis, local plasmonic properties and applications

Author: Institut Català de la Salut, [Genç A] Catalan Institute of Nanoscience and Nanotechnology, Barcelona, Spain. The Barcelona Institute of Science and Technology (BIST), Campus UAB, Bellaterra, Barcelona, Spain. Department of Metallurgy and Materials Engineering, Faculty of Engineering, Bartin University, Bartin, Turkey. [Patarroyo J] Catalan Institute of Nanoscience and Nanotechnology Barcelona, Spain. The Barcelona Institute of Science and Technology, Campus UAB, Bellaterra, Barcelona, Spain. [Sancho-Parramon J] Rudjer Boskovic Institute, Zagreb, Croatia. [Bastús N G] Catalan Institute of Nanoscience and Nanotechnology, Barcelona, Spain. The Barcelona Institute of Science and Technology (BIST), Campus UAB, Bellaterra, Barcelona, Spain. [Franco V] Catalan Institute of Nanoscience and Nanotechnology, Barcelona, Spain. The Barcelona Institute of Science and Technology (BIST), Campus UAB, Bellaterra, Barcelona, Spain. Vall d’Hebron Institut de Recerca, Barcelona, Spain. ICREA, Barcelona, Spain. [Arbiol J] Catalan Catalan Institute of Nanoscience and Nanotechnology, Barcelona, Spain. The Barcelona Institute of Science and Technology (BIST), Campus UAB, Bellaterra, Barcelona, Spain. ICREA, Barcelona, Spain., and Hospital Universitari Vall d'Hebron
Subjects: Nanoestructures, Tecnología, Industria y Agricultura::Materiales Manufacturados::Nanoestructuras [TECNOLOGÍA, INDUSTRIA, AGRICULTURA], Other subheadings::Other subheadings::/utilization [Other subheadings], Otros calificadores::Otros calificadores::/utilización [Otros calificadores], Investigative Techniques::Chemistry Techniques, Analytical::Surface Plasmon Resonance [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT], Técnicas de Investigación::Técnicas de Química Analítica::Resonancia por Plasmón de Superficie [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Ressonància de plasmons superficials, Technology, Industry, and Agriculture::Manufactured Materials::Nanostructures [TECHNOLOGY, INDUSTRY, AGRICULTURE]
Published: 2021

28. Immune cell profiling of the cerebrospinal fluid enables the characterization of the brain metastasis microenvironment

Author: Paolo Nuciforo, Domenica Marchese, Carlota Rubio-Perez, Juan L. Trincado, Juan Sahuquillo, Josep Tabernero, Estela Pineda, Ester Bonfill-Teixidor, Holger Heyn, Francisco Martínez-Ricarte, Josep Maria Mesquida González, Genís Parra, Sara Ruiz, Leire Pedrosa, Marta Cicuendez, Joan Seoane, Catia Moutinho, Garazi Serna, Ester Planas-Rigol, Esteban Cordero, Laura Escudero, Alexandra Arias, Raffaella Iurlaro, Institut Català de la Salut, [Rubio-Perez C, Planas-Rigol E, Bonfill-Teixidor E, Arias A, Serna G, Iurlaro R, Escudero L, Nuciforo P] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Trincado JL] CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. Josep Carreras Leukemia Research Institute and Department of Biomedicine, School of Medicine, University of Barcelona, Barcelona, Spain. [Marchese D] CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. [Martínez-Ricarte F, Cordero E, Cicuendez M, Sahuquillo J] Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Tabernero J] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. CIBERONC, Barcelona, Spain. [Seoane J] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. CIBERONC, Barcelona, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: 0301 basic medicine, Cancer microenvironment, Lung Neoplasms, Science, Immune checkpoint inhibitors, General Physics and Astronomy, Adenocarcinoma of Lung, CD8-Positive T-Lymphocytes, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Metàstasi, Political science, Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents::Antineoplastic Agents, Immunological [CHEMICALS AND DRUGS], Leukocytes, Tumor Microenvironment, Humans, Sistema nerviós -- Càncer, Immune Checkpoint Inhibitors, Cerebrospinal Fluid, Multidisciplinary, Brain Neoplasms, Neoplasms::Neoplastic Processes::Neoplasm Metastasis [DISEASES], Brain, neoplasias::neoplasias por localización::neoplasias del sistema nervioso::neoplasias del sistema nervioso central::neoplasias cerebrales [ENFERMEDADES], General Chemistry, Prognosis, Cervell - Tumors, Neoplasms::Neoplasms by Site::Nervous System Neoplasms::Central Nervous System Neoplasms::Brain Neoplasms [DISEASES], 030104 developmental biology, neoplasias::procesos neoplásicos::metástasis neoplásica [ENFERMEDADES], 030220 oncology & carcinogenesis, Càncer - Immunoteràpia, Tumour immunology, Christian ministry, acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos::inmunoterapia antineoplásica [COMPUESTOS QUÍMICOS Y DROGAS], Humanities, Genètica
Abstract: Brain metastases are the most common tumor of the brain with a dismal prognosis. A fraction of patients with brain metastasis benefit from treatment with immune checkpoint inhibitors (ICI) and the degree and phenotype of the immune cell infiltration has been used to predict response to ICI. However, the anatomical location of brain lesions limits access to tumor material to characterize the immune phenotype. Here, we characterize immune cells present in brain lesions and matched cerebrospinal fluid (CSF) using single-cell RNA sequencing combined with T cell receptor genotyping. Tumor immune infiltration and specifically CD8+ T cell infiltration can be discerned through the analysis of the CSF. Consistently, identical T cell receptor clonotypes are detected in brain lesions and CSF, confirming cell exchange between these compartments. The analysis of immune cells of the CSF can provide a non-invasive alternative to predict the response to ICI, as well as identify the T cell receptor clonotypes present in brain metastasis., The use of CSF for diagnosis of metastatic brain tumors could be of clinical and patient benefit. Here the authors undertake a single-cell RNA analysis of CSF and brain to determine whether the phenotype in the CSF is reflective of the phenotype in the tumor.
Published: 2021

29. Multifunctional homogeneous calcium phosphate coatings: Toward antibacterial and cell adhesive titanium scaffolds

Author: Jordi Guillem-Marti, Elia Vidal, Elisa Rupérez, Maria-Pau Ginebra, Daniel Rodríguez, Christèle Combes, Universitat Politècnica de Catalunya [Barcelona] (UPC), Barcelona Institute of Science and Technology (BIST), Centre interuniversitaire de recherche et d'ingenierie des matériaux (CIRIMAT), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Barcelona Institute of Science and Technology - BIST (SPAIN), Centre National de la Recherche Scientifique - CNRS (FRANCE), Institute for Bioengineering of Catalonia - IBEC (SPAIN), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Universitat Politècnica de Catalunya - UPC (SPAIN), Centre Interuniversitaire de Recherche et d'Ingénierie des Matériaux - CIRIMAT (Toulouse, France), Universitat Politècnica de Catalunya. Doctorat en Ciència i Enginyeria dels Materials, Universitat Politècnica de Catalunya. Departament de Ciència i Enginyeria de Materials, Universitat Politècnica de Catalunya. BBT - Biomaterials, Biomecànica i Enginyeria de Teixits, Institut de Bioenginyeria de Catalunya, and Université Toulouse III - Paul Sabatier
Subjects: Scaffold, Materials science, Biocompatibility, Titanium scaffolds, Matériaux, One-step pulse electrodeposition, 0206 medical engineering, Biocompatibilitat, Enginyeria biomèdica::Biomaterials [Àrees temàtiques de la UPC], 02 engineering and technology, engineering.material, Osseointegration, [SPI.MAT]Engineering Sciences [physics]/Materials, chemistry.chemical_compound, Coating, Chlorhexidine digluconate, Materials Chemistry, Brushite, Cell adhesion, Octacalcium phosphate, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, Calcium phosphate coating, Titani, Surfaces and Interfaces, General Chemistry, Adhesion, 021001 nanoscience & nanotechnology, Condensed Matter Physics, 020601 biomedical engineering, Surfaces, Coatings and Films, Antibacterial, chemistry, Chemical engineering, engineering, 0210 nano-technology
Abstract: International audience; Implants for orthopedic applications need to be biocompatible and bioactive, with mechanical properties similar to those of surrounding natural bone. Given this scenario titanium (Ti) scaffolds obtained by Direct Ink Writing technique offer the opportunity to manufacture customized structures with controlled porosity and mechanical properties. Considering that 3D Ti scaffolds have a significant surface area, it is necessary to develop strategies against the initial bacterial adhesion in order to prevent infection in the early stages of the implantation, while promoting cell adhesion to the scaffold. The challenge is not only achieving a balance between antibacterial activity and osseointegration, it is also to develop a homogeneous coating on the inner and outer surface of the scaffold. The purpose of this work was the development of a single-step electrodeposition process in order to uniformly cover Ti scaffolds with a layer of calcium phosphate (CaP) loaded with chlorhexidine digluconate (CHX). Scaffold characterization was assessed by scanning electron microscopy, Energy dispersive X-ray spectroscopy, X-ray diffraction, micro-Raman microscopy and compressive strength tests. Results determined that the surface of scaffolds was covered by plate-like and whisker-like calcium phosphate crystals, which main phases were octacalcium phosphate and brushite. Biological tests showed that the as-coated scaffolds reduced bacteria adhesion (73 ± 3% for Staphylococcus aureus and 70 ± 2% for Escherichia coli). In vitro cell studies and confocal analysis revealed the adhesion and spreading of osteoblast-like SaOS-2 on coated surfaces. Therefore, the proposed strategy can be a potential candidate in bone replacing surgeries.
Published: 2021
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30. Specific Susceptibility to COVID-19 in Adults with Down Syndrome

Author: Ilan Green, Hefziba Lifshitz, Arya Biragyn, Milana Frenkel-Morgenstern, Marie-Claude Potier, Alexandra Botté, Benjamin Sredni, William C. Mobley, Lisi Flores-Aguilar, Ilario De Toma, Jacqueline London, Stylianos E. Antonarakis, Alessandro Gorohovski, Eugene Yu, Eugene Merzon, Yann Herault, Eitan Okun, Ronit Sarid, Andre Strydom, Florencia Iulita, Randall J. Roper, Orly Weissberg, Tomer Illouz, Mara Dierssen, Bar-Ilan University [Israël], National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Tel Aviv University [Tel Aviv], Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), McGill University = Université McGill [Montréal, Canada], The Barcelona Institute for Science and Technology [Barcelona, Spain], Universitat Pompeu Fabra [Barcelona] (UPF), Centre for Biomedical Research on Rare Diseases [Barcelona, Spain] (CIBERER), Hospital Sant Joan de Déu [Barcelona], Barcelona Institute of Science and Technology (BIST), University of Geneva [Switzerland], Institute of Genetics and Genomics in Geneva (iGE3), Université de Genève (UNIGE), Roswell Park Comprehensive Cancer Center [Buffalo, NY, USA] (RP3C), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Indiana University - Purdue University Indianapolis (IUPUI), Indiana University System, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), University of California [San Diego] (UC San Diego), University of California, King‘s College London, and South London and Maudsley NHS Foundation Trust
Subjects: 0301 basic medicine, medicine.medical_specialty, Down syndrome, Population, Disease, medicine.disease_cause, COVID-19 (Malaltia), 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Pandemic, medicine, education, Intensive care medicine, education.field_of_study, Original Paper, [SDV.GEN]Life Sciences [q-bio]/Genetics, Respiratory tract infections, business.industry, SARS-CoV-2, Incidence (epidemiology), Outbreak, COVID-19, Immune dysregulation, Down, Síndrome de, medicine.disease, 3. Good health, Vaccine, 030104 developmental biology, Neurology, Molecular Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: The current SARS-CoV-2 outbreak, which causes COVID-19, is particularly devastating for individuals with chronic medical conditions, in particular those with Down Syndrome (DS) who often exhibit a higher prevalence of respiratory tract infections, immune dysregulation and potential complications. The incidence of Alzheimer's disease (AD) is much higher in DS than in the general population, possibly increasing further the risk of COVID-19 infection and its complications. Here we provide a biological overview with regard to specific susceptibility of individuals with DS to SARS-CoV-2 infection as well as data from a recent survey on the prevalence of COVID-19 among them. We see an urgent need to protect people with DS, especially those with AD, from COVID-19 and future pandemics and focus on developing protective measures, which also include interventions by health systems worldwide for reducing the negative social effects of long-term isolation and increased periods of hospitalization. This research was supported by the Trisomy-21 Research Society (T21RS) and in part by the Intramural Research Program of the National Institute on Aging
Published: 2021
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31. Soybean aphid biotype 1 genome: Insights into the invasive biology and adaptive evolution of a major agricultural pest

Author: Nick Miller, Richard Hall, Jose A.P. Marcelino, Chiun-Cheng Ko, Deirdre Prischmann-Voldseth, Michela Panini, Ravi Kiran Donthu, Giulia Melchiori, Christina D. DiFonzo, Minh Nguyen, Everett Weber, Curt B. Hill, Brian W. Diers, Anthony Bretaudeau, Alejandra Flores, George E. Heimpel, Toni Gabaldon, John F. Tooker, Jonathan H. Badger, Andrew Aschwanden, Ana Micijevic, Anitha Chirumamilla, Tugrul Giray, Peter Desborough, Rosanna Giordano, Massimo Pessino, Brad S. Coates, Fabrice Legeai, Janet Knodel, David J. Voegtlin, Matthew E. O'Neal, Manuella van Munster, Bruce D Potter, Glen L. Hartman, Christopher J. Fields, Doris Lagos-Kutz, Brian A. Nault, Joon-Ho Lee, Hojun Song, Giuseppe E. Massimino Cocuzza, Aleksey V. Zimin, Felipe N. Soto-Adames, Olga Chiesa, Hugh M. Robertson, Genevieve Labrie, Sijun Liu, Arian Avalos, Eileen Cullen, Bryony C. Bonning, Seunghwan Lee, Mauro Mandrioli, Emanuele Mazzoni, Mark Band, Yongping Huanga, Irene Consuelo Julca Chavez, Kelley J. Tilmon, Kongming Wu, Theresa K. Herman, Lawrence Hon, Andi Nasuddin, Tatsiana Akraiko, Gian Carlo Manicardi, Shuai Zhan, Puerto Rico Science, Know Your Bee Inc, Johns Hopkins University (JHU), Barcelona Institute of Science and Technology (BIST), Barcelona Supercomputing Center - Centro Nacional de Supercomputacion (BSC - CNS), Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), Plant Health Institute of Montpellier (UMR PHIM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Université de Montpellier (UM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Color Genomics, Pacific Biosciences [Menlo Park], Pacific Biosciences of California, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Columbia University Irving Medical Center (CUIMC), University of Illinois at Urbana-Champaign [Urbana], University of Illinois System, Southwest Research and Outreach Center [Lamberton], University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, University of Puerto Rico (UPR), University of Florida [Gainesville] (UF), Agricen Sciences, USDA-ARS : Agricultural Research Service, Pennsylvania State University (Penn State), Penn State System, Institut de Génétique, Environnement et Protection des Plantes (IGEPP), Université de Rennes (UR)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-INSTITUT AGRO Agrocampus Ouest, Università cattolica del Sacro Cuore [Piacenza e Cremona] (Unicatt), North Dakota State University (NDSU), Iowa State University (ISU), University of Catania [Italy], University of Wisconsin - Milwaukee, New South Wales Department of Primary Industries (NSW DPI), Michigan State University [East Lansing], Michigan State University System, University of Minnesota [Morris], University of Minnesota System, Chinese Academy of Sciences [Beijing] (CAS), National Taiwan University [Taiwan] (NTU), Centre de Recherche sur les Grains [Québec] (CEROM), United States Department of Agriculture (USDA), Seoul National University [Seoul] (SNU), University of Haifa [Haifa], Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Università cattolica del Sacro Cuore [Milano] (Unicatt), South Dakota State University (SDSTATE), Illinois Institute of Technology (IIT), Hasanuddin University (Unhas), Cornell AgriTech, College of Agriculture and Life Sciences [Cornell University] (CALS), Cornell University [New York]-Cornell University [New York], Department of Entomology [CALS], Texas A&M University [College Station], Ohio State University [Columbus] (OSU), Chinese Academy of Agricultural Sciences (CAAS), United Soybean Board, Agricultural Research Service, 432114, Integrated Management of Soybean Pathogens and Pests, 2018-67015-28199, USDA NIFA, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Innovation et Développement dans l'Agriculture et l'Alimentation (UMR Innovation), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-AGROCAMPUS OUEST, Scalable, Optimized and Parallel Algorithms for Genomics (GenScale), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-GESTION DES DONNÉES ET DE LA CONNAISSANCE (IRISA-D7), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Università degli Studi di Modena e Reggio Emilia, and Cornell University [New York]
Subjects: 0106 biological sciences, Pesticide resistance, Population genetics, [SDV]Life Sciences [q-bio], Genome, Insect, Adaptation, Biological, Zoology, SNP, Phylome, Polymorphism, Single Nucleotide, 01 natural sciences, Biochemistry, 03 medical and health sciences, Animals, Polymorphism, Adaptation, Soybean aphid, Biotype 1, Molecular Biology, Rhamnus cathartica, Aphid, Alleles, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Ecotype, 0303 health sciences, Genome, biology, food and beverages, Aphididae, Single Nucleotide, Biological, biology.organism_classification, Biological Evolution, Hemiptera, United States, 010602 entomology, Settore AGR/11 - ENTOMOLOGIA GENERALE E APPLICATA, Aphids, Insect Science, PEST analysis, Aphis glycines, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Introduced Species, Insect
Abstract: International audience; The soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae) is a serious pest of the soybean plant, Glycine max, a major world-wide agricultural crop. We assembled a de novo genome sequence of Ap. glycines Biotype 1, from a culture established shortly after this species invaded North America. 20.4% of the Ap. glycines proteome is duplicated. These in-paralogs are enriched with Gene Ontology (GO) categories mostly related to apoptosis, a possible adaptation to plant chemistry and other environmental stressors. Approximately one-third of these genes show parallel duplication in other aphids. But Ap. gossypii, its closest related species, has the lowest number of these duplicated genes. An Illumina GoldenGate assay of 2380 SNPs was used to determine the world-wide population structure of Ap. Glycines. China and South Korean aphids are the closest to those in North America. China is the likely origin of other Asian aphid populations. The most distantly related aphids to those in North America are from Australia. The diversity of Ap. glycines in North America has decreased over time since its arrival. The genetic diversity of Ap. glycines North American population sampled shortly after its first detection in 2001 up to 2012 does not appear to correlate with geography. However, aphids collected on soybean Rag experimental varieties in Minnesota (MN), Iowa (IA), and Wisconsin (WI), closer to high density Rhamnus cathartica stands, appear to have higher capacity to colonize resistant soybean plants than aphids sampled in Ohio (OH), North Dakota (ND), and South Dakota (SD). Samples from the former states have SNP alleles with high FST values and frequencies, that overlap with genes involved in iron metabolism, a crucial metabolic pathway that may be affected by the Rag-associated soybean plant response. The Ap. glycines Biotype 1 genome will provide needed information for future analyses of mechanisms of aphid virulence and pesticide resistance as well as facilitate comparative analyses between aphids with differing natural history and host plant range.
Published: 2020
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32. Structural basis of a histidine-DNA nicking/joining mechanism for gene transfer and promiscuous spread of antibiotic resistance

Author: Coll, Miquel [Barcelona Institute of Science and Technology, Barcelona (Spain); Molecular Biology Institute of Barcelona, Barcelona (Spain)]
Published: 2017
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33. Influence of orbital symmetry on diffraction imaging with rescattering electron wave packets

Author: Biegert, J. [The Barcelona Institute of Science and Technology, Castelldefels (Barcelona) (Spain); ICREA-Institucio Catalana de Recerca i Estudis Avancats, Barcelona (Spain)]
Published: 2016
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34. Variable interplay of UV-induced DNA damage and repair at transcription factor binding sites

Author: Radhakrishnan Sabarinathan, Abel Gonzalez-Perez, Nuria Lopez-Bigas, Joan Frigola, Institut Català de la Salut, [Frigola J] Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain. Thoracic Tumors & Head and Neck Cancer Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Sabarinathan R] National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India. [Gonzalez-Perez A] Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain. Research Program on Biomedical Informatics, Universitat Pompeu Fabra,Barcelona, Catalonia, Spain. [Lopez-Bigas N] Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain. Research Program on Biomedical Informatics, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Mutation rate, Skin Neoplasms, Neoplasms::Neoplasms by Histologic Type::Neoplasms::Neoplasms by Histologic Type::Neoplasms::Neoplasms by Histologic Type::Nevi and Melanomas::Melanoma [DISEASES], DNA Repair, AcademicSubjects/SCI00010, Ultraviolet Rays, DNA repair, DNA damage, Radiació - Efectes fisiològics, Genome Integrity, Repair and Replication, Biology, medicine.disease_cause, Other subheadings::/radiation effects [Other subheadings], 03 medical and health sciences, Genetic Phenomena::DNA Damage [PHENOMENA AND PROCESSES], 0302 clinical medicine, Genetics, medicine, Humans, Binding site, Transcription factor, Melanoma, Otros calificadores::/efectos de la radiación [Otros calificadores], 030304 developmental biology, 0303 health sciences, Mutation, Binding Sites, Whole Genome Sequencing, Mutagenesis, ADN - Dany, Chromosome Mapping, DNA, Neoplasm, fenómenos genéticos::daño del ADN [FENÓMENOS Y PROCESOS], 3. Good health, Cell biology, DNA binding site, Pyrimidine Dimers, neoplasias::neoplasias por tipo histológico::neoplasias::neoplasias por tipo histológico::neoplasias::neoplasias por tipo histológico::nevos y melanomas::melanoma [ENFERMEDADES], 030217 neurology & neurosurgery, DNA Damage, Transcription Factors
Abstract: Llocs d’unió; Dany en l'ADN; Factor de transcripció Sitios de unión; Daño en el ADN; Factor de transcripcion Binding sites; Dna damage; Transcription factor An abnormally high rate of UV-light related mutations appears at transcription factor binding sites (TFBS) across melanomas. The binding of transcription factors (TFs) to the DNA impairs the repair of UV-induced lesions and certain TFs have been shown to increase the rate of generation of these lesions at their binding sites. However, the precise contribution of these two elements to the increase in mutation rate at TFBS in these malignant cells is not understood. Here, exploiting nucleotide-resolution data, we computed the rate of formation and repair of UV-lesions within the binding sites of TFs of different families. We observed, at certain dipyrimidine positions within the binding site of TFs in the Tryptophan Cluster family, an increased rate of formation of UV-induced lesions, corroborating previous studies. Nevertheless, across most families of TFs, the observed increased mutation rate within the entire DNA region covered by the protein results from the decreased repair efficiency. While the rate of mutations across all TFBS does not agree with the amount of UV-induced lesions observed immediately after UV exposure, it strongly agrees with that observed after 48 h. This corroborates the determinant role of the impaired repair in the observed increase of mutation rate. N.L.-B. acknowledges funding from the European Research Council [consolidator grant 682398]; Spanish Ministry of Economy and Competitiveness [SAF2015-66084-R, MINECO/FEDER to U.E.]; IRB Barcelona is a recipient of a Severo Ochoa Centre of Excellence Award from the Spanish Ministry of Economy and Competitiveness (MINECO; Government of Spain) and is supported by CERCA (Generalitat de Catalunya); R.S. acknowledges funding support from the National Centre for Biological Sciences (NCBS-TIFR), Bangalore, India. Funding for open access charge: Spanish Ministry of Economy and Competitiveness.
Published: 2020

35. From whole-organ imaging to in-silico blood flow modeling: a new multi-scale network analysis for revisiting tissue functional anatomy

Author: Jacques Rouquette, Anne Lorsignol, Pol Kennel, Jules Dichamp, Lise Teyssedre, Julien Colombelli, Franck Plouraboué, Christophe Guissard, Louis Casteilla, Corinne Barreau, (OATAO), Open Archive Toulouse Archive Ouverte, Institut de mécanique des fluides de Toulouse (IMFT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, STROMALab, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Institut des Technologies Avancées en sciences du Vivant (ITAV), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Barcelona Institute of Science and Technology (BIST), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), Barcelona Institute of Science and Technology - BIST (SPAIN), Centre National de la Recherche Scientifique - CNRS (FRANCE), Etablissement Français du Sang - EFS Midi-Pyrénées (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), and Institut National Polytechnique de Toulouse - INPT (FRANCE)
Subjects: Male, 0301 basic medicine, Physiology, Computer science, Mécanique des fluides, In-silico modeling, [SPI.MECA.MEFL] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Fluids mechanics [physics.class-ph], Biochemistry, [SPI.MECA.MEFL]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Fluids mechanics [physics.class-ph], Fats, Mice, Fluorescence Microscopy, 0302 clinical medicine, Animal Cells, Blood Flow, 11. Sustainability, Medicine and Health Sciences, Adipocytes, Micro-vascular clusters, Biology (General), Connective Tissue Cells, Microscopy, Ecology, Light-Sheet, Community structure, Light Microscopy, Arteries, Lipids, Body Fluids, Blood, Community Ecology, Computational Theory and Mathematics, Connective Tissue, Modeling and Simulation, Blood Circulation, Graph (abstract data type), Light-Sheet Fluorescence Microscopy, Anatomy, Cellular Types, Biological system, Fat pad, Research Article, Network analysis, Strongly connected component, QH301-705.5, In silico, Research and Analysis Methods, Models, Biological, Fluorescence, Veins, 03 medical and health sciences, Cellular and Molecular Neuroscience, Genetics, Animals, Computer Simulation, Community Structure, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Clustering coefficient, Ecology and Environmental Sciences, Biology and Life Sciences, Cell Biology, Blood flow, Mice, Inbred C57BL, Biological Tissue, 030104 developmental biology, Light sheet fluorescence microscopy, Cardiovascular Anatomy, Blood Vessels, Tissue micro-environment, 030217 neurology & neurosurgery
Abstract: We present a multi-disciplinary image-based blood flow perfusion modeling of a whole organ vascular network for analyzing both its structural and functional properties. We show how the use of Light-Sheet Fluorescence Microscopy (LSFM) permits whole-organ micro-vascular imaging, analysis and modelling. By using adapted image post-treatment workflow, we could segment, vectorize and reconstruct the entire micro-vascular network composed of 1.7 million vessels, from the tissue-scale, inside a ∼ 25 × 5 × 1 = 125mm3 volume of the mouse fat pad, hundreds of times larger than previous studies, down to the cellular scale at micron resolution, with the entire blood perfusion modeled. Adapted network analysis revealed the structural and functional organization of meso-scale tissue as strongly connected communities of vessels. These communities share a distinct heterogeneous core region and a more homogeneous peripheral region, consistently with known biological functions of fat tissue. Graph clustering analysis also revealed two distinct robust meso-scale typical sizes (from 10 to several hundred times the cellular size), revealing, for the first time, strongly connected functional vascular communities. These community networks support heterogeneous micro-environments. This work provides the proof of concept that in-silico all-tissue perfusion modeling can reveal new structural and functional exchanges between micro-regions in tissues, found from community clusters in the vascular graph., Author summary New optical microscopy called light-sheet fluorescence microscopy (LSFM) allows for 3D optical scan imaging of an entire tissue, at the micron scale, for reconstructing its complete microvascular bed. The 3D reconstruction of a vectorized vascular network can display as many as 1.7 million vessels inside a 125mm3 volume of mouse fat tissue. This 3D reconstruction allows for vessel visualisation and also the complete virtual “dissection” and analysis of the vascular bed. Described as a graph, the vascular network provides a new tissue anatomy description, similar to city maps built on a road graph, showing structural clusters emerging as tissue “districts”. These clusters provide a new basis for lobule description in fat tissue. Even more can be obtained from virtual perfusion simulated inside the tissue by using in-silico modeling tools. This virtual perfusion reveals the functional properties of the vascular network, such as perfusion fluxes, and exchanges between clusters and infusion time (time for the blood to reach a site from the principal entry).
Published: 2020
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36. Hierarchical chromatin organization detected by TADpole

Author: Irene Farabella, Marc A. Marti-Renom, Paula Soler-Vila, Pol Cuscó, Marco Di Stefano, Institut Català de la Salut, [Soler-Vila P, Farabella I, Di Stefano M] CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona 08028, Spain. [Cuscó P] Gastrointestinal and Endocrine Tumors Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Marti-Renom MA] CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona 08028, Spain. Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Dr. Aiguader 88, Barcelona 08003, Spain. Universitat Pompeu Fabra (UPF), Pg. Lluis Companys 23, Barcelona 08003, Spain. ICREA, Pg. Lluis Companys 23, Barcelona 08010, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Genetic Phenomena::Genetic Structures::Chromosome Structures::Chromatin [PHENOMENA AND PROCESSES], Cohesin complex, AcademicSubjects/SCI00010, Computational biology, Medicina - Informàtica, Chromosome conformation capture, Cromatina, Mice, 03 medical and health sciences, 0302 clinical medicine, Other subheadings::/chemistry [Other subheadings], Genetics, Animals, Ratolins, Ciencias de la información::metodologías computacionales::soporte lógico (informática) [CIENCIA DE LA INFORMACIÓN], Eukaryota::Animals::Chordata::Vertebrates::Mammals::Eutheria::Rodentia::Muridae::Murinae::Mice [ORGANISMS], Otros calificadores::/química [Otros calificadores], Narese/7, 030304 developmental biology, 0303 health sciences, Cohesin, biology, Hierarchy (mathematics), fenómenos genéticos::estructuras genéticas::estructuras cromosómicas::cromatina [FENÓMENOS Y PROCESOS], Tadpole (physics), Chromatin, Hierarchical clustering, Narese/24, Histone, CTCF, biology.protein, Methods Online, Information Science::Computing Methodologies::Software [INFORMATION SCIENCE], Eukaryota::animales::Chordata::vertebrados::mamíferos::Eutheria::Rodentia::Muridae::Murinae::ratones [ORGANISMOS], Algorithms, Software, 030217 neurology & neurosurgery
Abstract: Mètodes computacionals; Genòmica Métodos computacionales; Genómica Computational Methods; Genomics The rapid development of Chromosome Conformation Capture (3C-based techniques), as well as imaging together with bioinformatics analyses, has been fundamental for unveiling that chromosomes are organized into the so-called topologically associating domains or TADs. While TADs appear as nested patterns in the 3C-based interaction matrices, the vast majority of available TAD callers are based on the hypothesis that TADs are individual and unrelated chromatin structures. Here we introduce TADpole, a computational tool designed to identify and analyze the entire hierarchy of TADs in intra-chromosomal interaction matrices. TADpole combines principal component analysis and constrained hierarchical clustering to provide a set of significant hierarchical chromatin levels in a genomic region of interest. TADpole is robust to data resolution, normalization strategy and sequencing depth. Domain borders defined by TADpole are enriched in main architectural proteins (CTCF and cohesin complex subunits) and in the histone mark H3K4me3, while their domain bodies, depending on their activation-state, are enriched in either H3K36me3 or H3K27me3, highlighting that TADpole is able to distinguish functional TAD units. Additionally, we demonstrate that TADpole's hierarchical annotation, together with the new DiffT score, allows for detecting significant topological differences on Capture Hi-C maps between wild-type and genetically engineered mouse. European Research Council under the Seventh Framework Program FP7/2007-2013 [609989, in part]; European Union's Horizon 2020 Research and Innovation Programme [676556]; Spanish Ministry of Science and Innovation [BFU2013-47736-P, BFU2017-85926-P to M.A.M-R., IJCI-2015-23352 to I.F., BES-2014-070327 to P.S-V.]; ‘Centro de Excelencia Severo Ochoa 2013–2017’, SEV-2012-0208; CERCA Programme/Generalitat de Catalunya (to C.R.G.). Funding for open access charge: European Research Council under the Seventh Framework Program FP7/2007-2013 [609989]. We also acknowledge the support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the ‘Centro de Excelencia Severo Ochoa 2013-2017’, SEV-2012-0208, the CERCA Programme/Generalitat de Catalunya, Spanish Ministry of Science and Innovation through the Instituto de Salud Carlos III, the Generalitat de Catalunya through Departament de Salut and Departament d’Empresa i Coneixement and the Co-financing by the Spanish Ministry of Science and Innovation with funds from the European Regional Development Fund (ERDF) corresponding to the 2014-2020 Smart Growth Operating Program to the CRG.
Published: 2020

37. Identification of enhancer-promoter contacts in embryoid bodies by quantitative chromosome conformation capture (4C)

Author: Enrique Vidal, Gregoire Stik, Thomas Graf, Tian V. Tian, Institut Català de la Salut, [Tian TV] Center for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain. Universitat Pompeu Fabra, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Vidal E, Graf T, Stik G] Center for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain. Universitat Pompeu Fabra, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Pluripotent Stem Cells, células::células madre::células madre pluripotentes::células madre embrionarias::cuerpos embrioides [ANATOMÍA], General Chemical Engineering, Computational biology, Embryoid body, Cell fate determination, Biology, Polymerase Chain Reaction, Chromosomes, General Biochemistry, Genetics and Molecular Biology, Chromosome conformation capture, Embrions, Mice, Investigative Techniques::Genetic Techniques::Sequence Analysis::High-Throughput Nucleotide Sequencing [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Animals, Promoter Regions, Genetic, Induced pluripotent stem cell, Enhancer, Gene, Embryoid Bodies, Seqüència de nucleòtids, Embriologia, General Immunology and Microbiology, General Neuroscience, Computational Biology, High-Throughput Nucleotide Sequencing, Promoter, DNA Restriction Enzymes, Cells::Stem Cells::Pluripotent Stem Cells::Embryonic Stem Cells::Embryoid Bodies [ANATOMY], Cromosomes, Restriction enzyme, Enhancer Elements, Genetic, técnicas de investigación::técnicas genéticas::análisis de secuencias::secuenciación de nucleótidos de alto rendimiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Genètica
Abstract: Cèl·lules mare embrionàries; Seqüenciació d'alt rendiment Células madre embrionarias; Secuenciación de alto rendimiento Embryonic stem cells; High-throughput sequencing During mammalian development, cell fates are determined through the establishment of regulatory networks that define the specificity, timing, and spatial patterns of gene expression. Embryoid bodies (EBs) derived from pluripotent stem cells have been a popular model to study the differentiation of the main three germ layers and to define regulatory circuits during cell fate specification. Although it is well-known that tissue-specific enhancers play an important role in these networks by interacting with promoters, assigning them to their relevant target genes still remains challenging. To make this possible, quantitative approaches are needed to study enhancer-promoter contacts and their dynamics during development. Here, we adapted a 4C method to define enhancers and their contacts with cognate promoters in the EB differentiation model. The method uses frequently cutting restriction enzymes, sonication, and a nested-ligation-mediated PCR protocol compatible with commercial DNA library preparation kits. Subsequently, the 4C libraries are subjected to high-throughput sequencing and analyzed bioinformatically, allowing detection and quantification of all sequences that have contacts with a chosen promoter. The resulting sequencing data can also be used to gain information about the dynamics of enhancer-promoter contacts during differentiation. The technique described for the EB differentiation model is easy to implement. We would like to thank F. Le Dily, R. Stadhouders and members of the Graf laboratory for their advice and discussions. G.S. was supported by a Marie Sklodowska-Curie fellowship (H2020-MSCA-IF-2016, miRStem), T.V.T by a Juan de la Cierva postdoctoral fellowship (MINECO, FJCI-2014-22946). This work was supported by the European Research Council under the 7th Framework Programme FP7 (ERC Synergy Grant 4D-Genome, grant agreement 609989 to T.G.), the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership, Centro de Excelencia Severo Ochoa 2013-2017 and CERCA Program Generalitat de Catalunya.
Published: 2020

38. A high-throughput screening identifies microRNA inhibitors that influence neuronal maintenance and/or response to oxidative stress

Author: Pallarès-Albanell, Joan, Zomeño-Abellán, M. Teresa, Escaramís, Georgia, Pantano, Lorena, Soriano, Aroa, Segura, Miguel F., Martí, Eulàlia, Universitat Autònoma de Barcelona, [Pallarès-Albanell J, Zomeño-Abellán MT] Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology, Barcelona, Spain. [Escaramís G] Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology, Barcelona, Spain. Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain. Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain. Research Group on Statistics, Econometrics and Health, Universitat de Girona, Girona, Spain. Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Ministerio de Ciencia Innovación y Universidades, Madrid, Spain. [Pantano L] Bioinformatics Core, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. [Soriano A, Segura MF] Recerca Translacional en Càncer en la Infància i l'Adolescència, Vall d'Hebron Institut de Recerca, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: 0301 basic medicine, Oligonucleotides, Druggability, Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, RNA [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Mirnas, técnicas de investigación::técnicas genéticas::análisis de secuencias::análisis de secuencias de ARN [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], medicine.disease_cause, Non-coding RNAs, Basal (phylogenetics), 0302 clinical medicine, Drug Discovery, Gene expression, oxidative stress, small RNA sequencing, Radicals lliures, Malalties neurodegeneratives, Neurodegeneration, neurodegeneration, High-throughput screening, Oligonucleòtids, Neurodegenerative Diseases, fenómenos fisiológicos::estrés fisiológico::estrés oxidativo [FENÓMENOS Y PROCESOS], Genètica - Tècnica, Cell biology, 030220 oncology & carcinogenesis, miRNAs, non-coding RNAs, Molecular Medicine, Small RNA sequencing, expression profiles, RNA -- Models matemàtics, Expression profiles, Cèl·lules, Cells, Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Untranslated::RNA, Small Untranslated::MicroRNAs [CHEMICALS AND DRUGS], Physiological Phenomena::Stress, Physiological::Oxidative Stress [PHENOMENA AND PROCESSES], Biology, high-throughput screening, Article, 03 medical and health sciences, mitochondrial function, Origin of life, microRNA, Origen de la vida, medicine, Econometrics, Viability assay, MicroARN, lcsh:RM1-950, medicine.disease, RNA -- Mathematical models, lcsh:Therapeutics. Pharmacology, 030104 developmental biology, Oxidative stress, Mitochondrial function, Biogenesis, Econometria, nucleótidos y nucleósidos de ácidos nucleicos::nucleótidos y nucleósidos de ácidos nucleicos::ácidos nucleicos::ARN::nucleótidos y nucleósidos de ácidos nucleicos::ácidos nucleicos::ARN::ARN no traducido::ARN pequeño no traducido::microARN [COMPUESTOS QUÍMICOS Y DROGAS]
Abstract: Oxidative stress; Small RNA sequencing; Neurodegeneration Estrés oxidativo; Secuenciación de ARN pequeño; Neurodegeneración Estrès oxidatiu; Seqüenciació d'ARN petit; Neurodegeneració Small non-coding RNAs (sncRNAs), including microRNAs (miRNAs) are important post-transcriptional gene expression regulators relevant in physiological and pathological processes. Here, we combined a high-throughput functional screening (HTFS) platform with a library of antisense oligonucleotides (ASOs) to systematically identify sncRNAs that affect neuronal cell survival in basal conditions and in response to oxidative stress (OS), a major hallmark in neurodegenerative diseases. We considered hits commonly detected by two statistical methods in three biological replicates. Forty-seven ASOs targeting miRNAs (miRNA-ASOs) consistently decreased cell viability under basal conditions. A total of 60 miRNA-ASOs worsened cell viability impairment mediated by OS, with 36.6% commonly affecting cell viability under basal conditions. In addition, 40 miRNA-ASOs significantly protected neuronal cells from OS. In agreement with cell viability impairment, damaging miRNA-ASOs specifically induced increased free radical biogenesis. miRNAs targeted by the detrimental ASOs are enriched in the fraction of miRNAs downregulated by OS, suggesting that the miRNA expression pattern after OS contributes to neuronal damage. The present HTFS highlighted potentially druggable sncRNAs. However, future studies are needed to define the pathways by which the identified ASOs regulate cell survival and OS response and to explore the potential of translating the current findings into clinical applications. This work was supported by the Spanish Ministry of Economy and Competitiveness and FEDER funds (SAF2014-60551-R and SAF2017-88452-R). We acknowledge the support of the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership and the Centro de Excelencia Severo Ochoa 2013-2017 (SEV-2012-0208). We acknowledge the support of the Spanish Ministry of Science Innovation and Universities, Maria Maeztu Unit of Excellence Programme. We thank the staff of the Genomics Unit for the preparation of sRNA libraries and sequencing and the staff of the Biomolecular Screening and Protein Technologies Unit for their help in the setting up the high-throughput screening.
Published: 2019

39. Energy Expenditure in Older People Hospitalized for an Acute Episode

Author: Bonnefoy, M., Gilbert, T., Normand, S., Jauffret, M., Roy, P., Morio, B., Cornu, C., Roche, S., Laville, M., Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Service de médecine gériatrique, centre hospitalier Lyon Sud, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Motricité, interactions, performance EA 4334 / Movement - Interactions - Performance (MIP), Le Mans Université (UM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR des Sciences et Techniques des Activités Physiques et Sportives (UFR STAPS), Université de Nantes (UN)-Université de Nantes (UN), Catalan Institute of Nanoscience and Nanotechnology (ICN2), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Barcelona Institute of Science and Technology (BIST), Institució Catalana de Recerca i Estudis Avançats (ICREA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Biostatistiques [Lyon], Hospices Civils de Lyon (HCL), INRAE Transfert, CarMeN, laboratoire, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Laboratoire Motricité, Interactions, Performance, Université de Nantes (UN), Consejo Superior de Investigaciones Científicas [Spain] (CSIC)-Barcelona Institute of Science and Technology (BIST), Université de Nantes - UFR des Sciences et Techniques des Activités Physiques et Sportives (UFR STAPS), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Le Mans Université (UM)
Subjects: Aged, 80 and over, Male, body composition, [SDV]Life Sciences [q-bio], Nutritional Requirements, Nutritional Status, Calorimetry, Indirect, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, frail elderly, Article, doubly labeled water, energy requirements, Hospitalization, [SDV] Life Sciences [q-bio], aged, Acute Disease, Weight Loss, energy expenditure, energy metabolism, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Female, Energy Intake, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Weight loss and worsening of nutritional state is a frequent downfall of acute hospitalization in older people. It is usually accepted that acute inflammation is responsible for hypercatabolism. However, several studies suggest, on the contrary, a reduction in resting energy expenditure (REE). This study aimed to obtain a reliable measure of REE and total energy expenditure (TEE) in older patients hospitalized for an acute episode in order to better assess patients&rsquo, energy requirements and help understand the mechanisms of weight loss in this situation. Nineteen hospitalized older patients (mean age 83 years) with C-reactive protein (CRP) level &gt, 20mg/L were recruited. REE and TEE were measured using gold standard methods of indirect calorimetry and doubly labeled water (DLW), respectively. REE was then compared to data from a previous study on aged volunteers from nursing homes who were free of an acute stressor event. Energy requirements measured by DLW were confirmed at 1.3 &times, REE. Energy intake covered the needs but did not prevent weight loss in these patients. TEE was not increased in hospitalized patients and was not influenced by inflammation, while the relationship between REE and inflammation was uncertain. Our results suggest that lean mass remains the major determinant of REE in hospitalized older people and that weight loss may not be explained solely by a state of hypercatabolism.
Published: 2019
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40. Spinning superfluid 4He nanodroplets

Author: Ancilotto, Francesco, Barranco, Manuel, Pi, Martí, Dipartimento di Fisica e Astronomia 'Galileo Galilei', Universita degli Studi di Padova = University of Padua = Université de Padoue, CNR-IOM-Democritos, Théorie (LCAR), Laboratoire Collisions Agregats Reactivite ( LCAR ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), Facultat de Fisica - Universitat de Barcelona, Catalan Institute of Nanoscience and Nanotechnology ( ICN2 ), Consejo Superior de Investigaciones Científicas [Spain] ( CSIC ) -The Barcelona Institute of Science and Technology, Universita degli Studi di Padova, Laboratoire Collisions Agrégats Réactivité (LCAR), Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Catalan Institute of Nanoscience and Nanotechnology (ICN2), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Barcelona Institute of Science and Technology (BIST), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse)
Subjects: [PHYS.COND]Physics [physics]/Condensed Matter [cond-mat], ComputingMilieux_MISCELLANEOUS, [ PHYS.COND ] Physics [physics]/Condensed Matter [cond-mat]
Abstract: International audience
Published: 2018
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41. Dicer-2 promotes mRNA activation through cytoplasmic polyadenylation

Author: Catherine Papin, Olga Coll, Ana Villalba, Tanit Guitart, Martine Simonelig, Fátima Gebauer, ene Regulation, Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, 08003-Barcelona, Spain., Universitat Pompeu Fabra [Barcelona] (UPF), Gene Regulation, Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, 08003-Barcelona, Spain, Institut de génétique humaine (IGH), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Ribonuclease III, 0301 basic medicine, Translation, Polyadenylation, Cytoplasmic polyadenylation element, [SDV]Life Sciences [q-bio], genetic processes, Wispy, translation, Article, Dicer-2, Xenopus laevis, 03 medical and health sciences, 0302 clinical medicine, RNA interference, Cytoplasmic polyadenylation, Animals, Drosophila Proteins, RNA, Messenger, Molecular Biology, Polymerase, mRNA Cleavage and Polyadenylation Factors, Messenger RNA, [SDV.GEN]Life Sciences [q-bio]/Genetics, biology, Toll-Like Receptors, fungi, Polynucleotide Adenylyltransferase, RNA-Binding Proteins, food and beverages, RNA 3' Polyadenylation Signals, Translation (biology), cytoplasmic polyadenylation, biology.organism_classification, Cell biology, enzymes and coenzymes (carbohydrates), Drosophila melanogaster, 030104 developmental biology, Protein Biosynthesis, biology.protein, RNA Helicases, 030217 neurology & neurosurgery, Dicer
Abstract: Cytoplasmic polyadenylation is a widespread mechanism to regulate mRNA translation. In vertebrates, this process requires two sequence elements in target 3' UTRs: the U-rich cytoplasmic polyadenylation element and the AAUAAA hexanucleotide. In Drosophila melanogaster, cytoplasmic polyadenylation of Toll mRNA occurs independently of these canonical elements and requires a machinery that remains to be characterized. Here we identify Dicer-2 as a component of this machinery. Dicer-2, a factor previously involved in RNA interference (RNAi), interacts with the cytoplasmic poly(A) polymerase Wispy. Depletion of Dicer-2 from polyadenylation-competent embryo extracts and analysis of wispy mutants indicate that both factors are necessary for polyadenylation and translation of Toll mRNA. We further identify r2d2 mRNA, encoding a Dicer-2 partner in RNAi, as a Dicer-2 polyadenylation target. Our results uncover a novel function of Dicer-2 in activation of mRNA translation through cytoplasmic polyadenylation. This work was supported by MINECO and the European Regional Development Fund (ERDF) under BFU2012-37135, BFU2015-68741, and Consolider CSD2009-00080 grants to F.G., and by the CNRS UMR9002, ANR (ANR-2010-BLAN-1201-01 and ANR-15-CE12-0019-01), and FRM (Equipe FRM 2013 DEQ20130326534) to M.S. We acknowledge support of MINECO “Centro de Excelencia Severo Ochoa 2013-2017,” SEV-2012-0208.
Published: 2018
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42. Multiple Micronutrient Plasma Level Changes Are Related to Oxidative Stress Intensity in Critically Ill Children

Author: Charlotte Cuerq, Marion Pitance, Etienne Javouhey, Emilie Blond, Amandine Bellon, Tiphanie Ginhoux, Sylvain Roche, Aurélie Portefaix, Jenna Ridout, Carole Ford-Chessel, Muriel Bost, René Ecochard, Frédéric V. Valla, Hospices Civils de Lyon (HCL), Catalan Institute of Nanoscience and Nanotechnology (ICN2), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Barcelona Institute of Science and Technology (BIST), Institució Catalana de Recerca i Estudis Avançats (ICREA), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Division of Pediatric Intensive Care, Hôpital Femme Mère Enfant, Laboratoire de Mécanique des Systèmes et des Procédés (LMSP), Centre National de la Recherche Scientifique (CNRS), Consejo Superior de Investigaciones Científicas [Spain] (CSIC)-Barcelona Institute of Science and Technology (BIST), Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Department of Biochemistry, Lyon Sud Hospital, Laboratoire d'Analyse de Traces et Métaux Toxiques, hospices civils de Lyon, Service de Biostatistique, Université de Lyon, Paediatric Intensive Care Unit, Addensbrooke's Hospital, EPICIME-CIC 1407 de Lyon, Inserm, Service de Pharmacologie Clinique, CHU-Lyon, Department of Pediatric Anestesiology, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Service diététique, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR_T9405), Université de Lyon-Université de Lyon-Université Gustave Eiffel (UNIV GUSTAVE EIFFEL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), and Université de Lyon-Université de Lyon-Université Gustave Eiffel
Subjects: Male, Micronutrient deficiency, medicine.medical_treatment, [SDV]Life Sciences [q-bio], vitamin C, vitamin E, Critical Care and Intensive Care Medicine, medicine.disease_cause, Severity of Illness Index, Pediatrics, clinical-trial, chemistry.chemical_compound, 0302 clinical medicine, SANTE, 030212 general & internal medicine, Micronutrients, Prospective Studies, Child, selenium, 2. Zero hunger, chemistry.chemical_classification, pediatric critical illness, Glutathione peroxidase, zinc, Micronutrient, 3. Good health, Child, Preschool, controlled-trial, Female, Vitamin, medicine.medical_specialty, EPIDEMIOLOGIE, Adolescent, Critical Illness, critical-care medicine, antioxidant status, CAROTENE, 03 medical and health sciences, support therapy, Internal medicine, General & Internal Medicine, medicine, Humans, enteral nutrition, carotene, Vitamin C, business.industry, Vitamin E, Infant, 030208 emergency & critical care medicine, medicine.disease, Malnutrition, Oxidative Stress, Cross-Sectional Studies, american, society, chemistry, Case-Control Studies, copper, Pediatrics, Perinatology and Child Health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, inflammatory response syndrome, patient society, business, Oxidative stress, Biomarkers
Abstract: Objectives: Micronutrient supplementation in critically ill adults remains controversial. In the pediatric setting, the impact of oxidative stress on the overall micronutrient status has been poorly explored, due to the limited number of studies and to confounding factors (i.e., malnutrition or extra losses). In order to better understand this phenomenon, we aim to describe micronutrient status, focusing on seven micronutrients, in well-nourished critically ill children presenting with severe oxidative stress. Design: Prospective, transversal, observational, single-center study. Setting: PICU, and anesthesiology department, Lyon, France. Patients: Three groups of patients were clinically defined: severe oxidative stress PICU group (at least two organ dysfunctions), moderate oxidative stress PICU group (single organ dysfunction), and healthy control group (prior to elective surgery); oxidative stress intensity was controlled by measuring plasma levels of glutathione peroxidase and glutathione. Children presenting any former condition leading to micronutrient deficiency were excluded (malnutrition, external losses). Interventions: Plasma levels of selenium, zinc, copper, vitamin A, vitamin E, vitamin C, and -carotene were measured in PICU oxidative stress conditions and compared with those of healthy children. Measurements and Main Results: Two hundred one patients were enrolled (51, 48, and 102 in severe, moderate, and healthy control groups, respectively). Median age was 7.1 years (interquartile range, 2.1-13.8 yr). There was a significant trend (p \textless 0.02) toward plasma level decrease of six micronutrients (selenium, zinc, copper, vitamin E, vitamin C, and -carotene) while oxidative stress intensity increased. Biological markers of oxidative stress (glutathione peroxidase and glutathione) were in accordance with the clinical definition of the three groups. Conclusions: A multiple micronutrient deficiency or redistribution occurs in critically ill children presenting with severe oxidative stress. These findings will help to better identify children who might benefit from micronutrient supplementation and to design adapted supplementation trials in this particular setting.
Published: 2018
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43. Synthèse aisée de nanoparticules du supraconducteur moléculaire κ-(BEDT-TTF)2Cu(NCS)2

Author: Pascale Satgé-De Caro, Christophe Faulmann, Jordi Fraxedas, Lydie Valade, Dominique de Caro, Benoit Cormary, Belén Ballesteros, Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de Chimie Agro-Industrielle (LCA), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Supérieure de Chimie de Toulouse, Catalan Institute of Nanoscience and Nanotechnology (ICN2), Consejo Superior de Investigaciones Científicas [Spain] (CSIC)-Barcelona Institute of Science and Technology (BIST), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Chimie Agro-Industrielle (CAI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole nationale supérieure des ingénieurs en arts chimiques et technologiques-Institut National de la Recherche Agronomique (INRA), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Barcelona Institute of Science and Technology (BIST), Centre National de la Recherche Scientifique (CNRS), CERCA programme/Generalitat de Catalunya, Severo Ochoa programme of the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) [SEV-2013-0295], Centre National de la Recherche Scientifique (France), Generalitat de Catalunya, Ministerio de Economía y Competitividad (España), Ministerio de Economía, Industria y Competitividad (España), Laboratoire de physique et chimie des nano-objets (LPCNO), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UPS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UPS), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), UMR 1010 - Laboratoire de Chimie Agro-industrielle, Institut National de la Recherche Agronomique (INRA), Universitat Autònoma de Barcelona [Barcelona] (UAB), Barcelona Institute of Science and Technology - BIST (SPAIN), Centre National de la Recherche Scientifique - CNRS (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Institut National de la Recherche Agronomique - INRA (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Universitat Autònoma de Barcelona - UAB (SPAIN), Laboratoire de Chimie Agro-Industrielle - LCA (Toulouse, France), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT), Institut National de la Recherche Agronomique (INRA)-Ecole nationale supérieure des ingénieurs en arts chimiques et technologiques (ENSIACET), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), and Institut National Polytechnique de Toulouse - INPT (FRANCE)
Subjects: Diffraction, Materials science, Matériaux, General Chemical Engineering, Donor–acceptor systems, Nanoparticle, 02 engineering and technology, Conductivity, 010402 general chemistry, 01 natural sciences, [SPI.MAT]Engineering Sciences [physics]/Materials, Systèmes donneur–accepteur, High resolution electron microscopy, Electron microscopy, Molecule, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Microscopie électronique, Superconductors, Génie des procédés, Donor-acceptor systems, ComputingMilieux_MISCELLANEOUS, Superconductivity, Range (particle radiation), Atomic force microscopy, General Chemistry, [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Nanostructures, Physical chemistry, Supraconducteurs, 0210 nano-technology
Abstract: [EN]: Well-dispersed roughly spherical nano-objects of the molecule-based superconductor κ-(BEDT-TTF)2Cu(NCS)2 have been prepared in an organic solution by using an easy synthetic route. Long alkyl-chain aconitate esters have been used as growth controlling agents. Nano-objects exhibiting sizes in the 35–120 nm range are made of aggregated individual smaller nanoparticles ranging from 3 to 10 nm. Nanoparticle powders have been studied by X-ray diffraction, high resolution electron microscopy and atomic force microscopy in the conductivity mode., [FR]: Des nano-objets sphériques et bien dispersés du supraconducteur moléculaire κ-(BEDT-TTF)2Cu(NCS)2 ont été préparés en solution organique à l'aide d'une méthode de synthèse relativement aisée. Des aconitates à longue chaîne alkyle ont été utilisés comme régulateurs de croissance. Ces nano-objets de taille comprise entre 35 et 120 nm sont constitués de petites particules dont le diamètre individuel est de l'ordre de 3 à 10 nm. Les poudres nanoparticulaires ont été étudiées par diffraction des rayons X, par microscopie électronique à haute résolution et enfin par microscopie à force atomique en mode conducteur., B. Cormary thanks the Centre National de la Recherche Scientifique (CNRS) for a post-doctoral fellowship. The authors thank S. Ladeira for XRD characterization and M. Tassé for AFM and IV curves. The authors also thank the GDRI HC3A (Heteroelements and Coordination Chemistry: from Concepts to Applications). The ICN2 is funded by the CERCA programme/Generalitat de Catalunya. The ICN2 is supported by the Severo Ochoa programme of the Spanish Ministry of Economy, Industry and Competitiveness (MINECO, grant no. SEV-2013-0295).
Published: 2018
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44. Dynamic Maternal Gradients Control Timing and Shift-Rates for Drosophila Gap Gene Expression

Author: Anton Crombach, Johannes Jaeger, Berta Verd, Systems Biology Research Unit [Barcelone, Espagne], Centre for Genomic Regulation [Barcelone, Espagne], Barcelona Institute of Science and Technology (BIST)-European Molecular Biology Laboratory [Barcelone, Espagne] (EMBL Barcelone)-Barcelona Institute of Science and Technology (BIST)-European Molecular Biology Laboratory [Barcelone, Espagne] (EMBL Barcelone), Universitat Pompeu Fabra [Barcelona] (UPF), Konrad Lorentz Institute for Evolution and Cognition Research [Klosterneuburg, Autriche] (KLI), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Wissenschaftskolleg zu Berlin, The authors thankfully acknowledge the computer resources, technical expertise and assistance provided by the Barcelona Supercomputing Center - Centro Nacional de Supercomputacion. BV was supported by a 'la Caixa' fellowship, and a Writing-Up Fellowship at the KLI Klosterneuburg. The research group of JJ was supported by the MEC-EMBL agreement for the EMBL/CRG Research Unit in Systems Biology, European Commission grant FP7-KBBE-2011-5/289434 (BioPreDyn), and grants BFU2009-10184 and BFU2012-33775 from MINECO. JJ thanks the Wissenschaftskolleg zu Berlin (Wiko) for a 10-month fellowship in 2014/15 and AC, for a half-year fellowship in 2014/15. The Centre for Genomic Regulation (CRG) acknowledges support from MINECO, 'Centro de Excelencia Severo Ochoa 2013±2017' SEV-2012-0208., European Project: 289434,EC:FP7:KBBE,FP7-KBBE-2011-5,BIOPREDYN(2011), Bodescot, Myriam, From Data to Models: New Bioinformatics Methods and Tools for Data-Driven Predictive Dynamic Modelling in Biotechnological Applications - BIOPREDYN - - EC:FP7:KBBE2011-10-01 - 2015-03-31 - 289434 - VALID, École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris)
Subjects: 0301 basic medicine, Pattern formation, Computational biology, Biology, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Synthetic genetic networks, [SDV.BDD] Life Sciences [q-bio]/Development Biology, Genetics, Transcription factors, Control (linguistics), Molecular Biology, lcsh:QH301-705.5, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Ecology, Evolution, Behavior and Systematics, Gap gene, Regulation of gene expression, Gene expression regulation, Ecology, Embryonic pattern formation, Drosophila embryogenesis, biology.organism_classification, Expression (mathematics), 030104 developmental biology, Computational Theory and Mathematics, lcsh:Biology (General), Modeling and Simulation, Drosophila, Drosophila melanogaster, 030217 neurology & neurosurgery, Morphogen
Abstract: Pattern formation during development is a highly dynamic process. In spite of this, few experimental and modelling approaches take into account the explicit time-dependence of the rules governing regulatory systems. We address this problem by studying dynamic morphogen interpretation by the gap gene network in Drosophila melanogaster. Gap genes are involved in segment determination during early embryogenesis. They are activated by maternal morphogen gradients encoded by bicoid (bcd) and caudal (cad). These gradients decay at the same time-scale as the establishment of the antero-posterior gap gene pattern. We use a reverse-engineering approach, based on data-driven regulatory models called gene circuits, to isolate and characterise the explicitly time-dependent effects of changing morphogen concentrations on gap gene regulation. To achieve this, we simulate the system in the presence and absence of dynamic gradient decay. Comparison between these simulations reveals that maternal morphogen decay controls the timing and limits the rate of gap gene expression. In the anterior of the embyro, it affects peak expression and leads to the establishment of smooth spatial boundaries between gap domains. In the posterior of the embryo, it causes a progressive slow-down in the rate of gap domain shifts, which is necessary to correctly position domain boundaries and to stabilise the spatial gap gene expression pattern. We use a newly developed method for the analysis of transient dynamics in non-autonomous (time-variable) systems to understand the regulatory causes of these effects. By providing a rigorous mechanistic explanation for the role of maternal gradient decay in gap gene regulation, our study demonstrates that such analyses are feasible and reveal important aspects of dynamic gene regulation which would have been missed by a traditional steady-state approach. More generally, it highlights the importance of transient dynamics for understanding complex regulatory processes in development. The authors thankfully acknowledge the computer resources, technical expertise and assistance provided by the Barcelona Supercomputing Center-Centro Nacional de Supercomputación. BV was supported by a “la Caixa” fellowship, and a Writing-Up Fellowship at the KLI Klosterneuburg. The research group of JJ was supported by the MEC-EMBL agreement for the EMBL/CRG Research Unit in Systems Biology, European Commission grant FP7-KBBE-2011-5/289434 (BioPreDyn), and grants BFU2009-10184 and BFU2012-33775 from MINECO. JJ thanks the Wissenschaftskolleg zu Berlin (Wiko) for a 10-month fellowship in 2014/15 and AC, for a half-year fellowship in 2014/15. The Centre for Genomic Regulation (CRG) acknowledges support from MINECO, “Centro de Excelencia Severo Ochoa 2013-2017” SEV-2012-0208.
Published: 2017
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45. Hollow metal nanostructures for enhanced plasmonics: synthesis, local plasmonic properties and applications

Author: Jordi Arbiol, Aziz Genç, Jordi Sancho-Parramon, Javier Patarroyo, Víctor F. Puntes, Neus G. Bastús, Institut Català de la Salut, [Genç A] Catalan Institute of Nanoscience and Nanotechnology, Barcelona, Spain. The Barcelona Institute of Science and Technology (BIST), Campus UAB, Bellaterra, Barcelona, Spain. Department of Metallurgy and Materials Engineering, Faculty of Engineering, Bartin University, Bartin, Turkey. [Patarroyo J] Catalan Institute of Nanoscience and Nanotechnology Barcelona, Spain. The Barcelona Institute of Science and Technology, Campus UAB, Bellaterra, Barcelona, Spain. [Sancho-Parramon J] Rudjer Boskovic Institute, Zagreb, Croatia. [Bastús N G] Catalan Institute of Nanoscience and Nanotechnology, Barcelona, Spain. The Barcelona Institute of Science and Technology (BIST), Campus UAB, Bellaterra, Barcelona, Spain. [Franco V] Catalan Institute of Nanoscience and Nanotechnology, Barcelona, Spain. The Barcelona Institute of Science and Technology (BIST), Campus UAB, Bellaterra, Barcelona, Spain. Vall d’Hebron Institut de Recerca, Barcelona, Spain. ICREA, Barcelona, Spain. [Arbiol J] Catalan Catalan Institute of Nanoscience and Nanotechnology, Barcelona, Spain. The Barcelona Institute of Science and Technology (BIST), Campus UAB, Bellaterra, Barcelona, Spain. ICREA, Barcelona, Spain., Vall d'Hebron Barcelona Hospital Campus, European Commission, Ministerio de Ciencia e Innovación (España), Generalitat de Catalunya, and Hospital Universitari Vall d'Hebron
Subjects: Materials science, Nanostructure, Hollow nanostructures, Surface plasmon resonances (SPRs), QC1-999, Nanoparticle, Physics::Optics, Nanotechnology, 02 engineering and technology, Electron energyloss spectroscopy (EELS), Técnicas de Investigación::Técnicas de Química Analítica::Resonancia por Plasmón de Superficie [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Investigative Techniques::Chemistry Techniques, Analytical::Surface Plasmon Resonance [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT], 010402 general chemistry, 01 natural sciences, Nanomaterials, Technology, Industry, and Agriculture::Manufactured Materials::Nanostructures [TECHNOLOGY, INDUSTRY, AGRICULTURE], Condensed Matter::Materials Science, Plasmon hybridization, Electrical and Electronic Engineering, Surface plasmon resonance, Ressonància de plasmons superficials, tecnología, industria y agricultura::productos manufacturados::nanoestructuras [TECNOLOGÍA, INDUSTRIA Y AGRICULTURA], Plasmon, Electron energy-loss spectroscopy (EELS), Nanoestructures, Tecnología, Industria y Agricultura::Materiales Manufacturados::Nanoestructuras [TECNOLOGÍA, INDUSTRIA, AGRICULTURA], Physics, Surface plasmon, Otros calificadores::Otros calificadores::/utilización [Otros calificadores], Surface-enhanced Raman spectroscopy, 021001 nanoscience & nanotechnology, técnicas de investigación::técnicas de química analítica::resonancia de plasmones de superficie [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Atomic and Molecular Physics, and Optics, 0104 chemical sciences, Electronic, Optical and Magnetic Materials, Characterization (materials science), hollow nanostructures, surface plasmon resonances (SPRs), plasmon hybridization, electron energy-loss spectroscopy (EELS), applications, electron energy-loss spectroscopy (eels), Applications, Other subheadings::Other subheadings::/utilization [Other subheadings], 0210 nano-technology, Biotechnology
Abstract: Metallic nanostructures have received great attention due to their ability to generate surface plasmon resonances, which are collective oscillations of conduction electrons of a material excited by an electromagnetic wave. Plasmonic metal nanostructures are able to localize and manipulate the light at the nanoscale and, therefore, are attractive building blocks for various emerging applications. In particular, hollow nanostructures are promising plasmonic materials as cavities are known to have better plasmonic properties than their solid counterparts thanks to the plasmon hybridization mechanism. The hybridization of the plasmons results in the enhancement of the plasmon fields along with more homogeneous distribution as well as the reduction of localized surface plasmon resonance (LSPR) quenching due to absorption. In this review, we summarize the efforts on the synthesis of hollow metal nanostructures with an emphasis on the galvanic replacement reaction. In the second part of this review, we discuss the advancements on the characterization of plasmonic properties of hollow nanostructures, covering the single nanoparticle experiments, nanoscale characterization via electron energy-loss spectroscopy and modeling and simulation studies. Examples of the applications, i.e. sensing, surface enhanced Raman spectroscopy, photothermal ablation therapy of cancer, drug delivery or catalysis among others, where hollow nanostructures perform better than their solid counterparts, are also evaluated., J.A. and A.G. acknowledge the funding from Generalitat de Catalunya 2014 SGR 1638 and Spanish MICINN project e-ATOM (MAT2014-51480-ERC). J.P., N.G.B., and V.P. acknowledge financial support from the Generalitat de Catalunya 2014-SGR-612, Spanish MICINN (MAT2012-33330) and European Community (EU-FP7) through the FutureNanoNeeds project. N.G.B. acknowledges financial support by MINECO through the Ramon y Cajal program (RYC-2012- 10991) and by the European Commission Seventh Framework Programme (FP7) through the Marie Curie Career Integration Grant (322153-MINE). ICN2 acknowledges support from the Severo Ochoa Program (MINECO, Grant SEV-2013-0295).
Published: 2016

46. Optical Control of High-Harmonic Generation at the Atomic Thickness

Author: Yadong Wang, Fadil Iyikanat, Xueyin Bai, Xuerong Hu, Susobhan Das, Yunyun Dai, Yi Zhang, Luojun Du, Shisheng Li, Harri Lipsanen, F. Javier García de Abajo, Zhipei Sun, Zhipei Sun Group, Barcelona Institute of Science and Technology, Centre of Excellence in Quantum Technology, QTF, Department of Electronics and Nanoengineering, National Institute for Materials Science, Aalto-yliopisto, and Aalto University
Subjects: Static High-Harmonic Generation, Mechanical Engineering, Electronic States, Transient High-Harmonic Generation, Interband Carrier Transition, General Materials Science, Bioengineering, General Chemistry, Condensed Matter Physics, Real-Time Quantitative Theory of Nonlinear Optics, All-Optical Control
Abstract: openaire: EC/H2020/834742/EU//ATOP High-harmonic generation (HHG), an extreme nonlinear optical phenomenon beyond the perturbation regime, is of great significance for various potential applications, such as high-energy ultrashort pulse generation with outstanding spatiotemporal coherence. However, efficient active control of HHG is still challenging due to the weak light–matter interaction displayed by currently known materials. Here, we demonstrate optically controlled HHG in monolayer semiconductors via the engineering of interband polarization. We find that HHG can be efficiently controlled in the excitonic spectral region with modulation depths up to 95% and ultrafast response speeds of several picoseconds. Quantitative time-domain theory of the nonlinear optical susceptibilities in monolayer semiconductors further corroborates these experimental observations. Our demonstration not only offers an in-depth understanding of HHG but also provides an effective approach toward active optical devices for strong-field physics and extreme nonlinear optics.
Published: 2022
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47. Evaluation of triple negative breast cancer with heterogeneous immune infiltration

Author: Ángela Quintana, Enrique Javier Arenas, Cristina Bernadó, José Fernández Navarro, Jonatan González, Anna Esteve-Codina, Teresa Moliné, Merce Marti, Giuseppe Curigliano, Peter Schmid, Vicente Peg, Joaquín Arribas, Javier Cortés, Institut Català de la Salut, [Quintana Á] Breast Cancer Unit, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Arenas EJ] Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Biomedical Research Network Centre in Oncology (CIBERONC), Madrid, Spain. [Bernadó C] Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Fernández Navarro J, González J] Bioinformatics Department, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Esteve-Codina A] CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Spain. [Moliné T] Servei d’Anatomia Patològica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Peg V] Biomedical Research Network Centre in Oncology (CIBERONC), Madrid, Spain. Servei d’Anatomia Patològica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Arribas J] Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Biomedical Research Network Centre in Oncology (CIBERONC), Madrid, Spain. Departament de Medicina i Ciències de la Vida, Universitat Pompeu Fabra, Barcelona, Spain. Catalan Institution for Research and Advanced Studies, (ICREA), Barcelona, Spain. Cancer Research Program, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Barcelona, Spain. [Cortés J] Breast Cancer Unit, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Department of Medicine, Madrid, Spain. International Breast Cancer Center, Pangaea Oncology, Quironsalud Group, Barcelona, Spain. Medica Scientia Innovation Research (MedSIR), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Mama - Càncer - Prognosi, Immune cell abundance, células::células sanguíneas::leucocitos::leucocitos mononucleares::linfocitos::linfocitos infiltrantes de tumor [ANATOMÍA], Marcadors tumorals, Immunology, Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Lymphocytes, Tumor-Infiltrating [ANATOMY], Tumor-infiltrating lymphocytes, Limfòcits, neoplasias::neoplasias por localización::neoplasias de la mama::neoplasias de mama triple negativos [ENFERMEDADES], Neoplasms::Neoplasms by Site::Breast Neoplasms::Triple Negative Breast Neoplasms [DISEASES], Intratumor heterogeneity, Immunology and Allergy, Triple negative breast cancer, Transcriptomics, Diagnosis::Prognosis [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], diagnóstico::pronóstico [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS]
Abstract: Intratumor heterogeneity; Transcriptomics; Tumor-infiltrating lymphocytes Heterogeneïtat intratumoral; Transcriptòmica; Limfòcits infiltrants de tumors Heterogeneidad intratumoral; Transcriptómica; Linfocitos infiltrantes de tumores Introduction: Tumor infiltrating lymphocytes (TILs) are known to be a prognostic and predictive biomarker in breast cancer, particularly in triple negative breast cancer (TNBC) patients. International guidelines have been proposed to evaluate them in the clinical setting as a continuous variable, without a clear defined cut-off. However, there are scenarios where the immune infiltration is heterogeneous that some areas of the patient’s tumour have high numbers of TILs while other areas completely lack them. This spontaneous presentation of a heterogeneous immune infiltration could be a great opportunity to study why some tumours present TILs at diagnosis but others do not, while eliminating inter patient’s differences. Methods: In this study, we have identified five TNBC patients that showed great TIL heterogeneity, with areas of low (≤5%) and high (≥50%) numbers of TILs in their surgical specimens. To evaluate immune infiltration heterogeneity, we performed and analyzed bulk RNA-sequencing in three independent triplicates from the high and low TIL areas of each patient. Results: Gene expression was homogeneous within the triplicates in each area but was remarkable different between TILs regions. These differences were not only due to the presence of TILs as there were other non-inflammatory genes and pathways differentially expressed between the two areas. Discussion: This highlights the importance of intratumour heterogeneity driving the immune infiltration, and not patient’s characteristics like the HLA phenotype, germline DNA or immune repertoire. This research has received funding from “Contigo contra el cancer de la mujer” Foundation and FERO Foundation.
Published: 2023
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48. Synthesis, characterization, and thermoelectric properties of superconducting (BEDT-TTF)(2)I-3 nanoparticles

Author: Christophe Faulmann, Eden Steven, Lydie Valade, Jordi Fraxedas, I. Chtioui-Gay, Etienne Yvenou, Shermane M. Benjamin, Kane Jacob, Belén Ballesteros, Alexandre Carella, Eun Sang Choi, D. de Caro, Jean-Pierre Simonato, Minseong Lee, P. de Caro, Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Chimie Agro-Industrielle (CAI), Institut National de la Recherche Agronomique (INRA)-Ecole nationale supérieure des ingénieurs en arts chimiques et technologiques (ENSIACET), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), Catalan Institute of Nanoscience and Nanotechnology (ICN2), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Barcelona Institute of Science and Technology (BIST), Barcelona Institute of Science and Technology (BIST), Facultad de Ciencias y Tecnologias Quimicas, Universidad de Castilla-La Mancha = University of Castilla-La Mancha (UCLM), Instituto de Combustión y Contaminación, National High Magnetic Field Laboratory (NHMFL), National High Magnetic Field Laboratory, Département des Technologies des NanoMatériaux (DTNM), Laboratoire d'Innovation pour les Technologies des Energies Nouvelles et les nanomatériaux (LITEN), Institut National de L'Energie Solaire (INES), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Institut National de L'Energie Solaire (INES), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Ministere de l'Enseignement Superieur et de la Recherche, DGA, Severo Ochoa Program (MINECO) [SEV-2013-0295], NSF-DMR [1309146], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de Chimie Agro-Industrielle (LCA), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Supérieure de Chimie de Toulouse, Consejo Superior de Investigaciones Científicas [Spain] (CSIC)-Barcelona Institute of Science and Technology (BIST), Universidad de Castilla-La Mancha (UCLM), Institut de Chimie de Toulouse (ICT-FR 2599), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Departamento de Química Física, Facultad de Ciencias Quimicas, Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de L'Energie Solaire (INES), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Department of Chemistry, Università degli studi di Napoli Federico II, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole nationale supérieure des ingénieurs en arts chimiques et technologiques-Institut National de la Recherche Agronomique (INRA), National Science Foundation (US), Ministère de l’Enseignement supérieur et de la Recherche (France), and Ministerio de Economía y Competitividad (España)
Subjects: Materials science, PHASE, Analytical chemistry, Nanoparticle, Nanotechnology, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, power, alpha-(bedt-ttf)2i3, organic conductors, beta-(bedt-ttf)2i3, nanocrystals, Phase (matter), Thermoelectric effect, Materials Chemistry, [CHIM]Chemical Sciences, [CHIM.COOR]Chemical Sciences/Coordination chemistry, arrays, Superconductivity, Amphiphilic molecule, Atomic force microscopy, General Chemistry, [CHIM.MATE]Chemical Sciences/Material chemistry, gold, 021001 nanoscience & nanotechnology, Magnetic susceptibility, 0104 chemical sciences, Characterization (materials science), thin-films, 0210 nano-technology, absorption
Abstract: The synthesis of (BEDT-TTF)I in the presence of two neutral amphiphilic molecules [N-octylfurfurylimine and 1-octanamine, N-(2-thienylmethylene)] leads to single and aggregated nanoparticles of 2 to 6 nm size. The samples contain highly crystalline nanoparticles of the β-(BEDT-TTF)I phase, confirmed by XRD. Temperature dependent resistance and magnetic susceptibility studies evidence the superconducting transition characteristics of the β-(BEDT-TTF)I phase. The I-V curve of a single nanoparticle aggregate, measured using AFM, exhibits an expected semiconductor-like behaviour. Thermoelectric studies led to a ZT of 1.47 × 10 at 300 K., I. C.-G. thanks the Ministere de l’Enseignement Superieur et de la Recherche for a PhD grant. The authors acknowledge DGA for funding the E. Y. PhD ICN2 acknowledges support from the Severo Ochoa Program (MINECO, Grant SEV-2013-0295). E. S., E. S. C., M. L. and S. M. B. are supported by NSF-DMR 1309146.
Published: 2016
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49. Multiomic analysis of malignant pleural mesothelioma identifies molecular axes and specialized tumor profiles driving intertumor heterogeneity

Author: Lise Mangiante, Nicolas Alcala, Alexandra Sexton-Oates, Alex Di Genova, Abel Gonzalez-Perez, Azhar Khandekar, Erik N. Bergstrom, Jaehee Kim, Xiran Liu, Ricardo Blazquez-Encinas, Colin Giacobi, Nolwenn Le Stang, Sandrine Boyault, Cyrille Cuenin, Severine Tabone-Eglinger, Francesca Damiola, Catherine Voegele, Maude Ardin, Marie-Cecile Michallet, Lorraine Soudade, Tiffany M. Delhomme, Arnaud Poret, Marie Brevet, Marie-Christine Copin, Sophie Giusiano-Courcambeck, Diane Damotte, Cecile Girard, Veronique Hofman, Paul Hofman, Jérôme Mouroux, Charlotte Cohen, Stephanie Lacomme, Julien Mazieres, Vincent Thomas de Montpreville, Corinne Perrin, Gaetane Planchard, Nathalie Rousseau, Isabelle Rouquette, Christine Sagan, Arnaud Scherpereel, Francoise Thivolet, Jean-Michel Vignaud, Didier Jean, Anabelle Gilg Soit Ilg, Robert Olaso, Vincent Meyer, Anne Boland-Auge, Jean-Francois Deleuze, Janine Altmuller, Peter Nuernberg, Alejandro Ibáñez-Costa, Justo P. Castaño, Sylvie Lantuejoul, Akram Ghantous, Charles Maussion, Pierre Courtiol, Hector Hernandez-Vargas, Christophe Caux, Nicolas Girard, Nuria Lopez-Bigas, Ludmil B. Alexandrov, Françoise Galateau-Salle, Matthieu Foll, Lynnette Fernandez-Cuesta, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Stanford University, Universidad de O'Higgins (UOH), Centre de modélisation mathématique (CMM), Universitad de Chile-Centre National de la Recherche Scientifique (CNRS), Barcelona Institute of Science and Technology (BIST), Instituto de Salud Carlos III [Madrid] (ISC), University of California [San Diego] (UC San Diego), University of California (UC), Cornell University [New York], Maimonides Institute of Biomedical Research of Cordoba, Partenaires INRAE, Universidad de Córdoba = University of Córdoba [Córdoba], Hospital Universitario Reina Sofia [Cordoue, Espagne], CIBER Fisiopatología de la Obesidad y Nutrición [Cordoue, Espagne] (CIBEROBN), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Cypath and Cypath-rb [Villeurbanne] (2C), Tumorothèque du Centre de Référence Régional en Cancérologie [CHRU Lille] (T-C2RC), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut de Pathologie de Lille (IPL), Hôpital Nord [CHU - APHM], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Tumorothèque - Centre de Ressources Biologiques Cancer Cochin [Hôpital Cochin AP-HP] (T-CRB Cancer Cochin), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupes hospitalo-universitaires Paris Centre AP-HP [Paris] (GHU Paris Centre), FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Université Côte d'Azur (UCA), Université Côte d'Azur (UCA), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Pasteur [Nice] (CHU), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Marie-Lannelongue, Tissu-Tumorothèque Est - Centre de Ressources Biologiques [HCL, Lyon] (2TE - CRB HCL), Hospices Civils de Lyon (HCL), Réseau d'expertise anatomopathologique et de recherche sur les tumeurs de la plèvre [CHU Caen] (MESOPATH), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Ressources Biologiques - Cancer - IUCT Oncopole [Toulouse] (CRB - Cancer Toulouse), Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Cologne Centre for Genomics [Cologne, Germany] (2CG), Instituto Maimonides de Investigación Biomédica de Cordoba (IMIBIC), Universidad de Córdoba = University of Córdoba [Córdoba]-Hospital Universitario Reina Sofía, Université Grenoble Alpes (UGA), Owkin [New York, NY, USA] (O), Institut Curie [Paris], Institut Mutualiste de Montsouris (IMM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, and Institució Catalana de Recerca i Estudis Avançats (ICREA)
Subjects: [SDV]Life Sciences [q-bio], Genetics, Technology Platforms
Abstract: Malignant pleural mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Through a large series of whole-genome sequencing data, integrated with transcriptomic and epigenomic data using multiomics factor analysis, we demonstrate that the current World Health Organization classification only accounts for up to 10% of interpatient molecular differences. Instead, the MESOMICS project paves the way for a morphomolecular classification of MPM based on four dimensions: ploidy, tumor cell morphology, adaptive immune response and CpG island methylator profile. We show that these four dimensions are complementary, capture major interpatient molecular differences and are delimited by extreme phenotypes that—in the case of the interdependent tumor cell morphology and adapted immune response—reflect tumor specialization. These findings unearth the interplay between MPM functional biology and its genomic history, and provide insights into the variations observed in the clinical behavior of patients with MPM.
Published: 2023
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50. The DES view of the Eridanus supervoid and the CMB cold spot

Author: Kovács, A, Jeffrey, N, Gatti, M, Chang, C, Whiteway, L, Hamaus, N, Lahav, O, Pollina, G, Bacon, D, Kacprzak, T, Mawdsley, B, Nadathur, S, Zeurcher, D, García-Bellido, J, Alarcon, A, Amon, A, Bechtol, K, Bernstein, G M, Campos, A, Rosell, A Carnero, Kind, M Carrasco, Cawthon, R, Chen, R, Choi, A, Cordero, J, Davis, C, Derose, J, Doux, C, Drlica-Wagner, A, Eckert, K, Elsner, F, Elvin-Poole, J, Everett, S, Ferté, A, Giannini, G, Gruen, D, Gruendl, R A, Harrison, I, Hartley, W G, Herner, K, Huff, E M, Huterer, D, Kuropatkin, N, Jarvis, M, Leget, P F, Maccrann, N, Mccullough, J, Muir, J, Myles, J, Navarro-Alsina, A, Pandey, S, Prat, J, Raveri, M, Rollins, R P, Ross, A J, Rykoff, E S, Sánchez, C, Secco, L F, Sevilla-Noarbe, I, Sheldon, E, Shin, T, Troxel, M A, Tutusaus, I, Varga, T N, Yanny, B, Yin, B, Zhang, Y, Zuntz, J, Aguena, M, Allam, S, Andrade-Oliveira, F, Annis, J, Bertin, E, Brooks, D, Burke, D, Carretero, J, Costanzi, M, da&nbsp, Costa, L N, Pereira, M E S, Davis, T, Deundefined, Vicente, J, Desai, S, Diehl, H T, Ferrero, I, Flaugher, B, Fosalba, P, Frieman, J, Gaztañaga, E, Gerdes, D, Giannantonio, T, Gschwend, J, Gutierrez, G, Hinton, S, Hollowood, D L, Honscheid, K, James, D, Kuehn, K, Lima, M, Maia, M A G, Marshall, J L, Melchior, P, Menanteau, F, Miquel, R, Morgan, R, Ogando, R, Paz-Chinchon, F, Pieres, A, Plazas, A A, Monroy, M Rodriguez, Romer, K, Roodman, A, Sanchez, E, Schubnell, M, Serrano, S, Smith, M, Soares-Santos, M, Suchyta, E, Swanson, M E C, Tarle, G, Thomas, D, C-H, To, Weller, J, UAM. Departamento de Física Teórica, Instituto de Astrofísica de Canarias (IAC), Tenerife, Univer Sité de Paris, University College London, The Barcelona Institute of Science and Technology, University of Pennsylvania, University of Chicago, Univer Sity of Chica Go, Ludwig-Maximilians Univer- Sität München, University of Portsmouth, ETH Zurich, Universidad Autonoma de Madrid, Argonne National Laboratory, Stanford University, University of Wisconsin- Madison, Carnegie Mellon University, Laboratório Interinstitucional de E-Astronomia - LIneA, National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Duke University, The Ohio State Univer- Sity, University of Manchester, University of California, Santa Cruz Institute for Particle Physics, Fermi National Accelerator Laboratory, The Ohio State University, California Institute of Technology, SLAC National Accelerator Laboratory, University of Oxford, University of Gene Va, University of Michigan, University of Cambridge, Perimeter Institute for Theoretical Physics, Univer Sidade Estadual de Campinas, Medioambientales y Tecnológicas (CIEMAT), Brookhaven National Laboratory, Institut D'Estudis Espacials de Catalunya (IEEC), CSIC), Max Planck Institute for Extraterrestrial Physics, University of Edinb Urgh, Universidade de São Paulo (USP), Universidade Estadual Paulista (UNESP), Institut D'Astrophysique de Paris, University of Trieste, INAF-Osservatorio Astronomico di Trieste, Institute for Fundamental Physics of the Universe, Observatório Nacional, University of Queensland, IIT Hyderabad, University of Oslo, Univer Sity of Cambridge, Harvard and Smithsonian, Lowell Observatory, Macquarie University, Texas A&M Univer Sity, Princeton University, Institució Catalana de Recerca i Estudis Avan C Ats, Univer Sity of Sussex, University of Southampton, Oak Ridge National Labo- Ratory, Kovács, A, Jeffrey, N, Gatti, M, Chang, C, Whiteway, L, Hamaus, N, Lahav, O, Pollina, G, Bacon, D, Kacprzak, T, Mawdsley, B, Nadathur, S, Zeurcher, D, García-Bellido, J, Alarcon, A, Amon, A, Bechtol, K, Bernstein, G M, Campos, A, Rosell, A Carnero, Kind, M Carrasco, Cawthon, R, Chen, R, Choi, A, Cordero, J, Davis, C, Derose, J, Doux, C, Drlica-Wagner, A, Eckert, K, Elsner, F, Elvin-Poole, J, Everett, S, Ferté, A, Giannini, G, Gruen, D, Gruendl, R A, Harrison, I, Hartley, W G, Herner, K, Huff, E M, Huterer, D, Kuropatkin, N, Jarvis, M, Leget, P F, Maccrann, N, Mccullough, J, Muir, J, Myles, J, Navarro-Alsina, A, Pandey, S, Prat, J, Raveri, M, Rollins, R P, Ross, A J, Rykoff, E S, Sánchez, C, Secco, L F, Sevilla-Noarbe, I, Sheldon, E, Shin, T, Troxel, M A, Tutusaus, I, Varga, T N, Yanny, B, Yin, B, Zhang, Y, Zuntz, J, Aguena, M, Allam, S, Andrade-Oliveira, F, Annis, J, Bertin, E, Brooks, D, Burke, D, Carretero, J, Costanzi, M, da&nbsp, Costa, L N, Pereira, M E S, Davis, T, De&nbsp, Vicente, J, Desai, S, Diehl, H T, Ferrero, I, Flaugher, B, Fosalba, P, Frieman, J, Gaztañaga, E, Gerdes, D, Giannantonio, T, Gschwend, J, Gutierrez, G, Hinton, S, Hollowood, D L, Honscheid, K, James, D, Kuehn, K, Lima, M, Maia, M A G, Marshall, J L, Melchior, P, Menanteau, F, Miquel, R, Morgan, R, Ogando, R, Paz-Chinchon, F, Pieres, A, Plazas, A A, Monroy, M Rodriguez, Romer, K, Roodman, A, Sanchez, E, Schubnell, M, Serrano, S, Smith, M, Soares-Santos, M, Suchyta, E, Swanson, M E C, Tarle, G, Thomas, D, C-H, To, Weller, J, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Ministerio de Economía y Competitividad (España), European Research Council, National Science Foundation (US), European Commission, and Agenzia Spaziale Italiana
Subjects: Cosmology and Nongalactic Astrophysics (astro-ph.CO), Cosmic Background Radiation, FOS: Physical sciences, Física, Astronomy and Astrophysics, cosmic background radiation, Surveys, gravitational lensing: weak, surveys, Space and Planetary Science, Weak [Gravitational Lensing], survey, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract: A. Kovács et al., The Cold Spot is a puzzling large-scale feature in the Cosmic Microwave Background temperature maps and its origin has been subject to active debate. As an important foreground structure at low redshift, the Eridanus supervoid was recently detected, but it was subsequently determined that, assuming the standard ΛCDM model, only about 10–20 per cent of the observed temperature depression can be accounted for via its Integrated Sachs–Wolfe imprint. However, R ≳ 100 h−1Mpc supervoids elsewhere in the sky have shown ISW imprints AISW ≈ 5.2 ± 1.6 times stronger than expected from ΛCDM (AISW = 1), which warrants further inspection. Using the Year-3 redMaGiC catalogue of luminous red galaxies from the Dark Energy Survey, here we confirm the detection of the Eridanus supervoid as a significant underdensity in the Cold Spot’s direction at z < 0.2. We also show, with S/N ≳ 5 significance, that the Eridanus supervoid appears as the most prominent large-scale underdensity in the dark matter mass maps that we reconstructed from DES Year-3 gravitational lensing data. While we report no significant anomalies, an interesting aspect is that the amplitude of the lensing signal from the Eridanus supervoid at the Cold Spot centre is about 30 per cent lower than expected from similar peaks found in N-body simulations based on the standard ΛCDM model with parameters Ωm = 0.279 and σ8 = 0.82. Overall, our results confirm the causal relation between these individually rare structures in the cosmic web and in the CMB, motivating more detailed future surveys in the Cold Spot region., AK has been supported by a Juan de la Cierva Incorporación fellowship with project number IJC2018-037730-I, and funding for this project was also available in part through SEV-2015-0548 and AYA2017-89891-P. Funding for the DES Projects has been provided by the U.S. Department of Energy, the U.S. National Science Foundation, the Ministry of Science and Education of Spain, the Science and Technology Facilities Council of the United Kingdom, the Higher Education Funding Council for England, the National Center for Supercomputing Applications at the University of Illinois at Urbana-Champaign, the Kavli Institute of Cosmological Physics at the University of Chicago, the Center for Cosmology and Astro-Particle Physics at the Ohio State University, the Mitchell Institute for Fundamental Physics and Astronomy at Texas A&M University, Financiadora de Estudos e Projetos, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Conselho Nacional de Desenvolvimento Científico e Tecnológico and the Ministério da Ciência, Tecnologia e Inovação, the Deutsche Forschungsgemeinschaft and the Collaborating Institutions in the Dark Energy Survey. The DES data management system is supported by the National Science Foundation under Grant Numbers AST-1138766 and AST-1536171. The DES participants from Spanish institutions are partially supported by MICINN under grants ESP2017-89838, PGC2018-094773, PGC2018-102021, SEV-2016-0588, SEV-2016-0597, and MDM-2015-0509, some of which include ERDF funds from the European Union. IFAE is partially funded by the CERCA program of the Generalitat de Catalunya. Research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Program (FP7/2007-2013) including ERC grant agreements 240672, 291329, and 306478. We acknowledge support from the Brazilian Instituto Nacional de Ciência e Tecnologia (INCT) do e-Universo (CNPq grant 465376/2014-2).
Published: 2021
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