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207 results on '"IT University of Copenhagen (ITU)"'

1. Affiliated Participation in Open Source Communities

Author: Adam Alami, Andrzej Wasowski IT University of Copenhagen (ITU), Copenhagen, and Denmark
Subjects: business.industry, Distribution (economics), 020207 software engineering, Citizen journalism, 02 engineering and technology, Open source software, Public relations, Intellectual property, Investment (macroeconomics), Open source, Affiliated Participation, 020204 information systems, Free and Open Source Software Development, Commercial Participation in FOSS, 0202 electrical engineering, electronic engineering, information engineering, Business, Observation data, Senior management
Abstract: Background: The adoption of Free/Libre and Open Source Software (FOSS) by institutions is significantly increasing, and so is the affiliated participation (the participation of industry engineers in open source communities as part of their jobs). Aims: This study is an investigation into affiliated participation in FOSS communities. So far, little is known about the affiliated participation and the forces that influence it, even though the FOSS innovation model is increasingly becoming a serious contender for the private investment model in many sectors. Method: We present a qualitative inquiry into affiliated participation in the Robot Operating System (ROS) and Linux Kernel communities, using twenty-one in-depth interviews and participatory observation data from twenty-nine community events. Results: Our results show that affiliated participation in these communities is constrained by several barriers: objections of senior management, protection of the company’s image, protection of intellectual property, undefined processes and policies, the high cost of participation, and unfamiliarity with the FOSS system. Conclusions: These barriers should be addressed in any organization considering using FOSS as a significant acquisition, distribution, and development strategy.
Published: 2019
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2. Siberian carbon sink reduced by forest disturbances

Author: Lei Fan, Jean-Pierre Wigneron, Philippe Ciais, Jérome Chave, Martin Brandt, Stephen Sitch, Chao Yue, Ana Bastos, Xin Li, Yuanwei Qin, Wenping Yuan, Dmitry Schepaschenko, Liudmila Mukhortova, Xiaojun Li, Xiangzhuo Liu, Mengjia Wang, Frédéric Frappart, Xiangming Xiao, Jingming Chen, Mingguo Ma, Jianguang Wen, Xiuzhi Chen, Hui Yang, Dave van Wees, Rasmus Fensholt, Southwest University [Chongqing], Interactions Sol Plante Atmosphère (UMR ISPA), Ecole Nationale Supérieure des Sciences Agronomiques de Bordeaux-Aquitaine (Bordeaux Sciences Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Evolution et Diversité Biologique (EDB), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Department of Geosciences and Natural Resource Management [Copenhagen] (IGN), Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), College of Life and Environmental Sciences [Exeter], University of Exeter, Northwest A and F University, Max Planck Institute for Biogeochemistry (MPI-BGC), Max-Planck-Gesellschaft, Institute of Tibetan Plateau Research, Chinese Academy of Sciences [Beijing] (CAS), Department of Microbiology and Plant Biology, University of Oklahoma (OU), National Sun Yat-Sen University (NSYSU), Sun Yat-Sen University [Guangzhou] (SYSU), V.N. Sukachev Institute of Forest, Siberian Branch of the Russian Academy of Sciences (SB RAS), Siberian Federal University (SibFU), University of Toronto, State Key Laboratory of Remote Sensing Science, Institute of Remote Sensing and Digital Earth (RADI), Chinese Academy of Sciences [Beijing] (CAS)-Chinese Academy of Sciences [Beijing] (CAS), Vrije Universiteit Brussel (VUB), IT University of Copenhagen (ITU), and Earth Sciences
Subjects: [SDU.OCEAN]Sciences of the Universe [physics]/Ocean, Atmosphere, [SDE]Environmental Sciences, General Earth and Planetary Sciences, [SDU.ENVI]Sciences of the Universe [physics]/Continental interfaces, environment, SDG 15 - Life on Land
Abstract: International audience; Siberian forests are generally thought to have acted as an important carbon sink over recent decades, but exposure to severe droughts and fire disturbances may have impacted their carbon dynamics. Limited available forest inventories mean the carbon balance remains uncertain. Here we analyse annual live and dead above-ground carbon changes derived from low-frequency passive microwave observations from 2010 to 2019. We find that during this period, the carbon balance of Siberian forests was close to neutral, with the forests acting as a small carbon sink of +0.02+0.03+0.01 PgC yr−1. Carbon storage in dead wood increased, but this was largely offset by a decrease in live biomass. Substantial losses of live above-ground carbon are attributed to fire and drought, such as the widespread fires in northern Siberia in 2012 and extreme drought in eastern Siberia in 2015. These live above-ground carbon losses contrast with ‘greening’ trends seen in leaf area index over the same period, a decoupling explained by faster post-disturbance recovery of leaf area than live above-ground carbon. Our study highlights the vulnerability of large forest carbon stores in Siberia to climate-induced disturbances, challenging the persistence of the carbon sink in this region of the globe.
Published: 2023

3. Dynamic neutron and X-ray three-dimensional imaging of fluid flow and mixing during mineral precipitation in porous rocks

Author: Paiman Shafabakhsh, Tanguy Le Borgne, Joachim Mathiesen, Gaute Linga, Benoît Cordonnier, Anne Pluymakers, Anders Kaestner, François Renard, University of Oslo (UiO), Géosciences Rennes (GR), Université de Rennes (UR)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR), Université de Rennes (UR)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS), IT University of Copenhagen (ITU), European Synchroton Radiation Facility [Grenoble] (ESRF), Delft University of Technology (TU Delft), Paul Scherrer Institute (PSI), Institut des Sciences de la Terre (ISTerre), Institut national des sciences de l'Univers (INSU - CNRS)-Institut de recherche pour le développement [IRD] : UR219-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Gustave Eiffel-Université Grenoble Alpes (UGA), and European Geosciences Union
Subjects: [PHYS.MECA.MEFL]Physics [physics]/Mechanics [physics]/Fluid mechanics [physics.class-ph], [SDU.STU.HY]Sciences of the Universe [physics]/Earth Sciences/Hydrology
Abstract: International audience; Flow and mixing processes in porous media control many natural and industrial systems, such as microbial clogging, oil extraction, and effluent disposal. In many systems, the porosity may evolve during mineral precipitation, such as in rocks, and control fluid mixing and fluid transport properties. Here, we use three-dimensional in situ dynamic neutron and X-ray micro-tomography imaging to explore fluid transport into Berea sandstone core samples during in-situ carbonate precipitation. Neutron imaging can track fluid flow inside the rock, whereas X-ray imaging illuminates the regions where mineral precipitation occurs. We control the precipitation of calcium carbonate in the rock through reactive-mixing between solutions containing CaCl2 and Na2CO3. By solving the advection-diffusion equation using the contrast in neutron attenuation from time-lapse images, we derive the 3D velocity field of the injected fluids and characterize the evolution of the permeability field into the rock during mineral precipitation. We also investigate the mixing between heavy water and a cadmium solution under the influence of mineral precipitation. Results show that, under the effect of mineral precipitation, a wide range of local flow velocities develop in the sample, under the same fluid injection rate, and we quantify the distribution of flow velocities in the sample. Moreover, we observe more efficient mixing between heavy water and a cadmium solution after mineral precipitation. The finding of this experimental study is useful in progressing the knowledge in the domain of reactive solute and contaminant transport in the subsurface.
Published: 2023

4. Iliac Branch Devices in the Repair of Ruptured Aorto-iliac Aneurysms: A Multicenter Study

Author: Angelos Karelis, Björn Sonesson, Enrico Gallitto, Nikolaos Tsilimparis, Claes Forsell, Nicola Leone, Roberto Silingardi, Thomas Mesnard, Jonathan Sobocinski, Giacomo Isernia, Timothy Resch, Mauro Gargiulo, Nuno V. Dias, Skane University Hospital [Lund], University of Bologna/Università di Bologna, University Heart Center [Hamburg], Linköping university hospital, Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Médicaments et biomatériaux à libération contrôlée: mécanismes et optimisation - Advanced Drug Delivery Systems - U 1008 (MBLC - ADDS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Ospedale 'Santa Maria della Misericordia' = University Hospital 'Santa Maria della Misericordia', and IT University of Copenhagen (ITU)
Subjects: endovascular aneurysm repair, hypogastric artery, abdominal aortic aneurysm, [SDV]Life Sciences [q-bio], Radiology, Nuclear Medicine and imaging, Surgery, common iliac artery aneurysm, Cardiology and Cardiovascular Medicine, iliac branch device
Abstract: Purpose: To evaluate the outcomes of preserving the internal iliac artery (IIA) with iliac branched devices (IBDs) during acute endovascular repair of ruptured aortoiliac aneurysms. Material and Methods: This is a multicenter retrospective review of all consecutive patients undergoing acute endovascular repair of ruptured aortoiliac aneurysm with an IBD at 8 aortic centers between December 2012 and June 2020. A control group was used where the IIA was intentionally occluded from the same study period. The main outcome measures were 30-day mortality, major adverse events, technical success, and clinical success. Secondary outcomes were buttock claudication, primary patency, primary-assisted and secondary patency of the IBD, occurrence of endoleak types I/III, and reintervention. Values are presented as numbers and percentages or interquartile range in parenthesis. Results: Forty-eight patients were included in the study: 24 with IBD and 24 with IIA occlusion. There was no difference in demographics, cardiovascular risk factors, and aneurysm extent. Twenty (83%) of them were hemodynamically stable during the procedure as opposed to 14 (58%, p=.23) with the IIA occlusion. Technical success was achieved in all cases with a procedure time of 180 (133–254) minutes, 45 (23–65) of which were from IBD. There were 2 (8%) deaths during the first 30 days and 2 (8%) major complications unrelated to the IBD, whereas in the IIA occlusion, the figures were 10 (42%) and 7 (29%), respectively. No patient in the IBD group developed buttock claudication compared to 8 (57%, pConclusion: IBD is a valid alternative for maintaining the pelvic circulation for endovascular aortic aneurysm repair of ruptured aortoiliac aneurysms. The technical success and midterm outcomes are very satisfactory but require patient selection particularly regarding hemodynamic stability. The reintervention rate is considerable, mandating continuous follow-up. Clinical Impact This multicenter study demonstrates that ruptured aortoiliac aneurysms do not necessarily require mandatory occlusion of hypogastric arteries. Iliac branch devices are shown to be a valid alternative in highly selected cases, with good midterm results, even if reinterventions are required in a significant proportion of patients.
Published: 2023

5. FUS regulates a subset of snoRNA expression and modulates the level of rRNA modifications

Author: Kishor Gawade, Patrycja Plewka, Sophia J. Häfner, Anders H. Lund, Virginie Marchand, Yuri Motorin, Michal W. Szczesniak, Katarzyna D. Raczynska, Adam Mickiewicz University in Poznań (UAM), IT University of Copenhagen (ITU), Ingénierie, Biologie et Santé en Lorraine (IBSLor), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), and GONNET, JULIE
Subjects: Multidisciplinary, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology
Abstract: FUS is a multifunctional protein involved in many aspects of RNA metabolism, including transcription, splicing, translation, miRNA processing, and replication-dependent histone gene expression. In this work, we show that FUS depletion results in the differential expression of numerous small nucleolar RNAs (snoRNAs) that guide 2’-O methylation (2’-O-Me) and pseudouridylation of specific positions in ribosomal RNAs (rRNAs) and small nuclear RNAs (snRNAs). Using RiboMeth-seq and HydraPsiSeq for the profiling of 2’-O-Me and pseudouridylation status of rRNA species, we demonstrated considerable hypermodification at several sites in HEK293T and SH-SY5Y cells with FUS knockout (FUS KO) compared to wild-type cells. We observed a similar direction of changes in rRNA modification in differentiated SH-SY5Y cells with the FUS mutation (R495X) related to the severe disease phenotype of amyotrophic lateral sclerosis (ALS). Furthermore, the pattern of modification of some rRNA positions was correlated with the abundance of corresponding guide snoRNAs in FUS KO and FUS R495X cells. Our findings reveal a new role for FUS in modulating the modification pattern of rRNA molecules, that in turn might generate ribosome heterogeneity and constitute a fine-tuning mechanism for translation efficiency/fidelity. Therefore, we suggest that increased levels of 2’-O-Me and pseudouridylation at particular positions in rRNAs from cells with the ALS-linked FUS mutation may represent a possible new translation-related mechanism that underlies disease development and progression.
Published: 2023

6. Clostridium botulinum type C, D, C/D, and D/C: An update

Author: Meurens, François, Carlin, Frédéric, Federighi, Michel, Filippitzi, Maria-Eleni, Fournier, Matthieu, Fravalo, Philippe, Vaillancourt, Jean-Pierre, Ganière, Jean-Pierre, Grisot, Lionel, Guillier, Laurent, Hilaire, Didier, Kooh, Pauline, Woudstra, Cédric, Le Bouquin-Leneveu, Sophie, Le Maréchal, Caroline, Mazuet, Christelle, Petit, Karine, Morvan, Hervé, Biologie, Epidémiologie et analyse de risque en Santé Animale (BIOEPAR), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Saskatchewan [Saskatoon] (U of S), Sécurité et Qualité des Produits d'Origine Végétale (SQPOV), Avignon Université (AU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Sécurité des Aliments (SECALIM), Aristotle University of Thessaloniki, Morphodynamique Continentale et Côtière (M2C), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Metabiot (Metabiot), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Faculté de Médecine Vétérinaire [UdeM-Saint-Hyacinthe] (FMV - UdeM), Université de Montréal (UdeM), Retired, Clinique des Tourbières, Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Maîtrise nucléaire, radiologique, bactériologique et chimique (MNRBC), Direction générale de l'Armement (DGA), IT University of Copenhagen (ITU), Laboratoire de Ploufragan-Plouzané-Niort [ANSES], Centre National de Référence des Bactéries Anaérobies et Botulisme - National Reference Center Anaerobic Bacteria and Botulism (CNR), and Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité)
Subjects: Microbiology (medical), Clostridium, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, botulism, cattle, poultry, [SDV]Life Sciences [q-bio], toxins, zoonosis, Microbiology
Abstract: We are grateful to the ANSES expert committee panel in charge of assessing animal health and animal welfare risk, and to the working group “Botulism,” including the authors as well as Catherine Belloc, Stéphane Bertagnoli, Alain Boissy, Henri-Jean Boulouis, Eric Collin, Jean-Claude Desfontis, David Fretin, Emmanuelle Gilot-Fromont, Etienne Giraud, Nadia Haddad, Viviane Hénaux, Elsa Jourdain, Sophie Le Poder-Alcon, Monique L’Hostis, Gilles Meyer, Elodie Monchatre-Leroy, Pierre Mormède, Carine Paraud, Ariane Payne, Carole Peroz-Sapede, Claire Ponsart, Claude Saegerman, Gaëlle Simon, Michèle Tremblay, Nathalie Arnich, Isabelle Attig, Carole Catastini, Charlotte Dunoyer, Nabila Haddache, and Elissa Khamisse.; International audience; Clostridium botulinum is the main causative agent of botulism, a neurological disease encountered in humans as well as animals. Nine types of botulinum neurotoxins (BoNTs) have been described so far. Amongst these “toxinotypes,” the A, the B and E are the most frequently encountered in humans while the C, D, C/D and D/C are mostly affecting domestic and wild birds as well as cattle. In France for instance, many cases and outbreaks are reported in these animal species every year. However, underestimation is very likely at least for avifauna species where the detection of dead animals can be challenging. Knowledge about BoNTs C, D, C/D, and D/C and the diseases they cause in animals and humans is still scarce and unclear. Specifically, the potential role of animal botulism outbreaks in cattle and poultry as a source of human illness needs to be further assessed. In this narrative review, we present the current knowledge about toxinotypes C, D, C/D, and D/C in cattle and poultry with, amongst various other aspects, their epidemiological cycles. We also discuss the zoonotic potential of these toxinotypes and some possible ways of risk mitigation. An adapted and effective management of botulism outbreaks in livestock also requires a better understanding of these less common and known toxinotypes.
Published: 2023

7. Beyond the boom-bust cycle:An interdisciplinary framework for analysing crop booms

Author: Jean-Christophe Castella, Juliet Lu, Cecilie Friis, Thilde Bech Bruun, Robert Cole, Victoria Junquera, Miles Kenney-Lazar, Sango Mahanty, Christine Ornetsmüller, Pin Pravalprukskul, Isabelle Vagneron, Savoirs, ENvironnement et Sociétés (SENS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Paul-Valéry - Montpellier 3 (UPVM)-Institut de Recherche pour le Développement (IRD), Cornell University [New York], IT University of Copenhagen (ITU), National University of Singapore (NUS), Princeton University, Australian National University (ANU), Département Environnements et Sociétés (Cirad-ES), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Montpellier Interdisciplinary center on Sustainable Agri-food systems (Social and nutritional sciences) (UMR MoISA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, and 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)
Subjects: Global and Planetary Change, Crop boom cycles, Governance, Ecology, Variegated pathways, Conceptual framework, Geography, Planning and Development, [SDE]Environmental Sciences, Nested scales, Mekong Region, Management, Monitoring, Policy and Law, [SHS]Humanities and Social Sciences
Abstract: International audience; The expansion of commercial agriculture is one of the primary drivers of livelihood and land-use changes in the world. Globalisation and other factors have intensified this expansion to the point where booms in single cash crops overtake entire regions before going bust, a pattern that is particularly pervasive in resource frontiers. Using case studies across the Mekong Region, a place which serves as a harbinger for crop booms globally, we propose a new analytical framework for understanding and governing crop booms. We combine multiple theoretical approaches to study crop booms and draw on insights from case study work conducted across temporal and spatial scales. The framework consists of three components: 1) the nested nature of crop boom-bust trajectories, 2) the cyclical spatial and temporal patterns of crop booms, and 3) the variegated pathways and impacts of agrarian change. The framework presents new insights into the processes of agricultural intensification in frontier spaces. As such, it facilitates a better understanding of the drivers, characteristics and impacts of crop booms for researchers and decision-makers alike with the intention of supporting efforts to develop more sustainable pathways in the region and beyond.
Published: 2023

8. A species-level trait dataset of bats in Europe and beyond

Author: Jérémy S. P. Froidevaux, Nia Toshkova, Luc Barbaro, Ana Benítez-López, Christian Kerbiriou, Isabelle Le Viol, Michela Pacifici, Luca Santini, Clare Stawski, Danilo Russo, Jasja Dekker, Antton Alberdi, Francisco Amorim, Leonardo Ancillotto, Kévin Barré, Yves Bas, Lisette Cantú-Salazar, Dina K. N. Dechmann, Tiphaine Devaux, Katrine Eldegard, Sasan Fereidouni, Joanna Furmankiewicz, Daniela Hamidovic, Davina L. Hill, Carlos Ibáñez, Jean-François Julien, Javier Juste, Peter Kaňuch, Carmi Korine, Alexis Laforge, Gaëlle Legras, Camille Leroux, Grzegorz Lesiński, Léa Mariton, Julie Marmet, Vanessa A. Mata, Clare M. Mifsud, Victoria Nistreanu, Roberto Novella-Fernandez, Hugo Rebelo, Niamh Roche, Charlotte Roemer, Ireneusz Ruczyński, Rune Sørås, Marcel Uhrin, Adriana Vella, Christian C. Voigt, Orly Razgour, University of Stirling, Centre d'Ecologie et des Sciences de la COnservation (CESCO), Muséum national d'Histoire naturelle (MNHN)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Bristol [Bristol], National Museum of Natural History, Sofia, Bulgaria (NMNHS), Bulgarian Academy of Sciences (BAS), Dynamiques et écologie des paysages agriforestiers (DYNAFOR), École nationale supérieure agronomique de Toulouse (ENSAT), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Estación Biológica de Doñana (EBD), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Universidad de Granada = University of Granada (UGR), Dipartimento INFOCOM [Roma], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Norwegian University of Science and Technology (NTNU), University of the Sunshine Coast (USC), University of Naples Federico II = Università degli studi di Napoli Federico II, Auteur indépendant, IT University of Copenhagen (ITU), Centro de Investigação em Biodiversidade e Recursos Genéticos [Vairao] (CIBIO), Universidade do Porto = University of Porto, Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Université Paul-Valéry - Montpellier 3 (UPVM)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, 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)-Université de Montpellier (UM), Luxembourg Institute of Science and Technology (LIST), Max Planck Institute of Animal Behavior, University of Konstanz, Office français de la biodiversité (OFB), Norwegian University of Life Sciences (NMBU), University of Veterinary Medicine [Vienna] (Vetmeduni), University of Wrocław [Poland] (UWr), Croatian Biospeleological Society, University of Glasgow, CIBER de Epidemiología y Salud Pública (CIBERESP), Ecosystèmes Insulaires Océaniens (UMR 241) (EIO), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de la Polynésie Française (UPF)-Institut Louis Malardé [Papeete] (ILM), Institut de Recherche pour le Développement (IRD), Station de Biologie Marine de Concarneau, Direction générale déléguée à la Recherche, à l’Expertise, à la Valorisation et à l’Enseignement-Formation (DGD.REVE), Muséum national d'Histoire naturelle (MNHN)-Muséum national d'Histoire naturelle (MNHN), University of Southampton, School of Biological Sciences, University of P. J. Safarik in Kosice, University of Malta [Malta], Leibniz Institute for Zoo and Wildlife Research (IZW), Leibniz Association, University of Exeter, and Jeremy Froidevaux was funded by the Région Bretagne (SAD grant number 19041) and the Leverhulme Trust (grant number: ECF-2020-571). Nia Toshkova was funded by the Bulgarian National Science Fund (CP-06-COST/15from 16.12.2020) and а PhD Fellowship from Karoll Knowledge Foundation.
Subjects: Statistics and Probability, [SDV]Life Sciences [q-bio], ddc:570, Library and Information Sciences, Statistics, Probability and Uncertainty, Computer Science Applications, Education, Information Systems
Abstract: Knowledge of species’ functional traits is essential for understanding biodiversity patterns, predicting the impacts of global environmental changes, and assessing the efficiency of conservation measures. Bats are major components of mammalian diversity and occupy a variety of ecological niches and geographic distributions. However, an extensive compilation of their functional traits and ecological attributes is still missing. Here we present EuroBaTrait 1.0, the most comprehensive and up-to-date trait dataset covering 47 European bat species. The dataset includes data on 118 traits including genetic composition, physiology, morphology, acoustic signature, climatic associations, foraging habitat, roost type, diet, spatial behaviour, life history, pathogens, phenology, and distribution. We compiled the bat trait data obtained from three main sources: (i) a systematic literature and dataset search, (ii) unpublished data from European bat experts, and (iii) observations from large-scale monitoring programs. EuroBaTrait is designed to provide an important data source for comparative and trait-based analyses at the species or community level. The dataset also exposes knowledge gaps in species, geographic and trait coverage, highlighting priorities for future data collection.
Published: 2023

9. Estimating Aboveground Carbon Dynamic of China Using Optical and Microwave Remote-Sensing Datasets from 2013 to 2019

Author: Chang, Zhongbing, Fan, Lei, J.-P., Wigneron, Wang, Ying-Ping, Ciais, Philippe, Chave, Jérôme, Fensholt, Rasmus, Chen, Jing M., Yuan, Wenping, Ju, Weimin, Li, Xin, Jiang, Fei, Wu, Mousong, Chen, Xiuzhi, Qin, Yuanwei, Frappart, Frédéric, Li, Xiaojun, Wang, Mengjia, Liu, Xiangzhuo, Tang, Xuli, Hobeichi, Sanaa, Yu, Mengxiao, Ma, Mingguo, Xiao, Qing, Wen, Jianguang, Shi, Weiyu, Liu, Dexin, Yan, Junhua, Chinese Academy of Sciences [Beijing] (CAS), Southwest University [Chongqing], Interactions Sol Plante Atmosphère (UMR ISPA), Ecole Nationale Supérieure des Sciences Agronomiques de Bordeaux-Aquitaine (Bordeaux Sciences Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CSIRO Atmospheric Research, Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Evolution et Diversité Biologique (EDB), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), IT University of Copenhagen (ITU), University of Toronto, Sun Yat-Sen University [Guangzhou] (SYSU), Nanjing University (NJU), University of Oklahoma (OU), Laboratoire d'études en Géophysique et océanographie spatiales (LEGOS), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), and University of New South Wales [Sydney] (UNSW)
Subjects: [SDU]Sciences of the Universe [physics]
Abstract: Over the past 2 to 3 decades, Chinese forests are estimated to act as a large carbon sink, yet the magnitude and spatial patterns of this sink differ considerably among studies. Using 3 microwave (L- and X-band vegetation optical depth [VOD]) and 3 optical (normalized difference vegetation index, leaf area index, and tree cover) remote-sensing vegetation products, this study compared the estimated live woody aboveground biomass carbon (AGC) dynamics over China between 2013 and 2019. Our results showed that tree cover has the highest spatial consistency with 3 published AGC maps (mean correlation value R = 0.84), followed by L-VOD ( R = 0.83), which outperform the other VODs. An AGC estimation model was proposed to combine all indices to estimate the annual AGC dynamics in China during 2013 to 2019. The performance of the AGC estimation model was good (root mean square error = 0.05 Pg C and R 2 = 0.90 with a mean relative uncertainty of 9.8% at pixel scale [0.25°]). Results of the AGC estimation model showed that carbon uptake by the forests in China was about +0.17 Pg C year −1 from 2013 to 2019. At the regional level, provinces in southwest China including Guizhou (+22.35 Tg C year −1 ), Sichuan (+14.49 Tg C year −1 ), and Hunan (+11.42 Tg C year −1 ) provinces had the highest carbon sink rates during 2013 to 2019. Most of the carbon-sink regions have been afforested recently, implying that afforestation and ecological engineering projects have been effective means for carbon sequestration in these regions.
Published: 2023

10. Diverse Lava Flow Morphologies in the Stratigraphy of the Jezero Crater Floor

Author: S. Alwmark, B. Horgan, A. Udry, A. Bechtold, S. Fagents, E. Ravanis, L. Crumpler, N. Schmitz, E. Cloutis, A. Brown, D. Flannery, O. Gasnault, J. Grotzinger, S. Gupta, L. Kah, P. Kelemen, K. Kinch, J. Núñez, Lund University [Lund], IT University of Copenhagen (ITU), Purdue University [West Lafayette], University of Nevada [Las Vegas] (WGU Nevada), University of Vienna [Vienna], Austrian Academy of Sciences (OeAW), University of Hawai‘i [Mānoa] (UHM), New Mexico Museum of Natural History and Science (NMMNHS), DLR Institute of Planetary Research, German Aerospace Center (DLR), Department of Geography [Winnipeg], University of Winnipeg, Queensland University of Technology [Brisbane] (QUT), Institut de recherche en astrophysique et planétologie (IRAP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Christian-Albrechts-Universität zu Kiel (CAU), Department of Earth Science and Technology [Imperial College London], Imperial College London, The University of Tennessee [Knoxville], Lamont-Doherty Earth Observatory (LDEO), Columbia University [New York], Department of Earth and Environmental Sciences [New York], University of Copenhagen = Københavns Universitet (UCPH), and Johns Hopkins University Applied Physics Laboratory [Laurel, MD] (APL)
Subjects: Jezero crater, Geophysics, [SDU.STU.PL]Sciences of the Universe [physics]/Earth Sciences/Planetology, Mars2020 Perseverance Geology Geomorphology stratigraphy Jezero crater, Space and Planetary Science, Geochemistry and Petrology, [SDU]Sciences of the Universe [physics], Maaz formation, Earth and Planetary Sciences (miscellaneous), [SDU.ASTR.EP]Sciences of the Universe [physics]/Astrophysics [astro-ph]/Earth and Planetary Astrophysics [astro-ph.EP], Mars 2020 Perseverance, Artuby, Lava
Abstract: International audience; We present a combined geomorphologic, multispectral, and geochemical analysis of crater floor rocks in Jezero crater based on data obtained by the Mastcam-Z and SuperCam instruments onboard the NASA Mars 2020 Perseverance rover. The combined data from this analysis together with the results of a comparative study with geologic sites on Earth allows us to interpret the origins of rocks exposed along the Artuby ridge, a ∼900 m long scarp of lower Máaz formation rocks. The ridge exposes rocks belonging to two morphologically distinct members, Artuby and Rochette, that both have basaltic composition and are spectrally indistinguishable in our analysis. Artuby rocks consist of morphologically distinct units that alternate over the ridge, bulbous, hummocky, layers with varying thicknesses that in places appear to have flowed over underlying strata, and sub-planar thinner laterally continuous layers with variable friability. The Rochette member has a massive appearance with pronounced pitting and sub-horizontal partings. Our findings are most consistent with a primary igneous emplacement as lava flows, through multiple eruptions, and we propose that the thin layers result either from preferential weathering, interbedded ash/tephra layers, ʻaʻā clinker layers, or aeolian deposition. Our analyses provide essential geologic context for the Máaz formation samples that will be returned to Earth and highlight the diversity and complexity of geologic processes on Mars not visible from orbit.
Published: 2023

11. Impact of Comorbid Affective Disorders on Longitudinal Clinical Outcomes in Individuals at Ultra-high Risk for Psychosis

Author: Nadine C van der Burg, Philip McGuire, Birte Glenthøj, Stephan Ruhrmann, Jim van Os, Bart P. F. Rutten, Neus Barrantes-Vidal, Patrick D. McGorry, Frederike Schirmbeck, Gabriele Sachs, Rodrigo A. Bressan, Barnaby Nelson, Marie-Odile Krebs, Jentien M Vermeulen, Anita Riecher-Rössler, G. Paul Amminger, Matthijs Blankers, Lucia Valmaggia, Mark van der Gaag, Christos Pantelis, Paolo Fusar-Poli, Merete Nordentoft, Lieuwe de Haan, Matthew J. Kempton, Adult Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, VU University Medical Center [Amsterdam], Arkin Institute for Mental Health [Amsterdam, The Netherlands] (AIMH), GGZ Centraal [Amersfoort, The Netherlands], Trimbos Institute, Netherlands Institute of Mental Health and Addiction, King‘s College London, Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), Psychosis Research Institute [The Hague, Netherlands], University of Basel (Unibas), Universidade Federal de São Paulo, Universitat Autònoma de Barcelona (UAB), Spanish Mental Health Research Network (CIBERSAM), Orygen [Parkville, Victoria], University of Melbourne, Melbourne Health [Carlton South, Victoria], Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Groupement de recherche en Psychiatrie (GDR Psychiatrie (3557)), Centre National de la Recherche Scientifique (CNRS), University of Cologne, Medizinische Universität Wien = Medical University of Vienna, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], University Medical Center [Utrecht], IT University of Copenhagen, South London and Maudsley NHS Foundation Trust, University of Pavia, EU-GEI High Risk Study Group Authors: Maria Calem, Stefania Tognin, Gemma Modinos, Sara Pisani, Emily Hedges, Eva Velthorst, Tamar C Kraan, Daniella S van Dam, Nadine Burger, Athena Politis, Joanne Goodall, Stefan Borgwardt, Erich Studerus, Ary Gadelha, Elisa Brietzke, Graccielle Asevedo, Elson Asevedo, Andre Zugman, Tecelli Domínguez-Martínez, Manel Monsonet, Lidia Hinojosa, Anna Racioppi, Thomas R Kwapil, Mathilde Kazes, Claire Daban, Julie Bourgin, Olivier Gay, Célia Mam-Lam-Fook, Dorte Nordholm, Lasse Randers, Kristine Krakauer, Louise Birkedal Glenthøj, Dominika Gebhard, Julia Arnhold, Joachim Klosterkötter, Iris Lasser, Bernadette Winklbaur, Philippe A Delespaul, VU University Amsterdam, Martinez Rico, Clara, Vrije Universiteit Amsterdam [Amsterdam] (VU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), IT University of Copenhagen (ITU), Università degli Studi di Pavia = University of Pavia (UNIPV), RS: MHeNs - R3 - Neuroscience, Psychiatrie & Neuropsychologie, MUMC+: MA Psychiatrie (3), RS: MHeNs - R2 - Mental Health, and MUMC+: Hersen en Zenuw Centrum (3)
Subjects: Male, Ultra-high risk, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Comorbid, Comorbidity, Anxiety, Logistic regression, 0302 clinical medicine, Longitudinal Studies, psychosis, Depression (differential diagnoses), Depression, anxiety, DEPRESSION, Anxiety Disorders, STATE, EXPERIENCES, CHILDHOOD TRAUMA, Europe, Psychiatry and Mental health, YOUTH, Schizophrenia, Female, medicine.symptom, Anxiety disorder, Adult, Risk, medicine.medical_specialty, Psychosis, Adolescent, AcademicSubjects/MED00810, Prodromal Symptoms, comorbid, Lower risk, ultra-high risk, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Risk factor, METAANALYSIS, Depressive Disorder, Mood Disorders, business.industry, PERSISTENCE, prediction, medicine.disease, 030227 psychiatry, schizophrenia, Psychotic Disorders, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, ONSET, Gene-Environment Interaction, business, Prediction, 030217 neurology & neurosurgery, AT-RISK, Regular Articles, Follow-Up Studies
Abstract: Introduction Diagnoses of anxiety and/or depression are common in subjects at Ultra-High Risk for Psychosis (UHR) and associated with extensive functional impairment. Less is known about the impact of affective comorbidities on the prospective course of attenuated psychotic symptoms (APS). Method Latent class mixed modelling identified APS trajectories in 331 UHR subjects assessed at baseline, 6, 12, and 24 months follow-up. The prognostic value of past, baseline, and one-year DSM-IV depressive or anxiety disorders on trajectories was investigated using logistic regression, controlling for confounders. Cox proportional hazard analyses investigated associations with transition risk. Results 46.8% of participants fulfilled the criteria for a past depressive disorder, 33.2% at baseline, and 15.1% at one-year follow-up. Any past, baseline, or one-year anxiety disorder was diagnosed in 42.9%, 37.2%, and 27.0%, respectively. Participants were classified into one of three latent APS trajectory groups: (1) persistently low, (2) increasing, and (3) decreasing. Past depression was associated with a higher risk of belonging to the increasing trajectory group, compared to the persistently low (OR = 3.149, [95%CI: 1.298–7.642]) or decreasing group (OR = 3.137, [1.165–8.450]). In contrast, past (OR = .443, [.179–1.094]) or current (OR = .414, [.156–1.094]) anxiety disorders showed a trend-level association with a lower risk of belonging to the increasing group compared to the persistently low group. Past depression was significantly associated with a higher risk of transitioning to psychosis (HR = 2.123, [1.178–3.828]). Conclusion A past depressive episode might be a particularly relevant risk factor for an unfavorable course of APS in UHR individuals. Early affective disturbances may be used to advance detection, prognostic, and clinical strategies.
Published: 2022

12. First assessment of optical and microwave remotely sensed vegetation proxies in monitoring aboveground carbon in tropical Asia

Author: Cui, Tianxiang, Fan, Lei, Ciais, Philippe, Fensholt, R., Frappart, Frédéric, Sitch, Stephen A., Chave, Jérôme, Chang, Zhongbing, Li, Xiaojun, Wang, Mengjia, Liu, Xiangzhuo, Ma, Mingguo, Wigneron, Jean Pierre, Nanjing Forestry University (NFU), Southwest University [Chongqing], Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), IT University of Copenhagen (ITU), Interactions Sol Plante Atmosphère (UMR ISPA), Ecole Nationale Supérieure des Sciences Agronomiques de Bordeaux-Aquitaine (Bordeaux Sciences Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Exeter, Université Toulouse III Paul Sabatier - Faculté de médecine Purpan (UTPS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT), Zhengzhou University, European Space Agency, ESA: ESRIN/4000123002/18/I-NB, National Natural Science Foundation of China, NSFC: 42171339, 42201364, Centre National d’Etudes Spatiales, CNES, Natural Science Foundation of Jiangsu Province: BK20190764, State Key Laboratory of Remote Sensing Science, SKLRSS: OFSLRSS202005, and This work was supported by the National Natural Science Foundation of China ( 42201364 , 42171339 ), Natural Science Foundation of Jiangsu Province ( BK20190764 ), and the Open Fund of State Key Laboratory of Remote Sensing Science ( OFSLRSS202005 ). J.-P·W acknowledges funding support from the CNES ( Centre National d’Etudes Spatiales , France) TOSCA programme. P.C. and J.-P·W acknowledge support from the ESA CCI RECCAP2-A project ( ESRIN/4000123002/18/I-NB ).
Subjects: Microwave remote sensing, [SDE]Environmental Sciences, Soil Science, Optical vegetation proxies, Vegetation optical depth, Geology, Computers in Earth Sciences, Above ground carbon, Tropical Asia
Abstract: International audience; Tropical Asia has shown a strong greening trend in recent years. However, detailed knowledge about changes in carbon stocks remain uncertain as only few studies have used remotely sensed vegetation products for monitoring spatial and temporal changes of aboveground live biomass carbon (AGC) in that region. This study aims at evaluating optical- and microwave-based vegetation proxies (i.e., LAI, percent tree cover (PTC), L−/X-/C-band vegetation optical depths (VOD)) for understanding the spatio-temporal variations of tropical Asian AGC between 2013 and 2019. Our results indicated that the spatial distributions of L-VOD and PTC were highly spatially correlated with four benchmark AGC maps used for comparison (R > 0.79 and R > 0.75, respectively). By employing L-VOD as the reference data in assessing AGC dynamics, the X-/C-VOD showed advantages in capturing AGC changes for low-medium (20–40 Mg C/ha) carbon density vegetation, respectively, while other vegetation proxies showed limited capabilities. All proxies presented limitations in tracking AGC dynamics at high AGC density (> 60 Mg C/ha). Tropical Asian AGC stocks estimated using the L-VOD product indicated that tropical Asia accumulated carbon in biomass at a rate of +44+39+53 Tg C/yr between 2013 and 2019. This small sink is dominated by non-forest biomes (65.9%). The non-forest regions in southern India, southwest China, and southern Vietnam and southwest China showed a continuous AGC increase while forests in northern Laos, Malaysia, and central Indonesia experienced continuous decreases between 2013 and 2019 caused by deforestation.
Published: 2023

13. The Management of Type 1 Diabetes in Adults. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

Author: Amy Hess-Fischl, M. Sue Kirkman, Irl B. Hirsch, Barbara Ludwig, Anne L. Peters, Eric Renard, Richard I. G. Holt, Tomasz Klupa, Ruth S. Weinstock, Jeremy Pettus, J. Hans DeVries, Jay S. Skyler, Frank J. Snoek, Kirsten Nørgaard, University of Southampton, University Hospital Southampton NHS Foundation Trust, University of Amsterdam [Amsterdam] (UvA), Amsterdam UMC, Profil Institute for Metabolic Research GmbH, University of Chicago, Seattle University [Seattle], University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), IT University of Copenhagen, Steno Diabetes Center of Copenhagen, University of California [San Diego] (UC San Diego), University of California, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), University of Miami Leonard M. Miller School of Medicine (UMMSM), Vrije Universiteit Amsterdam [Amsterdam] (VU), SUNY Upstate Medical University, State University of New York (SUNY), Keck School of Medicine [Los Angeles], University of Southern California (USC), Amsterdam UMC - Amsterdam University Medical Center, IT University of Copenhagen (ITU), University of California (UC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Guerineau, Nathalie C., Medical psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, Amsterdam Reproduction & Development (AR&D), General Internal Medicine, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Endocrinology, Medical Psychology, University of Zurich, and Holt, Richard I G
Subjects: Blood Glucose, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 10265 Clinic for Endocrinology and Diabetology, 0302 clinical medicine, Diabetic ketoacidosis, Glucose monitoring, Diagnosis, Health care, Insulin, Medicine, Adjunctive therapy, 030212 general & internal medicine, Psychosocial care, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, 3. Good health, [SDV] Life Sciences [q-bio], 2712 Endocrinology, Diabetes and Metabolism, Type 1 diabetes, Psychosocial, Schedule of care, Adult, medicine.medical_specialty, Consensus, Consensus Report, 610 Medicine & health, 030209 endocrinology & metabolism, Hypoglycemia, 03 medical and health sciences, Diabetes mellitus, Internal Medicine, Hypoglycemic Agents, Humans, Association (psychology), Exercise, Nutrition, American diabetes association, Advanced and Specialized Nursing, Transplantation, business.industry, Blood Glucose Self-Monitoring, medicine.disease, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, 2724 Internal Medicine, Family medicine, Hypoglycaemia, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) convened a writing group to develop a consensus statement on the management of type 1 diabetes in adults. The writing group has considered the rapid development of new treatments and technologies and addressed the following topics: diagnosis, aims of management, schedule of care, diabetes self-management education and support, glucose monitoring, insulin therapy, hypoglycaemia, behavioural considerations, psychosocial care, diabetic ketoacidosis, pancreas and islet transplantation, adjunctive therapies, special populations, inpatient management and future perspectives. Although we discuss the schedule for follow-up examinations and testing, we have not included the evaluation and treatment of the chronic microvascular and macrovascular complications of diabetes as these are well-reviewed and discussed elsewhere. The writing group was aware of both national and international guidance on type 1 diabetes and did not seek to replicate this but rather aimed to highlight the major areas that healthcare professionals should consider when managing adults with type 1 diabetes. Though evidence-based where possible, the recommendations in the report represent the consensus opinion of the authors. [Figure not available: see fulltext.]
Published: 2021

14. Regional variation of effects of new antidiabetic medications in cardiovascular outcome trials

Author: Olav W. Nielsen, Aldo P. Maggioni, Christopher L. Edwards, Marco Metra, Naoki Sato, Barry H. Greenberg, Faiez Zannad, Gad Cotter, Alexandre Mebazaa, Georg Ertl, Beth A. Davison, Alain Cohen-Solal, Ovidiu Chioncel, Stefanie Senger, John R. Teerlink, Momentum Research Inc. [Durham, NC, USA] (MRI), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, University of California [San Francisco] (UC San Francisco), University of California (UC), Veterans Affairs Medical Center, San Francisco, California, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Service de Cardiologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), IT University of Copenhagen (ITU), Università degli Studi di Brescia = University of Brescia (UniBs), Civic Hospital of Brescia, Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), University of California [San Diego] (UC San Diego), Associazione Nazionale Medici Cardiologi Ospedalieri [Firenze] (ANMCO), University of Würzburg = Universität Würzburg, Nippon Medical School [Tokyo, Japon], Hôpital Lariboisière-Fernand-Widal [APHP], and leboeuf, Christophe
Subjects: medicine.medical_specialty, 030204 cardiovascular system & hematology, Glucagon-Like Peptide-1 Receptor, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Heart Failure, Humans, Hypoglycemic Agents, Regression Analysis, Sodium-Glucose Transporter 2 Inhibitors, Treatment Outcome, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Diabetes Mellitus, medicine, Treatment effect, 030212 general & internal medicine, business.industry, medicine.disease, Random effects model, Differential effects, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Heart failure, Cardiology and Cardiovascular Medicine, business, Type 2, Mace
Abstract: International audience; Background In international trials, glucagon-like protein-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2Is) were effective in improving cardiovascular (CV) outcomes. Methods We assessed the effect of GLP-1RAs and SGLT2Is treatment effect on CV endpoints by geographical region in multiple international trials using random effects weighted least squares meta-regressions. Results The estimated effects of both SGLT2Is and GLP-1RAs on major adverse CV events (MACE) in North America (SGLT2Is n = 12,399, HR 0.90, 95% CI 0.81-1.01; GLP-1RAs n = 12,515, HR 0.95, 95% CI 0.83-1.09) and in Europe (SGLT2Is n = 19,435, HR 0.93, 95% CI 0.85-1.02; GLP-1RAs n = 22,812, HR 0.88, 95% CI 0.79-0.99) were numerically lower but not statistically different to the rest of the world (ROW) (SGLT2Is n = 15,127, HR 0.83, 95% CI 0.75-0.92, p-value for interaction 0.26; GLP-1RAs n = 17,494, HR 0.82, 95% CI 0.73-0.92, p-value for interaction 0.28). Effects of SGLT2Is on heart failure readmission or CV death varied significantly by region (P = 0.0094). The effect of SGLT2Is was significantly smaller in Europe (n = 18,653, HR 0.86, 95% CI 0.78-0.95) than in the ROW (n = 12,463, HR 0.68, 95% CI 0.61-0.76, P = 0.0024). The smaller effect in North America (n = 9776, HR 0.76, 95% CI 0.66-0.87) did not differ significantly from that in the ROW (P = 0.2370). Conclusion The effects of SGLT2Is on HF events are larger in the ROW. Further analyses and studies are needed to better elucidate the differential effects of SGLTIs and GLP-1RAs by geographical regions.
Published: 2021

15. Current challenges in understanding the role of enhancers in disease

Author: Judith Barbara Zaugg, Pelin Sahlén, Robin Andersson, Meritxell Alberich-Jorda, Wouter de Laat, Bart Deplancke, Jorge Ferrer, Susanne Mandrup, Gioacchino Natoli, Dariusz Plewczynski, Alvaro Rada-Iglesias, Salvatore Spicuglia, European Molecular Biology Laboratory (EMBL), Royal Institute of Technology, IT University of Copenhagen (ITU), Medicine Charles University and General Faculty Hospital in Prague, University Medical Center [Utrecht], School of Life Sciences [Lausanne], Ecole Polytechnique Fédérale de Lausanne (EPFL), Barcelona Institute of Science and Technology (BIST), University of Southern Denmark (SDU), IRCCS Istituto Nazionale dei Tumori [Milano], University of Warsaw (UW), University of Cantabria, Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Project: 286079,EC:FP7:PEOPLE,FP7-PEOPLE-2011-IAPP,AIRFORS(2012), and European Commission
Subjects: Epigenomics, variants, super-enhancers, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Genomics, single-cell, burkitt-lymphoma, dissection, Structural Biology, beta-globin gene, expression, chromatin, identification, Molecular Biology, shadow enhancers
Abstract: Enhancers play a central role in the spatiotemporal control of gene expression and tend to work in a cell-type-specific manner. In addition, they are suggested to be major contributors to phenotypic variation, evolution and disease. There is growing evidence that enhancer dysfunction due to genetic, structural or epigenetic mechanisms contributes to a broad range of human diseases referred to as enhanceropathies. Such mechanisms often underlie the susceptibility to common diseases, but can also play a direct causal role in cancer or Mendelian diseases. Despite the recent gain of insights into enhancer biology and function, we still have a limited ability to predict how enhancer dysfunction impacts gene expression. Here we discuss the major challenges that need to be overcome when studying the role of enhancers in disease etiology and highlight opportunities and directions for future studies, aiming to disentangle the molecular basis of enhanceropathies., All authors are members of the EU-funded Innovative Training Network ‘Molecular Basis of Human Enhanceropathies’ (Enhpathy, www.enhpathy.eu) and received funding from the Horizon 2020 research and innovation program under Marie Sklodowska-Curie grant agreement no. 860002.
Published: 2022

16. WASCO: A Wasserstein-based statistical tool to compare conformational ensembles of intrinsically disordered proteins

Author: Javier González-Delgado, Amin Sagar, Christophe Zanon, Kresten Lindorff-Larsen, Pau Bernadó, Pierre Neuvial, Juan Cortés, Institut de Mathématiques de Toulouse UMR5219 (IMT), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Équipe Robotique et InteractionS (LAAS-RIS), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT), Centre de Biologie Structurale [Montpellier] (CBS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Service Informatique : Développement, Exploitation et Assistance (LAAS-IDEA), Linderstrøm-Lang Centre for Protein Science [Copenhagen], IT University of Copenhagen (ITU), ANR-19-P3IA-0004,ANITI,Artificial and Natural Intelligence Toulouse Institute(2019), ANR-11-LABX-0040,CIMI,Centre International de Mathématiques et d'Informatique (de Toulouse)(2011), ANR-10-LABX-0012,EpiGenMed,From Genome and Epigenome to Molecular Medicine: turning new paradigms in biology into the therapeutic strategies of tomorrow(2010), ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), and European Project: 648030,H2020,ERC-2014-CoG,chemREPEAT(2015)
Subjects: Wasserstein distance matrices, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [STAT]Statistics [stat], SAXS/NMR ensemble refinement, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Structural Biology, conformational ensembles, intrinsically disordered proteins, molecular dynamics simulations, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Molecular Biology
Abstract: The structural investigation of intrinsically disordered proteins (IDPs) requires ensemble models describing the diversity of the conformational states of the molecule. Due to their probabilistic nature, there is a need for new paradigms that understand and treat IDPs from a purely statistical point of view, considering their conformational ensembles as well-defined probability distributions. In this work, we define a conformational ensemble as an ordered set of probability distributions and provide a suitable metric to detect differences between two given ensembles at the residue level, both locally and globally. The underlying geometry of the conformational space is properly integrated, one ensemble being characterized by a set of probability distributions supported on the three-dimensional Euclidean space (for global-scale comparisons) and on the two-dimensional flat torus (for local-scale comparisons). The inherent uncertainty of the data is also taken into account to provide finer estimations of the differences between ensembles. Additionally, an overall distance between ensembles is defined from the differences at the residue level. We illustrate the potential of the approach with several examples of applications for the comparison of conformational ensembles: (i) produced from molecular dynamics (MD) simulations using different force fields, and (ii) before and after refinement with experimental data. We also show the usefulness of the method to assess the convergence of MD simulations, and discuss other potential applications such as in machine-learning-based approaches. The numerical tool has been implemented in Python through easy-to-use Jupyter Notebooks available at https://gitlab.laas.fr/moma/WASCO. The structural investigation of intrinsically disordered proteins (IDPs) requires ensemble models describing the diversity of the conformational states of the molecule. Due to their probabilistic nature, there is a need for new paradigms that understand and treat IDPs from a purely statistical point of view, considering their conformational ensembles as well-defined probability distributions. In this work, we define a conformational ensemble as an ordered set of probability distributions and provide a suitable metric to detect differences between two given ensembles at the residue level, both locally and globally. The underlying geometry of the conformational space is properly integrated, one ensemble being characterized by a set of probability distributions supported on the three-dimensional Euclidean space (for global-scale comparisons) and on the two-dimensional flat torus (for local-scale comparisons). The inherent uncertainty of the data is also taken into account to provide finer estimations of the differences between ensembles. Additionally, an overall distance between ensembles is defined from the differences at the residue level. We illustrate the potential of the approach with several examples of applications for the comparison of conformational ensembles: (i) produced from molecular dynamics (MD) simulations using different force fields, and (ii) before and after refinement with experimental data. We also show the usefulness of the method to assess the convergence of MD simulations, and discuss other potential applications such as in machine-learning-based approaches. The numerical tool has been implemented in Python through easy-to-use Jupyter Notebooks available at https://gitlab.laas.fr/moma/WASCO.
Published: 2022

17. Nutri-Score: its benefits and limitations in children's feeding

Author: Jean-Pierre, Chouraqui, Christophe, Dupont, André, Briend, Dominique, Darmaun, Noel, Peretti, Alain, Bocquet, Martin, Chalumeau, Arnaud, De Luca, François, Feillet, Marie-Laure, Frelut, Dominique, Guimber, Alexandre, Lapillonne, Agnès, Linglart, Jean-Christophe, Rozé, Umberto, Simeoni, Dominique, Turck, CHU Grenoble, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Clinique Marcel Sembat (CCBB) - Ramsay Santé [Boulogne Billancourt], IT University of Copenhagen (ITU), University of Tampere [Finland], Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Association Française de Pédiatrie Ambulatoire (AFPA), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier d'Albi, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Fédération pour la recherche en explorations et thérapeutiques innovantes in utéro (FETUS (URP 7328)), Université Paris Cité (UPCité), Centre de Référence des Maladies Rares du Métabolisme du Phosphore et du Calcium and Filière de Santé Maladies Rares (OSCAR), Hôpital Bicêtre, Centre d'Investigation Clinique [Nantes] (CIC004), Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Lausanne = University of Lausanne (UNIL), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and CarMeN, laboratoire
Subjects: [SDV.BA] Life Sciences [q-bio]/Animal biology, [SDV.BA]Life Sciences [q-bio]/Animal biology, Pediatrics, Perinatology and Child Health, Gastroenterology
Abstract: International audience; Reducing the burden of non-communicable diseases (NCDs) is one of the top priorities of public health policies worldwide. One of the recognized means of achieving this objective is to improve the diet quality. The Nutri-Score (N-S) is a [five-color - A, B, C, D, E letters] front-of-pack labelling logo intended to help consumers quickly identify the healthier prepackaged foods within a food category. Available studies have shown that the N-S is an efficient tool to achieve this aim in terms of consumers' awareness, perception, understanding and purchasing and that its use may help to reduce the prevalence of NCDs. The N-S is currently implemented on a voluntary basis in seven European countries and a discussion is underway within the European Commission to achieve a harmonized mandatory label. However, no study on the putative impact of the N-S on children's dietary patterns and health is available. The N-S is not applicable to infants' and young children's formulas and to specific baby foods, the compositions of which are already laid down in European Union regulations. The N-S does not replace age-appropriate dietary guidelines. As children consume an increasing number of adult type and processed foods, the relevance of the N-S for children should be evaluated considering the children's high specific requirements, especially in younger children. This is especially necessary for fitting fat and iron requirements, whereas protein-rich foods should be better framed. Moreover, efforts should be made to inform on how to use the N-S and in education on healthy diets.
Published: 2022

18. Inhibition of lytic polysaccharide monooxygenase by natural plant extracts

Author: Berrin, Jean-Guy, Tokin, Radina, Frandsen, Kristian, Ipsen, Johan Ørskov, Lo Leggio, Leila, Poojary, Mahesha, Berrin, Jean‐Guy, Grisel, Sacha, Brander, Søren, Jensen, Poul Erik, Johansen, Katja Salomon, IT University of Copenhagen (ITU), Biodiversité et Biotechnologie Fongiques (BBF), and Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0106 biological sciences, cinnamtannin B1, Physiology, Cinnamomum cassia, Plant Science, Lentinula, Polysaccharide, 01 natural sciences, Mixed Function Oxygenases, Fungal Proteins, 03 medical and health sciences, chemistry.chemical_compound, Polysaccharides, Cassia, LPMO, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Binding site, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Cinnamtannin B1, biology, Plant Extracts, Chemistry, Monooxygenase, biology.organism_classification, Lentinus similis, inhibitor, ddc:580, Enzyme, Biochemistry, Polyphenol, plant extract, lytic polysaccharide monooxygenase, 010606 plant biology & botany, Cinnamomum
Abstract: Lytic polysaccharide monooxygenases (LPMOs) are monocopper enzymes of industrial and biological importance. In particular, LPMOs play important roles in fungal lifestyle. No inhibitors of LPMOs have yet been reported. In this study, a diverse library of 100 plant extracts was screened for LPMO activity-modulating effects. By employing protein crystallography and LC-MS we successfully identified a natural LPMO inhibitor. Extract screening revealed a significant LPMO inhibition by methanolic extract of Cinnamomum cassia (cinnamon), which inhibited LsAA9A LPMO from Lentinus similis in a concentration-dependent manner. With a notable exception, other microbial LPMOs from families AA9 and AA10 were also inhibited by this cinnamon extract. The polyphenol cinnamtannin B1 was identified as the inhibitory component by crystallography. Cinnamtannin B1 was bound to the surface of LsAA9A at two distinct binding sites, one close to the active site and another at a pocket on the opposite side of the protein. Independent characterization of cinnamon extract by LC-MS and subsequent activity measurements confirmed that the compound inhibiting LsAA9A was cinnamtannin B1. The results of this study show that specific natural LPMO inhibitors of plant origin exist in nature, providing the opportunity for future exploitation of such compounds within various biotechnological contexts. Lytic polysaccharide monooxygenases (LPMOs) are monocopper enzymes of industrial and biological importance. In particular, LPMOs play important roles in fungal lifestyle. No inhibitors of LPMOs have yet been reported.In this study, a diverse library of 100 plant extracts was screened for LPMO activity-modulating effects. By employing protein crystallography and LC–MS, we successfully identified a natural LPMO inhibitor.Extract screening revealed a significant LPMO inhibition by methanolic extract of Cinnamomum cassia (cinnamon), which inhibited LsAA9A LPMO from Lentinus similis in a concentration-dependent manner. With a notable exception, other microbial LPMOs from families AA9 and AA10 were also inhibited by this cinnamon extract. The polyphenol cinnamtannin B1 was identified as the inhibitory component by crystallography. Cinnamtannin B1 was bound to the surface of LsAA9A at two distinct binding sites: one close to the active site and another at a pocket on the opposite side of the protein. Independent characterization of cinnamon extract by LC–MS and subsequent activity measurements confirmed that the compound inhibiting LsAA9A was cinnamtannin B1.The results of this study show that specific natural LPMO inhibitors of plant origin exist in nature, providing the opportunity for future exploitation of such compounds within various biotechnological contexts.
Published: 2021

19. An Interdisciplinary Perspective on Evaluation and Experimental Design for Visual Text Analytics: Position Paper

Author: Kucher, Kostiantyn, Sultanum, Nicole, Daza, Angel, Simaki, Vasiliki, Skeppstedt, Maria, Plank, Barbara, Fekete, Jean-Daniel, Mahyar, Narges, Linköping University (LIU), Linnaeus University, University of Toronto, Vrije Universiteit Amsterdam [Amsterdam] (VU), Lund University [Lund], Uppsala University, IT University of Copenhagen (ITU), Analysis and Visualization (AVIZ), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Interdisciplinaire des Sciences du Numérique (LISN), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Interaction avec l'Humain (IaH), Laboratoire Interdisciplinaire des Sciences du Numérique (LISN), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), University of Massachusetts [Lowell] (UMass Lowell), and University of Massachusetts System (UMASS)
Subjects: FOS: Computer and information sciences, Computer Science - Computation and Language, Human-centered computing, Computer Science - Human-Computer Interaction, [INFO.INFO-HC]Computer Science [cs]/Human-Computer Interaction [cs.HC], Visualization design and evaluation methods, Computation and Language (cs.CL), Human-Computer Interaction (cs.HC), Visualization
Abstract: Appropriate evaluation and experimental design are fundamental for empirical sciences, particularly in data-driven fields. Due to the successes in computational modeling of languages, for instance, research outcomes are having an increasingly immediate impact on end users. As the gap in adoption by end users decreases, the need increases to ensure that tools and models developed by the research communities and practitioners are reliable, trustworthy, and supportive of the users in their goals. In this position paper, we focus on the issues of evaluating visual text analytics approaches. We take an interdisciplinary perspective from the visualization and natural language processing communities, as we argue that the design and validation of visual text analytics include concerns beyond computational or visual/interactive methods on their own. We identify four key groups of challenges for evaluating visual text analytics approaches (data ambiguity, experimental design, user trust, and "big picture" concerns) and provide suggestions for research opportunities from an interdisciplinary perspective., Published in Proceedings of the 2022 IEEE Workshop on Evaluation and Beyond - Methodological Approaches to Visualization (BELIV '22). ACM 2012 CCS: Human-centered computing, Visualization, Visualization design and evaluation methods
Published: 2022

20. Multi-PGS enhances polygenic prediction: weighting 937 polygenic scores

Author: Clara Albiñana, Zhihong Zhu, Andrew J. Schork, Andrés Ingason, Hugues Aschard, Isabell Brikell, Cynthia M. Bulik, Liselotte V. Petersen, Esben Agerbo, Jakob Grove, Merete Nordentoft, David M. Hougaard, Thomas Werge, Anders D. Børglum, Preben Bo Mortensen, John J. McGrath, Benjamin M. Neale, Florian Privé, Bjarni J. Vilhjálmsson, Bioinformatics Research Center, Aarhus University [Aarhus], Department of Neurosciences [Univ California San Diego] (Neuro - UC San Diego), School of Medicine [Univ California San Diego] (UC San Diego), University of California [San Diego] (UC San Diego), University of California (UC)-University of California (UC)-University of California [San Diego] (UC San Diego), University of California (UC)-University of California (UC), Department of Cognitive Sciences [Univ California San Diego] (CogSci - UC San Diego), Metacohorts Consortium, Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Karolinska Institutet [Stockholm], University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), IT University of Copenhagen (ITU), Statens Serum Institut [Copenhagen], Center for Genomics and Personalized Medicine [Aarhus, Denmark] (CGPM), Department of Genomics, and MR Solutions Guildford
Subjects: [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
Abstract: The predictive performance of polygenic scores (PGS) is largely dependent on the number of samples available to train the PGS. Increasing the sample size for a specific phenotype is expensive and takes time, but this sample size can be effectively increased by using genetically correlated phenotypes. We propose a framework to generate multi-PGS from thousands of publicly available genome-wide association studies (GWAS) with no need to individually select the most relevant ones. In this study, the multi-PGS framework increased prediction accuracy over single PGS for all included psychiatric disorders and other available outcomes, with prediction R2 increases of up to 9-fold for attention-deficit/hyperactivity disorder (ADHD) compared to a single PGS. We also generate multi-PGS for phenotypes without an existing GWAS and for case-case predictions, with up to 15-fold increases in prediction accuracy. We benchmark the multi-PGS framework against other methods and highlight its potential application to new emerging biobanks.
Published: 2022

21. Phylogenomic analysis and metabolic role reconstruction of mutualistic Rhizobiales hindgut symbionts of Acromyrmex leaf-cutting ants

Author: Mariya Zhukova, Panagiotis Sapountzis, Morten Schiøtt, Jacobus J Boomsma, IT University of Copenhagen (ITU), Microbiologie Environnement Digestif Santé (MEDIS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Unit for Fish and Shellfish Diseases, National Institute of Aquatic Resources, and Danmarks Tekniske Universitet = Technical University of Denmark (DTU)-Danmarks Tekniske Universitet = Technical University of Denmark (DTU)
Subjects: Ecology, Ants, Nitrogen, [SDV]Life Sciences [q-bio], Fungi, gene loss, Arginine, Applied Microbiology and Biotechnology, Microbiology, domestication, antioxidants, CRISPR/Cas, complementary mutualistic functionality, Animals, riboflavin, Symbiosis, Phylogeny, Alphaproteobacteria
Abstract: Rhizobiales are well-known plant-root nitrogen-fixing symbionts, but the functions of insect-associated Rhizobiales are poorly understood. We obtained genomes of three strains associated with Acromyrmex leaf-cutting ants and show that, in spite of being extracellular gut symbionts, they lost all pathways for essential amino acid biosynthesis, making them fully dependent on their hosts. Comparison with 54 Rhizobiales genomes showed that all insect-associated Rhizobiales lost the ability to fix nitrogen and that the Acromyrmex symbionts had exceptionally also lost the urease genes. However, the Acromyrmex strains share biosynthesis pathways for riboflavin vitamin, queuosine and a wide range of antioxidant enzymes likely to be beneficial for the ant fungus-farming symbiosis. We infer that the Rhizobiales symbionts catabolize excess of fungus-garden-derived arginine to urea, supplementing complementary Mollicutes symbionts that turn arginine into ammonia and infer that these combined symbiont activities stabilize the fungus-farming mutualism. Similar to the Mollicutes symbionts, the Rhizobiales species have fully functional CRISPR/Cas and R-M phage defenses, suggesting that these symbionts are important enough for the ant hosts to have precluded the evolution of metabolically cheaper defenseless strains.
Published: 2022

22. Grey wolf genomic history reveals a dual ancestry of dogs

Author: Anders Bergström, David W. G. Stanton, Ulrike H. Taron, Laurent Frantz, Mikkel-Holger S. Sinding, Erik Ersmark, Saskia Pfrengle, Molly Cassatt-Johnstone, Ophélie Lebrasseur, Linus Girdland-Flink, Daniel M. Fernandes, Morgane Ollivier, Leo Speidel, Shyam Gopalakrishnan, Michael V. Westbury, Jazmin Ramos-Madrigal, Tatiana R. Feuerborn, Ella Reiter, Joscha Gretzinger, Susanne C. Münzel, Pooja Swali, Nicholas J. Conard, Christian Carøe, James Haile, Anna Linderholm, Semyon Androsov, Ian Barnes, Chris Baumann, Norbert Benecke, Hervé Bocherens, Selina Brace, Ruth F. Carden, Dorothée G. Drucker, Sergey Fedorov, Mihály Gasparik, Mietje Germonpré, Semyon Grigoriev, Pam Groves, Stefan T. Hertwig, Varvara V. Ivanova, Luc Janssens, Richard P. Jennings, Aleksei K. Kasparov, Irina V. Kirillova, Islam Kurmaniyazov, Yaroslav V. Kuzmin, Pavel A. Kosintsev, Martina Lázničková-Galetová, Charlotte Leduc, Pavel Nikolskiy, Marc Nussbaumer, Cóilín O’Drisceoil, Ludovic Orlando, Alan Outram, Elena Y. Pavlova, Angela R. Perri, Małgorzata Pilot, Vladimir V. Pitulko, Valerii V. Plotnikov, Albert V. Protopopov, André Rehazek, Mikhail Sablin, Andaine Seguin-Orlando, Jan Storå, Christian Verjux, Victor F. Zaibert, Grant Zazula, Philippe Crombé, Anders J. Hansen, Eske Willerslev, Jennifer A. Leonard, Anders Götherström, Ron Pinhasi, Verena J. Schuenemann, Michael Hofreiter, M. Thomas P. Gilbert, Beth Shapiro, Greger Larson, Johannes Krause, Love Dalén, Pontus Skoglund, Bergström, Anders [0000-0002-4096-9268], Frantz, Laurent [0000-0001-8030-3885], Sinding, Mikkel-Holger S [0000-0003-1371-219X], Lebrasseur, Ophélie [0000-0003-0687-8538], Fernandes, Daniel M [0000-0002-7434-6552], Ollivier, Morgane [0000-0002-8361-4221], Westbury, Michael V [0000-0003-0478-3930], Ramos-Madrigal, Jazmin [0000-0002-1661-7991], Feuerborn, Tatiana R [0000-0003-1610-3402], Conard, Nicholas J [0000-0002-4633-0385], Haile, James [0000-0002-8521-8337], Linderholm, Anna [0000-0002-1613-9926], Barnes, Ian [0000-0001-8322-6918], Baumann, Chris [0000-0002-1001-8621], Bocherens, Hervé [0000-0002-0494-0126], Brace, Selina [0000-0003-2126-6732], Drucker, Dorothée G [0000-0003-0854-4371], Germonpré, Mietje [0000-0001-8865-0937], Jennings, Richard P [0000-0001-9996-7518], Kuzmin, Yaroslav V [0000-0002-4512-2269], Orlando, Ludovic [0000-0003-3936-1850], Outram, Alan [0000-0003-3360-089X], Perri, Angela R [0000-0002-4349-1060], Plotnikov, Valerii V [0000-0002-4870-3499], Sablin, Mikhail [0000-0002-2773-7454], Crombé, Philippe [0000-0002-4198-8057], Hansen, Anders J [0000-0002-1890-2702], Willerslev, Eske [0000-0002-7081-6748], Leonard, Jennifer A [0000-0003-0291-7819], Pinhasi, Ron [0000-0003-1629-8131], Shapiro, Beth [0000-0002-2733-7776], Larson, Greger [0000-0002-4092-0392], Krause, Johannes [0000-0001-9144-3920], Dalén, Love [0000-0001-8270-7613], Skoglund, Pontus [0000-0002-3021-5913], Apollo - University of Cambridge Repository, The Francis Crick Institute [London], Swedish Museum of Natural History (NRM), Ludwig Maximilian University [Munich] (LMU), University of Copenhagen = Københavns Universitet (UCPH), Trinity College Dublin, University of Greenland, University of Tübingen, University of Oxford, Ecosystèmes, biodiversité, évolution [Rennes] (ECOBIO), Université de Rennes (UR)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR), Université de Rennes (UR)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS), University College of London [London] (UCL), IT University of Copenhagen (ITU), Max Planck Institute for the Science of Human History (MPI-SHH), Max-Planck-Gesellschaft, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Globe Institute, Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Texas A&M University System, Stockholm University, Natural History Museum [Oslo], University of Oslo (UiO), German Archaeological Institute (DAI), The Natural History Museum [London] (NHM), UCD School of Biology and Environmental Science, UCD, Royal Belgian Institute of Natural Sciences (RBINS), North-Eastern Federal University, School of Archaeology, Histoire naturelle de l'Homme préhistorique (HNHP), Muséum national d'Histoire naturelle (MNHN)-Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Centre d'anthropologie et de génomique de Toulouse (CAGT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), University of Vienna [Vienna], Max Planck Institute for Evolutionary Anthropology [Leipzig], This work was supported by grants to P. Skoglund from the European Research Council (grant no. 852558), the Erik Philip Sörensen Foundation and the Science for Life Laboratory, Swedish Biodiversity Program, made available by support from the Knut and Alice Wallenberg Foundation. A.B., L.S., P. Swali and P. Skoglund were supported by Francis Crick Institute core funding (FC001595) from Cancer Research UK, the UK Medical Research Council and the Wellcome Trust. P. Skoglund was also supported by the Vallee Foundation, the European Molecular Biology Organisation and the Wellcome Trust (217223/Z/19/Z). Computations were supported by SNIC-UPPMAX. We also acknowledge support from Science for Life Laboratory, the Knut and Alice Wallenberg Foundation, the National Genomics Infrastructure funded by the Swedish Research Council and the Uppsala Multidisciplinary Center for Advanced Computational Science for assistance with massively parallel sequencing and access to the UPPMAX computational infrastructure. We thank the Yukon gold mining community and First Nations, including the Tr’ondëk Hwëch’in, for continued support of our palaeontology research in the Yukon Territories, Canada. We thank the Danish National High-Throughput Sequencing Centre and BGI-Europe for assistance in sequencing data generation and the Danish National Supercomputer for Life Sciences–Computerome (https://computerome.dtu.dk) for computational resources. We thank National Museum Wales for continued sampling support. M. Germonpré acknowledges support from the Brain.be 2.0 ICHIE project (BELSPO B2/191/P2/ICHIE). M.T.P.G. was supported by the European Research Council (grant no. 681396). M.-H.S.S. was supported by the Velux Foundations through the Qimmeq Project, the Aage og Johanne Louis-Hansens Fond and the Independent Research Fund Denmark (8028-00005B). L.D. acknowledges support from FORMAS (2018-01640). D.W.G.S. received funding for this project from the European Union’s Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant agreement no. 796877. M.P. was supported by the Polish National Agency for Academic Exchange–NAWA (grant no. PPN/PPO/2018/1/00037). V.J.S. was supported by the University of Zurich’s University Research Priority Program ‘Evolution in Action: From Genomes to Ecosystems’. This research was done with the participation of ZIN RAS (grant no. 075-15-2021-1069). We are grateful to the museum of the Institute of Plant and Animal Ecology UB RAS (Ekaterinburg, Russia) for provision of samples. R.P.J. and C.O’D. were supported by the Standing Committee for Archaeology of the Royal Irish Academy through the Archaeological Excavation Research Grant Scheme. E.Y.P., P.N. and V.V.P. are supported by the Russian Science Foundation (grant no. 16-18-10265-RNF and 21-18-00457-RNF). Y.V.K. was supported by the Russian Science Foundation (grant no. 20-17-00033). M.H. was supported by the European Research Council (consolidator grant GeneFlow no. 310763). M.L.-G. was supported by the Czech Science Foundation GAČR (grant no. 15-06446S) and institutional financing of the Moravian Museum from the Czech Ministry of Culture (IP DKRVO 2019-2023, MK000094862). L.S. is supported by the Sir Henry Wellcome fellowship (220457/Z/20/Z). We thank Staatliches Museum für Naturkunde Stuttgart for sample access. L.F. and G.L. were supported by European Research Council grants (ERC-2013-StG-337574-UNDEAD and ERC-2019-StG-853272-PALAEOFARM) and Natural Environmental Research Council grants (NE/K005243/1, NE/K003259/1, NE/S007067/1 and NE/S00078X/1). L.F. was also supported by the Wellcome Trust (210119/Z/18/Z). This research was funded in whole, or in part, by the Wellcome Trust (FC001595). For the purpose of open access, the author has applied a CC-BY public copyright licence to any author accepted manuscript version arising from this submission., Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut Ecologie et Environnement (INEE), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS), Department of Geosciences and Geography, and Faculty of Science
Subjects: History, RUSSIAN FEDERATION, 631/158/2464, CANIS LUPUS, ANIMAL EXPERIMENT, Domestication, Ecology,Evolution & Ethology, MIDDLE EAST, DOG, History, Ancient, Phylogeny, CANID, WOLF, Multidisciplinary, Genome, ORIGIN, article, 45/77, Genomics, CC, ADMIXTURE, CONTAMINATION, Europe, GENOME, EXTINCTION, DOGS, COMPLETE MITOCHONDRIAL GENOME, Genetics & Genomics, NATURAL SELECTION, 1171 Geosciences, AFRICA, EUROPE, NORTH AMERICA, GENETICS, SIBERIA, General Science & Technology, PHYLOGENY, PLEISTOCENE, LIBRARY PREPARATION, 45/23, Infectious Disease, ANCESTRY, SEQUENCE, EURASIA, Ancient, TIME SERIES ANALYSIS, 631/181/27, Middle East, QH301, Dogs, UPPER PLEISTOCENE, Genetic, EVOLUTIONARY HISTORY, WOLVES, GENE MUTATION, ANCIENT DNA, Animals, NONHUMAN, 631/181/457, DNA, Ancient, Selection, Genetic, ARTICLE, Selection, QH426, QL, Wolves, History and Archaeology, Tumor Suppressor Proteins, ANIMALS, Biology and Life Sciences, DNA, ANIMAL, GENE, Siberia, CONTROLLED STUDY, DOMESTICATION, 631/181/2474, Africa, Mutation, North America, 570 Life sciences, biology, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, GENOMICS
Abstract: The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canis familiaris) lived1–8. Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT88 40,000–30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located. © 2022, The Author(s). 8028-00005B; IP DKRVO 2019-2023, MK000094862; 220457/Z/20/Z, ERC-2013-StG-337574-UNDEAD, ERC-2019-StG-853272-PALAEOFARM; 075-15-2021-1069; European Molecular Biology Organization, EMBO: 217223/Z/19/Z; Vallee Foundation; Velux Fonden; Wellcome Trust, WT; Francis Crick Institute, FCI: FC001595; Horizon 2020 Framework Programme, H2020: 796877; Medical Research Council, MRC; Natural Environment Research Council, NERC: 210119/Z/18/Z, NE/K003259/1, NE/K005243/1, NE/S00078X/1, NE/S007067/1; Cancer Research UK, CRUK; European Research Council, ERC: 852558; Grantová Agentura České Republiky, GA ČR: 15-06446S; Svenska Forskningsrådet Formas: 2018-01640; Knut och Alice Wallenbergs Stiftelse; Vetenskapsrådet, VR: 681396, BELSPO B2/191/P2/ICHIE; Russian Science Foundation, RSF: 16-18-10265-RNF, 20-17-00033, 21-18-00457-RNF, 310763; Science for Life Laboratory, SciLifeLab; Narodowa Agencja Wymiany Akademickiej, NAWA: PPN/PPO/2018/1/00037 This work was supported by grants to P. Skoglund from the European Research Council (grant no. 852558), the Erik Philip Sörensen Foundation and the Science for Life Laboratory, Swedish Biodiversity Program, made available by support from the Knut and Alice Wallenberg Foundation. A.B., L.S., P. Swali and P. Skoglund were supported by Francis Crick Institute core funding (FC001595) from Cancer Research UK, the UK Medical Research Council and the Wellcome Trust. P. Skoglund was also supported by the Vallee Foundation, the European Molecular Biology Organisation and the Wellcome Trust (217223/Z/19/Z). Computations were supported by SNIC-UPPMAX. We also acknowledge support from Science for Life Laboratory, the Knut and Alice Wallenberg Foundation, the National Genomics Infrastructure funded by the Swedish Research Council and the Uppsala Multidisciplinary Center for Advanced Computational Science for assistance with massively parallel sequencing and access to the UPPMAX computational infrastructure. We thank the Yukon gold mining community and First Nations, including the Tr’ondëk Hwëch’in, for continued support of our palaeontology research in the Yukon Territories, Canada. We thank the Danish National High-Throughput Sequencing Centre and BGI-Europe for assistance in sequencing data generation and the Danish National Supercomputer for Life Sciences–Computerome ( https://computerome.dtu.dk ) for computational resources. We thank National Museum Wales for continued sampling support. M. Germonpré acknowledges support from the Brain.be 2.0 ICHIE project (BELSPO B2/191/P2/ICHIE). M.T.P.G. was supported by the European Research Council (grant no. 681396). M.-H.S.S. was supported by the Velux Foundations through the Qimmeq Project, the Aage og Johanne Louis-Hansens Fond and the Independent Research Fund Denmark (8028-00005B). L.D. acknowledges support from FORMAS (2018-01640). D.W.G.S. received funding for this project from the European Union’s Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant agreement no. 796877. M.P. was supported by the Polish National Agency for Academic Exchange–NAWA (grant no. PPN/PPO/2018/1/00037). V.J.S. was supported by the University of Zurich’s University Research Priority Program ‘Evolution in Action: From Genomes to Ecosystems’. This research was done with the participation of ZIN RAS (grant no. 075-15-2021-1069). We are grateful to the museum of the Institute of Plant and Animal Ecology UB RAS (Ekaterinburg, Russia) for provision of samples. R.P.J. and C.O’D. were supported by the Standing Committee for Archaeology of the Royal Irish Academy through the Archaeological Excavation Research Grant Scheme. E.Y.P., P.N. and V.V.P. are supported by the Russian Science Foundation (grant no. 16-18-10265-RNF and 21-18-00457-RNF). Y.V.K. was supported by the Russian Science Foundation (grant no. 20-17-00033). M.H. was supported by the European Research Council (consolidator grant GeneFlow no. 310763). M.L.-G. was supported by the Czech Science Foundation GAČR (grant no. 15-06446S) and institutional financing of the Moravian Museum from the Czech Ministry of Culture (IP DKRVO 2019-2023, MK000094862). L.S. is supported by the Sir Henry Wellcome fellowship (220457/Z/20/Z). We thank Staatliches Museum für Naturkunde Stuttgart for sample access. L.F. and G.L. were supported by European Research Council grants (ERC-2013-StG-337574-UNDEAD and ERC-2019-StG-853272-PALAEOFARM) and Natural Environmental Research Council grants (NE/K005243/1, NE/K003259/1, NE/S007067/1 and NE/S00078X/1). L.F. was also supported by the Wellcome Trust (210119/Z/18/Z). This research was funded in whole, or in part, by the Wellcome Trust (FC001595). For the purpose of open access, the author has applied a CC-BY public copyright licence to any author accepted manuscript version arising from this submission.
Published: 2022

23. Standards for practical intravenous rapid drug desensitization & delabeling: A WAO committee statement

Author: Emilio Alvarez-Cuesta, Ricardo Madrigal-Burgaleta, Ana D. Broyles, Javier Cuesta-Herranz, Maria Antonieta Guzman-Melendez, Michelle C. Maciag, Elizabeth J. Phillips, Jason A. Trubiano, Johnson T. Wong, Ignacio Ansotegui, F. Runa Ali, Denisse Angel-Pereira, Aleena Banerji, Maria Pilar Berges-Gimeno, Lorena Bernal-Rubio, Knut Brockow, Ricardo Cardona Villa, Mariana C. Castells, Jean-Christoph Caubet, Yoon-Seok Chang, Luis Felipe Ensina, Manana Chikhladze, Anca Mirela Chiriac, Weng-Hung Chung, Motohiro Ebisawa, Bryan Fernandes, Lene Heise Garvey, Maximiliano Gomez, Javier Gomez Vera, Sandra Gonzalez Diaz, David I. Hong, Juan Carlos Ivancevich, Hye-Ryun Kang, David A. Khan, Merin Kuruvilla, Jose Ignacio Larco Sousa, Patricia Latour-Staffeld, Anne Y. Liu, Eric Macy, Hans Jorgen Malling, Jorge Maspero, Sara M. May, Cristobalina Mayorga, Miguel A. Park, Jonathan Peter, Matthieu Picard, Tito Rodriguez-Bouza, Antonino Romano, Mario Sanchez-Borges, Luciana Kase Tanno, Maria Jose Torres, Alicia Ureña-Tavera, Rocco L. Valluzzi, Gerald W. Volcheck, Masao Yamaguchi, Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), St Bartholomew's Hospital (London), Barts Health NHS Trust [London, UK], Catalan Institute of Oncology (ICO), Boston Children's Hospital, Harvard Medical School [Boston] (HMS), Fundación Jiménez Díaz, Fundacion Jimenez Diaz [Madrid] (FJD), RETIC ARADyAL, University of Chile Clinical Hospital, Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], University of Melbourne, Massachusetts General Hospital [Boston], Hospital Quirónsalud Bizkaia [Bilbao], Hospital Universitario De Canarias, Technische Universität München = Technical University of Munich (TUM), Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Hôpitaux Universitaires de Genève (HUG), Seoul National University Bundang Hospital (SNUBH), Seoul National University [Seoul] (SNU), Federal University of Sao Paulo (Unifesp), Akaki Tsereteli State University, Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service d'allergologie et de pneumologie [Hôpital Arnaud de Villeneuve], Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Chang Gung Memorial Hospital [Taipei] (CGMH), Sagamihara National Hospital [Kanagawa, Japan], Copenhagen University Hospital, IT University of Copenhagen (ITU), Catholic University of Salta, Regional Hospital Lic. Adolfo Lopez Mateos (ISSSTE), Hospital Universitario Dr. José Eleuterio González, Brigham & Women’s Hospital [Boston] (BWH), Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Seoul National University College of Medicine [Séoul, Corée du Sud] (SNUCM), University of Texas Southwestern Medical Center [Dallas], Emory University School of Medicine, Emory University [Atlanta, GA], Clinica San Felipe, Centro Avanzado de Alergia y Asma de Santo Domingo, Stanford University Medical Center, University of California Medical Center [San Diego], University of California [San Diego] (UC San Diego), University of California (UC)-University of California (UC), Fundación Cidea Allergy and Respiratory Research Unit, University of Nebraska Medical Center, University of Nebraska System, Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain], Allergy Unit [Malaga, Spain] (National Network ARADyAL), Mayo Clinic [Rochester], University of Cape Town, Hôpital Maisonneuve-Rosemont, Centro de Patología Alérgica, Oasi Maria Santissima Srl [Troina, Italy], Centro Médico Docente La Trinidad, Clínica Unión Medica del Norte, Bambino Gesù Children’s Hospital [Rome, Italy], Chiba University Hospital, CHIRIAC, Anca Mirela, [Madrigal-Burgaleta, Ricardo] Ramon & Cajal Univ Hosp, Madrid, Spain, and [Madrigal-Burgaleta, Ricardo] St Bartholomews Hosp, Resp Dept, Allergy & Severe Asthma Serv, Barts Hlth NHS Trust, 4th Floor,King George 5 Bldg, London EC1A 7BE, England
Subjects: Pulmonary and Respiratory Medicine, Drug desensitization, Immunology, Basophil activation test, Reported penicillin allergy, Monoclonal-antibodies, Penicillins, In-vitro diagnosis, Antibiotic desensitization, Risk-stratification, Biological agents, Skin test, Antibiotics, Carboplatin hypersensitivity, Immunology and Allergy, Chemotherapy, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Beta-lactam allergy, Drug challenge, Risk stratification, Betalactams, Precision medicine, Cross-reactivity, Drug allergy, Delabeling, Personalized medicine, Drug provocation test, Delabel-ing, Ige-mediated hypersensitivity, Immediate allergic reactions, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology
Abstract: International audience; Drug hypersensitivity reactions (DHRs) to intravenous drugs can be severe and might leave patients and doctors in a difficult position where an essential treatment or intervention has to be suspended. Even if virtually any intravenous medication can potentially trigger a life-threatening DHR, chemotherapeutics, biologics, and antibiotics are amongst the intravenous drugs most frequently involved in these reactions. Admittedly, suspending such treatments may negatively impact the survival outcomes or the quality of life of affected patients. Delabeling pathways and rapid drug desensitization (RDD) can help reactive patients stay on first-choice therapies instead of turning to less efficacious, less cost-effective, or more toxic alternatives. However, these are high-complexity and high-risk techniques, which usually need expert teams and allergy-specific techniques (skin testing, in vitro testing, drug provocation testing) to ensure safety, an accurate diagnosis, and personalized management. Unfortunately, there are significant inequalities within and among countries in access to allergy departments with the necessary expertise and resources to offer these techniques and tackle these DHRs optimally. The main objective of this consensus document is to create a great benefit for patients worldwide by aiding allergists to expand the scope of their practice and support them with evidence, data, and experience from leading groups from around the globe. This statement of the Drug Hypersensitivity Committee of the World Allergy Organization (WAO) aims to be a comprehensive practical guide on the technical aspects of implementing acute-onset intravenous hypersensitivity delabeling and RDD for a wide range of drugs. Thus, the manuscript does not only focus on clinical pathways. Instead, it also provides guidance on topics usually left unaddressed, namely, internal validation, continuous quality improvement, creating a healthy multidisciplinary environment, and redesigning care (including a specific supplemental section on a real-life example of how to design a dedicated space that can combine basic and complex diagnostic and therapeutic techniques in allergy).
Published: 2022

24. Zinc determines dynamical properties and aggregation kinetics of human insulin

Author: Geoffrey W. Grime, Daria Noferini, Tilo Seydel, Kevin Pounot, Alessandro Longo, Martin Weik, Vito Foderà, Michaela Zamponi, Viviana Cristiglio, Elspeth F. Garman, Giorgio Schirò, Applied Physics, University of Tübingen, University of Surrey Ion Beam Centre, Istituto per lo Studio dei Materiali Nanostrutturati, Palermo, Consiglio Nazionale delle Ricerche [Roma] (CNR), Jülich Centre for Neutron Science (JCNS), Institut Laue-Langevin (ILL), ILL, Biochemistry, University of Oxford [Oxford], Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Pharmacy, IT University of Copenhagen, University of Surrey (UNIS), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), University of Oxford, Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), and IT University of Copenhagen (ITU)
Subjects: Amyloid, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Biophysics, chemistry.chemical_element, Zinc, Protein aggregation, 010402 general chemistry, Fibril, 01 natural sciences, 03 medical and health sciences, 0302 clinical medicine, ddc:570, medicine, Humans, Insulin, Binding site, 030304 developmental biology, [PHYS]Physics [physics], 0303 health sciences, Amyloidosis, Biomaterial, Articles, medicine.disease, 0104 chemical sciences, Kinetics, X-Ray Absorption Spectroscopy, chemistry, 030217 neurology & neurosurgery
Abstract: Protein aggregation is a widespread process leading to deleterious consequences in the organism, with amyloid aggregates being important not only in biology but also for drug design and biomaterial production. Insulin is a protein largely used in diabetes treatment and its amyloid aggregation is at the basis of the so-called insulin-derived amyloidosis. Here we uncover the major role of zinc in both insulin dynamics and aggregation kinetics at low pH, where the formation of different amyloid superstructures (fibrils and spherulites) can be thermally induced. Amyloid aggregation is accompanied by zinc release and the suppression of water-sustained insulin dynamics, as shown by particle-induced X-ray emission and X-ray absorption spectroscopy and by neutron spectroscopy, respectively. Our study shows that zinc binding stabilizes the native form of insulin by facilitating hydration of this hydrophobic protein and suggests that introducing new binding sites for zinc can improve insulin stability and tune its aggregation propensity.Statement of SignificanceLocalized amyloidosis occurs at insulin injection sites for diabetes treatment, leading to deleterious inflammations known as insulin-derived amyloidosis. Amyloid superstructures are also promising candidates in the field of biomaterials. Here we revealed that zinc, coordinated to insulin in the native form, is released upon amyloid aggregation, when insulin forms superstructures known as fibrils and spherulites. Zinc release leads to a full suppression of functionally essential protein dynamics through a modification of the protein’s hydration properties and completely modifies insulin amyloid kinetics. The results suggest that changes in protein hydration upon zinc binding/release modifies both stability and dynamics of insulin and might then be a general strategy to control protein stability and tune protein aggregation into amorphous and ordered superstructures.
Published: 2021

25. Communities of Collembola show functional resilience in a long-term field experiment simulating climate change

Author: Jonathan Bonfanti, Mickaël Hedde, Jérôme Cortet, Paul Henning Krogh, Klaus S. Larsen, Martin Holmstrup, Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Université Paul-Valéry - Montpellier 3 (UPVM)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, 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)-Université de Montpellier (UM), Ecologie fonctionnelle et biogéochimie des sols et des agro-écosystèmes (UMR Eco&Sols), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, 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), Aarhus University [Aarhus], IT University of Copenhagen (ITU), Villum Foundation, Air Liquide Denmark A/S, DONG Energy, and European Project: 227628,EC:FP7:INFRA,FP7-INFRASTRUCTURES-2008-1,INCREASE(2009)
Subjects: Resilience, Trait, Community-weighted mean, Soil Science, Climate change, Collembola, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Ecology, Evolution, Behavior and Systematics, Soil fauna
Abstract: Soil ecosystems, and the fauna they host, are known to provide many services and communities of Collembola can be used as bioindicators of soil functionality. Climate change is often expected to threaten Collembola, however, it is possible that it could also favour them. Previous studies have shown that the structure of collembolan communities can be shaped by long-term adaptation to climate, and that temperature plays a major role in the variation of species traits. In this study, we evaluated how the functional composition and structure of collembolan communities are impacted by climate change using an experimental climate manipulation design. The study used data from the CLIMAITE experiment, which was carried out in Denmark in an unmanaged heath/grassland ecosystem that was subjected to the simulated predicted climate for the year 2075. The climate manipulation experiment parameters included elevated temperature, elevated concentration of atmospheric CO 2 and extended drought, which were tested alone and in combination on a total of 48 plots, including controls. Collembola were sampled using 10-cm-depth soil cores after 1, 2 and 8 years of climate manipulation. We posited (i) that a stimulating factor (elevated CO 2) would increase mean body length, and (ii) that an inhibiting factor (drought) would favour traits indicating a euedaphic life or an ability to present resistance mechanisms (scales, ecomorphosis) and would reduce functional structure indices through environmental filtering. The results did not support these hypotheses. While the findings showed sporadic effects of the climatic treatments on the functional composition and structure, they did not demonstrate any general community response pattern. This may be due to limitations of the study in terms of climatic intensity or community assembly, opening perspectives for future experiments in terms of the choice of traits and measurements.
Published: 2022

26. Herbivory on the pedunculate oak along an urbanization gradient in Europe : Effects of impervious surface, local tree cover, and insect feeding guild

Author: Elena Valdés‐Correcher, Anna Popova, Andrea Galmán, Andreas Prinzing, Andrey V. Selikhovkin, Andy G. Howe, Anna Mrazova, Anne‐Maïmiti Dulaurent, Arndt Hampe, Ayco Jerome Michel Tack, Christophe Bouget, Daniela Lupaștean, Deborah Harvey, Dmitry L. Musolin, Gábor L. Lövei, Giada Centenaro, Inge Van Halder, Jonas Hagge, Jovan Dobrosavljević, Juha‐Matti Pitkänen, Julia Koricheva, Katerina Sam, Luc Barbaro, Manuela Branco, Marco Ferrante, Maria Faticov, Markéta Tahadlová, Martin Gossner, Maxime Cauchoix, Michał Bogdziewicz, Mihai‐Leonard Duduman, Mikhail V. Kozlov, Mona C. Bjoern, Nikita A. Mamaev, Pilar Fernandez‐Conradi, Rebecca L. Thomas, Ross Wetherbee, Samantha Green, Slobodan Milanović, Xoaquín Moreira, Yannick Mellerin, Yasmine Kadiri, Bastien Castagneyrol, Biodiversité, Gènes & Communautés (BioGeCo), Université de Bordeaux (UB)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), A.N. Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences [Moscow] (RAS), Martin-Luther-University Halle-Wittenberg, Ecosystèmes, biodiversité, évolution [Rennes] (ECOBIO), Université de Rennes (UR)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR), Université de Rennes (UR)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS), Saint Petersburg University (SPBU), University of Copenhagen = Københavns Universitet (UCPH), University of South Bohemia, Agro-écologie, Hydrogéochimie, Milieux et Ressources (AGHYLE), UniLaSalle, Stockholm University, Groupement d'Interêt Public Ecosystèmes Forestiers GIP ECOFOR (GIP ECOFOR ), University Stefan cel Mare of Suceava (USU), Royal Holloway [University of London] (RHUL), St Petersburg State University (SPbU), Aarhus University [Aarhus], Georg-August-University = Georg-August-Universität Göttingen, University of Belgrade [Belgrade], Natural Resources Institute Finland (LUKE), University of London [London], Czech Academy of Sciences [Prague] (CAS), Centre d'Ecologie et des Sciences de la COnservation (CESCO), Muséum national d'Histoire naturelle (MNHN)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Dynamiques et écologie des paysages agriforestiers (DYNAFOR), École nationale supérieure agronomique de Toulouse (ENSAT), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universidade de Lisboa = University of Lisbon (ULISBOA), Institut Fédéral de Recherches sur la Forêt, la Neige et le Paysage (WSL), Institut Fédéral de Recherches [Suisse], Station d'Ecologie Théorique et Expérimentale (SETE), Centre National de la Recherche Scientifique (CNRS)-Fédération de Recherche Agrobiosciences, Interactions et Biodiversité (FR AIB), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des EcoSystèmes et des Sociétés en Montagne (UR LESSEM), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Turku, IT University of Copenhagen (ITU), Ecologie des Forêts Méditerranéennes (URFM), Norwegian University of Life Sciences (NMBU), Coventry University, Mision Biologica de Galicia (MBG), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), ANR‐10‐LABX‐45, Agence Nationale de la Recherche, Fondation BNP Paribas, ANR-10-LABX-0045,COTE,COntinental To coastal Ecosystems: evolution, adaptability and governance(2010), Agence Nationale de la Recherche (France), BNP Paribas Foundation, Valdés-Correcher, Elena, Sam, Katerina, Ferrante, Marco, Bogdziewicz, Michał, Castagneyrol, Bastien, Research Centre for Ecological Change, and Department of Agricultural Sciences
Subjects: impervious surface, local canopy cover, insect herbivory, DIVERSITY, PLANT DEFENSES, HEAT, LEAF HERBIVORY, URBAN, Insect Herbivory, Leaf Miners, citizen science, Impervious Surface, Local Canopy Cover, leaf gallers, Ecology, Evolution, Behavior and Systematics, Nature and Landscape Conservation, Leaf Gallers, GLOBAL PATTERNS, Ecology, LANDSCAPE CONTEXT, Citizen Science, fungi, FOREST, Protect, restore and promote sustainable use of terrestrial ecosystems, sustainably manage forests, combat desertification, and halt and reverse land degradation and halt biodiversity loss, 1181 Ecology, evolutionary biology, ABUNDANCE, leaf miners, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Quercus robur, TOP-DOWN
Abstract: 14 páginas, 3 figuras, Urbanization is an important driver of the diversity and abundance of tree-associated insect herbivores, but its consequences for insect herbivory are poorly understood. A likely source of variability among studies is the insufficient consideration of intra-urban variability in forest cover. With the help of citizen scientists, we investigated the independent and interactive effects of local canopy cover and percentage of impervious surface on insect herbivory in the pedunculate oak (Quercus robur L.) throughout most of its geographic range in Europe. We found that the damage caused by chewing insect herbivores as well as the incidence of leaf-mining and gall-inducing herbivores consistently decreased with increasing impervious surface around focal oaks. Herbivory by chewing herbivores increased with increasing forest cover, regardless of impervious surface. In contrast, an increase in local canopy cover buffered the negative effect of impervious surface on leaf miners and strengthened its effect on gall inducers. These results show that-just like in non-urban areas-plant-herbivore interactions in cities are structured by a complex set of interacting factors. This highlights that local habitat characteristics within cities have the potential to attenuate or modify the effect of impervious surfaces on biotic interactions., This study was carried out with financial support from the French National Research Agency (ANR) in the frame of the Investments for the Future Programme, within the Cluster of Excellence COTE (Continental To coastal Ecosystems: evolution, adaptability, and governance) (ANR-10-LABX-45) and was further funded by the BNP Paribas Foundation as part of its Climate & Biodiversity Initiative the citizen science project Tree Bodyguards. The authors warmly thank all the young European citizens and their teachers who made this study possible. They also thank the professional scientists who kindly agreed to participate in this study: Alexander Kozel (Belarusian State Technological University and American Psychological Association), Andreas Schuldt (Forest Nature Conservation, Georg-August-University Göttingen, Göttingen, German), Aurélien Sallé (Laboratoire de Biologie des Ligneux et des Grandes Cultures, INRAE, Université d'Orléans), Chloe Mendiondo and Claire Colliaux (Department of Agroecology, Aarhus University, Flakkebjerg Research Centre, DK-4200 Slagelse, Denmark), György Csóka (Department of Forest Protection, NARIC Forest Research Institute, Mátrafüred, Hungary), Lars Opgennoorth (Biodiversity and Conservation Biology, Ecological Genetics, Swiss Federal Research Institute WSL, Birmensdorf, Switzerland), Laurent Augusto (INRAE, Bordeaux Sciences Agro), Marija Popović (Faculty of Forestry, University of Belgrade, Belgrade, Serbia), Mickael Pihain (Research Unit “Ecosystèmes, Biodiversité, Evolution”, University of Rennes 1/CNRS, 35042 Rennes, France), Olivier Bouriaud (Applied Ecology Laboratory, Forestry Faculty, “Ștefan cel Mare, University of Suceava, Suceava, Romania), Stefan K. Müller (Freie evangelische Schule Lörrach), Tomas Roslin (Department of Ecology; Swedish University of Agricultural Sciences), Valentin Queloz (Forest Entomology, Swiss Federal Research Institute WSL), and Vojtech Lanta (Institute of Botany CAS, Dukelská 135, 37901 Třeboň, Czech Republic). They also thank Michael Scherer-Lorenzen (Geobotany, Faculty of Biology, University of Freiburg) for the help during the coordination of the research.
Published: 2022

27. Microbiome and metabolome features of the cardiometabolic disease spectrum

Author: Sebastien Fromentin, Sofia K. Forslund, Kanta Chechi, Judith Aron-Wisnewsky, Rima Chakaroun, Trine Nielsen, Valentina Tremaroli, Boyang Ji, Edi Prifti, Antonis Myridakis, Julien Chilloux, Petros Andrikopoulos, Yong Fan, Michael T. Olanipekun, Renato Alves, Solia Adiouch, Noam Bar, Yeela Talmor-Barkan, Eugeni Belda, Robert Caesar, Luis Pedro Coelho, Gwen Falony, Soraya Fellahi, Pilar Galan, Nathalie Galleron, Gerard Helft, Lesley Hoyles, Richard Isnard, Emmanuelle Le Chatelier, Hanna Julienne, Lisa Olsson, Helle Krogh Pedersen, Nicolas Pons, Benoit Quinquis, Christine Rouault, Hugo Roume, Joe-Elie Salem, Thomas S. B. Schmidt, Sara Vieira-Silva, Peishun Li, Maria Zimmermann-Kogadeeva, Christian Lewinter, Nadja B. Søndertoft, Tue H. Hansen, Dominique Gauguier, Jens Peter Gøtze, Lars Køber, Ran Kornowski, Henrik Vestergaard, Torben Hansen, Jean-Daniel Zucker, Serge Hercberg, Ivica Letunic, Fredrik Bäckhed, Jean-Michel Oppert, Jens Nielsen, Jeroen Raes, Peer Bork, Michael Stumvoll, Eran Segal, Karine Clément, Marc-Emmanuel Dumas, S. Dusko Ehrlich, Oluf Pedersen, Commission of the European Communities, Wellcome Trust, Imperial College Healthcare NHS Trust- BRC Funding, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), European Molecular Biology Laboratory [Heidelberg] (EMBL), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche en Nutrition Humaine - Ile de France (CRNH - IDF), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universitätsklinikum Leipzig, IT University of Copenhagen (ITU), University of Gothenburg (GU), Chalmers University of Technology [Göteborg], Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD [France-Nord]), Imperial College London, Guangzhou Medical University, Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Our study, Metagenomics in Cardiometabolic Diseases, with the acronym METACARDIS, was sponsored by the European Union’s Seventh Framework Program for research, technological development and demonstration under grant agreement HEALTH-F4-2012-305312. Assistance Publique-Hôpitaux de Paris is the promoter of the clinical investigation. Parts of the studies were also supported by Metagenopolis grant ANR-11-DPBS-0001, the Leducq Foundation, the Novo Nordisk Foundation and the NIHR Imperial Biomedical Research Centre and by grants from the French National Research Agency (ANR-10-LABX-46 (European Genomics Institute for Diabetes)), the National Center for Precision Diabetic Medicine, which is jointly supported by the French National Agency for Research (ANR-18-IBHU-0001), the European Union (FEDER), the Hauts-de-France Regional Council (Agreement 20001891/NP0025517), the European Metropolis of Lille (agreement 2019_ESR_11) and site ULNE (R-002-20-TALENT-DUMAS), which is also jointly funded by ANR (ANR-16-IDEX-0004-ULNE), the Hauts-de-France Regional Council (20002845) and the European Metropolis of Lille. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research institution at the University of Copenhagen, partially funded by an unrestricted donation from the Novo Nordisk Foundation. K. Chechi is supported by the Medical Research Council Skills Development Fellowship (grant no. MR/S020039/1) and the Wellcome Trust-funded Institutional Strategic Support Fellowship (grant no. 204834/Z/16/Z). L.H. was in receipt of a Medical Research Council Intermediate Research Fellowship in Data Science (grant no. MR/L01632X/1, UK Med-Bio). S.K.F. was supported by the German Centre for Cardiovascular Research, the German Research Council (projects SFB1365, SFB1470 and KFO339) and the German Ministry of Education and Research., We are indebted to the MetaCardis study participants and patient associations (Alliance du Coeur and CNAO) for their input and interface. Similarly, we are indebted to the MetaCardis consortium (http://www.metacardis.net/) collaborators for contributions at multiple levels since the consortium start in 2012. A full list of collaborators is given in the Supplementary Information. We further thank D. Bonnefont-Rousselot (Department of Metabolic Biochemistry, Pitié-Salpêtrière Hospital) for the analysis of plasma lipid profiles. We greatly appreciate the assistance of nurses, dietitians, laboratory technicians, clinical research assistants and data managers at the Novo Nordisk Foundation Center for Basic Metabolic Research, the Clinical Research Unit at Fredriksberg and Bispebjerg Hospitals, Copenhagen, the Clinical Investigation Platform at the Institute of Cardiometabolism and Nutrition for Patient Investigations and the Clinical Investigation Center from Pitié-Salpêtrière Hospital, Paris, and the University of Leipzig Medical Center, Leipzig. Quanta Medical provided regulatory oversight of the clinical study and contributed to the processing and management of electronic data, ANR-18-IBHU-0001,PreciDIAB,PreciDIAB Institute, the holistic approach of personal diabets care(2018), ANR-16-IDEX-0004,ULNE,ULNE(2016), European Project: 305312,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,METACARDIS(2012), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP]
Subjects: Biochemistry & Molecular Biology, IMPACT, [SDV]Life Sciences [q-bio], Immunology, Research & Experimental Medicine, General Biochemistry, Genetics and Molecular Biology, SERUM, Humans, Longitudinal Studies, cardiovascular diseases, SIGNATURES, 11 Medical and Health Sciences, P-CRESOL, RISK, Science & Technology, PLASMA, Microbiota, GUT MICROBIOTA, General Medicine, Cell Biology, Middle Aged, Medicine, Research & Experimental, Diabetes Mellitus, Type 2, Cardiovascular and Metabolic Diseases, Cardiovascular Diseases, Metabolome, CORONARY-ARTERY-DISEASE, HEART, HEALTH, Life Sciences & Biomedicine
Abstract: Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and response to treatment over time, mirroring a longitudinal study that would otherwise be difficult to perform given the protracted nature of IHD pathogenesis. We recruited 1,241 middle-aged Europeans, including healthy individuals, individuals with dysmetabolic morbidities (obesity and type 2 diabetes) but lacking overt IHD diagnosis and individuals with IHD at three distinct clinical stages-acute coronary syndrome, chronic IHD and IHD with heart failure-and characterized their phenome, gut metagenome and serum and urine metabolome. We found that about 75% of microbiome and metabolome features that distinguish individuals with IHD from healthy individuals after adjustment for effects of medication and lifestyle are present in individuals exhibiting dysmetabolism, suggesting that major alterations of the gut microbiome and metabolome might begin long before clinical onset of IHD. We further categorized microbiome and metabolome signatures related to prodromal dysmetabolism, specific to IHD in general or to each of its three subtypes or related to escalation or de-escalation of IHD. Discriminant analysis based on specific IHD microbiome and metabolome features could better differentiate individuals with IHD from healthy individuals or metabolically matched individuals as compared to the conventional risk markers, pointing to a pathophysiological relevance of these features. ispartof: NATURE MEDICINE vol:28 issue:2 pages:303-+ ispartof: location:United States status: published
Published: 2022

28. Critical Assessment of Metagenome Interpretation: the second round of challenges

Author: Fernando Meyer, Adrian Fritz, Zhi-Luo Deng, David Koslicki, Till Robin Lesker, Alexey Gurevich, Gary Robertson, Mohammed Alser, Dmitry Antipov, Francesco Beghini, Denis Bertrand, Jaqueline J. Brito, C. Titus Brown, Jan Buchmann, Aydin Buluç, Bo Chen, Rayan Chikhi, Philip T. L. C. Clausen, Alexandru Cristian, Piotr Wojciech Dabrowski, Aaron E. Darling, Rob Egan, Eleazar Eskin, Evangelos Georganas, Eugene Goltsman, Melissa A. Gray, Lars Hestbjerg Hansen, Steven Hofmeyr, Pingqin Huang, Luiz Irber, Huijue Jia, Tue Sparholt Jørgensen, Silas D. Kieser, Terje Klemetsen, Axel Kola, Mikhail Kolmogorov, Anton Korobeynikov, Jason Kwan, Nathan LaPierre, Claire Lemaitre, Chenhao Li, Antoine Limasset, Fabio Malcher-Miranda, Serghei Mangul, Vanessa R. Marcelino, Camille Marchet, Pierre Marijon, Dmitry Meleshko, Daniel R. Mende, Alessio Milanese, Niranjan Nagarajan, Jakob Nissen, Sergey Nurk, Leonid Oliker, Lucas Paoli, Pierre Peterlongo, Vitor C. Piro, Jacob S. Porter, Simon Rasmussen, Evan R. Rees, Knut Reinert, Bernhard Renard, Espen Mikal Robertsen, Gail L. Rosen, Hans-Joachim Ruscheweyh, Varuni Sarwal, Nicola Segata, Enrico Seiler, Lizhen Shi, Fengzhu Sun, Shinichi Sunagawa, Søren Johannes Sørensen, Ashleigh Thomas, Chengxuan Tong, Mirko Trajkovski, Julien Tremblay, Gherman Uritskiy, Riccardo Vicedomini, Zhengyang Wang, Ziye Wang, Zhong Wang, Andrew Warren, Nils Peder Willassen, Katherine Yelick, Ronghui You, Georg Zeller, Zhengqiao Zhao, Shanfeng Zhu, Jie Zhu, Ruben Garrido-Oter, Petra Gastmeier, Stephane Hacquard, Susanne Häußler, Ariane Khaledi, Friederike Maechler, Fantin Mesny, Simona Radutoiu, Paul Schulze-Lefert, Nathiana Smit, Till Strowig, Andreas Bremges, Alexander Sczyrba, Alice Carolyn McHardy, Braunschweig Integrated Centre of Systems Biology [Braunschweig] (BRICS), Technische Universität Braunschweig = Technical University of Braunschweig [Braunschweig]-Helmholtz Centre for Infection Research (HZI), Pennsylvania State University (Penn State), Penn State System, German Center for Infection Research - partner site Hannover-Braunschweig (DZIF), Saint Petersburg State University (SPBU), Department of Information Technology and Electrical Engineering [Zürich] (D-ITET), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Center for Algorithmic Biotechnology [Saint Petersburg], Institute of Translational Biomedicine [Saint-Petersburg], Saint Petersburg University (SPBU)-Saint Petersburg University (SPBU), Centre for Integrative Biology (CIBIO), University of Trento (CIBIO), University of Trento [Trento], Genome Institute of Singapore (GIS), University of Southern California (USC), University of California [Davis] (UC Davis), University of California (UC), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Institut Pasteur [Paris] (IP), National Food Institute [Lyngby] (Forside), Drexel University, Robert Koch Institute [Berlin] (RKI), University of Technology Sydney (UTS), DOE Joint Genome Institute [Walnut Creek], University of California [Los Angeles] (UCLA), Intel Corporation [Santa Clara], Intel Corporation [USA], Department of Plant and Environmental Sciences [Frederiksberg], University of Copenhagen = Københavns Universitet (UCPH), Fudan University [Shanghai], Beijing Genomics Institute [Shenzhen] (BGI), Novo Nordisk Foundation Center for Biosustainability, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Université de Genève = University of Geneva (UNIGE), The Arctic University of Norway [Tromsø, Norway] (UiT), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of California [San Diego] (UC San Diego), University of Wisconsin-Madison, 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 Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-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)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Hasso Plattner Institute [Potsdam, Germany], The University of Sydney, Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria), Amsterdam UMC - Amsterdam University Medical Center, Structural and Computational Biology, European Molecular Biology Laboratory [Heidelberg] (EMBL), DTU Electrical Engineering [Lyngby], National Institutes of Health [Bethesda] (NIH), Department of Biology [ETH Zürich] (D-BIOL), University of Virginia, IT University of Copenhagen (ITU), Freie Universität Berlin, University of Potsdam = Universität Potsdam, Florida International University [Miami] (FIU), National Research Council of Canada (NRC), Phase Genomics [Seattle], Max Planck Institute for Plant Breeding Research (MPIPZ), Helmholtz Centre for Infection Research (HZI), Aarhus University [Aarhus], Center for Biotechnology (CeBiTec), Universität Bielefeld = Bielefeld University, Open access funding provided by Helmholtz-Zentrum für Infektionsforschung GmbH (HZI), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-19-P3IA-0001,PRAIRIE,PaRis Artificial Intelligence Research InstitutE(2019), and Medical Microbiology and Infection Prevention
Subjects: 06 Biological Sciences, 10 Technology, 11 Medical and Health Sciences, Reproducibility of Results, Cell Biology, DNA, Sequence Analysis, DNA, Biochemistry, Archaea, Software, Metagenome, Metagenomics, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Molecular Biology, Sequence Analysis, Biotechnology, Developmental Biology
Abstract: Evaluating metagenomic software is key for optimizing metagenome interpretation and focus of the Initiative for the Critical Assessment of Metagenome Interpretation (CAMI). The CAMI II challenge engaged the community to assess methods on realistic and complex datasets with long- and short-read sequences, created computationally from around 1,700 new and known genomes, as well as 600 new plasmids and viruses. Here we analyze 5,002 results by 76 program versions. Substantial improvements were seen in assembly, some due to long-read data. Related strains still were challenging for assembly and genome recovery through binning, as was assembly quality for the latter. Profilers markedly matured, with taxon profilers and binners excelling at higher bacterial ranks, but underperforming for viruses and Archaea. Clinical pathogen detection results revealed a need to improve reproducibility. Runtime and memory usage analyses identified efficient programs, including top performers with other metrics. The results identify challenges and guide researchers in selecting methods for analyses., Nature Methods, 19 (8), ISSN:1548-7105, ISSN:1548-7091
Published: 2022

29. Reducing the Vertex Cover Number via Edge Contractions

Author: Lima, Paloma T., dos Santos, Vinicius F., Sau, Ignasi, Souza, Uéverton S., Tale, Prafullkumar, IT University of Copenhagen (ITU), Departamento de Ciência da Computação [Minas Gerais] (DCC - UFMG), Universidade Federal de Minas Gerais [Belo Horizonte] (UFMG), Algorithmes, Graphes et Combinatoire (ALGCO), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Instituto de Computação [Niteroi-Rio de Janeiro] (IC-UFF), Universidade Federal Fluminense [Rio de Janeiro] (UFF), Helmholtz Center for Information Security [Saarbrücken] (CISPA), CAPES-PRINT Institutional Internationalization Program, process 88887.371209/ 2019-00, ANR-16-CE40-0028,DE-MO-GRAPH,Décomposition de Modèles Graphiques(2016), ANR-17-CE23-0010,ESIGMA,Efficacité et structure pour les applications de la fouille de graphes(2017), ANR-20-CE48-0008,ELIT,Un Parcours par les Limites de l'Efficacité(2020), ANR-20-CE92-0027,UTMA,Théories Unifiantes dans les Algorithmes Multivarieés(2020), European Project: 714704,CUTACOMBS, European Project: 725978,SYSTEMATICGRAPH(2017), Szeider, Stefan, Ganian, Robert, Silva, Alexandra, Universidade Federal de Minas Gerais = Federal University of Minas Gerais [Belo Horizonte, Brazil] (UFMG), and Vinicius F. dos Santos: Grant APQ-01707-21 Minas Gerais Research Support Foundation (FAPEMIG) and Grant 312069/2021-9 National Council for Scientific and Technological Development (CNPq).Ignasi Sau: CAPES-PRINT Institutional Internationalization Program, process 88887.371209/ 2019-00, and projects DEMOGRAPH (ANR-16-CE40-0028), ESIGMA (ANR-17-CE23-0010), ELIT (ANR-20-CE48-0008-01), and UTMA (ANR-20-CE92-0027).Uéverton S. Souza: This research has received funding from Rio de Janeiro Research Support Foundation (FAPERJ) under grant agreement E-26/201.344/2021, National Council for Scientific and Technological Development (CNPq) under grant agreement 309832/2020-9, and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation pro- gramme under grant agreement CUTACOMBS (No. 714704).
Subjects: FOS: Computer and information sciences, General Computer Science, Blocker problems, Computer Networks and Communications, Applied Mathematics, G.2.2, F.2.2, Computational Complexity (cs.CC), vertex cover, Theoretical Computer Science, Computer Science - Computational Complexity, 05C15, Computational Theory and Mathematics, edge contraction, Computer Science - Data Structures and Algorithms, FOS: Mathematics, Theory of computation → Parameterized complexity and exact algorithms, Mathematics - Combinatorics, Data Structures and Algorithms (cs.DS), [INFO]Computer Science [cs], Combinatorics (math.CO), [MATH]Mathematics [math], phrases Blocker problems, parameterized complexity
Abstract: The CONTRACTION(vc) problem takes as input a graph $G$ on $n$ vertices and two integers $k$ and $d$, and asks whether one can contract at most $k$ edges to reduce the size of a minimum vertex cover of $G$ by at least $d$. Recently, Lima et al. [JCSS 2021] proved, among other results, that unlike most of the so-called blocker problems, CONTRACTION(vc) admits an XP algorithm running in time $f(d) \cdot n^{O(d)}$. They left open the question of whether this problem is FPT under this parameterization. In this article, we continue this line of research and prove the following results: 1. CONTRACTION(vc) is W[1]-hard parameterized by $k + d$. Moreover, unless the ETH fails, the problem does not admit an algorithm running in time $f(k + d) \cdot n^{o(k + d)}$ for any function $f$. In particular, this answers the open question stated in Lima et al. [JCSS 2021] in the negative. 2. It is NP-hard to decide whether an instance $(G, k, d)$ of CONTRACTION(vc) is a yes-instance even when $k = d$, hence enhancing our understanding of the classical complexity of the problem. 3. CONTRACTION(vc) can be solved in time $2^{O(d)} \cdot n^{k - d + O(1)}$. This XP algorithm improves the one of Lima et al. [JCSS 2021], which uses Courcelle's theorem as a subroutine and hence, the $f(d)$-factor in the running time is non-explicit and probably very large. On the other hard, it shows that when $k=d$, the problem is FPT parameterized by $d$ (or by $k$)., 35 pages, 5 figures
Published: 2022

30. Efficacy and safety of finerenone in patients with chronic kidney disease and type 2 diabetes by GLP-1RA treatment:A subgroup analysis from the FIDELIO-DKD trial

Author: Stefan D. Anker, Aslam Amod, Luis M. Ruilope, Gerasimos Filippatos, Amer Joseph, Michel Marre, Bertram Pitt, Charlie Scott, Andrea Lage, Rajiv Agarwal, George L. Bakris, Peter Rossing, IT University of Copenhagen, Indiana University School of Medicine, Indiana University System, Charité Campus Virchow-Klinikum (CVK), National and Kapodistrian University of Athens (NKUA), University of Michigan [Ann Arbor], University of Michigan System, University of KwaZulu-Natal (UKZN), 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 de Paris (UP), Bayer Pharma AG [Berlin], The University of Chicago Medicine [Chicago], IT University of Copenhagen (ITU), University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN), 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), and Gestionnaire, HAL Sorbonne Université 5
Subjects: medicine.medical_specialty, Finerenone, Endocrinology, Diabetes and Metabolism, Enfermedad cardiovascular, glucagon-like peptide-1 receptor agonist, Urology, Renal function, Subgroup analysis, Type 2 diabetes, 030204 cardiovascular system & hematology, Placebo, Tratamiento médico, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Myocardial infarction, mineralocorticoid receptor antagonist, Naphthyridines, Renal Insufficiency, Chronic, finerenone, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Fallo renal crónico, business.industry, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, 3. Good health, Diabetes mellitus tipo 2, Sistema endocrino, Diabetes Mellitus, Type 2, Heart failure, type 2 diabetes, business, chronic kidney disease, Glomerular Filtration Rate, Kidney disease
Abstract: Aims Finerenone significantly reduced the risk of kidney and cardiovascular (CV) outcomes in patients with chronic kidney disease and type 2 diabetes in the FIDELIO-DKD trial (NCT02540993). This exploratory subgroup analysis investigates the effect of glucagon-like peptide-1 receptor agonist (GLP-1RA) use on the treatment effect of finerenone. Materials and Methods Patients with type 2 diabetes, urine albumin-to-creatinine ratio (UACR) 30-5000 mg/g and estimated glomerular filtration rate 25
Published: 2022

31. Dansgaard-Oeschger and Heinrich event temperature anomalies in the North Atlantic set by sea ice, frontal position and thermocline structure

Author: J.B. Pedro, C. Andersson, G. Vettoretti, A.H.L. Voelker, C. Waelbroeck, T.M. Dokken, M.F. Jensen, S.O. Rasmussen, E.G. Sessford, M. Jochum, K.H. Nisancioglu, Australian Antarctic Division (AAD), Australian Government, Department of the Environment and Energy, Institute for Marine and Antarctic Studies [Hobart] (IMAS), University of Tasmania [Hobart, Australia] (UTAS), IT University of Copenhagen (ITU), NORCE Norwegian Research Center, Instituto Português de Investigação do Mar e da Atmosfera (IPMA), Centro de Ciências do Mar [Faro] (CCMAR), Universidade do Algarve (UAlg), Processus et interactions de fine échelle océanique (PROTEO), Laboratoire d'Océanographie et du Climat : Expérimentations et Approches Numériques (LOCEAN), Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut Pierre-Simon-Laplace (IPSL (FR_636)), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut Pierre-Simon-Laplace (IPSL (FR_636)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Department of Earth Science [Bergen] (UiB), University of Bergen (UiB), Bjerknes Centre for Climate Research (BCCR), Department of Biological Sciences [Bergen] (BIO / UiB), University of Bergen (UiB)-University of Bergen (UiB), Center for Earth Evolution and Dynamics, University of Oslo, University of Oslo (UiO), European Project: 610055,EC:FP7:ERC,ERC-2013-SyG,ICE2ICE(2014), and European Project: 339108,EC:FP7:ERC,ERC-2013-ADG,ACCLIMATE(2014)
Subjects: Archeology, Global and Planetary Change, Dansgaard-Oeschger event, [SDU]Sciences of the Universe [physics], marine sediment core, Heinrich event, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, Geology, ice core, Ecology, Evolution, Behavior and Systematics, sea ice, abrupt climate change
Abstract: We use eighteen timescale-synchronised near-surface temperature reconstructions spanning 10-50 thousand years before present to clarify the regional expression of Dansgaard-Oeschger (D-O) and Heinrich (H) events in the North Atlantic. The North Atlantic Drift region shows D-O temperature variations of ca. 2-5?? with Greenland-like structure. The Western Iberian Margin region also shows Greenland-like structure, but with more pronounced surface cooling between interstadials and Heinrich stadials (ca. 6-9 ??C) than between interstadials and non-Heinrich stadials (ca. 2-3 ??C). The southern Nordic Seas show smaller D-O temperature anomalies (ca. 1-2 ??C) that appear out of phase with Greenland. These spatial patterns are replicated in a new global climate model simulation that features unforced (D-O-like) and freshwater forced (H-like) abrupt climate changes. The model simulations and observations suggest consistently that the spatial expression and amplitude of D-O and H event temperature anomalies are dominated by coupled changes in the Atlantic Meridional Overturning, sea ice extent, polar front position and thermocline structure. ?? 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). info:eu-repo/semantics/publishedVersion
Published: 2022

32. The path towards herd immunity: Predicting COVID-19 vaccination uptake through results from a stated choice study across six continents

Author: Stephane Hess, Emily Lancsar, Petr Mariel, Jürgen Meyerhoff, Fangqing Song, Eline van den Broek-Altenburg, Olufunke A. Alaba, Gloria Amaris, Julián Arellana, Leonardo J. Basso, Jamie Benson, Luis Bravo-Moncayo, Olivier Chanel, Syngjoo Choi, Romain Crastes dit Sourd, Helena Bettella Cybis, Zack Dorner, Paolo Falco, Luis Garzón-Pérez, Kathryn Glass, Luis A. Guzman, Zhiran Huang, Elisabeth Huynh, Bongseop Kim, Abisai Konstantinus, Iyaloo Konstantinus, Ana Margarita Larranaga, Alberto Longo, Becky P.Y. Loo, Malte Oehlmann, Vikki O'Neill, Juan de Dios Ortúzar, María José Sanz, Olga L. Sarmiento, Hazvinei Tamuka Moyo, Steven Tucker, Yacan Wang, Yu Wang, Edward J.D. Webb, Junyi Zhang, Mark H.P. Zuidgeest, University of Leeds, Australian National University (ANU), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Technical University of Berlin / Technische Universität Berlin (TU), University College of London [London] (UCL), University of Vermont [Burlington], University of Cape Town, Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU), Universidad del Norte, Barranquilla, Universidad de Chile = University of Chile [Santiago] (UCHILE), Universidad de Las Américas [Ecuador] (UDLA), Universidad Técnica del Norte (UTN), Aix-Marseille Sciences Economiques (AMSE), École des hautes études en sciences sociales (EHESS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Seoul National University [Seoul] (SNU), Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS), University of Waikato [Hamilton], IT University of Copenhagen (ITU), Universidad de los Andes [Bogota] (UNIANDES), The University of Hong Kong (HKU), Ndatara surveys, Namibia Institute of Pathology, Queen's University [Belfast] (QUB), Technische Universität München = Technical University of Munich (TUM), Pontificia Universidad Católica de Chile (UC), Basque Centre for Climate Change (BC3), Ikerbasque - Basque Foundation for Science, Beijing Jiaotong University (BJTU), Hiroshima University, CN Chinese National Natural Science Foundation (72071017), the joint project of the National Natural Science Foundation of China and the Joint Programming Initiative Urban Europe (NSFC – JPI UE) (‘U-PASS’, 71961137005)., CL Instituto Sistemas Complejos de Ingeniería (ISCI), through grant ANID PIA/BASAL AFB180003., ES FEDER/Ministry of Science, Innovation and Universities through grant PID2020-113650RB-I00, Basque Government through grant IT1359-19 (UPV/EHU Econometrics Research Group), BERC 2018–2021 programme, MICINN María de Maeztu excellence accreditation (MDM-2017-0714)., KR Creative-Pioneering Researchers Program through Seoul National University., NA Ndatara Surveys., NZ Waikato Management School., ANR-17-EURE-0020,AMSE (EUR),Aix-Marseille School of Economics(2017), ANR-11-IDEX-0001,Amidex,INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE(2011), and European Project: 615596,EC:FP7:ERC,ERC-2013-CoG,DECISIONS(2014)
Subjects: Vaccines, Health (social science), History and Philosophy of Science, SDG 3 - Good Health and Well-being, COVID-19, COVID-19 vaccines, immunity, herd, SDG 10 - Reduced Inequalities, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, humans, vaccination
Abstract: Despite unprecedented progress in developing COVID-19 vaccines, global vaccination levels needed to reach herd immunity remain a distant target, while new variants keep emerging. Obtaining near universal vaccine uptake relies on understanding and addressing vaccine resistance. Simple questions about vaccine acceptance however ignore that the vaccines being offered vary across countries and even population subgroups, and differ in terms of efficacy and side effects. By using advanced discrete choice models estimated on stated choice data collected in 18 countries/territories across six continents, we show a substantial influence of vaccine characteristics. Uptake increases if more efficacious vaccines (95% vs 60%) are offered (mean across study areas=3.9%, range of 0.6%-8.1%) or if vaccines offer at least 12 months of protection (mean across study areas=2.4%, range of 0.2%-5.8%), while an increase in severe side effects (from 0.001% to 0.01%) leads to reduced uptake (mean=-1.3%, range of -0.2% to -3.9%). Additionally, a large share of individuals (mean=55.2%, range of 28%-75.8%) would delay vaccination by 3 months to obtain a more efficacious (95% vs 60%) vaccine, where this increases further if the low efficacy vaccine has a higher risk (0.01% instead of 0.001%) of severe side effects (mean=65.9%, range of 41.4%-86.5%). Our work highlights that careful consideration of which vaccines to offer can be beneficial. In support of this, we provide an interactive tool to predict uptake in a country as a function of the vaccines being deployed, and also depending on the levels of infectiousness and severity of circulating variants of COVID-19. We acknowledge financial support as follows: CN Chinese National Natural Science Foundation (72071017), the joint project of the National Natural Science Foundation of China and the Joint Programming Initiative Urban Europe (NSFC – JPI UE) (‘U- PASS’, 71961137005). CL Instituto Sistemas Complejos de Ingeniería (ISCI), through grant ANID PIA/BASAL AFB180003. ES FEDER/Ministry of Science, Innovation and Universities through grant PID2020-113650RB-I00; Basque Government through grant IT1359-19 (UPV/EHU Econometrics Research Group); BERC 2018–2021 programme; MICINN María de Maeztu excellence accreditation (MDM- 2017-0714). FR FR French National Research Agency Grants ANR-17-EURE-0020 and the Excellence Initiative of Aix-Marseille University - A*MIDEX. KR Creative-Pioneering Researchers Program through Seoul Na- tional University. NA Ndatara Surveys. NZ Waikato Management School. UK European Research Council through the consolidator grant 615596-DECISIONS; internal funding through the Choice Modelling Centre (CMC). We would also like to express our thanks to technical support from Aix-Marseille University, and thank Sofia Hern ́andez Benavides (CL), Simon Dec Pedersen (DK) and Robbie Maris (NZ) for help in data preparation and analysis.
Published: 2022

33. Larger Corner-Free Sets from Combinatorial Degenerations

Author: Christandl, M., Fawzi, O., Ta, H., Zuiddam, J., Braverman, M., Algebra, Geometry & Mathematical Physics (KDV, FNWI), IT University of Copenhagen (ITU), Laboratoire de l'Informatique du Parallélisme (LIP), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), Traitement optimal de l'information avec des dispositifs quantiques (QINFO), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Grenoble Alpes (UGA)-Inria Lyon, Institut National de Recherche en Informatique et en Automatique (Inria), University of Amsterdam [Amsterdam] (UvA), ANR-10-LABX-0070,MILYON,Community of mathematics and fundamental computer science in Lyon(2010), European Project: 851716,ERC-2019-STG,AlgoQIP(2021), and Braverman, Mark
Subjects: FOS: Computer and information sciences, Theory of computation → Communication complexity, Mathematics of computing �� Discrete mathematics, number on the forehead, Mathematics of computing → Discrete mathematics, Corner-free sets, Computational Complexity (cs.CC), Computer Science::Computational Complexity, combinatorial degeneration, Theory of computation �� Communication complexity, 05D10, 05C65, Computer Science - Computational Complexity, hypergraphs, Shannon capacity, FOS: Mathematics, Mathematics - Combinatorics, communication complexity, [INFO]Computer Science [cs], Combinatorics (math.CO), Theory of computation → Algebraic complexity theory, eval problem, Theory of computation �� Algebraic complexity theory
Abstract: There is a large and important collection of Ramsey-type combinatorial problems, closely related to central problems in complexity theory, that can be formulated in terms of the asymptotic growth of the size of the maximum independent sets in powers of a fixed small (directed or undirected) hypergraph, also called the Shannon capacity. An important instance of this is the corner problem studied in the context of multiparty communication complexity in the Number On the Forehead (NOF) model. Versions of this problem and the NOF connection have seen much interest (and progress) in recent works of Linial, Pitassi and Shraibman (ITCS 2019) and Linial and Shraibman (CCC 2021). We introduce and study a general algebraic method for lower bounding the Shannon capacity of directed hypergraphs via combinatorial degenerations, a combinatorial kind of "approximation" of subgraphs that originates from the study of matrix multiplication in algebraic complexity theory (and which play an important role there) but which we use in a novel way. Using the combinatorial degeneration method, we make progress on the corner problem by explicitly constructing a corner-free subset in $F_2^n \times F_2^n$ of size $\Omega(3.39^n/poly(n))$, which improves the previous lower bound $\Omega(2.82^n)$ of Linial, Pitassi and Shraibman (ITCS 2019) and which gets us closer to the best upper bound $4^{n - o(n)}$. Our new construction of corner-free sets implies an improved NOF protocol for the Eval problem. In the Eval problem over a group $G$, three players need to determine whether their inputs $x_1, x_2, x_3 \in G$ sum to zero. We find that the NOF communication complexity of the Eval problem over $F_2^n$ is at most $0.24n + O(\log n)$, which improves the previous upper bound $0.5n + O(\log n)$., Comment: A short version of this paper will appear in the proceedings of ITCS 2022. This paper improves results that appeared in arxiv:2104.01130v1
Published: 2022

34. Cardiac Outcomes in Adults With Mitochondrial Diseases

Author: Konstantinos Savvatis, Christoffer Rasmus Vissing, Lori Klouvi, Anca Florian, Mehjabin Rahman, Anthony Béhin, Abdallah Fayssoil, Marion Masingue, Tanya Stojkovic, Henri Marc Bécane, Nawal Berber, Fanny Mochel, Denis Duboc, Bertrand Fontaine, Bjørg Krett, Caroline Stalens, Julie Lejeune, Robert D.S. Pitceathly, Luis Lopes, Malika Saadi, Thomas Gossios, Vincent Procaccio, Marco Spinazzi, Céline Tard, Pascal De Groote, Claire-Marie Dhaenens, Claire Douillard, Andoni Echaniz-Laguna, Ros Quinlivan, Michael G. Hanna, Ali Yilmaz, John Vissing, Pascal Laforêt, Perry Elliott, Karim Wahbi, Queen Mary University of London (QMUL), IT University of Copenhagen (ITU), Association française contre les myopathies (AFM-Téléthon), University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), University College of London [London] (UCL), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Raymond Poincaré [Garches], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris Cité (UPCité), Sorbonne Université (SU), Hôpital Cochin [AP-HP], Aristotle University of Thessaloniki, MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Biochimie et Génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Hôpital Claude Huriez [Lille], CHU Lille, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), MR/S005021/1, Association Française contre les Myopathies, AFM, Medical Research Council, MRC: MR/S002065/1, Department of Health and Social Care, DH, University College London Hospitals NHS Foundation Trust, UCLH, NIHR Cambridge Biomedical Research Centre, This study was funded by grants from the Association Française contre les Myopathies (French Alliance against Myopathies), which was not involved in the design and conduct of the study, the collection, management, analysis, and interpretation of the data, the preparation, review or approval of the manuscript, and nor in the decision to submit the manuscript for publication. Dr Pitceathly is supported by a Medical Research Council (United Kingdom) Clinician Scientist Fellowship (MR/S002065/1). Drs Pitceathly and Hanna receive funding from a Medical Research Council (United Kingdom) strategic award to establish an International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD) (MR/S005021/1). Dr Lopes is supported by a Medical Research Council (United Kingdom) clinical academic partnership (CARP) award. Dr Quinlivan was funded by National Institute for Health and Care Research Biomedical Research Centre, University College Hospitals Foundation Trust. The University College London Hospitals/University College London Queen Square Institute of Neurology sequencing facility receives a proportion of funding from the Department of Health's National Institute for Health and Care Research Biomedical Research Centre’s funding scheme. The clinical and diagnostic 'Rare Mitochondrial Disorders' Service in London is funded by the U.K. NHS Highly Specialised Commissioners. Dr Elliott has received consultancy fees from Pfizer, Sanofi, Sarepta, DinaQor, Freeline, Novo Nordisk, and Bristol Myers Squibb. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Subjects: Adult, conduction disease, mitochondrial diseases, [SDV]Life Sciences [q-bio], heart failure, sudden death, Heart, Stroke Volume, Prognosis, DNA, Mitochondrial, Ventricular Function, Left, single large-scale deletions, Risk Factors, Humans, Hypertrophy, Left Ventricular, Cardiology and Cardiovascular Medicine, G%22">m3243A>G
Abstract: International audience; Background: Patients with mitochondrial diseases are at risk of heart failure (HF) and arrhythmic major adverse cardiac events (MACE). Objectives: We developed prediction models to estimate the risk of HF and arrhythmic MACE in this population. Methods: We determined the incidence and searched for predictors of HF and arrhythmic MACE using Cox regression in 600 adult patients from a multicenter registry with genetically confirmed mitochondrial diseases. Results: Over a median follow-up time of 6.67 years, 29 patients (4.9%) reached the HF endpoint, including 19 hospitalizations for nonterminal HF, 2 cardiac transplantations, and 8 deaths from HF. Thirty others (5.1%) reached the arrhythmic MACE, including 21 with third-degree or type II second-degree atrioventricular blocks, 4 with sinus node dysfunction, and 5 sudden cardiac deaths. Predictors of HF were the m.3243A>G variant (HR: 4.3; 95% CI: 1.8-10.1), conduction defects (HR: 3.0; 95% CI: 1.3-6.9), left ventricular (LV) hypertrophy (HR: 2.6; 95% CI: 1.1-5.8), LV ejection fraction
Published: 2022

35. Patient characteristics, management and outcomes in a Nordic subset of the 'large observational study to understand the global impact of severe acute respiratory failure' (LUNG SAFE) study

Author: Laake, Jon Henrik, Småstuen, Milada Cvancarova, Møller, Morten Hylander, Larsson, Anders Sune, Aslam, Tayyba Naz, Hofsø, Kristin, Pham, Tài, Fan, Eddy, Bellani, Giacomo, Laffey, John Gerard, HAL UVSQ, Équipe, Oslo University Hospital [Oslo], Oslo Metropolitan University (OsloMet), IT University of Copenhagen (ITU), Uppsala University Hospital, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), University of Toronto, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), National University of Ireland [Galway] (NUI Galway), University Hospital Galway, We gratefully recognise the efforts by ICU-staff in Scandinavian hospitals who contributed patient data for the LUNG SAFE study., Laake, J, Småstuen, M, Møller, M, Larsson, A, Aslam, T, Hofsø, K, Pham, T, Fan, E, Bellani, G, and Laffey, J
Subjects: Adult, Male, Respiratory Distress Syndrome, Anestesi och intensivvård, Anesthesiology and Intensive Care, [SDV]Life Sciences [q-bio], General Medicine, Respiration, Artificial, [SDV] Life Sciences [q-bio], Intensive Care Units, Anesthesiology and Pain Medicine, Humans, ARDS, Female, Hospital Mortality, Respiratory Insufficiency, Lung
Abstract: International audience; Background: The “Large observational study to understand the global impact of severe acute respiratory failure” (LUNG SAFE) study described the worldwide epidemiology and management of patients with acute hypoxaemic respiratory failure (AHRF). Here, we present the Nordic subset of data from the LUNG SAFE cohort. Methods: We extracted LUNG SAFE data for adults fulfilling criteria for AHRF in intensive care units (ICU) in Denmark, Norway and Sweden, including demographics, co-morbidities, clinical assessment and management characteristics, 90-day survival and length-of-stay (LOS). We analysed ICU LOS with linear regression, and associations between risk factors and mortality were quantified using Cox regression. Results: We included 192 patients, with a median age of 64 years (IQR 55, 72), and a male-to-female ratio of 2:1. The majority had one or more co-morbidities, and clinicians identified pneumonia as the primary cause of respiratory failure in 56% and acute respiratory distress syndrome (ARDS) in 21%. Median ICU LOS and duration of invasive mechanical ventilation (IMV) were 5 and 3 days. Tidal volumes (TV) were frequently larger than that supported by evidence and IMV allowing for spontaneous ventilation was common. Younger age, co-morbidity, surgical admission and ARDS were associated with ICU LOS. Sixty-one patients (32%) were dead at 90 days. Age and a non-surgical cause of admission were associated with death. Conclusions: In this subset of LUNG SAFE, ARDS was often not recognised in patients with AHRF and management frequently deviated from evidence-based practices. ICU LOS was generally short, and mortality was attributable to known risk factors.
Published: 2022

36. Evolution of putative barrier loci at an intermediate stage of speciation with gene flow in campions (Silene)

Author: Sylvain Glémin, Xiaodong Liu, Sophie Karrenberg, Uppsala University, IT University of Copenhagen, Ecosystèmes, biodiversité, évolution [Rennes] (ECOBIO), Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), VetenskapsradetSwedish Research Council [2012-03622], IT University of Copenhagen (ITU), Université de Rennes (UR)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR), and Université de Rennes (UR)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Gene Flow, 0106 biological sciences, 0301 basic medicine, Genetic Speciation, media_common.quotation_subject, Population, 010603 evolutionary biology, 01 natural sciences, Gene flow, Evolutionsbiologi, 03 medical and health sciences, Effective population size, demographic modelling, Gene density, ecological speciation, Genetics, Speciation and Hybridization, Selection, Genetic, Genetik, Silene, education, Ecology, Evolution, Behavior and Systematics, media_common, Isolation by distance, Evolutionary Biology, education.field_of_study, Genome, barrier loci, biology, Genetic Drift, genomic landscape, Genomics, 15. Life on land, biology.organism_classification, Silene dioica, Speciation, 030104 developmental biology, Evolutionary biology, Original Article, ORIGINAL ARTICLES, [SDE.BE]Environmental Sciences/Biodiversity and Ecology
Abstract: International audience; Understanding the origin of new species is a central goal in evolutionary biology. Diverging lineages often evolve highly heterogeneous patterns of genetic differentiation; however, the underlying mechanisms are not well understood. We investigated evolutionary processes governing genetic differentiation between the hybridizing campionsSilene dioica(L.) Clairv. andS. latifoliaPoiret. Demographic modelling indicated that the two species diverged with gene flow. The best-supported scenario with heterogeneity in both migration rate and effective population size suggested that a small proportion of the loci evolved without gene flow. Differentiation (F-ST) and sequence divergence (d(XY)) were correlated and both tended to peak in the middle of most linkage groups, consistent with reduced gene flow at highly differentiated loci. Highly differentiated loci further exhibited signatures of selection. In between-species population pairs, isolation by distance was stronger for genomic regions with low between-species differentiation than for highly differentiated regions that may contain barrier loci. Moreover, differentiation landscapes within and between species were only weakly correlated, suggesting that linked selection due to shared recombination and gene density landscapes is not the dominant determinant of genetic differentiation in these lineages. Instead, our results suggest that divergent selection shaped the genomic landscape of differentiation between the twoSilenespecies, consistent with predictions for speciation in the face of gene flow.
Published: 2020

37. Revealing the mechanism of repressor inactivation during switching of a temperate bacteriophage

Author: Martin Blackledge, Leila Lo Leggio, Karin Hammer, Torsten Herrmann, Habiba El-Wali, Mogens Kilstrup, Anders K. Varming, K.K. Rasmussen, Malene Ringkjøbing Jensen, Andrés Palencia, Elisabetta Boeri Erba, Department of Chemistry, IT University of Copenhagen (ITU), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Metabolic Signaling and Regulation, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), ISBG NMR, ISBG mass spectrometry, ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), ANR-18-ERC1-0007,MAPKassembly,Visualisation de l'assemblage de complexes de signalisation cellulaire MAPK par spectroscopie RMN(2018), European Project: 341400,EC:FP7:PEOPLE,FP7-Adhoc-2007-13,ERCSC-CHAIRS-SUP2013(2013), European Project: R249-2017-977, European Project: Grant 653706, European Project: Grant 4002-00107, European Project: Grant 7055-00001B, Thomas, Frank, Infrastructure Française pour la Biologie Structurale Intégrée - - FRISBI2010 - ANR-10-INBS-0005 - INBS - VALID, CBH-EUR-GS - - CBH-EUR-GS2017 - ANR-17-EURE-0003 - EURE - VALID, TREMPLIN-ERC - Visualisation de l'assemblage de complexes de signalisation cellulaire MAPK par spectroscopie RMN - - MAPKassembly2018 - ANR-18-ERC1-0007 - TERC - VALID, Support to the Chair and Vice-Chairs of the ERC Scientific Council 2013 - ERCSC-CHAIRS-SUP2013 - - EC:FP7:PEOPLE2013-01-01 - 2013-12-31 - 341400 - VALID, Lundbeck Foundation - R249-2017-977 - INCOMING, iNEXT - Grant 653706 - INCOMING, Danish Council for Independent Research - Grant 4002-00107 - INCOMING, Danish Ministry for Higher Education and Science - Grant 7055-00001B - INCOMING, IT University of Copenhagen, and Technical University of Denmark [Lyngby] (DTU)
Subjects: 0301 basic medicine, Genetic switch, Operator Regions, Genetic, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Protein Conformation, Repressor, Protein dynamics, Molecular Dynamics Simulation, 010402 general chemistry, 01 natural sciences, Bacteriophage, 03 medical and health sciences, chemistry.chemical_compound, Lysogenic cycle, Temperate bacteriophage, Bacteriophages, Viral Regulatory and Accessory Proteins, genetic switch, Lysogeny, Psychological repression, X-ray crystallography, Multidisciplinary, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], biology, temperate bacteriophage, Lactococcus lactis, Promoter, Biological Sciences, biology.organism_classification, NMR, 0104 chemical sciences, Cell biology, Repressor Proteins, Kinetics, 030104 developmental biology, chemistry, Lytic cycle, Host-Pathogen Interactions, protein dynamics, Genome, Bacterial, DNA
Abstract: Temperate bacteriophages can enter one of two life cycles following infection of a sensitive host: the lysogenic or the lytic life cycle. The choice between the two alternative life cycles is dependent upon a tight regulation of promoters and their cognate regulatory proteins within the phage genome. We investigated the genetic switch of TP901-1, a bacteriophage of Lactococcus lactis, controlled by the CI repressor and the modulator of repression (MOR) antirepressor and their interactions with DNA. We determined the solution structure of MOR, and we solved the crystal structure of MOR in complex with the N-terminal domain of CI, revealing the structural basis of MOR inhibition of CI binding to the DNA operator sites. 15N NMR Carr–Purcell–Meiboom–Gill (CPMG) relaxation dispersion and rotating frame R1ρ measurements demonstrate that MOR displays molecular recognition dynamics on two different time scales involving a repacking of aromatic residues at the interface with CI. Mutations in the CI:MOR binding interface impair complex formation in vitro, and when introduced in vivo, the bacteriophage switch is unable to choose the lytic life cycle showing that the CI:MOR complex is essential for proper functioning of the genetic switch. On the basis of sequence alignments, we show that the structural features of the MOR:CI complex are likely conserved among a larger family of bacteriophages from human pathogens implicated in transfer of antibiotic resistance.
Published: 2020

38. Combinatorial, additive and dose-dependent drug-microbiome associations

Author: Forslund, SK, Chakaroun, R, Zimmermann-Kogadeeva, M, Markó, L, Aron-Wisnewsky, J, Nielsen, T, Moitinho-Silva, L, Schmidt, TSB, Falony, G, Vieira-Silva, S, Adriouch, S, Alves, RJ, Assmann, K, Bastard, J-P, Birkner, T, Caesar, R, Chilloux, J, Coelho, LP, Fezeu, L, Galleron, N, Helft, G, Isnard, R, Ji, B, Kuhn, M, Le Chatelier, E, Myridakis, A, Olsson, L, Pons, N, Prifti, E, Quinquis, B, Roume, H, Salem, J-E, Sokolovska, N, Tremaroli, V, Valles-Colomer, M, Lewinter, C, Søndertoft, NB, Pedersen, HK, Hansen, TH, Amouyal, C, Andersson Galijatovic, EA, Andreelli, F, Barthelemy, O, Batisse, J-P, Belda, E, Berland, M, Bittar, R, Blottière, H, Bosquet, F, Boubrit, R, Bourron, O, Camus, M, Cassuto, D, Ciangura, C, Collet, J-P, Dao, M-C, Djebbar, M, Doré, A, Engelbrechtsen, L, Fellahi, S, Fromentin, S, Galan, P, Gauguier, D, Giral, P, Hartemann, A, Hartmann, B, Holst, JJ, Hornbak, M, Hoyles, L, Hulot, J-S, Jaqueminet, S, Jørgensen, NR, Julienne, H, Justesen, J, Kammer, J, Krarup, N, Kerneis, M, Khemis, J, Kozlowski, R, Lejard, V, Levenez, F, Lucas-Martini, L, Massey, R, Martinez-Gili, L, Maziers, N, Medina-Stamminger, J, Montalescot, G, Moute, S, Neves, AL, Olanipekun, M, Le Pavin, LP, Poitou, C, Pousset, F, Pouzoulet, L, Rodriguez-Martinez, A, Rouault, C, Silvain, J, Svendstrup, M, Swartz, T, Vanduyvenboden, T, Vatier, C, Walther, S, Gøtze, JP, Køber, L, Vestergaard, H, Hansen, T, Zucker, J-D, Hercberg, S, Oppert, J-M, Letunic, I, Nielsen, J, Bäckhed, F, Ehrlich, SD, Dumas, M-E, Raes, J, Pedersen, O, Clément, K, Stumvoll, M, Bork, P, The MetaCardis Consortium (Hoyles, L.), European Molecular Biology Laboratory [Heidelberg] (EMBL), Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), German Center for Cardiovascular Research (DZHK), Universität Leipzig, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Copenhagen = Københavns Universitet (UCPH), University of New South Wales [Sydney] (UNSW), Paul Scherrer Institute (PSI), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Heidelberg University, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Henri Mondor [Créteil], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], University of Gothenburg (GU), Imperial College London, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris-Saclay, Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Chalmers University of Technology [Gothenburg, Sweden], Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD [France-Nord]), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Biobyte Solutions [Heidelberg, Germany] (BS), IT University of Copenhagen (ITU), Sahlgrenska University Hospital [Gothenburg], Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, McGill University and Genome Quebec Innovation Centre, Helmholtz Institute Ulm (HIU), Helmholtz Zentrum München = German Research Center for Environmental Health, University of Würzburg = Universität Würzburg, Yonsei University, MetaCardis Consortium*: Chloe Amouyal, Ehm Astrid Andersson Galijatovic, Fabrizio Andreelli, Olivier Barthelemy, Jean-Paul Batisse, Eugeni Belda, Magalie Berland, Randa Bittar, Hervé Blottière, Frederic Bosquet, Rachid Boubrit, Olivier Bourron, Mickael Camus, Dominique Cassuto, Cecile Ciangura, Jean-Philippe Collet, Maria-Carlota Dao, Morad Djebbar, Angélique Doré, Line Engelbrechtsen, Soraya Fellahi, Sebastien Fromentin, Pilar Galan, Dominique Gauguier, Philippe Giral, Agnes Hartemann, Bolette Hartmann, Jens Juul Holst, Malene Hornbak, Lesley Hoyles, Jean-Sebastien Hulot, Sophie Jaqueminet, Niklas Rye Jørgensen, Hanna Julienne, Johanne Justesen, Judith Kammer, Nikolaj Krarup, Mathieu Kerneis, Jean Khemis, Ruby Kozlowski, Véronique Lejard, Florence Levenez, Lea Lucas-Martini, Robin Massey, Laura Martinez-Gili, Nicolas Maziers, Jonathan Medina-Stamminger, Gilles Montalescot, Sandrine Moute, Ana Luisa Neves, Michael Olanipekun, Laetitia Pasero Le Pavin, Christine Poitou, Francoise Pousset, Laurence Pouzoulet, Andrea Rodriguez-Martinez, Christine Rouault, Johanne Silvain, Mathilde Svendstrup, Timothy Swartz, Thierry Vanduyvenboden, Camille Vatier, Stefanie Walther., ANR-16-IDEX-0004,ULNE,ULNE(2016), ANR-18-IBHU-0001,PreciDIAB,PreciDIAB Institute, the holistic approach of personal diabets care(2018), Dumas, Marc-Emmanuel, Universität Leipzig [Leipzig], Service de Nutrition [CHU Pitié-Salpétrière], Institut E3M [CHU Pitié-Salpêtrière], CHU Henri Mondor, Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-1901(ex CIC-1421)), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Imperial College London - National Heart and Lung Institute, and Division of Computational and Systems Medicine, Imperial College London, London, SW7 2AZ, UK
Subjects: Clostridiales, Science & Technology, Multidisciplinary, ANTIBIOTIC USE, IMPACT, Microbiota, [SDV]Life Sciences [q-bio], HUMAN GUT MICROBIOME, Atherosclerosis, Gastrointestinal Microbiome, [SDV] Life Sciences [q-bio], Multidisciplinary Sciences, PROTON PUMP INHIBITORS, Cardiovascular and Metabolic Diseases, GUIDELINE, Metabolome, MANAGEMENT, Humans, Science & Technology - Other Topics, ALTERS
Abstract: During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1-5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug-host-microbiome interactions in cardiometabolic disease. ispartof: NATURE vol:600 issue:7889 pages:500-+ ispartof: location:England status: published
Published: 2021

39. Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits

Author: Sun, Daokun, Richard, Melissa, Musani, Solomon, Sung, Yun Ju, Winkler, Thomas, Schwander, Karen, Chai, Jin Fang, Guo, Xiuqing, Kilpeläinen, Tuomas, Vojinovic, Dina, Aschard, Hugues, Bartz, Traci, Bielak, Lawrence, Brown, Michael, Chitrala, Kumaraswamy, Hartwig, Fernando, Horimoto, Andrea R.V.R., Liu, Yongmei, Manning, Alisa, Noordam, Raymond, Smith, Albert, Harris, Sarah, Kühnel, Brigitte, Lyytikäinen, Leo-Pekka, Nolte, Ilja, Rauramaa, Rainer, van Der Most, Peter, Wang, Rujia, Ware, Erin, Weiss, Stefan, Wen, Wanqing, Yanek, Lisa, Arking, Dan, Arnett, Donna, Barac, Ana, Boerwinkle, Eric, Broeckel, Ulrich, Chakravarti, Aravinda, Chen, Yii-Der Ida, Cupples, L. Adrienne, Davigulus, Martha, de Las Fuentes, Lisa, de Mutsert, Renée, de Vries, Paul, Delaney, Joseph A.C., Diez Roux, Ana, Dörr, Marcus, Faul, Jessica, Fretts, Amanda, Gallo, Linda, Grabe, Hans Jörgen, Gu, C. Charles, Harris, Tamara, Hartman, Catharina C.A., Heikkinen, Sami, Ikram, M. Arfan, Isasi, Carmen, Johnson, W. Craig, Jonas, Jost Bruno, Kaplan, Robert, Komulainen, Pirjo, Krieger, Jose, Levy, Daniel, Liu, Jianjun, Lohman, Kurt, Luik, Annemarie, Martin, Lisa, Meitinger, Thomas, Milaneschi, Yuri, O’connell, Jeff, Palmas, Walter, Peters, Annette, Peyser, Patricia, Pulkki-Råback, Laura, Raffel, Leslie, Reiner, Alex, Rice, Kenneth, Robinson, Jennifer, Rosendaal, Frits, Schmidt, Carsten Oliver, Schreiner, Pamela, Schwettmann, Lars, Shikany, James, Shu, Xiao-Ou, Sidney, Stephen, Sims, Mario, Smith, Jennifer, Sotoodehnia, Nona, Strauch, Konstantin, Tai, E. Shyong, Taylor, Kent, Uitterlinden, André, van Duijn, Cornelia, Waldenberger, Melanie, Wee, Hwee-Lin, Wei, Wen-Bin, Wilson, Gregory, Xuan, Deng, Yao, Jie, Zeng, Donglin, Zhao, Wei, Zhu, Xiaofeng, Zonderman, Alan, Becker, Diane, Deary, Ian, Gieger, Christian, Lakka, Timo, Lehtimäki, Terho, North, Kari, Oldehinkel, Albertine, Penninx, Brenda W.J.H., Snieder, Harold, Wang, Ya-Xing, Weir, David, Zheng, Wei, Evans, Michele, Gauderman, W. James, Gudnason, Vilmundur, Horta, Bernardo, Liu, Ching-Ti, Mook-Kanamori, Dennis, Morrison, Alanna, Pereira, Alexandre, Psaty, Bruce, Amin, Najaf, Fox, Ervin, Kooperberg, Charles, Sim, Xueling, Bierut, Laura, Rotter, Jerome, Kardia, Sharon L.R., Franceschini, Nora, Rao, Dabeeru, Fornage, Myriam, Horimoto, Andrea, Cupples, L Adrienne, Delaney, Joseph, Roux, Ana, Gu, C Charles, Hartman, Catharina, Ikram, M Arfan, Johnson, W Craig, O'Connell, Jeff, Tai, E Shyong, Penninx, Brenda, Gauderman, W James, Kardia, Sharon, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, APH - Mental Health, APH - Digital Health, HUS Abdominal Center, Faculty of Medicine, University of Helsinki, Department of Psychology and Logopedics, Psychosocial factors and health, University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), University of Mississippi Medical Center (UMMC), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), University of Regensburg, National University of Singapore (NUS), Harbor UCLA Medical Center [Torrance, Ca.], IT University of Copenhagen (ITU), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Harvard School of Public Health, Département de Génomes et Génétique - Department of Genomes and Genetics, Institut Pasteur [Paris] (IP), University of Washington [Seattle], University of Michigan [Ann Arbor], University of Michigan System, National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Universidade Federal de Pelotas = Federal University of Pelotas (UFPel), Universidade de São Paulo = University of São Paulo (USP), Wake Forest University, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Leiden University Medical Center (LUMC), Universiteit Leiden, University of Edinburgh, This project was largely supported by grant R01HL118305 from the US National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health, with additional support from R01HL105756. A full set of study-specific funding sources and acknowledgments is provided in the Supplemental subjects and methods., We thank all study participants for contributing to this work., Tampere University, Clinical Medicine, Department of Clinical Chemistry, Epidemiology, Radiology & Nuclear Medicine, Child and Adolescent Psychiatry / Psychology, Internal Medicine, Life Course Epidemiology (LCE), and Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE)
Subjects: Mean arterial pressure, hypertension, Genome-wide association study, QH426-470, Biology, Article, GxE, 03 medical and health sciences, Social support, 0302 clinical medicine, depressive symptoms, SDG 3 - Good Health and Well-being, Genetics, medicine, GWAS, Gene–environment interaction, psychosocial factors, gene-environment interaction, genome-wide association study, blood pressure, hypertension, psychosocial factors,depressive symptoms, GWAS, GxE, Genetics (clinical), 030304 developmental biology, [STAT.AP]Statistics [stat]/Applications [stat.AP], 0303 health sciences, genome-wide association study, blood pressure, 3. Good health, Pulse pressure, gene-environment interaction, Blood pressure, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Molecular Medicine, Anxiety, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 3111 Biomedicine, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], medicine.symptom, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Psychosocial, 030217 neurology & neurosurgery
Abstract: Publisher Copyright: © 2020 The Author(s) Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP, taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from five ancestry groups. In the combined meta-analyses of stages 1 and 2, we identified 59 loci (p value < 5e−8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (PLCL2), synaptic function and neurotransmission (LIN7A and PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5 and CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations.
Published: 2021

40. Runs of homozygosity in killer whale genomes provide a global record of demographic histories

Author: Kelly M. Robertson, Rebecca Hooper, Rochelle Constantine, Renaud de Stephanis, Sara Tavares, Alana Alexander, Guangyi Fan, John A. Totterdell, Ruth Esteban, Nicholas J. Davison, Tim Gerrodette, Lisa T. Ballance, John W. Durban, Songhai Li, Paul Tixier, Phillip A. Morin, Michael D. Martin, C. S. Baker, Sarah L. Fordyce Martin, Robin W. Baird, Jay Barlow, Luciano Dalla Rosa, Filipa I. P. Samarra, Andrew Brownlow, Tim Collins, Laurent Excoffier, Andrew D. Foote, M. Bradley Hanson, Jochen B. W. Wolf, M. Thomas P. Gilbert, Karin A. Forney, Christophe Guinet, Paul R. Wade, Yaolei Zhang, NTNU University Museum [Trondheim], Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU)-Norwegian University of Science and Technology (NTNU), School of Biological Sciences [Bangor], Bangor University, Institute of Ecology and Evolution [Bern, Switzerland], University of Bern, University of Exeter, University of Otago [Dunedin, Nouvelle-Zélande], Cascadia Research [Washington, USA], Marine Mammal Institute, Oregon State University (OSU), School of Biological Sciences [Auckland], University of Auckland [Auckland], Marine Mammal and Turtle Division (MMTD), Southwest Fisheries Science Center (SWFSC), NOAA National Marine Fisheries Service (NMFS), National Oceanic and Atmospheric Administration (NOAA)-National Oceanic and Atmospheric Administration (NOAA)-NOAA National Marine Fisheries Service (NMFS), National Oceanic and Atmospheric Administration (NOAA)-National Oceanic and Atmospheric Administration (NOAA), Scottish Marine Animal Stranding Scheme, SRUC Veterinary Service, Scotland's Rural College (SRUC), Wildlife Conservation Society (WCS), Laboratório de Ecologia e Conservação da Megafauna Marinha [Rio Grande, Brazil], Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS), CIRCE (Conservation, Information and Research on Cetaceans), Moss Landing Marine Laboratories [CA, USA] (San José State University), San Jose State University [San Jose] (SJSU), Section for Evolutionary Genomics, IT University of Copenhagen (ITU)-GLOBE Institute, Centre d'Études Biologiques de Chizé - UMR 7372 (CEBC), La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Northwest Fisheries Science Center (NWFSC), Sanya Key Laboratory of Marine Mammal and Marine Bioacoustics, Institute of Deep-sea Science and Engineering, Vestmannaeyjar Research and Study Center, Scottish Oceans Institute [University of St Andrews] (SOI), School of Biology [University of St Andrews], University of St Andrews [Scotland]-University of St Andrews [Scotland], Fisheries and Oceans Canada (DFO), MARine Biodiversity Exploitation and Conservation (UMR MARBEC), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), James Cook University (JCU), Alaska Fisheries Science Center (AFSC), Ludwig Maximilian University [Munich] (LMU), BGI Qingdao, Partenaires INRAE, Beijing Genomics Institute [Shenzhen] (BGI), China National GeneBank, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Université de La Rochelle (ULR)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut de Recherche pour le Développement (IRD)
Subjects: 0106 biological sciences, Male, Demographic history, Population, inbreeding, Biology, Runs of Homozygosity, 010603 evolutionary biology, 01 natural sciences, Identity by descent, Polymorphism, Single Nucleotide, Coalescent theory, 03 medical and health sciences, Effective population size, Genetics, Inbreeding depression, Animals, Inbreeding, 14. Life underwater, education, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Demography, Population Density, 0303 health sciences, education.field_of_study, whole genome sequencing, Genome, Orcinus orca, Homozygote, Killer whales, killer whale, Evolutionary biology, Whole genome sequencing, [SDE]Environmental Sciences, 570 Life sciences, biology, Whale, Killer
Abstract: International audience; Runs of homozygosity (ROH) occur when offspring inherit haplotypes that are identical by descent from each parent. Length distributions of ROH are informative about population history; specifically, the probability of inbreeding mediated by mating system and/or population demography. Here, we investigated whether variation in killer whale (Orcinus orca) demographic history is reflected in genome-wide heterozygosity and ROH length distributions, using a global data set of 26 genomes representative of geographic and ecotypic variation in this species, and two F1 admixed individuals with Pacific-Atlantic parentage. We first reconstructed demographic history for each population as changes in effective population size through time using the pairwise sequential Markovian coalescent (PSMC) method. We found a subset of populations declined in effective population size during the Late Pleistocene, while others had more stable demography. Genomes inferred to have undergone ancestral declines in effective population size, were autozygous at hundreds of short ROH (1.5 Mb) were found in low latitude populations, and populations of known conservation concern. These include a Scottish killer whale, for which 37.8% of the autosomes were comprised of ROH >1.5 Mb in length. The fate of this population, in which only two adult males have been sighted in the past five years, and zero fecundity over the last two decades, may be inextricably linked to its demographic history and consequential inbreeding depression.
Published: 2021

41. Probing the polarity of spontaneous perisomatic GABAergic synaptic transmission in the mouse CA3 circuit in vivo

Author: Hajime Hirase, Anna Beyeler, Arnaldo Ferreira Gomes Da Silva, Olivier Dubanet, Xavier Leinekugel, Andreas Frick, Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U1249), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), IT University of Copenhagen (ITU), pellegrino, Christophe, Physiopathologie de la Plasticité Neuronale (Neurocentre Magendie - U1215 Inserm), and IT University of Copenhagen
Subjects: Male, Time Factors, hippocampus, Action Potentials, Hippocampus, Hippocampal formation, SHARP-WAVE-RIPPLES, GABAergic transmission, Synaptic Transmission, Epileptogenesis, GABA, Mice, TEMPORAL-LOBE EPILEPSY, GABAergic Neurons, 050207 economics, Biology (General), Kainic Acid, 050208 finance, Chemistry, Pyramidal Cells, musculoskeletal, neural, and ocular physiology, 05 social sciences, CA3 Region, Hippocampal, inhibition, Parvalbumins, EXCITABILITY, Acute Disease, Excitatory postsynaptic potential, GABAergic, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], CATION-CHLORIDE COTRANSPORTERS, INTERNEURONS, QH301-705.5, INHIBITION, Neurotransmission, Inhibitory postsynaptic potential, Seizures, In vivo, 0502 economics and business, EXCITATORY ACTIONS, Animals, Gene Silencing, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], HIPPOCAMPAL SCLEROSIS, interneurons, Optogenetics, Disease Models, Animal, Inhibitory Postsynaptic Potentials, nervous system, CELLS, epilepsy, Neuroscience
Abstract: The hypothesis that reversed, excitatory GABA may be involved in various brain pathologies, including epileptogenesis, is appealing but controverted. A direct assessment of the excitatory GABA hypothesis has been hindered by the technical difficulty of probing endogenous GABAergic synaptic function in vivo. We have overcome this challenge by non-invasive extracellular recording of neuronal firing responses to optogenetically-evoked and spontaneously occurring unitary inhibitory perisomatic GABAergic field-potentials, generated by individual Parvalbumine-interneurons on their target pyramidal cells. Our direct probing of GABAergic transmission suggests a rather anecdotal participation of excitatory GABA in epileptogenesis in the mouse CA3 circuit in vivo, even though this does not exclude its expression in other brain areas or pathological conditions. Our approach successfully detected distinct alterations of inhibition in spontaneous activity in vivo, with high sensitivity. It therefore represents a promising tool for the investigation of excitatory GABA in different pathological conditions that may affect the hippocampal circuit.
Published: 2021

42. Author Correction: In situ recording of Mars soundscape

Author: Maurice, S., Chide, B., Murdoch, N., Lorenz, R, Mimoun, D., Wiens, R., Stott, A., Jacob, X., Bertrand, T., Montmessin, Franck, Lanza, N, Alvarez-Llamas, C., Angel, S, Aung, M., Balaram, J., Beyssac, O., Cousin, A., Delory, G., Forni, O., Fouchet, T., Gasnault, O., Grip, H., Hecht, M., Hoffman, J., Laserna, J., Lasue, Jérémie, Maki, J., Mcclean, J., Meslin, P.-Y., Le Mouélic, S., Munguira, A., Newman, C., Rodríguez Manfredi, J., Moros, J., Ollila, A., Pilleri, P., Schröder, S., de La Torre Juárez, M., Tzanetos, T., Stack, K., Farley, K., Williford, K., Acosta-Maeda, T., Anderson, R., Applin, D., Arana, G., Bassas-Portus, M., Beal, R., Beck, P., Benzerara, K., Bernard, S., Bernardi, P., Bosak, T., Bousquet, B., Brown, A., Cadu, A., Caïs, P., Castro, K., Clavé, E., Clegg, S, Cloutis, E., Connell, S., Debus, A., Dehouck, E., Delapp, D., Donny, C., Dorresoundiram, A., Dromart, G., Dubois, B., Fabre, C., Fau, A., Fischer, W., Francis, R., Frydenvang, J., Gabriel, T., Gibbons, E., Gontijo, I., Johnson, J., Kalucha, H., Kelly, E., Knutsen, Elise Wright, Lacombe, Gaetan, Legett, C., Leveille, R., Lewin, E., Lopez-Reyes, G., Lorigny, E., Madariaga, J., Madsen, M., Madsen, S., Mandon, L., Mangold, N., Mann, M., Manrique, J.-A., Martinez-Frias, J., Mayhew, L., Mcconnochie, T., Mclennan, S., Melikechi, N., Meunier, F., Montagnac, G., Mousset, V., Nelson, T., Newell, R, Parot, Y., Pilorget, C., Pinet, P., Pont, G., Poulet, F., Quantin-Nataf, C., Quertier, B., Rapin, W., Reyes-Newell, A., Robinson, S., Rochas, L., Royer, C., Rull, F., Sautter, V., Sharma, S., Shridar, V., Sournac, A., Toplis, M., Torre-Fdez, I., Turenne, N., Udry, A., Veneranda, M., Venhaus, D., Vogt, D., Willis, P., Institut de recherche en astrophysique et planétologie (IRAP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Los Alamos National Laboratory (LANL), Institut Supérieur de l'Aéronautique et de l'Espace (ISAE-SUPAERO), Johns Hopkins University Applied Physics Laboratory [Laurel, MD] (APL), Department of Earth, Atmospheric, and Planetary Sciences [West Lafayette] (EAPS), Purdue University [West Lafayette], Institut de mécanique des fluides de Toulouse (IMFT), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT), Laboratoire d'études spatiales et d'instrumentation en astrophysique = Laboratory of Space Studies and Instrumentation in Astrophysics (LESIA), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), PLANETO - LATMOS, Laboratoire Atmosphères, Milieux, Observations Spatiales (LATMOS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universidad de Málaga [Málaga] = University of Málaga [Málaga], Department of Chemistry and Biochemistry [Columbia, South Carolina], University of South Carolina [Columbia], Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Heliospace Corporation, MIT Haystack Observatory, Massachusetts Institute of Technology (MIT), Department of Aeronautics and Astronautics [Cambridge], Laboratoire de Planétologie et Géosciences [UMR_C 6112] (LPG), Université d'Angers (UA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Escuela de Ingeniería de Bilbao, Universidad del Pais Vasco / Euskal Herriko Unibertsitatea [Espagne] (UPV/EHU), Aeolis Corporation, Centro de Astrobiologia [Madrid] (CAB), Instituto Nacional de Técnica Aeroespacial (INTA)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), DLR Institute of Optical Sensor Systems, Deutsches Zentrum für Luft- und Raumfahrt [Berlin] (DLR), Blue Marble Space Institute of Science (BMSIS), University of Hawai‘i [Mānoa] (UHM), US Geological Survey [Flagstaff], United States Geological Survey [Reston] (USGS), University of Winnipeg, University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Institut de Planétologie et d'Astrophysique de Grenoble (IPAG), Centre National d'Études Spatiales [Toulouse] (CNES)-Observatoire des Sciences de l'Univers de Grenoble (OSUG ), Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Météo-France -Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Météo-France, Department of Earth, Atmospheric and Planetary Sciences [MIT, Cambridge] (EAPS), Centre d'Etudes Lasers Intenses et Applications (CELIA), Université de Bordeaux (UB)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Plancius Research LLC, Laboratoire d'Astrophysique de Bordeaux [Pessac] (LAB), Université de Bordeaux (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National d'Études Spatiales [Toulouse] (CNES), Laboratoire de Géologie de Lyon - Terre, Planètes, Environnement (LGL-TPE), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France, Université de Lyon, GeoRessources, Institut national des sciences de l'Univers (INSU - CNRS)-Centre de recherches sur la géologie des matières premières minérales et énergétiques (CREGU)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), California Institute of Technology (CALTECH), University of Copenhagen = Københavns Universitet (UCPH), McGill University = Université McGill [Montréal, Canada], Universidad de Valladolid [Valladolid] (UVa), IT University of Copenhagen (ITU), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Department of Geological Sciences [Boulder], University of Colorado [Boulder], University of Maryland [College Park], University of Maryland System, Stony Brook University [SUNY] (SBU), State University of New York (SUNY), Department of Physics and Applied Physics [Lowell], University of Massachusetts [Lowell] (UMass Lowell), University of Massachusetts System (UMASS)-University of Massachusetts System (UMASS), Institut d'astrophysique spatiale (IAS), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Centre National d’Études Spatiales [Paris] (CNES), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), University of Nevada [Las Vegas] (WGU Nevada), and NASA’s Mars Exploration ProgramCNES
Subjects: Multidisciplinary, Carbon dioxide, Modélisation, [SDU]Sciences of the Universe [physics], Atmospheric Turbulence, Atmospheric Sound, Microphone, Mars, Attenuation, CO2, Perseverance, Acoustic Environment
Abstract: International audience
Published: 2022

43. Machine learning for medical imaging: methodological failures and recommendations for the future

Author: Gaël Varoquaux, Veronika Cheplygina, Méthodes computationnelles et mathématiques pour comprendre la société et la santé à partir de données (SODA), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), IT University of Copenhagen (ITU), and ANR-17-CE23-0018,DirtyData,Intégration et nettoyage de données pour l'analyse statistique(2017)
Subjects: [PHYS.PHYS.PHYS-ATOM-PH]Physics [physics]/Physics [physics]/Atomic Physics [physics.atom-ph], Health Information Management, Medicine (miscellaneous), Health Informatics, Computer Science Applications
Abstract: Research in computer analysis of medical images bears many promises to improve patients’ health. However, a number of systematic challenges are slowing down the progress of the field, from limitations of the data, such as biases, to research incentives, such as optimizing for publication. In this paper we review roadblocks to developing and assessing methods. Building our analysis on evidence from the literature and data challenges, we show that at every step, potential biases can creep in. On a positive note, we also discuss on-going efforts to counteract these problems. Finally we provide recommendations on how to further address these problems in the future.
Published: 2021

44. Monitoring methods adapted to different perceptions and uses of functional biodiversity: Insights from a European qualitative study

Author: Cardona, Aurélie, Tchamitchian, Marc, Penvern, Servane, Dufils, Arnaud, Kramer Jacobsen, Stine, Korsgaard, Maren, Porcel, Mario, Świergiel, Weronika, Tasin, Marco, Warlop, François, Sigsgaard, Lene, Unité de recherche d'Écodéveloppement (ECODEVELOPPEMENT), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), IT University of Copenhagen (ITU), Ecoadvice, Swedish University of Agricultural Sciences (SLU), Colombian Corporation for Agricultural Research (Agrosavia), Groupe de Recherche en Agriculture Biologique (GRAB), (AIP P00308), the Swedish Research Council for Sustainable Development (Formas, 2014-01905), the Green Development and Demonstration Program under the Ministry of Environment and Food of Denmark (GUDP j.nr: 34009-14-0906), European Project: 618107,EC:FP7:KBBE,FP7-ERANET-2013-RTD,CORE ORGANIC PLUS(2013), and IT University of Copenhagen
Subjects: Stakeholders, [SHS.SOCIO]Humanities and Social Sciences/Sociology, Ecology, Attitudes, Participatory action research, [SDV.SA.AGRO]Life Sciences [q-bio]/Agricultural sciences/Agronomy, Orchard, Ecosystem services, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, [SDV.SA.HORT]Life Sciences [q-bio]/Agricultural sciences/Horticulture, QH540-549.5, Management
Abstract: International audience; The role of functional biodiversity for favouring natural regulation and reducing pesticide use in fruit production is generally acknowledged. Although a number of farmers attempt to favour biodiversity through different strategies (e.g. diversified hedges, nesting boxes), they often lack means to evaluate how their actions contribute in practice to functional biodiversity. We assumed here that to create useful and appropriate monitoring methods, it is necessary to take into account the variety of knowledge, perceptions and interests about functional biodiversity. To test our hypothesis, we adopted a comprehensive and participative approach based on interviews and workshops with farmers, advisors and field agronomists involved in apple orchard management. Our objective was to understand their different perceptions and uses of functional biodiversity and then, to design monitoring methods adapted to those perceptions and pre-existing uses. Our findings revealed both a plurality of perceptions of functional biodiversity along with a diversity of objectives and uses of monitoring methods. Based on these results, we identified four main attitudes towards the management of functional biodiversity: the wait-and-see attitude, the naturalist attitude, the regulation attitude and the multifunctional attitude. These attitudes do not correspond to person's profiles, since one person can adopt different attitudes in regard to different biodiversity components or in regard to the different practices supporting biodiversity. In addition, attitudes can vary over time. The identification of these attitudes allowed us to design, with the workshops' participants, a guiding framework to create monitoring programs (i.e. combinations of monitoring methods) adapted to a variety of uses and targeted services.
Published: 2021

45. Network Analyses Reveal Negative Link Between Changes in Adipose Tissue GDF15 and BMI During Dietary-induced Weight Loss

Author: Aline Charpagne, Ondine Walter, Nathalie Viguerie, Julien Marquis, Jörg Hager, Nathalie Boulet, Sylviane Metairon, Julie Vion, Claire Laurens, Arne Astrup, Dominique Langin, Armand Valsesia, Nathalie Vialaneix, Alyssa Imbert, Wim H. M. Saris, Gregory Lefebvre, Cedric Moro, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, Humane Biologie, Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRAE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Lausanne, Genomic Technologies Facility, Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Franco-czech Laboratory for clinical research on obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse University Hospitals, Laboratory of Clinical Biochemistry, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], IT University of Copenhagen (ITU), Institut National de la Sante et de la Recherche Medicale (Inserm), Paul Sabatier University, Innovative Medicines Initiative Joint Undertaking115372, European CommissionFP6-513946 DiOGenes, and Vialaneix, Nathalie
Subjects: FOS: Computer and information sciences, Male, Weight loss, low calorie diet, PROMOTES, Macrophage, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Adipose tissue, Biochemistry, Body Mass Index, Transcriptome, chemistry.chemical_compound, network analyses, Endocrinology, [STAT.AP] Statistics [stat]/Applications [stat.AP], Adipocyte, Gene expression, Faculty of Science, OSTEOPONTIN, Gene Regulatory Networks, MACROPHAGES, [STAT.AP]Statistics [stat]/Applications [stat.AP], Prognosis, DIFFERENTIATION, Adipose Tissue, Network analyses, Female, medicine.symptom, EXPRESSION, Adult, medicine.medical_specialty, Growth Differentiation Factor 15, Diet, Reducing, Calorie restriction, Context (language use), macrophage, Biology, Statistics - Applications, Internal medicine, Weight Loss, medicine, Humans, Applications (stat.AP), Obesity, Low calorie diet, Inflammation, RECEPTOR, Biochemistry (medical), Gene expression profiling, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, CYTOKINE, REDUCTION, MICE, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, inflammation, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, sense organs, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Biomarkers, Follow-Up Studies
Abstract: Context Adipose tissue (AT) transcriptome studies provide holistic pictures of adaptation to weight and related bioclinical settings changes. Objective To implement AT gene expression profiling and investigate the link between changes in bioclinical parameters and AT gene expression during 3 steps of a 2-phase dietary intervention (DI). Methods AT transcriptome profiling was obtained from sequencing 1051 samples, corresponding to 556 distinct individuals enrolled in a weight loss intervention (8-week low-calorie diet (LCD) at 800 kcal/day) followed with a 6-month ad libitum randomized DI. Transcriptome profiles obtained with QuantSeq sequencing were benchmarked against Illumina RNAseq. Reverse transcription quantitative polymerase chain reaction was used to further confirm associations. Cell specificity was assessed using freshly isolated cells and THP-1 cell line. Results During LCD, 5 modules were found, of which 3 included at least 1 bioclinical variable. Change in body mass index (BMI) connected with changes in mRNA level of genes with inflammatory response signature. In this module, change in BMI was negatively associated with changes in expression of genes encoding secreted protein (GDF15, CCL3, and SPP1). Through all phases of the DI, change in GDF15 was connected to changes in SPP1, CCL3, LIPA and CD68. Further characterization showed that these genes were specific to macrophages (with LIPA, CD68 and GDF15 expressed in anti-inflammatory macrophages) and GDF15 also expressed in preadipocytes. Conclusion Network analyses identified a novel AT feature with GDF15 upregulated with calorie restriction induced weight loss, concomitantly to macrophage markers. In AT, GDF15 was expressed in preadipocytes and macrophages where it was a hallmark of anti-inflammatory cells.
Published: 2021

46. Computer-Supported Knotworking

Author: Abou Amsha, Khuloud, Bossen, Claus, Grönvall, Erik, Lewkowicz, Myriam, Laboratoire Informatique et Société Numérique (LIST3N), Université de Technologie de Troyes (UTT), TECHnologies pour la Coopération, l’Interaction et les COnnaissances dans les collectifs (Tech-CICO), Université de Technologie de Troyes (UTT)-Université de Technologie de Troyes (UTT), Aarhus University [Aarhus], and IT University of Copenhagen (ITU)
Subjects: [INFO.INFO-IR]Computer Science [cs]/Information Retrieval [cs.IR], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021

47. Structural insights into protein folding, stability and activity using in vivo perdeuteration of hen egg-white lysozyme

Author: Valerie Laux, V. Trevor Forsyth, Michael Haertlein, Elisabetta Boeri Erba, Katherine McAuley, Estelle Mossou, Sine Larsen, Joao Ramos, Annette Eva Langkilde, Institut Laue-Langevin (ILL), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), DIAMOND Light source, IT University of Copenhagen (ITU), Department of Drug Design and Pharmacology [Copenhagen] (ILF), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), MS platform of the Grenoble Instruct-ERIC center (ISBG, UAR 3518 CNRS-CEA-UGA-EMBL), Diamond Light Source for beamtime at I03 and MAX IV for beamtime at BioMAX, ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), ANR-10-LABX-0049,GRAL,Grenoble Alliance for Integrated Structural Cell Biology(2010), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), European Project: GR/R99393/01, European Project: EP/C015452/1, ILL, IT University of Copenhagen, and University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)
Subjects: biophysical characterization, perdeuterated lysozyme, protein refolding, 010402 general chemistry, Q1, 01 natural sciences, Biochemistry, Pichia pastoris, 03 medical and health sciences, chemistry.chemical_compound, Protein structure, structural biology, General Materials Science, Thermal stability, protein structure, 030304 developmental biology, X-ray crystallography, chemistry.chemical_classification, 0303 health sciences, Crystallography, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Protein dynamics, HEWL, General Chemistry, Condensed Matter Physics, biology.organism_classification, Research Papers, R1, 0104 chemical sciences, Enzyme, chemistry, Structural biology, QD901-999, Biophysics, Protein folding, Lysozyme, QD415, isotope effect
Abstract: Perdeuteration and in vitro refolding of hen egg-white lysozyme impact protein thermal stability and activity. Deuteration appears to primarily affect enzymatic function through changes in protein dynamics, while refolding contributes to a small decrease in protein thermal stability., This structural and biophysical study exploited a method of perdeuterating hen egg-white lysozyme based on the expression of insoluble protein in Escherichia coli followed by in-column chemical refolding. This allowed detailed comparisons with perdeuterated lysozyme produced in the yeast Pichia pastoris, as well as with unlabelled lysozyme. Both perdeuterated variants exhibit reduced thermal stability and enzymatic activity in comparison with hydrogenated lysozyme. The thermal stability of refolded perdeuterated lysozyme is 4.9°C lower than that of the perdeuterated variant expressed and secreted in yeast and 6.8°C lower than that of the hydrogenated Gallus gallus protein. However, both perdeuterated variants exhibit a comparable activity. Atomic resolution X-ray crystallographic analyses show that the differences in thermal stability and enzymatic function are correlated with refolding and deuteration effects. The hydrogen/deuterium isotope effect causes a decrease in the stability and activity of the perdeuterated analogues; this is believed to occur through a combination of changes to hydrophobicity and protein dynamics. The lower level of thermal stability of the refolded perdeuterated lysozyme is caused by the unrestrained Asn103 peptide-plane flip during the unfolded state, leading to a significant increase in disorder of the Lys97–Gly104 region following subsequent refolding. An ancillary outcome of this study has been the development of an efficient and financially viable protocol that allows stable and active perdeuterated lysozyme to be more easily available for scientific applications.
Published: 2021

48. A Sound Algorithm for Asynchronous Session Subtyping and its Implementation

Author: Bravetti, Mario, Carbone, Marco, Lange, Julien, Yoshida, Nobuko, Zavattaro, Gianluigi, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Foundations of Component-based Ubiquitous Systems (FOCUS), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Dipartimento di Informatica - Scienza e Ingegneria [Bologna] (DISI), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO)-Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), IT University of Copenhagen, Department of Computer Science (Royal Holloway University of London), Computer Learning Research Centre [Royal Holloway, University of London], Royal Holloway [University of London] (RHUL)-Royal Holloway [University of London] (RHUL), Imperial College London, Alma Mater Studiorum University of Bologna (UNIBO), Bravetti M., Carbone M., Lange J., Yoshida N., Zavattaro G., IT University of Copenhagen (ITU), Engineering & Physical Science Research Council (E, Engineering & Physical Science Research Council (EPSRC), Engineering and Physical Sciences Research Council, and The National Cyber Security Centre (NCSC)
Subjects: FOS: Computer and information sciences, session types, asynchronous communication, subtyping, Computer Science - Programming Languages, [INFO.INFO-PL]Computer Science [cs]/Programming Languages [cs.PL], 0803 Computer Software, 0101 Pure Mathematics, 0802 Computation Theory and Mathematics, Programming Languages (cs.PL)
Abstract: Logical Methods in Computer Science ; Volume 17, Issue 1 ; 1860-5974, Session types, types for structuring communication between endpoints in distributed systems, are recently being integrated into mainstream programming languages. In practice, a very important notion for dealing with such types is that of subtyping, since it allows for typing larger classes of system, where a program has not precisely the expected behaviour but a similar one. Unfortunately, recent work has shown that subtyping for session types in an asynchronous setting is undecidable. To cope with this negative result, the only approaches we are aware of either restrict the syntax of session types or limit communication (by considering forms of bounded asynchrony). Both approaches are too restrictive in practice, hence we proceed differently by presenting an algorithm for checking subtyping which is sound, but not complete (in some cases it terminates without returning a decisive verdict). The algorithm is based on a tree representation of the coinductive definition of asynchronous subtyping; this tree could be infinite, and the algorithm checks for the presence of finite witnesses of infinite successful subtrees. Furthermore, we provide a tool that implements our algorithm. We use this tool to test our algorithm on many examples that cannot be managed with the previous approaches, and to provide an empirical evaluation of the time and space cost of the algorithm., Comment: This is an extended version of the CONCUR'19 version
Published: 2021

49. Interplay between FLI-1 and the LDB1 complex in murine erythroleukemia cells and during megakaryopoiesis

Author: Boris Guyot, Michèle Weiss-Gayet, Jente van Staalduinen, Ilias Boltsis, Frank Grosveld, François Morlé, Guillaume Giraud, Petros Kolovos, Wilfred F. J. van IJcken, PES R&D Department, RTE, IT University of Copenhagen (ITU), 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), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Guyot, Boris, IT University of Copenhagen, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Cell biology
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Chromosome Organization, 02 engineering and technology, Biology, Article, 03 medical and health sciences, Megakaryocyte, SDG 3 - Good Health and Well-being, medicine, lcsh:Science, Enhancer, Molecular Biology, Transcription factor, ComputingMilieux_MISCELLANEOUS, Megakaryopoiesis, Multidisciplinary, fungi, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Promoter, 021001 nanoscience & nanotechnology, Chromatin, Cell biology, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, Regulatory sequence, Erythropoiesis, lcsh:Q, 0210 nano-technology
Abstract: Summary Transcription factors are key players in a broad range of cellular processes such as cell-fate decision. Understanding how they act to control these processes is of critical importance for therapy purposes. FLI-1 controls several hematopoietic lineage differentiation including megakaryopoiesis and erythropoiesis. Its aberrant expression is often observed in cancer and is associated with poor prognosis. We showed that FLI-1 interacts with the LDB1 complex, which also plays critical roles in erythropoiesis and megakaryopoiesis. In this study, we aimed to unravel how FLI-1 and the LDB1 complex act together in murine erythroleukemia cells and in megakaryocyte. Combining omics techniques, we show that FLI-1 enables the recruitment of the LDB1 complex to regulatory sequences of megakaryocytic genes and to enhancers. We show as well for the first time that FLI-1 is able to modulate the 3D chromatin organization by promoting chromatin looping between enhancers and promoters most likely through the LDB1 complex., Graphical abstract, Highlights • FLI-1 is important for the recruitment of the LDB1 complex • FLI-1 is important for chromatin looping • FLI-1 and the LDB1 complex co-regulate megakaryopoiesis, Molecular Biology; Chromosome Organization
Published: 2021

50. Rad52 SUMOylation functions as a molecular switch that determines a balance between the Rad51- and Rad59-dependent survivors

Author: Ferose Charifi, Nadine Eckert-Boulet, Michael Lisby, Frederic Jourquin, Dmitri Churikov, Marie-Noëlle Simon, Vincent Géli, Christopher Minguet, Julien Hardy, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), University of Copenhagen = Københavns Universitet (UCPH), University of Copenhagen = Københavns Universitet (KU), IT University of Copenhagen (ITU), ANR-19-CE12-0023,NIRO,Contrôle des voies de réparation des fourches de réplication par les pores nucléaires(2019), GELI, Vincent, and Contrôle des voies de réparation des fourches de réplication par les pores nucléaires - - NIRO2019 - ANR-19-CE12-0023 - AAPG2019 - VALID
Subjects: 0301 basic medicine, Telomerase, [SDV]Life Sciences [q-bio], RAD52, genetic processes, RAD51, SUMO protein, 02 engineering and technology, Article, 03 medical and health sciences, Nuclear pore, lcsh:Science, Molecular Biology, Multidisciplinary, biology, Chemistry, Cell Biology, Biological Sciences, 021001 nanoscience & nanotechnology, 3. Good health, Ubiquitin ligase, Telomere, Cell biology, [SDV] Life Sciences [q-bio], enzymes and coenzymes (carbohydrates), 030104 developmental biology, biology.protein, lcsh:Q, 0210 nano-technology, Recombination
Abstract: Summary Functional telomeres in yeast lacking telomerase can be restored by rare Rad51- or Rad59-dependent recombination events that lead to type I and type II survivors, respectively. We previously proposed that polySUMOylation of proteins and the SUMO-targeted ubiquitin ligase Slx5-Slx8 are key factors in type II recombination. Here, we show that SUMOylation of Rad52 favors the formation of type I survivors. Conversely, preventing Rad52 SUMOylation partially bypasses the requirement of Slx5-Slx8 for type II recombination. We further report that SUMO-dependent proteasomal degradation favors type II recombination. Finally, inactivation of Rad59, but not Rad51, impairs the relocation of eroded telomeres to the Nuclear Pore complexes (NPCs). We propose that Rad59 cooperates with non-SUMOylated Rad52 to promote type II recombination at NPCs, resulting in the emergence of more robust survivors akin to ALT cancer cells. Finally, neither Rad59 nor Rad51 is required by itself for the survival of established type II survivors., Graphical abstract, Highlights • RPA SUMOylation is dispensable for est2Δ type II survivor formation • Rad52 SUMOylation promotes Rad51-dependent type I survivor pathway • Rad52 deSUMOylation shifts the balance in favor of type II survivor formation • Rad59 is required for relocalization of eroded telomeres to the Nuclear Pore complex, Biological Sciences; Molecular Biology; Cell Biology
Published: 2021

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