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1. CEP receptor signalling controls root system architecture in Arabidopsis and Medicago

Author: Ariel Ivanovici, Malcolm J. Bennett, Craig J. Sturrock, Nadiatul A. Mohd-Radzman, Michael A. Djordjevic, Jason Liang Pin Ng, Kelly Chapman, Michael Taleski, Ulrike Mathesius, Florian Frugier, Division of Plant Sciences, Research School of Biology, Australian National University (ANU)-Australian National University (ANU), The Hounsfield Facility, Sutton Bonington Campus, University of Nottingham, UK (UON)-University of Nottingham, UK (UON), Institut des Sciences des Plantes de Paris-Saclay (IPS2 (UMR_9213 / UMR_1403)), Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), School of Bioscience, French National Research Agency (ANR)Australian GovernmentAustralian Research Council No. DP150104250Centre National de la Recherche Scientifique (CNRS)H2020 Research Infrastructures 731013A.W. Howard fellowship Lidex 'Plant Phenotyping Pipeline', and Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0106 biological sciences, 0301 basic medicine, Receptors, Peptide, Physiology, Mutant, Arabidopsis, Plant Science, Plant Roots, lateral root, 01 natural sciences, 03 medical and health sciences, Gene Expression Regulation, Plant, Auxin, Medicago, CEPR1, Receptor, root system architecture, chemistry.chemical_classification, CEP, Indoleacetic Acids, peptide hormone, biology, Arabidopsis Proteins, fungi, Lateral root, food and beverages, biology.organism_classification, Phenotype, rootward auxin transport, Cell biology, [SDV.BV.AP]Life Sciences [q-bio]/Vegetal Biology/Plant breeding, 030104 developmental biology, chemistry, Shoot, CRA2, gravitropic set-point angle, 010606 plant biology & botany
Abstract: International audience; Root system architecture (RSA) influences the effectiveness of resources acquisition from soils but the genetic networks that control RSA remain largely unclear.We used rhizoboxes, X-ray computed tomography, grafting, auxin transport measurements and hormone quantification to demonstrate that Arabidopsis and Medicago CEP (C-TERMINALLY ENCODED PEPTIDE)-CEP RECEPTOR signalling controls RSA, the gravitropic set-point angle (GSA) of lateral roots (LRs), auxin levels and auxin transport.We showed that soil-grown Arabidopsis and Medicago CEP receptor mutants have a narrower RSA, which results from a steeper LR GSA. Grafting showed that CEPR1 in the shoot controls GSA. CEP receptor mutants exhibited an increase in rootward auxin transport and elevated shoot auxin levels. Consistently, the application of auxin to wild-type shoots induced a steeper GSA and auxin transport inhibitors counteracted the CEP receptor mutant's steep GSA phenotype. Concordantly, CEP peptides increased GSA and inhibited rootward auxin transport in wild-type but not in CEP receptor mutants.The results indicated that CEP-CEP receptor-dependent signalling outputs in Arabidopsis and Medicago control overall RSA, LR GSA, shoot auxin levels and rootward auxin transport. We propose that manipulating CEP signalling strength or CEP receptor downstream targets may provide means to alter RSA.
Published: 2020

2. International Survey to Establish Prioritized Outcomes for Trials in People With Coronavirus Disease 2019

Author: Andrew Conway Morris, Ning Shen, Nicole Evangelidis, Sally Crowe, Derek P. Chew, Mervyn Mer, Saad Nseir, Alan R. Smyth, Emma Liu, Peter Horby, Luciano Cesar Pontes Azevedo, Andrea K. Viecelli, Ella Flemyng, Deena Lynch, Andrew D. Bersten, Jonathan C. Craig, Laila Woc-Colburn, Antoni Torres, Anne McKenzie, Martin Howell, Yeoungjee Cho, Julian Elliott, Sebastián Cabrera, Eduardo Lorca, John C. Marshall, Junhua Zhang, Paula R Williamson, Yasser Sakr, Andrea Matus Gonzalez, Steve Webb, Sangeeta Mehta, Jaehee Lee, Amanda Baumgart, Giovanni F.M. Strippoli, Charlie McLeod, Mark Reid, Ivor S. Douglas, Allison Tong, Tari Turner, Valeria Saglimbene, Pedro Póvoa, Patrizia Natale, Lilia Cervantes, Chandana Guha, Tom Snelling, Armando Teixeira-Pinto, Tess E Cooper, The University of Sydney, Monash University [Melbourne], Flinders University [Adelaide, Australia], University of Colorado [Denver], University of Oxford [Oxford], Kyungpook National University [Daegu], Universidad de Chile = University of Chile [Santiago] (UCHILE), University of Toronto, University of the Witwatersrand [Johannesburg] (WITS), University of Cambridge [UK] (CAM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Jena University Hospital [Jena], University of Nottingham, UK (UON), Università degli studi di Bari Aldo Moro (UNIBA), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of Liverpool, Baylor College of Medecine, Tianjin University (TJU), University of Queensland [Brisbane], CNRS, University of Oxford, Kyungpook National University [Daegu] [KNU], Universidad de Chile = University of Chile [Santiago] [UCHILE], University of the Witwatersrand [Johannesburg] [WITS], University of Cambridge [UK] [CAM], Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Universidade Nova de Lisboa = NOVA University Lisbon [NOVA], University of Nottingham, UK [UON], Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro [UNIBA], Institut d'Investigacions Biomèdiques August Pi i Sunyer [IDIBAPS], Centro de Investigación Biomédica en Red Enfermedades Respiratorias [CIBERES], Tianjin University [TJU], Kyungpook National University [Daegu] (KNU), and Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA)
Subjects: Research design, Male, Psychological intervention, coronavirus, Disease, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, patients, Health Services Accessibility, Health Priorities/organization & administration, sepsis, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pandemic, Outcome Assessment, Health Care, Pandemics/prevention & control, Randomized Controlled Trials as Topic, Pneumonia, Viral/prevention & control, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, clinical trial, Middle Aged, 3. Good health, Research Design, Preparedness, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Anxiety, Female, medicine.symptom, Symptom Assessment, Coronavirus Infections, Adult, medicine.medical_specialty, Critical Care, Patients, Pneumonia, Viral, MEDLINE, critical care, infection, 03 medical and health sciences, Betacoronavirus, medicine, Humans, Clinical Investigation, Pandemics, Aged, Randomized Controlled Trials as Topic/standards, business.industry, Health Priorities, SARS-CoV-2, COVID-19, 030208 emergency & critical care medicine, Coronavirus Infections/drug therapy, Health Services Accessibility/standards, COVID-19 Drug Treatment, Coronavirus, Clinical trial, 030228 respiratory system, Family medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Supplemental Digital Content is available in the text., Objectives: There are over 4,000 trials conducted in people with coronavirus disease 2019. However, the variability of outcomes and the omission of patient-centered outcomes may diminish the impact of these trials on decision-making. The aim of this study was to generate a consensus-based, prioritized list of outcomes for coronavirus disease 2019 trials. Design: In an online survey conducted in English, Chinese, Italian, Portuguese, and Spanish languages, adults with coronavirus disease 2019, their family members, health professionals, and the general public rated the importance of outcomes using a 9-point Likert scale (7–9, critical importance) and completed a Best-Worst Scale to estimate relative importance. Participant comments were analyzed thematically. Setting: International. Subjects: Adults 18 years old and over with confirmed or suspected coronavirus disease 2019, their family members, members of the general public, and health professionals (including clinicians, policy makers, regulators, funders, and researchers). Interventions: None. Measurements: None. Main Results: In total, 9,289 participants from 111 countries (776 people with coronavirus disease 2019 or family members, 4,882 health professionals, and 3,631 members of the public) completed the survey. The four outcomes of highest priority for all three groups were: mortality, respiratory failure, pneumonia, and organ failure. Lung function, lung scarring, sepsis, shortness of breath, and oxygen level in the blood were common to the top 10 outcomes across all three groups (mean > 7.5, median ≥ 8, and > 70% of respondents rated the outcome as critically important). Patients/family members rated fatigue, anxiety, chest pain, muscle pain, gastrointestinal problems, and cardiovascular disease higher than health professionals. Four themes underpinned prioritization: fear of life-threatening, debilitating, and permanent consequences; addressing knowledge gaps; enabling preparedness and planning; and tolerable or infrequent outcomes. Conclusions: Life-threatening respiratory and other organ outcomes were consistently highly prioritized by all stakeholder groups. Patients/family members gave higher priority to many patient-reported outcomes compared with health professionals.
Published: 2020
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3. Ernica consensus conference on the management of patients with long-gap esophageal atresia:perioperative, surgical, and long-term management

Author: Janne S. Suominen, Rene M. H. Wijnen, Paolo De Coppi, Graham Slater, Sabine Pirr, Piergiorgio Gamba, Pietro Bagolan, Stefaan H. A. J. Tytgat, Lars S. Rasmussen, Frédéric Gottrand, JoAnne Fruithof, Imeke Goldschmidt, Benno M. Ure, Joergen M. Thorup, Kate Cross, Anke Widenmann-Grolig, David C. van der Zee, Simon Eaton, Gunnar Aksnes, Wilhelm Zetterquist, Jan F. Svensson, Lucas Wessel, Carmen Dingemann, Rony Sfeir, CHU Lille, Inserm, Université de Lille, Hannover Medical School [Hannover] [MHH], University College of London [London] [UCL], Oslo University College [OUC], Bambino Gesù Children’s Hospital [Rome, Italy], Great Ormond Street Hospital for Children [London] [GOSH], Università degli Studi di Padova = University of Padua [Unipd], Lille Inflammation Research International Center (LIRIC) - U995, Odense University Hospital [OUH], Environnement Périnatal et Santé - EA 4489, University of Nottingham, UK [UON], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Karolinska University Hospital [Stockholm], University of Copenhagen = Københavns Universitet [UCPH], University Medical Center [Utrecht], University of Heidelberg, Medical Faculty, Universität Stuttgart [Stuttgart], Erasmus University Medical Center [Rotterdam] [Erasmus MC], Hannover Medical School [Hannover] (MHH), University College of London [London] (UCL), Oslo University College (OUC), Great Ormond Street Hospital for Children [London] (GOSH), Università degli Studi di Padova = University of Padua (Unipd), Lille Inflammation Research International Center - U 995 (LIRIC), 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 Hospitalier Régional Universitaire [Lille] (CHRU Lille), Odense University Hospital (OUH), Environnement périnatal et croissance - EA 4489 (EPS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Nottingham, UK (UON), University of Copenhagen = Københavns Universitet (UCPH), Erasmus University Medical Center [Rotterdam] (Erasmus MC), and Pediatric Surgery
Subjects: medicine.medical_specialty, consensus conference, COLONIC INTERPOSITION, [SDV]Life Sciences [q-bio], MEDLINE, Aftercare, CHILDREN, Anastomosis, Pediatrics, Pyloroplasty, TRACHEOESOPHAGEAL FISTULA, Perioperative Care, PEDIATRIC-SURGERY, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Pediatric surgery, medicine, follow-up, pediatric surgery, Humans, Esophageal Atresia, EUROPEAN REFERENCE NETWORKS, REPAIR, COMPLICATIONS, OUTCOMES, Science & Technology, business.industry, General surgery, Infant, Newborn, Consensus conference, Perioperative, Long gap esophageal atresia, medicine.disease, 3. Good health, REPLACEMENT, Treatment Outcome, Esophagoplasty, Atresia, Settore MED/20, Pediatrics, Perinatology and Child Health, long-gap esophageal atresia, 030211 gastroenterology & hepatology, Surgery, management, business, Life Sciences & Biomedicine
Abstract: Introduction Evidence supporting best practice for long-gap esophageal atresia is limited. The European Reference Network for Rare Inherited Congenital Anomalies (ERNICA) organized a consensus conference on the management of patients with long-gap esophageal atresia based on expert opinion referring to the latest literature aiming to provide clear and uniform statements in this respect. Materials and Methods Twenty-four ERNICA representatives from nine European countries participated. The conference was prepared by item generation, item prioritization by online survey, formulation of a final list containing items on perioperative, surgical, and long-term management, and literature review. The 2-day conference was held in Berlin in November 2019. Anonymous voting was conducted via an internet-based system using a 1 to 9 scale. Consensus was defined as ≥75% of those voting scoring 6 to 9. Results Ninety-seven items were generated. Complete consensus (100%) was achieved on 56 items (58%), e.g., avoidance of a cervical esophagostomy, promotion of sham feeding, details of delayed anastomosis, thoracoscopic pouch mobilization and placement of traction sutures as novel technique, replacement techniques, and follow-up. Consensus ≥75% was achieved on 90 items (93%), e.g., definition of long gap, routine pyloroplasty in gastric transposition, and avoidance of preoperative bougienage to enable delayed anastomosis. Nineteen items (20%), e.g., methods of gap measurement were discussed controversially (range 1–9). Conclusion This is the first consensus conference on the perioperative, surgical, and long-term management of patients with long-gap esophageal atresia. Substantial statements regarding esophageal reconstruction or replacement and follow-up were formulated which may contribute to improve patient care.
Published: 2020

4. Accurate Measurement of Dynamic ON-state Resistances of GaN Devices under Reverse and Forward Conduction in High Frequency Power Converter

Author: Ke Li, Christopher Mark Johnson, Nadir Idir, Paul Evans, Arnaud Videt, Laboratoire d'Électrotechnique et d'Électronique de Puissance (L2EP) - EA 2697, Coventry University, Laboratoire d’Électrotechnique et d’Électronique de Puissance - ULR 2697 [L2EP], 407023|||University of Nottingham, UK [UON], Laboratoire d’Électrotechnique et d’Électronique de Puissance - ULR 2697 (L2EP), Centrale Lille-Université de Lille-Arts et Métiers Sciences et Technologies, 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)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), and University of Nottingham, UK (UON)
Subjects: soft switching, 02 engineering and technology, GaN transistor, Dynamic ON-state resistance, High switching frequency, Reverse conduction, Forward conduction, Soft switching, law.invention, [SPI]Engineering Sciences [physics], law, MOSFET, 0202 electrical engineering, electronic engineering, information engineering, Sensitivity (control systems), Electrical and Electronic Engineering, Physics, high switching frequency, business.industry, 020208 electrical & electronic engineering, Transistor, Order (ring theory), reverse conduction, Converters, forward conduction, Power (physics), Dynamic on-state resistance, Parasitic element, GaN transistor, Optoelectronics, Constant current, business
Abstract: Because of trapped charges in GaN transistor structure, device dynamic on -state resistance $R_\mathrm{DSon}$ is increased when it is operated in high frequency switched power converters, in which device is possibly operated by zero voltage switching (ZVS) to reduce its turn- on switching losses. When GaN transistor finishes ZVS during one switching period, device has been operated under both reverse and forward conduction. Therefore its dynamic $R_\mathrm{DSon}$ under both conduction modes needs to be carefully measured to understand device power losses. For this reason, a measurement circuit with simple structure and fast dynamic response is proposed to characterize device reverse and forward $R_\mathrm{DSon}$ . In order to improve measurement sensitivity when device switches at high frequency, a trapezoidal current mode is proposed to measure device $R_\mathrm{DSon}$ under almost constant current, which resolves measurement sensitivity issues caused by unavoidable measurement circuit parasitic inductance and measurement probes deskew in conventional device characterization method by triangle current mode. Proposed measurement circuit and measurement method is then validated by first characterizing a SiC- mosfet with constant $R_\mathrm{DSon}$ . Then, the comparison on GaN-HEMT dynamic $R_\mathrm{DSon}$ measurement results demonstrates the improved accuracy of proposed trapezoidal current mode over conventional triangle current mode when device switches at 1 MHz.
Published: 2020

5. Core Outcomes Set for Trials in People With Coronavirus Disease 2019

Author: Ella Flemyng, Antoni Torres, Sangeeta Mehta, Saad Nseir, Armando Teixeira-Pinto, Tess E Cooper, Andrea K. Viecelli, Luciano Cesar Pontes Azevedo, Peter Horby, Lilia Cervantes, Tom Snelling, Amanda Baumgart, Eduardo Lorca, John C. Marshall, Ivor S. Douglas, Paula R Williamson, Andrea Matus Gonzalez, Julian Elliott, Junhua Zhang, Allison Tong, Giovanni F.M. Strippoli, Jaehee Lee, Steve Webb, Sally Crowe, Mark Reid, Andrew Conway Morris, Charlie McLeod, Alan R. Smyth, Pedro Póvoa, Deena Lynch, Elyssa Hannan, Yasser Sakr, Yeoungjee Cho, Martin Howell, Tari Turner, Laila Woc-Colburn, Ning Shen, Nicole Evangelidis, Andrew D. Bersten, Derek P. Chew, Karine E. Manera, Emma Liu, Mervyn Mer, Anne McKenzie, Jonathan C. Craig, The University of Sydney, Monash University [Melbourne], Flinders University [Adelaide, Australia], University of Queensland [Brisbane], University of Colorado [Denver], University of Oxford, Kyungpook National University [Daegu] (KNU), Universidad de Chile = University of Chile [Santiago] (UCHILE), University of Toronto, University of the Witwatersrand [Johannesburg] (WITS), University of Cambridge [UK] (CAM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Jena University Hospital [Jena], University of Nottingham, UK (UON), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of Liverpool, Baylor College of Medecine, Tianjin University (TJU), Université de Lille, CNRS, Kyungpook National University [Daegu] [KNU], Universidad de Chile = University of Chile [Santiago] [UCHILE], University of the Witwatersrand [Johannesburg] [WITS], University of Cambridge [UK] [CAM], Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], University of Nottingham, UK [UON], Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro [UNIBA], Institut d'Investigacions Biomèdiques August Pi i Sunyer [IDIBAPS], Centro de Investigación Biomédica en Red Enfermedades Respiratorias [CIBERES], Tianjin University [TJU], University of Oxford [Oxford], Kyungpook National University [Daegu], Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Università degli studi di Bari Aldo Moro (UNIBA)
Subjects: Male, Research design, Clinical trial, Coronavirus, Critical care, Infection, Patients, Sepsis, Adult, Aged, COVID-19, Coronavirus Infections, Female, Health Services Accessibility, Humans, Middle Aged, Outcome Assessment, Health Care, Pandemics, Pneumonia, Viral, Randomized Controlled Trials as Topic, Research Design, SARS-CoV-2, Symptom Assessment, Betacoronavirus, Outcome Assessment, Psychological intervention, coronavirus, Disease, medicine.disease_cause, Critical Care and Intensive Care Medicine, patients, sepsis, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine and Health Sciences, Viral, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, clinical trial, 3. Good health, Psychosocial, medicine.medical_specialty, SOCIETY, critical care, infection, 03 medical and health sciences, medicine, Clinical Investigation, Intensive care medicine, business.industry, 030208 emergency & critical care medicine, Pneumonia, medicine.disease, COVID-19 Drug Treatment, Health Care, 030228 respiratory system, Respiratory failure, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Objectives: The outcomes reported in trials in coronavirus disease 2019 are extremely heterogeneous and of uncertain patient relevance, limiting their applicability for clinical decision-making. The aim of this workshop was to establish a core outcomes set for trials in people with suspected or confirmed coronavirus disease 2019. Design: Four international online multistakeholder consensus workshops were convened to discuss proposed core outcomes for trials in people with suspected or confirmed coronavirus disease 2019, informed by a survey involving 9,289 respondents from 111 countries. The transcripts were analyzed thematically. The workshop recommendations were used to finalize the core outcomes set. Setting: International. Subjects: Adults 18 years old and over with confirmed or suspected coronavirus disease 2019, their family members, members of the general public and health professionals (including clinicians, policy makers, regulators, funders, researchers). Interventions: None. Measurements: None. Main Results: Six themes were identified. “Responding to the critical and acute health crisis” reflected the immediate focus on saving lives and preventing life-threatening complications that underpinned the high prioritization of mortality, respiratory failure, and multiple organ failure. “Capturing different settings of care” highlighted the need to minimize the burden on hospitals and to acknowledge outcomes in community settings. “Encompassing the full trajectory and severity of disease” was addressing longer term impacts and the full spectrum of illness (e.g. shortness of breath and recovery). “Distinguishing overlap, correlation and collinearity” meant recognizing that symptoms such as shortness of breath had distinct value and minimizing overlap (e.g. lung function and pneumonia were on the continuum toward respiratory failure). “Recognizing adverse events” refers to the potential harms of new and evolving interventions. “Being cognizant of family and psychosocial wellbeing” reflected the pervasive impacts of coronavirus disease 2019. Conclusions: Mortality, respiratory failure, multiple organ failure, shortness of breath, and recovery are critically important outcomes to be consistently reported in coronavirus disease 2019 trials.
Published: 2020

6. Development and characterization of sorafenib-loaded lipid nanocapsules for the treatment of glioblastoma

Author: Clément Tétaud, Emilie Roger, Laurent Lemaire, Philippe Menei, Anne Clavreul, Milad Pourbaghi-Masouleh, Design and Application of Innovative Local Treatments in Glioblastoma (CRCINA-ÉQUIPE 17), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Département de neurochirurgie [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Division of Drug Delivery and Tissue Engineering [Nottingham, UK], University of Nottingham, UK (UON)-School of Pharmacy [Nottingham, UK], Plate-forme de Recherche en Imagerie et Spectroscopie Multi-modales [SFR ICAT - UA] (PRISM), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA)-Université d'Angers (UA), This research was supported by grants from the ‘Fondation de France,’‘Ligue contre le Cancer du Grand-Ouest, Comite Departemental duMaine-et-Loire,’ ‘Association en Avant la Vie,’ and the EuropeanCommission, Education, Audiovisual and Culture Executive Agency(EACEA), through the NanoFar Erasmus Mundus joint Doctoral program., Bernardo, Elizabeth, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), School of Pharmacy [Nottingham, UK]-University of Nottingham, UK (UON), and Plate-forme de Recherche en Imagerie et Spectroscopie Multi-modales (PRISM [SFR ICAT - UA])
Subjects: Drug, Sorafenib, medicine.drug_class, Angiogenesis, media_common.quotation_subject, Drug Compounding, Pharmaceutical Science, Mice, Nude, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antineoplastic Agents, 02 engineering and technology, Tyrosine-kinase inhibitor, 03 medical and health sciences, Mice, 0302 clinical medicine, Drug Delivery Systems, [SDV.CAN] Life Sciences [q-bio]/Cancer, Nanocapsules, In vivo, Cell Line, Tumor, medicine, Animals, Humans, Viability assay, media_common, lipid nanocapsules, Chemistry, Brain Neoplasms, lcsh:RM1-950, glioblastoma, General Medicine, 021001 nanoscience & nanotechnology, Lipids, 3. Good health, lcsh:Therapeutics. Pharmacology, 030220 oncology & carcinogenesis, Drug delivery, Cancer research, Nanocarriers, 0210 nano-technology, medicine.drug, Research Article
Abstract: International audience; Anticancer agents that target both tumor cells and angiogenesis are of potential interest for glioblastoma (GB) therapy. One such agent is sorafenib (SFN), a tyrosine kinase inhibitor. However, poor aqueous solubility and undesirable side effects limit its clinical application, including local treatment. We encapsulated SFN in lipid nanocapsules (LNCs) to overcome these drawbacks. LNCs are nanocarriers formulated according to a solvent-free process, using only components that have received regulatory approval. SFN-LNCs had a diameter of 54 ± 1 nm, high encapsulation efficiency (>90%), and a drugpayload of 2.11 ± 0.03mg/g of LNC dispersion. They inhibited in vitro angiogenesis and decreased human U87MG GB cell viability similarly to free SFN. In vivo studies showed that the intratumoral administration of SFN-LNCs or free SFN in nude mice bearing an orthotopic U87MG human GB xenograft decreased the proportion of proliferating cells in the tumor relative to control groups. SFN-LNCs were more effective than free SFN for inducing early tumor vascular normalization, characterized by increases in tumor blood flow and decreases in tumor vessel area. These results highlight the potentialof LNCs as delivery systems for SFN. The vascular normalization induced by SFN-LNCs could be used to improve the efficacy of chemotherapy or radiotherapy for treating GB.
Published: 2018

7. Mediterranean intermittent rivers and ephemeral streams: Challenges in monitoring complexity

Author: Alexander Borg Galea, Jonathan P. Sadler, David M. Hannah, Stephen J. Dugdale, Thibault Datry, School of Geography, Earth and Environmental Sciences [Birmingham], University of Birmingham [Birmingham], Milieux aquatiques, écologie et pollutions (UR MALY), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Faculty of Social Sciences, School of Geography, and University of Nottingham, UK (UON)-University of Nottingham, UK (UON)
Subjects: Mediterranean climate, 010504 meteorology & atmospheric sciences, 0207 environmental engineering, 02 engineering and technology, Aquatic Science, 01 natural sciences, Ecosystem services, environmental management, remote sensing, 11. Sustainability, structure-from-Motion photogrammetry, 020701 environmental engineering, Ecology, Evolution, Behavior and Systematics, 0105 earth and related environmental sciences, Earth-Surface Processes, Ecology, business.industry, Environmental resource management, 15. Life on land, 6. Clean water, 13. Climate action, Remote sensing (archaeology), Ephemeral streams, Mediterranean intermittent streams, [SDE]Environmental Sciences, Environmental science, unmanned aerial vehicles, business, ecosystem services
Abstract: In most cases, intermittent rivers and ephemeral streams (IRES) form the principal surface water bodies in Mediterranean regions and people are heavily dependent on them. Strong reliance on such streams results in numerous pressures, and complex relationships are formed between their various natural and anthropogenic components, which creates numerous challenges to decision-makers who require a better understanding of IRES to establish effective measures to restore ecosystem functionality and implement changes, while maintaining human well-being. In this paper, we present a conceptual framework that identifies process cascades and links to identify the variables governing Mediterranean IRES and map their complex interrelations. Climate is the main external driver, and it affects IRES through precipitation, temperature, wind action, and geomorphic factors, which in turn influence the physical and biological attributes of IRES. Monitoring challenges and knowledge gaps are presented from the conceptual framework, highlighting the need to identify solutions for the monitoring and mapping the spatio-temporal variability of flow regimes and their influence on bio-physical variables and mapping and quantifying ecosystem services for integrated environmental management. Finally, we argue that remote sensing techniques, specifically, the combined use of unmanned aerial vehicles and structure from motion photogrammetry, are key to bridging gaps in understanding and meeting the challenges of managing Mediterranean IRES.
Published: 2019

8. Seasonal and habitat-based variations in vertical export of biogenic sea-ice proxies in Hudson Bay

Author: Tiia Luostarinen, Kaarina Weckström, Jens Ehn, Michelle Kamula, Amanda Burson, Aura Diaz, Guillaume Massé, Suzanne McGowan, Zou Zou Kuzyk, Maija Heikkilä, Helsinki Institute of Sustainability Science (HELSUS), Faculty of Biological and Environmental Sciences [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Geological Survey of Denmark and Greenland (GEUS), Centre for Earth Observation Science [Winnipeg], University of Manitoba [Winnipeg], British Antarctic Survey (BAS), Natural Environment Research Council (NERC), University of Nottingham, UK (UON), Variabilité de l'Océan et de la Glace de mer (VOG), 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), Netherlands Institute of Ecology (NIOO-KNAW), Ecosystems and Environment Research Programme, Environmental Change Research Unit (ECRU), and Aquatic Ecology (AqE)
Subjects: Diatoms, Canada, Dinoflagellate cysts, Quebec, Fresh-water, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, Biomarker, North-atlantic, 1181 Ecology, evolutionary biology, General Earth and Planetary Sciences, Variability, Manitounuk sound, Late quaternary, General Environmental Science
Abstract: Despite their wide use in past sea-ice reconstructions, the seasonal, habitat and species-based sources of sedimentary sea-ice proxies are poorly understood. Here, we conduct direct observations of the community composition of diatoms, dinoflagellate cysts and highly branched isoprenoid lipids within the sea ice, water column, sediment traps and sediment surface in the Belcher Islands Archipelago, Hudson Bay throughout spring 2019. We find that Arctic diatom and dinoflagellate cysts species commonly used as sea-ice proxies appear to be only indirectly linked to sea-ice conditions, and that the sediment assemblages of these groups overrepresent summertime pelagic blooms. Species contributing to the diverse sea-ice diatom communities are rare in the sediment. Dinoflagellate cysts form a typical Arctic assemblage in the sediment, although they are virtually absent in the sea ice and water column in spring. We also find that certain highly branched isoprenoid lipids that were previously considered indicators of open water, can be produced in sea-ice. We conclude that contextual knowledge and a multiproxy approach are necessary in reconstruction, encouraging further studies on the sources and controls of sea-ice proxy production in different geographic areas. Sedimentary assemblages of biogenic sea-ice proxies incorporate limited representation of the diverse sea-ice connected communities, according to direct springtime observations in the Belcher Islands Archipelago, Hudson Bay, Canada.Despite their wide use in past sea-ice reconstructions, the seasonal, habitat and species-based sources of sedimentary sea-ice proxies are poorly understood. Here, we conduct direct observations of the community composition of diatoms, dinoflagellate cysts and highly branched isoprenoid lipids within the sea ice, water column, sediment traps and sediment surface in the Belcher Islands Archipelago, Hudson Bay throughout spring 2019. We find that Arctic diatom and dinoflagellate cysts species commonly used as sea-ice proxies appear to be only indirectly linked to sea-ice conditions, and that the sediment assemblages of these groups overrepresent summertime pelagic blooms. Species contributing to the diverse sea-ice diatom communities are rare in the sediment. Dinoflagellate cysts form a typical Arctic assemblage in the sediment, although they are virtually absent in the sea ice and water column in spring. We also find that certain highly branched isoprenoid lipids that were previously considered indicators of open water, can be produced in sea-ice. We conclude that contextual knowledge and a multiproxy approach are necessary in reconstruction, encouraging further studies on the sources and controls of sea-ice proxy production in different geographic areas.
Published: 2023

9. Where is the father? Challenges and solutions to the inclusion of fathers in child feeding and nutrition research

Author: Moura, Andreia F., Philippe, Kaat, University of Nottingham, UK (UON), Aarhus University [Aarhus], Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Dijon, 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), University College Dublin [Dublin] (UCD), Projet EDULIA, and European Project: 764985,Marie Sklodowska-Curie
Subjects: Recruitment methods, Fathers, Sociology, Eating behaviour, Child feeding, Psychology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Involvement, Gender ideology, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; Despite an increasing acknowledgement of fathers’ involvement in and impact on children’s lives, fathers remain underrepresented in child feeding and childhood obesity prevention research, interventions, and actions. Built on our own experiences with conducting research with fathers and recent evidence on this topic, this Research in Practice article has three aims. It will first substantiate the importance of including and studying fathers in the field of child feeding and childhood obesity prevention based on recent study results. Secondly, the article will present and discuss barriers to fathers' inclusion and participation (why isn't it happening?), among other issues, by drawing on sociological and gender ideological insights. Finally, it will provide recommendations and suggestions related to recruitment, focus and methods that can facilitate fathers’ involvement in future research, interventions, and practice. Taken together, this article aims to provide tools for giving fathers a voice in the field of child nutrition and by doing so, to decrease maternal-only “burden” of care. We hope our experiences and theoretical reflections will inspire and support researchers and practitioners to be as successful as possible in the realm of family care.
Published: 2023

10. The Face-Processing Network Is Resilient to Focal Resection of Human Visual Cortex

Author: Corentin Jacques, Sophie Colnat-Coulbois, Kevin S. Weiner, Jesse Gomez, Bruno Rossion, Michael Barnett, Jacques Jonas, David Loftus, Hélène Brissart, Anthony Stigliani, Kalanit Grill-Spector, Louis Maillard, Gabriela Hossu, Institute for the Study of Genetics, Institute for the Study of Genetics Biorisks and Society, University of Nottingham, UK (UON)-University of Nottingham, UK (UON), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain (UCL), Universidad Industrial de Santander [Bucaramanga] (UIS), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut National de la Santé et de la Recherche Médicale (INSERM), Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurochirurgie [CHRU Nancy], Stanford University, Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre d'Investigation Clinique - Innovation Technologique [Nancy] (CIC-IT), 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), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), and Pomona College
Subjects: Male, 0301 basic medicine, Visual space, fusiform face area, Neuropsychological Tests, Visual system, Electroencephalography, Brain mapping, 0302 clinical medicine, Face perception, Cortex (anatomy), Image Processing, Computer-Assisted, hierarchical networks, Visual Cortex, Brain Mapping, medicine.diagnostic_test, General Neuroscience, cortical plasticity, Articles, Middle Aged, Magnetic Resonance Imaging, Neoplasms, Neuroepithelial, medicine.anatomical_structure, Pattern Recognition, Visual, Female, Psychology, Adult, brain lesion, Young Adult, 03 medical and health sciences, occipital face area, brain lesion cortical plasticity face perception fusiform face area hierarchical networks occipital face area, medicine, Humans, Visual Pathways, Communication, Epilepsy, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Reproducibility of Results, Fusiform face area, Oxygen, 030104 developmental biology, Visual cortex, Face, face perception, Visual Fields, business, Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; Human face perception requires a network of brain regions distributed throughout the occipital and temporal lobes with a right hemisphere advantage. Present theories consider this network as either a processing hierarchy beginning with the inferior occipital gyrus (occipital face area; IOG-faces/OFA) or a multiple-route network with nonhierarchical components. The former predicts that removing IOG-faces/OFA will detrimentally affect downstream stages, whereas the latter does not. We tested this prediction in a human patient (Patient S.P.) requiring removal of the right inferior occipital cortex, including IOG-faces/OFA. We acquired multiple fMRI measurements in Patient S.P. before and after a preplanned surgery and multiple measurements in typical controls, enabling both within-subject/across-session comparisons (Patient S.P. before resection vs Patient S.P. after resection) and between-subject/across-session comparisons (Patient S.P. vs controls). We found that the spatial topology and selectivity of downstream ipsilateral face-selective regions were stable 1 and 8 month(s) after surgery. Additionally, the reliability of distributed patterns of face selectivity in Patient S.P. before versus after resection was not different from across-session reliability in controls. Nevertheless, postoperatively, representations of visual space were typical in dorsal face-selective regions but atypical in ventral face-selective regions and V1 of the resected hemisphere. Diffusion weighted imaging in Patient S.P. and controls identifies white matter tracts connecting retinotopic areas to downstream face-selective regions, which may contribute to the stable and plastic features of the face network in Patient S.P. after surgery. Together, our results support a multiple-route network of face processing with nonhierarchical components and shed light on stable and plastic features of high-level visual cortex following focal brain damage.SIGNIFICANCE STATEMENT Brain networks consist of interconnected functional regions commonly organized in processing hierarchies. Prevailing theories predict that damage to the input of the hierarchy will detrimentally affect later stages. We tested this prediction with multiple brain measurements in a rare human patient requiring surgical removal of the putative input to a network processing faces. Surprisingly, the spatial topology and selectivity of downstream face-selective regions are stable after surgery. Nevertheless, representations of visual space were typical in dorsal face-selective regions but atypical in ventral face-selective regions and V1. White matter connections from outside the face network may support these stable and plastic features. As processing hierarchies are ubiquitous in biological and nonbiological systems, our results have pervasive implications for understanding the construction of resilient networks.
Published: 2016

11. Co-ordinated structural and functional covariance in the adolescent brain underlies face processing performance

Author: Tomáš Paus, Marie Helene Grosbras, Radek Mareček, G. Bruce Pike, Gabriel Leonard, Daniel Joel Shaw, Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], School of Psychology [Nottingham], University of Nottingham, UK (UON), Laboratoire de Neurosciences Cognitives [Marseille] ( LNC ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Montreal Neurological Institute [Montréal], McGill University, University of Nottingham, UK ( UON ), and Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Adolescent, Nerve net, Cognitive Neuroscience, Experimental and Cognitive Psychology, Brain mapping, 050105 experimental psychology, Developmental psychology, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Neuroimaging, medicine, Humans, Interpersonal Relations, 0501 psychology and cognitive sciences, Longitudinal Studies, Child, ComputingMilieux_MISCELLANEOUS, Brain Mapping, Facial expression, [SCCO.NEUR]Cognitive science/Neuroscience, 05 social sciences, Brain morphometry, Age Factors, Brain, Original Articles, General Medicine, Covariance, Social cue, Magnetic Resonance Imaging, Facial Expression, medicine.anatomical_structure, Pattern Recognition, Visual, Face, Face (geometry), [ SCCO.NEUR ] Cognitive science/Neuroscience, Female, Cues, Nerve Net, Psychology, 030217 neurology & neurosurgery, Cognitive psychology
Abstract: Our ability to process complex social cues presented by faces improves during adolescence. Using multivariate analyses of neuroimaging data collected longitudinally from a sample of 38 adolescents (17 males) when they were 10, 11.5, 13 and 15 years old, we tested the possibility that there exists parallel variations in the structural and functional development of neural systems supporting face processing. By combining measures of task-related functional connectivity and brain morphology, we reveal that both the structural covariance and functional connectivity among ‘distal’ nodes of the face-processing network engaged by ambiguous faces increase during this age range. Furthermore, we show that the trajectory of increasing functional connectivity between the distal nodes occurs in tandem with the development of their structural covariance. This demonstrates a tight coupling between functional and structural maturation within the face-processing network. Finally, we demonstrate that increased functional connectivity is associated with age-related improvements of face-processing performance, particularly in females. We suggest that our findings reflect greater integration among distal elements of the neural systems supporting the processing of facial expressions. This, in turn, might facilitate an enhanced extraction of social information from faces during a time when greater importance is placed on social interactions.
Published: 2016

12. MicroRNA-based Drugs for Brain Tumours

Author: Jean-Paul Issartel, Shubaash Anthiya, Emmanuel Garcion, Audrey Griveau, Martin C. Garnett, Patrick Baril, Claire Loussouarn, School of Pharmacy [Nottingham, U.K.], University Park [Nottingham, U.K.]-University of Nottingham, UK (UON), Design and Application of Innovative Local Treatments in Glioblastoma (CRCINA-ÉQUIPE 17), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes (UN)-Université d'Angers (UA)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes (UN)-Université d'Angers (UA), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), University of Nottingham, UK (UON)-University Park [Nottingham, U.K.], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), This work was supported by Inca (Institut National du Cancer) through the PL-BIO 2014-2020 INCA project MARENGO - 'MicroRNA agonist and antagonist Nanomedicines for GliOblastoma treatment: from molecular programmation to preclinical validation'. It is also related to the LabEx IRON 'Innovative Radiopharmaceuticals in Oncology and Neurology' as part of the french government 'Investissements d’Avenir' program. The authors are also thankful to the European support in the frame of the NanoFar consortium, an Erasmus Mundus Joint Doctorate (EMJD) program in nanomedicine and pharmaceutical innovation. European Commission (NanoFar EMJD), 'Le Conseil Général de Maine-et-Loire' and Inca financially supported SA, AG and CL, respectively., and Bernardo, Elizabeth
Subjects: 0301 basic medicine, Cancer Research, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, Computational biology, exosomes, Biology, Genome, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, RNA interference, brain targeting, microRNA, medicine, Animals, Humans, cancer resistance, Gene, argonaute, Brain Neoplasms, glioblastoma, Cancer, Genetic Therapy, Argonaute, medicine.disease, Microvesicles, 3. Good health, MicroRNAs, 030104 developmental biology, Oncology, Blood-Brain Barrier, RNAi, drug delivery, nanoparticles
Abstract: Shubaash ANTHIYA and Audrey GRIVEAU contributed equally to this work.; International audience; MicroRNAs (miRNAs) are key regulatory elements coded by the genome. A single miRNA can downregulate expression of multiple genes involved in diverse functions. As cancer is a disease with multiple gene aberrations, developing novel approaches to identify and modulate miRNA-pathways may result in a breakthrough for cancer treatment. With a special focus on glioblastoma, this review provides an up-to-date understanding of miRNA biogenesis, role of miRNA in cancer resistance, essential tools for modulating miRNA expression, emerging list of clinically promising RNAi delivery systems and how they can be adapted for therapy.
Published: 2018

13. On the study of extremes with dependent random right-censoring

Author: Gilles Stupfler, School of Mathematical Sciences [ Nottingham], University of Nottingham, UK ( UON ), School of Mathematical Sciences [Nottingham], University of Nottingham, UK (UON), and Stupfler, Gilles
Subjects: Statistics and Probability, [ MATH ] Mathematics [math], Statistics::Theory, Economics, Econometrics and Finance (miscellaneous), Inference, [MATH] Mathematics [math], Statistics::Other Statistics, Tail censoring probability, 01 natural sciences, Copula (probability theory), Extreme value copula, 010104 statistics & probability, Extreme value index, 0502 economics and business, Econometrics, 050207 economics, 0101 mathematics, [MATH]Mathematics [math], Extreme value theory, Engineering (miscellaneous), Mathematics, Random right-censoring, 05 social sciences, Estimator, Random right-censoring, dependent censoring, extreme value copula, extreme value index, tail identi_ability, tail censoring probability, Missing data, Censoring (statistics), AMS Subject Classifcations: 62G32, 62N01, 62N02, Dependent censoring, Random variable, Tail identifiability
Abstract: The study of extremes in missing data frameworks is a recent developing field. In particular, the randomly right-censored case has been receiving a fair amount of attention in the last decade. All studies on this topic, however, essentially work under the usual assumption that the variable of interest and the censoring variable are independent. Furthermore, a frequent characteristic of estimation procedures developed so far is their crucial reliance on particular properties of the asymptotic behaviour of the response variable Z (that is, the minimum between time-to-event and time-to-censoring) and of the probability of censoring in the right tail of Z. In this paper, we focus instead on elucidating this asymptotic behaviour in the dependent censoring case, and, more precisely, when the structure of the dependent censoring mechanism is given by an extreme value copula. We then draw a number of consequences of our results, related to the asymptotic behaviour, in this dependent context, of a number of estimators of the extreme value index of the random variable of interest that were introduced in the literature under the assumption of independent censoring, and we discuss more generally the implications of our results on the inference of the extremes of this variable.
Published: 2017

14. Human mesenchymal stromal cells as cellular drug-delivery vectors for glioblastoma therapy: a good deal?

Author: Milad Pourbaghi-Masouleh, Philippe Menei, Anne Clavreul, Nolwenn Lautram, Emilie Roger, Claudia N. Montero-Menei, Service de neurochirurgie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Design and Application of Innovative Local Treatments in Glioblastoma (CRCINA-ÉQUIPE 17), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Division of Drug Delivery and Tissue Engineering [Nottingham, UK], School of Pharmacy [Nottingham, UK]-University of Nottingham, UK (UON), Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), This research was supported by grants from 'Fondation de France', 'Ligue contre le Cancer du Grand-Ouest, comité départemental du Maine-et-Loire', 'Association en avant la vie' and the European Commission, Education, Audiovisual and Culture Executive Agency (EACEA), through the NanoFar Erasmus Mundus joint Doctoral program., Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), University of Nottingham, UK (UON)-School of Pharmacy [Nottingham, UK], and Bernardo, Elizabeth
Subjects: 0301 basic medicine, Sorafenib, Niacinamide, Cancer Research, Angiogenesis, Cell Survival, Cell, Mesenchymal stromal cells, Mice, Nude, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pharmacology, Mesenchymal Stem Cell Transplantation, lcsh:RC254-282, 03 medical and health sciences, Mice, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, medicine, Animals, Humans, Administration, Intranasal, Cell Proliferation, Targeting, Temozolomide, business.industry, Brain Neoplasms, Research, Phenylurea Compounds, Mesenchymal stem cell, Mesenchymal Stem Cells, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Xenograft Model Antitumor Assays, 3. Good health, Endothelial stem cell, 030104 developmental biology, medicine.anatomical_structure, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Drug delivery, Nasal administration, business, Glioblastoma, medicine.drug
Abstract: International audience; Background: Glioblastoma (GB) is the most malignant brain tumor in adults. It is characterized by angiogenesis and a high proliferative and invasive capacity. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) is of limited efficacy. Innovative anticancer drugs targeting both tumor cells and angiogenesis are urgently required, together with effective systems for their delivery to the brain. We assessed the ability of human mesenchymal stromal cells (MSCs) to uptake the multikinase inhibitor, sorafenib (SFN), and to carry this drug to a brain tumor following intranasal administration. Method: MSCs were primed with SFN and drug content and release were quantified by analytical chemistry techniques. The ability of SFN-primed MSCs to inhibit the survival of the human U87MG GB cell line and endothelial cells was assessed in in vitro assays. These cells were then administered intranasally to nude mice bearing intracerebral U87MG xenografts. Their effect on tumor growth and angiogenesis was evaluated by magnetic resonance imaging and immunofluorescence analyses, and was compared with the intranasal administration of unprimed MSCs or SFN alone. Results: MSCs took up about 9 pg SFN per cell, with no effect on viability, and were able to release 60% of the primed drug. The cytostatic activity of the released SFN was entirely conserved, resulting in a significant inhibition of U87MG and endothelial cell survival in vitro. Two intranasal administrations of SFN-primed MSCs in U87MG-bearing mice resulted in lower levels of tumor angiogenesis than the injection of unprimed MSCs or SFN alone, but had no effect on tumor volume. We also observed an increase in the proportion of small intratumoral vessels in animals treated with unprimed MSCs; this effect being abolished if the MSCs were primed with SFN. Conclusion: We show the potential of MSCs to carry SFN to brain tumors following an intranasal administration. However, the therapeutic effect is modest probably due to the pro-tumorigenic properties of MSCs, which may limit the action of the released SFN. This calls into question the suitability of MSCs for use in GB therapy and renders it necessary to find methods guaranteeing the safety of this cellular vector after drug delivery.
Published: 2017

15. Occipital White Matter Tracts in Human and Macaque

Author: Winrich A. Freiwald, Kevin S. Weiner, Frank Q. Ye, Sofia M. Landi, David A. Leopold, Hiromasa Takemura, Brian A. Wandell, Franco Pestilli, Nikos K. Logothetis, Georgios A. Keliris, Michael Barnett, Julia Sliwa, Institute for the Study of Genetics, Institute for the Study of Genetics Biorisks and Society, University of Nottingham, UK (UON)-University of Nottingham, UK (UON), Rockefeller University [New York], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Microsoft Research [Redmond], Microsoft Corporation [Redmond, Wash.], Stanford University, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, Databases, Factual, Cognitive Neuroscience, Corpus callosum, Nerve Fibers, Myelinated, Macaque, Corpus Callosum, White matter, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Species Specificity, biology.animal, Neural Pathways, Fasciculus, Image Processing, Computer-Assisted, medicine, Animals, Humans, Vertical occipital fasciculus, Inferior longitudinal fasciculus, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Brain Mapping, biology, [SCCO.NEUR]Cognitive science/Neuroscience, Original Articles, Anatomy, biology.organism_classification, Macaca mulatta, White Matter, Diffusion Tensor Imaging, 030104 developmental biology, Visual cortex, medicine.anatomical_structure, nervous system, Female, Occipital Lobe, Human medicine, Psychology, Occipital lobe, Neuroscience, 030217 neurology & neurosurgery, Optic radiation
Abstract: We compare the major white matter tracts in human and macaque occipital lobe using diffusion MRI. The comparison suggests similarities but also significant differences in spatial arrangement and relative sizes of the tracts. There are several apparently homologous tracts in the two species, including the vertical occipital fasciculus (VOF), optic radiation, forceps major, and inferior longitudinal fasciculus (ILF). There is one large human tract, the inferior fronto-occipital fasciculus, with no corresponding fasciculus in macaque. The macaque VOF is compact and its fibers intertwine with the dorsal segment of the ILF, but the human VOF is much more elongated in the anterior-posterior direction and may be lateral to the ILF. These similarities and differences will be useful in establishing which circuitry in the macaque can serve as an accurate model for human visual cortex.Contact informationHiromasa Takemura, Center for Information and Neural Networks (CiNet), National Institute of Information and Communications Technology, and Osaka University, Japan htakemur@nict.go.jpAuthor contributionDesigned the study: HT FP BAW. Performed the experiments. HT FP GAK SML JS FQY DAL WAF NKL. Analyzed the data. HT FP KSW MAB BAW. Contributed analysis tools. FP KSW MAB. Wrote the paper. HT FP KSW BAW.
Published: 2017

16. Comparative genomics reveals high biological diversity and specific adaptations in the industrially and medically important fungal genus Aspergillus

Author: Giancarlo Perrone, Anna Lipzen, Igor V. Grigoriev, Ana Ramón, Claudio Scazzocchio, Karin M. Overkamp, David Cánovas, Alan Kuo, George Diallinas, Kristiina Hildén, Tabea Schütze, Asaf Salamov, Patricia A. vanKuyk, Anthony Levasseur, Cindy Choi, Tamás Emri, Bernard Henrissat, Erzsébet Sándor, Gerhard H. Braus, Evy Battaglia, Camila Caldana, María Harispe, Kurt LaButti, Nadhira Salih, Andrew MacCabe, Renato Augusto Corrêa dos Santos, Stefan Rauscher, Guillermo Aguilar-Osorio, François Piumi, Ellen Lagendijk, Axel A. Brakhage, Giuseppina Mulè, David B. Archer, Cristiane Uchima, André Damasio, Nada Kraševec, Tammi Camilla Vesth, Petter Melin, Rob Habgood, Susanna A. Braus-Stromeyer, Gavin Sherlock, Mojtaba Asadollahi, Marion Askin, Abeer Hossain, Miia R. Mäkelä, Fusheng Chen, Erzsébet Fekete, Natalia Mielnichuk, Márton Miskei, Jennifer R. Wortman, Diego Mauricio Riaño-Pachón, Manuel Sanguinetti, Ákos Molnár, Alicia Clum, Jaap Visser, Scott E. Baker, Jos Houbraken, Eric Record, Reinhard Fischer, Rob Samson, Isabelle Benoit, Christos Gournas, Kristina Sepčić, Harald Kusch, Paul S. Dyer, Diana van Rossen-Uffink, Nathalie van de Wiele, Antonio F. Logrieco, Eugenia Karabika, Jean Paul Ouedraogo, Roberto Ruller, Juliana Velasco de Castro Oliveira, Alla Lapidus, Gustavo C. Cerqueira, Margarita Orejas, Miaomiao Zhou, Vicky Sophianopoulou, Vera Meyer, Chew Yee Ngan, Levente Karaffa, Shiela E. Unkles, Hee-Soo Park, Iran Malavazi, Antonia Gallo, Sotiris Amillis, Adrian Tsang, Julian Röhrig, Ekaterina Shelest, Jens Christian Frisvad, Bernhard Seiboth, Tiziano Benocci, Ad Wiebenga, Erzsébet Orosz, Erika Lindquist, Gregor Anderluh, Vincent Robert, Ryan Hope, Matthieu Hainaut, Robert Riley, Ronald P. de Vries, Gustavo H. Goldman, Mikael Rørdam Andersen, István Pócsi, Zsolt Karányi, Hui Sun, Richard B. Todd, Jae-Hyuk Yu, Wanping Chen, Özgür Bayram, Berl R. Oakley, Antonia Susca, Michel Flipphi, Fabio M. Squina, Susanne Freyberg, Arthur F. J. Ram, Peter J. Punt, Kerrie Barry, US Department of Energy Joint Genome Institute, Walnut Creek CA, USA, Fungal Physiology, CBS‑KNAW Fungal Biodiversity Centre and Fungal, Utrecht University [Utrecht], Department for Molecular Biology and Nanobiotechnology, National Institute of chemitry, Slovenia, United States Department of Energy, Microbiology and Kluyver Centre for Genomics of Industrial Fermentation, Centre for Research in Neurodegenerative Diseases, University of Toronto, US Department of Energy Joint Genome Institute, U.S Department of Energy, U.S. Department of Energy [Washington] (DOE)-U.S. Department of Energy [Washington] (DOE), Faculty of Biology, University of Athens, Panepistimioupolis, University of Athens, Panepistimioupolis, Dept. of Biochemical Engineering, Faculty of Science and Technology, University of Debrecen, Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Joint Genome Institute, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Department of Energy / Joint Genome Institute (DOE), Los Alamos National Laboratory (LANL), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Department of Molecular Microbiology and Biotechnology, Leiden University, Institute of Biology Leiden, The Netherlands & Kluyver Centre for Genomics of Industrial Fermentation, Institute of Sciences of Food Production (ISPA), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Biologie du Développement et Reproduction (BDR), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Sección Bioquímica, Depto. de Biología Celular y Molecular, Facultad de Ciencias (UDELAR), Polytech Marseille (AMU POLYTECH), Aix Marseille Université (AMU), Biodiversité et Biotechnologie Fongiques (BBF), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM), University of Potsdam = Universität Potsdam, Institut Polytechnique des Sciences Avancées (IPSA), Institut de Mécanique Céleste et de Calcul des Ephémérides (IMCCE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Department of Plant Protection, University of Debrecen Egyetem [Debrecen], Stanford University, Istituto Scienze delle Produzioni Alimentari (ISPA), Centre for Structural and Functional Genomics, Concordia University [Montreal], School of Life Sciences, University of Nottingham, UK (UON), Dept Syst Biol, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Departement of Microbiology, Imperial College London, Research division biotechnology and microbiology, Institute of chemical engineering, Technische Univeritt Wien, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], School of Biology, Hungarian Scientific Research Fund K100464 NN116519 TAMOP 4.2.1./B-09/1/KONV-2010-0007 SROP-4.2.2.B-15/1/KONV-2015-001 / MINECO/FEDER AGL2011-29925 AGL2015-66131-AGL2015-66131-C2-2-R, Department of Food and Nutrition, Fungal Genetics and Biotechnology, European Commission, Ministerio de Economía y Competitividad (España), Westerdijk Fungal Biodiversity Institute, Westerdijk Fungal Biodiversity Institute - Fungal Physiology, Westerdijk Fungal Biodiversity Institute - Software and Databasing, Westerdijk Fungal Biodiversity Institute - Food and Indoor Mycology, COMBE, Isabelle, Consiglio Nazionale delle Ricerche (CNR), Consiglio Nazionale delle Ricerche [Roma] (CNR), Molecular Microbiology & Genetics, Georg-August-University [Göttingen], U.S. Department of Energy (DOE)-U.S. Department of Energy (DOE), INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU AMU), University of Helsinki, Institut National de la Recherche Agronomique (INRA), École Centrale de Marseille (ECM)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Universität Potsdam, PSL Research University (PSL)-PSL Research University (PSL)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), University of Debrecen, Stanford University [Stanford], Technical University of Denmark [Lyngby] (DTU), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Universidad de Sevilla. Departamento de Genética, Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), U.S. Department of Energy ( DOE ) -U.S. Department of Energy ( DOE ), Architecture et fonction des macromolécules biologiques ( AFMB ), Centre National de la Recherche Scientifique ( CNRS ) -Aix Marseille Université ( AMU ) -Institut National de la Recherche Agronomique ( INRA ), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes ( URMITE ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR48, INSB-INSB-Centre National de la Recherche Scientifique ( CNRS ), Institut Hospitalier Universitaire Méditerranée Infection ( IHU AMU ), DOE Joint Genome Institute, Institute of Sciences of Food Production ( ISPA ), National Research Council [Italy] ( CNR ), Biologie du Développement et Reproduction ( BDR ), Institut National de la Recherche Agronomique ( INRA ), Facultad de Ciencias ( UDELAR ), Polytech Marseille ( AMU POLYTECH ), Aix Marseille Université ( AMU ), Biodiversité et Biotechnologie Fongiques ( BBF ), Institut National de la Recherche Agronomique ( INRA ) -Aix Marseille Université ( AMU ) -Ecole Centrale de Marseille ( ECM ), Institut für Biochemie und Biologie, Institut Polytechnique des Sciences Avancées ( IPSA ), IPSA, Institut de Mécanique Céleste et de Calcul des Ephémérides ( IMCCE ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Observatoire de Paris-Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Istituto Scienze delle Produzioni Alimentari ( ISPA ), Consiglio Nazionale delle Ricerche [Roma] ( CNR ), Concordia University [Montreal, Canada], University of Nottingham, UK ( UON ), Technical University of Denmark [Lyngby] ( DTU ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ), Broad Institute of MIT and Harvard ( BROAD INSTITUTE ), and Broad Institute of MIT and Harvard
Subjects: 0301 basic medicine, champignon, Adaptation, Biological, Secondary Metabolism, Biológiai tudományok, Genome, Fungal biology, Cytochrome P-450 Enzyme System, Természettudományok, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Gene Expression Regulation, Fungal, Gene Regulatory Networks, Biomass, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Phylogeny, Fungal protein, Phylogenetic tree, biology, Microbiology and Parasitology, 1184 Genetics, developmental biology, physiology, Biodiversity, Genomics, Plants, Microbiologie et Parasitologie, 3. Good health, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Aspergillus, séquençage du génome, BBSRC, Multigene Family, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Genome sequencing, Comparative genomics, Genome, Fungal, Oxidoreductases, Biologie, Aspergillis, Metabolic Networks and Pathways, Signal Transduction, Life sciences, 030106 microbiology, education, FILOGENIA, Fungal Proteins, 03 medical and health sciences, Phylogenetics, Stress, Physiological, ddc:570, Genetic model, Humans, biodiversité fongique, génomique comparative, Research, aspergillus, RCUK, Computational Biology, Molecular Sequence Annotation, 15. Life on land, DNA Methylation, biology.organism_classification, Carbon, Evolutionary biology, 1182 Biochemistry, cell and molecular biology
Abstract: [Background] The fungal genus Aspergillus is of critical importance to humankind. Species include those with industrial applications, important pathogens of humans, animals and crops, a source of potent carcinogenic contaminants of food, and an important genetic model. The genome sequences of eight aspergilli have already been explored to investigate aspects of fungal biology, raising questions about evolution and specialization within this genus., [Results] We have generated genome sequences for ten novel, highly diverse Aspergillus species and compared these in detail to sister and more distant genera. Comparative studies of key aspects of fungal biology, including primary and secondary metabolism, stress response, biomass degradation, and signal transduction, revealed both conservation and diversity among the species. Observed genomic differences were validated with experimental studies. This revealed several highlights, such as the potential for sex in asexual species, organic acid production genes being a key feature of black aspergilli, alternative approaches for degrading plant biomass, and indications for the genetic basis of stress response. A genome-wide phylogenetic analysis demonstrated in detail the relationship of the newly genome sequenced species with other aspergilli., [Conclusions] Many aspects of biological differences between fungal species cannot be explained by current knowledge obtained from genome sequences. The comparative genomics and experimental study, presented here, allows for the first time a genus-wide view of the biological diversity of the aspergilli and in many, but not all, cases linked genome differences to phenotype. Insights gained could be exploited for biotechnological and medical applications of fungi., The sugar transporter analysis was supported by grants AGL2011-29925 and AGL2015-66131- AGL2015-66131-C2-2-R (MINECO/FEDER).
Published: 2017

17. H2O2-Responsive Nanocarriers Prepared by RAFT-Mediated Polymerization-Induced Self-Assembly of N-(2-(Methylthio)ethyl)acrylamide for Biomedical Applications

Author: Hien Phan, Robert Cavanagh, Damien Destouches, Francis Vacherot, Blandine Brissault, Vincenzo Taresco, Jacques Penelle, Benoit Couturaud, Institut de Chimie et des Matériaux Paris-Est (ICMPE), Institut de Chimie du CNRS (INC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), University of Nottingham, UK (UON), Résistances Thérapeutiques du Cancer de la Prostate (TRePCa), and Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: [CHIM.POLY]Chemical Sciences/Polymers, [SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology, Polymers and Plastics, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Process Chemistry and Technology, Organic Chemistry
Abstract: International audience; H2O2-sensitive block copolymer nanoparticles (NPs) composed of a hydrophilic macro-chain transfer agent (macro-CTA) and a hydrophobic thioether-bearing block were prepared by polymerization-induced self-assembly (PISA) approach. The PISA process first involved the chain extension of poly((poly(ethylene glycol) methyl ether methacrylate)-co-(poly(ethylene glycol) methacrylate)) macro-CTA with a H2O2-responsive N-(2-(methylthio)ethyl)acrylamide (MTEAM) monomer, which self-assembled into P((PEGMA-co-PEGMAOH)-b-PMTEAM) block copolymer NPs. The polymerization kinetics indicated the evolution of particle size and morphology from spherical micelles, fused micelles, to vesicles over time. Upon incubation with 0.1 to 10 mM H2O2, spheres were fragmented due to the oxidation of the PMTEAM cores, thus transforming the hydrophobic thioethers into hydrophilic sulfoxides and disassociating the nanocarriers. 43% of the hydrophobic Nile red dye was encapsulated into the spherical micelles and demonstrated a controlled release in H2O2 incubation. Spherical micelles and vesicles displayed no cytotoxicity in MCF-7, DU145, and 22Rv1 cells. Both spheres and vesicles were efficiently internalized into MCF-7 cells, with spheres showing a higher level of uptake than vesicles due to the smaller sizes. In summary, PISA of P((PEGMA-co-PEGMAOH)-b-PMTEAM) allowed the direct formation and loading of hydrophobic dye into spherical micelles, which showed a controlled drug release in H2O2.
Published: 2022

18. Infant BCG vaccination and risk of pulmonary and extrapulmonary tuberculosis throughout the life course: a systematic review and individual participant data meta-analysis

Author: Leonardo Martinez, Olivia Cords, Qiao Liu, Carlos Acuna-Villaorduna, Maryline Bonnet, Greg J Fox, Anna Cristina C Carvalho, Pei-Chun Chan, Julio Croda, Philip C Hill, Elisa Lopez-Varela, Simon Donkor, Katherine Fielding, Stephen M Graham, Marcos A Espinal, Beate Kampmann, Arthur Reingold, Helena Huerga, Julian A Villalba, Louis Grandjean, Giovanni Sotgiu, Uzochukwu Egere, Sarman Singh, Limei Zhu, Christian Lienhardt, Justin T Denholm, James A Seddon, Christopher C Whalen, Alberto L García-Basteiro, Rina Triasih, Cheng Chen, Jitendra Singh, Li-Min Huang, Surendra Sharma, Djohar Hannoun, Helena del Corral, Anna M Mandalakas, LaShaunda L Malone, Du-Lin Ling, Afrânio Kritski, Catherine M Stein, Richa Vashishtha, Fadila Boulahbal, Chi-Tai Fang, W Henry Boom, Eduardo Martins Netto, Antonio Carlos Lemos, Anneke C Hesseling, Alexander Kay, Edward C Jones-López, C Robert Horsburgh, Christoph Lange, Jason R Andrews, Boston University [Boston] (BU), University of California (UC), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), University of Nottingham, UK (UON), Infectious Diseases Epidemiology Unit, London School of Hygiene and Tropical Medicine (LSHTM), Medical Research Council Unit The Gambia (MRC), Imperial College London, and Universidad Peruana Cayetano Heredia (UPCH)
Subjects: Adult, Adolescent, MESH: Child, Humans, Tuberculosis, MESH: Tuberculosis, Child, Tuberculosis, Pulmonary, Aged, Retrospective Studies, MESH: Adolescent, MESH: Tuberculosis, Pulmonary, MESH: Aged, MESH: Humans, Vaccination, MESH: Child, Preschool, MESH: Infant, Newborn, Infant, Newborn, Infant, MESH: Adult, MESH: Retrospective Studies, MESH: Vaccination, General Medicine, MESH: Infant, MESH: BCG Vaccine, Child, Preschool, BCG Vaccine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: BACKGROUND: BCG vaccines are given to more than 100 million children every year, but there is considerable debate regarding the effectiveness of BCG vaccination in preventing tuberculosis and death, particularly among older children and adults. We therefore aimed to investigate the age-specific impact of infant BCG vaccination on tuberculosis (pulmonary and extrapulmonary) development and mortality. METHODS: In this systematic review and individual participant data meta-analysis, we searched MEDLINE, Web of Science, BIOSIS, and Embase without language restrictions for case-contact cohort studies of tuberculosis contacts published between Jan 1, 1998, and April 7, 2018. Search terms included "mycobacterium tuberculosis", "TB", "tuberculosis", and "contact". We excluded cohort studies that did not provide information on BCG vaccination or were done in countries that did not recommend BCG vaccination at birth. Individual-level participant data for a prespecified list of variables, including the characteristics of the exposed participant (contact), the index case, and the environment, were requested from authors of all eligible studies. Our primary outcome was a composite of prevalent (diagnosed at or within 90 days of baseline) and incident (diagnosed more than 90 days after baseline) tuberculosis in contacts exposed to tuberculosis. Secondary outcomes were pulmonary tuberculosis, extrapulmonary tuberculosis, and mortality. We derived adjusted odds ratios (aORs) using mixed-effects, binary, multivariable logistic regression analyses with study-level random effects, adjusting for the variable of interest, baseline age, sex, previous tuberculosis, and whether data were collected prospectively or retrospectively. We stratified our results by contact age and Mycobacterium tuberculosis infection status. This study is registered with PROSPERO, CRD42020180512. FINDINGS: We identified 14 927 original records from our database searches. We included participant-level data from 26 cohort studies done in 17 countries in our meta-analysis. Among 68 552 participants, 1782 (2·6%) developed tuberculosis (1309 [2·6%] of 49 686 BCG-vaccinated participants vs 473 [2·5%] of 18 866 unvaccinated participants). The overall effectiveness of BCG vaccination against all tuberculosis was 18% (aOR 0·82, 95% CI 0·74-0·91). When stratified by age, BCG vaccination only significantly protected against all tuberculosis in children younger than 5 years (aOR 0·63, 95% CI 0·49-0·81). Among contacts with a positive tuberculin skin test or IFNγ release assay, BCG vaccination significantly protected against tuberculosis among all participants (aOR 0·81, 95% CI 0·69-0·96), participants younger than 5 years (0·68, 0·47-0·97), and participants aged 5-9 years (0·62, 0·38-0·99). There was no protective effect among those with negative tests, unless they were younger than 5 years (0·54, 0·32-0·90). 14 cohorts reported on whether tuberculosis was pulmonary or extrapulmonary (n=57 421). BCG vaccination significantly protected against pulmonary tuberculosis among all participants (916 [2·2%] in 41 119 vaccinated participants vs 334 [2·1%] in 16 161 unvaccinated participants; aOR 0·81, 0·70-0·94) but not against extrapulmonary tuberculosis (106 [0·3%] in 40 318 vaccinated participants vs 38 [0·2%] in 15 865 unvaccinated participants; 0·96, 0·65-1·41). In the four studies with mortality data, BCG vaccination was significantly protective against death (0·25, 0·13-0·49). INTERPRETATION: Our results suggest that BCG vaccination at birth is effective at preventing tuberculosis in young children but is ineffective in adolescents and adults. Immunoprotection therefore needs to be boosted in older populations. FUNDING: National Institutes of Health.
Published: 2022

19. Somabotics Toolkit for Rapid Prototyping Human-Robot Interaction Experiences using Wearable Haptics

Author: Zhou, Feng, Price, Dominic, Kucukyilmaz, Ayse, Pacchierotti, Claudio, University of Nottingham, UK (UON), Sensor-based and interactive robotics (RAINBOW), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-RÉALITÉ VIRTUELLE, HUMAINS VIRTUELS, INTERACTIONS ET ROBOTIQUE (IRISA-D5), 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), and Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)
Subjects: [INFO.INFO-HC]Computer Science [cs]/Human-Computer Interaction [cs.HC]
Abstract: International audience
Published: 2023

20. Glutaredoxin regulation of primary root growth confers early drought stress tolerance in pearl millet

Author: Carla de la Fuente, Alexandre Grondin, Bassirou Sine, Marilyne Debieu, Christophe Belin, Amir Hajjarpoor, Jonathan A. Atkinson, Sixtine Passot, Marine Salson, Julie Orjuela, Christine Tranchant-Dubreuil, Jean-Rémy Brossier, Maxime Steffen, Charlotte Morgado, Hang Ngan Dinh, Bipin K. Pandey, Julie Darmau, Antony Champion, Anne- Sophie Petitot, Celia Barrachina, Marine Pratlong, Thibault Mounier, Pascal Gantet, Prakash Gangashetty, Yann Guédon, Vincent Vadez, Jean-Philippe Reichheld, Malcolm J. Bennett, Ndjido Kane, Soazig Guyomarc’h, Darren M. Wells, Yves Vigouroux, Laurent Laplaze, Diversité, adaptation, développement des plantes (UMR DIADE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), LMI Adaptation des Plantes et microorganismes associés aux Stress Environnementaux [Dakar] (LAPSE), Institut de Recherche pour le Développement (IRD), Centre d'Etude Regional Pour l'Amelioration de l'Adaptation A la Secheresse (CERAAS), Institut Sénégalais de Recherches Agricoles [Dakar] (ISRA), Laboratoire Génome et développement des plantes (LGDP), Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), University of Nottingham, UK (UON), Institut de Génomique Fonctionnelle - Montpellier GenomiX (IGF MGX), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), International Crops Research Institute for the Semi-Arid Tropics [Inde] (ICRISAT), Consultative Group on International Agricultural Research [CGIAR] (CGIAR), Amélioration génétique et adaptation des plantes méditerranéennes et tropicales (UMR AGAP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-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), Agropolis Fondation (NewPearl grant n° AF 1301-015 in the frame of the CERES initiative, ValoRoot grant n°2202-002, and Flagship Project CalClim grant no. 1802-002)Fondazione Cariplo (n° FC 2013-0891)- CGIAR Research Programme on Grain Legumes and Dryland Cereals (GLDC), ANR-17-CE20-0022,RootAdapt,Traits racinaires pour l'adaptation du mil au climat futur en Afrique de l'Ouest(2017), ANR-10-LABX-0001,AGRO,Agricultural Sciences for sustainable Development(2010), ANR-16-IDEX-0006,MUSE,MUSE(2016), and European Project
Subjects: [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BV.BOT]Life Sciences [q-bio]/Vegetal Biology/Botanics
Abstract: Seedling root traits impact plant establishment under challenging environments. Pearl millet is one of the most heat and drought tolerant cereal crops that provides a vital food source across the sub-Saharan Sahel region. Pearl millet’s early root system features a single fast-growing primary root which we hypothesize is an adaptation to the Sahelian climate. Using crop modelling, we demonstrate that early drought stress is an important constraint in agrosystems in the Sahel where pearl millet was domesticated. Furthermore, we show that increased pearl millet primary root growth is correlated with increased early water stress tolerance in field conditions. Genetics including GWAS and QTL approaches identify genomic regions controlling this key root trait. Combining gene expression data, re-sequencing and re- annotation of one of these genomic regions identified a glutaredoxin-encoding genePgGRXC9as the candidate stress resilience root growth regulator. Functional characterization of its closest Arabidopsis homologAtROXY19revealed a novel role for this glutaredoxin (GRX) gene clade in regulating cell elongation. In summary, our study suggests a conserved function for GRX genes in conferring root cell elongation and enhancing resilience of pearl millet to its Sahelian environment.
Published: 2023

21. Improved estimators of extreme Wang distortion risk measures for very heavy-tailed distributions

Author: Gilles Stupfler, Jonathan El Methni, MAP5 - Mathématiques Appliquées à Paris 5 (MAP5), Université Paris Descartes - Paris 5 (UPD5) - Institut National des Sciences Mathématiques et de leurs Interactions - Centre National de la Recherche Scientifique (CNRS), School of Mathematical Sciences [ Nottingham], University of Nottingham, UK (UON), Groupement de Recherche en Économie Quantitative d'Aix-Marseille (GREQAM), Centre National de la Recherche Scientifique (CNRS) - Université de la Méditerranée - Aix-Marseille 2 - Université Paul Cézanne - Aix-Marseille 3 - École des hautes études en sciences sociales (EHESS) - Aix Marseille Université (AMU) - Ecole Centrale de Marseille (ECM), Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), School of Mathematical Sciences [Nottingham], École Centrale de Marseille (ECM)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-École des hautes études en sciences sociales (EHESS), École des hautes études en sciences sociales (EHESS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Mathématiques Appliquées à Paris 5 ( MAP5 - UMR 8145 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National des Sciences Mathématiques et de leurs Interactions-Centre National de la Recherche Scientifique ( CNRS ), University of Nottingham, UK ( UON ), Groupement de Recherche en Économie Quantitative d'Aix-Marseille ( GREQAM ), Ecole Centrale de Marseille ( ECM ) -Centre National de la Recherche Scientifique ( CNRS ) -Aix Marseille Université ( AMU ) -École des hautes études en sciences sociales ( EHESS ), and El Methni, Jonathan
Subjects: Statistics and Probability, Economics and Econometrics, Wang distortion risk measure, asymptotic normality, Asymptotic distribution, 01 natural sciences, extreme value statistics, 010104 statistics & probability, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], Distortion, 0502 economics and business, Statistics, Econometrics, winsorising, [ MATH.MATH-ST ] Mathematics [math]/Statistics [math.ST], 0101 mathematics, Extreme value theory, heavy-tailed distribution, [MATH.MATH-ST] Mathematics [math]/Statistics [math.ST], AMS Subject Classifications: 62G05, 62G30, 62G30, 62G32, 050205 econometrics, Mathematics, trimming, 05 social sciences, Asymptotic normality, Extreme value statistics, Heavy-tailed distribution, Trimming, Wang distortion risk measure, Winsorising, Estimator, Distribution (mathematics), Heavy-tailed distribution, Statistics, Probability and Uncertainty, Random variable, Quantile
Abstract: International audience; A general way to study the extremes of a random variable is to consider the family of its Wang distortion risk measures. This class of risk measures encompasses several popular indicators such as the classical quantile/Value-at-Risk, the Tail-Value-at-Risk and the recently introduced Conditional Tail Moments, among others. A couple of very recent studies have focused on the estimation of extreme analogues of such quantities. In this paper, we consider trimmed and winsorised versions of the empirical counterparts of extreme Wang distortion risk measures. We analyse their asymptotic properties, and we show that we can construct bias-corrected trimmed or winsorised estimators of extreme Wang distortion risk measures who appear to perform overall better than their standard empirical counterparts in practice when the underlying distribution has a very heavy right tail. We also showcase our technique on a set of real fire insurance data.
Published: 2016

22. Reducing hypoxia and inflammation during invasive pulmonary aspergillosis by targeting the Interleukin-1 receptor

Author: Orhan Rasid, Amélie Savers, Eric Dannaoui, Oumaïma Ibrahim-Granet, Mark S. Gresnigt, Grégory Jouvion, Matthias Brock, Frank L. van de Veerdonk, Catherine Fitting, Jean-Marc Cavaillon, Abdessalem Rekiki, Marianna Parlato, Cytokines et Inflammation, Institut Pasteur [Paris] (IP), Radboud University Medical Center [Nijmegen], Immunité Innée - Innate Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), School of Life Sciences, University of Nottingham, UK (UON), Histopathologie humaine et Modèles animaux, Unité de Parasitologie-Mycologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), MG was supported by the Erasmus lifelong learning program. FvdV was supported by a Veni grant from ZonMw. OIG was supported by Institut Pasteur PTR 468 funding. OR was supported by a stipend from the Pasteur-Paris University (PPU) International PhD program. The authors are thankful to Marie-Anne Nicolas from Plateforme d’Imagerie Dynamique for her assistance in live imaging., Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunité Innée, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), University of Nottingham, UK ( UON ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and Ibrahim-Granet, oumaima
Subjects: 0301 basic medicine, medicine.drug_class, 030106 microbiology, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Inflammation, Biology, Interleukin-1 receptor, Aspergillosis, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Article, Receptors, Interleukin-8B, Aspergillus fumigatus, Immunocompromised Host, Mice, 03 medical and health sciences, Adrenal Cortex Hormones, medicine, Animals, Carbonic Anhydrase IX, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Invasive Pulmonary Aspergillosis, [ SDV.IMM.II ] Life Sciences [q-bio]/Immunology/Innate immunity, Multidisciplinary, Lung, Receptors, Interleukin-1, Interleukin, Hypoxia (medical), medicine.disease, biology.organism_classification, Receptor antagonist, Cell Hypoxia, 3. Good health, Disease Models, Animal, Interleukin 1 Receptor Antagonist Protein, Treatment Outcome, 030104 developmental biology, medicine.anatomical_structure, Immunology, Cytokines, medicine.symptom
Abstract: International audience; 1 Hypoxia as a result of pulmonary tissue damage due to unresolved inflammation during invasive pulmonary aspergillosis (IPA) is associated with a poor outcome. Aspergillus fumigatus can exploit the hypoxic microenvironment in the lung, but the inflammatory response required for fungal clearance can become severely disregulated as a result of hypoxia. Since severe inflammation can be detrimental to the host, we investigated whether targeting the interleukin IL-1 pathway could reduce inflammation and tissue hypoxia, improving the outcome of IPA. The interplay between hypoxia and inflammation was investigated by in vivo imaging of hypoxia and measurement of cytokines in the lungs in a model of corticosteroid immunocompromised and in Cxcr2 deficient mice. Severe hypoxia was observed following Aspergillus infection in both models and correlated with development of pulmonary inflammation and expression of hypoxia specific transcripts. Treatment with IL-1 receptor antagonist reduced hypoxia and slightly, but significantly reduced mortality in immunosuppressed mice, but was unable to reduce hypoxia in Cxcr2 −/− mice. Our data provides evidence that the inflammatory response during invasive pulmonary aspergillosis, and in particular the IL-1 axis, drives the development of hypoxia. Targeting the inflammatory IL-1 response could be used as a potential immunomodulatory therapy to improve the outcome of aspergillosis. Humans continuously inhale spores of the fungus Aspergillus fumigatus, which is a ubiquitous mould in soil and decaying organic debris. Although rarely causing disease in immunocompetent individuals, A. fumigatus can cause lethal invasive pulmonary aspergillosis (IPA) in immunocompromised patients, with mortality varying between 30% and 90%
Published: 2016

23. Infection-Mediated Priming of Phagocytes Protects against Lethal Secondary Aspergillus fumigatus Challenge

Author: Oumaïma Ibrahim-Granet, Amélie Savers, Bernhard Ryffel, Marianna Parlato, Gérard Eberl, Grégory Jouvion, Jean-Marc Cavaillon, Orhan Rasid, Matthias Brock, Cytokines et Inflammation, Institut Pasteur [Paris], School of Life Sciences, University of Nottingham, UK ( UON ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Histopathologie humaine et Modèles animaux, Immunologie et Neurogénétique Expérimentales et Moléculaires ( INEM ), Université d'Orléans ( UO ) -Centre National de la Recherche Scientifique ( CNRS ), Développement des Tissus Lymphoïdes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), This work was supported by funding from Institut Pasteur PTR 468 to OIG and AS, and the Transregio 124 'FungiNet' project A3 to AS and MB., University of Nottingham, UK (UON), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut Pasteur [Paris] (IP), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and BENEDIC, Bénédicte
Subjects: MESH : Bone Marrow, MESH : Spores, Fungal, medicine.medical_treatment, MESH : Cytokines, MESH: Flow Cytometry, Pathology and Laboratory Medicine, Aspergillosis, MESH: Phagocytes, Aspergillus fumigatus, Animal Cells, MESH : Aspergillosis, MESH: Animals, lcsh:Science, skin and connective tissue diseases, Lung, Disease Resistance, Fungal Pathogens, Phagocytes, Innate Immune System, MESH: Cytokines, Flow Cytometry, 3. Good health, [SDV] Life Sciences [q-bio], Aspergillus, Blood, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Aspergillus Fumigatus, Medical Microbiology, Spectrophotometry, Cytokines, MESH: Bone Marrow, Cytophotometry, Cellular Types, MESH : Receptors, Interleukin-8B, Immune Cells, Phagocytosis, Immunology, 030106 microbiology, Microbiology, 03 medical and health sciences, Microbial Pathogens, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Blood Cells, [ SDV ] Life Sciences [q-bio], Macrophages, lcsh:R, MESH: Host-Pathogen Interactions, Organisms, Biology and Life Sciences, Molecular Development, medicine.disease, Molds (Fungi), Mice, Inbred C57BL, 030104 developmental biology, lcsh:Q, Developmental Biology, 0301 basic medicine, Chemokine, Neutrophils, [SDV]Life Sciences [q-bio], lcsh:Medicine, MESH: Mice, Knockout, Receptors, Interleukin-8B, White Blood Cells, Spectrum Analysis Techniques, Bone Marrow, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Immune Physiology, Medicine and Health Sciences, MESH : Lectins, C-Type, CXC chemokine receptors, MESH : Host-Pathogen Interactions, Mice, Knockout, Mice, Inbred BALB C, Multidisciplinary, Bone Marrow/immunology/metabolism, biology, MESH: Receptors, Interleukin-8B, Hematology, Spores, Fungal, MESH: Chemokines, Body Fluids, Cytokine, Cell Processes, Host-Pathogen Interactions, MESH : Phagocytes, Aspergillus fumigatus/immunology, Chemokines, Pathogens, Anatomy, MESH: Aspergillus fumigatus, Research Article, MESH : Flow Cytometry, MESH : Lung, MESH: Mice, Inbred BALB C, MESH: Disease Resistance, Mycology, MESH : Mice, Inbred C57BL, Research and Analysis Methods, Immune system, MESH: Mice, Inbred C57BL, MESH: Spores, Fungal, medicine, MESH : Disease Resistance, Animals, Lectins, C-Type, MESH: Lung, MESH : Chemokines, MESH: Aspergillosis, MESH : Mice, Inbred BALB C, Innate immune system, Fungi, Cell Biology, Aspergillosis/immunology/microbiology, biology.organism_classification, Immune System, MESH : Aspergillus fumigatus, physiology, biology.protein, MESH : Mice, Knockout, MESH : Animals, MESH: Lectins, C-Type
Abstract: International audience; Phagocytes restrict the germination of Aspergillus fumigatus conidia and prevent the establishment of invasive pulmonary aspergillosis in immunecompetent mice. Here we report that immunecompetent mice recovering from a primary A. fumigatus challenge are protected against a secondary lethal challenge. Using RAGγc knock-out mice we show that this protection is independent of T, B and NK cells. In protected mice, lung phagocytes are recruited more rapidly and are more efficient in conidial phagocytosis and killing. Protection was also associated with an enhanced expression of CXCR2 and Dectin-1 on bone marrow phagocytes. We also show that protective lung cytokine and chemokine responses are induced more rapidly and with enhanced dynamics in protected mice. Our findings support the hypothesis that following a first encounter with a non-lethal dose of A. fumigatus conidia, the innate immune system is primed and can mediate protection against a secondary lethal infection.
Published: 2016

24. The antimalarial drug primaquine targets Fe–S cluster proteins and yeast respiratory growth

Author: Jérôme Clain, Grzegorz Pawlik, Marie-Pierre Golinelli-Cohen, Brigitte Meunier, Zehua Song, Cindy Vallières, Cécile Bouton, Sarah M. Tindall, Simon V. Avery, Anaïs Laleve, Biogenèse et fonctionnement des complexes OXPHOS mitochondriaux (BIOMIT), Département Biologie Cellulaire (BioCell), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), School of Life Sciences, University of Nottingham, UK (UON), Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), Université Paris Descartes - Paris 5 (UPD5), Biogenèse et fonctionnement des complexes OXPHOS mitochondriaux ( BIOMIT ), Département Biologie Cellulaire ( BioCell ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ), University of Nottingham, UK ( UON ), Institut de Chimie des Substances Naturelles ( ICSN ), Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Faculté de Pharmacie de Paris ( UPD5 Pharmacie ), Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), and Faculté de Pharmacie de Paris - Université Paris Descartes (UPD5 Pharmacie)
Subjects: 0301 basic medicine, Saccharomyces cerevisiae Proteins, Primaquine, [SDV]Life Sciences [q-bio], Clinical Biochemistry, SOD2, Saccharomyces cerevisiae, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Mitochondrion, Biology, Biochemistry, Aconitase, Mitochondria, Malaria, Aconitase, Sod2, Oxidative stress, Yeast model, Primaquine, Superoxide dismutase, Antimalarials, Gene Knockout Techniques, 03 medical and health sciences, Gene Expression Regulation, Fungal, medicine, Respiratory function, lcsh:QH301-705.5, Yeast model, Aconitate Hydratase, lcsh:R5-920, 030102 biochemistry & molecular biology, [ SDV ] Life Sciences [q-bio], Superoxide Dismutase, Organic Chemistry, Plasmodium falciparum, Sod2, biology.organism_classification, 3. Good health, Mitochondria, Malaria, 030104 developmental biology, lcsh:Biology (General), Mechanism of action, Oxidative stress, biology.protein, ATP-Binding Cassette Transporters, medicine.symptom, lcsh:Medicine (General), Cytochrome-B(5) Reductase, Research Paper, Molecular Chaperones, medicine.drug
Abstract: Malaria is a major health burden in tropical and subtropical countries. The antimalarial drug primaquine is extremely useful for killing the transmissible gametocyte forms of Plasmodium falciparum and the hepatic quiescent forms of P. vivax. Yet its mechanism of action is still poorly understood. In this study, we used the yeast Saccharomyces cerevisiae model to help uncover the mode of action of primaquine. We found that the growth inhibitory effect of primaquine was restricted to cells that relied on respiratory function to proliferate and that deletion of SOD2 encoding the mitochondrial superoxide dismutase severely increased its effect, which can be countered by the overexpression of AIM32 and MCR1 encoding mitochondrial enzymes involved in the response to oxidative stress. This indicated that ROS produced by respiratory activity had a key role in primaquine-induced growth defect. We observed that Δsod2 cells treated with primaquine displayed a severely decreased activity of aconitase that contains a Fe–S cluster notoriously sensitive to oxidative damage. We also showed that in vitro exposure to primaquine impaired the activity of purified aconitase and accelerated the turnover of the Fe–S cluster of the essential protein Rli1. It is suggested that ROS-labile Fe–S groups are the primary targets of primaquine. Aconitase activity is known to be essential at certain life-cycle stages of the malaria parasite. Thus primaquine-induced damage of its labile Fe–S cluster – and of other ROS-sensitive enzymes – could inhibit parasite development., Graphical abstract fx1, Highlights • The mode of action of the antimalarial drug primaquine is poorly understood. • The yeast model is used to decipher its mechanism of action. • SOD and respiratory function are key for yeast sensitivity to primaquine. • Primaquine treatment impairs Fe–S containing enzyme aconitase. • Its attack on Fe–S clusters could explain the primaquine-induced growth inhibition.
Published: 2016

25. Brain Regions Related to Impulsivity Mediate the Effects of Early Adversity on Antisocial Behavior

Author: Sarah Jurk, Gareth J. Barker, Tobias Banaschewski, Luise Poustka, Herta Flor, Robert R. Althoff, Catherine Orr, Uli Bromberg, Scott Mackey, Gunter Schumann, Kees-Jan Kan, Marie-Laure Paillère Martinot, Hugh Garavan, Eric Artiges, Dimitri Papadopoulos-Orfanos, Patricia J. Conrod, Andreas Heinz, Robert Whelan, Sylvane Desrivières, Michael N. Smolka, Arun L.W. Bokde, Christian Büchel, Bernd Ittermann, Penny A. Gowland, Bader Chaarani, Jürgen Gallinat, Anna Cattrell, Henrik Walter, Vincent Frouin, Philip A. Spechler, Frauke Nees, Animal Husbandry, Animal Science Group of Wageningen UR, Department of Child and Adolescent Psychiatry and Psychotherapy [Mannheim], Universität Heidelberg [Heidelberg] = Heidelberg University, Discipline of Psychiatry [Dublin], School of Medicine [Dublin], Trinity College Dublin-Trinity College Dublin, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Universität Mannheim, Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-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), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Sir Peter Mansfield Magnetic Resonance Centre [Nottingham], University of Nottingham, UK (UON), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Adolescent psychopathology and Medicine, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Technische Universität Dresden = Dresden University of Technology (TU Dresden), Berlin School of Mind and Brain [Berlin], Humboldt University Of Berlin, University College Dublin [Dublin] (UCD), University of Vermont [Burlington], Biological Psychology, Universität Heidelberg [Heidelberg], Universität Mannheim [Mannheim], 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 Paris-Saclay, Humboldt-Universität zu Berlin, Developmental Psychopathology (RICDE, FMG), Methods and Statistics (RICDE, FMG), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] ( UKE ), King's College, MRC- SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 8AF, UK, Service NEUROSPIN ( NEUROSPIN ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Charite-Universitatsmedizin Berlin [Berlin], University of Nottingham, UK ( UON ), Centre de recherche biomédicale Bichat-Beaujon ( CRB3 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Cochin [AP-HP], Technische Universität Dresden ( TUD ), Humboldt Universität zu Berlin, and University College Dublin [Dublin] ( UCD )
Subjects: 0301 basic medicine, Male, Impulsivity, Adolescent, Poison control, Neuropsychological Tests, Development, Adversity, Brain mapping, Developmental psychology, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Surveys and Questionnaires, medicine, Reaction Time, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Temporal discounting, Antisocial behavior, Biological Psychiatry, ComputingMilieux_MISCELLANEOUS, Psychiatric Status Rating Scales, Analysis of Variance, Brain Mapping, [ INFO.INFO-IM ] Computer Science [cs]/Medical Imaging, Antisocial personality disorder, Ventral striatum, Brain, Voxel-based morphometry, Antisocial Personality Disorder, medicine.disease, Magnetic Resonance Imaging, Europe, 030104 developmental biology, medicine.anatomical_structure, Impulsive Behavior, Female, medicine.symptom, Psychology, Insula, 030217 neurology & neurosurgery
Abstract: BACKGROUND: Individual differences in impulsivity and early adversity are known to be strong predictors of adolescent antisocial behavior. However, the neurobiological bases of impulsivity and their relation to antisocial behavior and adversity are poorly understood.METHODS: Impulsivity was estimated with a temporal discounting task. Voxel-based morphometry was used to determine the brain structural correlates of temporal discounting in a large cohort (n = 1830) of 14- to 15-year-old children. Mediation analysis was then used to determine whether the volumes of brain regions associated with temporal discounting mediate the relation between adverse life events (e.g., family conflict, serious accidents) and antisocial behaviors (e.g., precocious sexual activity, bullying, illicit substance use).RESULTS: Greater temporal discounting (more impulsivity) was associated with 1) lower volume in frontomedial cortex and bilateral insula and 2) greater volume in a subcortical region encompassing the ventral striatum, hypothalamus and anterior thalamus. The volume ratio between these cortical and subcortical regions was found to partially mediate the relation between adverse life events and antisocial behavior.CONCLUSIONS: Temporal discounting is related to regions of the brain involved in reward processing and interoception. The results support a developmental imbalance model of impulsivity and are consistent with the idea that negative environmental factors can alter the developing brain in ways that promote antisocial behavior.
Published: 2016

26. Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

Author: Derek W. Morris, Carles Soriano-Mas, Tomáš Paus, Henrik Walter, Dick J. Veltman, Yuqi Cheng, Benjamin S. Aribisala, Anna Cattrell, Hilleke E. Hulshoff Pol, Vatche G. Baboyan, Simon E. Fisher, Michael N. Smolka, Saskia P. Hagenaars, Sarah Jurk, Roberto Roiz-Santiañez, Nicholas G. Martin, Lars T. Westlye, Odile A. van den Heuvel, Lucija Abramovic, Jan Egil Nordvik, Guillén Fernández, Jürgen Gallinat, Je Yeon Yun, Benson Mwangi, Ignacio Martínez-Zalacaín, Bernd Kraemer, Gareth J. Barker, José M. Menchón, Marie-Laure Paillère Martinot, Zhen Wang, Jan K. Buitelaar, Jean-Luc Martinot, Herve Lemaitre, Aiden Corvin, Henry Brodaty, Thomas Wolfers, Silvia Brem, Christine Lochner, Derrek P. Hibar, Susanne Walitza, Susana Muñoz Maniega, Premika S.W. Boedhoe, Nathalie Tzourio-Mazoyer, Uli Bromberg, Sonja M C de Zwarte, Dan J. Stein, Mark E. Bastin, Clyde Francks, Tobias U. Hauser, Sinead Kelly, Hugh Garavan, Omar Mothersill, Gary Donohoe, Neda Jahanshad, Greig I. de Zubicaray, Yoshinari Abe, Roel A. Ophoff, Christian Büchel, Esther Walton, Pieter J. Hoekstra, Nils Opel, Gunter Schumann, Jian Xu, Dara M. Cannon, Elena Shumskaya, Ingrid Agartz, Bernhard T. Baune, A. Marten H. Onnink, Tomohiro Nakao, Rosa Ayesa-Arriola, David Mataix-Cols, Sylvane Desrivières, Klaus-Peter Lesch, Paul Pauli, Wei Wen, Nora C. Vetter, Martine Hoogman, Ganesan Venkatasubramanian, Miguel E. Rentería, Ole A. Andreassen, Penny A. Gowland, Ian J. Deary, Patricia J. Conrod, Nicola J. Armstrong, Masaki Fukunaga, Vince D. Calhoun, Volker Arolt, Dimitri Papadopoulos Orfanos, Benedicto Crespo-Facorro, Lachlan T. Strike, Natalie A. Royle, Joanna M. Wardlaw, Sarah E. Medland, Annette Conzelmann, Andrea Gonzalez Suarez, Arun L.W. Bokde, Ryota Hashimoto, Robert Whelan, Michelle Luciano, Pascual Sánchez-Juan, Neeltje E.M. van Haren, Hao Hu, Luise Poustka, Jun Soo Kwon, Hans J. Grabe, Andreas Heinz, Katharina Wittfeld, Michael Gill, Erik G. Jönsson, Frauke Nees, Perminder S. Sachdev, Oliver Gruber, David C. Glahn, Chaim Huyser, Anushree Bose, Herta Flor, Janardhan Y. C. Reddy, Bernd Ittermann, John Blangero, Dennis van der Meer, Andre F. Marquand, Xiufeng Xu, Tulio Guadalupe, Dominik Grotegerd, Jessica A. Turner, Annerine Roos, Tobias Banaschewski, Theo G.M. vanErp, Jean-Paul Fouche, Paul M. Thompson, Alejandro Arias-Vasquez, Christopher D. Whelan, Maria del C. Valdés Hernández, Eric Artiges, Janardhanan C. Narayanaswaamy, Thomas Espeseth, Bernard Mazoyer, Katie L. McMahon, Erlend S. Dørum, Samantha J. Brooks, Samuel R. Mathias, Vincent Frouin, Fleur M. Howells, Barbara Franke, Colm McDonald, Jingjing Zhao, Daniella Vuletic, Nhat Trung Doan, Harald Kugel, Lianne Schmaal, Marcel P. Zwiers, Fabrice Crivello, Anne Uhlmann, Karen A. Mather, René S. Kahn, Roberto Toro, Stefan Ehrlich, Udo Dannlowski, Jair C. Soares, Takashi Nakamae, Margaret J. Wright, RS: MHeNs - R3 - Neuroscience, Psychiatrie & Neuropsychologie, Psychiatry, Anatomy and neurosciences, Amsterdam Neuroscience - Brain Imaging, Child Psychiatry, Other departments, ANS - Complex Trait Genetics, International Max Planck Research School for Language Sciences (IMPRS ), Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Language and Genetics Department [Nijmegen], Yale University [New Haven], Department of Psychiatry and Human Behavior, University of California [Irvine] (UCI), University of California-University of California, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Department of Psychiatry, Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan, University Medical Center [Utrecht], KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], University of Oslo (UiO), Department of Human Genetics, Radboud University Medical Center [Nijmegen], Department of Psychiatry, Donders Centre for Neuroscience, Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen], University of Edinburgh, Lagos State University (LASU), Heriot-Watt University [Edinburgh] (HWU), Mental Health Sciences Unit, University College of London [London] (UCL), Adolescent psychopathology and Medicine, CHU Cochin [AP-HP], Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Hospital Sant Joan de Déu [Barcelona], Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), University of Southern California (USC), Department of Child and Adolescent Psychiatry and Psychotherapy [Mannheim], Universität Heidelberg [Heidelberg], Centre for Neuroimaging Sciences, Institute of Psychiatry, King‘s College London, University of Adelaide, The University of Texas Health Science Center at Houston (UTHealth), Texas Biomedical Research Institute [San Antonio, Texas], Discipline of Psychiatry [Dublin], School of Medicine [Dublin], Trinity College Dublin-Trinity College Dublin, VU University Medical Center [Amsterdam], National Institute of Mental Health and Neurosciences [Bagalore, India], Hospital of the University of Pennsylvania, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Dementia Collaborative Research Centre, University of New South Wales [Sydney] (UNSW), Centre for Healthy Brain Ageing, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud university [Nijmegen]-Radboud university [Nijmegen], The Mind Research Network, Department of Electrical and Computer Engineering [Albuquerque] (ECE Department), The University of New Mexico [Albuquerque], Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Institute of Psychiatry, Psychology & Neuroscience, King's College London, Center for disease control, China (Chinese CDC), Center for Disease Control, China, Department of Psychology (Biological Psychology, Clinical Psychology, and Psychotherapy), University of Würzburg, Germany, Tübingen, Würzburg, Germany, Neuropsychiatric Genetics Research Group, Trinity College Dublin, Trinity College Dublin-St. James's Hospital, Groupe d'imagerie neurofonctionnelle (GIN), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), School of Psychology, University of Queensland, University of Queensland [Brisbane], MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Department of Psychology [Oslo], Faculty of Social Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), sans affiliation, Universität Mannheim [Mannheim], Service NEUROSPIN (NEUROSPIN), 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 Paris-Saclay, Division of Cerebral Integration National Institute for Physiological Sciences Okazaki Japan, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, University of Calgary, Sir Peter Mansfield Magnetic Resonance Centre [Nottingham], University of Nottingham, UK (UON), Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University [Osaka], University Clinic for Child and Adolescent Psychiatry (UCCAP), University of Zürich [Zürich] (UZH), University Medical Center Groningen [Groningen] (UMCG), Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital [Stockholm], Brain Centre Rudolf Magnus [Utrecht], MetaCase [Jyväskylä], Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany, Department of Psychiatry & Behavioral Science Seoul National University College of Medicine Seoul Republic of Korea, Université de Cergy Pontoise (UCP), Université Paris-Seine, Institute of Human Genetics, Rheinische Friedrich-Wilhelms-Universität Bonn, Medstar Research Institute, Neuroimagerie en psychiatrie (U1000), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), IFR de Neuroimagerie Fonctionnelle (IFR 49), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia, Department of Life Sciences, Imperial College London, Centre for Advanced Imaging, Queensland Institute of Medical Research, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Universitat de Barcelona (UB), National University of Ireland [Galway] (NUI Galway), Climate Change Unit [Ispra], JRC Institute for Environment and Sustainability (IES), European Commission - Joint Research Centre [Ispra] (JRC)-European Commission - Joint Research Centre [Ispra] (JRC), Sunnaas Rehabilitation Hospital HT Nesodden Norway, University Medical Center [Utrecht]-Brain Center Rudolf Magnus, McConnell Brain Imaging Centre (MNI), Montreal Neurological Institute and Hospital, McGill University-McGill University, Texas A&M University [College Station], QIMR Berghofer Medical Research Institute, Universiteit van Amsterdam (UvA), Centre for Healthy Brain Ageing [Sydney], The University of Sydney, CIBER de Enfermedades Neurodegenerativas (CIBERNED), Göttingen Zentrum Geowissenschaften, Georg-August-Universität Göttingen, Technische Universität Dresden (TUD), Instituto de Geociências, Universidade de Brasília, Magnetic Resonance Imaging, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa, Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia, School of Psychology, University of Queensland, Brisbane 4072, Australia, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], University of York [York, UK], Centre for Cognitive Ageing & Cognitive Epidemiology, Department of Anatomy & Neurosciences, VU University Medical Center, Amsterdam, The Netherlands, University of Twente [Netherlands], Berlin School of Mind and Brain [Berlin], Humboldt Universität zu Berlin, Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Computational and Applied Mathematics [Houston], Rice University [Houston], Department of Physics [Kowloon], Hong Kong University of Science and Technology (HKUST), University College Dublin [Dublin] (UCD), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Greifswald University Hospital, University of Missouri [Columbia], University of Missouri System, Mechanics surfaces and materials processing (MSMP), École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM), Department of Genetics, North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC)-University of North Carolina System (UNC), Dpt of Psychiatry [New Haven], Yale University School of Medicine, University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Radboud University [Nijmegen], Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universität Heidelberg [Heidelberg] = Heidelberg University, Texas Biomedical Research Institute [San Antonio, TX], University of Pennsylvania-University of Pennsylvania, Radboud University [Nijmegen]-Radboud University [Nijmegen], [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Sans affiliation, Universität Mannheim, Université Paris-Saclay-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), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Universität Zürich [Zürich] = University of Zurich (UZH), Seoul National University [Seoul] (SNU), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Georg-August-University = Georg-August-Universität Göttingen, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), University of Twente, Humboldt University Of Berlin, Centre épigénétique et destin cellulaire (EDC), Department of Physics [Hong Kong University of Science and Technology], University of Missouri [Columbia] (Mizzou), 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), Yale School of Medicine [New Haven, Connecticut] (YSM), Hal, GIN, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Georg-August-University [Göttingen], Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Humboldt-Universität zu Berlin, International Max Planck Research School for Language Sciences ( IMPRS ), Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen 6525 XD, The Netherlands, Department of Psychiatry Yale School of Medicine New Haven USA, University of California [Irvine] ( UCI ), Laboratory of Neuro Imaging, David Geffen School of Medicine, University of California, Los Angeles, California, USA, Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands, University of Oslo ( UiO ) -Institute of Clinical Medicine-Oslo University Hospital, NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway, Donders Centre for Neuroscience, Radboud University Nijmegen Medical Centre, Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK, Department of Computer Science, Lagos State University, Lagos, Nigeria, Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH4 2XU, UK, Heriot-Watt University [Edinburgh] ( HWU ), University College of London [London] ( UCL ), Centro de Investigación Biomédica en Red de Salud Mental ( CIBERSAM ), Cibersam (Centro Investigación Biomédica en Red Salud Mental), Madrid 28029, Spain, Imaging Genetics Center, Mark & Mary Stevens Neuroimaging & Informatics Institute, University of Southern California, Marina del Rey, CA, USA, The University of Adelaide, University of Texas Health Science Center, San Antonio, Texas 78229, USA, Texas Biomedical Research Institute, San Antonio, Texas 78245, USA, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India, Hospital of the University of Pennsylvania, University of New South Wales [Sydney] ( UNSW ), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] ( UKE ), The Mind Research Network & LBERI, Albuquerque, New Mexico 87106, USA, Department of ECE, University of New Mexico, Albuquerque, New Mexico 87131, USA, National Institutes of Health ( NIH ) -National Institute of Mental Health (NIMH), King's College, Center for disease control, China ( Chinese CDC ), GIN - IMN UMR 5293 CNRS CEA Université de Bordeaux, Institut des Maladies Neurodégénératives [Bordeaux] ( IMN ), Université de Bordeaux ( UB ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Bordeaux ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK, MRC- SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 8AF, UK, Institut Armand Frappier ( INRS-IAF ), Institut National de la Recherche Scientifique [Québec] ( INRS ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut Armand Frappier, NORMENT - KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0424, Norway, Institut national de la recherche agronomique [Jouy en Josas] ( INRA Jouy en Josas ), Department of Psychology, University of Oslo, Oslo 0373, Norway, Service NEUROSPIN ( NEUROSPIN ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Charite-Universitatsmedizin Berlin [Berlin], University of Nottingham, UK ( UON ), University Medicine Greifswald,-HELIOS Hospital Stralsund, Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University, Osaka 565-0871, Japan, (UCCAP) University of Zurich Zurich Switzerland, University Medical Center Groningen, University of Groningen, Karolinska University Hospital (Solna), Université de Cergy Pontoise ( UCP ), Bonn Universität [Bonn], Institut de Physique Nucléaire d'Orsay ( IPNO ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Neuroimagerie en psychiatrie ( U1000 ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), IFR de Neuroimagerie Fonctionnelle ( IFR 49 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] ( IDIBELL ), Universitat de Barcelona ( UB ), National University of Ireland [Galway] ( NUI Galway ), JRC Institute for Environment and Sustainability ( IES ), European Commission - Joint Research Centre [Ispra] ( JRC ) -European Commission - Joint Research Centre [Ispra] ( JRC ), University Medical Center Utrecht-Brain Center Rudolf Magnus, McConnell Brain Imaging Centre ( MNI ), Montreal Neurological Institute [Montréal], Universiteit van Amsterdam ( UvA ), The University of Sydney [Sydney], Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam 1081 HL, The Netherlands, Technische Universität Dresden ( TUD ), Génétique humaine et Fonctions cognitives - Human Genetics and Cognitive Functions, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Centre épigénétique et destin cellulaire ( EDC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Hong Kong University of Science and Technology ( HKUST ), University College Dublin [Dublin] ( UCD ), German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Greifswald 17487, Germany, Department of Psychiatry, University Medicine Greifswald, Greifswald 17489, Germany, University of Missouri-Columbia, Mechanics surfaces and materials processing ( MSMP ), North Carolina State University [Raleigh] ( NCSU ), and Yale School of Medicine
Subjects: Male, Aging, Planum temporale, Caudate nucleus, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Subcortical brain asymmetry, Functional Laterality, Behavioral Neuroscience, 0302 clinical medicine, pathology [Aging], ddc:150, 130 000 Cognitive Neurology & Memory, Basal ganglia, YOUNG-ADULTS, Brain asymmetry, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Handedness, Original Research, Sex Characteristics, Age, Enigma, Heritability, Meta-analysis, Sex, Putamen, 05 social sciences, Brain, Human brain, Organ Size, Middle Aged, Magnetic Resonance Imaging, AMYGDALA VOLUME, Psychiatry and Mental health, genetics [Functional Laterality], Globus pallidus, medicine.anatomical_structure, Neurology, BASAL GANGLIA VOLUMES, Radiology Nuclear Medicine and imaging, genetics [Aging], [ SCCO.NEUR ] Cognitive science/Neuroscience, CAUDATE-NUCLEUS, Female, Psychology, Sex characteristics, MRI, Neuroinformatics, Adult, Adolescent, Cognitive Neuroscience, Clinical Neurology, BF, HAND PREFERENCE, 050105 experimental psychology, 150 000 MR Techniques in Brain Function, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, Quantitative Trait, Heritable, Meta-Analysis as Topic, medicine, Journal Article, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, diagnostic imaging [Brain], Aged, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], [SCCO.NEUR]Cognitive science/Neuroscience, TOURETTE-SYNDROME, [SCCO.NEUR] Cognitive science/Neuroscience, PLANUM TEMPORALE, NORMAL INDIVIDUALS, HEMISPHERIC-DIFFERENCES, nervous system, RC0321, Neurology (clinical), Neuroscience, anatomy & histology [Brain], 030217 neurology & neurosurgery
Abstract: The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders. Electronic supplementary material The online version of this article (doi:10.1007/s11682-016-9629-z) contains supplementary material, which is available to authorized users.
Published: 2016

27. Route knowledge and configural knowledge in typical and atypical development: a comparison of sparse and rich environments

Author: Farran, EK, Purser, HRM, Courbois, Y, Ballé, M, Sockeel, P, Mellier, D, Blades, M, Université de Lille, Psychologie : Interactions, Temps, Émotions, Cognition (PSITEC) - ULR 4072, Psychologie : Interactions, Temps, Émotions, Cognition (PSITEC) - EA 4072, University College of London [London] [UCL], University of Nottingham, UK [UON], Psychologie : Interactions, Temps, Emotions, Cognition (PSITEC) - ULR 4072 [PSITEC], Université de Rouen Normandie [UNIROUEN], University of Sheffield [Sheffield], University College of London [London] (UCL), University of Nottingham, UK (UON), Psychologie : Interactions, Temps, Emotions, Cognition (PSITEC) - ULR 4072 (PSITEC), Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)
Subjects: [SCCO]Cognitive science, Research, Williams syndrome, Down syndrome, Development, Navigation, Spatial cognition
Abstract: Background:\ud \ud Individuals with Down syndrome (DS) and individuals with Williams syndrome (WS) have poor\ud navigation skills, which impact their potential to become independent. Two aspects of navigation were investigated\ud in these groups, using virtual environments (VE): route knowledge (the ability to learn the way from A to B by\ud following a fixed sequence of turns) and configural knowledge (knowledge of the spatial relationships between\ud places within an environment).\ud \ud Methods:\ud \ud Typically developing (TD) children aged 5 to 11 years (N = 93), individuals with DS (N = 29) and individuals\ud with WS (N = 20) were presented with a sparse and a rich VE grid maze. Within each maze, participants were asked to\ud learn a route from A to B and a route from A to C before being asked to find a novel shortcut from B to C.\ud \ud Results:\ud \ud Performance was broadly similar across sparse and rich mazes. The majority of participants were able to learn\ud novel routes, with poorest performance in the DS group, but the ability to find a shortcut, our measure of configural knowledge, was limited for all three groups. That is, 59 % TD participants successfully found a shortcut, compared to 10 % participants with DS and 35 % participants with WS. Differences in the underlying mechanisms associated with route knowledge and configural knowledge and in the developmental trajectories of performance across groups were observed. Only the TD participants walked a shorter distance in the last shortcut trial compared to the first, indicative of\ud increased configural knowledge across trials. The DS group often used an alternative strategy to get from B to C, summing the two taught routes together.\ud \ud Conclusions:\ud \ud Our findings demonstrate impaired configural knowledge in DS and in WS, with the strongest deficit in DS. This suggests that these groups rely on a rigid route knowledge based method for navigating and as a result are\ud likely to get lost easily. Route knowledge was also impaired in both DS and WS groups and was related to different underlying processes across all three groups. These are discussed with reference to limitations in attention and/or visuo-spatial processing in the atypical groups.
Published: 2015

28. Vibration modelling of complex waveguide structures

Author: C.H.J. Fox, Atanas A. Popov, Stewart McWilliam, Benjamin Chouvion, Faculty of Engineering [Nottingham], University of Nottingham, UK (UON), Materials, Mechanics and Structures Division, and University of Nottingham, UK (UON)-University of Nottingham, UK (UON)
Subjects: Engineering, Wave propagation, Acoustics, Structural system, 01 natural sciences, 010305 fluids & plasmas, [PHYS.MECA.STRU]Physics [physics]/Mechanics [physics]/Structural mechanics [physics.class-ph], Optics, Flexural strength, Waveguide dispersion, 0103 physical sciences, General Materials Science, 0101 mathematics, Civil and Structural Engineering, [PHYS.MECA.VIBR]Physics [physics]/Mechanics [physics]/Vibrations [physics.class-ph], Scattering, business.industry, Mechanical Engineering, [SPI.MECA.VIBR]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Vibrations [physics.class-ph], Finite element method, Computer Science Applications, 010101 applied mathematics, Vibration, Ray tracing (physics), [SPI.MECA.STRU]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Structural mechanics [physics.class-ph], Modeling and Simulation, business
Abstract: International audience; In this paper, a general wave propagation approach for the vibration analysis of three-dimensional waveguide structures is presented. The analysis is based on a ray tracing method that considers wave propagation and scattering in the formulation, including the effects of decaying near-field wave components. The waveguide dispersion characteristics of straight and curved beams, which govern the propagation and decay of waves as they travel through the different components, are taken into account for different wave types (flexural, torsional, and axial). Separate elements are coupled using reflection and transmission coefficients, and these are derived for a general connection between several non-planar elements. A matrix formulation is used that offers an automatic and concise method for tackling free and forced vibrations problems of complex ring-beam structural systems. The general methodology is demonstrated on simple applications, and the predictions made using the proposed approach are shown to be in excellent agreement with a conventional finite element analysis, with the advantage of reduced computational costs.
Published: 2011

29. Serial small- and wide-angle X-ray scattering with laboratory sources

Author: Mark A. Levenstein, Karen Robertson, Thomas D. Turner, Liam Hunter, Cate O'Brien, Cedrick O'Shaughnessy, Alexander N. Kulak, Pierre Le Magueres, Jakub Wojciechowski, Oleksandr O. Mykhaylyk, Nikil Kapur, Fiona C. Meldrum, Laboratoire Interdisciplinaire sur l'Organisation Nanométrique et Supramoléculaire (LIONS), Nanosciences et Innovation pour les Matériaux, la Biomédecine et l'Energie (ex SIS2M) (NIMBE UMR 3685), Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Nottingham, UK (UON), School of Chemistry [Leeds], University of Leeds, University of Sheffield [Sheffield], Rigaku Americas Corporation, Rigaku Europe, The Engineering and Physical Sciences Research Council UK (EPSRC) for funding a Strategic Equipment Grant for Flow-Xl (grant No. EP/T006331/1 supporting KR, NK, FCM and TT), Programme Grant which funds the Crystallization in the Real World Consortium (grant No. EP/R018820/1 supporting CO’S and FCM), and European Project: 788968,DYNAMIN
Subjects: crystallization, microfluidics, General Materials Science, [CHIM.MATE]Chemical Sciences/Material chemistry, [PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph], General Chemistry, serial WAXS, Condensed Matter Physics, rapid structural analysis, Biochemistry, serial SAXS
Abstract: International audience; Recent advances in X-ray instrumentation and sample injection systems have enabled serial crystallography of protein nanocrystals and the rapid structural analysis of dynamic processes. However, this progress has been restricted to large-scale X-ray free-electron laser (XFEL) and synchrotron facilities, which are often oversubscribed and have long waiting times. Here, we explore the potential of state-of-the-art laboratory X-ray systems to perform comparable analyses when coupled to micro- and millifluidic sample environments. Our results demonstrate that commercial small- and wide-angle X-ray scattering (SAXS/WAXS) instruments and X-ray diffractometers are ready to access samples and timescales (≳5 ms) relevant to many processes in materials science including the preparation of pharmaceuticals, nanoparticles and functional crystalline materials. Tests of different X-ray instruments highlighted the importance of the optical configuration and revealed that serial WAXS/XRD analysis of the investigated samples was only possible with the higher flux of a microfocus setup. We expect that these results will also stimulate similar developments for structural biology.
Published: 2022

30. In-plane free vibration analysis of combined ring-beam structural systems by wave propagation

Author: Benjamin Chouvion, Stewart McWilliam, Atanas A. Popov, C.H.J. Fox, Faculty of Engineering [Nottingham], University of Nottingham, UK (UON), Materials, Mechanics and Structures Division, and University of Nottingham, UK (UON)-University of Nottingham, UK (UON)
Subjects: Acoustics and Ultrasonics, Wave propagation, Structural system, 02 engineering and technology, Classification of discontinuities, 01 natural sciences, [PHYS.MECA.STRU]Physics [physics]/Mechanics [physics]/Structural mechanics [physics.class-ph], Optics, Normal mode, 0103 physical sciences, 010301 acoustics, Mathematics, [PHYS.MECA.VIBR]Physics [physics]/Mechanics [physics]/Vibrations [physics.class-ph], Microelectromechanical systems, business.industry, Mechanical Engineering, Mathematical analysis, [SPI.MECA.VIBR]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Vibrations [physics.class-ph], 021001 nanoscience & nanotechnology, Condensed Matter Physics, Vibration, Ray tracing (physics), [SPI.MECA.STRU]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Structural mechanics [physics.class-ph], Mechanics of Materials, 0210 nano-technology, business, Beam (structure)
Abstract: International audience; This paper presents a systematic, wave propagation approach for the free vibration analysis of networks consisting of slender, straight and curved beam elements and complete rings. The analysis is based on a ray tracing method and a procedure to predict the natural frequencies and mode shapes of complex ring/beam networks is demonstrated. In the wave approach, the elements are coupled using reflection and transmission coefficients, and these are derived for discontinuities encountered in a MEMS rate sensor consisting of a ring supported on an array of folded beams. These are combined, taking into account wave propagation and decay, to provide a concise and efficient method for studying the free vibration problem. A simplification of the analysis that exploits cyclic symmetry in the structure is also presented. The effects of decaying near-field wave components are included in the formulation, ensuring that the solutions are exact. To illustrate the effectiveness of the approach, several numerical examples are presented. The predictions made using the proposed approach are shown to be in excellent agreement with a conventional FE analysis.
Published: 2010

31. Exploitation of a Type 1 Toxin–Antitoxin System as an Inducible Counter-Selective Marker for Genome Editing in the Acetogen Eubacterium limosum

Author: James Millard, Alexander Agius, Ying Zhang, Philippe Soucaille, Nigel Peter Minton, University of Nottingham, UK (UON), Toulouse Biotechnology Institute (TBI), 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 de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), UK Research & Innovation (UKRI)Biotechnology and Biological Sciences Research Council (BBSRC)BB/T010630/1BB/L013940/1, and ANR-17-COBI-0002,BIOMETCHEM,Une approche de biologie des systèmes et de biologie synthétique pour la production durable de produits chimiques par fermentation anaérobie du méthanol issu de la gazéification de la biomasse(2017)
Subjects: Microbiology (medical), RelBE, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Eubacterium limosum, Eubacterium callanderi, gene editing, Virology, CRISPR, [SDV]Life Sciences [q-bio], toxin–antitoxin systems, Microbiology, toxin-antitoxin systems
Abstract: International audience; Targeted mutations in the anaerobic methylotroph Eubacterium limosum have previously been obtained using CRISPR-based mutagenesis methods. In this study, a RelB-family toxin from Eubacterium callanderi was placed under the control of an anhydrotetracycline-sensitive promoter, forming an inducible counter-selective system. This inducible system was coupled with a nonreplicative integrating mutagenesis vector to create precise gene deletions in Eubacterium limosum B2. The genes targeted in this study were those encoding the histidine biosynthesis gene hisI, the methanol methyltransferase and corrinoid protein mtaA and mtaC, and mtcB, encoding an Mttb-family methyltransferase which has previously been shown to demethylate L-carnitine. A targeted deletion within hisI brought about the expected histidine auxotrophy, and deletions of mtaA and mtaC both abolished autotrophic growth on methanol. Deletion of mtcB was shown to abolish the growth of E. limosum on L-carnitine. After an initial selection step to isolate transformant colonies, only a single induction step was required to obtain mutant colonies for the desired targets. The combination of an inducible counter-selective marker and a non-replicating integrative plasmid allows for quick gene editing of E. limosum.
Published: 2023
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32. Climate and land-use shape the spread of zoonotic yellow fever virus

Author: Sarah C. Hill, Simon Dellicour, Ingra M. Claro, Patricia C. Sequeira, Talita Adelino, Julien Thézé, Chieh-Hsi Wu, Filipe Romero Rebello Moreira, Marta Giovanetti, Sabrina L. Li, Jaqueline G. de Jesus, Felipe J. Colón-González, Heather R. Chamberlain, Oliver Pannell, Natalia Tejedor-Garavito, Fernanda de Bruycker-Nogueira, Allison A. Fabri, Maria Angélica Mares-Guia, Joilson Xavier, Alexander E. Zarebski, Arran Hamlet, Maria Anice Mureb Sallum, Antonio C. da Costa, Erika R. Manuli, Anna S. Levin, Luís Filipe Mucci, Rosa Maria Tubaki, Regiane Maria Tironi de Menezes, Juliana Telles de Deus, Roberta Spinola, Leila Saad, Esper G. Kallas, G.R. William Wint, Pedro S. Peixoto, Andreza Aruska de Souza Santos, Jane P. Messina, Oliver J. Brady, Andrew J. Tatem, Marc A. Suchard, Jairo A. Mendez-Rico, André Abreu, Renato Santana Aguiar, Oliver G. Pybus, Guy Baele, Philippe Lemey, Felipe Iani, Mariana S. Cunha, Ana M. Bispo de Filippis, Ester C. Sabino, Nuno R. Faria, Royal Veterinary College [London], University of London [London], Department of Zoology, University of Oxford, Spatial Epidemiology Lab (SpELL), Université libre de Bruxelles (ULB), Rega Institute for Medical Research [Leuven, België], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Faculdade de Medicina da Universidade de São Paulo [São Paulo, Brésil], The Abdul Latif Jameel Institute for Disease and Emergency Analytics, Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Fundação Ezequiel Dias (FUNED), Unité Mixte de Recherche d'Épidémiologie des maladies Animales et zoonotiques (UMR EPIA), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), School of Mathematics [Southampton], University of Southampton, Institute for Life Sciences, Laboratório de Biologia Molecular de Flavivírus [Rio de Janeiro], Instituto Oswaldo Cruz / Oswaldo Cruz Institute [Rio de Janeiro] (IOC), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Universidade Federal de Minas Gerais = Federal University of Minas Gerais [Belo Horizonte, Brazil] (UFMG), School of Geography and the Environment [Oxford] (SoGE), School of Geography [Nottingham], University of Nottingham, UK (UON), Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population, Instituto de Ciências Biológicas [Goiânia, Brésil] (ICB), Imperial College London, Unité de Catalyse et Chimie du Solide - UMR 8181 (UCCS), Université d'Artois (UA)-Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Department of Zoology [Oxford]
Subjects: [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: Zoonotic viruses that originate in wildlife harm global human health and economic prosperity1. Understanding virus transmission at the human-animal-environment interface is a key component of pandemic risk-reduction2,3. Zoonotic disease emergence is highest in biodiverse, tropical forests undergoing intensive land-use change4,5. Phylodynamic analyses of virus genomes can powerfully test epidemiological hypotheses, but are rarely applied to viruses of animals inhabiting these habitats. Brazil’s densely-populated Atlantic Forest and Cerrado region experienced in 2016–2021 an explosive human outbreak of sylvatic yellow fever, caused by repeated virus spillover from wild neotropical primates6. Here we use yellow fever virus (YFV) genome sequences and epidemiological data from neotropical primates, humans, and mosquito vectors to identify the environmental, demographic, and climatic factors determining zoonotic virus spread. Using portable sequencing approaches we generated 498 YFV genomes, resulting in a well-sampled dataset of zoonotic virus genomes sampled from wild mammals. YFV dispersal velocity was slower at higher elevation, in colder regions, and further away from main roads. Virus lineage dispersal was more frequent through wetter areas, areas with high neotropical primate density and through landscapes covered by mosaic vegetation. Higher temperatures were associated with higher virus effective population sizes, and peaks of transmission in warmer, wetter seasons were associated with higher virus evolutionary rates. Our study demonstrates how zoonotic disease transmission is linked to land-use and climate, underscoring the need for One-Health approaches to reducing the rate of zoonotic spillover.
Published: 2023

33. Isolation and Characterization of a Novel Phage Collection against Avian-Pathogenic Escherichia coli

Author: Marianne Nicolas, Angélina Trotereau, Antoine Culot, Arshnee Moodley, Robert Atterbury, Jeroen Wagemans, Rob Lavigne, Philippe Velge, Catherine Schouler, Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Rime Bioinformatics SAS, University of Copenhagen = Københavns Universitet (UCPH), University of Nottingham, UK (UON), Laboratory of Gene Technology, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), DGAL through the EcoAntibio2 COLIPHAVI project, M.N. was supported by a Ph.D. stipend from Tours University. A.T. was supported by a training grant from the Federation de Recherche en Infectiologie (FeRI)., ANR-14-ANWA-0003,AntibioPhage,A bacteriophage-based approach to reducing infections caused by antibiotic resistant Escherichia coli(2014), and European Project: 291815,EC:FP7:KBBE,FP7-ERANET-2011-RTD,ANIHWA(2012)
Subjects: Microbiology (medical), [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, General Immunology and Microbiology, Ecology, Physiology, Escherichia coli, Genetics, bacteriophage therapy, Cell Biology, genome analysis
Abstract: The increase in antibiotic-resistant avian-pathogenic Escherichia coli (APEC), the causative agent of colibacillosis in poultry, warrants urgent research and the development of alternative therapies. This study describes the isolation and characterization of 19 genetically diverse, lytic coliphages, 8 of which were tested in combination for their efficacy in controlling in ovo APEC infections. Genome homology analysis revealed that the phages belong to nine different genera, one of them being a novel genus (Nouzillyvirus). One phage, REC, was derived from a recombination event between two Phapecoctavirus phages (ESCO5 and ESCO37) isolated in this study. Twenty-six of the 30 APEC strains tested were lysed by at least one phage. Phages exhibited varying infectious capacities, with narrow to broad host ranges. The broad host range of some phages could be partially explained by the presence of receptor-binding protein carrying a polysaccharidase domain. To demonstrate their therapeutic potential, a phage cocktail consisting of eight phages belonging to eight different genera was tested against BEN4358, an APEC O2 strain. In vitro, this phage cocktail fully inhibited the growth of BEN4358. In a chicken lethality embryo assay, the phage cocktail enabled 90% of phage-treated embryos to survive infection with BEN4358, compared with 0% of nontreated embryos, indicating that these novel phages are good candidates to successfully treat colibacillosis in poultry. IMPORTANCE Colibacillosis, the most common bacterial disease affecting poultry, is mainly treated by antibiotics. Due to the increased prevalence of multidrug-resistant avian-pathogenic Escherichia coli, there is an urgent need to assess the efficacy of alternatives to antibiotherapy, such as phage therapy. Here, we have isolated and characterized 19 coliphages that belong to nine phage genera. We showed that a combination of 8 of these phages was efficacious in vitro to control the growth of a clinical isolate of E. coli. Used in ovo, this phage combination allowed embryos to survive APEC infection. Thus, this phage combination represents a promising treatment for avian colibacillosis. ispartof: MICROBIOLOGY SPECTRUM vol:11 issue:3 ispartof: location:United States status: Published online
Published: 2023

34. Increased Clinical Signs and Mortality in IFNAR(−/−) Mice Immunised with the Bluetongue Virus Outer-Capsid Proteins VP2 or VP5, after Challenge with an Attenuated Heterologous Serotype

Author: Houssam Attoui, Fauziah Mohd Jaafar, Baptiste Monsion, Bernard Klonjkowski, Elizabeth Reid, Petra C. Fay, Keith Saunders, George Lomonossoff, David Haig, Peter P. C. Mertens, Virologie UMR1161 (VIRO), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Nottingham, UK (UON), Department of Biological Chemistry, John Innes Centre, Norwich, UK, John Innes Centre [Norwich], Biotechnology and Biological Sciences Research Council (BBSRC)-Biotechnology and Biological Sciences Research Council (BBSRC)-University of East Anglia [Norwich] (UEA), and European Project: 727393,H2020,H2020-EU.3.2.1.1.,PALE-Blu(2017)
Subjects: Microbiology (medical), Infectious Diseases, General Immunology and Microbiology, bluetongue virus (BTV), vaccination, VP2, VP5, heterologous serotype challenge, [SDV]Life Sciences [q-bio], Immunology and Allergy, Molecular Biology
Abstract: International audience; Bluetongue is an economically important disease of domesticated and wild ruminants caused by bluetongue virus (BTV). There are at least 36 different serotypes of BTV (the identity of which is determined by its outer-capsid protein VP2), most of which are transmitted by Culicoides biting midges. IFNAR(−/−) mice immunised with plant-expressed outer-capsid protein VP2 (rVP2) of BTV serotypes -1, -4 or -8, or the smaller outer-capsid protein rVP5 of BTV-10, or mock-immunised with PBS, were subsequently challenged with virulent strains of BTV-4 or BTV-8, or with an attenuated clone of BTV-1 (BTV-1RGC7). The mice that had received rVP2 generated a protective immune response against the homologous BTV serotype, reducing viraemia (as detected by qRT-PCR), the severity of clinical signs and mortality levels. No cross-serotype protection was observed after challenge with the heterologous BTV serotypes. However, the severity of clinical signs, viraemia and fatality levels after challenge with the attenuated strain of BTV-1 were all increased in mice immunised with rVP2 of BTV-4 and BTV-8, or with rVP5 of BTV10. The possibility is discussed that non-neutralising antibodies, reflecting serological relationships between the outer-capsid proteins of these different BTV serotypes, could lead to ‘antibody-dependent enhancement of infection’ (ADE). Such interactions could affect the epidemiology and emergence of different BTV strains in the field and would therefore be relevant to the design and implementation of vaccination campaigns.
Published: 2023
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35. The replicative DnaE polymerase of $Bacillus\ subtilis$ recruits the glycolytic Pyruvate Kinase (PykA) when bound to primed DNA templates

Author: Alexandria Holland, Matthaios Pitoulias, Panos Soultanas, Laurent Janniere, University of Nottingham, UK (UON), Génomique métabolique (UMR 8030), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-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 Paris-Saclay-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 d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), and BBSRC
Subjects: microbiology, metabolism, replication, PykA, DnaE, moonlighting activity, Space and Planetary Science, [SDV]Life Sciences [q-bio], Paleontology, General Biochemistry, Genetics and Molecular Biology, Ecology, Evolution, Behavior and Systematics
Abstract: International audience; The glycolytic enzyme PykA has been reported to drive the metabolic control of replication through a mechanism involving PykA moonlighting functions on the essential DnaE polymerase, the DnaC helicase and regulatory determinants of PykA catalytic activity in Bacillus subtilis. The mutants of this control suffer from critical replication and cell cycle defects, showing that the metabolic control of replication plays important functions in the overall rate of replication. Using biochemical approaches, we demonstrate here that PykA interacts with DnaE for modulating its activity when the replication enzyme is bound to a primed DNA template. This interaction is mediated by the CAT domain of PykA and possibly allosterically regulated by its PEPut domain, which also operates as a potent regulator of PykA catalytic activity. Furthermore, using fluorescence microscopy we show that the CAT and PEPut domains are important for the spatial localization of origins and replication forks, independently of their function in PykA catalytic activity. Collectively, our data suggest that the metabolic control of replication depends on the recruitment of PykA by DnaE at sites of DNA synthesis. This recruitment is likely highly dynamic, as DnaE is frequently recruited to and released from replication machineries to extend the several thousand RNA primers generated from replication initiation to termination. This implies that PykA and DnaE continuously associate and dissociate at replication machineries for ensuring a highly dynamic coordination of the replication rate with metabolism.
Published: 2023

36. Genesis and development of an interfluvial peatland in the central Congo Basin since the Late Pleistocene

Author: Donna Hawthorne, Ian T. Lawson, Greta C. Dargie, Yannick E. Bocko, Suspense A. Ifo, Yannick Garcin, Enno Schefuß, William Hiles, Antonio Jonay Jovani-Sancho, Genevieve Tyrrell, George E. Biddulph, Arnoud Boom, Brian M. Chase, Pauline Gulliver, Susan E. Page, Katherine H. Roucoux, Sofie Sjögersten, Dylan M. Young, Simon L. Lewis, University of St Andrews [Scotland], University of Leeds, Université Marien Ngouabi, Centre européen de recherche et d'enseignement des géosciences de l'environnement (CEREGE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Bremen, University of Nottingham, UK (UON), University of Leicester, NERC, University of St Andrews. Environmental Change Research Group, University of St Andrews. School of Geography & Sustainable Development, and University of St Andrews. Bell-Edwards Geographic Data Institute
Subjects: Swamp, MCC, Archeology, Global and Planetary Change, Vegetation, GE, Holocene, Climate, Peat, Palaeoecology, Geology, DAS, QE Geology, Congo Basin, Tropical forest, Africa, [SDE]Environmental Sciences, Pollen, QE, Ecology, Evolution, Behavior and Systematics, GE Environmental Sciences
Abstract: Funding: The core collection fieldwork was funded by the Royal Society, to S.L.L., Philip Leverhulme Prize to S.L.L. and a NERC CASE award to S.L.L. and G.C.D. The laboratory analysis, data analysis and write-up was funded by CongoPeat, a NERC Large Grant (NE/R016860/1) to S.L.L., I.T.L., A.B., S.E.P., P.G., supporting D.H., G.T., G.C.D., W.H., G.E.B., and Y.E.B.; and NERC Radiocarbon Facility grant (alloc. no. 1688.0313 and 1797.0414) to I.T.L., S.L.L. and G.C.D. Y. G. was supported by the Agence Nationale de la Recherche (ANR) grant ANR-19-CE01-0022. E.S. was supported by the Deutsche Forschungsgemeinschaft (DFG) grant SCHE 903/19–1 and the DFG-Cluster of Excellence ‘The Ocean in the Earth System’ at MARUM. The central Congo Basin contains the largest known peatland complex in the tropics. Here we present a detailed multi-proxy record from a peat core, CEN-17.4, from the centre of a 45 km wide interfluvial peatland (Ekolongouma), the first record of its kind from the central Congo peatlands. We use pollen, charcoal, sedimentological and geochemical data to reconstruct the site's history from the late Pleistocene to the present day. Peat began accumulating at the centre of the peatland ∼19,600 cal BP (∼17,500–20,400 cal BP, 95% confidence interval), and between ∼9500 (9430–9535 cal BP) and 10,500 (10,310–10,660 cal BP) cal BP towards the margins. Pollen data from the peatland centre show that an initial grass- and sedge-dominated vegetation, which burned frequently, was replaced by a Manilkara-type dominated flooded forest at ∼12,640 cal BP, replaced in turn by a more mixed swamp forest at ∼9670 cal BP. Mixed swamp forest vegetation has persisted to the present day, with variations in composition and canopy openness likely caused at least in part by changes in palaeo-precipitation. Stable isotope data (δDn-C29-v&icecorr) indicate a large reduction in precipitation beginning ∼5000 and peaking ∼2000 cal BP, associated with the near-complete mineralization of several metres of previously accumulated peat and with a transition to a drier, more heliophilic swamp forest assemblage, likely with a more open canopy. Although the peatland and associated vegetation recovered from this perturbation, the strong response to this climatic event underlines the ecosystem's sensitivity to changes in precipitation. We find no conclusive evidence for anthropogenic activity in our record; charcoal is abundant only in the Pleistocene part of the record and may reflect natural rather than anthropogenic fires. We conclude that autogenic succession and variation in the amount and seasonality of precipitation have been the most important drivers of ecological change in this peatland since the late Pleistocene. Publisher PDF
Published: 2023

37. ERS International Congress 2022: highlights from the Basic and Translational Science Assembly

Author: Sara Cuevas Ocaña, Natalia El-Merhie, Merian E. Kuipers, Mareike Lehmann, Sara Rolandsson Enes, Carola Voss, Lareb S.N. Dean, Matthew Loxham, Agnes W. Boots, Suzanne M. Cloonan, Catherine M. Greene, Irene H. Heijink, Audrey Joannes, Arnaud A. Mailleux, Nahal Mansouri, Niki L. Reynaert, Anne M. van der Does, Darcy E. Wagner, Niki Ubags, University of Nottingham, UK (UON), Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Leiden University Medical Center (LUMC), Universiteit Leiden, Philipps Universität Marburg = Philipps University of Marburg, Helmholtz Munich, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Lund University [Lund], University of Southampton, Maastricht University [Maastricht, Pays-Bas], Trinity College Dublin, Royal College of Surgeons in Ireland (RCSI), University of Groningen [Groningen], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Ecole Polytechnique Fédérale de Lausanne (EPFL), School of Nutrition and Translational Research in Metabolism [Maastricht] (NUTRIM), and Maastricht University [Maastricht]
Subjects: Pulmonary and Respiratory Medicine, CELL-DEATH, MOLECULAR-MECHANISMS, [SDV]Life Sciences [q-bio], NOMENCLATURE COMMITTEE, AIR-POLLUTION, BRONCHOPULMONARY DYSPLASIA, MATERNAL VASCULAR UNDERPERFUSION, COMPREHENSIVE ANALYSIS, LUNG, DISEASE, RECOMMENDATIONS
Abstract: International audience; In this review, the Basic and Translational Science Assembly of the European Respiratory Society provides an overview of the 2022 International Congress highlights. We discuss the consequences of respiratory events from birth until old age regarding climate change related alterations in air quality due to pollution caused by increased ozone, pollen, wildfires and fuel combustion as well as the increasing presence of microplastic and microfibres. Early life events such as the effect of hyperoxia in the context of bronchopulmonary dysplasia and crucial effects of the intrauterine environment in the context of pre-eclampsia were discussed. The Human Lung Cell Atlas (HLCA) was put forward as a new point of reference for healthy human lungs. The combination of single-cell RNA sequencing and spatial data in the HLCA has enabled the discovery of new cell types/states and niches, and served as a platform that facilitates further investigation of mechanistic perturbations. The role of cell death modalities in regulating the onset and progression of chronic lung diseases and its potential as a therapeutic target was also discussed. Translational studies identified novel therapeutic targets and immunoregulatory mechanisms in asthma. Lastly, it was highlighted that the choice of regenerative therapy depends on disease severity, ranging from transplantation to cell therapies and regenerative pharmacology.
Published: 2023

38. Auxin Influx Activity Is Associated with Frankia Infection during Actinorhizal Nodule Formation in Casuarina glauca

Author: Ranjan Swarup, Florence Auguy, Didier Bogusz, Benjamin Péret, Gaëlle Devos, Leentje Jansen, Myriam Collin, Laurent Laplaze, Malcolm J. Bennett, Carole Santi, Valérie Hocher, Claudine Franche, Centre for Plant Integrative Biology [Nothingham] (CPIB), University of Nottingham, UK (UON), UMR - Interactions Plantes Microorganismes Environnement (UMR IPME), Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Diversité, adaptation, développement des plantes (UMR DIADE), Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Laboratoire Génome et développement des plantes (LGDP), Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Diversité et adaptation des plantes cultivées (UMR DIAPC), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Ecole Nationale Vétérinaire de Lyon (ENVL), Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Centre for Plant Integrative Biology [Nothingham] ( CPIB ), University of Nottingham, UK ( UON ), UMR - Interactions Plantes Microorganismes Environnement ( UMR IPME ), Centre de Coopération Internationale en Recherche Agronomique pour le Développement ( CIRAD ) -Université de Montpellier ( UM ) -Institut de Recherche pour le Développement ( IRD [France-Sud] ), Ecologie microbienne ( EM ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Vétérinaire de Lyon ( ENVL ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique ( INRA ) -VetAgro Sup ( VAS ), Diversité, adaptation, développement des plantes ( DIADE ), Centre de Coopération Internationale en Recherche Agronomique pour le Développement ( CIRAD ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD [France-Sud] ), Laboratoire Génome et développement des plantes ( LGDP ), Université de Perpignan Via Domitia ( UPVD ) -Centre National de la Recherche Scientifique ( CNRS ), Diversité et adaptation des plantes cultivées ( DIAPC ), Centre de Coopération Internationale en Recherche Agronomique pour le Développement ( CIRAD ) -Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ), and Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, [ SDV.BV ] Life Sciences [q-bio]/Vegetal Biology, MESH : Molecular Sequence Data, Casuarinaceae, Root nodule, NODULATION, MESH: Sequence Homology, Amino Acid, Physiology, MESH: Glycolates, Frankia, Arabidopsis, MESH : Symbiosis, Gene Expression, MESH: Amino Acid Sequence, Plant Science, 01 natural sciences, MESH : Arabidopsis Proteins, MESH : Arabidopsis, MESH: Genes, Plant, Arabidopsis thaliana, MESH: Arabidopsis, MESH: Angiosperms, chemistry.chemical_classification, MESH: Genetic Complementation Test, 0303 health sciences, MESH: Symbiosis, biology, MESH : Amino Acid Sequence, food and beverages, MESH: Frankia, MESH : Indoleacetic Acids, Arts and Architecture, MESH : Sequence Homology, Amino Acid, Cell biology, MESH: Root Nodules, Plant, MESH : Angiosperms, Multigene Family, WHITE CLOVER, MESH : Carrier Proteins, Root Nodules, Plant, Actinorhizal plant, Research Article, EXPRESSION, Auxin influx, MESH: Indoleacetic Acids, MESH: Gene Expression, Molecular Sequence Data, MESH : Multigene Family, MESH: Carrier Proteins, MESH: Arabidopsis Proteins, TREE ALLOCASUARINA-VERTICILLATA, Genes, Plant, MESH : Glycolates, Magnoliopsida, MESH : Root Nodules, Plant, 03 medical and health sciences, Auxin, Botany, Genetics, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, CORTICAL-CELLS, Amino Acid Sequence, Symbiosis, LATERAL ROOT DEVELOPMENT, MESH : Genes, Plant, 030304 developmental biology, MESH: Molecular Sequence Data, FUNCTIONAL-ANALYSIS, Indoleacetic Acids, Sequence Homology, Amino Acid, MESH : Genetic Complementation Test, Arabidopsis Proteins, MESH : Frankia, Genetic Complementation Test, fungi, MEDICAGO-TRUNCATULA, biology.organism_classification, TRANSPORT, Glycolates, MESH : Gene Expression, chemistry, ARABIDOPSIS-THALIANA, MESH: Multigene Family, Carrier Proteins, 010606 plant biology & botany
Abstract: Plants from the Casuarinaceae family enter symbiosis with the actinomycete Frankia leading to the formation of nitrogen-fixing root nodules. We observed that application of the auxin influx inhibitor 1-naphtoxyacetic acid perturbs actinorhizal nodule formation. This suggests a potential role for auxin influx carriers in the infection process. We therefore isolated and characterized homologs of the auxin influx carrier (AUX1-LAX) genes in Casuarina glauca. Two members of this family were found to share high levels of deduced protein sequence identity with Arabidopsis (Arabidopsis thaliana) AUX-LAX proteins. Complementation of the Arabidopsis aux1 mutant revealed that one of them is functionally equivalent to AUX1 and was named CgAUX1. The spatial and temporal expression pattern of CgAUX1 promoter:β-glucuronidase reporter was analyzed in Casuarinaceae. We observed that CgAUX1 was expressed in plant cells infected by Frankia throughout the course of actinorhizal nodule formation. Our data suggest that auxin plays an important role during plant cell infection in actinorhizal symbioses.
Published: 2007

39. Cannabis use in early adolescence: Evidence of amygdala hypersensitivity to signals of threat

Author: Tomáš Paus, Tobias Banaschewski, Bernd Ittermann, Bader Chaarani, Frauke Nees, Hugh Garavan, Christian Büchel, Anna Cattrell, Scott Mackey, Gunter Schumann, Vincent Frouin, Jürgen Gallinat, Philip A. Spechler, Uli Bromberg, Henrik Walter, Michael N. Smolka, Stephen T. Higgins, Penny A. Gowland, Catherine Orr, Herta Flor, Luise Poustka, Kees-Jan Kan, Mitchell P. Snowe, Dimitri Papadopoulos, Aaron Morton, Jean-Luc Martinot, Arun L.W. Bokde, Patricia J. Conrod, Kelsey Hudson, Robert Whelan, Eric Artiges, Andreas Heinz, Robert R. Althoff, Animal Husbandry, Animal Science Group of Wageningen UR, Computer Vision and Multimedia Laboratory [Geneve] (CVML), Université de Genève = University of Geneva (UNIGE), Institute of Ecology, Evolution and Diversity, Frankfurt, Goethe-University Frankfurt am Main-Goethe-Universität Frankfurt am Main, Department of Child and Adolescent Psychiatry and Psychotherapy [Mannheim], Universität Heidelberg [Heidelberg] = Heidelberg University, Discipline of Psychiatry [Dublin], School of Medicine [Dublin], Trinity College Dublin-Trinity College Dublin, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-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), Sir Peter Mansfield Magnetic Resonance Centre [Nottingham], University of Nottingham, UK (UON), McConnell Brain Imaging Centre (MNI), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Neuroimagerie en psychiatrie (U1000), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Adolescent psychopathology and Medicine, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Technische Universität Dresden = Dresden University of Technology (TU Dresden), University of Vermont [Burlington], IMAGEN Consortium, Computer Vision and Multimedia Laboratory [Geneve] ( CVML ), Université de Genève ( UNIGE ), Goethe-University Frankfurt am Main-Goethe University, Universität Heidelberg [Heidelberg], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] ( UKE ), King's College, Service NEUROSPIN ( NEUROSPIN ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, University of Nottingham, UK ( UON ), McConnell Brain Imaging Centre ( MNI ), Montreal Neurological Institute [Montréal], McGill University-McGill University, Neuroimagerie en psychiatrie ( U1000 ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), CHU Cochin [AP-HP], Technische Universität Dresden ( TUD ), Université de Montréal. Faculté de médecine. Département de psychiatrie et d'addictologie, Université de Genève (UNIGE), 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 Paris-Saclay, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), and Technische Universität Dresden (TUD)
Subjects: Male, Marijuana Abuse, Cannabinoid receptor, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit, Functional Laterality, Developmental psychology, Longitudinal Studies, Faces, Reactivity (psychology), ComputingMilieux_MISCELLANEOUS, Cerebral Cortex, Intelligence Tests, Intelligence quotient, biology, [ INFO.INFO-IM ] Computer Science [cs]/Medical Imaging, lcsh:QP351-495, Smoking, fMRI, Fear, Amygdala, Magnetic Resonance Imaging, Adolescence, Facial Expression, Alcoholism, medicine.anatomical_structure, FMRI, Visual Perception, Female, Psychology, Clinical psychology, Adolescent, Cognitive Neuroscience, Article, medicine, Face processing, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Cannabis, Emotion, Facial expression, medicine.disease, biology.organism_classification, Dorsolateral prefrontal cortex, lcsh:Neurophysiology and neuropsychology, Mood disorders, Face, Psychomotor Performance
Abstract: Cannabis use in adolescence may be characterized by differences in the neural basis of affective processing. In this study, we used an fMRI affective face processing task to compare a large group (n = 70) of 14-year olds with a history of cannabis use to a group (n = 70) of never-using controls matched on numerous characteristics including IQ, SES, alcohol and cigarette use. The task contained short movies displaying angry and neutral faces. Results indicated that cannabis users had greater reactivity in the bilateral amygdalae to angry faces than neutral faces, an effect that was not observed in their abstinent peers. In contrast, activity levels in the cannabis users in cortical areas including the right temporal-parietal junction and bilateral dorsolateral prefrontal cortex did not discriminate between the two face conditions, but did differ in controls. Results did not change after excluding subjects with any psychiatric symptomology. Given the high density of cannabinoid receptors in the amygdala, our findings suggest cannabis use in early adolescence is associated with hypersensitivity to signals of threat. Hypersensitivity to negative affect in adolescence may place the subject at-risk for mood disorders in adulthood.
Published: 2015

40. New evidence of factor structure and measurement invariance of the SDQ across five European nations

Author: Marie-Laure Paillère-Martinot, Vincent Frouin, Anna Cattrell, Penny A. Gowland, Alvaro Moreno Velasco, Gunter Schumann, Edurne Chocarro de Luis, Javier Ortuño-Sierra, Tomáš Paus, Herta Flor, Henrik Walter, Arun L.W. Bokde, Tobias Banaschewski, Eduardo Fonseca-Pedrero, Christian Buechel, Frauke Nees, Dimitri Papadopoulos, Robert Whelan, Luise Poustka, Jean-Luc Martinot, Nora C. Vetter, Andreas Heinz, Patricia J. Conrod, Claire Lawrence, Rebeca Aritio-Solana, Maren Struve, Michael N. Smolka, Juergen Gallinat, Hugh Garavan, Uli Bromberg, Hereditary Cancer Program, Institut Català d'Oncologia, Girona Biomedical Research Institute, Josep Trueta University Hospital, Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Department of Child and Adolescent Psychiatry and Psychotherapy [Mannheim], Universität Heidelberg [Heidelberg], Discipline of Psychiatry [Dublin], School of Medicine [Dublin], Trinity College Dublin-Trinity College Dublin, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Service NEUROSPIN (NEUROSPIN), 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 Paris-Saclay, University of Vermont [Burlington], Sir Peter Mansfield Magnetic Resonance Centre [Nottingham], University of Nottingham, UK (UON), McConnell Brain Imaging Centre (MNI), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Neuroimagerie en psychiatrie (U1000), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Adolescent psychopathology and Medicine, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Technische Universität Dresden = Dresden University of Technology (TU Dresden), IMAGEN, Université de Montréal. Faculté de médecine. Département de psychiatrie et d'addictologie, King's College, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] ( UKE ), Service NEUROSPIN ( NEUROSPIN ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, University of Nottingham, UK ( UON ), McConnell Brain Imaging Centre ( MNI ), Montreal Neurological Institute [Montréal], McGill University-McGill University, Neuroimagerie en psychiatrie ( U1000 ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), CHU Cochin [AP-HP], Technische Universität Dresden ( TUD ), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Technische Universität Dresden (TUD), Universität Heidelberg [Heidelberg] = Heidelberg University, Université Paris-Saclay-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), and Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Adolescent, Psychometrics, Sample (statistics), Test validity, Adolescents, Measurement Invariance, Developmental psychology, SDQ, Goodness of fit, Surveys and Questionnaires, Ethnicity, Developmental and Educational Psychology, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Measurement invariance, Behavioural problems, [ INFO.INFO-IM ] Computer Science [cs]/Medical Imaging, General Medicine, Strengths and Difficulties Questionnaire, Confirmatory factor analysis, Test (assessment), Europe, Psychiatry and Mental health, Prosocial behavior, Pediatrics, Perinatology and Child Health, Female, Self Report, Factor Analysis, Statistical, Factorial Structure, Psychology, Self-report
Abstract: International audience; The main purpose of the present study was to analyse the internal structure and to test the measurement invariance of the Strengths and Difficulties Questionnaire (SDQ), self-reported version, in five European countries. The sample consisted of 3012 adolescents aged between 12 and 17 years (M = 14.20; SD = 0.83). The five-factor model (with correlated errors added), and the five-factor model (with correlated errors added) with the reverse-worded items allowed to cross-load on the Prosocial subscale, displayed adequate goodness of-fit indices. Multi-group confirmatory factor analysis showed that the five-factor model (with correlated errors added) had partial strong measurement invariance by countries. A total of 11 of the 25 items were non-invariant across samples. The level of internal consistency of the Total difficulties score was 0.84, ranging between 0.69 and 0.78 for the SDQ subscales. The findings indicate that the SDQ's subscales need to be modified in various ways for screening emotional and behavioural problems in the five European countries that were analysed.
Published: 2015

41. The Brain’s Response to Reward Anticipation and Depression in Adolescence: Dimensionality, Specificity, and Longitudinal Predictions in a Community-Based Sample

Author: Stringaris, Argyris, Vidal-Ribas Belil, Pablo, Artiges , Eric, Lemaitre, Hervé, Gollier-Briant, Fanny, Wolke, Selina, Vulser, Hélène, Miranda, Ruben, Penttilä, Jani, Struve, Maren, Fadai, Tahmine, Kappel, Viola, Grimmer, Yvonne, Goodman, Robert, Poustka, Luise, Conrod, Patricia, Poline, Jean-Baptiste, Cattrell, Anna, Banaschewski, Tobias, Bokde, Arun L.W., Bromberg, Uli, Büchel, Christian, Flor, Herta, Frouin, Vincent, Gallinat, Juergen, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Nees, Frauke, Papadopoulos, Dimitri, Paus, Tomas, Smolka, Michael N., Walter, Henrik, Whelan, Rob, Martinot, Jean-Luc, Schumann, Gunter, Paillère-Martinot, Marie-Laure, Consortium, The IMAGEN, Williams, Steven, Loth, Eva, Adolescent psychopathology and Medicine, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neuroimagerie en psychiatrie (U1000), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Instituto IMDEA Nanociencia [Madrid], Instituto Imdea Nanociencia, Imagerie Cerebrale en Psychiatrie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Child and Adolescent Psychiatry, King's College London Institute of Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Department of Child and Adolescent Psychiatry and Psychotherapy [Mannheim], Universität Heidelberg [Heidelberg], Discipline of Psychiatry [Dublin], School of Medicine [Dublin], Trinity College Dublin-Trinity College Dublin, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Service NEUROSPIN (NEUROSPIN), 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 Paris-Saclay, University of Vermont [Burlington], Sir Peter Mansfield Magnetic Resonance Centre [Nottingham], University of Nottingham, UK (UON), McConnell Brain Imaging Centre (MNI), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Technische Universität Dresden = Dresden University of Technology (TU Dresden), IMAGEN Consortium, CHU Cochin [AP-HP], Neuroimagerie en psychiatrie ( U1000 ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), King's College, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] ( UKE ), Service NEUROSPIN ( NEUROSPIN ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, University of Nottingham, UK ( UON ), McConnell Brain Imaging Centre ( MNI ), Montreal Neurological Institute [Montréal], McGill University-McGill University, Technische Universität Dresden ( TUD ), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universität Heidelberg [Heidelberg] = Heidelberg University, Université Paris-Saclay-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 Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), and Technische Universität Dresden (TUD)
Subjects: Male, medicine.medical_specialty, Adolescent, Anhedonia, behavioral disciplines and activities, Brain mapping, Article, 03 medical and health sciences, 0302 clinical medicine, Reward, Functional neuroimaging, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Psychiatry, Depression (differential diagnoses), Brain Mapping, [ INFO.INFO-IM ] Computer Science [cs]/Medical Imaging, Depression, Subthreshold conduction, Functional Neuroimaging, Ventral striatum, Magnetic Resonance Imaging, Anticipation, 030227 psychiatry, Affect, Psychiatry and Mental health, medicine.anatomical_structure, Mood, nervous system, Ventral Striatum, Female, medicine.symptom, Psychology, 030217 neurology & neurosurgery, psychological phenomena and processes, Clinical psychology
Abstract: International audience; OBJECTIVE: The authors examined whether alterations in the brain's reward network operate as a mechanism across the spectrum of risk for depression. They then tested whether these alterations are specific to anhedonia as compared with low mood and whether they are predictive of depressive outcomes.METHOD: Functional MRI was used to collect blood-oxygen-level-dependent (BOLD) responses to anticipation of reward in the monetary incentive task in 1,576 adolescents in a community-based sample. Adolescents with current subthreshold depression and clinical depression were compared with matched healthy subjects. In addition, BOLD responses were compared across adolescents with anhedonia, low mood, or both symptoms, cross-sectionally and longitudinally.RESULTS: Activity in the ventral striatum was reduced in participants with subthreshold and clinical depression relative to healthy comparison subjects. Low ventral striatum activation predicted transition to subthreshold or clinical depression in previously healthy adolescents at 2-year follow-up. Brain responses during reward anticipation decreased in a graded manner between healthy adolescents, adolescents with current or future subthreshold depression, and adolescents with current or future clinical depression. Low ventral striatum activity was associated with anhedonia but not low mood; however, the combined presence of both symptoms showed the strongest reductions in the ventral striatum in all analyses.CONCLUSIONS: The findings suggest that reduced striatal activation operates as a mechanism across the risk spectrum for depression. It is associated with anhedonia in healthy adolescents and is a behavioral indicator of positive valence systems, consistent with predictions based on the Research Domain Criteria.
Published: 2015

42. Common genetic variants influence human subcortical brain structures

Author: Hibar, Derrek P, Stein, Jason L, Aribisala, Benjamin S, de Zubicaray, Greig I, Dillman, Allissa, Duggirala, Ravi, Dyer, Thomas D, Erk, Susanne, Fedko, Iryna O, Ferrucci, Luigi, Foroud, Tatiana M, Fox, Peter T, Fukunaga, Masaki, Armstrong, Nicola J, Gibbs, J Raphael, Göring, Harald H H, Green, Robert C, Guelfi, Sebastian, Hansell, Narelle K, Hartman, Catharina A, Hegenscheid, Katrin, Heinz, Andreas, Hernandez, Dena G, Heslenfeld, Dirk J, Bernard, Manon, Hoekstra, Pieter J, Holsboer, Florian, Homuth, Georg, Hottenga, Jouke-Jan, Ikeda, Masashi, Jack, Clifford R, Jenkinson, Mark, Johnson, Robert, Kanai, Ryota, Keil, Maria, Bohlken, Marc M, Kent, Jack W, Kochunov, Peter, Kwok, John B, Lawrie, Stephen M, Liu, Xinmin, Longo, Dan L, McMahon, Katie L, Meisenzahl, Eva, Melle, Ingrid, Mohnke, Sebastian, Boks, Marco P, Montgomery, Grant W, Mostert, Jeanette C, Mühleisen, Thomas W, Nalls, Michael A, Nichols, Thomas E, Nilsson, Lars G, Nöthen, Markus M, Ohi, Kazutaka, Olvera, Rene L, Perez-Iglesias, Rocio, Bralten, Janita, Pike, G Bruce, Potkin, Steven G, Reinvang, Ivar, Reppermund, Simone, Rietschel, Marcella, Romanczuk-Seiferth, Nina, Rosen, Glenn D, Rujescu, Dan, Schnell, Knut, Schofield, Peter R, Brown, Andrew A, Smith, Colin, Steen, Vidar M, Sussmann, Jessika E, Thalamuthu, Anbupalam, Toga, Arthur W, Traynor, Bryan J, Troncoso, Juan, Turner, Jessica A, Valdés Hernández, Maria C, van 't Ent, Dennis, Chakravarty, M Mallar, van der Brug, Marcel, van der Wee, Nic J A, van Tol, Marie-Jose, Veltman, Dick J, Wassink, Thomas H, Westman, Eric, Zielke, Ronald H, Zonderman, Alan B, Ashbrook, David G, Hager, Reinmar, Chen, Qiang, Lu, Lu, McMahon, Francis J, Morris, Derek W, Williams, Robert W, Brunner, Han G, Buckner, Randy L, Buitelaar, Jan K, Cahn, Wiepke, Calhoun, Vince D, Cavalleri, Gianpiero L, Ching, Christopher R K, Crespo-Facorro, Benedicto, Dale, Anders M, Davies, Gareth E, Delanty, Norman, Depondt, Chantal, Djurovic, Srdjan, Drevets, Wayne C, Espeseth, Thomas, Gollub, Randy L, Ho, Beng-Choon, Renteria, Miguel E, Cuellar-Partida, Gabriel, Hoffmann, Wolfgang, Hosten, Norbert, Kahn, René S, Le Hellard, Stephanie, Meyer-Lindenberg, Andreas, Müller-Myhsok, Bertram, Nauck, Matthias, Nyberg, Lars, Pandolfo, Massimo, Penninx, Brenda W J H, den Braber, Anouk, Roffman, Joshua L, Sisodiya, Sanjay M, Smoller, Jordan W, van Bokhoven, Hans, van Haren, Neeltje E M, Völzke, Henry, Walter, Henrik, Weiner, Michael W, Wen, Wei, White, Tonya, Giddaluru, Sudheer, Agartz, Ingrid, Andreassen, Ole A, Blangero, John, Boomsma, Dorret I, Brouwer, Rachel M, Cannon, Dara M, Cookson, Mark R, de Geus, Eco J C, Deary, Ian J, Donohoe, Gary, Goldman, Aaron L, Fernández, Guillén, Fisher, Simon E, Francks, Clyde, Glahn, David C, Grabe, Hans J, Gruber, Oliver, Hardy, John, Hashimoto, Ryota, Hulshoff Pol, Hilleke E, Jönsson, Erik G, Grimm, Oliver, Kloszewska, Iwona, Lovestone, Simon, Mattay, Venkata S, Mecocci, Patrizia, McDonald, Colm, McIntosh, Andrew M, Ophoff, Roel A, Paus, Tomas, Pausova, Zdenka, Ryten, Mina, Guadalupe, Tulio, Sachdev, Perminder S, Saykin, Andrew J, Simmons, Andy, Singleton, Andrew, Soininen, Hilkka, Wardlaw, Joanna M, Weale, Michael E, Weinberger, Daniel R, Adams, Hieab H H, Launer, Lenore J, Hass, Johanna, Seiler, Stephan, Schmidt, Reinhold, Chauhan, Ganesh, Satizabal, Claudia L, Becker, James T, Yanek, Lisa, van der Lee, Sven J, Ebling, Maritza, Fischl, Bruce, Longstreth, W. T., Woldehawariat, Girma, Greve, Douglas, Schmidt, Helena, Nyquist, Paul, Vinke, Louis N, van Duijn, Cornelia M, Xue, Luting, Mazoyer, Bernard, Bis, Joshua C, Gudnason, Vilmundur, Seshadri, Sudha, Holmes, Avram J, Ikram, M Arfan, Initiative, Alzheimer’s Disease Neuroimaging, Consortium, CHARGE, EPIGEN, IMAGEN, SYS, Martin, Nicholas G, Wright, Margaret J, Schumann, Gunter, Franke, Barbara, Hoogman, Martine, Thompson, Paul M, Medland, Sarah E, Weiner, Michael, Aisen, Paul, Petersen, Ronald, Jagust, William, Trojanowki, John Q, Beckett, Laurel, Arias-Vasquez, Alejandro, Janowitz, Deborah, Morris, John, Shaw, Leslie M, Khachaturian, Zaven, Sorensen, Greg, Carrillo, Maria, Kuller, Lew, Raichle, Marc, Paul, Steven, Jia, Tianye, Davies, Peter, Fillit, Howard, Hefti, Franz, Holtzman, Davie, Mesulman, M Marcel, Potter, William, Snyder, Peter, Schwartz, Adam, Montine, Tom, Kim, Sungeun, Thomas, Ronald G, Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Jiminez, Gus, Harvey, Danielle, Klein, Marieke, Bernstein, Matthew, Fox, Nick, Thompson, Paul, Schuff, Norbert, DeCarli, Charles, Borowski, Bret, Gunter, Jeff, Senjem, Matt, Kraemer, Bernd, Vemuri, Prashanthi, Jones, David, Kantarci, Kejal, Ward, Chad, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Lee, Phil H, Landau, Susan, Cairns, Nigel J, Householder, Erin, Taylor-Reinwald, Lisa, Trojanowki, J. Q., Shaw, Les, Lee, Virginia M Y, Korecka, Magdalena, Figurski, Michal, Olde Loohuis, Loes M, Crawford, Karen, Neu, Scott, Potkin, Steven, Shen, Li, Faber, Kelley, Nho, Kwangsik, Luciano, Michelle, Thal, Leon, Frank, Richard, Snyder, Peter J, Buckholtz, Neil, Macare, Christine, Albert, Marilyn, Hsiao, John, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Carter, Raina, Dolen, Sara, Gutman, Boris A, Schneider, Lon S, Mather, Karen A, Pawluczyk, Sonia, Beccera, Mauricio, Teodoro, Liberty, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Fleisher, Adam, Heidebrink, Judith L, Lord, Joanne L, Desrivières, Sylvane, Mattheisen, Manuel, Mason, Sara S, Albers, Colleen S, Knopman, David, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Milaneschi, Yuri, Honig, Lawrence S, Bell, Karen L, Ances, Beau, Morris, John C, Carroll, Maria, Leon, Sue, Mintun, Mark A, Schneider, Stacy, Oliver, Angela, Marson, Daniel, Griffith, Randall, Clark, David, Geldmacher, David, Brockington, John, Roberson, Erik, Grossman, Hillel, Mitsis, Effie, deToledo-Morrell, Leyla, Shah, Raj C, Papmeyer, Martina, Duara, Ranjan, Varon, Daniel, Greig, Maria T, Roberts, Peggy, Onyike, Chiadi, D'Agostino, Daniel, Kielb, Stephanie, Galvin, James E, Pogorelec, Dana M, Ramasamy, Adaikalavan, Cerbone, Brittany, Michel, Christina A, Rusinek, Henry, de Leon, Mony J, Glodzik, Lidia, De Santi, Susan, Doraiswamy, P Murali, Petrella, Jeffrey R, Wong, Terence Z, Arnold, Steven E, Risacher, Shannon L, Karlawish, Jason H, Wolk, David, Smith, Charles D, Jicha, Greg, Hardy, Peter, Sinha, Partha, Oates, Elizabeth, Conrad, Gary, Lopez, Oscar L, Oakley, MaryAnn, Roiz-Santiañez, Roberto, Simpson, Donna M, Porsteinsson, Anton P, Goldstein, Bonnie S, Martin, Kim, Makino, Kelly M, Ismail, M Saleem, Brand, Connie, Mulnard, Ruth A, Thai, Gaby, Mc-Adams-Ortiz, Catherine, Rose, Emma J, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Diaz-Arrastia, Ramon, King, Richard, Weiner, Myron, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I, Lah, James J, Salami, Alireza, Cellar, Janet S, Burns, Jeffrey M, Anderson, Heather S, Swerdlow, Russell H, Apostolova, Liana, Tingus, Kathleen, Woo, Ellen, Silverman, Daniel H S, Lu, Po H, Bartzokis, George, Sämann, Philipp G, Graff-Radford, Neill R, Parfitt, Francine, Kendall, Tracy, Johnson, Heather, Farlow, Martin R, Hake, Ann Marie, Matthews, Brandy R, Herring, Scott, Hunt, Cynthia, van Dyck, Christopher H, Jahanshad, Neda, Schmaal, Lianne, Carson, Richard E, MacAvoy, Martha G, Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Caldwell, Curtis, Hsiung, Yuek Robin, Feldman, Howard, Schork, Andrew J, Mudge, Benita, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Munic, Donna, Kerwin, Diana, Mesulam, Marek-Marsel, Lipowski, Kristine, Shin, Jean, Wu, Chuang-Kuo, Johnson, Nancy, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A, Johnson, Keith A, Strike, Lachlan T, Marshall, Gad, Frey, Meghan, Yesavage, Jerome, Taylor, Joy L, Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan N, Belden, Christine M, Jacobson, Sandra A, Teumer, Alexander, Sirrel, Sherye A, Kowall, Neil, Killiany, Ronald, Budson, Andrew E, Norbash, Alexander, Johnson, Patricia Lynn, Obisesan, Thomas O, Wolday, Saba, Allard, Joanne, Lerner, Alan, van Donkelaar, Marjolein M J, Ogrocki, Paula, Hudson, Leon, Fletcher, Evan, Carmichael, Owen, Olichney, John, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Rob, van Eijk, Kristel R, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M, Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Reeder, Stephanie, Bates, Vernice, Walters, Raymond K, Capote, Horacio, Rainka, Michelle, Scharre, Douglas W, Kataki, Maria, Adeli, Anahita, Zimmerman, Earl A, Celmins, Dzintra, Brown, Alice D, Pearlson, Godfrey D, Blank, Karen, Westlye, Lars T, Anderson, Karen, Santulli, Robert B, Kitzmiller, Tamar J, Schwartz, Eben S, Sink, Kaycee M, Williamson, Jeff D, Garg, Pradeep, Watkins, Franklin, Ott, Brian R, Querfurth, Henry, Whelan, Christopher D, Tremont, Geoffrey, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J, Miller, Bruce L, Mintzer, Jacobo, Spicer, Kenneth, Bachman, David, Finger, Elizabether, Toro, Roberto, Winkler, Anderson M, Pasternak, Stephen, Rachinsky, Irina, Drost, Dick, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Schultz, Susan K, Ponto, Laura L Boles, Zwiers, Marcel P, Shim, Hyungsub, Smith, Karen Elizabeth, Relkin, Norman, Chaing, Gloria, Raudin, Lisa, Smith, Amanda, Fargher, Kristin, Raj, Balebail Ashok, Amin, Najaf, Becker, Diane, Alhusaini, Saud, Beiser, Alexa, Debette, Stéphanie, DeStefano, Anita, Hofer, Edith, Hofman, Albert, Niessen, Wiro J, Smith, Albert, Tzourio, Christophe, Vaidya, Dhananjay, Athanasiu, Lavinia, Vernooij, Meike W, Goldstein, David B, Heinzen, Erin L, Shianna, Kevin, Radtke, Rodney, Ottmann, Ruth, Albrecht, Lisa, Andrew, Chris, Arroyo, Mercedes, Artiges, Eric, Ehrlich, Stefan, Aydin, Semiha, Bach, Christine, Banaschewski, Tobias, Barbot, Alexis, Barker, Gareth, Boddaert, Nathalie, Bokde, Arun, Bricaud, Zuleima, Bromberg, Uli, Bruehl, Ruediger, Hakobjan, Marina M H, Büchel, Christian, Cachia, Arnaud, Cattrell, Anna, Conrod, Patricia, Constant, Patrick, Crombag, Hans, Czech, Katharina, Dalley, Jeffrey, Decideur, Benjamin, Desrivieres, Sylvane, Hartberg, Cecilie B, Fadai, Tahmine, Flor, Herta, Frouin, Vincent, Fuchs, Birgit, Gallinat, Jürgen, Garavan, Hugh, Briand, Fanny Gollier, Gowland, Penny, Head, Kay, Heinrichs, Bert, Haukvik, Unn K, Heym, Nadja, Hübner, Thomas, Ihlenfeld, Albrecht, Ireland, James, Ittermann, Bernd, Ivanov, Nikolay, Jones, Jennifer, Klaassen, Arno, Heister, Angelien J G A M, Lalanne, Christophe, Lathrop, Mark, Lanzerath, Dirk, Lemaitre, Hervé, Lüdemann, Katharina, Mallik, Catherine, Mangin, Jean-François, Mann, Karl, Mar, Adam, Hoehn, David, Martinot, Jean-Luc, Massicotte, Jessica, Mennigen, Eva, Mesquita de Carvahlo, Fabiana, Mignon, Xavier, Miranda, Ruben, Müller, Kathrin, Nees, Frauke, Nymberg, Charlotte, Paillere, Marie-Laure, Wittfeld, Katharina, Kasperaviciute, Dalia, Pena-Oliver, Yolanda, Poline, Jean-Baptiste, Poustka, Luise, Rapp, Michael, Reed, Laurence, Robert, Gabriel, Reuter, Jan, Liewald, David C M, Ripke, Stephan, Ripley, Tamzin, Robbins, Trevor, Rodehacke, Sarah, Romanowski, Alexander, Ruggeri, Barbara, Schilling, Christina, Schmäl, Christine, Schmidt, Dirk, Lopez, Lorna M, Schneider, Sophia, Schroeder, Markus, Schubert, Florian, Schwartz, Yannick, Smolka, Michael, Sommer, Wolfgang, Spanagel, Rainer, Speiser, Claudia, Spranger, Tade, Stedman, Alicia, Makkinje, Remco R R, Steiner, Sabina, Stephens, Dai, Strache, Nicole, Ströhle, Andreas, Struve, Maren, Subramaniam, Naresh, Theobald, David, Topper, Lauren, Vollstaedt-Klein, Sabine, Walaszek, Bernadeta, Matarin, Mar, Weiß, Katharina, Werts, Helen, Whelan, Robert, Williams, Steve, Yacubian, Juliana, Ziesch, Veronika, Zilbovicius, Monica, Wong, C Peng, Lubbe, Steven, Naber, Marlies A M, Martinez-Medina, Lourdes, Kepa, Agnes, Fernandes, Alinda, Tahmasebi, Amir, Abrahamowicz, Michal, Gaudet, Daniel, Leonard, Gabriel, Perron, Michel, Richer, Louis, Seguin, Jean, McKay, D Reese, Veillette, Suzanne, Needham, Margaret, Nugent, Allison C, Pütz, Benno, Abramovic, Lucija, Royle, Natalie A, Sprooten, Emma, Trabzuni, Daniah, van der Marel, Saskia S L, van Hulzen, Kimm J E, Walton, Esther, Wolf, Christiane, Almasy, Laura, Ames, David, Andersson, Micael, Arepalli, Sampath, Assareh, Amelia A, Bastin, Mark E, Brodaty, Henry, Bulayeva, Kazima B, Carless, Melanie A, Cichon, Sven, Corvin, Aiden, Curran, Joanne E, Czisch, Michael, MUMC+: DA Klinische Genetica (5), RS: GROW - Developmental Biology, RS: GROW - R4 - Reproductive and Perinatal Medicine, Université de Montréal. Faculté de médecine. Département de psychiatrie et d'addictologie, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), QIMR Berghofer Medical Research Institute, Department of Psychiatry, Donders Centre for Neuroscience, Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen], Department of Human Genetics, Radboud University Medical Center [Nijmegen], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, PRES Sorbonne Paris Cité, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Gènes, Synapses et Cognition (CNRS - UMR3571 ), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Greifswald University Hospital, University Medical Center [Utrecht], European Commission, University of Edinburgh, Lagos State University (LASU), Heriot-Watt University [Edinburgh] (HWU), Unité d'expérimentation sur les Ruminants de Theix, Institut National de la Recherche Agronomique (INRA), Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], University of Oslo (UiO), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], School of Technical Physics, Xidian University, Dept. of Mechanical Engineering, McMaster University [Hamilton, Ontario], Biological Psychology, Neuroscience Campus Amsterdam & EMGO Institute for Health and Care Research, VU University & VU Medical Center, Amsterdam 1081 BT, The Netherlands, Haukeland University Hospital, University of Bergen (UiB), Physicochimie des Processus de Combustion et de l’Atmosphère - UMR 8522 (PC2A), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Universität Heidelberg [Heidelberg] = Heidelberg University, Language and Genetics Department [Nijmegen], Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, International Max Planck Research School for Language Sciences (IMPRS ), Georgia Institute of Technology [Atlanta], National Institutes of Health [Bethesda] (NIH), Yale University [New Haven], Massachusetts General Hospital [Boston], Mental Health Sciences Unit, University College of London [London] (UCL), Beijing Normal University (BNU), Indiana University School of Medicine, Indiana University System, Indiana Alzheimer Disease Center, Indiana University System-Indiana University System, Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany, Scottish Fish Immunology Research Centre, School of Biological Sciences, University of Aberdeen, University of California (UC), Medstar Research Institute, Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia, Department of Genomics, Life and Brain Center, Universität Bonn = University of Bonn, Institute of Human Genetics, Department of Biomedicine and the Centre for Integrative Sequencing, Aarhus University [Aarhus], VU University Medical Center [Amsterdam], Respiratory Epidemiology and Public Health, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-MRC-HPA Centre for Environment and Health, Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Institut Parisien de Chimie Moléculaire (IPCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Umeå Centre for Functional Brain Imaging (UFBI), Umeå University, Umeå 901 87, Sweden, Aging Research Center [Karolinska Institutet] (ARC ), Stockholm University-Karolinska Institutet [Stockholm], Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, 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), Department of Cognitive Sciences [Univ California San Diego] (CogSci - UC San Diego), The Hospital for sick children [Toronto] (SickKids), Queensland Institute of Medical Research, School of Psychology, University of Queensland, Brisbane 4072, Australia, University of Queensland [Brisbane], Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia, Department of Genomics of Common Disease, Imperial College London, Department of Psychology [Oslo], Faculty of Social Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Deutsche Bundesbank, Department of Neurology and Neurosurgery [Montreal], McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), MetaGenoPolis, Department of Psychiatric Research and Development, Diakonhjemmet Hospital, Oslo 0319, Norway, UCL Institute of Neurology and Epilepsy Society, Department of Medicine, Clinical And Experimental Epilepsy, Dpt of Psychiatry [New Haven], Yale School of Medicine [New Haven, Connecticut] (YSM), Hartford Hospital, Neuropsychiatric Genetics Research Group and Department of Psychiatry, Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin 2, Ireland, Institute of Food & Health, University College Dublin, University College Dublin [Dublin] (UCD), Statistical Genetics Group, State Key Laboratory of Lead Compound Research, WuXi AppTec, Co., Ltd, Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL, Institute of Neurology [London], Department of Genetics, King Faisal Specialist Hospital and Research Centre (KFSH & RC), Centre épigénétique et destin cellulaire (EDC), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Dundee Technopole, CXR Biosciences Ltd, Ninewells Hospital and Medical School, Biomedical Research Centre, University of Dundee, Southwest Foundation for Biomedical Research, Department of Psychiatry and National Ageing Research Institute, University of Melbourne, Department of Clinical Genetics, Department of Medical Parasitology and Mycology, School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-Tehran University of Medical Siences, Centre for Healthy Brain Ageing, University of New South Wales [Sydney] (UNSW), Dementia Collaborative Research Centre, N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia, Texas Biomedical Research Institute [San Antonio, TX], Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Division of Medical Genetics, University of Basel (Unibas), Trinity College Dublin-St. James's Hospital, Neuropsychiatric Genetics Research Group, Trinity College Dublin, Department of Materials Science & Metallurgy, University of Cambridge [UK] (CAM), Bijvoet Center of Biomolecular Research [Utrecht], Utrecht University [Utrecht], School of Psychology, University of Queensland, Laboratory of Neurogenetics, The University of Texas Health Science Center at Houston (UTHealth), Department of Genomics, Department of Medical and Molecular Genetics, South Texas Veterans Health Care System, San Antonio, Texas 78229, USA, Biofunctional Imaging, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan, Public Health Genomics Unit, Department of Biomolecular Engineering, Rheinische Friedrich-Wilhelms-Universität Bonn, Estación Experimental de Pastos y Forrajes 'Indio Hatuey', University Medical Center Groningen [Groningen] (UMCG), Neuronal Plasticity / Mouse Behaviour, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Department of Psychiatry, Fujita Health University School of Medicine, Toyoake 470-1192, Japan, Department of Radiology, Mayo Clinic, Department of Clinical Neurology [Oxford], University of Oxford-FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital], University of Maryland School of Medicine, University of Maryland System, University of Sussex, Institute of Cognitive Neuroscience, United Kingdom Met Office [Exeter], University of Maryland [Baltimore County] (UMBC), University of Maryland System-University of Maryland System-University of Maryland School of Medicine, Department of Civil and Structural Engineering, The Hong Kong Polytechnic University [Hong Kong] (POLYU)-The Hong Kong Polytechnic University [Hong Kong] (POLYU), Columbia University Irving Medical Center (CUIMC), Lymphocyte Cell Biology Unit, Laboratory of Genetics, Centre for Advanced Imaging, Psychiatry and Psychotherapy, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Division of Mental Health and Addiction, Oslo University Hospital [Oslo], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Genetic Epidemiology Unit, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Statistics [Warwick], University of Warwick [Coventry], Osaka University [Osaka], Institute of Psychiatry, King’s College London, London SE5 8AF, UK, University of Calgary, Psychiatry and Human Behavior, University of California, Irvine, California 92617, USA, University of California [Irvine] (UC Irvine), Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], University Hospital Mannheim | Universitätsmedizin Mannheim-University Hospital Mannheim | Universitätsmedizin Mannheim, Space and Naval Warfare Systems Center, Klinik für Psychiatrie, Martin-Luther-University Halle-Wittenberg, Department of Psychiatry, Division of Medical Psychology, Genetics of Mental Illness and Brain Function, Neuroscience Research Australia, Développement et amélioration des plantes (UMR DAP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia, Laboratory of Neuro Imaging [Los Angeles] (LONI), Departamento de Física Aplicada, Universidade de Vigo, Georgia State University, University System of Georgia (USG), Genentech, Inc. [San Francisco], Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Universiteit Leiden, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Department of Neurobiology, Care Sciences and Society, Karolinska Institutet [Stockholm], University of Manchester [Manchester], The University of Tennessee Health Science Center [Memphis] (UTHSC), iangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong 226001, China, Centre for Ultrahigh Bandwidth Devices for Optical Systems (CUDOS), Macquarie University, Cognitive Neuroscience Laboratory (CNL), Harvard University, Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud University [Nijmegen]-Radboud University [Nijmegen], Icahn School of Medicine at Mount Sinai [New York] (MSSM), The Mind Research Network, Department of Electrical and Computer Engineering [Albuquerque] (ECE Department), The University of New Mexico [Albuquerque], Division of Molecular and Cellular Therapeutics, Scottish Association for Marine Science (SAMS), Structural Biology Laboratory, Department of Chemistry, University of York, Neurology Division, Beaumont Hospital, Dublin 9, Ireland, Beaumont Hospital, Department of Neurology, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Deparment of Medical Genetics, Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Department of Psychiatry, University of Iowa, University of Iowa [Iowa City], Institute for Community Medicine, Department Epidemiology of Health Care and Community Health, Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig-Universität Leipzig, Institute of Clinical Chemistry and Laboratory Medicine, Department of Health Science, Division of Health and Rehabilitation, Luleå University of Technology (LUT), Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Psychiatric and Neurodevelopmental Genetics Unit, 849 Department of Human Genetics, Institute for Community Medicine, Institute for Energy Systems and Thermodynamics, Renyi Institute, Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, NSW, Department of Child and Adolescent Psychiatry, Erasmus University Medical Centre, Rotterdam 3000 CB, The Netherlands, Department of Radiology, Erasmus University Medical Centre, Rotterdam 3015 CN, The Netherlands, Vrije Universiteit Amsterdam [Amsterdam] (VU), Cell Biology and Gene Expression Section, National Institute of Health, Bethesda, Dept of Psychology, Laboratoire de Recherche Magellan, Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Institut d'Administration des Entreprises (IAE) - Lyon, Institut de Socio-économie des Entreprises et des ORganisations (ISEOR), Institut de socio-économie des entreprises et des organisations, Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Laboratoire d'Informatique de Grenoble (LIG), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Centre for Allergy Research, Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital [Stockholm], Medical University of Łódź (MUL), Psychiatry Institute, Department of Health and Human Services, Institute of Gerontology and Geriatrics, Università degli Studi di Perugia = University of Perugia (UNIPG), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Australian Centre for Research into Injury in Sport and its Prevention, Monash University [Clayton], University Medical Center [Utrecht]-Brain Center Rudolf Magnus, School of Psychology [Nottingham], University of Nottingham, UK (UON), McConnell Brain Imaging Centre (MNI), SickKids - The Hospital for sick children, European Centre for Medium-Range Weather Forecasts (ECMWF), University of Eastern Finland, Centre for Population Health Sciences, Lieber Institute for Brain Development [Baltimore] (LIBD), Johns Hopkins University (JHU), Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz 8010, Austria, Austrian Institute of Technology [Vienna] (AIT), INSERM Research Center for Epidemiology and Biostatistics (U897) Team Neuroepidemiology, Bordeaux, France College of Health Sciences, University of Bordeaux, Bordeaux, France, INSERM, Neuroepidemiology U708, Bordeaux, France, Karlsruhe Institute of Technology (KIT), General Internal Medicine, Johns Hopkins School of Medicine, Johns Hopkins University School of Medicine [Baltimore], Harvard Medical School [Boston] (HMS), Computer Science and Artificial Intelligence Laboratory [Cambridge] (CSAIL), Massachusetts Institute of Technology (MIT), University of Washington [Seattle], Department of Physics [Stockholm], Stockholm University, Center for Medical Systems Biology, Netherlands Genomics Initiative, Leiden University Medical Center, Leiden, The Netherlands, Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Boston University [Boston] (BU), Groupe d'Imagerie Neurofonctionnelle (GIN - UMR 5296), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-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 Paris-Saclay-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 de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Faculty of Medicine, University of Iceland [Reykjavik], Icelandic Heart Association, Kopavogur, Iceland., Boston University School of Medicine (BUSM), Laboratoire d'Ingénierie des Matériaux de Bretagne (LIMATB), Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université de Brest (UBO), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University of California-University of California, Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen], Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Gènes, Synapses et Cognition, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), UE 1354 Unité d'expérimentation sur les Ruminants de Theix, Institut National de la Recherche Agronomique (INRA)-Physiologie Animale et Systèmes d'Elevage (PHASE), Institut National de la Recherche Agronomique (INRA)-Unité d'expérimentation sur les Ruminants de Theix (UE RT), Radboud university [Nijmegen], McGill University, University of Bergen (UIB), Universität Heidelberg [Heidelberg], Beijing Normal University, University of California, University of Bonn, Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Department of Neurosciences [San Diego], Department of Cognitive Sciences [San Diego], The Hospital for Sick Children, University of Toronto, Toronto M5G 1X8, Canada, McGill University-McGill University, US 1367 MetaGénoPolis, Institut National de la Recherche Agronomique (INRA)-Département Microbiologie et Chaîne Alimentaire (MICA), Institut National de la Recherche Agronomique (INRA)-MetaGénoPolis (MGP), Yale University School of Medicine, King Faisal Specialist Hospital and Research Centre, Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Texas Biomedical Research Institute [San Antonio, Texas], Bijvoet Center of Biomolecular Research, Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne 3101, Australia, Department of Genomics, Life & Brain Center, University of Bonn, Bonn D-53127, Germany, University of Oxford [Oxford]-FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital], School of Psychology, University of Sussex, Brighton BN1 9QH, UK, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Department of Neurology [University of Calgary], Department of Clinical Neuroscience [University of Calgary], University of California [Irvine] (UCI), Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Universidate de Vigo, Harvard University [Cambridge], Radboud university [Nijmegen]-Radboud university [Nijmegen], Université Libre de Bruxelles [Bruxelles] (ULB)-Hôpital Erasme (Bruxelles), Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Centre de Recherche Magellan, Institut d'Administration des Entreprises (IAE) - Lyon-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon, Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Università degli Studi di Perugia (UNIPG), Department of neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland, Department of neurology, University of Eastern Finland-University Hospital of Kuopio-University of Eastern Finland-University Hospital of Kuopio, Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Service NEUROSPIN (NEUROSPIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université de Bretagne Sud (UBS)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), The Alzheimer’s Disease Neuroimaging Initiative, The CHARGE Consortium, EPIGEN, IMAGEN, SYS, Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen], Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital]-University of Oxford [Oxford], Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF), 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 Paris-Saclay, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), University of Oxford [Oxford]- John Radcliffe Hospital [Oxford University Hospital]-FMRIB Centre, Neurology, Psychiatry, Anatomy and neurosciences, NCA - Neurobiology of mental health, EMGO - Mental health, NCA - Brain imaging technology, Biological Psychology, Cognitive Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Neuroscience Campus Amsterdam - Brain Imaging Technology, EMGO+ - Mental Health, Child and Adolescent Psychiatry / Psychology, Epidemiology, Radiology & Nuclear Medicine, Laboratory of Neuro Imaging, David Geffen School of Medicine, University of California, Los Angeles, California, USA, Donders Centre for Neuroscience, Radboud University Nijmegen Medical Centre, MRC- SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 8AF, UK, Génétique humaine et Fonctions cognitives - Human Genetics and Cognitive Functions, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Greifswald 17487, Germany, Department of Psychiatry, University Medicine Greifswald, Greifswald 17489, Germany, Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands, Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH4 2XU, UK, Department of Computer Science, Lagos State University, Lagos, Nigeria, Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK, Heriot-Watt University [Edinburgh] ( HWU ), Institut National de la Recherche Agronomique ( INRA ) -Physiologie Animale et Systèmes d'Elevage ( PHASE ) -Unité d'expérimentation sur les Ruminants de Theix ( UE RT ), Department of Human Genetics, Radboud university medical center, Nijmegen 6500 HB, The Netherlands, Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen 6500 HB, The Netherlands, NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway, NORMENT - KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0424, Norway, Montreal Neurological Institute [Montréal], NORMENT - KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway, Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen 5021, Norway, Physicochimie des Processus de Combustion et de l’Atmosphère - UMR 8522 ( PC2A ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen 6525 XD, The Netherlands, International Max Planck Research School for Language Sciences, Nijmegen 6525 XD, The Netherlands, Human Genetics Branch and Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland 20892, USA, Department of Psychology, Yale University, New Haven, Connecticut 06511, USA, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA, University College of London [London] ( UCL ), Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Center for Neurobehavioral Genetics, University of California, Los Angeles, California 90095, USA, Université de Bonn, Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam 1081 HL, The Netherlands, Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh EH10 5HF, UK, Imperial College London-School of public health-MRC-HPA Centre for Environment and Health, Cibersam (Centro Investigación Biomédica en Red Salud Mental), Madrid 28029, Spain, Institut Parisien de Chimie Moléculaire ( IPCM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Aging Research Center [Karolinska Institutet] ( ARC ), Max Planck Institute of Psychiatry, Munich 80804, Germany, Multimodal Imaging Laboratory, Department of Neurosciences, University of California, San Diego, California 92093, USA, Department of Cognitive Sciences, University of California, San Diego, California 92161, USA, Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia, Department of Psychology, University of Oslo, Oslo 0373, Norway, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal H3A 2B4, Canada, Molecular and Cellular Therapeutics, The Royal College of Surgeons, Dublin 2, Ireland, Institut National de la Recherche Agronomique ( INRA ) -MetaGénoPolis ( MGP ) -Microbiologie et Chaîne Alimentaire ( MICA ), UCL Institute of Neurology, London, United Kingdom and Epilepsy Society, London WC1N 3BG, UK, Department of Medicine, Imperial College London, London W12 0NN, UK, Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK, Yale School of Medicine, Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut 06106, USA, University College Dublin [Dublin] ( UCD ), Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK, Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia, Centre épigénétique et destin cellulaire ( EDC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), School of public health-Tehran University of Medical Siences, University of New South Wales [Sydney] ( UNSW ), Texas Biomedical Research Institute, San Antonio, Texas 78245, USA, Institute of Neuroscience and Medicine ( INM-1 ), University of Basel ( Unibas ), Cambridge University, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA, University of Texas Health Science Center, San Antonio, Texas 78229, USA, Clinical Research Branch, National Institute on Aging, Baltimore, Maryland 20892, USA, Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald 17475, Germany, University Medical Center Groningen, University of Groningen, University of Greifswald, Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA, NICHD Brain and Tissue Bank for Developmental Disorders, University of Maryland Medical School, Baltimore, Maryland 21201, USA, nstitute of Cognitive Neuroscience, University College London, London WC1N 3AR, UK, Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland, Baltimore, Maryland 21201, USA, Department of Pathology and Cell Biology, Columbia University Medical Center, New York 10032, USA, Lymphocyte Cell Biology Unit, Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA, University of Oslo ( UiO ) -Institute of Clinical Medicine-Oslo University Hospital, Oslo University Hospital, Institute of Clinical Medicine, University of Oslo ( UiO ) -European Network of Bipolar Research Expert Centers (ENBREC) Group, Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, CCM, Berlin 10117, Germany, Erasmus MC, Laboratory of Neurogenetics, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIH), Bethesda, Maryland, USA, Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Central Institute of Mental Health, UMR 1098 Développement et Amélioration des Plantes, Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -MontpellierSupAgro ( MontpellierSupAgro ) -Génétique et amélioration des plantes ( G.A.P. ) -Développement et Amélioration des Plantes ( DAP ), Laboratory of Neuro Imaging [Los Angeles] ( LONI ), University of California at Los Angeles [Los Angeles] ( UCLA ), Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK, Genentech, South San Francisco, California 94080, USA, Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands, LUMC, Carver College of Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm SE-141 83, Sweden, Behavioral Epidemiology Section, National Institute on Aging Intramural Research Program, Baltimore, Maryland 20892, USA, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK, Center for Integrative and Translational Genomics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA, Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA, Centre Interlangues - Texte, Image, Langage ( TIL ), Université de Bourgogne ( UB ), Centre for Ultrahigh Bandwidth Devices for Optical Systems ( CUDOS ), Icahn School of Medicine at Mount Sinai [New York], The Mind Research Network & LBERI, Albuquerque, New Mexico 87106, USA, Department of ECE, University of New Mexico, Albuquerque, New Mexico 87131, USA, Scottish Association for Marine Science ( SAMS ), Department of Neurology, Hopital Erasme, Universite Libre de Bruxelles, Brussels 1070, Belgium, National Institutes of Health ( NIH ) -National Institute of Mental Health (NIMH), Harvard Medical School [Boston] ( HMS ) -Massachusetts General Hospital [Boston], Department of Psychiatry, University of Iowa, Iowa City, Iowa 52242, USA, Luleå University of Technology ( LUT ), Broad Institute of MIT and Harvard, Massachusetts General Hospital, Vrije Universiteit Amsterdam [Amsterdam] ( VU ), Université Jean Moulin - Lyon III-Institut d'Administration des Entreprises (IAE) - Lyon, Institut de Socio-économie des Entreprises et des ORganisations ( ISEOR ), University Medicine Greifswald,-HELIOS Hospital Stralsund, Laboratoire d'Informatique de Grenoble ( LIG ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National Polytechnique de Grenoble ( INPG ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University, Osaka 565-0871, Japan, Karolinska University Hospital (Solna), Medical University of Łódź ( MUL ), National Institutes of Health ( NIH ), University of Perugia, Commonwealth Scientific and Industrial Research Organisation, University Medical Center Utrecht-Brain Center Rudolf Magnus, University of Nottingham, UK ( UON ), McConnell Brain Imaging Centre ( MNI ), The Hospital for sick children [Toronto] ( SickKids ), Department of Medical and Molecular Genetics, King’s College London, London SE1 9RT, UK, European Centre for Medium-Range Weather Forecasts ( ECMWF ), Lieber Institute for Brain Development, Baltimore, Maryland 21205, USA, Departments of Psychiatry, Neurology, Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, Austrian Institute of Technology [Vienna] ( AIT ), Karlsruhe Institute of Technology ( KIT ), General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA, Department of Radiology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA, Computer Science and Artificial Intelligence Laboratory [Cambridge] ( CSAIL ), Massachusetts Institute of Technology ( MIT ), Department of Epidemiology, University of Washington, Seattle, Washington, USA, Department of Neurology, University of Washington, Seattle, Washington, USA, Department of Physics, Stockholm University ( Department of Physics, Stockholm University ), Université de Lille, Sciences Humaines et Sociales, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA, Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands, Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA, Groupe d'Imagerie Neurofonctionnelle ( GIN - UMR 5296 ), Service NEUROSPIN ( NEUROSPIN ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université de Bordeaux ( UB ), Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA, Faculty of Medicine, University of Iceland, Reykjavik, Iceland, Department of Neurology, Boston University School of Medicine, Framingham Heart Study, Boston, MA, Department of Neurology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands, Laboratoire d'Ingénierie des Matériaux de Bretagne ( LIMATB ), Université de Bretagne Sud ( UBS ) -Institut Brestois du Numérique et des Mathématiques ( IBNM ), Université de Brest ( UBO ) -Université de Brest ( UBO ) -Université de Brest ( UBO ), King's College, Department of Psychiatry, Radboud university medical center, Nijmegen 6500 HB, The Netherlands, and Broad Institute of © 2012 Nature America, Inc. All rights reserved. Nature Ge N etics aDV a NCE ONLINE PUBLIC a TION 7 l e t t e r s Harvard and MIT, Cambridge, Massachusetts, US
Subjects: CHROMATIN, Male, Netherlands Twin Register (NTR), Aging, Identification, nervous-system, human geography, SEGMENTATION, Caudate nucleus, Apoptosis, Expression, Genome-wide association study, Striatum, Hippocampal formation, Hippocampus, BASAL GANGLIA, 130 000 Cognitive Neurology & Memory, Basal ganglia, genetics [Gene Expression Regulation, Developmental], Hippocampal, Child, anatomy & histology [Skull], Aged, 80 and over, Genetics, Sex Characteristics, KINECTIN, Genome-wide association, Multidisciplinary, Putamen, Brain, Gene Expression Regulation, Developmental, blood, brain, disease incidence, genetic variation, neurology, Organ Size, Human brain, Middle Aged, organization, Magnetic Resonance Imaging, genetics [Genetic Variation], Chromatin, Dynamics, genetics [Membrane Proteins], medicine.anatomical_structure, genetics [Aging], Anatomy & histology, [ SCCO.NEUR ] Cognitive science/Neuroscience, Female, ddc:500, anatomy & histology [Caudate Nucleus], Neuroinformatics, EXPRESSION, Adult, Adolescent, Evolution, anatomy & histology [Hippocampus], ORGANIZATION, genetics [Genetic Loci], Biology, Article, Young Adult, SDG 3 - Good Health and Well-being, Journal Article, medicine, Humans, GENOME-WIDE ASSOCIATION, General, genetics [Apoptosis], Kinectin, Aged, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], HIPPOCAMPAL, IDENTIFICATION, genetics [Organ Size], [SCCO.NEUR]Cognitive science/Neuroscience, Skull, segmentation, Genetic Variation, Membrane Proteins, NERVOUS-SYSTEM, anatomy & histology [Putamen], Genetic Loci, KTN1 protein, human, Caudate Nucleus, anatomy & histology [Brain], Neuroscience, Genome-Wide Association Study
Abstract: Contains fulltext : 144426.pdf (Publisher’s version ) (Closed access) Contains fulltext : 144426pre.pdf (Author’s version preprint ) (Open Access) The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 x 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. 6 p.
Published: 2015

43. Training Schr\'odinger's cat: quantum optimal control

Author: Glaser, Stefffen J., Boscain, Ugo, Calarco, Tommaso, Koch, Christiane P., Köckenberger, Walter, Kosloff, Ronnie, Kuprov, Ilya, Luy, Burkard, Schirmer, Sophie, Schulte-Herbrüggen, Thomas, Sugny, Dominique, Wilhelm, Frank K., Sigalotti, Mario, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Centre de Mathématiques Appliquées - Ecole Polytechnique (CMAP), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Geometric Control Design (GECO), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS)-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), Centre National de la Recherche Scientifique (CNRS), Institute for Quantum Information Processing, Universität Ulm - Ulm University [Ulm, Allemagne], Department of Biology, Division of Biochemistry, Friedrich-Alexander, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Sir Peter Mansfield Magnetic Resonance Centre [Nottingham], University of Nottingham, UK (UON), The Fritz Haber Research Center for Molecular Dynamics [Jerusalem], The Hebrew University of Jerusalem (HUJ), University of Southampton, Karlsruher Institut für Technologie (KIT), Institut de Recherche en Immunologie et en Cancérologie [UdeM-Montréal] (IRIC), Université de Montréal (UdeM), Laboratoire Interdisciplinaire Carnot de Bourgogne (LICB), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), European Synchrotron Radiation Facility (ESRF), Technische Universität München [München] ( TUM ), Centre de Mathématiques Appliquées - Ecole Polytechnique ( CMAP ), École polytechnique ( X ) -Centre National de la Recherche Scientifique ( CNRS ), Geometric Control Design ( GECO ), 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 ) -École polytechnique ( X ) -Centre National de la Recherche Scientifique ( CNRS ), Centre National de la Recherche Scientifique ( CNRS ), Universität Ulm, Friedrich-Alexander Universität Erlangen-Nürnberg ( FAU ), University of Nottingham, UK ( UON ), The Hebrew University of Jerusalem ( HUJ ), University of Southampton [Southampton], Karlsruher Institut für Technologie ( KIT ), Institut de Recherche en Immunologie et en Cancérologie ( IRIC ), Université de Montréal, Laboratoire Interdisciplinaire Carnot de Bourgogne ( LICB ), Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), European Synchrotron Radiation Facility ( ESRF ), and Laboratoire Interdisciplinaire Carnot de Bourgogne (ICB)
Subjects: Quantum Physics, [ PHYS.QPHY ] Physics [physics]/Quantum Physics [quant-ph], [PHYS.QPHY]Physics [physics]/Quantum Physics [quant-ph], [PHYS.QPHY] Physics [physics]/Quantum Physics [quant-ph]
Abstract: It is control that turns scientific knowledge into useful technology: in physics and engineering it provides a systematic way for driving a system from a given initial state into a desired target state with minimized expenditure of energy and resources -- as famously applied in the Apollo programme. As one of the cornerstones for enabling quantum technologies, optimal quantum control keeps evolving and expanding into areas as diverse as quantum-enhanced sensing, manipulation of single spins, photons, or atoms, optical spectroscopy, photochemistry, magnetic resonance (spectroscopy as well as medical imaging), quantum information processing and quantum simulation. --- Here state-of-the-art quantum control techniques are reviewed and put into perspective by a consortium uniting expertise in optimal control theory and applications to spectroscopy, imaging, quantum dynamics of closed and open systems. We address key challenges and sketch a roadmap to future developments., Comment: 31 pages; this is the starting point for a living document - we welcome feedback and discussion
Published: 2015

44. The development of route learning in Down syndrome, Williams syndrome and typical development: investigations with virtual environments

Author: Pascal Sockeel, Daniel Mellier, Emily K. Farran, Mark Blades, Yannick Courbois, Harry R.M. Purser, Axelle Lemahieu, University of Nottingham, UK (UON), Department of Psychology [Goldsmiths University of London], Goldsmiths, University of London (Goldsmiths College), University of London [London]-University of London [London], Psychologie : Interactions, Temps, Emotions, Cognition (PSITEC) - ULR 4072 (PSITEC), Université de Lille, Psychologie et Neurosciences de la Cognition et de l'affectivité (PSY-NCA), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Department of Psychology [Sheffield], University of Sheffield [Sheffield], Psychologie : Interactions, Temps, Émotions, Cognition (PSITEC) - ULR 4072, Psychologie : Interactions, Temps, Émotions, Cognition (PSITEC) - EA 4072, University of Nottingham, UK [UON], Psychologie : Interactions, Temps, Emotions, Cognition (PSITEC) - ULR 4072 [PSITEC], and Psychologie et Neurosciences de la Cognition et de l'affectivité [PSY-NCA]
Subjects: Adult, Male, Williams Syndrome, Down syndrome, Visual perception, Adolescent, Cognitive Neuroscience, [SHS.EDU]Humanities and Social Sciences/Education, Maze learning, Neuropsychological Tests, 050105 experimental psychology, Developmental psychology, User-Computer Interface, Young Adult, 03 medical and health sciences, Typically developing, [SCCO]Cognitive science, 0302 clinical medicine, Developmental and Educational Psychology, medicine, Humans, 0501 psychology and cognitive sciences, Child, Maze Learning, 10. No inequality, Landmark, Learning Disabilities, Long-term memory, 05 social sciences, Cognition, medicine.disease, Child, Preschool, Female, Williams syndrome, Down Syndrome, Cognition Disorders, Psychology, 030217 neurology & neurosurgery, Cognitive psychology
Abstract: The ability to navigate new environments has a significant impact on the daily life and independence of people with learning difficulties. The aims of this study were to investigate the development of route learning in Down syndrome (N = 50), Williams syndrome (N = 19), and typically developing children between 5 and 11 years old (N = 108); to investigate use of landmarks; and to relate cognitive functions to route-learning ability in these groups. Overall, measures of attention and long-term memory were strongly associated with route learning, even once non-verbal ability was controlled for. All of the groups, including 5- to 6-year-old TD children, demonstrated the ability to make use of all landmark types to aid route learning; those near junctions, those further from junctions, and also distant landmarks (e.g. church spire, radio mast). Individuals with WS performed better than a matched subset of TD children on more difficult routes; we suggest that this is supported by relatively strong visual feature recognition in the disorder. Participants with DS who had relatively high levels of non-verbal ability performed at a similar level to TD participants. 18;4
Published: 2015

45. PDRs4All: A JWST Early Release Science Program on Radiative Feedback from Massive Stars

Author: Olivier Berné, Émilie Habart, Els Peeters, Alain Abergel, Edwin A. Bergin, Jeronimo Bernard-Salas, Emeric Bron, Jan Cami, Emmanuel Dartois, Asunción Fuente, Javier R. Goicoechea, Karl D. Gordon, Yoko Okada, Takashi Onaka, Massimo Robberto, Markus Röllig, Alexander G. G. M. Tielens, Sílvia Vicente, Mark G. Wolfire, Felipe Alarcón, C. Boersma, Amélie Canin, Ryan Chown, Daniel Dicken, David Languignon, Romane Le Gal, Marc W. Pound, Boris Trahin, Thomas Simmer, Ameek Sidhu, Dries Van De Putte, Sara Cuadrado, Claire Guilloteau, Alexandros Maragkoudakis, Bethany R. Schefter, Thiébaut Schirmer, Stéphanie Cazaux, Isabel Aleman, Louis Allamandola, Rebecca Auchettl, Giuseppe Antonio Baratta, Salma Bejaoui, Partha P. Bera, Goranka Bilalbegović, John H. Black, Francois Boulanger, Jordy Bouwman, Bernhard Brandl, Philippe Brechignac, Sandra Brünken, Andrew Burkhardt, Alessandra Candian, Jose Cernicharo, Marin Chabot, Shubhadip Chakraborty, Jason Champion, Sean W. J. Colgan, Ilsa R. Cooke, Audrey Coutens, Nick L. J. Cox, Karine Demyk, Jennifer Donovan Meyer, Cécile Engrand, Sacha Foschino, Pedro García-Lario, Lisseth Gavilan, Maryvonne Gerin, Marie Godard, Carl A. Gottlieb, Pierre Guillard, Antoine Gusdorf, Patrick Hartigan, Jinhua He, Eric Herbst, Liv Hornekaer, Cornelia Jäger, Eduardo Janot-Pacheco, Christine Joblin, Michael Kaufman, Francisca Kemper, Sarah Kendrew, Maria S. Kirsanova, Pamela Klaassen, Collin Knight, Sun Kwok, Álvaro Labiano, Thomas S.-Y. Lai, Timothy J. Lee, Bertrand Lefloch, Franck Le Petit, Aigen Li, Hendrik Linz, Cameron J. Mackie, Suzanne C. Madden, Joëlle Mascetti, Brett A. McGuire, Pablo Merino, Elisabetta R. Micelotta, Karl Misselt, Jon A. Morse, Giacomo Mulas, Naslim Neelamkodan, Ryou Ohsawa, Alain Omont, Roberta Paladini, Maria Elisabetta Palumbo, Amit Pathak, Yvonne J. Pendleton, Annemieke Petrignani, Thomas Pino, Elena Puga, Naseem Rangwala, Mathias Rapacioli, Alessandra Ricca, Julia Roman-Duval, Joseph Roser, Evelyne Roueff, Gaël Rouillé, Farid Salama, Dinalva A. Sales, Karin Sandstrom, Peter Sarre, Ella Sciamma-O’Brien, Kris Sellgren, Matthew J. Shannon, Sachindev S. Shenoy, David Teyssier, Richard D. Thomas, Aditya Togi, Laurent Verstraete, Adolf N. Witt, Alwyn Wootten, Nathalie Ysard, Henning Zettergren, Yong Zhang, Ziwei E. Zhang, Junfeng Zhen, 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), 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), University of Western Ontario (UWO), Carl Sagan Center, SETI Institute, University of Michigan [Ann Arbor], University of Michigan System, Analytic and Computational Research, Inc. - Earth Sciences (ACRI-ST), Laboratoire d'Etude du Rayonnement et de la Matière en Astrophysique et Atmosphères = Laboratory for Studies of Radiation and Matter in Astrophysics and Atmospheres (LERMA), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-CY Cergy Paris Université (CY), Institut des Sciences Moléculaires d'Orsay (ISMO), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Observatorio Astronomico Nacional, Madrid, Instituto de Física Fundamental [Madrid] (IFF), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Universiteit Gent = Ghent University (UGENT), Space Telescope Science Institute (STSci), Physikalisches Institut [Köln], Universität zu Köln = University of Cologne, Meisei University, The University of Tokyo (UTokyo), Leiden Observatory [Leiden], Universiteit Leiden, Johns Hopkins University (JHU), Instituto de Astrofísica e Ciências do Espaço (IASTRO), University of Maryland [College Park], University of Maryland System, NASA Ames Research Center (ARC), 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, Institut de RadioAstronomie Millimétrique (IRAM), Centre National de la Recherche Scientifique (CNRS), Signal et Communications (IRIT-SC), Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-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)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT), Institut National Polytechnique (Toulouse) (Toulouse INP), Onsala Space Observatory (OSO), Chalmers University of Technology [Göteborg], Delft University of Technology (TU Delft), Universidade Federal de Itajubá, Bay Area Environmental Research Institute (BAER), Australian Synchrotron [Clayton], INAF - Osservatorio Astrofisico di Catania (OACT), Istituto Nazionale di Astrofisica (INAF), University of Zagreb, Laboratoire de physique de l'ENS - ENS Paris (LPENS), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Département de Physique de l'ENS-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), University of Colorado [Boulder], Institute for Molecules and Materials [Nijmegen], Radboud University [Nijmegen], Wellesley College, Laboratoire de Physique des 2 Infinis Irène Joliot-Curie (IJCLab), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de Physique de Rennes (IPR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), University of British Columbia (UBC), National Radio Astronomy Observatory [Charlottesville] (NRAO), National Radio Astronomy Observatory (NRAO), European Space Astronomy Centre (ESAC), Agence Spatiale Européenne = European Space Agency (ESA), Harvard-Smithsonian Center for Astrophysics (CfA), Harvard University-Smithsonian Institution, Institut d'Astrophysique de Paris (IAP), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Rice University [Houston], Yunnan Observatories, Chinese Academy of Sciences [Changchun Branch] (CAS), Universidad de Chile = University of Chile [Santiago] (UCHILE), University of Virginia, Aarhus University [Aarhus], Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Instituto de Astronomia, Geofísica e Ciências Atmosféricas [São Paulo] (IAG), Universidade de São Paulo = University of São Paulo (USP), San Jose State University [San Jose] (SJSU), European Southern Observatory (ESO), Academia Sinica Institute of Astronomy and Astrophysics (ASIAA), Academia Sinica, Institute of Astronomy of the Russian Academy of Sciences (INASAN), Russian Academy of Sciences [Moscow] (RAS), UK Astronomy Technology Centre (UK ATC), Science and Technology Facilities Council (STFC), Telespazio, Services par satellites, Infrared Processing and Analysis Center (IPAC), California Institute of Technology (CALTECH), University of Missouri [Columbia] (Mizzou), University of Missouri System, Max Planck Institute for Astronomy (MPIA), CAS Key Laboratory of Crust–Mantle Materials and Environments [Hefei], School of Earth and Space Sciences [Hefei], University of Science and Technology of China [Hefei] (USTC)-University of Science and Technology of China [Hefei] (USTC)-Chinese Academy of Sciences [Beijing] (CAS), Lawrence Berkeley National Laboratory [Berkeley] (LBNL), University of California [Berkeley] (UC Berkeley), University of California (UC), Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), 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)-Université Paris Cité (UPCité), Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1 (UB)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Massachusetts Institute of Technology (MIT), Instituto de Ciencia de Materiales de Madrid (ICMM), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Steward Observatory, University of Arizona, INAF - Osservatorio Astronomico di Cagliari (OAC), United Arab Emirates University (UAEU), National Astronomical Observatory of Japan (NAOJ), Banaras Hindu University [Varanasi] (BHU), University of Amsterdam [Amsterdam] (UvA), Laboratoire de Chimie et Physique Quantiques Laboratoire (LCPQ), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Fédération de recherche « Matière et interactions » (FeRMI), 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 de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS), University of California [San Diego] (UC San Diego), University of Nottingham, UK (UON), Ohio State University [Columbus] (OSU), Space Science Institute [Boulder] (SSI), Stockholm University, Texas State University, Ritter Astrophysical Research Center, University of Toledo, National Sun Yat-Sen University (NSYSU), Star and Planet Formation Laboratory, ITA, USA, GBR, FRA, DEU, ESP, AUS, BEL, BRA, CHL, TWN, HRV, DNK, JPN, IND, NLD, PRT, CHN, RUS, SWE, National Aeronautics and Space Administration (US), University of Maryland, University of Michigan, Centre National de la Recherche Scientifique (France), Centre National D'Etudes Spatiales (France), Natural Sciences and Engineering Research Council of Canada, Ministerio de Ciencia e Innovación (España), German Research Foundation, Japan Society for the Promotion of Science, San José State University Research Foundation, Berné, Olivier, Habart, Émilie, Peeters, Els, Abergel, Alain, Bergin, Edwin A., Bernard-Salas, Jeronimo, Bron, Emeric, Cami, Jan, Dartois, Emmanuel, Fuente, Asunción, Goicoechea, Javier R., Gordon, Karl D., Okada, Yoko, Onaka, Takashi, Robberto, Massimo, Röllig, Markus, Tielens, Alexander G.G.M., Vicente, Sílvia, Wolfire, Mark G., Alarcón, Felipe, Boersma, C., Canin, Amélie, Chown, Ryan, Dicken, Daniel, Le Gal, Romane, Pound, Marc W., Trahin, Boris, Sidhu, Ameek, Van De Putte, Dries, Cuadrado, Sara, Guilloteau, Claire, Maragkoudakis, Alexandros, Schefter, Bethany R., Schirmer, Thiébaut, Aleman, Isabel, Allamandola, Louis, Auchettl, Rebecca, Antonio Baratta, Giuseppe, Bejaoui, Salma, Bera, Partha P., Bilalbegović, Goranka, Black, John H., Boulanger, Francois, Bouwman, Jordy, Brandl, Bernhard, Brünken, Sandra, Burkhardt, Andrew, Candian, Alessandra, Cernicharo, José, Chakraborty, Shubhadip, Champion, Jason, Colgan, Sean W.J., Cooke, Ilsa R., Coutens, Audrey, Cox, Nick L.J., Demyk, Karine, Donovan Meyer, Jennifer, Engrand, Cécile, Foschino, Sacha, Gavilan, Lisseth, Gerin, Maryvonne, Godard, Marie, Gottlieb, Carl A., Guillard, Pierre, Gusdorf, Antoine, Hartigan, Patrick, He, Jinhua, Herbst, Eric, Hornekaer, Liv, Janot-Pacheco, Eduardo, Joblin, Christine, Kaufman, Michael, Kemper, Francisca, Kendrew, Sarah, Kirsanova, Maria S., Klaassen, Pamela, Knight, Collin, Kwok, Sun, Labiano, Álvaro, Lai, Thomas S.Y., Lee, Timothy J., Lefloch, Bertrand, Le Petit, Franck, Li, Aigen, Linz, Hendrik, MacKie, Cameron J., Madden, Suzanne C., Mascetti, Joëlle, McGuire, Brett A., Merino, Pablo, Micelotta, Elisabetta R., Morse, Jon A., Molecular Spectroscopy (HIMS, FNWI), and HIMS (FNWI)
Subjects: Gaseous Nebulae, FOS: Physical sciences, Astronomy and Astrophysics, Astrophysics::Cosmology and Extragalactic Astrophysics, FELIX Infrared and Terahertz Spectroscopy, Star Forming Regions, Astrophysics - Astrophysics of Galaxies, Infrared Telescopes, Space and Planetary Science, Astrophysics of Galaxies (astro-ph.GA), Astrophysics::Solar and Stellar Astrophysics, [INFO]Computer Science [cs], Photodissociation Regions, Astrophysics::Earth and Planetary Astrophysics, Polycyclic Aromatic Hydrocarbons, [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph], James Webb Space Telescope (JWST), Photo-Dissociation Regions (PDRs), Massive stars, Orion Bar, MIRI, NIRSpec, NIRCam, Astrophysics::Galaxy Astrophysics
Abstract: 22 pags., 8 figs., 1 tab., Massive stars disrupt their natal molecular cloud material through radiative and mechanical feedback processes. These processes have profound effects on the evolution of interstellar matter in our Galaxy and throughout the universe, from the era of vigorous star formation at redshifts of 1-3 to the present day. The dominant feedback processes can be probed by observations of the Photo-Dissociation Regions (PDRs) where the far-ultraviolet photons of massive stars create warm regions of gas and dust in the neutral atomic and molecular gas. PDR emission provides a unique tool to study in detail the physical and chemical processes that are relevant for most of the mass in inter-and circumstellar media including diffuse clouds, proto-planetary disks, and molecular cloud surfaces, globules, planetary nebulae, and star-forming regions. PDR emission dominates the infrared (IR) spectra of star-forming galaxies. Most of the Galactic and extragalactic observations obtained with the James Webb Space Telescope (JWST) will therefore arise in PDR emission. In this paper we present an Early Release Science program using the MIRI, NIRSpec, and NIRCam instruments dedicated to the observations of an emblematic and nearby PDR: the Orion Bar. These early JWST observations will provide template data sets designed to identify key PDR characteristics in JWST observations. These data will serve to benchmark PDR models and extend them into the JWST era. We also present the Science-Enabling products that we will provide to the community. These template data sets and Science-Enabling products will guide the preparation of future proposals on star-forming regions in our Galaxy and beyond and will facilitate data analysis and interpretation of forthcoming JWST observations., Support for JWST-ERS program ID 1288 was provided through grants from the STScI under NASA contract NAS5-03127 to STScI (K.G., D.V.D.P., M.R.), Univ. of Maryland (M.W., M.P.), Univ. of Michigan (E.B., F.A.), and Univ. of Toledo (T.S.-Y.L.). O.B. and E.H. are supported by the Programme National “Physique et Chimie du Milieu Interstellaire” (PCMI) of CNRS/INSU with INC/INP co-funded by CEA and CNES, and through APR grants 6315 and 6410 provided by CNES. E. P. and J.C. acknowledge support from the National Science and Engineering Council of Canada (NSERC) Discovery Grant program (RGPIN-2020-06434 and RGPIN-2021-04197 respectively). E.P. acknowledges support from a Western Strategic Support Accelerator Grant (ROLA ID 0000050636). J.R.G. and S.C. thank the Spanish MCINN for funding support under grant PID2019-106110GB-I00. Work by M.R. and Y.O. is carried out within the Collaborative Research Centre 956, subproject C1, funded by the Deutsche Forschungsgemeinschaft (DFG)—project ID 184018867. T.O. acknowledges support from JSPS Bilateral Program, grant No. 120219939. M.P. and M.W. acknowledge support from NASA Astrophysics Data Analysis Program award #80NSSC19K0573. C.B. is grateful for an appointment at NASA Ames Research Center through the San José State University Research Foundation (NNX17AJ88A) and acknowledges support from the Internal Scientist Funding Model (ISFM) Directed Work Package at NASA Ames titled: “Laboratory Astrophysics—The NASA Ames PAH IR Spectroscopic Database.”
Published: 2022

46. Improving crop Yield potential: Underlying biological processes and future prospects

Author: Burgess, Alexandra, Masclaux-Daubresse, Céline, Strittmatter, Günter, Weber, Andreas, Taylor, Samuel Harry, Harbinson, Jeremy, Yin, Xinyou, Long, Stephen, Paul, Matthew, Westhoff, Peter, Loreto, Francesco, Ceriotti, Aldo, Saltenis, Vandasue, Pribil, Mathias, Nacry, Philippe, Scharff, Lars, Jensen, Poul Erik, Muller, Bertrand, Cohan, Jean‐pierre, Foulkes, John, Rogowsky, Peter, Debaeke, Philippe, Meyer, Christian, Nelissen, Hilde, Inzé, Dirk, Klein Lankhorst, René, Parry, Martin, Murchie, Erik, Baekelandt, Alexandra, University of Nottingham, UK (UON), Institut Jean-Pierre Bourgin (IJPB), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Cluster of Excellence on Plant Sciences (CEPLAS), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf]-Max Planck Institute for Plant Breeding Research (MPIPZ)-Universität zu Köln = University of Cologne, Lancaster Environment Centre, Lancaster University, Wageningen University and Research [Wageningen] (WUR), University College of London [London] (UCL), University of Illinois at Urbana-Champaign [Urbana], University of Illinois System, Rothamsted Research, Biotechnology and Biological Sciences Research Council (BBSRC), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), University of Copenhagen = Københavns Universitet (UCPH), Biochimie et Physiologie Moléculaire des Plantes (BPMP), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Food Science [Copenhagen] (UCPH FOOD), Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Écophysiologie des Plantes sous Stress environnementaux (LEPSE), 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), ARVALIS - Institut du végétal [Paris], Reproduction et développement des plantes (RDP), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), AGroécologie, Innovations, teRritoires (AGIR), 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), Department of Plant Systems Biology, VIB, and Department of Plant Biotechnology and Bioinformatics, Universiteit Gent = Ghent University (UGENT), European Commission 817690, and European Project: 817690,ERC
Subjects: food supply, photosynthesis, [SDV]Life Sciences [q-bio], [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, crop yield, nutrient remobilisation, crop improvement, organ growth
Abstract: International audience; The growing world population and global increases in the standard of living both result in an increasing demand for food, feed and other plant- derived products. In the coming years, plant- based research will be among the major drivers ensuring food security and the expansion of the bio- based economy. Crop productivity is determined by several factors, including the available physical and agricultural resources, crop management, and the resource use efficiency, quality and intrinsic yield potential of the chosen crop. This review focuses on intrinsic yield potential, since understanding its determinants and their biological basis will allow to maximize the plant's potential in food and energy production. Yield potential is determined by a variety of complex traits that integrate strictly regulated processes and their underlying gene regulatory networks. Due to this inherent complexity, numerous potential targets have been identified that could be exploited to increase crop yield. These encompass diverse metabolic and physical processes at the cellular, organ and canopy level. We present an overview of some of the distinct biological processes considered to be crucial for yield determination that could further be exploited to improve future crop productivity.
Published: 2023

47. Time-Resolved Chiral X-Ray Photoelectron Spectroscopy with Transiently Enhanced Atomic Site Selectivity: A Free-Electron Laser Investigation of Electronically Excited Fenchone Enantiomers

Author: D. Faccialà, M. Devetta, S. Beauvarlet, N. Besley, F. Calegari, C. Callegari, D. Catone, E. Cinquanta, A. G. Ciriolo, L. Colaizzi, M. Coreno, G. Crippa, G. De Ninno, M. Di Fraia, M. Galli, G. A. Garcia, Y. Mairesse, M. Negro, O. Plekan, P. Prasannan Geetha, K. C. Prince, A. Pusala, S. Stagira, S. Turchini, K. Ueda, D. You, N. Zema, V. Blanchet, L. Nahon, I. Powis, C. Vozzi, CNR Istituto di Fotonica e Nanotecnologie [Milano] (IFN), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), 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), University of Nottingham, UK (UON), Deutsches Elektronen-Synchrotron [Hamburg] (DESY), Hamburg Centre for Ultrafast Imaging [Universität Hamburg], Universität Hamburg (UHH), Elettra Sincrotrone Trieste, Center for Free-Electron Laser Science (CFEL), Istituto di Struttura della Materia (CNR-ISM), Dipartimento di Fisica [Politecnico Milano] (POLIMI), Politecnico di Milano [Milan] (POLIMI), Laboratory of Quantum Optics, University of Nova Gorica, Università degli studi di Trieste = University of Trieste, Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Tohoku University [Sendai], School of Chemistry [Nottingham, UK] (School of Chemistry), and European Project: 682978,EXCITERS
Subjects: Chemical Physics (physics.chem-ph), photoelectron circular dichroism, [PHYS]Physics [physics], femtocemistry, Physics - Chemical Physics, XPS, FOS: Physical sciences, General Physics and Astronomy
Abstract: International audience; Chiral molecules are widespread in nature, playing a fundamental role in biochemical processes and in the origin of life itself. The observation of dynamics in chiral molecules is crucial for the understanding and control of the chiral activity of photo-excited states. One of the most promising techniques for the study of photo-excited chiral systems is time-resolved photoelectron circular dichroism (TR-PECD), which offers an intense and sensitive probe for vibronic and geometric molecular structure as well as electronic structures, and their evolution on a femtosecond timescale. However, the non-local character of the PECD effect, which is imprinted during the electron scattering off the molecule, makes the interpretation of TR-PECD experiments challenging. In this respect, core-photoionization is known to allow site-and chemical-sensitivity to photelectron spectroscopy. Here we demonstrate that TR-PECD utilising core-level photoemission enables probing the chiral electronic structure and its relaxation dynamics with atomic site sensitivity. Following UV pumped excitation to a 3s Rydberg state, fenchone enantiomers (C 10 H 16 O) were probed on a femtosecond scale using circularly polarized soft X-ray light pulses provided by the free-electron laser FERMI. C 1s binding energy shifts caused by the redistribution of valence electron density in this 3s-valence-Rydberg excitation allowed us to measure transient PECD chiral responses with an enhanced C-atom site-selectivity compared to that achievable in the ground state molecule. These results represent the first chemical-specific and site-specific, enantio-sensitive observations on the electronic structure of a photo-excited chiral molecule and pave the way towards chiral femtochemistry probed by core-level photoemission.
Published: 2023

48. Invisible dilaton

Author: Philippe Brax, Clare Burrage, Jose A. R. Cembranos, Patrick Valageas, Institut de Physique Théorique - UMR CNRS 3681 (IPHT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), University of Nottingham, UK (UON), IPARCOS Institute and EMFTEL Department, Universidad Complutense de Madrid, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), and ANR-10-LABX-0038,P2IO,Physics of the 2 infinities and the origins(2010)
Subjects: scalar, Astrophysics and Astronomy, potential, gr-qc, satellite, halo, field theory, symmetry breaking, dark matter, thermal, local, radiative correction, Particle Physics - Phenomenology, electroweak interaction, General Relativity and Cosmology, fluctuation, background, screening, effective potential, hep-ph, alignment, oscillation, stability, condensation, scalar particle, equivalence principle, gravitation, [PHYS.HPHE]Physics [physics]/High Energy Physics - Phenomenology [hep-ph], astro-ph.CO, [PHYS.GRQC]Physics [physics]/General Relativity and Quantum Cosmology [gr-qc], mass, violation, [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph], dilaton, Higgs, symmetron
Abstract: We analyze the dynamics of a light scalar field responsible for the μ term of the Higgs potential and coupled to matter via the Higgs-portal mechanism. We find that this dilaton model is stable under radiative corrections induced by the standard model particle masses. When the background value of the scalar field is stabilized at the minimum of the scalar potential, the scalar field fluctuations only couple quadratically to the massive fields of the standard model preventing the scalar direct decay into standard model particles. Cosmologically and prior to the electroweak symmetry breaking, the scalar field rolls down along its effective potential before eventually oscillating and settling down at the electroweak minimum. These oscillations can be at the origin of dark matter due to the initial misalignment of the scalar field compared to the electroweak minimum, and we find that, when the mass of the scalar field is less than the electron volt scale and acts as a condensate behaving like dark matter on large scales, the scalar particles cannot thermalize with the standard model thermal bath. As matter couples in a composition-dependent manner to the oscillating scalar, this could lead to a violation of the equivalence principle aboard satellites such as the MICROSCOPE experiment and the next generation of tests of the equivalence principle. Local gravitational tests are evaded thanks to the weakness of the quadratic coupling in the dark matter halo, and we find that, around other sources, these dilaton models could be subject to a screening akin to the symmetron mechanism. We analyse the dynamics of a light scalar field responsible for the $\mu$ term of the Higgs potential and coupled to matter via the Higgs-portal mechanism. We find that this dilaton model is stable under radiative corrections induced by the standard model particle masses. When the background value of the scalar field is stabilised at the minimum of the scalar potential, the scalar field fluctuations only couple quadratically to the massive fields of the standard model preventing the scalar direct decay into standard model particles. Cosmologically and prior to the electroweak symmetry breaking, the scalar field rolls down along its effective potential before eventually oscillating and settling down at the electroweak minimum. These oscillations can be at the origin of dark matter due to the initial misalignment of the scalar field compared to the electroweak minimum, and we find that, when the mass of the scalar field is less than the eV scale and acts as a condensate behaving like dark matter on large scales, the scalar particles cannot thermalise with the standard model thermal bath. As matter couples in a composition-dependent manner to the oscillating scalar, this could lead to a violation of the equivalence principle aboard satellites such as the MICROSCOPE experiment and the next generation of tests of the equivalence principle. Local gravitational tests are evaded thanks to the weakness of the quadratic coupling in the dark matter halo, and we find that, around other sources, these dilaton models could be subject to a screening akin to the symmetron mechanism.
Published: 2023

49. Paving the way towards future‐proofing our crops

Author: Alexandra Baekelandt, Vandasue L. R. Saltenis, Philippe Nacry, Aleksandra Malyska, Marc Cornelissen, Amrit Kaur Nanda, Abhishek Nair, Peter Rogowsky, Laurens Pauwels, Bertrand Muller, Jonas Collén, Jonas Blomme, Mathias Pribil, Lars B. Scharff, Jessica Davies, Ralf Wilhelm, Norbert Rolland, Jeremy Harbinson, Wout Boerjan, Erik H. Murchie, Alexandra J. Burgess, Jean‐Pierre Cohan, Philippe Debaeke, Sébastien Thomine, Dirk Inzé, René Klein Lankhorst, Martin A. J. Parry, Department of Plant Systems Biology, VIB, and Department of Plant Biotechnology and Bioinformatics, Universiteit Gent = Ghent University (UGENT), University of Copenhagen = Københavns Universitet (UCPH), Institut des Sciences des Plantes de Montpellier (IPSIM), Centre National de la Recherche Scientifique (CNRS)-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), European Commission - DG Research and Innovation, BASF Agricultural Solutions Belgium NV, Plants for the Future European Technology Platform, Wageningen University and Research [Wageningen] (WUR), Reproduction et développement des plantes (RDP), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Écophysiologie des Plantes sous Stress environnementaux (LEPSE), 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), Laboratoire de Biologie Intégrative des Modèles Marins (LBI2M), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Department of Plant and Environmental Sciences [Copenhagen], Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Julius Kühn-Institut - Federal Research Centre for Cultivated Plants (JKI), Dynamique du protéome et biogenèse du chloroplaste (ChloroGenesis), Physiologie cellulaire et végétale (LPCV), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), University of Nottingham, UK (UON), ARVALIS - Institut du Végétal [Ouzouer le Marché] (ARVALIS), ARVALIS - Institut du végétal [Paris], AGroécologie, Innovations, teRritoires (AGIR), 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), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Lancaster Environment Centre, Lancaster University, and European Project: 817690,H2020 CropBooster-P
Subjects: Marketing and Consumer Behaviour, [SDV.SA]Life Sciences [q-bio]/Agricultural sciences, DIVERSITY, Biophysics, IMPROVEMENT, METABOLISM, future- proofed crops, future world scenarios, future-proofed crops, plant research, LIGNIN DEPOSITION, PLANT, crop productivity, Renewable Energy, Sustainability and the Environment, BioSolar Cells, Biology and Life Sciences, Forestry, crop yield, PE&RC, AMARANTH, [SDV.BV.AP]Life Sciences [q-bio]/Vegetal Biology/Plant breeding, Biofysica, DOMESTICATION, PHOSPHOLIPASE, Marktkunde en Consumentengedrag, EPS, Agronomy and Crop Science, TRAITS, RESISTANCE, Food Science
Abstract: International audience; To meet the increasing global demand for food, feed, fibre and other plant- derivedproducts, a steep increase in crop productivity is a scientifically and technicallychallenging imperative. The CropBooster- P project, a response to the H2020call ‘Future proofing our plants’, is developing a roadmap for plant research toimprove crops critical for the future of European agriculture by increasing cropyield, nutritional quality, value for non- food applications and sustainability.However, if we want to efficiently improve crop production in Europe and pri-oritize methods for crop trait improvement in the coming years, we need to takeinto account future socio- economic, technological and global developments, in-cluding numerous policy and socio- economic challenges and constraints. Basedon a wide range of possible global trends and key uncertainties, we developedfour extreme future learning scenarios that depict complementary future devel-opments. Here, we elaborate on how the scenarios could inform and direct fu-ture plant research, and we aim to highlight the crop improvement approachesthat could be the most promising or appropriate within each of these four futureworld scenarios. Moreover, we discuss some key plant technology options thatwould need to be developed further to meet the needs of multiple future learningscenarios, such as improving methods for breeding and genetic engineering. Inaddition, other diverse platforms of food production may offer unrealized poten-tial, such as underutilized terrestrial and aquatic species as alternative sources ofnutrition and biomass production. We demonstrate that although several meth-ods or traits could facilitate a more efficient crop production system in some ofthe scenarios, others may offer great potential in all four of the future learningscenarios. Altogether, this indicates that depending on which future we are head-ing toward, distinct plant research fields should be given priority if we are to meetour food, feed and non- food biomass production needs in the coming decades.
Published: 2023

50. PlantACT! – how to tackle the climate crisis

Author: Hirt, Heribert, Al-Babili, Salim, Almeida-Trapp, Marilia, Antoine, Martin, Aranda, Manuel, Bartels, Dorothea, Bennett, Malcolm, Blilou, Ikram, Boer, Damian, Boulouis, Alix, Bowler, Chris, Brunel-Muguet, Sophie, Chardon, Fabien, Colcombet, Jean, Colot, Vincent, Daszkowska-Golec, Agata, Dinneny, Jose, Field, Ben, Froehlich, Katja, Gardener, Catherine, Gojon, Alain, Gomès, Eric, Álvarez, Eva María Gómez, Gutierrez, Crisanto, Havaux, Michel, Hayes, Scott, Heard, Edith, Hodges, Michael, Alghamdi, Amal Khalaf, Laplaze, Laurent, Lauersen, Kyle, Leonhard, Nathalie, Johnson, Xenie, Jones, Jonathan, Kollist, Hannes, Kopriva, Stanislav, Krapp, Anne, Masson, Mauricio Lopez-Portillo, Mccabe, Matthew, Merendino, Livia, Molina, Antonio, Moreno Ramirez, Jose, Müller-Röber, Bernd, Nicolas, Michaël, Nir, Ido, Orduna, Izamar Olivas, Pardo-Tomás, José, Reichheld, Jean-Philippe, Egea, Pedro Luis Rodriguez, Rouached, Hatem, Saad, Maged, Schlögelhofer, Peter, Singh, Kirti, de Smet, Ive, Stanschewski, Clara, Stra, Alice, Tester, Mark, Walshe, Catherine, Weber, Andreas, Weigel, Detlef, Wigge, Philip, Wrzaczek, Michael, Wulff, Brande, Young, Iain, Weber, Andreas P.M., King Abdullah University of Science and Technology (KAUST), Biological and Environmental Sciences and Engineering Division [Thuwal, Arabie saoudite] (BESE), Division of Biological and Environmental Sciences and Engineering, Bioscience Core Labs, Institut des Sciences des Plantes de Montpellier (IPSIM), Centre National de la Recherche Scientifique (CNRS)-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), Red Sea Research Centre (RSRC), IMBIO, Rheinische Friedrich-Wilhelms-Universität Bonn, Centre for Plant Integrative Biology [Nothingham] (CPIB), University of Nottingham, UK (UON), Wageningen University and Research Centre (WUR), Physiologie membranaire et moléculaire du chloroplaste (PMMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ecophysiologie Végétale, Agronomie et Nutritions (EVA), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Recherche Agronomique (INRA), Ecophysiologie Végétale, Agronomie et Nutritions NCS (EVA), Normandie Université (NU)-Normandie Université (NU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire des interactions plantes micro-organismes (LIPM), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Institut Jean-Pierre Bourgin (IJPB), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut des Sciences des Plantes de Paris-Saclay (IPS2 (UMR_9213 / UMR_1403)), Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biologie moléculaire des organismes photosynthétiques (UMR8186), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Ecophysiologie et Génomique Fonctionnelle de la Vigne (UMR EGFV), Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV)-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), Institut de Biosciences et Biotechnologies d'Aix-Marseille (ex-IBEB) (BIAM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-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), Photosynthèse & Environnement (P&E), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Institute of Plant Sciences Paris-Saclay, Institut de Recherche pour le Développement (IRD en Occitanie) (IRD (Occitanie)), Laboratoire Génome et développement des plantes (LGDP), Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), and Plant Mineral Nutrition: Sensing, Signaling, and Transport, Plant & Soil Sciences Building
Subjects: water use efficiency, food safety, greenhouse gas emission, climate change, [SDV]Life Sciences [q-bio], [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Biology and Life Sciences, Plant Science, carbon sequestration, nitrogen use efficiency, agriculture
Abstract: International audience; Greenhouse gas (GHG) emissions have created a global climate crisis which requires immediate interventions to mitigate the negative effects on all aspects of life on this planet. As current agriculture and land use contributes up to 25% of total GHG emissions, plant scientists take center stage in finding possible solutions for a transition to sustainable agriculture and land use. In this article, the PlantACT! (Plants for climate ACTion!) initiative of plant scientists lays out a road map of how and in which areas plant scientists can contribute to finding immediate, mid-term, and long-term solutions, and what changes are necessary to implement these solutions at the personal, institutional, and funding levels.
Published: 2023

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