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358 results on '"Région Pays de la Loire"'

1. Evaluation of the Effectiveness of a Protocol for the Management of Female Functional Urinary Signs (PharmaCyst')

Author: Direction Générale de l'Offre de Soins, Agence régionale de santé, région Pays de la Loire, and Union régionale des professionnels de santé Pharmacien, région Pays de la Loire
Published: 2024

2. Investigating Major Recurring Campylobacter jejuni Lineages in Luxembourg Using Four Core or Whole Genome Sequencing Typing Schemes

Author: Laboratoire National de Santé [research center], INRAE - Oniris (France) [research center], Fonds National de la Recherche - FnR [sponsor], RFI Food for Tomorrow of Région Pays de la Loire - France [sponsor], Nennig, Morgane, LLARENA, Ann-Katrin, HEROLD, Malte, MOSSONG, Joël, PENNY, Christian, LOSCH, Serge, TRESSE, Odile, Ragimbeau, Catherine, Laboratoire National de Santé [research center], INRAE - Oniris (France) [research center], Fonds National de la Recherche - FnR [sponsor], RFI Food for Tomorrow of Région Pays de la Loire - France [sponsor], Nennig, Morgane, LLARENA, Ann-Katrin, HEROLD, Malte, MOSSONG, Joël, PENNY, Christian, LOSCH, Serge, TRESSE, Odile, and Ragimbeau, Catherine
Abstract: Campylobacter jejuni is the leading cause of bacterial gastroenteritis, which has motivated the monitoring of genetic profiles circulating in Luxembourg since 13 years. From our integrated surveillance using a genotyping strategy based on an extended MLST scheme including gyrA and porA markers, an unexpected endemic pattern was discovered in the temporal distribution of genotypes. We aimed to test the hypothesis of stable lineages occurrence by implementing whole genome sequencing (WGS) associated with comprehensive and internationally validated schemes. This pilot study assessed four WGS-based typing schemes to classify a panel of 108 strains previously identified as recurrent or sporadic profiles using this in-house typing system. The strain collection included four common lineages in human infection (N = 67) initially identified from recurrent combination of ST-gyrA-porA alleles also detected in non-human samples: veterinary (N = 19), food (N = 20), and environmental (N = 2) sources. An additional set of 19 strains belonging to sporadic profiles completed the tested panel. All the strains were processed by WGS by using Illumina technologies and by applying stringent criteria for filtering sequencing data; we ensure robustness in our genomic comparison. Four typing schemes were applied to classify the strains: (i) the cgMLST SeqSphere+ scheme of 637 loci, (ii) the cgMLST Oxford scheme of 1,343 loci, (iii) the cgMLST INNUENDO scheme of 678 loci, and (iv) the wgMLST INNUENDO scheme of 2,795 loci. A high concordance between the typing schemes was determined by comparing the calculated adjusted Wallace coefficients. After quality control and analyses with these four typing schemes, 60 strains were confirmed as members of the four recurrent lineages regardless of the method used (N = 32, 12, 7, and 9, respectively). Our results indicate that, regardless of the typing scheme used, epidemic or endemic signals were detected as reflected by lineage B (ST2254-gyrA9-porA1) i
Published: 2021

3. Divergent selection for longevity in breeding does

Author: Garreau, Herve, Ducrocq, Vincent, Tudela, Francois, Saleil, Georges, Esparbié, Jean, Juin, Herve, Lamothe, Eddie, Sordello, J-Jacques, Larzul, Catherine, Chambre Régionale D’agriculture Des Pays-De-La-Loire, ., La Région Pays de La Loire, ., La Municipalité Du Mans, ., Station d'Amélioration Génétique des Animaux (SAGA), Institut National de la Recherche Agronomique (INRA), Station de Génétique Quantitative et Appliquée (SGQA), Station Expérimentale Lapins et Palmipèdes (SELAP), Elevage Alternatif et Santé des Monogastriques (UE EASM), Chambre Régionale d'Agriculture des Pays de la Loire, Consortium de la Recherche en Epigénétique de la Région Pays de la Loire [Nantes], Mairie du Mans, Partenaires INRAE, and ProdInra, Migration
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], [INFO]Computer Science [cs], [INFO] Computer Science [cs]
Abstract: National audience; Une sélection divergente pour la longévité fonctionnelle, basée sur un index estimé grâce aux techniques d’analyse de survie, a été conduite dans la souche INRA 1077. L’expérience a été mise en place pour vérifier l’efficacité de ce type de sélection et pour analyser les conséquences sur les autres caractères de reproduction. Sachant que ces femelles sont conduites en bande, le critère retenu pour estimer la durée de vie productive a été le nombre d’inséminations artificielles sans élimination pour infertilité. L’expérience s’est déroulée sur deux générations. Un total de 48 mâles ont été testés sur descendance (10 filles/père). Sur la base de leur valeur génétique, 5 mâles "haut" et 5 mâles "bas" ont été retenus et ont servi à produire une nouvelle génération de mâles (5/père). Ces 48 nouveaux mâles ont été testés sur descendance dans les mêmes conditions pour estimer la réponse à la sélection. Une différence significative de longévité (+0.92 IA soit 39 jours) a été mesurée entre les deux lignées. Hormis pour le nombre de nés totaux plus élevé dans la lignée basse, Il n’y avait pas de différence entre les deux lignées pour les caractères de reproduction enregistrés à chaque mise-bas.
Published: 2007

4. Canalising selection on within litter variability of birth weight in rabbits.Responses to selection and characteristics of the uterus of the does

Author: Bolet, Gerard, Garreau, Herve, Hurtaud, J., Saleil, Georges, Esparbié, Jean, Falières, Jacky, Theau Clément, Michèle, Bodin, Loys, Chambre Régionale d’Agriculture des Pays-de-la-Loire, ., La Région Pays de la Loire, ., La Municipalité du Mans, ., Station d'Amélioration Génétique des Animaux (SAGA), Institut National de la Recherche Agronomique (INRA), Grimaud Frères Sélection, Chambre Régionale d'Agriculture des Pays de la Loire, Consortium de la Recherche en Epigénétique de la Région Pays de la Loire [Nantes], Mairie du Mans, Partenaires INRAE, and ProdInra, Migration
Subjects: [SDV] Life Sciences [q-bio], VARIABILITE, [SDV]Life Sciences [q-bio], ECART-TYPE
Abstract: National audience; Une expérience de sélection divergente sur la variabilité intra-portée du poids des lapereaux à la naissance a été conduite par l'INRA. Deux lignées divergentes ont été sélectionnées à partir de la souche AGP22(Grimaud Frères sélection). Cette sélection "canalisante" implique un nouveau modèle incluant une valeur génétique pour la moyenne et une valeur génétique pour la variabilité environnementale. Il y a eu une divergence significative pour l'écart-type du poids des lapereaux intra-portée entre les lignées sélectionnées pour augmenter(HOM) et diminuer (HET)l'homogénéité de la portée. Une réponse corrélée favorable a été observée pour la viabilité des lapereaux à la naissance et entre la naissance et le sevrage il n'y a pas eu d'effet sur le poids moyen des lapereaux à la naissance. Des femelles ont été abattues à la fin de la 3ème et de la 6ème génération pour mesurer la longueur des cornes utérines et leur élasticité en ajoutant un poids de 50 g puis 70 g. la longueur et l'élasticité des cornes utérines de la lignée HOM étaient significativement supérieures à celles de la lignée HET,quel que soit le poids ajouté.
Published: 2007

5. Essais d'amélioration de la production d'embryons chez la lapine

Author: Salvetti, Pascal, Guérin, Pierre, Theau Clément, Michèle, Hurtaud, J, BECKERS, J.F., Joly, Thierry, Chambre Régionale d’Agriculture des Pays-de-la-Loire, ., La Région Pays de la Loire, ., La Municipalité du Mans, ., Ecole Nationale Vétérinaire de Lyon (ENVL), Institut supérieur d'agriculture et d'agroalimentaire Rhône-Alpes (ISARA), Station d'Amélioration Génétique des Animaux (SAGA), Institut National de la Recherche Agronomique (INRA), Grimaud Frères Sélection SAS, Partenaires INRAE, Department of Physiology of Reproduction, Faculty of Veterinary Medicine, Chambre Régionale d'Agriculture des Pays de la Loire, Consortium de la Recherche en Epigénétique de la Région Pays de la Loire [Nantes], and Mairie du Mans
Subjects: PRODUCTION D'EMBRYONS, [SDV]Life Sciences [q-bio]
Abstract: National audience; Résumé. Les traitements de superovulation sont fréquemment utilisés lors des opérations de congélation d’embryons mais leur efficacité est très variable selon les individus traités ce qui entraîne une production d’embryons irrégulière. L’objectif de ce travail est d’optimiser la production qualitative et quantitative d’embryons chez la lapine en étudiant l’effet de la LH (Luteinizing Hormone) dans les traitements de superovulation (expérience 1) ou en essayant de synchroniser les vagues folliculaires (expérience 2). L’effet de la LH a été évalué par comparaison de deux traitements de superovulation à base de FSH (Follicle Stimulating Hormone) porcine contenant ou non 20% de LH porcine. Le traitement de synchronisation utilisait, préalablement au même traitement de superovulation (+20% LH), la prostaglandine F2α sur lapines rendues pseudogestantes. Ces études n’ont pas conduit à une amélioration significative des résultats de production d’embryons par rapport aux traitements classiques bien que la variabilité des réponses semble pouvoir être réduite. Ces travaux mettent une fois de plus en évidence le manque de connaissances scientifiques sur la cinétique de la croissance folliculaire chez la lapine.
Published: 2007

6. Does selection for growth rate influence the fertilising ability of rabbit semen ?

Author: Theau Clément, Michèle, Brun, Jean- Michel, Esparbié, Jean, Falières, Jacky, Garvanèse, Julie, Lamothe, Eddie, Larzul, Catherine, Milcent, Nicole, Saleil, Georges, Chambre Régionale d’Agriculture des Pays-de-la-Loire, ., La Région Pays de la Loire, ., La Municipalité du Mans, ., ProdInra, Migration, Station d'Amélioration Génétique des Animaux (SAGA), Institut National de la Recherche Agronomique (INRA), Elevage Alternatif et Santé des Monogastriques (UE EASM), Chambre Régionale d'Agriculture des Pays de la Loire, Consortium de la Recherche en Epigénétique de la Région Pays de la Loire [Nantes], Mairie du Mans, and Partenaires INRAE
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], [INFO]Computer Science [cs], [INFO] Computer Science [cs], VITESSE DE CROISSANCE
Abstract: National audience; Dans l’objectif d’étudier si la sélection pour la vitesse de croissance des lapereaux (poids à 63 j)influence la fécondance ultérieure de la semence des mâles, 17 mâles de deux lignées divergentes pour la vitesse de croissance ont été utilisés. 101 femelles INRA 2666 et 124 femelles INRA 1067, ont été inséminées tous les 42 jours pendant 4 séries. Les mâles de la lignée basse produisent un plus grand volume de semence (0,62 vs 0,54 ml), de pH plus élevé (6,96 vs 6,88) de meilleure motilité massale (6,98 vs 6,72), mais de concentration inférieure (686 vs 771x106 spz/ml) à celle des mâles de la lignée haute. La fertilité, la taille de portée et la productivité au sevrage sont fortement influencées par l’élevage, la série d’inséminations et l’état physiologique des lapines, mais ne varient pas significativement en fonction de la lignée. Dans les conditions expérimentales décrites, une sélection sur le poids à 63 jours n’influence pas la fécondance de la semence des mâles.
Published: 2007

7. The Histone Chaperone Network Is Highly Conserved in Physarum polycephalum

Author: Axel Poulet, Ellyn Rousselot, Stéphane Téletchéa, Céline Noirot, Yannick Jacob, Josien van Wolfswinkel, Christophe Thiriet, Céline Duc, Yale University [New Haven], Unité en Sciences Biologiques et Biotechnologies de Nantes (US2B), Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRAE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), This research was funded by National Institutes of Health, grant numbers #R35GM128661 (to Y.J.) and #R35GM128619 (to J.v.W.), LA LIGUE-GRAND OUEST (to C.T.), and RÉGION PAYS DE LA LOIRE, grants PULSAR and Etoiles Montantes (to C.D.). and the APC was funded by RÉGION PAYS DE LA LOIRE grant PULSAR and US2B-UMR6286.
Subjects: [SDV]Life Sciences [q-bio], Organic Chemistry, histone chaperones, protein domains, General Medicine, phylogeny, cell cycle, Physarum, Catalysis, Computer Science Applications, Inorganic Chemistry, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy
Abstract: International audience; The nucleosome is composed of histones and DNA. Prior to their deposition on chromatin, histones are shielded by specialized and diverse proteins known as histone chaperones. They escort histones during their entire cellular life and ensure their proper incorporation in chromatin. Physarum polycephalum is a Mycetozoan, a clade located at the crown of the eukaryotic tree. We previously found that histones, which are highly conserved between plants and animals, are also highly conserved in Physarum. However, histone chaperones differ significantly between animal and plant kingdoms, and this thus probed us to further study the conservation of histone chaperones in Physarum and their evolution relative to animal and plants. Most of the known histone chaperones and their functional domains are conserved as well as key residues required for histone and chaperone interactions. Physarum is divergent from yeast, plants and animals, but PpHIRA, PpCABIN1 and PpSPT6 are similar in structure to plant orthologues. PpFACT is closely related to the yeast complex, and the Physarum genome encodes the animal-specific APFL chaperone. Furthermore, we performed RNA sequencing to monitor chaperone expression during the cell cycle and uncovered two distinct patterns during S-phase. In summary, our study demonstrates the conserved role of histone chaperones in handling histones in an early-branching eukaryote.
Published: 2023

8. Robust coherent spin centers from stable azafullerene radicals entrapped in cycloparaphenylene rings

Author: Anastasios Stergiou, Denis Arčon, Yuri Tanuma, Christopher P. Ewels, Hermann A. Wegner, Jannis Volkmann, Nikos Tagmatarchis, Jeremy Rio, Andreja Bužan Bobnar, Mattia Gaboardi, Institut des Matériaux Jean Rouxel (IMN), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN), Toyo University, National Hellenic Research Foundation [Athens], Jozef Stefan Institute [Ljubljana] (IJS), Elettra Sincrotrone Trieste, Justus-Liebig-Universität Gießen (JLU), University of Ljubljana, French Government ScholarshipsInoue Enryo Memorial Grant Toyo University.Slovenian Research Agency (Core Research Funding No. P1-0125 and Projects No. J1-9145 and No. N1-0052).Région Pays de la Loire Pari Scientifique project 'NEWTUBE'BI-FR/21-22-PROTEUS-003 projectproject 'National Infrastructure in Nanotechnology, Advanced Materials and Micro-/Nanoelectronics' (MIS 5002772), implemented under the 'Reinforcement of the Research and Innovation Infrastructures', funded by the Operational Program 'Competitiveness, Entrepreneurship, and Innovation' (NSRF 2014–2020) and co-financed by Greece and the European Union (European Regional Development Fund)cooperation between Greece and Germany, IKYDA 2020, Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), and French Government ScholarshipsInoue Enryo Memorial Grant Toyo University.Slovenian Research Agency (Core Research Funding No. P1-0125 and Projects No. J1-9145 and No. N1-0052)Région Pays de la Loire - Pari Scientifique project 'NEWTUBE'BI-FR/21-22-PROTEUS-003 projectProject 'National Infrastructure in Nanotechnology, Advanced Materials and Micro-/Nanoelectronics' (MIS 5002772),Program 'Competitiveness, Entrepreneurship, and Innovation' (NSRF 2014–2020)Greece and the European Union (European Regional Development Fund)Program for the promotion of the exchange and scientific cooperation between Greece and Germany, IKYDA 2020
Subjects: Rabi cycle, Materials science, 02 engineering and technology, 010402 general chemistry, 7. Clean energy, 01 natural sciences, law.invention, law, General Materials Science, Spin (physics), Electron paramagnetic resonance, Quantum, azafullerenes, Quantum computer, Pulsed EPR, cycloparaphenylenes, [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Quantum technology, Chemical physics, Qubit, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], EPR, qubits, 0210 nano-technology
Abstract: International audience; Molecular entities with robust spin-1/2 are natural two-level quantum systems for realizing qubits and are key ingredients of emerging quantum technologies such as quantum computing. Here we show that robust and abundant spin-1/2 species can be created in-situ in the solid state from spin-active azafullerene (C59N) cages supramolecularly hosted in crystals of [10]cycloparaphenylene ([10]CPP) nanohoops. This is achieved via a two-stage thermally-assisted homolysis of the parent diamagnetic [10]CPP⊃(C59N)2⊂[10]CPP supramolecular complex. Upon cooling, the otherwise unstable C59N• radical is remarkably persistent with a measured radical lifetime of several years. Additionally, pulsed electron paramagnetic resonance measurements show long coherence times, fulfilling a basic condition for any qubit manipulation, and observed Rabi oscillations demonstrate single qubit operation. These findings together with rapid recent advances on the synthesis of carbon nanohoops offer the potential to fabricate tailored cycloparaphenylene networks hosting C59N• centers, providing a promising platform for building complex qubit circuits.
Published: 2021

9. Structural insights into the catalytic mechanism of granzyme B upon substrate and inhibitor binding

Author: Mélanie Chesneau, Sophie Brouard, Adèle Laurent, Richard Danger, Neha Tripathi, Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Team 4 : Deciphering organ immune regulation in inflammation and transplantation (DORI-t) (U1064 Inserm - CR2TI), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), CIC biothérapies CBT 0503 [Nantes], Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), NT thanks the Région Pays de la Loire and the Centre National de la Recherche Scientifique (CNRS) for the financial support during her post-doctoral research. ADL acknowledges the Région des Pays de la Loire for financial support within the framework of Mim-Breg. The IHU-Cesti project was also supported by Nantes Métropole and Région Pays de la Loire., ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010), ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), ANR-18-CE17-0019,PRELUD,Prédiction de la dysfonction chronique du greffon après transplantation pulmonaire(2018), ANR-17-CE17-0008,Biket,Cellules B GZMB+, un facteur clé de l'immunité chez l'homme?(2017), ANR-17-RHUS-0010,KTD-INNOV,Kidney Transplantation Diagnostics Innovation(2017), European Project: 754995,EU-TRAIN, KERANDEL-DION, Céline, Instituts Hospitalo-Universitaires B - Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU) - - CESTI (TSI-IHU)2010 - ANR-10-IBHU-0005 - IBHU - VALID, Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Prédiction de la dysfonction chronique du greffon après transplantation pulmonaire - - PRELUD2018 - ANR-18-CE17-0019 - AAPG2018 - VALID, Cellules B GZMB+, un facteur clé de l'immunité chez l'homme? - - Biket2017 - ANR-17-CE17-0008 - AAPG2017 - VALID, Kidney Transplantation Diagnostics Innovation - - KTD-INNOV2017 - ANR-17-RHUS-0010 - RHUS - VALID, and The EUropean TRAnsplantation and INnovation (EU-TRAIN) consortium for improving diagnosis and risk stratification in kidney transplant patients - EU-TRAIN - 754995 - INCOMING
Subjects: Molecular Dynamics, Catalysis, Granzymes, Substrate Specificity, Serine, Catalytic Domain, Catalytic triad, Materials Chemistry, Humans, Binding site, Enzyme Inhibitors, Physical and Theoretical Chemistry, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Spectroscopy, Binding Sites, biology, Chemistry, Catalytic mechanism, Active site, Human Granzyme B, Computer Graphics and Computer-Aided Design, Granzyme B, Catalytic cycle, Granzyme, biology.protein, Biophysics, Salt bridge, Serine Proteases, In silico Mutation
Abstract: Human granzyme B (hGzmB), which is present in various immune cells, has attracted much attention due to its role in various pathophysiological conditions. The hGzmB activity is triggered at a catalytic triad (His59, Asp103, Ser198), cleaving its specific substrates. To date, the drug design strategy against hGzmB mainly targets the catalytic triad, which causes the non-specificity problem of inhibitors due to the highly conserved active site in serine proteases. In the present work, microsecond classical molecular dynamics simulations are devoted to exploring the structural dynamics of the hGzmB catalytic cycle in the presence of Ac-IEPD-AMC, a known substrate (active hGzmB), and Ac-IEPD-CHO, a known inhibitor (inactive hGzmB). By comparing active and inactive forms of hGzmB in the six different stages of the hGzmB catalytic cycle, we revealed, for the very first time, an additional network of interactions involving Arg216, a residue located outside the conventional binding site. Upon activation, the His59∙∙∙Asp103 hydrogen bond is broken due to the formation of the Asp103∙∙∙Arg216 salt bridge, expanding the active site to facilitate the substrate-binding. On the contrary, the binding of inhibitor Ac-IEPD-CHO to hGzmB prevents the Arg216-mediated interactions within the catalytic triad, thus preventing hGzmB activity. In silico Arg216Ala mutation confirms the role of Arg216 in enzyme activity, as the substrate Ac-IEPD-AMC failed to bind to the mutated hGzmB. Importantly, as Arg216 is not conserved amongst the various granzymes, the current findings can be a major step to guide the design of hGzmB specific therapeutics.
Published: 2022

10. Rapamycin-Loaded Lipid Nanocapsules Induce Selective Inhibition of the mTORC1-Signaling Pathway in Glioblastoma Cells

Author: Séhédic, Delphine, Roncali, Loris, Djoudi, Amel, Buchtova, Nela, Avril, Sylvie, Chérel, Michel, Boury, Frank, Lacoeuille, Franck, Hindré, François, Garcion, Emmanuel, 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), Nuclear Oncology (CRCINA-ÉQUIPE 13), EUROPE : EURONANOMED III 2019-075 (GLIOSILK : Silk-fibroin interventional nano-trap for the treatment of glioblastoma), Région Pays-de-la-Loire & Cancéropole Grand-Ouest : NanoFar+ program (International strategy) funded by La Région Pays-de-la-Loire., INCA = PL-BIO 2014–2020, consortium MARENGO (MicroRNA agonist and antagonist Nanomedicines for GliOblastoma treatment: from molecular programmation to preclinical validation)., Région Pays-de-la-Loire & Cancéropole Grand-Ouest : MuMoFRaT project (Multi-scale Modeling & simulation of the response to hypo-Fractionated Radiotherapy or repeated molecular radiation Therapies)., EUROPE : NanoFar program (European doctorate in nanomedicine and pharmaceutical innovation) (Erasmus Mundus Joint Doctorate) funded by EACEA, ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011), ANR-19-ENM3-0003,GLIOSILK,Silk-fibroin interventional nano-trap for the treatment of glioblastoma.(2019), 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), Garcion, Emmanuel, Radiopharmaceutiques Innovants en Oncologie et Neurologie - - IRON2011 - ANR-11-LABX-0018 - LABX - VALID, and Silk-fibroin interventional nano-trap for the treatment of glioblastoma. - - GLIOSILK2019 - ANR-19-ENM3-0003 - Euronanomed III - VALID
Subjects: Histology, rapamycin, hypoxia, lcsh:Biotechnology, Akt, [SDV]Life Sciences [q-bio], Biomedical Engineering, Bioengineering and Biotechnology, HIF-1α, Bioengineering, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, [SDV] Life Sciences [q-bio], radiation, [SDV.CAN] Life Sciences [q-bio]/Cancer, lcsh:TP248.13-248.65, mTOR, cancer, nanoparticles, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Biotechnology, Original Research
Abstract: International audience; Inhibition of the PI3K/Akt/mTOR signaling pathway represents a potential issue for the treatment of cancer, including glioblastoma. As such, rapamycin that inhibits the mechanistic target of rapamycin (mTOR), the downstream effector of this signaling pathway, is of great interest. However, clinical development of rapamycin has floundered due to the lack of a suitable formulation of delivery systems. In the present study, a novel method for the formulation of safe rapamycin nanocarriers is investigated. A phase inversion process was adapted to prepare lipid nanocapsules (LNCs) loaded with the lipophilic and temperature sensitive rapamycin. Rapamycin-loaded LNCs (LNC-rapa) are ∼110 nm in diameter with a low polydispersity index (
Published: 2021

11. Initiative et injonction juridiques à se former après la loi sur la liberté de choisir son avenir professionnel

Author: Pascal CAILLAUD, Université de Nantes - UFR Droit et Sciences Politiques (UFR DSP), Université de Nantes (UN), Centre National de la Recherche Scientifique (CNRS), Maison des Sciences de l'Homme Ange-Guépin (MSH Ange-Guépin), Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Le Mans Université (UM)-Université de Nantes (UN), Droit et changement social (DCS), Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR Droit et Sciences Politiques (UFR DSP), Université de Nantes (UN)-Université de Nantes (UN), Région Pays de la Loire, Université d’Angers - ESO UMR CNRS 6590, Appel à projets 'Paris scientifiques régionaux' 2016 - Région Pays de la Loire, Le Mans Université (UM)-Université d'Angers (UA)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), and Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SHS.DROIT]Humanities and Social Sciences/Law, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020

12. Hemodynamics biomarkers quantification in cardiovascular imaging by 4D phase-contrast magnetic resonance

Author: Levilly, Sébastien, Laboratoire des Sciences du Numérique de Nantes (LS2N), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), École centrale de Nantes, Jérôme Idier, Université de Nantes - Faculté des Sciences et des Techniques, Région Pays de la Loire à 50 % (Paris scientifiques), Ecole Centrale de Nantes à 50 %, Ecole Centale de Nantes, Jérôme Idier [Directeur de thèse], Perrine Paul-Gilloteaux [co-encadrant], David Le Touzé [co-encadrant], and Projet MRI-Quantif (Paris Scientifiques de la région Pays de la Loire)
Subjects: 4D flow IRM, Wall shear stress, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Simulation numérique des fluides, Computational fluid dynamics, 4D Flow MRI, Cisaillement à la paroi, Carotide, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Carotid, IRM de flux 4D
Abstract: In cardiovascular imaging, a biomarker is quantitative information correlated with an existing or growing cardiovascular pathology. Biomarkers are generally obtained by anatomy and blood flow imaging. Recently, the 4D Flow MRI sequence opened new opportunities in measuring the blood flow within a 3D volume along the cardiac cycle. However, this sequence is a compromise between signal-to-noise ratio, resolution, and acquisition time. Allocated time being limited, velocity measurements are noisy and low resolution. In that context, biomarkers' quantification is challenging. This thesis's purpose is to enhance biomarkers' quantification and particularly for the wall shear stress (WSS). Two strategies have been investigated to reach that objective. A first solution allowing the spatiotemporal filtering of the velocity field has been proposed. It revealed the importance of the wall for the velocity field modelization. A second approach, being the major contribution of this work, focused on the design of a WSS quantification algorithm. This algorithm, named PaLMA, is based on the local modelization of the wall to build a velocity model near a point of interest. The WSS is computed from the velocity model. This algorithm embeds an a posteriori regularization step to improve the WSS quantification. Besides, a blurring model of 4D Flow MRI is used for the first time in the WSS quantification context. Finally, this algorithm has been validated over synthetic datasets, with carotids' complex flows, concerning the signal-to-noise ratio, the resolution, and the segmentation. The performances of PaLMA are superior to a reference solution in that domain, within a clinical routine context.; En imagerie cardiovasculaire, un biomarqueur est une information quantitative permettant d'établir une corrélation avec la présence ou le développement d'une pathologie cardiovasculaire. Ces biomarqueurs sont généralement obtenus grâce à l'imagerie de l'anatomie et du flux sanguin. Récemment, la séquence d'acquisition d'IRM de flux 4D a ouvert la voie à la mesure du flux sanguin dans un volume 3D au cours du cycle cardiaque. Or, ce type d'acquisition résulte d'un compromis entre le rapport signal sur bruit, la résolution et le temps d'acquisition. Le temps d'acquisition est limité et par conséquent les données sont bruitées et sous-résolues. Dans ce contexte, la quantification de biomarqueurs est difficile. L'objectif de cette thèse est d'améliorer la quantification de biomarqueurs et en particulier du cisaillement à la paroi. Deux stratégies ont été mises en oeuvre pour atteindre cet objectif. Une première solution permettant le filtrage spatio-temporel du champ de vitesse a été proposée. Cette dernière a révélé l'importance de la paroi dans la modélisation d'un champ de vitesse. Une seconde approche, constituant la contribution majeure de cette thèse, s'est focalisée sur la conception d'un algorithme estimant le cisaillement à la paroi. L'algorithme, nommé PaLMA, s'appuie sur la modélisation locale de la paroi pour construire un modèle de vitesse autour d'un point d'intérêt. Le cisaillement est évalué à partir du modèle de la vitesse. Cet algorithme intègre une étape de régularisation a posteriori améliorant la quantification du cisaillement à la paroi. Par ailleurs, une approximation du filtre IRM est utilisée pour la première fois pour l'estimation du cisaillement. Enfin, cet algorithme a été évalué sur des données synthétiques, avec des écoulements complexes au sein de carotides, en fonction du niveau de bruit, de la résolution et de la segmentation. Il permet d'atteindre des performances supérieures à une méthode de référence dans le domaine, dans un contexte représentatif de la pratique clinique.
Published: 2020

13. Discovery of a Small-Molecule Inhibitor of Interleukin 15: Pharmacophore-Based Virtual Screening and Hit Optimization

Author: Yannick Jacques, Monique Mathé-Allainmat, Laurence Arzel, Mike Maillasson, Erwan Mortier, Jacques Lebreton, Romy Vomiandry, Didier Dubreuil, Agnès Quéméner, Benoit Sicard, 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), Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), This work was funded by the programs CIMATH2 (Ciblage Moléculaire et Applications Thérapeutiques 2) and PIRAMID (Protein‐protein Interactions in Rational Approaches for Medicinal Innovative Drugs) supported by La Région Pays de la Loire. R.V. was supported by a fellowship from La Région Pays de la Loire. We thank CHEM)Symbiose and IMPACT facilities for technical assistance., Bernardo, Elizabeth, 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), and Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, 01 natural sciences, Cell Line, Small Molecule Libraries, Mice, Structure-Activity Relationship, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Drug Discovery, medicine, Animals, Humans, Receptor, Cell Proliferation, Interleukin-15, Virtual screening, 010405 organic chemistry, Chemistry, Interleukin, Stereoisomerism, Triazoles, Small molecule, 0104 chemical sciences, 3. Good health, Cell biology, Interleukin-2 Receptor beta Subunit, Molecular Docking Simulation, 030104 developmental biology, Cytokine, Interleukin 15, Immunology, Phthalazines, Molecular Medicine, Pharmacophore, Databases, Chemical, CD8
Abstract: International audience; Interleukin (IL)-15 is a pleiotropic cytokine, which is structurally close to IL-2 and shares with it the IL-2 β and γ receptor (R) subunits. By promoting the activation and proliferation of NK, NK-T and CD8+ T cells, IL-15 plays important roles in innate and adaptative immunity. Moreover, the association of high levels of IL-15 expression with inflammatory and autoimmune diseases has led to the development of various antagonistic approaches targeting IL- 15. This study is an original approach aimed at discovering small-molecule inhibitors impeding IL-15/IL-15R interaction. A pharmacophore and docking-based virtual screening of compound libraries led to the selection of 240 high-scoring compounds, 36 of which were found to bind IL-15, to inhibit the binding of IL-15 to the IL-2Rβ chain and/or the proliferation of IL-15-dependent cells. One of them was selected as a hit, optimized by a structure-activity relationship approach, leading to the first small-molecule IL-15 inhibitor with sub-micromolar activity.
Published: 2017

14. Diuron exposure and Akt overexpression promote glioma formation through DNA hypomethylation

Author: Briand, Joséphine, Nadaradjane, Arulraj, Bougras-Cartron, Gwenola, Olivier, Christophe, Vallette, François M., Cartron, Pierre-François, Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9), 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), Laboratoire de Biologie des Cancers et de Théranostic [St Herblain, Nantes] (LabCT), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Réseau Epigénétique du Cancéropôle Grand-Ouest [Nantes] (REpiCGO), Cancéropôle Grand Ouest [Nantes]-Maison de la Recherche en Santé [Nantes], Epigénétique - Santé - AgroAlimentaire - Végétal - Mer - Environnement - Nutrition [Nantes] (EpiSAVMEN), Consortium de la Recherche en Epigénétique de la Région Pays de la Loire [Nantes], Service de pharmacologie et de Toxicologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), LabEX IGO Immunothérapie Grand Ouest, JB was supported by a fellowship from EpiSAVMEN/Région Pays de la Loire (Programme Dynamique Scientifique 2016). We also thank 'En Avant la Vie' (an association supporting the patients suffering from gliomas and their family, and the research on glioma field) for the partial funding of the JB’s fellowship., 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), Nantes Université (Nantes Univ), and Bernardo, Elizabeth
Subjects: PD-L1, DNA methylation, Brain Neoplasms, Research, Receptors, Cell Surface, Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Glioma, B7-H1 Antigen, Up-Regulation, Gene Expression Regulation, Neoplastic, Mice, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, Diuron, 5-Methylcytosine, Animals, Humans, Lectins, C-Type, Gliomagenesis, Apoptosis Regulatory Proteins, Proto-Oncogene Proteins c-akt, Neoplasm Transplantation
Abstract: International audience; Background: Diuron is an environmental component listed as a likely human carcinogen. Several other studies report that diuron can be oncogenic for bladder, urothelial, skin, and mammary cells. No study mentions the putative effect of diuron on the glioma occurrence. Objectives: We here wanted to investigate the effects of diuron exposure on the glioma occurrence while wishing to incriminate a putative implication of DNA methylation modulation in this process. Methods: In in vivo model of glioma, diuron exposure was firstly compared or combined with oncogenic overexpressions already known to promote gliomagenesis. ELISA quantifying the 5-methylcytosine level on DNA was performed to examine the global DNA methylation level. Quantitative real-time polymerase chain reaction and proximity ligation in situ assay were performed to identify the molecular causes of the diuron-induced changes of DNA methylation. The signatures diuron-induced changes of DNA methylation were analyzed in a cohort of 23 GBM patients. Results: Diuron exposure is not sufficient to promote glioma, such as the oncogenic overexpression of Akt or Ras. However, the combination of diuron exposure and Akt overexpression promotes glioma. We observed that the diuron/Akt-induced glioma is characterized by three phenotypic signatures characterizing cancer cells: a global DNA hypomethylation, a loss of sensitivity to cell death induction, and a gain of signals of immune escape. Our data associated these phenotypes with three aberrant DNA methylation signatures: the LLT1, PD-L1, and Bcl-w hypomethylations. Strikingly, we observed that these three concomitant hypomethylations were only observed in GBM patients having a potential exposure to diuron via their professional activity. Conclusions: As single player, diuron is not an oncogenic of glioma, but it can participate to the glioma formation in association with other events (also devoid of oncogenic property as single player) such as Akt overexpression.
Published: 2019

15. In vivo analysis of human immune responses in immunodeficient rats

Author: Menoret, Séverine, Ouisse, Laure-Hélène, Tesson, Laurent, Remy, Severine, Usal, Claire, Guiffes, Aude, Chenouard, Vanessa, Royer, Pierre-Joseph, Evanno, Gwénaëlle, Vanhove, Bernard, Piaggio, Eliane, Anegon, Ignacio, Le Bihan, Sylvie, Initiative d'excellence - Paris Sciences et Lettres - - PSL2010 - ANR-10-IDEX-0001 - IDEX - VALID, Instituts Hospitalo-Universitaires B - Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU) - - CESTI (TSI-IHU)2010 - ANR-10-IBHU-0005 - IBHU - VALID, Laboratoires communs organismes de recherche publics – PME/ETI - Nouveaux outils pour la création de rongeurs génétiquement modifiés - - SOURIRAT2014 - ANR-14-LAB5-0008 - LABCOM - VALID, Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), 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), Xenothera [Nantes, France], Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was performed in the context of different programs: Biogenouest by Région Pays de la Loire, IBiSA program, TEFOR (Investissements d’Avenir French Government program, ANRII-INSB-0014), LabCom SOURIRAT project (ANR-14-LAB5-0008), Labex IGO project (Investissements d’Avenir French Government program, ANR-11-LABX-0016-01), IHU-Cesti project (Investissements d’Avenir French Government program, ANR-10-IBHU-005, Nantes Métropole and Région Pays de la Loire) and Fondation Progreffe. TransImm team (E.P.) is supported by LabEx DCBIOL (ANR-10-IDEX-0001-02 PSL and ANR-11-LABX-0043), SIRIC INCa-DGOS-Inserm_12554, Center of Clinical Investigation (CIC IGR-Curie 1428)., ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010), ANR-14-LAB5-0008,SOURIRAT,Nouveaux outils pour la création de rongeurs génétiquement modifiés(2014), and ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011)
Subjects: Homeodomain Proteins, Immunoglobulin gamma-Chains, [SDV]Life Sciences [q-bio], Immunologic Deficiency Syndromes, Graft vs Host Disease, Breast Neoplasms, Antigens, Differentiation, Xenograft Model Antitumor Assays, Rats, Sprague-Dawley, [SDV] Life Sciences [q-bio], Disease Models, Animal, Immunocompromised Host, Original Basic Science—General, Cell Line, Tumor, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Leukocytes, Mononuclear, Animals, Heterografts, Humans, Female, Rats, Transgenic, Receptors, Immunologic, Antilymphocyte Serum
Abstract: Supplemental Digital Content is available in the text., Background. Humanized immune system immunodeficient mice have been extremely useful for the in vivo analyses of immune responses in a variety of models, including organ transplantation and graft versus host disease (GVHD) but they have limitations. Rat models are interesting complementary alternatives presenting advantages over mice, such as their size and their active complement compartment. Immunodeficient rats have been generated but human immune responses have not yet been described. Methods. We generated immunodeficient Rat Rag−/− Gamma chain−/− human signal regulatory protein alpha-positive (RRGS) rats combining Rag1 and Il2rg deficiency with the expression of human signal regulatory protein alpha, a negative regulator of macrophage phagocytosis allowing repression of rat macrophages by human CD47-positive cells. We then immune humanized RRGS animals with human peripheral blood mononuclear cells (hPBMCs) to set up a human acute GVHD model. Treatment of GVHD was done with a new porcine antihuman lymphocyte serum active through complement-dependent cytotoxicity. We also established a tumor xenograft rejection model in these hPBMCs immune system RRGS animals by subcutaneous implantation of a human tumor cell line. Results. RRGS animals receiving hPBMCs showed robust and reproducible reconstitution, mainly by T and B cells. A dose-dependent acute GVHD process was observed with progressive weight loss, tissue damage, and death censoring. Antihuman lymphocyte serum (L1S1) antibody completely prevented acute GVHD. In the human tumor xenograft model, detectable tumors were rejected upon hPBMCs injection. Conclusions. hPBMC can be implanted in RRGS animals and elicit acute GVHD or rejection of human tumor cells and these are useful models to test new immunotherapies.
Published: 2019

16. CD9+ Regulatory B Cells Induce T Cell Apoptosis via IL-10 and Are Reduced in Severe Asthmatic Patients

Author: Bousseau, Carole, Durand, Maxim, Colas, Luc, Durand, Eugenie, Foureau, Aurore, Cheminant, Marie-Aude, Bouchaud, Grégory, Castan, Laure, Klein, Martin, Magnan, Antoine, Brouard, Sophie, Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Immunoregulation And Immunointervention in Transplantation and Autoimmunity (Team 4 - U1064 Inserm - CRTI), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), INRA Centre Angers-Nantes [Nantes, France], CIC biothérapies CBT 0503 [Nantes], Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), This work was supported by a grant from l’Institut de Recherche en Santé Respiratoire-Pays de la Loire. This work was achieved in the context of the BASAL project financed by Région Pays de la Loire and the IHU-Cesti project, the DHU Oncogreffe and the LabEX IGO thanks to French government financial support managed by the National Research Agency via the Investment into the Future program (ANR-10-IBHU-005 and ANR-11-LABX-0016-01). The IHU-Cesti project is also supported by Nantes Métropole and Région Pays de la Loire., ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010), ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), Le Bihan, Sylvie, Instituts Hospitalo-Universitaires B - Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU) - - CESTI (TSI-IHU)2010 - ANR-10-IBHU-0005 - IBHU - VALID, Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID, Unité de recherche de l'institut du thorax (ITX-lab), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), and Institut National de la Recherche Agronomique (INRA)
Subjects: Adult, Male, severe asthma, [SDV.IMM] Life Sciences [q-bio]/Immunology, MAP Kinase Signaling System, Immunology, Cell Communication, Mitochondrial Dynamics, Severity of Illness Index, Tetraspanin 29, Mice, effector T cells, T-Lymphocyte Subsets, regulatory B cells, CD9(+) B cells, apoptosis, Animals, Humans, Prospective Studies, Lung, Original Research, Aged, B-Lymphocytes, Regulatory, CD9+ B cells, Middle Aged, G1 Phase Cell Cycle Checkpoints, Asthma, Interleukin-10, Disease Models, Animal, embryonic structures, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, CD9 + B cells
Abstract: International audience; CD9 was recently identified as a marker of murine IL-10-competent regulatory B cells. Functional impairments or defects in CD9 + IL-10-secreting regulatory B cells are associated with enhanced asthma-like inflammation and airway hyperresponsiveness. In mouse models, all asthma-related features can be abrogated by CD9 + B cell adoptive transfer. We aimed herein to decipher the profiles, features, and molecular mechanisms of the regulatory properties of CD9 + B cells in human and mouse. The profile of CD9 + B cells was analyzed using blood from severe asthmatic patients and normal and asthmatic mice by flow cytometry. The regulatory effects of mouse CD9 + B cells on effector T cell death, cell cycle arrest, apoptosis, and mitochondrial depolarization were determined using yellow dye, propidium iodide, Annexin V, and JC-1 staining. MAPK phosphorylation was analyzed by western blotting. Patients with severe asthma and asthmatic mice both harbored less CD19 + CD9 + B cells, although these cells displayed no defect in their capacity to induce T cell apoptosis. Molecular mechanisms of regulation of CD9 + B cells characterized in mouse showed that they induced effector T cell cycle arrest in sub G0/G1, leading to apoptosis in an IL-10-dependent manner. This process occurred through MAPK phosphorylation and activation of both the intrinsic and extrinsic pathways. This study characterizes the molecular mechanisms underlying the regulation of CD9 + B cells to induce effector T cell apoptosis in mice and humans via IL-10 secretion. Defects in CD9 + B cells in blood from patients with severe asthma reveal new insights into the lack of regulation of inflammation in these patients.
Published: 2018

17. Loss of vascular expression of nucleoside triphosphate diphosphohydrolase-1/CD39 in hypertension

Author: Antoine Caillon, Daniel Henrion, Ludovic Martin, Julie Favre, Daniele C. Nascimento, Jean Sévigny, Julie Tabiasco, Bernhard Ryffel, Jean Mérot, Charlotte Roy, Simon C. Robson, Gilles Kauffenstein, Yves Delneste, Anne-Laure Guihot, Euromov (EuroMov), Université de Montpellier (UM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de médecine moléculaire de Rangueil (I2MR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Physique et Physiologie Intégratives de l'Arbre Fruitier et Forestier (PIAF), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut National de la Recherche Agronomique (INRA), Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Département de microbiologie-infectiologie et d’immunologie [Québec City, QC, Canada], Faculté de médecine de l'Université Laval [Québec] (ULaval), Biologie et physiologie moléculaire du vaisseau, Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), 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), Unité de recherche de l'institut du thorax (ITX-lab), Division of Gastroenterology [Boston, MA, USA], Harvard University [Cambridge]-Harvard Medical School [Boston] (HMS)-Beth Israel Deaconess Medical Center [Boston] (BIDMC), Harvard Medical School [Boston] (HMS), Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Centre de recherche [CHU Québec, Canada], Medical Biology, Medicine / Université de Laval-Hôtel-Dieu de Québec [Canada]-CHU de Québec–Université Laval, MitoVasc Institute was supported by INSERM, CNRS, University of Angers, CHU of Angers, Région Pays de la Loire, Angers-Loire Métropole, and Département du Maine et Loire. CR was supported by grants from INSERM and Région Pays de la Loire., Bernardo, Elizabeth, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Faculté de médecine de l'Université Laval (Québec) [Canada], Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), 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), and Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO)
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Vascular smooth muscle, Nucleotidase activity, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Myocytes, Smooth Muscle, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030204 cardiovascular system & hematology, Proinflammatory cytokine, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Antigens, CD, Internal medicine, medicine, Animals, Ectonucleotidase, Endothelial dysfunction, Molecular Biology, ComputingMilieux_MISCELLANEOUS, CD39, Chemistry, Angiotensin II, Apyrase, Endothelial Cells, Arteries, Cell Biology, medicine.disease, 3. Good health, Mice, Inbred C57BL, ATP, 030104 developmental biology, Cytokine, Endocrinology, Hypertension, Original Article, Tumor necrosis factor alpha
Abstract: International audience; Ectonucleoside triphosphate diphosphohydrolase-1, the major vascular/immune ectonucleotidase, exerts anti-thrombotic and immunomodulatory actions by hydrolyzing extracellular nucleotides (danger signals). Hypertension is characterized by vascular wall remodeling, endothelial dysfunction, and immune infiltration. Here our aim was to investigate the impact of arterial hypertension on CD39 expression and activity in mice. Arterial expression of CD39 was determined by reverse transcription quantitative real-time PCR in experimental models of hypertension, including angiotensin II (AngII)-treated mice (1 mg/kg/day, 21 days), deoxycorticosterone acetate-salt mice (1% salt and uninephrectomy, 21 days), and spontaneously hypertensive rats. A decrease in CD39 expression occurred in the resistance and conductance arteries of hypertensive animals with no effect on lymphoid organs. In AngII-treated mice, a decrease in CD39 protein levels (Western blot) was corroborated by reduced arterial nucleotidase activity, as evaluated by fluorescent (etheno)-ADP hydrolysis. Moreover, serum-soluble ADPase activity, supported by CD39, was significantly decreased in AngII-treated mice. Experiments were conducted in vitro on vascular cells to determine the elements underlying this downregulation. We found that CD39 transcription was reduced by proinflammatory cytokines interleukin (IL)-1β and tumor necrosis factor alpha on vascular smooth muscle cells and by IL-6 and anti-inflammatory and profibrotic cytokine transforming growth factor beta 1 on endothelial cells. In addition, CD39 expression was downregulated by mechanical stretch on vascular cells. Arterial expression and activity of CD39 were decreased in hypertension as a result of both a proinflammatory environment and mechanical strain exerted on vascular cells. Reduced ectonucleotidase activity may alter the vascular condition, thus enhancing arterial damage, remodeling, or thrombotic events.
Published: 2018

18. TLR3 promotes MMP-9 production in primary human airway epithelial cells through Wnt/β-catenin signaling

Author: Royer, Pierre Joseph, Antoine, Martine, Cappello, Matteo, Souilamas, Redha, Ruiz, M., Sokolow, Youri, Vanden Eynden, Frédéric, Van Nooten, Guido, Barvais, Luc, Berré, Jacques, Brimioulle, Serge, De Backer, Daniel, Creteur, Jacques, Engelman, E., Huybrechts, Isabelle, Ickx, Brigitte, Preiser, T.J.C., Tuna, Tibel, Van Obbergh, Luc, Vancutsem, Nathalie, Vincent, Jean Louis, De Vuyst, Paul, Etienne, Isabelle, Féry, F., Jacobs, Frédérique, Knoop, Christiane, Vachiery, Jean-Luc, Van den Borne, Pleunie, Wellemans, Isabelle, Amand, G., Collignon, Laurent, Giroux, Martin, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de pneumologie [Hôpital Foch], Hôpital Foch [Suresnes], Pôle Thorax et Vaisseaux [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Faculté de Médecine - Université de Nantes, CIC biothérapies CBT 0503 [Nantes], Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), This research program was supported by Vaincre la Mucoviscidose, Association Gregory Lemarchal, Agence de Biomédecine, INSERM, Région Pays de La Loire, Institut de Recherche en Santé Respiratoire des Pays de la Loire, Fonds de Recherche en Santé Respiratoire, Fondation du Souffle and Fondation pour la Recherche Médicale. This work was realized in the context of the IHU-Cesti project, the DHU Oncogreffe, the LabEX IGO and the Labex TRANSPLANTEX thanks to French government financial support managed by the National Research Agency via the 'Investment Into The Future'. The IHU-Cesti project is also supported by Nantes Métropole and Région Pays de la Loire., Degauque, Nicolas, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Dr SPOC, Paris
Subjects: Lipopolysaccharides, 0301 basic medicine, Chemokine, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], medicine.medical_treatment, CCL3, Respiratory Mucosa, 03 medical and health sciences, 0302 clinical medicine, Transforming Growth Factor beta, medicine, Humans, CXCL10, Wnt Signaling Pathway, Cells, Cultured, beta Catenin, lcsh:RC705-779, Toll-like receptor, biology, Chemistry, Research, Wnt signaling pathway, Receptor Cross-Talk, lcsh:Diseases of the respiratory system, respiratory system, Toll-Like Receptor 3, 3. Good health, Cell biology, 030104 developmental biology, Cytokine, Matrix Metalloproteinase 9, 030228 respiratory system, TLR4, biology.protein, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Tumor necrosis factor alpha, Pneumologie, Chemokines
Abstract: Background: Airway epithelial cells (AEC) act as the first line of defence in case of lung infections. They constitute a physical barrier against pathogens and they participate in the initiation of the immune response. Yet, the modalities of pathogen recognition by AEC and the consequences on the epithelial barrier remain poorly documented. Method: We investigated the response of primary human AEC to viral (polyinosinic-polycytidylic acid, poly(I:C)) and bacterial (lipopolysaccharide, LPS) stimulations in combination with the lung remodeling factor Transforming Growth Factor-β (TGF-β). Results: We showed a strong production of pro-inflammatory cytokines (Interleukin (IL)-6, Tumor Necrosis Factor α, TNFα) or chemokines (CCL2, CCL3, CCL4, CXCL10, CXCL11) by AEC stimulated with poly(I:C). Cytokine and chemokine production, except CXCL10, was Toll Like Receptor (TLR)-3 dependent and although they express TLR4, we found no cytokine production after LPS stimulation. Poly(I:C), but not LPS, synergised with TGF-β for the production of matrix metalloproteinase-9 (MMP-9) and fibronectin. Mechanistic analyses suggest the secretion of Wnt ligands by AEC along with a degradation of the cellular junctions after poly(I:C) exposure, leading to the release of β-catenin from the cell membrane and stimulation of the Wnt/β-catenin pathway. Conclusion: Our results highlight the cross talk between TGF-β and TLR signaling in bronchial epithelium and its impact on the remodeling process., 0, SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2017

19. Interleukin-10 plays a key role in the modulation of neutrophils recruitment and lung inflammation during infection byStreptococcus pneumoniae

Author: Hernán F. Peñaloza, Pamela A. Nieto, Natalia Muñoz-Durango, María José Parga, Javiera Torres, Francisco J. Salazar-Echegarai, Manuel Álvarez-Lobos, Susan M. Bueno, Claudia A. Riedel, Alexis M. Kalergis, Departamento de Microbiologıa y Genetica Molecular [Santiago, Chile] (Facultad de Ciencias Biologicas), Pontificia Universidad Católica de Chile (UC), Departamento de Anatomia Patologica [Santiago, Chile] (Facultad de Medicina), Departamento de Gastroenterologıa [Santiago, Chile] (Facultad de Medicina), Departamento de Ciencias Biologicas [Santiago, Chile] (Facultad de Ciencias Biologicas y Facultad de Medicina), Universidad Andrés Bello [Santiago] (UNAB), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), 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), Departamento de Inmunologıa Clınica y Reumatologıa [Santiago, Chile] (Escuela de Medicina), This study was supported by the following grants: FONDO NACIONAL DE CIENCIA Y TECNOLOGIA DE CHILE (FONDECYT numbers 1140010, 1110604, 1100971, 1131012, 1150862 and 1110397), Millennium Institute on Immunology and Immunotherapy P09/016-F and Grant ‘Nouvelles Equipes-nouvelles thématiques’ from the La Région Pays De La Loire. HFP, PAN, NMD and MJP are supported by the Comision Nacional de Investigacion Cientıﬁca y Tecnologica (CONICYT). AMK is a Chaire De La Région Pays De La Loire, Chercheur Etranger D’excel-lence, France., and Le Bihan, Sylvie
Subjects: medicine.medical_treatment, Interleukin-1beta, Immunology, Inflammation, Biology, medicine.disease_cause, Pathogenesis, Sepsis, Interferon-gamma, Mice, 03 medical and health sciences, 0302 clinical medicine, neutrophils, Streptococcus pneumoniae, medicine, Animals, Immunology and Allergy, Lung, 030304 developmental biology, Mice, Knockout, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Tumor Necrosis Factor-alpha, bacterial infection, Brain, Original Articles, Pneumonia, Pneumococcal, medicine.disease, Bacterial Load, cytokines, Interleukin-10, respiratory tract diseases, 3. Good health, Mice, Inbred C57BL, Interleukin 10, Otitis, Cytokine, Neutrophil Infiltration, Pneumococcal pneumonia, systemic bacterial infection, medicine.symptom, lung inﬂammation, Spleen, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: International audience; Streptococcus pneumoniae is a major aetiological agent of pneumonia worldwide, as well as otitis media, sinusitis, meningitis and sepsis. Recent reports have suggested that inﬂammation of lungs due to S. pneumoniae infection promotes bacterial dissemination and severe disease. However, the contribution of anti-inﬂammatory molecules to the pathogenesis of S. pneumoniae remains unknown. To elucidate whether the production of the anti-inﬂammatory cytokine interleukin-10 (IL-10) is beneﬁcial or detrimental for the host during pneumococcal pneumonia, we performed S. pneumoniae infections in mice lacking IL-10 (IL-10[-/-] mice). The IL-10/[-/-] mice showed increased mortality, higher expression of proinﬂammatory cytokines, and an exacerbated recruitment of neutrophils into the lungs after S. pneumoniae infection. However, IL-10[-/-] mice showed signiﬁcantly lower bacterial loads in lungs, spleen, brain and blood, when compared with mice that produced this cytokine. Our results support the notion that production of IL-10 during S. pneumoniae infection modulates the expression of pro-inﬂammatory cytokines and the inﬁltration of neutrophils into the lungs. This feature of IL-10 is important to avoid excessive inﬂammation of tissues and to improve host survival, even though bacterial dissemination is less efﬁcient in the absence of this cytokine.
Published: 2015

20. Locoregional Confinement and Major Clinical Benefit of 188 Re-Loaded CXCR4-Targeted Nanocarriers in an Orthotopic Human to Mouse Model of Glioblastoma

Author: Séhédic, Delphine, Chourpa, Igor, Tétaud, Clément, Griveau, Audrey, Loussouarn, Claire, Avril, Sylvie, Legendre, Claire, Lepareur, Nicolas, Wion, Didier, Hindré, François, Davodeau, François, Garcion, Emmanuel, 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), Nanomédicaments et Nanosondes, EA 6295 (NMNS), Université de Tours, Plateforme de Radiobiologie et d’Imagerie EXperimentale - PRIMEX [Angers], Université d'Angers (UA), Département d'oncologie médicale [Rennes], CRLCC Eugène Marquis (CRLCC), BrainTech Laboratory [CHU Grenoble Alpes - Inserm U1205] (Brain Tech Lab ), CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Nuclear Oncology (CRCINA-ÉQUIPE 13), Plateforme d’Analyses Cellulaires et Moléculaires - PACeM [Angers], This work was supported by 'La Région Pays-de-la-Loire' through the Nuclear Technology for Health project (NucSan), by the 'Institut National de la Santé et de la Recherche Médicale' (INSERM), by 'La Ligue Nationale Contre le Cancer' through an 'Equipe Labellisée 2012' grant and by the 'Axe Vectorisation and Radiothérapies of the Cancéropôle Grand-Ouest'. Delphine Séhédic was a Ph.D. student from the NucSan project and received a fellowship from 'La Région Pays-de-la-Loire'. N.L., F.H., F.D. and E.G. are also member of the LabEx IRON 'Innovative Radiopharmaceuticals in Oncology and Neurology' as part of the French government 'Investissements d’Avenir' program. The presented work is also related to the PL-BIO 2014-2020 INCA (Institut National du Cancer) project MARENGO - 'MicroRNA agonist and antagonist Nanomedicines for GliOblastoma treatment: from molecular programmation to preclinical validation', to the ANR (French National Research Agency) program RADIOHEAD 'Nanocapsules for Selective Internal RadioTherapy of glioblastoma, and to the 'Région Pays-de-la-Loire' project IRAD' Pre-clinical validation of an innovative Internal RADiotherapy of glioma in a large spontaneous animal model'. C.Lo., and C.Le. were posdoctoral fellows Inca and Fondation ARC, respectively., Université de Tours (UT), Bernardo, Elizabeth, 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), Plateforme de Radiobiologie et d’Imageries EXpérimentale [SFR ICAT - UA] (PRIMEX), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), and Université d'Angers (UA)-Université d'Angers (UA)
Subjects: CXCR4, nanoparticle, [SDV.CAN] Life Sciences [q-bio]/Cancer, glioblastoma, immuno-targeting, spectral imaging, [SDV.CAN]Life Sciences [q-bio]/Cancer, macrophage, radiation therapy
Abstract: International audience; Purpose: Gold standard beam radiation for glioblastoma (GBM) treatment is challenged by resistance phenomena occurring in cellular populations well prepared to survive or to repair damage caused by radiation. Among signals that have been linked with radio-resistance, the SDF1/CXCR4 axis, associated with cancer stem-like cell, may be an opportune target. To avoid the problem of systemic toxicity and blood-brain barrier crossing, the relevance and efficacy of an original system of local brain internal radiation therapy combining a radiopharmaceutical with an immuno-nanoparticle was investigated.Experiment design: The nanocarrier combined lipophilic thiobenzoate complexes of rhenium-188 loaded in the core of a lipid nanocapsule (LNC188Re) with a function-blocking antibody, 12G5 directed at the CXCR4, on its surface. The efficiency of 12G5-LNC188Re was investigated in an orthotopic and xenogenic GBM model of CXCR4-positive U87MG cells implanted in the striatum of Scid mice.Results: We demonstrated that 12G5-LNC188Re single infusion treatment by convection-enhanced delivery resulted in a major clinical improvement in median survival that was accompanied by locoregional effects on tumor development including hypovascularization and stimulation of the recruitment of bone marrow derived CD11b- or CD68-positive cells as confirmed by immunohistochemistry analysis. Interestingly, thorough analysis by spectral imaging in a chimeric U87MG GBM model containing CXCR4-positive/red fluorescent protein (RFP)-positive- and CXCR4-negative/RFP-negative-GBM cells revealed greater confinement of DiD-labeled 12G5-LNCs than control IgG2a-LNCs in RFP compartments. Main conclusion: These findings on locoregional impact and targeting of disseminated cancer cells in tumor margins suggest that intracerebral active targeting of nanocarriers loaded with radiopharmaceuticals may have considerable benefits in clinical applications.
Published: 2017

21. T Cells Promote Bronchial Epithelial Cell Secretion of Matrix Metalloproteinase-9 via a C-C Chemokine Receptor Type 2 Pathway: Implications for Chronic Lung Allograft Dysfunction

Author: Pain, Mallory, Royer, Pierre-Joseph, Loy, Jennifer, Girardeau, Aurore, Tissot, A., Lacoste, P., Roux, A., Reynaud-Gaubert, M., Kessler, R., Mussot, S., Dromer, C., Brugiere, O., Mornex, J. -F., Guillemain, R., Dahan, M., Knoop, C., Botturi, Karine, Pison, C., Danger, R., Brouard, S., Magnan, Antoine, Consortium, COLT, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CTG - Italcementi Group, Ciments CALCIA-Italcementi Group, 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), Service de Pneumologie, Nouvel Hôpital Civil Strasbourg, Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), 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), Association Vaincre la Mucoviscidose, Agence de la Biomédecine, Fonds de Recherche en Santé Respiratoire, Fondation du Souffle, French government, Nantes Métropole and Région Pays de la Loire, Institut National de la Santé et de la Recherche Médicale, Fondation pour la Recherche Médicale, ANR-10-IBHU-005, Agence Nationale de la Recherche, Association Gregory Lemarchal, Région Pays de La Loire, Institut de Recherche en Santé Respiratoire des Pays de la Loire, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Graft Rejection, Lung Diseases, Male, 0301 basic medicine, Chemokine, translational research/science, T-Lymphocytes, 030230 surgery, Matrix metalloproteinase, Chemokine receptor, Postoperative Complications, 0302 clinical medicine, lung transplantation/pulmonology, Risk Factors, Transforming Growth Factor beta, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunology and Allergy, Medicine, Pharmacology (medical), Longitudinal Studies, Epithelial cell differentiation, biology, Graft Survival, Middle Aged, Allografts, Prognosis, Matrix Metalloproteinase 9, Cytokines, Female, Lung Transplantation, Adult, Receptors, CCR2, Bronchi, Proinflammatory cytokine, 03 medical and health sciences, Immune system, Humans, Secretion, Transplantation, business.industry, rejection: chronic, Epithelial Cells, Transforming growth factor beta, 030104 developmental biology, lung (allograft) function/dysfunction, Chronic Disease, Immunology, biology.protein, business, bronchiolitis obliterans (BOS), Biomarkers, Follow-Up Studies
Abstract: International audience; Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation. CLAD manifests as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). Alloimmune reactions and epithelial-to-mesenchymal transition have been suggested in BOS. However, little is known regarding the role of allogenicity in epithelial cell differentiation. Primary human bronchial epithelial cells (BECs) were treated with activated T cells in the presence or absence of transforming growth factor (TGF)-beta. The expression of epithelial and mesenchymal markers was investigated. The secretion of inflammatory cytokines and matrix metalloproteinase (MMP)-9 was measured in culture supernatants and in plasma from lung transplant recipients (LTRs): 49 stable, 29 with BOS, and 16 with RAS. We demonstrated that C-C motif chemokine 2 secreted by T cells supports TGF-beta-induced MMP-9 production by BECs after binding to C-C chemokine receptor type 2. Longitudinal investigation in LTRs revealed a rise in plasma MMP-9 before CLAD onset. Multivariate analysis showed that plasma MMP-9 was independently associated with BOS (odds ratio [OR] = 6.19, p = 0.002) or RAS (OR = 3.9, p = 0.024) and predicted the occurrence of CLAD 12 months before the functional diagnosis. Thus, immune cells support airway remodeling through the production of MMP-9. Plasma MMP-9 is a potential predictive biomarker of CLAD.
Published: 2017

22. Pro-inflammatory State in Monoclonal Gammopathy of Undetermined Significance and in Multiple Myeloma Is Characterized by Low Sialylation of Pathogen-Specific and Other Monoclonal Immunoglobulins

Author: Bosseboeuf, Adrien, Allain-Maillet, Sophie, Mennesson, Nicolas, Tallet, Anne, Rossi, Cédric, Garderet, Laurent, Caillot, Denis, Moreau, Philippe, Piver, Eric, Girodon, François, Perreault, Hélène, Brouard, Sophie, Nicot, Arnaud, Bigot-Corbel, Edith, Hermouet, Sylvie, Harb, Jean, Bernardo, Elizabeth, Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID, Molecular Mechanisms of Chronic Inflammation in Hematological Diseases (CRCINA-ÉQUIPE 16), 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), Laboratoire de Biochimie [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Département d'Hématologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Chemistry [Winnipeg, MB, Canada], University of Manitoba [Winnipeg], Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), 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), Laboratoire de Biochimie [CHU Nantes], Faculté de Pharmacie - Université de Nantes, Faculté de Médecine - Université de Nantes, Laboratoire d'Hematologie [CHU Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), This work was realized in the context of the IHU-Cesti project, which received funds from the French government via the Region Pays de la Loire. This work was realized in the context of the LabEX IGO program supported by the National Research Agency (ANR) via the 'Investment for the future' program ANR-11-LABX-0016-01. The study was also supported by grants from the Comités Départementaux of Loire-Atlantique, Maine et Loire, Vendée and Finistère from the Ligue Nationale contre le Cancer, to EB-C (2013–2014), by a grant from the Cancéropôle Grand Ouest and Région Pays de la Loire, to SH and JH (HII-GO project, 2015–2017), and by a grant from the Cancéropôle Grand Ouest and Région Centre, to EP (2015–2017). The Cancéropôle Grand Ouest and Région Pays de la Loire financed the salary of AB (2015–2016)., ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), 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), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, monoclonal immunoglobulin, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, immunoglobulin G sialylation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, cytokines, infection, myeloma, inflammation, hemic and lymphatic diseases, Immunology and Allergy, [SDV.IMM]Life Sciences [q-bio]/Immunology, Original Research, monoclonal gammopathy of undetermined significance
Abstract: International audience; Multiple myeloma (MM) and its pre-cancerous stage monoclonal gammopathy of undetermined significance (MGUS) allow to study immune responses and the chronology of inflammation in the context of blood malignancies. Both diseases are characterized by the production of a monoclonal immunoglobulin (mc Ig) which for subsets of MGUS and MM patients targets pathogens known to cause latent infection, a major cause of inflammation. Inflammation may influence the structure of both polyclonal (pc) Ig and mc Ig produced by malignant plasma cells via the sialylation of Ig Fc fragment. Here, we characterized the sialylation of purified mc and pc IgGs from 148 MGUS and MM patients, in comparison to pc IgGs from 46 healthy volunteers. The inflammatory state of patients was assessed by the quantification in serum of 40 inflammation-linked cytokines, using Luminex technology. While pc IgGs from MGUS and MM patients showed heterogeneity in sialylation level, mc IgGs from both MGUS and MM patients exhibited a very low level of sialylation. Furthermore, mc IgGs from MM patients were less sialylated than mc IgGs from MGUS patients (p
Published: 2017

23. Antigen-specific single B cell sorting and expression-cloning from immunoglobulin humanized rats: a rapid and versatile method for the generation of high affinity and discriminative human monoclonal antibodies

Author: Laetitia Gautreau-Rolland, Melinda Moyon, Laure-Hélène Ouisse, Xavier Saulquin, Jonathan Visentin, Frank Halary, Marie-Claire Devilder, Roland Buelow, Marianne Brüggemann, Ignacio Anegon, Michael J. Osborn, Structure fédérative de recherche François Bonamy (SFR François Bonamy), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), 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 de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Recombinant Antibody Technology Ltd. [Cambridge, UK], Babraham Bioscience Technologies Ltd [Cambridge, UK], Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Immunologie et Immunogénétique [Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Pellegrin - Bordeaux, Ligand Pharmaceuticals, This work was financially supported by the IHU-Cesti project funded by the « Investissements d'Avenir » French Government program, managed by the French National Research Agency (ANR) (ANR-10-IBHU-005). The IHU-Cesti project is also supported by Nantes Métropole and Région Pays de la Loire. This work was performed in the context of the Labex IGO and TEFOR projects which are also part of the « Investissements d’Avenir » French Government program managed by the ANR (ANR-11-LABX-0016-01 and ANRI I-INSB-0014), respectively. The work was also partially funded by Région Pays de la Loire through Biogenouest and by the IBiSA program., ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010), ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), Bernardo, Elizabeth, Instituts Hospitalo-Universitaires B - Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU) - - CESTI (TSI-IHU)2010 - ANR-10-IBHU-0005 - IBHU - VALID, and Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID
Subjects: 0301 basic medicine, Tetramers, Human antibodies, medicine.drug_class, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Separation, Yeast display, Protein Engineering, Monoclonal antibody, Major histocompatibility complex, Polymerase Chain Reaction, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Antigen, medicine, Animals, Humans, Cloning, Molecular, Humanized rats, B cell, B-Lymphocytes, biology, Methodology Article, Immunogenicity, pMHC, Antibodies, Monoclonal, Cytofluorimetry, Molecular biology, Rats, 3. Good health, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Immunoglobulin G, Expression cloning, biology.protein, Antibody, Biotechnology
Abstract: Background There is an ever-increasing need of monoclonal antibodies (mAbs) for biomedical applications and fully human binders are particularly desirable due to their reduced immunogenicity in patients. We have applied a strategy for the isolation of antigen-specific B cells using tetramerized proteins and single-cell sorting followed by reconstruction of human mAbs by RT-PCR and expression cloning. Results This strategy, using human peripheral blood B cells, enabled the production of low affinity human mAbs against major histocompatibility complex molecules loaded with peptides (pMHC). We then implemented this technology using human immunoglobulin transgenic rats, which after immunization with an antigen of interest express high affinity-matured antibodies with human idiotypes. Using rapid immunization, followed by tetramer-based B-cell sorting and expression cloning, we generated several fully humanized mAbs with strong affinities, which could discriminate between highly homologous proteins (eg. different pMHC complexes). Conclusions Therefore, we describe a versatile and more effective approach as compared to hybridoma generation or phage or yeast display technologies for the generation of highly specific and discriminative fully human mAbs that could be useful both for basic research and immunotherapeutic purposes. Electronic supplementary material The online version of this article (doi:10.1186/s12896-016-0322-5) contains supplementary material, which is available to authorized users.
Published: 2017

24. Joint speech and overlap detection: a benchmark over multiple audio setup and speech domains

Author: Lebourdais, Martin, Mariotte, Théo, Tahon, Marie, Larcher, Anthony, Laurent, Antoine, Montresor, Silvio, Meignier, Sylvain, Thomas, Jean-Hugh, Laboratoire d'Informatique de l'Université du Mans (LIUM), Le Mans Université (UM), Laboratoire d'Acoustique de l'Université du Mans (LAUM), Le Mans Université (UM)-Centre National de la Recherche Scientifique (CNRS), This work was performed using HPC resources from GENCI–IDRIS (Grant 2022-AD011012565), French ANR GEM (ANR-19-CE38-0012), LMAC grant from Région Pays de la Loire., Le Mans Université, ANR-19-CE38-0012,GEM,Mesure de l'égalité entre les sexes dans les médias(2019), and European Project: 101007666,Exchanges for SPEech ReseArch aNd TechnOlogies
Subjects: overlap speech detection, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, Speech segmentation, [INFO.INFO-SD]Computer Science [cs]/Sound [cs.SD], speech activity detection, multi-channel, [INFO.INFO-NE]Computer Science [cs]/Neural and Evolutionary Computing [cs.NE], [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI]
Abstract: Voice activity and overlapped speech detection (respectively VAD and OSD) are key pre-processing tasks for speaker diarization. The final segmentation performance highly relies on the robustness of these sub-tasks. Recent studies have shown VAD and OSD can be trained jointly using a multi-class classification model. However, these works are often restricted to a specific speech domain, lacking information about the generalization capacities of the systems. This paper proposes a complete and new benchmark of different VAD and OSD models, on multiple audio setups (single/multi-channel) and speech domains (e.g. media, meeting...). Our 2/3-class systems, which combine a Temporal Convolutional Network with speech representations adapted to the setup, outperform state-of-the-art results. We show that the joint training of these two tasks offers similar performances in terms of F1-score to two dedicated VAD and OSD systems while reducing the training cost. This unique architecture can also be used for single and multichannel speech processing.
Published: 2023

25. RORγt+ cells selectively express redundant cation channels linked to the Golgi apparatus

Author: Gaelle Beriou, Aurélie Lemoine, Melanie Lancien, Aurélie Moreau, Arnaud Nicot, Régis Josien, Jerome Martin, Elise Chiffoleau, Laurence Bouchet-Delbos, Géraldine Bienvenu, Thierry Cens, Maria-Cristina Cuturi, Pierre Charnet, Hans Jörg Fehling, Lucile Drujont, Cédric Louvet, Flora Guillot, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), 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), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Institute of Immunology [Ulm], Universitätsklinikum Ulm - University Hospital of Ulm, Faculté de Médecine - Université de Nantes, Laboratoire d'Immunologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), The IHU-Cesti project is also supported by Nantes Métropole and région Pays de la Loire. Inserm-Région Pays de la Loire fellowship, Fondation Progreffe., ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010), Centre de recherche en Biologie cellulaire de Montpellier (CRBM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Le Bihan, Sylvie, Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID, and Instituts Hospitalo-Universitaires B - Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU) - - CESTI (TSI-IHU)2010 - ANR-10-IBHU-0005 - IBHU - VALID
Subjects: 0301 basic medicine, Encephalomyelitis, Autoimmune, Experimental, T cell, Biology, Article, 03 medical and health sciences, Mice, Downregulation and upregulation, RAR-related orphan receptor gamma, medicine, Animals, Humans, Psoriasis, Cells, Cultured, Orphan receptor, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Multidisciplinary, Experimental autoimmune encephalomyelitis, Innate lymphoid cell, Membrane Proteins, T-Lymphocytes, Helper-Inducer, Nuclear Receptor Subfamily 1, Group F, Member 3, medicine.disease, Colitis, Cell biology, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Intracellular, Cation channel activity, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, trans-Golgi Network
Abstract: Retinoid-related orphan receptor gamma t (RORγt) is a master transcription factor central to type 17 immunity involving cells such as T helper 17, group 3 innate lymphoid cells or IL-17-producing γδ T cells. Here we show that the intracellular ion channel TMEM176B and its homologue TMEM176A are strongly expressed in these RORγt+ cells. We demonstrate that TMEM176A and B exhibit a similar cation channel activity and mainly colocalise in close proximity to the trans-Golgi network. Strikingly, in the mouse, the loss of Tmem176b is systematically associated with a strong upregulation of Tmem176a. While Tmem176b single-deficiency has no effect on the course of experimental autoimmune encephalomyelitis, T cell or DSS-induced colitis, it significantly reduces imiquimod-induced psoriasis-like skin inflammation. These findings shed light on a potentially novel specific process linked to post-Golgi trafficking for modulating the function of RORγt+ cells and indicate that both homologues should be simultaneously targeted to clearly elucidate the role of this intracellular ion flow.
Published: 2016

26. Modulation of antigen processing by haem-oxygenase 1. Implications on inflammation and tolerance

Author: Sebastián A. Riquelme, Janyra A. Espinoza, Claudia A. Riedel, Alexis M. Kalergis, Susan M. Bueno, Leandro J. Carreño, Manuel Álvarez-Lobos, Juan Pablo Mackern-Oberti, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), 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), Departamento de Microbiologıa y Genetica Molecular [Santiago, Chile] (Facultad de Ciencias Biologicas), Pontificia Universidad Católica de Chile (UC), Department of Microbiology and Immunology [Bronx, NY, USA], Albert Einstein College of Medicine [New York], Institute of Medicine and Experimental Biology of Cuyo [Mendoza, Argentina] (IMBECU), Science and Technology Center [Mendoza, Argentina] (CCT)-National Council of Scientific and Technical Research [Mendoza, Argentina], Institute of Physiology [Mendoza, Argentina] (School of Medicine), National University of Cuyo [Mendoza, Argentina], Departamento de Gastroenterologıa [Santiago, Chile] (Facultad de Medicina), Departamento de Ciencias Biologicas [Santiago, Chile] (Facultad de Ciencias Biologicas y Facultad de Medicina), Universidad Andrés Bello - UNAB (CHILE), Departamento de Endocrinología [Santiago, Chile] (Facultad de Medicina), This study was supported by the following grants: FONDO NACIONAL DE CIENCIA Y TECNOLOGIA DE CHILE (FONDECYT numbers 1110397, 1131012, 1140010 and 1110604), Millennium Institute on Immunology and Immunotherapy P09/016-F and Grant ‘Nouvelles Equipesnouvelles thématiques’ from the La Région Pays De La Loire. SAR and JAE are supported by the Comision Nacional de Investigacion Cientıfica y Tecnologica (CONICYT). LJC is a Latin American Pew Fellow. AMK is a Chaire De La Région Pays De La Loire, Chercheur Etranger D’excellence, France., Le Bihan, Sylvie, and Universidad Andrés Bello [Santiago] (UNAB)
Subjects: 0301 basic medicine, CIENCIAS MÉDICAS Y DE LA SALUD, T-Lymphocytes, Immunology, Inmunología, Priming (immunology), Inflammation, Lymphocyte Activation, DENDRITIC CELLS, HAEM-OXYGENASE 1, Immunomodulation, 03 medical and health sciences, Immune system, Immunity, ANTIGEN PRESENTATION, medicine, cytokine, Immune Tolerance, Immunology and Allergy, Animals, Humans, dendritic cells, Review Articles, haem-oxygenase 1, Antigen Presentation, Carbon Monoxide, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Graft rejection, Antigen processing, business.industry, CARBON MONOXIDE, Haem Oxygenase, 3. Good health, CYTOKINE, Medicina Básica, 030104 developmental biology, Immune System Diseases, Drug Design, medicine.symptom, Endotoxic shock, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Heme Oxygenase-1
Abstract: Haem-oxygenase-1 (HO-1) is an enzyme responsible for the degradation of haem that can suppress inflammation, through the production of carbon monoxide (CO). It has been shown in several experimental models that genetic and pharmacological induction of HO-1, as well as non-toxic administration of CO, can reduce inflammatory diseases, such as endotoxic shock, type 1 diabetes and graft rejection. Recently, it was shown that the HO-1/CO system can alter the function of antigen-presenting cells (APCs) and reduce T-cell priming, which can be beneficial during immune-driven inflammatory diseases. The molecular mechanisms by which the HO-1 and CO reduce both APC- and T-cell-driven immunity are just beginning to be elucidated. In this article we discuss recent findings related to the immune regulatory capacity of HO-1 and CO at the level of recognition of pathogen-associated molecular patterns and T-cell priming by APCs. Finally, we propose a possible regulatory role for HO-1 and CO over the recently described mitochondria-dependent immunity. These concepts could contribute to the design of new therapeutic tools for inflammation-based diseases. Fil: Riquelme, Sebastián A.. Pontificia Universidad Católica de Chile; Chile Fil: Carreño, Leandro J.. Pontificia Universidad Católica de Chile; Chile Fil: Espinoza, Janyra A.. Pontificia Universidad Católica de Chile; Chile Fil: Mackern Oberti, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina Fil: Alvarez Lobos, Manuel M.. Pontificia Universidad Católica de Chile; Chile Fil: Riedel, Claudia. Universidad Andrés Bello; Chile Fil: Bueno, Susan M.. Pontificia Universidad Católica de Chile; Chile Fil: Kalergis, Alexis M.. Pontificia Universidad Católica de Chile; Chile
Published: 2016

27. Heritability of aortic valve stenosis and bicuspid enrichment in families with aortic valve stenosis

Author: Anne-Sophie Boureau, Matilde Karakachoff, Solena Le Scouarnec, Romain Capoulade, Caroline Cueff, Laure de Decker, Thomas Senage, Jean-Philippe Verhoye, Christophe Baufreton, Jean-Christian Roussel, Christian Dina, Vincent Probst, Jean-Jacques Schott, Thierry Le Tourneau, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'investigation clinique (CIC) de Nantes -CIC Plurithématique (CIC 0004 - Nantes), Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pontchaillou, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by a PHRC Interregional (API20-20) grant to VP, an ANR & FRM grant [13-BSV6-0011, DCV20070409278] to JJS, by a PHRC Interregional (API12/N/019), a Fédération Française de Cardiologie, a Fondation Coeur et Recherche and an Inserm Translational Research grant to TLT, a 'Connect Talent' research chair from Région Pays de la Loire and Nantes Métropole to RC., ANR-13-BSV6-0011,CavsGen,Variation génétique, transcriptome et épigénome du rétrécissement aortique calcifié(2013), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Jonchère, Laurent, and Blanc 2013 - Variation génétique, transcriptome et épigénome du rétrécissement aortique calcifié - - CavsGen2013 - ANR-13-BSV6-0011 - Blanc 2013 - VALID
Subjects: [SDV.IB] Life Sciences [q-bio]/Bioengineering, Bicuspid aortic valve, Heart Valve Diseases, Calcinosis, Aortic Valve Stenosis, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Calcific aortic valve stenosis, Heritability, Bicuspid Aortic Valve Disease, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Aortic Valve, cardiovascular system, Genetics, Humans, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Cardiology and Cardiovascular Medicine
Abstract: International audience; BACKGROUND: Although a familial component of calcific aortic valve stenosis (CAVS) has been described, its heritability remains unknown. Hence, we aim to assess the heritability of CAVS and the prevalence of bicuspid aortic valve among CAVS families. METHODS: Probands were recruited following aortic valve replacement (AVR) for severe CAVS on either tricuspid (TAV) or bicuspid aortic valve (BAV). After screening, relatives underwent a Doppler-echocardiography to assess the aortic valve morphology as well as the presence and severity of CAVS. Families were classified in two types according to proband’s aortic valve phenotype: TAV or BAV families. Control families were recruited and screened for the presence of BAV. RESULTS: Among the 2371 relatives from 138 CAVS families (pedigree cohort), heritability of CAVS was significant (h(2) = 0.47, p
Published: 2022

28. SARS-CoV-2 E and 3a Proteins Are Inducers of Pannexin Currents

Author: Barbara B. R. Oliveira-Mendes, Malak Alameh, Béatrice Ollivier, Jérôme Montnach, Nicolas Bidère, Frédérique Souazé, Nicolas Escriou, Flavien Charpentier, Isabelle Baró, Michel De Waard, Gildas Loussouarn, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), LabEx Ion Channels Science and Therapeutics [France], Signaling in Oncogenesis, Angiogenesis and Permeability - SOAP (CRCI2NA / Eq 6), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Département de Santé Globale - Department Global Health, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), We thank the Agence Nationale de la Recherche for its financial support to the Région Pays de la Loire (ANR FLASH Covid-19 - CoV2-E-TARGET) and the laboratory of excellence ‘Ion Channels, Science and Therapeutics’ (grant No. ANR-11-LABX-0015)., ANR-20-COVI-0058,CoV2-E-TARGET,Criblage d'inhibiteurs de la protéine E du SARS-CoV-2(2020), ANR-11-LABX-0015,ICST,Canaux ioniques d'intérêt thérapeutique(2011), Loussouarn, Gildas, Criblage d'inhibiteurs de la protéine E du SARS-CoV-2 - - CoV2-E-TARGET2020 - ANR-20-COVI-0058 - COVID-19 - VALID, Laboratoires d'excellence - Canaux ioniques d'intérêt thérapeutique - - ICST2011 - ANR-11-LABX-0015 - LABX - VALID, Signaling in Oncogenesis, Angiogenesis and Permeability (CRCINA-ÉQUIPE 15), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), and 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)
Subjects: [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, COVID-19, SARS-CoV-2, viroporins, E protein, 3a protein, pannexin currents, cell death, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, General Medicine
Abstract: Controversial reports have suggested that SARS-CoV E and 3a proteins may be viroporins that conduct currents through the plasma membrane of the infected cells. If true, these proteins would represent accessible targets for the development of new antiviral drugs by using high-throughput patch-clamp techniques. Here we aimed at better characterizing the cell responses induced by E or 3a protein with a particular focus on the ion conductances measured at the cell surface. First, we show that expression of SARS-CoV-2 E or 3a protein in CHO cells gives rise to cells with newly-acquired round shape, tending to detach from the Petri dish. This suggests that cell death is induced upon expression of E or 3a protein. We confirmed this hypothesis by using flow cytometry, in agreement with earlier reports on other cell types. In adhering cells expressing E or 3a protein, whole-cell currents were in fact not different from the control condition indicating that E and 3a proteins are not plasma membrane viroporins. In contrast, recording currents on detached cells uncovered outwardly-rectifying currents, much larger than those observed in control. The current characteristics are reminiscent of what was previously observed in cells expressing SARS-CoV-1 E or 3a proteins. Herein, we illustrate for the first time that carbenoxolone blocks these outward currents suggesting that they are conducted by pannexin channels, mostly likely activated by cell morphology change and/or cell death. Alongside we also demonstrate that truncation of the C-terminal PDZ binding motifs reduces the proportion of dying cells but does not prevent pannexin currents suggesting distinct pathways for cell death and pannexin currents induced by E and 3a proteins. We conclude that SARS-CoV-2 E and 3a proteins are not acting as viroporins expressed at the plasma membrane.Author SummaryA viroporin (or viral porin) is a class of proteins that is encoded by a virus genome. It is named porin because its biological role is to conduct ions through a pore that it created in a lipid membrane such as the one surrounding a human cell. if such viroporin is present at the external membrane of a human cell infected by a virus, it can be an easy target of an antiviral agent which thus does not have to enter the cell to be active. One example of viroporin is the flu M2 protein that is the target of amantadine, an antiviral agent used against flu. In previous studies, two proteins of SARS-CoV viruses, named E protein and 3a protein, have been suggested to be viroporins at the surface of infected human cells, potentially opening a new research avenue against SARS. Here we demonstrate that both proteins are not viroporins at the external membrane but they rather trigger changes in the cell shape and promote cell death. They only indirectly induce the activity of a porin that is encoded by the cell genome, named pannexin.
Published: 2023
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29. Reconstructing pedigrees using probabilistic analysis of ISSR amplification

Author: Loïc Chaumont, Richard Pymar, Chaker Sbai, Valéry Malécot, Laboratoire Angevin de Recherche en Mathématiques (LAREMA), Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Horticulture et Semences (IRHS), Université d'Angers (UA)-Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, 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 of London [London] (UCL), Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Région des Pays de la Loire, This work was supported by MODEMAVE research project from the Région Pays de la Loire. Acces to molecular data was supported by both EUROGENI project, funded by Région Pays de la Loire (dynamiques de filière) and by BRIO project funded by same Région Pays de la Loire and the Fonds Unique Interministériel., AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA)-Université d'Angers (UA), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), Université d'Angers (UA)-AGROCAMPUS OUEST-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Dept Stat Sci, University College London (UCL), MODEMAVE research project from the Region Pays de la Loire, EUROGENI project - Region Pays de la Loire (dynamiques de filiere, BRIO project - Region Pays de la Loire + Fonds Unique Interministériel, Université d'Angers (UA)-AGROCAMPUS OUEST, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0301 basic medicine, carte génétique, [SDV]Life Sciences [q-bio], [SDV.SA.AGRO]Life Sciences [q-bio]/Agricultural sciences/Agronomy, Pedigree chart, 92D25, 92D10, 60F15, gène marqueur, 01 natural sciences, 010104 statistics & probability, probabilistic model, Probabilistic method, Statistics, [SDV.IDA]Life Sciences [q-bio]/Food engineering, 10. No inequality, [SDV.SA.HORT]Life Sciences [q-bio]/Agricultural sciences/Horticulture, Cytisus, Probability measure, Mathematics, Cytisus scoparius, [SHS.SOCIO]Humanities and Social Sciences/Sociology, biology, Applied Mathematics, General Medicine, [SDV.BV.BOT]Life Sciences [q-bio]/Vegetal Biology/Botanics, [QFIN.ST]Quantitative Finance [q-fin]/Statistical Finance [q-fin.ST], interaction isolat cultivar, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Pedigree, Modeling and Simulation, [SDV.SA.SPA]Life Sciences [q-bio]/Agricultural sciences/Animal production studies, genetic mapping, General Agricultural and Biological Sciences, Mathematics - Probability, Statistics and Probability, law of reproduction, ems, gene frequency, [QFIN.RM]Quantitative Finance [q-fin]/Risk Management [q-fin.RM], [SDV.SA.SDS]Life Sciences [q-bio]/Agricultural sciences/Soil study, bcs, General Biochemistry, Genetics and Molecular Biology, [SDV.GEN.GPL]Life Sciences [q-bio]/Genetics/Plants genetics, 03 medical and health sciences, ISSR amplification, Law of reproduction, Gene frequency, [SDV.SA.STA]Life Sciences [q-bio]/Agricultural sciences/Sciences and technics of agriculture, FOS: Mathematics, Probabilistic analysis of algorithms, 0101 mathematics, Allele, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Quantitative Biology - Populations and Evolution, [QFIN.TR]Quantitative Finance [q-fin]/Trading and Market Microstructure [q-fin.TR], Allele frequency, Alleles, cytisus scoparius, matrice de parenté combinée, Models, Genetic, General Immunology and Microbiology, modèle probabiliste, Probability (math.PR), Populations and Evolution (q-bio.PE), Mathematics Subject Classification (2000): 92D25, 92D10, 60F15, Statistical model, [SDV.SA.AEP]Life Sciences [q-bio]/Agricultural sciences/Agriculture, economy and politics, biology.organism_classification, [SDV.BV.PEP]Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy, diploïde, [MATH.MATH-PR]Mathematics [math]/Probability [math.PR], [SDV.BV.AP]Life Sciences [q-bio]/Vegetal Biology/Plant breeding, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, 030104 developmental biology, FOS: Biological sciences, [SDV.SA.STP]Life Sciences [q-bio]/Agricultural sciences/Sciences and technics of fishery, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: Data obtained from ISSR amplification may readily be extracted but only allows us to know, for each gene, if a specific allele is present or not. From this partial information we provide a probabilistic method to reconstruct the pedigree corresponding to some families of diploid cultivars. This method consists in determining for each individual what is the most likely couple of parent pair amongst all older individuals, according to some probability measure. The construction of this measure bears on the fact that the probability to observe the specific alleles in the child, given the status of the parents does not depend on the generation and is the same for each gene. This assumption is then justified from a convergence result of gene frequencies which is proved here. Our reconstruction method is applied to a family of 85 living accessions representing the common broom {\it Cytisus scoparius}., Comment: 5 figures
Published: 2015

30. Predicting makespan in Flexible Job Shop Scheduling Problem using Machine Learning

Author: Hashemi-Petroodi, S. Ehsan, Thevenin, Simon, Dolgui, Alexandre, Modélisation, Optimisation et DEcision pour la Logistique, l'Industrie et les Services (LS2N - équipe MODELIS), Laboratoire des Sciences du Numérique de Nantes (LS2N), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Nantes Université (Nantes Univ), Département Automatique, Productique et Informatique (IMT Atlantique - DAPI), IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Institut Mines-Télécom [Paris] (IMT), Région Pays de la Loire, and European Project: 101000165,ASSISTANT
Subjects: Control and Systems Engineering, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO]
Abstract: International audience; Machine learning tools have experienced a growing interest in the early 2010s, providing efficient predictive approaches for artificial intelligence and statistical analysis. These same prediction methods have also sparked interest in the operations research community for decision-making based on predictive analysis by exploiting massive histories and datasets. This study investigates the potential of machine learning tools to predict the feasibility of a production plan. Production schedules are often not able to adhere to the production plans because production plans are built without accounting for all the detailed requirements that arise at the scheduling level. We show that predicting the feasibility of a production plan with a decision tree yields a precision of around 90% versus 70% in the classical capacity constraints considered in planning tools.
Published: 2022

31. The impact of urbanization on soil organic carbon stocks and particle size and density fractions

Author: Aurélie Cambou, Tiphaine Chevallier, Bernard G. Barthès, Delphine Derrien, Patrice Cannavo, Adeline Bouchard, Victor Allory, Christophe Schwartz, Laure Vidal-Beaudet, Ecologie fonctionnelle et biogéochimie des sols et des agro-écosystèmes (UMR Eco&Sols), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Laboratoire Sols et Environnement (LSE), Université de Lorraine (UL)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Agence de l'Environnement et de la Maîtrise de l'Energie (ADEME), Unité de recherche Biogéochimie des Ecosystèmes Forestiers (BEF), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Recherche Environnement Physique de la plante Horticole (EPHOR), Université d'Angers (UA)-Institut Agro Rennes Angers, SUPRA project (grant number 1772C0021), financed by ADEME (French Environmental Agency), and PhD grant of the lead author, with the Région Pays de la Loire.
Subjects: Stratigraphy, [SDV.SA.SDS]Life Sciences [q-bio]/Agricultural sciences/Soil study, Earth-Surface Processes
Abstract: International audience; PurposeUrbanization is a major driver of land use change and can affect the soil organic carbon (SOC) pools. This study aimed to understand the urbanization impact on SOC stocks and pools at profile scale (0–100 cm).MethodsThe SOC was studied at 0–30 and 0–100 cm depths in park and sealed soils of three French cities (Marseille, Nancy, and Nantes). Physical fractionation was performed to gain insight on the size of different SOC pools (particulate and organo-mineral soil fractions).ResultsThe SOC stocks were seven to ten times higher in parks than in sealed soils, but lower than in natural soils according to literature data. The contribution of the first 30 cm to profile SOC stock was around 40%, with strong heterogeneity, especially in sealed soils. Considering the whole 0–100 cm profile, SOC stocks in particulate organic matter fractions (light fraction > 50 µm) were 25–48 times higher in parks than in sealed soils, while SOC stocks in mineral-associated fractions ( 50 µm, particularly in sealed soils (11% in average at 0–100 cm depth). This fraction associated to sand is usually poor in SOC in natural or agricultural soils. In these urban soils, it might be bitumen, a dense organic artifact.ConclusionThe SOC stocks up to 100 cm depth and their heterogeneity pleaded to strengthen and expand SOC studies in all urban soils.
Published: 2023

32. Experimental study of sediment transport processes by liquid water and brine under Martian pressure

Author: Philippe, M., Conway, S. J., Raack, J., Carpy, S., Masse, M., Patel, M. R., Sylvest, M. E., Lewis, S. R., Morino, C., Laboratoire de Planétologie et Géosciences [UMR_C 6112] (LPG), Université d'Angers (UA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Institut für Planetologie [Münster], Westfälische Wilhelms-Universität Münster = University of Münster (WWU), The Open University [Milton Keynes] (OU), Environnements, Dynamiques et Territoires de Montagne (EDYTEM), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Région Pays de la Loire project GeoPlaNet (convention N° 2016-10982), CNES, UK Space Agency, ANR-19-CE01-0010,Permolards,Les molards, marqueurs de l'évolution de la dégradation du pergélisol de montagne(2019), and European Project: 654208,H2020,H2020-INFRAIA-2014-2015,EPN2020-RI(2015)
Subjects: [SDU.STU.PL]Sciences of the Universe [physics]/Earth Sciences/Planetology, Space and Planetary Science, Experimental techniques, Geological processes, Mars, climate, Mars, surface, Mars, surface, Astronomy and Astrophysics, [SDU.STU.GM]Sciences of the Universe [physics]/Earth Sciences/Geomorphology, climate
Abstract: International audience; We present here an experimental study to compare the behaviour of water and brine releases over loose sediments under present-day Martian pressure. Water has been invoked to explain current or past Martian surface features for decades. Recent studies have indicated that current surface conditions are, in certain times and places, compatible with the transient existence of liquid water or brine. However, the behaviour of water or brine releases over loose sediments under low Martian atmospheric pressure has been poorly studied.We performed 33 experiments of water and brine (MgSO4 at 19 wt%) releases over sandy slopes of various temperatures (0 °C to 20 °C), in a chamber allowing the reproduction of Martian pressure 6–7 millibars (mbar). We observe sediment transport mechanisms, that do not occur on Earth, caused by the boiling of water or brine at Martian pressures: grain ejection and “levitation” of sand pellets on cushions of vapour. The main parameter controlling the behaviour of the flow is the temperature of the substrate. Water and brine flows transport similar volumes of sediment under Martian pressure. We show that the grain ejection is the most efficient transport mechanism, dominating the volumes of sediment transported. Pellet “levitation” should lead to longer features formed with brine than with pure water on Mars. Boiling induced sediment transport requires much less water than sediment transport by overland flow to form morphologies similar in size or volume. Moreover, our one-dimensional climate model runs reveal that the temperatures at which we observe those types of transport are predicted to occur at the Martian surface today and in the past. When scaled to Mars, the morphologies we observe with water and brine experiments should be resolvable using the High-Resolution Science Experiment (HiRISE) camera at ∼25 cm/pix. Overall, our results show that boiling must be taken into account when considering sediment-rich flows under recent or current Martian conditions.
Published: 2023

33. Protocole d'urgence en santé au travail ou milieu isolé. Généralités et mise à jour

Author: Descatha, A., Chanu, S., Jenkins, Jon, Savary, D, Lentz, T., Havette, P., Baer, M., École des Hautes Études en Santé Publique [EHESP] (EHESP), 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 ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Raymond Poincaré [Garches], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Le travail a bénéficié du soutien dans le cadre du projet TEC-TOP, de la région Pays-de-la-Loire, d’Angers Loire Métropole, de l’Université d’Angers et du CHU d’Angers.
Subjects: Procedure, [SDV]Life Sciences [q-bio], Emergency, Protocol, Protocole, Professionnel, Urgence, Procédure, Travail, Occupational work
Abstract: National audience; Le protocole d’urgence doit être adapté au contexte. Il doit être simple, court, exhaustif et facile à mémoriser. Il résume la conduite à tenir en cas d’urgence.Le protocole d’urgence est établi par le médecin du travail et validé par l’équipe notamment l’infirmier(ère) en santé au travail sous la responsabilité du médecin du travail. Il sera régulièrement actualisé en fonction de nouvelles connaissances et/ou de la situation locale.Deux types de protocoles sont à établir en fonction de la présence ou de l’absence de professionnel de Santé.Le protocole de gestion d’une urgence médicale en l’absence de professionnel de Santé est une procédure d’appel aux secouristes disponibles. L’objectif étant de déclencher les services d’urgence médicale en agissant de façon rationnelle.Le protocole d’urgences destiné au professionnel de Santé est basé sur le symptôme. Il permet de hiérarchiser l’urgence. Il se doit d’être ergonomique, adapté, traçable et (ré)évaluable.Cette mise au point est une mise à jour après la période COVID-19 à partir des généralités de l’ouvrage « Mémento et Protocoles » [1] et de l’article « six principes des protocoles de prise en charge des urgences en milieu de travail » [2]. L’objectif est de proposer un récapitulatif des principes permettant d’élaborer et d’appliquer un protocole pour l’équipe de santé au travail, en l’ouvrant à toute situation où le professionnel de santé en milieu isolé doit gérer les premières urgences avec peu de moyens. La principale différence entre le milieu de travail en France et un milieu isolé est le recours à la structure qui poursuivra la prise en charge, qui ne sera pas le SAMU mais une structure d’urgence et/ou d’évacuation.Après une brève introduction, nous rappellerons les bases du raisonnement de gestion des urgences en milieu de travail ou isolé, afin de poser les bases des protocoles dans ce cadre.
Published: 2023

34. Mitochondrial Complex I Disruption Causes Broad Reorchestration of Plant Lipidome Including Chloroplast Lipids

Author: Jean-Baptiste Domergue, Cinzia Bocca, Rosine De Paepe, Guy Lenaers, Anis M. Limami, Guillaume Tcherkez, Institut de Recherche en Horticulture et Semences (IRHS), Université d'Angers (UA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Rennes Angers, 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), IRHS - Équipe SMS (Source and sink Metabolism and Stress responses) (IRHS-SMS), 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 d'Angers (UA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Rennes Angers, MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 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), Research School of Biology, ANU Joint College of Science, Australian National University (ANU), Université Angers, and This research was funded by the Région Pays de la Loire and Angers Loire Métropole, grant Isoseed. The PhD scholarship to J.B.D. was funded by the University of Angers.
Subjects: cytoplasmic male sterility, photorespiration, sphingolipids, complex I, electron transfer chain, Organic Chemistry, General Medicine, mitochondrion, lipidomics, phospholipids, [SDV.BV.BOT]Life Sciences [q-bio]/Vegetal Biology/Botanics, Catalysis, Computer Science Applications, Inorganic Chemistry, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy
Abstract: International audience; Mitochondrial complex I (CI) plays a crucial role in oxidising NADH generated by the metabolism (including photorespiration) and thereby participates in the mitochondrial electron transfer chain feeding oxidative phosphorylation that generates ATP. However, CI mutations are not lethal in plants and cause moderate phenotypes, and therefore CI mutants are instrumental to examine consequences of mitochondrial homeostasis disturbance on plant cell metabolisms and signalling. To date, the consequences of CI disruption on the lipidome have not been examined. Yet, in principle, mitochondrial dysfunction should impact on lipid synthesis through chloroplasts (via changes in photorespiration, redox homeostasis, and N metabolism) and the endoplasmic reticulum (ER) (via perturbed mitochondrion–ER crosstalk). Here, we took advantage of lipidomics technology (by LC-MS), phospholipid quantitation by 31P-NMR, and total lipid quantitation to assess the impact of CI disruption on leaf, pollen, and seed lipids using three well-characterised CI mutants: CMSII in N. sylvestris and both ndufs4 and ndufs8 in Arabidopsis. Our results show multiple changes in cellular lipids, including galactolipids (chloroplastic), sphingolipids, and ceramides (synthesised by ER), suggesting that mitochondrial homeostasis is essential for the regulation of whole cellular lipidome via specific signalling pathways. In particular, the observed modifications in phospholipid and sphingolipid/ceramide molecular species suggest that CI activity controls phosphatidic acid-mediated signalling.
Published: 2022
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35. Driving with a Haptic Guidance System in Degraded Visibility Conditions: Behavioral Analysis and Identification of a Two-Point Steering Control Model

Author: Yishen Zhao, Philippe Chevrel, Fabien Claveau, Franck Mars, Département Automatique, Productique et Informatique (IMT Atlantique - DAPI), IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Commande, Observation, Diagnostic et Expérimentation (LS2N - équipe CODEx), Laboratoire des Sciences du Numérique de Nantes (LS2N), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Nantes Université (Nantes Univ), Perception, Action, Cognition pour la Conception et l’Ergonomie (LS2N - équipe PACCE), and RFI Atlanstic 2020 (Région Pays de la Loire)
Subjects: lateral control performance, visibility conditions, haptic guidance, [SCCO.PSYC]Cognitive science/Psychology, General Earth and Planetary Sciences, driver steering model, system identification, General Environmental Science, [SPI.AUTO]Engineering Sciences [physics]/Automatic
Abstract: International audience; The objective of this study is to determine the ability of a two-point steering control model to account for the influence of a haptic guidance system in different visibility conditions. For this purpose, the lateral control of the vehicle was characterized in terms of driving performance as well as through the identification of anticipation and compensation parameters of the driver model. The hypothesis is that if the structure of the model is valid in the considered conditions, the value of the parameters will change in coherence with the observed behavior. The results of an experiment conducted on a driving simulator demonstrate that the identified model can account for the cumulative influence of the haptic guidance system and degraded visibility. The anticipatory gain is sensitive to changes in driving conditions that have a direct influence on the produced trajectory, and the compensatory gain is sensitive to a decrease in the variability of the lateral position. However, a model with only the steering wheel angle as output is not able to determine whether the change in lateral position variability is due to the driver’s lack of anticipation or to the assistance provided by the haptic guidance system.
Published: 2022
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36. Characterization of Dystrophin Deficient Rats: A New Model for Duchenne Muscular Dystrophy

Author: Laurent Tesson, Helicia Goubin, Jean-Baptiste Renaud, Thibaut Larcher, Caroline Le Guiner, Yan Cherel, Carine Giovannangeli, Corinne Huchet, Maeva Dutilleul, Ignacio Anegon, Gilles Toumaniantz, Anne De Cian, Lydie Guigand, Jean-Paul Concordet, Séverine Remy, Charlotte Boix, A. Lafoux, Virginie François, Virginie Thepenier, Physiopathologie Animale et bioThérapie du muscle et du système nerveux (PAnTher), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Atlantic Gene Therapies, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-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), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), 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), Institut de Transplantation Urologie-Néphrologie (ITUN), Institut de Transplantation Urologie-Néphrologie ( ITUN), Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques (Inserm UMR 1089), Généthon, Structure et Instabilité des Génomes (STRING), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Région Pays de la Loire (Biogenouest), IBiSA program, Fondation Progreffe, TEFOR (Infrastructures d'Avenir du Gouvernement Français), Développement et Pathologie du Tissu Musculaire (DPTM), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Nantes, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Vétérinaire de Nantes-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes (UN), APEX - Plate-forme d'expertise en anatomie pathologique pour la Recherche [Nantes] (PAnTher), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-INRA - Oniris (INRA UMR0703), Institut National de la Recherche Agronomique (INRA)-Institut National de la Recherche Agronomique (INRA), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Thérapie génique translationnelle pour les maladies neuromusculaires et de la rétine, Recherche et développement [Généthon, Evry] (R & D Généthon), Généthon [Evry], Muséum national d'Histoire naturelle (MNHN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Région Pays de la Loire through Biogenouest, IBiSA program, Fondation Progreffe and TEFOR (Infrastructures d’Avenir of the French goverment), and the integrative genomic facility of Nantes for sequencing experiments., Muséum national d'Histoire naturelle (MNHN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Unité de recherche de l'institut du thorax (ITX-lab), Le Bihan, Sylvie, and Lafoux, Aude
Subjects: Male, Pathology, Necrosis, myopathie de duchenne, Physiology, Duchenne muscular dystrophy, Gene Expression, Adipose tissue, Dystrophin, 0302 clinical medicine, Medicine and Health Sciences, Medicine, rat, Muscular dystrophy, Creatine Kinase, 0303 health sciences, Muscle Weakness, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Multidisciplinary, Ventricular Remodeling, biology, Dilated cardiomyopathy, Exons, Diaphragm (structural system), Neurology, Gene Targeting, Female, medicine.symptom, Research Article, Biotechnology, musculoskeletal diseases, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Science, Médecine humaine et pathologie, modèle d'analyse, 03 medical and health sciences, Genetics, Congenital Disorders, Animals, RNA, Messenger, Muscle, Skeletal, Molecular Biology, 030304 developmental biology, Base Sequence, business.industry, Myocardium, Biology and Life Sciences, Muscle weakness, Cell Biology, Muscular Dystrophy, Animal, medicine.disease, Fibrosis, Rats, Muscular Dystrophy, Duchenne, Disease Models, Animal, Mutation, biology.protein, Human health and pathology, business, mutant déficient, Gene Deletion, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; A few animal models of Duchenne muscular dystrophy (DMD) are available, large ones such as pigs or dogs being expensive and difficult to handle. Mdx (X-linked muscular dystrophy) mice only partially mimic the human disease, with limited chronic muscular lesions and muscle weakness. Their small size also imposes limitations on analyses. A rat model could represent a useful alternative since rats are small animals but 10 times bigger than mice and could better reflect the lesions and functional abnormalities observed in DMD patients. Two lines of Dmd mutated-rats (Dmd[mdx]) were generated using TALENs targeting exon 23. Muscles of animals of both lines showed undetectable levels of dystrophin by western blot and less than 5% of dystrophin positive fibers by immunohistochemistry. At 3 months, limb and diaphragm muscles from Dmd[mdx] rats displayed severe necrosis and regeneration. At 7 months, these muscles also showed severe fibrosis and some adipose tissue infiltration. Dmd[mdx] rats showed significant reduction in muscle strength and a decrease in spontaneous motor activity. Furthermore, heart morphology was indicative of dilated cardiomyopathy associated histologically with necrotic and fibrotic changes. Echocardiography showed significant concentric remodeling and alteration of diastolic function. In conclusion, Dmd[mdx] rats represent a new faithful small animal model of DMD.
Published: 2014

37. Synthesis, Crystal Structure and 19F NMR Parameters Modelling of Catif6(H2o)2 Yielding to a Revision of the Bond-Valence Parameters for the Ti4+/F- Ion Pair

Author: Christophe Legein, Monique Body, J. Lhoste, Wei Li, Thibault Charpentier, Damien Dambournet, Institut des Molécules et Matériaux du Mans (IMMM), Le Mans Université (UM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), PHysicochimie des Electrolytes et Nanosystèmes InterfaciauX (PHENIX), Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Réseau sur le stockage électrochimique de l'énergie (RS2E), Aix Marseille Université (AMU)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Collège de France (CdF (institution))-Université de Picardie Jules Verne (UPJV)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Pau et des Pays de l'Adour (UPPA)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-Université Grenoble Alpes (UGA)-Nantes Université (Nantes Univ)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Université de Montpellier (UM), Laboratoire Structure et Dynamique par Résonance Magnétique (LCF) (LSDRM), 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), The CASTEP computations presented in this work have been carried out at the Centre Régional de Calcul Intensif des Pays de la Loire (CCIPL), financed by the French Ministère de la Recherche, the Région Pays de la Loire, and Université de Nantes. The authors thank CCIPL for financial support for CASTEP licenses., and This work was granted access to the HPC resources of TGCC (VASP calculations) under the allocation DARI-A0070906303 (2019) attributed by GENCI (Grand Equipement National de Calcul Intensif).
Subjects: History, 19 F solid state NMR, Inorganic hydrated hexafluorotitanate (or Inorganic fluorides), Polymers and Plastics, Crystal structure, Bond-valence, Powder X-ray diffraction, [CHIM.MATE]Chemical Sciences/Material chemistry, Business and International Management, DFT calculations, Industrial and Manufacturing Engineering
Abstract: International audience; CaTiF6(H2O)2 was synthetized by a solvothermal method and was found to be isostructural to SrTiF6(2H2O). The structure, refined from Powder X-Ray Diffraction (PXRD) data, is built from the connectivity of dimers [Ca2F10(H2O)4] of square antiprisms (SAP) [CaF5(H2O)3] and TiF6 octahedra. To assign the six 19F resonances to the six fluorine crystallographic sites of same multiplicity, 19 F magnetic shielding tensors have been calculated using the GIPAW method. Unusually, the plot of the experimental 19F isotropic chemical shift (δiso) values, as a function of the calculated 19F isotropic shielding (ssiso) values, shows a much better alignment for the experimental than for the DFT-optimized structure. Whereas, the dynamics of the structural water molecules under experimental conditions are not captured by the optimized structure, the experimental averaged structure provides a good account of the experimental data and a reliable assignment of the 19F resonances to the F sites. Finally, the previously established bond-valence (BV) parameter Rij for the Ti4+/F- ion pair (1.76 Å) leads to overestimated BV sum values for Ti. This trend has been observed for almost all other fluorotitanates. We then undertook to refine its value, using the Ti-F bond lengths from 70 carefully selected structures containing 134 Ti sites forming TiF6 octahedra, and leading to Rij. = 1.706 Å.
Published: 2022
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38. Modelling the effects of antimicrobial metaphylaxis and pen size on bovine respiratory disease in high and low risk fattening cattle

Author: Sébastien Picault, Pauline Ezanno, Kristen Smith, David Amrine, Brad White, Sébastien Assié, Biologie, Epidémiologie et analyse de risque en Santé Animale (BIOEPAR), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Kansas State University, Institut Carnot France Futur Élevage (F2E) — projet SEPTIME, Région Pays de la Loire (PULSAR), and European Project: 101000494,DECIDE
Subjects: MESH: Anti-Bacterial Agents / pharmacology, Farms, Epidemiological modelling, Respiratory Tract Diseases, Bovine Respiratory Disease Complex, MESH: Anti-Infective Agents / therapeutic use, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], Anti-Infective Agents, Disease control, Animals, MESH: Animals, Antimicrobial usage, MESH: Bovine Respiratory Disease Complex / diagnosis, Farming practices, MESH: Farms, MESH: Bovine Respiratory Disease Complex / drug therapy, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, General Veterinary, Bovine respiratory disease, MESH: Bovine Respiratory Disease Complex* / prevention & control, MESH: Anti-Infective Agents / pharmacology, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Anti-Bacterial Agents, Stochastic models, MESH: Cattle, MESH: Respiratory Tract Diseases / veterinary, [INFO.INFO-MA]Computer Science [cs]/Multiagent Systems [cs.MA], Cattle, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Anti-Bacterial Agents / therapeutic use
Abstract: Bovine respiratory disease (BRD) dramatically affects young calves, especially in fattening facilities, and is difficult to understand, anticipate and control due to the multiplicity of factors involved in the onset and impact of this disease. In this study we aimed to compare the impact of farming practices on BRD severity and on antimicrobial usage. We designed a stochastic individual-based mechanistic BRD model which incorporates not only the infectious process, but also clinical signs, detection methods and treatment protocols. We investigated twelve contrasted scenarios which reflect farming practices in various fattening systems, based on pen sizes, risk level, and individual treatment vs. collective treatment (metaphylaxis) before or during fattening. We calibrated model parameters from existing observation data or literature and compared scenario outputs regarding disease dynamics, severity and mortality. The comparison of the trade-off between cumulative BRD duration and number of antimicrobial doses highlighted the added value of risk reduction at pen formation even in small pens, and acknowledges the interest of collective treatments for high-risk pens, with a better efficacy of treatments triggered during fattening based on the number of detected cases.
Published: 2022

39. Coupling simulation and accelerated degradation model for reliability estimation: Application to a voltage regulator

Author: Jaber Al Rashid, Laurent Saintis, Mohsen Koohestani, Mihaela Barreau, ESEO - RF-EMC (RF-EMC), ESEO-Tech, Université Bretagne Loire (UBL)-École supérieure d'électronique de l'ouest [Angers] (ESEO)-Université Bretagne Loire (UBL)-École supérieure d'électronique de l'ouest [Angers] (ESEO), Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES), Institut d'Électronique et des Technologies du numéRique (IETR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Laboratoire Angevin de Recherche en Ingénierie des Systèmes (LARIS), Université d'Angers (UA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - pôle Sciences et technologie, Région Pays de la Loire - RFI WISE, and LifeLongEMC
Subjects: Reliability performance estimation, Degradation path modelAccelerated degradation, Condensed Matter Physics, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Accelerated degradation, Atomic and Molecular Physics, and Optics, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, [INFO.INFO-PF]Computer Science [cs]/Performance [cs.PF], [SPI]Engineering Sciences [physics], Failure threshold, Degradation path model, Lifetime data distribution, Electrical simulation model, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, Electrical and Electronic Engineering, Safety, Risk, Reliability and Quality
Abstract: International audience; This paper demonstrates the use of numerical simulation data, depending on the behavior of a low voltage dropout regulator, for reliability performance estimation based on the accelerated degradation test data. The regulator was designed using Cadence Virtuoso software in 180 nm AMS CMOS technology, and simulated to evaluate its output voltage variations to both temperature and input voltage. The output voltage degradation data were generated according to environmental parameters (input voltage and temperature) constraints, which makes it possible to define failure thresholds under accelerated conditions, making use of the numerical simulation model along with the proposed degradation model. Degradation path model has been adopted to determine the pseudo failure time under the specified failure criterion (5 %). Acceleration law model has then been derived to estimate the reliability model parameters by performing maximum likelihood estimation method not only to analyse but also to predict lifetime data distribution of the regulator under different voltage and temperature stress conditions.; Cet article démontre l'utilisation de données de simulation numérique, en fonction du comportement d'un régulateur à faible chute de tension, pour l'estimation des performances de fiabilité basée sur les données d’essais de dégradation accélérée. Le régulateur a été conçu à l'aide du logiciel Cadence Virtuoso en technologie CMOS AMS 180 nm, et simulé pour évaluer les variations de sa tension de sortie en fonction de la température et de la tension d'entrée. Les données de dégradation de la tension de sortie ont été générées en fonction de contraintes liées aux paramètres environnementaux (tension d'entrée et température), ce qui permet de définir des seuils de défaillance dans des conditions accélérées, en utilisant le modèle de simulation numérique ainsi que le modèle de dégradation proposé. Le modèle de trajectoire de dégradation a été adopté pour déterminer le temps de pseudo-défaillance sous le critère de défaillance spécifié (5 %). Un modèle de loi d'accélération a ensuite été utilisé pour estimer les paramètres du modèle de fiabilité en appliquant la méthode d'estimation du maximum de vraisemblance pour analyser et aussi pour prédire la distribution des données de durée de vie du régulateur dans différentes conditions de tension et de température.
Published: 2022

40. High throughput quantitative phenotyping of plant resistance using chlorophyll fluorescence image analysis

Author: Charles Manceau, Céline Rousseau, Marie-Agnès Jacques, Etienne Belin, Jacky Guillaumes, Romain Berruyer, Frédéric Fabre, Tristan Boureau, David Rousseau, Edouard Bove, Institut de Recherche en Horticulture et Semences (IRHS), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA)-Université d'Angers (UA), Laboratoire d'Ingéniérie des Systèmes Automatisés (LISA), Université d'Angers (UA), Station de Pathologie Végétale (AVI-PATHO), Institut National de la Recherche Agronomique (INRA), Laboratoire de la santé des végétaux, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), This work was supported by Angers Loire Métropole, Conseil Général Département de Maine-et-Loire and Région Pays de la Loire (Phenotic) and by Institut National de la Recherche Agronomique and Région Pays de la Loire., Université d'Angers (UA)-Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, 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), Unité de Pathologie Végétale (PV), Boureau, Tristan, BMC, Ed., Laboratoire de santé des végétaux (LSV Angers), Laboratoire de la santé des végétaux (LSV), and Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)
Subjects: 0106 biological sciences, [SDV.SA]Life Sciences [q-bio]/Agricultural sciences, détection de la maladie, fluorescence chlorophyllienne, Plant Science, Bioinformatics, 01 natural sciences, pixel, résistance des plantes aux agents pathogènes, Contrast (vision), Segmentation, logiciel r, Throughput (business), Chlorophyll fluorescence, media_common, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], 0303 health sciences, [SDV.SA] Life Sciences [q-bio]/Agricultural sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], résistance quantitative, mise au point de technique, Thresholding, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Agricultural sciences, automatisation, Biotechnology, notation des maladies, media_common.quotation_subject, Biology, analyse d'image, Image (mathematics), 03 medical and health sciences, Genetics, Cluster analysis, imagerie quantitative, 030304 developmental biology, modélisation, bactérie phytopathogène, Pixel, business.industry, imagerie in vivo, méthode de quantification, Methodology, Pattern recognition, phaseolus vulgaris, maladie des plantes, Artificial intelligence, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, xanthomonas fuscans, Sciences agricoles, 010606 plant biology & botany
Abstract: Background: In order to select for quantitative plant resistance to pathogens, high throughput approaches that can precisely quantify disease severity are needed. Automation and use of calibrated image analysis should provide more accurate, objective and faster analyses than visual assessments. In contrast to conventional visible imaging, chlorophyll fluorescence imaging is not sensitive to environmental light variations and provides single-channel images prone to a segmentation analysis by simple thresholding approaches. Among the various parameters used in chlorophyll fluorescence imaging, the maximum quantum yield of photosystem II photochemistry (Fv/Fm) is well adapted to phenotyping disease severity. Fv/Fm is an indicator of plant stress that displays a robust contrast between infected and healthy tissues. In the present paper, we aimed at the segmentation of Fv/Fm images to quantify disease severity., Results: Based on the Fv/Fm values of each pixel of the image, a thresholding approach was developed to delimit diseased areas. A first step consisted in setting up thresholds to reproduce visual observations by trained raters of symptoms caused by Xanthomonas fuscans subsp. fuscans (Xff) CFBP4834-R on Phaseolus vulgaris cv. Flavert. In order to develop a thresholding approach valuable on any cultivars or species, a second step was based on modeling pixel-wise Fv/Fm-distributions as mixtures of Gaussian distributions. Such a modeling may discriminate various stages of the symptom development but over-weights artifacts that can occur on mock-inoculated samples. Therefore, we developed a thresholding approach based on the probability of misclassification of a healthy pixel. Then, a clustering step is performed on the diseased areas to discriminate between various stages of alteration of plant tissues. Notably, the use of chlorophyll fluorescence imaging could detect pre-symptomatic area. The interest of this image analysis procedure for assessing the levels of quantitative resistance is illustrated with the quantitation of disease severity on five commercial varieties of bean inoculated with Xff CFBP4834-R., Conclusions: In this paper, we describe an image analysis procedure for quantifying the leaf area impacted by the pathogen. In a perspective of high throughput phenotyping, the procedure was automated with the software R downloadable at http://www.r-project.org/. The R script is available at http://lisa.univ-angers.fr/PHENOTIC/telechargements.html.
Published: 2013

41. Carbon monoxide decreases endosome-lysosome fusion andinhibits soluble antigen presentation by dendritic cells to tcells

Author: Alexis M. Kalergis, Claudia A. Riedel, Susan M. Bueno, Claudia M. Cortés, Séverine Remy, Thomas Simon, Virginie Tardif, Cédric Louvet, Leandro J. Carreño, Marcelo Hill, Jean Marie Bach, Sebastián A. Riquelme, Ignacio Anegon, Christine Chauveau, Philippe Blancou, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), 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), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN), Millenium Institute of Immunology and Immunotherapy, Pontificia Universidad Católica de Chile (UC), Universidad Andrés Bello [Santiago] (UNAB), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Departamento de Reumatologia, La Région Pays de la Loire through the 'Chaire d’excellence program'., IMBIO program., Agence de la Biomédecine., Ministère de la Recherche., Fondation CENTAURE., Fondation Progreffe., Grant 'Nouvelles Equipes-nouvelles thématiques' from the La Région Pays De La Loire., INSERM CDD grant., ECOS France-Chile grant., Millennium Institute on Immunology and Immunotherapy from Chile (P09/016-F)., École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), and Le Bihan, Sylvie
Subjects: CD4-Positive T-Lymphocytes, Lipopolysaccharides, Endosome, Ovalbumin, Immunology, Antigen presentation, Mice, Transgenic, Endosomes, Lymphocyte Activation, 03 medical and health sciences, Mice, 0302 clinical medicine, Immune system, Antigen, MHC class I, Immunology and Allergy, Animals, Cells, Cultured, 030304 developmental biology, 0303 health sciences, MHC class II, Antigen Presentation, Carbon Monoxide, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Cross-presentation, biology, Antigen processing, Histocompatibility Antigens Class I, Histocompatibility Antigens Class II, Membrane Proteins, Dendritic Cells, Endocytosis, Cell biology, Mice, Inbred C57BL, biology.protein, Lysosomes, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Heme Oxygenase-1, 030215 immunology
Abstract: International audience; Heme oxygenase-1 (HO-1) inhibits immune responses and inflammatory reactions via the catabolism of heme into carbon monoxide (CO), Fe 2+ , and biliverdin. We have previously shown that either induction of HO-1 or treatment with exogenous CO inhibits LPS-induced maturation of dendritic cells (DCs) and protects in vivo and in vitro antigen-specific inflammation. Here, we evaluated the capacity of HO-1 and CO to regulate antigen presentation on MHC class I and MHC class II molecules by LPS-treated DCs. We observed that HO-1 and CO treatment significantly inhibited the capacity of DCs to present soluble antigens to T cells. Inhibition was restricted to soluble OVA protein, as no inhibition was observed for antigenic OVA-derived peptides, bead-bound OVA protein, or OVA as an endogenous antigen. Inhibition of soluble antigen presentation was not due to reduced antigen uptake by DCs, as endocytosis remained functional after HO-1 induction and CO treatment. On the contrary, CO significantly reduced the efficiency of fusion between late endosomes and lysosomes and not by phagosomes and lysosomes. These data suggest that HO-1 and CO can inhibit the ability of LPS-treated DCs to present exogenous soluble antigens to naïve T cells by blocking antigen trafficking at the level of late endosome-lysosome fusion.
Published: 2013

42. Comparison of geophysical prospecting and geochemical prospecting at the medieval and modern Cistercian Abbey of Carnoët (Finistère, France)

Author: Arthur Laenger, Arnaud Martel, Fabien Boucher, Xavier François, Michel Dabas, Joséphine Rouillard, Aline Durand, Le Mans Université (UM), Centre de Recherche en Archéologie, Archéosciences, Histoire (CReAAH), Le Mans Université (UM)-Université de Rennes (UR)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC)-Nantes Université - UFR Histoire, Histoire de l'Art et Archéologie (Nantes Univ - UFR HHAA), Nantes Université - pôle Humanités, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Humanités, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Institut des Molécules et Matériaux du Mans (IMMM), Le Mans Université (UM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de Technologie du Mans (IUT Le Mans), Geocarta, Paris, France, Partenaires INRAE, Archéologie et Philologie d'Orient et d'Occident (AOROC), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Département des Sciences de l'Antiquité - ENS Paris (DSA ENS-PSL), École normale supérieure - Paris (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), Centre National de la Recherche Scientifique (CNRS), Chercheur indépendant, and Région Pays de la Loire
Subjects: Archeology, History, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, [SHS.HIST]Humanities and Social Sciences/History, [SDE.ES]Environmental Sciences/Environmental and Society
Abstract: International audience
Published: 2022

43. Automatic teeth segmentation on panoramic X-rays using deep neural networks

Author: Nader, Rafic, Smorodin, Andrey, de La Fourniere, Natalia, Amouriq, Yves, Autrusseau, Florent, Autrusseau, Florent, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Odessa National Polytechnic University, Artefakt-AI, Regenerative Medicine and Skeleton (RMeS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR Odontologie, Laboratoire de Thermique et d’Energie de Nantes (LTeN), Centre National de la Recherche Scientifique (CNRS)-Nantes Université - Ecole Polytechnique de l'Université de Nantes (Nantes Univ - EPUN), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, and ISITE NExT, Région pays de la Loire, Fonds Européen de Développement Régional (FEDER)
Subjects: [INFO.INFO-AI] Computer Science [cs]/Artificial Intelligence [cs.AI], ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, deep learning, [INFO]Computer Science [cs], location prior, [INFO] Computer Science [cs], Panoramic X-ray images, U-Net, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], Teeth segmentation
Abstract: International audience; In order to build an intelligent dental care process that both facilitates the treatment and improves the diagnosis, an accurate tooth segmentation and recognition on panoramic X-ray images might prove helpful. Although many studies have been conducted on teeth segmentation, few methods allow to perform tooth recognition and numbering at the same time. The existing methods allowing both those processes rely on instance segmentation architectures. To fill some gaps in the area of dental image segmentation, we propose a novel approach of automatic joint teeth segmentation and numbering using the pioneer U-Net model. We are first to employ the conventional U-Net model and show its limitations to provide accurate segmentation, being affected by noisy pixels outside the teeth region and by missing teeth in the X-ray images. To overcome this problem and reduce the misclassifications, we use a bounding box prior at the level of the skip connections. Such an approach helps guiding the network to better locate the teeth, and hence improves the segmentation. To validate the effectiveness of the method, we have conducted two experiments on the DNS Panoramic Dataset: a first one using manual bounding boxes and another one relying on a preliminary step of object detection. The implemented networks were evaluated using the Dice coefficient index and our results showed that consideration of location information onto the skip connections improves the performances of the semantic segmentation by 5% to 10% in average Dice accuracy depending on the quality of the bounding box labels.
Published: 2022

44. Multiple sclerosis clinical decision support system based on projection to reference datasets

Author: Chadia Ed‐driouch, Florent Chéneau, Françoise Simon, Guillaume Pasquier, Benoit Combès, Anne Kerbrat, Emmanuelle Le Page, Sophie Limou, Nicolas Vince, David‐Axel Laplaud, Franck Mars, Cédric Dumas, Gilles Edan, Pierre‐Antoine Gourraud, Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Perception, Action, Cognition pour la Conception et l’Ergonomie (LS2N - équipe PACCE), Laboratoire des Sciences du Numérique de Nantes (LS2N), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Nantes Université (Nantes Univ), Département Automatique, Productique et Informatique (IMT Atlantique - DAPI), IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Mount Sinai School of Medicine, Department of Psychiatry-Icahn School of Medicine at Mount Sinai [New York] (MSSM), Institut de Recherche Technologique b-com (IRT b-com), Neuroimagerie: méthodes et applications (EMPENN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAL, IMAGE ET LANGAGE (IRISA-D6), 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), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), École Centrale de Nantes (Nantes Univ - ECN), Centre hospitalier universitaire de Nantes (CHU Nantes), Bourse Région Pays de la Loire number 2019_11235, ANR-21-RHUS-0014,Primus,Transforming the care of patients with Multiple Sclerosis using a multidimensional data-driven clinical decision support system(2021), European Project: 754995,EU-TRAIN, Team 3 : Integrative transplantation, HLA, Immunology and genomics of kidney injury (U1064 Inserm - CR2TI), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Team 1 : Mononuclear phagocytes, Immunopathology, Immunovirology (U1064 Inserm - CR2TI), Team 5 : Neuroinflammation, mechanisms, therapeutic options (NEMO) (U1064 Inserm - CR2TI), Centre d'investigation clinique (CIC) de Nantes -CIC Plurithématique (CIC 0004 - Nantes), Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and This project has received funding from theEuropean Union’s Horizon 2020 Researchand Innovation Programme under GrantAgreement No. 754995, and the scholarship'Bourse Region Pays de la Loire' number2019_11235. MS Vista is part of the PRIMUSproject. This work was supported in part bythe French National Research Agency(Agence Nationale de la Recherche, ANR) asits 3rd PIA, integrated to France 2030 planunder reference [ANR-21-RHUS-0014].
Subjects: MESH: Humans, General Neuroscience, MESH: Magnetic Resonance Imaging / methods, MESH: Multiple Sclerosis, Relapsing-Remitting / diagnostic imaging, [SDV]Life Sciences [q-bio], [SCCO]Cognitive science, MESH: Interferon beta-1a / therapeutic use, MESH: Decision Support Systems, Clinical, MESH: Multiple Sclerosis, Relapsing-Remitting / drug therapy, MESH: Multiple Sclerosis / drug therapy, [INFO]Computer Science [cs], Neurology (clinical), MESH: Multiple Sclerosis, Relapsing-Remitting / pathology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Objective: Multiple sclerosis (MS) is a multifactorial disease with increasingly complicated management. Our objective is to use on-demand computational power to address the challenges of dynamically managing MS.Methods: A phase 3 clinical trial data (NCT00906399) were used to contextualize the medication efficacy of peg-interferon beta-1a vs placebo on patients with relapsing-remitting MS (RRMS). Using a set of reference patients (PORs), selected based on adequate features similar to those of an individual patient, we visualize disease activity by measuring the percentage of relapses, accumulation of new T2 lesions on MRI, and worsening EDSS during the clinical trial.Results: We developed MS Vista, a functional prototype of clinical decision support system (CDSS), with a user-centered design and distributed infrastructure. MS Vista shows the medication efficacy of peginterferon beta-1a versus placebo for each individual patient with RRMS. In addition, MS Vista initiated the integration of a longitudinal magnetic resonance imaging (MRI) viewer and interactive dual physician-patient data display to facilitate communication.Interpretation: The pioneer use of PORs for each individual patient enables personalized analytics sustaining the dialog between neurologists, patients and caregivers with quantified evidence.
Published: 2022

45. The Internal Conduit System of the Swine Inverted Lymph Node

Author: Dubreil, Laurence, Ledevin, Mireille, Hervet, Caroline, Menard, Déborah, Philippe, Claire, Michel, François J., Larcher, Thibaut, Meurens, François, Bertho, Nicolas, Expertise en Anatomie Pathologique (APEX), Physiopathologie Animale et bioThérapie du muscle et du système nerveux (PAnTher), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biologie, Epidémiologie et analyse de risque en Santé Animale (BIOEPAR), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U1249), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Saskatchewan [Saskatoon] (U of S), and APEX, PAnTher, INRAE, Oniris is supported by Pays de la Loire, IBISA and NeurATRIS translational research infrastructure for innovative therapies in NeuroSciences. Biogenouest (the network of technology core facilities in Western France in life sciences and the environment, and by the Conseil Régional des Pays de la Loire). APEX platform is a Center of Excellence Nikon. Reagents and equipment were purchased thanks to the establishment grant obtained by FM from the Région Pays de la Loire (RFI Food for tomorrow-Cap aliment).
Subjects: Follicle, B-Lymphocytes, Swine, Macrophages, [SDV]Life Sciences [q-bio], Immunology, Lymph Node, Second harmonic generation, Fluorescence imaging, Mice, Endothelial cell, Animals, Immunology and Allergy, Lymph Nodes, Lymphocytes, Whole organ imaging, Lymphatic Vessels, B lymphocytes
Abstract: International audience; Lymph nodes (LN) are the crossroad where naïve lymphocytes, peripheral antigens and antigen presenting cells contact together in order to mount an adaptive immune response. For this purpose, LN are highly organized convergent hubs of blood and lymphatic vessels that, in the case of B lymphocytes, lead to the B cell follicles. Herein take place the selection and maturation of B cell clones producing high affinity antibodies directed against various antigens. Whereas the knowledge on the murine and human LN distribution systems have reached an exquisite precision those last years, the organization of the antigens and cells circulation into the inverted porcine LN remains poorly described. Using up to date microscopy tools, we described the complex interconnections between afferent lymphatics and blood vessels, perifollicular macrophages, follicular B cells and efferent blood vessels. We observed that afferent lymphatic sinuses presented an asymmetric Lyve-1 expression similar to the one observed in murine LN, whereas specialized perifollicular sinuses connect the main afferent lymphatic sinus to the B cell follicles. Finally, whereas it was long though that mature B cells egress from the inverted LN in the T cell zone through HEV, our observations are in agreement with mature B cells accessing the efferent blood circulation in the efferent, subcapsular area. This understanding of the inverted porcine LN circuitry will allow a more accurate exploration of swine pathogens interactions with the immune cells inside the LN structures. Moreover, the mix between similarities and differences of porcine inverted LN circuitry with mouse and human normal LN shall enable to better apprehend the functions and malfunctions of normal LN from a new perspective.
Published: 2022

46. A tris-oxovanadium pyrogallate complex: synthesis, structure, and magnetic and electronic properties

Author: Hassan Mkhadder, Bernard Humbert, Thomas Devic, Philippe Poizot, Walter Cañon-Mancisidor, Elise Deunf, Mónica Giménez-Marqués, Morgane Denis, Institut des Matériaux Jean Rouxel (IMN), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN), Instituto de Ciencia Molecular (ICMol), Universitat de València (UV), Universidad de Santiago de Chile [Santiago] (USACH), Centro para el Desarrollo de la Nanociencia y Nanotecnología (CEDENNA), and Région Pays de la Loire (project PSR 'MatHySE2')Generalitat Valenciana, European Commission, General Electric - Grant number SEJI2020/036La Caixa Foundation - Grant number LCF/BQ/PI19/11690022Spanish MINECO - Grant number RYC-2019-027902-IComision Nacional de Investigacion Cientifica y Tecnologica (CONICYT), CONICYT PIA/BASAL - Grant number AFB180001
Subjects: Thermogravimetric analysis, Materials science, 010405 organic chemistry, Infrared, Química organometàl·lica, Vanadium, chemistry.chemical_element, Crystal structure, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, Inorganic Chemistry, Compostos orgànics Síntesi, symbols.namesake, Crystallography, chemistry, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], symbols, Metal-organic framework, Reactivity (chemistry), Diffuse reflection, Raman spectroscopy
Abstract: International audience; With the aim of identifying new cation-phenolate complexes, we herein investigated the reactivity of pyrogallol (H(3)pgal) with vanadium salts. A trimetallic anionic complex was identified, and found to be formed under a broad set of reaction conditions. This complex, with the formula V3O3(pgal)(3)(3-), consists of three oxovanadium(iv) units connected together by three pyrogallate ligands to afford a bowl-shaped species presenting a pseudo 3-fold symmetry axis. Its crystal structure is reported, as well as its characterisation by a broad set of techniques, including powder X-ray diffraction, thermogravimetric analysis, infrared and Raman spectroscopy, and solid state UV-visible diffuse reflectance. Its redox activity both in solution and in the solid state is described, together with its magnetic behavior. Finally, the relevance of this trimetallic unit in the field of phenolic-based biocoatings and Metal Organic Framework (MOF) synthesis is briefly discussed.
Published: 2021

47. Grain carbon isotope composition is a marker for allocation and harvest index in wheat

Author: Jean‐Baptiste Domergue, Cyril Abadie, Julie Lalande, Jean‐Charles Deswarte, Eric Ober, Valérie Laurent, Céline Zimmerli, Philippe Lerebour, Laure Duchalais, Camille Bédard, Jérémy Derory, Thierry Moittie, Marlène Lamothe‐Sibold, Katia Beauchêne, Anis M. Limami, Guillaume Tcherkez, Institut de Recherche en Horticulture et Semences (IRHS), Université d'Angers (UA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Rennes Angers, 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], Natl Inst Agr Bot, Cambridge, England, Partenaires INRAE, Physiopathologie et Thérapeutiques Respiratoires, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10, Département de Biologie Moléculaire Végétale, Université de Lausanne = University of Lausanne (UNIL), UNISIGMA, Société Ragt 2N, RAGT 2n, Biodiversité, Gènes & Communautés (BioGeCo), Université de Bordeaux (UB)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Union Française des Semenciers (UFS), Institut des Sciences des Plantes de Paris-Saclay (IPS2 (UMR_9213 / UMR_1403)), Institut National de la Recherche Agronomique (INRA)-Université Paris-Sud - Paris 11 (UP11)-Université Paris Diderot - Paris 7 (UPD7)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), IRHS - Équipe SMS (Source and sink Metabolism and Stress responses) (IRHS-SMS), 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 d'Angers (UA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Rennes Angers, Région Pays de la Loire, Institut de Biologie des Plantes (IBP), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), ARVALIS - Institut du Végétal, Université d'Angers (UA), and DUPRE, Olivier
Subjects: carbon 13, Carbon Isotopes, Physiology, food and beverages, Plant Science, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Carbon, post-photosynthetic fractionation, Plant Leaves, Plant Breeding, partitioning, respiration use efficiency, Edible Grain, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Triticum
Abstract: International audience; The natural C-13 abundance (delta C-13) in plant leaves has been used for decades with great success in agronomy to monitor water-use efficiency and select modern cultivars adapted to dry conditions. However, in wheat, it is also important to find genotypes with high carbon allocation to spikes and grains, and thus with a high harvest index (HI) and/or low carbon losses via respiration. Finding isotope-based markers of carbon partitioning to grains would be extremely useful since isotope analyses are inexpensive and can be performed routinely at high throughput. Here, we took the advantage of a set of field trials made of more than 600 plots with several wheat cultivars and measured agronomic parameters as well as delta C-13 values in leaves and grains. We find a linear relationship between the apparent isotope discrimination between leaves and grain (denoted as Delta delta(corr)), and the respiration use efficiency-to-HI ratio. It means that overall, efficient carbon allocation to grains is associated with a small isotopic difference between leaves and grains. This effect is explained by postphotosynthetic isotope fractionations, and we show that this can be modelled by equations describing the carbon isotope composition in grains along the wheat growth cycle. Our results show that C-13 natural abundance in grains could be useful to find genotypes with better carbon allocation properties and assist current wheat breeding technologies.
Published: 2022

48. ACCEPTABILITÉ DES SOLUTIONS IA EN CONTEXTE PROFESSIONNEL

Author: Agossah, Alexandre, Laboratoire des Sciences du Numérique de Nantes (LS2N), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ), École de design Nantes Atlantique, Groupe SIGMA, Thèse CIFRE ANRT - Groupe SIGMARFI Ouest Industries Créatives - Région Pays-de-la-Loire - Nantes Métropole, and Muséum d’histoire naturelle de Nantes Métropole en collaboration avec le Laboratoire des Sciences du Numérique de Nantes (LS2N) avec l'UFR Sciences et techniques de Nantes Université, Centrale Nantes
Subjects: Acceptabilité / Acceptation, Contexte professionnel, [INFO.INFO-HC]Computer Science [cs]/Human-Computer Interaction [cs.HC], Intelligence artificielle, UX Design, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI]
Abstract: International audience
Published: 2022

49. Déploiement de l'IA en situation de travail : une trop faible considération des employés ?

Author: Agossah, Alexandre, Krupa, Frédérique, Deconde, Guillaume, Perreira da Silva, Matthieu, Le Callet, Patrick, Laboratoire des Sciences du Numérique de Nantes (LS2N), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ), École de design Nantes Atlantique, Groupe SIGMA, and Thèse CIFRE ANRT - Groupe SIGMARFI Ouest Industries Créatives - Région Pays-de-la-Loire - Nantes Métropole
Subjects: Artificial intelligence, Acceptability, Acceptabilité / Acceptation, Professional context, Contexte professionnel, [INFO.INFO-HC]Computer Science [cs]/Human-Computer Interaction [cs.HC], UX Design, Intelligence artificielle, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI]
Abstract: International audience; Recent work on acceptability of AI-enabled professional tools has focused on the consideration of Human Factors such as user confidence as well as technical factors like model explainability as determinants of user-adoption and usage. These links are mainly established in simulated contexts or environments with low deployment constraints. However, the acceptability of AI tools in professional settings seems to be often restricted to the acceptance of performance and short-term return on investment (ROI) without questioning the technical appropriateness of AI capabilities to user's needs (and fears) or tasks at hand. Three deployment sites of AI-assisted decision-making tools were observed where AI acceptability was limited to the artefact's measurable time-based efficiency. In this article, we question the other UX design considerations in these ML-enhanced dashboards with rushed production cycles that produced AI gadgets rather than user-friendly tools. These AI gadgets ultimately resulted in negative user experiences, inconclusive ROI and/or sidelining of projects. We then suggest ways of limiting risks of end-user-rejection through a more holistic approach of UX design considerations. These include ascertaining needs of the stakeholder network, avoiding technical solutionism, optimizing user interfaces to reduce unnecessary complexity, and dimensioning technical solutions appropriately to the task.; Les récents travaux sur l’acceptabilité des solutions IA en situation de travail se focalisent sur la prise en compte des facteurs humains et des facteurs intrinsèques à l’outil comme déterminants de l’adoption par les employés. Dans cet article, nous retraçons le déploiement d’outils professionnels basés sur de l’IA dans trois cas d’usage. Nous avons exploré les motivations de ces acteurs novices dans ce type de technologie, les moyens déployés pour mener à bien leur projet ainsi que la place accordée aux employés dans le processus de conception. Nous constatons que l’acceptabilité des solutions IA dans ces cas d’usage semble se limiter à l’acceptation de la performance et à un retour sur investissement (ROI) à court terme au détriment de la prise en compte des besoins et craintes des employés. Les conséquences directement observables sont des expériences négatives pour les employés, un retour sur investissement peu concluant et/ou la mise à l’écart de projets. Pour limiter les risques de rejet, nous suggérons de renforcer une approche plus holistique avec des considérations mise en avant par l’UX Design. Cela se traduit notamment par le fait de déterminer les besoins du réseau de parties prenantes, d’éviter le solutionnisme technique, d’optimiser les interfaces utilisateur pour réduire la complexité inutile et de dimensionner les solutions techniques de manière appropriée à la tâche
Published: 2022

50. Benthic foraminifera as tracers of brine production in the Storfjorden 'sea ice factory'

Author: Fossile, Eleonora, Nardelli, Maria Pia, Jouini, Arbia, LANSARD, Bruno, Pusceddu, Antonio, Moccia, Davide, Michel, Elisabeth, Peron, Olivier, Howa, Hélène, Mojtahid, Meryem, Laboratoire de Planétologie et Géodynamique - Angers (LPG-ANGERS), Laboratoire de Planétologie et Géodynamique [UMR 6112] (LPG), Université d'Angers (UA)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Océan et Interfaces (OCEANIS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Department of Life and Environmental Sciences, Università degli Studi di Cagliari = University of Cagliari (UniCa), Paléocéanographie (PALEOCEAN), Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), The research was funded by the ABBA (Observatoire des Sciences de l'Univers de Nantes Atlantique), Bi-SMART (University of Angers) and TANDEM (Région Pays de la Loire) projects, Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), University of Cagliari, Universita degli Studi di Cagliari [Cagliari], and Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique)
Subjects: lcsh:Geology, lcsh:QH501-531, [SDU.STU.GC]Sciences of the Universe [physics]/Earth Sciences/Geochemistry, lcsh:QH540-549.5, lcsh:QE1-996.5, lcsh:Life, lcsh:Ecology, [SDU.STU.OC]Sciences of the Universe [physics]/Earth Sciences/Oceanography
Abstract: The rapid response of benthic foraminifera to environmental factors (e.g. organic matter quality and quantity, salinity, pH) and their high fossilisation potential make them promising bio-indicators for the intensity and recurrence of brine formation in Arctic seas. Such an approach, however, requires a thorough knowledge of their modern ecology in such extreme settings. To this aim, seven stations along a north–south transect across the Storfjorden (Svalbard archipelago) have been sampled using an interface multicorer. This fjord is an area of intense sea ice formation characterised by the production of brine-enriched shelf waters (BSW) as a result of a recurrent latent-heat polynya. Living (rose bengal-stained) foraminiferal assemblages were analysed together with geochemical and sedimentological parameters in the top 5 cm of the sediment. Three major biozones were distinguished. (i) The “inner fjord” zone, dominated by typical glacier proximal calcareous species, which opportunistically respond to fresh organic matter inputs. (ii) The “deep basins and sill” zone, characterised by glacier distal agglutinated fauna; these are either dominant because of the mostly refractory nature of organic matter and/or the brine persistence that hampers the growth of calcareous species and/or causes their dissolution. (iii) The “outer fjord” zone, characterised by typical North Atlantic species due to the intrusion of the North Atlantic water in the Storfjordrenna. The stressful conditions present in the deep basins and sill (i.e. acidic waters and low food quality) result in a high agglutinated ∕ calcareous ratio (A∕C). This supports the potential use of the A∕C ratio as a proxy for brine persistence and overflow in Storfjorden.
Published: 2020

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