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1. Survivre, renaître?

Author: Naissances. Approches transdisciplinaires d'une question de soin (27-31 août 2018: Fondation des Treilles), Zaccai-Reyners, Nathalie, Naissances. Approches transdisciplinaires d'une question de soin (27-31 août 2018: Fondation des Treilles), and Zaccai-Reyners, Nathalie
Abstract: info:eu-repo/semantics/nonPublished
Published: 2018

2. Bossuet en italien: Bibliographie indicative.

Author: Treilles, Nicolas GarrotéCe travail a bénéficié du soutien de la Fondation des Treilles. La Fondation des and Schlumberger, créée par Anne Gruner
Subjects: ITALIAN literature
Published: 2020

3. Soigner les criminels ? Pharmacologie et psychochirurgie

Author: Colloque « Crime et Folie » (1er au 6 novembre 2010: Fondation des Treilles, Tourtour), Missa, Jean-Noël, Colloque « Crime et Folie » (1er au 6 novembre 2010: Fondation des Treilles, Tourtour), and Missa, Jean-Noël
Abstract: info:eu-repo/semantics/nonPublished
Published: 2010

4. Localized structures and curvature instability in nonlinear optical systems

Author: Workshop on dissipative structures and non-equilibrium assisted self-assembly. Fondation des Treilles (5-9 September: Tourtour, France), Tlidi, Mustapha, Workshop on dissipative structures and non-equilibrium assisted self-assembly. Fondation des Treilles (5-9 September: Tourtour, France), and Tlidi, Mustapha
Abstract: info:eu-repo/semantics/nonPublished
Published: 2000

5. Targeting the DNA damage response in immuno-oncology: developments and opportunities

Author: Christopher J. Lord, Philippe Pasero, Mathieu Rouanne, Roman M. Chabanon, Jean-Charles Soria, Sophie Postel-Vinay, Programme ATIP - Avenir, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunologie anti-tumorale et immunothérapie des cancers (ITIC), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Foch [Suresnes], The institute of cancer research [London], Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Institut Gustave Roussy (IGR), Université Paris-Saclay, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), AstraZeneca, Roche, Association pour la Recherche sur le Cancer, ARC: PGA1 RF 20190208576, Boehringer Ingelheim, Merck KGaA, Ligue Contre le Cancer: INCa-DGOS-INSERM_12551, Cancéropôle Ile de France: 2017-1-EMERG-72, Fondation Bettencourt Schueller, Fondation des Treilles, The authors thank Y. L. Lin and H. Técher for their careful reading of the manuscript and insightful comments. The work in the laboratory of S.P.-V. is supported by programme grants from ATIP-Avenir INSERM / La Ligue Nationale Contre le Cancer, SIRIC SOCRATE-2 (INCa-DGOS-INSERM_12551), Cancéropôle Ile-de-France (2017-1-EMERG-72) and Association pour la Recherche contre le Cancer (ARC PGA1 RF 20190208576). R.M.C. received funding from Fondation Bettencourt-Schueller, Fondation des Treilles, Fondation Philanthropia-Lombard Odier, Institut Servier, and Cancéropôle Ile-De-France., and R.M.C., M.R. and P.P. have no conflicts of interest or financial interests to disclose. C.J.L. is a named inventor on patents describing the use of DNA repair inhibitors and stands to gain from their use as part of the Institute of Cancer Research Rewards to Inventor scheme. C.J.L. has received research funding from AstraZeneca, Merck KGaA, Artios and Pfizer, has received consultancy and/or advisory fees from Astra Zeneca, Merck KGaA, Artios, Tango and GLG, and is a shareholder of OviBio and Tango. J.-C.S. has received consultancy fees from Relay Therapeutics, is a shareholder of AstraZeneca, Gritstone and Daiichi Sankyo, and is a member of the Hookipa board of directors. S.P.-V. has received research funding from Merck KGaA, Boehringer Ingelheim and Roche for unrelated research projects. As part of the Drug Development Department (DITEP), S.P.-V. is a principal investigator or a subinvestigator on clinical trials by Abbvie, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca, Aveo, Bayer Healthcare AG, Bbb Technologies BV, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corporation, Chugai Pharmaceutical Co., Clovis Oncology, Daiichi Sankyo, Debiopharm S.A., Eisai, Eli Lilly, Exelixis, Forma, Gamamabs, Genentech Inc., Glaxosmithkline, H3 Biomedicine Inc., Hoffmann La Roche AG, Innate Pharma, Iris Servier, Janssen Cilag, Kyowa Kirin Pharmaceutical Development Inc., Loxo Oncology, Lytix Biopharma AS, Medimmune, Menarini Ricerche, Merck Sharp & Dohme-Chibret, Merrimack Pharmaceuticals, Merus, Millennium Pharmaceuticals, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology NV, Oncoethix, Onyx Therapeutics, Orion Pharma, Oryzon Genomics, Pfizer, PharmaMar, Pierre Fabre, Roche, Sanofi Aventis, Taiho Pharma, Tesaro Inc. and Xencor. S.P.-V. has participated in advisory boards for Merck KGaA.
Subjects: Antigenicity, DNA damage, General Mathematics, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Cancer immunotherapy, Medical Oncology, Genomic Instability, 03 medical and health sciences, 0302 clinical medicine, Immune system, Targeted therapies, Immunity, Adjuvanticity, Neoplasms, medicine, Animals, Humans, 030304 developmental biology, 0303 health sciences, business.industry, Applied Mathematics, Immunogenicity, Immunotherapy, 3. Good health, 030220 oncology & carcinogenesis, Cancer research, Immunogenic cell death, Tumour immunology, business, DNA Damage
Abstract: International audience; Immunotherapy has revolutionized cancer treatment and substantially improved patient outcome with regard to multiple tumour types. However, most patients still do not benefit from such therapies, notably because of the absence of pre-existing T cell infiltration. DNA damage response (DDR) deficiency has recently emerged as an important determinant of tumour immunogenicity. A growing body of evidence now supports the concept that DDR-targeted therapies can increase the antitumour immune response by (1) promoting antigenicity through increased mutability and genomic instability, (2) enhancing adjuvanticity through the activation of cytosolic immunity and immunogenic cell death and (3) favouring reactogenicity through the modulation of factors that control the tumour–immune cell synapse. In this Review, we discuss the interplay between the DDR and anticancer immunity and highlight how this dynamic interaction contributes to shaping tumour immunogenicity. We also review the most innovative preclinical approaches that could be used to investigate such effects, including recently developed ex vivo systems. Finally, we highlight the therapeutic opportunities presented by the exploitation of the DDR–anticancer immunity interplay, with a focus on those in early-phase clinical development.
Published: 2021
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6. Plasmodium yoelii Uses a TLR3-Dependent Pathway to Achieve Mammalian Host Parasitism

Author: Olivier Silvie, Claire Lambert, Jean-Michel Saliou, Pierre-André Cazenave, Marion Draheim, Sylviane Pied, Sophie Salomé-Desnoulez, Tarun Keswani, Delphine Delcroix-Genete, Fabien Herbert, Jacques Roland, Ines Leleu, Biome Tropical et Immuno-Pathophysiologie = Tropical Biome and ImmunoPhysiopathology [Lille] (TBIP), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)-Université de Guyane (UG), Plateforme BioImaging Center Lille (BICeL), Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 (PLBS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), This work was supported by Laboratory of Excellence/French Alliance for Parasitology and Health Care Grant ANR-11-LABX-0024 from the French National Agency of Research. T.K. is a recipient of a PRESTIGE (FP7 People: Marie Curie Actions/FP7/PCOFUND-GA-2013-609102 Sanction 2014-1-0043) and Région Haut-de-France (the French National Centre for Scientific Research, CNRS, Sanction No. 147894) Post-doctoral Fellowship and a Fondation des Treilles Young Researcher Prize 2016. The Fondation des Treilles, created by Anne Gruner Schlumberger, is intended in particular to open and foster dialog between the sciences and the arts in order to advance contemporary creation and research. It also welcomes researchers, writers and photographic artists in the area of Treilles (Var) (https://www.les-treilles.com). J.R.’s contribution to this work was carried out with the support of the Institut Pasteur de Lille., We acknowledge the support of Dr. Michel Chignard (Institut Pasteur Paris, France). We are grateful to Catherine Ronet for critical analysis of the manuscript and Jean-François Franetich and Maurel Tefit for the production of GFP-Luc sporozoites., ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), European Project: 609102,EC:FP7:PEOPLE,FP7-PEOPLE-2013-COFUND,PRESTIGE(2014), Plateformes Lilloises en Biologie et Santé - UMS 2014 - US 41 (PLBS), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Pied, Sylviane, Laboratoires d'excellence - Alliance française contre les maladies parasitaires - - ParaFrap2011 - ANR-11-LABX-0024 - LABX - VALID, and PRES Towards International Gain of Excellence - PRESTIGE - - EC:FP7:PEOPLE2014-09-01 - 2019-08-31 - 609102 - VALID
Subjects: [SDV.IMM] Life Sciences [q-bio]/Immunology, viruses, [SDV]Life Sciences [q-bio], Immunology, chemical and pharmacologic phenomena, Parasitemia, Biology, Proinflammatory cytokine, 03 medical and health sciences, 0302 clinical medicine, medicine, Immunology and Allergy, 030304 developmental biology, 0303 health sciences, Innate immune system, Wild type, virus diseases, hemic and immune systems, medicine.disease, Natural killer T cell, biology.organism_classification, 3. Good health, [SDV] Life Sciences [q-bio], TRIF, [SDV.IMM]Life Sciences [q-bio]/Immunology, Tumor necrosis factor alpha, Plasmodium yoelii, 030215 immunology
Abstract: Malaria is associated with complicated immunopathogenesis. In this study, we provide evidence for an unexpected role of TLR3 in promoting the establishment of Plasmodium yoelii infection through delayed clearance of parasitemia in wild type C57BL/6jRj (B6) compared with TLR3 knockout mice. In this study, we confirmed an increased expression of Tlr3, Trif, Tbk1, and Irf7/Irf3 in the liver 42 h postinfection and the initiation of an early burst of proinflammatory response such as Ifng, NF-kB, and Tnfa in B6 mice that may promote parasite fitness. Interestingly, in the absence of TLR3, we showed the involvement of high IFN-γ and lower type I IFN response in the early clearance of parasitemia. In parallel, we observed an increase in splenic NK and NKT cells expressing TLR3 in infected B6 mice, suggesting a role for TLR sensing in the innate immune response. Finally, we find evidence that the increase in the frequency of CD19+TLR3+ B cells along with reduced levels of total IgG in B6 mice possibly suggests the initiation of TLR3-dependent pathway early during P. yoelii infection. Our results thus reveal a new mechanism in which a parasite-activated TLR3 pathway promotes blood stage infection along with quantitative and qualitative differences in Ab responses.
Published: 2020
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7. L’essor des agglomérations laténiennes. Pour une lecture européenne

Author: Clara Filet, Archéologies et Sciences de l'Antiquité (ArScAn), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Institut national de recherches archéologiques préventives (Inrap)-Centre National de la Recherche Scientifique (CNRS), Statistique, Analyse et Modélisation Multidisciplinaire (SAmos-Marin Mersenne) (SAMM), Université Paris 1 Panthéon-Sorbonne (UP1), Fondation des Treilles, Hiriart, Eneko, Krausz, Sophie, Alcantara, Aurélien, Filet, Clara, Goláňová, Petra, Hantrais, Juliette, Mathé, Vivien, Filet, Clara, and Hiriart, Eneko, Krausz, Sophie, Alcantara, Aurélien, Filet, Clara, Goláňová, Petra, Hantrais, Juliette, Mathé, Vivien
Subjects: [SHS.ARCHEO] Humanities and Social Sciences/Archaeology and Prehistory, Ville, Âge du Fer, La Tène, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, Iron Age, Chronologie, Agglomérations, Urbanisation, Grouped settlements, Cities, Chronology
Abstract: From the Atlantic to the Carpathians, data on agglomerated, open or fortified, settlements have multiplied in recent decades. However, shared analytical tools have yet to be developed to study these processes at the transnational scale at which they develop.This article, which is the result of a doctoral thesis , aims to suggest a European perspective on the rhythm of La Tene settlements development between the 4th and 1st centuries BCE. To achieve this, however, several reassessments are proposed:•to develop terms that do not shape the understanding of the object of study (such as "oppidum" and "open agglomeration"), since the naming of things is already an interpretation;•to reassess the extent of the phenomenon thanks to updated data, by developing tools that allow its comparison;•to move away from any monolithic view that would see a period of open agglomerations and then a period of oppida, in order to consider the processes as multifaceted and multi-scalar, at the interface between European dynamics and regional specificities;•to abandon any site-centrism. Urbanisation can be seen as a territorial process on which changes in mobility have a major impact.The inventory of 855 grouped (open or fortified) settlements in ten countries, from France to Slovakia, provides a new picture of the extent of the agglomeration wave between the 4th and 1st centuries BCE. Its chronological and functional study thus offers a global perspective on the processes of settlement agglomeration in La Tène Europe, highlighting crucial periods, rhythms and regional specificities. Deconstructing any monolithic view of urbanisation processes during the La Tène, this article aims to highlight some of the common trends at the scale of transalpine Europe, but also the numerous regional peculiarities and chronological shifts that characterise this vast, multiform and interconnected space., De l’Atlantique aux Carpates, les données sur les habitats agglomérés, ouverts comme fortifiés se sont multipliées ces dernières décennies. Reste toutefois à élaborer des outils d’analyse partagés, pour étudier ces processus à l’échelle transnationale où ils se développent.Cet article, issu d’une thèse de doctorat , vise à proposer une perspective européenne des rythmes de développement des agglomérations laténiennes entre le IVe et le Ier s. a.C. Pour y parvenir, plusieurs réévaluations sont toutefois suggérées :•Élaborer des termes qui ne contraignent pas la compréhension de l’objet à étudier (« oppidum » et « agglomération ouverte »), puisque nommer les choses c’est déjà interpréter ;•Réévaluer l’ampleur du phénomène grâce à des données actualisées sur une échelle vaste, en concevant les outils permettant leur comparaison ;•Sortir de toute vision monolithique qui verrait un temps des agglo ouvertes puis un temps des oppida, pour envisager les processus comme multiples et multiscalaires, à l’articulation entre dynamiques européennes et spécificités régionales ;•Sortir du site centrisme. L’urbanisation peut être considérée comme un processus territorial, au sein duquel les transformations de la mobilité ont un effet majeur.Le recensement de 855 sites d’habitat groupé (ouverts ou fortifiées), dans dix pays de la France à la Slovaquie, permet de proposer une image renouvelée de l’ampleur de la vague de création d’agglomérations entre le IVe et le Ier s. a.C. Leur étude chronologique et fonctionnelle offre ainsi une perspective globale des processus d’agglomération de l’habitat à l’échelle de l’Europe laténienne, en soulignant les périodes charnières, les rythmes et certaines spécificités régionales. En déconstruisant toute vision monolithique des processus d’urbanisation au cours de La Tène, cet article vise à souligner certaines des tendances partagées à l’échelle de l’Europe transalpine, mais aussi les multiples spécificités régionales et décalages chronologiques qui caractérisent ce vaste espace, par essence multiforme et interconnecté.
Published: 2023
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8. Tolerant and intolerant macaques differ in the context specificity of their calls and how they 'comment' on the interactions of others

Author: Rebout, Nancy, Marco, Arianna De, Sanna, Andrea, Micheletta, Jérôme, Lone, Jean-Christophe, Berg, Reinier F. van den, Sterck, Elisabeth H. M., Langermans, Jan A. M., Thierry, Bernard, Lemasson, Alban, Sub Animal Behaviour and Cognition, AISS LAS/3'R Centre ULS, Animal Behaviour and Cognition, Fondazione Ethoikos, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Portsmouth, Universiteit Utrecht, Ethologie animale et humaine (EthoS), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), The Fondazione Ethoikos, Fondation des Treilles, Departement d'Ecologie, Physiologie et Ethologie (CNRS IPHC), The Japan Society for the Promotion of Science, French-Dutch Network, Sub Animal Behaviour and Cognition, AISS LAS/3'R Centre ULS, and Animal Behaviour and Cognition
Subjects: Primates, Ecology, Evolution, Communication, [SDV.BA]Life Sciences [q-bio]/Animal biology, Uncertainty, Social complexity, Acoustics, [SCCO]Cognitive science, Behavior and Systematics, Animal Science and Zoology, Flexibility, Ecology, Evolution, Behavior and Systematics
Abstract: International audience; The 'social complexity hypothesis for communicative complexity' posits that living in a complex social system requires complex communication skills. Since the complexity of a system can be measured by the amount of uncertainty it produces, we tested this hypothesis by studying species of macaque that differ in social tolerance and uncertainty of social interactions. We studied vocal communication in groups of macaques belonging to four species: Japanese and rhesus macaques, which are characterized by low levels of social tolerance and low uncertainty in the outcome of social interactions, and Tonkean and crested macaques, which display high levels of tolerance and uncertainty in interactions. We recorded the vocalizations emitted by adult females in agonistic, affiliative and neutral contexts. We measured call duration, entropy and time and frequency energy quantiles and processed these variables using cluster analyses and permutational multivariate analyses of variance. We found that tolerant macaques had a weaker relationship between the acoustic structure of calls and their context of emission compared to intolerant macaques. The study of 'commenting calls', i.e. calls made by individuals attending interactions between groupmates, also showed that their acoustic structure was more differentiated from other calls in tolerant Tonkean and crested macaques than in intolerant rhesus macaques. The flexibility of vocal production therefore appears to be correlated with the level of uncertainty of social interactions. Species with more complex social interactions were also those with higher degree of freedom in the association between acoustic structure and social context, which supports the social complexity hypothesis. Significance statement Is there a relationship between the complexity of social systems and the complexity of communication skills? Animals living in complex social environments are expected to use a wide variety of messages related to different goals and contexts. The complexity of a system can be assessed by the amount of uncertainty it can produce. We investigated the complexity of vocal communication by comparing two species of macaque displaying low uncertainty in their social interactions, with two other macaque species displaying high levels of uncertainty in their interactions. The comparison showed that call flexibility was related to uncertainty levels. Species with higher levels of uncertainty had weaker associations between acoustic structure and social context. These results support the hypothesis of a link between social system complexity and communication complexity, which has important implications for our understanding of the evolution of social and communication systems.
Published: 2022
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9. Compensation between Wnt-driven tumorigenesis and cellular responses to ribosome biogenesis inhibition in the murine intestinal epithelium

Author: Sabrina Coqueran, Aurélien Raveux, Béatrice Romagnolo, Michel Cohen-Tannoudji, Sandrine Vandormael-Pournin, Aline Stedman, Nick D.L. Owens, Embryon précoce de mammifères et cellules souches, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Collège doctoral [Sorbonne universités], Sorbonne Université (SU), Laboratoire de Biologie du Développement [Paris] (LBD), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Epigénétique des Cellules Souches - Epigenetics of Stem Cells, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Fondation ARC pour le Recherche sur le cancer (PGA120140200873), the Institut Pasteur, the Centre National de la Recherche Scientifique, the Agence Nationale de la Recherche (ANR-10-LABX-73-01 REVIVE) and the Institut National du Cancer (INCa 2007-1-COL-6-IC-1 and PLBIO09-070). A.R. was supported by the Université Pierre et Marie Curie and received fellowship from the French Ministère de l’Enseignement Supérieur et de la recherche, the Fondation ARC pour la Recherche sur le Cancer and the REVIVE Labex. AS received support from the Fondation des Treilles., Imaging analyses was performed at the Imagopole and the histopathology Unit of the Institut Pasteur. We are grateful to the staff of the animal facility of Institut Pasteur for animal care and their help during this work. We thank G. Comai for technical help and advices on RNAscope ISH., ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Collège Doctoral, Laboratoire de Biologie du Développement [IBPS] (LBD), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Adenomatous Polyposis Coli Protein, Ribosome biogenesis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, medicine.disease_cause, Article, Mice, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Intestinal Mucosa, Progenitor cell, Wnt Signaling Pathway, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Molecular Biology, Organelle Biogenesis, Wnt signaling pathway, Membrane Proteins, Cell Biology, Cell cycle, Wnt signaling, Colorectal cancer, Intestinal epithelium, 3. Good health, Cell biology, Mice, Inbred C57BL, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Cell Transformation, Neoplastic, 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer cell, Stem cell, Carcinogenesis, Ribosomes
Abstract: International audience; Ribosome biogenesis inhibition causes cell cycle arrest and apoptosis through the activation of tumor suppressor-dependent surveillance pathways. These responses are exacerbated in cancer cells, suggesting that targeting ribosome synthesis may be beneficial to patients. Here, we characterize the effect of the loss-of-function of Notchless (Nle), an essential actor of ribosome biogenesis, on the intestinal epithelium undergoing tumor initiation due to acute Apc loss-of-function. We show that ribosome biogenesis dysfunction strongly alleviates Wnt-driven tumor initiation by restoring cell cycle exit and differentiation in Apc-deficient progenitors. Conversely Wnt hyperactivation attenuates the cellular responses to surveillance pathways activation induced by ribosome biogenesis dysfunction, as proliferation was maintained at control-like levels in the stem cells and progenitors of double mutants. Thus, our data indicate that, while ribosome biogenesis inhibition efficiently reduces cancer cell proliferation in the intestinal epithelium, enhanced resistance of Apc-deficient stem and progenitor cells to ribosome biogenesis defects may be an important concern when using a therapeutic strategy targeting ribosome production for the treatment of Wnt-dependent tumorigenesis.
Published: 2020
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10. β4-Nicotinic Receptors Are Critically Involved in Reward-Related Behaviors and Self-Regulation of Nicotine Reinforcement

Author: Marianne Husson, Léa Tochon, Inés Ibañez-Tallon, Lauriane Harrington, Yoon H. Cho, Uwe Maskos, Vincent David, Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Neurobiologie intégrative des Systèmes cholinergiques / Integrative Neurobiology of Cholinergic Systems (NISC), Institut Pasteur [Paris] (IP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Rockefeller University [New York], This work was supported by FP7 ERANET program (NICO-GENE), the Institut Pasteur, Center National de la Recherche Scientifique CNRS UMR 3571 (U.M.) and CNRS UMR 5287 (V.D.) and the Agence Nationale pour la Recherche (ANR-10-BLAN-1437, project 'NICOSTOP'), the French National Cancer Institute (INCa-CANCEROPOLE-TABAC-01-16022), the EC FP7 Grant agreement 'NeuroCypres' project, Fondation EDF, the Fondation des Treilles, and the Foundation for Medical Research FMR. U.M. is a member of the Laboratory of Excellence, Bio-Psy Labex, as such this work was supported by French state funds managed by the Agence Nationale pour la Recherche (ANR) within the Investissements d'Avenir program under reference ANR-11-IDEX- 0004-02. The team of U.M. is part of the Ecole des Neurosciences de Paris Ile-de-France Network. Work in New York was supported by National Institute on Drug Abuse Grant P30DA035756. We thank Stéphanie Pons for constant support and discussions, and Martine Soudant for technical assistance., ANR-10-BLAN-1437,NICOSTOP(2010), European Project: 202088,EC:FP7:HEALTH,FP7-HEALTH-2007-A,NEUROCYPRES(2008), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), and Sorbonne Université (SU)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.medical_treatment, Self Administration, Receptors, Nicotinic, Pharmacology, Discrimination Learning, Nicotine, Mice, [SCCO]Cognitive science, 0302 clinical medicine, Nicotinic Agonists, ComputingMilieux_MISCELLANEOUS, Research Articles, reward, media_common, Mice, Knockout, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Behavior, Animal, General Neuroscience, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Ventral tegmental area, Nicotinic acetylcholine receptor, medicine.anatomical_structure, Habenula, Nicotine withdrawal, addiction, reward Significance Statement, medicine.drug, nicotinic receptors, Interpeduncular nucleus, media_common.quotation_subject, Nerve Tissue Proteins, Motor Activity, Self-Control, interpeduncular nucleus, 03 medical and health sciences, mental disorders, medicine, Animals, Motivation, habenula, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Addiction, Ventral Tegmental Area, medicine.disease, 030104 developmental biology, Conditioning, Operant, Smoking cessation, business, 030217 neurology & neurosurgery, nicotine
Abstract: Nicotine addiction, through smoking, is the principal cause of preventable mortality worldwide. Human genome-wide association studies have linked polymorphisms in theCHRNA5-CHRNA3-CHRNB4gene cluster, coding for the α5, α3, and β4 nicotinic acetylcholine receptor (nAChR) subunits, to nicotine addiction. β4*nAChRs have been implicated in nicotine withdrawal, aversion, and reinforcement. Here we show that β4*nAChRs also are involved in non-nicotine-mediated responses that may predispose to addiction-related behaviors. β4 knock-out (KO) male mice show increased novelty-induced locomotor activity, lower baseline anxiety, and motivational deficits in operant conditioning for palatable food rewards and in reward-based Go/No-go tasks. To further explore reward deficits we used intracranial self-administration (ICSA) by directly injecting nicotine into the ventral tegmental area (VTA) in mice. We found that, at low nicotine doses, β4KO self-administer less than wild-type (WT) mice. Conversely, at high nicotine doses, this was reversed and β4KO self-administered more than WT mice, whereas β4-overexpressing mice avoided nicotine injections. Viral expression of β4 subunits in medial habenula (MHb), interpeduncular nucleus (IPN), and VTA of β4KO mice revealed dose- and region-dependent differences: β4*nAChRs in the VTA potentiated nicotine-mediated rewarding effects at all doses, whereas β4*nAChRs in the MHb-IPN pathway, limited VTA-ICSA at high nicotine doses. Together, our findings indicate that the lack of functional β4*nAChRs result in deficits in reward sensitivity including increased ICSA at high doses of nicotine that is restored by re-expression of β4*nAChRs in the MHb-IPN. These data indicate that β4 is a critical modulator of reward-related behaviors.SIGNIFICANCE STATEMENTHuman genetic studies have provided strong evidence for a relationship between variants in theCHRNA5-CHRNA3-CHRNB4gene cluster and nicotine addiction. Yet, little is known about the role of β4 nicotinic acetylcholine receptor (nAChR) subunit encoded by this cluster. We investigated the implication of β4*nAChRs in anxiety-, food reward- and nicotine reward-related behaviors. Deletion of the β4 subunit gene resulted in an addiction-related phenotype characterized by low anxiety, high novelty-induced response, lack of sensitivity to palatable food rewards and increased intracranial nicotine self-administration at high doses. Lentiviral vector-induced re-expression of the β4 subunit into either the MHb or IPN restored a “stop” signal on nicotine self-administration. These results suggest that β4*nAChRs provide a promising novel drug target for smoking cessation.
Published: 2020
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11. Antibiotic prophylaxis in preterm premature rupture of membranes at 24–31 weeks’ gestation: Perinatal and 2‐year outcomes in the EPIPAGE‐2 cohort

Author: Lorthe, Elsa, Letouzey, Mathilde, Torchin, Héloïse, Foix L'Helias, Laurence, Gras‐le Guen, Christèle, Benhammou, Valérie, Boileau, Pascal, Charlier, Caroline, Kayem, Gilles, Ancel, Pierre‐yves, Arnaud, Catherine, Blanc, Julie, Debillon, Thierry, Delorme, Pierre, D’ercole, Claude, Desplanches, Thomas, Diguisto, Caroline, Gascoin, Géraldine, Gire, Catherine, Goffinet, François, Langer, Bruno, Maisonneuve, Emeline, Marret, Stéphane, Monier, Isabelle, Morgan, Andrei, Rozé, Jean‐christophe, Schmitz, Thomas, Sentilhes, Loïc, Subtil, Damien, Tosello, Barthélémy, Vayssière, Christophe, Winer, Norbert, Zeitlin, Jennifer, Astruc, D, Kuhn, P, Matis, J, Ramousset, C, Hernandorena, X, Chabanier, P, Joly‐pedespan, L, Costedoat, Mj, Leguen, A, Lecomte, B, Lemery, D, Vendittelli, F, Beucher, G, Dreyfus, M, Guillois, B, Toure, Y, Burguet, A, Couvreur, S, Gouyon, Jb, Sagot, P, Colas, N, Sizun, J, Beuchée, A, Pladys, P, Rouget, F, Dupuy, Rp, Soupre, D, Charlot, F, Roudaut, S, Favreau, A, Saliba, E, Reboul, L, Bednarek, N, Morville, P, Verrière, V, Thiriez, G, Balamou, C, Marpeau, L, Barbier, C, Durrmeyer, X, Granier, M, Ayoubi, M, Baud, O, Carbonne, B, Jarreau, Ph, Mitanchez, D, Duffaut, C, Cornu, L, Moras, R, Boulot, P, Cambonie, G, Daudé, H, Badessi, A, Tsaoussis, N, Bédu, A, Mons, F, Bahans, C, Binet, Mh, Fresson, J, Hascoët, Jm, Milton, A, Morel, O, Vieux, R, Hilpert, L, Alberge, C, Baron, M, Charkaluk, Ml, Pierrat, V, Truffert, P, Akowanou, S, Simeoni, U, Bongain, A, Deschamps, M, Branger, B, Rouger, V, Dupont, C, Gondry, Jean, Krim, G, Baby, B, Debeir, M, Claris, O, Picaud, Jc, Rubio‐gurung, S, Cans, C, Ego, A, Patural, H, Rannaud, A, Janky, E, Poulichet, A, Rosenthal, Jm, Coliné, E, Favre, A, Joly, N, Châlons, S, Pignol, J, Laurence, Pl, Robillard, Py, Samperiz, S, Ramful, D, Blondel, B, Bonet, M, Brinis, A, Coquelin, A, Durox, M, Kaminski, M, Khemache, K, Khoshnood, B, Lebeaux, C, Marchand‐martin, L, Rousseau, J, Saurel‐cubizolles, Mj, Tran, D, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Unité de Parasitologie-Mycologie, Service de Microbiologie [Hôpital Necker-Enfants-Malades, Paris], Assistance Publique - Hôpitaux de Paris, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service Epidémiologie clinique et santé publique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Unité de biostatistiques [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Médecine Néonatale et Réanimation Pédiatrique CHU Grenoble, CHU Grenoble, Service de gynécologie-obstétrique [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Service de Gynécologie Obstétrique, Médecine Foetale et Stérilité Conjugale - Chirurgie Gynécologie et Oncologique [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Néonatologie, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Recherches épidémiologiques en santé périnatale et santé des femmes, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Groupe de Recherche sur l'Analyse Multimodale de la Fonction Cérébrale - UMR INSERM_S 1105 (GRAMFC), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, Funding information:This work was partly supported by a postdoctoral grant from the Fondation des Treilles to EL. EPIPAGE-2 was funded by the French Institute of Public Health Research (IRESP TGIR 2009-01 programme)/Institute of Public Health and its partners: the French Health Ministry, the National Institute of Health and Medical Research (INSERM), the National Institute of Cancer, and the National Solidarity Fund for Autonomy (CNSA), the National Research Agency through the French EQUIPEX programme of investments for the future (grant number ANR-11-EQPX-0038), and the PREMUP Foundation. Additional funding was obtained from Fondation pour la Recherche Medicale (grant number SPF 20160936356) and Fondation de France (grant numbers 00050329, Grand Prix R18202KK]). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript., ANR-11-EQPX-0038,RE-CO-NAI,Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance(2011), Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Education, Formation, Travail, Savoirs (EFTS), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-École Nationale Supérieure de Formation de l'Enseignement Agricole de Toulouse-Auzeville (ENSFEA), École Nationale Supérieure de Formation de l'Enseignement Agricole de Toulouse-Auzeville (ENSFEA), Centre Hospitalier Universitaire [Grenoble] (CHU), Modélisation et Évaluation des données complexes en Santé Publique (TIMC-MESP), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), CHU Dijon, Hôpital Nord [CHU - APHM], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Department of Obstetrics and Gynecology, Les Hôpitaux Universitaires de Strasbourg (HUS), EPIPAGE-2 Study Group, and Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Fetal Membranes, Premature Rupture, obstetric intervention, [SDV]Life Sciences [q-bio], Gestational Age, antenatal management, Cohort Studies, Pregnancy, Escherichia coli, Humans, Prospective Studies, latency, amoxicillin, neurodevelopment, macrolides, prematurity, Infant, Newborn, Pregnancy Outcome, Obstetrics and Gynecology, Infant, prophylactic antibiotics, Antibiotic Prophylaxis, Anti-Bacterial Agents, perinatal outcome, cephalosporins, Premature Birth, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neonatal Sepsis, Infant, Premature
Abstract: To compare different antibiotic prophylaxis administered after preterm premature rupture of membranes to determine whether any were associated with differences in obstetric and/or neonatal outcomes and/or neurodevelopmental outcomes at 2 years of corrected age.Prospective, nationwide, population-based EPIPAGE-2 cohort study of preterm infants.France, 2011.We included 492 women with a singleton pregnancy and a diagnosis of preterm premature rupture of membranes at 24-31 weeks. Exclusion criteria were contraindication to expectant management or indication for antibiotic therapy other than preterm premature rupture of membranes. Antibiotic prophylaxis was categorised as amoxicillin (n = 345), macrolide (n = 30), third-generation cephalosporin (n = 45) or any combinations covering Streptococcus agalactiae and90% of Escherichia coli (n = 72), initiated within 24 hours after preterm premature rupture of membranes.Population-averaged robust Poisson models.Survival at discharge without severe neonatal morbidity, 2-year neurodevelopment.With amoxicillin, macrolide, third-generation cephalosporin and combinations, 78.5%, 83.9%, 93.6% and 86.0% of neonates were discharged alive without severe morbidity. The administration of third-generation cephalosporin or any E. coli-targeting combinations was associated with improved survival without severe morbidity (adjusted risk ratio 1.25 [95% confidence interval 1.08-1.45] and 1.10 [95 % confidence interval 1.01-1.20], respectively) compared with amoxicillin. We evidenced no increase in neonatal sepsis related to third-generation cephalosporin-resistant pathogen.In preterm premature rupture of membranes at 24-31 weeks, antibiotic prophylaxis based on third-generation cephalosporin may be associated with improved survival without severe neonatal morbidity when compared with amoxicillin, with no evidence of increase in neonatal sepsis related to third-generation cephalosporin-resistant pathogen.Antibiotic prophylaxis after PPROM at 24-31 weeks: 3rd-generation cephalosporins associated with improved neonatal outcomes.
Published: 2022
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12. Awareness of Cognitive Decline in Patients With Alzheimer's Disease: A Systematic Review and Meta-Analysis

Author: Federica Cacciamani, Marion Houot, Geoffroy Gagliardi, Bruno Dubois, Sietske Sikkes, Gonzalo Sánchez-Benavides, Elena Denicolò, José Luis Molinuevo, Patrizia Vannini, Stéphane Epelbaum, Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Alzheimer Center Amsterdam, VU University Medical Center [Amsterdam], Pasqual Maragall Foundation, University of Bologna, FC was funded by the Fondation pour la recherche sur Alzheimer, Fondation Thérèse et René Planiol, and Fondation des Treilles. SS received funding from Zon-MW Oﬀ Road (451001010). PV was funded by the NIH/National Institute on Aging 1R01 AG061083 and R21 AG064348., Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Bologna/Università di Bologna, Gestionnaire, HAL Sorbonne Université 5, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Aging, medicine.medical_specialty, Cognitive Neuroscience, metamemory, Neurosciences. Biological psychiatry. Neuropsychiatry, Disease, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Metamemory, mental disorders, medicine, Dementia, 0501 psychology and cognitive sciences, In patient, awareness, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cognitive decline, hypernosognosia, anosognosia, business.industry, Anosognosia, 05 social sciences, Cognition, Alzheimer's disease, medicine.disease, 3. Good health, Meta-analysis, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Systematic Review, business, 030217 neurology & neurosurgery, Neuroscience, RC321-571
Abstract: Background: Identifying a poor degree of awareness of cognitive decline (ACD) could represent an early indicator of Alzheimer's disease (AD).Objectives: (1) to understand whether there is evidence of poor ACD in the pre-dementia stages of AD; (2) to summarize the main findings obtained investigating ACD in AD; (3) to propose a conceptual framework.Data Sources: We searched Scopus, Pubmed, and the reference lists for studies published up to August 2020. Original research articles must report a measure of ACD and included individuals with AD dementia, or prodromal AD (or MCI), or being at risk for AD.Data Synthesis: All studies covering preclinical, prodromal, and AD dementia were systematically reviewed. We intended to perform a meta-analysis of empirical studies on preclinical AD or prodromal AD (or MCI), to compare ACD between clinical groups. Due to the paucity of literature on preclinical AD, meta-analysis was only possible for prodromal AD (or MCI) studies.Results: We systematically reviewed 283 articles, and conducted a meta-analysis of 18 articles on prodromal AD (or MCI), showing that ACD was not significantly different between patients with amnestic and non-amnestic MCI (SMD = 0.09, p = 0.574); ACD was significantly poorer in amnestic MCI (SMD = −0.56, p = 0.001) and mild AD (SMD = −1.39, p < 0.001) than in controls; ACD was also significantly poorer in mild AD than in amnestic MCI (SMD = −0.75, p < 0.001), as well as poorer than in non-amnestic MCI (SMD = −1.00, p < 0.001). We also discuss key findings on ACD in AD, such as its neural and cognitive correlates.Conclusions and Implications: We propose that patients may be complaining of their initial subtle cognitive changes, but ACD would soon start to decrease. The individual would show mild anosognosia in the MCI stage, and severe anosognosia in dementia. The evaluation of ACD (comparing self-report to cognitive scores or to informant-report) could be useful to guide the clinician toward a timely diagnosis, and in trials targeting early-stage AD.
Published: 2021
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13. Deciphering the Chemistry of Cultural Heritage: Targeting Material Properties by Coupling Spectral Imaging with Image Analysis

Author: Étienne Anheim, Loïc Bertrand, Pierre Gueriau, Mathieu Thoury, Serge X. Cohen, Photophysique et Photochimie Supramoléculaires et Macromoléculaires (PPSM), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), Institut photonique d'analyse non-destructive européen des matériaux anciens (IPANEMA), Muséum national d'Histoire naturelle (MNHN)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Centre de Recherches Historiques (CRH), École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), and We thank Barbara Berrie (National Gallery of Art, Washington, D.C., U.S.) and Agnès Desolneux (Centre Borelli, ENS Paris-Saclay, CNRS) for their careful rereading of our manuscript. The authors are particularly grateful to the large number of colleagues with whom we have discussed these aspects over many years of common work and interaction. Our very special thanks go to Marie-Angélique Languille (today at the Centre de Recherche sur la Conservation des Collections, Paris) and Sophie David (PPSM). We thank all of our coauthors from the papers discussed and the many colleagues with whom we have discussed these ideas, including Demetrios Anglos, Julie Arslanoglu, Bernadette Bensaude-Vincent, Uwe Bergmann, Barbara Berrie, Catherine Brechignac, Gilles Celeux, Antoine Chambaz, Pierre Chastang, Cynthia Colmellere, Marie Cornu, Jean-Paul Demoule, Agnès Desolneux, Jean-Philippe Échard, Douglas Galante, Pierre Galtier, Claire Gervais, Denis Gratias, Agnès Grimaud, Charlotte Guichard, Ineke Joosten, Katrien Keune, Andrew King, Bertrand Lavédrine, Pierre Laszlo, Erwan Le Pennec, Pierre Levitz, Alain Lusson, Lara Maldanis, Pascal Massard, Cristian Mocuta, Lionel Moisan, Emmanuel (Manolis) Pantos, André Rassat, Matthieu Réfrégiers, Luc Robbiola, Laurent Romary, Isabelle Rouget, Jean-Pascal Rueff, Solenn Réguer, Clément Sanchez, Sebastian Schoeder, Marika Spring, Maartje Stols-Witlox, Matija Strlic, Caroline Tokarski, Edward Vicenzi, Laurence de Viguerie, Kees van der Beek, Robert van Langh, Philippe Walter, Sam Webb, and many friends, students, and colleagues. L.B. acknowledges the support of the Fondation des Treilles and its wonderful team for the organization of two seminars (in 2013 and 2014) that enabled the scope of this research program to be critically defined. The construction of the IPANEMA laboratory was funded by a CPER grant from the French Ministère de la recherche, de l’enseignement supérieur et de l’innovation and Région Île-de-France.
Subjects: medicine.medical_specialty, Data processing, Materials science, 010405 organic chemistry, Chemistry, media_common.quotation_subject, Hyperspectral imaging, General Medicine, General Chemistry, Ambiguity, 010402 general chemistry, 01 natural sciences, Data science, 0104 chemical sciences, Spectral imaging, Characterization (materials science), Cultural heritage, Identification (information), medicine, [CHIM]Chemical Sciences, Spatial analysis, media_common
Abstract: International audience; ConspectusThe chemical study of materials from natural history and cultural heritage, which provide information for art history, archeology, or paleontology, presents a series of specific challenges. The complexity of these ancient and historical materials, which are chemically heterogeneous, the product of alteration processes, and inherently not reproducible, is a major obstacle to a thorough understanding of their making and long-term behavior (e.g., fossilization). These challenges required the development of methodologies and instruments coupling imaging and data processing approaches that are optimized for the specific properties of the materials. This Account discusses how these characteristics not only constrain their study but also open up specific innovative avenues for providing key historical information. Synchrotron methods have extensively been used since the late 1990s to study heritage objects, in particular for their potential to provide speciation information from excitation spectroscopies and to image complex heritage objects and samples in two and three dimensions at high resolution. We examine in practice how the identification of key intrinsic chemical specificities has offered fertile ground for the development of novel synchrotron approaches allowing a better stochastic description of the properties of ancient and historical materials. These developments encompass three main aspects: (1) The multiscale heterogeneity of these materials can provide an essential source of information in the development of probes targeting their multiple scales of homogeneity. (2) Chemical alteration can be described in many ways, e.g., by segmenting datasets in a semiquantitative way to jointly inform morphological and chemical transformation pathways. (3) The intrinsic individuality of chemical signatures in artifacts triggers the development of specific strategies, such as those focusing on weak signal detection. We propose a rereading of the advent of these new methodologies for analysis and characterization and examine how they have led to innovative strategies combining materials science, instrument development, history, and data science. In particular, we show that spectral imaging and the search for correlations in image datasets have provided a powerful way to address what archeologists have called the uncertainty and ambiguity of the material record. This approach has implications beyond synchrotron techniques and extends in particular to a series of rapidly developing approaches that couple spectral and spatial information, as in hyperspectral imaging and spatially resolved mass spectrometry. The preeminence of correlations holds promise for the future development of machine learning methods for processing data on historical objects. Beyond heritage, these developments are an original source of inspiration for the study of materials in many related fields, such as environmental, geochemical, or life sciences, which deal with systems whose alteration and heterogeneity cannot be neglected.
Published: 2021
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14. Tolerant and intolerant macaques show different levels of structural complexity in their vocal communication

Author: Rebout, Nancy, De Marco, Arianna, Lone, Jean-Christophe, Sanna, Andrea, Cozzolino, Roberto, Micheletta, Jérôme, Sterck, Elisabeth H M, Langermans, Jan A M, Lemasson, Alban, Thierry, Bernard, Sub Animal Ecology, AISS LAS/3'R Centre ULS, Animal Ecology, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Fondazione Ethoikos, Parco Faunistico di Piano dell'Abatino, Department of Psychology, University of Portsmouth, Portsmouth, England, UK, Macaca Nigra Project, Tangkoko Reserve, Department of Biology, Animal Ecology, Utrecht University [Utrecht], Animal Science Department, Biomedical Primate Research Center, Department Population Health Sciences, Ethologie animale et humaine (EthoS), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), The work was supported by the Fondazione Ethoikos (Radicondoli), the Fondation des Treilles (Tourtour), and the Department of Ecology, Physiology and Ethology (Strasbourg). Data collection in rhesus macaques was supported by an Eole Scholarship granted by the French-Dutch Network. Data collection in Japanese macaques was supported by the Japan Society for the Promotion of Science., Sub Animal Ecology, AISS LAS/3'R Centre ULS, Animal Ecology, Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre for comparative and evolutionary psychology, University of Portsmouth, Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Normandie Université (NU)-Normandie Université (NU)-Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]
Subjects: 0106 biological sciences, Vocal communication, primates, [SDV]Life Sciences [q-bio], Biology, 010603 evolutionary biology, 01 natural sciences, General Biochemistry, Genetics and Molecular Biology, Structural complexity, [SDV.BA.ZV]Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, Agonistic behaviour, Animals, 0501 psychology and cognitive sciences, Behaviour, 050102 behavioral science & comparative psychology, social system, Social Behavior, acoustics, social style, General Environmental Science, Call duration, General Immunology and Microbiology, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Communication, [SCCO.NEUR]Cognitive science/Neuroscience, [SDV.BA]Life Sciences [q-bio]/Animal biology, 05 social sciences, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Social complexity, General Medicine, Macaca mulatta, Social relation, Social system, comparison, Vocalization, Animal, General Agricultural and Biological Sciences, Cognitive psychology, cluster analysis
Abstract: International audience; We tested the social complexity hypothesis which posits that animals living in complex social environments should use complex communication systems. We focused on two components of vocal complexity: diversity (number of categories of calls) and flexibility (degree of gradation between categories of calls). We compared the acoustic structure of vocal signals in groups of macaques belonging to four species with varying levels of uncertainty (i.e. complexity) in social tolerance (the higher the degree of tolerance, the higher the degree of uncertainty): two intolerant species, Japanese and rhesus macaques, and two tolerant species, Tonkean and crested macaques. We recorded the vocalizations emitted by adult females in affiliative, agonistic and neutral contexts. We analysed several acoustic variables: call duration, entropy, time and frequency energy quantiles. The results showed that tolerant macaques displayed higher levels of vocal diversity and flexibility than intolerant macaques in situations with a greater number of options and consequences, i.e. in agonistic and affiliative contexts. We found no significant differences between tolerant and intolerant macaques in the neutral context where individuals are not directly involved in social interaction. This shows that species experiencing more uncertain social interactions displayed greater vocal diversity and flexibility, which supports the social complexity hypothesis.
Published: 2020
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15. ADAR1 mediated regulation of neural crest derived melanocytes and Schwann cell development

Author: Gacem, Nadjet, Kavo, Anthula, Zerad, Lisa, Richard, Laurence, Mathis, Stephane, Kapur, Raj, Parisot, Mélanie, Amiel, Jeanne, de La Grange, Pierre, Pingault, Veronique, Vallat, Jean, Bondurand, Nadege, Dufour, Sylvie, Embryology and genetics of human malformation (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Morphogénèse et Génétique Moléculaire [Créteil], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Department of Neurology [Limoges], Centre de référence national neuropathies périphériques rares [CHU Limoges], CHU Limoges-CHU Limoges, Nerve-Muscle Unit [Bordeaux], Department of Neurology [Bordeaux], Grand Sud-Ouest National Reference Center for Neuromuscular Disorders [Bordeaux], Pellegrin Hospital [Bordeaux], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux]-Pellegrin Hospital [Bordeaux], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux]-Grand Sud-Ouest National Reference Center for Neuromuscular Disorders [Bordeaux], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], University of Washington [Seattle], Plateforme de génomique [SFR Necker], Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), GenoSplice [Paris], Service de Génétique Moléculaire [Paris], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Eq. 6 - Morphogenèse et génétique moléculaire (Inserm U955 - IMRB), This work was supported by the Fondation ARC pour la recherche sur le cancer and AFM trampoline grant to N.B., Institut National Pour la Santé de la Recherche Médicale (INSERM), state funding from the Agence Nationale de la Recherche under the 'Investissements d’avenir' program [ANR-10-IAHU-01] and the MSDAvenir fund [DEVO—DECODE project]. N.G. and A.K. both received a 3-year Ph.D. fellowship from ED-SVS402, L.Z. received a 3-year Ph.D. fellowship from ED-BioSPC. N.G. is a beneficiary of an Institut Imagine 4th-year Ph.D. fellowship (7 months) from Fondation Bettencourt Schueller and supported by Fondation des treilles., ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Bodescot, Myriam, and Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID
Subjects: RNA editing, Adenosine Deaminase, Science, Neurogenesis, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Article, Mice, Developmental biology, Animals, lcsh:Science, Skin, Mice, Knockout, [SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Gene Expression Regulation, Developmental, Cell Differentiation, Heart, Sciatic Nerve, Up-Regulation, Disease Models, Animal, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Neural Crest, embryonic structures, Melanocytes, lcsh:Q, Interferons, Schwann Cells, Transcriptome, Gene Deletion
Abstract: The neural crest gives rise to numerous cell types, dysfunction of which contributes to many disorders. Here, we report that adenosine deaminase acting on RNA (ADAR1), responsible for adenosine-to-inosine editing of RNA, is required for regulating the development of two neural crest derivatives: melanocytes and Schwann cells. Neural crest specific conditional deletion of Adar1 in mice leads to global depigmentation and absence of myelin from peripheral nerves, resulting from alterations in melanocyte survival and differentiation of Schwann cells, respectively. Upregulation of interferon stimulated genes precedes these defects, which are associated with the triggering of a signature resembling response to injury in peripheral nerves. Simultaneous extinction of MDA5, a key sensor of unedited RNA, rescues both melanocytes and myelin defects in vitro, suggesting that ADAR1 safeguards neural crest derivatives from aberrant MDA5-mediated interferon production. We thus extend the landscape of ADAR1 function to the fields of neural crest development and disease., ADAR1 is an RNA editing protein known to regulate immune responses to dsRNA that has been connected to neural crest cell function. Here, the authors show RNA editing by ADAR1 is important for the normal development of neural crest derived melanocytes and Schwann cells.
Published: 2020
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16. Connecting Medieval Silver Mines

Author: Minvielle Larousse, Nicolas, Laboratoire d'Archéologie Médiévale et Moderne en Méditerranée (LA3M), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'excellence - Les sciences humaines et sociales au cœur de l’interdisciplinarité pour la Méditerranée (LabexMed), Ecole française de Rome (EFR), ANR-11-IDEX-0001-02, Fondation des Treilles, LabexMed-10-LABX-0090, ANR-11-IDEX-0001,Amidex,INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE(2011), and ANR-10-LABX-0090,LABEXMED,Social Sciences and Humanities at the Heart of the Multidisciplinarity for the Study of the Mediterranean(2010)
Subjects: [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, Silver mine, [SHS.HIST]Humanities and Social Sciences/History, Middle ages, ComputingMilieux_MISCELLANEOUS, Mediterraean
Abstract: International audience
Published: 2019

17. Le Minier : résultats de la campagne de prospection 2019

Author: Nicolas Minvielle Larousse, Alain Bernat, Jérôme Belmon, Françoise Galès, Laboratoire d'Archéologie Médiévale et Moderne en Méditerranée (LA3M), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Ecole française de Rome (EFR), Laboratoire d'excellence - Les sciences humaines et sociales au cœur de l’interdisciplinarité pour la Méditerranée (LabexMed), Association pour la sauvegarde du patrimoine archéologique aveyronnais (ASPAA), Ministère de la Culture et de la Communication, Service de la connaissance et de l’inventaire des patrimoines de la région Occitanie, Ministère de la Culture, Conseil départemental de l'Aveyron, and Fondation des Treilles
Subjects: Meule à minerai, Moyen âge, Minéralurgie, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, Architecture, Mines d'argent, Rouergue, [SHS.HIST]Humanities and Social Sciences/History, [SHS]Humanities and Social Sciences
Abstract: National audience; The thematic survey campaign that took place from the 17th of August to the 7th of September 2019 at the Minier focused on silver production vestiges in the valley of the Amalou, in the municipality of the Viala-du-Tarn (Occitanie, Aveyron). This valley was the site of a long-term mining and metallurgical activity during the High and Late Middle Ages (XIIth-XVth centuries), based on the exploitation of a few rich deposits of galena. This had a centralizing effect, leading to the creation of a permanent settlement, the current village of the Minier, and stimulated production by concentrating activities within a relatively restricted space. The goal of the 2019 campaign was to create a topographical survey, to record the remains linked to metal production already inventoried during the past two campaigns in 2017 and 2018, to expand on the architectural study of the medieval houses preserved at the Minier, and to continue the stripping of textual sources, in order to gather together and harmonize the resources.; La campaña de prospección temática realizada del 17 de agosto al 7 de septiembre del 2019 en el Minier concierne los restos de la producción argentífera del valle del Amalou en el municipio del Viala-du-Tarn (Occitania, Aveyron). Este valle fue escenario de una larga actividad minera y metalúrgica en la Edad Media central y tardía (s. XII-XV), basada en la explotación de algunos ricos yacimientos de plomo argentífero. Las tareas tuvieron un efecto polarizador con la creación de un hábitat permanente, el actual pueblo del Minier, y estimularon la actividad concentrando las empresas en un espacio relativamente reducido. El objetivo de la campaña 2019 era topografiar y documentar los vestigios de la producción, inventariados durante las dos campañas precedentes de 2017 y 2018, continuar el estudio arquitectónico de las casas medievales conservadas en el Minier el examen de las fuentes documentales, todo con el fin de reunir y armonizar la documentación.; La campagne de prospection thématique menée du 17 août au 7 septembre 2019 au Minier concerne les vestiges de la production argentifère de la vallée de l’Amalou, sur la commune du Viala-du-Tarn (Occitanie, Aveyron). Cette vallée a fait l’objet d’une longue activité minière et métallurgique au Moyen Âge central et tardif (XIIe-XVe s.), fondée sur l’exploitation de quelques riches gisements de plomb argentifère. Les travaux ont eu un effet polarisant avec la création d’un habitat permanent, le village actuel du Minier, et ont stimulé l’activité en concentrant les entreprises dans un espace relativement restreint. L’objectif de la campagne 2019 était de topographier et de documenter les vestiges de la production, inventoriés lors de deux campagnes précédentes en 2017 et 2018, de prolonger l’étude architecturale des maisons médiévales conservées au Minier et le dépouillement de sources documentaires, cela afin de rassembler et d’harmoniser la documentation.
Published: 2019

18. Differential regulation of the Wnt/β-catenin pathway by hepatitis C virus recombinants expressing core from various genotypes

Author: Annette Martin, Brigitte Blumen, Stephanie Aicher, Eliane F. Meurs, Penelope Mavromara, Athanasios Kakkanas, Lisette Cohen, Richard Njouom, Gabriela Oprişan, Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Pasteur Hellénique, Réseau International des Instituts Pasteur (RIIP), University of Patras, School of Medicine, Cantacuzino National Medico-Military Institute for Research Development [Bucharest], Cantacuzino Institute [Romania], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Titu Maiorescu University = Universitatea Titu Maiorescu [Buchares] (UTM), Centre Pasteur du Cameroun, Hépacivirus et Immunité innée, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Democritus University of Thrace (DUTH), This work was supported in part by an ACIP grant (#A23/2013) from the Institut Pasteur, Paris, France and by the Hellenic Pasteur Institute, Athens, Greece. SA, a PhD student of the University of Patras, School of Health Sciences, Department of Pharmacy, Greece was the recipient of doctoral fellowships from the Calmette and Yersin program and the Virology Department of the Institut Pasteur, and of a young researcher prize from the Fondation des Treilles., The authors gratefully acknowledge: Christine Neuveut (IP Paris) for helpful discussions and for sharing pFOP and pTOP plasmids, Alberto L. Epstein (Université Claude Bernard, Lyon) for sharing pA-EUA2 + lacZ plasmid, Amadou Sall (IP Cambodia) for sharing HCV 1aC isolate, Takaji Wakita (NIID, Tokyo, Japan), Ralf Bartenschlager (Univ. Heidelberg, Germany) and Charles Rice (Rockefeller Univ., New York, USA) for their respective generous gifts of pJFH1, cell-culture adapted pJFH1-2EI3-adapt cDNA, Huh7.5 cells and 1aH77 cDNA, Stephanie Dabo and Matthieu Fritz (IP Paris) for sharing experimental expertise, Sousana Kotanidou and Ksenia Rybkina for technical assistance, Pascal Roux and Anne Danckaert at the Imagopole core facility (IP Paris) for their help in the acquisition and processing of the immunofluorescence images, Sylvie van der Werf (Head of the Unit of Molecular Genetics of RNA Viruses) for her continuous support., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, MESH: Active Transport, Cell Nucleus / genetics, Viral pathogenesis, [SDV]Life Sciences [q-bio], lcsh:Medicine, Hepacivirus, medicine.disease_cause, Malignant transformation, MESH: Genotype, MESH: Wnt Signaling Pathway / genetics, MESH: Hepatitis C / genetics, Transcription (biology), T Cell Transcription Factor 1, MESH: Liver Neoplasms / genetics, lcsh:Science, Wnt Signaling Pathway, beta Catenin, MESH: Cell Proliferation / genetics, Multidisciplinary, Hepatitis C virus, Liver Neoplasms, Wnt signaling pathway, MESH: Carcinoma, Hepatocellular / pathology, MESH: Gene Expression Regulation, Neoplastic, Hepatitis C, 3. Good health, MESH: Hepacivirus / genetics, Gene Expression Regulation, Neoplastic, Cell Transformation, Neoplastic, MESH: HEK293 Cells, Cell signalling, Carcinoma, Hepatocellular, Genotype, Active Transport, Cell Nucleus, MESH: Liver Neoplasms / virology, Biology, Article, 03 medical and health sciences, Downregulation and upregulation, medicine, Humans, Gene, Cell Proliferation, MESH: beta Catenin / genetics, MESH: Liver Neoplasms / pathology, MESH: Humans, lcsh:R, MESH: Carcinoma, Hepatocellular / genetics, MESH: Cell Transformation, Neoplastic / genetics, Molecular biology, MESH: Carcinoma, Hepatocellular / virology, MESH: T Cell Transcription Factor 1 / genetics, 030104 developmental biology, HEK293 Cells, MESH: Hepacivirus / pathogenicity, Catenin, MESH: Hepatitis C / virology, MESH: Hepatitis C / pathology, lcsh:Q
Abstract: Clinical studies have suggested association of some hepatitis C virus (HCV) subtypes or isolates with progression toward hepatocellular carcinoma (HCC). HCV core protein has been reported to interfere with host Wnt/β-catenin pathway, a cell fate-determining pathway, which plays a major role in HCC. Here, we investigated the impact of HCV core genetic variability in the dysregulation of Wnt/β-catenin pathway. We used both transient expression of core proteins from clinical isolates of HCV subtypes 1a (Cambodia), 4a (Romania) and 4f (Cameroon) and infection systems based on a set of engineered intergenotypic recombinant viruses encoding core from these various clinical strains. We found that TCF transcription factor-dependent reporter activity was upregulated by core in a strain-specific manner. We documented core sequence-specific transcriptional upregulation of several β-catenin downstream target genes associated with cell proliferation and malignant transformation, fibrogenesis or fat accumulation. The extent of β-catenin nuclear translocation varied in accordance with β-catenin downstream gene upregulation in infected cells. Pairwise comparisons of subgenotypic core recombinants and mutated core variants unveiled the critical role of core residues 64 and 71 in these dysregulations. In conclusion, this work identified natural core polymorphisms involved in HCV strain-specific activation of Wnt/β-catenin pathway in relevant infection systems.
Published: 2018
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19. Control of the proportion of inner cells by asymmetric divisions and the ensuing resilience of cloned rabbit embryos

Author: Dimitri, Fabrèges, Nathalie, Daniel, Véronique, Duranthon, Nadine, Peyriéras, BioEmergences, Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Biologie du Développement et Reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), École nationale vétérinaire d'Alfort (ENVA), RGB-Net [TD 1101] and Epiconcept [FA 1201] COST actions, Ministère de l’Enseignement Supérieur et de la Recherche, Fondation des Treilles (Young Researcher Prize), France BioImaging infrastructure [ANR-10- INBS-04], Morphoscope2 [ANR-11-EQPX-0029], Région Île-de-France [InterDIM ISC11], CRB-Anim [ANR-11-INBS-0003], Revive [ANR-10-LABX-73], Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Biologie du développement et reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), and UMR INRA-ENVA 1198 (BDR)
Subjects: Male, Research Report, 3D+time 2-photon imaging, Cell death, MESH: Cell Death, MESH: Cell Differentiation, Nuclear Transfer Techniques, Cloning, Organism, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Green Fluorescent Proteins, MESH: Asymmetric Cell Division, Embryonic Development, MESH: Rabbits, Cell Count, MESH: Imaging, Three-Dimensional, Imaging, Three-Dimensional, MESH: Green Fluorescent Proteins, MESH: Pregnancy, MESH: Computer Simulation, Pregnancy, MESH: Cell Proliferation, MESH: Cloning, Organism, Animals, MESH: Embryonic Development, Cell Lineage, Computer Simulation, MESH: Animals, Cell Proliferation, Somatic cell nuclear transfer, Digital specimens, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, MESH: Cell Count, Asymmetric Cell Division, Spatial cell segregation, MESH: Blastocyst Inner Cell Mass, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Cell Differentiation, MESH: Nuclear Transfer Techniques, MESH: Cell Lineage, MESH: Male, Asymmetrical divisions, Rabbit pre-implantation development, Microscopy, Fluorescence, Multiphoton, In silico experimentation, Blastocyst Inner Cell Mass, MESH: Microscopy, Fluorescence, Multiphoton, Female, Rabbits, MESH: Female
Abstract: Mammalian embryo cloning by nuclear transfer has a low success rate. This is hypothesized to correlate with a high variability of early developmental steps that segregate outer cells, which are fated to extra-embryonic tissues, from inner cells, which give rise to the embryo proper. Exploring the cell lineage of wild-type embryos and clones, imaged in toto until hatching, highlights the respective contributions of cell proliferation, death and asymmetric divisions to phenotypic variability. Preferential cell death of inner cells in clones, probably pertaining to the epigenetic plasticity of the transferred nucleus, is identified as a major difference with effects on the proportion of inner cell. In wild type and clones, similar patterns of outer cell asymmetric divisions are shown to be essential to the robust proportion of inner cells observed in wild type. Asymmetric inner cell division, which is not described in mice, is identified as a regulator of the proportion of inner cells and likely gives rise to resilient clones., Summary: A unique quantitative approach based on complete reconstruction of the cell lineage that unveils an unknown mechanism of size control in cell populations of rabbit blastocysts, wild types or clones.
Published: 2018
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20. Plants and aromatics for embalming in Late Middle Ages and modern period: a synthesis of written sources and archaeobotanical data (France, Italy)

Author: Rémi Corbineau, Gino Fornaciari, Hélène Dupont, Delphine Barbier-Pain, Marie-Pierre Ruas, Rozenn Colleter, Laboratoire d'Archéologie Médiévale et Moderne en Méditerranée (LA3M), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Archéologie, Archéosciences, Histoire (CReAAH), Nantes Université (NU)-Ministère de la Culture (MC)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Le Mans Université (UM), Archéozoologie, archéobotanique : sociétés, pratiques et environnements (AASPE), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Institut national de recherches archéologiques préventives, centre archéologique de Cesson-Sévigné (Inrap, Cesson-Sévigné), Institut national de recherches archéologiques préventives (Inrap), Division of paleopathology, History of Medicine and Bioethics, University of Pisa - Università di Pisa, Anthropologie Moléculaire et Imagerie de Synthèse (AMIS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Franco-Italienne (programme VINCI 2009-2012), Fondation des Treilles, CNRS - GDR 3644 BioArcheodat, ANR-10-BLAN-2009,EXSUDARCH,EXSUDats et goudrons végétaux ARCHéologiques : chimie, fabrication et utilisations(2010), Le Mans Université (UM)-Université de Rennes (UR)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR Histoire, Histoire de l'Art et Archéologie (UFR HHAA), Université de Nantes (UN)-Université de Nantes (UN)-Ministère de la Culture (MC), Institut national de recherches archéologiques préventives - Centre de recherches archéologiques de Cesson-Sévigné (Inrap, Cesson-Sévigné), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Nantes (UN)-Le Mans Université (UM)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Université de Nantes - UFR Histoire, Histoire de l'Art et Archéologie (UFR HHAA), and Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC)-Université de Rennes 2 (UR2)
Subjects: Archeology, History, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, Embaumement, Modern history, Période moderne, Plant Science, Ancient history, Bas Moyen Age, Archéobotanique, 01 natural sciences, Late Middle Ages, Archéologie funéraire, 03 medical and health sciences, 0302 clinical medicine, Paleoethnobotany, written sources, Apothecaries' system, Middle Ages, 030216 legal & forensic medicine, Biogeosciences, Macro-restes végétaux, 010401 analytical chemistry, Paleontology, Archaeology, 0104 chemical sciences, 3. Good health, Pharmacy history, embalming, Italy, History of pharmacy, Palynologie, Embalming, France, Burial practices, archaeobotany, modern period
Abstract: International audience; Occasionally mentioned in written sources since the Early Middle Ages, embalming with evisceration spreads considerably and becomes quite usual practice for aristocratic elites from the late 13th century to the early 19th century. Apothecaries prepare aromatic powders including many plant organs and exudates supposed to preserve the body. Numerous encyclopaedias and treatises of medicine list these ingredients and show that the recipes are very diverse. Moreover, several studies of embalmed bodies have demonstrated the potential of archaeobotanical analyses coupling pollen and macro-remains for identifying this material. This paper aims to compile a synthesis of written and archaeological sources from France and Italy, and to assess the relevance of an interdisciplinary approach for a better understanding of this aristocratic burial practice. It demonstrates that both types of sources and approaches are strongly complementary and highlights their inherent advantages and methodological limitations. In order to understand which criteria were determinant in the composition of the embalming powders, their medicinal, odoriferous and symbolic properties are discussed. Finally, this work proposes some methodological perspectives and triggers new research avenues on the history of pharmacy in Late Medieval and modern Europe.
Published: 2018
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21. High-fat diet modifies the PPAR-γ pathway leading to disruption of microbial and physiological ecosystem in murine small intestine

Author: Thierry Pedron, Chek Kun Tan, Kalina Duszka, Robert Ducroc, Philippe J. Sansonetti, Céline Mulet, Rémy Burcelin, Azadeh Saffarian, Béatrice Regnault, Walter Wahli, Jean-Baptiste Cavin, Julie Tomas, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Pathogénie microbienne moléculaire, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Génotypage des Eucaryotes (Plate-Forme), Institut Pasteur [Paris], Nanyang Technological University [Singapour], Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées, Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Chaire Microbiologie et Maladies infectieuses, Collège de France (CdF (institution)), This work was supported in part by the Société Française de Nutrition, the Fondation des Treilles created by Anne Gruner Schlumberger (www.les-treilles.com), the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (Grant ANR-10-LABX-62-IBEID), the European Research Council Advanced Grants 339579-DECRYPT (to P.J.S.), a Start-Up Grant from the Lee Kong Chian School of Medicine, Nanyang Technological University, and the 7th EU program TORNADO., We thank Laurence Motreff for her help with the Illumina libraries preparation and the MiSeq run, Eeswari Paramalingam for animal handling and tissue preparation, Jacques Ravel for editing the manuscript, and Nathalie Bechon for her contribution during her fellowship. J.T. was in part funded by the Contrat Jeune Scientifique from the Institut National de la Recherche Agronomique (Jouy-en-Josas, France)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 339579,EC:FP7:ERC,ERC-2013-ADG,DECRYPT(2014), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Collège de France - Chaire Microbiologie et Maladies infectieuses, TOMAS, Julie, PEDRON, Thierry, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Decrypting signals in the crypt. - DECRYPT - - EC:FP7:ERC2014-04-01 - 2019-03-31 - 339579 - VALID, Sansonetti, Philippe J., Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT), and Lee Kong Chian School of Medicine (LKCMedicine)
Subjects: Male, 0301 basic medicine, Cystic Fibrosis Transmembrane Conductance Regulator, Peroxisome proliferator-activated receptor, MESH: Cecum/microbiology, Candidatus Arthromitus, MESH: Thiazolidinediones/pharmacology, Feces, antimicrobial peptides, MESH: Chlorides/metabolism, 0302 clinical medicine, Intestine, Small, [SDV.EE.ECO] Life Sciences [q-bio]/Ecology, environment/Ecosystems, MESH: Cystic Fibrosis Transmembrane Conductance Regulator/metabolism, MESH: Diet, High-Fat, MESH: Animals, CFTR, Receptor, Cecum, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, 2. Zero hunger, chemistry.chemical_classification, Multidisciplinary, biology, Microbiota, MESH: Intestine, Small/drug effects, MESH: Laser Capture Microdissection, MESH: Feces/microbiology, MESH: Gastrointestinal Microbiome*/drug effects, MESH: Intestine, Small/physiology, Cystic fibrosis transmembrane conductance regulator, 3. Good health, High-fat diet, Phenotype, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, medicine.anatomical_structure, high-fat diet, PNAS Plus, Biochemistry, Signal Transduction, medicine.medical_specialty, PPAR-γ, MESH: PPAR gamma/genetics, MESH: Rosiglitazone, Ileum, Laser Capture Microdissection, Diet, High-Fat, MESH: Phenotype, Rosiglitazone, 03 medical and health sciences, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, Chlorides, MESH: Mice, Inbred C57BL, Internal medicine, medicine, microbiota, Animals, MESH: Antimicrobial Cationic Peptides/metabolism, Intestinal permeability, MESH: Signal Transduction*/drug effects, [SDV.EE.IEO] Life Sciences [q-bio]/Ecology, environment/Symbiosis, medicine.disease, biology.organism_classification, Mucus, MESH: Gene Expression Regulation/drug effects, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Small intestine, MESH: Male, Gastrointestinal Microbiome, Mice, Inbred C57BL, PPAR gamma, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, MESH: PPAR gamma/metabolism, ecosytem, 030104 developmental biology, Endocrinology, Gene Expression Regulation, chemistry, MESH: Antimicrobial Cationic Peptides/genetics, biology.protein, Thiazolidinediones, MESH: Intestine, Small/microbiology, MESH: Mucus/metabolism, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, Antimicrobial Cationic Peptides, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: International audience; Diet is among the most important factors contributing to intestinal homeostasis, and basic functions performed by the small intestine need to be tightly preserved to maintain health. Little is known about the direct impact of high-fat (HF) diet on small-intestinal mucosal defenses and spatial distribution of the microbiota during the early phase of its administration. We observed that only 30 d after HF diet initiation, the intervillous zone of the ileum-which is usually described as free of bacteria-became occupied by a dense microbiota. In addition to affecting its spatial distribution, HF diet also drastically affected microbiota composition with a profile characterized by the expansion of Firmicutes (appearance of Erysipelotrichi), Proteobacteria (Desulfovibrionales) and Verrucomicrobia, and decrease of Bacteroidetes (family S24-7) and Candidatus arthromitus A decrease in antimicrobial peptide expression was predominantly observed in the ileum where bacterial density appeared highest. In addition, HF diet increased intestinal permeability and decreased cystic fibrosis transmembrane conductance regulator (Cftr) and the Na-K-2Cl cotransporter 1 (Nkcc1) gene and protein expressions, leading to a decrease in ileal secretion of chloride, likely responsible for massive alteration in mucus phenotype. This complex phenotype triggered by HF diet at the interface between the microbiota and the mucosal surface was reversed when the diet was switched back to standard composition or when mice were treated for 1 wk with rosiglitazone, a specific agonist of peroxisome proliferator-activated receptor-γ (PPAR-γ). Moreover, weaker expression of antimicrobial peptide-encoding genes and intervillous bacterial colonization were observed in Ppar-γ-deficient mice, highlighting the major role of lipids in modulation of mucosal immune defenses.
Published: 2016
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22. Role of beta 4*Nicotinic Acetylcholine Receptors in the Habenulo-Interpeduncular Pathway in Nicotine Reinforcement in Mice

Author: África Flores, Patricia Robledo, Lauriane Harrington, Xavier Viñals, Stefania Tolu, Andrea Herrera-Solís, Carole Morel, Philippe Faure, Rafael Maldonado, Uwe Maskos, Neurophysiologie et comportements = Neurophysiology and Behavior (NPS-06), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Spanish Instituto de Salud Carlos III [RD06/001/001, PI10/01708, PI14/00210], FEDER funds, Centre National de la Recherche Scientifique CNRS UMR, CNRS UMR, INSERM, Pierreet Marie Curie University, Agence Nationale pour la Recherche (ANR Neuroscience), FP7 ERANET program (NICO-GENE) [009 BLANC 20092009BLANC 20 NeuroCypres], Fondation EDF, Fondation des Treilles, Foundation for Medical Research FMR [Equipe FRMDEQ20130326488], [ANR-11-IDEX-0004-02], Ministerio de Ciencia e Innovacion [SAF2014-59648-P], Catalan Government AGAUR [2014-SGR-1547], Plan Nacional Sobre Drogas, Ministerio de Sanidad, Asuntos Sociales e Igualdad-MSASI [PNSD-2013-0068], FP7 ERANET program (NICO-GENE), ICREA Foundation (ICREA Academia), CONACyT, Institut Pasteur, Neurobiologie intégrative des Systèmes cholinergiques / Integrative Neurobiology of Cholinergic Systems (NISC), Institut Pasteur [Paris] (IP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universitat Pompeu Fabra [Barcelona] (UPF), 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)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), European Project: 680966,ERA-NET NEURON,NICO-GENE(2015), European Project: 202088,EC:FP7:HEALTH,FP7-HEALTH-2007-A,NEUROCYPRES(2008), Sorbonne Université (SU)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Neurosciences Paris Seine (NPS)
Subjects: Male, 0301 basic medicine, Nicotine, Interpeduncular nucleus, Dopamine, Interpeduncular Nucleus, Microdialysis, Green Fluorescent Proteins, Action Potentials, Mice, Transgenic, Nerve Tissue Proteins, Receptors, Nicotinic, Nicotina -- Efectes fisiològics, Nucleus accumbens, Pharmacology, Mice, 03 medical and health sciences, 0302 clinical medicine, Transduction, Genetic, medicine, Animals, Nicotinic Agonists, Receptor, Acetylcholine receptor, Habenula, Dose-Response Relationship, Drug, Chemistry, 3. Good health, Mice, Inbred C57BL, Ventral tegmental area, Phosphoglycerate Kinase, Psychiatry and Mental health, Nicotinic acetylcholine receptor, 030104 developmental biology, medicine.anatomical_structure, Nicotinic agonist, nervous system, Conditioning, Operant, Original Article, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Reinforcement, Psychology, 030217 neurology & neurosurgery, medicine.drug
Abstract: Nicotine exerts its psychopharmacological effects by activating the nicotinic acetylcholine receptor (nAChR), composed of alpha and/or beta subunits, giving rise to a diverse population of receptors with a distinct pharmacology. β4-containing (β4*) nAChRs are located almost exclusively in the habenulo-interpeduncular pathway. We examined the role of β4* nAChRs in the medial habenula (MHb) and the interpeduncular nucleus (IPN) in nicotine reinforcement using behavioral, electrophysiological, and molecular techniques in transgenic mice. Nicotine intravenous self-administration (IVSA) was lower in constitutive β4 knockout (KO) mice at all doses tested (7.5, 15, 30, and 60 μg/kg/infusion) compared with wild-type (WT) mice. In vivo microdialysis showed that β4KO mice have higher extracellular dopamine (DA) levels in the nucleus accumbens than in WT mice, and exhibit a differential sensitivity to nicotine-induced DA outflow. Furthermore, electrophysiological recordings in the ventral tegmental area (VTA) demonstrated that DA neurons of β4KO mice are more sensitive to lower doses of nicotine than that of WT mice. Re-expression of β4* nAChRs in IPN neurons fully restored nicotine IVSA, and attenuated the increased sensitivity of VTA DA neurons to nicotine. These findings suggest that β4* nAChRs in the IPN have a role in maintaining nicotine IVSA This work was supported by the Spanish Instituto de Salud Carlos III (RD06/001/001 and PI10/01708; PI14/00210), FEDER funds, Ministerio de Ciencia e Innovación (#SAF2014-59648-P), the Catalan Government AGAUR (#2014-SGR-1547), Plan Nacional Sobre Drogas, Ministerio de Sanidad, Asuntos Sociales e Igualdad-MSASI (#PNSD- 2013-0068), FP7 ERANET program (NICO-GENE), the ICREA Foundation (ICREA Academia-2008), and a postdoctoral fellowship from CONACyT to AHS. The work in Paris was supported by the Institut Pasteur, Centre National de la Recherche Scientifique CNRS UMR 3571 (UM) and CNRS UMR 8246 (PF), the INSERM U1130 (PF), the Pierre et Marie Curie University (UM119), the Agence Nationale pour la Recherche (ANR Neuroscience), and FP7 ERANET program (NICO-GENE), Grant agreement n009 BLANC 20092009BLANC 20 NeuroCypres" project), Fondation EDF, the Fondation des Treilles, and the Foundation for Medical Research FMR (Equipe FRMDEQ20130326488 to PF). The groups of UM and PF are members of the Bio-Psy Labex. As such this work was supported by French state funds managed by the ANR within the Investissements d'Avenir programme under reference ANR-11-IDEX-0004-02. The teams of UM and PF are part of the École des Neurosciences de Paris Ile-de-France Network. We would like to thank Martine Soudant, Stephanie Pons, and Dulce Real for technical support, and Inés Ibañes-Tallon and Jessica/nAbles for providing the Tg(Chrnb4-cre)OL57Gsat/+ transgenic mice
Published: 2016
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23. Neurodegenerative disease-associated mutants of a human mitochondrial aminoacyl-tRNA synthetase present individual molecular signatures

Author: Sauter, Claude, Lorber, Bernard, Gaudry, Agnès, Karim, Loukmane, SCHWENZER, Hagen, Wien, Frank, Roblin, Pierre, Florentz, Catherine, Sissler, Marie, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Département Caractérisation et Elaboration des Produits Issus de l'Agriculture (CEPIA), Institut National de la Recherche Agronomique (INRA), Universite de Strasbourg (UNISTRA), France Diplomatie [200930], French National Program 'Investissement d'Avenir' (Labex MitoCross), Region Alsace, Universite de Strasbourg, AFM, Fondation des Treilles, LabEx MitoCross, [ANR-09-BLAN-0091-01/03], and [ANR-PCV07-187047]
Subjects: [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Aspartate-tRNA Ligase, Article, Cell Line, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Mitochondrial Proteins, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Leukoencephalopathies, Cricetinae, Enzyme Stability, Mutation, Animals, Humans, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]
Abstract: International audience; Mutations in human mitochondrial aminoacyl-tRNA synthetases are associated with a variety of neurodegenerative disorders. The effects of these mutations on the structure and function of the enzymes remain to be established. Here, we investigate six mutants of the aspartyl-tRNA synthetase correlated with leukoencephalopathies. Our integrated strategy, combining an ensemble of biochemical and biophysical approaches, reveals that mutants are diversely affected with respect to their solubility in cellular extracts and stability in solution, but not in architecture. Mutations with mild effects on solubility occur in patients as allelic combinations whereas those with strong effects on solubility or on aminoacylation are necessarily associated with a partially functional allele. The fact that all mutations show individual molecular and cellular signatures and affect amino acids only conserved in mammals, points towards an alternative function besides aminoacylation. Mitochondria are the powerhouses of the eukaryotic cell, hosting the production of energy in the form of ATP by oxidative phosphorylation of ADP. They possess their own genome (mt-DNA), which codes in humans for 13 of the respiratory chain subunits, 22 tRNAs and 2 rRNAs. More than one thousand proteins, encoded by the nuclear genome, synthesized in the cytosol and subsequently imported into mitochondria, are also required for mitochondrial biogenesis and functioning (reviewed in e.g. 1). Defects in mt-DNA were correlated to human disorders more than 25 years ago 2. More recently, mitochondrial disorders were also associated with mutations within imported molecules, like factors of the mitochon-drial translation machinery 3–5. Among these are mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs), which catalyze the esterification of tRNAs with cognate amino acids, and are key actors of the synthesis of the 13 respiratory chain subunits. In 2007, it was shown for the first time that a mt-aaRS is implicated in a disease when mutations were found in the DARS2 gene coding for the mitochondrial aspartyl-tRNA synthetase (mt-AspRS) 6. This attracted the attention of the medical community and the steadily growing number of cases reported since then led to the current statement that all mt-aaRS genes (except WARS2) are affected by pathology-related mutations 1,7–12. Mt-aaRSs are impacted in various ways, despite being ubiquitously
Published: 2015
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24. Telomere length reflects individual quality in free-living adult king penguins

Author: Akiko Kato, Céline Le Bohec, Yan Ropert-Coudert, Yvon Le Maho, Claire Saraux, Maryline Le Vaillant, François Criscuolo, Vincent A. Viblanc, Department of Zoology, Stockholm University, Stockholm University, Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Paul-Valéry - Montpellier 3 (UM3), MARine Biodiversity Exploitation and Conservation (UMR MARBEC), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Scientifique de Monaco (CSM), Musee oceanographique de Monaco, Centre for Ecological and Evolutionary Synthesis (CEES), Department of Biosciences [Oslo], Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), IPEV (programme 137), Fondation Prince Albert II de Monaco, Fondation des Treilles, AXA Research Fund, ANR-10-BLAN-1728,PICASO,Les manchots bio-indicateurs de la vulnérabilité de l'Océan austral(2010), European Project: 235962,EC:FP7:PEOPLE,FP7-PEOPLE-IEF-2008,EVOLBIRD(2010), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Université Paul-Valéry - Montpellier 3 (UPVM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut de Recherche pour le Développement (IRD), Centre d'Études Biologiques de Chizé - UMR 7372 (CEBC), Université de La Rochelle (ULR)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université Paul-Valéry - Montpellier 3 (UPVM)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut National de la Recherche Agronomique (INRA)-La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Genetics, Body condition, natural antibody level, Zoology, long-lived seabird, Biology, Positive correlation, biology.organism_classification, Aptenodytes patagonicus, Long-lived seabird, Telomere, Natural antibody level, Breeding performances, biology.animal, [SDE]Environmental Sciences, Seabird, Life history, body condition, General Agricultural and Biological Sciences, Life stress, Natural antibody
Abstract: Growing evidence suggests that telomeres, non-coding DNA sequences that shorten with age and stress, are related in an undefined way to individual breeding performances and survival rates in several species. Short telomeres and elevated shortening rates are typically associated with life stress and low health. As such, telomeres could serve as an integrative proxy of individual quality, describing the overall biological state of an individual at a given age. Telomere length could be associated with the decline of an array of physiological traits in age-controlled individuals. Here, we investigated the links between individuals’ relative telomere length, breeding performance and various physiological (body condition, natural antibody levels) and life history (age, past breeding success) parameters in a long-lived seabird species, the king penguin Aptenodytes patagonicus. While we observed no link between relative telomere length and age, we found that birds with longer telomeres arrived earlier for breeding at the colony, and had higher breeding performances (i.e. the amount of time adults managed to maintain their chicks alive, and ultimately breeding success) than individuals with shorter telomeres. Further, we observed a positive correlation between telomere length and natural antibody levels. Taken together, our results add to the growing evidence that telomere length is likely to reflect individual quality difference in wild animal.
Published: 2015
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25. The SNARE Sec22b has a non-fusogenic function in plasma membrane expansion

Author: Maja Petkovic, Ignacio Izeddin, Antoine Triller, Aymen Jemaiel, Daniela Vorkel, David Tareste, Christian G. Specht, Xavier Darzacq, Jean-Marc Verbavatz, Thierry Galli, Catherine L. Jackson, Karl H Pfenninger, Frédéric Daste, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Trafic Membranaire et Morphogenèse Neuronale & Epithéliale, Institut National de la Santé et de la Recherche Médicale (INSERM), Ecole des Neurosciences de Paris Île de France (ENP), Ecole des Neurosciences de Paris, Ecole Doctorale Frontières du Vivant - Programme Bettencourt (FdV), Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Max-Planck-Gesellschaft, Laboratoire de biologie moléculaire eucaryote (LBME), Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Linda Crnic Institute for Down Syndrome and Department of Pediatrics, University of Colorado [Boulder], INSERM, CNRS, the Association Française contre les Myopathies (AFM), the Association pour la Recherche sur le Cancer (ARC), the Mairie de Paris Medical Research and Health Program, the Fondation pour la Recherche Médicale (FRM), the Ecole des Neurosciences de Paris (ENP), the Association Robert Debré pour la Recherche Médicale, ANR JC grant, the Ecole des Neurosciences de Paris (ENP), the Fondation des Treilles, Paris Descartes University, the PhD Program Ecole Doctorale Frontières du Vivant (FdV)--Programme Bettencourt., Institut de biologie de l'Ecole Normale Supérieure (IBENS), École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Ecole des Neurosciences de Paris Île de France ( ENP ), Ecole Doctorale Frontières du Vivant - Programme Bettencourt ( FdV ), Université Paris Descartes - Paris 5 ( UPD5 ) -PRES Sorbonne Paris Cité, Institut de biologie de l'Ecole Normale Supérieure ( IBENS ), École normale supérieure - Paris ( ENS Paris ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Max Planck Institute of Molecular Cell Biology and Genetics ( MPI-CBG ), Laboratoire de biologie moléculaire eucaryote du CNRS ( LBME ), Centre National de la Recherche Scientifique ( CNRS ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, University of Colorado Boulder [Boulder], Institut de biologie de l'ENS Paris (IBENS), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris
Subjects: Saccharomyces cerevisiae Proteins, Time Factors, Syntaxin 1, Gestational Age, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Endoplasmic Reticulum, Transfection, R-SNARE Proteins, 03 medical and health sciences, Mice, 0302 clinical medicine, SNAP23, Chlorocebus aethiops, Animals, Humans, Secretion, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Cerebral Cortex, Neurons, 0303 health sciences, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, Endoplasmic reticulum, Cell Membrane, Cell Biology, Lipid Metabolism, Membrane contact site, Cell biology, Transmembrane domain, Membrane, Animals, Newborn, COS Cells, RNA Interference, Signal transduction, Carrier Proteins, Plant lipid transfer proteins, 030217 neurology & neurosurgery, HeLa Cells, Signal Transduction
Abstract: International audience; Development of the nervous system requires extensive axonal and dendritic growth during which neurons massively increase their surface area. Here we report that the endoplasmic reticulum (ER)-resident SNARE Sec22b has a conserved non-fusogenic function in plasma membrane expansion. Sec22b is closely apposed to the plasma membrane SNARE syntaxin1. Sec22b forms a trans-SNARE complex with syntaxin1 that does not include SNAP23/25/29, and does not mediate fusion. Insertion of a long rigid linker between the SNARE and transmembrane domains of Sec22b extends the distance between the ER and plasma membrane, and impairs neurite growth but not the secretion of VSV-G. In yeast, Sec22 interacts with lipid transfer proteins, and inhibition of Sec22 leads to defects in lipid metabolism at contact sites between the ER and plasma membrane. These results suggest that close apposition of the ER and plasma membrane mediated by Sec22 and plasma membrane syntaxins generates a non-fusogenic SNARE bridge contributing to plasma membrane expansion, probably through non-vesicular lipid transfer.
Published: 2014
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26. Modulations of EEG Beta Power during Planning and Execution of Grasping Movements

Author: Bjørg Elisabeth Kilavik, Romain Trachel, Thomas Brochier, Manuel Zaepffel, Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Computational Imaging of the Central Nervous System (ATHENA), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Bourse doctorale MERS et bourse de la fondation des Treilles à Manuel ZaepffelBourse DGA à Romain Trachel, and Brochier, Thomas
Subjects: Central Nervous System, Male, Computer science, lcsh:Medicine, Electroencephalography, Signal, Behavioral Neuroscience, Cognition, 0302 clinical medicine, Beta (velocity), lcsh:Science, Clinical Neurophysiology, Multidisciplinary, Hand Strength, medicine.diagnostic_test, Movement (music), 05 social sciences, Power (physics), Electrophysiology, medicine.anatomical_structure, Medicine, Sensory Perception, Female, Research Article, Motor cortex, Adult, Cognitive Neuroscience, Movement, Neurophysiology, 050105 experimental psychology, Motor Reactions, Young Adult, 03 medical and health sciences, Diagnostic Medicine, Event-related potential, Control theory, Psychophysics, medicine, Humans, 0501 psychology and cognitive sciences, Biology, Sensory cue, Motor Systems, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, lcsh:R, Sensorimotor rhythm, lcsh:Q, 030217 neurology & neurosurgery, Neuroscience
Abstract: International audience; Although beta oscillations (< 13–35 Hz) are often considered as a sensorimotor rhythm, their functional role remains debated. In particular, the modulations of beta power during preparation and execution of complex movements in different contexts were barely investigated. Here, we analysed the beta oscillations recorded with electroencephalography (EEG) in a precued grasping task in which we manipulated two critical parameters: the grip type (precision vs. side grip) and the force (high vs. low force) required to pull an object along a horizontal axis. A cue was presented 3 s before a GO signal and provided full, partial or no information about the two movement parameters. We measured beta power over the centro-parietal areas during movement preparation and execution as well as during object hold. We explored the modulations of power in relation to the amount and type of prior information provided by the cue. We also investigated how beta power was affected by the grip and force parameters. We observed an increase in beta power around the cue onset followed by a decrease during movement preparation and execution. These modulations were followed by a transient power increase during object hold. This pattern of modulations did not differ between the 4 movement types (2 grips 62 forces). However, the amount and type of prior information provided by the cue had a significant effect on the beta power during the preparatory delay. We discuss how these results fit with current hypotheses on the functional role of beta oscillations. Citation: Zaepffel M, Trachel R, Kilavik BE, Brochier T (2013) Modulations of EEG Beta Power during Planning and Execution of Grasping Movements. PLoS ONE 8(3): e60060.
Published: 2013
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27. Explosions et transition flammes-détonation. Cas des supernovae

Author: Clavin, Paul, Boudoyan, Karine, Institut de Recherche sur les Phénomènes Hors Equilibre (IRPHE), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Fondation des Treilles, and Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)
Subjects: [SPI.MECA.MEFL] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Fluids mechanics [physics.class-ph], ComputingMilieux_MISCELLANEOUS, [SPI.MECA.MEFL]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Fluids mechanics [physics.class-ph]
Abstract: International audience
Published: 2012

28. Differential association of Plasmodium falciparum Na+/H+ exchanger polymorphism and quinine responses in field- and culture-adapted isolates of Plasmodium falciparum

Author: Daniel Parzy, Bruno Pradines, Lionel Bertaux, Sébastien Briolant, Stéphane Pelleau, Michael T. Ferdig, Véronique Sinou, Ronan Jambou, Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées, Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Centre National de Référence du Paludisme, Unité de Recherche en Biologie et Epidémiologie Parasitaires, Institut de Médecine Tropicale du Service de Santé des Armées-Centre National de la Recherche Scientifique (CNRS), Eck Institute for Global Health, University of Notre Dame [Indiana] (UND), 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), This work was supported by the French Army Health Service, De ́- le ́gation Ge ́ne ́rale de l'Armement (DGA, 08co404), Centre National de Re ́fe ́rence du Paludisme (Institut de Veille Sanitaire), and FSP from the French Ministry of Foreign Affairs. S.P. has been supported by the Lavoisier program from the French Ministry of Foreign Affairs and a grant from Fondation des Treilles., and Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Sequence Analysis, DNA, [SDV]Life Sciences [q-bio], Drug Resistance, Protozoan Proteins, Drug resistance, MESH: Parasitic Sensitivity Tests, MESH: Membrane Transport Proteins, chemistry.chemical_compound, 0302 clinical medicine, Parasitic Sensitivity Tests, Molecular marker, Pharmacology (medical), MESH: Animals, MESH: Protozoan Proteins, MESH: Plasmodium falciparum, MESH: Inhibitory Concentration 50, Genetics, 0303 health sciences, Quinine, biology, 3. Good health, Infectious Diseases, MESH: Drug Resistance, Microsatellite, Multidrug Resistance-Associated Proteins, MESH: Multidrug Resistance-Associated Proteins, medicine.drug, Sodium-Hydrogen Exchangers, MESH: Quinine, 030231 tropical medicine, Molecular Sequence Data, Plasmodium falciparum, 03 medical and health sciences, Antimalarials, Inhibitory Concentration 50, Mechanisms of Resistance, parasitic diseases, MESH: Polymorphism, Genetic, medicine, Animals, Humans, Gene, Pharmacology, Polymorphism, Genetic, MESH: Sodium-Hydrogen Antiporter, MESH: Humans, MESH: Molecular Sequence Data, 030306 microbiology, Haplotype, Membrane Transport Proteins, Sequence Analysis, DNA, biology.organism_classification, medicine.disease, MESH: Antimalarials, Culture Media, chemistry, MESH: Culture Media, Malaria
Abstract: Plasmodium falciparum isolates with decreased susceptibility to quinine are increasingly being found in malaria patients. Mechanisms involved in this resistance are not yet understood. Several studies claim that alongside mutations in the Pf crt and Pf mdr1 genes, the Pf nhe-1 Na + /H + exchanger polymorphism plays a role in decreasing susceptibility. However, conflicting results on the link between the Pf nhe-1 gene and quinine resistance arise from field- and culture-adapted isolates. We tested the association between Pf nhe-1 , Pf crt , and Pf mdr1 polymorphisms in field- and culture-adapted isolates from various countries with their in vitro susceptibility to quinine. Field isolates presented a higher diversity of the Pf nhe-1 microsatellite sequence than culture-adapted isolates. In culture-adapted isolates but not in field isolates, mutations in the Pf crt and Pf mdr1 genes, as well as a higher number of DNNND repeats in the Pf nhe-1 gene, were associated with a higher 50% inhibitory concentration (IC 50 ) of quinine. Furthermore, most of the culture-adapted isolates with more than one DNNND repeat in the Pf nhe-1 gene also harbored mutated Pf crt and Pf mdr1 genes with an apparent cumulative effect on quinine susceptibility. This study supports the involvement of the Pf nhe-1 gene in the modulation of the in vitro quinine response when associated with mutated Pf crt and Pf mdr1 genes. Culture adaptation could be responsible for selection of specific haplotypes of these three genes. Methods used for drug testing might thus influence the association between Pf nhe-1 polymorphism and quinine susceptibility. However, we do not exclude the possibility that in particular settings, Pf nhe-1 polymorphism can be used as a molecular marker for surveillance of quinine resistance.
Published: 2011
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29. Reformulating Prosodic Break Model into Segmental HMMs and Information Fusion

Author: Obin, Nicolas, Lanchantin, Pierre, Lacheret, Anne, Rodet, Xavier, Sciences et Technologies de la Musique et du Son (STMS), Institut de Recherche et Coordination Acoustique/Musique (IRCAM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Modèles, Dynamiques, Corpus (MoDyCo), Université Paris Nanterre (UPN)-Centre National de la Recherche Scientifique (CNRS), Fondation Des Treilles, and Obin, Nicolas
Subjects: [STAT.AP]Statistics [stat]/Applications [stat.AP], [INFO.INFO-TS] Computer Science [cs]/Signal and Image Processing, 020206 networking & telecommunications, Computer Science::Computation and Language (Computational Linguistics and Natural Language and Speech Processing), 02 engineering and technology, speech prosody, [SHS.LANGUE] Humanities and Social Sciences/Linguistics, 030507 speech-language pathology & audiology, 03 medical and health sciences, ComputingMethodologies_PATTERNRECOGNITION, Dempster-Shafer fusion, [STAT.AP] Statistics [stat]/Applications [stat.AP], [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, 0202 electrical engineering, electronic engineering, information engineering, segmental- HMM, [SHS.LANGUE]Humanities and Social Sciences/Linguistics, 0305 other medical science, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, prosodic break, [SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing
Abstract: International audience; In this paper, a method for prosodic break modelling based on segmental-HMMs and Dempster-Shafer fusion is presented, and the relative importance of linguistic and metric constraints in prosodic break modelling is assessed. A context-dependent segmental-HMM is used to explicitly model the linguistic and the metric constraints. Dempster-Shafer fusion is used to balance the relative importance of the linguistic and the metric constraints into the segmental-HMM. A linguistic processing chain based on surface and deep syntactic parsing is additionally used to extract linguistic informations of different nature. An objective evaluation proved evidence that the optimal combination of the linguistic and the metric constraints significantly outperforms both the conventional HMM (linguistic information only) and segmental-HMM (equal balance of linguistic and metric constraints), and confirmed that the linguistic constraint is prior to the metric.
Published: 2011

30. Discrete/Continuous Modelling of Speaking Style in HMM-based Speech Synthesis: Design and Evaluation

Author: Obin, Nicolas, Lanchantin, Pierre, Lacheret, Anne, Rodet, Xavier, Sciences et Technologies de la Musique et du Son (STMS), Institut de Recherche et Coordination Acoustique/Musique (IRCAM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Modèles, Dynamiques, Corpus (MoDyCo), Université Paris Nanterre (UPN)-Centre National de la Recherche Scientifique (CNRS), Fondation Des Treilles, and Obin, Nicolas
Subjects: [STAT.AP]Statistics [stat]/Applications [stat.AP], [INFO.INFO-TS] Computer Science [cs]/Signal and Image Processing, 020206 networking & telecommunications, 02 engineering and technology, average modelling, speech prosody, [SHS.LANGUE] Humanities and Social Sciences/Linguistics, 030507 speech-language pathology & audiology, 03 medical and health sciences, [STAT.AP] Statistics [stat]/Applications [stat.AP], speech synthesis, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, 0202 electrical engineering, electronic engineering, information engineering, speaking style, [SHS.LANGUE]Humanities and Social Sciences/Linguistics, 0305 other medical science, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, [SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing
Abstract: International audience; This paper assesses the ability of a HMM-based speech synthesis systems to model the speech characteristics of various speaking styles. A discrete/continuous HMM is presented to model the symbolic and acoustic speech characteristics of a speaking style. The proposed model is used to model the average characteristics of a speaking style that is shared among various speakers, depending on specific situations of speech communication. The evaluation consists of an identification experiment of 4 speaking styles based on delexicalized speech, and compared to a similar experiment on natural speech. The comparison is discussed and reveals that discrete/continuous HMM consistently models the speech characteristics of a speaking style.
Published: 2011

31. Late Pleistocene climatic change in the French Jura (Gigny) recorded in the delta(18)O of phosphate from ungulate tooth enamel

Author: François Martineau, Romain Amiot, Magali Fabre, Christophe Lécuyer, François Fourel, Jean-Philip Brugal, Laboratoire méditerranéen de préhistoire Europe-Afrique (LAMPEA), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Laboratoire de Géologie de Lyon - Terre, Planètes, Environnement [Lyon] (LGL-TPE), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Département Géotechnique, Eau et Risques (LCPC/GER), Laboratoire Central des Ponts et Chaussées (LCPC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fondation des Treilles CNRS Institut Universitaire de France, Laboratoire de Géologie de Lyon - Terre, Planètes, Environnement (LGL-TPE), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Central des Ponts et Chaussées (LCPC), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)
Subjects: Delta, Gigny, 010506 paleontology, Europe occidentale, paléontologie des vertébrés, Neanderthal, Ungulate, 010504 meteorology & atmospheric sciences, Pleistocene, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, δ18O, émail dentaire, [SDV]Life Sciences [q-bio], 01 natural sciences, Isotopes of oxygen, Arts and Humanities (miscellaneous), biology.animal, Jura, isotope, grand mammifère, Horse teeth, ComputingMilieux_MISCELLANEOUS, Franche-Comté, 0105 earth and related environmental sciences, Earth-Surface Processes, chimie, cerf, biology, climat, Ecology, Pléistocène supérieur, biology.organism_classification, Equus, environnement, 13. Climate action, [SDU]Sciences of the Universe [physics], General Earth and Planetary Sciences, Physical geography, France, cheval, Geology
Abstract: Oxygen isotope compositions of phosphate in tooth enamel from large mammals (i.e. horse and red deer) were measured to quantify past mean annual air temperatures and seasonal variations between 145 ka and 33 ka in eastern France. The method is based on interdependent relationships between the δ18O of apatite phosphate, environmental waters and air temperatures. Horse (Equus caballus germanicus) and red deer (Cervus elaphus) remains have δ18O values that range from 14.2‰ to 17.2‰, indicating mean air temperatures between 7°C and 13°C. Oxygen isotope time series obtained from two of the six horse teeth show a sinusoidal-like signal that could have been forced by temperature variations of seasonal origin. Intra-tooth oxygen isotope variations reveal that at 145 ka, winters were colder (− 7 ± 2°C) than at present (3 ± 1°C) while summer temperatures were similar. Winter temperatures mark a well-developed West–East thermal gradient in France of about − 9°C, much stronger than the −4°C difference recorded presently. Negative winter temperatures were likely responsible for the extent and duration of the snow cover, thus limiting the food resources available for large ungulates with repercussions for Neanderthal predators.
Published: 2011
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32. Le Ladakh (Jammu & Cachemire, Inde) de l'âge du Bronze à l'introduction du Bouddhisme: une étude de l'art rupestre

Author: Bruneau, Laurianne, Archéologie de L'Asie centrale, Archéologies et Sciences de l'Antiquité (ArScAn), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Institut national de recherches archéologiques préventives (Inrap)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Institut national de recherches archéologiques préventives (Inrap)-Centre National de la Recherche Scientifique (CNRS), Je remercie les instituts suivants pour leur participation financière à mes recherches : l’INHA, les Ministères des Affaires Etrangères français et italien, la Fondation Maison des sciences de l’homme (Paris) et la Higher Education Commission (Islamabad) gérant le Programme de Collaboration en Sciences Sociales entre la France et le Pakistan, la Chancellerie des Universités de Paris, le DAAD, la Fondation Pierre Ledoux-Jeunesse Internationale, l’EFEO, la Fondation Carlo Leone et Mariena Montandon (Suisse), la Fondation des Treilles (France)., Université Paris 1 Panthéon-Sorbonne, and Henri-Paul Francfort
Subjects: Bronze Age, Âge du Fer, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, Iron Age, Asie centrale, Himalaya, Pétroglyphe, India, Tibet, Chorten, Central Asia, Archéologie, Architecture, Art animalier des steppes, Buddhism, Carving, Art of the steppes, Himalayas, Histoire de l’art, Rock art studies, Stūpa, Protohistoire, Engraving, Art rupestre, History of art, Âge du Bronze, Archaeology, Bouddhisme, Ladakh, Animal style, Inde, Petroglyph, Gravure, Protohistory
Abstract: Ladakh is the largest, highest and westernmost region of the Himalayas. Although it belongs to India’s state of Jammu and Kashmir, it is located at the crossroads of Central Asia, China, Tibet and India. We may assume that this unique location resulted into a major historical importance. However Ladakh’s history prior the 15th century is rather fragmentary and legendary. Very limited archaeological researches have been conducted in this Himalayan region. In the light of successful rock art projects lead in Central Asia and in the northern areas of Pakistan, petroglyphs appeared as the most promising and easily available material to carry out the first systematic archaeological study of Ladakh. In the course of my PhD I gathered about 15, 000 petroglyphs scattered over 100 rock sites. A comparative analysis of zoomorphic and anthropomorphic representations shows that during the Bronze and Iron Ages (2500-300 BC) Ladakh shared thematic and stylistic traits with the Central Asian steppes. Later on, at the beginning of the 1st millennium AD, several rock inscriptions in kharosthi and brahmi are firm testimonies that Ladakh was under the influence of the Indian cultural expansion. Then, Tibetan rock inscriptions in Ladakh datable to the second half of the first millennium provide evidence for the expansion of the Tibetan empire (7th-11th centuries) into the western regions. These inscriptions are frequently accompanied by engraved representations of Buddhist stūpa. The typological and comparative study of these enables us to better apprehend the introduction and diffusion of Buddhism into Ladakh. In summary my researches on the rock art of Ladakh allows for the first time to propose a secure cultural sequence of the region from Protohistory to the Medieval Period. It also demonstrates that the Himalayas have never been a barrier between Central Asia, the Indian subcontinent and the Tibetan plateau and that Ladakh always has been a cultural crossroad.; Le Ladakh constitue la plus vaste, la plus élevée et la plus occidentale des régions naturelles de l’Himalaya. Bien que politiquement rattachée à l’état indien du Jammu et Cachemire, elle est géographiquement située aux confins de l’Asie Centrale, de la Chine, du Tibet et de l’Inde. Par conséquent nous pouvons présumer que cette situation privilégiée lui a conféré une importance historique majeure. Cependant, le Ladakh a fait l’objet de peu de recherches archéologiques : on compte seulement trois sondages. Le manque de données est aujourd’hui comblé par un matériel abondant, varié et fiable : l’art rupestre. Véritables créations picturales ou simples graffiti, les pétroglyphes sont des marqueurs spatio-temporels immuables, qui ne peuvent mentir ni sur leur provenance ni celle de leurs auteurs. De part leur quantité (on en connaît plusieurs milliers) et leur variété (ils illustrent des êtres anthropomorphes, zoomorphes, des monuments et des signes), ils recèlent des informations essentielles pour l’histoire du peuplement. Puisque les représentations rupestres couvrent une période s’étendant de la Préhistoire à l’époque moderne nous avons opéré un choix pour notre étude. Par une analyse comparative thématique et stylistique des images gravées nous sommes en mesure d’inscrire le Ladakh au sein du groupe des cultures des steppes à l’Âge du Bronze et à l’Âge du Fer ainsi que de l’identifier comme carrefour culturel pour la diffusion du Bouddhisme au Ier millénaire de notre ère. Les axes de recherches retenus s’inscrivent dans la thématique des recherches archéologiques menées actuellement en Asie centrale.
Published: 2010

33. Temperature shift and host cell contact up-regulate sporozoite expression of Plasmodium falciparum genes involved in hepatocyte infection

Author: Geert-Jaan van Gemert, Emmanuel Bischoff, Samir Yalaoui, Dominique Mazier, Patrick Froissard, Carine Marinach, Jean-François Franetich, Georges Snounou, Catherine Vaquero, Olivier Silvie, Anthony Siau, Peter H. David, Laurent Hannoun, Adrian J. F. Luty, Immunobiologie Cellulaire et Moléculaire des Infections Parasitaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Medical Microbiology [Nijmegen], Radboud University Medical Center [Nijmegen], Génopole, Institut Pasteur [Paris] (IP), Parasitologie moléculaire et Signalisation, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Parasitologie Comparée et Modèles Expérimentaux, Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière], Plasmodium pan genomic microarrays were financed by grants from the Délégation Générale pour l’Armement (DGA verst.nu22120/DSP/SREAF and Contract no 0434025), Programme PAL+/Fond National pour la Science, the Institut Pasteur and the Programme Génopole. The work was in part supported by the European Union (MALINV project no 012199). A. Siau was supported by MENRT, Fondation de la Recherche Médicale (FRM), and by the Fondation des Treilles., The authors are grateful to Anne Charlotte Grüner for constructive comments and criticisms of the manuscript and to Emilie Duvaltier, Anna Engström, and Marga van de Vegte-Bolmer for their technical help. Microarray analysis and confocal microscopy were performed using the Pitié-Salpêtrière genomic core facility (P3S) and the Plate-forme d'Imagerie Cellulaire, respectively., Vaquero, Catherine, Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN), Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Plasmodium, Hot Temperature, Host cells, [SDV]Life Sciences [q-bio], MESH: Malaria, Falciparum/metabolism, Protozoan Proteins, MESH: Plasmodium falciparum/metabolism, MESH: Hepatocytes/parasitology, Transcriptome, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Animals, Microbiology/Parasitology, Malaria, Falciparum, Biology (General), Cells, Cultured, Oligonucleotide Array Sequence Analysis, Infectivity, 0303 health sciences, MESH: Plasmodium falciparum/genetics, Reverse Transcriptase Polymerase Chain Reaction, MESH: Protozoan Proteins/biosynthesis, MESH: Gene Expression Profiling/methods, MESH: Hepatocytes/metabolism, 030302 biochemistry & molecular biology, Anopheles, MESH: Malaria, Falciparum/genetics, Genetics and Genomics/Gene Expression, Parasitic diseases, Up-Regulation, 3. Good health, Cell biology, Pathogenesis and modulation of inflammation [N4i 1], [SDV] Life Sciences [q-bio], medicine.anatomical_structure, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Sporozoites, Hepatocyte, MESH: Up-Regulation*/genetics, Transcriptome analysis, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Research Article, Infectious Diseases/Tropical and Travel-Associated Diseases, MESH: Cells, Cultured, QH301-705.5, Plasmodium falciparum, Immunology, MESH: Protozoan Proteins/genetics, Biology, Salivary glands, MESH: Hot Temperature, Microbiology, MESH: Oligonucleotide Array Sequence Analysis/methods, 03 medical and health sciences, Virology, Genetics, medicine, Animals, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Molecular Biology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, 030304 developmental biology, MESH: Humans, Microarray analysis techniques, Gene Expression Profiling, Infectious Diseases/Protozoal Infections, RC581-607, biology.organism_classification, Gene expression profiling, Hepatocytes, Parasitology, Microbial pathogenesis and host defense [UMCN 4.1], Gene expression, Immunologic diseases. Allergy, Immunity, infection and tissue repair [NCMLS 1]
Abstract: Plasmodium sporozoites are deposited in the skin by Anopheles mosquitoes. They then find their way to the liver, where they specifically invade hepatocytes in which they develop to yield merozoites infective to red blood cells. Relatively little is known of the molecular interactions during these initial obligatory phases of the infection. Recent data suggested that many of the inoculated sporozoites invade hepatocytes an hour or more after the infective bite. We hypothesised that this pre-invasive period in the mammalian host prepares sporozoites for successful hepatocyte infection. Therefore, the genes whose expression becomes modified prior to hepatocyte invasion would be those likely to code for proteins implicated in the subsequent events of invasion and development. We have used P. falciparum sporozoites and their natural host cells, primary human hepatocytes, in in vitro co-culture system as a model for the pre-invasive period. We first established that under co-culture conditions, sporozoites maintain infectivity for an hour or more, in contrast to a drastic loss in infectivity when hepatocytes were not included. Thus, a differential transcriptome of salivary gland sporozoites versus sporozoites co-cultured with hepatocytes was established using a pan-genomic P. falciparum microarray. The expression of 532 genes was found to have been up-regulated following co-culture. A fifth of these genes had no orthologues in the genomes of Plasmodium species used in rodent models of malaria. Quantitative RT-PCR analysis of a selection of 21 genes confirmed the reliability of the microarray data. Time-course analysis further indicated two patterns of up-regulation following sporozoite co-culture, one transient and the other sustained, suggesting roles in hepatocyte invasion and liver stage development, respectively. This was supported by functional studies of four hitherto uncharacterized proteins of which two were shown to be sporozoite surface proteins involved in hepatocyte invasion, while the other two were predominantly expressed during hepatic parasite development. The genome-wide up-regulation of expression observed supports the hypothesis that the shift from the mosquito to the mammalian host contributes to activate quiescent salivary gland sporozoites into a state of readiness for the hepatic stages. Functional studies on four of the up-regulated genes validated our approach as one means to determine the repertoire of proteins implicated during the early events of the Plasmodium infection, and in this case that of P. falciparum, the species responsible for the severest forms of malaria., Author Summary Sporozoites, the infective form of the malaria parasites Plasmodium, are deposited in the skin by Anopheles mosquitoes. They then find their way to the liver where they specifically invade hepatocytes, in which they develop to yield another form, the merozoite, infective to red blood cells. Relatively little is known of the molecular interactions during these initial obligatory phases of the infection. We studied the changes in gene expression in sporozoites, from the parasite species P. falciparum that infects humans, in an in vitro system where they were co-cultured with their natural host cells, primary human hepatocytes. The whole genome transcriptome profiling carried out led to the identification of 532 genes that were up-regulated following co-culture. This genome-wide up-regulation of expression supports the hypothesis that the shift from the mosquito to the mammalian host contributes to activate quiescent salivary gland sporozoites into a state of readiness for the hepatic stages. Functional studies on four of the up-regulated genes we identified validated our approach as one means to determine the repertoire of proteins implicated during the early events in the infection by P. falciparum, the species responsible for the severest forms of malaria.
Published: 2008
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34. Noms de pays et autoreprésentation dans le discours des périodiques nationaux français, anglophones, roumanophones et russes

Author: Georgeta Cislaru, CLESTHIA - Langage, systèmes, discours - EA 7345 (CLESTHIA), Université Sorbonne Nouvelle - Paris 3, and Fondation des Treilles
Subjects: 060201 languages & linguistics, 05 social sciences, presse nationale, national newspapers, 06 humanities and the arts, country-name, 0602 languages and literature, 0502 economics and business, nom de pays, self-representation, discourse, [SHS.LANGUE]Humanities and Social Sciences/Linguistics, discours, 050203 business & management, autoreprésentation
Abstract: Les noms entretiennent avec les entités qu’ils désignent des rapports complexes : sans en être des étiquettes, les noms finissent par véhiculer une représentation des choses; c’est d’autant plus vrai pour les noms de pays qui, en délimitant des frontières, fonctionnent comme des signes identitaires d’États et/ou de nations. Chaque nom de pays pourrait donc être appréhendé comme une forme d’autoreprésentation, marquée par des spécificités culturelles et idéologiques. Cette contribution propose une analyse contrastive du fonctionnement de six noms de pays dans le discours de la presse nationale des pays respectifs (États-Unis, Grande-Bretagne, France, Moldavie, Roumanie, Russie). De cette analyse qualitative et quantitative il ressort qu’au-delà des propriétés linguistico-discursives – comme la référence locative ou la référence agentive – que les noms de pays possèdent dans toutes les langues analysées, l’usage discursif des six noms est déterminé par les conceptions de l’identité collective circulant dans chacun des pays. The relationship between names and the entities they refer to is rather complex: names are not labels, but they do condense object representations. This feature is particularly common for country names which fix boundaries and thus have the status of identity marks of the State and/or the Nation. With respect to this feature, each country’s name may be regarded as a figure of self-representation imprinted by cultural and ideological particularities. This paper offers a comparative study of six country names in national newspapers published in the same six countries: France, Great-Britain, Moldova, Romania, Russia, the United States. The qualitative and quantitative analyses show that beyond common linguistic-discursive properties of country names in all the concerned languages, such as spatial and agentive reference, the discourse use of the six names is determined by the conception of cultural identity proper to each country.
Published: 2008
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35. Self-association of adenine-dependent hairpin ribozymes

Author: Christine Ebel, Giuseppe Zaccai, Vitaliy Pipich, Jacques Vergne, Marie-Christine Maurel, Yan-Li Li, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), institut fur festkorperforshung Forschungszentrum Juelich, institut fur feskorperforshung forschungszentrum juelich, Institut Laue-Langevin (ILL), ILL, Association pour l'Information et la Recherche en Oncologie', Fondation des Treilles, Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Base pair, Dimer, Biophysics, Neutron scattering, Models, Biological, 03 medical and health sciences, chemistry.chemical_compound, Scattering, Small Angle, RNA, Catalytic, Protein Structure, Quaternary, 030304 developmental biology, 0303 health sciences, biology, Chemistry, Adenine, 030302 biochemistry & molecular biology, Intermolecular force, Temperature, Ribozyme, Analytical centrifugation, RNA, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, General Medicine, RNA enzyme dimers, Kinetics, Neutron Diffraction, Crystallography, Docking (molecular), Mutation, biology.protein, Radius of gyration, Hairpin ribozyme, Dimerization, Ultracentrifugation, Protein Binding
Abstract: International audience; Hairpin ribozymes are flexible molecules that catalyse reversible self-cleavage after the docking of two independently folded internal loops, A and B. The activities, self-association and structures in solution of two 85 base adenine-dependent hairpin ribozymes (ADHR1 and ADHR2) were studied by native gel electrophoresis, analytical centrifugation, and small angle neutron scattering. Bi-molecular RNA interactions such as linear-linear, loop-loop, loop-linear or kissing interactions have been found to be important in the control of various biological functions, and hairpin loops present rich potential for establishing both intra- and intermolecular interactions through standard Watson-Crick base pairing or non-canonical interactions. Similar results were obtained for ADHR1 and ADHR2. At room temperature, they indicated end-to-end self-association of the ribozymes in rod-like structures with a cross-section corresponding to two double strands side-by-side. Dimers, which predominate at low concentration ( approximately 0.1 mg/ml), associate into longer rods, with increasing concentration ( approximately 1 mg/ml). Above 65 degrees C, the dimers and rods dissociated into compact monomers, with a radius of gyration similar to that of tRNA (about 70 bases). The dimers were non-active for catalysis, which suggests that dimer formation, probably by preventing the correct docking of loops A and B, could act as an inhibition mechanism for the regulation of hairpin ribozyme catalysis.
Published: 2007
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36. A Toxoplasma gondii Leucine-Rich Repeat Protein Binds Phosphatase Type 1 Protein and Negatively Regulates Its Activity

Author: Wassim Daher, Katia Cailliau, Jamal Khalife, Sylvain Fauquenoy, Gabrielle Oria, Stanislas Tomavo, Edith Browaeys, Schistosomiase, paludisme et inflammation, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), IFR 118 (UPRES EA 1033), Université de Lille, Sciences et Technologies, This work was supported by the INSERM U547-Université Lille II, Pasteur Institute of Lille, and the CNRS. Wassim Daher and Gabrielle Oria were supported by fellowships from the Fondation des Treilles and the Ministère de l'Enseignement Supérieur et de la Recherche (MESR), respectively. Wassim Daher gratefully acknowledges the current financial support of a European Molecular Biology Organization (EMBO) long-term fellowship., We thank the Toxoplasma Genome Sequencing Consortium for making available the genome database at http://ToxoDB.org., Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), and Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: Xenopus, Protozoan Proteins, Gene Expression, MESH: Amino Acid Sequence, Leucine-Rich Repeat Proteins, MESH: Phosphoprotein Phosphatases/genetics, Phosphoprotein Phosphatases, MESH: Proteins/genetics, MESH: Animals, MESH: Xenopus, MESH: Toxoplasma/chemistry, 0303 health sciences, biology, 030302 biochemistry & molecular biology, Articles, General Medicine, Cell cycle, MESH: RNA, Messenger/metabolism, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Toxoplasma, MESH: Gene Expression, Protein family, Immunoprecipitation, Molecular Sequence Data, Phosphatase, MESH: Protozoan Proteins/genetics, Leucine-rich repeat, MESH: Phosphoprotein Phosphatases/metabolism, Microbiology, MESH: Toxoplasma/metabolism, MESH: Oocytes, 03 medical and health sciences, Animals, Amino Acid Sequence, RNA, Messenger, Molecular Biology, MESH: Protozoan Proteins/metabolism, 030304 developmental biology, MESH: Protozoan Proteins/analysis, MESH: Molecular Sequence Data, Binding protein, Proteins, Toxoplasma gondii, biology.organism_classification, Molecular biology, MESH: Phosphoprotein Phosphatases/antagonists & inhibitors, MESH: Proteins/analysis, Oocytes, MESH: Toxoplasma/growth & development, MESH: Proteins/metabolism
Abstract: We have characterized the Toxoplasma gondii protein phosphatase type 1 (TgPP1) and a potential regulatory binding protein belonging to the leucine-rich repeat protein family, designated TgLRR1. TgLRR1 is capable of binding to TgPP1 to inhibit its activity and to override a G 2 /M cell cycle checkpoint in Xenopus oocytes. In the parasite, TgLRR1 mRNA and protein are both highly expressed in the rapidly replicating and virulent tachyzoites, while only low levels are detected in the slowly dividing and quiescent bradyzoites. TgPP1 mRNA and protein levels are equally abundant in tachyzoites and bradyzoites. Affinity pull down and immunoprecipitation experiments reveal that the TgLRR1-TgPP1 interaction takes place in the nuclear subcompartment of tachyzoites. These results are consistent with those of localization studies using both indirect immunofluorescence with specific polyclonal antibody and transient transfection of T. gondii vector expressing TgLRR1 and TgPP1. The inability to obtain stable transgenic tachyzoites suggested that overexpression of TgLRR1 and TgPP1 may impair the parasite's growth. Together with the activation of Xenopus oocyte meiosis reinitiation, these data indicate that TgLRR1 protein could play a role in the regulation of the T. gondii cell cycle through the modulation of phosphatase activity.
Published: 2007
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37. Carboxypeptidases B of Anopheles gambiae as Targets for a Plasmodium falciparum Transmission-Blocking Vaccine

Author: Sabine Thiberge, Catherine Lavazec, Christian Boudin, Rachida Tahar, Catherine Bourgouin, Renaud Lacroix, Sarah Bonnet, Bertrand Boisson, A. Diop, Biologie et Génétique du Paludisme, Institut Pasteur [Paris] (IP), Paludologie afrotropicale, Institut de recherche pour le développement [Dakar, Sénégal] (IRD Hann Maristes), Immunologie moléculaire des parasites, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and This project was supported by fellowships to C. Lavazec (F. Lacoste, CANAM, Fondation des Treilles) and research funds from the Pasteur Institute and the French Ministry of Research (PAL+ Special Program).
Subjects: Plasmodium berghei, Anopheles gambiae, [SDV]Life Sciences [q-bio], Immunology, Plasmodium falciparum, Biology, Microbiology, Plasmodium, Antibodies, Mice, parasitic diseases, Anopheles, Malaria Vaccines, medicine, Parasite hosting, Animals, Humans, Malaria, Falciparum, Reproduction, fungi, Midgut, biology.organism_classification, medicine.disease, Virology, Carboxypeptidase, Carboxypeptidase B, Malaria, Up-Regulation, Gastrointestinal Tract, Disease Models, Animal, Infectious Diseases, Microbial Immunity and Vaccines, biology.protein, Parasitology, Female
Abstract: Anopheles gambiae is the major African vector of Plasmodium falciparum , the most deadly species of human malaria parasite and the most prevalent in Africa. Several strategies are being developed to limit the global impact of malaria via reducing transmission rates, among which are transmission-blocking vaccines (TBVs), which induce in the vertebrate host the production of antibodies that inhibit parasite development in the mosquito midgut. So far, the most promising components of a TBV are parasite-derived antigens, although targeting critical mosquito components might also successfully block development of the parasite in its vector. We previously identified A. gambiae genes whose expression was modified in P. falciparum -infected mosquitoes, including one midgut carboxypeptidase gene, cpbAg1. Here we show that P. falciparum up-regulates the expression of cpbAg1 and of a second midgut carboxypeptidase gene, cpbAg2 , and that this up-regulation correlates with an increased carboxypeptidase B (CPB) activity at a time when parasites establish infection in the mosquito midgut. The addition of antibodies directed against CPBAg1 to a P. falciparum -containing blood meal inhibited CPB activity and blocked parasite development in the mosquito midgut. Furthermore, the development of the rodent parasite Plasmodium berghei was significantly reduced in mosquitoes fed on infected mice that had been immunized with recombinant CPBAg1. Lastly, mosquitoes fed on anti-CPBAg1 antibodies exhibited reduced reproductive capacity, a secondary effect of a CPB-based TBV that could likely contribute to reducing Plasmodium transmission. These results indicate that A. gambiae CPBs could constitute targets for a TBV that is based upon mosquito molecules.
Published: 2007
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38. Assessment of Plasmodium falciparum resistance to ferroquine (SSR97193) in field isolates and in W2 strain under pressure

Author: Jacques Brocard, Laurent Fraisse, Bruno Pradines, Christophe Biot, Thierry Fandeur, Wassim Daher, Jamal Khalife, Eric Viscogliosi, Daniel Dive, Lydie Pelinski, Hélène Jouin, Schistosomiase, paludisme et inflammation, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Unité de Catalyse et Chimie du Solide - UMR 8181 (UCCS), Centrale Lille Institut (CLIL)-Université d'Artois (UA)-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Lille, UMR INRA / Univ. Tours : Immunologie parasitaire, Institut National de la Recherche Agronomique (INRA)-Université Francois Rabelais [Tours], Biologie et Génétique du Paludisme, Institut Pasteur [Paris], Département découverte, Sanofi Aventis Recherche, Unité de Parasitologie, Institut de Médecine Tropicale du Service de Santé des Armées, This work and Wassim Daher were supported by grants of Sanofi-Aventis and Fondation des Treilles., Université d'Artois (UA)-Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), and Autard, Delphine
Subjects: Metallocenes, Drug Resistance, Protozoan Proteins, Drug resistance, Pharmacology, Parasitic Sensitivity Tests, Chloroquine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Genotype, Cells, Cultured, media_common, 0303 health sciences, Membrane transport protein, Flow Cytometry, 3. Good health, Infectious Diseases, Aminoquinolines, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, SDV:MHEP:MI, medicine.drug, Drug, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, media_common.quotation_subject, Plasmodium falciparum, Biology, lcsh:Infectious and parasitic diseases, Antimalarials, Inhibitory Concentration 50, 03 medical and health sciences, medicine, Animals, lcsh:RC109-216, Amino Acid Sequence, Ferrous Compounds, 030304 developmental biology, Blood Cells, 030306 microbiology, Research, Genetic Variation, Membrane Transport Proteins, biology.organism_classification, medicine.disease, Virology, Parasitology, biology.protein, Malaria
Abstract: Background Ferroquine (FQ), or SSR97193, is a novel antimalarial drug currently in phase I clinical trials. FQ is a unique organometallic compound designed to overcome the chloroquine (CQ) resistance problem. FQ revealed to be equally active on CQ-sensitive and CQ-resistant Plasmodium falciparum laboratory strains and field isolates. FQ is also curative on rodent malaria parasites. As FQ will be tested in patients, the potential for resistance to this drug was evaluated. Methods The relationship between CQ-resistant transporter gene genotype and susceptibility to FQ were studied in 33 Cambodian P. falciparum field isolates previously studied for their in vitro response to CQ. In parallel, the ability of the CQ-resistant strain W2, to become resistant to FQ under drug pressure was assessed. Results The IC50 values for FQ in field isolates were found to be unrelated to mutations occurring in the P. falciparum chloroquine resistance transporter (PfCRT) or to the level of expression of the corresponding mRNA. In vitro, under a drug pressure of 100 nM of FQ, transient survival was observed in only one of two experiments. Conclusion Field isolates studies and experimental drug pressure experiments showed that FQ overcomes CQ resistance, which reinforces the potential of this compound as a new antimalarial drug.
Published: 2006
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39. Probing the role of the covalent linkage of ferrocene into a chloroquine template

Author: Natascha Chavain, Christophe Biot, Cheikh M. N'Diaye, Patricia Melnyk, Jamal Khalife, Alain Pellet, Christian Jarry, Jacques Brocard, Lydie Pelinski, Isabelle Forfar-Bares, Daniel Dive, Wassim Daher, Bruno Pradines, Laurent Fraisse, Unité de Catalyse et Chimie du Solide - UMR 8181 (UCCS), Centrale Lille Institut (CLIL)-Université d'Artois (UA)-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Lille, Schistosomiase, paludisme et inflammation, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Université Lille 2 - Faculté de Médecine, Université de Lille, Institut de Médecine Tropicale du Service de Santé des Armées (IMTSSA), Service de Santé des Armées, SANOFI Recherche, Pharmacochimie (EA2962), Université Bordeaux Segalen - Bordeaux 2, This work was supported by Sanofi Aventis (fellowship attributed to W.D.), by the 'Fondation des Treilles' (fellowship attributed to W.D.) by the CNRS, by the Universités de Lille I and Lille II, and by the Inserm. A BDI fellowship from CNRS and Region Nord-Pas-de-Calais to N.C. is also gratefully acknowledged., C.B. thanks Timothy J. Egan for stimulating discussions and careful reading of the manuscript. L. Maciejewski is acknowledged for helpful discussions. I. Ricard, L. Cattiaux, H. Kalamou, and D. Lamberton are acknowledged for their expert technical intervention., Université d'Artois (UA)-Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Faculté de Médecine Henri Warembourg - Université de Lille
Subjects: MESH: Ferrous Compounds/chemistry, Metallocenes, MESH: Ferrous Compounds/chemical synthesis, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, MESH: Parasitic Sensitivity Tests, MESH: Quinolines/pharmacology, 01 natural sciences, Chemical synthesis, chemistry.chemical_compound, MESH: Structure-Activity Relationship, Parasitic Sensitivity Tests, MESH: Antimalarials/pharmacology, Drug Discovery, MESH: Aminoquinolines, Moiety, MESH: Animals, MESH: Quinolines/chemistry, MESH: Quinolines/chemical synthesis, biology, Chloroquine, MESH: Chloroquine/chemistry, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Covalent bond, Lipophilicity, Aminoquinolines, Quinolines, Molecular Medicine, MESH: Antimalarials/chemical synthesis, Metallocene, Hemeproteins, MESH: Plasmodium falciparum/drug effects, Stereochemistry, MESH: Hemeproteins/antagonists & inhibitors, Plasmodium falciparum, 010402 general chemistry, Antimalarials, Structure-Activity Relationship, MESH: Antimalarials/chemistry, Animals, Structure–activity relationship, Ferrous Compounds, MESH: Hemeproteins/chemical synthesis, 010405 organic chemistry, biology.organism_classification, MESH: Ferrous Compounds/pharmacology, 0104 chemical sciences, Ferrocene, chemistry
Abstract: A new therapeutic approach to malaria led to the discovery of ferroquine (FQ, SR97276). To assess the importance of the linkage of the ferrocenyl group to a 4-aminoquinoline scaffold, two series of 4-aminoquinolines, structurally related to FQ, were synthesized. Evaluation of antimalarial activity, physicochemical parameters, and the beta-hematin inhibition property indicate that the ferrocene moiety has to be covalently flanked by a 4-aminoquinoline and an alkylamine. Current data reinforced our choice of FQ as a drug candidate.
Published: 2006
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40. Navigation in Arthropods

Author: Durier, Virginie, Ethologie, éVolution, Ecologie (EVE), Ethologie animale et humaine (EthoS), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Fondation des Treilles, ETHOS, UMR6552, Normandie Université (NU)-Normandie Université (NU)-Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)-Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2005

41. cpbAg1 encodes an active carboxypeptidase B expressed in the midgut of Anopheles gambiae

Author: Catherine Lavazec, Catherine Bourgouin, I. Thiery, Sarah Bonnet, Bertrand Boisson, Biologie et Génétique du Paludisme, Institut Pasteur [Paris] (IP), Immunologie moléculaire des parasites, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and This project was supported by fellowships to C. Lavazec (F. Lacoste, CANAM, Fondation des Treilles) and B. Boisson (Pasteur Institute, GPH Anopheles) and research funds from the Pasteur Institute and the French Ministry of Research (PAL + Special Program). We are specially grateful to F. Lacoste for constant support of C. Lavazec.
Subjects: digestive enzyme, Protein Conformation, Sequence analysis, Recombinant Fusion Proteins, Anopheles gambiae, [SDV]Life Sciences [q-bio], Blotting, Western, Molecular Sequence Data, Down-Regulation, Genes, Insect, midgut, carboxypeptidase B, Anopheles, parasitic diseases, Genetics, Animals, Cluster Analysis, Amino Acid Sequence, RNA, Messenger, Molecular Biology, Gene, Peptide sequence, Conserved Sequence, Phylogeny, DNA Primers, Differential display, Base Sequence, biology, Reverse Transcriptase Polymerase Chain Reaction, fungi, Plasmodium falciparum, Midgut, Sequence Analysis, DNA, biology.organism_classification, Molecular biology, Carboxypeptidase, Gastrointestinal Tract, Multigene Family, Insect Science, biology.protein, gene family, Sequence Alignment
Abstract: International audience; We previously used differential display to identify several Anopheles gambiae genes, whose expression in the mosquito midgut was regulated upon ingestion of Plasmodium falciparum. Here, we report the characterization of one of these genes, cpbAg1 , which codes for the first zinc-carboxypeptidase B identified in An. gambiae and in any insect. Expression of cpbAg1 in baculovirus gave rise to an active enzyme, and determination of the N-terminal amino acids confirmed that CPBAg1 contains a signal peptide and a pro-peptide, typical features of digestive zinc carboxypeptidases. cpbAg1 mRNA was mainly produced in the mosquito midgut, where it accumulated in unfed females and was rapidly down-regulated upon blood feeding. Annotation of the An. gambiae genome predicts twentythree sequences coding for zinc-carboxypeptidases of which only two (cpbAg1 and cpbAg2) are expressed at a significant level in the mosquito midgut.
Published: 2005
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42. Polymorphisms in Anopheles gambiae Immune Genes Associated with Natural Resistance to Plasmodium falciparum

Author: Luc Abate, Caroline Harris, François Rousset, Isabelle Morlais, Didier Fontenille, Anna Cohuet, Louis Lambrechts, Sandrine E. Nsango, Caractérisation et contrôle des populations de vecteurs, Institut de Recherche pour le Développement (IRD), Département de Virologie - Department of Virology, Institut Pasteur [Paris] (IP), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement [Yaoundé, Cameroun] (IRD-OCEAC), Institut de Recherche en Sciences de la Santé Bobo Dioulasso (INSSA), Université Polytechnique Nazi Boni Bobo-Dioulasso (UNB), This project was funded by ANR (grant awarded to AC ANR-06-MIME-001-01) and Fondation des Treilles (http://www.les-treilles.com/newsite/ awarded to CH)., ANR-06-MIME-0001,API,Intéractions Anopheles-Plasmodium et transmission du paludime en conditions naturelles(2006), Institut Pasteur [Paris], Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), and Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)
Subjects: Linkage disequilibrium, Anopheles gambiae, Immunology/Innate Immunity, Genes, Insect, MESH: Genes, Insect, MESH: Africa, Polymerase Chain Reaction, Linkage Disequilibrium, MESH: Genotype, 0302 clinical medicine, MESH: Child, Genotype, MESH: Animals, Cameroon, Malaria, Falciparum, Biology (General), Child, Genetics and Genomics/Genetics of Disease, MESH: Plasmodium falciparum, Genetics, 0303 health sciences, biology, Genetics and Genomics/Functional Genomics, MESH: Malaria, Falciparum, MESH: Polymorphism, Single Nucleotide, Anopheles, Genetics and Genomics/Microbial Evolution and Genomics, 3. Good health, Phenotype, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Linkage Disequilibrium, Child, Preschool, Genetics and Genomics/Genetics of the Immune System, MESH: Immunity, Innate, Research Article, medicine.medical_specialty, QH301-705.5, Plasmodium falciparum, 030231 tropical medicine, Immunology, Single-nucleotide polymorphism, Genetics and Genomics/Complex Traits, MESH: Phenotype, Polymorphism, Single Nucleotide, MESH: Host-Parasite Interactions, Microbiology, Host-Parasite Interactions, MESH: Anopheles, 03 medical and health sciences, Immunology/Immunity to Infections, Virology, Molecular genetics, Genetics and Genomics/Population Genetics, parasitic diseases, Genetic variation, medicine, Animals, Humans, Molecular Biology, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, MESH: Child, Preschool, Infectious Diseases/Protozoal Infections, MESH: Polymerase Chain Reaction, RC581-607, MESH: Cameroon, biology.organism_classification, Immunity, Innate, Africa, Immunology/Immune Response, Parasitology, Immunologic diseases. Allergy, Immunology/Genetics of the Immune System
Abstract: Many genes involved in the immune response of Anopheles gambiae, the main malaria vector in Africa, have been identified, but whether naturally occurring polymorphisms in these genes underlie variation in resistance to the human malaria parasite, Plasmodium falciparum, is currently unknown. Here we carried out a candidate gene association study to identify single nucleotide polymorphisms (SNPs) associated with natural resistance to P. falciparum. A. gambiae M form mosquitoes from Cameroon were experimentally challenged with three local wild P. falciparum isolates. Statistical associations were assessed between 157 SNPs selected from a set of 67 A. gambiae immune-related genes and the level of infection. Isolate-specific associations were accounted for by including the effect of the isolate in the analysis. Five SNPs were significantly associated to the infection phenotype, located within or upstream of AgMDL1, CEC1, Sp PPO activate, Sp SNAKElike, and TOLL6. Low overall and local linkage disequilibrium indicated high specificity in the loci found. Association between infection phenotype and two SNPs was isolate-specific, providing the first evidence of vector genotype by parasite isolate interactions at the molecular level. Four SNPs were associated to either oocyst presence or load, indicating that the genetic basis of infection prevalence and intensity may differ. The validity of the approach was verified by confirming the functional role of Sp SNAKElike in gene silencing assays. These results strongly support the role of genetic variation within or near these five A. gambiae immune genes, in concert with other genes, in natural resistance to P. falciparum. They emphasize the need to distinguish between infection prevalence and intensity and to account for the genetic specificity of vector-parasite interactions in dissecting the genetic basis of Anopheles resistance to human malaria., Author Summary Anopheles gambiae is the main malaria vector in Africa, transmitting the parasite when it blood feeds on human hosts. The parasite undergoes several developmental stages in the mosquito to complete its life cycle, during which time it is confronted by the mosquito's immune system. The resistance of mosquitoes to malaria infection is highly variable in wild populations and is known to be under strong genetic control, but to date the specific genes responsible for this variation remain to be identified. The present study uncovers variations in A. gambiae immune genes that are associated with natural resistance to Plasmodium falciparum, the deadliest human malaria parasite. The association of some mosquito genetic loci with the level of infection depended on the P. falciparum isolate, suggesting that resistance is determined by interactions between the genome of the mosquito and that of the parasite. This finding highlights the need to account for the natural genetic diversity of malaria parasites in future research on vector-parasite interactions. The loci uncovered in this study are potential targets for developing novel malaria control strategies based on natural mosquito resistance mechanisms.
Published: 2010
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43. 'Aesthetic Controversies?'

Author: Bénédicte Coste, Coste, Bénédicte, Centre Interlangues : texte, image, langage [Dijon] ( TIL ), Université de Bourgogne ( UB ) -Université Bourgogne Franche-Comté ( UBFC ), Fondation des Treilles, Bénédicte Coste, Centre Interlangues : texte, image, langage [Dijon] (TIL), and Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: [SHS.LITT] Humanities and Social Sciences/Literature, [SHS.LITT]Humanities and Social Sciences/Literature, Dante Gabriel Rossetti, Algernon Charles Swinburne, [ SHS.LITT ] Humanities and Social Sciences/Literature, Robert Buchanan, British Aestheticism, controversy studies
Abstract: International audience; My presentation will be devoted to the study of one remarkable Aesthetic controversy, the ‘Fleshly School of Poetry’ opposing Robert Buchanan, poet and, at the time, literary journalist, and some aesthetes including William Morris, Algernon Charles Swinburne and Dante Gabriel Rossetti. The controversy erupted when Buchanan published a violent attack, ‘The Fleshly School of Poetry’ under the pseudonym of Thomas Maitland in the Contemporary Review in 1871, and lasted, I’ll argue, until the early 1880s. This case study is part of a larger project retracing the history of British Aestheticism through the many controversies, scandals and polemics the movement elicited from the early 1860s to the 1890s.The first part of my talk will be devoted to presenting definitions of ‘controversy’ and controversy studies. I contend that the study of literary controversies deserves a place within controversy studies, most of which focus on religious or scientific controversies. However controversies need to be carefully defined both as debates and disputes involving a third party and as political events and frames to shape and regulate the political debate as well. The second part of the talk will be devoted to presenting the ‘Fleshly School of Poetry’ controversy from its very inception to what is arguably its end with the publication of ‘Dante Gabriel Rossetti’ by Walter Pater in 1883. A precise timeline will accompany the presentation of a methodology for studying Victorian literary controversies: protagonists, networks of sociability, stakes of the controversy, media (magazines, newspapers, pamphlets and essays), texts (both published and unpublished) and genres of the controversy.In conclusion, I’ll discuss the ending of the controversy, its impact on the reception of Aestheticism and on canon formation. I’ll also point out some discursive dimensions that need to be more thoroughly explored to have a better understanding of controversies as discursive practices.Studying aesthetic and literary movement through the lens of controversies is valuable and should be situated within a larger political frame. This frame appears to be characterized by what could be termed a ‘culture of dissensus’. Within the larger frame of the late-Victorian politics characterized by democratisation, mass education and the contest of several political views for cultural and political hegemony, British Aestheticism should be seen as a political ‘dissenting event’.

44. La scrittura dello spazio minerario: Produzione e pratiche di scrittura documentaria intorno alle miniere d'argento della Linguadoca (XII-XV secolo)

Author: Nicolas Minvielle Larousse, Laboratoire d'Archéologie Médiévale et Moderne en Méditerranée (LA3M), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Ecole française de Rome (EFR), Laboratoire d'excellence - Les sciences humaines et sociales au cœur de l’interdisciplinarité pour la Méditerranée (LabexMed), LabexMed, Fondation des Treilles, and Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Moyen âge central, Medioevo, Miniere, Mines d'argent, Middle Ages XIIth-XVth c, [SHS.HIST]Humanities and Social Sciences/History, Languedoc -- France, Silver mines, Linguadoca, [SHS]Humanities and Social Sciences
Abstract: International audience; This contribution proposes to examine the production and practices of documentary writing generated by the actors of the silver mines of eastern Languedoc. In the absence of archives constituted for this field of the history of work and techniques, it is on the basis of a heterogeneous corpus of 261 documents from the 12th to the 15th century that the reflections will be conducted. The aim is to examine the place that writing took in the production process, to question its relationship with orality and to identify the different uses of writing, from their initial functions to their alterations.; Cette contribution propose d’examiner les productions et pratiques de l’écrit documentaire générées par les acteurs des mines argentifères du Languedoc oriental. En l’absence d’archives constituées pour ce domaine de l’histoire du travail et des techniques, c’est à partir d’un corpus hétérogène de 261 documents allant du xiie au xve siècle que les réflexions seront conduites. L’objectif est d’interroger la place que prenait l’écrit dans le processus de production, de questionner son rapport avec l’oralité et d’identifier les différents usages de l’écrit, de leurs fonctions initiales à leurs altérations.; Questo contributo si propone di esaminare la produzione e le pratiche di scrittura documentaria generate dagli attori delle miniere d'argento della Linguadoca orientale. In mancanza di archivi costituiti per questo campo della storia del lavoro e delle tecniche, è sulla base di un corpus eterogeneo di 261 documenti dal XII al XV secolo che si condurranno le riflessioni. L'obiettivo è quello di esaminare il posto che la scrittura occupava nel processo di produzione, di mettere in discussione la sua relazione con l'oralità e di identificare i diversi usi della scrittura, dalle loro funzioni iniziali alle loro alterazioni.
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45. La(es) valeur(s) de la biodiversité à travers le prisme des quotas de pêche

Author: Sophie GAMBARDELLA, Droits International, Comparé et Européen / Centre d'études et de recherches internationales et communautaires (CERIC) (DICE / CERIC), Droits International, Comparé et Européen (DICE), Centre National de la Recherche Scientifique (CNRS)-Université de Toulon (UTLN)-Université de Pau et des Pays de l'Adour (UPPA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Université de Toulon (UTLN)-Université de Pau et des Pays de l'Adour (UPPA)-Aix Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS)-Université de Toulon (UTLN)-Université de Pau et des Pays de l'Adour (UPPA)-Aix Marseille Université (AMU), Eve Truilhé-Marengo et Mathilde Boutonnet, Aix Marseille Université (AMU)-Université de Pau et des Pays de l'Adour (UPPA)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Université de Pau et des Pays de l'Adour (UPPA)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Université de Pau et des Pays de l'Adour (UPPA)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Sociétés, Acteurs, Gouvernement en Europe (SAGE), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Fondation des Treilles, and Gambardella, Sophie
Subjects: [SHS.DROIT]Humanities and Social Sciences/Law, [SHS.DROIT] Humanities and Social Sciences/Law, valeur, Droit international de l'environnement, Droit international de la mer, ComputingMilieux_MISCELLANEOUS, biodiversité
Abstract: International audience; « La(es) valeur(s) de la biodiversité à travers le prisme des quotas de pêche », in BOUTONNET (M.), TRUILHE-MARENGO (E.) (Dirs.), « Affirmer que quelque chose existe, ce n'est pas seulement affirmer l'être auquel cette chose se rattache, c'est-à-dire une nécessité dont elle dépend et qui lui permet de s'offrir à nos sens, c'est encore et d'abord affirmer que quelque chose doit-être, c'est-à dire a une valeur » 1 Engager une réflexion sur la ou les valeur(s) de la biodiversité marine à travers le prisme d'un des instruments de régulation des pêches-le quota de pêche-nécessite, au préalable, de s'interroger sur la notion même de « valeur ». Du latin valor, la notion de valeur est utilisée dans de nombreux domaines-en économie, en philosophie, en mathématiques notamment-sans qu'elle ne recouvre le même sens dans chacune de ces disciplines. Polysémique, la notion de « valeur » est aussi bien souvent accompagnée d'un qualificatif. Nous parlons communément de valeurs morales, de valeurs économiques, de valeurs écologiques ou encore de valeurs esthétiques. De manière tout à fait singulière, alors que l'usage du terme de valeur se banalise, sa signification est effritée au point que la notion de valeur est couramment associée à la notion d'évaluation, entendue comme un jugement porté sur un objet ou une personne. Déterminer la ou les valeur(s) de quelque chose ou de quelqu'un reviendrait à se livrer à une évaluation de l'objet ou de la personne concernée. Cette approche de la notion de valeur empêche alors de considérer qu'il existe des valeurs intrinsèques et objectives puisque la valeur n'est que le résultat d'une considération subjective liée à la libre appréciation de chacun. A notre sens, il nous faut changer de paradigme pour apprécier la notion de valeur dans toute sa dimension. Partant du postulat que l'appréciation de la ou des valeur(s) d'un objet ou d'une personne nécessite l'intervention d'un tiers pour les mettre en exergue, cela conduit-il nécessairement à se livrer à une évaluation, au sens d'un jugement porté sur un objet ou sur une personne ? Pas nécessairement. Le terme d'évaluation vient du latin valere qui signifie être fort, avoir de l'importance et le terme de valeur en dérive directement. L'évaluation ne se résumerait alors pas nécessairement à porter un jugement. Evaluer ne signifierait pas décider ce qui a de l'importance mais seulement constater ce qui en a. Entendue de la sorte le premier degré d'évaluation qui consisterait à rechercher les valeurs d'un objet ou d'une personne ne serait qu'un processus de reconnaissance de ces valeurs et non de hiérarchisation de celles-ci en fonction de préférences. Ainsi, l'évaluation de la biodiversité devrait davantage conduire à se demander de quelle(s) valeur(s) est porteuse la biodiversité plutôt que de se demander quelle(s) valeur(s) nous attribuons à la biodiversité. Ce changement de perspective invite ainsi à refuser de penser la biodiversité à partir du regard 1 LAGNEAU (J.), Célèbres leçons et fragments, Presses Universitaires de France, 1950, p. 259.

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