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154. Peripheral neuropathy and livedoid vasculopathy

Author

Antoine Soulages, Thierry Maisonobe, Pascal Auzou, Antoine Petit, Yves Allenbach, Stéphane Barète, Sophie Skopinski, Emmanuel Ribeiro, Marie-Laure Jullié, Laurence Lamant, Françoise Brevet, Xavier Soulages, Jean-Michel Vallat, Marie-Laure Martin-Négrier, Guilhem Solé, Fanny Duval, Louis Carla, Gwendal Le Masson, Stéphane Mathis, Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital Pellegrin, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional d'Orléans (CHRO), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Bordeaux [Bordeaux], Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Dupuytren [CHU Limoges], Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), and Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Male, Vasculitis, [SDV]Life Sciences [q-bio], Livedoid Vasculopathy, Mononeuropathies, Peripheral Nervous System Diseases, Middle Aged, Neurology, Humans, Female, Neurology (clinical), Aged, Skin
Abstract

Livedoid vasculopathy (LV) is a chronic dermatosis associated with micro-thrombosis of the vessels of the dermis, leading to ischemic lesions and painful skin ulcerations of the lower limbs. This thrombosing occlusive vasculopathy, clearly distinct from 'classical vasculitis' (not related to alteration of vessel walls), may lead to peripheral neuropathy.To clarify the main clinical, electrophysiological and pathological characteristics of peripheral neuropathy linked to LV.We presented a series of personal cases of peripheral neuropathy due to LV. We also conducted a review of the literature (since the first description of LV in 1974) using multiple combinations of keywords from 'PubMed', 'Google Scholar' and 'ScienceDirect' databases according to the 'Preferred Reporting Items for Systematic reviews and Meta-Analyses' guidelines.We identified 16 patients (6 personal cases and 10 cases from the medical literature). Our personal cases were five females and one male, with a median age (at the onset of cutaneous signs of LV) of 38 (range 25-62). Several types of skin lesions of the lower limbs were observed. Median age at the onset of peripheral neuropathy symptoms was 48 years (range 29-66), with a main clinical and electrophysiological pattern of mononeuropathy multiplex.We observed a typical pattern of peripheral neuropathy, mostly mononeuropathy multiplex, whose pathophysiology might be related to occlusions of the small vessels of the nerves, as seen in the dermis. Moreover, LV may also be associated with other types of peripheral neuropathies (sometimes of autoimmune etiology) not directly related to the skin lesions.The 'ischemic form' of peripheral neuropathy linked to LV is mainly responsible for sensory disturbances (with multifocal distribution), sometimes for motor disturbances. This type of peripheral neuropathy has to be distinguished from 'classical vasculitic neuropathies' which are usually treated with antithrombotic therapies.

Published
2022
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155. Supplemental Tables 1 through 3 from Lysyl Oxidase Is a Strong Determinant of Tumor Cell Colonization in Bone

Author

Philippe Clézardin, Marie Brevet, Antoine E. Karnoub, Géraldine Aimond, Clémence Thomas, Floriane Pez, Edith Bonnelye, Martine Croset, Casina Kan, Paola Di Mauro, Laura Ferreras, and Caroline Reynaud

Abstract

Supplementary Table S1. Primer pairs used for quantitative real-time PCR analysis. Supplementary Table S2. Summary of the gene expression datasets used for meta-analysis. Supplementary Table S3. Expression levels of LOX-like mRNAs in Hct116 cells transduced for LOX overexpression (LOX+) or silencing (LOX-), compared to mock-transduced Hct116 cells (Ctrl).

Published
2023
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156. Data from Lysyl Oxidase Is a Strong Determinant of Tumor Cell Colonization in Bone

Author

Philippe Clézardin, Marie Brevet, Antoine E. Karnoub, Géraldine Aimond, Clémence Thomas, Floriane Pez, Edith Bonnelye, Martine Croset, Casina Kan, Paola Di Mauro, Laura Ferreras, and Caroline Reynaud

Abstract

Lysyl oxidase (LOX) is a secreted copper-dependent amine oxidase whose primary function is to drive collagen crosslinking and extracellular matrix stiffness. LOX in colorectal cancer synergizes with hypoxia-inducible factor-1 (HIF-1) to promote tumor progression. Here we investigated whether LOX/HIF1 endows colorectal cancer cells with full competence for aggressive colonization in bone. We show that a high LOX expression in primary tumors from patients with colorectal cancer was associated with poor clinical outcome, irrespective of HIF-1. In addition, LOX was expressed by tumor cells in the bone marrow from colorectal cancer patients with bone metastases. In vivo experimental studies show that LOX overexpression in colorectal cancer cells or systemic delivery of the conditioned medium from LOX-overexpressing colorectal cancer cells promoted tumor cell dissemination in the bone marrow and enhanced osteolytic lesion formation, irrespective of HIF-1. Conversely, silencing or pharmacologic inhibition of LOX activity blocked dissemination of colorectal cancer cells in the bone marrow and tumor-driven osteolytic lesion formation. In vitro, tumor-secreted LOX supported the attachment and survival of colorectal cancer cells to and in the bone matrix, and inhibited osteoblast differentiation. LOX overexpression in colorectal cancer cells also induced a robust production of IL6. In turn, both LOX and IL6 were acting in concert to promote RANKL-dependent osteoclast differentiation, thereby creating an imbalance between bone resorption and bone formation. Collectively, our findings show that LOX supports colorectal cancer cell dissemination in the bone marrow and they reveal a novel mechanism through which LOX-driven IL6 production by colorectal cancer cells impairs bone homeostasis. Cancer Res; 77(2); 268–78. ©2016 AACR.

Published
2023
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158. Supplemental Figures 1 through 7 from Lysyl Oxidase Is a Strong Determinant of Tumor Cell Colonization in Bone

Author

Philippe Clézardin, Marie Brevet, Antoine E. Karnoub, Géraldine Aimond, Clémence Thomas, Floriane Pez, Edith Bonnelye, Martine Croset, Casina Kan, Paola Di Mauro, Laura Ferreras, and Caroline Reynaud

Abstract

Figure S1: LOX expression and clinical outcomes. Figure S2:The LOX inhibitor βAPN inhibits osteolytic lesion formation in vivo. Figure S3: Measurement of LOX enzymatic activity. Figure S4: Correlation analysis of the expression intensity of LOX and IL-6. Figure S5: Effects of LOX expression on EMT in Hct116 colorectal cancer cells. Figure S6: Effect of LOX on attachment of colorectal cancer cells to fibronectin. Figure S7: LOX enhances survival of Hct116 colorectal cancer cells.

Published
2023
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159. Multiomic analysis of malignant pleural mesothelioma identifies molecular axes and specialized tumor profiles driving intertumor heterogeneity

Author

Lise Mangiante, Nicolas Alcala, Alexandra Sexton-Oates, Alex Di Genova, Abel Gonzalez-Perez, Azhar Khandekar, Erik N. Bergstrom, Jaehee Kim, Xiran Liu, Ricardo Blazquez-Encinas, Colin Giacobi, Nolwenn Le Stang, Sandrine Boyault, Cyrille Cuenin, Severine Tabone-Eglinger, Francesca Damiola, Catherine Voegele, Maude Ardin, Marie-Cecile Michallet, Lorraine Soudade, Tiffany M. Delhomme, Arnaud Poret, Marie Brevet, Marie-Christine Copin, Sophie Giusiano-Courcambeck, Diane Damotte, Cecile Girard, Veronique Hofman, Paul Hofman, Jérôme Mouroux, Charlotte Cohen, Stephanie Lacomme, Julien Mazieres, Vincent Thomas de Montpreville, Corinne Perrin, Gaetane Planchard, Nathalie Rousseau, Isabelle Rouquette, Christine Sagan, Arnaud Scherpereel, Francoise Thivolet, Jean-Michel Vignaud, Didier Jean, Anabelle Gilg Soit Ilg, Robert Olaso, Vincent Meyer, Anne Boland-Auge, Jean-Francois Deleuze, Janine Altmuller, Peter Nuernberg, Alejandro Ibáñez-Costa, Justo P. Castaño, Sylvie Lantuejoul, Akram Ghantous, Charles Maussion, Pierre Courtiol, Hector Hernandez-Vargas, Christophe Caux, Nicolas Girard, Nuria Lopez-Bigas, Ludmil B. Alexandrov, Françoise Galateau-Salle, Matthieu Foll, Lynnette Fernandez-Cuesta, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Stanford University, Universidad de O'Higgins (UOH), Centre de modélisation mathématique (CMM), Universitad de Chile-Centre National de la Recherche Scientifique (CNRS), Barcelona Institute of Science and Technology (BIST), Instituto de Salud Carlos III [Madrid] (ISC), University of California [San Diego] (UC San Diego), University of California (UC), Cornell University [New York], Maimonides Institute of Biomedical Research of Cordoba, Partenaires INRAE, Universidad de Córdoba = University of Córdoba [Córdoba], Hospital Universitario Reina Sofia [Cordoue, Espagne], CIBER Fisiopatología de la Obesidad y Nutrición [Cordoue, Espagne] (CIBEROBN), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Cypath and Cypath-rb [Villeurbanne] (2C), Tumorothèque du Centre de Référence Régional en Cancérologie [CHRU Lille] (T-C2RC), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut de Pathologie de Lille (IPL), Hôpital Nord [CHU - APHM], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Tumorothèque - Centre de Ressources Biologiques Cancer Cochin [Hôpital Cochin AP-HP] (T-CRB Cancer Cochin), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupes hospitalo-universitaires Paris Centre AP-HP [Paris] (GHU Paris Centre), FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Université Côte d'Azur (UCA), Université Côte d'Azur (UCA), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Pasteur [Nice] (CHU), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Marie-Lannelongue, Tissu-Tumorothèque Est - Centre de Ressources Biologiques [HCL, Lyon] (2TE - CRB HCL), Hospices Civils de Lyon (HCL), Réseau d'expertise anatomopathologique et de recherche sur les tumeurs de la plèvre [CHU Caen] (MESOPATH), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Ressources Biologiques - Cancer - IUCT Oncopole [Toulouse] (CRB - Cancer Toulouse), Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Cologne Centre for Genomics [Cologne, Germany] (2CG), Instituto Maimonides de Investigación Biomédica de Cordoba (IMIBIC), Universidad de Córdoba = University of Córdoba [Córdoba]-Hospital Universitario Reina Sofía, Université Grenoble Alpes (UGA), Owkin [New York, NY, USA] (O), Institut Curie [Paris], Institut Mutualiste de Montsouris (IMM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, and Institució Catalana de Recerca i Estudis Avançats (ICREA)

Subjects
[SDV]Life Sciences [q-bio], Genetics, Technology Platforms
Abstract

Malignant pleural mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Through a large series of whole-genome sequencing data, integrated with transcriptomic and epigenomic data using multiomics factor analysis, we demonstrate that the current World Health Organization classification only accounts for up to 10% of interpatient molecular differences. Instead, the MESOMICS project paves the way for a morphomolecular classification of MPM based on four dimensions: ploidy, tumor cell morphology, adaptive immune response and CpG island methylator profile. We show that these four dimensions are complementary, capture major interpatient molecular differences and are delimited by extreme phenotypes that—in the case of the interdependent tumor cell morphology and adapted immune response—reflect tumor specialization. These findings unearth the interplay between MPM functional biology and its genomic history, and provide insights into the variations observed in the clinical behavior of patients with MPM.

Published
2023
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160. Rare CNVs and phenome-wide profiling highlight brain structural divergence and phenotypical convergence

Author

Jakub Kopal, Kuldeep Kumar, Karin Saltoun, Claudia Modenato, Clara A. Moreau, Sandra Martin-Brevet, Guillaume Huguet, Martineau Jean-Louis, Charles-Olivier Martin, Zohra Saci, Nadine Younis, Petra Tamer, Elise Douard, Anne M. Maillard, Borja Rodriguez-Herreros, Aurèlie Pain, Sonia Richetin, Leila Kushan, Ana I. Silva, Marianne B. M. van den Bree, David E. J. Linden, Michael J. Owen, Jeremy Hall, Sarah Lippé, Bogdan Draganski, Ida E. Sønderby, Ole A. Andreassen, David C. Glahn, Paul M. Thompson, Carrie E. Bearden, Sébastien Jacquemont, and Danilo Bzdok

Subjects
Behavioral Neuroscience, Social Psychology, Experimental and Cognitive Psychology
Published
2023
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162. La réponse anti-fibrinogène carbamylé dans la polyarthrite rhumatoïde est associée à un pronostic structural plus sévère (cohorte ESPOIR) et cible des épitopes sans cross-réaction avec les ACPA.

Author

Brevet, P., Gérard, B., De Maleprade, B., Candon, S., Boyer, O., Lequerré, T., Vittecoq, O., and Freret, M.

Abstract

La double positivité ACPA (anti-protéines citrullinées)/anti-CarP (anti-protéines carbamylées) semble être associée à un pronostic plus sombre de la polyarthrite rhumatoïde (PR). Les cibles antigéniques in situ des anti-CarP étant encore inconnues, du sérum de veau fœtal (SVF) carbamylé a été jusqu'à présent utilisé comme cible pour les dosages ELISA. Les antigènes cibles des anti-CarP pourraient être différents selon le statut ACPA des patients. Ainsi, Jones et coll. ont montré que chez des patients ACPA-, les anti-CarP reconnaissaient préférentiellement la chaine β du fibrinogène carbamylé [1]. Nos précédents travaux ont permis d'identifier la chaine ϒ du fibrinogène comme un antigène spécifique de la réponse anticorps anti-fibrinogène carbamylé (ACa-Fib). Nous avons montré que la présence des ACa-Fib IgG semblait associée à une inflammation systémique tandis que le pronostic structural sombre restait associé aux ACPA chez les patients de la cohorte régionale VerA [2]. Truchetet et coll. ayant montré des atteintes radiologiques plus sévères chez les patients PR ACPA+/anti-CarP + (SVF) de la cohorte nationale ESPOIR à un temps donné [3]. Notre objectif est de confirmer nos Résultats dans la cohorte ESPOIR et de déterminer la signification clinique des ACa-Fib IgG et IgA à différents temps, comparativement aux ACPA. Un objectif secondaire étant l'identification des épitopes immunodominants reconnus par les ACa-Fib et d'étudier leur réactivité vis-à-vis de ces épitopes, comparativement aux ACPA. Nous avons mis au point des dosages sériques par ELISA pour la détection des ACa-Fib IgG et IgA chez les patients de la cohorte ESPOIR, et ainsi évalué leurs valeurs diagnostique et pronostique. Nous avons également réalisé un mapping épitopique sur la chaine α du fibrinogène carbamylé (15 peptides 27-Mer chevauchants sur 3 acides aminés) pour la reconnaissance des ACa-Fib IgG. 28 % des patients atteints de PR de la cohorte ESPOIR (n = 575) sont positifs pour les ACa-Fib IgG et 8 % pour les ACa-Fib IgA. La prévalence des ACa-Fib IgG diminue après 2 ans (11 %) mais reste stable pour les ACa-Fib IgA (6 %). Parmi les patients ACPA-, 17 % d'entre eux sont ACa-Fib+ pour les IgG et 6 % pour les IgA, démontrant un intérêt diagnostique pour les ACa-Fib. Si la positivité ACa-Fib IgG ou IgA ne semble pas impacter l'activité de la PR, nous montrons que la double positivité ACPA/ACa-Fib IgG est associée à un pronostic structural significativement plus sévère à 2 ans comparativement aux ACPA seuls (p -value = 0,0125). Nous montrons également la valeur pronostique des ACa-Fib IgG et IgA avec un pourcentage plus important de patients ayant une progression radiologique rapide lorsque ceux-ci possèdent une double positivité ACPA/ACa-Fib, comparativement aux ACPA seuls (42 % pour les patients ACPA+/ACa-Fib+ IgG contre 27 % pour les ACPA+ ; 50 % pour les ACPA+/ACa-Fib+ IgA contre 31 % pour les ACPA +). Enfin, nous avons mis en évidence, à l'aide de sérums de patients PR ACa-Fib+ IgG, 3 épitopes immunodominants sur la chaine α du fibrinogène carbamylé, avec une cross-réaction très faible, voire nulle, de la réponse anti-fibrinogène citrulliné. Ceci renforçant leur intérêt diagnostique dans la PR ACPA-. Les ACa-Fib IgG et IgA possèdent un intérêt diagnostique chez les patients PR ACPA-, et également une valeur pronostique chez les patients ACPA+ constituant un facteur de gravité supplémentaire. De plus, la réponse auto-immune IgG contre le fibrinogène carbamylé reconnaît majoritairement des épitopes immunodominants sans cross-réaction avec la réponse citrullinée, renforçant leur intérêt diagnostique. [ABSTRACT FROM AUTHOR]

Published
2024
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163. Le Minier (France, Aveyron) : fouille et dosage géochimique d'ateliers du XIIIe siècle de préparation de minerais argentifères

Author

Minvielle Larousse, Nicolas, Brevet, Lucille, Laurent, Sarah, Rinalducci, Véronique, Tomczyk, Céline, Ecole française de Rome (EFR), Laboratoire d'Archéologie Médiévale et Moderne en Méditerranée (LA3M), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut national de recherches archéologiques préventives (Inrap), Centre européen de recherche et d'enseignement des géosciences de l'environnement (CEREGE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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)-Centre National de la Recherche Scientifique (CNRS), Archéologies environnementales, 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)-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)-Centre National de la Recherche Scientifique (CNRS), Archéologie et Philologie d'Orient et d'Occident (AOROC), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Département des Sciences de l'Antiquité - ENS Paris (DSA ENS-PSL), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL), Ministère de la Culture, Région Occitanie, Conseil départemental de l'Aveyron, SAFEMM, 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)-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), and École pratique des hautes études (EPHE)

Subjects
lead, workshop, pxrf, [CHIM]Chemical Sciences, silver, Mining archaeology, Middle ages, [SHS]Humanities and Social Sciences
Abstract

International audience

Published
2022

169. Harmonic generation at the nanoscale.

Author

Bonacina, Luigi, Brevet, Pierre-François, Finazzi, Marco, and Celebrano, Michele

Subjects
*HARMONIC generation, *MATERIALS science, *COHERENCE (Optics), *IMAGE processing, *LIGHT sources, *NANOMEDICINE
Abstract

Nonlinear photon conversion is a fundamental physical process that lies on the basis of many modern disciplines, from bioimaging and theranostics in nanomedicine to material characterization in materials science and nanotechnology. It also holds great promise in laser physics with applications in information technology for optical signal processing and in the development of novel coherent light sources. The capability to efficiently generate harmonics at the nanoscale will have an enormous impact on all these fields, since it would allow one to realize much more compact devices and to interrogate matter in extremely confined volumes. Here, we present a perspective on the most recent advances in the generation of nonlinear optical processes at the nanoscale and their applications, proposing a palette of future perspectives that range from material characterization and the development of novel compact platforms for efficient photon conversion to bioimaging and sensing. [ABSTRACT FROM AUTHOR]

Published
2020
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170. Multistep Micellization of Standard Surfactants Evidenced by Second Harmonic Scattering

Author

Emmanuel Benichou, Pierre F. Brevet, Oriane Bonhomme, L. Sanchez, Optique non linéaire et interfaces (ONLI), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
Ammonium bromide, Materials science, Surfactants, Thermodynamics, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Micelle, [SPI]Engineering Sciences [physics], Surface-Active Agents, chemistry.chemical_compound, Materials Chemistry, [CHIM]Chemical Sciences, Molecule, Physical and Theoretical Chemistry, Sodium dodecyl sulfate, Micelles, [PHYS]Physics [physics], Optical properties, Scattering, Sodium Dodecyl Sulfate, Nonlinear optics, Micellization, Molecules, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Surfaces, Coatings and Films, Monomer, chemistry, Second Harmonic Generation Microscopy, Critical micelle concentration, 0210 nano-technology
Abstract

International audience; Processes involving in solution a reduced number of molecules are difficult to identify and characterize. Here, we show that micellization of standard surfactants, namely sodium dodecyl sulfate and trimethyl tetradecyl ammonium bromide, two nonefficient compounds for quadratic nonlinear optics, can be investigated by second harmonic scattering (SHS). In particular, the formation of aggregates at concentrations smaller than the critical micellar concentration is evidenced through a nonmonotonic behavior of the SHS intensity as a function of the surfactant concentration. A simple model based on chemical equilibria between monomers and micelles is proposed to account for the experimental observations. Signature of long-range molecular orientation correlation is revealed by polarization resolved experiments and is discussed regarding micellization and charge-induced effects.

Published
2021
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171. Vascularites à ANCA précédées d’une atteinte articulaire isolée. À propos de deux cas et revue de la littérature

Author

Charles Zarnitsky, P. Brevet, C. Princivil, A. Curie, and D. Alcaix

Subjects
030203 arthritis & rheumatology, 0301 basic medicine, Gynecology, medicine.medical_specialty, Anca vasculitis, business.industry, Gastroenterology, ANCA-Associated Vasculitis, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Internal Medicine, Medicine, business
Abstract

Resume Introduction Les manifestations articulaires des vascularites associees aux ANCA (anticorps anti-cytoplasmiques des polynucleaires neutrophiles) sont extremement frequentes dans l’evolution des atteintes systemiques. L’atteinte articulaire est rarement isolee. Le diagnostic et le traitement sont difficiles dans cette situation particuliere et peu de donnees sont disponibles sur le sujet. Observation Nous avons observe deux cas de manifestations articulaires isolees de vascularites a ANCA que nous decrivons ici. L’evolution vers une forme systemiques souleve la question de la prise en charge initiale. La place de la recherche d’ANCA par rapport aux autres tests immunitaires dans cette situation est egalement abordee. Conclusion Les manifestations rhumatologiques isolees de vascularites a ANCA sont rares mais peuvent entrainer un retard diagnostique prejudiciable qui doit etre evoque en cas de polyarthrites symetriques seronegatives en recherchant la presence d’ANCA dans un bilan de seconde ligne. Le methotrexate est la premiere option therapeutique a envisager. En cas de reponse insuffisante ou d’echec, le Rituximab semble une option interessante dans ce contexte.

Published
2021
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172. Clusters and Colloids

Author

Perez, Alain, Mélinon, Patrice, Lermé, Jean, Brevet, P.-F., Dupas, Claire, editor, Houdy, Philippe, editor, and Lahmani, Marcel, editor

Published
2007
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173. Combining second harmonic generation and multiphoton excited photo-luminescence to investigate TiO2 nanoparticle powders.

Author

Jonin, Christian, Salmon, Estelle, Ahmed, Faheem, Kanoun, Mohammed Benali, Awada, Chawki, and Brevet, Pierre-Francois

Abstract

Disentangling Second Harmonic Generation (SHG) and Multiphoton Excited Photoluminescence (MEPL) signals in microscopy experiments is not an easy task. Two methods have been so far proposed based either on a time domain or a spectral domain analysis of the collected signals. In this report, a new method based on polarization discrimination is proposed to separate these SHG and MEPL contributions. In order to demonstrate this operation, intensity depth profiles are recorded for an anatase titanium dioxide powder consisting of 22 nm diameter nanoparticles using ultrafast femtosecond laser excitation. Polarization analysis of these intensity depth profiles is therefore performed and demonstrates a polarization angle shift for the SHG intensity contribution as compared to the MEPL one, allowing for the discrimination of the two SHG and MEPL contributions. The fundamental beam is set at two different wavelengths in order to provide a SHG photon energy above and below the anatase TiO2 band-gap of 3.2 eV, leading to a change in the relative intensity weight and a spectral shift between the SHG and MEPL contributions. This operation further demonstrates the potential of the method when the spectral domain disentangling cannot be performed. SHG profiles are by far narrower than those of MEPL. This study where both SHG and MEPL contributions are observed offers perspectives in photonics of powder materials as the different origin and properties of the two processes can be separated. [ABSTRACT FROM AUTHOR]

Published
2023
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176. Taxonomy based analysis of force exchanges during object grasping and manipulation.

Author

Sandra Martin-Brevet, Nathanaël Jarrassé, Etienne Burdet, and Agnès Roby-Brami

Subjects
Medicine, Science
Abstract

The flexibility of the human hand in object manipulation is essential for daily life activities, but remains relatively little explored with quantitative methods. On the one hand, recent taxonomies describe qualitatively the classes of hand postures for object grasping and manipulation. On the other hand, the quantitative analysis of hand function has been generally restricted to precision grip (with thumb and index opposition) during lifting tasks. The aim of the present study is to fill the gap between these two kinds of descriptions, by investigating quantitatively the forces exerted by the hand on an instrumented object in a set of representative manipulation tasks. The object was a parallelepiped object able to measure the force exerted on the six faces and its acceleration. The grasping force was estimated from the lateral force and the unloading force from the bottom force. The protocol included eleven tasks with complementary constraints inspired by recent taxonomies: four tasks corresponding to lifting and holding the object with different grasp configurations, and seven to manipulating the object (rotation around each of its axis and translation). The grasping and unloading forces and object rotations were measured during the five phases of the actions: unloading, lifting, holding or manipulation, preparation to deposit, and deposit. The results confirm the tight regulation between grasping and unloading forces during lifting, and extend this to the deposit phase. In addition, they provide a precise description of the regulation of force exchanges during various manipulation tasks spanning representative actions of daily life. The timing of manipulation showed both sequential and overlapping organization of the different sub-actions, and micro-errors could be detected. This phenomenological study confirms the feasibility of using an instrumented object to investigate complex manipulative behavior in humans. This protocol will be used in the future to investigate upper-limb dexterity in patients with sensory-motor impairments.

Published
2017
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177. Le Minier (France) : history and archaeology of medieval silver companies

Author

Minvielle Larousse, Nicolas, Belmon, Jérôme, Bompaire, Marc, Bernat, Alain, Brevet, Lucille, Calastrenc, Carine, Denizeau, Clément, Fleury, Jules, Galès, Françoise, Laurent, Sarah, Poirier, Nicolas, Rinalducci, Véronique, Tămaş, Călin Gabriel, Tomczyk, Céline, Vaissière, Marc, Sarah, Guillaume, Shah, Mehmet, Ecole française de Rome (EFR), Laboratoire d'Archéologie Médiévale et Moderne en Méditerranée (LA3M), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Ministère de la Culture (MC), IRAMAT - Centre Ernest Babelon (IRAMAT-CEB), Institut de Recherche sur les Archéomatériaux (IRAMAT), Université de Technologie de Belfort-Montbeliard (UTBM)-Université d'Orléans (UO)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Belfort-Montbeliard (UTBM)-Université d'Orléans (UO)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés (TRACES), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Centre européen de recherche et d'enseignement des géosciences de l'environnement (CEREGE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de la connaissance et de l’inventaire des patrimoines de la région Occitanie, Institut national de recherches archéologiques préventives (Inrap), Babes-Bolyai University [Cluj-Napoca] (UBB), 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), Archéologies environnementales, 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), Archéologie et Philologie d'Orient et d'Occident (AOROC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Département des Sciences de l'Antiquité - ENS Paris (DSA ENS-PSL), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL), Archéologie des Sociétés Méditerranéennes (ASM), Université Paul-Valéry - Montpellier 3 (UPVM)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Ministère de la Culture, Région Occitanie, Conseil départemental de l'Aveyron, École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Ministère de la Culture et de la Communication (MCC)-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)-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)-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)-Centre National de la Recherche Scientifique (CNRS), and École Pratique des Hautes Études (EPHE)

Subjects
Silver, Lead, [CHIM]Chemical Sciences, Mining archaeology, Middle ages, Languedoc -- France, [SHS]Humanities and Social Sciences
Abstract

International audience

Published
2022

179. Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity

Author

A. Huyghe, G. Furlan, J. Schroeder, E. Cascales, A. Trajkova, M. Ruel, F. Stüder, M. Larcombe, Y. Bo Yang Sun, F. Mugnier, L. De Matteo, A. Baygin, J. Wang, Y. Yu, N. Rama, B. Gibert, J. Kielbassa, L. Tonon, P. Wajda, N. Gadot, M. Brevet, M. Siouda, P. Mulligan, R. Dante, P. Liu, H. Gronemeyer, M. Mendoza-Parra, J. M. Polo, F. Lavial, Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard [Lyon], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Monash University [Clayton], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génomique métabolique (UMR 8030), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), The Wellcome Trust Sanger Institute [Cambridge], Synergie Lyon Cancer-Platform of Bioinformatics-Gilles Thomas, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of South Australia [Adelaide], and ANR-17-CONV-0002,PLASCAN,Institut François Rabelais pour la recherche multidisciplinaire sur le cancer(2017)

Subjects
SOXB1 Transcription Factors, Tumor Suppressor Proteins, [SDV]Life Sciences [q-bio], Cell Plasticity, Induced Pluripotent Stem Cells, Cell Biology, Cellular Reprogramming, Octamer Transcription Factor-3, Transcription Factors
Abstract

Coordinated changes of cellular plasticity and identity are critical for pluripotent reprogramming and oncogenic transformation. However, the sequences of events that orchestrate these intermingled modifications have never been comparatively dissected. Here, we deconvolute the cellular trajectories of reprogramming (via Oct4/Sox2/Klf4/c-Myc) and transformation (via Ras/c-Myc) at the single-cell resolution and reveal how the two processes intersect before they bifurcate. This approach led us to identify the transcription factor Bcl11b as a broad-range regulator of cell fate changes, as well as a pertinent marker to capture early cellular intermediates that emerge simultaneously during reprogramming and transformation. Multiomics characterization of these intermediates unveiled a c-Myc/Atoh8/Sfrp1 regulatory axis that constrains reprogramming, transformation and transdifferentiation. Mechanistically, we found that Atoh8 restrains cellular plasticity, independent of cellular identity, by binding a specific enhancer network. This study provides insights into the partitioned control of cellular plasticity and identity for both regenerative and cancer biology.

Published
2022
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180. 16p11.2 Locus modulates response to satiety before the onset of obesity

Author

Maillard, A M, Hippolyte, L, Rodriguez-Herreros, B, Chawner, S J R A, Dremmel, D, Agüera, Z, Fagundo, A B, Pain, A, Martin-Brevet, S, Hilbert, A, Kurz, S, Etienne, R, Draganski, B, Jimenez-Murcia, S, Männik, K, Metspalu, A, Reigo, A, Isidor, B, Le Caignec, C, David, A, Mignot, C, Keren, B, van den Bree, M B M, Munsch, S, Fernandez-Aranda, F, Beckmann, J S, Reymond, A, and Jacquemont, S

Published
2016
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181. High in vitro and in vivo synergistic activity between mTORC1 and PLK1 inhibition in adenocarcinoma NSCLC

Author

Leila Zemoura, Damien Treguer, Nicolas Girard, Marie Brevet, A. Chapelier, Didier Decaudin, Olivier Deas, Sophie Chateau-Joubert, Stefano Cairo, Rania El Botty, Sergio Roman-Roman, André Nicolas, Didier Meseure, Ivan Bièche, Sophie Vacher, Ludmilla de Plater, Elodie Montaudon, Elisabetta Marangoni, Catherine Daniel, Fariba Nemati, Adnan Naguez, and Alain Livartowski

Subjects
0301 basic medicine, Everolimus, business.industry, Volasertib, mTORC1, Carbonic Anhydrase 9, medicine.disease, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Oncology, chemistry, In vivo, 030220 oncology & carcinogenesis, Cancer research, Medicine, Adenocarcinoma, business, Protein kinase B, PI3K/AKT/mTOR pathway, medicine.drug
Abstract

Significant rational is available for specific targeting of PI3K/AKT/mTOR pathway in the treatment of non-small cell lung cancer (NSCLC). However, almost all clinical trials that have evaluated Pi3K pathway-based monotherapies/combinations did not observe an improvement of patient's outcome. The aim of our study was therefore to define combination of treatment based on the determination of predictive markers of resistance to the mTORC1 inhibitor RAD001/Everolimus. An in vivo study showed high efficacy of RAD001 in NSCLC Patient-Derived Xenografts (PDXs). When looking at biomarkers of resistance by RT-PCR study, three genes were found to be highly expressed in resistant tumors, i.e., PLK1, CXCR4, and AXL. We have then focused our study on the combination of RAD001 + Volasertib, a PLK1 inhibitor, and observed a high antitumor activity of the combination in comparison to each monotherapy; similarly, a clear synergistic effect between the two compounds was found in an in vitro study. Pharmacodynamics study demonstrated that this synergy was due to (1) tumor vascularization decrease, increase of the HIF1 protein expression and decrease of the intracellular pH, and (2) decrease of the Carbonic Anhydrase 9 (CAIX) protein that could not correct intracellular acidosis. In conclusion, all these preclinical data strongly suggest that the inhibition of mTORC1 and PLK1 proteins may be a promising therapeutic approach for NSCLC patients.

Published
2021
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182. Gold Raspberry Shell Grown onto Nonspherical Lithium Niobate Nanoparticles for Second Harmonic Generation and Photothermal Applications

Author

Taitt, Rachael, primary, Urbain, Mathias, additional, Bredillet, Kévin, additional, Behel, Zacharie, additional, Ceccone, Giacomo, additional, Bañuls‐Ciscar, Jorge, additional, Beauquis, Sandrine, additional, Mugnier, Yannick, additional, Brevet, Pierre‐François, additional, Le Dantec, Ronan, additional, Chevolot, Yann, additional, and Monnier, Virginie, additional

Published
2022
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184. Embryonated Chicken Tumor Xenografts Derived from Circulating Tumor Cells as a Relevant Model to Study Metastatic Dissemination: A Proof of Concept

Author

Rousset, Xavier, primary, Maillet, Denis, additional, Grolleau, Emmanuel, additional, Barthelemy, David, additional, Calattini, Sara, additional, Brevet, Marie, additional, Balandier, Julie, additional, Raffin, Margaux, additional, Geiguer, Florence, additional, Garcia, Jessica, additional, Decaussin-Petrucci, Myriam, additional, Peron, Julien, additional, Benzerdjeb, Nazim, additional, Couraud, Sébastien, additional, Viallet, Jean, additional, and Payen, Léa, additional

Published
2022
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187. Embryonated Chicken Tumor Xenografts Derived from Circulating Tumor Cells as a Relevant Model to Study Metastatic Dissemination: A Proof of Concept

Author

Xavier Rousset, Denis Maillet, Emmanuel Grolleau, David Barthelemy, Sara Calattini, Marie Brevet, Julie Balandier, Margaux Raffin, Florence Geiguer, Jessica Garcia, Myriam Decaussin-Petrucci, Julien Peron, Nazim Benzerdjeb, Sébastien Couraud, Jean Viallet, and Léa Payen

Subjects
Cancer Research, Oncology, CTCs, CAM assay, metastasis, Alu sequences
Abstract

Patient-Derived Xenografts (PDXs) in the Chorioallantoic Membrane (CAM) are a representative model for studying human tumors. Circulating Tumor Cells (CTCs) are involved in cancer dissemination and treatment resistance mechanisms. To facilitate research and deep analysis of these few cells, significant efforts were made to expand them. We evaluated here whether the isolation of fresh CTCs from patients with metastatic cancers could provide a reliable tumor model after a CAM xenograft. We enrolled 35 patients, with breast, prostate, or lung metastatic cancers. We performed microfluidic-based CTC enrichment. After 48–72 h of culture, the CTCs were engrafted onto the CAM of embryonated chicken eggs at day 9 of embryonic development (EDD9). The tumors were resected 9 days after engraftment and histopathological, immunochemical, and genomic analyses were performed. We obtained in ovo tumors for 61% of the patients. Dedifferentiated small tumors with spindle-shaped cells were observed. The epithelial-to-mesenchymal transition of CTCs could explain this phenotype. Beyond the feasibility of NGS in this model, we have highlighted a genomic concordance between the in ovo tumor and the original patient’s tumor for constitutional polymorphism and somatic alteration in one patient. Alu DNA sequences were detected in the chicken embryo’s distant organs, supporting the idea of dedifferentiated cells with aggressive behavior. To our knowledge, we performed the first chicken CAM CTC-derived xenografts with NGS analysis and evidence of CTC dissemination in the chicken embryo.

Published
2022

188. Clinical and ultrasonographic evaluation of the window of opportunity for retreatment with rituximab in rheumatoid arthritis patients from a multicentre real-life study

Author

Olivier Vittecoq, Marie Kozyreff-Meurice, Estelle Houivet, Nathalie Leon, Laure Berard, Maud Gauthier-Prieur, Sophie Pouplin, Gilles Avenel, Pauline Brevet, Jacques Benichou, Paul Michelin, Christian Marcelli, and Thierry Lequerre

Subjects
Rheumatology, Immunology, Immunology and Allergy
Abstract

To determine a potential window of opportunity for retreatment with rituximab in patients with rheumatoid arthritis (RA) from a multicentre longitudinal real-life study based on tight monitoring with ultrasonography (US).Thirty RA patients treated with rituximab were included. US parameters were collected at each time (8 visits) of the 18-month follow-up, notably the global score of power Doppler (PD) activity. Clinical relapse was defined as a DAS28 ESR of3.2 after 6 months in responders while US relapse was defined as an increase of ≥20% of the global score of PD activity. The decision of retreatment was based exclusively on clinical findings.A total of 29 patients were analysed (mean (SD) age: 57.2 (12.2) years; female gender: 66%). The mean (SD) PD score decreased from 8.8 (5.2) at baseline to 4.9 (4.3) at 6 months (p0.0001). A clinical response was observed at Month 4 or Month 6 for 93% of patients. A total of 19 patients had a first clinical relapse (with or without US relapse) after Month 6 (18 of them were retreated with rituximab). Among 10 patients without clinical relapse, 3 had US relapse (only one was retreated) and 7 had no US relapse (but 4 were retreated).This study highlights a great heterogeneity in terms of sequence of clinical relapse, US relapse and retreatment in RA patients receiving rituximab. Therefore, US monitoring does not seem to be relevant to determine the best time for retreatment with rituximab.

Published
2022

189. Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs

Author

Sønderby, Ida E., Ching, Christopher R.K., Thomopoulos, Sophia I., van der Meer, Dennis, Sun, Daqiang, Villalon-Reina, Julio E., Agartz, Ingrid, Amunts, Katrin, Arango, Celso, Armstrong, Nicola J., Ayesa-Arriola, Rosa, Bakker, Geor, Bassett, Anne S., Boomsma, Dorret I., Bülow, Robin, Butcher, Nancy J., Calhoun, Vince D., Caspers, Svenja, Chow, Eva W.C., Cichon, Sven, Ciufolini, Simone, Craig, Michael C., Crespo-Facorro, Benedicto, Cunningham, Adam C., Dale, Anders M., Dazzan, Paola, de Zubicaray, Greig I., Djurovic, Srdjan, Doherty, Joanne L., Donohoe, Gary, Draganski, Bogdan, Durdle, Courtney A., Ehrlich, Stefan, Emanuel, Beverly S., Espeseth, Thomas, Fisher, Simon E., Ge, Tian, Glahn, David C., Grabe, Hans J., Gur, Raquel E., Gutman, Boris A., Haavik, Jan, Håberg, Asta K., Hansen, Laura A., Hashimoto, Ryota, Hibar, Derrek P., Holmes, Avram J., Hottenga, Jouke Jan, Hulshoff Pol, Hilleke E., Jalbrzikowski, Maria, Knowles, Emma E.M., Kushan, Leila, Linden, David E.J., Liu, Jingyu, Lundervold, Astri J., Martin-Brevet, Sandra, Martínez, Kenia, Mather, Karen A., Mathias, Samuel R., McDonald-McGinn, Donna M., McRae, Allan F., Medland, Sarah E., Moberget, Torgeir, Modenato, Claudia, Monereo Sánchez, Jennifer, Moreau, Clara A., Mühleisen, Thomas W., Paus, Tomas, Pausova, Zdenka, Prieto, Carlos, Ragothaman, Anjanibhargavi, Reinbold, Céline S., Reis Marques, Tiago, Repetto, Gabriela M., Reymond, Alexandre, Roalf, David R., Rodriguez-Herreros, Borja, Rucker, James J., Sachdev, Perminder S., Schmitt, James E., Schofield, Peter R., Silva, Ana I., Stefansson, Hreinn, Stein, Dan J., Tamnes, Christian K., Tordesillas-Gutiérrez, Diana, Ulfarsson, Magnus O., Vajdi, Ariana, van 't Ent, Dennis, van den Bree, Marianne B.M., Vassos, Evangelos, Vázquez-Bourgon, Javier, Vila-Rodriguez, Fidel, Walters, G. Bragi, Wen, Wei, Westlye, Lars T., Wittfeld, Katharina, Zackai, Elaine H., Stefánsson, Kári, Jacquemont, Sebastien, Thompson, Paul M., Bearden, Carrie E., Andreassen, Ole A., other, and, Sønderby, Ida E., Ching, Christopher R.K., Thomopoulos, Sophia I., van der Meer, Dennis, Sun, Daqiang, Villalon-Reina, Julio E., Agartz, Ingrid, Amunts, Katrin, Arango, Celso, Armstrong, Nicola J., Ayesa-Arriola, Rosa, Bakker, Geor, Bassett, Anne S., Boomsma, Dorret I., Bülow, Robin, Butcher, Nancy J., Calhoun, Vince D., Caspers, Svenja, Chow, Eva W.C., Cichon, Sven, Ciufolini, Simone, Craig, Michael C., Crespo-Facorro, Benedicto, Cunningham, Adam C., Dale, Anders M., Dazzan, Paola, de Zubicaray, Greig I., Djurovic, Srdjan, Doherty, Joanne L., Donohoe, Gary, Draganski, Bogdan, Durdle, Courtney A., Ehrlich, Stefan, Emanuel, Beverly S., Espeseth, Thomas, Fisher, Simon E., Ge, Tian, Glahn, David C., Grabe, Hans J., Gur, Raquel E., Gutman, Boris A., Haavik, Jan, Håberg, Asta K., Hansen, Laura A., Hashimoto, Ryota, Hibar, Derrek P., Holmes, Avram J., Hottenga, Jouke Jan, Hulshoff Pol, Hilleke E., Jalbrzikowski, Maria, Knowles, Emma E.M., Kushan, Leila, Linden, David E.J., Liu, Jingyu, Lundervold, Astri J., Martin-Brevet, Sandra, Martínez, Kenia, Mather, Karen A., Mathias, Samuel R., McDonald-McGinn, Donna M., McRae, Allan F., Medland, Sarah E., Moberget, Torgeir, Modenato, Claudia, Monereo Sánchez, Jennifer, Moreau, Clara A., Mühleisen, Thomas W., Paus, Tomas, Pausova, Zdenka, Prieto, Carlos, Ragothaman, Anjanibhargavi, Reinbold, Céline S., Reis Marques, Tiago, Repetto, Gabriela M., Reymond, Alexandre, Roalf, David R., Rodriguez-Herreros, Borja, Rucker, James J., Sachdev, Perminder S., Schmitt, James E., Schofield, Peter R., Silva, Ana I., Stefansson, Hreinn, Stein, Dan J., Tamnes, Christian K., Tordesillas-Gutiérrez, Diana, Ulfarsson, Magnus O., Vajdi, Ariana, van 't Ent, Dennis, van den Bree, Marianne B.M., Vassos, Evangelos, Vázquez-Bourgon, Javier, Vila-Rodriguez, Fidel, Walters, G. Bragi, Wen, Wei, Westlye, Lars T., Wittfeld, Katharina, Zackai, Elaine H., Stefánsson, Kári, Jacquemont, Sebastien, Thompson, Paul M., Bearden, Carrie E., Andreassen, Ole A., and other, and

Abstract

The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q-ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest-ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi-site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene-dosage effects on distinct brain regions also emerged, providing further insight into genotype–phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This “genotype-first” approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.

Published
2022

190. Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs

Author

Universidad de Sevilla. Departamento de Psiquiatría, Sønderby, Ida E., Ching, Christopher R.K., Arango, Celso, Crespo Facorro, Benedicto, Martin Brevet, Sandra, Jacquemont, Sebastien, Universidad de Sevilla. Departamento de Psiquiatría, Sønderby, Ida E., Ching, Christopher R.K., Arango, Celso, Crespo Facorro, Benedicto, Martin Brevet, Sandra, and Jacquemont, Sebastien

Abstract

The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q-ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest-ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi-site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene-dosage effects on distinct brain regions also emerged, providing further insight into genotype–phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This “genotype-first” approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.

Published
2022

191. Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity

Author

Huyghe, A, Furlan, G, Schroeder, J, Cascales, E, Trajkova, A, Ruel, M, Studer, F, Larcombe, M, Yang Sun, YB, Mugnier, F, De Matteo, L, Baygin, A, Wang, J, Yu, Y, Rama, N, Gibert, B, Kielbassa, J, Tonon, L, Wajda, P, Gadot, N, Brevet, M, Siouda, M, Mulligan, P, Dante, R, Liu, P, Gronemeyer, H, Mendoza-Parra, M, Polo, JM, Lavial, F, Huyghe, A, Furlan, G, Schroeder, J, Cascales, E, Trajkova, A, Ruel, M, Studer, F, Larcombe, M, Yang Sun, YB, Mugnier, F, De Matteo, L, Baygin, A, Wang, J, Yu, Y, Rama, N, Gibert, B, Kielbassa, J, Tonon, L, Wajda, P, Gadot, N, Brevet, M, Siouda, M, Mulligan, P, Dante, R, Liu, P, Gronemeyer, H, Mendoza-Parra, M, Polo, JM, and Lavial, F

Abstract

Coordinated changes of cellular plasticity and identity are critical for pluripotent reprogramming and oncogenic transformation. However, the sequences of events that orchestrate these intermingled modifications have never been comparatively dissected. Here, we deconvolute the cellular trajectories of reprogramming (via Oct4/Sox2/Klf4/c-Myc) and transformation (via Ras/c-Myc) at the single-cell resolution and reveal how the two processes intersect before they bifurcate. This approach led us to identify the transcription factor Bcl11b as a broad-range regulator of cell fate changes, as well as a pertinent marker to capture early cellular intermediates that emerge simultaneously during reprogramming and transformation. Multiomics characterization of these intermediates unveiled a c-Myc/Atoh8/Sfrp1 regulatory axis that constrains reprogramming, transformation and transdifferentiation. Mechanistically, we found that Atoh8 restrains cellular plasticity, independent of cellular identity, by binding a specific enhancer network. This study provides insights into the partitioned control of cellular plasticity and identity for both regenerative and cancer biology.

Published
2022

192. Prefrontal cortex and impulsivity : interest of noninvasive brain stimulation

Author

Brevet-Aeby, Charlotte, Brunelin, Jerome, Iceta, Sylvain, Padovan, Catherine, Poulet, Emmanuel, Brevet-Aeby, Charlotte, Brunelin, Jerome, Iceta, Sylvain, Padovan, Catherine, and Poulet, Emmanuel

Abstract

Introduction: Impulsivity has been reported in many psychiatric conditions and includes deficits in several cognitive functions such as attention, inhibitory control, risk taking, delay discounting and planning. Many studies have shown that noninvasive brain stimulation (NIBS) techniques modulate the activity of the prefrontal cortex and the functions involved in impulsivity. Objective: This article aims to review the literature on the effect of NIBS on impulsivity in healthy subjects aged 18–65 years old, and to highlight research avenues to develop therapeutic alternatives for such disorders. Method: We performed a systematic review of the literature in the PubMed database following PRISMA method with “transcranial magnetic stimulation”, “repetitive transcranial magnetic stimulation”, “transcranial direct current stimulation”, “inhibition”, “risk”, “impulsive behavior”, “attention”, “reward”, “delay discounting”, “delay task”, “planning”, “prefrontal cortex” as key words. Results: We selected fifty-six studies showing modulation of the cognitive functions involved in impulsivity through NIBS. Conclusions: The data led us to consider new therapeutic alternatives in impulsive disorders by modulating prefrontal cortex activity through NIBS.

Published
2022

193. Ligand impact on reactive oxygen species generation of Au10 and Au25 nanoclusters upon one- and two-photon excitation.

Author

Fakhouri, Hussein, Bakulić, Martina Perić, Zhang, Issan, Yuan, Hao, Bain, Dipankar, Rondepierre, Fabien, Brevet, Pierre-François, Maršić, Željka Sanader, Antoine, Rodolphe, Bonačić-Koutecký, Vlasta, and Maysinger, Dusica

Subjects
REACTIVE oxygen species, GOLD clusters, PHOTOEXCITATION, PHOTODYNAMIC therapy, EXCITED states, MASS spectrometry
Abstract

In photodynamic therapy (PDT), light-sensitive photosensitizers produce reactive oxygen species (ROS) after irradiation in the presence of oxygen. Atomically-precise thiolate-protected gold nanoclusters are molecule-like nanostructures with discrete energy levels presenting long lifetimes, surface biofunctionality, and strong near-infrared excitation ideal for ROS generation in PDT. We directly compare thiolate-gold macromolecular complexes (Au10) and atomically-precise gold nanoclusters (Au25), and investigate the influence of ligands on their photoexcitation. With the ability of atomically-precise nanochemistry, we produce Au10SG10, Au10AcCys10, Au25SG18, and Au25AcCys18 (SG: glutathione; AcCys: N-acetyl-cysteine) fully characterized by high-resolution mass spectrometry. Our theoretical investigation reveals key factors (energetics of excited states and structural influence of surface ligands) and their relative importance in singlet oxygen formation upon one- and two-photon excitation. Finally, we explore ROS generation by gold nanoclusters in living cells with one- and two-photon excitation. Our study presents in-depth analyses of events within gold nanoclusters when photo-excited both in the linear and nonlinear optical regimes, and possible biological consequences in cells. Atomically precise thiolate-protected gold nanoclusters present strong near-infrared excitation, long lifetimes, and surface biofunctionality, making them ideal candidates as photosensitizers in photodynamic therapy. Here, the authors evaluate the influence of the ligands and metal core on the efficiency of photoexcited Au10 and Au25 clusters to produce reactive oxygen species, as well as possible biological consequences in living cells. [ABSTRACT FROM AUTHOR]

Published
2023
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196. OP0066 IMPACT OF DIAGNOSIS AND TREATMENT OF TROPHERYMA WHIPPLEI INFECTION IN PATIENTS WITH PRE-EXISTING CHRONIC INFLAMMATORY RHEUMATIC DISEASES: DATA FROM THE NATIONAL Tw-IRD REGISTRY

Author

Damien, C. P., primary, Puéchal, X., additional, Degboe, Y., additional, Kostine, M., additional, Michaut, A., additional, Ramon, A., additional, Wendling, D., additional, Costedoat-Chalumeau, N., additional, Richette, P., additional, Marotte, H., additional, Vix, J., additional, Dubost, J. J., additional, Ottaviani, S., additional, Mouterde, G., additional, Grasland, A., additional, Frazier-Mironer, A., additional, Germain, V., additional, Coury-Lucas, F., additional, Tournadre, A., additional, Soubrier, M., additional, Brevet, P., additional, Cavalie, L., additional, Arnaud, L., additional, Richez, C., additional, Ruyssen-Witrand, A., additional, and Constantin, A., additional

Published
2022
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198. Clinical and ultrasonographic evaluation of the window of opportunity for retreatment with rituximab in rheumatoid arthritis patients from a multicentre real-life study

Author

Vittecoq, Olivier, primary, Kozyreff-Meurice, Marie, additional, Houivet, Estelle, additional, Leon, Nathalie, additional, Berard, Laure, additional, Gauthier-Prieur, Maud, additional, Pouplin, Sophie, additional, Avenel, Gilles, additional, Brevet, Pauline, additional, Benichou, Jacques, additional, Michelin, Paul, additional, Marcelli, Christian, additional, and Lequerre, Thierry, additional

Published
2022
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