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1. Maternal occupational exposure to organic solvents and intrauterine growth in the ELFE cohort

Author: Isabelle Enderle, Virginie De Lauzun, Marie Astrid Metten, Marion Monperrus, Fleur Delva, Pauline Blanc-Petitjean, Brigitte Dananche, Christophe Paris, Cécile Zaros, Maela Le Lous, Rémi Béranger, Ronan Garlantézec, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], CHU Anne-de-Bretagne (Rennes), École des Hautes Études en Santé Publique [EHESP] (EHESP), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Etude longitudinale française depuis l'enfance (UMS : Ined-Inserm-EFS) (ELFE), Institut national d'études démographiques (INED)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), The ELFE survey is a joint project between the French Institute for Demographic Studies (INED) and the National Institute of Health and Medical Research (INSERM), in partnership with the French blood transfusion service (Etablissement français du sang, EFS), Santé publique France, the National Institute for Statistics and Economic Studies (INSEE), the Direction générale de la santé (DGS, part of the Ministry of Health and Social Affairs), the Direction générale de la prévention des risques (DGPR, Ministry for the Environment), the Direction de la recherche, des études, de l’évaluation et des statistiques (DREES, Ministry of Health and Social Affairs), the Département des études, de la prospective et des statistiques (DEPS, Ministry of Culture), and the Caisse nationale des allocations familiales (CNAF), with the support of the Ministry of Higher Education and Research and the Institut national de la jeunesse et de l’éducation populaire (INJEP). Via the RECONAI platform, it receives a government grant managed by the National Research Agency under the 'Investissements d'avenir' program (ANR-11-EQPX-0038)., and ANR-11-EQPX-0038,RE-CO-NAI,Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance(2011)
Subjects: Fetal growth retardation, Pregnancy, [SDV]Life Sciences [q-bio], Solvents, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Head circumference, Occupational exposure, Biochemistry, General Environmental Science
Abstract: International audience; BACKGROUND: In developed countries, about 15% of women are occupationally exposed to solvents. Associations between this maternal occupational exposure and intrauterine fetal growth are inconsistent, but almost no existing study has investigated this relation by solvent family (oxygenated, petroleum, and chlorinated), although they may affect fetal growth differently. OBJECTIVES: To investigate the relations between maternal occupational solvent exposure, by solvent family, and the risk of neonates born small for gestational age (SGA), or with low birthweight, or with small head circumference (HC). METHODS: Among the 18,040 women included in the Elfe birth cohort, we included 13,026 women who worked during pregnancy (72% of the cohort). Information about maternal occupations and industrial activities during pregnancy was collected by questionnaire at the maternity ward, and completed at 2-month when necessary. Using Matgéné job-exposure matrices, we assessed maternal occupational exposure to solvents. Logistic and multiple linear regressions were used to assess the association between maternal occupational solvent exposure and SGA status, birth weight, and HC. Analyses were conducted for exposure during pregnancy and also stratified by the trimester that pregnancy leave began. RESULTS: We observed a higher risk of SGA newborns among mothers occupationally exposed during pregnancy to petroleum solvents (OR(adjusted) = 1.26; 95%CI: 1.01 to 1.57). Among women working until the third trimester of pregnancy, we observed a higher risk of SGA newborns to those occupationally exposed to oxygenated solvents (OR(adjusted) = 1.75; 95%CI: 1.11 to 2.75), a significantly lower birthweight for infants of mothers exposed to petroleum solvents (β(adjusted) = -47.37 g; -89.33 to -5.42), and a lower HC among newborns of those occupationally exposed to oxygenated solvents (β(adjusted) = -0.28; -0.49 to -0.07) and to chlorinated solvents (β(adjusted) = -0.29; -0.53 to -0.05). DISCUSSION: Our results suggest that maternal occupational solvent exposure may influence fetal growth, especially exposure into the third trimester of pregnancy.
Published: 2022
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2. LC-PUFA enrichment in infant formula and neurodevelopment up to age 3.5 years in the French nationwide ELFE birth cohort

Author: Pauline Martinot, Moufidath Adjibade, Marion Taine, Camille Davisse-Paturet, Sandrine Lioret, Marie-Aline Charles, Blandine de Lauzon-Guillain, Jonathan Y. Bernard, de Lauzon-Guillain, Blandine, Influence de l'alimentation infantile sur la croissance et le développement de l'enfant - - InfaDiet2019 - ANR-19-CE36-0008 - AAPG2019 - VALID, Equipements d'excellence - Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance - - RE-CO-NAI2011 - ANR-11-EQPX-0038 - EQPX - VALID, Resarch platform on cohorts of children followed from birth - - RE-CO-NAI (COHORTES)2019 - ANR-19-COHO-0001 - COHO - VALID, 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), Etude longitudinale française depuis l'enfance (UMS : Ined-Inserm-EFS) (ELFE), Institut national d'études démographiques (INED)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Singapore Institute for Clinical Sciences, Agency for science, technology and research [Singapore] (A*STAR), The present study is part of the InfaDiet project, funded by an ANR grant (InfaDiet project, Grant No.: ANR-19-CE36-0008). The ELFE study is a joint project between the French Institute for Demographic Studies (INED) and the National Institute of Health and Medical Research (INSERM), in partnership with the French blood transfusion service (Etablissement français du sang [EFS]), Santé pub- lique France, the National Institute for Statistics and Economic Studies (INSEE), the Direction générale de la santé (DGS, part of the Ministry of Health and Social Affairs), the Direction générale de la prévention des risques (DGPR, Ministry for the Environment), the Direction de la recherche, des études, de l’évaluation et des statistiques (DREES, Ministry of Health and Social Affairs), the Département des études, de la prospective et des statistiques (DEPS, Ministry of Culture), and the Caisse nationale des allocations familiales (CNAF), with the sup- port of the Ministry of Higher Education and Research and the Institut national de la jeunesse et de l’éducation populaire (INJEP). Via the RECONAI platform, it receives a government grant managed by the National Research Agency under the 'Investissements d'avenir' pro- gramme (ANR-11-EQPX-0038, ANR-19-COHO-0001). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript., ANR-19-CE36-0008,InfaDiet,Influence de l'alimentation infantile sur la croissance et le développement de l'enfant(2019), ANR-11-EQPX-0038,RE-CO-NAI,Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance(2011), and ANR-19-COHO-0001,RE-CO-NAI (COHORTES),Resarch platform on cohorts of children followed from birth(2019)
Subjects: Nutrition and Dietetics, Long-chain polyunsaturated fatty acids, Docosahexaenoic Acids, Milk, Human, neurodevelopment, Fatty Acids, Medicine (miscellaneous), Infant, infant formula, birth cohort, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Child, Preschool, Fatty Acids, Unsaturated, Humans, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Child
Abstract: International audience; Purpose: For decades, consistent associations between breastfeeding and children’s neurodevelopement have been attributed to breastmilk content in long-chain polyunsaturated fatty acids (LC-PUFAs). However, the beneficial effect of LC-PUFA enrichment of infant formula on neurodevelopment remains controversial. This study examined the association of LC-PUFA enrichment of infant formulas with neurodevelopment up to age 3.5 years. Methods: Analyses were based on 9,372 children from the French nationwide ELFE birth cohort. Monthly from 2 to 10 months, parents declared their infant’s feeding mode, including breastfeeding and the name of the infant formula, which allowed for identifying formulas enriched in arachidonic (ARA), eicosapentaenoic (EPA) and/or docosahexaenoic (DHA) acids. Neurodevelopment was assessed at age 1 and 3.5 years with the Child Development Inventory (CDI-1 and CDI-3.5); at 2 years with the MacArthur-Bates Communicative Development Inventories (MB-2); and at 3.5 years with the Picture Similarities subtest of the British Ability Scale (BAS-3.5). Associations were assessed by linear regression adjusted for any breastfeeding duration and main confounding factors, including socioeconomic characteristics.Results: One third of formula-fed infants consumed LC-PUFA–enriched formulas. Most of these formulas were enriched in both DHA and ARA, and about 10% of infants consumed formula further enriched in EPA. LC-PUFA enrichment of infant formula was not associated with neurodevelopmental scores at age 1 (CDI-1, -0.16 [-0.39, 0.07]), age 2 (MB-2, 0.78 [-0.33, 1.89]), or age 3.5 (CDI-3.5, -0.05 [-0.27, 0.17]; BAS-3.5, -0.93 [-2.85, 0.98]).Conclusion: In the ELFE study, LC-PUFA enrichment of infant formula was not associated with neurodevelopmental scores up to 3.5 years.
Published: 2022
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3. Extraction and sequencing of single nuclei from murine skeletal muscles

Author: Frédéric Relaix, Stamatia Gioftsidi, Philippos Mourikis, Stéphanie Backer, Léo Machado, Pascal Maire, Matthieu Dos Santos, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), 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, École nationale vétérinaire d'Alfort (ENVA), Etablissement Français du Sang (EFS), Créteil, France., Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and École nationale vétérinaire - Alfort (ENVA)
Subjects: Science (General), Satellite Cells, Skeletal Muscle, Cellular differentiation, [SDV]Life Sciences [q-bio], Muscle Fibers, Skeletal, Cell Culture Techniques, Single Cell, Cell Separation, Computational biology, Biology, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, Q1-390, 0302 clinical medicine, Multinucleate, Gene expression, Protocol, Animals, Cell isolation, Flow Cytometry/Mass Cytometry, Muscle, Skeletal, 030304 developmental biology, Cell Nucleus, 0303 health sciences, General Immunology and Microbiology, Sequence Analysis, RNA, General Neuroscience, Stem Cells, RNA, Cell Differentiation, RNAseq, 3. Good health, Single-Cell Analysis, 030217 neurology & neurosurgery
Abstract: Summary Single-nucleus RNA sequencing allows the profiling of gene expression in isolated nuclei. Here, we describe a step-by-step protocol optimized for adult mouse skeletal muscles. This protocol provides two main advantages compared to the widely used single-cell protocol. First, it allows us to sequence the myonuclei of the multinucleated myofibers. Second, it circumvents the cell-dissociation-induced transcriptional modifications. For complete details on the use and execution of this protocol, please refer to Dos Santos et al. (2020) and Machado, Geara et al. (2021)., Graphical abstract, Highlights • snRNA-seq captures essentially all cell populations present in the skeletal muscle tissue • Can identify rare myonuclei populations, like neuromuscular and myotendinous myonuclei • snRNA-seq circumvents cell-dissociation-induced modifications on gene expression • In contrast to single-cell RNA-seq, snRNA-seq allows us to process snap frozen biopsies, Single-nucleus RNA sequencing allows the profiling of gene expression in isolated nuclei. Here, we describe a step-by-step protocol optimized for adult mouse skeletal muscles. This protocol provides two main advantages compared to the widely used single-cell protocol. First, it allows us to sequence the myonuclei of the multinucleated myofibers. Second, it circumvents the cell-dissociation-induced transcriptional modifications.
Published: 2021
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4. Enrichment of infant formula with long-chain polyunsaturated fatty acids and risk of infection and allergy in the nationwide ELFE birth cohort

Author: Camille Davisse-Paturet, Moufidath Adjibade, Karine Adel-Patient, Sandrine Lioret, Amandine Divaret-Chauveau, Blandine de Lauzon-Guillain, Marie-Aline Charles, Jonathan Y. Bernard, 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), Singapore Institute for Clinical Sciences, Agency for science, technology and research [Singapore] (A*STAR), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Développement, Adaptation et Handicap. Régulations cardio-respiratoires et de la motricité (DevAH), Université de Lorraine (UL), Service d’allergologie pédiatrique [CHRU de Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Etude longitudinale française depuis l'enfance (UMS : Ined-Inserm-EFS) (ELFE), Institut national d'études démographiques (INED)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), This study is funded by an ANR grant (InfaDiet project, ANR-19-CE36-0008).The ELFE survey is a joint project between the French Institute for Demographic Studies (INED) and the French National Institute of Health and Medical Research (INSERM), in partnership with the French blood transfusion service (Etablissement français du sang [EFS]), Santé publique France, the National Institute for Statistics and Economic Studies (INSEE), the Direction générale de la santé (DGS, part of the Ministry of Health and Social Affairs), the Direction générale de la prévention des risques (DGPR, Ministry for the Environment), the Direction de la recherche, des études, de l’évaluation et des statistiques (DREES, Ministry of Health and Social Affairs), the Département des études, de la prospective et des statistiques (DEPS, Ministry of Culture), and the Caisse nationale des allocations familiales (CNAF), with the support of the Ministry of Higher Education and Research and the Institut national de la jeunesse et de l’éducation populaire (INJEP). Via the RECONAI platform, it receives a government grant managed by the National Research Agency under the 'Investissements d'avenir' programme (ANR-11-EQPX-0038). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript., ANR-19-CE36-0008,InfaDiet,Influence de l'alimentation infantile sur la croissance et le développement de l'enfant(2019), de Lauzon-Guillain, Blandine, Influence de l'alimentation infantile sur la croissance et le développement de l'enfant - - InfaDiet2019 - ANR-19-CE36-0008 - AAPG2019 - VALID, and Unité d'Allergologie Pédiatrique
Subjects: Allergy, medicine.medical_specialty, Docosahexaenoic Acids, Immunology, Lower risk, Food allergy, Internal medicine, medicine, Humans, Immunology and Allergy, infections, Asthma, chemistry.chemical_classification, Arachidonic Acid, business.industry, allergies, Fatty Acids, Infant, infant formula, medicine.disease, Eicosapentaenoic acid, chemistry, Infant formula, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Docosahexaenoic acid, Child, Preschool, LCPUFA enrichment, Birth Cohort, lipids (amino acids, peptides, and proteins), [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Food Hypersensitivity, Polyunsaturated fatty acid
Abstract: International audience; Background: The new European regulations require the enrichment of formulas with docosahexaenoic acid (DHA) because of the positive effects of long-chain polyunsaturated fatty acids (LCPUFAs) on neurodevelopment and visual acuity. In this observational study, we aimed to evaluate whether the consumption of LCPUFA-enriched formula was associated with the risk of infection and allergy in early childhood.Methods: Analyses involved data from 8,389 formula-fed infants from the ELFE birth cohort. Formula enrichment was identified from the list of ingredients of the formula consumed at 2 months. Infections (gastro-intestinal, lower respiratory tract [LRTI], upper respiratory tract) and allergies (wheezing, itchy rash, asthma medication, food allergy) from age 2 months to 5.5 years were reported by parents during follow-up surveys. Multivariable logistic regression models were used to assess associations between the consumption of LCPUFA-enriched formula and the risk of infection and allergy.Results: Among formula-fed infants at 2 months, 36% consumed formula enriched with DHA and arachidonic acid (ARA), and 11% consumed formula additionally enriched with eicosapentaenoic acid (EPA). Enriched formula consumption was not associated with infection or allergy, except for an association between consumption of DHA/ARA/EPA-enriched formula and lower use of asthma medications. Furthermore, as compared with non-DHA/ARA/EPA-enriched formula, consumption of formula with high EPA content (≥3.2 mg/100 kcal) was related to lower risk of LRTI and lower use of asthma medications.Conclusion: This study suggests that consumption of DHA/ARA/EPA-enriched formula (especially those with high EPA content) is associated with a lower risk of LRTI and lower use of asthma medications.
Published: 2021
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5. Progressive and Coordinated Mobilization of the Skeletal Muscle Niche throughout Tissue Repair Revealed by Single-Cell Proteomic Analysis

Author: Borok, Matthew, Didier, Nathalie, Gattazzo, Francesca, Ozturk, Teoman, Corneau, Aurélien, Rouard, Helene, Relaix, Frédéric, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Cytométrie Pitié-Salpêtrière (PASS-CYPS), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), École nationale vétérinaire d'Alfort (ENVA), Etablissement Français du Sang (EFS), Créteil, France., APHP, Hopitaux Universitaires Henri Mondor, DHU Pepsy & Centre de Référence des Maladies Neuromusculaires GNMH, Créteil, France, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and École nationale vétérinaire - Alfort (ENVA)
Subjects: Proteomics, satellite cells, muscle niche, Wound Healing, Proteome, Stem Cells, [SDV]Life Sciences [q-bio], Muscle Development, Article, Mice, muscle stem cells, lcsh:Biology (General), regeneration, Animals, Cell Lineage, CyTOF, Single-Cell Analysis, skeletal muscle, Muscle, Skeletal, lcsh:QH301-705.5, ComputingMilieux_MISCELLANEOUS
Abstract: Background: Skeletal muscle is one of the only mammalian tissues capable of rapid and efficient regeneration after trauma or in pathological conditions. Skeletal muscle regeneration is driven by the muscle satellite cells, the stem cell population in interaction with their niche. Upon injury, muscle fibers undergo necrosis and muscle stem cells activate, proliferate and fuse to form new myofibers. In addition to myogenic cell populations, interaction with other cell types such as inflammatory cells, mesenchymal (fibroadipogenic progenitors—FAPs, pericytes) and vascular (endothelial) lineages are important for efficient muscle repair. While the role of the distinct populations involved in skeletal muscle regeneration is well characterized, the quantitative changes in the muscle stem cell and niche during the regeneration process remain poorly characterized. Methods: We have used mass cytometry to follow the main muscle cell types (muscle stem cells, vascular, mesenchymal and immune cell lineages) during early activation and over the course of muscle regeneration at D0, D2, D5 and D7 compared with uninjured muscles. Results: Early activation induces a number of rapid changes in the proteome of multiple cell types. Following the induction of damage, we observe a drastic loss of myogenic, vascular and mesenchymal cell lineages while immune cells invade the damaged tissue to clear debris and promote muscle repair. Immune cells constitute up to 80% of the mononuclear cells 5 days post-injury. We show that muscle stem cells are quickly activated in order to form new myofibers and reconstitute the quiescent muscle stem cell pool. In addition, our study provides a quantitative analysis of the various myogenic populations during muscle repair. Conclusions: We have developed a mass cytometry panel to investigate the dynamic nature of muscle regeneration at a single-cell level. Using our panel, we have identified early changes in the proteome of stressed satellite and niche cells. We have also quantified changes in the major cell types of skeletal muscle during regeneration and analyzed myogenic transcription factor expression in satellite cells throughout this process. Our results highlight the progressive dynamic shifts in cell populations and the distinct states of muscle stem cells adopted during skeletal muscle regeneration. Our findings give a deeper understanding of the cellular and molecular aspects of muscle regeneration.
Published: 2021
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6. M-Cadherin Is a PAX3 Target During Myotome Patterning

Author: Joana Esteves de Lima, Reem Bou Akar, Myriam Mansour, Didier Rocancourt, Margaret Buckingham, Frédéric Relaix, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Etablissement Français du Sang (EFS), Créteil, France., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), École nationale vétérinaire - Alfort (ENVA), and École nationale vétérinaire d'Alfort (ENVA)
Subjects: Cell and Developmental Biology, PAX3, lcsh:Biology (General), [SDV]Life Sciences [q-bio], embryonic structures, myogenesis, myotome, CDH15, musculoskeletal system, lcsh:QH301-705.5, M-Cadherin, Original Research
Abstract: International audience; PAX3 belongs to the paired-homeobox family of transcription factors and plays a key role as an upstream regulator of muscle progenitor cells during embryonic development. Pax3 -mutant embryos display impaired somite development, yet the consequences for myotome formation have not been characterized. The early myotome is formed by PAX3-expressing myogenic cells that delaminate from the dermomyotomal lips and migrate between the dermomyotome and sclerotome where they terminally differentiate. Here we show that in Pax3 -mutant embryos, myotome formation is impaired, displays a defective basal lamina and the regionalization of the structural protein Desmin is lost. In addition, this phenotype is more severe in embryos combining Pax3 -null and Pax3 dominant-negative alleles. We identify the adhesion molecule M-Cadherin as a PAX3 target gene, the expression of which is modulated in the myotome according to Pax3 gain- and loss-of-function alleles analyzed. Taken together, we identify M-Cadherin as a PAX3-target linked to the formation of the myotome.
Published: 2021
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7. Isolation and Phospholipid Enrichment of Muscle Mitochondria and Mitoplasts

Author: Aymeline Vandestienne, Alexandre Prola, Fanny Pilot-Storck, Laurent Tiret, Nabil Baroudi, Frederic Joubert, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), École nationale vétérinaire d'Alfort (ENVA), Etablissement Français du Sang (EFS), Créteil, France., 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, Laboratoire Jean Perrin (LJP), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-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), École nationale vétérinaire - Alfort (ENVA), and Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: 0303 health sciences, ATP synthase, biology, Strategy and Management, Mechanical Engineering, Vesicle, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Metals and Alloys, Phospholipid, Oxidative phosphorylation, Mitochondrion, Industrial and Manufacturing Engineering, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, Phosphatidylcholine, biology.protein, Cardiolipin, Biophysics, Methods Article, lipids (amino acids, peptides, and proteins), Inner mitochondrial membrane, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: The efficient ATP production in mitochondria relies on the highly specific organization of its double membrane. Notably, the inner mitochondrial membrane (IMM) displays a massive surface extension through its folding into cristae, along which concentrate respiratory complexes and oligomers of the ATP synthase. Evidence has accumulated to highlight the importance of a specific phospholipid composition of the IMM to support mitochondrial oxidative phosphorylation. Contribution of specific phospholipids to mitochondrial ATP production is classically studied by modulating the activity of enzymes involved in their synthesis, but the interconnection of phospholipid synthesis pathways often impedes the determination of the precise role of each phospholipid. Here, we describe a protocol to specifically enrich mitochondrial membranes with cardiolipin or phosphatidylcholine, as well as a fluorescence-based method to quantify phospholipid enrichment. This method, based on the fusion of lipid vesicles with isolated mitochondria, may further allow a precise evaluation of phospholipid contribution to mitochondrial functions.
Published: 2021
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8. Hydroxycarbamide decreases the free alpha‐hemoglobin pool in red blood cells of adult patients with sickle cell anemia

Author: Elisa Domingues-Hamdi, Anoosha Habibi, Véronique Baudin-Creuza, Pablo Bartolucci, Stéphane Moutereau, Corinne Vasseur, Frédéric Galactéros, Sadaf Pakdaman, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), 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, Laboratory of Excellence GR-Ex ' The red cell : from genesis to death ', PRES Sorbonne Paris Cité, laboratory of Excellence GR-Ex, Paris, France, Etablissement Français du Sang (EFS), Créteil, France., Département de Biochimie-Biologie Moléculaire, Pharmacologie, Génétique Médicale [CHU Henri Mondor], CHU Henri Mondor, Unité des Maladies Génétiques du Globule Rouge [CHU Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and BAUDIN-CREUZA, Véronique
Subjects: 0303 health sciences, medicine.medical_specialty, Adult patients, business.industry, [SDV]Life Sciences [q-bio], Hematology, Alpha hemoglobin, medicine.disease, Gastroenterology, Sickle cell anemia, 3. Good health, [SDV] Life Sciences [q-bio], Hydroxycarbamide, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, business, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 030215 immunology, medicine.drug
Abstract: International audience; No abstract available
Published: 2020
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9. From whole-organ imaging to in-silico blood flow modeling: a new multi-scale network analysis for revisiting tissue functional anatomy

Author: Jacques Rouquette, Anne Lorsignol, Pol Kennel, Jules Dichamp, Lise Teyssedre, Julien Colombelli, Franck Plouraboué, Christophe Guissard, Louis Casteilla, Corinne Barreau, (OATAO), Open Archive Toulouse Archive Ouverte, Institut de mécanique des fluides de Toulouse (IMFT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, STROMALab, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Institut des Technologies Avancées en sciences du Vivant (ITAV), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Barcelona Institute of Science and Technology (BIST), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), Barcelona Institute of Science and Technology - BIST (SPAIN), Centre National de la Recherche Scientifique - CNRS (FRANCE), Etablissement Français du Sang - EFS Midi-Pyrénées (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), and Institut National Polytechnique de Toulouse - INPT (FRANCE)
Subjects: Male, 0301 basic medicine, Physiology, Computer science, Mécanique des fluides, In-silico modeling, [SPI.MECA.MEFL] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Fluids mechanics [physics.class-ph], Biochemistry, [SPI.MECA.MEFL]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Fluids mechanics [physics.class-ph], Fats, Mice, Fluorescence Microscopy, 0302 clinical medicine, Animal Cells, Blood Flow, 11. Sustainability, Medicine and Health Sciences, Adipocytes, Micro-vascular clusters, Biology (General), Connective Tissue Cells, Microscopy, Ecology, Light-Sheet, Community structure, Light Microscopy, Arteries, Lipids, Body Fluids, Blood, Community Ecology, Computational Theory and Mathematics, Connective Tissue, Modeling and Simulation, Blood Circulation, Graph (abstract data type), Light-Sheet Fluorescence Microscopy, Anatomy, Cellular Types, Biological system, Fat pad, Research Article, Network analysis, Strongly connected component, QH301-705.5, In silico, Research and Analysis Methods, Models, Biological, Fluorescence, Veins, 03 medical and health sciences, Cellular and Molecular Neuroscience, Genetics, Animals, Computer Simulation, Community Structure, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Clustering coefficient, Ecology and Environmental Sciences, Biology and Life Sciences, Cell Biology, Blood flow, Mice, Inbred C57BL, Biological Tissue, 030104 developmental biology, Light sheet fluorescence microscopy, Cardiovascular Anatomy, Blood Vessels, Tissue micro-environment, 030217 neurology & neurosurgery
Abstract: We present a multi-disciplinary image-based blood flow perfusion modeling of a whole organ vascular network for analyzing both its structural and functional properties. We show how the use of Light-Sheet Fluorescence Microscopy (LSFM) permits whole-organ micro-vascular imaging, analysis and modelling. By using adapted image post-treatment workflow, we could segment, vectorize and reconstruct the entire micro-vascular network composed of 1.7 million vessels, from the tissue-scale, inside a ∼ 25 × 5 × 1 = 125mm3 volume of the mouse fat pad, hundreds of times larger than previous studies, down to the cellular scale at micron resolution, with the entire blood perfusion modeled. Adapted network analysis revealed the structural and functional organization of meso-scale tissue as strongly connected communities of vessels. These communities share a distinct heterogeneous core region and a more homogeneous peripheral region, consistently with known biological functions of fat tissue. Graph clustering analysis also revealed two distinct robust meso-scale typical sizes (from 10 to several hundred times the cellular size), revealing, for the first time, strongly connected functional vascular communities. These community networks support heterogeneous micro-environments. This work provides the proof of concept that in-silico all-tissue perfusion modeling can reveal new structural and functional exchanges between micro-regions in tissues, found from community clusters in the vascular graph., Author summary New optical microscopy called light-sheet fluorescence microscopy (LSFM) allows for 3D optical scan imaging of an entire tissue, at the micron scale, for reconstructing its complete microvascular bed. The 3D reconstruction of a vectorized vascular network can display as many as 1.7 million vessels inside a 125mm3 volume of mouse fat tissue. This 3D reconstruction allows for vessel visualisation and also the complete virtual “dissection” and analysis of the vascular bed. Described as a graph, the vascular network provides a new tissue anatomy description, similar to city maps built on a road graph, showing structural clusters emerging as tissue “districts”. These clusters provide a new basis for lobule description in fat tissue. Even more can be obtained from virtual perfusion simulated inside the tissue by using in-silico modeling tools. This virtual perfusion reveals the functional properties of the vascular network, such as perfusion fluxes, and exchanges between clusters and infusion time (time for the blood to reach a site from the principal entry).
Published: 2020
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10. Potential added value of a RT-qPCR method of SOX 11 expression, in the context of a multidisciplinary diagnostic assessment of B cell malignancies

Author: Adrien Chauchet, Julien Magne, Francine Garnache-Ottou, Christophe Ferrand, Alizée Jenvrin, Olivier Casasnovas, Anne Donzel, Dewi Vernerey, Nathalie Nadal, Julien Guy, Bernard Aral, Laurence Jego, P. Callier, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Inserm UMR 1098, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Service d'hématologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -hopital Jean Minjoz, Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Etablissement Français du Sang (EFS) - Bourgogne Franche-Comté, EFS, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Etablissement Français du Sang de Bourgogne Franche-Comté (site de Chalon-sur-Saône), and EFS-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])
Subjects: 0301 basic medicine, Cancer Research, RT-qPCR-reference genes, [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), lcsh:RC254-282, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, SOX11, Medicine, B cell, Mantle cell lymphoma, biology, business.industry, lcsh:RC633-647.5, Area under the curve, Hematology, lcsh:Diseases of the blood and blood-forming organs, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Minimal residual disease, Molecular biology, 3. Good health, Housekeeping gene, 030104 developmental biology, medicine.anatomical_structure, Testis determining factor, Oncology, 030220 oncology & carcinogenesis, ROC curve analysis-threshold, biology.protein, Antibody, business, Rapid Communication
Abstract: Background Expression of SRY [sex-determining region Y]-box11 (SOX11) is specific to mantle cell lymphoma (MCL) and contributes, in conjunction with immunoglobulin variable heavy chain gene mutation status, to the identification of two forms of this disease. Methods The aim of this report was firstly, to design an easy and suitable RT-qPCR method to quantify SOX11 mRNA expression in mantle cell lymphoma and other B cell malignancies with the proper reference gene; secondly, to define the best threshold of relative quantity of SOX11 mRNA in order to reach the best compromise between sensitivity and specificity. Results For best discrimination of MCL and non-MCL groups we determined an area under the curve (AUC) of 0.9750 and a threshold of 1.76 with 100% sensitivity and 88% specificity. AUC and threshold values of respectively 0.91/1.346 [87% sensitivity, 80% specificity] and 0.9525/1.7120 [100% sensitivity, 88% specificity] for GAPDH and RPLP0 respectively denote that the RPLP0 reference gene alone is sufficient for PCR housekeeping gene. Conclusion This work describes an RT-qPCR assay for SOX11 expression in order to better characterize MCL at diagnosis. Further studies on larger cohorts are needed to evaluate this molecular tool, especially for the follow-up of minimal residual disease. Electronic supplementary material The online version of this article (10.1186/s40164-018-0097-6) contains supplementary material, which is available to authorized users.
Published: 2018
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11. 3D analysis of the whole subcutaneous adipose tissue reveals a complex spatial network of interconnected lobules with heterogeneous browning ability

Author: Audrey Carrière, Yves Martinez, Luc Pénicaud, Franck Plouraboué, Jacques Rouquette, Anne Lorsignol, Christophe Guissard, Louis Casteilla, Jules Dichamp, Xavier Descombes, Corinne Barreau, Institut de mécanique des fluides de Toulouse (IMFT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, STROMALab, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Fédération de Recherche Agrobiosciences, Interactions et Biodiversité (FR AIB), Morphologie et Images (MORPHEME), 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)-Institut de Biologie Valrose (IBV), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Signal, Images et Systèmes (Laboratoire I3S - SIS), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Institut des Technologies Avancées en sciences du Vivant (ITAV), 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)-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)-Signal, Images et Systèmes (Laboratoire I3S - SIS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), BIGNAU, Suzy, Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), 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)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 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)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Signal, Images et Systèmes (Laboratoire I3S - SIS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), 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 (FRANCE), Etablissement Français du Sang - EFS Midi-Pyrénées (FRANCE), Ecole Nationale Vétérinaire de Toulouse - ENVT (FRANCE), Institut National Polytechnique de Toulouse - INPT (FRANCE), Institut National de la Santé et de la Recherche Médicale - INSERM (FRANCE), Université Nice Sophia Antipolis (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Cell type, 3D analysis, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Confocal, [SDV]Life Sciences [q-bio], Subcutaneous Fat, Adipose tissue, Fluorescent Antibody Technique, lcsh:Medicine, Network, Lobules, heterogeneous browning ability, Biology, Fat pad, Article, law.invention, whole subcutaneous adipose tissue, 03 medical and health sciences, 0302 clinical medicine, Imaging, Three-Dimensional, Image processing, Confocal microscopy, law, Adipocytes, Image Processing, Computer-Assisted, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, lcsh:Science, Process (anatomy), Multidisciplinary, Microscopy, Confocal, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Mesenchymal stem cell, lcsh:R, Soft tissue, Lipid Metabolism, Cell biology, [SDV] Life Sciences [q-bio], 030104 developmental biology, Biologie cellulaire, lcsh:Q, Browning, Fat metabolism, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 3D
Abstract: Adipose tissue, as the main energy storage organ and through its endocrine activity, is interconnected with all physiological functions. It plays a fundamental role in energy homeostasis and in the development of metabolic disorders. Up to now, this tissue has been analysed as a pool of different cell types with very little attention paid to the organization and putative partitioning of cells. Considering the absence of a complete picture of the intimate architecture of this large soft tissue, we developed a method that combines tissue clearing, acquisition of autofluorescence or lectin signals by confocal microscopy, segmentation procedures based on contrast enhancement, and a new semi-automatic image analysis process, allowing accurate and quantitative characterization of the whole 3D fat pad organization. This approach revealed the unexpected anatomic complexity of the murine subcutaneous fat pad. Although the classical picture of adipose tissue corresponds to a superposition of simple and small ellipsoidal lobules of adipose cells separated by mesenchymal spans, our results show that segmented lobules display complex 3D poly-lobular shapes. Despite differences in shape and size, the number of these poly-lobular subunits is similar from one fat pad to another. Finally, investigation of the relationships of these subunits between each other revealed a never-described organization in two clusters with distinct molecular signatures and specific vascular and sympathetic nerve densities correlating with different browning abilities. This innovative procedure reveals that subcutaneous adipose tissue exhibits a subtle functional heterogeneity with partitioned areas, and opens new perspectives towards understanding its functioning and plasticity.
Published: 2019
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12. Breastfeeding Status and Duration and Infections, Hospitalizations for Infections and Antibiotic Use in the First Two Years of Life in the ELFE Cohort

Author: Davisse-Paturet, Camille, Adel-Patient, Karine, Divaret-Chauveau, Amandine, Pierson, Juliette, Lioret, Sandrine, Cheminat, Marie, Dufourg, Marie-Noëlle, Charles, Marie-Aline, De Lauzon-Guillain, Blandine, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pharmacologie et Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Biologie et de Technologies du CEA Saclay, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Etude longitudinale française depuis l'enfance (UMS : Ined-Inserm-EFS) (ELFE), Institut national d'études démographiques (INED)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), The ELFE survey is a joint project between the French Institute for Demographic Studies (INED) and the National Institute of Health and Medical Research (INSERM), in partnership with the French blood transfusion service (Etablissement français du sang, EFS), Santé publique France, the National Institute for Statistics and Economic Studies (INSEE), the Direction générale de la santé (DGS, part of the Ministry of Health and Social Affairs), the Direction générale de la prévention des risques (DGPR, Ministry for the Environment), the Direction de la recherche, des études, de l’évaluation et des statistiques (DREES, Ministry of Health and Social Affairs), the Département des études, de la prospective et des statistiques (DEPS, Ministry of Culture), and the Caisse nationale des allocations familiales (CNAF), with the support of the Ministry of Higher Education and Research and the Institut national de la jeunesse et de l’éducation populaire (INJEP). Via the RECONAI platform, it received a government grant managed by the National Research Agency under the 'Investissements d’avenir' program (ANR-11-EQPX-0038)., ANR-11-EQPX-0038/11-EQPX-0038,RE-CO-NAI,Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance(2011), de Lauzon-Guillain, Blandine, Equipements d'excellence - Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance - - RE-CO-NAI2011 - ANR-11-EQPX-0038 - EQPX - VALID, Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, ANR-11-EQPX-0038,RE-CO-NAI,Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance(2011), Médicaments et Technologies pour la Santé (MTS), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Adult, Male, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, breastfeeding, Infant, lcsh:TX341-641, birth cohort, Article, Anti-Bacterial Agents, Cohort Studies, Hospitalization, antibiotic use, Breast Feeding, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Communicable Disease Control, Humans, Female, Infant Food, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, infections, hospitalizations, lcsh:Nutrition. Foods and food supply
Abstract: In low- and middle-income countries, the protective effect of breastfeeding against infections is well established, but in high-income countries, the effect could be weakened by higher hygienic conditions. We aimed to examine the association between breastfeeding and infections in the first 2 years of life, in a high-income country with relatively short breastfeeding duration. Among 10,349 young children from the nationwide Etude Longitudinale Française depuis l’Enfance (ELFE) birth cohort, breastfeeding and parent-reported hospitalizations, bronchiolitis and otitis events, and antibiotic use were prospectively collected up to 2 years. Never-breastfed infants were used as reference group. Any breastfeeding for
Published: 2019
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13. Social Inequalities in Prenatal Folic Acid Supplementation: Results from the ELFE Cohort

Author: Camier, Aurore, Kadawathagedara, Manik, Lioret, Sandrine, Bois, Corinne, Cheminat, Marie, Dufourg, Marie-Noëlle, Charles, Marie Aline, de Lauzon-Guillain, Blandine, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Etude longitudinale française depuis l'enfance (UMS : Ined-Inserm-EFS) (ELFE), Institut national d'études démographiques (INED)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), This analysis was funded by an ANR grant within the framework 'Social determinants of health' (grant number: ANR-12-DSSA-0001). The Elfe survey is a joint project between the French Institute for Demographic Studies (INED) and the National Institute of Health and Medical Research (INSERM), in partnership with the French blood transfusion service (Etablissement français du sang, EFS), Santé publique France, the National Institute for Statistics and Economic Studies (INSEE), the Direction générale de la santé (DGS, part of the Ministry of Health and Social Affairs), the Direction générale de la prévention des risques (DGPR, Ministry for the Environment), the Direction de la recherche, des études, de l’évaluation et des statistiques (DREES, Ministry of Health and Social Affairs), the Département des études, de la prospective et des statistiques (DEPS, Ministry of Culture), and the Caisse nationale des allocations familiales (CNAF), with the support of the Ministry of Higher Education and Research and the Institut national de la jeunesse et de l’éducation populaire (INJEP). Via the RECONAI platform, it receives a government grant managed by the National Research Agency under the 'Investissements d’avenir' programme (ANR-11-EQPX-0038)., ANR-11-EQPX-0038/11-EQPX-0038,RE-CO-NAI,Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance(2011), ANR-12-DSSA-0001,SOFI,Déterminants socio-culturel des pratiques alimentaires dans l'enfance(2012), ANR-11-EQPX-0038,RE-CO-NAI,Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance(2011), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), de Lauzon-Guillain, Blandine, Equipements d'excellence - Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance - - RE-CO-NAI2011 - ANR-11-EQPX-0038 - EQPX - VALID, and Déterminants sociaux de santé - Déterminants socio-culturel des pratiques alimentaires dans l'enfance - - SOFI2012 - ANR-12-DSSA-0001 - DSS - VALID
Subjects: Adult, social inequalities, lcsh:TX341-641, Article, Young Adult, Folic Acid, Socioeconomic Factors, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Dietary Supplements, Humans, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, epidemiology, France, Neural Tube Defects, pregnancy, Child, Prenatal Nutritional Physiological Phenomena, lcsh:Nutrition. Foods and food supply, folic acid supplementation
Abstract: Most professional and international organizations recommend folic acid supplementation for women planning pregnancy. Various studies have shown high levels of non-compliance with this recommendation. This study aimed to identify sociodemographic characteristics related to this compliance. The analyses were based on 16,809 women from the French nationwide ELFE cohort (Etude Longitudinale Fran&ccedil, aise depuis l&rsquo, Enfance). Folic acid supplementation was assessed at delivery, and sociodemographic characteristics were collected at two months postpartum. The association between sociodemographic characteristics and compliance with recommendations on folic acid supplementation (no supplementation, periconceptional supplementation, and supplementation only after the periconceptional period) was examined using multivariate multinomial logistic regression. Only 26% of French women received folic acid supplementation during the periconceptional period, 10% of women received supplementation after the periconceptional period, and 64% received no supplementation. Young maternal age, low education level, low family income, multiparity, single parenthood, maternal unemployment, maternal overweight, and smoking during pregnancy were related to lower likelihood of folic acid supplementation during the periconceptional period compared to no supplementation. These associations were not explained by unplanned pregnancy. Immigrant and underweight women were more likely to receive folic acid supplementation after the periconceptional period. Our study confirms great social disparities in France regarding the compliance with the recommendations on folic acid supplementation.
Published: 2019
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14. Toward a clinical diagnostic pipeline for SPINK1 intronic variants

Author: Zhuan Liao, Claude Férec, David Neil Cooper, Jin-Huan Lin, Emmanuelle Masson, Arnaud Boulling, Zhao-Shen Li, Xin-Ying Tang, Jian-Min Chen, Shun-Jiang Deng, Wen-Bin Zou, The Secondary Military Medical University [Shanghai, China], Shanghai Institute of Pancreatic Diseases [Shanghai, China], Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Génétique Moléculaire et d'Histocompatibilité [Brest], Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Cardiff University, Université de Brest (UBO), Etablissement Français du Sang (EFS), EFS, INSERM U1078, and Chen, Jian-Min
Subjects: Splice site consensus sequence, lcsh:Medicine, Deep intronic variants, Gene Frequency, Drug Discovery, Protein Isoforms, Cells, Cultured, 0303 health sciences, education.field_of_study, 030305 genetics & heredity, 3. Good health, Genetic Techniques, Trypsin Inhibitor, Kazal Pancreatic, RNA splicing, SPINK1 gene, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Molecular Medicine, Primary Research, Chronic pancreatitis, lcsh:QH426-470, In silico, Population, Context (language use), Cryptic splice site, Computational biology, Biology, Aberrant splicing, White People, 03 medical and health sciences, Asian People, In silico splicing prediction, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Pancreatitis, Chronic, Genetics, SPINK1 Gene, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Computer Simulation, education, Molecular Biology, Gene, [SDV.GEN]Life Sciences [q-bio]/Genetics, Alamut software suite, lcsh:R, genomAD, Missing heritability, Introns, Human genetics, Minor allele frequency, lcsh:Genetics
Abstract: Background The clinical significance of SPINK1 intronic variants in chronic pancreatitis has been previously assessed by various approaches including a cell culture-based full-length gene assay. A close correlation between the results of this assay and in silico splicing prediction was apparent. However, until now, a clinical diagnostic pipeline specifically designed to classify SPINK1 intronic variants accurately and efficiently has been lacking. Herein, we present just such a pipeline and explore its efficacy and potential utility in potentiating the classification of newly described SPINK1 intronic variants. Results We confirm a close correlation between in silico splicing prediction and results from the cell culture-based full-length gene assay in the context of three recently reported pathogenic SPINK1 intronic variants. We then integrated in silico splicing prediction and the full-length gene assay into a stepwise approach and tested its utility in the classification of two novel datasets of SPINK1 intronic variants. The first dataset comprised 16 deep intronic variants identified in 52 genetically unexplained Chinese chronic pancreatitis patients by sequencing the entire intronic sequence of the SPINK1 gene. The second dataset comprised five novel rare proximal intronic variants identified through the routine analysis of the SPINK1 gene in French pancreatitis patients. Employing a minor allele frequency of > 5% as a population frequency filter, 6 of the 16 deep intronic variants were immediately classified as benign. In silico prediction of the remaining ten deep intronic variants and the five rare proximal intronic variants with respect to their likely impact on splice site selection suggested that only one proximal intronic variant, c.194 + 5G > A, was likely to be of functional significance. Employing the cell culture-based full-length gene assay, we functionally analyzed c.194 + 5G > A, together with seven predicted non-functional variants, thereby validating their predicted effects on splicing in all cases. Conclusions We demonstrated the accuracy and efficiency of in silico prediction in combination with the cell culture-based full-length gene assay for the classification of SPINK1 intronic variants. Based upon these findings, we propose an operational pipeline for classifying SPINK1 intronic variants in the clinical diagnostic setting. Electronic supplementary material The online version of this article (10.1186/s40246-019-0193-7) contains supplementary material, which is available to authorized users.
Published: 2019
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15. Cellular localization of the cell cycle inhibitor Cdkn1c controls growth arrest of adult skeletal muscle stem cells

Author: Despoina Mademtzoglou, Matthew J Borok, Philippos Mourikis, Yoko Asakura, Frédéric Relaix, Sonia Alonso-Martin, Amrudha Mohan, Atsushi Asakura, Yusaku Kodaka, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Stem Cell Institute, Paul and Sheila Wellstone Muscular Dystrophy Center, Department of Neurology, University of Minnesota Medical School, Minneapolis, United States., Ecole Nationale Veterinaire d'Alfort, Faculté de medecine, F-94000, Université Paris-Est Creteil, Maison Alfort, France, Etablissement Français du Sang (EFS), Créteil, France., APHP, Hopitaux Universitaires Henri Mondor, DHU Pepsy & Centre de Référence des Maladies Neuromusculaires GNMH, Créteil, France, Mademtzoglou, Despoina, and École nationale vétérinaire - Alfort (ENVA)
Subjects: 0301 basic medicine, Mouse, Cellular differentiation, [SDV]Life Sciences [q-bio], Muscle Development, p57, Myoblasts, Mice, cyclin-dependent kinase inhibitors, Myocyte, Biology (General), Cellular localization, satellite cells, muscle regeneration, General Neuroscience, Gene Expression Regulation, Developmental, Cell Differentiation, General Medicine, Cell cycle, Stem Cells and Regenerative Medicine, Cell biology, [SDV] Life Sciences [q-bio], Adult Stem Cells, medicine.anatomical_structure, Medicine, cell cycle, Stem cell, Adult stem cell, Research Article, Satellite Cells, Skeletal Muscle, QH301-705.5, Science, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, stem cells, medicine, Animals, Regeneration, Muscle, Skeletal, Cyclin-Dependent Kinase Inhibitor p57, Cell Proliferation, General Immunology and Microbiology, Cell growth, Skeletal muscle, Cell Cycle Checkpoints, 030104 developmental biology, Developmental Biology
Abstract: International audience; Adult skeletal muscle maintenance and regeneration depend on efficient muscle stem cell (MuSC) functions. The mechanisms coordinating cell cycle with activation, renewal, and differentiation of MuSCs remain poorly understood. Here, we investigated how adult MuSCs are regulated by CDKN1c (p57 kip2), a cyclin-dependent kinase inhibitor, using mouse molecular genetics. In the absence of CDKN1c, skeletal muscle repair is severely impaired after injury. We show that CDKN1c is not expressed in quiescent MuSCs, while being induced in activated and proliferating myoblasts and maintained in differentiating myogenic cells. In agreement, isolated Cdkn1c-deficient primary myoblasts display differentiation defects and increased proliferation. We further show that the subcellular localization of CDKN1c is dynamic; while CDKN1c is initially localized to the cytoplasm of activated/proliferating myoblasts, progressive nuclear translocation leads to growth arrest during differentiation. We propose that CDKN1c activity is restricted to differentiating myoblasts by regulated cyto-nuclear relocalization, coordinating the balance between proliferation and growth arrest.
Published: 2018
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16. Hepatitis A: an epidemiological survey in blood donors, France 2015 to 2017

Author: Lina Mouna, Elodie Pouchol, Pierre Gallian, Catherine Visse, Benoit Flan, Elisabeth Couturier, Françoise Wind, Rachid Djoudi, Valérie Barlet, Sylvie Gross, Henriette de Valk, Sophie Lecam, Anne-Marie Roque-Afonso, Pierre Tiberghien, Céline Ricard, Cécile Fabra, Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Etablissement Français du Sang [Nantes], Etablissement Français du Sang Hauts-de-France - Normandie (EFS Hauts-de-France - Normandie), Etablissement Français du Sang [Occitanie] (EFS Occitanie), LFB Biomédicaments, Institut de Veille Sanitaire (INVS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Pathogénèse et traitement de l'hépatite fulminante et du cancer du foie, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement Français du Sang (EFS Haut de France), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC)
Subjects: Male, food-borne infections, Epidemiology, viruses, Virologie, [SDV]Life Sciences [q-bio], CNR des Virus des hépatites à transmission entérique, Blood Donors, 030204 cardiovascular system & hematology, Disease Outbreaks, Men who have sex with men, Blood donations, 0302 clinical medicine, Surveys and Questionnaires, Genotype, France 4 AP-HP, Medicine, 030212 general & internal medicine, Marseille, Hepatitis A, virus diseases, Middle Aged, Hepatitis a virus, 3. Good health, Hôpital Paul Brousse, France 3 Etablissement Français du Sang Auvergne Rhône Alpes, outbreaks, Female, France, Rapid Communication, Saint Denis-La, laboratory surveillance, Adult, medicine.medical_specialty, Adolescent, viral infections, Villejuif, Beynost, 03 medical and health sciences, hepatitis A virus, Virology, Humans, INSERM U1993, Homosexuality, Male, 2 Unité des Virus Emergents (UVE: Aix-Marseille Univ -IRD 190 -Inserm 1207 -IHU Méditerranée Infection), sexually transmitted infections, Aged, business.industry, men who have sex with men - MSM, Public Health, Environmental and Occupational Health, Outbreak, France 5 Etablissement Français du Sang, medicine.disease, business
Abstract: International audience; Since mid-2016, hepatitis A virus (HAV) outbreaks, involving predominantly men who have sex with men (MSM), have affected countries in Europe and overseas. In France, HAV screening of blood donations in 2017 revealed a HAV-RNA prevalence ca fivefold higher than during 2015-16 (4.42/106 vs 0.86/106; p = 0.0005). In 2017, despite a higher male-to-female ratio (5.5 vs 0.7) and the identification of MSM-associated outbreak strains, only one of 11 infected male donors self-reported being a MSM. Since mid-2016, outbreaks involving mainly men who have sex with men (MSM) have been reported in European countries and overseas [1-6]. The outbreaks were associated with three genotype IA hepatitis A virus (HAV) strains: VDR_521_2016, RIVM_HAV16-090 and V16-25801. In this study, we report epidemiological and clinical findings pertaining to HAV infected blood donors before and during the recent outbreak in France.
Published: 2018
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17. A new model for the emergence of blood capillary networks

Author: Benjamin Aymard, Diane Peurichard, Louis Casteilla, Pierre Degond, Anne Lorsignol, Pol Kennel, Pedro Aceves-Sanchez, Franck Plouraboué, Institut de mécanique des fluides de Toulouse (IMFT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria), Modelling and Analysis for Medical and Biological Applications (MAMBA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jacques-Louis Lions (LJLL (UMR_7598)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Geroscience and rejuvenation research center (RESTORE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Mathématiques de Toulouse UMR5219 (IMT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), This project was supported by the Région Midi-Pyrénées, France, under contract ref. APRTCN 14050455. PD acknowledges support by the Engineering and Physical Sciences Research Council (EPSRC) under grants no. EP/M006883/1 and EP/N014529/1, by the Royal Society and the Wolfson Foundation through a Royal Society Wolfson Research Merit Award no. WM130048 and by the National Science Foundation (NSF) under grant no. RNMS11-07444 (KI-Net). PAS was supported by EPSRC under grant no. EP/M006883/1., Mathématiques pour les Neurosciences (MATHNEURO), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), STROMALab, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Imperial College London, Degond, Pierre, The Royal Society, Engineering & Physical Science Research Council (EPSRC), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique - CNRS (FRANCE), Etablissement Français du Sang - EFS Midi-Pyrénées (FRANCE), Ecole Nationale Vétérinaire de Toulouse - ENVT (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Institut National de la Recherche en Informatique et en Automatique - INRIA (FRANCE), Institut National de la Santé et de la Recherche Médicale - INSERM (FRANCE), Université Nice Sophia Antipolis (FRANCE), North Carolina State University (USA), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Imperial College London (UNITED KINGDOM), and Centre de recherche INRIA Sophia-Antipolis Méditerranée (Nice, France)
Subjects: Statistics and Probability, Materials science, Capillary action, Mécanique des fluides, Diffusion, Hydraulic conductivity, [SDV]Life Sciences [q-bio], [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Positive feedback, 01 natural sciences, Oxygen gradient, [MATH.MATH-MP]Mathematics [math]/Mathematical Physics [math-ph], 0102 Applied Mathematics, Creation/deletion process, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Cell Behavior (q-bio.CB), 0101 mathematics, [MATH.MATH-MP] Mathematics [math]/Mathematical Physics [math-ph], Convection-diffusion-reaction, Darcy's law, Advection, 0103 Numerical and Computational Mathematics, Applied Mathematics, Wall-sheer-stress, Darcy law, General Engineering, Mechanics, Computer Science Applications, Capillaries, 010101 applied mathematics, Coupling (electronics), FOS: Biological sciences, Quantitative Biology - Cell Behavior, Limiting oxygen concentration, Porous medium, Mathematics Subject Classification: Primary: 92C15, 76Z05, Secondary: 92C42, 76S05
Abstract: International audience; We propose a new model for the emergence of blood capillary networks. We assimilate the tissue and extra cellular matrix as a porous medium, using Darcy's law for describing both blood and intersticial fluid flows. Oxygen obeys a convection-diffusionreaction equation describing advection by the blood, diffusion and consumption by the tissue. Discrete agents named capillary elements and modelling groups of endothelial cells are created or deleted according to different rules involving the oxygen concentration gradient, the blood velocity, the sheer stress or the capillary element density. Once created, a capillary element locally enhances the hydraulic conductivity matrix, contributing to a local increase of the blood velocity and oxygen flow. No connectivity between the capillary elements is imposed. The coupling between blood, oxygen flow and capillary elements provides a positive feedback mechanism which triggers the emergence of a network of channels of high hydraulic conductivity which we identify as new blood capillaries. We provide two different, biologically relevant geometrical settings and numerically analyze the influence of each of the capillary creation mechanism in detail. All mechanisms seem to concur towards a harmonious network but the most important ones are those involving oxygen gradient and sheer stress. A detailed discussion of this model with respect to the literature and its potential future developments concludes the paper.
Published: 2018
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18. Osteogenic Potential of Mesenchymal Stromal Cells Contributes to Primary Myelofibrosis

Author: Lisa Pieri, Johanna Konopacki, Adrienne Anginot, Rachel Golub, Olivier Pierre-Louis, Jean-Christophe Ianotto, Alessandro M. Vannucchi, Bernadette Guerton, Nathalie Rochet, Marie-Françoise Bourgeade, Thierry de Revel, Christophe Martinaud, Brigitte Dupriez, Jean-Jacques Lataillade, Sandrine Schmutz, Patricia Albanese, Christophe Desterke, Jean-Baptiste Souraud, Emilie Henault, Frédéric Torossian, Marie-Caroline Le Bousse-Kerdilès, Interactions cellules souches-niches : physiologie, tumeurs et réparation tissulaire, Université Paris-Sud - Paris 11 (UP11)-Service de Santé des Armées-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), SFR89, University Paris-Sud, Département de biologie clinique, Hôpital d'instruction des Armées Percy, Service de Santé des Armées-Service de Santé des Armées, FIM, French Intergroup on Myeloproliferative neoplasmss, Département d'hématologie, MPN-CRIMM, Azienda Ospedaliera-Universitaria, Université Paris Diderot - Paris 7 (UPD7), Lymphopoïèse, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie Valrose (IBV), 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), EAC 7149, Etablissement Français du Sang (EFS), EFS, Centre Hospitalier de Lens, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Studies in Florence were supported by a grant from Associazione Italiana per la Ricerca sul Cancro (AIRC, Milan, Italy), Special Program Molecular Clinical Oncology 5×1000 to AIRC-Gruppo Italiano Malattie Mieloproliferative (AGIMM) project #1005 (A.M. Vannucchi)., Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (... - 2019) (UNS), and Institut de Recherche Biomédicale des Armées (IRBA)
Subjects: Adult, Male, Cancer Research, Pathology, medicine.medical_specialty, Stromal cell, Cellular differentiation, Mice, Nude, Biology, Polymerase Chain Reaction, Mice, medicine, Animals, Humans, Myelofibrosis, Cells, Cultured, Myeloproliferative neoplasm, Aged, Aged, 80 and over, Ossification, Heterotopic, Mesenchymal stem cell, Cell Differentiation, Mesenchymal Stem Cells, Middle Aged, medicine.disease, 3. Good health, Extramedullary hematopoiesis, Haematopoiesis, medicine.anatomical_structure, Oncology, Primary Myelofibrosis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Heterografts, Female, Bone marrow
Abstract: Primary myelofibrosis is a myeloproliferative neoplasm that is a precursor to myeloid leukemia. Dysmegakaryopoiesis and extramedullary hematopoiesis characterize primary myelofibrosis, which is also associated with bone marrow stromal alterations marked by fibrosis, neoangiogenesis, and osteomyelosclerosis. In particular, contributions to primary myelofibrosis from mesenchymal stromal cells (MSC) have been suggested by mouse studies, but evidence in humans remains lacking. In this study, we show that bone marrow MSCs from primary myelofibrosis patients exhibit unique molecular and functional abnormalities distinct from other myeloproliferative neoplasms and these abnormalities are maintained stably ex vivo in the absence of leukemic cells. Primary myelofibrosis-MSC overexpressed heparin-binding cytokines, including proinflammatory TGFβ1 and osteogenic BMP-2, as well as glycosaminoglycans such as heparan sulfate and chondroitin sulfate. Transcriptome and functional analyses revealed alterations in MSC differentiation characterized by an increased osteogenic potential and a TGFβ1 signaling signature. Accordingly, phospho-Smad2 levels were intrinsically increased in primary myelofibrosis-MSC along with enhanced expression of the master bone regulator RUNX2, while inhibition of the endogenous TGFβ1 receptor TGFβR1 impaired osteogenic differentiation in these MSCs. Taken together, our results define the source of a critical osteogenic function in primary myelofibrosis that supports its pathophysiology, suggesting that combined targeting of both the hematopoietic and stromal cell compartments in primary myelofibrosis patients may heighten therapeutic efficacy. Cancer Res; 75(22); 4753–65. ©2015 AACR.
Published: 2015
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19. Rabbit antithymocyte globulin–induced serum sickness disease and human kidney graft survival

Author: Gwénaëlle Evanno, Arnaud Nicot, Ludmilla Le Berre, Yohann Foucher, Stéphanie Castagnet, Jean Harb, Pavel Vesely, Sophie Brouard, Ondrej Viklicky, Juliette Rousse, Evelyn Ang, Apolline Salama, Magali Giral, Jean-Marie Bach, Hélène Perreault, Thomas Dejoie, Béatrice Charreau, Petra Hruba, Pierrick Guerif, Grégoire Couvrat-Desvergnes, Jean-Paul Soulillou, Marine Lorent, Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Société d’Accélération du Transfert de Technologies Ouest Valorisation [Rennes, France], Xenothera [Nantes, France], Department of Nephrology [Prague, Czech Republic] (Transplant Center), Institute for Clinical and Experimental Medicine (IKEM), CEITEC - Central European Institute of Technology [Brno, Czech Republic], Laboratoire de Biochimie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Department of Chemistry [Winnipeg, MB, Canada], University of Manitoba [Winnipeg], Biostatistique, Pharmacoépidémiologie et Mesures Subjectives en Santé, PRES Université Nantes Angers Le Mans (UNAM), Etablissement Français du Sang [Nantes], Labex Transplantex, the Natural Science and Engineering Research Council of Canada (RGPIN/170241) and Canadian Foundation for Innovation (22391), the Région Pays de la Loire., ANR-11-JSV1-0008,CSM (Composite Surrogate Marker),Construction d'un marqueur composite de substitution de la survie à long terme : application à la transplantation rénale(2011), European Project: 603049,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,TRANSLINK(2013), Immuno-Endocrinologie Cellulaire et Moléculaire [Nantes] (IECM), Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Recherche Agronomique (INRA), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Etablissement Français du Sang EFS [Nantes] (Laboratoire HLA), ANR: ANR-11-JSV1-0008-01, Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Soulillou, Jean-Paul, Le Bihan, Sylvie, Jeunes Chercheuses et Jeunes Chercheurs - Construction d'un marqueur composite de substitution de la survie à long terme : application à la transplantation rénale - - CSM (Composite Surrogate Marker)2011 - ANR-11-JSV1-0008 - JCJC - VALID, and Defining the role of xeno-directed and autoimmune events in patients receiving animal-derived bioprosthetic heart valves - TRANSLINK - - EC:FP7:HEALTH2013-09-01 - 2017-08-31 - 603049 - VALID
Subjects: Adult, Graft Rejection, Male, Kidney, Isoantibodies, Serum Sickness, Antigen, medicine, Animals, Humans, lapin, Prospective Studies, Kidney transplantation, Aged, Antilymphocyte Serum, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, business.industry, Graft Survival, Kidney metabolism, General Medicine, Middle Aged, medicine.disease, Kidney Transplantation, 3. Good health, Transplantation, Serum sickness, Immunology, Sialic Acids, biology.protein, Female, Rabbits, Clinical Medicine, Antibody, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Immune complex disease
Abstract: Grégoire Couvrat-Desvergnes, Apolline Salama, and Ludmilla Le Berre contributed equally to this work.; International audience; BACKGROUND: Rabbit-generated antithymocyte globulins (ATGs), which target human T cells, are widely used as immunosuppressive agents during treatment of kidney allograft recipients. However, ATGs can induce immune complex diseases, including serum sickness disease (SSD). Rabbit and human IgGs have various antigenic differences, including expression of the sialic acid Neu5Gc and α-1-3-Gal (Gal), which are not synthesized by human beings. Moreover, anti-Neu5Gc antibodies have been shown to preexist and be elicited by immunization in human subjects. This study aimed to assess the effect of SSD on long-term kidney allograft outcome and to compare the immunization status of grafted patients presenting with SSD following ATG induction treatment.METHODS: We analyzed data from a cohort of 889 first kidney graft recipients with ATG induction (86 with SSD [SSD(+)] and 803 without SSD [SSD(-)]) from the Données Informatisées et Validées en Transplantation data bank. Two subgroups of SSD(+) and SSD(-) patients that had received ATG induction treatment were then assessed for total anti-ATG, anti-Neu5Gc, and anti-Gal antibodies using ELISA assays on sera before and after transplantation.RESULTS: SSD was significantly associated with long-term graft loss (>10 years, P = 0.02). Moreover, SSD(+) patients exhibited significantly elevated titers of anti-ATG (P = 0.043) and anti-Neu5Gc (P = 0.007) IgGs in late post-graft samples compared with SSD(-) recipients.CONCLUSION: In conclusion, our data indicate that SSD is a major contributing factor of late graft loss following ATG induction and that anti-Neu5Gc antibodies increase over time in SSD(+) patients.FUNDING: This study was funded by Société d'Accélération du Transfert de Technologies Ouest Valorisation, the European FP7 "Translink" research program, the French National Agency of Research, Labex Transplantex, the Natural Science and Engineering Research Council of Canada, and the Canadian Foundation for Innovation.
Published: 2015
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20. Elaboration and evaluation of alginate foam scaffolds for soft tissue engineering

Author: Benjamin Duployer, Philippe Bourin, Caroline Ceccaldi, Brigitte Sallerin, Angelo Parini, Christophe Tenailleau, Daniel Cussac, Sophie Girod Fullana, Raya Bushkalova, Centre interuniversitaire de recherche et d'ingenierie des matériaux (CIRIMAT), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), 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, EFS ALPES MEDITERRANEE, CHU Toulouse [Toulouse], Centre National de la Recherche Scientifique - CNRS (FRANCE), Etablissement Français du Sang - EFS Midi-Pyrénées (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Institut National de la Santé et de la Recherche Médicale - INSERM (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), and Centre Hospitalier Universitaire de Toulouse - CHU Toulouse (FRANCE)
Subjects: 0301 basic medicine, Pore size, Scaffold, Materials science, Alginates, Matériaux, Surfactants, Foam-based scaffolds, Pharmaceutical Science, Paracrine activity, Nanotechnology, Biocompatible Materials, 02 engineering and technology, 03 medical and health sciences, Glucuronic Acid, Soft tissue engineering, Humans, Polymer scaffold, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, Tissue Engineering, Tissue Scaffolds, Hexuronic Acids, Mesenchymal stem cell, Alginate, 021001 nanoscience & nanotechnology, Biocompatible material, Porous scaffold, 030104 developmental biology, [CHIM.POLY]Chemical Sciences/Polymers, Mesenchymal stem cells, 0210 nano-technology, Porosity
Abstract: International audience; Controlling microarchitecture in polymer scaffolds is a priority in material design for soft tissue applications. This paper reports for the first time the elaboration of alginate foam-based scaffolds for mesenchymal stem cell (MSC) delivery and a comparative study of various surfactants on the final device performance. The use of surfactants permitted to obtain highly interconnected porous scaffolds with tunable pore size on surface and in cross-section. Their mechanical properties in compression appeared to be adapted to soft tissue engineering. Scaffold structures could sustain MSC proliferation over 14 days. Paracrine activity of scaffold-seeded MSCs varied with the scaffold structure and growth factors release was globally improved in comparison with control alginate scaffolds. Our results provide evidence that exploiting different surfactant types for alginate foam preparation could be an original method to obtain biocompatible scaffolds with tunable architecture for soft tissue engineering.
Published: 2017
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21. LXR agonist treatment of blastic plasmacytoid dendritic cell neoplasm restores cholesterol efflux and triggers apoptosis

Author: Adam Ceroi, Fanny Angelot-Delettre, Sabeha Biichle, Francis Bonnefoy, Christophe Roumier, Laure Philippe, Baptiste Lamarthée, Claude Preudhomme, Thierry Gauthier, Francine Garnache-Ottou, Anne Roggy, Elisabeth Macintyre, David Masson, Philippe Saas, Sylvain Perruche, Cécile Chagué, Laurent Lagrost, Etablissement Français du Sang de Bourgogne Franche-Comté (site de Chalon-sur-Saône), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-EFS, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang (EFS) - Bourgogne Franche-Comté, EFS, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Université de Franche-Comté (UFC)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), EFS-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Université de Franche-Comté ( UFC ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer ( LabEx LipSTIC ), Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École pratique des hautes études ( EPHE ) -Institut Gustave Roussy ( IGR ) -Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ) -Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Institut Necker Enfants-Malades (INEM) ( INEM - UM 111 (UMR 8253 / U1151) ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: 0301 basic medicine, Male, Cell, Proliferation, Apoptosis, Expression, Plasmacytoid dendritic cell, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Biochemistry, Mice, 0302 clinical medicine, polycyclic compounds, STAT5 Transcription Factor, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, ATP Binding Cassette Transporter, Subfamily G, Member 1, Liver X Receptors, Inhibition, Myeloid Neoplasia, biology, Myeloid leukemia, food and beverages, Myeloid-Leukemia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Interleukin-3 Receptor, 3. Good health, Leukemia, medicine.anatomical_structure, Cholesterol, 030220 oncology & carcinogenesis, Female, lipids (amino acids, peptides, and proteins), In-Vivo, ATP Binding Cassette Transporter 1, Immunology, Activation, Antineoplastic Agents, digestive system, 03 medical and health sciences, Cell Line, Tumor, medicine, Animals, Humans, Liver X receptor, Protein kinase B, Cell Proliferation, Cell growth, Cell Biology, Dendritic Cells, medicine.disease, Xenograft Model Antitumor Assays, 030104 developmental biology, Prostate-Cancer Cells, ABCA1, biology.protein, Cancer research, Density-Lipoprotein Receptor, Interleukin-3, Proto-Oncogene Proteins c-akt
Abstract: International audience; Blastic plasmacytoid dendritic cell (PDC) neoplasm (BPDCN) is an aggressive hematological malignancy with a poor prognosis that derives from PDCs. No consensus for optimal treatment modalities is available today and the full characterization of this leukemia is still emerging. We identified here a BPDCN-specific transcriptomic profile when compared with those of acute myeloid leukemia and T-acute lymphoblastic leukemia, as well as the transcriptomic signature of primary PDCs. This BPDCN gene signature identified a dysregulation of genes involved in cholesterol homeostasis, some of them being liver X receptor (LXR) target genes. LXR agonist treatment of primary BPDCN cells and BPDCN cell lines restored LXR target gene expression and increased cholesterol efflux via the upregulation of adenosine triphosphate-binding cassette (ABC) transporters, ABCA1 and ABCG1. LXR agonist treatment was responsible for limiting BPDCN cell proliferation and inducing intrinsic apoptotic cell death. LXR activation in BPDCN cells was shown to interfere with 3 signaling pathways associated with leukemic cell survival, namely: NF-kB activation, as well as Akt and STAT5 phosphorylation in response to the BPDCN growth/survival factor interleukin-3. These effects were increased by the stimulation of cholesterol efflux through a lipid acceptor, the apolipoprotein A1. In vivo experiments using a mouse model of BPDCN cell xenograft revealed a decrease of leukemic cell infiltration and BPDCN-induced cytopenia associated with increased survival after LXR agonist treatment. This demonstrates that cholesterol homeostasis is modified in BPDCN and can be normalized by treatment with LXR agonists which can be proposed as a new therapeutic approach.
Published: 2016
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22. Severe Symptomatic Primary Human Cytomegalovirus Infection despite Effective Innate and Adaptive Immune Responses

Author: Céline Bressollette-Bodin, François Raffi, David Senitzer, Audrey Rodallec, Berthe-Marie Imbert-Marcille, Christelle Retière, David Boutoille, Katia Gagne, Raphaëlle Riou, Maeva Lefebvre, Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Etablissement Français du Sang [Nantes], Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de virologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d'Histocompatibilité et d'Immunogénétique [EFS Nantes], LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), Service des maladies infectieuses et tropicales [CHU Nantes], Division of Hematology and Bone Marrow Transplantation [Duarte, California, USA], City of Hope National Medical Center-City of Hope Comprehensive Cancer Center [Duarte], This work was financially supported by the Etablissement Français du Sang (EFS)/ Pays de la Loire and by grants from EFS (2014-11), Région des Pays de la Loire (ARMINA Project), Leucémie Espoir Atlantique Famille (LEAF), and Nantes Atlantique Greffe de Moelle Osseuse (NAGMO). R.R. is a Ph.D. student supported by Région des Pays de la Loire (ARMINA Project)., Bernardo, Elizabeth, and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: 0301 basic medicine, Human cytomegalovirus, Male, Lymphocytosis, medicine.medical_treatment, viruses, Cytomegalovirus, NK cells, Adaptive Immunity, 0302 clinical medicine, innate immunity, Cell Differentiation, Middle Aged, Acquired immune system, 3. Good health, Killer Cells, Natural, Cytokine, medicine.anatomical_structure, Cytomegalovirus Infections, Female, Disease Susceptibility, medicine.symptom, Adult, T cell, Immunology, T lymphocytes, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Microbiology, 03 medical and health sciences, Young Adult, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, Virology, medicine, Humans, Lymphocyte Count, HCMV, Aged, Cell Proliferation, Innate immune system, biochemical phenomena, metabolism, and nutrition, medicine.disease, Immunity, Innate, 030104 developmental biology, Insect Science, Case-Control Studies, Pathogenesis and Immunity, Transcriptome, CD8, 030215 immunology
Abstract: Primary human cytomegalovirus (HCMV) infection usually goes unnoticed, causing mild or no symptoms in immunocompetent individuals. However, some rare severe clinical cases have been reported without investigation of host immune responses or viral virulence. In the present study, we investigate for the first time phenotypic and functional features, together with gene expression profiles in immunocompetent adults experiencing a severe primary HCMV infection. Twenty primary HCMV-infected patients (PHIP) were enrolled, as well as 26 HCMV-seronegative and 39 HCMV-seropositive healthy controls. PHIP had extensive lymphocytosis marked by massive expansion of natural killer (NK) and T cell compartments. Interestingly, PHIP mounted efficient innate and adaptive immune responses with a deep HCMV imprint, revealed mainly by the expansion of NKG2C + NK cells, CD16 + Vδ2(−) γδ T cells, and conventional HCMV-specific CD8 + T cells. The main effector lymphocytes were activated and displayed an early immune phenotype that developed toward a more mature differentiated status. We suggest that both massive lymphocytosis and excessive lymphocyte activation could contribute to massive cytokine production, known to mediate tissue damage observed in PHIP. Taken together, these findings bring new insights into the comprehensive understanding of immune mechanisms involved during primary HCMV infection in immunocompetent individuals. IMPORTANCE HCMV-specific immune responses have been extensively documented in immunocompromised patients and during in utero acquisition. While it usually goes unnoticed, some rare severe clinical cases of primary HCMV infection have been reported in immunocompetent patients. However, host immune responses or HCMV virulence in these patients has not so far been investigated. In the present study, we show massive expansion of NK and T cell compartments during the symptomatic stage of acute HCMV infection. The patients mounted efficient innate and adaptive immune responses with a deep HCMV imprint. The massive lymphocytosis could be the result of nonadapted or uncontrolled immune responses limiting the effectiveness of the specific responses mounted. Both massive lymphocytosis and excessive lymphocyte activation could contribute to massive cytokine production, known to mediate tissue damage. Furthermore, we cannot exclude a delayed immune response caused by immune escape established by HCMV strains.
Published: 2016
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23. Impact of Graft-Versus-Graft Natural Killer Cell Alloreactivity on Single Unit Dominance After Double Umbilical Cord Blood Transplantation

Author: Laurence Lodé, David Senitzer, Marc Bonneville, Philippe Moreau, Christelle Volteau, Julie Esbelin, Catherine Willem, Anne Cesbron, Nolwenn Legrand, Patrice Chevallier, Pauline Rettman, Christelle Retière, Katia Gagne, Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Etablissement Français du Sang [Nantes], Plateforme de Biométrie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie Clinique [Nantes], Hôpital Hôtel Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d'Hématologie Biologique [Hôpital Hôtel-Dieu, Nantes], Hôpital Hôtel-Dieu [Nantes] (Centre Hospitalier Universitaire de Nantes), Hôpital Mère-Enfant [Hôpital Hôtel Dieu, Nantes], Laboratoire d'Histocompatibilité et d'Immunogénétique [EFS Nantes], LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Division of Hematology and Bone Marrow Transplantation [Duarte, California, USA], City of Hope National Medical Center-City of Hope Comprehensive Cancer Center [Duarte], This work was supported by EFS Pays de la Loire and by grants from International Research Group on unrelated HEmatopoietic stem cell Transplantation (IRGHET 2009, IRGHET 2014), Association Recherche et Transfusion 2009 (ART 2009), Agence de la BioMédecine (ABM 2011, ABM 2014), Etablissement Français du Sang (EFS 2011-06, EFS 2014-06), Ligue contre le Cancer Grand Ouest 2013, LabEx Transplantex 2014, Association Leucémie Espoir Atlantique Famille (LEAF) and Nantes Atlantique Greffe de Moëlle Osseuse (NAGMO). PR is a PhD student supported by a EFS PL/Region Pays de la Loire grant., and Bernardo, Elizabeth
Subjects: 0301 basic medicine, Cytotoxicity, Immunologic, Genotype, Cell, Graft vs Host Disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, Apoptosis, Cord Blood Stem Cell Transplantation, Human leukocyte antigen, Biology, Lymphocyte Activation, Natural killer cell, 03 medical and health sciences, fluids and secretions, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, HLA Antigens, medicine, Humans, Receptor, Cells, Cultured, Retrospective Studies, Transplantation, Umbilical Cord Blood Transplantation, Receptors, KIR3DL1, Histocompatibility, Killer Cells, Natural, 030104 developmental biology, medicine.anatomical_structure, Phenotype, Treatment Outcome, Cord blood, Immunology, embryonic structures, France, 030215 immunology
Abstract: International audience; BACKGROUND:Natural killer (NK) cell alloreactivity is favored after double umbilical cord blood transplantation (dUCBT) in which cord blood (UCB) units and patients are often HLA class I mismatched. Generally, only 1 UCB unit persists after dUCBT. We hypothesize, that NK cell alloreactivity mediated by killer cell immunoglobulin-like receptor (KIR)-HLA interactions may explain the dominance of 1UCB unit over the other after dUCBT.METHODS:We investigated the impact of KIR NK cell alloreactivities on the dominance of 1 full UCB unit in 50 dUCBT. We analyzed the effects of the KIR/HLA genetic incompatibilities and studied cord blood cells at both the phenotypic and functional levels.RESULTS:The genetic combination of KIR3DL1 loser UCB unit/Bw4 winner UCB unit determined both the dominance of 1 UCB unit (hazards ratio, 2.88 [1.32-6.27], P = 0.0077) and correlated with an increased incidence of relapse (hazards ratio, 4.91 [1.39-17.3], P = 0.0134). It is interesting to note that cord blood cells exhibited extremely low HLA class I expression. Moreover, resting cord blood KIR3DL1 NK cells exhibited a basal alloreactivity against Bw4 target cells that increased upon activation, thus triggering death by apoptosis.CONCLUSIONS:Our unicentric study suggests, for the first time, the significant impact of KIR NK cell alloreactivity in the determination of which UCB unit will dominate in dUCBT.
Published: 2016
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24. Regionalization of browning revealed by whole subcutaneous adipose tissue imaging

Author: Barreau, Corinne, Labit, Elodie, Guissard, Christophe, Rouquette, Jacques, Boizeau, Marie-Laure, Gani Koumassi, Souleymane, Carrière, Audrey, Jeanson, Yannick, Berger-Müller, Sandra, Dromard, Cécile, Plouraboué, Franck, Casteilla, Louis, Lorsignol, Anne, STROMALab, Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Technologies Avancées en sciences du Vivant (ITAV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut de mécanique des fluides de Toulouse (IMFT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), 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, (OATAO), Open Archive Toulouse Archive Ouverte, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique - CNRS (FRANCE), Etablissement Français du Sang - EFS Midi-Pyrénées (FRANCE), Institut National Polytechnique de Toulouse - INPT (FRANCE), Institut National de la Santé et de la Recherche Médicale - INSERM (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), and Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE)
Subjects: Segmentation, Adipose tissue, Mécanique des fluides, [SPI.MECA.MEFL] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Fluids mechanics [physics.class-ph], Lobules, [SPI.MECA.MEFL]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Fluids mechanics [physics.class-ph]
Abstract: International audience; Objective: White and brown adipose tissues play a major role in the regulation of metabolic functions. With the explosion of obesity and metabolic disorders, the interest in adipocyte biology is growing constantly. While several studies have demonstrated functional differences between adipose fat pads, especially in their involvement in metabolic diseases, there are no data available on possible heterogeneity within an adipose depot. Methods: This study investigated the three-dimensional (3-D) organization of the inguinal fat pad in adult mice by combining adipose tissue clearing and autofluorescence signal acquisition by confocal microscopy. In addition, the study analyzed the expression of genes involved in adipocyte biology and browning at the mARN and protein levels in distinct areas of the inguinal adipose tissue, in control conditions andafter cold exposure. Results: Semiautomated 3-D image analysis revealed an organization of the fat depot showing two regions: the core was structured into segmented lobules, whereas the periphery appeared unsegmented. Perilipin immunostaining showed that most of the adipocytes located in the core region had smaller lipid droplets, suggesting a brown-like phenotype. qPCR analysis showed a higher expression of the browning markers Ucp1, Prdm16, Ppargc1a, and Cidea in the core region than at the periphery. Finally, cold exposureinduced upregulation of thermogenic gene expression associated with an increase of UCP1 protein, specifically in the core region of the inguinal fat depot.Conclusions: Altogether, these data demonstrate a structural and functional heterogeneity of the inguinal fat pad, with an anatomically restricted browning process in the core area.
Published: 2016
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25. Postpartum hemorrhage: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians (CNGOF): in collaboration with the French Society of Anesthesiology and Intensive Care (SFAR)

Author: Loïc, Sentilhes, Christophe, Vayssière, Catherine, Deneux-Tharaux, Antoine Guy, Aya, Françoise, Bayoumeu, Marie-Pierre, Bonnet, Rachid, Djoudi, Patricia, Dolley, Michel, Dreyfus, Chantal, Ducroux-Schouwey, Corinne, Dupont, Anne, François, Denis, Gallot, Jean-Baptiste, Haumonté, Cyril, Huissoud, Gilles, Kayem, Hawa, Keita, Bruno, Langer, Alexandre, Mignon, Olivier, Morel, Olivier, Parant, Jean-Pierre, Pelage, Emmanuelle, Phan, Mathias, Rossignol, Véronique, Tessier, Frédéric J, Mercier, François, Goffinet, Service de Gynécologie-Obstétrique, CHU Bordeaux, 33076 Bordeaux, France, CHU Bordeaux [Bordeaux], Service de Gynécologie-Obstétrique, Hôpital Paule de Viguier, CHU Toulouse, 31059 Toulouse, France, UMR 1027 Inserm Université Toulouse III « Epidémiologie Périnatale et handicap de l'enfant, Santé des adolescents », 31000 Toulouse, France., Centre Hospitalier Universitaire de Toulouse - CHU Toulouse (FRANCE), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5) - Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A 1125)), Institut National de la Recherche Agronomique (INRA) - Université Sorbonne Paris Cité (USPC) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Institut National de la Recherche Agronomique (INRA) - Université Sorbonne Paris Cité (USPC) - Institut National de la Santé et de la Recherche Médicale (INSERM), Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1) - Université de Montpellier (UM), CHU de Toulouse, Pole d'anesthésie Réanimation, Hôpital Paule de Viguier, Toulouse F-31059, France, CHU Toulouse [Toulouse], Service d'Anesthésie-Réanimation (COCHIN - Anesthésie-Réanimation), Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Descartes - Paris 5 (UPD5), Etablissement Français du Sang, 20, Avenue du Stade de France, 93218 La Plaine Saint-Denis Cedex, France, Etablissement Français du Sang (EFS), Service de Gynécologie-Obstétrique, CHU Caen et UFR de Médecine Caen, 14033 Caen, France., CHU Caen, Service de Gynécologie-Obstétrique, CHU Caen et UFR de Médecine Caen, 14033 Caen, France, UFR de Médecine Caen, 14033 Caen, France., Association d'usagers, Collectif interassociatif autour de la naissance (CIANE), Paris, France, Réseau périnatal Aurore - Hôpital de la Croix Rousse, université Lyon 1, Lyon, France, EA 4129, laboratoire « Santé, individu, société », faculté de médecine Laennec, 69372 Lyon, France., Université Claude Bernard Lyon 1 (UCBL), Université de Lyon - Université de Lyon, Etablissement Français du Sang Ile de France, site de l'Hôpital Européen Georges-Pompidou, APHP, Paris, France., Service de Gynécologie-Obstétrique, CHU Estaing [Clermont-Ferrand], Service de Gynécologie-Obstétrique, CHU Marseille, Hôpital Nord, AP-HM, 13015 Marseille, France., CHU Marseille, INSERM U846, Stem Cell and Brain Research Institute, Lyon, France., Service de Gynécologie-Obstétrique, Hôpital Louis-Mourier, AP-HP, 92701 Colombes, France., Hopital Louis Mourier - AP-HP [Colombes], Service d'Anesthésie, CHU Louis-Mourier, AP-HP/Université Paris-7, 178, rue des Renouilliers, 92700 Colombes, France, Université Paris-Diderot, Sorbonne Paris Cité, EA recherche clinique coordonnée ville-hôpital, méthodologies et société (REMES), 75010 Paris, France., CHU Louis Mourrier, Département de Gynécologie-Obstétrique, Hôpital de Hautepierre, Avenue Molière, 67098 Strasbourg, France., Hôpital de Hautepierre [Strasbourg], Service d'Obstétrique et de Médecine fœtale [CHRU Nancy], Pôle de Gynécologie-Obstétrique et Reproduction, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy) - Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy) - Université de Lorraine (UL), Inserm, UMR1027, Toulouse F-31073, France, Université de Toulouse III, UMR1027, Toulouse F-31073, France, CHU Toulouse, Pole de Gynécologie Obstétrique, Hôpital Paule de Viguier, Toulouse F-31059, France., Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Radiologie, CHU Caen, 14033 Caen, France., Département d'Anesthésie Réanimation SMUR [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) - Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], DHU Risques Et Grossesse, Assistance publique - Hôpitaux de Paris (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), Société Française d'Anesthésie et de Réanimation, France, Département d'Anesthésie, Hôpital Antoine Béclère, APHP, Clamart, France, Faculté de Médecine de K. Bicêtre, Université Paris-Sud, France., Hôpital Antoine-Béclère AP-HP, and AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris]
Subjects: Postpartum hemorrhage, [SDV] Life Sciences [q-bio], Pregnancy, Oxytocics, Placenta accreta, Transfusion, Humans, Female, Peripartum hysterectomy, Delivery, Obstetric, Oxytocin
Abstract: International audience; Postpartum haemorrhage (PPH) is defined as blood loss ≥500mL after delivery and severe PPH as blood loss ≥1000mL, regardless of the route of delivery (professional consensus). The preventive administration of uterotonic agents just after delivery is effective in reducing the incidence of PPH and its systematic use is recommended, regardless of the route of delivery (Grade A). Oxytocin is the first-line prophylactic drug, regardless of the route of delivery (Grade A); a slowly dose of 5 or 10 IU can be administered (Grade A) either IV or IM (professional consensus). After vaginal delivery, routine cord drainage (Grade B), controlled cord traction (Grade A), uterine massage (Grade A), and routine bladder voiding (professional consensus) are not systematically recommended for PPH prevention. After caesarean delivery, placental delivery by controlled cord traction is recommended (grade B). The routine use of a collector bag to assess postpartum blood loss at vaginal delivery is not systematically recommended (Grade B), since the incidence of severe PPH is not affected by this intervention. In cases of overt PPH after vaginal delivery, placement of a blood collection bag is recommended (professional consensus). The initial treatment of PPH consists in a manual uterine examination, together with antibiotic prophylaxis, careful visual assessment of the lower genital tract, a uterine massage, and the administration of 5-10 IU oxytocin injected slowly IV or IM, followed by a maintenance infusion not to exceed a cumulative dose of 40IU (professional consensus). If oxytocin fails to control the bleeding, the administration of sulprostone is recommended within 30minutes of the PPH diagnosis (Grade C). Intrauterine balloon tamponade can be performed if sulprostone fails and before recourse to either surgery or interventional radiology (professional consensus). Fluid resuscitation is recommended for PPH persistent after first line uterotonics, or if clinical signs of severity (Grade B). The objective of RBC transfusion is to maintain a haemoglobin concentration (Hb) >8g/dL. During active haemorrhaging, it is desirable to maintain a fibrinogen level ≥2g/L (professional consensus). RBC, fibrinogen and fresh frozen plasma (FFP) may be administered without awaiting laboratory results (professional consensus). Tranexamic acid may be used at a dose of 1 g, renewable once if ineffective the first time in the treatment of PPH when bleeding persists after sulprostone administration (professional consensus), even though its clinical value has not yet been demonstrated in obstetric settings. It is recommended to prevent and treat hypothermia in women with PPH by warming infusion solutions and blood products and by active skin warming (Grade C). Oxygen administration is recommended in women with severe PPH (professional consensus). If PPH is not controlled by pharmacological treatments and possibly intra-uterine balloon, invasive treatments by arterial embolization or surgery are recommended (Grade C). No technique for conservative surgery is favoured over any other (professional consensus). Hospital-to-hospital transfer of a woman with a PPH for embolization is possible once hemoperitoneum is ruled out and if the patient's hemodynamic condition so allows (professional consensus).
Published: 2016

26. Risk factors and outcome of graft failure after HLA matched and mismatched unrelated donor hematopoietic stem cell transplantation: a study on behalf of SFGM-TC and SFHI

Author: Thomas Cluzeau, Isabelle Jollet, R Peffault de La Tour, Jean-Luc Taupin, Béatrice Pédron, Pascale Loiseau, Françoise Hau, Myriam Labalette, Pascal Perrier, Vincent Dubois, Damien Masson, M Fort, K Dessaux, Christophe Picard, Florent Delbos, Matthieu Filloux, Dominique Charron, Nicole Raus, Anne Devys, F Quainon, M de Matteis, Virginie Renac, Jason Lambert, L. Absi, P Van Endert, Brigitte Mercier, A Ramounau-Pigot, Service d'hématologie adulte [Hôpital de Saint Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre méditerranéen de médecine moléculaire (C3M), 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)-Université Côte d'Azur (UCA), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Etablissement français du sang, Auvergne-Loire [Saint-Etienne] (EFS), Etablissement Français du Sang, Etablissement Français du Sang (EFS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Etablissement Français du Sang [Pays de la Loire] (EFS - Site de Nantes), Hôpital Hôtel-Dieu [Nantes] (Centre Hospitalier Universitaire de Nantes), Etablissement français du sang [Nice] (EFS), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Etablissement Français du Sang Rhone-Alpes Auvergne, Etablissement français du sang [Rouen], Etablissement français du sang [Poitiers] (EFS), Laboratoire d'Immunologie (EA 2686), Université de Lille, Droit et Santé, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service Immunologie Biologique [Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Etablissement français du sang [Clermont-Ferrand] (EFS), Laboratoire de Biologie Médicale [Rennes], Etablissement français du sang [Rennes] (EFS Bretagne), Diabète de Type 1 : mécanismes et traitements immunologiques, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Institut de Recherche pour le Développement (IRD [France-Sud]), Institut de Recherche de Chimie Paris (IRCP), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Université Nice Sophia Antipolis (... - 2019) (UNS), CHU Saint Louis [APHP], Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Recherche en Informatique (LRI), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri-Mondor, Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Laboratoire de Recherche en Informatique ( LRI ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Département Imagerie et Simulation pour le Contrôle ( DISC ), Laboratoire d'Intégration des Systèmes et des Technologies ( LIST ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Groupe Immunité des Muqueuses et Agents Pathogènes ( GIMAP ), Université Jean Monnet [Saint-Étienne] ( UJM ), Développement du Systeme Immunitaire, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Paul Painlevé - UMR 8524 ( LPP ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Etablissement français du sang [Nice] ( EFS ), Politique, Religion, Institutions et Sociétés : Mutations Européennes - Groupe de Sociologie Politique Européenne ( PRISME-GSPE ), Centre National de la Recherche Scientifique ( CNRS ), Contrôle de la Réponse Immune B et des Lymphoproliférations ( CRIBL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Etablissement français du sang [Poitiers] ( EFS ), Laboratoire d'Immunologie ( EA 2686 ), EFS Rhône-Alpes, EFS, Centre International de Recherche en Infectiologie ( CIRI ), École normale supérieure - Lyon ( ENS 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 ), Etablissement Français du Sang - Alpes-Méditerranée ( EFS - Alpes-Méditerranée ), Anthropologie bio-culturelle, Droit, Ethique et Santé ( ADES ), Aix Marseille Université ( AMU ) -EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique ( CNRS ), Etablissement français du sang [Clermont-Ferrand] ( EFS ), Etablissement français du sang [Rennes] ( EFS Bretagne ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Armand Frappier ( INRS-IAF ), Institut National de la Recherche Scientifique [Québec] ( INRS ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut Armand Frappier, Institut de Recherche pour le Développement - IRD, Institut de Recherche de Chimie Paris ( IRCP ), and Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP )
Subjects: Oncology, Adult, Graft Rejection, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Hematopoietic stem cell transplantation, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Transplantation Immunology, Internal medicine, Neoplasms, medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Humans, Risk factor, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Transplantation, Univariate analysis, [ SDV ] Life Sciences [q-bio], business.industry, Hazard ratio, Hematopoietic Stem Cell Transplantation, Retrospective cohort study, Hematology, Middle Aged, medicine.disease, 3. Good health, Histocompatibility, Survival Rate, Graft-versus-host disease, Treatment Outcome, surgical procedures, operative, 030220 oncology & carcinogenesis, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, Unrelated Donors, 030215 immunology
Abstract: International audience; Graft failure remains a severe complication of hematopoietic stem cell transplantation (HSCT). Several risk factors have already beenpublished. In this study, we re-evaluated them in a large cohort who had the benefit of the recent experience in HSCT (2006–2012).Data from 4684 unrelated donor HSCT from 2006 to 2012 were retrospectively collected from centers belonging to the FrenchSociety for Stem Cell Transplantation. Among the 2716 patients for whom HLA typing was available, 103 did not engraft leading toa low rate of no engraftment at 3.8%. In univariate analysis, only type of disease and status of disease at transplant for malignantdiseases remained significant risk factors (P = 0.04 and Po0.0001, respectively). In multivariate analysis, only status of disease was asignificant risk factor (Po0.0001). Among the 61 patients who did not engraft and who were mismatched for 1 HLA class I and/orHLA-DP, 5 donor-specific antibodies (DSAs) were detected but only 1 was clearly involved in graft failure, for the others their rolewas more questionable. Second HSCT exhibited a protective although not statistically significant effect on OS (hazard ratio = 0.57[0.32–1.02]). In conclusion, only one parameter (disease status before graft) remains risk factor for graft failure in this recent cohort.
Published: 2016
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27. Adipose stromal cells improve healing of vocal fold scar: Morphological and functional evidences

Author: Bonnecaze, Guillaume De, Chaput, Benoît, Woisard, Virginie, Uro-Coste, Emmanuelle, Swider, Pascal, Vergez, Sébastien, Serrano, Elie, Casteilla, Louis, Planat-Benard, Valerie, Centre National de la Recherche Scientifique - CNRS (FRANCE), Etablissement Français du Sang - EFS Midi-Pyrénées (FRANCE), Ecole Nationale Vétérinaire de Toulouse - ENVT (FRANCE), Institut National Polytechnique de Toulouse - INPT (FRANCE), Institut National de la Santé et de la Recherche Médicale - INSERM (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Institut de mécanique des fluides de Toulouse (IMFT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, STROMALab, Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), (OATAO), Open Archive Toulouse Archive Ouverte, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS)
Subjects: [PHYS.PHYS.PHYS-FLU-DYN]Physics [physics]/Physics [physics]/Fluid Dynamics [physics.flu-dyn], [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Dynamique des Fluides, Biochimie, Biologie Moléculaire, Adipose stromal cells, Médecine humaine et pathologie, Wound healing, Biomechanical analysis, [PHYS.PHYS.PHYS-FLU-DYN] Physics [physics]/Physics [physics]/Fluid Dynamics [physics.flu-dyn], Cytotherapy, Vocal fold scar, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; OBJECTIVES/HYPOTHESIS: Adipose derived stromal cells (ASCs) are abundant and easy to prepare. Such cells may be useful for treating severe vocal disturbance caused by acute vocal fold scars. STUDY DESIGN: Prospective animal experiments with controls. METHODS: Twenty New-Zealand white rabbits were used in the present study. We evaluated vocal fold healing, with or without injection of autologous ASCs, after acute scarring. A defined lesion was created and the ASCs were immediately injected. Vocal fold regeneration was evaluated histomorphometrically and via viscoelastic analysis using an electrodynamic shaker. RESULTS: Six weeks after ASC injection, vocal folds exhibited significantly less inflammation than control folds (P < 0.005). In addition, hypertrophy of the lamina propria and fibrosis were significantly reduced upon ASC injection (P < 0.02). The decrease in viscoelastic parameters was less important in the ASC injected group compared to the noninjected group (P = 0.08). CONCLUSION: Injection of autologous ASCs improved vocal fold healing in our preclinical model. Further studies are needed, but this method may be useful in humans. LEVEL OF EVIDENCE: NA. Laryngoscope, 126:E278-E285, 2016.
Published: 2016
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28. Hypoxia Preconditioned Mesenchymal Stem Cells Improve Vascular and Skeletal Muscle Fiber Regeneration After Ischemia Through a Wnt4-dependent Pathway.: role of hypoxia on MSC regenerative properties

Author: Zoran Ivanovic, Nancy Ferreira Tojais, Pierre Oses, Jean-Michel Boiron, Danièle Daret, Thierry Couffinhal, Lionel Leroux, Jean-Marie Daniel Lamazière, Cécile Duplàa, Betty Descamps, Pascale Dufourcq, Catherine Moreau, Benjamin Seguy, Adaptation cardiovasculaire à l'ischemie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de cardiologie, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Etablissement Français du Sang (EFS), EFS-Groupe hospitalier Pellegrin, Laboratoire de Biochimie, and Université Bordeaux Segalen - Bordeaux 2
Subjects: Muscle Fibers, Skeletal, Ischemia, Biology, Mesenchymal Stem Cell Transplantation, Myoblasts, 03 medical and health sciences, Mice, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cell Movement, Wnt4 Protein, Drug Discovery, medicine, Genetics, Myocyte, Animals, Molecular Biology, Cells, Cultured, 030304 developmental biology, Mice, Knockout, Pharmacology, 0303 health sciences, Regeneration (biology), Mesenchymal stem cell, Skeletal muscle, Endothelial Cells, Cell Differentiation, medicine.disease, Cell biology, Hindlimb, Transplantation, Endothelial stem cell, Wnt Proteins, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunology, Molecular Medicine, Original Article, Stem cell, Signal Transduction
Abstract: International audience; Mesenchymal stem cells (MSC) are multipotent postnatal stem cells, involved in the treatment of ischemic vascular diseases. We investigate the ability of MSC, exposed to short-term hypoxic conditions, to participate in vascular and tissue regeneration in an in vivo model of hindlimb ischemia. Transplantation of hypoxic preconditioned murine MSC (HypMSC) enhanced skeletal muscle regeneration at day 7, improved blood flow and vascular formation compared to injected nonpreconditioned MSC (NormMSC). These observed effects were correlated with an increase in HypMSC engraftment and a putative role in necrotic skeletal muscle fiber clearance. Moreover, HypMSC transplantation resulted in a large increase in Wnt4 (wingless-related MMTV integration site 4) expression and we demonstrate its functional significance on MSC proliferation and migration, endothelial cell (EC) migration, as well as myoblast differentiation. Furthermore, suppression of Wnt4 expression in HypMSC, abrogated the hypoxia-induced vascular regenerative properties of these cells in the mouse hindlimb ischemia model. Our data suggest that hypoxic preconditioning plays a critical role in the functional capabilities of MSC, shifting MSC location in situ to enhance ischemic tissue recovery, facilitating vascular cell mobilization, and skeletal muscle fiber regeneration via a paracrine Wnt-dependent mechanism.
Published: 2010
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29. Virosome-mediated delivery of tumor antigen to plasmacytoid dendritic cells

Author: Laurence Chaperot, Juliette Angel, Mario Amacker, Jean-Paul Molens, Paulette Mezin, Rinaldo Zurbriggen, Jo ¨ el Plumas, Alexei Grichine, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire recherche et développement, EFS, Département d'anatomie et cythologie pathologique, CHU Grenoble-Hôpital Michallon, Pevion Biotech Ltd, INSERM U823, équipe 9 (Immunobiologie et Immunothérapie des Cancers), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Laboratoire recherche et développement, This work was supported by Etablissement Français du sang (EFS) Grant 2003.26 and Institut National du Cancer – Cancéropôle 2004-05. JA receives funding from Ministère Français de la Recherche et de l'Enseignement Supérieur., and Chaperot, Laurence
Subjects: MESH: Neoplasm Proteins, MESH: Antigens, Neoplasm, CD8-Positive T-Lymphocytes, Lymphocyte Activation, 0302 clinical medicine, Cytotoxic T cell, Melanoma, MESH: Orthomyxoviridae, Antigen Presentation, 0303 health sciences, MESH: Dendritic Cells, biology, hemic and immune systems, Orthomyxoviridae, MESH: CD8-Positive T-Lymphocytes, Tumor antigen, Neoplasm Proteins, 3. Good health, Virosome, Cell biology, Infectious Diseases, medicine.anatomical_structure, 030220 oncology & carcinogenesis, MESH: Immunotherapy, Active, [SDV.IMM]Life Sciences [q-bio]/Immunology, Molecular Medicine, Virosomes, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Melanoma, T cell, macromolecular substances, 03 medical and health sciences, MART-1 Antigen, Antigen, Antigens, Neoplasm, MHC class I, medicine, Humans, MESH: Lymphocyte Activation, 030304 developmental biology, MESH: Humans, General Veterinary, General Immunology and Microbiology, Public Health, Environmental and Occupational Health, Immunotherapy, Active, Dendritic Cells, Dendritic cell, MESH: Virosomes, Virology, CTL, MESH: Antigen Presentation, biology.protein
Abstract: International audience; Cytotoxic T lymphocytes (CTL) are crucial in viral clearance and tumor growth control. Thus the induction of CTL activity is an important aim in vaccine development. We investigate an innovative delivery system for peptide transfer to the MHC class I processing pathway of APC with the aim to trigger CTL in the context of an antitumoral response. The strategy relies on a novel antigen delivery system termed "chimeric immunopotentiating reconstituted influenza virosomes" (CIRIV) targeting plasmacytoid dendritic cells (PDC). By using virosomes containing encapsulated Melan-A peptide and a PDC line developed in our laboratory, we evaluated the response of Melan-A specific T cells. Virosomes have the capacity to bind PDC and are endocyted within vesicles in the cytosol. This endocytosis is inhibited by neuraminidase, suggesting that it is mediated by sialic acid present on cell surface. Furthermore, PDC loaded with Melan-A virosomes can induce a Melan-A specific T cell activation. Interestingly, they activate T cells with a better efficiency than PDC loaded with a free peptide and when PDC where previously activated by a TLR ligand. These results indicate that virosomes could be a suitable delivery system for tumor peptide in immunotherapy of cancer.
Published: 2007
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30. Baseline sensitivity of T cells to alpha-IFN correlates with sustained virological response to IFN-based triple therapy in HCV infection

Author: Christophe Hézode, Cécile Alanio, G. Uze, Armanda Casrouge, Vincent Mallet, I. Rosa-Hézode, P. Pellet, Estelle Mottez, Matthew L. Albert, Philippe Renard, Stanislas Pol, Philippe Sultanik, Laurence Bousquet, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie Humaine (CIH), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Victor Dupouy, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by grants from the Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS 11416) and ERC Starting award (M.A.). We thank the Fondation pour la Recherche Médicale for master and PhD student bursaries, We thank the Fondation pour la Recherche Médicale for master and PhD student bursaries, the Etablissement Français du Sang (EFS) for healthy donors samples, S. Pellegrini for critical review, S. Feton and K. Sperber for coordination of the clinical protocol, J. Gaston, S. Lagaye and M. Andrieu for technical assistance. We would also like to acknowledge the Department of Development, Reproduction and Cancer, Institut Cochin, Paris, the Department of Immunology, Institut Cochin, Paris, and the Centre d'Immunologie Humaine (CIH), Institut Pasteur, Paris, for support and technical expertise, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Pitié-Salpêtrière [APHP], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut Cochin (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), Institut Pasteur [Paris] - Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Montpellier 1 (UM1) - Université Montpellier 2 - Sciences et Techniques (UM2) - Université de Montpellier (UM) - Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Cochin [AP-HP]
Subjects: Male, MESH: T-Lymphocytes/metabolism, T-Lymphocytes, Drug Resistance, MESH: Hepatitis C, Chronic/virology, MESH: Leukocytes, Mononuclear/drug effects, Telaprevir, chemistry.chemical_compound, Pegylated interferon, Phosphorylation, MESH: Treatment Outcome, MESH: Aged, MESH: STAT1 Transcription Factor/metabolism, MESH: Middle Aged, biology, MESH: Polymorphism, Single Nucleotide, IFNα desensitization, IFN-based triple therapy, MESH: T-Lymphocytes/immunology, Middle Aged, Viral Load, MESH: Antiviral Agents/pharmacology, MESH: Interleukins/genetics, MESH: Case-Control Studies, 3. Good health, STAT1 Transcription Factor, Treatment Outcome, Infectious Diseases, MESH: Interferon-alpha/therapeutic use, [SDV.IMM]Life Sciences [q-bio]/Immunology, Drug Therapy, Combination, Female, MESH: Viral Load, medicine.drug, MESH: Leukocytes, Mononuclear/metabolism, MESH: Hepatitis C, Chronic/drug therapy, [SDV.IMM] Life Sciences [q-bio]/Immunology, CD3, MESH: T-Lymphocytes/drug effects, T cells, Alpha interferon, Antiviral Agents, Polymorphism, Single Nucleotide, Peripheral blood mononuclear cell, Virology, Boceprevir, medicine, Humans, Aged, MESH: Hepatitis C, Chronic/immunology, MESH: Humans, Hepatology, MESH: Phosphorylation, business.industry, Interleukins, Ribavirin, MESH: Drug Resistance/genetics, Interferon-alpha, Hepatitis C, Chronic, MESH: Male, MESH: Drug Therapy, Combination, MESH: Interferon-alpha/pharmacology, chemistry, MESH: Leukocytes, Mononuclear/immunology, Case-Control Studies, Immunology, MESH: Antiviral Agents/therapeutic use, Leukocytes, Mononuclear, biology.protein, chronic HCV infection, Interferons, business, MESH: Female, Ex vivo, MESH: Hepatitis C, Chronic/genetics
Abstract: International audience; Chronic infection with HCV is a public health problem with approximately 170 million people infected worldwide. Interferon alpha (IFNα) sensitivity in liver and IL28B genotype has been identified as important determinants of HCV clearance in the setting of pegylated interferon/ribavirin treatment. Herein, we explored IFNα sensitivity in PBMC from 21 healthy donors and 21 HCV-infected patients treated with pegylated interferon/ribavirin and HCV nonstructural protein-3 inhibitors (i.e. telaprevir/boceprevir). We explored phospho-STAT1 level as read-out for IFN signalling pathway activation in PBMC, T cells and monocytes and correlated results with virological response. We found that PBMC from healthy donors are desensitized to IFNα after priming and challenged with IFNα, with a subsequent decrease of phospho-STAT1 and interferon-stimulated genes. Furthermore, we show that CD3+ T cells, but not monocytes, become desensitized after 4 weeks of treatment, with a significant decrease of phospho-STAT1 after ex vivo IFNα stimulation. Finally, we identified baseline phospho-STAT1 level in CD3+ T cells as a potential biomarker of sustained virological response, regardless of the IL28B genotype. In the upcoming costly era of IFN-sparing regimen, baseline IFNα sensitivity could act as biomarker to define cost-effectiveness strategies of treatment by identifying patients who will or will not respond to IFN-based treatments.
Published: 2015
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31. Delivery of molecules into human corneal endothelial cells by carbon nanoparticles activated by femtosecond laser

Author: Jumelle, Clothile, Mauclair, Cyril, Houzet, Julien, Bernard, Aurelien, He, Zhiguo, Forest, Fabien, Peoc'H, Michel, Acquart, Sophie, Gain, Philippe, Thuret, Gilles, Biologie, Ingénierie et Imagerie de la Greffe de Cornée (EA 2521, JE2521, IFR143), Université Jean Monnet [Saint-Étienne] (UJM), Laboratoire Hubert Curien [Saint Etienne] (LHC), Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS)-Institut d'Optique Graduate School (IOGS), Service d'Anatomie et Cytologie Pathologiques, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Department of Pathology, Saint Etienne University Hospital, Etablissement Français du Sang (EFS), EFS, Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), and Institut d'Optique Graduate School (IOGS)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2015

32. Hémorragie du post-partum : recommandations pour la pratique clinique — Texte des recommandations (texte court)

Author: Corinne Dupont, Bruno Langer, M. Rossignol, F. Bayoumeu, Olivier Morel, Loïc Sentilhes, François Goffinet, A.G. Aya, C. Deneux-Taraux, F.J. Mercier, J. P. Pelage, Chantal Ducroux-Schouwey, M. Dreyfus, Jean-Baptiste Haumonte, Véronique Tessier, A. François, Marie-Pierre Bonnet, Gilles Kayem, E. Phan, Olivier Parant, C. Huissoud, Alexandre Mignon, Denis Gallot, R. Djoudi, Christophe Vayssière, P. Dolley, H. Keita-Meyer, Service de gynécologie-obstétrique, CHU d'Angers, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Société Française d'Anesthésie et de Réanimation, France, Département d'Anesthésie, Hôpital Antoine Béclère, APHP, Clamart, France, Faculté de Médecine de K. Bicêtre, Université Paris-Sud, France., Hôpital Antoine-Béclère AP-HP, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), CHU de Toulouse, Pole d'anesthésie Réanimation, Hôpital Paule de Viguier, Toulouse F-31059, France, CHU Toulouse [Toulouse], Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants (UMR_S 953), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11), Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Service de Gynécologie-Obstétrique et Médecine de la Reproduction [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Association d'usagers, Collectif interassociatif autour de la naissance (CIANE), Paris, France, Santé Individu Société - SIS (SIS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université Lumière - Lyon 2 (UL2), Etablissement Français du Sang Ile de France, site de l'Hôpital Européen Georges-Pompidou, APHP, Paris, France., Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Service de Gynécologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Gynécologie-Obstétrique, CHU Marseille, Hôpital Nord, AP-HM, 13015 Marseille, France., CHU Marseille, Institut cellule souche et cerveau (U846 Inserm - UCBL1), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Gynécologie-Obstétrique, Hôpital Louis-Mourier, AP-HP, 92701 Colombes, France., Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Recherche Clinique ville-hôpital, Méthodologies et Société (REMES), Université Paris Diderot - Paris 7 (UPD7), Département de Gynécologie-Obstétrique, Hôpital de Hautepierre, Avenue Molière, 67098 Strasbourg, France., Hôpital de Hautepierre [Strasbourg], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Obstétrique et de Médecine fœtale [CHRU Nancy], Pôle de Gynécologie-Obstétrique et Reproduction, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Lorraine (UL), Service d'Imagerie Diagnostique et de Radiologie Thérapeutique [CHU Caen], Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Département d'Anesthésie Réanimation SMUR [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], DHU Risques Et Grossesse, 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), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Pôle Anesthésie Réanimation [CHU de Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Santé Individu Société (SIS), Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC), Institut cellule souche et cerveau (SBRI), Université de Lorraine (UL)-Service d'Obstétrique et de Gynécologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-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), CHU Angers, Épidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps, Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département anesthésie-douleur, CHU Caremeau, Nîmes, Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants ( UMR_S 953 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris-Sud - Paris 11 ( UP11 ), Etablissement Français du Sang [La Plaine Saint-Denis] ( EFS ), Service de Gynécologie-Obstétrique et Médecine de la Reproduction [Caen], Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -CHU Caen, Santé Individu Société - SIS ( SIS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Hospices Civils de Lyon ( HCL ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Université Jean Moulin - Lyon III ( UJML ) -Université Lumière - Lyon 2 ( UL2 ), Etablissement Français du Sang (EFS), Service de Gynécologie-Obstétrique, Réseau périnatal Aurore - Hôpital de la Croix Rousse, université Lyon 1, Lyon, France, INSERM U846, Stem Cell and Brain Research Institute, Lyon, France., Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon, Hopital Louis Mourier - AP-HP [Colombes], Service d'Anesthésie, CHU Louis-Mourier, AP-HP/Université Paris-7, 178, rue des Renouilliers, 92700 Colombes, France, Université Paris-Diderot, Sorbonne Paris Cité, EA recherche clinique coordonnée ville-hôpital, méthodologies et société (REMES), 75010 Paris, France., CHU Louis Mourrier, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ) -Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ) -Université de Lorraine ( UL ), Service d'Imagerie Diagnostique et de Radiologie Thérapeutique [Caen], Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (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 ), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique ( CRESS - U1153 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Université de Montpellier (UM)-Université Montpellier 1 (UM1), Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (SBRI), Université Claude Bernard Lyon 1 (UCBL), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Lyon-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 03 medical and health sciences, 030219 obstetrics & reproductive medicine, 0302 clinical medicine, Reproductive Medicine, [ SDV ] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], Obstetrics and Gynecology, 030212 general & internal medicine, General Medicine, ComputingMilieux_MISCELLANEOUS
Abstract: Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 43 - N° 10 - p. 1170-1179
Published: 2014
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33. First evidence of subclinical renal tubular injury during sickle-cell crisis

Author: Pablo Bartolucci, Bertrand Godeau, Bertrand Renaud, Mehdi Khellaf, Vincent Audard, Frédéric Galactéros, Gaetana Vandemelebrouck, Yves Levy, Philippe Lang, Anoosha Habibi, Sylvain Loric, Philippe Grimbert, Stéphane Moutereau, Service de Néphrologie et Transplantation, Institut Francilien de recherche en Néphrologie et Transplantation (IFRNT), 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, Departement de Biochimie-Pharmacotoxicologie, Hôpital Henri Mondor, Unité INSERM 955, Equipe 2, Etablissement Français du Sang (EFS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Centre de Référence des Syndromes Drépanocytaires Majeurs, Service de Médecine Interne, Service d'Accueil des Urgences, Service d'immunologie clinique [Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Equipe 21 Inserm, Institut Francilien de recherche en Néphrologie et Transplantation (IFRNT)-Institut Francilien de recherche en Néphrologie et Transplantation (IFRNT)-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, Equipe 2 Inserm, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut Mondor de Recherche Biomédicale (IMRB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Service de Médecine Interne, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB), BMC, Ed., 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), and Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Adult, Male, medicine.medical_specialty, 030232 urology & nephrology, Urine, [SDV.GEN] Life Sciences [q-bio]/Genetics, Anemia, Sickle Cell, Gastroenterology, Nephropathy, Kidney Tubules, Proximal, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Humans, Genetics(clinical), Pharmacology (medical), Endothelial dysfunction, Genetics (clinical), 030304 developmental biology, Subclinical infection, Medicine(all), 0303 health sciences, Creatinine, Kidney, Univariate analysis, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Research, Acute kidney injury, General Medicine, Acute Kidney Injury, medicine.disease, medicine.anatomical_structure, Endocrinology, chemistry, Female, business
Abstract: International audience; BackgroundThe pathophysiologic mechanisms classically involved in sickle-cell nephropathy include endothelial dysfunction and vascular occlusion. Arguments demonstrating that ischemia-reperfusion injury-related kidney damage might coincide with vaso-occlusive crisis (VOC) are lacking.MethodsIn this prospective study, we sought to determine whether tubular cells and glomerular permeability might be altered during VOC. Urine neutrophil gelatinase-associated lipocalin (NGAL) levels and albumin-excretion rates (AER) of 25 patients were evaluated prospectively during 25 VOC episodes and compared to their steady state (ST) values.ResultsDuring VOC, white blood-cell counts (WBC) and C-reactive protein (CRP) were significantly higher than at ST but creatinine levels were comparable. Urine NGAL levels were significantly increased during VOC vs ST (P = 0.007) and remained significant when normalized to urine creatinine (P = 0.004), while AER did not change significantly. The higher urine NGAL concentration was not associated with subsequent (24-48 hour) acute kidney injury. Univariate analysis identified no significant correlations between urine NGAL levels and laboratory parameters during VOC.ConclusionsThese results demonstrated that subclinical ischemia-reperfusion tubular injury is common during VOC and highlight the importance of hydroelectrolyte monitoring and correction during VOC.
Published: 2014
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34. Targeting a G-Protein-Coupled Receptor Overexpressed in Endocrine Tumors by Magnetic Nanoparticles To Induce Cell Death

Author: Darine El Hajj Diab, Julian Carrey, Etienne Meunier, Reasmey P. Tan, Bruno Payré, Bernard Pipy, Véronique Gigoux, Vincent Connord, Pascal Clerc, Daniel Fourmy, Michel Gougeon, Claire Sanchez, Polarisation des Macrophages et Récepteurs Nucléaires dans les Pathologies Inflammatoires et Infectieuses, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR50, Laboratoire de physique et chimie des nano-objets (LPCNO), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie de Toulouse (ICT-FR 2599), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées, Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre interuniversitaire de recherche et d'ingenierie des matériaux (CIRIMAT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Réceptologie et Ciblage Thérapeutique en Cancérologie (RCTC), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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 National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), INSERM grant no. PC201310, European Project: 262943,EC:FP7:NMP,FP7-NMP-2010-LARGE-4,MULTIFUN(2011), Centre National de la Recherche Scientifique - CNRS (FRANCE), Etablissement Français du Sang - EFS Midi-Pyrénées (FRANCE), Ecole Nationale Vétérinaire de Toulouse - ENVT (FRANCE), Institut National Polytechnique de Toulouse - INPT (FRANCE), Institut National des Sciences Appliquées de Toulouse - INSA (FRANCE), Institut National de la Santé et de la Recherche Médicale - INSERM (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Centre Hospitalier Universitaire de Toulouse - CHU Toulouse (FRANCE), Centre de Microscopie Electronique Appliquée à la Biologie - CMEAB (Toulouse, france), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-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), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Matériaux, media_common.quotation_subject, General Physics and Astronomy, 02 engineering and technology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Ferric Compounds, Cell Line, Receptors, G-Protein-Coupled, Magnetics, Mice, 03 medical and health sciences, chemistry.chemical_compound, Iron oxide nanoparticles, Cell surface receptor, Endocrine Gland Neoplasms, Gastrins, Endocrine tumors, Animals, Humans, General Materials Science, Epidermal growth factor receptor, Internalization, Receptor, 030304 developmental biology, media_common, Dynamin, G protein-coupled receptor, 0303 health sciences, Alternating magnetic field, Cell Death, biology, Macrophages, Lysosomal cell death pathways, General Engineering, [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, Cholecystokinin-2 receptor, Ingénierie biomédicale, Cell biology, HEK293 Cells, chemistry, Biochemistry, Apoptosis, biology.protein, Nanoparticles, 0210 nano-technology, Intracellular trafficking
Abstract: International audience; Nanotherapy using targeted magnetic nanoparticles grafted with peptidic ligands of receptors overexpressed in cancers is a promising therapeutic strategy. However, nanoconjugation of peptides can dramatically affect their properties with respect to receptor recognition, mechanism of internalization, intracellular trafficking, and fate. Furthermore, investigations are needed to better understand the mechanism whereby application of an alternating magnetic field to cells containing targeted nanoparticles induces cell death. Here, we designed a nanoplatform (termed MG-IONP-DY647) composed of an iron oxide nanocrystal decorated with a ligand of a G-protein coupled receptor, the cholecystokinin-2 receptor (CCK2R) that is overexpressed in several malignant cancers. MG-IONP-DY647 did not stimulate inflammasome of Raw 264.7 macrophages. They recognized cells expressing CCK2R with a high specificity, subsequently internalized via a mechanism involving recruitment of β-arrestins, clathrin-coated pits, and dynamin and were directed to lysosomes. Binding and internalization of MG-IONP-DY647 were dependent on the density of the ligand at the nanoparticle surface and were slowed down relative to free ligand. Trafficking of CCK2R internalized with the nanoparticles was slightly modified relative to CCK2R internalized in response to free ligand. Application of an alternating magnetic field to cells containing MG-IONP-DY647 induced apoptosis and cell death through a lysosomal death pathway, demonstrating that cell death is triggered even though nanoparticles of low thermal power are internalized in minute amounts by the cells. Together with pioneer findings using iron oxide nanoparticles targeting tumoral cells expressing epidermal growth factor receptor, these data represent a solid basis for future studies aiming at establishing the proof-of-concept of nanotherapy of cancers using ligand-grafted magnetic nanoparticles specifically internalized via cell surface receptors.
Published: 2014
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35. Prospects of apoptotic cell-based therapies for transplantation and inflammatory diseases

Author: Philippe Saas, Sandra Kaminski, Sylvain Perruche, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Etablissement Français du Sang de Bourgogne Franche-Comté (site de Dijon) (EFS BFC (site de Dijon)), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), This work was supported by recurrent grants from the INSERM, EFS and Université of Franche Comté,as well as the Agence Nationale de la Recherche (LabEXLipSTIC, ANR-11-LABX-0021and ECellFrance consortium, ANR-11-INBS-0005), the LigueContre le Cancer (to S.P.), theEtablissementFrançais du Sang (No. 2011-05 to S.P.), The Arthritis Foundation Courtin (to S.P.), theConseil Régional de Franche-Comté ('soutien au LabEXLipSTIC' to P.S.), and The Fondation pour laRecherche Médicale (FRM) 'espoirs de la recherche' to SK., Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Université de Franche-Comté (UFC)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), EFS Bourgogne Franche-Comté (EFS-BFC), Etablissement Français du Sang (EFS), Saas, Philippe, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer ( LabEx LipSTIC ), Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École pratique des hautes études ( EPHE ) -Institut Gustave Roussy ( IGR ) -Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ) -Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Université de Franche-Comté ( UFC ), and EFS Bourgogne Franche-Comté ( EFS-BFC )
Subjects: Graft Rejection, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.medical_treatment, Immunology, Cell, Cell- and Tissue-Based Therapy, Arthritis, Graft vs Host Disease, Inflammation, Apoptosis, regulatory T cells, Autoimmune Diseases, Cell therapy, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, Animals, Humans, dendritic cells, 030304 developmental biology, Immunosuppression Therapy, 0303 health sciences, tolerance, business.industry, Immunosuppression, Immunotherapy, apoptotic cells, medicine.disease, 3. Good health, macrophages, Transplantation, medicine.anatomical_structure, Oncology, arthritis, inflammation, Models, Animal, [SDV.IMM]Life Sciences [q-bio]/Immunology, immunotherapy, medicine.symptom, cell therapy, business, 030215 immunology, transplantation
Abstract: International audience; Apoptotic cell removal or interactions of early-stage apoptotic cells with immune cells are associated with an immunomodulatory microenvironment that can be harnessed to exert therapeutic effects. While the involved immune mechanisms are still being deciphered, apoptotic cell infusion has been tested in different experimental models where inflammation is deregulated. This includes chronic and acute inflammatory disorders such as arthritis, contact hypersensitivity and acute myocardial infarction. Apoptotic cell infusion has also been used in transplantation settings to prevent or treat acute and chronic rejection, as well as to limit acute graft-versus-host disease associated with allogeneic hematopoietic cell transplantation. Here, we review the mechanisms involved in apoptotic cell-induced immunomodulation and data obtained in preclinical models of transplantation and inflammatory diseases.
Published: 2013
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36. Caspase-3 Is Involved in the Signalling in Erythroid Differentiation by Targeting Late Progenitors

Author: Daniela Boehm, Christelle Mazurier, Dhouha Darghouth, Marie-Catherine Giarratana, Luc Douay, Laurence Harmand, Anne-Marie Faussat, HAL UPMC, Gestionnaire, Différenciation et prolifération des cellules souches adultes. application à la thérapie cellulaire hématopoiétique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Saint-Antoine (UMRS893), Etablissement Français du Sang (EFS), EFS, Cytométrie et Imagerie Saint-Antoine (CISA), Unité Mixte de Service d'Imagerie et de Cytométrie (UMS LUMIC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Myeloid, Cell division, Cellular differentiation, Red Cells, lcsh:Medicine, Apoptosis, Biochemistry, 0302 clinical medicine, hemic and lymphatic diseases, Molecular Cell Biology, lcsh:Science, Erythroid Precursor Cells, Cells, Cultured, 0303 health sciences, Multidisciplinary, Caspase 3, Stem Cells, Cell Differentiation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Cell cycle, Caspase Inhibitors, Cell biology, Enzymes, Adult Stem Cells, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Medicine, Cell Division, Signal Transduction, Research Article, G2 Phase, Biology, Cell Growth, 03 medical and health sciences, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, Cell Lineage, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Progenitor cell, 030304 developmental biology, Cell Proliferation, Cell growth, lcsh:R, Hematopoietic Stem Cells, Hematopoiesis, Enzyme Activation, lcsh:Q, Developmental Biology
Abstract: International audience; A role for caspase activation in erythroid differentiation has been established, yet its precise mode of action remains elusive. A drawback of all previous investigations on caspase activation in ex vivo erythroid differentiation is the lack of an in vitro model producing full enucleation of erythroid cells. Using a culture system which renders nearly 100% enucleated red cells from human CD34 + cells, we investigated the role of active caspase-3 in erythropoiesis. Profound effects of caspase-3 inhibition were found on erythroid cell growth and differentiation when inhibitors were added to CD34 + cells at the start of the culture and showed dose-response to the concentration of inhibitor employed. Enucleation was only reduced as a function of the reduced maturity of the culture and the increased cell death of mature cells while the majority of cells retained their ability to extrude their nuclei. Cell cycle analysis after caspase-3 inhibition showed caspase-3 to play a critical role in cell proliferation and highlighted a novel function of this protease in erythroid differentiation, i.e. its contribution to cell cycle regulation at the mitotic phase. While the effect of caspase-3 inhibitor treatment on CD34 + derived cells was not specific to the erythroid lineage, showing a similar reduction of cell expansion in myeloid cultures, the mechanism of action in both lineages appeared to be distinct with a strong induction of apoptosis causing the decreased yield of myeloid cells. Using a series of colony-forming assays we were able to pinpoint the stage at which cells were most sensitive to caspase-3 inhibition and found activated caspase-3 to play a signalling role in erythroid differentiation by targeting mature BFU-E and CFU-E but not early BFU-E.
Published: 2013
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37. Autoantibodies specific for the phospholipase A2 receptor in recurrent and De Novo membranous nephropathy

Author: Laurent Mesnard, Eric Rondeau, Christiane Mousson, G. Dautin, Pierre Ronco, Hanna Debiec, Chantal Jouanneau, L. Martin, Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Urgences Néphrologiques & Transplantation Rénale, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], UFR des Sciences de Santé (Université de Bourgogne), Université de Bourgogne ( UB ), Service de Pathologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), EFS Bourgogne Franche-Comté ( EFS-BFC ), Etablissement Français du Sang (EFS), Service de néphrologie (CHU de Dijon), Agence de la Biomédecine, Fondation pour la Recherche Médicale and 'Association pour l'Utilisation du Rein Artificiel' (AURA). H.D. is the recipient of a 'Contrat d'Interface' from Assistance Publique-Hôpitaux de Paris., Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Bourgogne (UB), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Etablissement Français du Sang de Bourgogne Franche-Comté (site de Dijon) (EFS BFC (site de Dijon)), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), RONCO, Pierre, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)
Subjects: Male, MESH : Recurrence, MESH : DNA, Complementary, MESH: Glomerulonephritis, Membranous, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Glomerulonephritis, Membranous, 0302 clinical medicine, Recurrence, [ SHS.INFO ] Humanities and Social Sciences/Library and information sciences, Immunology and Allergy, Medicine, MESH: Autoantibodies, MESH : Fluorescent Antibody Technique, Direct, Pharmacology (medical), MESH : Female, MESH : Glomerulonephritis, Membranous, Receptor, MESH: Middle Aged, biology, MESH : Receptors, Phospholipase A2, Glomerulonephritis, Middle Aged, respiratory system, MESH : Adult, 3. Good health, Fluorescent Antibody Technique, Direct, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, lipids (amino acids, peptides, and proteins), De novo, Antibody, MESH: Fluorescent Antibody Technique, Direct, Adult, DNA, Complementary, [SHS.INFO]Humanities and Social Sciences/Library and information sciences, MESH : Male, macromolecular substances, [SHS.INFO] Humanities and Social Sciences/Library and information sciences, 03 medical and health sciences, recurrent, Antigen, Membranous nephropathy, stomatognathic system, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH : Autoantibodies, MESH: Receptors, Phospholipase A2, Humans, MESH : Middle Aged, Direct fluorescent antibody, PLA2R1, Autoantibodies, Transplantation, MESH: Humans, business.industry, Receptors, Phospholipase A2, MESH : Humans, Autoantibody, membranous nephropathy, MESH: Adult, MESH: DNA, Complementary, medicine.disease, equipment and supplies, MESH: Male, MESH: Recurrence, Immunology, biology.protein, business, MESH: Female
Abstract: International audience; Recent findings in idiopathic membranous nephropathy (MN) suggest that in most patients, the disease is because of anti-phospholipase A(2) receptor (PLA(2) R1) autoantibodies. Our aim was to analyze the prevalence and significance of anti-PLA(2) R1 antibodies in recurrent and de novo MN after transplantation. We assessed circulating PLA(2) R1 autoantibodies by a direct immunofluorescence assay based on human embryonic kidney cells transfected with a PLA(2) R1 cDNA, and the presence of PLA(2) R1 antigen in immune deposits. We showed that PLA(2) R1 was involved in 5 of 10 patients with recurrent MN, but in none of the 9 patients with de novo MN. We also showed a marked heterogeneity in the kinetics and titers of anti-PLA(2) R1, which may relate to different pathogenic potential. We provide evidence that some patients with PLA(2) R1-related idiopathic MN and anti-PLA(2) R1 antibodies at the time of transplantation will not develop recurrence. Because PLA(2) R1 autoantibody was not always associated with recurrence, its predictive value should be carefully analyzed in prospective studies.
Published: 2011
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38. Evolutionary history of hepatitis C virus genotype 5a in France, a multicenter ANRS study

Author: Juliette Foucher, Ghassan Riachi, Sophie Vallet, Julien Guglielmini, Hélène Le Guillou-Guillemette, Arielle R. Rosenberg, Sophie Alain, Jacques Izopet, Evelyne Schvoerer, Véronique Loustaud-Ratti, Cécile Henquell, Hélène Peigue-Lafeuille, Philippe Podevin, Henri Coppere, Armand Abergel, Vincent Thibault, Dominique Roulot, Syria Laperche, Elisabeth André, Jean-Luc Bailly, Jean-Christophe Plantier, Sophie Metivier, Catherine Gaudy, Rafael Juan Pérez-Serra, Olivier Garraud, Jannick Verbeeck, Marc Van Ranst, Jérôme Gournay, Cyrille Feray, Antoine Mahul, Isabelle Fouchard-Hubert, Florence Legrand-Abravanel, Gilles Bommelaer, Audrey Mirand, Pascale Trimoulet, Henia Saoudin, Jean-Baptiste Nousbaum, Hélène Odent-Malaure, Yazid Baazia, Pascal Lebray, Louis d’Alteroche, Samir Gourari, François Habersetzer, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Génétique et Physiologie bactériennes [Gosselies], Université libre de Bruxelles (ULB), Laboratory of Clinical Virology, Rega Institute for Medical Research, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Laboratoire d'Informatique, de Modélisation et d'optimisation des Systèmes (LIMOS), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-SIGMA Clermont (SIGMA Clermont)-Ecole Nationale Supérieure des Mines de St Etienne-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes], CHU Paris, Centre National de Référence Virus des hépatites B, C et Delta, Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Gastro-entérologie - Hépatologie [Purpan], CHU Toulouse [Toulouse], Service de bactériologie-virologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Virologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Laboratoire de Biologie Cellulaire, UPRES 1833, CHU Rouen, Normandie Université (NU), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet [Saint-Étienne] (UJM), Institute of Computer Science - University of Augsburg (ICS), Universität Augsburg [Augsburg], Service d'hépato-gastro-entérologie, Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Service de gastroenterologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de bactériologie-Virologie-Hygiène [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Université de Limoges (UNILIM), Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Laboratoire de Virologie, CHU Strasbourg, Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, Epidémiologie et pathogénie des infections à entérovirus (EPIE), Université d'Auvergne - Clermont-Ferrand I (UdA), Etablissement Français du Sang (EFS), EFS, VIROLOGIE, Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Clinical and Epidemiological Virology, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Rega Institute for medical research, Service d'Hépatogastroentérologie, Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), SIGMA Clermont (SIGMA Clermont)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Ecole Nationale Supérieure des Mines de St Etienne-Centre National de la Recherche Scientifique (CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, CHU Saint-Eloi, Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-SIGMA Clermont (SIGMA Clermont)-Ecole Nationale Supérieure des Mines de St Etienne (ENSM ST-ETIENNE)-Centre National de la Recherche Scientifique (CNRS), Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Université Jean Monnet - Saint-Étienne (UJM), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges, Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Université Libre de Bruxelles [Bruxelles] (ULB), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Sigma CLERMONT (Sigma CLERMONT)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure des Mines de St Etienne, Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Service d'Hépato-Gastroentérologie [Rouen], Hôpital Hôtel-Dieu [Paris]-Centre hospitalier universitaire de Nantes (CHU Nantes), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Jean Verdier [Bondy], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Microbiology (medical), Adult, Male, Genotype, Population, Molecular Sequence Data, Mutation, Missense, Hepacivirus, Microbiology, Coalescent theory, Evolution, Molecular, 03 medical and health sciences, Flaviviridae, 0302 clinical medicine, Viral Envelope Proteins, Phylogenetics, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Genetics, Prevalence, Humans, education, Molecular clock, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Phylogeny, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Aged, 0303 health sciences, education.field_of_study, Cross Infection, biology, Molecular epidemiology, Phylogenetic tree, Transfusion Reaction, Bayes Theorem, Middle Aged, biology.organism_classification, Virology, Hepatitis C, 3. Good health, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 030211 gastroenterology & hepatology, Female, France
Abstract: The epidemic history of HCV genotype 5a is poorly documented in France, where its prevalence is very low, except in a small central area, where it accounts for 14.2% of chronic hepatitis C cases. A Bayesian coalescent phylogenetic investigation based on the E1 envelope gene and a non-structural genomic segment (NS3/4) was carried out to trace the origin of this epidemic using a large sample of genotype 5a isolates collected throughout France. The dates of documented transmissions by blood transfusion were used to calibrate five nodes in the phylogeny. The results of the E1 gene analysis showed that the best-fitting population dynamic model was the expansion growth model under a relaxed molecular clock. The rate of nucleotide substitutions and time to the most recent common ancestors (tMRCA) of genotype 5a isolates were estimated. The divergence of all the French HCV genotype 5a strains included in this study was dated to 1939 [95% HPD: 1921–1956], and the tMRCA of isolates from central France was dated to 1954 [1942–1967], which is in agreement with epidemiological data. NS3/4 analysis provided similar estimates with strongly overlapping HPD values. Phylodynamic analyses give a plausible reconstruction of the evolutionary history of HCV genotype 5a in France, suggesting the concomitant roles of transfusion, iatrogenic route and intra-familial transmission in viral diffusion.
Published: 2011
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39. Hypoxia Preconditioned Mesenchymal Stem Cells Improve Vascular and Skeletal Muscle Fiber Regeneration After Ischemia Through a Wnt4-dependent Pathway

Author: Leroux, Lionel, Descamps, Betty, Ferreira Tojais, Nancy, Séguy, Benjamin, Oses, Pierre, Moreau, Catherine, Daret, Danièle, Ivanovic, Zoran, Boiron, Jean-Michel, Daniel Lamazière, Jean-Marie, Dufourcq, Pascale, Couffinhal, Thierry, Duplàa, Cécile, Boullé, Christelle, Adaptation cardiovasculaire à l'ischemie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de cardiologie, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Etablissement Français du Sang (EFS), EFS-Groupe hospitalier Pellegrin, Laboratoire de Biochimie, and Université Bordeaux Segalen - Bordeaux 2
Subjects: [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: International audience; Mesenchymal stem cells (MSC) are multipotent postnatal stem cells, involved in the treatment of ischemic vascular diseases. We investigate the ability of MSC, exposed to short-term hypoxic conditions, to participate in vascular and tissue regeneration in an in vivo model of hindlimb ischemia. Transplantation of hypoxic preconditioned murine MSC (HypMSC) enhanced skeletal muscle regeneration at day 7, improved blood flow and vascular formation compared to injected nonpreconditioned MSC (NormMSC). These observed effects were correlated with an increase in HypMSC engraftment and a putative role in necrotic skeletal muscle fiber clearance. Moreover, HypMSC transplantation resulted in a large increase in Wnt4 (wingless-related MMTV integration site 4) expression and we demonstrate its functional significance on MSC proliferation and migration, endothelial cell (EC) migration, as well as myoblast differentiation. Furthermore, suppression of Wnt4 expression in HypMSC, abrogated the hypoxia-induced vascular regenerative properties of these cells in the mouse hindlimb ischemia model. Our data suggest that hypoxic preconditioning plays a critical role in the functional capabilities of MSC, shifting MSC location in situ to enhance ischemic tissue recovery, facilitating vascular cell mobilization, and skeletal muscle fiber regeneration via a paracrine Wnt-dependent mechanism.
Published: 2010
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40. Endothelial Morphometry by Image Analysis of Corneas Organ Cultured at 31 degrees C

Author: Gilles Thuret, M. Zhao, Yann Gavet, Simone Piselli, A. Defreyn, Sophie Acquart, Olivier Garraud, Philippe Gain, Etablissement Français du Sang (EFS), EFS, Service d'ophtalmologie [CHU de Saint-Etienne] (SAINTOPH), CHU Saint-Etienne, Biologie, Ingénierie et Imagerie de la Greffe de Cornée (EA 2521, JE2521, IFR143), Université Jean Monnet [Saint-Étienne] (UJM), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Département Imagerie et Morphologie (DIM-ENSMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-CIS, Laboratoire des Procédés en Milieux Granulaires (LPMG-EMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS), Institut Fédératif de Recherche en Sciences et Ingénierie de la Santé (IFRESIS-ENSMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-IFR143, Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Etablissement Français du Sang, Université Jean Monnet Saint Etienne, and CHU de Saint-Etienne
Subjects: Adult, Male, medicine.medical_specialty, Pathology, Endothelium, Adolescent, genetic structures, Coefficient of variation, medicine.medical_treatment, Cell Count, Biology, Organ culture, Eye Banks, Cornea, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Organ Culture Techniques, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, image analysis, Ophthalmology, medicine, Humans, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Corneal transplantation, Aged, Image Cytometry, Aged, 80 and over, Endothelium, Corneal, Eye bank, Organ Preservation, Middle Aged, corneal transplantation, medicine.anatomical_structure, corneal endothelial cells, SPECULAR MICROSCOPY, 030221 ophthalmology & optometry, Female, corneal organ culture, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, 030217 neurology & neurosurgery, morphometry
Abstract: To determine the factors influencing endothelial morphometry by using image analysis of corneas stored in organ culture to determine the coefficient of variation (CV) in cell area and percentage of hexagonal cells.The endothelia of 505 of the 559 corneas consecutively stored at the eye bank were routinely analyzed with Sambacornea image-analysis software (ver. 1.2.10; Tribvn, Châtillon, France) on three large-field images of 750 x 1000 microm, obtained after osmotic dilation of the intercellular spaces with 0.9% sodium chloride. Analysis was performed on at least 300 cells. The quality of the three-image set was graded poor, average, or good by an independent observer. The studied parameters were donor age and sex, lens status, storage time, and intrinsic quality of captured images. Statistics were analyzed by nonparametric tests.Image analysis was possible for 504 of the 505 assessed corneas. Donor age correlated significantly with endothelial cell density (ECD; r = -0.343), CV (r = 0.221), and hexagonality (r = -0.314; P0.001 for the three). Image quality significantly influenced these three parameters. ECD and hexagonality decreased parallel to image quality, whereas the CV increased. In the 258 corneas assessed twice (on average, at day [D] +4, then D +14) ECD, CV, and hexagonality decreased during storage.Despite the sometimes mediocre quality of the transmitted light microscopy images, endothelial parameters supplied by the analyzer were clinically reliable, since variations similar to those long known in specular microscopy were found. Endothelial morphometry (CV and hexagonality) is likely to provide further information on the endothelial function of the graft tissue, perhaps particularly for grafts of borderline ECD, close to the discard threshold.
Published: 2010
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41. Sensitivity of two hepatitis B virus, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) nucleic acid test systems relative to hepatitis B surface antigen, anti-HCV, anti-HIV, and p24/anti-HIV combination assays in seroconversion panels

Author: Isabelle Dupont, Valérie Barlet, Pascal Morel, Nico Lelie, Marie Deschaseaux, Harry van Drimmelen, Pierre Gallian, Cathy Guitton, Philippe de Micco, B. David, Azzedine Assal, Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Université Paris 8 Vincennes-Saint-Denis (UP8), Joseph Louis LAGRANGE (LAGRANGE), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Université de Bordeaux (UB), UMR 6578 : Anthropologie Bio-Culturelle (UAABC), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), 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 des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang (EFS), and EFS
Subjects: HBsAg, Time Factors, Hepatitis C virus, Immunology, [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, Hepacivirus, 030204 cardiovascular system & hematology, Biology, medicine.disease_cause, Sensitivity and Specificity, 03 medical and health sciences, 0302 clinical medicine, medicine, BDNA test, Immunology and Allergy, Humans, Serologic Tests, 030212 general & internal medicine, Viremia, Seroconversion, Hepatitis B virus, Hepatitis B Surface Antigens, medicine.diagnostic_test, Nucleic acid test, HIV, Reproducibility of Results, virus diseases, patitis C virus (HCV), Hematology, Hepatitis B, medicine.disease, Virology, 3. Good health, human immunodeficiency virus (HIV), DNA, Viral, RNA, Viral, Regression Analysis, Viral hepatitis, Nucleic Acid Amplification Techniques, hepatitis B virus
Abstract: BACKGROUND: Accurate determination of the infectious window period (IWP) that remains with individual-donation (ID) or minipool (MP) NAT compared to those with serology assays is essential for residual risk estimations. STUDY DESIGN AND METHODS: The relative sensitivity of the Procleix Tigris system (Gen-Probe/Chiron) used in ID-NAT format and cobas s 201 (Roche Molecular Systems) applied in 1:6 diluted samples to mimic six-minipool (MP6) nucleic acid test (NAT) was assessed by quadruplicate testing of five seroconversion panels per marker. A mathematical analysis based on the log-linear increase of viremia in the ramp-up phase, as established with bDNA 3.0 assays enabled estimation of the IWP for human immunodeficiency virus (HIV) and hepatitis B virus (HBV) assays. RESULTS: The mean IWPs were Tigris HIV RNA 5.5 days, s 201 (1:6) HIV RNA 7.4 days, GenScreen Plus p24/anti-HIV 17.8 days, PRISM anti-HIV 19.0 days, Tigris HBV DNA 20.6 days, s 201 (1:6) HBV DNA 22.6 days, Bio-Rad hepatitis B surface antigen (HBsAg) 37.8 days, and PRISM HBsAg 35.5 days. At estimated 50 percent NAT seroconversion rates, s 201 (1:6) and Tigris showed mean window-period reduction times (WPRTs) of 30.5 to 35.5 days to hepatitis C virus antibody (anti-HCV) assays, 10.4 to 13.5 days to anti-HIV, or combination p24/anti-HIV assays and 12.8 to 17.2 days to HBsAg assays. CONCLUSIONS: Tigris ID-NAT detected HIV RNA 2 days earlier than s 201 MP6-NAT, but the difference in sensitivity between the two NAT systems was not significant in HBV seroconversion panels. Insufficient seroconversion samples were available for reliable modeling of WPRT in early HCV infection, but 1.4 to 2.0 days could be predicted by translating analytical sensitivity data. Both multiplex NAT systems demonstrate significant WPRTs compared to (combined) antigen and antibody assays.
Published: 2009
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42. Reproducibility of endothelial assessment during corneal organ culture: comparison of a computer-assisted analyzer with manual methods

Author: Gilles Thuret, Sophie Acquart, Nilanjana Deb-Joardar, Yann Gavet, Olivier Garraud, Philippe Gain, Harald Egelhoffer, Service d'ophtalmologie [CHU de Saint-Etienne] (SAINTOPH), CHU Saint-Etienne, Institut Fédératif de Recherche en Sciences et Ingénierie de la Santé (IFRESIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-IFR143, Centre Ingénierie et Santé (CIS-ENSMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Département Imagerie et Statistiques (DIS-ENSMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-CIS, Laboratoire des Procédés en Milieux Granulaires (LPMG-EMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang (EFS), EFS, CHU de Saint Etienne, and Etablissement Français du Sang
Subjects: Organ Culture Technique, Spectrum analyzer, Pathology, medicine.medical_specialty, genetic structures, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Intraclass correlation, preservation, Cell Count, system, Diagnostic Techniques, Ophthalmological, Eye Banks, image-analysis, donor corneas, 03 medical and health sciences, 0302 clinical medicine, Organ Culture Techniques, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, Cell density, medicine, Image Processing, Computer-Assisted, Humans, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Observer Variation, Reproducibility, reliability, business.industry, Computer aid, Endothelium, Corneal, Reproducibility of Results, Confidence interval, Endothelial cell density, quality, specular microscopy ancillary, 030221 ophthalmology & optometry, sp-2000p, Tissue Preservation, Nuclear medicine, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, 030217 neurology & neurosurgery, cell density
Abstract: PURPOSE. To investigate the reproducibility of endothelial assessment of organ-cultured corneas with the computer-assisted Sambacornea analyzer in comparison with manual methods. METHODS. Seven observers of two eye banks determined the endothelial cell density (ECD) of 30 corneas through a grid overlay placed on endothelial photographs using two manual modes, unaided (naked-eye) and pointing (point-out). ECD was measured with the analyzer, first in automated mode, where analysis was completely machine determined, and then in touched-up mode, where the observer selected the analysis zone and corrected poorly drawn cell borders. Interobserver variability of ECD for the different methods was compared. Reproducibility of morphometry parameters was determined for the touched-up mode. RESULTS. Interobserver variability was +/- 19.2% (95% confidence interval [CI], 13.0-25.4) and +/- 17.6% (95% CI, 11.9-23.3) for the naked-eye and point-out mode, respectively, whereas the touched-up mode gave the least variability of +/- 9.6% (95% Cl, 6.5-12.7), confirmed by the highest intraclass correlation coefficient of 0.95 (95% CI, 0.91-0.97). Interobserver variability increased with worsening image quality. Manual modes underestimated ECD (naked-eye by a mean 10.7% [SD, 2.9%]; point-out by a mean 6.9% [SD, 2.3%]), whereas the automated mode overestimated ECD by a mean 14.7% (SD, 24.3%). Reproducibility of morphometric parameters by the touched-up mode was acceptable but was influenced by endothelial pleomorphism. CONCLUSIONS. Manual counting shows systematic underestimation of ECD with high interobserver variability. The analyzer in automated mode overestimates ECD and is absolutely unreliable. Detection of cell contours by the specific algorithm, combined with manual correction by a skilled technician, appears to be the most reliable method of ECD and morphometry determination.
Published: 2007
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43. Morphométrie endothéliale par analyse d'image des cornées conservées en organoculture : étude prospective de 505 cornées consécutives Endothelial morphometry of organ cultured corneas using image analysis: prospective study of 505 consecutive corneas

Author: Thuret, Gilles, Defreyn, Alexandre, Acquart, Sophie, Deb-Joardar, Nilanjana, Zhao, Min, Gavet, Yann, Theilliere, C., Pereira, S., Peoc'H, Michel, Garraud, Olivier, Maugery, Jean, Gain, Phillipe, Service d'ophtalmologie [CHU de Saint-Etienne] (SAINTOPH), CHU Saint-Etienne, Etablissement Français du Sang (EFS), EFS, Biologie, Ingénierie et Imagerie de la Greffe de Cornée (EA 2521, JE2521, IFR143), Université Jean Monnet [Saint-Étienne] (UJM), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Département Imagerie et Morphologie (DIM-ENSMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-CIS, Laboratoire des Procédés en Milieux Granulaires (LPMG-EMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS), Institut Fédératif de Recherche en Sciences et Ingénierie de la Santé (IFRESIS-ENSMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-IFR143, Département de pathologie, CHU Saint-Etienne-Hôpital Bellevue, Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang, Université Jean Monnet Saint Etienne, and CHU de Saint-Etienne
Subjects: cellules hexagonales, organoculture, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, cornées, densité cellulaire endothéliale, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, coefficient de variation de surface cellulaire (CV), analyse d'image, morphométrie endothéliale, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing
Abstract: International audience; But Déterminer les facteurs influençant la morphométrie endothéliale des cornées en organoculture (mesure par analyse d'image) : coefficient de variation de surface cellulaire (CV) et pourcentage de cellules hexagonales. Matériels et Méthodes L'endothélium de 505 cornées consécutives conditionnées à la banque de cornée de l'EFS Loire/Auvergne a été analysé en routine par l'analyseur Sambacornea sur 3 images grand champ, après dilatation osmotique des espaces intercellulaires et comptage d'au moins 300 cellules. La qualité du set d'images était classée en mauvaise, acceptable, ou bonne par un observateur indépendant. Paramètres étudiés : âge et sexe du donneur, statut cristallinien, délai postmortem, type de milieu de conservation, durée de conservation avant analyse, qualité intrinsèque des images saisies. Résultats L'analyse d'image a été possible sur 504 des 505 cornées évaluées. L'âge du donneur était significativement corrélé à la densité cellulaire endothéliale (r =-0343) au CV (r = 0,221) et à l'hexagonalité (r =-0,314) (p < 0,001 pour les 3). La qualité des images influençait significativement ces 3 paramètres, DCE et hexagonalité baissant parallèlement à la qualité des images tandis que le CV augmentait. Pour les 258 cornées évaluées 2 fois (en moyenne à J + 4 puis à J + 14) DCE, CV et hexagonalité diminuaient en cours de conservation. Il n'existait pas d'influence du milieu sur la morphométrie. Discussion Malgré les conditions difficiles de l'organoculture et la qualité des images de microscopie optique parfois médiocre, l'analyse par Sambacornea de l'endothélium des greffons fournit des paramètres endothéliaux qui sont cliniquement fiables puisque superposables à celles connues de longue date en microscopie spéculaire. La morphométrie (CV et hexagonalité) est susceptible d'apporter des informations supplémentaires sur la fonction endothéliale, peut être en particulier pour les greffons proches du seuil conventionnel de cession de 2000 cell/mm2. Conclusion Des essais cliniques prospectifs utilisant l'analyse d'image devront évaluer l'influence de la morphométrie endothéliale sur la survie du greffon à long terme chez le receveur.
Published: 2007
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44. Stratégies de comptage par analyse d'image de l'endothélium des cornées conservées en organoculture : détection de contour versus pointage du centre . Counting strategies for endothelial assessment of organ cultured corneas using image analysis: comparison of border versus center method

Author: Thuret, Gilles, Deb-Joardar, Nilanjana, Zhao, Min, Robert, Pierre-Yves, Gavet, Yann, Acquart, Sophie, Chavarin, Patricia, Dumollard, Jean-Marc, Peoc'H, Michel, Maugery, Jean, Gain, Phillipe, Service d'ophtalmologie [CHU de Saint-Etienne] (SAINTOPH), CHU Saint-Etienne, Biologie, Ingénierie et Imagerie de la Greffe de Cornée (EA 2521, JE2521, IFR143), Université Jean Monnet [Saint-Étienne] (UJM), Biologie moléculaire et cellulaire des microorganismes (EA3175), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Limoges (UNILIM), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Département Imagerie et Morphologie (DIM-ENSMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-CIS, Laboratoire des Procédés en Milieux Granulaires (LPMG-EMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS), Institut Fédératif de Recherche en Sciences et Ingénierie de la Santé (IFRESIS-ENSMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-IFR143, Etablissement Français du Sang (EFS), EFS, Auvergne-Loire Regional Blood Bank (EFS Auvergne-Loire), Saint-Etienne, Ministère de la santé, Department of Pathology, Saint Etienne University Hospital, Département de pathologie, CHU Saint-Etienne-Hôpital Bellevue, Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang, Université Jean Monnet Saint Etienne, CHU de Saint-Etienne, CHU Limoges, and Université de Limoges
Subjects: border methods, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, endothelial cell density (ECD), coefficient of variation (CV), cell count strategies, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, endothelial assessment, center methods, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, corneal storage
Abstract: International audience; Aim To compare two different cell count strategies, border and center methods for endothelial assessment during corneal storage. Material and Methods Seven observers determined the endothelial cell density (ECD), coefficient of variation (CV) of cell area, and percentage hexagonality of 30 organ cultured corneas by the border (contour detection and manual retouch) and center method (indicating cell centers) using Sambacornea analyser. Interobserver variability for ECD and agreement between the two methods was determined. The accuracy of the center method was verified by counting on ten standard photolithographic mosaics (called keratotest) by border (reference method) and center methods, first as fast and next as precise as possible (fast and slow modes respectively) and the time noted. Data between border and center methods was compared using nonparametric paired tests. Results For stored corneas, interobserver variability was ±9.6% (95%CI [6.5-12.7]) for border method and ±9.3% (95%CI[6.3-12.3]) for center method. ECD [mean±SD (range), median] was [2948±565 (1644-3878), 3081] and [2961±568 (1736-3914), 3037] respectively and showed excellent correlation (Pearson coefficient r=0.998, p
Published: 2007
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45. CRCI 2 NA inaugural symposium: A meeting on tumor and immune ecosystems.

Author: Guen VJ, André-Grégoire G, Beauvillain C, Boury F, Chauvet M, Dupuy AMM, Fonteneau JF, Gagne K, Gavard J, Gomez-Bougie P, Grasset E, Jardine J, Lamoureux F, Laurent-Blond M, Letouzé É, Macé Y, Maurice S, Pecqueur C, Pouliquen D, Rbah-Vidal L, Pellat-Deceunynck C, and Juin PP
Subjects: Humans, Immunotherapy methods, Animals, Neoplasms therapy, Neoplasms immunology, Tumor Microenvironment
Abstract: The CRCI 2 NA inaugural symposium, a meeting on tumor and immune ecosystems, took place in the vibrant and picturesque city of Nantes. The meeting gathered world-renowned experts in cancer biology and immunology. It showcased the most advanced science on mechanisms driving cellular heterogeneity, plasticity, and signaling in normal and cancer cellular ecosystems, which contribute to cancer development, progression, and therapeutic resistance. Recent developments in cancer immunotherapy and anti-tumor strategies were also discussed to collectively assess new therapeutic vulnerabilities to defeat cancer., (© 2024 The Author(s). Biology of the Cell published by Wiley‐VCH GmbH on behalf of Société Française des Microscopies and Société de Biologie Cellulaire de France.)
Published: 2024
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46. A review of cell-free DNA and epigenetics for non-invasive diagnosis in solid organ transplantation.

Author: Sebastian A, Silvy M, Coiffard B, Reynaud-Gaubert M, Magdinier F, Chiaroni J, Picard C, and Pedini P
Abstract: Introduction: Circulating cell-free DNA (cfDNA) is emerging as a non-invasive biomarker in solid organ transplantation (SOT) monitoring and data on its diagnostic potential have been increasing in recent years. This review aims to summarize the main advances in technologies, clinical applications and future perspectives of cfDNA for transplantation, and to approach the contribution of epigenetics to improve the specific detection of rejection., Methods: Published literature investigating cfDNA as a biomarker for the diagnosis of transplant rejection was systematically reviewed, specifically clinical trials evaluating the test performance of algorithms predicting rejection based on cfDNA fraction. Literature highlighting epigenetic features in transplant rejection was also reviewed to outline the potential contribution of the epigenomic analysis to the needs of rejection-specific diagnosis., Results: 40 articles were reviewed, and results were extracted and summarized. 16 met the inclusion criteria by evaluating the diagnostic performance of a predictive test for the discrimination of rejection vs. non-rejection patients (2 heart, 3 liver, 4 kidney, and 7 lung transplantations). The recurring conclusion is the kinetics of dd-cfDNA levels, strongly increasing immediately after transplantation and reaching basal levels after days to weeks and remaining stable in non-rejection patients. On the other hand, rejection is characterized by an increase in dd-cfDNA levels, depending on the transplanted organs. In addition, the epigenetic signature can help improve the specificity of the diagnosis of rejection by searching for specific epigenetic features that are by the clinical status of patients., Conclusion: Cell-free DNA is a promising non-invasive biomarker but still needs standardization of technologies and protocols to be used for diagnostic purposes. Moreover, the lack of specificity of this marker can be compensated by the contribution of epigenetic analysis for which data are growing, although progress is still needed for its use in a clinical context., Competing Interests: Authors AS and MS are employed by company BeDia Genomics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Sebastian, Silvy, Coiffard, Reynaud-Gaubert, Magdinier, Chiaroni, Picard and Pedini.)
Published: 2024
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47. An Innovative One Health Approach: BIOQUALIM, a Transdisciplinary Research Action Protocol-From Cultivated Biodiversity to Human Health Prevention.

Author: Murat-Ringot A, Lan R, Fraticelli L, Fayet Y, Bourgeois D, Nugem R, Piton M, Goetz E, Préau M, Dutertre F, Bernoud-Hubac N, Basbous L, Lastmann A, Charreyre MT, and Carrouel F
Subjects: Humans, Diet, Healthy methods, Interdisciplinary Research, Noncommunicable Diseases prevention & control, Diet, Vegetarian, Neoplasms prevention & control, Quality of Life, Biodiversity, One Health
Abstract: Background/objectives: The "One Health" approach underscores the connection between human, animal, and environmental health, promoting solutions to global challenges like climate change and biodiversity loss. The Planetary Health Diet (PHD) promotes a plant-based diet with organically grown plants to reduce the environmental impact of meat production and decrease the risk of non-communicable diseases (NCDs). The BIOQUALIM project will evaluate the PHD's effectiveness in preventing NCDs like periodontal diseases and cancers through four inter-related studies., Methods: The clinical study will involve volunteers reducing their meat consumption and incorporating einkorn into their diet, allow for analysis of their interdental microbiota, oral health, general health, and quality of life. The chemical analysis will study nutrients and anti-cancer compounds in einkorn and common wheat varieties. The behavioral study will explore PHD knowledge, attitudes, and behaviors related to PHD. The psycho-social study will evaluate the impact of peer-support workshops on plant-based dietary cooking among post-therapy cancer patients., Results: The results are expected to demonstrate that einkorn varieties possess nutritional properties that, when incorporated into the PHD enriched with einkorn, can enhance health markers. This study will identify barriers to and facilitators of PHD adoption and highlight how peer-support workshops can improve dietary adherence., Conclusions: BIOQUALIM's transdisciplinary approach will demonstrate the PHD's role in preventing NCDs.
Published: 2024
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48. The MKK3 module integrates nitrate and light signals to modulate secondary dormancy in Arabidopsis thaliana .

Author: Regnard S, Otani M, Keruzore M, Teinturier A, Blondel M, Kawakami N, Krapp A, and Colcombet J
Subjects: Abscisic Acid metabolism, Light, Seeds growth & development, Seeds genetics, Signal Transduction, Arabidopsis genetics, Arabidopsis metabolism, Arabidopsis physiology, Arabidopsis Proteins metabolism, Arabidopsis Proteins genetics, Gene Expression Regulation, Plant, Germination genetics, MAP Kinase Kinase 3 metabolism, MAP Kinase Kinase 3 genetics, Nitrates metabolism, Plant Dormancy genetics
Abstract: Seed dormancy corresponds to a reversible blockage of germination. Primary dormancy is established during seed maturation, while secondary dormancy is set up on the dispersed seed, following an exposure to unfavorable factors. Both dormancies are relieved in response to environmental factors, such as light, nitrate, and coldness. Quantitive Trait Locus (QTL) analyses for preharvest sprouting identified MKK3 kinase in cereals as a player in dormancy control. Here, we showed that MKK3 also plays a role in secondary dormancy in Arabidopsis within a signaling module composed of MAP3K13/14/19/20, MKK3, and clade-C MAPKs. Seeds impaired in this module acquired heat-induced secondary dormancy more rapidly than wild-type (WT) seeds, and this dormancy is less sensitive to nitrate, a signal able to release dormancy. We also demonstrated that MPK7 was strongly activated in the seed during dormancy release, especially in response to light and nitrate. This activation was greatly reduced in map3 k13/14/19/20 and mkk3 mutants. Finally, we showed that the module was not regulated and apparently did not regulate the genes controlling abscisic acid/gibberellin acid hormone balance, one of the crucial mechanisms of seed dormancy control. Overall, our work identified a MAPK module controlling seed germination and enlarged the panel of functions of the MKK3-related modules in plants., Competing Interests: Competing interests statement:The authors declare no competing interest.
Published: 2024
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49. Performance evaluation of the new Access HIV Ag/Ab combo assay on the DxI 9000 Access Immunoassay Analyzer.

Author: Lemée V, Gréaume S, Gautier J, Dzamitika SA, Coignard C, Jortani SA, Grillet B, Badawi M, and Plantier JC
Subjects: Humans, Immunoassay methods, HIV Antigens blood, HIV Antigens immunology, HIV-2 immunology, HIV-2 genetics, Reagent Kits, Diagnostic standards, HIV Infections diagnosis, Sensitivity and Specificity, HIV Antibodies blood, HIV-1 immunology, HIV-1 genetics, HIV Core Protein p24 blood, HIV Core Protein p24 immunology
Abstract: Fourth-generation HIV immunoassays have been developed to reduce the window period of detection during seroconversion period, allowing for the detection of early and established infections. The aim of this work was to evaluate a newly developed assay, Access HIV Ag/Ab combo on the novel high throughput DxI 9000 Access Immunoassay Analyzer (Beckman Coulter, Inc.). The assay allows for simultaneous qualitative detection and differentiation of HIV-1 p24 antigen and HIV-1/2 antibodies. Assay performance was compared to two gold standard assays, the Abbott Architect HIV Ag/Ab Combo and Roche Elecsys HIV Duo, and assessed in a multicenter study, using a wide panel of samples (n > 9000, clinical samples and viral lysates) representative of genetic diversity for both antibodies and antigens, early phases of infection, negative, and cross-reacting samples. The clinical sensitivity was 100 % for clinical samples as well as for viral lysates. Data on viral lysates and early detection on seroconversion panels showed a better result with the Access assay. Analytical sensitivity showed a limit of p24 detection determined around 0.2 IU/mL. The overall specificity was 99.91 %, and no interference was found using the potentially cross-reactive samples. In conclusion, the Access HIV Ag/Ab combo assay demonstrated its ability for accurate diagnosis of chronic as well as primary HIV infections on the DxI 9000 Analyzer, despite the high level of genetic diversity of these viruses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
Published: 2024
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50. Saccharomyces cerevisiae as a platform for vaccination against bovine mastitis.

Author: Danzelle C, Cunha P, Noleto PG, Gilbert FB, Santos KR, Staub C, Pinard A, Deslis A, Barbey S, Germon P, De Craene JO, Rainard P, Blondel M, and Martins RP
Abstract: Mastitis is a major issue for the dairy industry. Despite multiple attempts, the efficacy of available mastitis vaccines is limited and this has been attributed to their incapacity to trigger robust cell-mediated immunity. Yeasts have recently been identified as promising antigen vectors capable of inducing T-cell responses, surpassing the antibody-biased mechanisms elicited by conventional adjuvanted vaccines. In this study, we combine in vitro, ex vivo, and in vivo approaches to evaluate the potential of the yeast Saccharomyces cerevisiae as a platform for novel vaccines against bovine mastitis. We demonstrate that S. cerevisiae is safe for intramuscular and intramammary immunisation in dairy cows. Vaccination resulted in a significant increase of IFNγ and IL-17 responses against the yeast platform but not against the vaccine antigen. These observations highlight that strategies to counterbalance the immunodominance of S. cerevisiae antigens are necessary for the development of successful vaccine candidates., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rodrigo Prado Martins reports financial support, administrative support, article publishing charges, and equipment, drugs, or supplies were provided by French National Research Agency. Kamila Reis Santos reports financial support was provided by Campus France. Pablo Gomes Noleto reports financial support was provided by French National Institute for Agricultural Research INRAE. Celya Danzelle reports financial support was provided by University of Tours. Rodrigo Prado Martins has patent pending to INRAE, Université de Tours. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Published: 2024
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