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1. Circulating Human Metabolites Resulting From TOTUM-070 Absorption (a Plant-Based, Polyphenol-Rich Hypocholesterolemic Ingredient) Improve Lipid Metabolism in Human Hepatocytes: Lessons From an Original ex vivo Clinical Trial

Author: Wauquier, Fabien, Langhi, Cédric, Boutin-Wittrant, Line, Otero, Yolanda, Le Joubioux, Florian, Maugard, Thierry, Roux, Véronique, Macian, Nicolas, Pickering, Gisele, Bargetto, Maxime, Cazaubiel, Murielle, Peltier, Sébastien, Sirvent, Pascal, Wittrant, Yohann, Clinic'n'Cell SAS, Valbiotis R & D [Riom], Valbiotis SAS, Partenaires INRAE-Partenaires INRAE, Valbiotis R&D [Perigny], La Rochelle Université (ULR), CIC Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-Centre de Pharmacologie Clinique, Unité de Nutrition Humaine (UNH), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: Introduction: TOTUM-070 is a patented polyphenol-rich compound which has shown hypocholesterolemic properties in preclinical studies. However, clinically validated approaches and further investigations on the mode of action at cellular level especially in humans are required for optimized care management. In this study, we designed an ex-vivo clinical innovative approach considering the metabolites produced by the digestive tract following the ingestion of TOTUM-070 in humans.Methods: Human serum was collected in healthy subjects before and following acute intake of 5g of TOTUM-070. Availability of circulating metabolites was confirmed and characterized by UPLC-MS. Human serum enriched with metabolites deriving from TOTUM-070 absorption was further incubated with human hepatocytes, pretreated or not with palmitate (250 μM). In such lipotoxic environment, hepatocyte behavior was monitored to determine whether and how TOTUM-070 metabolites may improve cholesterol metabolism in human.Results: In the presence of the human metabolites from TOTUM-070, human hepatocytes were protected from an induced lipotoxic stress. No effect on cell toxicity was detected in the presence of enriched sera. Hepatocyte protection was characterized by (1) the inhibition of both triglycerides (-41%, p
Published: 2022

2. In Cellulo Mössbauer and EPR Studies Bring New Evidence to the Long‐Standing Debate on Iron–Sulfur Cluster Binding in Human Anamorsin

Author: Geneviève Blondin, Martin Clémancey, Lucia Banci, Francesca Camponeschi, Simone Ciofi-Baffoni, Sara Matteucci, University of Florence, Department of Chemistry and Magnetic Resonance Center (CERM), Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine (CIRMMP), Università degli Studi di Siena = University of Siena (UNISI)-Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)-University of Bologna-Partenaires INRAE, Physiochimie des Métaux (PMB), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Department of Chemistry, University of Florence, ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), ANR-11-LABX-0003,ARCANE,Grenoble, une chimie bio-motivée(2011), Università degli Studi di Firenze = University of Florence (UniFI), and Università degli Studi di Siena = University of Siena (UNISI)-Università degli Studi di Firenze = University of Florence (UniFI)-University of Bologna/Università di Bologna-Partenaires INRAE
Subjects: Iron-Sulfur Proteins, anamorsin, Protein family, Stereochemistry, metalloproteins, Iron–sulfur cluster, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 010402 general chemistry, 01 natural sciences, Catalysis, law.invention, 03 medical and health sciences, Spectroscopy, Mossbauer, chemistry.chemical_compound, in cellulo EPR spectroscopy, law, Mössbauer spectroscopy, Iron-sulfur cluster binding, Cluster (physics), Metalloprotein, Humans, in cellulo Mcssbauer spectroscopy, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Electron paramagnetic resonance, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, 010405 organic chemistry, Communication, Electron Spin Resonance Spectroscopy, Intracellular Signaling Peptides and Proteins, General Medicine, General Chemistry, Communications, iron-sulfur clusters, 0104 chemical sciences, chemistry, Iron–Sulfur Clusters, in cellulo Mössbauer spectroscopy, [PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph], Biogenesis, Protein Binding
Abstract: Human anamorsin is an iron–sulfur (Fe–S)‐cluster‐binding protein acting as an electron donor in the early steps of cytosolic iron–sulfur protein biogenesis. Human anamorsin belongs to the eukaryotic CIAPIN1 protein family and contains two highly conserved cysteine‐rich motifs, each binding an Fe–S cluster. In vitro works by various groups have provided rather controversial results for the type of Fe–S clusters bound to the CIAPIN1 proteins. In order to unravel the knot on this topic, we used an in cellulo approach combining Mössbauer and EPR spectroscopies to characterize the iron–sulfur‐cluster‐bound form of human anamorsin. We found that the protein binds two [2Fe–2S] clusters at both its cysteine‐rich motifs., A combined in cellulo Mössbauer‐ and EPR‐based approach is applied to address controversial aspects of Fe–S cluster‐binding properties of human anamorsin, a protein involved in the biogenesis of cytosolic [4Fe–4S] cluster‐binding proteins. We show that human anamorsin binds two [2Fe–2S] clusters in‐cell in two highly conserved cysteine‐rich motifs typical of the eukaryotic CIAPIN1 protein family, with different electron‐spin‐relaxation properties.
Published: 2021
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3. TOTUM-63, a plant-based polyphenol-rich extract, improves glycaemic control in subjects with prediabetes or early stage newly-diagnosed type 2 diabetes in a randomized, double-blind, placebo-controlled trial

Author: Pascal Sirvent, Vivien Chavanelle, Yolanda F. Otero, Maxime Bargetto, Florian Le Joubioux, Nathalie Boisseau, Thierry Maugard, Murielle Cazaubiel, Bruno Pereira, Bruno Guigas, Samy Hadjadj, Sebastien L. Peltier, André Marette, Jean‐Marie Bard, Valbiotis R&D [Perigny], Valbiotis SAS, Partenaires INRAE-Partenaires INRAE, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Clermont Auvergne (UCA)-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Auvergne (UFR STAPS - UCA), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), La Rochelle Université (ULR), LIttoral ENvironnement et Sociétés (LIENSs), La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS), CHU Clermont-Ferrand, Leiden University Medical Center (LUMC), Universiteit Leiden, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Quebec Heart and Lung Institute, Université Laval [Québec] (ULaval), FR 3473 Institut universitaire Mer et Littoral (IUML), Le Mans Université (UM)-Université d'Angers (UA)-Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-École Centrale de Nantes (Nantes Univ - ECN), and Nantes Université (Nantes Univ)
Subjects: Male, Blood Glucose, botanical extract, Plant Extracts, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Polyphenols, Glycemic Control, glycaemia, TOTUM-63, Middle Aged, Overweight, metabolic syndrome, Prediabetic State, weight management, Endocrinology, Diabetes Mellitus, Type 2, Double-Blind Method, Internal Medicine, diabetic, Humans, Female, Obesity, prediabetic, Aged
Abstract: Aim The plant-based polyphenol-rich extract TOTUM-63 improves glucose homeostasis in various preclinical models of obesity and type 2 diabetes (T2D). A pilot exploratory study showed that TOTUM-63 has good safety and tolerability profiles, and beneficial effects on postprandial glucose control in healthy individuals with overweight. The aim of this study was to assess the effects of TOTUM-63 on glycaemic control in individuals with prediabetes or early stage newly-diagnosed T2D (which does not require pharmacological treatment). Materials and Methods This study was a multicentre, randomized, double-blind, placebo-controlled trial. Individuals with prediabetes or early stage newly-diagnosed T2D and with overweight/abdominal obesity received TOTUM-63 (5 g/day) or placebo for 6 months. The primary outcome was the change in fasting blood glucose. Results Fifty-one participants (age: 57.1 +/- 10 years; body mass index: 31.3 +/- 5.7 kg.m(2); 35 women and 16 men) completed the study (n = 38 TOTUM-63, n = 13 placebo). After 6 months, blood glucose concentration after fasting and after the 2-h oral glucose tolerance test was reduced in the TOTUM-63-treated group compared with the placebo group (placebo-corrected difference between baseline and month 6: -0.71 mmol/L, p < .05, and -1.93 mmol/L, p < .05, respectively). TOTUM-63 was safe and well tolerated and significantly reduced body weight gain (-1.9 kg; p < .05), waist circumference (-4.5 cm; p < .001), circulating triglycerides (-0.54 mmol/L; p < .01) and low-density lipoprotein-cholesterol (-0.38 mmol/L; p < .05) compared with placebo. Conclusions TOTUM-63 lowered fasting blood glucose in participants with impaired fasting glycaemia and glucose intolerance. Moreover, TOTUM-63 showed a good safety and tolerability profile and improved several metabolic syndrome features. Therefore, TOTUM-63 is a promising candidate for T2D prevention.
Published: 2022
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4. Impact of TOTUM-63, a fibre and polyphenol rich plant-based composition, on gut and pancreatic hormone secretion in diet-induced obese mice

Author: Vivien Chavanelle, Stéphanie Chanon, Claudie Pinteur, Emmanuelle Loizon, Guillaume Vial, Yolanda F. Otero, Florian Le Joubioux, Thierry Maugard, Sébastien L. Peltier, Pascal Sirvent, Béatrice Morio, Valbiotis R & D [Riom], Valbiotis SAS, Partenaires INRAE-Partenaires INRAE, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Valbiotis R&D [Perigny], LIttoral ENvironnement et Sociétés (LIENSs), La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS), and Vial, Guillaume
Subjects: Blood Glucose, Male, hormonal regulation, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Mice, Obese, Gastric Inhibitory Polypeptide, Diet, High-Fat, Weight Gain, Mice, Glucagon-Like Peptide 1, Animals, Humans, Insulin, glucose homeostasis, Peptide YY, Pyruvates, Nutrition, Nutrition and Dietetics, enteroendocrine cells, Plant Extracts, Body Weight, digestive, oral, and skin physiology, Polyphenols, Glucagon, Mice, Inbred C57BL, [SDV] Life Sciences [q-bio], plant-based food supplement, Metabolism and Cardiovascular Diseases glucose homeostasis, Cardiology and Cardiovascular Medicine, hormones, hormone substitutes, and hormone antagonists
Abstract: International audience; Background and AimsTOTUM-63, a fibre and polyphenol rich plant-based composition, has been demonstrated to significantly improve body weight and glucose homeostasis in animal models of obesity. Our study aimed at exploring whether the mechanisms include modulation of gut (glucose-dependent insulinotropic peptide (GIP), glucagon-like petide-1 (GLP-1), cholecystokinin (CCK), peptide YY (PYY)) and pancreatic (insulin, glucagon) hormones, all important regulators of glucose control, appetite and body weight.Methods and ResultsMale C57BL/6JRJ mice were assigned to either standard chow (CON), high fat diet (HF, 60% energy from fat) or HF-TOTUM-63 (HF diet 60% supplemented with TOTUM-63 2.7%) for 10 weeks. In vivo glucose homeostasis (oral glucose tolerance test (OGTT), intraperitoneal pyruvate tolerance test (ipPTT)), glucose-induced portal vein hormone concentration, gut hormone gene expression and protein content as well as enteroendocrine cell contents were assessed at the end of the dietary intervention. The present study evidenced that TOTUM-63 reduced food intake, limited weight gain and improved glucose and pyruvate tolerance of HF-fed animals. This was associated with an increase in PYY content in the colon, an altered pattern of PYY secretion between fasted and glucose-stimulated states, and with a significant improvement in the portal vein concentration of GLP-1, insulin and glucagon, but not GIP and CCK, in response to glucose stimulation.ConclusionOverall, these data suggest that TOTUM-63 might have a specific impact on gut L-cells and on the expression and secretion of GLP-1 and PYY incretins, potentially contributing to the reduced food intake, body weight gain and improved glucose homeostasis.
Published: 2022
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5. Inhibitory Potential of α-Amylase, α-Glucosidase, and Pancreatic Lipase by a Formulation of Five Plant Extracts: TOTUM-63

Author: Quentin Haguet, Florian Le Joubioux, Vivien Chavanelle, Hugo Groult, Nathan Schoonjans, Cédric Langhi, Arnaud Michaux, Yolanda F. Otero, Nathalie Boisseau, Sébastien L. Peltier, Pascal Sirvent, Thierry Maugard, LIttoral ENvironnement et Sociétés (LIENSs), La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS), Valbiotis R & D [La Rochelle], Valbiotis SAS, Partenaires INRAE-Partenaires INRAE, Valbiotis R & D [Riom], Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Clermont Auvergne (UCA)-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Auvergne (UFR STAPS - UCA), and Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA)
Subjects: enzyme assay, plant extracts, [SDV]Life Sciences [q-bio], Organic Chemistry, General Medicine, Catalysis, Computer Science Applications, Inorganic Chemistry, α-glucosidase, type 2 diabetes, Physical and Theoretical Chemistry, cardiometabolic diseases, Molecular Biology, Spectroscopy
Abstract: Controlling post-prandial hyperglycemia and hyperlipidemia, particularly by regulating the activity of digestive enzymes, allows managing type 2 diabetes and obesity. The aim of this study was to assess the effects of TOTUM-63, a formulation of five plant extracts (Olea europaea L., Cynara scolymus L., Chrysanthellum indicum subsp. afroamericanum B.L.Turner, Vaccinium myrtillus L., and Piper nigrum L.), on enzymes involved in carbohydrate and lipid absorption. First, in vitro inhibition assays were performed by targeting three enzymes: α-glucosidase, α-amylase, and lipase. Then, kinetic studies and binding affinity determinations by fluorescence spectrum changes and microscale thermophoresis were performed. The in vitro assays showed that TOTUM-63 inhibited all three digestive enzymes, particularly α-glucosidase (IC50 of 13.1 µg/mL). Mechanistic studies on α-glucosidase inhibition by TOTUM-63 and molecular interaction experiments indicated a mixed (full) inhibition mechanism, and higher affinity for α-glucosidase than acarbose, the reference α-glucosidase inhibitor. Lastly, in vivo data using leptin receptor-deficient (db/db) mice, a model of obesity and type 2 diabetes, indicated that TOTUM-63 might prevent the increase in fasting glycemia and glycated hemoglobin (HbA1c) levels over time, compared with the untreated group. These results show that TOTUM-63 is a promising new approach for type 2 diabetes management via α-glucosidase inhibition.
Published: 2023
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6. The TOTUM-63 Supplement and High-Intensity Interval Training Combination Limits Weight Gain, Improves Glycemic Control, and Influences the Composition of Gut Mucosa-Associated Bacteria in Rats on a High Fat Diet

Author: DUPUIT, Marine, Chavanelle, Vivien, Chassaing, Benoit, Perriere, Fanny, Etienne, Monique, Plissonneau, Claire, Boscaro, Audrey, Barnich, Nicolas, Pialoux, Vincent, Maugard, Thierry, Le Joubioux, Florian, Peltier, Sébastien, Sirvent, Pascal, Otero, Yolanda, BOISSEAU, Nathalie, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Clermont Auvergne (UCA)-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Auvergne (UFR STAPS - UCA), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Valbiotis R & D [Riom], Valbiotis SAS, Partenaires INRAE-Partenaires INRAE, 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 Paris Cité (UPCité), Laboratoire Microorganismes : Génome et Environnement (LMGE), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), LIttoral ENvironnement et Sociétés (LIENSs), La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS), Valbiotis R & D [La Rochelle], Valbiotis, Kenneth Rainin Foundation, ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), European Project: ERC-2018-StG804135, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), LIttoral ENvironnement et Sociétés - UMRi 7266 (LIENSs), and Université de La Rochelle (ULR)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, plant extract supplementation, Diet, High-Fat, Weight Gain, Article, MESH: obesity / therapy, Prediabetic State, MESH: high-intensity interval training, Physical Conditioning, Animal, microbiota, Animals, TX341-641, Obesity, Intestinal Mucosa, Rats, Wistar, high-intensity interval training, MESH: polyphenols / administration & dosage, body composition, Plant Extracts, MESH: physical conditioning, animal / methods, Nutrition. Foods and food supply, digestive, oral, and skin physiology, Polyphenols, food and beverages, MESH: dietary supplements, Combined Modality Therapy, Gastrointestinal Microbiome, Rats, Disease Models, Animal, Diabetes Mellitus, Type 2, MESH: plant extracts / administration & dosage, Dietary Supplements, glycemic control, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH: rats, Wistar
Abstract: Obesity and prediabetes are the two strongest risk factors of type 2 diabetes. It has been reported that TOTUM-63, a polyphenol-rich plant extract, has beneficial effects on body weight (BW) and insulin resistance in mice fed a high fat diet (HFD). The study aim was to determine whether high-intensity interval training (HIIT) and/or TOTUM-63 supplementation improved body composition and glycemic control and gut microbiota composition in a Western diet-induced obesity rat model. Wistar rats received a standard diet (CTRL; control; n = 12) or HFD (HFD; n = 48) for 16 weeks. Then, HFD rats were divided in four groups: HFD, HFD + TOTUM-63 (T63), HFD + HIIT (HIIT), and HFD + HIIT +T63 (HIIT + T63). Training was performed 4 days/week for 12 weeks. TOTUM-63 was included in diet composition (2%). The HIIT + T63 combination significantly limited BW gain, without any energy intake modulation, and improved glycemic control. BW variation was correlated with increased α-diversity of the colon mucosa microbiota in the HIIT + T63 group. Moreover, the relative abundance of Anaeroplasma, Christensenellaceae and Oscillospira was higher in the HIIT + T63 group. Altogether, these results suggest that the HIIT and TOTUM-63 combination could be proposed for the management of obesity and prediabetes.
Published: 2021
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7. Altered visual processing in the mdx52 mouse model of Duchenne muscular dystrophy

Author: Alvaro Rendon, Anneka Joachimsthaler, Cyrille Vaillend, Jerome E. Roger, Jan Kremers, Dora Fix Ventura, Mirella Telles Salgueiro Barboni, Andre Liber, Amel Saoudi, Aurélie Goyenvalle, Semmelweis University [Budapest], University of São Paulo (USP), Section for Retinal Physiology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, Sction for Retinal Physiology, University Hospital Erlangen, This study was supported by the Centre National de la Recherche Scientifique (CNRS), the Universit ́e Paris-Sud (France), the DIM Gene Therapy Region Ile-de-France to JER, the Deutscher Akademischer Austauschdienst (DAAD #57513929) in Germany and Tempus Public Foundation in Hungary to JK and MTSB, the Sao Paulo Research Foundation (FAPESP # 2019/007771 to AMPL, 2016/04538–3 and 2014/26818–2 to DFV), the National Council for Scientific and Tech-nological Development (CNPq grant number 404239/2016–1 to MTSB), a project award from the Association Mon ́egasque contre les Myopathies (AMM, Monaco) to CV, a National Research, Development, and Inno-vation Fund of Hungary OTKA (PD134799), a fellowship from Campus France (dossier 931,824 L) and a short-term scientific mission from COST Action CA17103 to MTSB and a CNPq 1A productivity fellowship (CNPq 309,409/2015–2) to DFV., PERIGNON, Alain, Universidade de São Paulo = University of São Paulo (USP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Duchenne muscular dystrophy, Photoreceptors, genetic structures, Mesopic vision, Dp427, media_common.quotation_subject, B-wave, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Biology, Synaptic Transmission, Retina, lcsh:RC321-571, Mouse model, Dystrophin, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, medicine, Electroretinography, Contrast (vision), Animals, Scotopic vision, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, media_common, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Retinal, Electroretinogram, medicine.disease, Muscular Dystrophy, Duchenne, 030104 developmental biology, Neurology, chemistry, Optomotor response, Mice, Inbred mdx, Visual Perception, Dp260, Dp140, sense organs, Erg, Neuroscience, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 030217 neurology & neurosurgery, Photopic vision
Abstract: International audience; The mdx52 mouse model of Duchenne muscular dystrophy (DMD) is lacking exon 52 of the DMD gene that is located in a hotspot mutation region causing cognitive deficits and retinal anomalies in DMD patients. This deletion leads to the loss of the dystrophin proteins, Dp427, Dp260 and Dp140, while Dp71 is preserved. The flash electroretinogram (ERG) in mdx52 mice was previously characterized by delayed dark-adapted b-waves. A detailed description of functional ERG changes and visual performances in mdx52 mice is, however, lacking. Here an extensive full-field ERG repertoire was applied in mdx52 mice and WT littermates to analyze retinal physiology in scotopic, mesopic and photopic conditions in response to flash, sawtooth and/or sinusoidal stimuli. Behavioral contrast sensitivity was assessed using quantitative optomotor response (OMR) to sinusoidally modulated luminance gratings at 100% or 50% contrast. The mdx52 mice exhibited reduced amplitudes and delayed implicit times in dark-adapted ERG flash responses, particularly in their b-wave and oscillatory potentials, and diminished amplitudes of light-adapted flash ERGs. ERG responses to sawtooth stimuli were also diminished and delayed for both mesopic and photopic conditions in mdx52 mice and the first harmonic amplitudes to photopic sine-wave stimuli were smaller at all temporal frequencies. OMR indices were comparable between genotypes at 100% contrast but significantly reduced in mdx52 mice at 50% contrast. The complex ERG alterations and disturbed contrast vision in mdx52 mice include features observed in DMD patients and suggest altered photoreceptor-to-bipolar cell transmission possibly affecting contrast sensitivity. The mdx52 mouse is a relevant model to appraise the roles of retinal dystrophins and for preclinical studies related to DMD.
Published: 2021
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8. YAP protects the eye from uveitic glaucoma by preserving retinal and anterior chamber homeostases

Author: Bitard, Juliette, Grellier, Elodie-Kim, Lourdel, Sophie, Filipe, Helena, Hamon, Annaïg, Fenaille, François, Castelli, Florence, Chu-Van, Emeline, Roger, Jérôme E., Locker, Morgane, Perron, Muriel, Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, Universidade de Lisboa = University of Lisbon (ULISBOA), 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 ), CEA- Saclay (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Retina France, UNADEV, ARVO Association for Research in Vision and Ophthalmology, Universidade de Lisboa (ULISBOA), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 ), and Université Paris-Saclay
Subjects: genetic structures, [SDV]Life Sciences [q-bio], sense organs, ComputingMilieux_MISCELLANEOUS, eye diseases
Abstract: https://iovs.arvojournals.org/article.aspx?articleid=2775349; International audience; The role of the transcription coactivator YAP has been studied during eye development but its implication in ocular homeostasis and diseases is much less documented. YAP is expressed by several ocular cell types including the non-pigmented cells of the ciliary body (CB) as well as Müller glial cells (MGs) of the neuroretina. Here, we assessed whether postnatal Yap deletion in these two cell types could affect eye homeostasis during aging.Methods : Specific Yap deletion in CB and MGs was induced in a conditional mouse model (Yap cKO) at P10. The phenotype was investigated by western-blot, immunohistochemistry, and RNA-sequencing (RNA-seq). Blood defects were identified by fluorescein angiography. Optic nerve degeneration was assessed by optical coherence tomography. Intraocular pressure (IOP) was recorded by a rebound tonometer. Imaging of the CB in healthy and uveitic human patients was performed by ultrasound biomicroscopy.
Published: 2021

9. Current challenges and future perspectives in oral absorption research : an opinion of the UNGAP network

Author: Saskia N. de Wildt, Patrick Augustijns, Anette Müllertz, Mark McAllister, Cordula Stillhart, Brendan T. Griffin, James Butler, Kateřina Valentová, Andreas Bernkop-Schnürch, Nigel Davies, Caitriona M. O'Driscoll, Christos Reppas, Hannah Batchelor, Clive G. Wilson, Filippos Kesisoglou, Mirko Koziolek, Maria Vertzoni, Alan R. Mackie, Bertil Abrahamsson, Christopher J.H. Porter, Kiyohiko Sugano, Jadwiga Paszkowska, Zahari Vinarov, Didier Dupont, Martin Kuentz, Nikoletta Fotaki, Janneke Keemink, Jens Ceulemans, Petr Pavek, Gøril Eide Flaten, Elena Toader, Per Artursson, Vincent Jannin, Philippe Berben, Neil Parrott, Antonio J. Meléndez-Martínez, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Department of Chemical and Pharmaceutical Engineering, Medical University of Sofia [Bulgarie], Oral Product Development, Pharmaceutical Technology & Development, Operations, ASTRAZENECA R/D GLOBAL SAFETY ASSESSMENT SODERTALJE SWE, Partenaires IRSTEA, Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Partenaires IRSTEA, Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Department of Pharmacy, Uppsala University, Uppsala University, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UCB Pharma S.A.[Braine-l'Alleud], Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, GlaxoSmithKline, Glaxo Smith Kline, Janssen Pharmaceutica N.V. [Beerse, Belgium], AstraZeneca, Gothenburg, Sweden, Science et Technologie du Lait et de l'Oeuf (STLO), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Department of Pharmacy, University of Tromsø (UiT), Department of Pharmacy and Pharmacology, University of Bath [Bath], School of Pharmacy, University College Cork (UCC), Lonza Pharma & Biotech, Lonza AG, Valais Works, CH-3930 Visp, Switzerland, Partenaires INRAE-Partenaires INRAE, Pharmaceutical Sciences, Merck & Co. Inc., Merck Research laboratories, Merck & Co. Inc-Merck & Co. Inc, AbbVie Deutschland GmbH & Co KG, Abbott GmbH & Co KG, Institute for Pharma Technology, University of Applied Sciences and Arts Northwestern Switzerland (HES-SO), School of Food Science & Nutrition, University of Leeds, Food Colour & Quality Laboratory, Area of Nutrition & Food Science, Universidad de Sevilla, Drug Product Design, Pfizer PGRD, Pfizer-Pfizer, University of Copenhagen = Københavns Universitet (KU), F. Hoffmann-La Roche Ltd. [Basel, Switzerland], Physiolution Polska Sp. Z o.o., Wroclaw, Poland, Faculty of Pharmacy, Charles University Faculty of Medicine and Faculty Hospital in Hradec Kralove, Monash Institute of Pharmaceutical Sciences, Department of Drug Delivery, Disposition and Dynamics, Faculty of Pharmacy and Pharmaceutical Science, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia, Department of Pharmaceutical Technology, National and Kapodistrian University of Athens, College of Pharmaceutical Sciences, Ritsumeikan University, Shiga, Faculty of Medicine, University of Medicine and Pharmacy of Iasi, Romania, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic, and Department of Pharmacology and Toxicology, Radboud University Medical Center
Subjects: VIVO PERFORMANCE, Administration, Oral, Pharmaceutical Science, 02 engineering and technology, Absorption (psychology), Pharmaceutical Sciences, INTESTINAL PERMEABILITY, Medicine, FED STATE, Food-drug interactions, 0303 health sciences, Specific patient populations, BIOPHARMACEUTICS TOOLS PROJECT, 021001 nanoscience & nanotechnology, In vitro tools, 3. Good health, Pharmaceutical Preparations, Colonic absorption, BIORELEVANT DISSOLUTION, Engineering ethics, 0210 nano-technology, Amorphous solid dispersions, Advanced formulations, Drug Compounding, DOSAGE FORMS, RS, 03 medical and health sciences, Lipid-based formulations, Animals, Humans, Regional differences, Computer Simulation, 030304 developmental biology, PHARMACOKINETIC PBPK, DRUG-DELIVERY SYSTEMS, PBPK modeling, IN-VITRO MODELS, business.industry, VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Pharmacology: 728, Farmaceutiska vetenskaper, Gastrointestinal Tract, Intestinal Absorption, LIPID-BASED FORMULATIONS, VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Farmakologi: 728, Microbiome, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Oral retinoid
Abstract: Although oral drug delivery is the preferred administration route and has been used for centuries, modern drug discovery and development pipelines challenge conventional formulation approaches and highlight the insufficient mechanistic understanding of processes critical to oral drug absorption. This review presents the opinion of UNGAP scientists on four key themes across the oral absorption landscape: (1) specific patient populations, (2) regional differences in the gastrointestinal tract, (3) advanced formulations and (4) food-drug interactions. The differences of oral absorption in pediatric and geriatric populations, the specific issues in colonic absorption, the formulation approaches for poorly water-soluble (small molecules) and poorly permeable (peptides, RNA etc.) drugs, as well as the vast realm of food effects, are some of the topics discussed in detail. The identified controversies and gaps in the current understanding of gastrointestinal absorption-related processes are used to create a roadmap for the future of oral drug absorption research.(c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).
Published: 2021
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10. Effects of Totum-63 on glucose homeostasis and post-prandial glycemia: a translational study

Author: Christophe Montaurier, Gisèle Pickering, Yolanda F. Otero, Geoffroy Marceau, Florian Le Joubioux, Gilles Ducheix, M. Bargetto, Pascal Sirvent, Vincent Sapin, Aurore Vluggens, Claude Dubray, Doriane Ripoche, Bruno Guigas, Murielle Cazaubiel, Sylvia Boulliau, Nathalie Boisseau, Vivien Chavanelle, Nicolas Macian, Sébastien Peltier, Thierry Maugard, Frédéric Dutheil, Christian Dualé, Valbiotis R & D [Riom], Valbiotis R&D [Perigny], Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), CIC Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-Centre de Pharmacologie Clinique, Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Leiden University Medical Center (LUMC), LIttoral ENvironnement et Sociétés - UMRi 7266 (LIENSs), Université de La Rochelle (ULR)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Clermont Auvergne (UCA)-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Auvergne (UFR STAPS - UCA), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), MMPC/DiaComp [DK076169], [DK115255], Valbiotis SAS, Partenaires INRAE-Partenaires INRAE, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Universiteit Leiden, LIttoral ENvironnement et Sociétés (LIENSs), and La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Blood Glucose, Male, Physiology, Chrysanthemum, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Vaccinium myrtillus, Pilot Projects, Type 2 diabetes, Translational Research, Biomedical, Mice, 0302 clinical medicine, prevention, Cynara scolymus, Glucose homeostasis, Homeostasis, glucose, 2. Zero hunger, biology, diabetes, translational, Middle Aged, Postprandial Period, Postprandial, 030220 oncology & carcinogenesis, Piper nigrum, Research Article, Adult, medicine.medical_specialty, Glycemic Control, 03 medical and health sciences, Physiology (medical), Internal medicine, Diabetes mellitus, Olea, medicine, Animals, Humans, business.industry, Plant Extracts, Insulin, nutritional and metabolic diseases, Overweight, medicine.disease, Mice, Inbred C57BL, Insulin receptor, 030104 developmental biology, Endocrinology, Hyperglycemia, biology.protein, Lean body mass, Steatosis, business
Abstract: International audience; Global prevalence of type 2 diabetes (T2D) is rising and may affect 700 million people by 2045. Totum-63 is a polyphenol-rich natural composition developed to reduce the risk of T2D. We first investigated the effects of Totum-63 supplementation in highfat diet (HFD)-fed mice for up to 16 wk and thereafter assessed its safety and efficacy (2.5 g or 5 g per day) in 14 overweight men [mean age 51.5 yr, body mass index (BMI) 27.6 kg.m(-2)] for 4 wk. In HFD-fed mice, Totum-63 reduced body weight and fat mass gain, whereas lean mass was unchanged. Moreover, fecal energy excretion was higher in Totum-63-supplemented mice, suggesting a reduction of calorie absorption in the digestive tract. In the gut, metagenomic analyses of fecal microbiota revealed a partial restoration of HFD-induced microbial imbalance, as shown by principal coordinate analysis of microbiota composition. HFD-induced increase in HOMA-IR score was delayed in supplemented mice, and insulin response to an oral glucose tolerance test was significantly reduced, suggesting that Totum-63 may prevent HFD-related impairments in glucose homeostasis. Interestingly, these improvements could be linked to restored insulin signaling in subcutaneous adipose tissue and soleus muscle. In the liver, HFD-induced steatosis was reduced by 40% (as shown by triglyceride content). In the subsequent study in men, Totum-63 (5g.day-1) improved glucose and insulin responses to a high-carbohydrate breakfast test (84% kcal carbohydrates). It was well tolerated, with no clinically significant adverse events reported. Collectively, these data suggest that Totum-63 could improve glucose homeostasis in both HFD-fed mice and overweight individuals, presumably through a multitargeted action on different metabolic organs.NEW & NOTEWORTHY Totum-63 is a novel polyphenol-rich natural composition developed to reduce the risk of T2D. Totum-63 showed beneficial effects on glucose homeostasis in HFD-fed mice, presumably through a multitargeted action on different metabolic organs. Totum-63 was well tolerated in humans and improved postprandial glucose and insulin responses to a high-carbohydrate breakfast test.
Published: 2021
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11. Detection of Metabolite–Protein Interactions in Complex Biological Samples by High-Resolution Relaxometry: Toward Interactomics by NMR

Author: Jean-Max Tyburn, Simone Pisano, Ziqing Wang, Veronica Ghini, Philippe Pelupessy, Morgan Kazmierczak, Giacomo Parigi, Thorsten Marquardsen, Fabien Ferrage, Guillaume Bouvignies, Claudio Luchinat, Pavel Kadeřávek, Milan Zachrdla, Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine (CIRMMP), Università degli Studi di Siena = University of Siena (UNISI)-Università degli Studi di Firenze = University of Florence (UniFI)-University of Bologna/Università di Bologna-Partenaires INRAE, Structure et Dynamique des Biomolécules (LBM-E3), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Chimie Moléculaire de Paris Centre (FR 2769), Ecole Polytechnique Fédérale de Lausanne (EPFL), Bruker BioSpin MRI GmbH [Ettlingen, Germany], Università degli Studi di Firenze = University of Florence (UniFI), Gestionnaire, HAL Sorbonne Université 5, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli Studi di Siena = University of Siena (UNISI)-Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)-University of Bologna-Partenaires INRAE, Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, and Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)
Subjects: Relaxometry, Human blood, Chemistry, Metabolite, High resolution, General Chemistry, Computational biology, 010402 general chemistry, 01 natural sciences, Biochemistry, Small molecule, Catalysis, NMR, 0104 chemical sciences, Protein–protein interaction, chemistry.chemical_compound, Colloid and Surface Chemistry, Metabolomics, [CHIM] Chemical Sciences, [CHIM]Chemical Sciences, Interactomics, Macromolecule
Abstract: International audience; Metabolomics, the systematic investigation of metabolites in biological fluids, cells or tissues, reveals essential information about metabolism and diseases. Metabolites have functional roles in myriads of biological processes, as substrates and products of enzymatic reactions, but also as cofactors and regulators of large numbers of biochemical mechanisms. These functions involve interactions of metabolites with macromolecules. Yet, methods to systematically investigate these interactions are hitherto still scarce. In particular, there is a need for techniques suited to identify and characterize weak metabolite-macromolecule interactions directly in complex media such as biological fluids. Here, we introduce a method to investigate weak interactions between metabolites and macromolecules in biological fluids. Our approach is based on high-resolution NMR relaxometry and does not require any invasive procedure or separation step. We show that we can detect interactions between small and large molecules in human blood serum and quantify the size of the complex. Our work opens the way for investigations of metabolite-(or other small molecules) protein interactions in biological fluids for interactomics or pharmaceutical applications.
Published: 2021
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12. Population genomic evidence that human and animal infections in Africa come from the same populations of Dracunculus medinensis

Author: Guillaume Sallé, Makoy Yibi Logora, Hayley M. Bennett, Stephen R. Doyle, Geetha Sankaranarayanan, Michael J. Yabsley, Mesfin Wossen, Zahra Abdellah, Mark L. Eberhard, Magda E. Lotkowska, Jeremy M. Foster, Matthew Berriman, Cheick Oumar Coulibaly, Christopher A. Cleveland, Nancy Holroyd, Adam Weiss, Thomas Huckvale, Alan Tracey, James Cotton, Albrecht I. Schulte-Hostedde, Ouakou Tchindebet, Caroline Durrant, Elizabeth A. Thiele, Ernesto Ruiz-Tiben, Parasites and Microbes, The Wellcome Trust Sanger Institute [Cambridge], Department of Biology, Vassar College, Infectiologie et Santé Publique (UMR ISP), Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Guinea Worm Eradication Program, The Carter Center, Partenaires INRAE-Partenaires INRAE, Laurentian University, New England Biolabs, Southeastern Cooperative Wildlife Disease Study, University of Georgia [USA], Warnell School of Forestry and Natural Resources, Parasitic Diseases Branch, Centers for Disease Control and Prevention (CDC), Wellcome (https://wellcome.ac.uk/, n° 098051 and 206194), BBSRC (https://bbsrc.ukri.org/, n° BB/M003949/1), and Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Male, Life Cycles, Nematoda, [SDV]Life Sciences [q-bio], RC955-962, Dracunculus Medinensis, Geographical Locations, Larvae, 0302 clinical medicine, Arctic medicine. Tropical medicine, Invertebrate Genomics, Epidemiology, Dog Diseases, Mammals, 2. Zero hunger, 0303 health sciences, education.field_of_study, Mammalian Genomics, Transmission (medicine), Dracunculiasis, Eukaryota, Genomics, Dracunculus Nematode, 3. Good health, Infectious Diseases, Vertebrates, Female, Public aspects of medicine, RA1-1270, Disease transmission, Research Article, Dracunculus medinensis, Burden of disease, medicine.medical_specialty, Chad, 030231 tropical medicine, Population, Zoology, Biology, 03 medical and health sciences, Dogs, Helminths, parasitic diseases, Genetics, medicine, Animals, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, education, Disease Reservoirs, 030304 developmental biology, Genome, Helminth, Evolutionary Biology, Dracunculus, Population Biology, Host (biology), Organisms, Public Health, Environmental and Occupational Health, Biology and Life Sciences, Invertebrates, Population bottleneck, Animal Genomics, Africa, People and Places, Amniotes, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Population Genetics, Developmental Biology
Abstract: Background Guinea worm–Dracunculus medinensis–was historically one of the major parasites of humans and has been known since antiquity. Now, Guinea worm is on the brink of eradication, as efforts to interrupt transmission have reduced the annual burden of disease from millions of infections per year in the 1980s to only 54 human cases reported globally in 2019. Despite the enormous success of eradication efforts to date, one complication has arisen. Over the last few years, hundreds of dogs have been found infected with this previously apparently anthroponotic parasite, almost all in Chad. Moreover, the relative numbers of infections in humans and dogs suggests that dogs are currently the principal reservoir on infection and key to maintaining transmission in that country. Principal findings In an effort to shed light on this peculiar epidemiology of Guinea worm in Chad, we have sequenced and compared the genomes of worms from dog, human and other animal infections. Confirming previous work with other molecular markers, we show that all of these worms are D. medinensis, and that the same population of worms are causing both infections, can confirm the suspected transmission between host species and detect signs of a population bottleneck due to the eradication efforts. The diversity of worms in Chad appears to exclude the possibility that there were no, or very few, worms present in the country during a 10-year absence of reported cases. Conclusions This work reinforces the importance of adequate surveillance of both human and dog populations in the Guinea worm eradication campaign and suggests that control programs aiming to interrupt disease transmission should stay aware of the possible emergence of unusual epidemiology as pathogens approach elimination., Author summary Guinea worm–Dracunculus medinensis–was historically one of the major parasites of humans and has been known since antiquity. Guinea worm is now on the brink of eradication, as a global effort seeking to make this parasite extinct has reduced the number of people infected each year from millions in the 1980s to only 54 human cases in 2019. Despite the enormous success of eradication efforts to date, one complication has arisen. Over the last few years, hundreds of dogs have been found infected with Guinea worm, which was previously considered to be transmitted between people. Almost all of these infected animals are in Chad. We have used whole-genome sequence data to try and understand this peculiar situation. We confirm that the same population of worms are causing both infections and show suspected transmission from humans to dogs. The diversity of worms in Chad appears to exclude the possibility that there were no, or very few, worms present in the country during a 10-year absence of reported cases. This work reinforces the importance of adequate surveillance of both human and dog populations and suggests that control programs should stay aware of the emergence of unusual epidemiology as pathogens approach elimination.
Published: 2020
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13. Full compliance with Respiratory syncytial virus prophylaxis was associated with fewer respiratory-related hospital admissions in preterm children: A cohort study

Author: Ludovic Treluyer, Jessica Rousseau, Héloïse Torchin, Pierre-Henri Jarreau, Alexandra Nuytten, Pierre-Yves Ancel, Laetitia Marchand-Martin, Patrick Truffert, Marie-Laure Charkaluk, 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)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Neonatal Medicine, Maternité Cochin-Port Royal, Partenaires INRAE-Partenaires INRAE, Department of neonatology, Saint Vincent de Paul University Hospital, Clinical Research Unit, Center for Clinical Investigation, Center for Clinical Investigation P1419 [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Jeanne de Flandre [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssance RE-CO-NAI ANR-11-AQPX-0038, and French Institute of Public Health ResearchFrench Health MinistryNational Institute of Health and Medical ResearchNational Institute of CancerNational Solidarity Fund for AutonomyPremUp FoundationAbbVie
Subjects: Palivizumab, Pediatrics, medicine.medical_specialty, hospital admissions, respiratory syncytial virus, Respiratory Syncytial Virus Infections, Logistic regression, Antibodies, Monoclonal, Humanized, Antiviral Agents, Virus, Odds, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, acute respiratory illness, 030225 pediatrics, medicine, Humans, 030212 general & internal medicine, Respiratory system, Child, preterm children, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, Infant, Newborn, Infant, General Medicine, Odds ratio, Confidence interval, Hospitals, respiratory tract diseases, 3. Good health, Hospitalization, Pediatrics, Perinatology and Child Health, prophylaxis, France, business, medicine.drug, Cohort study
Abstract: International audience; Aim Although well documented in randomised trials, the efficacy of prophylaxis against respiratory syncytial virus (RSV) in real-word conditions is less studied. The objective was to assess the impact of partial versus full RSV prophylaxis for acute respiratory infections (ARIs) and ARI-related hospital admissions in preterm children.Methods This study included children born preterm in 2011 in France who were eligible for RSV prophylaxis and received at least one palivizumab dose from October 2011 to March 2012. Full prophylaxis was defined as receiving at least one palivizumab dose for each month of RSV exposure in the community. Children with full and partial prophylaxis were matched, and odds of ARIs and ARI-related hospital admission were compared by logistic regression.Results Full prophylaxis concerned 861/1083 (80%) children. As compared with full prophylaxis, partial prophylaxis was not associated with ARI occurrence (odds ratio OR 1.3, 95% confidence interval CI 0.9-1.9) but was significantly associated with ARI-related hospital admission during the RSV epidemic (OR 1.9, 95% CI 1.2-2.9).Conclusion During the 2011-2012 RSV epidemic, hospital admission rates were higher for preterm children with partial than full RSV prophylaxis. Improving compliance could help alleviate the burden of RSV on healthcare systems.
Published: 2020
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14. Impact of dams and climate change on suspended sediment flux to the Mekong delta

Author: Gianbattista Bussi, Li Jin, Craig W. Hutton, Tristan Berchoux, Daniel R. Parsons, Christopher Hackney, Simon Dadson, Hal Voepel, Paul Whitehead, Grigorios Vasilopoulos, Stephen E. Darby, Andrew Nicholas, School of Geography and the Environment [Oxford] (SoGE), University of Oxford [Oxford], School of Geography and Environmental Sciences, University of Southampton, Geology Department, Suny Cortland, Partenaires INRAE-Partenaires INRAE, Energy and Environment Institute, University of Hull [United Kingdom], School of Geography, Politics and Sociology, Newcastle University, Newcastle upon Tyne, UK., Newcastle University [Newcastle], Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM), Territoires, Environnement, Télédétection et Information Spatiale (UMR TETIS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-AgroParisTech-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Exeter University - Department of geography, University of Exeter, and Biotechnology and Biological Sciences Research Council (BBSRC)NERC Natural Environment Research Council
Subjects: Delta, ASIE DU SUD EST, Environmental Engineering, 010504 meteorology & atmospheric sciences, CLIMATIC CHANGE, MODELS, Drainage basin, Fluvial, Climate change, 010501 environmental sciences, 01 natural sciences, [SHS]Humanities and Social Sciences, MODELE, DELTAS, BARRAGE, Environmental Chemistry, SOIL FERTILITY, 14. Life underwater, Waste Management and Disposal, SEDIMENTATION, DAMS, 0105 earth and related environmental sciences, Hydrology, geography, geography.geographical_feature_category, DELTA, FERTILITE DU SOL, Sediment, [SDV.SA.AEP]Life Sciences [q-bio]/Agricultural sciences/Agriculture, economy and politics, 15. Life on land, Pollution, 6. Clean water, Current (stream), BASSIN VERSANT, WATERSHEDS, 13. Climate action, CHANGEMENT CLIMATIQUE, Environmental science, Climate model, SOUTH EAST ASIA, Sediment transport
Abstract: International audience; The livelihoods of millions of people living in the world's deltas are deeply interconnected with the sediment dynamics of these deltas. In particular a sustainable supply of fluvial sediments from upstream is critical for ensuring the fertility of delta soils and for promoting sediment deposition that can offset rising sea levels. Yet, in many large river catchments this supply of sediment is being threatened by the planned construction of large dams. In this study, we apply the INCA hydrological and sediment model to the Mekong River catchment in South East Asia. The aim is to assess the impact of several large dams (both existing and planned) on the suspended sediment fluxes of the river. We force the INCA model with a climate model to assess the interplay of changing climate and sediment trapping caused by dam construction. The results show that historical sediment flux declines are mostly caused by dams built in PR China and that sediment trapping will increase in the future due to the construction of new dams in PDR Lao and Cambodia. If all dams that are currently planned for the next two decades are built, they will induce a decline of suspended sediment flux of 50% (47–53% 90% confidence interval (90%CI)) compared to current levels (99 Mt/year at the delta apex), with potentially damaging consequences for local livelihoods and ecosystems.
Published: 2020
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15. Development of a Virus‐Induced Gene Silencing System for Dioecious Coccinia grandis

Author: Anjan K. Banerjee, Ravi Suresh Devani, Sangram Sinha, Sheeba John, Supriya Adhikari, Apurva Kute, Indian Institute of Science Education and Research Pune (IISER Pune), Institut des Sciences des Plantes de Paris-Saclay (IPS2 (UMR_9213 / UMR_1403)), Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Botany, Tripura University, Partenaires INRAE-Partenaires INRAE, CSIR, HRDG, New Delhi Department of Biotechnology (DBT) IndiaBT/PR16399/NER/95/125/2015IISER Pune, and Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0106 biological sciences, Agroinfiltration, Coccinia grandis, food.ingredient, Genetic Vectors, Mechanical inoculation, Virus-induced gene silencing, Bioengineering, Biology, 01 natural sciences, Applied Microbiology and Biotechnology, Biochemistry, Chenopodium quinoa, Transcriptome, Apple latent spherical virus, 03 medical and health sciences, food, Gene Expression Regulation, Plant, 010608 biotechnology, Gene silencing, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene Silencing, Molecular Biology, Gene, 030304 developmental biology, Genetics, 0303 health sciences, Gene knockdown, Photobleaching, Secoviridae, Phenotype, Plant Leaves, Cucurbitaceae, Biotechnology
Abstract: International audience; Coccinia grandisis an interesting model system to understand dioecy in Cucurbitaceae family. Recent transcriptomics and proteomics studies carried out to understand the sex expression inC. grandishave resulted in identification of many candidate sex-biased genes. In absence of an efficient genetic transformation protocol forC. grandis, virus-induced gene silencing (VIGS) would be a powerful tool to enable gene functional analysis. In current study, we explored the apple latent spherical virus (ALSV) for gene knockdown inC. grandis.The viral infection was achieved through mechanical inoculation of ALSV-infectedChenopodium quinoaleaf extract onto the cotyledons ofC. grandis. ALSV-VIGS mediated knockdown ofCgPDSgene was successfully achieved inC. grandisby mechanical inoculation method resulting in characteristic photobleaching. Subsequently, we developed agroinfiltration compatible vectors for direct infection ofC. grandisand shortened the time-frame by skipping viral propagation inC. quinoa. Typical yellow-leaf phenotype was observed inC. grandisplants agroinfiltrated with ALSV-CgSUconstructs, indicating robust silencing ofCgSUgene. In addition, we improved the infection efficiency of ALSV by co-infiltration of P19 viral silencing suppressor. These results suggest that ALSV-VIGS is suitable for characterization of gene function in dioeciousC. grandisand it can help us understand the mechanism of sex expression.
Published: 2020
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16. « Les stratégies de marquages collectifs : Un outil au service de l’implication des acteurs et de la valorisation des produits sur un territoire. Le cas de la « Clémentine de Corse »

Author: Thérèse Albertini, Corinne Rochette, cédrine Zumbo-Lebrument, Delphine Bereni, Graziella Luisi, UMR LISA, Université de Corse Pasquale Paoli (UCPP), Clermont Recherche Management (CleRMa), École Supérieure de Commerce (ESC) - Clermont-Ferrand (ESC Clermont-Ferrand)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Lieux, Identités, eSpaces, Activités (LISA), Université Pascal Paoli (UPP)-Centre National de la Recherche Scientifique (CNRS), Zumbo-Lebrument, Cédrine, Università di Corsica Pasquale Paoli [Université de Corse Pascal Paoli], and Partenaires INRAE-Partenaires INRAE
Subjects: [SHS.GESTION]Humanities and Social Sciences/Business administration, [SHS.GESTION] Humanities and Social Sciences/Business administration, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020

17. Pias3 is necessary for dorso-ventral patterning and visual response of retinal cones but is not required for rod photoreceptor differentiation

Author: Hannah Breit, Anand Swaroop, Jerome E. Roger, Christie K Campla, Jessica D. Gumerson, Lijin Dong, National Institutes of Health [Bethesda] (NIH), National Eye Institute [Bethesda, MD, États-Unis] (NEI), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, Institut des Neurosciences Paris-Saclay (NeuroPSI), and Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, genetic structures, Vision, QH301-705.5, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Science, Stimulation, Biology, General Biochemistry, Genetics and Molecular Biology, Retina development, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Mouse knockout, Protein inhibitor of activated STAT, Biology (General), Genetics, Regulation of gene expression, Retina, medicine.diagnostic_test, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Retinal, eye diseases, SUMOylation, Cell biology, Gene regulation, 030104 developmental biology, medicine.anatomical_structure, chemistry, Cell type specification, sense organs, General Agricultural and Biological Sciences, 030217 neurology & neurosurgery, Electroretinography, Visual phototransduction, Photopic vision, Research Article
Abstract: Protein inhibitor of activated Stat 3 (Pias3) is implicated in guiding specification of rod and cone photoreceptors through post-translational modification of key retinal transcription factors. To investigate its role during retinal development, we deleted exon 2-5 of the mouse Pias3 gene, which resulted in complete loss of the Pias3 protein. Pias3−/− mice did not show any overt phenotype, and retinal lamination appeared normal even at 18 months. We detected reduced photopic b-wave amplitude by electroretinography following green light stimulation of postnatal day (P)21 Pias3−/− retina, suggesting a compromised visual response of medium wavelength (M) cones. No change was evident in response of short wavelength (S) cones or rod photoreceptors until 7 months. Increased S-opsin expression in the M-cone dominant dorsal retina suggested altered distribution of cone photoreceptors. Transcriptome profiling of P21 and 18-month-old Pias3−/− retina revealed aberrant expression of a subset of photoreceptor genes. Our studies demonstrate functional redundancy in SUMOylation-associated transcriptional control mechanisms and identify a specific, though limited, role of Pias3 in modulating spatial patterning and optimal function of cone photoreceptor subtypes in the mouse retina., Summary: Loss of Pias3 in mice results in altered dorso-ventral patterning of retinal cone photoreceptors by modulating the expression of a subset of genes, but does not affect rod development.
Published: 2017
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18. Usher syndrome type 1–associated cadherins shape the photoreceptor outer segment

Author: Amrit Estivalet, Asadollah Aghaie, Aziz El-Amraoui, Cataldo Schietroma, Karine Parain, José-Alain Sahel, Muriel Perron, Christine Petit, Jacques Boutet de Monvel, Serge Picaud, Syndrome de Usher et autres atteintes rétino-cochléaires, Institut de la Vision, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique et Physiologie de l'Audition, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-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)-Centre National de la Recherche Scientifique (CNRS), ED 515 - Complexité du vivant, Université Pierre et Marie Curie - Paris 6 (UPMC), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, Collège de France (CdF (institution)), This work was supported by the FAUN Stiftung (Suchert Foundation), LHW-Stiftung, Retina France, the European Research Council advanced grant 'Hair bundle' (ERC-2011-AdG 294570), the European Union Seventh Framework Program, under grant agreement HEALTH-F2-2010-242013 (TREATRUSH), the French Agence Nationale pour la Recherche as part of the second Investissements d’Avenir program (light4deaf, ANR-15-RHUS-0001), and the LabEx Lifesenses (ANR-10-LABX-65)., ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), European Project: 294570,EC:FP7:ERC,ERC-2011-ADG_20110310,HAIRBUNDLE(2012), European Project: 242013,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,TREATRUSH(2010), Oficjalska, Danuta, Sorbonne Universités à Paris pour l'Enseignement et la Recherche - - SUPER2011 - ANR-11-IDEX-0004 - IDEX - VALID, Assembling the puzzle of the operating auditory hair bundle - HAIRBUNDLE - - EC:FP7:ERC2012-12-01 - 2017-11-30 - 294570 - VALID, Fighting blindness of Usher syndrome: diagnosis, pathogenesis and retinal treatment (TreatRetUsher) - TREATRUSH - - EC:FP7:HEALTH2010-02-01 - 2014-01-31 - 242013 - VALID, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Chaire Génétique et physiologie cellulaire
Subjects: 0301 basic medicine, genetic structures, Xenopus, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Xenopus Proteins, Article, 03 medical and health sciences, 0302 clinical medicine, CDH23, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], otorhinolaryngologic diseases, medicine, Animals, Research Articles, Actin, Retina, Gene knockdown, biology, Cadherin, Usher Syndrome Type 1, Gene Expression Regulation, Developmental, Cell Biology, Anatomy, Cadherins, Retinal Photoreceptor Cell Outer Segment, Rod Cell Outer Segment, biology.organism_classification, Photoreceptor outer segment, eye diseases, Cell biology, Actin Cytoskeleton, 030104 developmental biology, medicine.anatomical_structure, Gene Knockdown Techniques, Larva, Retinal Cone Photoreceptor Cells, sense organs, Usher Syndromes, 030217 neurology & neurosurgery
Abstract: Usher syndrome type 1 (USH1) causes combined hearing and sight defects, but USH1 protein function in the retina is unclear. Schietroma et al. use Xenopus to model the deficiency in two USH1 proteins—protocadherin-15 and cadherin-23—and identify crucial roles for these molecules in shaping the photoreceptor outer segment., Usher syndrome type 1 (USH1) causes combined hearing and sight defects, but how mutations in USH1 genes lead to retinal dystrophy in patients remains elusive. The USH1 protein complex is associated with calyceal processes, which are microvilli of unknown function surrounding the base of the photoreceptor outer segment. We show that in Xenopus tropicalis, these processes are connected to the outer-segment membrane by links composed of protocadherin-15 (USH1F protein). Protocadherin-15 deficiency, obtained by a knockdown approach, leads to impaired photoreceptor function and abnormally shaped photoreceptor outer segments. Rod basal outer disks displayed excessive outgrowth, and cone outer segments were curved, with lamellae of heterogeneous sizes, defects also observed upon knockdown of Cdh23, encoding cadherin-23 (USH1D protein). The calyceal processes were virtually absent in cones and displayed markedly reduced F-actin content in rods, suggesting that protocadherin-15–containing links are essential for their development and/or maintenance. We propose that calyceal processes, together with their associated links, control the sizing of rod disks and cone lamellae throughout their daily renewal.
Published: 2017
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19. Baseline predictors for visual acuity loss during observation in diabetic macular oedema with good baseline visual acuity

Author: Pierre-Henry Gabrielle, Jay Chhablani, Dinah Zur, Patricio J. Rodríguez-Valdés, Ermete Giancipoli, Catharina Busch, Voraporn Chaikitmongkol, Matias Iglicki, Matus Rehak, Marco Lupidi, Zafer Cebeci, Ana Rita Santos, Małgorzata Ozimek, Paradee Kunavisarut, Inês Laíns, Mali Okada, Valentin Degenhardt, Adrian T. Fung, Samantha Fraser-Bell, Anna Sala-Puigdollers, Assaf Hilely, Anat Loewenstein, Department of Ophthalmology [Leipzig], University Hospital Leipzig, Royal Victorian Eye and Ear Hospital, Division of Ophthalmology, Tel Aviv Sourasky Medical Center [Te Aviv], Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], Discipline of Clinical Ophthalmology and Eye Health, The University of Sydney, Instituto de Oftalmología y Ciencias Visuales, Escuela de Medicina, Tecnológico de Monterrey (ITESM)-Tecnológico de Monterrey (ITESM), Department of Ophthalmology, Istanbul Faculty of Medicine, Istanbul University -Istanbul University, Department of Biomedical and Surgical Sciences, Section of Ophthalmology, University of Perugia-University of Perugia, Westmead Hospital [Sydney], Faculty of Medicine and Health Sciences, Macquarie University Hospital, Partenaires INRAE-Partenaires INRAE, Ophthalmology Department, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Surgical, Microsurgical and Medical Sciences, Eye Clinic, University of Sassari-University of Sassari-Eye Clinic, University of Sassari-University of Sassari, Department of Biomedical Sciences, University of Sassari, Retina Division, Faculty of Medicine, Chiang Mai University (CMU)-Chiang Mai University (CMU)-Faculty of Medicine, Chiang Mai University (CMU)-Chiang Mai University (CMU), University of Coimbra [Portugal] (UC), Association for Innovation and Biomedical Research on Light and Image (AIBILI), Massachusetts Eye and Ear, Harvard Medical School [Boston] (HMS), Department of Orthoptics, Superior School of Health, Polytechnic Institute of Porto-Polytechnic Institute of Porto, Institut Clínic d'Oftalmologia (ICOF), Hospital Clínic de Barcelona, UPMC Eye Center, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), L.V. Prasad Eye Institute, Partenaires INRAE, Department of General Ophthalmology and Pediatric Ophthalmology Service, Medical University of Lublin, Heidelberg University Hospital [Heidelberg], Incumbent, Sydney A. Fox chair in Ophthalmology, Tel Aviv University [Tel Aviv]-Tel Aviv University [Tel Aviv], Private Retina Service, University of Buenos Aires [Argentina], and Repositório Científico do Instituto Politécnico do Porto
Subjects: Male, Vascular Endothelial Growth Factor A, Visual acuity, observation, genetic structures, goog visual acuity, [SDV]Life Sciences [q-bio], Visual Acuity, Observation, Angiogenesis Inhibitors, Diabetic macular oedema, 0302 clinical medicine, Diabetic retinopathy, Fluorescein Angiography, intravitreal therapy, diabetes, Diabetes, General Medicine, Middle Aged, Bevacizumab, Treatment Outcome, diabetic macular oedema, Cohort, Female, medicine.symptom, Tomography, Optical Coherence, medicine.medical_specialty, Fundus Oculi, Macular Edema, 03 medical and health sciences, Visual acuity loss, Diabetes mellitus, Ophthalmology, Ranibizumab, medicine, Humans, Good visual acuity, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Retrospective Studies, Diabetic Retinopathy, macular oedema, business.industry, Intravitreal therapy, Retrospective cohort study, Odds ratio, medicine.disease, eye diseases, Macular Oedema, 030221 ophthalmology & optometry, sense organs, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: International audience; Purpose: To investigate clinical baseline characteristics and optical coherence tomography biomarkers predicting visual loss during observation in eyes with diabetic macular oedema (DMO) and good baseline visual acuity (VA). Methods: A sub-analysis of a 12-month, retrospective study, including patients with baseline VA ≤0.1 logMAR (≥20/25 Snellen) and centre-involving DMO. The primary outcome measure was the correlation between baseline characteristics and VA loss ≥10 letters during follow-up. Results: A total of 249 eyes were included in the initial study, of which 147 eyes were observed and 80 eyes received anti-vascular endothelial growth factor (VEGF) treatment at baseline. Visual acuity (VA) loss ≥10 letters occurred in 21.8% (observed cohort) and in 24.3% (treated cohort), respectively. Within observed eyes, presence of hyperreflective foci [HRF; odds ratio (OR): 3.18, p = 0.046], and disorganization of inner retina layers (DRIL; OR: 2.71, p = 0.026) were associated with a higher risk of VA loss ≥10 letters. In observed eyes with a combined presence of HRF, DRIL and ellipsoid zone (EZ) disruption, the risk of VA loss was further increased (OR: 3.86, p = 0.034). In eyes with combined presence of DRIL, HRF and EZ disruption, risk of VA loss was 46.7% (7/15 eyes) in the observed cohort, and 26.3% (5/19 eyes) in the treated cohort (p = 0.26). Conclusion: Patients with DMO and good baseline VA, managed by observation, are of increased risk for VA loss if DRIL, HRF and EZ disruption are present at baseline. Earlier treatment with anti-VEGF in these patients may potentially decrease the risk of VA loss at 12 months.
Published: 2019
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20. Correction to: In Vitro Seeding Activity of Glycoform-Deficient Prions from Variably Protease-Sensitive Prionopathy and Familial CJD Associated with PrPV180I Mutation

Author: Jan P. M. Langeveld, Wen-Quan Zou, Mohammed Moudjou, Romany Abskharon, Jiachun Feng, Zerui Wang, Ling Xu, Tetsuyuki Kitamoto, Brian S. Appleby, Robert B. Petersen, Qingzhong Kong, Jiafeng Chen, Pingping Shen, Johnny Dang, Hyoung Gon Lee, Li Cui, Alise Adornato, Jue Yuan, Yong-Sun Kim, Jiyan Ma, Yue Lang, Jilin University (JLU), The first hospital of Jilin University, Case Western Reserve University [Cleveland], Center for Neurodegenerative Science, Van Andel Research Institute, Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Tohoku University [Sendai], Tohoku University Graduate School of Medicine, Department of Biology (Texas State University), Texas State University, Hallym University College of Medicine, Wageningen BioVeterinary Research, Wageningen University and Research [Wageningen] (WUR), National Prion Disease Pathology Surveillance Center, Department of Neurology University Hospitals of Cleveland Case Western Reserve University Cleveland, Central Michigan University College of Medicine Foundation Sciences, Partenaires INRAE, Vrije Universiteit Brussel (VUB), College of Engineering [Beijing], China Agricultural University (CAU), Department of Pathology, Wageningen University and Research Centre (WUR), Department of Molecular and Cellular Biochemistry, Ohio State University [Columbus] (OSU), Hanyang University, Department of Neurology, The First Hospital of Jilin University, Case Western Reserve University School of Medicine, Center for Neurodegenerative Science, Van Andel Research Institute, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Center for Prion Diseases, Department of Biology, College of Sciences, The University of Texas at San Antonio (UTSA)-The University of Texas at San Antonio (UTSA), Department of Microbiology, College of Medicine, Hallym University-Hallym University, Foundation Sciences, Partenaires INRAE-Partenaires INRAE, State Key Laboratory for Infectious Disease prevention and Control, Beijing Institute of Technology (BIT), and United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS)R21 NS096626R01 NS088604R01 NS109532
Subjects: Protein Folding, Glycosylation, [SDV]Life Sciences [q-bio], Neuroscience (miscellaneous), Variably protease-sensitive prionopathy, Mice, Transgenic, Molecular neuroscience, Biology, Creutzfeldt-Jakob Syndrome, Prion Proteins, Substrate Specificity, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Life Science, Animals, Humans, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Host Pathogen Interaction & Diagnostics, 0303 health sciences, [SCCO.NEUR]Cognitive science/Neuroscience, Bacteriologie, Correction, Brain, Bacteriology, Bacteriology, Host Pathogen Interaction & Diagnostics, Molecular biology, In vitro, Host Pathogen Interactie & Diagnostiek, 3. Good health, Neurology, Mutation (genetic algorithm), Bacteriologie, Host Pathogen Interactie & Diagnostiek, Mutation, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030217 neurology & neurosurgery, Peptide Hydrolases
Abstract: International audience; The original version of this article unfortunately contained a mistake. The email address Dr. Wen-Quan Zou, one of the corresponding authors should be written as wxz6@case.edu instead of wxz@case.edu.
Published: 2019
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21. Glycosylation Pattern and in vitro Bioactivity of Reference Follitropin alfa and Biosimilars

Author: Laura Riccetti, Samantha Sperduti, Clara Lazzaretti, Danièle Klett, Francesco De Pascali, Elia Paradiso, Silvia Limoncella, Francesco Potì, Simonetta Tagliavini, Tommaso Trenti, Eugenio Galano, Angelo Palmese, Abhijeet Satwekar, Jessica Daolio, Alessia Nicoli, Maria Teresa Villani, Lorenzo Aguzzoli, Eric Reiter, Manuela Simoni, Livio Casarini, Università degli Studi di Modena e Reggio Emilia (UNIMORE), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Università degli studi di Parma [Parme, Italie], LE STUDIUM Loire Valley Institute for Advanced Studies, This project has been supported by LE STUDIUM Loire Valley Institute for Advanced Studies, Orléans & Tours, France with funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 665790, Department of Obstetrics and Gynaecology, Fertility Center, University - Hospital of Modena and Reggio Emilia [Modena, Italy], Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Unit of Neurosciences, Department of Medicine and Surgery, University of Parma, Department of Laboratory Medicine and Pathological Anatomy, Azienda USL, Analytical Development Biotech Products, Chemistry Department, Merck Serono S.p.A., Center for Genomic Research, University of Modena and Reggio Emilia, Partenaires INRAE-Partenaires INRAE, Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria, ANR-10-LABX-0053,MAbImprove,Optimization of therapeutic monoclonal antibodies development - Better antibodies, better developed and better used(2010), European Project: 665790,H2020,H2020-MSCA-COFUND-2014,SMART LOIRE VALLEY(2015), University of Parma = Università degli studi di Parma [Parme, Italie], ANR-10-LABX-0053,MAbImprove,Optimization of therapeutic monoclonal antibodies development Better antibodies, better developed AND better used(2010), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Università degli studi di Parma = University of Parma (UNIPR)
Subjects: 0301 basic medicine, endocrine system, Glycan, Glycosylation, glycosylation, medicine.drug_class, [SDV]Life Sciences [q-bio], FSH, biosimilar, gonal-F, bemfola, ovaleap, assisted reproduction (ART), Endocrinology, Diabetes and Metabolism, This article was submitted to Reproduction, 030209 endocrinology & metabolism, Pharmacology, lcsh:Diseases of the endocrine glands. Clinical endocrinology, follitropine, law.invention, réponse cellulaire, 03 medical and health sciences, chemistry.chemical_compound, Endocrinology, 0302 clinical medicine, law, Biologie de la reproduction, medicine, procréation médicalement assistée, Original Research, Reproductive Biology, lcsh:RC648-665, biology, Chemistry, Lectin, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, hormone folliculo-stimulante, In vitro, 030104 developmental biology, a section of the journal Frontiers in Endocrinology FSH, biology.protein, Recombinant DNA, réponse induite, Gonadotropin, Intracellular, Hormone
Abstract: Recombinant follicle-stimulating hormone (FSH) (follitropin alfa) and biosimilar preparations are available for clinical use. They have specific FSH activity and a unique glycosylation profile dependent on source cells. The aim of the study is to compare the originator (reference) follitropin alfa (Gonal-f (R))- with biosimilar preparations (Bemfola (R) and Ovaleap (R))-induced cellular responses in vitro. Gonadotropin N-glycosylation profiles were analyzed by ELISA lectin assay, revealing preparation specific-patterns of glycan species (Kruskal-Wallis test; p < 0.05, n = 6) and by glycotope mapping. Increasing concentrations of Gonal-f (R) or biosimilar (1 x 10(-3) -1 x 10(3) ng/ml) were used for treating human primary granulosa lutein cells (hGLC) and FSH receptor (FSHR)-transfected HEK293 cells in vitro. Intracellular cAMP production, Ca2+ increase and beta-arrestin 2 recruitment were evaluated by BRET, CREB, and ERK1/2 phosphorylation by Western blotting. 12-h gene expression, and 8- and 24-h progesterone and estradiol synthesis were measured by real-time PCR and immunoassay, respectively. We found preparation-specific glycosylation patterns by lectin assay (Kruskal-Wallis test; p < 0.001; n = 6), and similar cAMP production and beta-arrestin 2 recruitment in FSHR-transfected HEK293 cells (cAMP EC50 range = 12 +/- 0.9-24 +/- 1.7 ng/ml; beta-arrestin 2 EC50 range = 140 +/- 14.1-313 +/- 18.7 ng/ml; Kruskal-Wallis test; p >= 0.05; n = 4). Kinetics analysis revealed that intracellular Ca2+ increased upon cell treatment by 4 mu g/ml Gonal-f (R), while equal concentrations of biosimilars failed to induced a response (Kruskal-Wallis test; p < 0.05; n = 3). All preparations induced both 8 and 24 h-progesterone and estradiol synthesis in hGLC, while no different EC(50)s were demonstrated (Kruskal -Wallis test; p > 0.05; n = 5). Apart from preparation-specific intracellular Ca2+ increases achieved at supra-physiological hormone doses, all compounds induced similar intracellular responses and steroidogenesis, reflecting similar bioactivity, and overall structural homogeneity.
Published: 2019
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22. Five simultaneous artificial intelligence data challenges on ultrasound, CT, and MRI

Author: B. Bresson, N. Poussange, M. Majer, Marc Zins, D. Guenoun, Olivier Hauger, S. Si-Mohamed, D. Istrati, Théo Estienne, M. Azoulay, S. Molière, Nathalie Lassau, E. Jehanno, C. Balleyguier, Caroline Caramella, A. Bergère, M. Boisserie, J. Behr, F. Dubrulle, J.-F. Meder, François Cornelis, E. Poncelet, A. Paisant, Raphaëlle Renard-Penna, N. Peyron Faure, H. Cauliez, Caroline Malhaire, T. Caramella, A. Perrey, P. de Vomecourt, François Bidault, C. Bordonne, S. Montagne, Alain Luciani, S. Caius Giurca, G. Garcia, M. Faivre-Pierre, Nicolas Amoretti, F. Desmots, Anne Cotten, M. Abitbol, V. Herreros, Aurélie Jalaguier-Coudray, Olivier Rouvière, J.-F. Budzik, J. Cagnol, Laure Fournier, Valérie Juhan, M. Faruch, C. Cyteval, T. Jacques, J. Bocquet, R. Lotte, T. Willaume, J.-L. Drape, S. Brunelle, A. Blum, M. Garetier, L. Di Marco, F. Pigneur, Institut Gustave Roussy (IGR), Imagerie multimodale en cancérologie. (IR4M/U8081 éq.3), Institut Gustave Roussy (IGR)-Imagerie par Résonance Magnétique Médicale et Multi-Modalités (IR4M), Université Paris-Sud - Paris 11 (UP11)-Hôpital Bicêtre-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Bicêtre-Centre National de la Recherche Scientifique (CNRS), Direction de la recherche [Gustave Roussy], Radiothérapie Moléculaire et Innovation Thérapeutique (RaMo-IT), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Direction de la Transformation Numérique et des Systèmes d’Information, Mathématiques et Informatique pour la Complexité et les Systèmes (MICS), CentraleSupélec-Université Paris-Saclay, Comité de Cancérologie (CCAFU), Association Française d'Urologie, Département de radiothérapie [Gustave Roussy], Service de Radiologie et Imagerie Musculosquelettique, Centre de Consultations et d’Imagerie de l’Appareil Locomoteur, Service de Radiologie (LILLE - Radio), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de radiologie [CHRU Besancon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Clinique du sport de Bordeaux-Mérignac, Clinique Saint-Jean - Toulon, Polytech'Paris - Sorbonne Université, Sorbonne Université (SU), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Universitaire de Nice (CHU Nice), inconnu temporaire UPEMLV, Inconnu, Service de radiologie et imagerie médicale [Rennes] = Radiology [Rennes], CHU Pontchaillou [Rennes], Application des ultrasons à la thérapie (LabTAU), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre de résonance magnétique des systèmes biologiques (CRMSB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Hôpital d'Instruction des Armées Clermont Tonnerre, Service de Santé des Armées, Hôpital Henri Mondor, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Department of Radiology, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université de Lyon, Hôpital Cochin [AP-HP], Service Imagerie de la femme, CH de Valenciennes, Hôpital Hôtel-Dieu [Paris], Centre Hospitalier de Lens, Université catholique de Lille (UCL), Institut Bergonié [Bordeaux], UNICANCER, Hôpital de Hautepierre [Strasbourg], Clinique du Val d'Ouest, Centre d’ Imagerie du Chinonais, Hôpital Européen [Fondation Ambroise Paré - Marseille], Institut du Sein, Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Pathologie Infectieuse et Tropicale [HIA Laveran, Marseille], Hôpital d'instruction des armées Laveran, Clinique du Pont Saint-Vaast, Douai, Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, 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), Département de Radiologie, Armentières (59), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Institut des Sciences du Mouvement Etienne Jules Marey (ISM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Sciences pour l'environnement (SPE), Université Pascal Paoli (UPP)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier Saint-Joseph [Paris], Service de neuroradiologie [Paris], Hôpital Sainte-Anne, Marrow Adiposity & Bone Lab - Adiposité Médullaire et Os - ULR 4490 (MABLab (ex-pmoi)), Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Radiologie Viscèrale, CHRU de Jean-Minjoz, CHU Toulouse [Toulouse], Service de radiologie et imagerie médicale [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM), Résonance magnétique des systèmes biologiques (RMSB), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), CHU Clermont-Ferrand, 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)-Aix Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS)-Université Pascal Paoli (UPP), Groupe hospitalier Paris Saint-Joseph - Hôpital, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CCSD, Accord Elsevier, Imagerie par Résonance Magnétique Médicale et Multi-Modalités (IR4M), Centre National de la Recherche Scientifique (CNRS)-Hôpital Bicêtre-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Bicêtre-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR), and Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)
Subjects: Kidney Cortex, [SPI] Engineering Sciences [physics], Interprofessional Relations, education, Meniscal tears, Datasets as Topic, Computed tomography, Breast Neoplasms, Artificial intelligence (AI), 030218 nuclear medicine & medical imaging, 03 medical and health sciences, [SPI]Engineering Sciences [physics], 0302 clinical medicine, Multidisciplinary approach, Artificial Intelligence, Ultrasound, Medicine, Data Protection Act 1998, Humans, Radiology, Nuclear Medicine and imaging, Neoplasm Invasiveness, Thyroid Neoplasms, Magnetic resonance imaging (MRI), Computer Security, Ultrasonography, Modalities, Radiological and Ultrasound Technology, medicine.diagnostic_test, business.industry, Communication, Liver Neoplasms, Computed Tomography (CT), Deep learning, General Medicine, Magnetic Resonance Imaging, Tibial Meniscus Injuries, 030220 oncology & carcinogenesis, General Data Protection Regulation, Thyroid Cartilage, Artificial intelligence, business, Tomography, X-Ray Computed
Abstract: Summary Purpose The goal of this data challenge was to create a structured dynamic with the following objectives: (1) teach radiologists the new rules of General Data Protection Regulation (GDPR), while building a large multicentric prospective database of ultrasound, computed tomography (CT) and MRI patient images; (2) build a network including radiologists, researchers, start-ups, large companies, and students from engineering schools, and; (3) provide all French stakeholders working together during 5 data challenges with a secured framework, offering a realistic picture of the benefits and concerns in October 2018. Materials and methods Relevant clinical questions were chosen by the Societe Francaise de Radiologie. The challenge was designed to respect all French ethical and data protection constraints. Multidisciplinary teams with at least one radiologist, one engineering student, and a company and/or research lab were gathered using different networks, and clinical databases were created accordingly. Results Five challenges were launched: detection of meniscal tears on MRI, segmentation of renal cortex on CT, detection and characterization of liver lesions on ultrasound, detection of breast lesions on MRI, and characterization of thyroid cartilage lesions on CT. A total of 5,170 images within 4 months were provided for the challenge by 46 radiology services. Twenty-six multidisciplinary teams with 181 contestants worked for one month on the challenges. Three challenges, meniscal tears, renal cortex, and liver lesions, resulted in an accuracy > 90%. The fourth challenge (breast) reached 82% and the lastone (thyroid) 70%. Conclusion Theses five challenges were able to gather a large community of radiologists, engineers, researchers, and companies in a very short period of time. The accurate results of three of the five modalities suggest that artificial intelligence is a promising tool in these radiology modalities.
Published: 2019
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23. PhenoMeNal: processing and analysis of metabolomics data in the cloud

Author: Daniel J. Jacob, Noureddin Sadawi, Kristian Peters, Reza M. Salek, Christoph Ruttkies, Kim Kultima, Susanna-Assunta Sansone, James Bradbury, Rico Rueedi, Steffen Neumann, Ralf J. M. Weber, Kenneth Haug, Sven Bergmann, Merlijn van Rijswijk, Evangelos Handakas, Marco Capuccini, Alina Peluso, Pedro de Atauri, Bita Khalili, Michelle A.C. Reed, Claire O'Donovan, Ulrich L. Günther, Namrata Kale, Philippe Rocca-Serra, Vitaly A. Selivanov, Alejandra Gonzalez-Beltran, Antonio Rosato, Massimiliano Izzo, Pablo Moreno, Pierrick Roger, Christoph Steinbeck, Etienne A. Thévenot, Luca Pireddu, Gianluigi Zanetti, Michael van Vliet, Timothy M. D. Ebbels, Fabien Jourdan, Jon Ander Novella, Anders Larsson, Robert C. Glen, Ibrahim Karaman, Jake T M Pearce, Payam Emami Khoonsari, Stephanie Herman, Marco Enrico Piras, Petr Holub, Mattia Tomasoni, Marta Cascante, Christian Ludwig, Daniel Schober, Thomas Hankemeier, David Johnson, Samuel Lampa, Ola Spjuth, Carles Foguet, Mark R. Viant, European Molecular Biology Laboratory, Imperial College Healthcare NHS Trust- BRC Funding, National Institutes of Health, Department of Stress and Developmental Biology, Leibniz Institute of Plant Biochemistry (IPB), School of Biosciences, University of Birmingham [Birmingham], Université de Lausanne (UNIL), Swiss Institute of Bioinformatics [Lausanne] (SIB), Uppsala University, Department of Pharmaceutical Biosciences, Department of Biochemistry and Molecular Biomedicine, Faculty of Science and Technology, Biochemistry and Molecular Biology, Instituto de Salud Carlos III [Madrid] (ISC), Department of Surgery & Cancer, Imperial College London, University of Cambridge [UK] (CAM), Department of Engineering Science, University of Oxford [Oxford], University of Birmingham, Leiden University, European Molecular Biology Laboratory European Bioinformatics Institute, Department of Medical Sciences, Clinical Chemistry, BBMRI-ERIC, Partenaires INRAE, Biologie du fruit et pathologie (BFP), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1, Department of Informatics and Media, Brandenburg University of Applied Sciences, Métabolisme et Xénobiotiques (ToxAlim-MeX), ToxAlim (ToxAlim), 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-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), School of Public Health - Department of Epidemiology and Biostatistics, German Centre for Integrative Biodiversity Research (iDiv), CRS4 Bioinformat, Laboratoire Sciences des Données et de la Décision (LS2D), Département Métrologie Instrumentation & Information (DM2I), Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Univ Florence, Magnet Resonance Ctr CERM, I-50019 Florence, Italy, Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine (CIRMMP), Università degli Studi di Siena = University of Siena (UNISI)-Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)-University of Bologna-Partenaires INRAE, Univ Florence, Dept Chem, I-50019 Florence, Italy, Brunel University London [Uxbridge], Netherlands Metabolomics Centre, Life Sciences, Institute of Analytical Chemistry, European Project: 654241,H2020,H2020-EINFRA-2014-2,PhenoMeNal(2015), Université de Lausanne = University of Lausanne (UNIL), University of Oxford, Universiteit Leiden, European research infrastructure for biobanking (BBMRI-ERIC), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1 (UB), Plateforme Bordeaux Metabolome, Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Bordeaux, MetaboHUB-MetaboHUB, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), 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)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT), Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Università degli Studi di Firenze = University of Florence (UniFI), Università degli Studi di Siena = University of Siena (UNISI)-Università degli Studi di Firenze = University of Florence (UniFI)-University of Bologna/Università di Bologna-Partenaires INRAE, Glen, Robert [0000-0003-1759-2914], and Apollo - University of Cambridge Repository
Subjects: Life Sciences & Biomedicine - Other Topics, Computer science, Interoperability, data analysis, Cloud computing, METABOLITES, ANNOTATION, Field (computer science), Workflow, NMR, cloud computing, computational workflows, e-infrastructures, mass spectrometry, metabolomics, standardization, Technical Note, TOOL, Orchestration (computing), 0303 health sciences, 030302 biochemistry & molecular biology, Small molecule, Multidisciplinary Sciences, Open data, Statistical analysis, statistics, [SDE]Environmental Sciences, Science & Technology - Other Topics, User interface, Life Sciences & Biomedicine, INTEGRATION, STANDARDS, REPOSITORY, Process (engineering), Phenome, 03 medical and health sciences, Metabolomics, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Metabolome, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, SPECTRA, Humans, Adaptation (computer science), signal processing, Biology, 030304 developmental biology, Reproducibility, Science & Technology, business.industry, PLATFORM, Metabolism, MASS-SPECTROMETRY, Omics, Data science, Spectrum analysis, galaxy, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, Cloud Computing, Metabolomics/methods, Software, SYSTEM
Abstract: International audience; Background Metabolomics is the comprehensive study of a multitude of small molecules to gain insight into an organism's metabolism. The research field is dynamic and expanding with applications across biomedical, biotechnological, and many other applied biological domains. Its computationally intensive nature has driven requirements for open data formats, data repositories, and data analysis tools. However, the rapid progress has resulted in a mosaic of independent, and sometimes incompatible, analysis methods that are difficult to connect into a useful and complete data analysis solution. Findings PhenoMeNal (Phenome and Metabolome aNalysis) is an advanced and complete solution to set up Infrastructure-as-a-Service (IaaS) that brings workflow-oriented, interoperable metabolomics data analysis platforms into the cloud. PhenoMeNal seamlessly integrates a wide array of existing open-source tools that are tested and packaged as Docker containers through the project's continuous integration process and deployed based on a kubernetes orchestration framework. It also provides a number of standardized, automated, and published analysis workflows in the user interfaces Galaxy, Jupyter, Luigi, and Pachyderm. Conclusions PhenoMeNal constitutes a keystone solution in cloud e-infrastructures available for metabolomics. PhenoMeNal is a unique and complete solution for setting up cloud e-infrastructures through easy-to-use web interfaces that can be scaled to any custom public and private cloud environment. By harmonizing and automating software installation and configuration and through ready-to-use scientific workflow user interfaces, PhenoMeNal has succeeded in providing scientists with workflow-driven, reproducible, and shareable metabolomics data analysis platforms that are interfaced through standard data formats, representative datasets, versioned, and have been tested for reproducibility and interoperability. The elastic implementation of PhenoMeNal further allows easy adaptation of the infrastructure to other application areas and omics research domains.
Published: 2019
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24. Retinal Degeneration Triggers the Activation of YAP/TEAD in Reactive Müller Cells

Author: Hamon, Annaïg, Masson, Christel, Bitard, Juliette, Gieser, Linn, Roger, Jérôme E., Perron, Muriel, Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), National Institutes of Health [Bethesda] (NIH), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, and Partenaires INRAE-Partenaires INRAE
Subjects: MESH: Signal Transduction, retina, MESH: Retinal Degeneration, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Blotting, Western, Ependymoglial Cells, Hippo/YAP pathway, Cell Cycle Proteins, Real-Time Polymerase Chain Reaction, MESH: Phosphoproteins, Mice, MESH: Photoreceptor Cells, MESH: Mice, Inbred C57BL, MESH: Blotting, Western, Animals, MESH: Animals, Photoreceptor Cells, RNA, Messenger, MESH: Mice, MESH: Adaptor Proteins, Signal Transducing, MESH: RNA, Messenger, photoreceptor degeneration, Adaptor Proteins, Signal Transducing, Müller cells, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, MESH: Real-Time Polymerase Chain Reaction, Retinal Degeneration, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Nuclear Proteins, TEA Domain Transcription Factors, MESH: Immunohistochemistry, YAP-Signaling Proteins, MESH: Transcription Factors, MESH: Ependymoglial Cells, Phosphoproteins, MESH: Gene Expression Regulation, Immunohistochemistry, DNA-Binding Proteins, Mice, Inbred C57BL, Disease Models, Animal, Retinal Cell Biology, Gene Expression Regulation, sense organs, MESH: Disease Models, Animal, MESH: Nuclear Proteins, MESH: DNA-Binding Proteins, Signal Transduction, Transcription Factors
Abstract: Purpose During retinal degeneration, Müller glia cells respond to photoreceptor loss by undergoing reactive gliosis, with both detrimental and beneficial effects. Increasing our knowledge of the complex molecular response of Müller cells to retinal degeneration is thus essential for the development of new therapeutic strategies. The purpose of this work was to identify new factors involved in Müller cell response to photoreceptor cell death. Methods Whole transcriptome sequencing was performed from wild-type and degenerating rd10 mouse retinas at P30. The changes in mRNA abundance for several differentially expressed genes were assessed by quantitative RT-PCR (RT-qPCR). Protein expression level and retinal cellular localization were determined by western blot and immunohistochemistry, respectively. Results Pathway-level analysis from whole transcriptomic data revealed the Hippo/YAP pathway as one of the main signaling pathways altered in response to photoreceptor degeneration in rd10 retinas. We found that downstream effectors of this pathway, YAP and TEAD1, are specifically expressed in Müller cells and that their expression, at both the mRNA and protein levels, is increased in rd10 reactive Müller glia after the onset of photoreceptor degeneration. The expression of Ctgf and Cyr61, two target genes of the transcriptional YAP/TEAD complex, is also upregulated following photoreceptor loss. Conclusions This work reveals for the first time that YAP and TEAD1, key downstream effectors of the Hippo pathway, are specifically expressed in Müller cells. We also uncovered a deregulation of the expression and activity of Hippo/YAP pathway components in reactive Müller cells under pathologic conditions.
Published: 2017
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25. Outcome of Stage IV Completely Necrotic Wilms Tumour and Local Stage III Treated According to the SIOP 2001 Protocol

Author: Reem Al-Saadi, Xavier Muracciole, Kathy Pritchard-Jones, Daniel Saunders, Gema L Ramírez Villar, Rhoikos Furtwängler, Raquel Davila Fajardo, Arnauld Verschuur, Geert O. Janssens, Marry M. van den Heuvel-Eibrink, Beatriz de Camargo, Patrick Melchior, Martine van Grotel, Claudia Pasqualini, Norbert Graf, Christian Rübe, Harm van Tinteren, Princess Máxima Center for Pediatric Oncology, University Medical Center [Utrecht], Saarland University Hospital (UKS), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Great Ormond Street Institute of Child Health (UCL), University College of London [London] (UCL), Instituto Nacional de Câncer [Rio de Janeiro] (INCA), Hospital Universitario Virgen del Rocío [Sevilla], Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), 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)-Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de radiothérapie - [Hôpital de la Timone - Hôpital Nord - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE)- Hôpital Nord [CHU - APHM], Centre de Recherche en Cancérologie de Marseille (CRCM), The Christie NHS Foundation Trust [Manchester, Royaume-Uni], Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Department of Radiotherapy [Utrecht], Princess Máxima Center for Pediatric Oncology [Utrecht, Pays-Bas], Department of Paediatric Oncology and Haematology, Saarland University Hospital, Trial and Data Center, Princess Máxima Center for Pediatric Oncology [Utrecht, Netherlands], Developmental Biology & Cancer Research & Teaching Department, UCL Great Ormond Street Institute of Child Health, Partenaires INRAE-Partenaires INRAE, and Unidad de Oncología Pediátrica
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Arterial embolism, medicine.medical_treatment, Wilms tumour, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, Inferior vena cava, Article, 03 medical and health sciences, 0302 clinical medicine, medicine, Stage (cooking), Lung, business.industry, completely necrotic, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 3. Good health, Radiation therapy, 030104 developmental biology, medicine.anatomical_structure, Oncology, medicine.vein, 030220 oncology & carcinogenesis, nephroblastoma, Radiology, Renal vein, business, Stage iv, metastatic disease
Abstract: Objective: Wilms tumour (WT) patients with a localised completely necrotic nephroblastoma after preoperative chemotherapy are a favourable outcome group. Since the introduction of the SIOP 2001 protocol, the SIOP– Renal Tumour Study Group (SIOP–RTSG) has omitted radiotherapy for such patients with low-risk, local stage III in an attempt to reduce treatment burden. However, for metastatic patients with local stage III, completely necrotic WT, the recommendations led to ambiguous use. The purpose of this descriptive study is to demonstrate the outcomes of patients with metastatic, completely necrotic and local stage III WT in relation to the application of radiotherapy or not. Methods and materials: all metastatic patients with local stage III, completely necrotic WT after 6 weeks of preoperative chemotherapy who were registered in the SIOP 2001 study were included in this analysis. The pattern of recurrence according to the usage of radiation treatment and 5 year event-free survival (EFS) and overall survival (OS) was analysed. Results: seven hundred and three metastatic WT patients were registered in the SIOP 2001 database. Of them, 47 patients had a completely necrotic, local stage III WT: 45 lung metastases (11 combined localisations), 1 liver/peritoneal, and 1 tumour thrombus in the renal vein and the inferior vena cava with bilateral pulmonary arterial embolism. Abdominal radiotherapy was administered in 29 patients (62%, 29 flank/abdominal irradiation and 9 combined with lung irradiation). Eighteen patients did not receive radiotherapy. Median follow-up was 6.6 years (range 1–151 months). Two of the 47 patients (4%) developed disease recurrence in the lung (one combined with abdominal relapse) and eventually died of the disease. Both patients had received abdominal radiotherapy, one of them combined with lung irradiation. Five-year EFS and OS were 95% and 95%, respectively. Conclusions: the outcome of patients with stage IV, local stage III, completely necrotic Wilms tumours is excellent. Our results suggest that abdominal irradiation in this patient category may not be of added value in first-line treatment, consistent with the current recommendation in the SIOP–RTSG 2016 UMBRELLA protocol.
Published: 2021
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26. International consensus conference on stool banking for faecal microbiota transplantation in clinical practice

Author: Max Nieuwdorp, Colleen R. Kelly, Gianluca Ianiro, Luca Masucci, Dina Kao, E.M. Terveer, Patrizia Kump, Maria J G T Vehreschild, Ailsa Hart, Antonio Gasbarrini, Franco Scaldaferri, Antonio López-Sanromán, Benjamin H. Mullish, Reetta Satokari, Juozas Kupcinskas, Zain Kassam, Josbert J. Keller, Stacy A. Kahn, Lorenza Putignani, Giovanni Cammarota, Perttu Arkkila, Jessica R. Allegretti, Herbert Tilg, Loris Riccardo Lopetuso, Ed J. Kuijper, Monika Fischer, Samuel P Costello, Harry Sokol, Cristina Pintus, Experimental Vascular Medicine, Vascular Medicine, ACS - Diabetes & metabolism, AGEM - Digestive immunity, AGEM - Endocrinology, metabolism and nutrition, Internal Medicine and Gastroenterology, Day Hospital of Gastroenterology and Intestinal Microbiota Transplantation, Fondazione Policlinico A Gemelli IRCCS, Catholic University of Medicine-Catholic University of Medicine, Warren Alpert Medical School of Brown University, Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Microbiology, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London-Imperial College London, Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School [Boston] (HMS)-Harvard Medical School [Boston] (HMS), Microbiome Informatics, Massachusetts Institute of Technology (MIT), OpenBiome, Parasitology Unit and Human Microbiome Unit, IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Department of Medicine, Indiana State University, Department of Gastroenterologyand Hepatology, Haaglanden Medical Center, National Donor Feces Bank, Department of Gastroenterology, The Queen Elizabeth Hospital, University of South Australia [Adelaide]-University of South Australia [Adelaide], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), French Group of Fecal Microbiota Transplantation, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Karl-Franzens-Universität [Graz, Autriche]-Karl-Franzens-Universität [Graz, Autriche], Human Microbiome Research Program, University of Helsinki-University of Helsinki, Hepatology and Nutrition, Boston Children's Hospital-Boston Children's Hospital, University of Alberta-University of Alberta, Department of Clinic of Gastroenterology, University of Helsinki, Department of Medical Microbiology, LeidenUniversity Medical Centre, Department I of Internal Medicine, German Centre for Infection Research, University Hospital of Cologne [Cologne]-University Hospital of Cologne [Cologne], Tissues and Cells Area, Italian National Transplant Center, Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Microbiology, VU University Medical Center [Amsterdam], Gastroenterology and Hepatology Department, Hospital Universitario Ramon y Cajal, Partenaires INRAE-Partenaires INRAE, Institute for Digestive Research, Medical Academy, Lithuanian University of health Sciences-Lithuanian University of health Sciences-Medical Academy, Lithuanian University of health Sciences-Lithuanian University of health Sciences, St Mark's Hospital, Department of Internal Medicine I, Gastroenterology, Endocrinology & Metabolism, Innsbruck Medical University [Austria] (IMU), Catholic University of Rome, Line D-1, Service de Gastroenterologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, University of Graz-University of Graz, Reetta Maria Satokari / Principal Investigator, HUMI - Human Microbiome Research, HUS Abdominal Center, University Management, Gastroenterologian yksikkö, Clinicum, and Internal medicine
Subjects: 0301 basic medicine, Delphi method, Donor Feces, Frozen, 0302 clinical medicine, stool bank, Medicine, Gastroenterology, Consensus conference, fecal microbiota transplantation, Metaanalysis, 3. Good health, Clinical Practice, Editorial, 030211 gastroenterology & hepatology, Medical emergency, Recurrent, guideline, Consensus, Efficacy, Settore MED/12 - GASTROENTEROLOGIA, Faecal microbiota transplantation, Donor Selection, Specimen Handling, 03 medical and health sciences, microbiota, Humans, Organ donation, Active Ulcerative-colitis, Gastroenterology & Hepatology, business.industry, 1103 Clinical Sciences, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Guideline, Clostridium difficile, medicine.disease, Gastrointestinal Microbiome, 030104 developmental biology, Workflow, 3121 General medicine, internal medicine and other clinical medicine, Intestinal Microbiota, Insulin Sensitivity, Organ Donation, clostridioides difficile, Clostridium Infections, Fecal Microbiota Transplantation, 1114 Paediatrics and Reproductive Medicine, business, Clostridium-difficile Infection, Clostridioides
Abstract: Although faecal microbiota transplantation (FMT) has a well-established role in the treatment of recurrent Clostridioides difficile infection (CDI), its widespread dissemination is limited by several obstacles, including lack of dedicated centres, difficulties with donor recruitment and complexities related to regulation and safety monitoring. Given the considerable burden of CDI on global healthcare systems, FMT should be widely available to most centres.Stool banks may guarantee reliable, timely and equitable access to FMT for patients and a traceable workflow that ensures safety and quality of procedures. In this consensus project, FMT experts from Europe, North America and Australia gathered and released statements on the following issues related to the stool banking: general principles, objectives and organisation of the stool bank; selection and screening of donors; collection, preparation and storage of faeces; services and clients; registries, monitoring of outcomes and ethical issues; and the evolving role of FMT in clinical practice,Consensus on each statement was achieved through a Delphi process and then in a plenary face-to-face meeting. For each key issue, the best available evidence was assessed, with the aim of providing guidance for the development of stool banks in order to promote accessibility to FMT in clinical practice.
Published: 2019
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27. Linking YAP to Müller Glia Quiescence Exit in the Degenerative Retina

Author: Deniz Dalkara, Muriel Perron, Juliette Bitard, Jerome E. Roger, Annaïg Hamon, Diana García-García, Albert Chesneau, Divya Ail, Morgane Locker, Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), PERRON, Muriel, and Gestionnaire, Hal Sorbonne Université
Subjects: 0301 basic medicine, Transcription, Genetic, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV]Life Sciences [q-bio], Hippo/YAP pathway, Cell Cycle Proteins, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Xenopus Proteins, Photoreceptor cell, Xenopus laevis, 0302 clinical medicine, lcsh:QH301-705.5, Retinal regeneration, Mice, Knockout, Cell Cycle, Retinal Degeneration, Cell biology, Up-Regulation, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Reprogramming, Muller glia, Neuroglia, Photoreceptor Cells, Vertebrate, Signal Transduction, Ependymoglial Cells, Biology, General Biochemistry, Genetics and Molecular Biology, Retina, 03 medical and health sciences, reactive gliosis, Downregulation and upregulation, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], medicine, Animals, Humans, EGFR pathway, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, retinal regeneration, Adaptor Proteins, Signal Transducing, Cell Proliferation, Müller cells, Hippo signaling pathway, Epidermal Growth Factor, Regeneration (biology), [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, YAP-Signaling Proteins, Mice, Inbred C57BL, 030104 developmental biology, lcsh:Biology (General), Trans-Activators, sense organs, 030217 neurology & neurosurgery
Abstract: Summary: Contrasting with fish or amphibian, retinal regeneration from Müller glia is largely limited in mammals. In our quest toward the identification of molecular cues that may boost their stemness potential, we investigated the involvement of the Hippo pathway effector YAP (Yes-associated protein), which is upregulated in Müller cells following retinal injury. Conditional Yap deletion in mouse Müller cells prevents cell-cycle gene upregulation that normally accompanies reactive gliosis upon photoreceptor cell death. We further show that, in Xenopus, a species endowed with efficient regenerative capacity, YAP is required for their injury-dependent proliferative response. In the mouse retina, where Müller cells do not spontaneously proliferate, YAP overactivation is sufficient to induce their reprogramming into highly proliferative cells. Overall, we unravel a pivotal role for YAP in tuning Müller cell proliferative response to injury and highlight a YAP-EGFR (epidermal growth factor receptor) axis by which Müller cells exit their quiescence state, a critical step toward regeneration. : While fish and amphibian Müller cells behave as retinal stem cells upon injury, their regenerative potential is limited in mammals. Hamon et al. show that YAP is required for their cell-cycle re-entry in Xenopus and is sufficient in mouse to awake them from quiescence and trigger their proliferative response. Keywords: Müller cells, reactive gliosis, retinal regeneration, Hippo/YAP pathway, EGFR pathway
Published: 2018
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28. Population Pharmacokinetics of the Antimalarial Amodiaquine: a Pooled Analysis To Optimize Dosing

Author: Ali, Ali Mohamed, Penny, Melissa, Smith, Thomas, Workman, Lesley, Sasi, Philip, Adjei, George O, Aweeka, Francesca, Kiechel, Jean-René, Jullien, Vincent, Rijken, Marcus, Mcgready, Rose, Mwesigwa, Julia, Kristensen, Kim, Stepniewska, Kasia, Tarning, Joel, Barnes, Karen, Denti, Paolo, Massougbodji, Achille, Gansané, Adama, Adeothy, Adicat, Aubouy, Agnès, Ouedraogo, Alphonse, Annerberg, Anna, Bruneel, Arnaud, Phyo, Aung Pyae, Win, Aye Kyi, Benakis, A., Goka, Bamenla, Gourmel, Bernard, Ogutu, Bernhards, Schramm, Birgit, McGee, Bryan, Morgan, Caroline, Obonyo, Charles, Mazinda, Charles, Parzy, D., Ashley, Elizabeth, Baudin, Elisabeth, Juma, Elizabeth, Comte, Eric, Ouedraogo, Esperance, Nosten, François, Sugnaux, F., Cottrell, Gilles, Dorsey, Grant, Carn, Gwenaelle, Kossou, Hortense, Amedome, Hyacinthe, Kalyango, Joan, Faucher, Jean-François, Jones, Joel, Simpson, Julie, Doritchamou, Justin, Kurtzhals, J., Pinoges, Loretxu, Hoegberg, Lotte, BERTAUX, L., Malaika, L. Tshilolo Muepu, Bergstrand, Martin, Alifrangis, Michael, Branger, Michel, Cot, Michel, Cammas, Mireille, Kamya, Moses, Day, Nicholas, White, Nicholas, Taudon, N., Rodrigues, Onike, Chotsiri, Palang, Valeh, Parastou, Houzé, Pascal, Deloron, Philippe, Guérin, Philippe, Rosenthal, Philip, Hsi, Poe, German, Polina, Singhasivanon, Pratap, Smith, Richard, Lwango, R., Sirima, Sodiomon, Parikh, Sunil, Alegre, S. Sese, Clark, Tamara, Sundaygar, Timothy, Drysdale, Troy, Taylor, Walter, Sinou, V., Zolia, Yah, Swiss Tropical and Public Health Institute [Basel], University of Basel (Unibas), Ifakara Health Institute, University of Cape Town, Muhimbili University of Health and Allied Sciences, University of Ghana, University of California, Drugs for Neglected Diseases Initiative, Service de Pharmacologie, Hôpital Européen George Pompidou, Université Paris Descartes, Paris, France, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Mahidol University [Bangkok], University of Oxford [Oxford], London School of Hygiene & Tropical Medicine [Fajara, The Gambia], University of Antwerp (UA), Development DMPK-PKPD, Novo Nordisk, Copenhagen, Denmark, Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Dis Syst Biol,Ctr Prot Res, Copenhagen, Denmark, and Partenaires INRAE-Partenaires INRAE
Subjects: pediatrics, dose optimization, malaria, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, NONMEM
Abstract: International audience; Amodiaquine plus artesunate is the recommended antimalarial treatment in many countries where malaria is endemic. However, pediatric doses are largely based on a linear extrapolation from adult doses. We pooled data from previously published studies on the pharmacokinetics of amodiaquine, to optimize the dose across all age groups. Adults and children with uncomplicated malaria received daily weight-based doses of amodiaquine or artesunate-amodiaquine over 3 days. Plasma concentration-time profiles for both the parent drug and the metabolite were characterized using nonlinear mixed-effects modeling. Amodiaquine pharmacokinetics were adequately described by a two-compartment disposition model, with first-order elimination leading to the formation of desethylamodiaquine, which was best described by a three-compartment disposition model. Body size and age were the main covariates affecting amodiaquine clearance. After adjusting for the effect of weight, clearance rates for amodiaquine and desethylamodiaquine reached 50% of adult maturation at 2.8 months (95% confidence interval [CI], 1.5 to 3.7 months) and 3.9 months (95% CI, 2.6 to 5.3 months) after birth, assuming that the baby was born at term. Bioavailability was 22.4% (95% CI, 15.6 to 31.9%) lower at the start of treatment than during convalescence, which suggests a malaria disease effect. Neither the drug formulation nor the hemoglobin concentration had an effect on any pharmacokinetic parameters. Results from simulations showed that current manufacturer dosing recommendations resulted in low desethylamodiaquine exposure in patients weighing 8 kg, 15 to 17 kg, 33 to 35 kg, and >62 kg compared to that in a typical 50-kg patient. We propose possible optimized dosing regimens to achieve similar drug exposures among all age groups, which require further validation.
Published: 2018
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29. Cone-rod homeobox CRX controls presynaptic active zone formation in photoreceptors of mammalian retina

Author: Robert N. Fariss, Soo-Young Kim, Koray Dogan Kaya, Juthaporn Assawachananont, Anand Swaroop, Jerome E. Roger, National Institutes of Health [Bethesda] (NIH), National Eye Institute [Bethesda, MD, États-Unis] (NEI), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, and Partenaires INRAE-Partenaires INRAE
Subjects: 0301 basic medicine, MESH: Signal Transduction, genetic structures, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Leber Congenital Amaurosis, Ribbon synapse, Mice, 0302 clinical medicine, MESH: Eye Proteins, Retinal Rod Photoreceptor Cells, MESH: Gene Expression Regulation, Developmental, MESH: Leber Congenital Amaurosis, MESH: Presynaptic Terminals, MESH: Animals, Rod cell, MESH: Nerve Tissue Proteins, Genetics (clinical), biology, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, MESH: Retina, Gene Expression Regulation, Developmental, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Cell Differentiation, General Medicine, Cell biology, medicine.anatomical_structure, Retinal Cone Photoreceptor Cells, General Article, Presynaptic active zone, Signal Transduction, MESH: Cell Differentiation, MESH: Mice, Transgenic, MESH: Trans-Activators, Presynaptic Terminals, Mice, Transgenic, Nerve Tissue Proteins, Synaptic vesicle, Retina, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH: Homeodomain Proteins, Genetics, medicine, Animals, Active zone, Eye Proteins, Molecular Biology, MESH: Mice, MESH: Retinal Rod Photoreceptor Cells, Homeodomain Proteins, Gene Expression Profiling, eye diseases, Disease Models, Animal, 030104 developmental biology, MESH: Retinal Cone Photoreceptor Cells, biology.protein, Trans-Activators, Homeobox, Pikachurin, sense organs, MESH: Disease Models, Animal, 030217 neurology & neurosurgery
Abstract: International audience; In the mammalian retina, rod and cone photoreceptors transmit the visual information to bipolar neurons through highly specialized ribbon synapses. We have limited understanding of regulatory pathways that guide morphogenesis and organization of photoreceptor presynaptic architecture in the developing retina. While neural retina leucine zipper (NRL) transcription factor determines rod cell fate and function, cone-rod homeobox (CRX) controls the expression of both rod- and cone-specific genes and is critical for terminal differentiation of photoreceptors. A comprehensive immunohistochemical evaluation of Crx-/- (null), CrxRip/+ and CrxRip/Rip (models of dominant congenital blindness) mouse retinas revealed abnormal photoreceptor synapses, with atypical ribbon shape, number and length. Integrated analysis of retinal transcriptomes of Crx-mutants with CRX- and NRL-ChIP-Seq data identified a subset of differentially expressed CRX target genes that encode presynaptic proteins associated with the cytomatrix active zone (CAZ) and synaptic vesicles. Immunohistochemistry of Crx-mutant retina validated aberrant expression of REEP6, PSD95, MPP4, UNC119, UNC13, RGS7 and RGS11, with some reduction in Ribeye and no significant change in immunostaining of RIMS1, RIMS2, Bassoon and Pikachurin. Our studies demonstrate that CRX controls the establishment of CAZ and anchoring of ribbons, but not the formation of ribbon itself, in photoreceptor presynaptic terminals.
Published: 2018
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30. L'adaptation au changement climatique en agriculture sur le territoire guadeloupéen

Author: Blondel, Olivia, Artimix, Agence Nationale de Valorisation de la Recherche, Partenaires INRAE-Partenaires INRAE, and ANR-17-CE03-0005,ARTIMIX,Articulation multiniveaux des combinaisons d'instruments de politique pour l'adaptation au changement climatique des territoires tropicaux agricoles vulnérables(2017)
Subjects: [SDE]Environmental Sciences, [SHS]Humanities and Social Sciences
Published: 2018

31. Abeilles mellifères et pollinisateurs sauvages sur le territoire de Dijon Métropole : enjeux de préservation et mode de gestion

Author: Marage, Damien, Fougeron, Agnès, Laboratoire Dynamiques Sociales et Recomposition des Espaces (LADYSS), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Direction régionale de l’environnement, de l’aménagement et du logement de Bourgogne-Franche-Comté (DREAL BFC), Jardin des Sciences et biodiversité [Dijon], Partenaires INRAE-Dijon Métropole, Jardins des Sciences Dijon, and Partenaires INRAE
Subjects: [SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, [SHS.ARCHI]Humanities and Social Sciences/Architecture, space management, [SDE.MCG]Environmental Sciences/Global Changes, [SHS.GEO]Humanities and Social Sciences/Geography, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, [SDE.ES]Environmental Sciences/Environmental and Society, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: International audience; Les premiers résultats d'une étude sur les abeilles sauvages menée en 2017 avec le soutien de la DREA L Bourgogne Franche-Comté, ont démontré la richesse des différents cortèges et lots d'espèces remarquables présents sur le territoire, ainsi que l'isolement relatif des réservoirs identifiés. Dans la dynamique des programmes menés pour la biodiversité sur le territoire métropolitain, un plan d'actions en faveur des pollinisateurs est mis en place, il vise à développer :-les connaissances (mise en évidence des cortèges d'espèces, des réservoirs de pollinisateurs sauvages, de la disponibilité des ressources alimentaires, localisation des ruchers dans le SIG de la collectivité. . .);-la prise en compte des enjeux liés à la préservation des pollinisateurs , aux niveaux des aménagements et de la gestion des espaces de nature identifiés (préservation des habitats, gestion différentiée, augmentation de la disponibilité des ressources alimentaires en nectar et pollen, conciliation d'une riche diversité en abeilles sauvages avec la présence de ruchers sur le territoire. . .);-la mobilisation citoyenne (sensibilisation des publics via la valorisation du programme d'apiculture urbaine•Miel de Dijon" , accompagnement des programmes nationaux de science participative • SPIP0LL», végé talisation participative des espaces publics ... ).
Published: 2018

32. Repopulating retinal microglia restore endogenous organization and function under CX3CL1-CX3CR1 regulation

Author: Adam Lazere, Mones Abu-Asab, Wai T. Wong, Haohua Qian, Jun Zhang, Xu Wang, Lian Zhao, Yikui Zhang, Jerome E. Roger, Robert N. Fariss, Wenxin Ma, National Eye Institute [Bethesda, MD, États-Unis] (NEI), National Institutes of Health [Bethesda] (NIH), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, Institut des Neurosciences Paris-Saclay (NeuroPSI), and Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Aging, Chemokine, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Immunology, CX3C Chemokine Receptor 1, Mice, Transgenic, Endogeny, Retina, 03 medical and health sciences, Cell Movement, CX3CR1, medicine, Animals, 10. No inequality, CX3CL1, Research Articles, Cell Proliferation, Multidisciplinary, biology, Microglia, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Chemokine CX3CL1, Calcium-Binding Proteins, Microfilament Proteins, SciAdv r-articles, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, eye diseases, 030104 developmental biology, medicine.anatomical_structure, biology.protein, sense organs, Signal transduction, Neuroscience, Homeostasis, Signal Transduction, Research Article
Abstract: Chemokine signaling via CX3CL1-CX3CR1 helps regulate homeostasis in the population of microglia in the adult mouse retina., Microglia have been discovered to undergo repopulation following ablation. However, the functionality of repopulated microglia and the mechanisms regulating microglia repopulation are unknown. We examined microglial homeostasis in the adult mouse retina, a specialized neural compartment containing regular arrays of microglia in discrete synaptic laminae that can be directly visualized. Using in vivo imaging and cell-fate mapping techniques, we discovered that repopulation originated from residual microglia proliferating in the central inner retina that subsequently spread by centrifugal migration to fully recapitulate pre-existing microglial distributions and morphologies. Repopulating cells fully restored microglial functions including constitutive “surveying” process movements, behavioral and physiological responses to retinal injury, and maintenance of synaptic structure and function. Microglial repopulation was regulated by CX3CL1-CX3CR1 signaling, slowing in CX3CR1 deficiency and accelerating with exogenous CX3CL1 administration. Microglial homeostasis following perturbation can fully recover microglial organization and function under the regulation of chemokine signaling between neurons and microglia.
Published: 2018
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33. Müller glial cell‐dependent regeneration of the neural retina: An overview across vertebrate model systems

Author: Jerome E. Roger, Muriel Perron, Xian-Jie Yang, Annaïg Hamon, Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, Jules Stein Eye Institute University of California at Los Angeles, University of California [Los Angeles] (UCLA), and University of California-University of California-Jules Stein Eye Institute
Subjects: 0301 basic medicine, retina, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Ependymoglial Cells, Reviews, Context (language use), Biology, Regenerative medicine, 03 medical and health sciences, stem cells, Animals, Humans, Progenitor cell, Müller cells, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Regeneration (biology), [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Anatomy, 3. Good health, Transplantation, 030104 developmental biology, regeneration, Stem cell, Reprogramming, Neuroscience, Retinal Dystrophies, Developmental Biology
Abstract: Retinal dystrophies are a major cause of blindness for which there are currently no curative treatments. Transplantation of stem cell‐derived neuronal progenitors to replace lost cells has been widely investigated as a therapeutic option. Another promising strategy would be to trigger self‐repair mechanisms in patients, through the recruitment of endogenous cells with stemness properties. Accumulating evidence in the past 15 year0s has revealed that several retinal cell types possess neurogenic potential, thus opening new avenues for regenerative medicine. Among them, Müller glial cells have been shown to be able to undergo a reprogramming process to re‐acquire a stem/progenitor state, allowing them to proliferate and generate new neurons for repair following retinal damages. Although Müller cell–dependent spontaneous regeneration is remarkable in some species such as the fish, it is extremely limited and ineffective in mammals. Understanding the cellular events and molecular mechanisms underlying Müller cell activities in species endowed with regenerative capacities could provide knowledge to unlock the restricted potential of their mammalian counterparts. In this context, the present review provides an overview of Müller cell responses to injury across vertebrate model systems and summarizes recent advances in this rapidly evolving field. Developmental Dynamics 245:727–738, 2016. © 2015 The Authors. Developmental Dynamics published by Wiley Periodicals, Inc., Key findings The present review provides an overview of Müller cell responses to injury across vertebrate model systems and summarizes recent advances in this rapidly evolving field.
Published: 2016
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34. Win-wins for biodiversity and ecosystem service conservation depend on the trophic levels of the species providing services

Author: Laura E. Dee, Eve McDonald-Madden, Iadine Chadès, Régis Sabbadin, Martin Stringer, Nathalie Peyrard, Hui Xiao, Centre for Biodiversity and Conservation Science, School of Earth and Environmental Sciences, University of Queensland, Partenaires INRAE, CSIRO, EcoSciences Precinct, Department of Fisheries, Wildlife and Conservation Biology (FWCB), University of Minnesota-Partenaires INRAE, Institute on the Environment [Minesota], ARC Centre for Excellence for Environmental Decisions, University of Queensland, Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRA), Institut National de la Recherche Agronomique (INRA), and Centre for Bioviersity and Conservation Science, School of Earth and Environmental Sciences, University of Queensland
Subjects: 0106 biological sciences, 0301 basic medicine, DYNAMICS, Biodiversity, DECISION-MAKING, 010603 evolutionary biology, 01 natural sciences, Ecosystem services, network theory, FOOD WEBS, 03 medical and health sciences, ecosystem-based management, MANAGEMENT, Ecosystem, EXTINCTIONS, [INFO]Computer Science [cs], [MATH]Mathematics [math], Trophic level, COMPLEXITY, Ecology, LANDSCAPE, STABILITY, business.industry, conservation prioritisation, Environmental resource management, 15. Life on land, Network dynamics, Ecosystem-based management, Food web, NETWORKS, 030104 developmental biology, trade-offs, 13. Climate action, Markov Decision Processes, Ecosystem management, business, ecosystem services, COMMUNITIES
Abstract: Confronted by significant impacts to ecosystems world-wide, decision makers face the challenge of maintaining both biodiversity and the provision of ecosystem services (ES). However, the objectives of managing biodiversity and supplying ES may not always be in concert, resulting in the need for trade-offs. Understanding these potential trade-offs is crucial for identifying circumstances under which conservation strategies designed to maximise either biodiversity or ES will result in win-win or win-lose outcomes. One important factor that may influence these outcomes are species interactions and the structure of the networks in which they are embedded. We combine optimisation and network theory to investigate the difference in species prioritisation and management outcomes when targeting biodiversity or ES, by considering trophic interactions between species. We analyse 360 simulated ecosystem networks with different ecosystem structures, including the trophic level of the species providing the ES, the number of ES considered, and the food web connectivity. We then illustrate the framework on a saltmarsh case study. We find that trade-offs between biodiversity and ES depend on the network structure of the ecosystem being managed. The trophic level of the species providing the ES is an important determinant of optimal species protection priorities and the biodiversity-ES trade-offs. A strategy targeting ES leads to similar levels of biodiversity conservation (a win-win situation) only when basal species provide the services. In contrast, food web connectivity and the number of services considered have little impact on biodiversity-ES trade-offs. Synthesis and applications. Our research provides the first optimisation model to examine trade-offs between a biodiversity- or ecosystem service-based approach for managing a network of interacting species that provide services. Importantly, results from considering species-services interactions in ecosystem network dynamics can provide managers with quantitative insights to identify opportunities for win-wins and or to avoid win-loss outcomes, by focusing on the trophic level of the species providing services. Future research could build on our model to add multiple interaction types among species, ecosystem functions, and ecosystem services to analyse optimal ecosystem management for multiple conservation objectives.
Published: 2018
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35. Adsorption Characteristics of Bixin on Acid- and Alkali-Treated Kaolinite in Aprotic Solvents

Author: Zéphirin Mouloungui, Thamrin Usman, Jean-François Fabre, Winda Rahmalia, Laboratoire de Chimie Agro-Industrielle (LCA), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Supérieure de Chimie de Toulouse, Study Program Chemistry of Education, Department of Mathematics and Natural Science Education, Tanjungpura University, University of Tanjungpura, Institut National Polytechnique de Toulouse - INPT (FRANCE), Institut National de la Recherche Agronomique - INRA (FRANCE), Tanjungpura University (INDONESIA), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Chimie Agro-Industrielle (CAI), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole nationale supérieure des ingénieurs en arts chimiques et technologiques-Institut National de la Recherche Agronomique (INRA), Tanjungpura University, Partenaires INRAE-Partenaires INRAE, and Mouloungui, Zephirin
Subjects: Article Subject, lcsh:Biotechnology, Kinetics, solvant, 020101 civil engineering, 02 engineering and technology, Biochemistry, 0201 civil engineering, Inorganic Chemistry, chemistry.chemical_compound, symbols.namesake, Adsorption, lcsh:TP248.13-248.65, Acetone, lcsh:Inorganic chemistry, Kaolinite, kaolinite, Organic Chemistry, chimie agroindustrielle, Bixin, Langmuir adsorption model, bixine, [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, lcsh:QD146-197, Alkali-treated kaolinite, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, chemistry, Chemisorption, symbols, Dimethyl carbonate, 0210 nano-technology, bixin, adsorption, kinetics, Langmuir, Sciences agricoles, Research Article, Nuclear chemistry
Abstract: The adsorption of bixin in aprotic solvents onto acid- and alkali-treated kaolinite was investigated. Kaolinite was treated three times, for 6 h each, with 8 M HCl or 5 M KOH. The adsorbents were characterized by XRD, FT-IR, EDS, and BET-N2. The effects of contact time and dye concentration on adsorption capacity and kinetics, electronic transition of bixin before and after adsorption, and also mechanism of bixin-kaolinite adsorption were investigated. Dye adsorption followed pseudo-second order kinetics and was faster in acetone than in dimethyl carbonate. The best adsorption results were obtained for KOH-treated kaolinite. In both of the solvents, the adsorption isotherm followed the Langmuir model and adsorption capacity was higher in dimethyl carbonate (qm = 0.43 mg/g) than in acetone (0.29 mg/g). The adsorption capacity and kinetics of KOH-treated kaolinite (qm = 0.43 mg/g,k2 = 3.27 g/mg·min) were better than those of HCl-treated kaolinite (qm = 0.21 mg/g,k2 = 0.25 g/mg·min) and natural kaolinite (qm = 0.18 mg/g,k2 = 0.32 g/mg·min). There are shift in the band position of maximum intensity of bixin after adsorption on this adsorbent. Adsorption in this system seemed to be based essentially on chemisorption due to the electrostatic interaction of bixin with the strong basic and reducing sites of kaolinite.
Published: 2018
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36. Effects of high-intensity interval training and moderate-intensity continuous training on glycaemic control and skeletal muscle mitochondrial function in db/db mice

Author: Chavanelle, Vivien, Boisseau, Nathalie, Otero, Yolanda F, Combaret, Lydie, Dardevet, Dominique, Montaurier, Christophe, Delcros, Geoffrey, Peltier, Sébastien L., Sirvent, Pascal, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Faculté des Sciences du SportFaculté des Sciences du Sport, UFR STAPS, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Ferrand (UFR STAPS - UBP), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Valbiotis R & D [La Rochelle], Valbiotis SAS, Partenaires INRAE-Partenaires INRAE, and Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: diabète de type 2, Science, High-Intensity Interval Training, Article, Diabetes Mellitus, Experimental, activité physique, Mice, physical exercise, Physical Conditioning, Animal, Animals, rat, Phosphorylation, métabolisme du glucose, Muscle, Skeletal, Glycated Hemoglobin, Glucose Transporter Type 4, fonction mitochondriale, type ii diabetes, Mitochondria, glycemia, Diabetes Mellitus, Type 2, Gene Expression Regulation, Medicine, glycémie, Proto-Oncogene Proteins c-akt, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: The authors wish to thank Mr Mehdi Djelloul-Mazouz and Mr Philippe Denis from INRA Unité de Nutrition Humaine (UNH, UMR 1019), CRNH Auvergne (France) for the care and the attention to the animals. We also thank Mrs Monique Etienne from AME2P Lab (Clermont-Ferrand, France) and Mrs Anne-Sophie Galvardon for their excellent assistance during the experiments; International audience; Physical activity is known as an effective strategy for prevention and treatment of Type 2 Diabetes. The aim of this work was to compare the effects of a traditional Moderate Intensity Continuous Training (MICT) with a High Intensity Interval Training (HIIT) on glucose metabolism and mitochondrial function in diabetic mice. Diabetic db/db male mice (N = 25) aged 6 weeks were subdivided into MICT, HIIT or control (CON) group. Animals in the training groups ran on a treadmill 5 days/week during 10 weeks. MICT group ran for 80 min (0 degrees slope) at 50-60% of maximal speed (Vmax) reached during an incremental test. HIIT group ran thirteen times 4 minutes (20 degrees slope) at 85-90% of Vmax separated by 2-min-rest periods. HIIT lowered fasting glycaemia and HbA1c compared with CON group (p < 0.05). In all mitochondrial function markers assessed, no differences were noted between the three groups except for total amount of electron transport chain proteins, slightly increased in the HIIT group vs CON. Western blot analysis revealed a significant increase of muscle Glut4 content (about 2 fold) and higher insulin-stimulated Akt phosphorylation ratios in HIIT group. HIIT seems to improve glucose metabolism more efficiently than MICT in diabetic mice by mechanisms independent of mitochondrial adaptations
Published: 2017
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37. Retinal Degeneration and Regeneration-Lessons From Fishes and Amphibians

Author: Ail, Divya, Perron, Muriel, Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, and Partenaires INRAE-Partenaires INRAE
Subjects: Xenopus and Zebrafish Models for Pathobiology (W Goessling and A Zorn, Section Editors), Retinal regeneration, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Retinal stem cells, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Ciliary marginal zone, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Müller glial cells, Retinal degeneration, Retinal pigment epithelium
Abstract: Purpose of Review Retinal degenerative diseases have immense socio-economic impact. Studying animal models that recapitulate human eye pathologies aids in understanding the pathogenesis of diseases and allows for the discovery of novel therapeutic strategies. Some non-mammalian species are known to have remarkable regenerative abilities and may provide the basis to develop strategies to stimulate self-repair in patients suffering from these retinal diseases. Recent Findings Non-mammalian organisms, such as zebrafish and Xenopus, have become attractive model systems to study retinal diseases. Additionally, many fish and amphibian models of retinal cell ablation and cell lineage analysis have been developed to study regeneration. These investigations highlighted several cellular sources for retinal repair in different fish and amphibian species. Moreover, major differences in repair mechanisms have been reported in these animal models. Summary This review aims to emphasize first on the importance of zebrafish and Xenopus models in studying the pathogenesis of retinal diseases and, second, on the different modes of regeneration processes in these model organisms.
Published: 2017
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38. Telomeres expand sphere of influence: emerging molecular impact of telomeres in non-telomeric functions

Author: Soujanya Vinayagamurthy, Sulochana Bagri, Jean-Louis Mergny, Shantanu Chowdhury, CSIR Institute of Genomics and Integrative Biology [New Delhi] (IGIB), Academy of Scientific and Innovative Research [Ghaziabad, India] (AcSIR), Partenaires INRAE, Laboratoire d'Optique et Biosciences (LOB), École polytechnique (X)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute of Biophysics of the Czech Academy of Sciences (IBP / CAS), Czech Academy of Sciences [Prague] (CAS), and Mergny, Jean-Louis
Subjects: [SDV.GEN]Life Sciences [q-bio]/Genetics, G-quadruplex, aging, telomere signaling, [SDV.CAN]Life Sciences [q-bio]/Cancer, TRF2, [SDV.GEN] Life Sciences [q-bio]/Genetics, pluripotency, [SDV.CAN] Life Sciences [q-bio]/Cancer, gene-regulation, non-telomeric function, telomeric factors, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetics, cancer, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Abstract: International audience; Although the impact of telomeres on physiology stands well established, a question remains: how do telomeres impact cellular functions at a molecular level? This is because current understanding limits the influence of telomeres to adjacent subtelomeric regions despite the wide-ranging impact of telomeres. Emerging work in two distinct aspects offers opportunities to bridge this gap. First, telomere-binding factors were found with non-telomeric functions. Second, locally induced DNA secondary structures called G-quadruplexes are notably abundant in telomeres, and gene regulatory regions genome wide. Many telomeric factors bind to G-quadruplexes for non-telomeric functions. Here we discuss a more general model of how telomeres impact the non-telomeric genome – through factors that associate at telomeres and genome wide – and influence cell-intrinsic functions, particularly aging, cancer, and pluripotency.
Published: 2023
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39. 0D/2D Co3O4/Ti3C2 MXene Composite: A Dual-Functional Electrocatalyst for Energy-Saving Hydrogen Production and Urea Oxidation

Author: Yi Zhang, Zhaohui Zhang, Ahmed Addad, Qi Wang, Pascal Roussel, Mohammed A. Amin, Sabine Szunerits, Rabah Boukherroub, NanoBioInterfaces - IEMN (NBI - IEMN), Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), School of Oceanography [Seattle], University of Washington [Seattle], Unité Matériaux et Transformations - UMR 8207 (UMET), Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Anhui University [Hefei], Unité de Catalyse et Chimie du Solide - UMR 8181 (UCCS), Université d'Artois (UA)-Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Taif University (TU), and Partenaires INRAE
Subjects: [SPI]Engineering Sciences [physics], Materials Chemistry, Electrochemistry, Energy Engineering and Power Technology, Chemical Engineering (miscellaneous), Electrical and Electronic Engineering
Abstract: International audience; Electrocatalytic water splitting to produce hydrogen (H2) is a sustainable way of meeting energy demands at no environmental cost. However, the sluggish anodic reaction imposes a considerable overpotential requirement. By contrast, the electrocatalytic urea oxidation reaction offers the prospect of energy-saving H2 production together with urea-rich wastewater purification. In this work, a 0D/2D Co3O4/Ti3C2 MXene composite was synthesized by a simple solution reaction approach under mild conditions and applied as an efficient and stable electrocatalyst for hydrogen evolution reaction (HER) and urea oxidation reaction (UOR) in basic medium (1 M KOH+0.5 M urea). The Co3O4/Ti3C2 MXene electrodes delivered a current density of 10 mA cm–2 at an overpotential of 124 mV for HER and required 1.40 V to reach 10 mA cm–2 for UOR. The hybrid catalyst could maintain high activity after 40 h continuous catalytic reaction for both UOR and HER. Its catalytic performance was significantly improved compared to that of pure Ti3C2 MXene and Co3O4 solving the problem of insufficient exposure of active sites caused by too large particle size and agglomeration of Co3O4 particles. Notably, Co3O4/Ti3C2 MXene was applied as a bifunctional catalyst for overall urea-containing water splitting, and showed certain energy saving advantages compared with other reported Co-based catalysts. This work provides a strategy for application other than noble metal-based electrode materials for urea-containing wastewater purification coupled with H2 production.
Published: 2022
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40. Bactrocera dorsalis in the Indian Ocean: A tale of two invasions

Author: Pablo Deschepper, Sam Vanbergen, Yue Zhang, Zhihong Li, Issa Mze Hassani, Nausheen Azhaar Patel, Henriette Rasolofoarivao, Sandeep Singh, Suk Ling Wee, Marc De Meyer, Massimiliano Virgilio, Hélène Delatte, Royal Museum for Central Africa [Tervuren] (RMCA), China Agricultural University (CAU), Institut National de la Recherche pour l'Agriculture, la Pêche et l'Environnement (INRAPE), Ministry of Agro Industry and Food Security, Partenaires INRAE, Centre National de Recherche Appliquée au Développement Rural (FOFIFA), Punjab Agricultural University (PAU), Universiti Kebangsaan Malaysia (UKM), Peuplements végétaux et bioagresseurs en milieu tropical (UMR PVBMT), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Université de La Réunion (UR)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département Systèmes Biologiques (Cirad-BIOS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), and The authors acknowledge the Plant Protection Platform (3P, IBISA) where DNA extractions were conducted and David Nestel for providing us with samples of B. zonata. Funding for this research was provided by the EU-FF-IPM H2020 FF-IPM project (Grant ID: 818184), and the National Natural Science Foundation of China (Grant ID: 31972341). The computational resources (Stevin Supercomputer Infrastructure) and services used in this work were provided by the VSC (Flemish Supercomputer Center), funded by Ghent University, FWO, and the Flemish Government—department EWI.
Subjects: [SDV]Life Sciences [q-bio], phylogeography, invasive species, pest species, Genetics, Indian Ocean, Ecology, Evolution, Behavior and Systematics, Tephritidae, H10 - Ravageurs des plantes, Bactrocera dorsalis, General Agricultural and Biological Sciences, Génotype, Espèce envahissante
Abstract: International audience; An increasing number of invasive fruit fly pests are colonizing new grounds. With this study, we aimed to uncover the invasion pathways of the oriental fruit fly, Bactrocera dorsalis into the islands of the Indian Ocean. By using genome-wide SNP data and a multipronged approach consisting of PCA, ancestry analysis, phylogenetic inference, and kinship networks, we were able to resolve two independent invasion pathways. A western invasion pathway involved the stepping-stone migration of B. dorsalis from the east African coast into the Comoros, along Mayotte and into Madagascar with a decreasing genetic diversity. The Mascarene islands (Reunion and Mauritius), on the contrary, were colonized directly from Asia and formed a distinct cluster. The low nucleotide diversity suggests that only a few genotypes invaded the Mascarenes. The presence of many long runs of homozygosity (ROH) in the introduced populations is indicative of population bottlenecks, with evidence of a more severe bottleneck for populations along the western migration pathway than on the Mascarene islands. More strict phytosanitary regulations are recommended in order to prevent the further spread of B. dorsalis.
Published: 2022
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41. What Does Ecological Farming Mean for Farm Labour?

Author: Sophia Davidova, Nathalie Hostiou, Maria Alebaki, Alastair Bailey, Zoltan Bakucs, Julie Duval, Penelope Gouta, Stuart Henderson, Anne‐Lise Jacquot, Philippe Jeanneaux, Błażej Jendrzejewski, Kevin Kilcline, Vasilia Konstantidelli, Philip Kostov, Laure Latruffe, Lena Schaller, Kato Van Ruymbeke, Lionel Védrine, Jacques Veslot, Liesbet Vranken, Peter Walder, University of Kent, Territoires (Territoires), AgroParisTech-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Hellenic Agricultural Organization Demeter (HAO Demeter), MTA KRTK, Partenaires INRAE, Institut Agro Rennes Angers, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut du développement de l'agriculture et de la campagne (IRWIR PAN), Polska Akademia Nauk = Polish Academy of Sciences (PAN), Teagasc - The Agriculture and Food Development Authority (Teagasc), University of Central Lancashire, Bordeaux Sciences Economiques (BSE), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Universität für Bodenkultur Wien = University of Natural Resources and Life [Vienne, Autriche] (BOKU), Department of Earth and Environmental Sciences - KU Leuven, Leuven, Centre d'Economie et de Sociologie Rurales Appliquées à l'Agriculture et aux Espaces Ruraux (CESAER), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), LICOS Center for Institutions and Economic Performance, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Department of Earth and Environmental Sciences [Leuven-Heverlee], and The European Union’s H2020 research and innovation programme under grant agreement No 770747 (https:// www.lift-h2020.eu/).
Subjects: Geography, Planning and Development, [SHS]Humanities and Social Sciences
Abstract: Ecological farming, such as organic and low-input farming, is gaining popularity in the public discourse. One question is how this type of farming may impact farm labour from a socio- economic point of view. The article first discusses how low-input farming practices (i.e. with lower reliance on inputs derived from fossil fuels) may affect the economic returns to labour, measured as the farm’s revenue per hour of labour input, on data from the Farm Accountancy Data Network (FADN) in 2004-2015 for four European countries. Returns to labour appear to be highest at the two extremes – very low-input farms and highly intensive farms. Farms in the low-input end of the spectrum are in the minority, while the overwhelming majority of farms are intensive and have internal economic incentives to intensify further. The article also analyses how working conditions differ between organic and conventional dairy farms in two European countries based on interviews with farmers in 2019. Results show that all dimensions of working conditions are affected by being an organic farm or not, but this is not the only factor. There are many influences on working conditions, such as the production context and workforce composition.
Published: 2022
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42. Redox equilibrium and retinal stem cell proliferation

Author: Lainé, Anaïs, Perron, Muriel, Locker, Morgane, Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, and Lainé, Anaïs
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2016

43. An atlas of Wnt activity during embryogenesis in Xenopus tropicalis

Author: Caroline Borday, Hong Thi Tran, Karine Parain, Anne-Hélène Monsoro-Burq, Kris Vleminckx, Muriel Perron, Signalisation normale et pathologique de l'embryon aux thérapies innovantes des cancers, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Department of Biomedical Molecular Biology [Ghent], Universiteit Gent = Ghent University [Belgium] (UGENT), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, and Partenaires INRAE-Partenaires INRAE
Subjects: 0301 basic medicine, Embryology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Xenopus, lcsh:Medicine, Xenopus Proteins, BETA-CATENIN, OPTIC CUP, Cell Signaling, Neural Stem Cells, Animal Cells, Medicine and Health Sciences, lcsh:Science, Wnt Signaling Pathway, Zebrafish, WNT Signaling Cascade, In Situ Hybridization, Multidisciplinary, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Stem Cells, Wnt signaling pathway, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Eukaryota, Gene Expression Regulation, Developmental, Neural crest, Animal Models, Signaling Cascades, Cell biology, Cell Motility, medicine.anatomical_structure, Experimental Organism Systems, Neural Crest, SIGNALING, Vertebrates, Frogs, Cellular Types, Cellular Structures and Organelles, CYCLIN D1 GENE, STEM-CELLS, Research Article, Signal Transduction, EXPRESSION, Neural Tube, Beta-catenin, Molecular Probe Techniques, Embryonic Development, Cell Migration, Biology, Research and Analysis Methods, Amphibians, 03 medical and health sciences, Model Organisms, Developmental Neuroscience, NEURAL CREST INDUCTION, medicine, Animals, Vesicles, Molecular Biology Techniques, Molecular Biology, CILIARY MARGIN, ZEBRAFISH, Embryos, lcsh:R, Embryogenesis, Organisms, Neural tube, Biology and Life Sciences, PATHWAYS, Cell Biology, Gastrula, biology.organism_classification, Probe Hybridization, Wnt Proteins, Gastrulation, PLATE BORDER, 030104 developmental biology, Cellular Neuroscience, biology.protein, lcsh:Q, Developmental Biology, Neuroscience
Abstract: International audience; Wnt proteins form a family of highly conserved secreted molecules that are critical mediators of cell-cell signaling during embryogenesis. Partial data on Wnt activity in different tissues and at different stages have been reported in frog embryos. Our objective here is to provide a coherent and detailed description of Wnt activity throughout embryo development. Using a transgenic Xenopus tropicalis line carrying a Wnt-responsive reporter sequence, we depict the spatial and temporal dynamics of canonical Wnt activity during embryogenesis. We provide a comprehensive series of in situ hybridization in whole-mount embryos and in cross-sections, from gastrula to tadpole stages, with special focus on neural tube, retina and neural crest cell development. This collection of patterns will thus constitute a valuable resource for developmental biologists to picture the dynamics of Wnt activity during development.
Published: 2018
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44. Protein ingredient quality within infnat formulas impacts digestion and amino acid bioavailability: a combined in vitro and in vivo approach

Author: Chauvet, Lucile, Le Gouar, Yann, Ménard, Olivia, Alexis, Brunel, Cochet, Marie-Françoise, Jardin, Julien, Guerin, Sylvie, Janvier, Regis, Cahu, Armelle, Croguennec, Thomas, van Audenhaege, Marieke, Dupont, Didier, Le Huërou-Luron, Isabelle, Lemaire, Marion, Deglaire, Amélie, Science et Technologie du Lait et de l'Oeuf (STLO), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Rennes Angers, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Sodiaal International, Department of Research and Innovation, Partenaires INRAE, and American Dairy Science Association
Subjects: Whey, Infant formula, micellar casein, kinetics of digestion, bioavailability, Dairy protein, Microstructure, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Nutrition
Abstract: International audience; Infant formula (IF) is a complex matrix requiring numerous ingredients and processing steps. The objective was to understand how the quality of protein ingredients impacts IF structure and, in turn, their kinetics of digestion. Four powdered IFs (A/B/C/D), based on commercial whey protein (WP) ingredients, with different protein denaturation levels and composition (A/B/C), and on caseins with different supramolecular organisations (C/D), were produced at a semi-industrial level after homogenization and spray-drying. Once reconstituted in water (13 %, wt/wt), the IF microstructure was analysed with asymmetrical flow field-flow fractionation coupled with multi-angle light scattering and differential refractometer, transmission electron microscopy and electrophoresis. The rehydrated IFs were subjected to simulated infant in vitro dynamic digestion (DIDGI®). Digesta were regularly sampled to follow structural changes (confocal microscopy, laser-light scattering) and proteolysis (OPA, SDS-PAGE, LC-MS/MS, cation-exchange chromatography). Before digestion, different microstructures were observed among IFs. IF-A, characterized by more denatured WPs, presented star-shaped mixed aggregates, with protein aggregates bounded to casein micelles, themselves adsorbed at the fat droplet interface. Non-micellar caseins, brought by non-micellar casein powder (IF-D) underwent rearrangement and aggregation at the interface of flocculated fat droplets, leading to a largely different microstructure of IF emulsion, with large aggregates of lipids and proteins. During digestion, IF-A more digested (degree of proteolysis + 16 %) at 180 min of intestinal phase than IF-C/D. The modification of the supramolecular organisation of caseins implied different kinetics of peptide release derived from caseins during the gastric phase (more abundant at G80 for IF-D). Bioactive peptide release kinetics were also different during digestion with IF-C presenting a maximal abundance for a large proportion of them. Overall, the present study highlights the importance of the structure and composition of the protein ingredients (WPs and caseins) selected for IF formulation on the final IF structure and, in turn, on proteolysis. Whether it has some physiological consequences remains to be investigated.
Published: 2023

45. Design of a surgical stapler for laparoscopic colectomy

Author: Dhruva Khanzode, Ranjan Jha, Alexandra Thomieres, Emilie Duchalais, damien chablat, Central Scientific Instruments Organisation (CSIR), Academy of Scientific and Innovative Research [Ghaziabad, India] (AcSIR), Partenaires INRAE, Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire des Sciences du Numérique de Nantes (LS2N), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, and Nantes Université (Nantes Univ)
Subjects: laparoscopy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Surgical stapler, anastomosis, tensegrity mechanism, [SPI.AUTO]Engineering Sciences [physics]/Automatic
Abstract: International audience; In this article, a flexible surgical stapler mechanism is designed to serve as a basis for laparoscopic rectal cancer surgery in which conventional tools cannot be easily accessed. The mechanism is designed by implementing a stacked tensegrity mechanism with a flexible beam as the central spine. The workspace analysis for the stapler was done by studying collaborative data of CT scans of the surgical site from the Axial, Coronal, and Sagittal planes at different intervals. The kinematic equations for the mechanism were synthesized using Hooke's law with a rotational spring and bending moment. For the tensegrity mechanism, singularities and simulations of the mechanism were also analyzed incorporating the eyelet friction parameter. The results of the study signify that the friction parameter can modify the radius of curvature of the mechanism and needs to be analyzed correctly.
Published: 2023

46. Uncertainties in the adaptation of alpine pastures to climate change based on remote sensing products and modelling

Author: L. Brilli, R. Martin, G. Argenti, M. Bassignana, M. Bindi, R. Bonet, P. Choler, E. Cremonese, M. Della Vedova, C. Dibari, G. Filippa, M. Galvagno, L. Leolini, M. Moriondo, A. Piccot, L. Stendardi, S. Targetti, G. Bellocchi, Institute for BioEconomy [Sesto Fiorentino] (IBE | CNR), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Unité Mixte de Recherche sur l'Ecosystème Prairial - UMR (UREP), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Università degli Studi di Firenze = University of Florence (UniFI), Institut Agricole Régional, Partenaires INRAE, Parc national des Ecrins, Laboratoire Environnement de Conception & Architecture (LECA), Université Paris-Saclay-Département Systèmes et Circuits Intégrés Numériques (DSCIN), Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Climate Change Unit [Ispra], JRC Institute for Environment and Sustainability (IES), European Commission - Joint Research Centre [Ispra] (JRC)-European Commission - Joint Research Centre [Ispra] (JRC), University of Bologna/Università di Bologna, and The present work was produced under the co-finance of the EC LIFE programme for the Environment and Climate Action (2014–2020) in the framework of the Project LIFE PASTORALP ‘Pastures vulnerability and adaptation strategies to climate change impacts in the Alps’ (LIFE16/CCA/IT/000060).
Subjects: Environmental Engineering, Alpine pastures, [SDE]Environmental Sciences, Climate change adaptation, General Medicine, Management, Monitoring, Policy and Law, Remote sensing, Waste Management and Disposal, Modelling
Abstract: International audience; Over the last century, the management of pastoral systems has undergone major changes to meet the livelihood needs of alpine communities. Faced with the changes induced by recent global warming, the ecological status of many pastoral systems has seriously deteriorated in the western alpine region. We assessed changes in pasture dynamics by integrating information from remote-sensing products and two process-based models, i.e. the grassland-specific, biogeochemical growth model PaSim and the generic crop-growth model DayCent. Meteo-rological observations and satellite-derived Normalised Difference Vegetation Index (NDVI) trajectories of three pasture macro-types (high, medium and low productivity classes) in two study areas -Parc National des ' Ecrins (PNE) in France and Parco Nazionale Gran Paradiso (PNGP) in Italy -were used as a basis for the model cali-bration work. The performance of the models was satisfactory in reproducing pasture production dynamics (R2 = 0.52 to 0.83). Projected changes in alpine pastures due to climate-change impacts and adaptation strategies indicate that: i) the length of the growing season is expected to increase between 15 and 40 days, resulting in changes in the timing and amount of biomass production, ii) summer water stress could limit pasture produc-tivity; iii) earlier onset of grazing could enhance pasture productivity; iv) higher livestock densities could in-crease the rate of biomass regrowth, but major uncertainties in modelling processes need to be considered; and v) the carbon sequestration potential of pastures could decrease under limited water availability and warming.
Published: 2023
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47. YAP controls retinal stem cell DNA replication timing and genomic stability

Author: Juliette Bitard, Christel Masson, Karine Parain, Kristine A. Henningfeld, Odile Bronchain, Marie Hedderich, Romain Chemouny, Muriel Perron, Guillermo A. Vega-Lopez, Morgane Locker, Pauline Cabochette, Caroline Borday, Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, and Center for Nanoscale Microscopy and Molecular Physiology of the Brain
Subjects: Genome instability, retina, Cell division, DNA Replication Timing, QH301-705.5, DNA damage, Xenopus, Science, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, YAP, DNA, genomic stability, Xenopus Proteins, Biology, Genomic Instability, General Biochemistry, Genetics and Molecular Biology, neural stem cell, ciliary marginal zone, Animals, Biology (General), neural stem cells, Genetics, Hippo signaling pathway, General Immunology and Microbiology, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Stem Cells, General Neuroscience, DNA replication, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, YAP-Signaling Proteins, General Medicine, Neural stem cell, Cell biology, Developmental Biology and Stem Cells, cell proliferation, Hippo/Yap pathway, Trans-Activators, Medicine, Stem cell, Cell Division, Research Article
Abstract: The adult frog retina retains a reservoir of active neural stem cells that contribute to continuous eye growth throughout life. We found that Yap, a downstream effector of the Hippo pathway, is specifically expressed in these stem cells. Yap knock-down leads to an accelerated S-phase and an abnormal progression of DNA replication, a phenotype likely mediated by upregulation of c-Myc. This is associated with an increased occurrence of DNA damage and eventually p53-p21 pathway-mediated cell death. Finally, we identified PKNOX1, a transcription factor involved in the maintenance of genomic stability, as a functional and physical interactant of YAP. Altogether, we propose that YAP is required in adult retinal stem cells to regulate the temporal firing of replication origins and quality control of replicated DNA. Our data reinforce the view that specific mechanisms dedicated to S-phase control are at work in stem cells to protect them from genomic instability. DOI: http://dx.doi.org/10.7554/eLife.08488.001, eLife digest In animals, stem cells divide to produce the new cells needed to grow and renew tissues and organs. Understanding the biology of these cells is of the utmost importance for developing new treatments for a wide range of human diseases, including neurodegenerative diseases and cancer. Before a stem cell divides, it copies its DNA and the two sets of genetic instructions are then separated so that the two daughter cells both have a complete set. This process needs to be as accurate as possible because any errors would result in incorrect genetic information being passed on to the daughter cells. Stem cells in the light-sensitive part of the eye—called the retina—divide to produce the cells that detect light and relay visual information to the brain. In many animals, these stem cells stop dividing soon after birth and the retina stops growing. However, the stem cells in frogs and fish continue to divide throughout the life of the animal, which enables the eye to keep on growing. A protein called YAP regulates the growth of organs in animal embryos, but it is not clear what role this protein plays in stem cells, particularly after birth. To address this question, Cabochette et al. studied YAP in the retina of frog tadpoles. The experiments show that YAP is produced in the stem cells of the retina after birth and is required for the retina to continue to grow. Cabochette et al. used tools called ‘photo-cleavable Morpholinos’ to alter the production of YAP in adult stem cells. The cells that produced less YAP copied their DNA more quickly and more of their DNA became damaged, which eventually led to the death of these cells. Further experiments revealed that YAP interacts with a protein called PKNOX1, which is involved in maintaining the integrity of DNA. Cabochette et al.'s findings provide the first insights into how YAP works in the stem cells of the retina and demonstrate that it plays a crucial role in regulating when DNA is copied. A future challenge is to find out whether YAP plays a similar role in the stem cells of other organs in adult animals. DOI: http://dx.doi.org/10.7554/eLife.08488.002
Published: 2015
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48. Les nouvelles recommandations du PNNS sur la diversification alimentaire

Author: Bocquet, A., Briend, A., Chalumeau, M., Dupont, C., Darmaun, Dominique, de Luca, A., Feillet, F., Frelut, M.-L., Guimber, D., Lapillonne, A., Linglart, A., Peretti, N., Rozé, Jean-Christophe, Simeoni, U., Turck, D., Chouraqui, J.-P., Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut de Recherche pour le Développement (IRD), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Clinique Marcel Sembat (CCBB) - Ramsay Santé [Boulogne Billancourt], Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Tours (UT), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cabinet de pédiatrie, Partenaires INRAE, Université de Lille, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: [SDV]Life Sciences [q-bio], General Medicine, PNNS Diversification alimentaire Nutrition Enfant Recommandations Néophobie Diversification menée par l'enfant PNNS Complementary feeding Nutrition Child Recommendations Neophobia Baby-led weaning
Abstract: International audience
Published: 2022
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49. Multiple detection of both attractants and repellents by the <scp>dCache</scp> ‐chemoreceptor SO_1056 of Shewanella oneidensis

Author: Anne Boyeldieu, Jean‐Pierre Poli, Amine Ali Chaouche, Henri‐Pierre Fierobe, Marie‐Thérèse Giudici‐Orticoni, Vincent Méjean, Cécile Jourlin‐Castelli, Bioénergétique et Ingénierie des Protéines (BIP ), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Università di Corsica Pasquale Paoli [Université de Corse Pascal Paoli], Partenaires INRAE, and Laboratoire de chimie bactérienne (LCB)
Subjects: dCache domain, ligand binding, Chemotaxis, Malates, Methyl-Accepting Chemotaxis Proteins, Cell Biology, chemoreceptors, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Biochemistry, isothermal titration calorimetry, bacterial chemotaxis, thermal shift assay, Bacterial Proteins, Nickel, Molecular Biology
Abstract: International audience; Chemoreceptors are usually transmembrane proteins dedicated to the detection of compound gradients or signals in the surroundings of a bacterium. After detection, they modulate the activation of CheA-CheY, the core of the chemotactic pathway, to allow cells to move upwards or downwards depending on whether the signal is an attractant or a repellent, respectively. Environmental bacteria such as Shewanella oneidensis harbour dozens of chemoreceptors or MCPs (methyl-accepting chemotaxis proteins). A recent study revealed that MCP SO_1056 of S. oneidensis binds chromate. Here, we show that this MCP also detects an additional attractant (L-malate) and two repellents (nickel and cobalt). The experiments were performed in vivo by the agarose-in-plug technique after overproducing MCP SO_1056 and in vitro, when possible, by submitting the purified ligand-binding domain (LBD) of SO_1056 to a thermal shift assay (TSA) coupled to isothermal titration calorimetry (ITC). ITC assays revealed a K D of 3.4 lM for L-malate and of 47.7 lM for nickel. We conclude that MCP SO_1056 binds attractants and repellents of unrelated composition. The LBD of SO_1056 belongs to the double Cache_1 family and is highly homologous to PctA, a chemoreceptor from Pseudomonas aeruginosa that detects several amino acids. Therefore, LBDs of the same family can bind diverse compounds, confirming that experimental approaches are required to define accurate LBD-binding molecules or signals.
Published: 2022
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50. First-line single-agent pembrolizumab for PD-L1-positive (tumor proportion score ≥ 50%) advanced non-small cell lung cancer in the real world: impact in brain metastasis: a national French multicentric cohort (ESCKEYP GFPC study)

Author: Renaud Descourt, Laurent Greillier, Maurice Perol, Charles Ricordel, Jean-Bernard Auliac, Lionel Falchero, Radj Gervais, Rémi Veillon, Sabine Vieillot, Florian Guisier, Marie Marcq, Grégoire Justeau, Laurence Bigay-Game, Marie Bernardi, Pierre Fournel, Hélène Doubre, Julian Pinsolle, Karim Amrane, Christos Chouaïd, Chantal Decroisette, Service d'Oncologie Thoracique (BREST - ICH), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Institut de cancérologie et hématologie, CHU Marseille, Aix Marseille Université (AMU), Hospices Civils de Lyon (HCL), Centre Léon Bérard [Lyon], Service de pneumologie [Rennes] = Pneumology [Rennes], CHU Pontchaillou [Rennes], CH, Mantes-La-Jolie, Centre Hospitalier de Villefranche sur Saône, Partenaires INRAE, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Bordeaux [Bordeaux], Catalan Institute of Oncology [Perpignan], Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Hôpital Foch [Suresnes], Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois]
Subjects: safety, Cancer Research, geriatric assessment, efficacy, MESH: Neoplasms, Glandular and Epithelial, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Guidelines, Thymic carcinoma, Non-small cell lung cancer, Chemotherapy, Immunology and Allergy, MESH: Cohort Studies, [STAT.AP]Statistics [stat]/Applications [stat.AP], Advanced stage, MESH: Humans, MESH: Thymoma, Radiotherapy, toxicity, Brain metastases, MESH: Retrospective Studies, Real-world study, MESH: Neoplasm Staging, targeted therapy, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, MESH: Prospective Studies, lung cancer, quality of life, Oncology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Surgery, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pembrolizumab, [PHYS.PHYS.PHYS-DATA-AN]Physics [physics]/Physics [physics]/Data Analysis, Statistics and Probability [physics.data-an], MESH: Thymus Neoplasms
Abstract: Few real-world data are available in patients with advanced metastatic non-small cell lung cancer (NSCLC) treated with first-line immunotherapy, particularly in those with brain metastases at treatment initiation.This was a national, retrospective, multicenter study that consecutively included all patients with PD-L1-positive (tumor proportion score ≥ 50%) advanced NSCLC who initiated first-line treatment with pembrolizumab as a single agent between May 2017 (date of availability of pembrolizumab in this indication in France) to November 22, 2019 (approval of the pembrolizumab-chemotherapy combination). Data were collected from medical records with local response assessment.The cohort included 845 patients and 176 (20.8%) had brain metastases at diagnosis. There were no significant differences in outcomes for patients with and without brain metastases: 9.2 (95% CI 5.6-15) and 8 (95% CI 6.7-9.2, p = 0.3) months for median progression-free survival (PFS) and, 29.5 (95% CI 17.2-NA) and 22 (95% CI 17.8-27.1, p = 0.3) months for median overall survival (OS), respectively. Overall response rates were 47% and 45% in patients with and without cerebral metastases. In multivariate analysis, performance status 2-4 vs. 0-1 and neutrophil-to-lymphocyte ratio ≥ 4 vs. 4 were the main independent negative factors for OS; brain metastasis was not an independent factor for OS.In this large multicenter cohort, nearly 20% of patients initiating pembrolizumab therapy for advanced NSCLC had cerebral metastases. There was no significant difference in response rates, PFS and OS between patients with and without brain metastases.
Published: 2022
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