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4. Diagnosis and management of childhood asthma in primary care.

Author

Lo, David, Gaillard, Brigitte, Bullous, Louise, and Gaillard, Erol

Abstract

Although asthma is the most common non-communicable disease of childhood, there is no standardised definition nor gold-standard test available to diagnose the condition. Asthma is a complex airways disorder where genetic, environmental and host immunity are likely to play a part. Misdiagnosis in children is common, although objective lung function tests aid accuracy, when combined with a clinical history. Adopting a stepwise approach to achieving complete, or good, control of symptoms enhances management and regular treatment reviews should include provision of mutually-agreed, written personalised asthma action plans, which should also be given to children's schools. When control is poor or diagnosis uncertain, patients should be referred to specialist care. [ABSTRACT FROM AUTHOR]

Published
2016
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5. Involvement of the collagenase produced by Corynebacterium rathayii in its adhesion to collagen

Author

Labadie, J.C., GAILLARD, Brigitte, Potier, Patrick, ProdInra, Migration, Station de recherches sur la viande, Institut National de la Recherche Agronomique (INRA), and Unité de Microbiologie (MIC)

Subjects
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, ComputingMilieux_MISCELLANEOUS, MICROSCOPIE ELECTRONIQUE A TRANSMISSION
Abstract

International audience

Published
1991

7. Ultrastructural study of two rumen fungi: Piromonas communis and Sphaeromonas communis.

Author

Gaillard, Brigitte and Citron, Anne

Abstract

Two species of strictly anaerobic rumen fungi, Sphaeromonas communis and Piromonas communis, were examined by light and electron microscopy (scanning and transmission). Although morphologically different (vegetative body, number of flagella per zoospore), the ultrastructure of these two microorganisms was rather similar to that of Neocallimastix frontalis and N. patriciarum. Two types of organelles were regularly found, i.e., isolated or associated ribosomes in the form of aggregates and hydrogenosome-like organelles with an amorphous content that may be involved in energy generation for these mitochondria-free strictly anaerobic fungi. Unlike N. frontalis, the distribution of organelles was homogenous. [ABSTRACT FROM AUTHOR]

Published
1989
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12. Effect of exercise on energy expenditure and body composition in astronauts onboard the International Space Station

Author

Pierre, Bourdier, Alexandre, Zahariev, Dale, Schoeller, Isabelle, Chery, Le Roux, Elisa, Cécile, Thevenot, Alain, Maillet, Maël, Garnotel, Guillemette, Gauquelin-Koch, Audrey, Bergouignan, Stéphane, Blanc, Simon, Chantal, Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), University of Wisconsin-Madison, Institut de Médecine et de Physiologie Spatiales (MEDES), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université de Bordeaux (UB)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Université Jean Monnet - Saint-Étienne (UJM)-Université de Tours (UT)-Université de Clermont-Ferrand-Centre National d'Études Spatiales [Toulouse] (CNES), CADMOS-CNES, Centre National d’Études Spatiales [Paris] (CNES), University of Colorado [Denver], 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), Hospices Civils de Lyon (HCL), and Gaillard, Brigitte

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

International audience; Objective: Body mass (BM) loss and body composition (BC) changes threaten astronauts' health and mission success. However, the energetics contribution of the exercise countermeasure to these changes has never been investigated during long-term missions. We studied energy balance and BC in astronauts during 6-month missions onboard the International Space Station. Methods: Before and after at least 3 months in space, BM, BC, total and activity energy expenditure (TEE and AEE) were measured using the doubly labeled water method in 11 astronauts (2011-2017). Physical activity (PA) was assessed by the SensewearPro® activity-device. Results: Three-month spaceflight decreased BM (-1.20kg (SE 0.5); P=0.04), mainly due to non-significant fat-free mass loss (FFM;-0.94kg (0.59)). The decrease in walking time (-63.2min/day (11.5); P

Published
2022
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13. Editorial: Metabolic Flexibility

Author

Jose E. Galgani, Audrey Bergouignan, Jennifer Rieusset, Cedric Moro, Julie-Anne Nazare, Pontificia Universidad Católica de Chile (UC), Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), 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), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), and Gaillard, Brigitte

Subjects
[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, ComputingMilieux_MISCELLANEOUS, Food Science
Abstract

International audience

Published
2022
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14. Physiology of physical inactivity, sedentary behaviours and non‐exercise activity: insights from the space bedrest model

Author

Stéphane Blanc, Audrey Bergouignan, Daniel H. Bessesen, Elisa Le Roux, Nathan P. De Jong, Chantal Simon, Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Division of Endocrinology metaboism and diabetes, Anschutz Health & Wellness Center, 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), CNRS GDR Sport & Activite PhysiqueNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institute for Health (NIH)F31DK125061Colorado Nutrition Obesity Research CentreNORC P30DK048520Centre National D'etudes Spatiales, and Gaillard, Brigitte

Subjects
0301 basic medicine, non, medicine.medical_specialty, Physiology, [SDV]Life Sciences [q-bio], Health outcomes, Muscle mass, 03 medical and health sciences, 0302 clinical medicine, Regular exercise, Adverse health effect, medicine, Humans, Daily living, Metabolic health, Exercise activity, exercise, business.industry, bedrest, moderate to vigorous physical activity, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Increased risk, physical inactivity, Physical therapy, light physical activity, Sedentary Behavior, business, metabolism, Bed Rest, ‐exercise activity, 030217 neurology & neurosurgery
Abstract

International audience; Physical inactivity, i.e., not reaching the recommended level of physical activity (PA) and sedentary behaviors (SB), i.e., sitting time have been associated with increased risk for common metabolic diseases. Recent epidemiological data suggest that high volumes of SB are detrimental for metabolic health, even in the presence of regular exercise, i.e., moderate/vigorous (MVPA). This suggests that the health effects of SB are independent from those of exercise. However, experimentally testing this hypothesis is complicated because of the difficulty in disassociating SB from PA. Bedrest studies, a traditional space science model, can offer new insights. In some bedrest studies, an exercise training protocol has been used to counteract the harmful effects of inactivity. While bedrest induces an inactive and sedentary state, exercise with bedrest represents a unique model of sedentary yet physically active people. Here, we review bedrest studies with and without exercise training. Although exercise training prevents the loss of muscle mass and function, even large volumes of exercise are not sufficient to fully counteract the negative metabolic adaptations triggered by inactivity. This observation supports the existence of independent adverse health effects of SB, but also the potential benefits of non‐exercise activity, i.e., daily living light‐intensity activities (LPA). We gathered available data to examine the complex relationships between exercise, non‐exercise activity, SB and health outcomes. Given the large amount of SB in modern societies, the sole promotion of exercise, i.e., MVPA may be insufficient, and promotion of LPA may be a complimentary approach to improve health.

Published
2021
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15. Animal social networks: Towards an integrative framework embedding social interactions, space and time

Author

Mathieu Lihoreau, Sebastian Sosa, David M. P. Jacoby, Cédric Sueur, Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Zoological Society of London - ZSL (UNITED KINGDOM), Centre de Recherches sur la Cognition Animale - UMR5169 (CRCA), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, and Gaillard, Brigitte

Subjects
[SDV] Life Sciences [q-bio], Theoretical computer science, Spacetime, Computer science, [SDV]Life Sciences [q-bio], Ecological Modeling, Embedding, ComputingMilieux_MISCELLANEOUS, Ecology, Evolution, Behavior and Systematics
Abstract

International audience

Published
2021
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16. Measuring fitness and inferring natural selection from long-term field studies: different measures lead to nuanced conclusions

Author

Vincent A. Viblanc, Claire Saraux, Anouch Tamian, François Criscuolo, David W. Coltman, Shirley Raveh, Jan O. Murie, F. Stephen Dobson, and Gaillard, Brigitte

Subjects
[SDV] Life Sciences [q-bio], Animal Science and Zoology, Ecology, Evolution, Behavior and Systematics
Abstract

Measuring individual reproductive success in the wild is often achieved by counting the number of descendants produced by individuals. In seeking to understand how reproductive success can inform us about natural selection, however, we are faced with a conundrum. In terms of timing, what is the most relevant measure for examining selection? We might count the number of offspring born, surviving to the termination of parental care, surviving to adulthood, or only those surviving to themselves reproduce. Clearly, only the latter are passing on genes and traits to future generations, but this estimate may not always be available. So, are different estimates of fitness consistent? Do they provide us with similar inferences of selection on phenotypic traits? We examined these questions on a 29-year long-term study of individually monitored male and female Columbian ground squirrels (Urocitellus columbianus). We used the long-term data to calculate male and female fitness based on an annual measure of adult survival and the yearly production of offspring counted at the stages of birth, weaning, and yearling age. We then decomposed fitness into its constitutive elements including (1) adult survival to the next spring, and (2) the yearly production of offspring counted at the stages previously mentioned. We then compared fitness metrics to evaluate if they provided similar or contrasting information in the wild. Next, we used those fitness metrics to test for selection on the date of emergence from annual hibernation, a phenotypic trait previously shown to be highly variable, heritable, and associated with reproduction. Finally, we partitioned selection on emergence date into additive episodes of selection by looking at how selection changed from reproduction measured at birth, weaning and when offspring reached yearling age. Overall, fitness metrics were well correlated, but correlations weakened the further offspring were counted from birth. We generally found directional selection for earlier emergence dates both in males and females. The strength of selection depended on

Published
2022

17. A near-infrared fluorogenic dimer enables background-free imaging of endogenous GPCRs in living mice

Author

David Brasse, Thierry Durroux, Dominique Bonnet, Lucie Esteoulle, Patrice Marchand, Iuliia A. Karpenko, Andrey S. Klymchenko, Stéphanie Riché, François Daubeuf, Mayeul Collot, Laboratoire d'Innovation Thérapeutique (LIT), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC), Laboratoire de Bioimagerie et Pathologies (LBP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Département de Radiobiologie, Hadronthérapie et Imagerie Moléculaire (DRHIM-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Gaillard, Brigitte, Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0303 health sciences, [SDV]Life Sciences [q-bio], Dimer, Quantum yield, General Chemistry, 010402 general chemistry, Ligand (biochemistry), 01 natural sciences, Oxytocin receptor, Fluorescence, 0104 chemical sciences, [SDV] Life Sciences [q-bio], Folding (chemistry), 03 medical and health sciences, chemistry.chemical_compound, chemistry, Biophysics, Receptor, 030304 developmental biology, G protein-coupled receptor
Abstract

International audience; Fluorescent probes are commonly used in studying G protein-coupled receptors in living cells; however their application to the whole animal receptor imaging is still challenging. To address this problem, we report the design and the synthesis of the first near-infrared emitting fluorogenic dimer with environment-sensitive folding. Due to the formation of non-fluorescent H-aggregates in an aqueous medium, the near-infrared fluorogenic dimer displays a strong turn-on response (up to 140-fold) in an apolar environment and exceptional brightness: 56% quantum yield and ≈444 000 M−1 cm−1 extinction coefficient. Grafted on a ligand of the oxytocin receptor, it allows the unprecedented background-free and target-specific imaging of the naturally expressed receptor in living mice.

Published
2020
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18. Radiosensitizing Pancreatic Cancer with PARP Inhibitor and Gemcitabine: An In Vivo and a Whole-Transcriptome Analysis after Proton or Photon Irradiation

Author

Georges Noël, Hélène Burckel, D. Jarnet, Anaïs Nicol, Waisse Waissi, Matthieu Jung, Marc Rousseau, Centre Léon Bérard [Lyon], Institut de Cancérologie de Strasbourg Europe (ICANS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Département de Radiobiologie, Hadronthérapie et Imagerie Moléculaire (DRHIM-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Gaillard, Brigitte, CRLCC Paul Strauss, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Cancer Research, medicine.medical_treatment, [SDV]Life Sciences [q-bio], pancreatic cancer, DNA repair, lcsh:RC254-282, Article, Olaparib, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, In vivo, Pancreatic cancer, medicine, proton therapy, transcriptome, radiotherapy, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Chemistry, gemcitabine, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Gemcitabine, 3. Good health, Radiation therapy, [SDV] Life Sciences [q-bio], 030104 developmental biology, PARP inhibitor, Oncology, 030220 oncology & carcinogenesis, Cancer research, Growth inhibition, Chemoradiotherapy, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract

Over the past few years, studies have focused on the development of targeted radiosensitizers such as poly(ADP-ribose) polymerase inhibitors. We performed an in vivo study and a whole-transcriptome analysis to determine whether PARP inhibition enhanced gemcitabine-based chemoradiosensitization of pancreatic cancer xenografts, combined with either proton or photon irradiation. NMRI mice bearing MIA PaCa-2 xenografts were treated with olaparib and/or gemcitabine and irradiated with 10 Gy photon or proton. First, a significant growth inhibition was obtained after 10 Gy proton irradiation compared to 10 Gy photon irradiation (p = 0.046). Moreover, the combination of olaparib, gemcitabine and proton therapy significantly sensitized tumor xenografts, compared to gemcitabine (p = 0.05), olaparib (p = 0.034) or proton therapy (p &lt, 0.0001) alone or to the association of olaparib, gemcitabine and radiotherapy (p = 0.024). Simultaneously, whole RNA sequencing profiling showed differentially expressed genes implicated in categories such as DNA repair, type I interferon signaling and cell cycle. Moreover, a large amount of lncRNA was dysregulated after proton therapy, gemcitabine and olaparib. This is the first study showing that addition of olaparib to gemcitabine-based chemoradiotherapy improved significantly local control in vivo, especially after proton therapy. RNA sequencing profiling analysis presented dynamic alteration of transcriptome after chemoradiation and identified a classifier of gemcitabine response.

Published
2021
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19. Proteo3Dnet: a web server for the integration of structural information with interactomics data

Author

Postic, Guillaume, Andreani, Jessica, Marcoux, Julien, Reys, Victor, Guerois, Raphaël, Rey, Julien, Mouton-Barbosa, Emmanuelle, Vandenbrouck, Yves, Cianferani, Sarah, Burlet-Schiltz, Odile, Labesse, Gilles, Tufféry, Pierre, Gaillard, Brigitte, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Français de Bioinformatique - UMS CNRS 3601 (IFB-CORE), Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre de Biochimie Structurale [Montpellier] (CBS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), BioSanté (UMR BioSanté), Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), UMS3601, Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM U1292, Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018)

Subjects
Proteomics, Ribosome Subunits, Small, Eukaryotic, Internet, AcademicSubjects/SCI00010, Protein Conformation, [SDV]Life Sciences [q-bio], Mass Spectrometry, [SDV] Life Sciences [q-bio], 14-3-3 Proteins, Web Server Issue, Protein Interaction Mapping, Protein Interaction Domains and Motifs, Protein Interaction Maps, Software
Abstract

Proteo3Dnet is a web server dedicated to the analysis of mass spectrometry interactomics experiments. Given a flat list of proteins, its aim is to organize it in terms of structural interactions to provide a clearer overview of the data. This is achieved using three means: (i) the search for interologs with resolved structure available in the protein data bank, including cross-species remote homology search, (ii) the search for possibly weaker interactions mediated through Short Linear Motifs as predicted by ELM—a unique feature of Proteo3Dnet, (iii) the search for protein–protein interactions physically validated in the BioGRID database. The server then compiles this information and returns a graph of the identified interactions and details about the different searches. The graph can be interactively explored to understand the way the core complexes identified could interact. It can also suggest undetected partners to the experimentalists, or specific cases of conditionally exclusive binding. The interest of Proteo3Dnet, previously demonstrated for the difficult cases of the proteasome and pragmin complexes data is, here, illustrated in the context of yeast precursors to the small ribosomal subunits and the smaller interactome of 14–3–3zeta frequent interactors. The Proteo3Dnet web server is accessible at http://bioserv.rpbs.univ-paris-diderot.fr/services/Proteo3Dnet/., Graphical Abstract Graphical AbstractProteo3Dnet: integrating structural information with interactomics data.

Published
2021
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20. Iron Stearate Structures: An Original Tool for Nanoparticles Design

Author

Jean-Marc Strub, Nathalie Parizel, Benoît Heinrich, Damien Mertz, Céline Kiefer, Benoit P. Pichon, Sarah Cianférani, Sylvie Begin-Colin, Geoffrey Cotin, Francis Perton, Jean-Marc Greneche, Institut de Physique et Chimie des Matériaux de Strasbourg (IPCMS), Université de Strasbourg (UNISTRA)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut des Molécules et Matériaux du Mans (IMMM), Le Mans Université (UM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie de Strasbourg, Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), RENARD (TGE Réseau National de RPE interdisciplinaire - 3443 ), Aix Marseille Université (AMU)-Université de Strasbourg (UNISTRA)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Université de Lille-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Grenoble Alpes (UGA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Université de Lille-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Grenoble Alpes (UGA), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and Gaillard, Brigitte

Subjects
[CHIM.INOR] Chemical Sciences/Inorganic chemistry, 02 engineering and technology, [CHIM.INOR]Chemical Sciences/Inorganic chemistry, 010402 general chemistry, 01 natural sciences, Chloride, Catalysis, Inorganic Chemistry, chemistry.chemical_compound, Stearate, Polymer chemistry, medicine, Lamellar structure, Carboxylate, Physical and Theoretical Chemistry, iron stearate synthesis mechanisms, Thermal decomposition, nucleation mechanism, iron oxide nanoparticles, 021001 nanoscience & nanotechnology, 0104 chemical sciences, iron stearate, chemistry, Chimie/Chimie inorganique, iron stearate composition and structure, Stearic acid, 0210 nano-technology, Iron oxide nanoparticles, medicine.drug
Abstract

International audience; Iron carboxylates are widely used as iron precursors in the thermal decomposition process or considered as in situ formed intermediate precursors. Their molecular and three-dimensional (3D)-structural nature has been shown to affect the shape, size, and composition of the resulting iron oxide nanoparticles (NPs). Among carboxylate precursors, stearates are particularly attractive because of their higher stability to aging and hydration and they are used as additives in many applications. Despite the huge interest of iron stearates, very few studies aimed up to now at deciphering their full metal-ligand structures and the mechanisms allowing us to achieve in a controlled manner the bottom-up NP formation. In this work, we have thus investigated the molecular structure and composition of two iron stearate precursors, synthesized by introducing either two (FeSt2) or three (FeSt3) stearate (St) chains. Interestingly, both iron stearates consist of lamellar structures with planes of iron polynuclear complexes (polycations) separated with stearate chains in all-trans conformation. The iron content in polycations was found very different between both iron stearates. Their detailed characterizations indicate that FeSt2 is mainly composed of [Fe3-(μ3-O)St6·xH2O]Cl, with no (or few) free stearate, whereas FeSt3 is a mixture of mainly [Fe7(μ3-O(H))6(μ2-OH)xSt12–2x]St with some [Fe3(μ3-O)St6·xH2O]St and free stearic acid. The formation of bigger polynuclear complexes with FeSt3 was related to higher hydrolysis and condensation rates within the iron(III) chloride solution compared to the iron(II) chloride solution. These data suggested a nucleation mechanism based on the condensation of polycation radicals generated by the catalytic departure of two stearate chains from an iron polycation-based molecule.

Published
2021
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21. How interdisciplinary research at the crossroad between socio-cultural anthropology, nutritional and physical activity physiology can help addressing the obesity epidemic

Author

Julie-Anne Nazare, Chantal Simon, Stéphane Blanc, Priscilla Duboz, Abdou Ka, Emmanuel Cohen, Audrey Bergouignan, Enguerran Macia, Pierre Bourdier, Gilles Boëtsch, Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Environnement, Santé, Sociétés (ESS), Centre National de la Recherche Scientifique (CNRS), Université Assane SECK de Ziguinchor (UASZ), 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), Éco-Anthropologie (EAE), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), University of the Witwatersrand [Johannesburg] (WITS), Division of Endocrinology metaboism and diabetes, Anschutz Health & Wellness Center, Gaillard, Brigitte, Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and Éco-Anthropologie (EA)

Subjects
Cultural anthropology, 030309 nutrition & dietetics, [SDV]Life Sciences [q-bio], Physical activity, Medicine (miscellaneous), Body weight, Fat mass, Pre-industrial populations, 03 medical and health sciences, Environmental health, medicine, 0303 health sciences, Nutrition and Dietetics, business.industry, Epidemiological transition, medicine.disease, Obesity, 3. Good health, [SDV] Life Sciences [q-bio], Metabolism, Metabolic control analysis, Anthropology, business
Abstract

International audience; Despite large global initiatives to manage obesity, its prevalence reaches pandemic levels. A potential reason is that the complex interactions between biological, behavioral, and socio-ecological factors and their respective role in the regulation of body weight (BW) and fat mass are still not well understood. Our view is that as long as physical activity (PA) is above a certain level, diet, genes and other factors play a role, but their contribution is less pronounced. However, PA levels below a certain threshold uncouple energy intake and energy needs, and impair metabolic control, thus promoting long term excessive BW and fat mass gain. Technological advances of the past centuries have most likely decreased PA below this threshold in our societies. The epidemiological transition model summarizes the changes in lifestyle, diet and PA that initiated the onset of obesity in Westernized countries. We believe that to identify which factors pose the greatest risk for excessive BW gain, scientists need to study lifestyles, diet, PA and the metabolism of pre-industrial populations, who are undergoing this transition, in a comprehensive metabolic, behavioral and socio-anthropological approach. Here we are presenting the related state-of-the-arts, current gaps in knowledge and future directions.

Published
2021
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22. Effect of simulated foregut digestion on the antioxidant capacity of plants naturally consumed by horses

Author

Diane Julien-David, Zélie Triaux, Odile Petit, Léa Briard, Eric Marchioni, Gaillard, Brigitte, Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur la Cognition Animale - UMR5169 (CRCA), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), 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), and 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)

Subjects
Oxygen radical absorbance capacity, TAC total antioxidant capacity, 030309 nutrition & dietetics, [SDV]Life Sciences [q-bio], Trolox equivalent antioxidant capacity, 2-azinobis-(3ethylbenzothiazoline-6-sulfonic acid) (ABTS), in vitro digestion. Manuscript category Non-ruminant, Context (language use), Crataegus, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, TEAC Trolox equivalent antioxidant capacity using 22-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), Food science, Medicinal plants, Salix cinerea, 0303 health sciences, ABTS, biology, Chemistry, Equine, TEAC Trolox equivalent antioxidant capacity using 2, food and beverages, Salix purpurea, biology.organism_classification, 3. Good health, [SDV] Life Sciences [q-bio], Herbal extract, 030221 ophthalmology & optometry, Animal Science and Zoology, ORAC oxygen radical absorbance capacity, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Herbal medicine has impacted veterinary medicine including equine practice. Many of the postulated health-promoting effects of medicinal plants are discussed in the context of their antioxidative properties, but different factors such as digestion can have an effect on the activities of compounds. The effect of simulated foregut digestion conditions on the antioxidant capacity of seven different plants commonly consumed by horses and/or present in their complementary diet was investigated. Plants included willow tree (Salix cinerea), purple willow (Salix purpurea), willow regrowth (new sprouts growing at the foot of willows (Salix cinerea), oak tree (Quercus spp.), meadowsweet (Filipendula ulmaria spp.), hawthorn (Crataegus), and blackthorn (Prunus spinosa). Aqueous extracts obtained from the bark and from the leaves were compared. Two methods, Oxygen Radical Absorbance Capacity (ORAC) and Trolox equivalent antioxidant capacity (TEAC) using 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays, were used to measure the total antioxidant capacity (TAC) of the extracts before and after the digestion process. The results showed that the TAC of all studied plant extracts decreased (P < 0.05) following the digestion process indicating that the active compounds present in the extracts were degraded. In fact, a decrease in TAC values of up to 80 % and 83 % was observed using TEAC and ORAC assays respectively. Such a drop in the TAC must be taken into account when considering the antioxidative efficiency of plants consumed by animals.

Published
2021
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23. Anti-hyperalgesic Properties of Menthol and Pulegone

Author

Charlet, Alexandre, Hilfiger, Louis, Triaux, Zélie, Marcic, Christophe, Emhemmed, Fathi, Darbon, Pascal, Marchioni, Eric, Petitjean, Hugues, Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Benephyt, and Gaillard, Brigitte

Subjects
Menthol, Inflammatory pain, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Pulegone, [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, rodent, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Pain, [CHIM.THER]Chemical Sciences/Medicinal Chemistry
Abstract

International audience; Context: Menthol, the main monoterpene found in Mentha piperita L (M. piperita). is known to modulate nociceptive threshold and is present in different curative preparations that reduces sensory hypersensitivities in pain conditions. While pulegone is a menthol-like monoterpene, only a limited number of studies focuses on its putative analgesic effects. Pulegone is the most abundant monoterpene presents in Calamintha nepeta (L.) Savi (C. nepeta), a Lamiaceae plant used in traditional medicine to alleviate rheumatic disorders, a chronic inflammatory disease.Objectives: Here, we analyzed the monoterpenes composition of extracts C. nepeta and M. piperita. We then compared the putative anti-hyperalgesic effects of the main monoterpenes found, menthol and pulegone, in acute inflammatory pain conditions.Methods: C. nepeta and M. piperita extracts were obtained through pressurized liquid extraction and analyzed by gas chromatography-mass spectrometry. The in vitro anti-inflammatory activity of menthol and pulegone were evaluated by measuring the secretion of the tumor necrosis factor from LPS-stimulated THP-1 cells. The in vivo anti-hyperalgesic effects of menthol and pulegone were tested on a rat model inflammatory pain model.Results: Pulegone and menthol are the most abundant monoterpene found in C. nepeta (49.41 %) and M. piperita (42.85 %) extracts, respectively. In vitro, both pulegone and menthol act as strong anti-inflammatory molecules, with EC50 values of 1.2±0.2 and 1.5±0.1 mM, respectively; and with a cytotoxicity with EC50 values of 6.6±0.3 and 3.5±0.2 mM, respectively. In vivo, 100 mg/kg pulegone exert a transient anti-hyperalgesic effect on both mechanical (pulegone: 274.25 ± 68.89 g, n=8; vehicle: 160.88±35.17 g, n=8, p

Published
2021

24. A class of valuable (pro-)activity-based protein profiling probes: application to the redox-active antiplasmodial agent, plasmodione

Author

Sarah Cianférani, Vrushali Khobragade, Christine Schaeffer-Reiss, Leandro Cotos, Maxime Donzel, Mourad Elhabiri, Elisabeth Davioud-Charvet, Bogdan Adam Cichocki, Stéphanie Blandin, Jean-Marc Strub, Gaillard, Brigitte, Laboratoire d'innovation moléculaire et applications (LIMA), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Réponse immunitaire et developpement chez les insectes (RIDI - UPR 9002), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Modèles Insectes de l'Immunité Innée (M3I), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011)

Subjects
quinone, [SDV]Life Sciences [q-bio], [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 010402 general chemistry, 01 natural sciences, Interactome, Article, electrophile, chemistry.chemical_compound, 3-benz(o)ylmenadione, [CHIM] Chemical Sciences, [CHIM]Chemical Sciences, Binding site, Mode of action, photoaffinity labelling, Heme, QD1-999, antimalarial, Photoaffinity labeling, 010405 organic chemistry, Activity-based proteomics, Combinatorial chemistry, photoredox, 0104 chemical sciences, 3. Good health, Quinone, [SDV] Life Sciences [q-bio], Chemistry, chemistry, Activity-based protein profiling, Chimie/Chimie thérapeutique, CuAAC, photoaffinity labeling, Protein ligand
Abstract

International audience; Plasmodione (PD) is a potent antimalarial redox-active drug acting at low nM range concentrations on different malaria parasite stages. In this study, in order to determine the precise PD protein interactome in parasites, we developed a class of (pro-)activity-based protein profiling probes (ABPP) as precursors of photoreactive benzophenonelike probes based on the skeleton of PD metabolites (PDO) generated in a cascade of redox reactions. Under UV-photoirradiation, we clearly demonstrate that benzylic oxidation of 3-benzylmenadione 11 produces the 3-benzoylmenadione probe 7, allowing investigation of the proof-of-concept of the ABPP strategy with 3-benzoylmenadiones 7-10. The synthesized 3-benzoylmenadiones, probe 7 with an alkyne group or probe 9 with-NO2 in para position of the benzoyl chain, were found to be the most efficient photoreactive and clickable probes. In the presence of various H-donor partners, the UV-irradiation of the photo-reactive ABPP probes generates different adducts, the expected 'benzophenone-like' adducts (pathway 1) in addition to 'benzoxanthone' adducts (via two other pathways, 2 and 3). Using both human and Plasmodium falciparum glutathione reductases three protein ligand binding sites were identified following photolabeling with probes 7 or 9. The photoreduction of 3-benzoylmenadiones (PDO and probe 9) promoting the formation of both the corresponding benzoxanthone and the derived enone could be replaced by the glutathione reductase-catalyzed reduction step. In particular, the electrophilic character of the benzoxanthone was evidenced by its ability to alkylate heme, as a relevant event supporting the antimalarial mode of action of PD. This work provides a proof-of-principle that (pro-)ABPP probes can generate benzophenonelike metabolites enabling optimized activity-based protein profiling conditions that will be instrumental to analyse the interactome of early-lead antiplasmodial 3-benzylmenadiones displaying an original and innovative mode of action.

Published
2021
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25. Catestatin in innate immunity and Cateslytin-derived peptides against superbugs

Author

Jean-Marc Strub, Sophie Hellé, Francis Schneider, Sylvette Chasserot-Golaz, Marie-Hélène Metz-Boutigue, Angela Mutschler, Francesco Scavello, Youssef Haikel, Sarah Cianférani, Gaillard, Brigitte, Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and BioMaterials and BioEngeneering - INSERM - UMR_S 1121

Subjects
0301 basic medicine, Staphylococcus aureus, Science, CD14, [SDV]Life Sciences [q-bio], Antimicrobial peptides, Diseases, Peptide, medicine.disease_cause, Biochemistry, Microbiology, Article, 03 medical and health sciences, Endocrinology, 0302 clinical medicine, Immune system, Anti-Infective Agents, [CHIM] Chemical Sciences, medicine, Animals, Humans, [CHIM]Chemical Sciences, chemistry.chemical_classification, Multidisciplinary, Innate immune system, Antimicrobial, Immunity, Innate, 3. Good health, [SDV] Life Sciences [q-bio], CTL, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Medicine, Cattle, Peptides
Abstract

Chromogranin A (CgA) is the precursor of several antimicrobial peptides, such as Catestatin (Cts, bovine CgA344-364), initially described as a potent inhibitor of catecholamines. This peptide displays direct antimicrobial activities and contributes to immune system regulation. The aim of the present study is to investigate a designed peptide based on Cts to fight infections against superbugs and more particularly Staphylococcus aureus. In addition to Cateslytin (Ctl, bovine CgA344-358), the active domain of Catestatin, several peptides including dimers, D-isomer and the new designed peptide DOPA-K-DOPA-K-DOPA-TLRGGE-RSMRLSFRARGYGFR (Dopa5T-Ctl) were prepared and tested. Cateslytin is resistant to bacterial degradation and does not induce bacterial resistance. The interaction of Catestatin with immune dermal cells (dendritic cells DC1a, dermal macrophages CD14 and macrophages) was analyzed by using confocal microscopy and cytokine release assay. The dimers and D-isomer of Ctl were tested against a large variety of bacteria showing the potent antibacterial activity of the D-isomer. The peptide Dopa5T-Ctl is able to induce the self-killing of S. aureus after release of Ctl by the endoprotease Glu-C produced by this pathogen. It permits localized on-demand delivery of the antimicrobial drug directly at the infectious site.

Published
2021
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26. Are All Conservation Measures for Endangered Species Legitimate? Lines of Thinking With the European Hamster

Author

Florian Kletty, Caroline Habold, Marie Pelé, Fabrice Capber, Gaillard, Brigitte, Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), ETHICS EA 7446, Lille Catholic University, Lille, Hauts-de-France, France, Clinique vétérinaire Colmar, and Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDE] Environmental Sciences, 0106 biological sciences, population reinforcement, Population, lcsh:Evolution, Endangered species, environmental ethics, 010603 evolutionary biology, 01 natural sciences, Animal monitoring, European hamster, lcsh:QH540-549.5, Urbanization, lcsh:QH359-425, education, Environmental planning, Ecology, Evolution, Behavior and Systematics, agriculture, education.field_of_study, Ecology, biology, business.industry, conservation measures, 04 agricultural and veterinary sciences, 15. Life on land, biology.organism_classification, Geography, Habitat, Agriculture, [SDE]Environmental Sciences, animal ethics, 040103 agronomy & agriculture, Animal ethics, 0401 agriculture, forestry, and fisheries, animal monitoring, lcsh:Ecology, business
Abstract

When dealing with the protection of an endangered species, it appears more and more important to address the ethical limits and the societal perception of the implemented conservation measures. This will be illustrated here through the example of conservation programs of the European hamster (Cricetus cricetus) in France. The main threats for this critically endangered rodent are the impoverishment and fragmentation of its habitat due to recent changes in agricultural practices and urbanization. Thus, the status of this species changed from harmful to endangered in only a few decades. This must lead to acceptance of the species by citizens and especially farmers paid to destroy this species until the 1990s while nowadays to protect it. To stem the decline, several measures have been taken through the last 20 years including population reinforcement, wild animal tracking, and implementation of suitable habitats. One can, therefore, discuss the efficiency of these measures and their integration in the entire socio-ecosystem. Population reinforcement and the questions that can arise from it will first be addressed. Secondly, in situ animal monitoring and implications of the methods used will be discussed. Third, we will deal with agricultural practices favorable to the species. Finally, we will highlight the links between European hamster conservation measures and wider problematics.

Published
2020
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27. Effects of topical corticosteroids and lidocaine on Borrelia burgdorferi sensu lato in mouse skin: potential impact to human clinical trials

Author

Lefeuvre, Bastien, Cantero, Paola, Ehret-Sabatier, Laurence, Lenormand, Cedric, Barthel, Cathy, Po, Chrystelle, Parveen, Nikhat, Grillon, Antoine, Jaulhac, Benoit, Boulanger, Nathalie, Virulence bactérienne précoce : fonctions cellulaires et contrôle de l'infection aiguë et subaiguë, Université de Strasbourg (UNISTRA), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Rutgers New Jersey Medical School (NJMS), Rutgers University System (Rutgers), Gaillard, Brigitte, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Les Hôpitaux Universitaires de Strasbourg (HUS), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and ANR-16-CE17-0003,DIABOLYC,Diagnostic cutané de la borréliose de Lyme tardive(2016)

Subjects
Lyme Disease, Bacteria, [SDV]Life Sciences [q-bio], Infectious-disease diagnostics, lcsh:R, Aucun, Lidocaine, lcsh:Medicine, Diseases, bacterial infections and mycoses, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Microbiology, Article, [SDV] Life Sciences [q-bio], Mice, Borrelia burgdorferi Group, Adrenal Cortex Hormones, Borrelia burgdorferi, Animals, Infectious diseases, lcsh:Q, lcsh:Science, ComputingMilieux_MISCELLANEOUS, Skin
Abstract

International audience; Lyme borreliosis is the most prevalent vector-borne disease in northern hemisphere. Borrelia burgdorferi sensu lato spirochetes are transmitted by Ixodes species ticks. During a blood meal, these spirochetes are inoculated into the skin where they multiply and often spread to various target organs: disseminated skin sites, the central nervous system, the heart and large joints. The usual diagnosis of this disease relies on serological tests. However, in patients presenting persistent clinical manifestations, this indirect diagnosis is not capable of detecting an active infection. If the serological tests are positive, it only proves that exposure of an individual to Lyme spirochetes had occurred. Although culture and quantitative PCR detect active infection, currently used tests are not sensitive enough for wide-ranging applications. Animal models have shown that B. burgdorferi persists in the skin. We present here our targeted proteomics results using infected mouse skin biopsies that facilitate detection of this pathogen. We have employed several novel approaches in this study. First, the effect of lidocaine, a local anesthetic used for human skin biopsy, on B. burgdorferi presence was measured. We further determined the impact of topical corticosteroids to reactivate Borrelia locally in the skin. This local immunosuppressive compound helps follow-up detection of spirochetes by proteomic analysis of Borrelia present in the skin. This approach could be developed as a novel diagnostic test for active Lyme borreliosis in patients presenting disseminated persistent infection. Although our results using topical corticosteroids in mice are highly promising for recovery of spirochetes, further optimization will be needed to translate this strategy for diagnosis of Lyme disease in patients.

Published
2020
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28. Specific shifts in the endocannabinoid system in hibernating brown bears

Author

Boyer, Christian, Cussonneau, Laura, Brun, Charlotte, Deval, Christiane, Pais de Barros, Jean-Paul, Chanon, Stéphanie, Bernoud-Hubac, Nathalie, Daira, Patricia, Evans, Alina L., Arnemo, Jon M., Swenson, Jon E., Gauquelin-Koch, Guillemette, Simon, Chantal, Blanc, Stéphane, Combaret, Lydie, Bertile, Fabrice, Lefai, Etienne, Unité de Nutrition Humaine (UNH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-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), Laboratoire de Mécanique des Contacts et des Structures [Villeurbanne] (LaMCoS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Institut Multidisciplinaire de Biochimie des Lipides (IMBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Covalab-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Inland Norway University of Applied Sciences - Høgskolen i Innlandet, Norwegian University of Life Sciences (NMBU), Centre National d’Études Spatiales [Paris] (CNES), Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Centre National D'etudes SpatialesiSITE Challenge 3 Mobility program (UCA) Centre National de la Recherche Scientifique (CNRS)Strasbourg University (H2E project, MyoBears project of the PEPS ExoMod program)French Proteomic Infrastructure (ProFI) ANR-10-INSB-08-03 MESRI INRAE Clermont Metropole Swedish Environmental Protection Agency Norwegian Environment Agency Austrian Science Fund (FWF) Swedish Association for Hunting and Wildlife Management, ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), Gaillard, Brigitte, Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation - - METABOHUB2011 - ANR-11-INBS-0010 - INBS - VALID, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)

Subjects
hal-03054587, Endocannabinoid system, N-oleoylethanolamide, Research, Lipidomic, Anandamide, 2-arachidonoylglycerol, Docosahexaenoic acid, Metabolism, Hibernation, Brown bear, [SDV.BA.ZV]Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, [SDV.BA.ZV] Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, lipids (amino acids, peptides, and proteins), Cannabinoid receptor 1, Cannabinoid receptor 2, Zoology, VDP::Matematikk og Naturvitenskap: 400::Zoologiske og botaniske fag: 480
Abstract

In small hibernators, global downregulation of the endocannabinoid system (ECS), which is involved in modulating neuronal signaling, feeding behavior, energy metabolism, and circannual rhythms, has been reported to possibly drive physiological adaptation to the hibernating state. In hibernating brown bears (Ursus arctos), we hypothesized that beyond an overall suppression of the ECS, seasonal shift in endocannabinoids compounds could be linked to bear’s peculiar features that include hibernation without arousal episodes and capacity to react to external disturbance. We explored circulating lipids in serum and the ECS in plasma and metabolically active tissues in free-ranging subadult Scandinavian brown bears when both active and hibernating. In winter bear serum, in addition to a 2-fold increase in total fatty acid concentration, we found significant changes in relative proportions of circulating fatty acids, such as a 2-fold increase in docosahexaenoic acid C22:6 n-3 and a decrease in arachidonic acid C20:4 n-6. In adipose and muscle tissues of hibernating bears, we found significant lower concentrations of 2-arachidonoylglycerol (2-AG), a major ligand of cannabinoid receptors 1 (CB1) and 2 (CB2). Lower mRNA level for genes encoding CB1 and CB2 were also found in winter muscle and adipose tissue, respectively. The observed reduction in ECS tone may promote fatty acid mobilization from body fat stores, and favor carbohydrate metabolism in skeletal muscle of hibernating bears. Additionally, high circulating level of the endocannabinoid-like compound N-oleoylethanolamide (OEA) in winter could favor lipolysis and fatty acid oxidation in peripheral tissues. We also speculated on a role of OEA in the conservation of an anorexigenic signal and in the maintenance of torpor during hibernation, while sustaining the capacity of bears to sense stimuli from the environment.

Published
2020
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29. Successful reproduction of Trachemys scripta in the Altrhein of Kehl (Germany) and simultaneous increase in population estimate

Author

Carsten Schradin, Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and Gaillard, Brigitte

Subjects
0106 biological sciences, [SDE] Environmental Sciences, education.field_of_study, media_common.quotation_subject, Population, 010607 zoology, Introduced species, 01 natural sciences, Invasive species, Fishery, Population estimate, Geography, Trachemys scripta, [SDE]Environmental Sciences, media_common.cataloged_instance, Animal Science and Zoology, 14. Life underwater, European union, Reproduction, education, Hatchling, Ecology, Evolution, Behavior and Systematics, media_common
Abstract

International audience; The European Union categorises pond sliders (Trachemys scripta) as invasive species for which all member countries have to develop an action plan. To date it has been assumed that the climate in Germany is too cold for T. scripta to survive for long or to reproduce. Data collected annually from 2016 to 2020 showed that the population of exotic pond turtles in an oxbow lake (Althrein of Kehl, Germany) did not decrease but increased. In addition, the diversity of species released was found to be high, five other exotic species in addition to T. scripta were observed. The population of T. scripta in particular appeared to be increasing, with no indication of high mortality due to cold winters and apparently regular successful reproduction (hatchlings observed in four out of five study years and caught in two years). The current action plan in Germany for T. scripta will have to change if potential negative impacts are to be avoided. Other west and central European countries might also have to modify their action plans accordingly.

Published
2020

30. Solvent extraction fractionation of manganese, cobalt, nickel and lithium using ionic liquids and deep eutectic solvents

Author

Arthur Braun, Guillaume Zante, Rémi Barillon, Abderrazak Masmoudi, Maria Boltoeva, Dominique Trébouet, Département Recherches Subatomiques (DRS-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Gaillard, Brigitte

Subjects
Inorganic chemistry, chemistry.chemical_element, 02 engineering and technology, Manganese, 010501 environmental sciences, 01 natural sciences, Diluent, Chloride, [PHYS.PHYS.PHYS-CHEM-PH] Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph], 020501 mining & metallurgy, chemistry.chemical_compound, medicine, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences, Mechanical Engineering, Extraction (chemistry), General Chemistry, Geotechnical Engineering and Engineering Geology, 6. Clean water, Nickel, 0205 materials engineering, chemistry, Control and Systems Engineering, Ionic liquid, Lithium, [PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph], Cobalt, medicine.drug
Abstract

The recycling of spent lithium-ion batteries remains a challenging task due to the complexity of the leach liquors, which contains several metals in acidic solution. The recovery of valuable metals, viz. Co, Li, Mn, Ni, is also difficult due to the similar chemical behavior of the divalent metal ions. Solvent extraction is mainly used for the separation of these metals, but the conventional extractants used in combination with molecular diluents usually lack of selectivity. We report a new solvent extraction system based on N,N,N',N'-Tetra-n-octyldiglycolamide (TODGA) diluted in the room temperature hydrophobic ionic liquid 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide. Up to 99% of manganese can be extracted in one step with separation factors in the range 40–60 for Mn/Co separation and higher than 200 for the other metals. The mechanism of extraction was detailed. Cobalt separation was done using the ionic liquid tri-hexyltetradecylphosphonium chloride. More than 90% of cobalt can be extracted with very high separation factors. Nickel and lithium separation was carried out by deep eutectic solvents (DESs) based on lidocaine and carboxylic acids. The use of a DES made of decanoic acid and lidocaine shows a high extraction efficiency for nickel while lithium is left in solution.

Published
2020

31. Exploration of natural phosphatidylcholine sources from six beans by UHPLC-Q-HRMS

Author

Yang, Fu, Zhang, Minghao, Li, Zhou, Liu , Jikai, Marchioni, Eric, Gaillard, Brigitte, South-Central University for Nationalities, Institut Pluridisciplinaire Hubert Curien (IPHC), and Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[CHIM] Chemical Sciences, [CHIM]Chemical Sciences, food and beverages
Abstract

International audience; BACKGROUND: Bean is a rich source of phosphatidylcholine (PC). This study aims to explore natural PC sources rich in polyunsaturated fatty acid (PUFA) with nutritional interest. PCs from six beans were purified (purity > 98.2%) by thin layer chromatography, and subsequently identified by UHPLC-Q-Exactive Orbitrap/MS.RESULTS: Results showed that chickpea and soybean contained the highest quantity of PC among the six beans, making up 50.0 mg/g and 34.0 mg/g, respectively. Gas chromatographic analysis showed that soybean fatty acids contained high proportion of polyunsaturated fatty acid (58.78%), and chickpea contained high proportion of DHA (22:6, 2.73%). A total of 49 molecular species were identified by UHPLC-Q-Exactive Orbitrap/MS. (18:2-18:2)PC was predominant in soybean, red bean, red kidney bean and white kidney bean. (16:0-18:1)PC was the major species of chickpea PC and many plasmanyl-PC species and DHA (22:6)-PC were identified. The Principal Component Analysis (PCA) analysis and hierarchical cluster analysis indicated that the molecular profiles of chickpea PC were significantly different compared to other beans studied.CONCLUSION: The findings suggest that chickpea appears to be an interesting plant source of DHA and ether lipids for dietary supplement.Keywords: Bean PC, UHPLC-Q-Exactive Orbitrap/MS, Molecular species, Identification, PCA

Published
2020

32. F autoradiography with the Mimosa-28: Characterisation and Application

Author

Truong, Pham Nguyen, Marchand, Patrice, Finck, Christian, Boisson, Frédéric, Boisson, David, Brasse, David, Laquerriere, Patrice, Gaillard, Brigitte, Institut Pluridisciplinaire Hubert Curien (IPHC), and Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[PHYS.PHYS.PHYS-BIO-PH] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], CMOS APS, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], brain, Autoradiography, fluorine 18
Abstract

International audience; Autoradiography is a technique used to record the spatial distribution of a radiotracer into an ex-vivo tissue slice. Within the section, the radioactive molecules emit charged particles from specific binding sites. These particles pass through the tissue before being detected by a sensor. Autoradiography gives the distribution of a radioactive molecule with a spatial resolution of approximately one hundred microns. In this work, we investigated the feasibility of autoradiography with a CMOS-APS sensor using radioactive isotope 18 F. This sensor works in digital mode by collecting charges. It presents a linear response with isotope 18 F for activity between 1 kBq and 1 MBq. The detection efficiency is 44,0 ± 0,5% for this range of activity with a spatial resolution of 144 ± 3 µm by using the absorber edge method. The Mimosa-28 sensor performs autoradiography imaging with a rose leaf and a mouse brain section which has a thickness of 50 µm and an activity of 4 kBq in the slice.

Published
2020

33. Molecular determinants of MED1 interaction with the DNA bound VDR–RXR heterodimer

Author

Anna Y. Belorusova, Maxime Bourguet, Bruno Kieffer, Sandra Chalhoub, Natacha Rochel, Sarah Cianférani, Steve Hessmann, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Gaillard, Brigitte, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), and Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
AcademicSubjects/SCI00010, [SDV]Life Sciences [q-bio], Protein domain, Aucun, Plasma protein binding, Retinoid X receptor, Biology, Ligands, Calcitriol receptor, MED1, Mediator Complex Subunit 1, 03 medical and health sciences, Mediator, Protein Domains, Structural Biology, Coactivator, Genetics, Humans, 030304 developmental biology, 0303 health sciences, Retinoid X Receptor alpha, 030302 biochemistry & molecular biology, hal-02962412, DNA, Cell biology, [SDV] Life Sciences [q-bio], Nuclear receptor, Receptors, Calcitriol, Protein Multimerization, Protein Binding
Abstract

The MED1 subunit of the Mediator complex is an essential coactivator of nuclear receptor-mediated transcriptional activation. While structural requirements for ligand-dependent binding of classical coactivator motifs of MED1 to numerous nuclear receptor ligand-binding domains have been fully elucidated, the recognition of the full-length or truncated coactivator by full nuclear receptor complexes remain unknown. Here we present structural details of the interaction between a large part of MED1 comprising its structured N-terminal and the flexible receptor-interacting domains and the mutual heterodimer of the vitamin D receptor (VDR) and the retinoid X receptor (RXR) bound to their cognate DNA response element. Using a combination of structural and biophysical methods we show that the ligand-dependent interaction between VDR and the second coactivator motif of MED1 is crucial for complex formation and we identify additional, previously unseen, interaction details. In particular, we identified RXR regions involved in the interaction with the structured N-terminal domain of MED1, as well as VDR regions outside the classical coactivator binding cleft affected by coactivator recruitment. These findings highlight important roles of each receptor within the heterodimer in selective recognition of MED1 and contribute to our understanding of the nuclear receptor-coregulator complexes.

Published
2020
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34. Growth and differentiation factor 15 is secreted by skeletal muscle during exercise and promotes lipolysis in humans

Author

Julie Vion, Dominique Larrouy, Virginie Bourlier, Stéphane Blanc, I. Harant, Claire Laurens, Sylvie Caspar-Bauguil, Coralie Fontaine, Dominique Langin, Claire Thalamas, Pauline Maes, Marie Adeline Marques, Nathalie Viguerie, Isabelle de Glisezinski, Deborah Carper, Benjamin Lair, Emilie Montastier, Cedric Moro, Jean Louis Grolleau, Donal J. O’Gorman, Enda Murphy, Geneviève Tavernier, Fabrice Bertile, Anne Bouloumié, Nathalie Boulet, Anisha Parmar, Gaillard, Brigitte, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation clinique de Toulouse (CIC 1436), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Dublin City University [Dublin] (DCU), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut de médecine moléculaire de Rangueil (I2MR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Dublin City University (DCU), Ireland's university of Enterprise, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Adult, Male, [SDE] Environmental Sciences, medicine.medical_specialty, Growth Differentiation Factor 15, Lipolysis, Adipose tissue, Stimulation, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Myokine, medicine, Humans, Muscle, Skeletal, Exercise, Muscle biopsy, medicine.diagnostic_test, Myogenesis, Chemistry, Skeletal muscle, General Medicine, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDE]Environmental Sciences, GDF15, Research Article
Abstract

International audience; We hypothesized that skeletal muscle contraction produces a cellular stress signal, triggering adipose tissue lipolysis to sustain fuel availability during exercise. The present study aimed at identifying exercise-regulated myokines, also known as exerkines, able to promote lipolysis. Human primary myotubes from lean healthy volunteers were submitted to electrical pulse stimulation (EPS) to mimic either acute intense or chronic moderate exercise. Conditioned media (CM) experiments with human adipocytes were performed. CM and human plasma samples were analyzed using unbiased proteomic screening and/or ELISA. Real-time qPCR was performed in cultured myotubes and muscle biopsy samples. CM from both acute intense and chronic moderate exercise increased basal lipolysis in human adipocytes. Growth and differentiation factor 15 (GDF15) gene expression and secretion increased rapidly upon skeletal muscle contraction. GDF15 protein was upregulated in CM from both acute and chronic exercise–stimulated myotubes. We further showed that physiological concentrations of recombinant GDF15 protein increased lipolysis in human adipose tissue, while blocking GDF15 with a neutralizing antibody abrogated EPS CM-mediated lipolysis. We herein provide the first evidence to our knowledge that GDF15 is a potentially novel exerkine produced by skeletal muscle contraction and able to target human adipose tissue to promote lipolysis.

Published
2020
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35. Seasonal variation in telomere dynamics in African striped mice

Author

Criscuolo, Francois, Pillay, Neville, Zahn, Sandrine, Schradin, Carsten, Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), University of the Witwatersrand [Johannesburg] (WITS), and Gaillard, Brigitte

Subjects
[SDE] Environmental Sciences, seasonal variation, mice, age, fungi, [SDE]Environmental Sciences, telomere length, telomere lengthening
Abstract

International audience; Telomere shortening has been used as an indicator of aging and is believed to accelerate under harsh environmental conditions. This can be attributed to the fact that telomere shortening has often been regarded as non-reversible and negatively impacting fitness. However, studies of laboratory mice indicate that they may be able to repair telomere loss to recover from environmental harshness, as indicated by recent studies in hibernating rodents. We studied seasonal variation in telomere dynamics in African striped mice (Rhabdomys pumilio) living in a highly seasonal environment. In our annual species, individuals born in the moist spring (high food availability) need to survive the harsh dry summer (low food availability) to be able to reproduce in the following spring. We studied the effect of the harsh dry vs. the benign moist season on telomere dynamics. We also tested whether telomere length and changes in telomere length were associated with the probability that individuals disappeared form the population during the dry season. Male but not female stripped mice showed age-related telomere erosion. Telomeres were longer at the beginning of the dry season compared to the rest of the year. Telomeres increased significantly in length during the moist season. Neither telomere length at the onset of the dry season nor telomere loss over the dry season predicted whether or not individuals disappeared. In conclusion, our data suggest that seasonal attrition and restoring of telomeres also occurs in non-hibernating wild rodents living in hot food restricted environments

Published
2020

36. Confusion Effect

Author

Schradin, Carsten, Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Gaillard, Brigitte

Subjects
[SDE] Environmental Sciences, [SDE]Environmental Sciences, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019

37. Promoting healthspan and lifespan with caloric restriction in primates

Author

Stéphane Blanc, Marc Dhenain, Fabien Pifferi, Jean-Luc Picq, Jérémy Terrien, Fabienne Aujard, Martine Perret, Jacques Epelbaum, Mécanismes Adaptatifs et Evolution (MECADEV), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Psychopathologie et Neuropsychologie (LPN), Université Paris 8 Vincennes-Saint-Denis (UP8), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), CEA [Fontenay-aux-Roses] (UGRA / SETA), Centre de Psychiatrie et Neurosciences (U894), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Mécanismes adaptatifs : des organismes aux communautés (MECADEV), Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN), Mécanismes adaptatifs : des organismes aux communautés (MAOAC), Muséum national d'Histoire naturelle (MNHN)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Service MIRCEN (MIRCEN), Institut de Biologie François JACOB (JACOB), 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 Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and Gaillard, Brigitte

Subjects
Primates, [SDE] Environmental Sciences, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Longevity, MEDLINE, Medicine (miscellaneous), Kaplan-Meier Estimate, Bioinformatics, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Mice, 0302 clinical medicine, Medicine, Animals, Behavioral interventions, Adverse effect, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, media_common, Caloric Restriction, 0303 health sciences, business.industry, Comment, Caloric theory, 3. Good health, [SDE]Environmental Sciences, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], General Agricultural and Biological Sciences, business, 030217 neurology & neurosurgery
Abstract

Recent data confirmed the efficiency of caloric restriction for promoting both healthspan and lifespan in primates, but also revealed potential adverse effects at the central level. This paper proposes perspectives and future directions to counterbalance potential adverse effects. Efforts should be made in combining nutrition-based clinical protocols with therapeutic and/or behavioral interventions to aim for synergetic effects, and therefore delay the onset of age-related diseases without adverse effects., Fabien Pifferi et al. discuss the latest research in using caloric restriction for promoting healthspan and lifespan in primates. Their Comment touches on their previous study, addressing how to combine nutrition-based clinical protocols with interventions to delay the onset of age-related diseases.

Published
2019
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38. Lipidomics Reveals Seasonal Shifts in a Large-Bodied Hibernator, the Brown Bear

Author

Giroud, Sylvain, Chery, Isabelle, Bertile, Fabrice, Bertrand-Michel, Justine, Tascher, Georg, Gauquelin-Koch, Guillemette, Arnemo, Jon, Swenson, Jon, Singh, Navinder, Lefai, Etienne, Evans, Alina, Simon, Chantal, Blanc, Stéphane, Gaillard, Brigitte, Research Institute of Wildlife Ecology, University of Veterinary Medicine, University of Veterinary Medicine, Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Plateau MetaToul-LIPIDOMIQUE = MetaToul-Lipidomics, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaboHUB-MetaToul, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-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 National d'Études Spatiales [Toulouse] (CNES), Department of Forestry and Wildlife Management, Hedmark University College, Norwegian Institute for Nature Research (NINA), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Norwegian Environmental Agency, Swedish Environmental Protection Agency, Polish-Norwegian Research Program [POL-NOR/198352/85/2013], Austrian Science Fund (FWF) [P27267-B25], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaToul-MetaboHUB, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), MetaToul-Lipidomic Core Facility, MetaboHUB, Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL)

Subjects
glycerophospholipids, [SDE] Environmental Sciences, Physiology, Physiology (medical), [SDE]Environmental Sciences, lipids (amino acids, peptides, and proteins), ceramide, hibernation, body temperature, metabolism, fatty acids, Original Research, sphingomyelin
Abstract

International audience; Prior to winter, heterotherms retain polyunsaturated fatty acids ("PUFA"), resulting in enhanced energy savings during hibernation, through deeper and longer torpor bouts. Hibernating bears exhibit a less dramatic reduction (2-5 degrees C) in body temperature, but lower their metabolism to a degree close to that of small hibernators. We determined the lipid composition, via lipidomics, in skeletal muscle and white adipose tissues ("WAT"), to assess lipid retention, and in blood plasma, to reflect lipid trafficking, of winter hibernating and summer active wild Scandinavian brown bears (Ursus arctos). We found that the proportion of monounsaturated fatty acids in muscle of bears was significantly higher during winter. During hibernation, omega-3 PUFAs were retained in WAT and short-length fatty acids were released into the plasma. The analysis of individual lipid moieties indicated significant changes of specific fatty acids, which are in line with the observed seasonal shift in the major lipid categories and can be involved in specific regulations of metabolisms. These results strongly suggest that the shift in lipid composition is well conserved among hibernators, independent of body mass and of the animals' body temperature.

Published
2019
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39. Synthesis and biological evaluation of 2.4 nm thiolate-protected gold nanoparticles conjugated to Cetuximab for targeting glioblastoma cancer cells via the EGFR

Author

Jean-Marc Strub, Mariel Donzeau, Nadja Groysbeck, Guy Zuber, Kassiogé Dembélé, Elisabete Cruz Da Silva, Maxime Lehmann, Audrey Stoessel, Sarah Cianférani, Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Bioimagerie et Pathologies (LBP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de Physique et Chimie des Matériaux de Strasbourg (IPCMS), Université de Strasbourg (UNISTRA)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Gaillard, Brigitte, Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Materials science, Gold nanoparticle, Aucun, Cetuximab, Metal Nanoparticles, Bioengineering, 02 engineering and technology, Conjugated system, 010402 general chemistry, 01 natural sciences, targeted cancer therapy, chemistry.chemical_compound, Drug Delivery Systems, Cell Line, Tumor, antibody, [CHIM] Chemical Sciences, medicine, Humans, [CHIM]Chemical Sciences, General Materials Science, Epidermal growth factor receptor, Electrical and Electronic Engineering, Particle Size, Polyacrylamide gel electrophoresis, biology, Mechanical Engineering, General Chemistry, 021001 nanoscience & nanotechnology, site-directed bioconjugation, 0104 chemical sciences, 3. Good health, Neoplasm Proteins, ErbB Receptors, chemistry, Mechanics of Materials, Colloidal gold, Cancer cell, biology.protein, TCEP, Biophysics, Gold, 0210 nano-technology, Glioblastoma, epidermal growth factor receptor, medicine.drug, Conjugate
Abstract

International audience; Therapeutic monoclonal antibodies benefit to patients and the conjugation to gold nanoparticles (AuNPs) might bring additional activities to these macromolecules. However, the behavior of the conjugate will largely depend on the bulkiness of the AuNP and small sizes are moreover preferable for diffusion. Water-soluble thiolate-protected AuNPs having diameters of 2–3 nm can be synthesized with narrow polydispersity and can selectively react with incoming organic thiols via a SN2-like mechanism. We therefore synthesized a mixed thionitrobenzoic acid- , thioaminobenzoic acid-monolayered AuNP of 2.4 nm in diameter and developed a site-selective conjugation strategy to link the AuNP to Cetuximab, an anti-epidermal growth factor receptor (EGFR) antibody used in clinic. The water-soluble 80 kDa AuNP was fully characterized and then reacted to the hinge area of Cetuximab, which was selectively reduced using mild concentration of TCEP. The conjugation proceeded smoothly and could be analyzed by polyacrylamide gel electrophoresis, indicating the formation of a 1:1 AuNP-IgG conjugate as the main product. When added to EGFR expressing glioblastoma cells, the AuNP-Cetuximab conjugate selectively bound to the cell surface receptor, inhibited EGFR autophosphorylation and entered into endosomes like Cetuximab. Altogether, we describe a simple and robust protocol for a site-directed conjugation of a thiolate-protected AuNP to Cetuximab, which could be easily monitored, thereby allowing to assess the quality of the product formation. The conjugated 2.4 nm AuNP did not majorly affect the biological behavior of Cetuximab, but provided it with the electronic properties of the AuNP. This offers the ability to detect the tagged antibody and opens application for targeted cancer radiotherapy.

Published
2019
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40. Huddling

Author

Schradin, Carsten, Ancel, André, and Gaillard, Brigitte

Subjects
[SDE] Environmental Sciences, ComputingMilieux_MISCELLANEOUS
Published
2019

41. Instrumentation Challenges in (S)PE(C)T Systems

Author

Frederic Boisson, David Brasse, Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Kuntner-Hannes, Claudia, Haemisch, York, and Gaillard, Brigitte

Subjects
[PHYS]Physics [physics], Modalities, medicine.diagnostic_test, business.industry, Computer science, Ultrasound, Magnetic resonance imaging, Computed tomography, [PHYS] Physics [physics], Positron emission tomography, medicine, Instrumentation (computer programming), Molecular imaging, business, Emission computed tomography, ComputingMilieux_MISCELLANEOUS, Biomedical engineering
Abstract

To date, molecular imaging is globally recognized as a powerful tool to assess in vivo anatomical and functional structures within a living subject [1, 2]. A wide range of imaging modalities based on different physical principles is available. Used individually, the value of modalities such as X-ray computed tomography (CT), single-photon emission computed tomography (SPECT), positron emission tomography (PET), magnetic resonance imaging (MRI), and ultrasound (US) is well recognized, both in clinical and preclinical fields [3–12]. Although established for decades, these modalities are still subject to much research, both on the development of new detection components and the design of new probes to artificially improve the natural contrast induced by physical processes.

Published
2019

42. Alternative Reproductive Tactics

Author

Schradin, Carsten, Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Gaillard, Brigitte

Subjects
[SDE] Environmental Sciences, [SDE]Environmental Sciences, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019
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43. Metabolomics of Small Intestine Neuroendocrine Tumors and Related Hepatic Metastases

Author

Philippe Bachellier, Izzie Jacques Namer, Stephanie Battini, Bernard Goichot, Valérie Hervieu, Alessio Imperiale, A. Ercument Cicek, Elisa Ruhland, Marie Pierrette Chenard, Colette Roche, Thomas Walter, Gilles Poncet, Pietro Addeo, Biophysique et médecine nucléaire Hôpitaux Universitaires de Strasbourg, Département de Radiobiologie, Hadronthérapie et Imagerie Moléculaire (DRHIM-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Tumeurs endocrines digestives : mécanismes de la tumorigenèse et de la progression tumorale, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle des Pathologies Digestives Hépatiques et Transplantation [Hôpital Hautepierre-Strasbourg], Hôpital de Hautepierre [Strasbourg], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital universitaire de Strasbourg, Bilkent University [Ankara], Département de Médecine Interne et Nutrition, CHU Strasbourg, Service de Chirurgie Générale, Hépatique, Endocrinienne et Transplantation, Les Hôpitaux Universitaires de Strasbourg (HUS), Université de Lyon, Service de Biophysique et Médecine Nucléaire, CHU Strasbourg-Université Louis Pasteur - Strasbourg I-Hôpital de Hautepierre [Strasbourg], Çiçek, A. Ercüment, Gaillard, Brigitte, and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, carcinoid, medicine.medical_specialty, Taurine, spectroscopy, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Neuroendocrine tumors, Creatine, Biochemistry, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Metabolomics, Internal medicine, medicine, Metabolome, Choline, Molecular Biology, Spectroscopy, Phosphocholine, medicine.disease, Carcinoid, metabolomics, Small intestine, NMR, [SDV] Life Sciences [q-bio], 030104 developmental biology, Endocrinology, medicine.anatomical_structure, chemistry, 030220 oncology & carcinogenesis, neuroendocrine tumors
Abstract

International audience; To assess the metabolomic fingerprint of small intestine neuroendocrine tumors (SI-NETs) and related hepatic metastases, and to investigate the influence of the hepatic environment on SI-NETs metabolome. Ninety-four tissue samples, including 46 SI-NETs, 18 hepatic NET metastases and 30 normal SI and liver samples, were analyzed using 1H-magic angle spinning (HRMAS) NMR nuclear magnetic resonance (NMR) spectroscopy. Twenty-seven metabolites were identified and quantified. Differences between primary NETs vs. normal SI and primary NETs vs. hepatic metastases, were assessed. Network analysis was performed according to several clinical and pathological features. Succinate, glutathion, taurine, myoinositol and glycerophosphocholine characterized NETs. Normal SI specimens showed higher levels of alanine, creatine, ethanolamine and aspartate. PLS-DA revealed a continuum-like distribution among normal SI, G1-SI-NETs and G2-SI-NETs. The G2-SI-NET distribution was closer and clearly separated from normal SI tissue. Lower concentration of glucose, serine and glycine, and increased levels of choline-containing compounds, taurine, lactate and alanine, were found in SI-NETs with more aggressive tumors. Higher abundance of acetate, succinate, choline, phosphocholine, taurine, lactate and aspartate discriminated liver metastases from normal hepatic parenchyma. Higher levels of alanine, ethanolamine, glycerophosphocholine and glucose was found in hepatic metastases than in primary SI-NETs. The present work gives for the first time a snapshot of the metabolomic characteristics of SI-NETs, suggesting the existence of complex metabolic reality, maybe characteristic of different tumor evolution.

Published
2019
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44. Acute toxicity of two pesticides (dursban, mancozeb) and their combined mixture on the terrestrial isopod Armadillidium vulgare (Oniscidea, Isopoda)

Author

Benmouhoub Hachemaoui, Karima, Moumene, Maya, Mouhoub Sayah, Chafika, Nait Mouloud, Mohamed, Djoudad Kadji, Hafsa, Yesguer, Saddek, Mahdeb, Mokrane, Mouzaia-Salhi, Aouba, Charfi, Faouzia, Montesanto, Giuseppe, Habold, Caroline, University of Bejaia (Ministère de l’enseignement supérieur et de la recherche scientifique), University of Bouira, INRA Oued Ghir Bejaia, Unité de biologie animale et de systématique évolutive, Université de Tunis El Manar (UTM), Department of Biology, University of Pisa, Pisa, Italy, Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Gaillard, Brigitte

Subjects
[SDE] Environmental Sciences, [SDE]Environmental Sciences
Abstract

International audience; Our study focused on evaluating an acute toxicity test, where woodlice (Armadillidium vulgare) which is the most abandoned in our region , were exposed to pesticides (dursban and mancozeb) most used in Algeria.The concentrations of the pesticids tested are 720 mg/kg,360 mg/kg,90 mg/kg, 45 mg/kg for dursban; 800 mg/kg, 400 mg/kg, 200 mg/kg,100 mg/kg for mancozeb and 720/800 mg/kg, 360/400 mg/kg,90/200 mg/kg, 45/100 mg/kg for the mixture of dursban and mancozeb.Our results show that dursban was highly toxic (69% mortality after 28 days of the test) compared to mancozeb (19.5% mortality). On the other hand, in the case of the mixture (dursban ± mancozeb), the toxicity was lower (63% mortality) compared to the dursban tested alone. Contamination of woodlice with dursban and a mixture of dursban and mancozeb revealed morphological effects such as alteration of the marsupial cavity and expulsion of eggs from the outside of this cavity. Dursban and the mixture of dursban and mancozeb are toxic to Armadillidium vulgare, but mancozeb alone is not toxic. Dursban should be banned because it is bad for soil fauna and therefore probably for biodiversity in general and even human health.

Published
2019

45. Limited oxidative stress favors resistance to skeletal muscle atrophy in hibernating brown bears (Ursus Arctos)

Author

Alina L. Evans, Blandine Chazarin, Anna Ziemianin, Stéphane Blanc, Guillemette Gauquelin-Koch, Jon M. Arnemo, Jon E. Swenson, Isabelle Chery, Emmanuelle Meugnier, Etienne Lefai, Chantal Simon, Emmanuelle Loizon, Fabrice Bertile, Bertile, F., Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre National d'Etudes Spatiales, Department of Forestry and Wildlife Management Inland Norway University of Applied Sciences, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Department of Wildlife, Fish and Environmental Studies, Swedish University of Agricultural Sciences (SLU), Faculty of Environmental Sciences and Natural Resource Management, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Gaillard, Brigitte, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016), Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Unité de Nutrition Humaine - Clermont Auvergne (UNH), and Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA)

Subjects
[SDE] Environmental Sciences, Hibernation, medicine.medical_specialty, Physiology, Clinical Biochemistry, brown bears, Oxidative phosphorylation, medicine.disease_cause, Biochemistry, CIRBP, NRF2, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Internal medicine, medicine, oxidative stress, skeletal muscle, hibernation, Molecular Biology, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Reactive oxygen species, lcsh:RM1-950, Skeletal muscle, Cell Biology, medicine.disease, Muscle atrophy, lcsh:Therapeutics. Pharmacology, Endocrinology, medicine.anatomical_structure, chemistry, cold response, [SDE]Environmental Sciences, medicine.symptom, 030217 neurology & neurosurgery, Oxidative stress, Autre (Sciences du Vivant)
Abstract

Oxidative stress, which is believed to promote muscle atrophy, has been reported to occur in a few hibernators. However, hibernating bears exhibit efficient energy savings and muscle protein sparing, despite long-term physical inactivity and fasting. We hypothesized that the regulation of the oxidant/antioxidant balance and oxidative stress could favor skeletal muscle maintenance in hibernating brown bears. We showed that increased expressions of cold-inducible proteins CIRBP and RBM3 could favor muscle mass maintenance and alleviate oxidative stress during hibernation. Downregulation of the subunits of the mitochondrial electron transfer chain complexes I, II, and III, and antioxidant enzymes, possibly due to the reduced mitochondrial content, indicated a possible reduction of the production of reactive oxygen species in the hibernating muscle. Concomitantly, the upregulation of cytosolic antioxidant systems, under the control of the transcription factor NRF2, and the maintenance of the GSH/GSSG ratio suggested that bear skeletal muscle is not under a significant oxidative insult during hibernation. Accordingly, lower levels of oxidative damage were recorded in hibernating bear skeletal muscles. These results identify mechanisms by which limited oxidative stress may underlie the resistance to skeletal muscle atrophy in hibernating brown bears. They may constitute therapeutic targets for the treatment of human muscle atrophy.

Published
2019
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46. Synthesis of a Novel Electrospun Polycaprolactone Scaffold Functionalized with Ibuprofen for Periodontal Regeneration: An In Vitro andIn Vivo Study

Author

Laetitia Keller, David-Nicolas Morand, Javier Aragón, Isaac Maximiliano Bugueno, Nadia Benkirane-Jessel, Henri Tenenbaum, Lionel Thomas, Silvia Irusta, Olivier Huck, Fareeha Batool, Regenerative NanoMedicine (UMR 1260), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de chirurgie dentaire - Strasbourg, Université de Strasbourg (UNISTRA), Département de Radiobiologie, Hadronthérapie et Imagerie Moléculaire (DRHIM-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Department of chemical engineering INA University of Zaragoza, Hopitaux universitaires de Strasbourg Pole de médecine et chirurgie bucco-dentaire, Gaillard, Brigitte, and Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Lipopolysaccharide, NSAIDs, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Cell, Integrin, 02 engineering and technology, lcsh:Technology, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, In vivo, medicine, General Materials Science, lcsh:Microscopy, periodontitis, membrane, ComputingMilieux_MISCELLANEOUS, lcsh:QC120-168.85, Periodontitis, [PHYS.PHYS.PHYS-BIO-PH] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], lcsh:QH201-278.5, biology, lcsh:T, Regeneration (biology), technology, industry, and agriculture, 030206 dentistry, 021001 nanoscience & nanotechnology, medicine.disease, In vitro, Cell biology, regeneration, GTR, medicine.anatomical_structure, chemistry, lcsh:TA1-2040, biology.protein, lcsh:Descriptive and experimental mechanics, lcsh:Electrical engineering. Electronics. Nuclear engineering, lcsh:Engineering (General). Civil engineering (General), 0210 nano-technology, Wound healing, lcsh:TK1-9971
Abstract

Ibuprofen (IBU) has been shown to improve periodontal treatment outcomes. The aim of this study was to develop a new anti-inflammatory scaffold by functionalizing an electrospun nanofibrous poly-ε-caprolactone membrane with IBU (IBU-PCL) and to evaluate its impact on periodontal inflammation, wound healing and regeneration in vitro and in vivo. IBU-PCL was synthesized through electrospinning. The effects of IBU-PCL on the proliferation and migration of epithelial cells (EC) and fibroblasts (FB) exposed to Porphyromonas gingivlais lipopolysaccharide (Pg-LPS) were evaluated through the AlamarBlue test and scratch assay, respectively. Anti-inflammatory and remodeling properties were investigated through Real time qPCR. Finally, the in vivo efficacy of the IBU-PCL membrane was assessed in an experimental periodontitis mouse model through histomorphometric analysis. The results showed that the anti-inflammatory effects of IBU on gingival cells were effectively amplified using the functionalized membrane. IBU-PCL reduced the proliferation and migration of cells challenged by Pg-LPS, as well as the expression of fibronectin-1, collagen-IV, integrin α3β1 and laminin-5. In vivo, the membranes significantly improved the clinical attachment and IBU-PCL also reduced inflammation-induced bone destruction. These data showed that the IBU-PCL membrane could efficiently and differentially control inflammatory and migratory gingival cell responses and potentially promote periodontal regeneration.

Published
2018
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47. Multi-OMICS analyses unveil STAT1 as a potential modifier gene in mevalonate kinase deficiency

Author

Carapito, Raphael, Carapito, Christine, Morlon, Aurore, Paul, Nicodème, Vaca Jacome, Alvaro Sebastian, Alsaleh, Ghada, Rolli, Véronique, Tahar, Ouria, Aouadi, Ismaïl, Rompais, Magali, Delalande, Francois, Pichot, Angélique, Georgel, Philippe, Messer, Laurent, Sibilia, Jean, Cianférani, Sarah, Van Dorsselaer, Alain, Bahram, Seiamak, Immuno-Rhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Functional Genomics and Cancer, Service de rhumatologie (Hôpitaux Civils de Colmar), Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Immunorhumathologie moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Gaillard, Brigitte, and Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Proteomics, Genes, Modifier, gene polymorphism, Gene Expression Profiling, Mutation, Missense, Middle Aged, Polymorphism, Single Nucleotide, Phenotype, STAT1 Transcription Factor, inflammation, [CHIM] Chemical Sciences, Humans, [CHIM]Chemical Sciences, Exome, Female, Mevalonate Kinase Deficiency, Basic and Translational Research, familial mediterranean fever
Abstract

International audience; Objectives The objective of the present study was to explain why two siblings carrying both the same homozygous pathogenic mutation for the autoinflammatory disease hyper IgD syndrome, show opposite phenotypes, that is, the first being asymptomatic, the second presenting all classical characteristics of the disease.Methods Where single omics (mainly exome) analysis fails to identify culprit genes/mutations in human complex diseases, multiomics analyses may provide solutions, although this has been seldom used in a clinical setting. Here we combine exome, transcriptome and proteome analyses to decipher at a molecular level, the phenotypic differences between the two siblings.Results This multiomics approach led to the identification of a single gene—STAT1—which harboured a rare missense variant and showed a significant overexpression of both mRNA and protein in the symptomatic versus the asymptomatic sister. This variant was shown to be of gain of function nature, involved in an increased activation of the Janus kinase/signal transducer and activator of transcription signalling (JAK/STAT) pathway, known to play a critical role in inflammatory diseases and for which specific biotherapies presently exist. Pathway analyses based on information from differentially expressed transcripts and proteins confirmed the central role of STAT1 in the proposed regulatory network leading to an increased inflammatory phenotype in the symptomatic sibling.Conclusions This study demonstrates the power of a multiomics approach to uncover potential clinically actionable targets for a personalised therapy. In more general terms, we provide a proteogenomics analysis pipeline that takes advantage of subject-specific genomic and transcriptomic information to improve protein identification and hence advance individualised medicine.This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

Published
2018
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48. Preclinical PET and SPECT Part 5

Author

R., Steven, Z., Andre, Kench, Peter, Boisson, Frederic, Parmar, Arvind, Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Australian Nuclear Science and Technology Organisation [Australie] (ANSTO), Magnus Dahlbom, and Gaillard, Brigitte

Subjects
[PHYS]Physics [physics], ComputingMilieux_MISCELLANEOUS, [PHYS] Physics [physics]
Abstract

International audience

Published
2017

49. Mutations in cytoplasmic dynein lead to a Huntington's disease-like defect in energy metabolism of brown and white adipose tissues

Author

Jose-Luis Gonzalez de Aguilar, Jean-Patrice Robin, Judith Eschbach, Frédérique René, Anissa Fergani, Yves Larmet, Birgit Schwalenstöcker, Luc Dupuis, Majid Hafezparast, Jean-Philippe Loeffler, Albert C. Ludolph, Joffrey Zoll, Hugues Oudart, Gaillard, Brigitte, Laboratoire de signalisation moléculaire et neurodégénerescence, Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale (INSERM), Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Departement physiologie et explorations fonctionnelles, CHU Strasbourg, University of Sussex, Department of neurology, Universität Ulm - Ulm University [Ulm, Allemagne], and Service de Neurologie

Subjects
[SDE] Environmental Sciences, Cytoplasmic Dyneins, Male, Huntingtin, Gene Expression, Adipose tissue, White adipose tissue, Brown adipose tissue, Mice, Norepinephrine, chemistry.chemical_compound, Adipose Tissue, Brown, Adipocyte, Huntingtin Protein, Reverse Transcriptase Polymerase Chain Reaction, Nuclear Proteins, Huntington's disease, Thermogenesis, Cell biology, Huntington Disease, medicine.anatomical_structure, Biochemistry, [SDE]Environmental Sciences, Molecular Medicine, Female, Adrenergic alpha-Agonists, Signal Transduction, Adipose Tissue, White, Lipolysis, Blotting, Western, Dynein, Nerve Tissue Proteins, macromolecular substances, Biology, 3T3-L1 Cells, medicine, Animals, Humans, Molecular Biology, Molecular motors, Lipid droplets, Mice, Mutant Strains, Oxidative Stress, chemistry, Mutation, Axoplasmic transport, Receptors, Adrenergic, beta-2, Energy Metabolism
Abstract

International audience; The molecular motor dynein is regulated by the huntingtin protein, and Huntington's disease (HD) mutations of huntingtin disrupt dynein motor activity. Besides abnormalities in the central nervous system, HD animal models develop prominent peripheral pathology, with defective brown tissue thermogenesis and dysfunctional white adipocytes, but whether this peripheral phenotype is recapitulated by dynein dysfunction is unknown. Here, we observed prominently increased adiposity in mice harboring the legs at odd angles (Loa/+) or the Cramping mutations (Cra/+) in the dynein heavy chain gene. In Cra/+ mice, hyperadiposity occurred in the absence of energy imbalance and was the result of impaired norepinephrine-stimulated lipolysis. A similar phenotype was observed in 3T3L1 adipocytes upon chemical inhibition of dynein showing that loss of functional dynein leads to impairment of lipolysis. Ex vivo, dynein mutant adipose tissue displayed increased reactive oxygen species production that was, at least partially, responsible for the decreased cellular responses to norepinephrine and subsequent defect in stimulated lipolysis. Dynein mutation also affected norepinephrine efficacy to elicit a thermogenic response and led to morphological abnormalities in brown adipose tissue and cold intolerance in dynein mutant mice. Interestingly, protein levels of huntingtin were decreased in dynein mutant adipose tissue. Collectively, our results provide genetic evidence that dynein plays a key role in lipid metabolism and thermogenesis through a modulation of oxidative stress elicited by norepinephrine. This peripheral phenotype of dynein mutant mice is similar to that observed in various animal models of HD, lending further support for a functional link between huntingtin and dynein.

Published
2011
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50. Proximate and ultimate mechanisms underlying immunosuppression during the incubation fast in female eiders: Roles of triiodothyronine and corticosterone

Author

Sophie Bourgeon, Thierry Raclot, Yvon Le Maho, Gaillard, Brigitte, Norwegian Institute for Nature Research (NINA), Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), and Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS)

Subjects
medicine.medical_specialty, medicine.medical_treatment, media_common.quotation_subject, Zoology, Biology, cost of reproduction, resource-limitation hypothesis, Birds, chemistry.chemical_compound, Endocrinology, Immunity, Corticosterone, Internal medicine, [SDV.BID.EVO] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], medicine, Animals, Acquired immunity, Incubation, media_common, Immunosuppression Therapy, Triiodothyronine, Natural selection, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Immunosuppression, Acquired immune system, trade-offs, chemistry, immunopathology-avoidance hypothesis, Female, Animal Science and Zoology, Reproduction
Abstract

International audience; Abstract: Available resources being limited, life-history theory predicts that natural selection favours the evolution of physiological mechanisms that ensure their optimal allocation between competing activities. Accordingly, to maximize their selective value, long-lived species face a trade-off between survival and reproduction. Immunity is hypothesized to share limited resources with other physiological functions and this may partly account for the fitness costs of reproduction. However, both ultimate and proximate factors underlying the observed trade-off between reproductive effort and immunocompetence remain poorly documented. Using female common eiders (Somateria mollissima) as a model, it was earlier shown that acquired immunity is negatively affected during the incubation fast, while its activation has a negative impact on females' fitness. The current paper reports data about hormone (corticosterone and triiodothyronine) manipulations we designed to shed more light onto both ultimate and proximate mechanisms contributing to explain immunosuppression in breeding female eiders. Corticosterone does not seem to be the main proximate factor for immunosuppression. Interestingly, the immunosuppressive effects of the tested hormones seem to be mediated by their negative effects on body mass. This lends support to the proposed link between the immune system and body fat reserves and is also in agreement with the resource-limitation hypothesis. It appears that the immnunopathology-avoidance hypothesis and the resource-limitation hypothesis are not mutually exclusive in breeding eiders. Further experiments are required to determine the relationship between body condition and immunocompetence during the incubation fast in long-lived birds.

Published
2009
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