1,047 results on '"Lille"'
Search Results
2. Application of cyclodextrins as second-sphere coordination ligands for gold recovery
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Eric Monflier, Anne Ponchel, Université de Lille, CNRS, Centrale Lille, ENSCL, Univ. Artois, UCCS Équipe Catalyse Supramoléculaire, Unité de Catalyse et Chimie du Solide (UCCS) - UMR 8181, Unité de Catalyse et Chimie du Solide - UMR 8181 (UCCS), and Université d'Artois (UA)-Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université d'Artois (UA)-Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
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Multidisciplinary ,Environmental chemistry ,Environmental sciences ,Pollution remediation ,[CHIM]Chemical Sciences ,General Physics and Astronomy ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology - Abstract
International audience; Supramolecular chemistry based on cyclodextrin receptors as second-sphere ligands contribute to developing non-covalent materials with synergistic functionalities. Herein, we comment on a recent investigation of this concept, describing selective gold recovery through a hierarchical host-guest assembly specifically built from β-CD.
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- 2023
3. Seeded free-electron laser driven by a compact laser plasma accelerator
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Marie Labat, Jurjen Couperus Cabadağ, Amin Ghaith, Arie Irman, Anthony Berlioux, Philippe Berteaud, Frédéric Blache, Stefan Bock, François Bouvet, Fabien Briquez, Yen-Yu Chang, Sébastien Corde, Alexander Debus, Carlos De Oliveira, Jean-Pierre Duval, Yannick Dietrich, Moussa El Ajjouri, Christoph Eisenmann, Julien Gautier, René Gebhardt, Simon Grams, Uwe Helbig, Christian Herbeaux, Nicolas Hubert, Charles Kitegi, Olena Kononenko, Michael Kuntzsch, Maxwell LaBerge, Stéphane Lê, Bruno Leluan, Alexandre Loulergue, Victor Malka, Fabrice Marteau, Manh Huy N. Guyen, Driss Oumbarek-Espinos, Richard Pausch, Damien Pereira, Thomas Püschel, Jean-Paul Ricaud, Patrick Rommeluere, Eléonore Roussel, Pascal Rousseau, Susanne Schöbel, Mourad Sebdaoui, Klaus Steiniger, Keihan Tavakoli, Cédric Thaury, Patrick Ufer, Mathieu Valléau, Marc Vandenberghe, José Vétéran, Ulrich Schramm, Marie-Emmanuelle Couprie, Synchrotron SOLEIL [SSOLEIL], Helmholtz-Zentrum Dresden-Rossendorf [HZDR], Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 [PhLAM], Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Laboratoire d'optique appliquée (LOA), École Nationale Supérieure de Techniques Avancées (ENSTA Paris)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Institute of Radiation Physics [Dresden], Weizmann Institute of Science [Rehovot, Israël], DYnamique des Systèmes COmplexes (DYSCO), Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 (PhLAM), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lille-Centre National de la Recherche Scientifique (CNRS), ANR-11-LABX-0007,CEMPI,Centre Européen pour les Mathématiques, la Physique et leurs Interactions(2011), ANR-19-CE30-0031,ULTRASYNC,Exploration et contrôle ULTRArapide de la dynamique des paquets d'électrons dans les sources de lumière SYNChrotron(2019), European Project: 340015,EC:FP7:ERC,ERC-2013-ADG,COXINEL(2014), European Project: 653782,H2020,H2020-INFRADEV-1-2014-1,EuPRAXIA(2015), European Project: 339128,EC:FP7:ERC,ERC-2013-ADG,X-FIVE(2014), European Project: M-PAC, European Project: 871124, and The University of Texas at Austin
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[PHYS]Physics [physics] ,seeded FEL driven by LPA beams ,[PHYS.PHYS.PHYS-PLASM-PH]Physics [physics]/Physics [physics]/Plasma Physics [physics.plasm-ph] ,[PHYS.PHYS.PHYS-ACC-PH]Physics [physics]/Physics [physics]/Accelerator Physics [physics.acc-ph] ,[SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic ,free electron laser ,laser plasma accelerator ,Atomic and Molecular Physics, and Optics ,Electronic, Optical and Magnetic Materials - Abstract
Free-electron lasers generate high-brilliance coherent radiation at wavelengths spanning from the infrared to the X-ray domains. The recent development of short-wavelength seeded free-electron lasers now allows for unprecedented levels of control on longitudinal coherence[1], opening new scientific avenues as ultra-fast dynamics on complex systems and X-ray nonlinear optics. While those devices rely on state-of-the-art large-scale accelerators, advancements on laser-plasma accelerators, which harness giga-volt-per-centimeter accelerating fields, showcase a promising technology as compact drivers for free-electron lasers. Using such miniaturized accelerators, exponential amplification of a shot-noise type of radiation in a self-amplified spontaneous emission configuration was recently achieved [2]. However, employing this compact approach for the delivery of temporally coherent pulses in a controlled manner remained a major challenge. Here, we present the experimental demonstration of a laser-plasma accelerator driven free-electron laser in a seeded configuration, where control over the radiation wavelength is accomplished. Furthermore, the appearance of interference fringes, resulting from the interaction between the phase-locked emitted radiation and the seed, confirms longitudinal coherence. Building on our scientific achievements, we anticipate a straightforward scaling to extreme-ultraviolet wavelengths, paving the way towards university-scale free-electron lasers, unique tools for a multitude of applications. [1] Meyer, M. FELs of europe: Whitebook on science with free electron lasers 8–19 (2016). [2] Wang, W. et al. Free-electron lasing at 27 nanometres based on a laser wakefield accelerator.
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- 2023
4. Pozzolanic activity of kaolins containing aluminum hydroxide
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Antoine Elimbi, Claudia Charlotte Tchamo Leussa, Chafika Djelal, Chantale Njiomou Djangang, Laurent Libessart, Laboratoire de Génie Civil et Géo-Environnement (LGCgE) - ULR 4515 (LGCgE), Université d'Artois (UA)-Université de Lille-Ecole nationale supérieure Mines-Télécom Lille Douai (IMT Lille Douai), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-JUNIA (JUNIA), Université d'Artois (UA), and Université catholique de Lille (UCL)-Université catholique de Lille (UCL)
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0301 basic medicine ,inorganic chemicals ,Pollution remediation ,chemistry.chemical_element ,lcsh:Medicine ,Mechanical properties ,complex mixtures ,Article ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,law ,Aluminium ,Pozzolanic activity ,lcsh:Science ,Gibbsite ,ComputingMilieux_MISCELLANEOUS ,Composites ,Cement ,Multidisciplinary ,lcsh:R ,[SPI.GCIV]Engineering Sciences [physics]/Civil Engineering ,Portland cement ,030104 developmental biology ,Compressive strength ,chemistry ,Chemical engineering ,Hydroxide ,lcsh:Q ,Cementitious ,030217 neurology & neurosurgery - Abstract
The addition of 10 wt% aluminum hydroxide to two crude kaolinitic clays, a commercial and a natural freshly mined one, has enhanced their pozzolanic activity, more substantially in the natural sample containing gibbsite. The obtained blends were used as replacement of 20 wt% of Portland cement in the formulations of pastes and mortars which exhibited significant decrease of setting time and increase of compressive strength from early age to 28 days. Also, SEM/EDX analyses showed very heterogeneous structures with hydrated phases identified from XRD. Specific interpretation of the role played by aluminum hydroxide revealed its aptitude to promote the formation of metastable hydrated phases (CAH10/C2AH8) at early age, which temporally inhibited the hydration of cement. This progressive transformation led to the formation of more stable hydrated phases such as C–A–S–H which favored the increase of mechanical strength of the specimens. The sequence of transformation reactions is fully obtained with limited aluminum hydroxide content in clays. Either added as synthetic or naturally occurring in clays, aluminum hydroxide has close role in the strengthening process of cement. Hence, kaolinitic clays that naturally contain gibbsite are suggested as suitable supplementary cementitious material for partial replacement of cement.
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- 2020
5. Influenza infection rewires energy metabolism and induces browning features in adipose cells and tissues
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Ayari, Asma, Rosa-Calatrava, Manuel, Lancel, Steve, Barthelemy, Johanna, Pizzorno, Andrés, Mayeuf-Louchart, Alicia, Baron, Morgane, Hot, David, Deruyter, Lucie, Soulard, Daphnée, Julien, Thomas, Faveeuw, Christelle, Molendi-Coste, Olivier, Dombrowicz, David, Sedano, Laura, Sencio, Valentin, Le Goffic, Ronan, Trottein, François, Wolowczuk, Isabelle, Noel, Anne-Laure, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Virologie et Immunologie Moléculaires (VIM (UR 0892)), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), The CPER-Région Hauts-de-France’s financial contribution to the acquisition of the Oroboros O2k-respirometer is acknowledged. This study was supported by the Centre National de la Recherche Scientifique (CNRS) and the Institut National de la Santé et de la Recherche Médicale (INSERM). AA received a grant from Lille University. I.W. and F.T. received a grant from CNRS., We appreciate valuable discussions with Drs. Kassem Makki and Sandra Weller, and advice and support from Drs. Jean-Claude Sirard and Jean Dubuisson, and from Sia Praline and Nor Snø. We thank Dr. Corinne Grangette for providing reagents needed for mouse preadipocyte and adipocyte culture and differentiation, Dr. Odile Poulain-Godefroy for the kind gift of human primary Preadipocytes, and Marie-Josée Ghoris for technical help. Jérôme Lecardonnel (INRA, UMR GABI, Jouy-en-Josas, France) and Marie-Hélène Gevaert (Laboratoire d’Histologie, Faculté de Médecine, Lille, France) are acknowledged for their expert technical assistance in, respectively, microarray hybridization (adipose cells) and WAT histology. We also thank Denis Ressnikoff and Elisabeth Erazzuriz (Centre Imagerie Quantitative Lyon Est (CIQLE), Université Lyon 1, Lyon, France) for their technical assistance in confocal and transmission electron microscopy. We thank Antonino Bongiovanni and Sophie Salomé-Desnoulez as well as Drs. Elizabeth Werkmeister, Nicolas Barois and Hélène Bauderlique of the BioImaging Center Lille (BICeL, Lille, France) for access to systems and expert advises on microscopy and flow cytometry. Dr. Cécile Lecoeur and Peggy Bouquet (Transcriptomics and Applied Genomics Group, Lille) are thanked for, respectively, advice on transcriptomic analyses, and technical assistance in microarray hybridization (adipose tissues). Institut Pasteur’s animal facility staff is also thanked for its assistance., Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-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)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS 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)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control [Virpath], Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD], and Virologie et Immunologie Moléculaires [VIM (UR 0892)]
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Male ,[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Adipose Tissue, White ,Thermogenesis ,Article ,Mice, Inbred C57BL ,Disease Models, Animal ,Mice ,Metabolism ,Adipose Tissue, Brown ,Orthomyxoviridae Infections ,lcsh:Biology (General) ,Influenza, Human ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Animals ,Humans ,Influenza virus ,Fat metabolism ,Energy Metabolism ,lcsh:QH301-705.5 - Abstract
Like all obligate intracellular pathogens, influenza A virus (IAV) reprograms host cell’s glucose and lipid metabolism to promote its own replication. However, the impact of influenza infection on white adipose tissue (WAT), a key tissue in the control of systemic energy homeostasis, has not been yet characterized. Here, we show that influenza infection induces alterations in whole-body glucose metabolism that persist long after the virus has been cleared. We report depot-specific changes in the WAT of IAV-infected mice, notably characterized by the appearance of thermogenic brown-like adipocytes within the subcutaneous fat depot. Importantly, viral RNA- and viral antigen-harboring cells are detected in the WAT of infected mice. Using in vitro approaches, we find that IAV infection enhances the expression of brown-adipogenesis-related genes in preadipocytes. Overall, our findings shed light on the role that the white adipose tissue, which lies at the crossroads of nutrition, metabolism and immunity, may play in influenza infection., Asma Ayari et al. report that mice infected with influenza A virus show persistent altered glucose metabolism. They find that infection is associated with the browning of the subcutaneous white adipose tissue (WAT), and this change is linked to viral infection in the fat tissues.
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- 2020
6. Kinetics and detectability of the bridgmanite to post-perovskite transformation in the Earth's D″ layer
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Langrand, Christopher, Andrault, Denis, Durand, Stéphanie, Konôpková, Zuzana, Hilairet, Nadège, Thomas, Christine, Merkel, Sébastien, Université de Lille, CNRS, INRA, ENSCL, Unité Matériaux et Transformations - UMR 8207 [UMET], Unité Matériaux et Transformations - UMR 8207 (UMET), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Ecole Nationale Supérieure de Chimie de Lille (ENSCL)-Institut National de la Recherche Agronomique (INRA), ANR-17-CE31-0025,TIMEleSS,Transformations de phase, microstructures, et leur signatures sismiques dans le manteau terrestre(2017), European Project: CALIPSO, Laboratoire Magmas et Volcans (LMV), Institut national des sciences de l'Univers (INSU - CNRS)-Université Jean Monnet - Saint-Étienne (UJM)-Institut de Recherche pour le Développement et la société-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)-Observatoire de Physique du Globe de Clermont-Ferrand (OPGC), Institut national des sciences de l'Univers (INSU - CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Supérieure de Chimie de Lille (ENSCL)-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Universite de Lille Region Hauts-de-France Programme National de Planetologie (PNP) of the CNRS bilateral PROCOPE Grant 40555PCFrench National Research Agency (ANR) TH 1530/18-1 SA 2585/3-1ARCHI-CM project Estonian Research Council FR 2638Region Hauts-de-France FR 2638European Union (EU) FR 2638German Research Foundation (DFG) HAADES DU1634/1-1project CALIPSOplus under EU Framework Programme for Research and Innovation HORIZON 2020 730872, Institut national des sciences de l'Univers (INSU - CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut de Recherche pour le Développement et la société-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)-Observatoire de Physique du Globe de Clermont-Ferrand (OPGC), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut national des sciences de l'Univers (INSU - CNRS), and Institut de Chimie du CNRS (INC)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Ecole Nationale Supérieure de Chimie de Lille (ENSCL)
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[SDU.ASTR]Sciences of the Universe [physics]/Astrophysics [astro-ph] ,Science ,[SDU.STU]Sciences of the Universe [physics]/Earth Sciences ,[PHYS.PHYS.PHYS-GEO-PH]Physics [physics]/Physics [physics]/Geophysics [physics.geo-ph] ,[CHIM.MATE]Chemical Sciences/Material chemistry ,Mineralogy ,Article ,[PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci] ,lcsh:Q ,ddc:500 ,[PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph] ,lcsh:Science ,Seismology ,ComputingMilieux_MISCELLANEOUS - Abstract
Nature Communications 10(1), 5680 (2019). doi:10.1038/s41467-019-13482-x, Bridgmanite, the dominant mineral in the Earth’s lower mantle, crystallizes in the perovskite structure and transforms into post-perovskite at conditions relevant for the D′′ layer. This transformation affects the dynamics of the Earth’s lowermost mantle and can explain a range of seismic observations. The thickness over which the two phases coexist, however, can extend over 100 km, casting doubt on the assignment of the observed seismic boundaries. Here, experiments show that the bridgmanite to post-perovskite transition in (Mg0.86,Fe0.14)SiO3 is fast on geological timescales. The transformation kinetics, however, affects reflection coefficients of P and S waves by more than one order of magnitude. Thick layers of coexisting bridgmanite and post-perovskite can hence be detected using seismic reflections. Morever, the detection and wave period dependence of D′′ reflections can be used to constrain significant features of the Earth’s lowermost mantle, such as the thickness of the coexistence layer, and obtain information on temperature and grain sizes., Published by Nature Publishing Group UK, [London]
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- 2019
7. Circulating proteomic signature of early death in heart failure patients with reduced ejection fraction
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Vincent Vandewalle, Audrey Hulot, Guillemette Marot, Christophe Bauters, Florence Pinet, Pascal de Groote, Maxime Brunin, Olivia Beseme, Marie Cuvelliez, Philippe Amouyel, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Remodeling in Valvulopathy and Heart Failure [CHU Rouen] (FHU REMOD-VHF ), CHU Rouen, Normandie Université (NU)-Normandie Université (NU), MOdel for Data Analysis and Learning (MODAL), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Paul Painlevé - UMR 8524 (LPP), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-École polytechnique universitaire de Lille (Polytech Lille)-Université de Lille, Sciences et Technologies, BILILLE, This work was supported by grants from the French Clinical Research Infrastructure Network INI-CRCT (Investigation Network Initiative-Cardiovascular and Renal Clinical Trialists), the E.U. FP7 HOMAGE (305507), 'Agence Nationale de Recherche' 15-CEA-U16/'Direction Générale de l’Offre de Soins' (5–013) and CHRU de Lille (Bonus H2018). We acknowledge Somalogic Inc. as the provider of the proteomics analysis and EdgeLeap B.V. for the systems biology analysis., Laboratoire Paul Painlevé (LPP), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-École polytechnique universitaire de Lille (Polytech Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Laboratoire Paul Painlevé - UMR 8524 (LPP), Pinet, Florence, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS], Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE], METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694, and Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167
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Oncology ,Male ,Proteomics ,medicine.medical_specialty ,Proteome ,[SDV]Life Sciences [q-bio] ,lcsh:Medicine ,Context (language use) ,Cardiovascular System ,Article ,Gene regulatory networks ,Prognostic markers ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Risk Factors ,Internal medicine ,Cause of Death ,Medicine ,Humans ,lcsh:Science ,Cathepsin S ,Heart Failure ,Ejection fraction ,business.industry ,lcsh:R ,Middle Aged ,medicine.disease ,Blood proteins ,[SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,3. Good health ,Extracellular Matrix ,[SDV] Life Sciences [q-bio] ,Clinical research ,Heart failure ,Biomarker (medicine) ,Female ,lcsh:Q ,business ,Extracellular matrix organization - Abstract
Background: Heart failure (HF) remains a main cause of mortality worldwide. Risk stratification of patients with systolic chronic HF is critical to identify those who may benefit from advanced HF therapies. The aim of this study is to identify plasmatic proteins that could predict early death of HF patients. Methods: The subproteome targeted by the aptamer-based assay (SOMAscan) of 1310 proteins was profiled in blood samples from 168 HF patients with reduced ejection fraction hospitalized in CHRU de Lille. Patient's outcome was assessed 3 years after inclusion. Findings: Among the 1310 proteins, 203 were significantly modulated between dead and alive patients (Wilcoxon tests, FDR 5%). The INCA molecular network was built using these 203 proteins and contained 2881 molecules (1639 proteins, 1072 microRNAs, 170 metabolites). To assess mechanistic context of HF, molecules were assigned to 34 clusters annotated to biological pathways from Gene Ontology. Analysis of the INCA network model allowed to highlight extracellular matrix organization as mechanism involved in HF. In parallel, an adaptive LASSO was performed on these 203 proteins and six proteins were selected as candidates to predict early death of HF patients: complement C3, cathepsin S and FAM107B were decreased and MAPKAPK5, MMP1 and MMP7 increased in dead patients compared with patients alive. By conventional assays, complement C3, MMP1 and MMP7 were validated but not cathepsin S due to the low sensitivity and specificity of the assay used. Interpretation: A proteomic signature of 6 plasma proteins allows identifying HF patients with a risk of early death. Funding Statement: This work was supported by grants from French Clinical Research Infrastructure Network INI-CRT (Investigation Network Initiative-Cardiovascular and Renal Clinical Trialists), the E.U. FP7 HOMAGE (305507), “Agence Nationale de Recherche” 15-CEA-U16/”Direction Generale de l'Offre de Soins” (5- 013) and CHRU de Lille (Bonus H2018).We acknowledged Somalogic Inc as the provider of the proteomics analysis and EdgeLeap B.V. for the system biology analysis. Declaration of Interests: MC, VV, MB, OB, AH, PDG, PA, CB, GM, FP have no conflict of interest to disclose for the study performed. Ethics Approval Statement: The INCA study was approved by the ethics committee of the “Centre Hospitalier de Lille” (CP98/94, 5 November 1998) , and written informed consent was obtained for each patient.
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- 2019
8. Fanconi anemia proteins counteract the implementation of the oncogene-induced senescence program
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Caroline Evrard, Françoise Dessarps-Freichey, Anne Helbling-Leclerc, Filippo Rosselli, Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), and Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille
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DNA Replication ,Senescence ,congenital, hereditary, and neonatal diseases and abnormalities ,DNA Repair ,Cathepsin L ,[SDV]Life Sciences [q-bio] ,lcsh:Medicine ,Article ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Ubiquitin ,Downregulation and upregulation ,Fanconi anemia ,hemic and lymphatic diseases ,FANCD2 ,medicine ,Humans ,Monoubiquitination ,lcsh:Science ,Cellular Senescence ,ComputingMilieux_MISCELLANEOUS ,Cell Proliferation ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,Fanconi Anemia Complementation Group A Protein ,biology ,Oncogene ,Fanconi Anemia Complementation Group D2 Protein ,lcsh:R ,Ubiquitination ,nutritional and metabolic diseases ,Oncogenes ,medicine.disease ,FANCA ,Cell Transformation, Neoplastic ,Fanconi Anemia ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,lcsh:Q ,Reactive Oxygen Species ,DNA Damage - Abstract
Fanconi Anemia (FA), due to the loss-of-function of the proteins that constitute the FANC pathway involved in DNA replication and genetic stability maintainance, is a rare genetic disease featuring bone marrow failure, developmental abnormalities and cancer predisposition. Similar clinical stigmas have also been associated with alterations in the senescence program, which is activated in physiological or stress situations, including the unscheduled, chronic, activation of an oncogene (oncogene induced senescence, OIS). Here, we wanted to determine the crosstalk, if any, between the FANC pathway and the OIS process. OIS was analyzed in two known cellular models, IMR90-hTERT/ER:RASG12V and WI38-hTERT/ER:GFP:RAF1, harboring 4-hydroxytamoxifen-inducible oncogenes. We observed that oncogene activation induces a transitory increase of both FANCA and FANCD2 as well as FANCD2 monoubiquitination, readout of FANC pathway activation, followed by their degradation. FANCD2 depletion, which leads to a pre-senescent phenotype, anticipates OIS progression. Coherently, FANCD2 overexpression or inhibition of its proteosomal-dependent degradation slightly delays OIS progression. The pro-senescence protease cathepsin L, which activation is anticipated during OIS in FANCD2-depleted cells, also participates to FANCD2 degradation. Our results demonstrate that oncogene activation is first associated with FANCD2 induction and activation, which may support initial cell proliferation, followed by its degradation/downregulation when OIS proceeds.
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- 2019
9. Combinatorial, additive and dose-dependent drug-microbiome associations
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Forslund, SK, Chakaroun, R, Zimmermann-Kogadeeva, M, Markó, L, Aron-Wisnewsky, J, Nielsen, T, Moitinho-Silva, L, Schmidt, TSB, Falony, G, Vieira-Silva, S, Adriouch, S, Alves, RJ, Assmann, K, Bastard, J-P, Birkner, T, Caesar, R, Chilloux, J, Coelho, LP, Fezeu, L, Galleron, N, Helft, G, Isnard, R, Ji, B, Kuhn, M, Le Chatelier, E, Myridakis, A, Olsson, L, Pons, N, Prifti, E, Quinquis, B, Roume, H, Salem, J-E, Sokolovska, N, Tremaroli, V, Valles-Colomer, M, Lewinter, C, Søndertoft, NB, Pedersen, HK, Hansen, TH, Amouyal, C, Andersson Galijatovic, EA, Andreelli, F, Barthelemy, O, Batisse, J-P, Belda, E, Berland, M, Bittar, R, Blottière, H, Bosquet, F, Boubrit, R, Bourron, O, Camus, M, Cassuto, D, Ciangura, C, Collet, J-P, Dao, M-C, Djebbar, M, Doré, A, Engelbrechtsen, L, Fellahi, S, Fromentin, S, Galan, P, Gauguier, D, Giral, P, Hartemann, A, Hartmann, B, Holst, JJ, Hornbak, M, Hoyles, L, Hulot, J-S, Jaqueminet, S, Jørgensen, NR, Julienne, H, Justesen, J, Kammer, J, Krarup, N, Kerneis, M, Khemis, J, Kozlowski, R, Lejard, V, Levenez, F, Lucas-Martini, L, Massey, R, Martinez-Gili, L, Maziers, N, Medina-Stamminger, J, Montalescot, G, Moute, S, Neves, AL, Olanipekun, M, Le Pavin, LP, Poitou, C, Pousset, F, Pouzoulet, L, Rodriguez-Martinez, A, Rouault, C, Silvain, J, Svendstrup, M, Swartz, T, Vanduyvenboden, T, Vatier, C, Walther, S, Gøtze, JP, Køber, L, Vestergaard, H, Hansen, T, Zucker, J-D, Hercberg, S, Oppert, J-M, Letunic, I, Nielsen, J, Bäckhed, F, Ehrlich, SD, Dumas, M-E, Raes, J, Pedersen, O, Clément, K, Stumvoll, M, Bork, P, The MetaCardis Consortium (Hoyles, L.), European Molecular Biology Laboratory [Heidelberg] (EMBL), Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), German Center for Cardiovascular Research (DZHK), Universität Leipzig, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Copenhagen = Københavns Universitet (UCPH), University of New South Wales [Sydney] (UNSW), Paul Scherrer Institute (PSI), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Heidelberg University, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Henri Mondor [Créteil], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], University of Gothenburg (GU), Imperial College London, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris-Saclay, Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Chalmers University of Technology [Gothenburg, Sweden], Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD [France-Nord]), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Biobyte Solutions [Heidelberg, Germany] (BS), IT University of Copenhagen (ITU), Sahlgrenska University Hospital [Gothenburg], Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, McGill University and Genome Quebec Innovation Centre, Helmholtz Institute Ulm (HIU), Helmholtz Zentrum München = German Research Center for Environmental Health, University of Würzburg = Universität Würzburg, Yonsei University, MetaCardis Consortium*: Chloe Amouyal, Ehm Astrid Andersson Galijatovic, Fabrizio Andreelli, Olivier Barthelemy, Jean-Paul Batisse, Eugeni Belda, Magalie Berland, Randa Bittar, Hervé Blottière, Frederic Bosquet, Rachid Boubrit, Olivier Bourron, Mickael Camus, Dominique Cassuto, Cecile Ciangura, Jean-Philippe Collet, Maria-Carlota Dao, Morad Djebbar, Angélique Doré, Line Engelbrechtsen, Soraya Fellahi, Sebastien Fromentin, Pilar Galan, Dominique Gauguier, Philippe Giral, Agnes Hartemann, Bolette Hartmann, Jens Juul Holst, Malene Hornbak, Lesley Hoyles, Jean-Sebastien Hulot, Sophie Jaqueminet, Niklas Rye Jørgensen, Hanna Julienne, Johanne Justesen, Judith Kammer, Nikolaj Krarup, Mathieu Kerneis, Jean Khemis, Ruby Kozlowski, Véronique Lejard, Florence Levenez, Lea Lucas-Martini, Robin Massey, Laura Martinez-Gili, Nicolas Maziers, Jonathan Medina-Stamminger, Gilles Montalescot, Sandrine Moute, Ana Luisa Neves, Michael Olanipekun, Laetitia Pasero Le Pavin, Christine Poitou, Francoise Pousset, Laurence Pouzoulet, Andrea Rodriguez-Martinez, Christine Rouault, Johanne Silvain, Mathilde Svendstrup, Timothy Swartz, Thierry Vanduyvenboden, Camille Vatier, Stefanie Walther., ANR-16-IDEX-0004,ULNE,ULNE(2016), ANR-18-IBHU-0001,PreciDIAB,PreciDIAB Institute, the holistic approach of personal diabets care(2018), Dumas, Marc-Emmanuel, Universität Leipzig [Leipzig], Service de Nutrition [CHU Pitié-Salpétrière], Institut E3M [CHU Pitié-Salpêtrière], CHU Henri Mondor, Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-1901(ex CIC-1421)), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Imperial College London - National Heart and Lung Institute, and Division of Computational and Systems Medicine, Imperial College London, London, SW7 2AZ, UK
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Clostridiales ,Science & Technology ,Multidisciplinary ,ANTIBIOTIC USE ,IMPACT ,Microbiota ,[SDV]Life Sciences [q-bio] ,HUMAN GUT MICROBIOME ,Atherosclerosis ,Gastrointestinal Microbiome ,[SDV] Life Sciences [q-bio] ,Multidisciplinary Sciences ,PROTON PUMP INHIBITORS ,Cardiovascular and Metabolic Diseases ,GUIDELINE ,Metabolome ,MANAGEMENT ,Humans ,Science & Technology - Other Topics ,ALTERS - Abstract
During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1-5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug-host-microbiome interactions in cardiometabolic disease. ispartof: NATURE vol:600 issue:7889 pages:500-+ ispartof: location:England status: published
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- 2021
10. Uprooting defects to enable high-performance III–V optoelectronic devices on silicon
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Gilles Patriarche, Mourad Jellite, Nadi Braidy, Dominique Drouin, Richard Arès, Ali Soltani, Maksym Myronov, Abderraouf Boucherif, Youcef A. Bioud, Institut Interdisciplinaire d'Innovation Technologique [Sherbrooke] (3IT), Université de Sherbrooke (UdeS), Laboratoire Nanotechnologies Nanosystèmes (LN2 ), Université de Sherbrooke (UdeS)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), University of Warwick [Coventry], Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Puissance - IEMN (PUISSANCE - IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Laboratoire de photonique et de nanostructures (LPN), Centre National de la Recherche Scientifique (CNRS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Sherbrooke (UdeS)-École supérieure de Chimie Physique Electronique de Lyon (CPE)-Centre National de la Recherche Scientifique (CNRS)
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Materials science ,Silicon ,Science ,TK ,General Physics and Astronomy ,chemistry.chemical_element ,02 engineering and technology ,Substrate (electronics) ,01 natural sciences ,Article ,General Biochemistry, Genetics and Molecular Biology ,[SPI]Engineering Sciences [physics] ,Surfaces, interfaces and thin films ,Etching (microfabrication) ,0103 physical sciences ,Lasers, LEDs and light sources ,Porous materials ,Wafer ,lcsh:Science ,ComputingMilieux_MISCELLANEOUS ,QC ,010302 applied physics ,Nanoscale materials ,Multidisciplinary ,business.industry ,General Chemistry ,Orders of magnitude (numbers) ,021001 nanoscience & nanotechnology ,chemistry ,Optoelectronics ,lcsh:Q ,Photonics ,Dislocation ,0210 nano-technology ,business ,Layer (electronics) ,Materials for optics - Abstract
The monolithic integration of III-V compound semiconductor devices with silicon presents physical and technological challenges, linked to the creation of defects during the deposition process. Herein, a new defect elimination strategy in highly mismatched heteroepitaxy is demonstrated to achieve a ultra-low dislocation density, epi-ready Ge/Si virtual substrate on a wafer scale, using a highly scalable process. Dislocations are eliminated from the epilayer through dislocation-selective electrochemical deep etching followed by thermal annealing, which creates nanovoids that attract dislocations, facilitating their subsequent annihilation. The averaged dislocation density is reduced by over three orders of magnitude, from ~108 cm−2 to a lower-limit of ~104 cm−2 for 1.5 µm thick Ge layer. The optical properties indicate a strong enhancement of luminescence efficiency in GaAs grown on this virtual substrate. Collectively, this work demonstrates the promise for transfer of this technology to industrial-scale production of integrated photonic and optoelectronic devices on Si platforms in a cost-effective way., The use of promising group III-V materials for optoelectronic applications is hindered by the high density of threading dislocations when integrated with silicon technology. Here, the authors present an electrochemical deep etching strategy to drastically reduce the the defect density.
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- 2019
11. Increased levels of the megakaryocyte and platelet expressed cysteine proteases stefin A and cystatin A prevent thrombosis
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Marie-Christine Alessi, Anna Mezzapesa, Marie Maraninchi, Delphine Bastelica, Christophe Dubois, Lydie Crescence, Michel Grino, Marjorie Poggi, Jean-Claude Bordet, Annabelle Dupont, Laurence Panicot-Dubois, Franck Peiretti, René Valéro, Matthias Canault, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, 'Fondation de France' (grant 00056841) and the Société Francophone du Diabète, Centre recherche en CardioVasculaire et Nutrition (C2VN), Récepteurs nucléaires, maladies cardiovasculaires et diabète (EGID), Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Prémilleux, Annick
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0301 basic medicine ,Male ,Platelet Aggregation ,[SDV]Life Sciences [q-bio] ,lcsh:Medicine ,cathepsine ,Cathepsin B ,Mice ,0302 clinical medicine ,Megakaryocyte ,mégacaryocyte ,Platelet ,thrombose ,Receptor ,lcsh:Science ,Mice, Knockout ,Multidisciplinary ,Chemistry ,analyse de l'expression génique ,[SDV] Life Sciences [q-bio] ,medicine.anatomical_structure ,Megakaryocytes ,Blood Platelets ,Platelets ,Médecine humaine et pathologie ,Article ,Diabetes Mellitus, Experimental ,03 medical and health sciences ,Downregulation and upregulation ,medicine ,Animals ,Humans ,Cystatin A ,Platelet activation ,Calcium Signaling ,Obesity ,Thrombus ,Rats, Wistar ,protéase à cystéine ,lcsh:R ,Thrombosis ,medicine.disease ,Platelet Activation ,Molecular biology ,Rats ,Mice, Inbred C57BL ,[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition ,030104 developmental biology ,Human health and pathology ,lcsh:Q ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,030217 neurology & neurosurgery - Abstract
Increased platelet activity occurs in type 2 diabetes mellitus (T2DM) and such platelet dysregulation likely originates from altered megakaryopoiesis. We initiated identification of dysregulated pathways in megakaryocytes in the setting of T2DM. We evaluated through transcriptomic analysis, differential gene expressions in megakaryocytes from leptin receptor-deficient mice (db/db), exhibiting features of human T2DM, and control mice (db/+). Functional gene analysis revealed an upregulation of transcripts related to calcium signaling, coagulation cascade and platelet receptors in diabetic mouse megakaryocytes. We also evidenced an upregulation (7- to 9.7-fold) of genes encoding stefin A (StfA), the human ortholog of Cystatin A (CSTA), inhibitor of cathepsin B, H and L. StfA/CSTA was present in megakaryocytes and platelets and its expression increased during obesity and diabetes in rats and humans. StfA/CSTA was primarily localized at platelet membranes and granules and was released upon agonist stimulation and clot formation through a metalloprotease-dependent mechanism. StfA/CSTA did not affect platelet aggregation, but reduced platelet accumulation on immobilized collagen from flowing whole blood (1200 s−1). In-vivo, upon laser-induced vascular injury, platelet recruitment and thrombus formation were markedly reduced in StfA1-overexpressing mice without affecting bleeding time. The presence of CA-074Me, a cathepsin B specific inhibitor significantly reduced thrombus formation in-vitro and in-vivo in human and mouse, respectively. Our study identifies StfA/CSTA as a key contributor of platelet-dependent thrombus formation in both rodents and humans.
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- 2019
12. Direct measurement of the mechanical properties of a chromatin analog and the epigenetic effects of para-sulphonato-calix[4]arene
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Anthony W. Coleman, Yannick Tauran, Gregoire Perret, Hiroyuki Fujita, Laurent Jalabert, Momoko Kumemura, Mehmet C. Tarhan, Dominique Collard, Florent Perret, Laboratoire des Multimatériaux et Interfaces (LMI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratory for Integrated Micro Mechatronics Systems (LIMMS), The University of Tokyo (UTokyo)-Centre National de la Recherche Scientifique (CNRS), Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Thermodynamique des solutions et des polymères (TSP), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Universitaire Lorrain d'Histoire (CRULH), Université de Lorraine (UL), and The University of Tokyo (UTokyo)
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0301 basic medicine ,Optical Tweezers ,[SDV]Life Sciences [q-bio] ,lcsh:Medicine ,Microscopy, Atomic Force ,Proof of Concept Study ,Article ,Histones ,03 medical and health sciences ,Methyllysine ,chemistry.chemical_compound ,0302 clinical medicine ,Nucleosome ,Animals ,Chromosomes, Artificial ,Epigenetics ,lcsh:Science ,Regulation of gene expression ,Multidisciplinary ,biology ,Chemistry ,lcsh:R ,[CHIM.MATE]Chemical Sciences/Material chemistry ,Bacteriophage lambda ,Chromatin ,3. Good health ,Cell biology ,Nucleosomes ,030104 developmental biology ,Histone ,DNA, Viral ,biology.protein ,Nucleic Acid Conformation ,Cattle ,lcsh:Q ,Histone deacetylase ,030217 neurology & neurosurgery ,DNA - Abstract
International audience; By means of Silicon Nano Tweezers (SNTs) the effects on the mechanical properties of λ-phage DNA during interaction with calf thymus nucleosome to form an artificial chromatin analog were measured. At a concentration of 100 nM, a nucleosome solution induced a strong stiffening effect on DNA (1.1 N m −1). This can be compared to the effects of the histone proteins, H1, H2A, H3 where no changes in the mechanical properties of DNA were observed and the complex of the H3/H4 proteins where a smaller increase in the stiffness is observed (0.2 N m −1). Para-sulphonato-calix[4]arene, SC4, known for epigenetic activity by interacting specifically with the lysine groups of histone proteins, was studied for its effect on an artificial chromatin. Using a microfluidic SNT device, SC4 was titrated against the artificial chromatin, at a concentration of 1 mM in SC4 a considerable increase in stiffness, 15 N m −1 , was observed. Simultaneously optical microscopy showed a physical change in the DNA structure between the tips of the SNT device. Electronic and Atomic Force microscopy confirmed this structural rearrangement. Negative control experiments confirmed that these mechanical and physical effects were induced neither by the acidity of SC4 nor through nonspecific interactions of SC4 on DNA. With the recent and better knowledge on how gene regulation occurs and after intense debate in the academic community 1 , epigenetics has been commonly defined as "the study of changes in gene function that are mitoti-cally and/or meiotically heritable and that do not entail a change in DNA sequence" 2. Over the past years, epigenetics has been shown to play a central role in many different key functions at the cellular level, including differentiation, replication, and gene transcription 3. In a larger context, its contribution in physiological disorders has been revealed in cardio vascular illnesses, mental disorders and various cancers 4. Despite its inheritable character, epigenetics paradoxically possesses a reversible nature 5 that can be illustrated through its two main covalent modifications either directly on DNA with the methylation of cytosine nucleic bases or indirectly with various post translational modifications on proteins interacting with DNA such as histone proteins or other proteins called writers, erasers or readers 6. New therapeutic treatments are expected to target and reverse these modifications by inactivating the enzymes responsible for the deregulation of specific genes 7. Some inhibitors have been already approved by FDA, such as Azacitidine and Decitabine as DNA methyltrans-ferase inhibitors for the treatment of myelodysplastic syndrome 8 and Vorinostat and Romidepsin as inhibitors of histone deacetylase for the treatment of peripheral T-cell lymphoma 9. A new class of DNA artificial binders that directly block the methyllysine reading functions of reader enzymes in charge of conveying the methylation signal downstream has recently arisen as promising epigenetic drugs 10 .
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- 2019
13. Whole-Exome Sequencing in the Isolated Populations of Cilento from South Italy
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F. Marangio, Anthony F. Herzig, Alfonsina Tirozzi, Rossella Sorice, Marina Ciullo, Anne-Louise Leutenegger, Stefania Nappo, Teresa Nutile, Daniela Ruggiero, Céline Bellenguez, Institute of Genetics and Biophysics 'A. Buzzati Traverso', Consiglio Nazionale delle Ricerche [Roma] (CNR), Istituto Neurologico Mediterraneo (NEUROMED I.R.C.C.S.), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]-Università degli studi di Napoli Federico II, Variabilité Génétique et Maladies Humaines, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), AORN Santobono-Pausilipon Hospital [Naples, Italy], Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), The research leading to these results has received funding from the Seventh Framework Programme [FP7/2007–2013] under grant agreement no. 262055. This work was supported by grants from the Italian Ministry of Universities and CNR (Interomics Flagship Project, PON03PE_00060_7), the Assessorato Ricerca Regione Campania (POR CAMPANIA 2000/2006 MISURA 3.16). A.F.H. was funded by an international Ph.D. fellowship from Sorbonne Paris Cité (convention HERZI15RDXMTSPC1LIETUE) and by the Fondation Recherche Médicale (convention FRM FDT201805005384)., We address special thanks to the populations of Campora, Gioi, and Cardile for their participation in the study. We thank dr. Debora Chirico, dr. Michelina De Cristofaro, dr. Raffaele D’Urso and dr. Giovanni D’Arena for Cilento data collection. We thank Mariarosaria Aletta for bibliographic support. ESGI, European Project: 262055,EC:FP7:INFRA,FP7-INFRASTRUCTURES-2010-1,ESGI(2011), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA)-University of Naples Federico II = Università degli studi di Napoli Federico II, Leutenegger, Anne-Louise, and European Sequencing and Genotyping Infrastructure - ESGI - - EC:FP7:INFRA2011-02-01 - 2015-07-31 - 262055 - VALID
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0301 basic medicine ,Male ,Genotype ,Population ,Population genetics ,lcsh:Medicine ,Biology ,[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics ,Polymorphism, Single Nucleotide ,Article ,Populations of Cilento ,03 medical and health sciences ,0302 clinical medicine ,Gene Frequency ,Human Genome Project ,Exome Sequencing ,Humans ,Exome ,1000 Genomes Project ,education ,lcsh:Science ,Allele frequency ,Exome sequencing ,Genetics ,education.field_of_study ,Multidisciplinary ,[SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE] ,Genome, Human ,lcsh:R ,Human genetics ,030104 developmental biology ,Genetics, Population ,Italy ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,[SDV.GEN.GPO] Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE] ,Female ,lcsh:Q ,030217 neurology & neurosurgery ,Imputation (genetics) - Abstract
The present study describes the genetic architecture of the isolated populations of Cilento, through the analysis of exome sequence data of 245 representative individuals of these populations. By annotating the exome variants and cataloguing them according to their frequency and functional effects, we identified 347,684 variants, 67.4% of which are rare and low frequency variants, and 1% of them (corresponding to 319 variants per person) are classified as high functional impact variants; also, 39,946 (11.5% of the total) are novel variants, for which we determined a significant enrichment for deleterious effects. By comparing the allele frequencies in Cilento with those from the Tuscan population from the 1000 Genomes Project Phase 3, we highlighted an increase in allele frequency in Cilento especially for variants which map to genes involved in extracellular matrix formation and organization. Furthermore, among the variants showing increased frequency we identified several known rare disease-causing variants. By different population genetics analyses, we corroborated the status of the Cilento populations as genetic isolates. Finally, we showed that exome data of Cilento represents a useful local reference panel capable of improving the accuracy of genetic imputation, thus adding power to genetic studies of human traits in these populations.
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- 2019
14. Pathogenic variants in E3 ubiquitin ligase RLIM/RNF12 lead to a syndromic X-linked intellectual disability and behavior disorder
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Kees E. P. van Roozendaal, Molka Kammoun, Michael Field, Andreas Dufke, Joris Vermeesch, Annick Toutain, Hao Hu, Theresa Mihalic Mosher, Joep P.M. Geraedts, Hans-Hilger Ropers, Peter White, Jan Liebelt, Sungjin Moon, Vera M. Kalscheuer, Joost Gribnau, Bas de Hoon, Germán Rodríguez Criado, Marie Shaw, Ute Grasshoff, Stefan A. Haas, Benjamin J. Kelly, Lynne Hobson, Marjan De Rademaeker, Christelle Golzio, Suzanna G.M. Frints, Olaf Riess, Claudia S. Bauer, Eric Haan, Nicholas Katsanis, Peter Bauer, Karen W. Gripp, Renee Carroll, Jozef Gecz, Jean Pierre Fryns, Cristina Gontan, Aysegul Ozanturk, Eveline Rentmeester, Martine Raynaud, Scott E. Hickey, Daniel C. Koboldt, Sylvie Manouvrier-Hanu, Lucinda Murray, Koen Devriendt, Christopher Schroeder, Kathryn Friend, Developmental Biology, Obstetrics & Gynecology, MUMC+: DA KG Bedrijfsbureau (9), RS: GROW - R4 - Reproductive and Perinatal Medicine, Klinische Genetica, MUMC+: DA KG Lab Centraal Lab (9), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Duke University [Durham], Hospital Universitario Virgen del Rocío [Sevilla], University of Tübingen, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hunter Genetics, Clinique de Génétique médicale Guy Fontaine [CHRU LIlle], Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 (RADEME), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Nationwide Children's Hospital, Ohio State University [Columbus] (OSU), University Hospitals Leuven [Leuven], Nemours/Alfred I. du Pont Hospital for Children, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Max Planck Institute for Molecular Genetics (MPIMG), Max-Planck-Gesellschaft, University of Adelaide, Women’s and Children’s Hospital [Adelaide], SA Pathology [Adelaide, SA, Australia], Vrije Universiteit Brussel (VUB), South Australian Health and Medical Research Institute [ Adelaide] (SAHMRI), 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), univOAK, Archive ouverte, Reproduction and Genetics, Clinical sciences, and Medical Genetics
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Male ,0301 basic medicine ,X-linked intellectual disability ,PROTEIN ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,FUNCTIONAL-ACTIVITY ,Mice ,0302 clinical medicine ,Genes, X-Linked ,X Chromosome Inactivation ,RNF12 ,Missense mutation ,TRANSCRIPTION ,Child ,Zebrafish ,Genetics ,Middle Aged ,Phenotype ,Pedigree ,Ubiquitin ligase ,Psychiatry and Mental health ,medicine.anatomical_structure ,Child, Preschool ,Female ,Adult ,Conduct Disorder ,Adolescent ,Ubiquitin-Protein Ligases ,NPAS3 ,Biology ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Intellectual Disability ,medicine ,Ring finger ,Animals ,Humans ,Molecular Biology ,Transcription factor ,RLIM ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,CHROMOSOME INACTIVATION ,MUTATIONS ,Infant, Newborn ,Ubiquitination ,Wild type ,Zebrafish Proteins ,medicine.disease ,biology.organism_classification ,HEK293 Cells ,030104 developmental biology ,Mutation ,Mental Retardation, X-Linked ,biology.protein ,LIM COFACTORS ,030217 neurology & neurosurgery ,Transcription Factors ,GENE UBE2A CAUSE - Abstract
RLIM, also known as RNF12, is an X-linked E3 ubiquitin ligase acting as a negative regulator of LIM-domain containing transcription factors and participates in X-chromosome inactivation (XCI) in mice. We report the genetic and clinical findings of 84 individuals from nine unrelated families, eight of whom who have pathogenic variants in RLIM (RING finger LIM domain-interacting protein). A total of 40 affected males have X-linked intellectual disability (XLID) and variable behavioral anomalies with or without congenital malformations. In contrast, 44 heterozygous female carriers have normal cognition and behavior, but eight showed mild physical features. All RLIM variants identified are missense changes co-segregating with the phenotype and predicted to affect protein function. Eight of the nine altered amino acids are conserved and lie either within a domain essential for binding interacting proteins or in the C-terminal RING finger catalytic domain. In vitro experiments revealed that these amino acid changes in the RLIM RING finger impaired RLIM ubiquitin ligase activity. In vivo experiments in rlim mutant zebrafish showed that wild type RLIM rescued the zebrafish rlim phenotype, whereas the patient-specific missense RLIM variants failed to rescue the phenotype and thus represent likely severe loss-of-function mutations. In summary, we identified a spectrum of RLIM missense variants causing syndromic XLID and affecting the ubiquitin ligase activity of RLIM, suggesting that enzymatic activity of RLIM is required for normal development, cognition and behavior.
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- 2019
15. Proteasomal degradation of NOD2 by NLRP12 in monocytes promotes bacterial tolerance and colonization by enteropathogens
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Normand, Sylvain, Waldschmitt, Nadine, Neerincx, Andreas, Martinez-Torres, Ruben Julio, Chauvin, Camille, Couturier-Maillard, Aurelie, Boulard, Olivier, Cobret, Laetitia, Awad, Fawaz, Huot, Ludovic, Ribeiro-Ribeiro, Andre, Lautz, Katja, Ruez, Richard, Delacre, Myriam, Bondu, Clovis, Guilliams, Martin, Scott, Charlotte, Segal, Anthony, Amselem, Serge, Hot, David, Karabina, Sonia, Bohn, Erwin, Ryffel, Bernhard, Poulin, Lionel F, Kufer, Thomas A, Chamaillard, Mathias, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), University of Cambridge [UK] (CAM), University College of London [London] (UCL), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Cologne, Universiteit Gent = Ghent University (UGENT), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Université d'Orléans (UO), University of Hohenheim, We thank Yvonne Postma for technical assistance., Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Technische Universität München [München] (TUM), Physiopathologie des maladies génétiques d'expression pédiatrique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Trafic, Signalisation et Ciblage Intracellulaires, Institut Curie, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Unit of Immunoregulation and Mucosal Immunology [Ghent, Belgium], VIB Inflammation Research Center [Ghent, Belgium], UCL, Dept Med, Eberhard Karls Universität Tübingen, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Physiopathologie des maladies génétiques d'expression pédiatrique (UMRS_933), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universiteit Gent = Ghent University [Belgium] (UGENT), Gestionnaire, Hal Sorbonne Université, Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), and UF de Génétique moléculaire [CHU Trousseau]
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Male ,MONARCH-1 ,[SDV]Life Sciences [q-bio] ,Nod2 Signaling Adaptor Protein ,ATG16L1 ,PROTEIN ,MESH: Mice, Knockout ,ACTIVATION ,Mice ,ATTENUATES COLON INFLAMMATION ,MESH: Intracellular Signaling Peptides and Proteins/genetics ,Medicine and Health Sciences ,MESH: Animals ,lcsh:Science ,MESH: Inflammation/immunology ,ComputingMilieux_MISCELLANEOUS ,MESH: Enterobacteriaceae Infections/immunology ,MESH: HSP90 Heat-Shock Proteins/metabolism ,Mice, Knockout ,CITROBACTER-RODENTIUM ,Enterobacteriaceae Infections ,Intracellular Signaling Peptides and Proteins ,NF-kappa B ,MESH: HEK293 Cells ,MESH: Immune Tolerance/immunology ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,SENSORS NOD1 ,MESH: NF-kappa B/metabolism ,Acetylmuramyl-Alanyl-Isoglutamine ,MESH: Citrobacter rodentium/immunology ,MESH: Nod2 Signaling Adaptor Protein/metabolism ,EXPRESSION ,MESH: Intracellular Signaling Peptides and Proteins/metabolism ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,Science ,MESH: Acetylmuramyl-Alanyl-Isoglutamine/metabolism ,DENDRITIC CELLS ,Article ,Cell Line ,MESH: Bacterial Capsules/metabolism ,Immune Tolerance ,MESH: Enterobacteriaceae Infections/microbiology ,Animals ,Humans ,HSP90 Heat-Shock Proteins ,MESH: Mice ,Bacterial Capsules ,Inflammation ,MESH: Humans ,MUTATIONS ,MESH: Gastrointestinal Microbiome/immunology ,Ubiquitination ,Biology and Life Sciences ,MESH: Inflammation/microbiology ,MESH: Male ,Gastrointestinal Microbiome ,MESH: Cell Line ,HEK293 Cells ,Citrobacter rodentium ,MESH: Ubiquitination ,lcsh:Q - Abstract
Mutations in the nucleotide-binding oligomerization domain protein 12 (NLRP12) cause recurrent episodes of serosal inflammation. Here we show that NLRP12 efficiently sequesters HSP90 and promotes K48-linked ubiquitination and degradation of NOD2 in response to bacterial muramyl dipeptide (MDP). This interaction is mediated by the linker-region proximal to the nucleotide-binding domain of NLRP12. Consequently, the disease-causing NLRP12 R284X mutation fails to repress MDP-induced NF-κB and subsequent activity of the JAK/STAT signaling pathway. While NLRP12 deficiency renders septic mice highly susceptible towards MDP, a sustained sensing of MDP through NOD2 is observed among monocytes lacking NLRP12. This loss of tolerance in monocytes results in greater colonization resistance towards Citrobacter rodentium. Our data show that this is a consequence of NOD2-dependent accumulation of inflammatory mononuclear cells that correlates with induction of interferon-stimulated genes. Our study unveils a relevant process of tolerance towards the gut microbiota that is exploited by an attaching/effacing enteric pathogen., Mutations in nucleotide-binding oligomerization domain protein 12 (NLRP12) are known to effect inflammatory processes. Here the authors show that NLRP12-mediated proteasomal degradation of NOD2 in monocytes promotes bacterial tolerance and colonisation in a model of enteric infection.
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- 2018
16. Early movement restriction leads to maladaptive plasticity in the sensorimotor cortex and to movement disorders
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Delcour, Maxime, Russier, Michaël, Castets, Francis, Turle-Lorenzo, Nathalie, Canu, Marie-Hélène, Cayetanot, Florence, Barbe, Mary, Coq, Jacques-Olivier, Neurosciences sensorielles et cognitives (NSC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369 - ULR 4488 (URePSSS), Université d'Artois (UA)-Université de Lille-Université du Littoral Côte d'Opale (ULCO), Temple University [Philadelphia], Pennsylvania Commonwealth System of Higher Education (PCSHE), Gestionnaire, Hal Sorbonne Université, Université de Montréal (UdeM), Unité de Neurobiologie des canaux Ioniques et de la Synapse (UNIS - Inserm U1072), Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Université d'Artois (UA)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille, Institut de Neurosciences de la Timone (INT), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Neurophysiologie Respiratoire Expérimentale et Clinique, Université de Montréal [Montréal], Activité Physique, Muscle, Santé (EA4488), Université de Lille, Droit et Santé, Neuropeptides centraux et régulations hydrique et cardiovasculaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurobiologie intégrative et adaptative (NIA), Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), Univ. Littoral Côte d’Opale, Univ. Artois, Université de Lille, Laboratoire de Neurosciences intégratives et adaptatives [LNIA], Neurobiologie des Canaux Ioniques, Centre de recherche en neurobiologie - neurophysiologie de Marseille [CRN2M], Aix Marseille Université [AMU], Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369 - ULR 4488 [URePSSS], Institut de Neurosciences de la Timone [INT], and Dpt of Anatomy and Cell Biology [Oklahoma]
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Male ,Neurons ,Principal Component Analysis ,Movement Disorders ,Neuronal Plasticity ,[SDV]Life Sciences [q-bio] ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Developmental disorders ,Neurodevelopmental disorders ,lcsh:R ,[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,lcsh:Medicine ,Adaptation, Physiological ,Article ,Rats ,[SDV] Life Sciences [q-bio] ,Hindlimb Suspension ,Animals ,Female ,lcsh:Q ,Sensorimotor Cortex ,lcsh:Science ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience; Motor control and body representations in the central nervous system are built, i.e., patterned, during development by sensorimotor experience and somatosensory feedback/reafference. Yet, early emergence of locomotor disorders remains a matter of debate, especially in the absence of brain damage. For instance, children with developmental coordination disorders (DCD) display deficits in planning, executing and controlling movements, concomitant with deficits in executive functions. Thus, are early sensorimotor atypicalities at the origin of long-lasting abnormal development of brain anatomy and functions? We hypothesize that degraded locomotor outcomes in adulthood originate as a consequence of early atypical sensorimotor experiences that induce developmental disorganization of sensorimotor circuitry. We showed recently that postnatal sensorimotor restriction (SMR), through hind limb immobilization from birth to one month, led to enduring digitigrade locomotion with ankle-knee overextension, degraded musculoskeletal tissues (e.g., gastrocnemius atrophy), and clear signs of spinal hyperreflexia in adult rats, suggestive of spasticity; each individual disorder likely interplaying in self-perpetuating cycles. In the present study, we investigated the impact of postnatal SMR on the anatomical and functional organization of hind limb representations in the sensorimotor cortex and processes representative of maladaptive neuroplasticity. We found that 28 days of daily SMR degraded the topographical organization of somatosensory hind limb maps, reduced both somatosensory and motor map areas devoted to the hind limb representation and altered neuronal response properties in the sensorimotor cortex several weeks after the cessation of SMR. We found no neuroanatomical histopathology in hind limb sensorimotor cortex, yet increased glutamatergic neurotransmission that matched clear signs of spasticity and hyperexcitability in the adult lumbar spinal network. Thus, even in the absence of a brain insult, movement disorders and brain dysfunction can emerge as a consequence of reduced and atypical patterns of motor outputs and somatosensory feedback that induce maladaptive neuroplasticity. Our results may contribute to understanding the inception and mechanisms underlying neurodevelopmental disorders, such as DCD.
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- 2018
17. Frustration wave order in iron(II) oxide spinels
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Angel M. Arevalo-Lopez, Clemens Ritter, J. Paul Attfield, Giuditta Perversi, Unité de Catalyse et Chimie du Solide - UMR 8181 (UCCS), Centrale Lille Institut (CLIL)-Université d'Artois (UA)-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Lille, Institut Laue-Langevin (ILL), ILL, Center for Science at Extreme Conditions, University of Edinburgh, and Université d'Artois (UA)-Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
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media_common.quotation_subject ,Pyrochlore ,General Physics and Astronomy ,Frustration ,lcsh:Astrophysics ,02 engineering and technology ,engineering.material ,01 natural sciences ,Condensed Matter::Disordered Systems and Neural Networks ,0103 physical sciences ,lcsh:QB460-466 ,Antiferromagnetism ,[CHIM]Chemical Sciences ,010306 general physics ,Quantum fluctuation ,ComputingMilieux_MISCELLANEOUS ,Spin-½ ,media_common ,Physics ,[PHYS]Physics [physics] ,Condensed matter physics ,[CHIM.MATE]Chemical Sciences/Material chemistry ,021001 nanoscience & nanotechnology ,lcsh:QC1-999 ,Spin ice ,Ferromagnetism ,engineering ,Condensed Matter::Strongly Correlated Electrons ,Quantum spin liquid ,[PHYS.COND.CM-SCE]Physics [physics]/Condensed Matter [cond-mat]/Strongly Correlated Electrons [cond-mat.str-el] ,0210 nano-technology ,lcsh:Physics - Abstract
Frustrated magnetic materials can show unconventional correlations such as quantum spin liquid states and monopole excitations in spin ices. These phenomena are observed on uniformly frustrated lattices such as triangular, kagome or pyrochlore types, where all nearest neighbour interactions are equivalent. Here we report incommensurate long-range spin amplitude waves in the spinels Fe2GeO4 and γ-Fe2SiO4 at low temperatures, which indicate that the degree of frustration may itself be a fluctuating quantity that can spontaneously order without a lattice distortion as a ‘frustration wave’. Fe2GeO4 with propagation vector (2/3 + δ 2/3 + δ 0) has ordered Fe2+ moments that vary between fully saturated 4 μB and 0 values, consistent with a frustration wave order. γ-Fe2SiO4 has a more complex (¾ + δ ¾ + δ 0) order that coexists with an ordered spin ice phase. Dynamic orbital fluctuations are proposed to give rise to locally correlated patterns of ferromagnetic and antiferromagnetic interactions consistent with the observed orders.
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- 2018
18. 3D MALDI mass spectrometry imaging reveals specific localization of long-chain acylcarnitines within a 10-day time window of spinal cord injury
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Quanico, Jusal, Hauberg-Lotte, Lena, Devaux, Stephanie, Laouby, Zahra, Meriaux, Celine, Raffo-Romero, Antonella, Rose, Melanie, Westerheide, Leia, Vehmeyer, Jost, Rodet, Franck, Maass, Peter, Cizkova, Dasa, Zilka, Norbert, Cubinkova, Veronika, Fournier, Isabelle, Salzet, Michel, Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Bremen, State Veterinary Institute Košice, Slovak Academy of Sciences (SAS), SALZET, Michel, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
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Male ,Macrophages ,[SDV]Life Sciences [q-bio] ,lcsh:R ,lcsh:Medicine ,Article ,Rats ,[SDV] Life Sciences [q-bio] ,Imaging, Three-Dimensional ,Carnitine ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Image Processing, Computer-Assisted ,Animals ,lcsh:Q ,Microglia ,Rats, Wistar ,lcsh:Science ,Spinal Cord Injuries - Abstract
International audience; We report, for the first time, the detection and specific localization of long-chain acylcarnitines (LC ACs) along the lesion margins in an experimental model of spinal cord injury (SCI) using 3D mass spectrometry imaging (MSI). Acylcarnitines palmitoylcarnitine (AC(16:0)), palmitoleoylcarnitine (AC(16:1)), elaidic carnitine (AC(18:1)) and tetradecanoylcarnitine (AC(14:1)) were detected as early as 3 days post injury, and were present along the lesion margins 7 and 10 days after SCI induced by balloon compression technique in the rat. 3D MSI revealed the heterogeneous distribution of these lipids across the injured spinal cord, appearing well-defined at the lesion margins rostral to the lesion center, and becoming widespread and less confined to the margins at the region located caudally. The assigned acylcarnitines co-localize with resident microglia/macrophages detected along the lesion margins by immunofluorescence. Given the reported pro-inflammatory role of these acylcarnitines, their specific spatial localization along the lesion margin could hint at their potential pathophysiological roles in the progression of SCI.
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- 2018
19. A general procedure to measure the pacing of body movements timed to music and metronome in younger and older adults
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Dawn Rose, Laurent Ott, Ségolène M. R. Guérin, Lucy E. Annett, Peter Lovatt, Yvonne N. Delevoye-Turrell, Université de Lille, CNRS, CHU Lille, University of Hertfordshire [Hatfield] [UH], Lucerne University of Applied Sciences and Arts [Luzern], 415060|||Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193 [SCALab], 374570|||Université de Lille, University of Hertfordshire [Hatfield] (UH), Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193 (SCALab)
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Science ,[SCCO.PSYC]Cognitive science/Psychology ,Medicine - Abstract
International audience; Abstract Finger-tapping tasks are classically used to investigate sensorimotor synchronization in relation to neutral auditory cues, such as metronomes. However, music is more commonly associated with an entrained bodily response, such as toe tapping, or dancing. Here we report an experimental procedure that was designed to bridge the gap between timing and intervention studies by directly comparing the effects of metronome and musical cue types on motor timing abilities across the three naturalistic voluntary actions of finger tapping, toe tapping, and stepping on the spot as a simplified case of whole body movement. Both pacing cues were presented at slow, medium, and fast tempi. The findings suggested that the task of stepping on the spot enabled better timing performances than tapping both in younger and older adults (75+). Timing performances followed an inverse U shape with best performances observed in the medium tempi that were set close to the spontaneous motor tempo in each movement type. Finally, music provided an entrainment effect in addition to pace setting that enabled better motor timing and greater stability than classically reported using a metronome. By applying time-stamp analyses to kinetic data, we demonstrate that tapping and stepping engage different timing modes. This work details the importance of translational research for a better understanding of motor timing. It offers a simple procedure that strengthens the validity of applying academic work and contributes in knowledge towards a wide range of therapeutic interventions.
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- 2021
20. The dark exciton ground state promotes photon-pair emission in individual perovskite nanocrystals
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Tamarat, Philippe, Hou, Lei, Trebbia, Jean-Baptiste, Swarnkar, Abhishek, Biadala, Louis, Louyer, Yann, Bodnarchuk, Maryna I., Kovalenko, Maksym V., Even, Jacky, Lounis, Brahim, Laboratoire Photonique, Numérique et Nanosciences (LP2N), Université de Bordeaux (UB)-Institut d'Optique Graduate School (IOGS)-Centre National de la Recherche Scientifique (CNRS), Swiss Federal Laboratories for Materials Science and Technology [Dübendorf] (EMPA), Department of Chemistry and Applied Biosciences [ETH Zürich] (D-CHAB), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Physique - IEMN (PHYSIQUE - IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Laboratoire Ondes et Matière d'Aquitaine (LOMA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut des Fonctions Optiques pour les Technologies de l'informatiON (Institut FOTON), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Nationale Supérieure des Sciences Appliquées et de Technologie (ENSSAT)-Centre National de la Recherche Scientifique (CNRS), Physique-IEMN (PHYSIQUE-IEMN), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-École Nationale Supérieure des Sciences Appliquées et de Technologie (ENSSAT)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), and Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)
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[PHYS]Physics [physics] ,Condensed Matter::Materials Science ,[PHYS.QPHY]Physics [physics]/Quantum Physics [quant-ph] ,Quantum dots ,Condensed Matter::Other ,Science ,Physics::Optics ,lcsh:Q ,lcsh:Science ,Condensed Matter::Mesoscopic Systems and Quantum Hall Effect ,Article - Abstract
Cesium lead halide perovskites exhibit outstanding optical and electronic properties for a wide range of applications in optoelectronics and for light-emitting devices. Yet, the physics of the band-edge exciton, whose recombination is at the origin of the photoluminescence, is not elucidated. Here, we unveil the exciton fine structure of individual cesium lead iodide perovskite nanocrystals and demonstrate that it is governed by the electron-hole exchange interaction and nanocrystal shape anisotropy. The lowest-energy exciton state is a long-lived dark singlet state, which promotes the creation of biexcitons at low temperatures and thus correlated photon pairs. These bright quantum emitters in the near-infrared have a photon statistics that can readily be tuned from bunching to antibunching, using magnetic or thermal coupling between dark and bright exciton sublevels., Nature Communications, 11 (1), ISSN:2041-1723
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- 2020
21. The nuclear receptor FXR inhibits Glucagon-Like Peptide-1 secretion in response to microbiota-derived Short-Chain Fatty Acids
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Alexis Boulinguiez, Jean-Sébastien Annicotte, Laura Butruille, Anne Tailleux, Olivier Briand, Mohamed-Sami Trabelsi, Laure B. Bindels, Emilie Dorchies, Simon Peschard, Véronique Touche, Sandrine Caron, Emmanuelle Vallez, Sophie Lestavel, Sarah Ducastel, Steve Lancel, Oscar Chávez-Talavera, Nathalie M. Delzenne, Kadiombo Bantubungi, Bart Staels, Margaux Nawrot, UCL - SSS/LDRI - Louvain Drug Research Institute, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Metabolism and Nutrition Research Group [Bruxelles, Belgique], Louvain Drug Research Institute [Bruxelles, Belgique] (LDRI), Université Catholique de Louvain = Catholic University of Louvain (UCL)-Université Catholique de Louvain = Catholic University of Louvain (UCL), This work was supported by grants from 'European Genomic Institute for Diabetes' (E.G.I.D., ANR-10-LABX-46), European Commission and Agence Nationale pour la Recherche (ANR-FXREn). B.S. holds a 'European Research Council advanced Grant' (694717). A.B., M.N., O.C.T. and M.S.T. received a PhD fellowship from the French Ministry of Research., ANR-11-BSV1-0032,FXRen,Rôle du récepteur nucléaire Farnesoid X Receptor (FXR) dans l'homéostasie énergétique(2011), European Project: 694717,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) ,ImmunoBile(2016), Récepteurs nucléaires, maladies cardiovasculaires et diabète (EGID), Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Louvain Drug Research Institute [Bruxelles, Belgique], Université Catholique de Louvain (UCL)-Université Catholique de Louvain (UCL), Bodescot, Myriam, BLANC - Rôle du récepteur nucléaire Farnesoid X Receptor (FXR) dans l'homéostasie énergétique - - FXRen2011 - ANR-11-BSV1-0032 - BLANC - VALID, Bile acid, immune-metabolism, lipid and glucose homeostasis - ImmunoBile - - H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) 2016-09-01 - 2021-08-31 - 694717 - VALID, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M)
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Male ,0301 basic medicine ,medicine.medical_specialty ,Colon ,medicine.drug_class ,Receptors, Cytoplasmic and Nuclear ,lcsh:Medicine ,Incretin ,030209 endocrinology & metabolism ,Enteroendocrine cell ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Article ,Receptors, G-Protein-Coupled ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Nuclear receptors ,Glucagon-Like Peptide 1 ,Internal medicine ,medicine ,Animals ,Secretion ,Gastrointestinal hormones ,lcsh:Science ,Receptor ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,Mice, Knockout ,Multidisciplinary ,Bile acid ,Chemistry ,Microbiota ,lcsh:R ,digestive, oral, and skin physiology ,Endocrine system and metabolic diseases ,Nutrient signalling ,Fatty Acids, Volatile ,Glucagon-like peptide-1 ,3. Good health ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,Nuclear receptor ,Preclinical research ,lcsh:Q ,Farnesoid X receptor - Abstract
The gut microbiota participates in the control of energy homeostasis partly through fermentation of dietary fibers hence producing short-chain fatty acids (SCFAs), which in turn promote the secretion of the incretin Glucagon-Like Peptide-1 (GLP-1) by binding to the SCFA receptors FFAR2 and FFAR3 on enteroendocrine L-cells. We have previously shown that activation of the nuclear Farnesoid X Receptor (FXR) decreases the L-cell response to glucose. Here, we investigated whether FXR also regulates the SCFA-induced GLP-1 secretion. GLP-1 secretion in response to SCFAs was evaluated ex vivo in murine colonic biopsies and in colonoids of wild-type (WT) and FXR knock-out (KO) mice, in vitro in GLUTag and NCI-H716 L-cells activated with the synthetic FXR agonist GW4064 and in vivo in WT and FXR KO mice after prebiotic supplementation. SCFA-induced GLP-1 secretion was blunted in colonic biopsies from GW4064-treated mice and enhanced in FXR KO colonoids. In vitro FXR activation inhibited GLP-1 secretion in response to SCFAs and FFAR2 synthetic ligands, mainly by decreasing FFAR2 expression and downstream Gαq-signaling. FXR KO mice displayed elevated colonic FFAR2 mRNA levels and increased plasma GLP-1 levels upon local supply of SCFAs with prebiotic supplementation. Our results demonstrate that FXR activation decreases L-cell GLP-1 secretion in response to inulin-derived SCFA by reducing FFAR2 expression and signaling. Inactivation of intestinal FXR using bile acid sequestrants or synthetic antagonists in combination with prebiotic supplementation may be a promising therapeutic approach to boost the incretin axis in type 2 diabetes.
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- 2020
22. A sister lineage of the Mycobacterium tuberculosis complex discovered in the African Great Lakes region
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Ngabonziza, Jean Claude Semuto, Loiseau, Chloé, Marceau, Michael, Jouet, Agathe, Menardo, Fabrizio, Tzfadia, Oren, Antoine, Rudy, Niyigena, Esdras Belamo, Mulders, Wim, Fissette, Kristina, Diels, Maren, Gaudin, Cyril, Duthoy, Stéphanie, Ssengooba, Willy, André, Emmanuel, Kaswa, Michel K., Habimana, Yves Mucyo, Brites, Daniela, Affolabi, Dissou, Mazarati, Jean Baptiste, de Jong, Bouke Catherine, Rigouts, Leen, Gagneux, Sebastien, Meehan, Conor Joseph, Supply, Philip, Rwanda Biomedical Center (RBC), Institute of Tropical Medicine [Antwerp] (ITM), Universiteit Antwerpen [Antwerpen], Swiss Tropical and Public Health Institute [Basel], University of Basel (Unibas), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Genoscreen [Lille], Institut Pasteur de Lille, Makerere University [Kampala, Ouganda] (MAK), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), National Tuberculosis Program [Kinshasa], Laboratoire de Référence des Mycobactéries [Cotonou, Benin], Hôpital Centre LAZARET [Cotonou, Bénin], University of Bradford, This work was supported by EDCTP2 grant DRIA2014-326—DIAMA of the European Union, the Belgian General Directorate for Development Cooperation (PhD fellowship to J.C.S.N.), Grant ANR-16-CE35-0009 from Agence Nationale de la Recherche, the Swiss National Science Foundation (Grants 310030_188888, IZRJZ3_164171, IZLSZ3_170834 and CRSII5_177163), and the European Research Council (309540-EVODRTB)., ANR-16-CE35-0009,TBemerg,Naissance d'un tueur: facteurs génétiques et adaptations métaboliques impliquées dans l'émergence des bacilles tuberculeux épidémiques(2016), European Project: 309540,EC:FP7:ERC,ERC-2012-StG_20111109,EVODRTB(2013), Universiteit Antwerpen = University of Antwerpen [Antwerpen], and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)
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DNA, Bacterial ,Male ,Genotype ,Classification and taxonomy ,[SDV]Life Sciences [q-bio] ,PULMONARY TUBERCULOSIS ,Science ,SEQUENCE ,Article ,Evolutionary genetics ,Evolution, Molecular ,Limit of Detection ,Tuberculosis, Multidrug-Resistant ,Humans ,Uganda ,lcsh:Science ,MUTATION ,Bacterial genomics ,Phylogeny ,GENOMIC DELETIONS ,Aged ,DRUG-RESISTANCE ,Likelihood Functions ,Science & Technology ,RESISTANT TUBERCULOSIS ,Rwanda ,Genetic Variation ,Genomics ,Mycobacterium tuberculosis ,ASSOCIATION ,FRAMEWORK ,EVOLUTION ,Multidisciplinary Sciences ,INSIGHTS ,Phenotype ,Mutation ,Science & Technology - Other Topics ,lcsh:Q ,Pathogens ,Rifampin ,Engineering sciences. Technology ,Genome, Bacterial - Abstract
The human- and animal-adapted lineages of the Mycobacterium tuberculosis complex (MTBC) are thought to have expanded from a common progenitor in Africa. However, the molecular events that accompanied this emergence remain largely unknown. Here, we describe two MTBC strains isolated from patients with multidrug resistant tuberculosis, representing an as-yet-unknown lineage, named Lineage 8 (L8), seemingly restricted to the African Great Lakes region. Using genome-based phylogenetic reconstruction, we show that L8 is a sister clade to the known MTBC lineages. Comparison with other complete mycobacterial genomes indicate that the divergence of L8 preceded the loss of the cobF genome region - involved in the cobalamin/vitamin B12 synthesis - and gene interruptions in a subsequent common ancestor shared by all other known MTBC lineages. This discovery further supports an East African origin for the MTBC and provides additional molecular clues on the ancestral genome reduction associated with adaptation to a pathogenic lifestyle., The human- and animal-adapted lineages of the Mycobacterium tuberculosis complex (MTBC) are thought to be evolved from a common progenitor in Africa. Here, the authors identify two MTBC strains isolated from patients with multidrug-resistant tuberculosis, representing an as-yet-unknown lineage further supporting an East African origin for the MTBC.
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- 2020
23. Targeting nonsense-mediated mRNA decay in colorectal cancers with microsatellite instability
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Dem Bokhari, A., Vincent Jonchere, Anaïs Lagrange, Romane Bertrand, Magali Svrcek, Laëtitia Marisa, Olivier Buhard, Malorie Greene, Anastasia Demidova, Jieshuang Jia, Eric Adriaenssens, Thierry Chassat, Denis Biard, Jean-François Fléjou, Fabrice Lejeune, Alexis Duval, Ada Collura, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Site de recherche intégrée en cancérologie (SiRIC CURAMUS), Institut Universitaire de Cancérologie [Sorbonne Université] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Mécanismes de tumorigenèse et thérapies ciblées, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Signalisation des facteurs de croissance dans le cancer du sein. Protéomique fonctionnelle, Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme d'Expérimentations et de Hautes Technologies Animales [Lille], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Universitaire de Cancérologie [Paris] (IUC), and Collura, Ada
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[SDV] Life Sciences [q-bio] ,[SDV]Life Sciences [q-bio] ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,neoplasms ,lcsh:RC254-282 ,digestive system diseases - Abstract
International audience; Abstract Nonsense-mediated mRNA decay (NMD) is responsible for the degradation of mRNAs with a premature termination codon (PTC). The role of this system in cancer is still quite poorly understood. In the present study, we evaluated the functional consequences of NMD activity in a subgroup of colorectal cancers (CRC) characterized by high levels of mRNAs with a PTC due to widespread instability in microsatellite sequences (MSI). In comparison to microsatellite stable (MSS) CRC, MSI CRC expressed increased levels of two critical activators of the NMD system, UPF1/2 and SMG1/6/7. Suppression of NMD activity led to the re-expression of dozens of PTC mRNAs. Amongst these, several encoded mutant proteins with putative deleterious activity against MSI tumorigenesis (e.g., HSP110DE9 chaperone mutant). Inhibition of NMD in vivo using amlexanox reduced MSI tumor growth, but not that of MSS tumors. These results suggest that inhibition of the oncogenic activity of NMD may be an effective strategy for the personalized treatment of MSI CRC.
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- 2018
24. Flickering in Information Spreading Precedes Critical Transitions in Financial Markets
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Hayette Gatfaoui, Philippe de Peretti, IÉSEG School Of Management [Puteaux], Centre d'économie de la Sorbonne [CES], Lille économie management - UMR 9221 [LEM], Centre d'économie de la Sorbonne (CES), Université Paris 1 Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS), Lille économie management - UMR 9221 (LEM), and Université d'Artois (UA)-Université catholique de Lille (UCL)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
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0301 basic medicine ,Multidisciplinary ,Warning system ,Computer science ,Flicker ,Financial market ,lcsh:R ,lcsh:Medicine ,[SHS.ECO]Humanities and Social Sciences/Economics and Finance ,Article ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Financial crisis ,Systemic risk ,Econometrics ,lcsh:Q ,Cluster analysis ,lcsh:Science ,030217 neurology & neurosurgery ,Stock (geology) ,ComputingMilieux_MISCELLANEOUS - Abstract
As many complex dynamical systems, financial markets exhibit sudden changes or tipping points that can turn into systemic risk. This paper aims at building and validating a new class of early warning signals of critical transitions. We base our analysis on information spreading patterns in dynamic temporal networks, where nodes are connected by short-term causality. Before a tipping point occurs, we observe flickering in information spreading, as measured by clustering coefficients. Nodes rapidly switch between "being in" and "being out" the information diffusion process. Concurrently, stock markets start to desynchronize. To capture these features, we build two early warning indicators based on the number of regime switches, and on the time between two switches. We divide our data into two sub-samples. Over the first one, using receiver operating curve, we show that we are able to detect a tipping point about one year before it occurs. For instance, our empirical model perfectly predicts the Global Financial Crisis. Over the second sub-sample, used as a robustness check, our two statistical metrics also capture, to a large extent, the 2016 financial turmoil. Our results suggest that our indicators have informational content about a future tipping point, and have therefore strong policy implications.
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- 2019
25. Occurrence and repair of alkylating stress in the intracellular pathogen Brucella abortus
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Xavier De Bolle, Arnaud Machelart, Katy Poncin, Eric Muraille, Emanuele G. Biondi, Nayla Francis, Agnès Roba, Kevin Willemart, Nicolas Zeippen, Georges Potemberg, Antonella Fioravanti, Stéphane P. Vincent, Ravikumar Jimmidi, Department of Bio-engineering Sciences, Research Unit in Molecular Biology (URBM-NARILIS), Université de Namur [Namur] (UNamur), Unité de Chimie Organique University of Namur, Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de chimie bactérienne (LCB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut de Microbiologie de la Méditerranée (IMM), University of Oxford [Oxford], Fédération Wallonie-Bruxelles (ARC 17/22-087) and by the FRS-FNRS 'Brucell-cycle' (PDR T.0060.15), ANR-11-JSV3-0003,CASTACC,Analyse comparative des facteurs de transduction des signaux contrôlant la régulation du cycle cellulaire chez les alpha-protéobactéries(2011), Université de Namur [Namur], Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), ANR: Analyse comparative des facteurs de transduction des signaux contrôlant la régulation du cycle cellulaire chez les alpha-protéobactéries – CASTACC,Projet CASTACC,ANR-JCJC-2011-Castacc, Université de Lille-Centre National de la Recherche Scientifique (CNRS), and University of Oxford
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0301 basic medicine ,Alkylation ,DNA Repair ,[SDV]Life Sciences [q-bio] ,Cellular microbiology ,Brucella abortus ,General Physics and Astronomy ,medicine.disease_cause ,DNA damage response ,Mice ,chemistry.chemical_compound ,lcsh:Science ,Pathogen ,Multidisciplinary ,3. Good health ,Technologie de l'environnement, contrôle de la pollution ,Host-Pathogen Interactions ,Pathogens ,DNA repair ,Science ,030106 microbiology ,Biology ,Article ,Brucellosis ,General Biochemistry, Genetics and Molecular Biology ,Microbiology ,03 medical and health sciences ,Stress, Physiological ,medicine ,Animals ,Chimie ,Gene ,Escherichia coli ,Transcription factor ,Physique ,Macrophages ,DNA adducts ,Pathogenic bacteria ,General Chemistry ,DNA Methylation ,Astronomie ,RAW 264.7 Cells ,030104 developmental biology ,chemistry ,Vacuoles ,lcsh:Q ,DNA ,DNA Damage - Abstract
It is assumed that intracellular pathogenic bacteria have to cope with DNA alkylating stress within host cells. Here we use single-cell reporter systems to show that the pathogen Brucella abortus does encounter alkylating stress during the first hours of macrophage infection. Genes encoding direct repair and base-excision repair pathways are required by B. abortus to face this stress in vitro and in a mouse infection model. Among these genes, ogt is found to be under the control of the conserved cell-cycle transcription factor GcrA. Our results highlight that the control of DNA repair in B. abortus displays distinct features that are not present in model organisms such as Escherichia coli., SCOPUS: ar.j, info:eu-repo/semantics/published
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- 2019
26. Effectiveness of in-Line Filters to Completely Remove Particulate Contamination During a Pediatric Multidrug Infusion Protocol
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Maxime, Perez, Bertrand, Décaudin, Wadih, Abou Chahla, Brigitte, Nelken, Laurent, Storme, Morgane, Masse, Christine, Barthélémy, Gilles, Lebuffe, Pascal, Odou, Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Jeanne de Flandre [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Environnement périnatal et croissance - EA 4489 (EPS), CHU Lille, Université de Lille, Environnement Périnatal et Santé - EA 4489, Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - EA 7365, Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA], Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], and Environnement périnatal et croissance - EA 4489 [EPS]
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[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics ,Leukemia ,lcsh:R ,lcsh:Medicine ,Article ,Intensive Care Units ,Pharmaceutical Preparations ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Humans ,Drug Therapy, Combination ,Particulate Matter ,lcsh:Q ,Particle Size ,Child ,Drug Contamination ,Infusions, Intravenous ,lcsh:Science ,Filtration - Abstract
International audience; The large number of drugs administered simultaneously to neonates and children in hospital results in the formation of particles that are potentially infused. We have investigated the ability of IV in-line filters to eliminate particulate matter from multidrug infusion lines and so prevent contamination. The impact on particle occurrence of the internal volume of the IV line below the in-line filter was then evaluated. The multidrug therapy given to children was reproduced with and without in-line filtration. Three combinations with a filter were tested to vary the internal volume (V) between the filter and the catheter egress. The catheter was then connected to a dynamic particle count to evaluate the particulate matter potentially administered to children during infusion. The introduction of in-line filters led to a significant reduction in overall particulate matter, from 416,974 [208,479-880,229] to 7,551 [1,985-11,287] particles (p
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- 2018
27. Spatiotemporal control of DNA-based chemical reaction network via electrochemical activation in microfluidics
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Guillaume Gines, Yannick Rondelez, Yannick Coffinier, Alexis Vlandas, Ievgen Kurylo, Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Laboratory for Integrated Micro Mechatronics Systems (LIMMS), The University of Tokyo (UTokyo)-Centre National de la Recherche Scientifique (CNRS), Gulliver (UMR 7083), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), NanoBioInterfaces - IEMN (NBI - IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Bio-Micro-Electro-Mechanical Systems - IEMN (BIOMEMS - IEMN), I.K. would like to thank the CNRS and the region Haut de France for financial support. A.V. would like to thank the region Haut de France for support for funding the NanoTrami (Project Emergent)., and Renatech Network
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0301 basic medicine ,[SDV.BIO]Life Sciences [q-bio]/Biotechnology ,Dynamical systems theory ,Computer science ,Distributed computing ,Microfluidics ,lcsh:Medicine ,Molecular systems ,Electrochemistry ,Network topology ,Chemical reaction ,Article ,law.invention ,Autocatalysis ,03 medical and health sciences ,chemistry.chemical_compound ,DNA computing ,law ,Microfluidic channel ,[SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics ,lcsh:Science ,Electrodes ,Multidisciplinary ,lcsh:R ,DNA ,Electrochemical Techniques ,030104 developmental biology ,chemistry ,Scalability ,Key (cryptography) ,lcsh:Q ,Gold ,Unconventional computing ,Biosensor - Abstract
In recent years, DNA computing frameworks have been developed to create dynamical systems which can be used for information processing. These emerging synthetic biochemistry tools can be leveraged to gain a better understanding of fundamental biology but can also be implemented in biosensors and unconventional computing. Most of the efforts so far have focused on changing the topologies of DNA molecular networks or scaling them up. Several issues have thus received little attention and remain to be solved to turn them into real life technologies. In particular, the ability to easily interact in real-time with them is a key requirement. The previous attempts to achieve this aim have used microfluidic approaches, such as valves, which are cumbersome. We show that electrochemical triggering using DNA-grafted micro-fabricated gold electrodes can be used to give instructions to these molecular systems. We demonstrate how this approach can be used to release at specific times and locations DNA- based instructions. In particular, we trigger reaction-diffusion autocatalytic fronts in microfluidic channels. While limited by the stability of the Au-S bond, this easy to implement, versatile and scalable technique can be used in any biology laboratory to provide new ways to interact with any DNA-based computing framework.
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- 2018
28. Protactinium and the intersection of actinide and transition metal chemistry
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Wilson, Richard E., De Sio, Stephanie, Vallet, Valérie, Chemical Sciences and Engineering Division, Argonne National Laboratory [Lemont] (ANL), Physico-Chimie Moléculaire Théorique (PCMT), Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 (PhLAM), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Hauts de France council and European Regional Development Fund (ERDF) through the Contrat de Projets Etat-Region (CPER CLIMIBIO)., and ANR-11-LABX-0005,Cappa,Physiques et Chimie de l'Environnement Atmosphérique(2011)
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Science ,Protactinium ,General Physics and Astronomy ,chemistry.chemical_element ,010402 general chemistry ,01 natural sciences ,Article ,General Biochemistry, Genetics and Molecular Biology ,Transition metal ,Atomic orbital ,Reactivity (chemistry) ,lcsh:Science ,ComputingMilieux_MISCELLANEOUS ,Multidisciplinary ,010405 organic chemistry ,Chemistry ,General Chemistry ,Actinide ,3. Good health ,0104 chemical sciences ,[CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry ,Chemical physics ,Polyoxometalate ,Density functional theory ,lcsh:Q ,[PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph] ,Relativistic quantum chemistry - Abstract
The role of the 5f and 6d orbitals in the chemistry of the actinide elements has been of considerable interest since their discovery and synthesis. Relativistic effects cause the energetics of the 5f and 6d orbitals to change as the actinide series is traversed left to right imparting a rich and complex chemistry. The 5f and 6d atomic states cross in energy at protactinium (Pa), making it a potential intersection between transition metal and actinide chemistries. Herein, we report the synthesis of a Pa-peroxo cluster, A6(Pa4O(O2)6F12) [A = Rb, Cs, (CH3)4N], formed in pursuit of an actinide polyoxometalate. Quantum chemical calculations at the density functional theory level demonstrate equal 5f and 6d orbital participation in the chemistry of Pa and increasing 5f orbital participation for the heavier actinides. Periodic changes in orbital character to the bonding in the early actinides highlights the influence of the 5f orbitals in their reactivity and chemical structure., The role of the 5f and 6d orbitals in the chemical bonding of the actinide elements remains debated. Here, the authors synthesize and study a tetranuclear protactinium peroxo cluster and demonstrate that protactinium represents an intersection of actinide (5f) and transition metal (6d) chemistries.
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- 2018
29. Dovitinib in patients with gastrointestinal stromal tumour refractory and/or intolerant to imatinib
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Stefania Crippa, Javier Martin-Broto, Axel Le Cesne, Claudia Weiss, Sebastian Bauer, Elena Fumagalli, Olivier Bouché, Alessandro Comandone, Jean-Yves Blay, Antoine Adenis, M. Camozzi, Carlo Barone, Xavier Garcia del Muro, Antoine Italiano, Giovanni Grignani, Ramon Castellana, Claudia Valverde, Heikki Joensuu, Antonio López Pousa, University of Helsinki, Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard [Lyon], Gradenigo Hospital, Hospital Universitario Virgen del Rocío [Sevilla], Medical Genetics Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Candiolo Cancer Institute (IRCCS), Institut Català d'Oncologia-IDIBELL, 08907 L’Hospitalet (Barcelona) and Universitat de, Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Vall d'Hebron University Hospital [Barcelona], Hospital de la Santa Creu i Sant Pau, Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Bergonié [Bordeaux], UNICANCER, Universität Duisburg-Essen [Essen], Observatoire sociologique du changement (OSC), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), Novartis Pharma AG, Novartis Vaccines and Diagnostics [Siena], Novartis Farmacéutica SA, Sarcome, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut Gustave Roussy (IGR), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Université de Lille-UNICANCER, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Università cattolica del Sacro Cuore [Milano] (Unicatt), Clinicum, Heikki Joensuu / Principal Investigator, and Department of Oncology
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0301 basic medicine ,Oncology ,Male ,Cancer Research ,MULTICENTER ,Medizin ,Salvage therapy ,RESISTANT ,Quinolones ,gastrointestinal stromal tumour ,0302 clinical medicine ,Clinical endpoint ,FAILURE ,Gastrointestinal Neoplasms ,KIT MUTATIONS ,GiST ,Sunitinib ,Middle Aged ,Prognosis ,3. Good health ,Tolerability ,SAFETY ,030220 oncology & carcinogenesis ,PHASE-II ,Imatinib Mesylate ,Female ,TYROSINE KINASE INHIBITOR ,medicine.drug ,GIST ,Adult ,medicine.medical_specialty ,Gastrointestinal Stromal Tumors ,3122 Cancers ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,SUNITINIB ,03 medical and health sciences ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,MESH: Benzimidazoles/pharmacology ,Biomarkers, Tumor/metabolism ,Drug resistance, Neoplasm/drug therapy ,Adverse effect ,neoplasms ,Protein Kinase Inhibitors ,Aged ,Neoplasm Staging ,Salvage Therapy ,business.industry ,Imatinib ,EFFICACY ,refractory ,030104 developmental biology ,Imatinib mesylate ,imatinib ,Drug Resistance, Neoplasm ,Clinical Study ,Benzimidazoles ,dovitinib ,business ,Follow-Up Studies - Abstract
Background: This multicentre phase II trial (DOVIGIST) evaluated the antitumour activity of dovitinib as second-line treatment of patients with gastrointestinal stromal tumour (GIST) refractory to imatinib or who do not tolerate imatinib. Methods: Patients received oral dovitinib 500 mg day(-1), 5 days on/2 days off, until GIST progression or unacceptable toxicity, with an objective to evaluate efficacy, assessed as the disease control rate (DCR) at 12 weeks. Tumour assessment and response to dovitinib therapy were evaluated by Response Evaluation Criteria In Solid Tumours (RECIST v1.1) and the Choi criteria. Secondary objectives included assessment of progression-free survival (PFS), safety and tolerability, and DCR at the end of treatment. Results: Thirty-eight of the 39 patients enrolled had histologically confirmed GIST. The DCR at 12 weeks was 52.6% (90% confidence interval (CI), 38.2-66.7%) meeting the preset efficacy criterion for the primary end point. The objective response rate (complete response+partial response) was 2.6% (1 of 38; 90% CI, 0.1-11.9%), and 5.3% (n = 2; 90% CI, 0.9-15.7%) at the end of the study. The median PFS was 4.6 months (90% CI, 2.8-7.4 months). Dose interruption was required in 26 patients (66.7%), of which 18 (69.2%) were due to adverse events. The most frequently observed grade 3 adverse events included hypertension (n = 7), fatigue (n = 5), vomiting (n = 4), hypertriglyceridaemia (n = 4), and gamma-glutamyltransferase increase (n = 4). Conclusions: Dovitinib is an active treatment for patients with GIST who are intolerant to imatinib or whose GIST progresses on imatinib.
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- 2017
30. Predicting poor prognosis recurrence in women with endometrial cancer: a nomogram developed by the FRANCOGYN study group
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Emile Daraï, Gilles Body, Vincent Lavoué, Sofiane Bendifallah, Marcos Ballester, Lobna Ouldamer, Pierre Collinet, Emilie Raimond, Jean Lévêque, Charles Coutant, Olivier Graesslin, Cyril Touboul, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Epidemiologie, Systèmes d'information, Modélisation, Institut National de la Santé et de la Recherche Médicale (INSERM), Gynécologie-obstétrique et médecine de la reproduction - Maternité [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Expert en Endométriose [CHU Tenon] (GRC6 C3E), Institut Mère Enfant Alix de Champagne, Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, CHU Pontchaillou [Rennes], Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupe de recherche clinique Centre Expert en Endométriose (GRC 6 - C3E), Sorbonne Université (SU), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)
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0301 basic medicine ,Oncology ,Risk ,Cancer Research ,medicine.medical_specialty ,recurrence ,medicine.medical_treatment ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,nomogram ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,medicine ,metastasis ,Humans ,10. No inequality ,Retrospective Studies ,Receiver operating characteristic ,Proportional hazards model ,business.industry ,Endometrial cancer ,peritoneal carcinomatosis ,Retrospective cohort study ,Nomogram ,medicine.disease ,Prognosis ,Confidence interval ,Endometrial Neoplasms ,Nomograms ,030104 developmental biology ,030220 oncology & carcinogenesis ,endometrial cancer ,Clinical Study ,Lymphadenectomy ,Female ,business - Abstract
International audience; Background - The purpose of this study was to develop a nomogram to predict 'poor prognosis recurrence' (PPR) in women treated for endometrial cancer (EC). Methods - The data of 861 women who received primary surgical treatment between January 2001 and December 2013 were abstracted from a prospective multicenter database. Data were randomly split into two sets: training and validation with a predefined 2/3 ratio. A Cox proportional hazards multivariate model of selected prognostic features was performed in the training cohort (n=574) to develop a nomogram predicting PPRs. The nomogram was validated in the validation cohort of 287 patients. Results - In the training cohort, 82 (14.3%) developed subsequent PPR. Age, histologic type and grade, lymphovascular space invasion status, FIGO stage, and nodal staging (SLN±pelvic and/or para-aortic lymphadenectomy) were independently associated with subsequent PPR. The nomogram showed an area under the receiver operating characteristic curve (AUC) of 0.82 (95% confidence interval (CI), 0.73-0.89) in the training set. The validation set showed a good discrimination with an AUC of 0.75 (95% CI, 0.65-0.83). Conclusions - We have developed a robust tool that is able to predict subsequent PPRs in women with FIGO I-III EC.
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- 2016
31. A ferroptosis-based panel of prognostic biomarkers for amyotrophic lateral sclerosis
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Devos, David, Moreau, Caroline, Kyheng, Maeva, Garçon, Guillaume, Rolland, Anne Sophie, Blasco, Hélène, Gelé, Patrick, Timothée Lenglet, T, Veyrat-Durebex, C, Corcia, Philippe, Dutheil, Mary, Bede, Peter, Jeromin, Andreas, Oeckl, Patrick, Otto, Markus, Meininger, Vincent, Danel-Brunaud, Véronique, Devedjian, Jean-Christophe, Duce, James A, Pradat, Pierre François, CHU Lille, CNRS, Inserm, Institut Pasteur de Lille, Université de Lille, IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - EA 4483, Troubles cognitifs dégénératifs et vasculaires - U1171, IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483, Service de Biostatistiques [CHRU Lille], Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301 [CIC Lille], Troubles cognitifs dégénératifs et vasculaires - U 1171 [TCDV], Devos, David [0000-0002-2417-799X], Otto, Markus [0000-0003-4273-4267], and Apollo - University of Cambridge Repository
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Adult ,Male ,Neurons ,Aldehydes ,Iron ,Amyotrophic Lateral Sclerosis ,Isoprostanes ,Middle Aged ,Prognosis ,8-Hydroxy-2'-Deoxyguanosine ,Neurofilament Proteins ,Predictive Value of Tests ,Ferritins ,Disease Progression ,Ferroptosis ,Humans ,Female ,Lipid Peroxidation ,Biomarkers ,Follow-Up Studies - Abstract
Accurate patient stratification into prognostic categories and targeting Amyotrophic Lateral Sclerosis (ALS)-associated pathways may pave the way for promising trials. We evaluated blood-based prognostic indicators using an array of pathological markers. Plasma samples were collected as part of a large, phase III clinical trial (Mitotarget/TRO19622) at months 1, 6, 12 and 18. The ALSFRS-r score was used as a proxy of disease progression to assess the predictive value of candidate biological indicators. First, established clinical predictors were evaluated in all 512 patients. Subsequently, pathologic markers, such as proxies of neuronal integrity (Neurofilament light chain and phosphorylated heavy chain), DNA oxidation (8-oxo-2'-desoxyguanosine), lipid peroxidation (4-hydroxy-2-nonenal, isoprostane), inflammation (interleukin-6) and iron status (ferritin, hepcidin, transferrin) were assessed in a subset of 109 patients that represented the whole cohort. Markers of neuronal integrity, DNA and lipid oxidation, as well as iron status at baseline are accurate predictors of disability at 18-month follow-up. The composite scores of these markers in association with established clinical predictors enable the accurate forecasting of functional decline. The identified four biomarkers are all closely associated with 'ferroptosis', a recently discovered form of programmed cell death with promising therapeutic targets. The predictive potential of these pathophysiology-based indicators may offer superior patient stratification for future trials, individualised patient care and resource allocation. 9;1
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- 2019
32. ERRα promotes breast cancer cell dissemination to bone by increasing RANK expression in primary breast tumors
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Jane E. Aubin, Geoffrey Vargas, Edith Bonnelye, Sophie Vacher, Marie Brevet, Pascal Reboul, M Filipits, Ivan Bièche, C Boyault, W Jacot, Lamia Bouazza, Sandra Geraci, Keltouma Driouch, Francesco Pantano, Michael Gnant, Catherine Alix-Panabières, M Gervais, Laure Cayrefourcq, Philippe Clézardin, M Bouchet, M Mazel, Martine Croset, Claire Benetollo, C Kan, Martine Duterque-Coquillaud, Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases [LYOS], Institut de Génomique Fonctionnelle de Lyon [IGFL], Ingénierie Moléculaire et Physiopathologie Articulaire [IMoPA], Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) [IAB], The University of Sydney, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center [CRNL], Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 [AIDMP], Institut Curie [Paris], Università Campus Bio-Medico di Roma / University Campus Bio-Medico of Rome [ UCBM], Medizinische Universität Wien = Medical University of Vienna, Institut de Recherche en Cancérologie de Montpellier [IRCM - U1194 Inserm - UM], Institut de biologie de Lille - IBL [IBLI], Mécanismes de tumorigenèse et thérapies ciblées, Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Institut Curie, Università Campus Bio-Medico di Roma / University Campus Bio-Medico of Rome ( UCBM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Biochemistry [University of Toronto], University of Toronto, Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, This work was supported by the National Center for Scientific Research (CNRS) to EB, the National Institute of Health and Medical Research (INSERM), the University of Lyon1, La Ligue Nationale (Drôme), Inserm-Transfert (EB). GV was supported by the Labex DEVweCAN, MG, MB by the French National Cancer Institute (INCa), CK by the Marie-Curie-Individual-Fellowship (655777-miR-OMeS). CAP, LC, and MM by CANCER-ID (FP7/2007-2013) and EFPIA., The authors thank Anne Flourens, Cyprien Tilmant, Tina Louadj, and both CeCIL and ALECS platforms (Faculté de Médecine Laennec, Lyon) for their assistance., Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER], Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biochimie Générale et Médicale, INSERM-CNRS U.189 Faculté de Médecine Lyon-Sud, Centre de Recherche en Géomatique [Laval] (CRG), Université Laval, Swiss Federal Office for the Environment FOEN, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de Génétique [Institut Curie, Paris] (Unité de Pharmacogénomique), Department of Surgery, Breast Health Center, Medical University Vienna, Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Université Grenoble Alpes (UGA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de biologie et chimie des protéines [Lyon] (IBCP), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
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0301 basic medicine ,Cancer Research ,Breast Neoplasms/pathology ,Bone Neoplasms/secondary ,[SDV]Life Sciences [q-bio] ,MESH: Gene Expression Regulation, Neoplastic ,Transcriptome ,Mammary Neoplasms, Animal/genetics ,Mice ,0302 clinical medicine ,Circulating tumor cell ,Neoplasm Proteins/genetics ,MESH: Breast Neoplasms/genetics ,MESH: Animals ,MESH: Breast Neoplasms/metabolism ,ComputingMilieux_MISCELLANEOUS ,MESH: Breast Neoplasms/pathology ,Mice, Inbred BALB C ,Receptor Activator of Nuclear Factor-kappa B ,Receptors, Estrogen/genetics ,MESH: Receptor Activator of Nuclear Factor-kappa B/genetics ,Metastatic breast cancer ,Primary tumor ,Neoplasm Proteins ,3. Good health ,Gene Expression Regulation, Neoplastic ,Receptors, Estrogen ,RANKL ,030220 oncology & carcinogenesis ,MESH: Bone Neoplasms/metabolism ,Female ,MESH: Bone Neoplasms/secondary ,Breast Neoplasms/metabolism ,MESH: Bone Neoplasms/genetics ,Receptor Activator of Nuclear Factor-kappa B/biosynthesis ,MESH: Mice, Inbred BALB C ,Bone Neoplasms ,Breast Neoplasms ,Mammary Neoplasms, Animal ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Mammary Neoplasms, Animal/metabolism ,Neoplasm Proteins/metabolism ,Biology ,Breast Neoplasms/genetics ,03 medical and health sciences ,Breast cancer ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Genetics ,medicine ,Animals ,Humans ,MESH: Neoplasm Proteins/genetics ,MESH: Receptors, Estrogen/metabolism ,MESH: Neoplasm Proteins/metabolism ,MESH: Mammary Neoplasms, Animal/pathology ,Mammary Neoplasms, Animal/pathology ,Molecular Biology ,MESH: Mice ,PI3K/AKT/mTOR pathway ,Receptor Activator of Nuclear Factor-kappa B/genetics ,MESH: Humans ,MESH: Receptors, Estrogen/genetics ,Bone Neoplasms/genetics ,medicine.disease ,Receptors, Estrogen/metabolism ,MESH: Mammary Neoplasms, Animal/genetics ,030104 developmental biology ,Cancer cell ,Bone Neoplasms/metabolism ,Cancer research ,biology.protein ,MESH: Receptor Activator of Nuclear Factor-kappa B/biosynthesis ,MESH: Female ,Bone Neoplasms/pathology ,MESH: Mammary Neoplasms, Animal/metabolism ,MESH: Bone Neoplasms/pathology - Abstract
International audience; Bone is the most common metastatic site for breast cancer. Estrogen-related-receptor alpha (ERRα) has been implicated in cancer cell invasiveness. Here, we established that ERRα promotes spontaneous metastatic dissemination of breast cancer cells from primary mammary tumors to the skeleton. We carried out cohort studies, pharmacological inhibition, gain-of-function analyses in vivo and cellular and molecular studies in vitro to identify new biomarkers in breast cancer metastases. Meta-analysis of human primary breast tumors revealed that high ERRα expression levels were associated with bone but not lung metastases. ERRα expression was also detected in circulating tumor cells from metastatic breast cancer patients. ERRα overexpression in murine 4T1 breast cancer cells promoted spontaneous bone micro-metastases formation when tumor cells were inoculated orthotopically, whereas lung metastases occurred irrespective of ERRα expression level. In vivo, Rank was identified as a target for ERRα. That was confirmed in vitro in Rankl stimulated tumor cell invasion, in mTOR/pS6K phosphorylation, by transactivation assay, ChIP and bioinformatics analyses. Moreover, pharmacological inhibition of ERRα reduced primary tumor growth, bone micro-metastases formation and Rank expression in vitro and in vivo. Transcriptomic studies and meta-analysis confirmed a positive association between metastases and ERRα/RANK in breast cancer patients and also revealed a positive correlation between ERRα and BRCA1 mut carriers. Taken together, our results reveal a novel ERRα/RANK axis by which ERRα in primary breast cancer promotes early dissemination of cancer cells to bone. These findings suggest that ERRα may be a useful therapeutic target to prevent bone metastases.
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- 2019
33. β-catenin knockdown promotes nherf1-mediated survival of colorectal cancer cells: implications for a double-targeted therapy
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Michel Salzet, Valeria Famiglini, Concetta Saponaro, Luca Mologni, Giuseppe La Regina, Sara Sergio, Michele Maffia, Romano Silvestri, Candice Gautier, Valentina Naccarato, Addolorata Coluccia, Stefano Gianni, Antonio Coluccia, Carlo Gambacorti Passerini, Daniele Vergara, Maria De Luca, Cecilia Bucci, Isabelle Fournier, Daniela Bonetti, Istituto Tumori 'Giovanni Paolo II' [Bari], Liceo Classico Giovanni Paolo II [Lecce LE, Italie], University of Salento [Lecce], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Laboratorio Pasteur [Istituto Pasteur-Fondazione Cenci Bolognetti, Rome], Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), SALZET, Michel, Saponaro, C, Sergio, S, Coluccia, A, De Luca, M, La Regina, G, Mologni, L, Famiglini, V, Naccarato, V, Bonetti, D, Gautier, C, Gianni, S, Vergara, D, Salzet, M, Fournier, I, Bucci, C, Silvestri, R, Passerini, C, Maffia, M, Passerini, Cg, and Coluccia, Aml
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0301 basic medicine ,Cancer Research ,Sodium-Hydrogen Exchangers ,Cell Survival ,[SDV]Life Sciences [q-bio] ,beta-catenin ,nherf1 ,colorectal cancer cells ,Apoptosis ,Biology ,medicine.disease_cause ,Small hairpin RNA ,03 medical and health sciences ,Transcription Factor 4 ,Genetic ,Cell Line, Tumor ,Antineoplastic Combined Chemotherapy Protocols ,Genetics ,Gene Knockdown Techniques ,medicine ,Humans ,Molecular Biology ,beta Catenin ,Gene knockdown ,Sulfonamides ,Wnt signaling pathway ,Phosphoproteins ,3. Good health ,Gene Expression Regulation, Neoplastic ,[SDV] Life Sciences [q-bio] ,Protein Transport ,030104 developmental biology ,Catenin ,Mutation ,Cancer research ,KRAS ,Carcinogenesis ,Colorectal Neoplasms ,Chromatin immunoprecipitation - Abstract
International audience; Nuclear activated β-catenin plays a causative role in colorectal cancers (CRC) but remains an elusive therapeutic target. Using human CRC cells harboring different Wnt/β-catenin pathway mutations in APC/KRAS or β-catenin/KRAS genes, and both genetic and pharmacological knockdown approaches, we show that oncogenic β-catenin signaling negatively regulates the expression of NHERF1 (Na+/H+ exchanger 3 regulating factor 1), a PDZ-adaptor protein that is usually lost or downregulated in early dysplastic adenomas to exacerbate nuclear β-catenin activity. Chromatin immunoprecipitation (ChIP) assays demonstrated that β-catenin represses NHERF1 via TCF4 directly, while the association between TCF1 and the Nherf1 promoter increased upon β-catenin knockdown. To note, the occurrence of a cytostatic survival response in settings of single β-catenin-depleted CRC cells was abrogated by combining NHERF1 inhibition via small hairpin RNA (shRNA) or RS5517, a novel PDZ1-domain ligand of NHERF1 that prevented its ectopic nuclear entry. Mechanistically, dual NHERF1/β-catenin targeting promoted an autophagy-to-apoptosis switch consistent with the activation of Caspase-3, the cleavage of PARP and reduced levels of phospho-ERK1/2, Beclin-1, and Rab7 autophagic proteins compared with β-catenin knockdown alone. Collectively, our data unveil novel β-catenin/TCF-dependent mechanisms of CRC carcinogenesis, also offering preclinical proof of concept for combining β-catenin and NHERF1 pharmacological inhibitors as a mechanism-based strategy to augment apoptotic death of CRC cells refractory to current Wnt/β-catenin-targeted therapeutics.
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- 2018
34. Strong Reduction of Thermal Conductivity and Enhanced Thermoelectric Properties in CoSbS1-xSex Paracostibite
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Georg K. H. Madsen, Sandip Bhattacharya, Gilles Dennler, Pascal Roussel, Daniel Péré, Radoslaw Chmielowski, Alain Jacob, Kenzo Moriya, Stéphane Jacob, Bruno Delatouche, Unité de Catalyse et Chimie du Solide - UMR 8181 (UCCS), Centrale Lille Institut (CLIL)-Université d'Artois (UA)-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Lille, Swiss Fed Inst Aquat Sci & Technol, CH-6047 Kastanienbaum, Université de Lausanne, IMRA Europe - Sophia Antipolis, IMRA Europe, Université d'Artois (UA)-Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Université de Lausanne = University of Lausanne (UNIL)
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Multidisciplinary ,Materials science ,Condensed matter physics ,business.industry ,Alloy ,02 engineering and technology ,engineering.material ,[CHIM.INOR]Chemical Sciences/Inorganic chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Thermoelectric materials ,01 natural sciences ,0104 chemical sciences ,Reduction (complexity) ,Thermal conductivity ,Semiconductor ,Phase (matter) ,Thermoelectric effect ,engineering ,Density functional theory ,0210 nano-technology ,business ,ComputingMilieux_MISCELLANEOUS - Abstract
In order to reduce the thermal conductivity of CoSbS, a newly developed thermoelectric semiconductor, we have aimed at intentionally induce atomic disorder in its structure. This endeavor was guided by Density Functional Theory(DFT) calculations which indicated that substituting sulfur with selenium might be easily achievable experimentally because of the low formation energy of this point defect. Thereby, CoSbS1−xSex compounds having 0 ≤ x ≤ 1 have been synthesized by solid state reaction. Besides the expected semiconducting paracostibite phase, we have observed the appearance of a semimetallic costibite phase, never reported experimentally before. This cross-fertilized theoretical and experimental approach allowed us to reduce by 50% the thermal conductivity of paracostibite and therefore reach a maximum zT of 0.62 at 730 K. This makes this entirely new CoSbS1−xSex alloy very attractive for further optimizations and potential usage in thermoelectric applications.
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- 2017
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35. Strain-specific estimation of epidemic success provides insights into the transmission dynamics of tuberculosis
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Gérard Carret, Véronique Jacomo, Oana Dumitrescu, Ghislaine Blasquez, Gerard Lina, Maxime Barbier, Jean-Philippe Rasigade, Isabelle Fredenucci, Jean-Pierre Flandrois, Sandrine Boisset, Anne Carricajo, Philip Supply, Michèle Pérouse de Montclos, Thierry Wirth, Catherine Pichat, Anne-Sophie Ronnaux-Baron, Christine Godin-Benhaim, Florence Ader, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), Comité Départemental d’Hygiène Sociale - CLAT69 [Lyon), Agence régionale de santé Auvergne Rhône Alpes (ARS), Laboratoire de Bactériologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Eurofins Biomnis, Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Muséum national d'Histoire naturelle (MNHN)-École Pratique des Hautes Études (EPHE), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS 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)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
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0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Tuberculosis ,Genotype ,Minisatellite Repeats ,Biology ,Article ,law.invention ,03 medical and health sciences ,law ,Risk Factors ,Epidemiology ,medicine ,Humans ,Aged ,Estimation ,Multidisciplinary ,Sputum ,Genetic Variation ,Mycobacterium tuberculosis ,Middle Aged ,medicine.disease ,Virology ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,3. Good health ,030104 developmental biology ,Minisatellite ,Transmission (mechanics) ,Haplotypes ,Cohort ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,medicine.symptom ,Demography - Abstract
The transmission dynamics of tuberculosis involves complex interactions of socio-economic and, possibly, microbiological factors. We describe an analytical framework to infer factors of epidemic success based on the joint analysis of epidemiological, clinical and pathogen genetic data. We derive isolate-specific, genetic distance-based estimates of epidemic success, and we represent success-related time-dependent concepts, namely epidemicity and endemicity, by restricting analysis to specific time scales. The method is applied to analyze a surveillance-based cohort of 1,641 tuberculosis patients with minisatellite-based isolate genotypes. Known predictors of isolate endemicity (older age, native status) and epidemicity (younger age, sputum smear positivity) were identified with high confidence (P
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- 2017
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36. In vivo imaging of the Muc5b gel-forming mucin
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Mylene Magnien, Céline Portal, Jean Luc Desseyn, Valérie Gouyer, Ségolène Plet, Frédéric Gottrand, Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Inserm, Université de Lille, CHU Lille, and Lille Inflammation Research International Center - U 995 [LIRIC]
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0301 basic medicine ,[SDV]Life Sciences [q-bio] ,Mice, Transgenic ,Article ,Green fluorescent protein ,Mice ,03 medical and health sciences ,Organ Culture Techniques ,0302 clinical medicine ,Live cell imaging ,medicine ,Animals ,Humans ,Secretion ,Lung ,Goblet cell ,Interleukin-13 ,Multidisciplinary ,Chemistry ,Mucin ,respiratory system ,Mucin-5B ,Mucus ,Molecular Imaging ,3. Good health ,Cell biology ,Trachea ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Vagina ,Interleukin 13 ,Female ,Goblet Cells ,Nasal Cavity ,Preclinical imaging - Abstract
Gel-forming mucins are macromolecules produced by goblet cells and responsible for the mucus gel formation. Changes in goblet cell density and in gel-forming mucin production have emerged as sensitive indicators for mucosal diseases. A Muc5b-GFP tagged reporter mouse was used to assess Muc5b production in mouse tissues by immunofluorescence microscopy and fluorescent activity using stereromicroscopy and probe-based confocal laser endomicroscopy. Muc5b production was followed longitudinally by recording the fluorescent activity in vagina and in embryonic lung explants under stimulation by interleukin 13. We show that the GFP is easily visualized in the mouse adult ear, nose, trachea, gallbladder, and cervix. Live Muc5b is also easily monitored in the nasal cavity, trachea and vagina where its production varies during the estrus cycle with a peak at the proestrus phase and in pregnant mice. Explant culture of reporter mouse embryonic whole lung shows that interleukin 13 stimulates Muc5b production. The transgenic Muc5b-GFP mouse is unique and suitable to study the mechanisms that regulate Muc5b production/secretion and mucous cell differentiation by live imaging and can be applied to test drug efficacy in mucosal disease models.
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- 2017
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37. Experimental evidence for circular inference in schizophrenia
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Jardri, Renaud, Duverne, Sandrine, Litvinova, Alexandra S, Denève, Sophie, Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neurosciences Cognitives & Computationnelles (LNC2), Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lomonosov Moscow State University (MSU), Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193 (SCALab), Laboratoire de Neurosciences cognitives (LNC), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université de Lille, CNRS, CHU Lille, Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193, Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 [SCALab], Laboratoire de Neurosciences Cognitives & Computationnelles [LNC2], Lomonosov Moscow State University [MSU], Institut National de la Santé et de la Recherche Médicale (INSERM)-Département d'Etudes Cognitives - ENS Paris (DEC), and École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)
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Adult ,Male ,Psychological Tests ,Hallucinations ,Science ,[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences ,Bayes Theorem ,Models, Psychological ,behavioral disciplines and activities ,Article ,Delusions ,[SCCO]Cognitive science ,[SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health ,Case-Control Studies ,mental disorders ,Schizophrenia ,Humans ,Female ,Schizophrenic Psychology - Abstract
Schizophrenia (SCZ) is a complex mental disorder that may result in some combination of hallucinations, delusions and disorganized thinking. Here SCZ patients and healthy controls (CTLs) report their level of confidence on a forced-choice task that manipulated the strength of sensory evidence and prior information. Neither group's responses can be explained by simple Bayesian inference. Rather, individual responses are best captured by a model with different degrees of circular inference. Circular inference refers to a corruption of sensory data by prior information and vice versa, leading us to ‘see what we expect' (through descending loops), to ‘expect what we see' (through ascending loops) or both. Ascending loops are stronger for SCZ than CTLs and correlate with the severity of positive symptoms. Descending loops correlate with the severity of negative symptoms. Both loops correlate with disorganized symptoms. The findings suggest that circular inference might mediate the clinical manifestations of SCZ., Schizophrenia is a mental disorder characterized by hallucinations and delusions. Here the authors report a novel probabilistic inference task in which compared to healthy subjects, schizophrenia patients show greater degree of circular inference that matches the severity of their clinical symptoms.
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- 2017
38. Sorafenib and irinotecan (NEXIRI) as second- or later-line treatment for patients with metastatic colorectal cancer and KRAS-mutated tumours: a multicentre Phase I/II trial
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Pierre Laurent-Puig, Sylvain Poujol, Françoise Desseigne, S. Thezenas, Thibault Mazard, Evelyne Crapez, Emmanuelle Samalin, E. Francois, Antoine Adenis, T. Conroy, J.F. Seitz, Julien Taieb, M.P. Galais, Jaafar Bennouna, F. Boissière, Marc Ychou, Eric Assenat, O. Bouche, Frédéric Bibeau, CRLCC Val d'Aurelle - Paul Lamarque, Hôpital universitaire Robert Debré [Reims], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon], Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CRLC Val d'Aurelle-Paul Lamarque, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Lille Nord de France (COMUE)-UNICANCER, UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, CRLCC Oscar Lambret, Institut de Cancérologie de l'Ouest, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), and Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
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Male ,Cancer Research ,Colorectal cancer ,medicine.medical_treatment ,Camptothecin/administration & dosage/analogs & derivatives ,Gastroenterology ,tyrosine kinase inhibitor ,Antineoplastic Combined Chemotherapy Protocols ,Clinical endpoint ,80 and over ,clinic ,Aged, 80 and over ,education.field_of_study ,metastatic colorectal cancer ,ras Proteins/*genetics ,Mutation ,Middle Aged ,Sorafenib ,3. Good health ,Oncology ,Disease Progression ,Female ,Colorectal Neoplasms ,medicine.drug ,Adult ,Niacinamide ,medicine.medical_specialty ,Niacinamide/administration & dosage/analogs & derivatives ,Population ,Colorectal Neoplasms/*drug therapy/genetics ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Neutropenia ,Irinotecan ,Disease-Free Survival ,Proto-Oncogene Proteins p21(ras) ,Internal medicine ,Proto-Oncogene Proteins ,medicine ,Humans ,Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ,education ,neoplasms ,Aged ,Chemotherapy ,business.industry ,Phenylurea Compounds ,medicine.disease ,digestive system diseases ,Surgery ,KRAS gene mutation ,Regimen ,Phenylurea Compounds/administration & dosage ,Clinical Study ,ras Proteins ,Proto-Oncogene Proteins/*genetics ,Camptothecin ,business - Abstract
IMPACT: 5.922; International audience; BACKGROUND: This trial evaluated the feasibility and efficacy of combined sorafenib and irinotecan (NEXIRI) as second- or later-line treatment of patients with KRAS-mutated metastatic colorectal cancer (mCRC), who had progressed after irinotecan-based chemotherapy. METHODS: In Phase I, in a 3+3 dose escalation schedule, patients received irinotecan (125, 150 or 180 mg m(-2) every 2 weeks), in combination with 400 mg sorafenib b.d. The primary end point was the maximum-tolerated dose of irinotecan. In Phase II, the primary end point was disease control rate (DCR). Secondary end points were progression-free survival (PFS), overall survival (OS) and toxicity. RESULTS: Phase I included 10 patients (median age 63 (49-73)); no dose-limiting toxicity was seen. In Phase II, 54 patients (median age 60 (43-80) years) received irinotecan 180 mg m(-)(2) every 2 weeks with sorafenib 400 mg b.d. Nine patients (17%) remained on full-dose sorafenib. The DCR was 64.9% (95% CI, 51-77). Median PFS and OS were 3.7 (95% CI, 3.2-4.7) and 8.0 (95% CI, 4.8-9.7) months, respectively. Toxicities included Grade 3 diarrhoea (37%), neutropenia (18%), hand-foot syndrome (13%) and Grade 4 neutropenia (17%). CONCLUSION: The NEXIRI regimen showed promising activity as second- or later-line treatment in this heavily pretreated mCRC population (ClinicalTrials.gov NCT00989469).
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- 2014
39. Brønsted acid sites based on penta-coordinated aluminum species
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Jean-Paul Amoureux, Catherine Stampfl, Zichun Wang, Kyung Duk Kim, Yijiao Jiang, Jun Huang, Julien Trébosc, Alfons Baiker, Olivier Lafon, Univ Sydney, Sch Chem & Biomol Engn, Sydney, NSW 2006, Australia, The University of Sydney, Department of Engineering, Macquarie University, Sydney, Unité de Catalyse et Chimie du Solide - UMR 8181 (UCCS), Centrale Lille Institut (CLIL)-Université d'Artois (UA)-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Lille, School of Physics [Sydney], Institute for Chemical and Bioengineering [ETH Zurich] (ICB), Department of Chemistry and Applied Biosciences [ETH Zürich] (D-CHAB), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), and Université d'Artois (UA)-Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
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Science ,Inorganic chemistry ,General Physics and Astronomy ,chemistry.chemical_element ,02 engineering and technology ,Solid acid ,010402 general chemistry ,01 natural sciences ,General Biochemistry, Genetics and Molecular Biology ,Article ,Catalysis ,Ammonia ,chemistry.chemical_compound ,Aluminium ,ComputingMilieux_MISCELLANEOUS ,Multidisciplinary ,Direct observation ,[CHIM.MATE]Chemical Sciences/Material chemistry ,General Chemistry ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Amorphous solid ,chemistry ,0210 nano-technology ,Brønsted–Lowry acid–base theory ,High magnetic field - Abstract
Zeolites and amorphous silica-alumina (ASA), which both provide Brønsted acid sites (BASs), are the most extensively used solid acid catalysts in the chemical industry. It is widely believed that BASs consist only of tetra-coordinated aluminum sites (AlIV) with bridging OH groups in zeolites or nearby silanols on ASA surfaces. Here we report the direct observation in ASA of a new type of BAS based on penta-coordinated aluminum species (AlV) by 27Al-{1H} dipolar-mediated correlation two-dimensional NMR experiments at high magnetic field under magic-angle spinning. Both BAS-AlIV and -AlV show a similar acidity to protonate probe molecular ammonia. The quantitative evaluation of 1H and 27Al sites demonstrates that BAS-AlV co-exists with BAS-AlIV rather than replaces it, which opens new avenues for strongly enhancing the acidity of these popular solid acids., Nature Communications, 7, ISSN:2041-1723
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- 2016
40. A rapid and practical technique for real-time monitoring of biomolecular interactions using mechanical responses of macromolecules
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Hiroyuki Fujita, Laurent Jalabert, Mehmet C. Tarhan, Momoko Kumemura, Yannick Tauran, Anthony W. Coleman, Dominique Collard, Gregoire Perret, Beom Joon Kim, Nicolas Lafitte, Laboratory for Integrated Micro Mechatronics Systems (LIMMS), The University of Tokyo (UTokyo)-Centre National de la Recherche Scientifique (CNRS), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Multimatériaux et Interfaces (LMI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), The University of Tokyo (UTokyo), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
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0301 basic medicine ,Chemical substance ,Materials science ,Macromolecular Substances ,[SDV]Life Sciences [q-bio] ,Microfluidics ,Nanotechnology ,Biosensing Techniques ,02 engineering and technology ,Article ,03 medical and health sciences ,Humans ,Microelectromechanical systems ,Multidisciplinary ,Force spectroscopy ,DNA ,[CHIM.MATE]Chemical Sciences/Material chemistry ,Micro-Electrical-Mechanical Systems ,Microfluidic Analytical Techniques ,021001 nanoscience & nanotechnology ,Mechanical system ,030104 developmental biology ,Optical tweezers ,0210 nano-technology ,Biosensor ,Macromolecule - Abstract
International audience; Monitoring biological reactions using the mechanical response of macromolecules is an alternative approach to immunoassays for providing real-time information about the underlying molecular mechanisms. Although force spectroscopy techniques, e.g. AFM and optical tweezers, perform precise molecular measurements at the single molecule level, sophisticated operation prevent their intensive use for systematic biosensing. Exploiting the biomechanical assay concept, we used micro-electro mechanical systems (MEMS) to develop a rapid platform for monitoring bio/chemical interactions of bio macromolecules, e.g. DNA, using their mechanical properties. The MEMS device provided real-time monitoring of reaction dynamics without any surface or molecular modifications. A microfluidic device with a side opening was fabricated for the optimal performance of the MEMS device to operate at the air-liquid interface for performing bioassays in liquid while actuating/sensing in air. The minimal immersion of the MEMS device in the channel provided long-term measurement stability (>10 h). Importantly, the method allowed monitoring effects of multiple solutions on the same macromolecule bundle (demonstrated with DNA bundles) without compromising the reproducibility. We monitored two different types of effects on the mechanical responses of DNA bundles (stiffness and viscous losses) exposed to pH changes (2.1 to 4.8) and different Ag + concentrations (1 μM to 0.1 M). Mechanical properties of molecules are used to investigate a wide range of biological and chemical mechanisms varying from nucleic acid conformation to enzymatic reaction kinetics and from cell manipulation to motor protein operation 1. Unlike some of the other well-established methods that are often limited to smaller sized molecules , e.g. nuclear magnetic resonance (NMR) 2 and surface plasmon resonance (SPR) 3 , force spectroscopy techniques , e.g. optical tweezers 4,5 , magnetic tweezers 6-8 and AFM 9,10 , provide sensitive measurements on mechanical properties spanning six orders of magnitude in length (10 −10-10 −4 m) including macromolecules 1,11,12. These techniques provide information at the single molecule level to reveal novel properties of various different molecules. However, low throughput, surface modification, high-level operational skills and complicated calibra-tion/setup procedures exclude these techniques for rapid routine tests that are essential to provide statistically significant biomechanical information especially for clinical studies 13. As a result, a rapid, practical, time-and cost-efficient, automated and preferably portable method is beneficial as a complementary or alternative method to the conventional techniques to be employed even by non-specialists. MEMS technology presents certain advantages to cover the mentioned requirements for routinely performed assays on mechanical responses of macromolecules. MEMS, capable of conducting real-time mechanical sensing with electrical readouts associated with low noise and high stability measurements 14 , allows low
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- 2016
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41. Gradient Index Devices for the Full Control of Elastic Waves in Plates
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Daniel Torrent, Yabin Jin, Yan Pennec, Yongdong Pan, Bahram Djafari-Rouhani, Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Centre de Recherche Paul Pascal (CRPP), Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de dynamique et structure des matériaux moléculaires (LDSMM), Université de Lille, Sciences et Technologies-Université du Littoral Côte d'Opale (ULCO)-Centre National de la Recherche Scientifique (CNRS), Tongji University, Grant No. 443 ANR-11-ASTR-015, LabEx AMADEus (ANR-10- 444 LABX-42) in the framework of IdEx Bordeaux(ANR-10- 445IDEX-03-02), School of Aerospace Engineering and Applied Mechanics, Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), and Université catholique de Lille (UCL)-Université catholique de Lille (UCL)
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Physics ,Work (thermodynamics) ,Multidisciplinary ,Index (economics) ,Acoustics ,02 engineering and technology ,021001 nanoscience & nanotechnology ,01 natural sciences ,Article ,law.invention ,Lens (optics) ,[CHIM.POLY]Chemical Sciences/Polymers ,law ,Dispersion relation ,0103 physical sciences ,Broadband ,Acoustic metamaterials ,010306 general physics ,0210 nano-technology - Abstract
In this work, we present a method for the design of gradient index devices for elastic waves in plates. The method allows the design of devices to control the three fundamental modes, despite the fact that their dispersion relation is managed by different elastic constants. It is shown that by means of complex graded phononic crystals and thickness variations it is possible to independently design the three refractive indexes of these waves, allowing therefore their simultaneous control. The effective medium theory required for this purpose is presented and the method is applied to the design of the Luneburg and Maxwell lenses as well as to the design of a flat gradient index lens. Finally, numerical simulations are used to demonstrate the performance of the method in a broadband frequency region.
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- 2016
42. The proprotein convertase PC1/3 regulates TLR9 trafficking and the associated signaling pathways
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Robert Day, Adriana-Natalia Murgoci, Michel Salzet, Hugo Gagnon, Roxanne Desjardins, Franck Rodet, Isabelle Fournier, Marie Duhamel, Maxence Wisztorski, Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Sherbrooke (UdeS), SALZET, Michel, and Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
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STAT3 Transcription Factor ,0301 basic medicine ,endocrine system ,Endosome ,[SDV]Life Sciences [q-bio] ,Regulator ,Mice, Transgenic ,Proprotein convertase 1 ,Endosomes ,Biology ,Article ,Mice ,03 medical and health sciences ,Macrophages, Alveolar ,Animals ,Mice, Knockout ,Multidisciplinary ,NF-kappa B ,hemic and immune systems ,Proprotein convertase ,Hedgehog signaling pathway ,Rats ,Cell biology ,Enzyme Activation ,[SDV] Life Sciences [q-bio] ,Protein Transport ,CXCL2 ,030104 developmental biology ,Oligodeoxyribonucleotides ,Proprotein Convertase 1 ,Toll-Like Receptor 9 ,Proteolysis ,Macrophages, Peritoneal ,TLR4 ,Cytokines ,Signal transduction ,Protein Binding ,Signal Transduction - Abstract
Endosomal TLR9 is considered as a potent anti-tumoral therapeutic target. Therefore, it is crucial to decipher the mechanisms controlling its trafficking since it determines TLR9 activation and signalling. At present, the scarcity of molecular information regarding the control of this trafficking and signalling is noticeable. We have recently demonstrated that in macrophages, proprotein convertase 1/3 (PC1/3) is a key regulator of TLR4 Myd88-dependent signalling. In the present study, we established that PC1/3 also regulates the endosomal TLR9. Under CpG-ODN challenge, we found that PC1/3 traffics rapidly to co-localize with TLR9 in CpG-ODN-containing endosomes with acidic pH. In PC1/3 knockdown macrophages, compartmentalization of TLR9 was altered and TLR9 clustered in multivesicular bodies (MVB) as demonstrated by co-localization with Rab7. This demonstrates that PC1/3 controls TLR9 trafficking. This clustering of TLR9 in MVB dampened the anti-inflammatory STAT3 signalling pathway while it promoted the pro-inflammatory NF-kB pathway. As a result, macrophages from PC1/3 KO mice and rat PC1/3-KD NR8383 macrophages secreted more pro-inflammatory cytokines such as TNF-α, IL6, IL1α and CXCL2. This is indicative of a M1 pro-inflammatory phenotype. Therefore, PC1/3 KD macrophages represent a relevant mean for cell therapy as “Trojan” macrophages.
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- 2016
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43. Transcriptional, epigenetic and retroviral signatures identify regulatory regions involved in hematopoietic lineage commitment
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Silvio Bicciato, Fulvio Mavilio, Alessandro Ambrosi, Guidantonio Malagoli Tagliazucchi, Marco Severgnini, Oriana Romano, Gianluca De Bellis, Giuliana Ferrari, Annarita Miccio, Alessia Cavazza, Ermanno Rizzi, Valentina Poletti, Fabienne Cocchiarella, Clelia Peano, Claudia Rossi, Pasqualepaolo Pagliaro, Luca Petiti, Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Pierantoni-Morgagni Hospital, Partenaires INRAE, San Raffaele Telethon (TIGET), Institute for Gene Therapy, Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon, Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), École pratique des hautes études (EPHE), Romano, Oriana, Peano, Clelia, Tagliazucchi, Guidantonio Malagoli, Petiti, Luca, Poletti, Valentina, Cocchiarella, Fabienne, Rizzi, Ermanno, Severgnini, Marco, Cavazza, Alessia, Rossi, Claudia, Pagliaro, Pasqualepaolo, Ambrosi, Alessandro, Ferrari, Giuliana, Bicciato, Silvio, De Bellis, Gianluca, Mavilio, Fulvio, and Miccio, Annarita
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0301 basic medicine ,Gene Expression Regulation, Viral ,Cellular differentiation ,[SDV]Life Sciences [q-bio] ,Enhancer RNAs ,Biology ,Regulatory Sequences, Nucleic Acid ,Article ,Epigenesis, Genetic ,Histones ,03 medical and health sciences ,Consensus Sequence ,Epigenetic Profile ,Humans ,Position-Specific Scoring Matrices ,Cell Lineage ,Epigenetics ,Enhancer ,Promoter Regions, Genetic ,Transcription Initiation, Genetic ,Genetics ,Multidisciplinary ,epigenetics ,Base Sequence ,Multipotent Stem Cells ,Cell Differentiation ,differentiation ,Hematopoietic Stem Cells ,Cap analysis gene expression ,Chromatin ,030104 developmental biology ,Enhancer Elements, Genetic ,Retroviridae ,Organ Specificity ,Transcriptome ,Adult stem cell - Abstract
Genome-wide approaches allow investigating the molecular circuitry wiring the genetic and epigenetic programs of human somatic stem cells. Hematopoietic stem/progenitor cells (HSPC) give rise to the different blood cell types; however, the molecular basis of human hematopoietic lineage commitment is poorly characterized. Here, we define the transcriptional and epigenetic profile of human HSPC and early myeloid and erythroid progenitors by a combination of Cap Analysis of Gene Expression (CAGE), ChIP-seq and Moloney leukemia virus (MLV) integration site mapping. Most promoters and transcripts were shared by HSPC and committed progenitors, while enhancers and super-enhancers consistently changed upon differentiation, indicating that lineage commitment is essentially regulated by enhancer elements. A significant fraction of CAGE promoters differentially expressed upon commitment were novel, harbored a chromatin enhancer signature, and may identify promoters and transcribed enhancers driving cell commitment. MLV-targeted genomic regions co-mapped with cell-specific active enhancers and super-enhancers. Expression analyses, together with an enhancer functional assay, indicate that MLV integration can be used to identify bona fide developmentally regulated enhancers. Overall, this study provides an overview of transcriptional and epigenetic changes associated to HSPC lineage commitment, and a novel signature for regulatory elements involved in cell identity.
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- 2016
44. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance
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John R. B. Perry, James B. Meigs, José Dupuis, Luigi Ferrucci, Johan G. Eriksson, Vilmundur Gudnason, Eric J.G. Sijbrands, Jeanette S. Andrews, Jonna L. Grimsby, Lawrence F. Bielak, Peter Kovacs, Panos Deloukas, Marijana Peričić, Johannes H. Smit, Ruth J. F. Loos, Gonneke Willemsen, Eric Boerwinkle, Ben A. Oostra, Manuel Serrano-Ríos, Alena Stančáková, Meena Kumari, Antti Jula, Michael Marmot, Caroline S. Fox, Simon Heath, Guo Li, Ola Hansson, Gerard Waeber, Anne U. Jackson, Nicholas L. Smith, Markku Laakso, George Dedoussis, Aarno Palotie, Sara M. Willems, John F. Peden, Elisabeth Widen, Caroline Hayward, Alan F. Wright, Claes Ladenvall, May E. Montasser, María Teresa Martínez-Larrad, Peter Vollenweider, Louis Pérusse, Tamara B. Harris, Wen Hong L. Kao, Danijela Budimir, Denis Rybin, David B. Savage, Michael A. Province, Alisa K. Manning, Bruna Gigante, Najaf Amin, Lenore J. Launer, Naveed Sattar, Lori L. Bonnycastle, Göran Hallmans, Jeffrey R. O'Connell, Stéphane Lobbens, Jacques S. Beckmann, Gemma Cadby, J. Wouter Jukema, Maria Dimitriou, Michael Stumvoll, Max Vikström, Rona J. Strawbridge, Hugh Watkins, Lyle J. Palmer, Johanna Kuusisto, Aimo Ruokonen, Hanieh Yaghootkar, Yan V. Sun, Inês Barroso, Amy J. Swift, Nancy L. Pedersen, Lars Lind, Mladen Boban, Nita G. Forouhi, Ken K. Ong, Ivana Kolcic, Anke Tönjes, Timothy M. Frayling, Paul W. Franks, Narisu Narisu, Karin Leander, Serge Hercberg, Diana Zelenika, Sharon L.R. Kardia, Min A. Jhun, Marjo-Riitta Järvelin, Stella Trompet, Jaakko Kaprio, Toshiko Tanaka, David S. Siscovick, Toby Johnson, Cornelia M. van Duijn, Veikko Salomaa, Jose C. Florez, James F. Wilson, Leena Peltonen, Pilar Galan, Robert Clarke, Andrew A. Hicks, Claudia Langenberg, Anders Hamsten, David Couper, Albert Hofman, Dawn M. Waterworth, John Blangero, James S. Pankow, Nabila Bouatia-Naji, Sirkka Keinänen-Kiukaanniemi, Mark I. McCarthy, Valeriya Lyssenko, Leif Groop, Brenda W.J.H. Penninx, Ching-Ti Liu, Anuj Goel, Marina Pehlić, Michael Boehnke, Mika Kivimäki, Maria Sabater-Lleal, Emil Rehnberg, Ingrid B. Borecki, Ozren Polasek, Eco J. C. de Geus, Peter P. Pramstaller, Igor Rudan, Richard M. Watanabe, Pierre Meneton, Iva Miljkovic, Vincent Mooser, G. Mark Lathrop, John Beilby, Laura J. Rasmussen-Torvik, Arturo Corbató-Anchuelo, Yvonne Böttcher, Richard N. Bergman, Daniel R. Barnes, Paul C. D. Johnson, Mustafa Atalay, Aroon D. Hingorani, Olga D. Carlson, Perttu Salo, Jacqueline C.M. Witteman, Udo Seedorf, Timo Saaristo, Jian'an Luan, Nicholas J. Wareham, Gudny Eiriksdottir, Matti Uusitupa, Yongmei Liu, Jaakko Tuomilehto, Yurii S. Aulchenko, Peter Schwarz, Robert A. Scott, Lina Zgaga, Joseph Hung, Reedik Mägi, Maria Grazia Franzosi, Eric J. Brunner, Claude Bouchard, Ian Ford, Francis S. Collins, Ulf de Faire, Benjamin F. Voight, Erik Ingelsson, Mario A. Morken, Stefania Bandinelli, Nicole L. Glazer, Dmitry Shungin, Lars Lannfelt, André G. Uitterlinden, Tatijana Zemunik, Markus Perola, Kenneth Rice, Veronique Vitart, Kerrin S. Small, Jouke-Jan Hottenga, Han Chen, Jerome I. Rotter, Philippe Froguel, Karen L. Mohlke, Marie-Claude Vohl, Dorret I. Boomsma, Harry Campbell, Peter S. Chines, Pau Navarro, Vasiliki Lagou, Albert V. Smith, Kathleen Stirrups, Josephine M. Egan, Alan R. Shuldiner, Katri Räikkönen, Inga Prokopenko, Ping An, Rainer Rauramaa, Beverley Balkau, Thor Aspelund, Eleanor Wheeler, Mariza de Andrade, Richa Saxena, Jari Lahti, Cécile Lecoeur, Timo A. Lakka, Jennie Hui, Michael R. Erdos, Stavroula Kanoni, Kirsten Ohm Kyvik, Bengt Sennblad, Sarah H. Wild, Patricia A. Peyser, Patrik K. E. Magnusson, Claire Bellis, Elodie Eury, Jaana Lindström, Boston University [Boston] (BU), Broad Institute of Harvard and MIT, Partenaires INRAE, Massachusetts General Hospital, Massachusetts General Hospital [Boston], Department of Genetics [Boston], Harvard Medical School [Boston] (HMS), Department of Medicine, Université de Sherbrooke (UdeS), Addenbrooke's Hospital, Harvard Medical School [Boston] (HMS)-Beth Israel Deaconess Medical Center [Boston] (BIDMC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Université Lille Nord de France (COMUE), Department of Epidemiology, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System-Center for Social Epidemiology and Population Health, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford [Oxford], The Wellcome Trust Centre for Human Genetics [Oxford], The Netherlands Cancer Institute, Ontario Institute for Cancer Research, Mount Sinai Hospital [Toronto, Canada] (MSH), VU University Amsterdam, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], University of Michigan System, Queen Mary University of London (QMUL), The Wellcome Trust Sanger Institute [Cambridge], Lund University [Lund], Diabetes Centre, Lund University, University of Helsinki, Wake Forest School of Medicine, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, University of Maryland School of Medicine, University of Maryland System, University of Edinburgh, University of Exeter, Department of Twin Research and Genetic Epidemiology, King's College London, London, Northwestern University [Evanston], National Institute of Health and Welfare, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Lund University Diabetes Centre, Umeå University, National Institutes of Health, Centre for Medical Systems Biology, Netherlands Genomics Initiative, Washington University in Saint Louis (WUSTL), Department of Health Sciences Research, Mayo Clinic, Wake Forest University, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, University of Iceland, Institute of Biomedicine, Physiology, University of Eastern Finland, Institut National de la Santé et de la Recherche Médicale (INSERM), UMR S 1018, Université Paris-Sud - Paris 11 (UP11), Azienda Sanitaria Firenze, Department of Medical Genetics, Université de Lausanne (UNIL), Centre Hospitalier Universitaire Vaudois (CHUV), Queen Elizabeth II Medical Centre, Research Institute, University of Southern California (USC), University of Split, The University of Texas Health Science Center at Houston (UTHealth), Leipzig University, Pennington Biomedical Research Center, Department of Epidemiology & Public Health, University College of London [London] (UCL), San Carlos Clinical Hospital, University of North Carolina, Harokopio University, National Institute on Aging, Folkhälsan Research Centre, Vaasa Central Hospital, Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Psychiatry, EMGO - Lifestyle, overweight and diabetes, Epidemiology, Immunology, Erasmus School of Social and Behavioural Sciences, Clinical Genetics, Ophthalmology, Internal Medicine, DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Multiple Tissue Human Expression Resource (MUTHER) Consortium, Ahmadi, K.R., Ainali, C., Barrett, A., Bataille, V., Bell, J.T., Buil, A., Deloukas, P., Dermitzakis, E.T., Dimas, A.S., Durbin, R., Glass, D., Grundberg, E., Hassanali, N., Hedman, Å.K., Ingle, C., Knowles, D., Krestyaninova, M., Lindgren, C.M., Lowe, C.E., McCarthy, M.I., Meduri, E., di Meglio, P., Min, J.L., Montgomery, S.B., Nestle, F.O., Nica, A.C., Nisbet, J., O'Rahilly, S., Parts, L., Potter, S., Sekowska, M., Shin, S.Y., Small, K.S., Soranzo, N., Spector, T.D., Surdulescu, G., Travers, M.E., Tsaprouni, L., Tsoka, S., Wilk, A., Yang, T.P., Zondervan, K.T., Voight, B.F., Scott, L.J., Steinthorsdottir, V., Morris, A.P., Dina, C., Welch, R.P., Zeggini, E., Huth, C., Aulchenko, Y.S., Thorleifsson, G., McCulloch, L.J., Ferreira, T., Grallert, H., Amin, N., Wu, G., Willer, C.J., Raychaudhuri, S., McCarroll, S.A., Langenberg, C., Hofmann, O.M., Dupuis, J., Qi, L., Segrè, A.V., van Hoek, M., Navarro, P., Ardlie, K., Balkau, B., Benediktsson, R., Bennett, A.J., Blagieva, R., Boerwinkle, E., Bonnycastle, L.L., Boström, K.B., Bravenboer, B., Bumpstead, S., Burtt, N.P., Charpentier, G., Chines, P.S., Cornelis, M., Couper, D.J., Crawford, G., Doney, A.S., Elliott, K.S., Elliott, A.L., Erdos, M.R., Fox, C.S., Franklin, C.S., Ganser, M., Gieger, C., Grarup, N., Green, T., Griffin, S., Groves, C.J., Guiducci, C., Hadjadj, S., Herder, C., Isomaa, B., Jackson, A.U., Johnson, P.R., Jørgensen, T., Kao, W.H., Klopp, N., Kong, A., Kraft, P., Kuusisto, J., Lauritzen, T., Li, M., Lieverse, A., Lyssenko, V., Marre, M., Meitinger, T., Midthjell, K., Morken, M.A., Narisu, N., Nilsson, P., Owen, K.R., Payne, F., Perry, J.R., Petersen, A.K., Platou, C., Proença, C., Prokopenko, I., Rathmann, W., Rayner, N.W., Robertson, N.R., Rocheleau, G., Roden, M., Sampson, M.J., Saxena, R., Shields, B.M., Shrader, P., Sigurdsson, G., Sparsø, T., Strassburger, K., Stringham, H.M., Sun, Q., Swift, A.J., Thorand, B., Tichet, J., Tuomi, T., van Dam, R.M., van Haeften, T.W., van Herpt, T., van Vliet-Ostaptchouk, J.V., Walters, G.B., Weedon, M.N., Wijmenga, C., Witteman, J., Bergman, R.N., Cauchi, S., Collins, F.S., Gloyn, A.L., Gyllensten, U., Hansen, T., Hide, W.A., Hitman, G.A., Hofman, A., Hunter, D.J., Hveem, K., Laakso, M., Mohlke, K.L., Morris, A.D., Palmer, C.N., Pramstaller, P.P., Rudan, I., Sijbrands, E., Stein, L.D., Tuomilehto, J., Uitterlinden, A., Walker, M., Wareham, N.J., Watanabe, R.M., Abecasis, G.R., Boehm, B.O., Campbell, H., Daly, M.J., Hattersley, A.T., Hu, F.B., Meigs, J.B., Pankow, J.S., Pedersen, O., Wichmann, H.E., Barroso, I., Florez, J.C., Frayling, T.M., Groop, L., Sladek, R., Thorsteinsdottir, U., Wilson, J.F., Illig, T., Froguel, P., van Duijn, C.M., Stefansson, K., Altshuler, D., Boehnke, M., Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA)
- Subjects
Blood Glucose ,Netherlands Twin Register (NTR) ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,LOCI ,Genome-wide association study ,Type 2 diabetes ,SUSCEPTIBILITY ,Body Mass Index ,GLUCOSE ,Blood Glucose/metabolism ,Cholesterol, HDL/metabolism ,Diabetes Mellitus, Type 2/genetics ,Genome-Wide Association Study ,Humans ,Insulin/metabolism ,Insulin Resistance/genetics ,Polymorphism, Single Nucleotide ,0302 clinical medicine ,Insulin ,2. Zero hunger ,Genetics ,0303 health sciences ,COMMON VARIANTS ,3. Good health ,ENVIRONMENT INTERACTION ,OBESITY ,CORONARY-ARTERY-DISEASE ,medicine.medical_specialty ,030209 endocrinology & metabolism ,Accounting ,Biology ,Article ,03 medical and health sciences ,Insulin resistance ,SDG 3 - Good Health and Well-being ,Internal medicine ,Diabetes mellitus ,medicine ,030304 developmental biology ,Genetic association ,Glycemic ,loci ,SNP ,insulin ,business.industry ,Cholesterol, HDL ,medicine.disease ,Obesity ,POLYMORPHISM ,ASSOCIATION ANALYSIS ,Endocrinology ,Diabetes Mellitus, Type 2 ,TYPE-2 DIABETES RISK ,Insulin Resistance ,business - Abstract
Group Authors : DIAGRAM Consortium MUTHER Consortium variants influencing fasting glycemic traits and insulin resistance Seuls les 100 premiers auteurs ont été conservés dans la publication. La liste complète des auteurs et des des affiliations est disponible sur la publication https://www.nature.com/articles/ng.2274.pdf p. 667-669.; International audience; Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 x 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.
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- 2012
45. New insights into the genetic etiology of Alzheimer's disease and related dementias
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Bellenguez, C., Küçükali, F., Jansen, I. E., Kleineidam, L., Moreno-Grau, S., Amin, N., Naj, A. C., Campos-Martin, R., Grenier-Boley, B., Andrade, V., Holmans, P. A., Boland, A., Damotte, V., van der Lee, S. J., Costa, M. R., Kuulasmaa, T., Yang, Q., de Rojas, I., Bis, J. C., Yaqub, A., Prokic, I., Chapuis, J., Ahmad, S., Giedraitis, V., Aarsland, D., Garcia-Gonzalez, P., Abdelnour, C., Alarcón-Martín, E., Alcolea, D., Alegret, M., Alvarez, I., Álvarez, V., Armstrong, N. J., Tsolaki, A., Antúnez, C., Appollonio, I., Arcaro, M., Archetti, S., Pastor, A. A., Arosio, B., Athanasiu, L., Bailly, H., Banaj, N., Baquero, M., Barral, S., Beiser, A., Pastor, A. B., Below, J. E., Benchek, P., Benussi, L., Berr, C., Besse, C., Bessi, V., Binetti, G., Bizarro, A., Blesa, R., Boada, M., Boerwinkle, E., Borroni, B., Boschi, S., Bossù, P., Bråthen, G., Bressler, J., Bresner, C., Brodaty, H., Brookes, K. J., Brusco, L. I., Buiza-Rueda, D., Bûrger, K., Burholt, V., Bush, W. S., Calero, M., Cantwell, L. B., Chene, G., Chung, J., Cuccaro, M. L., Carracedo, Á., Cecchetti, R., Cervera-Carles, L., Charbonnier, C., Chen, H. -H., Chillotti, C., Ciccone, S., Claassen, J. A. H. R., Clark, C., Conti, E., Corma-Gómez, A., Costantini, E., Custodero, C., Daian, D., Dalmasso, M. C., Daniele, A., Dardiotis, E., Dartigues, J. -F., de Deyn, P. P., de Paiva Lopes, K., de Witte, L. D., Debette, S., Deckert, J., del Ser, T., Denning, N., Destefano, A., Dichgans, M., Diehl-Schmid, J., Diez-Fairen, M., Rossi, P. D., Djurovic, S., Duron, E., Düzel, E., Dufouil, C., Eiriksdottir, G., Engelborghs, S., Escott-Price, V., Espinosa, A., Ewers, M., Faber, K. M., Fabrizio, T., Nielsen, S. F., Fardo, D. W., Farotti, L., Fenoglio, C., Fernández-Fuertes, M., Ferrari, R., Ferreira, C. B., Ferri, E., Fin, B., Fischer, P., Fladby, T., Fließbach, K., Fongang, B., Fornage, M., Fortea, J., Foroud, T. M., Fostinelli, S., Fox, N. C., Franco-Macías, E., Bullido, M. J., Frank-García, A., Froelich, L., Fulton-Howard, B., Galimberti, D., García-Alberca, J. M., García-González, P., Garcia-Madrona, S., Garcia-Ribas, G., Ghidoni, R., Giegling, I., Giorgio, G., Goate, A. M., Goldhardt, O., Gomez-Fonseca, D., González-Pérez, A., Graff, C., Grande, G., Green, E., Grimmer, T., Grünblatt, E., Grunin, M., Gudnason, V., Guetta-Baranes, T., Haapasalo, A., Hadjigeorgiou, G., Haines, J. L., Hamilton-Nelson, K. L., Hampel, H., Hanon, O., Hardy, J., Hartmann, A. M., Hausner, L., Harwood, J., Heilmann-Heimbach, S., Helisalmi, S., Heneka, M. T., Hernández, I., Herrmann, M. J., Hoffmann, P., Holmes, C., Holstege, H., Vilas, R. H., Hulsman, M., Humphrey, J., Biessels, G. J., Jian, X., Johansson, C., Jun, G. R., Kastumata, Y., Kauwe, J., Kehoe, P. G., Kilander, L., Ståhlbom, A. K., Kivipelto, M., Koivisto, A., Kornhuber, J., Kosmidis, M. H., Kukull, W. A., Kuksa, P. P., Kunkle, B. W., Kuzma, A. B., Lage, C., Laukka, E. J., Launer, L., Lauria, A., Lee, C. -Y., Lehtisalo, J., Lerch, O., Lleó, A., Longstreth, W., Lopez, O., de Munain, A. L., Love, S., Löwemark, M., Luckcuck, L., Lunetta, K. L., Ma, Y., Macías, J., Macleod, C. A., Maier, W., Mangialasche, F., Spallazzi, M., Marquié, M., Marshall, R., Martin, E. R., Montes, A. M., Rodríguez, C. M., Masullo, C., Mayeux, R., Mead, S., Mecocci, P., Medina, M., Meggy, A., Mehrabian, S., Mendoza, S., Menéndez-González, M., Mir, P., Moebus, S., Mol, M., Molina-Porcel, L., Montrreal, L., Morelli, L., Moreno, F., Morgan, K., Mosley, T., Nöthen, M. M., Muchnik, C., Mukherjee, S., Nacmias, B., Ngandu, T., Nicolas, G., Nordestgaard, B. G., Olaso, R., Orellana, A., Orsini, M., Ortega, G., Padovani, A., Paolo, C., Papenberg, G., Parnetti, L., Pasquier, F., Pastor, P., Peloso, G., Pérez-Cordón, A., Pérez-Tur, J., Pericard, P., Peters, O., Pijnenburg, Y. A. L., Pineda, J. A., Piñol-Ripoll, G., Pisanu, C., Polak, T., Popp, J., Posthuma, D., Priller, J., Puerta, R., Quenez, O., Quintela, I., Thomassen, J. Q., Rábano, A., Rainero, I., Rajabli, F., Ramakers, I., Real, L. M., Reinders, M. J. T., Reitz, C., Reyes-Dumeyer, D., Ridge, P., Riedel-Heller, S., Riederer, P., Roberto, N., Rodriguez-Rodriguez, E., Rongve, A., Allende, I. R., Rosende-Roca, M., Royo, J. L., Rubino, E., Rujescu, D., Sáez, M. E., Sakka, P., Saltvedt, I., Sanabria, Á., Sánchez-Arjona, M. B., Sanchez-Garcia, F., Juan, P. S., Sánchez-Valle, R., Sando, S. B., Sarnowski, C., Satizabal, C. L., Scamosci, M., Scarmeas, N., Scarpini, E., Scheltens, P., Scherbaum, N., Scherer, M., Schmid, M., Schneider, A., Schott, J. M., Selbæk, G., Seripa, D., Serrano, M., Sha, J., Shadrin, A. A., Skrobot, O., Slifer, S., Snijders, G. J. L., Soininen, H., Solfrizzi, V., Solomon, A., Song, Y. E., Sorbi, S., Sotolongo-Grau, O., Spalletta, G., Spottke, A., Squassina, A., Stordal, E., Tartan, J. P., Tárraga, L., Tesí, N., Thalamuthu, A., Thomas, T., Tosto, G., Traykov, L., Tremolizzo, L., Tybjærg-Hansen, A., Uitterlinden, A., Ullgren, A., Ulstein, I., Valero, S., Valladares, O., Broeckhoven, C. V., Vance, J., Vardarajan, B. N., van der Lugt, A., Dongen, J. V., van Rooij, J., van Swieten, J., Vandenberghe, R., Verhey, F., Vidal, J. -S., Vogelgsang, J., Vyhnalek, M., Wagner, M., Wallon, D., Wang, L. -S., Wang, R., Weinhold, L., Wiltfang, J., Windle, G., Woods, B., Yannakoulia, M., Zare, H., Zhao, Y., Zhang, X., Zhu, C., Zulaica, M., Laczo, J., Matoska, V., Serpente, M., Assogna, F., Piras, F., Ciullo, V., Shofany, J., Ferrarese, C., Andreoni, S., Sala, G., Zoia, C. P., Zompo, M. D., Benussi, A., Bastiani, P., Takalo, M., Natunen, T., Laatikainen, T., Tuomilehto, J., Antikainen, R., Strandberg, T., Lindström, J., Peltonen, M., Abraham, R., Al-Chalabi, A., Bass, N. J., Brayne, C., Brown, K. S., Collinge, J., Craig, D., Deloukas, P., Fox, N., Gerrish, A., Gill, M., Gwilliam, R., Harold, D., Hollingworth, P., Johnston, J. A., Jones, L., Lawlor, B., Livingston, G., Lovestone, S., Lupton, M., Lynch, A., Mann, D., Mcguinness, B., Mcquillin, A., O’Donovan, M. C., Owen, M. J., Passmore, P., Powell, J. F., Proitsi, P., Rossor, M., Shaw, C. E., Smith, A. D., Gurling, H., Todd, S., Mummery, C., Ryan, N., Lacidogna, G., Adarmes-Gómez, A., Mauleón, A., Pancho, A., Gailhajenet, A., Lafuente, A., Macias-García, D., Martín, E., Pelejà, E., Carrillo, F., Merlín, I. S., Garrote-Espina, L., Vargas, L., Carrion-Claro, M., Marín, M., Labrador, M., Buendia, M., Alonso, M. 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T., Olivar, N., Cano, A., Macias, J., Maroñas, O., Nuñez-Llaves, R., Olivé, C., Adarmes-Gómez, A. D., Amer-Ferrer, G., Antequera, M., Burguera, J. A., Casajeros, M. J., Martinez de Pancorbo, M., Hevilla, S., Espinosa, M. A. L., Legaz, A., Manzanares, S., Marín-Muñoz, J., Marín, T., Martínez, B., Martínez, V., Martínez-Lage Álvarez, P., Iriarte, M. M., Periñán-Tocino, M. T., Real de Asúa, D., Rodrigo, S., Sastre, I., Vicente, M. P., Vivancos, L., Epelbaum, J., Hannequin, D., Campion, D., Deramecourt, V., Tzourio, C., Brice, A., Dubois, B., Williams, A., Thomas, C., Davies, C., Nash, W., Dowzell, K., Morales, A. C., Bernardo-Harrington, M., Turton, J., Lord, J., Brown, K., Vardy, E., Fisher, E., Warren, J. D., Ryan, N. S., Guerreiro, R., Uphill, J., Bass, N., Heun, R., Kölsch, H., Schürmann, B., Lacour, A., Herold, C., Powell, J., Patel, Y., Hodges, A., Becker, T., Warden, D., Wilcock, G., Clarke, R., Ben-Shlomo, Y., Hooper, N. M., Pickering-Brown, S., Sussams, R., Warner, N., Bayer, A., Heuser, I., Drichel, D., Klopp, N., Mayhaus, M., Riemenschneider, M., Pinchler, S., Feulner, T., Gu, W., van den Bussche, H., Hüll, M., Frölich, L., Wichmann, H. -E., Jöckel, K. -H., O’Donovan, M., Owen, M., Bahrami, S., Bosnes, I., Selnes, P., Bergh, S., Palotie, A., Daly, M., Jacob, H., Matakidou, A., Runz, H., John, S., Plenge, R., Mccarthy, M., Hunkapiller, J., Ehm, M., Waterworth, D., Fox, C., Malarstig, A., Klinger, K., Call, K., Behrens, T., Loerch, P., Mäkelä, T., Kaprio, J., Virolainen, P., Pulkki, K., Kilpi, T., Perola, M., Partanen, J., Pitkäranta, A., Kaarteenaho, R., Vainio, S., Turpeinen, M., Serpi, R., Laitinen, T., Mäkelä, J., Kosma, V. -M., Kujala, U., Tuovila, O., Hendolin, M., Pakkanen, R., Waring, J., Riley-Gillis, B., Liu, J., Biswas, S., Diogo, D., Marshall, C., Hu, X., Gossel, M., Graham, R., Cummings, B., Ripatti, S., Schleutker, J., Arvas, M., Carpén, O., Hinttala, R., Kettunen, J., Mannermaa, A., Laukkanen, J., Julkunen, V., Remes, A., Kälviäinen, R., Peltola, J., Tienari, P., Rinne, J., Ziemann, A., Esmaeeli, S., Smaoui, N., Lehtonen, A., Eaton, S., Lahdenperä, S., van Adelsberg, J., Michon, J., Kerchner, G., Bowers, N., Teng, E., Eicher, J., Mehta, V., Gormley, P., Linden, K., Whelan, C., Xu, F., Pulford, D., Färkkilä, M., Pikkarainen, S., Jussila, A., Blomster, T., Kiviniemi, M., Voutilainen, M., Georgantas, B., Heap, G., Rahimov, F., Usiskin, K., Lu, T., Oh, D., Kalpala, K., Miller, M., Mccarthy, L., Eklund, K., Palomäki, A., Isomäki, P., Pirilä, L., Kaipiainen-Seppänen, O., Huhtakangas, J., Lertratanakul, A., Hochfeld, M., Bing, N., Gordillo, J. 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Kathleen, A Welsh-Bohmer, Patrice, L Whitehead, Ellen, M Wijsman, Kirk, C Wilhelmsen, Benjamin, Williams, Jennifer, Williamson, Henrik, Wilms, Thomas, S Wingo, Thomas, Wisniewski, Randall, L Woltjer, Martin, Woon, Clinton, B Wright, Chuang-Kuo, Wu, Steven, G Younkin, Chang-En, Yu, Lei, Yu, Yuanchao, Zhang, Zhao, Yi, Xiongwei, Zhu, Hieab, Adams, Rufus, O Akinyemi, Muhammad, Ali, Nicola, Armstrong, Hugo, J Aparicio, Maryam, Bahadori, Monique, Breteler, Daniel, Chasman, Ganesh, Chauhan, Hata, Comic, Simon, Cox, Adrienne, L Cupples, Gail, Davies, Charles, S DeCarli, Marie-Gabrielle, Duperron, Josée, Dupuis, Tavia, Evans, Frank, Fan, Annette, Fitzpatrick, Alison, E Fohner, Mary, Ganguli, Mirjam, Geerlings, Stephen, J Glatt, Hector, M Gonzalez, Monica, Goss, Hans, Grabe, Mohamad, Habes, Susan, R Heckbert, Edith, Hofer, Elliot, Hong, Timothy, Hughes, Tiffany, F Kautz, Maria, Knol, William, Kremen, Paul, Lacaze, Jari, Lahti, Quentin Le Grand, Elizabeth, Litkowski, Shuo, Li, Dan, Liu, Xuan, Liu, Marisa, Loitfelder, Alisa, Manning, Pauline, Maillard, Riccardo, Marioni, Bernard, Mazoyer, Debora Melo van Lent, Hao, Mei, Aniket, Mishra, Paul, Nyquist, Jeffrey, O'Connell, Yash, Patel, Tomas, Paus, Zdenka, Pausova, Katri, Raikkonen-Talvitie, Moeen, Riaz, Stephen, Rich, Jerome, Rotter, Jose, Romero, Gena, Roshchupkin, Yasaman, Saba, Murali, Sargurupremraj, Helena, Schmidt, Reinhold, Schmidt, Joshua, M Shulman, Jennifer, Smith, Hema, Sekhar, Reddy, Rajula, Jean, Shin, Jeannette, Simino, Eeva, Sliz, Alexander, Teumer, Alvin, Thomas, Adrienne, Tin, Elliot, Tucker-Drob, Dina, Vojinovic, Yanbing, Wang, Galit, Weinstein, Dylan, Williams, Katharina, Wittfeld, Lisa, Yanek, Yunju, Yang, Bellenguez, C, Küçükali, F, Jansen, I, Kleineidam, L, Moreno-Grau, S, Amin, N, Naj, A, Campos-Martin, R, Grenier-Boley, B, Andrade, V, Holmans, P, Boland, A, Damotte, V, van der Lee, S, Costa, M, Kuulasmaa, T, Yang, Q, de Rojas, I, Bis, J, Yaqub, A, Prokic, I, Chapuis, J, Ahmad, S, Giedraitis, V, Aarsland, D, Garcia-Gonzalez, P, Abdelnour, C, Alarcón-Martín, E, Alcolea, D, Alegret, M, Alvarez, I, Álvarez, V, Armstrong, N, Tsolaki, A, Antúnez, C, Appollonio, I, Arcaro, M, Archetti, S, Pastor, A, Arosio, B, Athanasiu, L, Bailly, H, Banaj, N, Baquero, M, Barral, S, Beiser, A, Below, J, Benchek, P, Benussi, L, Berr, C, Besse, C, Bessi, V, Binetti, G, Bizarro, A, Blesa, R, Boada, M, Boerwinkle, E, Borroni, B, Boschi, S, Bossù, P, Bråthen, G, Bressler, J, Bresner, C, Brodaty, H, Brookes, K, Brusco, L, Buiza-Rueda, D, Bûrger, K, Burholt, V, Bush, W, Calero, M, Cantwell, L, Chene, G, Chung, J, Cuccaro, M, Carracedo, Á, Cecchetti, R, Cervera-Carles, L, Charbonnier, C, Chen, H, Chillotti, C, Ciccone, S, Claassen, J, Clark, C, Conti, E, Corma-Gómez, A, Costantini, E, Custodero, C, Daian, D, Dalmasso, M, Daniele, A, Dardiotis, E, Dartigues, J, de Deyn, P, de Paiva Lopes, K, de Witte, L, Debette, S, Deckert, J, Del Ser, T, Denning, N, Destefano, A, Dichgans, M, Diehl-Schmid, J, Diez-Fairen, M, Rossi, P, Djurovic, S, Duron, E, Düzel, E, Dufouil, C, Eiriksdottir, G, Engelborghs, S, Escott-Price, V, Espinosa, A, Ewers, M, Faber, K, Fabrizio, T, Nielsen, S, Fardo, D, Farotti, L, Fenoglio, C, Fernández-Fuertes, M, Ferrari, R, Ferreira, C, Ferri, E, Fin, B, Fischer, P, Fladby, T, Fließbach, K, Fongang, B, Fornage, M, Fortea, J, Foroud, T, Fostinelli, S, Fox, N, Franco-Macías, E, Bullido, M, Frank-García, A, Froelich, L, Fulton-Howard, B, Galimberti, D, García-Alberca, J, García-González, P, Garcia-Madrona, S, Garcia-Ribas, G, Ghidoni, R, Giegling, I, Giorgio, G, Goate, A, Goldhardt, O, Gomez-Fonseca, D, González-Pérez, A, Graff, C, Grande, G, Green, E, Grimmer, T, Grünblatt, E, Grunin, M, Gudnason, V, Guetta-Baranes, T, Haapasalo, A, Hadjigeorgiou, G, Haines, J, Hamilton-Nelson, K, Hampel, H, Hanon, O, Hardy, J, Hartmann, A, Hausner, L, Harwood, J, Heilmann-Heimbach, S, Helisalmi, S, Heneka, M, Hernández, I, Herrmann, M, Hoffmann, P, Holmes, C, Holstege, H, Vilas, R, Hulsman, M, Humphrey, J, Biessels, G, Jian, X, Johansson, C, Jun, G, Kastumata, Y, Kauwe, J, Kehoe, P, Kilander, L, Ståhlbom, A, Kivipelto, M, Koivisto, A, Kornhuber, J, Kosmidis, M, Kukull, W, Kuksa, P, Kunkle, B, Kuzma, A, Lage, C, Laukka, E, Launer, L, Lauria, A, Lee, C, Lehtisalo, J, Lerch, O, Lleó, A, Longstreth, W, Lopez, O, de Munain, A, Love, S, Löwemark, M, Luckcuck, L, Lunetta, K, Ma, Y, Macías, J, Macleod, C, Maier, W, Mangialasche, F, Spallazzi, M, Marquié, M, Marshall, R, Martin, E, Montes, A, Rodríguez, C, Masullo, C, Mayeux, R, Mead, S, Mecocci, P, Medina, M, Meggy, A, Mehrabian, S, Mendoza, S, Menéndez-González, M, Mir, P, Moebus, S, Mol, M, Molina-Porcel, L, Montrreal, L, Morelli, L, Moreno, F, Morgan, K, Mosley, T, Nöthen, M, Muchnik, C, Mukherjee, S, Nacmias, B, Ngandu, T, Nicolas, G, Nordestgaard, B, Olaso, R, Orellana, A, Orsini, M, Ortega, G, Padovani, A, Paolo, C, Papenberg, G, Parnetti, L, Pasquier, F, Pastor, P, Peloso, G, Pérez-Cordón, A, Pérez-Tur, J, Pericard, P, Peters, O, Pijnenburg, Y, Pineda, J, Piñol-Ripoll, G, Pisanu, C, Polak, T, Popp, J, Posthuma, D, Priller, J, Puerta, R, Quenez, O, Quintela, I, Thomassen, J, Rábano, A, Rainero, I, Rajabli, F, Ramakers, I, Real, L, Reinders, M, Reitz, C, Reyes-Dumeyer, D, Ridge, P, Riedel-Heller, S, Riederer, P, Roberto, N, Rodriguez-Rodriguez, E, Rongve, A, Allende, I, Rosende-Roca, M, Royo, J, Rubino, E, Rujescu, D, Sáez, M, Sakka, P, Saltvedt, I, Sanabria, Á, Sánchez-Arjona, M, Sanchez-Garcia, F, Juan, P, Sánchez-Valle, R, Sando, S, Sarnowski, C, Satizabal, C, Scamosci, M, Scarmeas, N, Scarpini, E, Scheltens, P, Scherbaum, N, Scherer, M, Schmid, M, Schneider, A, Schott, J, Selbæk, G, Seripa, D, Serrano, M, Sha, J, Shadrin, A, Skrobot, O, Slifer, S, Snijders, G, Soininen, H, Solfrizzi, V, Solomon, A, Song, Y, Sorbi, S, Sotolongo-Grau, O, Spalletta, G, Spottke, A, Squassina, A, Stordal, E, Tartan, J, Tárraga, L, Tesí, N, Thalamuthu, A, Thomas, T, Tosto, G, Traykov, L, Tremolizzo, L, Tybjærg-Hansen, A, Uitterlinden, A, Ullgren, A, Ulstein, I, Valero, S, Valladares, O, Broeckhoven, C, Vance, J, Vardarajan, B, van der Lugt, A, Dongen, J, van Rooij, J, van Swieten, J, Vandenberghe, R, Verhey, F, Vidal, J, Vogelgsang, J, Vyhnalek, M, Wagner, M, Wallon, D, Wang, L, Wang, R, Weinhold, L, Wiltfang, J, Windle, G, Woods, B, Yannakoulia, M, Zare, H, Zhao, Y, Zhang, X, Zhu, C, Zulaica, M, Andreoni, S, Ferrarese, C, Sala, G, Zoia, C, Farrer, L, Psaty, B, Ghanbari, M, Raj, T, Sachdev, P, Mather, K, Jessen, F, Ikram, M, de Mendonça, A, Hort, J, Tsolaki, M, Pericak-Vance, M, Amouyel, P, Williams, J, Frikke-Schmidt, R, Clarimon, J, Deleuze, J, Rossi, G, Seshadri, S, Andreassen, O, Ingelsson, M, Hiltunen, M, Sleegers, K, Schellenberg, G, van Duijn, C, Sims, R, van der Flier, W, Ruiz, A, Ramirez, A, Lambert, J, VU University medical center, Amsterdam Neuroscience - Neurodegeneration, Neurology, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, APH - Personalized Medicine, APH - Methodology, Bellenguez, Céline [0000-0002-1240-7874], Küçükali, Fahri [0000-0002-3835-9639], Amin, Najaf [0000-0002-8944-1771], Holmans, Peter A [0000-0003-0870-9412], van der Lee, Sven J [0000-0003-1606-8643], Costa, Marcos R [0000-0002-4928-2163], Kuulasmaa, Teemu [0000-0002-1795-7314], Yang, Qiong [0000-0002-3658-1375], de Rojas, Itziar [0000-0002-2148-381X], Bis, Joshua C [0000-0002-3409-1110], Yaqub, Amber [0000-0002-3579-8054], Prokic, Ivana [0000-0002-0370-1473], Chapuis, Julien [0000-0002-5802-2857], Ahmad, Shahzad [0000-0002-8658-3790], Giedraitis, Vilmantas [0000-0003-3423-2021], Garcia-Gonzalez, Pablo [0000-0003-0125-5403], Alcolea, Daniel [0000-0002-3819-3245], Alvarez, Ignacio [0000-0002-8537-3935], Tsolaki, Anthoula [0000-0002-5563-7776], Baquero, Miquel [0000-0002-6861-1831], Pastor, Ana Belén [0000-0001-9637-4688], Berr, Claudine [0000-0001-5254-7655], Bessi, Valentina [0000-0002-6176-3584], Boada, Mercè [0000-0003-2617-3009], Bossù, Paola [0000-0002-1432-0078], Bråthen, Geir [0000-0003-3224-7983], Bressler, Jan [0000-0001-6578-4772], Bresner, Catherine [0000-0003-2673-9762], Brodaty, Henry [0000-0001-9487-6617], Brookes, Keeley J [0000-0003-2427-2513], Burholt, Vanessa [0000-0002-6789-127X], Bush, William S [0000-0002-9729-6519], Calero, Miguel [0000-0001-5366-3324], Chung, Jaeyoon [0000-0002-6431-9454], Cervera-Carles, Laura [0000-0003-2286-200X], Costantini, Emanuele [0000-0002-1096-8221], Dalmasso, Maria Carolina [0000-0002-4901-9955], de Paiva Lopes, Katia [0000-0002-0240-0126], de Witte, Lot D [0000-0002-7235-9958], Debette, Stéphanie [0000-0001-8675-7968], Del Ser, Teodoro [0000-0001-9806-7083], Dichgans, Martin [0000-0002-0654-387X], Diehl-Schmid, Janine [0000-0002-7745-1382], Diez-Fairen, Mónica [0000-0003-1882-0309], Djurovic, Srdjan [0000-0002-8140-8061], Dufouil, Carole [0000-0003-2442-4476], Escott-Price, Valentina [0000-0003-1784-5483], Ewers, Michael 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[0000-0002-7493-8777], Peloso, Gina [0000-0002-5355-8636], Pérez-Cordón, Alba [0000-0002-6028-0791], Pérez-Tur, Jordi [0000-0002-9111-1712], Pericard, Pierre [0000-0001-8167-6448], Pineda, Juan A [0000-0002-3751-0296], Pisanu, Claudia [0000-0002-9151-4319], Posthuma, Danielle [0000-0001-7582-2365], Puerta, Raquel [0000-0002-1191-5893], Quenez, Olivier [0000-0002-8273-8505], Thomassen, Jesper Qvist [0000-0003-3484-9531], Real, Luis M [0000-0003-4932-7429], Reinders, Marcel JT [0000-0002-1148-1562], Reitz, Christiane [0000-0001-8757-7889], Riedel-Heller, Steffi [0000-0003-4321-6090], Rodriguez-Rodriguez, Eloy [0000-0001-7742-677X], Rongve, Arvid [0000-0002-0476-4134], Sáez, María Eugenia [0000-0001-9299-2534], Saltvedt, Ingvild [0000-0002-7897-9808], Juan, Pascual Sánchez [0000-0002-6081-8037], Sarnowski, Chloé [0000-0002-6090-7099], Satizabal, Claudia L [0000-0002-1115-4430], Schott, Jonathan M [0000-0003-2059-024X], Selbæk, Geir [0000-0001-6511-8219], Shadrin, Alexey A 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Sachdev, Perminder [0000-0002-9595-3220], Mather, Karen [0000-0003-4143-8941], Ikram, M Arfan [0000-0003-0372-8585], Tsolaki, Magda [0000-0002-2072-8010], Pericak-Vance, Margaret A [0000-0001-7283-8804], Amouyel, Philippe [0000-0001-9088-234X], Williams, Julie [0000-0002-4069-0259], Frikke-Schmidt, Ruth [0000-0003-4084-5027], Seshadri, Sudha [0000-0001-6135-2622], Andreassen, Ole A [0000-0002-4461-3568], Sleegers, Kristel [0000-0002-0283-2332], van Duijn, Cornelia M [0000-0002-2374-9204], Sims, Rebecca [0000-0002-3885-1199], van der Flier, Wiesje M [0000-0001-8766-6224], Ramirez, Alfredo [0000-0003-4991-763X], Lambert, Jean-Charles [0000-0003-0829-7817], Apollo - University of Cambridge Repository, Complex Trait Genetics, Clinical sciences, Neuroprotection & Neuromodulation, Pathologic Biochemistry and Physiology, Clinical Biology, Epidemiology, Internal Medicine, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Med Staf Spec Psychiatrie (9), UAM. Departamento de Biología Molecular, University of Helsinki, Department of Neurosciences, HUS Internal Medicine and Rehabilitation, Timo Strandberg / Principal Investigator, Department of Medicine, Clinicum, HUS Neurocenter, Neurologian yksikkö, Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Institut Pasteur, Institut National de la Santé et de la Recherche Médicale (France), European Commission, LabEx DISTALZ, Pérez-Tur, Jordi, University Children’s Hospital Basel (Suiza), INSERM (Francia), Lille Métropole Communauté Urbaine, Government of France (Francia), EADB, GR@ACE, DEGESCO, EADI, GERAD, Demgene, FinnGen, ADGC, CHARGE, Holmans, Peter A. [0000-0003-0870-9412], van der Lee, Sven J. [0000-0003-1606-8643], Costa, Marcos R. [0000-0002-4928-2163], Bis, Joshua C. [0000-0002-3409-1110], Brookes, Keeley J. [0000-0003-2427-2513], Bush, William S. [0000-0002-9729-6519], de Witte, Lot D. [0000-0002-7235-9958], del Ser, Teodoro [0000-0001-9806-7083], Fox, Nick C. [0000-0002-6660-657X], Bullido, María J. [0000-0002-6477-1117], Goate, Alison M. [0000-0002-0576-2472], Herrmann, Martin J. [0000-0001-9970-2122], Jun, Gyungah R. [0000-0002-3230-8697], Kehoe, Patrick G. [0000-0002-7542-1139], Kosmidis, Mary H. [0000-0001-8790-1220], Lunetta, Kathryn L. [0000-0002-9268-810X], MacLeod, Catherine A. [0000-0002-9314-7380], Nöthen, Markus M. [0000-0002-8770-2464], Nordestgaard, Børge G. [0000-0002-1954-7220], Pineda, Juan A. [0000-0002-3751-0296], Real, Luis M. [0000-0003-4932-7429], Reinders, Marcel J. T. [0000-0002-1148-1562], Satizabal, Claudia L. [0000-0002-1115-4430], Schott, Jonathan M. [0000-0003-2059-024X], Shadrin, Alexey A. [0000-0002-7467-250X], Farrer, Lindsay A. [0000-0001-5533-4225], Psaty, Bruce M. [0000-0002-7278-2190], Ikram, M. Arfan [0000-0003-0372-8585], Pericak-Vance, Margaret A. [0000-0001-7283-8804], Andreassen, Ole A. [0000-0002-4461-3568], van Duijn, Cornelia M. [0000-0002-2374-9204], van der Flier, Wiesje M. [0000-0001-8766-6224], and Molecular Neuroscience and Ageing Research (MOLAR)
- Subjects
tau Proteins/genetics ,Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1] ,Neurologi ,MED/03 - GENETICA MEDICA ,45/43 ,Medizin ,Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] ,genetics [Alzheimer Disease] ,Genome-Wide Association Study ,Humans ,tau Proteins ,Alzheimer Disease ,Cognitive Dysfunction ,VARIANTS ,pathology [Alzheimer Disease] ,Tau Proteins ,Settore BIO/13 - Biologia Applicata ,Cognitive Dysfunction/psychology ,692/699/375/365/1283 ,IMPUTATION ,article ,1184 Genetics, developmental biology, physiology ,Biología y Biomedicina / Biología ,AMYLOID-BETA ,Settore MED/26 - NEUROLOGIA ,Neurology ,psychology [Cognitive Dysfunction] ,Medical Genetics ,Human ,Neuroscience(all) ,631/208/205/2138 ,All institutes and research themes of the Radboud University Medical Center ,SDG 3 - Good Health and Well-being ,ddc:570 ,Genetics ,Genetic Predisposition to Disease ,GENOME-WIDE ASSOCIATION ,METAANALYSIS ,Medicinsk genetik ,MED/26 - NEUROLOGIA ,Alzheimer Disease/genetics ,neurology ,tau Protein ,NECROSIS-FACTOR-ALPHA ,RISK LOCI ,genetics [tau Proteins] ,PREDICTION MODELS ,Human medicine ,GENERATION ,RESPONSES - Abstract
25 páginas, 6 figuras, 2 tablas, Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele., This work was funded by a grant (EADB) from the EU Joint Programme – Neurodegenerative Disease Research. INSERM UMR1167 is also funded by the INSERM, Institut Pasteur de Lille, Lille Métropole Communauté Urbaine and French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Full consortium acknowledgements and funding are in the Supplementary Not
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- 2022
46. Role of the Tau N-terminal region in microtubule stabilization revealed by new endogenous truncated forms
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Luc Buée, Coline Leghay, Maxime Derisbourg, Yann Verdier, Valérie Buée-Scherrer, Francisco-Jose Fernandez-Gomez, Sébastien Carrier, David Blum, Joëlle Vinh, Malika Hamdane, Nicolas Sergeant, Dominique Demeyer, Giovanni Chiappetta, Cyril Laurent, Spectrométrie de Masse Biologique et Protéomique (USR3149 / FRE2032) (SMBP), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Alzheimer & Tauopathies [JPArc], Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Neurobiologie et diversité cellulaire (NDC), Neuroendocrinologie et physiopathologie neuronale, Institut National de la Santé et de la Recherche Médicale (INSERM), Alzheimer & Tauopathies (Equipe 1), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, and Verdier, Yann
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Proteomics ,[SDV]Life Sciences [q-bio] ,Cell ,Endogeny ,tau Proteins ,Bioinformatics ,Cleavage (embryo) ,Microtubule stabilization ,Microtubules ,Article ,Cell Line ,Microtubule ,Alzheimer Disease ,Tubulin ,mental disorders ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,medicine ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Functional studies ,Phosphorylation ,Multidisciplinary ,Chemistry ,Brain ,Acetylation ,Human brain ,Cell biology ,[SDV] Life Sciences [q-bio] ,medicine.anatomical_structure ,Nerve Degeneration ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Protein Processing, Post-Translational ,Protein Binding - Abstract
Tau is a central player in Alzheimer's disease (AD) and relatedTauopathies, where it is found as aggregates in degenerating neurons. Abnormalpost-translational modifications, such as truncation, are likely involved in thepathological process. A major step forward in understanding the role of Tautruncation would be to identify the precise cleavage sites of the several truncatedTau fragments that are observed until now in AD brains, especially those truncatedat the N-terminus, which are less characterized than those truncated at theC-terminus. Here, we optimized a proteomics approach and succeeded in identifying anumber of new N-terminally truncated Tau species from the human brain. We initiatedcell-based functional studies by analyzing the biochemical characteristics of twoN-terminally truncated Tau species starting at residues Met11 and Gln124respectively. Our results show, interestingly, that the Gln124-Tau fragment displaysa stronger ability to bind and stabilize microtubules, suggesting that the TauN-terminal domain could play a direct role in the regulation of microtubulestabilization. Future studies based on our new N-terminally truncated-Tau speciesshould improve our knowledge of the role of truncation in Tau biology as well as inthe AD pathological process.
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- 2015
47. Airway structural cells regulate TLR5-mediated mucosal adjuvant activity
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Laure Janot, L Van Maele, L Vande Walle, Selma Boulenouar, Mohamed Lamkanfi, J-C Sirard, Bernhard Ryffel, Martín Rumbo, Julien Tabareau, Tracy Hussell, Yves Lemoine, Arndt Benecke, Delphine Fougeron, Delphine Cayet, François Erard, A Didierlaurent, S Corvo-Chamaillard, David Hot, Simon A. Jeffs, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), National Heart and Lung Institute, Imperial College London, Laboratorio de Investigaciones en el Sistema Inmune (LISIN), Facultad de Ciencias Exactas [La Plata], Universidad Nacional de la Plata [Argentine] (UNLP)-Universidad Nacional de la Plata [Argentine] (UNLP), Jefferiss Trust Research Lab, Department of Medical Protein Research, VIB, Department of Biochemistry, Universiteit Gent = Ghent University (UGENT), Manchester Collaborative Centre for Inflammation Research, University of Manchester [Manchester], Institut des Hautes Études Scientifiques (IHES), IHES, INSERM Institut Pasteur de Lille Region Nord Pas de Calais (ARCir Europe n°1R07028EE and PhD fellowship) Univ Lille Nord de France Agence Nationale de Recherche sur le SIDA (n°12008/058) INSERM-CONICET joint project (n°1174) Reseau National des Genopoles (n°1203) Genopole Evry, Institut des Hautes Etudes Scientifiques (IHES), Sirard, Jean-Claude, Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), and Universiteit Gent = Ghent University [Belgium] (UGENT)
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CIENCIAS MÉDICAS Y DE LA SALUD ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,medicine.medical_treatment ,Immunology ,Inmunología ,Antigen-Presenting Cells ,Respiratory Mucosa ,Biology ,Adaptive Immunity ,Cell Line ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,medicine ,Animals ,Humans ,Immunology and Allergy ,Antigen-presenting cell ,Immunity, Mucosal ,Administration, Intranasal ,030304 developmental biology ,Mice, Knockout ,0303 health sciences ,Gene Expression Profiling ,Toll-Like Receptors ,Mucosal Immunology ,purl.org/becyt/ford/3.1 [https] ,Acquired immune system ,3. Good health ,CCL20 ,Toll-Like Receptor 5 ,Medicina Básica ,Gene Expression Regulation ,Mucosal immunology ,TLR5 ,Proteolysis ,biology.protein ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,purl.org/becyt/ford/3 [https] ,Adjuvant ,Flagellin ,Signal Transduction ,030215 immunology - Abstract
Antigen-presenting cell (APC) activation is enhanced by vaccine adjuvants. Most vaccines are based on the assumption that adjuvant activity of Toll-like receptor (TLR) agonists depends on direct, functional activation of APCs. Here, we sought to establish whether TLR stimulation in non-hematopoietic cells contributes to flagellin’s mucosal adjuvant activity. Nasal administration of flagellin enhanced T-cell-mediated immunity, and systemic and secretory antibody responses to coadministered antigens in a TLR5-dependent manner. Mucosal adjuvant activity was not affected by either abrogation of TLR5 signaling in hematopoietic cells or the presence of flagellin-specific, circulating neutralizing antibodies. We found that flagellin is rapidly degraded in conducting airways, does not translocate into lung parenchyma and stimulates an early immune response, suggesting that TLR5 signaling is regionalized. The flagellin-specific early response of lung was regulated by radioresistant cells expressing TLR5 (particularly the airway epithelial cells). Flagellin stimulated the epithelial production of a small set of mediators that included the chemokine CCL20, which is known to promote APC recruitment in mucosal tissues. Our data suggest that (i) the adjuvant activity of TLR agonists in mucosal vaccination may require TLR stimulation of structural cells and (ii) harnessing the effect of adjuvants on epithelial cells can improve mucosal vaccines. Fil: Van Maele, Laurye. Institut Pasteur de Lille. Lille; Francia. Univ Lille Nord de France. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia Fil: Fougeron, Delphine. Institut Pasteur de Lille. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Univ Lille Nord de France. Lille; Francia Fil: Janot, Laurent. University of Orléans. Orléans; Francia. Institut de Transgenose. Orleans; Francia Fil: Didierlaurent, A.. Imperial College of London. Londres; Reino Unido Fil: Cayet, D.. Institut Pasteur de Lille. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Univ Lille Nord de France. Lille; Francia Fil: Tabareau, J.. Institut Pasteur de Lille. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Univ Lille Nord de France. Lille; Francia Fil: Rumbo, Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina Fil: Corvo Chamaillard, S.. Institut Pasteur de Lille. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Univ Lille Nord de France. Lille; Francia Fil: Boulenoir, S.. Institut Pasteur de Lille. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Univ Lille Nord de France. Lille; Francia Fil: Jeffs, S. Imperial College of London. Londres; Reino Unido Fil: Vande Walle, L. Department of Medical Protein Research. Ghent; Bélgica. University of Ghent; Bélgica Fil: Lamkanfi, M.. Department of Medical Protein Research. Ghent; Bélgica. University of Ghent; Bélgica Fil: Lemoine, Y.. Univ Lille Nord de France. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Institut Pasteur de Lille. Lille; Francia Fil: Erard, F.. Institut de Transgenose. Orleans; Francia. University of Orléans. Orléans; Francia Fil: Hot, D.. Univ Lille Nord de France. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Institut Pasteur de Lille. Lille; Francia Fil: Hussell, Tracy. Imperial College of London. Londres; Reino Unido. University of Manchester; Reino Unido Fil: Ryffel, B.. Institut de Transgenose. Orleans; Francia. University of Orléans. Orléans; Francia Fil: Benecke, Arndt G.. Institut des Hautes Études Scientifiques and Centre National de la Recherche Scientifique; Francia Fil: Sirard, J.C.. Univ Lille Nord de France. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Institut Pasteur de Lille. Lille; Francia
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- 2014
48. Efficient gate-tunable light-emitting device made of defective boron nitride nanotubes: from ultraviolet to the visible
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Attaccalite, Claudio, Wirtz, Ludger, Marini, Andrea, Rubio, Angel, European Research Council, European Commission, Eusko Jaurlaritza, Universidad del País Vasco, Ikerbasque Basque Foundation for Science, Ministerio de Economía y Competitividad (España), Ministero dell'Istruzione, dell'Università e della Ricerca, Théorie de la Matière Condensée (TMC), Institut Néel (NEEL), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS), Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), European Theoretical Spectroscopy Facility (ETSF), European Theoretical Spectroscopy Facility, Dipartimento di Fisica, Università degli Studi di Roma Tor Vergata [Roma], IKERBASQUE, Basque Foundation for Science, Nano-Bio Spectroscopy Group, Universidad del Pais Vasco / Euskal Herriko Unibertsitatea [Espagne] (UPV/EHU), Théorie de la Matière Condensée (NEEL - TMC), and Ikerbasque - Basque Foundation for Science
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Materials science ,Physics [G04] [Physical, chemical, mathematical & earth Sciences] ,FOS: Physical sciences ,Physics::Optics ,02 engineering and technology ,Substrate (electronics) ,medicine.disease_cause ,01 natural sciences ,7. Clean energy ,Article ,law.invention ,nanotubes ,crystal ,state ,chemistry.chemical_compound ,Condensed Matter::Materials Science ,ELECTRONICS ,law ,0103 physical sciences ,medicine ,FIELD ,010306 general physics ,Condensed Matter - Materials Science ,Multidisciplinary ,CRYSTAL ,business.industry ,Graphene ,VACANCIES ,MULTIDISCIPLINARY SCIENCES ,electronics ,Doping ,Materials Science (cond-mat.mtrl-sci) ,021001 nanoscience & nanotechnology ,vacancies ,field ,BN NANOTUBES ,STATE ,chemistry ,Physique [G04] [Physique, chimie, mathématiques & sciences de la terre] ,Boron nitride ,[PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci] ,Optoelectronics ,Light emission ,0210 nano-technology ,business ,Luminescence ,Lasing threshold ,Ultraviolet - Abstract
This work is licensed under a Creative Commons Attribution 3.0 Unported license., Boron nitride is a promising material for nanotechnology applications due to its two-dimensional graphene-like, insulating, and highly-resistant structure. Recently it has received a lot of attention as a substrate to grow and isolate graphene as well as for its intrinsic UV lasing response. Similar to carbon, one-dimensional boron nitride nanotubes (BNNTs) have been theoretically predicted and later synthesised. Here we use first principles simulations to unambiguously demonstrate that i) BN nanotubes inherit the highly efficient UV luminescence of hexagonal BN; ii) the application of an external perpendicular field closes the electronic gap keeping the UV lasing with lower yield; iii) defects in BNNTS are responsible for tunable light emission from the UV to the visible controlled by a transverse electric field (TEF). Our present findings pave the road towards optoelectronic applications of BN-nanotube-based devices that are simple to implement because they do not require any special doping or complex growth., We acknowledge financial support also from the European Research Council Advanced Grant DYNamo (ERC-2010-AdG-267374), Spanish Grant (FIS2010-21282-C02-01), Grupos Consolidados UPV/EHU del Gobierno Vasco (IT578-13), Ikerbasque and the European Commission project CRONOS (Grant number 280879-2). Computational time was granted by i2basque and BSC Red Espanola de Supercomputacion and GENCI-IDRIS (Nos. 100063 and No. 091827). A. M. acknowledges funding by MIUR FIRB Grant No. RBFR12SW0J.
- Published
- 2013
49. Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease
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P. Bosco, Rebecca Sims, Monique M.B. Breteler, L. Concari, Giuseppe Tosto, María J. Bullido, Kristel Sleegers, Fernando Valdivieso, Diana Zelenika, T. Feulner, Raffaele Ferri, Christophe Tzourio, P. Caffara, Davide Seripa, Benjamin Grenier-Boley, Paola Bossù, C. Chillotti, Marc Delepine, C. Deniz-Naranjo, Daniela Galimberti, David-Alexandre Trégouët, Benedetta Nacmias, Elisabeth M. C. Schrijvers, Karolien Bettens, Anne Boland, Christiane Reitz, Florentino Sanchez-Garcia, Dominique Campion, R. Rogers, C. Van Broeckhoven, Jean-Charles Lambert, Denise Harold, Amy Gerrish, Didier Hannequin, Mohammad Arfan Ikram, Michael Conlon O'Donovan, Elio Scarpini, Giorgio Annoni, Vincent Chouraki, Marc Lathrop, Francesco Panza, Chandra A. Reynolds, Gabriele Siciliano, Sandro Sorbi, Philippe Amouyel, Florence Pasquier, Luc Buée, Mikko Hiltunen, Claudine Berr, Eliecer Coto, Victoria Alvarez, Caroline Graff, Vincenzo Solfrizzi, Julie Williams, Jonathan A. Prince, Martin Ingelsson, Michael John Owen, Laura Fratiglioni, Jennifer Chapman, Ignacio Mateo, Annick Alpérovitch, H. Soininen, Michelangelo Mancuso, G. Spalletta, Matthias Riemenschneider, Andrea Pilotto, C. Van Cauwenberghe, Jacques Epelbaum, M. Del Zompo, Onofre Combarros, Lars Lannfelt, Yoichiro Kamatani, Beatrice Arosio, Jean-François Dartigues, Inserm U744, Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Cardiff University, Bioinformatics, GlaxoSmithKline, Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d'Etude du Polymorphisme Humain (CEPH), Université Paris Diderot - Paris 7 (UPD7)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset, Neurodegenerative Brain Diseases group, Department of Molecular Genetics, VIB, Antwerpen, Belgium, Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerpen, Belgium, University of Antwerp (UA), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Eastern Finland, G.H. Sergievsky Center, Columbia University, New York, NY, USA, Columbia University Irving Medical Center (CUIMC), Service of Neurology, University Hospital Marques de Valdecilla, University of Cantabria, Santander, Spain, Department of Psychiatry and Psychotherapy, Universitätsklinikum des Saarlandes, Universität des Saarlandes Saarbruecken, Germany, Centro de Biología Molecular Severo Ochoa [Madrid] (CBMSO), Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Centro Dino Ferrari [Milano], Università degli Studi di Milano = University of Milan (UNIMI)-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Department of Neuroscience, University of Parma, Parma, Italy, Università degli studi di Parma = University of Parma (UNIPR), Genética Molecular-Laboratorio de Medicina, Hospital Universitario Central Asturias, Oviedo, Spain, Servicio de Inmunología. Hospital Unviersitario de Gran Canaria Dr Negrín. Bco, Las Palmas de Gran Canaria, Spain, Department of Geriatrics, Center for aging brain, Memory unit, University of Bari, Bari, Italy, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Department of neurological and psychiatric Sciences, University of Florence, Florence, Italy, Università degli Studi di Firenze = University of Florence (UniFI), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Clinical and Behavioral Neurology, IRCCS Fondazione Santa Lucia, Roma, Italy, Clinical and Behavioral Neurology - Neuroscienze e riabilitazione, IRCCS Fondazione Santa Lucia [Roma], Neurological clinic, University of Pisa, Pisa, Italy, University of Pisa - Università di Pisa, Centre de Psychiatrie et Neurosciences (U894), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Aging Research Center [Karolinska Institutet] (ARC ), Stockholm University-Karolinska Institutet [Stockholm], Department of Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden, KI-Alzheimer's Disease Reseach Center, Department NVS, Karolinska Institutet, KIADRC, Stockholm, Sweden, IRCCS Associazione Oasi Maria SS, Institute for Research on Mental Retardation and Brain Aging, Troina (EN), Italy, Department of Psychology [Riverside], University of California [Riverside] (UC Riverside), University of California (UC)-University of California (UC), Department of Public health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden, Uppsala University, Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden, Unit of Clinical Pharmacology, Teaching Hospital of Cagliari, Cagliari, Italy, Geriatric Unit & Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences, I.R.C.C.S. 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Italy, Università degli Studi di Cagliari = University of Cagliari (UniCa), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, DZNE, Bonn, Germany, Génomique cardiovasculaire, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), This work was supported by the National Foundation for Alzheimer's disease and related disorders, the Institut Pasteur de Lille, the Centre National de Génotypage, Inserm, FRC (fondation sur la recherche sur le cerveau) and Rotary., EADI consortium, GERAD consortium, Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Neurosciences and Mental Health Research Institute, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Department of neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland, Department of neurology, University of Eastern Finland-University Hospital of Kuopio-University of Eastern Finland-University Hospital of Kuopio, Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Università degli Studi di Milano [Milano] (UNIMI)-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli studi di Bari Aldo Moro (UNIBA), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Institut de psychiatrie et neurosciences (U894 / UMS 1266), University of California [Riverside] (UCR), University of California-University of California, Section of Clinical Pharmacology, Department of Neurosciences 'B.B. Brodie', University of Cagliari, Cagliari, Italy, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Lambert, J, Grenier Boley, B, Harold, D, Zelenika, D, Chouraki, V, Kamatani, Y, Sleegers, K, Ikram, M, Hiltunen, M, Reitz, C, Mateo, I, Feulner, T, Bullido, M, Galimberti, D, Concari, L, Alvarez, V, Sims, R, Gerrish, A, Chapman, J, Deniz Naranjo, C, Solfrizzi, V, Sorbi, S, Arosio, B, Spalletta, G, Siciliano, G, Epelbaum, J, Hannequin, D, Dartigues, J, Tzourio, C, Berr, C, Schrijvers, E, Rogers, R, Tosto, G, Pasquier, F, Bettens, K, Van Cauwenberghe, C, Fratiglioni, L, Graff, C, Delepine, M, Ferri, R, Reynolds, C, Lannfelt, L, Ingelsson, M, Prince, J, Chillotti, C, Pilotto, A, Seripa, D, Boland, A, Mancuso, M, Bossù, P, Annoni, G, Nacmias, B, Bosco, P, Panza, F, Sanchez Garcia, F, Del Zompo, M, Coto, E, Owen, M, O'Donovan, M, Valdivieso, F, Caffara, P, Scarpini, E, Combarros, O, Buée, L, Campion, D, Soininen, H, Breteler, M, Riemenschneider, M, Van Broeckhoven, C, Alpérovitch, A, Lathrop, M, Trégouët, D, Williams, J, Amouyel, P, Epidemiology, Radiology & Nuclear Medicine, Neurology, Grenier-Boley, Benjamin, Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé-Institut Pasteur de Lille, Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, Centre National de Génotypage ( CNG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs ( INM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Centre d'Etude du Polymorphisme Humain ( CEPH ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut Universitaire d'Hématologie ( IUH ), Université Paris Diderot - Paris 7 ( UPD7 ) -Fondation Jean Dausset, Departement of Epidemiology and Radiology, Erasmus MC, Rotterdam, Centro de Biologia Molecular Severo Ochoa (UAM-CSIC) and CIBERNED, Universidad Autonoma, Madrid, Spain, Università degli studi di Milano [Milano]-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Department of Internal Medicine, Geriatric Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy, University of Pisa [Pisa], Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Génétique du cancer et des maladies neuropsychiatriques ( GMFC ), Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Neuropsychiatrie : recherche épidémiologique et clinique, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), Department of Epidemiology and Neurology, Erasmus MC, Rotterdam, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Aging Reasearch Center, Department NVS, Karolinska Institutet and Stockholm University, Stockholm, Sweden, University of California [Riverside] ( UCR ), Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, Department of Epidemiology, Erasmus MC, Rotterdam, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition ( ICAN ), and Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP]
- Subjects
Apolipoprotein E ,haplotype ,FERM domain-containing protein 4A, human ,genetics [Alzheimer Disease] ,Genome-wide association study ,Disease ,Genome ,Plasma ,0302 clinical medicine ,genetics [Adaptor Proteins, Signal Transducing] ,blood [Amyloid beta-Peptides] ,GWAS ,genetics [Genetic Predisposition to Disease] ,[ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics ,Genetics ,0303 health sciences ,FRMD4A gene ,amyloid ,[ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie ,GWAS study ,Alzheimer ,FRMD4A ,Alzheimer's disease ,3. Good health ,Psychiatry and Mental health ,Chemistry ,genetics [Polymorphism, Single Nucleotide] ,Original Article ,Corrigendum ,medicine.medical_specialty ,Amyloid ,Single-nucleotide polymorphism ,Locus (genetics) ,genome wide haplotype association study ,[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,blood [Alzheimer Disease] ,Alzheimer Disease ,genetics [Haplotypes] ,Genetic predisposition ,medicine ,Humans ,Genetic Predisposition to Disease ,ddc:610 ,Psychiatry ,Molecular Biology ,plasma ,Genetic association ,Adaptor Proteins, Signal Transducing ,030304 developmental biology ,Amyloid beta-Peptides ,business.industry ,Haplotype ,Case-control study ,Haplotypes ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,Case-Control Studies ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Human medicine ,business ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Recently, several genome-wide association studies (GWASs) have led to the discovery of nine new loci of genetic susceptibility in Alzheimer’s disease (AD). However, the landscape of the AD genetic susceptibility is far away to be complete and in addition to single-SNP (single-nucleotide polymorphism) analyses as performed in conventional GWAS, complementary strategies need to be applied to overcome limitations inherent to this type of approaches. We performed a genome-wide haplotype association (GWHA) study in the EADI1 study (n = 2025 AD cases and 5328 controls) by applying a sliding-windows approach. After exclusion of loci already known to be involved in AD (APOE, BIN1 and CR1), 91 regions with suggestive haplotype effects were identified. In a second step, we attempted to replicate the best suggestive haplotype associations in the GERAD1 consortium (2820 AD cases and 6356 controls) and observed that 9 of them showed nominal association. In a third step, we tested relevant haplotype associations in a combined analysis of five additional case– control studies (5093 AD cases and 4061 controls). We consistently replicated the association of a haplotype within FRMD4A on Chr.10p13 in all the data set analyzed (OR: 1.68; 95% CI: (1.43–1.96); P= 1.11010). We finally searched for association between SNPs within the FRMD4A locus and Ab plasma concentrations in three independent non-demented populations (n = 2579). We reported that polymorphisms were associated with plasma Ab42/Ab40 ratio (best signal, P = 5.4107). In conclusion, combining both GWHA study and a conservative three-stage replication approach, we characterised FRMD4A as a new genetic risk factor of AD.
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- 2012
50. Scattering and absorbing aerosols in the climate system
- Author
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Jing Li, Barbara E. Carlson, Yuk L. Yung, Daren Lv, James Hansen, Joyce E. Penner, Hong Liao, V. Ramaswamy, Ralph A. Kahn, Peng Zhang, Oleg Dubovik, Aijun Ding, Andrew A. Lacis, Lu Zhang, Yueming Dong, Laboratoire d’Optique Atmosphérique - UMR 8518 (LOA), and Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Atmospheric Science ,[SDU]Sciences of the Universe [physics] ,respiratory system ,Pollution ,complex mixtures ,Nature and Landscape Conservation ,Earth-Surface Processes - Abstract
International audience; Tropospheric anthropogenic aerosols contribute the second-largest forcing to climate change, but with high uncertainty owing to their spatio-temporal variability and complicated optical properties. In this Review, we synthesize understanding of aerosol observations and their radiative and climate effects. Aerosols offset about one-third of the warming effect by anthropogenic greenhouse gases. Yet, in regions and seasons where the absorbing aerosol fraction is high — such as South America and East and South Asia — substantial atmospheric warming can occur. The internal mixing and the vertical distribution of aerosols, which alters both the direct effect and aerosol-cloud interactions, might further enhance this warming. Despite extensive research in aerosol-cloud interactions, there is still at least a 50% spread in total aerosol forcing estimates. This ongoing uncertainty is linked, in part, to the poor measurement of anthropogenic and natural aerosol absorption, as well as the little-understood effects of aerosols on clouds. Next-generation, space-borne, multi-angle polarization and active remote sensing, combined with in situ observations, offer opportunities to better constrain aerosol scattering, absorption and size distribution, thus, improving models to refine estimates of aerosol forcing and climate effects.
- Published
- 2022
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