Philippe JEAN-PIERRE

---

• Type de publi. : Article dans une revue
• Date de publi. : 01/05/2021
• Auteurs : Roxana AmélieCharles R.G. GuttmannJuan Carlos PrietoFabien RollotMiklos PalotaiSandra VukusicRomain MarignierFrançois CottonRené AnxionnatJean-Paul ArmspachBertrand AudoinChristian BarillotIsabelle BerryFabrice BonnevilleClaire BoutetGiovanni CastelnovoFrédéric CervenanskyMikael CohenOlivier CommowickJérôme de SèzeVincent DoussetFrançoise Durand-DubiefGilles EdanJean-Christophe FerréDamien GalanaudTristan GlatardSylvie GrandJustine GuillaumontRémy GuillevinSalem HannounFabrice HeitzAlexandre KrainikStéphane KremerPierre M. LabaugeNicolas Menjot de ChampfleurJean‐philippe RanjevaJean-Amédée RochDominique Sappey-MarinierJulien SavatovskyBruno StankoffAyman TourbahThomas TourdiasBruno BrochetMichel ClanetNathalie DufayDavid-Axel LaplaudMarie-Claire MazeThibault MoreauCédric TrollietBernard FrangoulisJavier OlaizJean PelletierBertrand BourreDavid BrassatPhilippe CabreJean-Philippe CamdessanchéWilliam CamuOlivier CasezPierre ClavelouNicolas CollonguesAlain CreangeGilles DeferMarc DebouverieOlivier GoutChristine Lebrun-FrénayCatherine LubetzkiCaroline PapeixPatrick VermerschHélène Zéphir
• Organismes : Service de Radiologie [Hôpital Femme Mère Enfant - HCL] Department of Radiology [Boston] Department of Radiology [Boston] Observatoire Français de la Sclérose En Plaques [Lyon] Department of Radiology [Boston] Service de Neurologie [Lyon] Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé Imagerie Adaptative Diagnostique et Interventionnelle Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie Centre de résonance magnétique biologique et médicale Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] Neuroimagerie: méthodes et applications Service de Médecine Nucléaire - Pierre-Paul Riquet [CHU Toulouse] Pôle Neurosciences [CHU Toulouse] Service de Radiologie [CHU Saint-Etienne] CHU Pitié-Salpêtrière [AP-HP] Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé Service de Neurologie [CHU Nice] Neuroimagerie: méthodes et applications Centre Hospitalier Universitaire [Strasbourg] Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé Neuroimagerie: méthodes et applications Neuroimagerie: méthodes et applications CHU Pitié-Salpêtrière [AP-HP] Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé Service de neuroradiologie [Grenoble] Neuroimagerie: méthodes et applications Centre hospitalier universitaire de Poitiers = Poitiers University Hospital Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie Service de neuroradiologie [Grenoble] Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie Département de neurologie [Montpellier] Institut d’Imagerie Fonctionnelle Humaine [CHU Montpellier] Centre de résonance magnétique biologique et médicale Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] Hôpital privé Jean Mermoz [Lyon] Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé CHU Rothschild [AP-HP] CHU Tenon [AP-HP] Université de Reims Champagne-Ardenne Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale Service de neurologie [Bordeaux] Neurologie Vasculaire [Toulouse] Service de Neurologie [Lyon] Service de neurochirurgie [CHU Nantes] Service de Neurologie [Lyon] Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon) Observatoire Français de la Sclérose En Plaques [Lyon] Fondation Eugène Devic EDMUS Fondation Eugène Devic EDMUS Centre de résonance magnétique biologique et médicale Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] Hôpital Charles Nicolle [Rouen] Pôle Neurosciences [CHU Toulouse] Hôpital Albert Clarac [CHU de la Martinique] Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] Institut de Biologie Computationnelle Département de neurologie Service Neurologie [CHU Clermont-Ferrand] Hôpital de Hautepierre [Strasbourg] Département de neurosciences Service de Neurologie [CHU Caen] Service de neurologie [CHRU Nancy] CHU Rothschild [AP-HP] Service de Neurologie [CHU Nice] CHU Pitié-Salpêtrière [AP-HP] CHU Pitié-Salpêtrière [AP-HP] Département de neurologie [Lille] Département de neurologie [Lille]
• Publié dans Journal de Neuroradiologie / Journal of Neuroradiology le 26/10/2020

---

Résumé : Background and purposeTo determine the precise incidence of lesions at sites of high Aquaporin-4 expression (hAQP4) and their possible association with known neuromyelitis optica spectrum disease (NMOSD) lesions patterns.Materials and methodsA retrospective analysis of brain and, when available, spinal cord MRI scans of 54 NMOSD patients recruited among the French NMOSD cohort was performed. Brain lesions were annotated as MS-like, non-specific, or evocative of NMOSD. The topography of hAQP4 was reassessed by human brain atlas. The incidence of lesions in hAQP4 and their association with lesions evocative of NMOSD was estimated.ResultsAmong those included (41/54 female, mean age: 45 years) 47/54 (87%) presented brain lesions. Twenty-six/47 (55%) had lesions in hAQP4. Thirty-two/54 patients (60%) had lesions considered evocative of NMOSD. The majority of them also presented lesions in hAQP4 (65%, 21/32). Patients with lesions in hAQP4 and lesions evocative of NMOSD demonstrated more extensive myelitis compared to the other patients (7 [6–10] versus 4 [3–5] vertebral segments, P = 0.009).ConclusionThe coexistence of lesions evocative of NMOSD and in hAQP4 is associated with significantly more extensive myelitis, and might have pathophysiological and clinical significance.

---

Source

---

• Type de publi. :
• Date de publi. : 01/05/2021
• Auteurs : Garance CroquantDoriane AguannoA. PeyrottesLoïc BrotChristine BelloirLoïc BriandJean-Pierre GrillSophie ThenetLuisa de SordiPhilippe Seksik
• Organismes : Sorbonne Université École Pratique des Hautes Études École normale supérieure - Paris Sorbonne Université Centre des Sciences du Goût et de l'Alimentation [Dijon] Centre des Sciences du Goût et de l'Alimentation [Dijon] Sorbonne Université École Pratique des Hautes Études Centre de Recherche Saint-Antoine Sorbonne Université Sorbonne Université Centre de Recherche Saint-Antoine
• Publié dans Journal of Crohn's and Colitis le 31/10/2020

---

Résumé : Background Acyl-Homoserine Lactones (AHLs) are Quorum Sensing molecules involved in the communication network of bacteria and can also have an impact on the host’s cells. We recently showed, in the gut ecosystems, the presence AHLs and among them we identified one that has never been described: 3-oxo-C12:2. This molecule was decreased in Inflammatory Bowel Disease (IBD) patients, especially during flare, and its presence was correlated to normobiosis. Interestingly, 3-oxo-C12:2 is structurally close to an AHL well described and synthesized by P. aeruginosa, 3-oxo-C12. We intent to describe 3-oxo-C12:2 effects on gut inflammation and to identified which signalling pathways are involved. Given its analogous structure to 3-oxo-C12, we hypothesized that 3-oxo-C12:2 can interact with the same cellular partners, in particular a bitter taste receptor (BTR), called T2R138, which is a GPCR expressed by immune and epithelial gut cells. Methods To test our hypothesis, we used murine macrophages cell line RAW264.7, stimulated by interferon-ɣ (IFN-g, 20U/mL) and lipopolysaccharide (LPS, 10ng/mL). We performed a transcriptome analysis using RNAseq to identify inflammatory pathways involved in the effects. Inflammatory response was monitored by measuring cytokine secretion TFNα via ELISA. Probenecid, a known allosteric inhibitor for T2R138, was used to study T2R138 role in AHL signalling. BTR screening assay was performed to extend search for 3-oxo-C12:2 receptors. Cytotoxicity was measured via Lactate Dehydrogenase release. Results After LPS/IFN-γ activation, we observed a decrease of secreted TNFα when cells are exposed to 3-oxo-C12:2, in a dose dependent manner: 15μM (-30%, p<0.05), 25μM (-50%, p<0.001) et 50μM (-65%, p<0.0001), no change were observed in steady state. Itreflects an anti-inflammatory effect, without increasing cytotoxicity. To identify mechanisms behind those effects, we analysed the transcriptome of RAW264.7 cells exposed to AHL. JAK-STAT and NF-κB pathways were differentially down-regulated in presence of 3-oxo-C12:2. In addition, the anti-inflammatory effects were lost in presence of Probenecid, a T2R138 inhibitor. In a BTR screening assay, we confirmed that 3-oxo-C12:2 activates T2R38, but also five other BTR (T2R13, T2R8, T2R14, T2R1, T2R10). Conclusion 3-oxo-C12:2 exerts a dose dependent anti-inflammatory effect on murine immune cells. This response is partly mediated by the bitter taste receptor T2R138. This receptor is a potential target of our AHL of interest and we are currently studying the inflammatory pathways involved behind those effects. Studying the signalling between the receptor and the anti-inflammatory response would allow us to better understand the inter-kingdom dialogue between microbiota involving AHL in IBD.

---

Source

---

• Type de publi. : Article dans une revue
• Date de publi. : 01/05/2021
• Auteurs : Manel AllegMorgane SolisSeyyid BalogluFrançois CottonPhilippe KerschenBertrand BourreGuido AhleJean-Pierre PruvoXavier LeclercPatrick VermerschCaroline PapeixÉlisabeth MaillartCaroline HouillierCécile Moluçon ChabrotBéatrice ClaiseSandra MalakGuillaume Martin-BlondelFabrice BonnevilleAlexis CaulierJean-Pierre MarolleauJérôme Tamburini BonnefoyPhilippe AgapeCéline KennelXavier RousselAdrien ChauchetJérôme de SèzeSamira Fafi-KremerStéphane Kremer
• Organismes : Hôpitaux Universitaires de Strasbourg Laboratoire de Virologie [Strasbourg] Hôpitaux Universitaires de Strasbourg Centre Hospitalier Lyon Sud [CHU - HCL] Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé Centre Hospitalier de Luxembourg [Luxembourg] CHU Rouen Service de Neurologie [Hôpitaux Civils de Colmar] Lille Neurosciences & Cognition - U 1172 Lille Neurosciences & Cognition - U 1172 Lille Neurosciences & Cognition - U 1172 Departement de Neuroradiologie [Lille] CHU Pitié-Salpêtrière [AP-HP] CHU Pitié-Salpêtrière [AP-HP] Sorbonne Université CHU Pitié-Salpêtrière [AP-HP] CHU Clermont-Ferrand CHU Clermont-Ferrand Institut Curie - Saint Cloud Service Maladies infectieuses et tropicales [CHU Toulouse] Centre de Physiopathologie Toulouse Purpan Service Neuroradiologie Diagnostique et Thérapeutique [CHU Toulouse] Laboratoire d'Hématologie [CHU Amiens] Laboratoire d'Hématologie [CHU Amiens] AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris] Institut de Cancérologie de l'Ouest [Angers/Nantes] CHU Limoges Centre Hospitalier Régional Universitaire de Besançon Centre Hospitalier Régional Universitaire de Besançon Hôpital de Hautepierre [Strasbourg] Laboratoire de Virologie [Strasbourg] Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie Hôpitaux Universitaires de Strasbourg
• Publié dans European Radiology le 23/10/2020

---

Résumé : Objectives: To compare brain MRI findings in progressive multifocal leukoencephalopathy (PML) associated to rituximab and natalizumab treatments and HIV infection. Materials and methods: In this retrospective, multicentric study, we analyzed brain MRI exams from 72 patients diagnosed with definite PML: 32 after natalizumab treatment, 20 after rituximab treatment, and 20 HIV patients. We compared T2- or FLAIR-weighted images, diffusion-weighted images, T2*-weighted images, and contrast enhancement features, as well as lesion distribution, especially gray matter involvement. Results: The three PML entities affect U-fibers associated with low signal intensities on T2*-weighted sequences. Natalizumab-associated PML showed a punctuate microcystic appearance in or in the vicinity of the main PML lesions, a potential involvement of the cortex, and contrast enhancement. HIV and rituximab-associated PML showed only mild contrast enhancement, punctuate appearance, and cortical involvement. The CD4/CD8 ratio showed a trend to be higher in the natalizumab group, possibly mirroring a more efficient immune response. Conclusion: Imaging features of rituximab-associated PML are different from those of natalizumab-associated PML and are closer to those observed in HIV-associated PML.

---

Source

---

• Type de publi. : Article dans une revue
• Date de publi. : 01/05/2021
• Auteurs : Elisabeth ChenNicolas NesselerRaphaël P MartinsCéline GoéminneAndré VincentelliClément DelmasJean PorterieKarine NubretMathieu PernotMichel KindoTam Hoang MinhPhilippe GaudardPhilippe RouvièreMagali MichelThomas SénageAude BoignardOlivier ChavanonConstance VerdonkMarylou ParaEdeline PelcéVlad GariboldiMatteo PozziGuillaume CoutancePierre-Yves LitzlerFrédéric AnselmeKatrien BlanchartGerard BabatasiFabien GarnierMarie BielefeldCostin RaduNicolas LelloucheThierry BourguignonThibaud GenetRomain EschalierNicolas D’ostrevyMarie-Cécile BoriesPierre BaudinaudFabrice VanhuyseHugues BlangyChristophe LeclercqErwan FlécherVincent Galand
• Organismes : Laboratoire Traitement du Signal et de l'Image Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Laboratoire Traitement du Signal et de l'Image Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Laboratoire Traitement du Signal et de l'Image Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Institut Coeur Poumon [CHU Lille] Institut Coeur Poumon [CHU Lille] Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 Centre Hospitalier Universitaire de Toulouse Centre Hospitalier Universitaire de Toulouse Institut de rythmologie et modélisation cardiaque [Pessac] Institut de rythmologie et modélisation cardiaque [Pessac] Hôpitaux Universitaires de Strasbourg Hôpitaux Universitaires de Strasbourg Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] Centre Hospitalier Régional Universitaire [Montpellier] Centre Hospitalier Régional Universitaire [Montpellier] Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Hôpital Michallon Hôpital Michallon AP-HP - Hôpital Bichat - Claude Bernard [Paris] AP-HP - Hôpital Bichat - Claude Bernard [Paris] Hôpital de la Timone [CHU - APHM] Hôpital de la Timone [CHU - APHM] Hôpital Louis Pradel [CHU - HCL] Hôpital Louis Pradel [CHU - HCL] Hôpital Charles Nicolle [Rouen] Hôpital Charles Nicolle [Rouen] CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand CHU Henri Mondor [Créteil] CHU Henri Mondor [Créteil] Centre Hospitalier Régional Universitaire de Tours Centre Hospitalier Régional Universitaire de Tours CHU Clermont-Ferrand CHU Clermont-Ferrand Hôpital Européen Georges Pompidou [APHP] Hôpital Européen Georges Pompidou [APHP] Centre Hospitalier Régional Universitaire de Nancy Centre Hospitalier Régional Universitaire de Nancy Laboratoire Traitement du Signal et de l'Image Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Laboratoire Traitement du Signal et de l'Image Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Laboratoire Traitement du Signal et de l'Image
• Publié dans American Journal of Cardiology le 22/10/2020

---

Résumé : LVAD implantation in patients with a recently diagnosed cardiomyopathy has been poorly investigated. This work aims at describing the characteristics and outcomes of patients receiving a LVAD within 30 days following the diagnosis of cardiomyopathy. Patients from the ASSIST-ICD study was divided into recently and remotely diagnosed cardiomyopathy based on the time from initial diagnosis of cardiomyopathy to LVAD implantation using the cut point of 30 days. The primary end point of the study was all-cause mortality at 30-day and during follow-up. A total of 652 patients were included and followed during a median time of 9.1 (2.5 to 22.1) months. In this population, 117 (17.9%) had a recently diagnosed cardiomyopathy and had LVAD implantation after a median time of 15.0 (9.0 to 24.0) days following the diagnosis. This group of patients was significantly younger, with more ischemic cardiomyopathy, more sudden cardiac arrest (SCA) events at the time of the diagnosis and were more likely to receive temporary mechanical support before LVAD compared with the remotely diagnosed group. Postoperative in-hospital survival was similar in groups, but recently diagnosed patients had a better long-term survival after hospital discharge. SCA before LVAD and any cardiac surgery combined with LVAD implantation were identified as 2 independent predictors of postoperative mortality in recently diagnosed patients. In conclusion, rescue LVAD implantation for recently diagnosed severe cardiomyopathy is common in clinical practice. Such patients experience a relatively low postoperative mortality and have a better long-term survival compared with remotely diagnosed patients.

---

Fichiers liés : Chen et al. - 2021 - Comparison of Outcomes and Mortality in Patients H.pdf

---

Source

---

• Type de publi. : Article dans une revue
• Date de publi. : 01/05/2021
• Auteurs : Tae-Hwi Schwantes-AnRebecca DarlayPhilippe MathurinSteven MassonSuthat LiangpunsakulSebastian MuellerGuruprasad P. AithalFlorian EyerDermot GleesonAndrew ThompsonBeat MuellhauptFelix StickelMichael SoykaDavid GoldmanTiebing LiangLawrence LumengMunir PirmohamedBertrand NalpasJean-Marc JacquetRomain MoirandPierre NahonSylvie S. NaveauPascal PerneyGreg BotwinPaul S HaberHelmut K. SeitzChristopher P. DayTatiana M ForoudAnn K. DalyHeather J. CordellJohn B WhitfieldTimothy R MorganDevanshi Seth
• Organismes : Indiana University System Newcastle University [Newcastle] Centre Hospitalier Régional Universitaire [CHU Lille] Newcastle University [Newcastle] Indiana University System University of Heidelberg, Medical Faculty University of Nottingham, UK Technische Universität Munchen = Technical University Munich = Université Technique de Munich Royal Hallamshire Hospital University of Liverpool University hospital of Zurich [Zurich] University hospital of Zurich [Zurich] Klinikum der Universität [München] Indiana University System Indiana University System University of Liverpool Service Addictologie [CHU Nîmes] Service Addictologie [CHU Nîmes] Nutrition, Métabolismes et Cancer Hôpital Jean Verdier [AP-HP] AP-HP - Hôpital Antoine Béclère [Clamart] Service Addictologie [CHU Nîmes] Veterans Affairs Long Beach Healthcare System NSW Government The University of Sydney University of Heidelberg, Medical Faculty Newcastle University [Newcastle] Indiana University System Newcastle University [Newcastle] Newcastle University [Newcastle] QIMR Berghofer Medical Research Institute Veterans Affairs Long Beach Healthcare System NSW Government The University of Sydney
• Publié dans Hepatology le 30/10/2020

---

Résumé : Background and aims - Only a minority of heavy drinkers progress to alcohol-associated cirrhosis (ALC). The aim of this study was to identify common genetic variants that underlie risk for ALC. Approach and results - We analyzed data from 1,128 subjects of European ancestry with ALC and 614 heavy-drinking subjects without known liver disease from Australia, the United States, the United Kingdom, and three countries in Europe. A genome-wide association study (GWAS) was performed, adjusting for principal components and clinical covariates (alcohol use, age, sex, body mass index, and diabetes). We validated our GWAS findings using UK Biobank. We then performed a meta-analysis combining data from our study, the UK Biobank, and a previously published GWAS. Our GWAS found genome-wide significant risk association of rs738409 in patatin-like phospholipase domain containing 3 (PNPLA3) (odds ratio [OR] = 2.19 [G allele], P = 4.93 × 10 ) and rs4607179 near HSD17B13 (OR = 0.57 [C allele], P = 1.09 × 10 ) with ALC. Conditional analysis accounting for the PNPLA3 and HSD17B13 loci identified a protective association at rs374702773 in Fas-associated factor family member 2 (FAF2) (OR = 0.61 [del(T) allele], P = 2.56 × 10 ) for ALC. This association was replicated in the UK Biobank using conditional analysis (OR = 0.79, P = 0.001). Meta-analysis (without conditioning) confirmed genome-wide significance for the identified FAF2 locus as well as PNPLA3 and HSD17B13. Two other previously known loci (SERPINA1 and SUGP1/TM6SF2) were also genome-wide significant in the meta-analysis. GeneOntology pathway analysis identified lipid droplets as the target for several identified genes. In conclusion, our GWAS identified a locus at FAF2 associated with reduced risk of ALC among heavy drinkers. Like the PNPLA3 and HSD17B13 gene products, the FAF2 product has been localized to fat droplets in hepatocytes. Conclusions - Our genetic findings implicate lipid droplets in the biological pathway(s) underlying ALC.

---

Fichiers liés : Schwantes‐An et al-2020-Genome-wide association study and meta-analysis on alcohol-related liver.pdf

---

Source

---

• Type de publi. : Article dans une revue
• Date de publi. : 30/04/2021
• Auteurs : Vincent BondetMathieu P RoderoCéline PossemePierre BostJérémie DecalfLiis HaljasmägiNassima BekaddourGillian I. RiceVinit UpasaniJean Philippe HerbeuvalJohn A. ReynoldsTracy A. BriggsIan N. BruceClaudia MauriDavid IsenbergMadhvi MenonDavid HuntBenno SchwikowskiXavier MarietteStanislas PolNathalie BoddaertTineke CantaertJ. Eric GottenbergKai KisandDarragh Duffy
• Organismes : Immunologie Translationnelle - Translational Immunology lab Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques Immunologie Translationnelle - Translational Immunology lab Université Paris Cité Biologie systémique - Systems Biology Ecole Doctorale Complexité du Vivant Immunobiologie des Cellules dendritiques Tartu University Hospital Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques University of Manchester [Manchester] Manchester University NHS Foundation Trust Immunologie [Phnom Penh] Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques University of Manchester [Manchester] University of Birmingham [Birmingham] Sandwell and West Birmingham Hospitals NHS Trust University of Manchester [Manchester] Manchester University NHS Foundation Trust University of Manchester [Manchester] University College London [UCL] University College London [UCL] University College London [UCL] University of Manchester [Manchester] The University of Edinburgh Biologie systémique - Systems Biology Ecole Doctorale Complexité du Vivant Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes Service de Rhumatologie [CHU Bicêtre] Service d'hépatologie médicale [CHU Cochin] Service de Virologie [CHU Cochin] Université Paris Cité Immunologie [Phnom Penh] Université de Strasbourg Tartu University Hospital Immunologie Translationnelle - Translational Immunology lab
• Publié dans Cytokine le 31/10/2020

---

Résumé : Type I interferons are essential for host response to viral infections, while dysregulation of their response can result in autoinflammation or autoimmunity. Among IFNα (alpha) responses, 13 subtypes exist that signal through the same receptor, but have been reported to have different effector functions. However, the lack of available tools for discriminating these closely related subtypes, in particular at the protein level, has restricted the study of their differential roles in disease. We developed a digital ELISA with specificity and high sensitivity for the IFNα2 subtype. Application of this assay, in parallel with our previously described pan-IFNα assay, allowed us to study different IFNα protein responses following cellular stimulation and in diverse patient cohorts. We observed different ratios of IFNα protein responses between viral infection and autoimmune patients. This analysis also revealed a small percentage of autoimmune patients with high IFNα2 protein measurements but low pan-IFNα measurements. Correlation with an ISG score and functional activity showed that in this small sub group of patients, IFNα2 protein measurements did not reflect its biological activity. This unusual phenotype was partly explained by the presence of anti-IFNα auto-antibodies in a subset of autoimmune patients. This study reports ultrasensitive assays for the study of IFNα proteins in patient samples and highlights the insights that can be obtained from the use of multiple phenotypic readouts in translational and clinical studies.

---

Fichiers liés : 1-s2.0-S1043466621001137-main.pdf

---

Source

---

• Type de publi. : Article dans une revue
• Date de publi. : 29/04/2021
• Auteurs : Steven Le GouillHervé GhesquieresLucie ObéricFranck MorschhauserHervé TillyVincent RibragThierry LamyCatherine ThieblemontHerve Gerard MaisonneuveRemy GressinKrimo BouabdallahCorinne HaiounGandhi DamajLuc-Matthieu ForneckerReda BouabdallahPierre FeugierDavid SibonGuillaume CartronChristophe BonnetMarc AndréLoic ChartierPhilippe RuminyF Kraeber-BodereC Bodet-MilinAlina Berriolo-RiedingerJosette BriereJean-Philippe JaisThierry MolinaEmmanuel IttiOlivier Casasnovas
• Organismes : Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma Immuno-Biologie des Lymphomes [CIRI] Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL] Institut Universitaire du Cancer de Toulouse - Oncopole Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen Institut Gustave Roussy Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse Microenvironment, Cell Differentiation, Immunology and Cancer Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Service d'Hémato-oncologie [CHU Saint-Louis] Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon Hôpital Michallon CHU Pessac CHI Créteil Institut d'Hématologie de Basse-Normandie Hôpitaux Universitaires de Strasbourg Institut Paoli-Calmettes Centre Hospitalier Régional Universitaire de Nancy Nutrition-Génétique et Exposition aux Risques Environnementaux Hôpital Necker - Enfants Malades [AP-HP] Institut de Génétique Moléculaire de Montpellier Centre Hospitalier Régional Universitaire [Montpellier] Centre Hospitalier Universitaire de Liège CHU UCL Namur The Lymphoma Academic Research Organisation [Lyon] Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] Hopital Saint-Louis [AP-HP] Université Paris Descartes - Paris 5 Hôpital Necker - Enfants Malades [AP-HP] CHI Créteil CHU Dijon
• Publié dans Blood le 28/10/2020

---

Résumé : Rituximab plus polychemotherapy is the standard of care in diffuse large B-cell lymphoma (DLBCL). GAINED, a randomized phase 3 trial, compared obinutuzumab to rituximab. Transplant-eligible patients (18-60 years) with an untreated age-adjusted International Prognostic Index (aaIPI) score ≥1 DLBCL were randomized (1:1) between obinutuzumab or rituximab and stratified by aaIPI (1; 2-3) and chemotherapy regimen (doxorubicin, cyclophosphamide, prednisone plus vindesine, bleomycin [ACVBP] or vincristine [CHOP]). Consolidation treatment was determined according to response to interim positron emission tomography (PET). Responders after cycle 2 and 4 (PET2-/PET4-) received immunochemotherapy. Responders after only cycle 4 (PET2+/4-) received transplantation. The primary objective was an 8% improvement (hazard ratio [HR] = 0.73; 80% power; α risk, 2.5%; 1-sided) in 2-year event-free survival (EFS) in the obinutuzumab arm. From September 2012, 670 patients were enrolled (obinutuzumab, n = 336; rituximab, n = 334). A total of 383 (57.2%) were aaIPI 2-3, 339 (50.6%) received CHOP. Median follow-up was 38.7 months. The 2-year EFS was similar in both groups (59.8% vs 56.6%; P = .123; HR = 0.88). The 2-year PFS in the whole cohort was 83.1% (95% confidence interval, 80% to 85.8%). PET2-/4- and PET2+/4- had similar 2-year progression-free survival (PFS) and overall survival (OS): 89.9% vs 83.9% and 94.8% vs 92.8%. The 2-year PFS and OS for PET4+ patients were 62% and 83.1%. Grade 3-5 infections were more frequent in the obinutuzumab arm (21% vs 12%). Obinutuzumab is not superior to rituximab in aaIPI ≥1 DLBCL transplant-eligible patients. This trial was registered at www.clinicaltrials.gov as #NCT01659099.

---

Fichiers liés : Le Gouill et al-2020-Obinutuzumab versus Rituximab in young patients with advanced DLBCL.pdf

---

Source

---

• Type de publi. : Article dans une revue
• Date de publi. : 28/04/2021
• Auteurs : Émilie BoulangerNicolas LoiseauAlice ValentiniVéronique ArnalPierre BoisseryTony DejeanJulie DeterNacim GuellatiFlorian HolonJean-Baptiste JuhelPhilippe LenfantStéphanie ManelDavid Mouillot
• Organismes : Centre d’Ecologie Fonctionnelle et Evolutive MARine Biodiversity Exploitation and Conservation MARine Biodiversity Exploitation and Conservation SPYGEN [Le Bourget-du-Lac] Centre d’Ecologie Fonctionnelle et Evolutive Agence de l'eau Rhône Méditerranée Corse SPYGEN [Le Bourget-du-Lac] Andromède Océanologie MARine Biodiversity Exploitation and Conservation Andromède Océanologie MARine Biodiversity Exploitation and Conservation Centre de Formation et de Recherche sur les Environnements Méditérranéens Centre d’Ecologie Fonctionnelle et Evolutive MARine Biodiversity Exploitation and Conservation Institut universitaire de France
• Publié dans Proceedings of the Royal Society B: Biological Sciences le 25/10/2020

---

Résumé : Although we are currently experiencing worldwide biodiversity loss, local species richness does not always decline under anthropogenic pressure. This conservation paradox may also apply in protected areas but has not yet received conclusive evidence in marine ecosystems. Here, we survey fish assemblages in six Mediterranean no-take reserves and their adjacent fishing grounds using environmental DNA (eDNA) while controlling for environmental conditions. We detect less fish species in marine reserves than in nearby fished areas. The paradoxical gradient in species richness is accompanied by a marked change in fish species composition under different managements. This dissimilarity is mainly driven by species that are often overlooked by classical visual surveys but detected with eDNA: cryptobenthic, pelagic, and rare fishes. These results do not negate the importance of reserves in protecting biodiversity but shed new light on how under-represented species groups can positively react to fishing pressure and how conservation efforts can shape regional biodiversity patterns.

---

Fichiers liés : 83492.pdf

---

Source

---

• Type de publi. : Article dans une revue
• Date de publi. : 28/04/2021
• Auteurs : Alemu GonsamoPhilippe CiaisB. MirallesStephen SitchWouter DorigoDanica LombardozziPierre FriedlingsteinJulia NabelDaniel S GollMichael O’sullivanAlmut ArnethPeter AnthoniAtul JainP. PeylinAlessandro Cescatti
• Organismes : School of Geography and earth sciences Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] ICOS-ATC Environnement, Ville, Société Université Lumière - Lyon 2 LabEx Intelligences des Mondes Urbains University of Exeter Department of Geodesy and Geoinformation [TU Wien] National Center for Atmospheric Research [Boulder] Laboratoire de Météorologie Dynamique (UMR 8539) Institut Pierre-Simon-Laplace Max Planck Institute for Meteorology Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] Contrôles des cycles biogéochimiques terrestres College of Life and Environmental Sciences [Exeter] Institut für Meteorologie und Klimaforschung - Atmosphärische Umweltforschung Institute of Meteorology and Climate Research Department of Atmospheric Sciences [Urbana] Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] JRC Institute for Environment and Sustainability
• Publié dans Global Change Biology le 25/10/2020

---

Résumé : The rising atmospheric CO2 concentration leads to a CO2 fertilization effect on plants—that is, increased photosynthetic uptake of CO2 by leaves and enhanced water-use efficiency (WUE). Yet, the resulting net impact of CO2 fertilization on plant growth and soil moisture (SM) savings at large scale is poorly understood. Drylands provide a natural experimental setting to detect the CO2 fertilization effect on plant growth since foliage amount, plant water-use and photosynthesis are all tightly coupled in water-limited ecosystems. A long-term change in the response of leaf area index (LAI, a measure of foliage amount) to changes in SM is likely to stem from changing water demand of primary productivity in water-limited ecosystems and is a proxy for changes in WUE. Using 34-year satellite observations of LAI and SM over tropical and subtropical drylands, we identify that a 1% increment in SM leads to 0.15% (±0.008, 95% confidence interval) and 0.51% (±0.01, 95% confidence interval) increments in LAI during 1982‒1998 and 1999‒2015, respectively. The increasing response of LAI to SM has contributed 7.2% (±3.0%, 95% confidence interval) to total dryland greening during 1999‒2015 compared to 1982‒1998. The increasing response of LAI to SM is consistent with the CO2 fertilization effect on WUE in water-limited ecosystems, indicating that a given amount of SM has sustained greater amounts of photosynthetic foliage over time. The LAI responses to changes in SM from seven dynamic global vegetation models are not always consistent with observations, highlighting the need for improved process knowledge of terrestrial ecosystem responses to rising atmospheric CO2 concentration.

---

Source

---

• Type de publi. : Article dans une revue
• Date de publi. : 28/04/2021
• Auteurs : Guillaume GuérinChristelle LahayeMaryam HeydariMartin AutzenJan-Pieter BuylaertPierre GuibertMayank JainSebastian KreutzerLebrun BriceAndrew MurrayKristina ThomsenPetra UrbanováAnne Philippe
• Organismes : IRAMAT-Centre de recherche en physique appliquée à l’archéologie Géosciences Rennes IRAMAT-Centre de recherche en physique appliquée à l’archéologie IRAMAT-Centre de recherche en physique appliquée à l’archéologie Danmarks Tekniske Universitet = Technical University of Denmark Danmarks Tekniske Universitet = Technical University of Denmark IRAMAT-Centre de recherche en physique appliquée à l’archéologie Danmarks Tekniske Universitet = Technical University of Denmark IRAMAT-Centre de recherche en physique appliquée à l’archéologie Aberystwyth University IRAMAT-Centre de recherche en physique appliquée à l’archéologie Aarhus University [Aarhus] Danmarks Tekniske Universitet = Technical University of Denmark IRAMAT-Centre de recherche en physique appliquée à l’archéologie Laboratoire de Mathématiques Jean Leray
• Publié dans Geochronology le 10/09/2020

---

Résumé : Abstract. Statistical analysis has become increasingly important in optically stimulated luminescence (OSL) dating since it has become possible to measure signals at the single-grain scale. The accuracy of large chronological datasets can benefit from the inclusion, in chronological modelling, of stratigraphic constraints and shared systematic errors. Recently, a number of Bayesian models have been developed for OSL age calculation; the R package “BayLum” presented herein allows different models of this type to be implemented, particularly for samples in stratigraphic order which share systematic errors. We first show how to introduce stratigraphic constraints in BayLum; then, we focus on the construction, based on measurement uncertainties, of dose covariance matrices to account for systematic errors specific to OSL dating. The nature (systematic versus random) of errors affecting OSL ages is discussed, based – as an example – on the dose rate determination procedure at the IRAMAT-CRP2A laboratory (Bordeaux). The effects of the stratigraphic constraints and dose covariance matrices are illustrated on example datasets. In particular, the benefit of combining the modelling of systematic errors with independent ages, unaffected by these errors, is demonstrated. Finally, we discuss other common ways of estimating dose rates and how they may be taken into account in the covariance matrix by other potential users and laboratories. Test datasets are provided as a Supplement to the reader, together with an R markdown tutorial allowing the reproduction of all calculations and figures presented in this study.

---

Fichiers liés : gchron-3-229-2021.pdf

---

Source