250,760 results on '"[SDV]Life Sciences [q-bio]"'
Search Results
2. Acute tubulointerstitial nephritis with or without uveitis: a novel form of post-acute COVID-19 syndrome in children
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Marina Avramescu, Pierre Isnard, Sarah Temmam, Agnès Chevalier, Paul Bastard, Mikael Attia, Romain Berthaud, Marc Fila, Claire Dossier, Julien Hogan, Tim Ulinski, Damia Leguevaques, Férielle Louillet, Edouard Martinez Casado, Jean-Michel Halimi, Sylvie Cloarec, Ariane Zaloszyc, Camille Faudeux, Caroline Rousset-Rouvière, Stéphanie Clavé, Jérôme Harambat, Edouard Rollot, Thomas Simon, Megan Nallet-Amate, Bruno Ranchin, Justine Bacchetta, Florence Porcheret, Josselin Bernard, Amélie Ryckewaert, Anne Jamet, Jacques Fourgeaud, Nicolas Da Rocha, Philippe Pérot, Nicolas Kuperwasser, Naïm Bouazza, Marion Rabant, Jean-Paul Duong Van Huyen, Matthieu P Robert, Julien Zuber, Jean-Laurent Casanova, Marc Eloit, Isabelle Sermet-Gaudelus, Olivia Boyer, Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte [CHU-Necker] (MARHEA), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Découverte de pathogènes – Pathogen discovery, Institut Pasteur [Paris] (IP), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Rockefeller University [New York], Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), AP-HP Hôpital universitaire Robert-Debré [Paris], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Rouen, Normandie Université (NU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Strasbourg, Centre Hospitalier Universitaire de Nice (CHU Nice), Assistance Publique - Hôpitaux de Marseille (APHM), CHU Bordeaux [Bordeaux], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Pontchaillou [Rennes], Pharmacologie et évaluations thérapeutiques chez l'enfant et la femme enceinte (URP_7323), Université Paris Cité (UPCité), Site Tarnier (hôpital Cochin) - APHP, CIC - Mère Enfant Necker Cochin Paris Centre (CIC 1419), Hôpital Cochin [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
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pediatric ,SARS-CoV ,Nephrology ,[SDV]Life Sciences [q-bio] ,2 TINUs ,tubule-interstitial nephritis ,uveitis ,COVID-19 - Abstract
BackgroundCOVID-19 is a complex multisystem disease, frequently associated with kidney injury. Since the beginning of the COVID-19 pandemic, we observed a striking increase in the incidence of acute tubulointerstitial nephritis (aTIN) without or with uveitis (TINUs) among children. This prompted us to examine whether SARS-CoV-2 might be the underlying trigger.MethodsWe conducted a French nationwide retrospective cohort study. We included all consecutive children diagnosed with aTIN or TINUs of undetermined cause between April-2020 and March-2021. SARS-CoV-2 antibody responses were tested by a luciferase immunoprecipitation system and compared to age-matched controls. Immunohistochemistry, immunofluorescence and molecular microbiology analyses were performed on kidney biopsies.ResultsForty-eight children were included with a median age at diagnosis of 14.7 years (9.4-17.6). aTIN and TINUs incidence rates increased 3-fold and 12-fold, respectively, compared to pre-pandemic years. All patients had impaired kidney function with a median eGFR of 31.9 ml/min/1.73m² at diagnosis. Kidney biopsies showed lesions of acute tubulointerstitial nephritis and 25% of patients had fibrosis. No patient had concomitant acute COVID-19. All 16 children tested had high anti-N IgG titers and one had anti-S IgGs. Next-generation sequencing failed to detect any infectious agents in kidney biopsies. However, SARS-CoV-2 RNA was detected by PCR in two kidney samples supporting a potential direct link between SARS-CoV-2 and aTIN/TINUs.ConclusionsWe describe a novel form of post-acute COVID-19 syndrome in children, unique in its exclusive kidney and eye involvement, and its distinctive anti-SARS-CoV-2 N+/S-serological profile. Our results support a causal association linking SARS-CoV-2 infection to this newly-reported burst of renal/eye inflammation.
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- 2023
3. Lab-On-Chip UHF-Dielectrophoretic Cytometer for Colorectal Cancer Stem Cells Sorting
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Elisa Lambert, Elodie Barthout, Thomas Provent, Remi Manczak, Sofiane Saada, Barbara Bessette, Muriel Mathonnet, Fabrice Lalloué, Claire Dalmay, Arnaud Pothier, RF-ELITE : RF-Electronique Imprimée pour les Télécommunications et l'Energie (XLIM-RFEI), XLIM (XLIM), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS), Contrôle de l’Activation Cellulaire, Progression Tumorale et Résistance thérapeutique (CAPTuR), Institut National de la Santé et de la Recherche Médicale (INSERM)-OmégaHealth (ΩHealth), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Service de Chirurgie digestive, endocrinienne et générale [CHU Limoges], CHU Limoges, PLATINOM: PLATeforme de technologie et d’INstrumentation pour l’Optique et les Microondes - Service commun de l’Université de Limoges (PLATINOM), Region Nouvelle Aquitaine : projet Oncosometrack project No 1R30217, FEDER- CPER PILIM (2015-2020) Etat Region Nouvelle Aquitaine, and European Project: 207249, H2020-EU.1.2.1. - FET Open,737164,SUMCASTEC(2017)
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[SPI]Engineering Sciences [physics] ,Radiation ,Biological cell manipulation ,microfluidic biosensors ,[SDV]Life Sciences [q-bio] ,colorectal cancer stem cells ,label-free cell sorting ,Radiology, Nuclear Medicine and imaging ,UHF dielectrophoresis ,Instrumentation - Abstract
International audience; In this article, we introduce a method to exploit ultra-high dielectrophoresis (UHF-DEP) with a microfluidic radio frequency device able to sort biological cells by deflecting the trajectory of the targeted population in a continuous flow. This study highlights the capability of a high frequency lab-on-chip implemented UHF-DEP cytometer to isolate cancer stem cells (CSCs). Actually, CSCs sorting by an efficient, fast and low-cost method remains an issue. Above 20 MHz, the intracellular dielectric properties of cells determine the dielectrophoretic behavior of cells and is then very sensitive to the cell cytoplasm content. The proposed cell sorting principle exploits the combination of the fluidic drag and the repulsive dielectrophoretic forces in order to isolate CSCs hidden within differentiated cancer cells. We previously demonstrated the UHF-DEP behavior of cells, as a new type of electromagnetic biomarkers to discriminate cancer stem cells among a tumor population from colorectal cancer cell line.
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- 2023
4. Functional and developmental convergence in the reproductive 'nurse cells' of flowering plants
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Doll, Nicolas Max, Truskina, Jekaterina, Ingram, Gwyneth, Reproduction et développement des plantes (RDP), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
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[SDV]Life Sciences [q-bio] ,General Medicine - Published
- 2023
5. Alcohol consumption, alcohol expectancies, and drinking contexts in young Argentinean college students before and during the COVID-19 pandemic: a one-year follow-up study
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Lorena Cecilia López Steinmetz, Candela Abigail Leyes, Shao Bing Fong, Juan Carlos Godoy, Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes - UFR d'Odontologie (UR Odontologie), and Université de Rennes (UR)
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Psychiatry and Mental health ,Clinical Psychology ,alcohol drinking in college ,[SDV]Life Sciences [q-bio] ,quarantine ,COVID-19 ,longitudinal studies ,Medicine (miscellaneous) ,Alcohol drinking ,developing countries ,expectations - Abstract
International audience; Background: The COVID-19 pandemic and lockdowns are known to affect alcohol consumption. This study examines drinking expectancies and contexts upon alcohol consumption of Argentinean students.Objectives: To assess within-person changes in alcohol consumption in Argentinean college students (aged 18-24), from August 2019 with a one-year follow-up during the COVID-19 lockdown, considering alcohol expectancies, drinking contexts, and main socio-demographic variables. To validate the stability of these predictors, we discuss the effects on the alcohol consumption across dependent and independent measures.Methods: We assessed one longitudinal (N = 300, 70% female) and one cross-sectional (N = 165, 78% female) sample via online surveys and applied multilevel analysis and regressions, respectively.Results: Alcohol consumption significantly increased during lockdown compared to one-year before (mean: 6.91 and 8.26 alcohol units, correspondingly). In the longitudinal sample, social facilitation (medium effect sizes [ES]: 0.21, 0.22) and parental presence (medium ES: 0.12, 0.21) significantly and stable (through time) predicted increasing effects on consumption. In the cross-sectional sample, stress control (high ES: 0.78) and parental presence (high ES: 0.42) were associated with higher consumption during lockdown.Conclusion: College students increased their alcohol consumption during lockdown, suggesting that restrictive sanitary measures may negatively affect consumption. Literature is not conclusive as both decreases and increases in alcohol consumption in students from developed countries were reported. Before and during COVID-19 lockdown, parental presence is a stable predictor of increased alcohol consumption, though unusual according to the literature. Health policies aimed at modifying the behavior of parents who promote/share alcohol consumption with their offspring may help reduce drinking in college students.
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- 2023
6. RF sensor dedicated to the dielectric characterization of spheroids between 500 MHz and 20 GHz
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Olivia Peytral-Rieu, David Dubuc, Katia Grenier, Équipe Micro et nanosystèmes HyperFréquences Fluidiques (LAAS-MH2F), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université Toulouse Capitole (UT Capitole), and Université de Toulouse (UT)
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Coplanar waveguide (CPW) ,Label-free analysis ,[PHYS]Physics [physics] ,Electromagnetic waves ,Cells ,[SDV]Life Sciences [q-bio] ,Dielectric characterization ,Spheroids ,Electrical and Electronic Engineering ,Microwave ,Biosensor ,Biosensor Microwave Electromagnetic waves Dielectric characterization Coplanar waveguide (CPW) Label-free analysis Spheroids Cells - Abstract
To achieve better accuracy in their investigations, biologists have recently been using three-dimensional models as intermediates between two-dimensional cell culture and the in vivo study of tissues. Some of these models are based on spheroids, which are cellular aggregates retaining many characteristics of in vivo behaviors while being still easy to use and implement in labs. To study such objects, multiple observation techniques can be used according to the objective of the study, including those using electromagnetic waves as nondestructive, noninvasive, and label-free analysis. Low-frequency (
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- 2023
7. A Review of the Health-Promoting Properties of Spirulina with a Focus on athletes’ Performance and Recovery
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Mehdi Chaouachi, Sophie Vincent, Carole Groussard, Laboratoire Mouvement Sport Santé (M2S), Université de Rennes (UR)-École normale supérieure - Rennes (ENS Rennes)-Université de Brest (UBO)-Université de Rennes 2 (UR2)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and None
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body composition ,muscle damage ,Nutrition and Dietetics ,inflammation ,[SDV]Life Sciences [q-bio] ,Spirulina ,Pharmacology (medical) ,athletic performance ,Antioxidants ,Food Science - Abstract
International audience; Spirulina species are photosynthetic and filamentous bacteria, commonly called 'blue-green microalgae'. Spirulina has a high nutrient content. It contains 60-70% protein with all essential amino acids present, and is rich in several vitamins, minerals, and bioactive compounds. Spirulina is also rich in essential fatty acids, and antioxidants. This rich nutritional content provides to Spirulina several health benefits including antioxidant, anti-inflammatory, immunomodulation, and insulin-sensitizing properties as well as positive effects in various diseases which could be also interesting for athletes. This paper mainly aims to review the interest and effects of Spirulina supplementation in athletes at rest, and in relation to exercise/training. Spirulina's biochemical composition, health properties/effects in humans, and effects in athletes including nutritional status, body composition, physical performance and intense exercise-related disorders were discussed in this review. Literature data showed that Spirulina seems to have positive effects on body composition especially in overweight and obese subjects which could not be the case in other pathologies and athletes. Spirulina appears to be also effective in improving aerobic fitness especially in untrained and moderately trained subjects. Results reported in the literature suggest that Spirulina may improve strength and power performance despite the minor or no significant effects in highly trained subjects. Most studies have shown that Spirulina improves antioxidant status, prevents and accelerates the recovery of exercise-induced lipid peroxidation, muscle damage and inflammation in trained and untrained subjects. Taken together, the results from these studies are encouraging and may demonstrate the potential benefits of Spirulina supplementation in athletes despite methodological differences.
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- 2023
8. Impact of phosphorus limitation on medium-chain-length polyhydroxyalkanoate production by activated sludge
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Emilie Alaux, Bastien Marie, Marion Couvreur, Mansour Bounouba, Guillermina Hernandez-Raquet, Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), BIOPLAST Interreg POCTEFA project EFA253/16, ECOPLAST project 20009834, and Région Occitanie
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[SDV.BIO]Life Sciences [q-bio]/Biotechnology ,Mixed culturesBacterial diversity ,[SDV]Life Sciences [q-bio] ,Phosphorus limitation ,General Medicine ,Medium-chain-length polyhydroxyalkanoates ,Applied Microbiology and Biotechnology ,Bioplastics ,Biotechnology - Abstract
International audience; For a sustainable economy, biodegradable biopolymers polyhydroxyalkanoates (PHA) are desirable substitutes to petroleum-based plastics that contaminate our environment. Medium-chain-length (MCL) PHA bioplastics are particularly interesting due to their thermoplastic properties. To hamper the high cost associated to PHA production, the use of bacterial mixed cultures cultivated in open systems and using cheap resources is a promising strategy. Here, we studied the operating conditions favouring direct MCL accumulation by activated sludge, using oleic acid as a model substrate and phosphorus limitation in fed-batch bioreactors. Our results confirm the presence of PHA-accumulating organisms (PHAAO) in activated sludge able to accumulate MCL from oleic acid. A positive correlation between phosphorus (P) limitation and PHA accumulation was demonstrated, allowing up to 26% PHA/total biomass accumulation, and highlighted its negative impact on the MCL/PHA fraction in the polymer. Diversity analysis through 16S rRNA amplicon sequencing revealed a differential selection of PHAAO according to the P-limitation level. A differential behaviour for the orders Pseudomonadales and Burkholderiales at increasing P-limitation levels was revealed, with a higher abundance of the latter at high levels of P-limitation. The PHA accumulation observed in activated sludge open new perspectives for MCL-PHA production system based on P-limitation strategy applied to mixed microbial communities.
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- 2023
9. A Novel Stereo Camera Fusion Scheme for Generating and Tracking Real-Time 3-D Patient-Specific Head/Face Kinematics and Facial Muscle Movements
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Tan-Nhu Nguyen, Abbass Ballit, Tien-Tuan Dao, Laboratoire de Mécanique, Multiphysique, Multiéchelle - UMR 9013 (LaMcube), and Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
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[SDV]Life Sciences [q-bio] ,Electrical and Electronic Engineering ,Instrumentation - Published
- 2023
10. Defining genomic epidemiology thresholds for common-source bacterial outbreaks: a modelling study
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Duval, Audrey, Opatowski, Lulla, Brisse, Sylvain, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials (EMAE), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, We acknowledge the financial support of the MedVetKlebs project, a component of European Joint Programme One Health EP, which has received funding from the European Union Horizon 2020 Research and Innovation Programme (grant number 773830). We thank Xavier Didelot and Olivier Tenaillon for critical feedback on an earlier version of the manuscript, David Smith for helpful comments, and Chiara Crestani for help in manuscript and figure formatting., and European Project: 773830,H2020-SFS-2017-1,MedVetKlebs (a component of European Joint Programme One Health)(2018)
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Microbiology (medical) ,Infectious Diseases ,[SDV]Life Sciences [q-bio] ,Virology ,Microbiology - Abstract
Summary Background Epidemiological surveillancerelies on microbial strain typing, which defines genomic relatedness among isolates to identify case clusters and their potential sources. Although predefined thresholds are often applied, known outbreak-specific features such aspathogenmutation rateand duration of source contamination are rarely considered. We aimed to develop a hypothesis-based model that estimates genetic distance thresholds and mutation rates for point-source single-strain food or environmental outbreaks. Methods In this modelling study, we developed a forward model to simulate bacterial evolution at a specific mutation rate (μ) over a defined outbreak duration (D). From the distribution of genetic distances expected under the given outbreak parameters and sample isolation dates, we estimated a distance threshold beyond which isolates should not be considered as part of the outbreak. We embedded the model into a Markov Chain Monte Carlo inference framework to estimate the most probable mutation rate or time since source contamination, which are both often imprecisely documented. A simulation study validated the model over realistic durations and mutation rates. We then identified and analysed 16 published datasets of bacterial source-related outbreaks; datasets were included if they were from an identified foodborne outbreak and if whole-genome sequence data and collection dates for the described isolates were available. Findings Analysis of simulated data validated the accuracy of our framework in both discriminating between outbreak and non-outbreak cases and estimating the parametersDand μ from outbreak data. Precision of estimation was much higher for high values ofDand μ. Sensitivity of outbreak cases was always very high, and specificity in detecting non-outbreak cases was poor for low mutation rates. For 14 of the 16 outbreaks, the classification of isolates as being outbreak-related or sporadic is consistent with the original dataset. Four of these outbreaks included outliers, which were correctly classified as being beyond the threshold of exclusion estimated by our model, except for one isolate of outbreak 4. For two outbreaks, both foodborneListeria monocytogenes, conclusions from our model were discordant with published results: in one outbreak two isolates were classified as outliers by our model and in another outbreak our algorithm separated food samples into one cluster and human samples into another, whereas the isolates were initially grouped together based on epidemiological and genetic evidence. Re-estimated values of the duration of outbreak or mutation rate were largely consistent with a priori defined values. However, in several cases the estimated values were higher and improved the fit with the observed genetic distance distribution, suggesting that early outbreak cases are sometimes missed. Interpretation We propose here an evolutionary approach to the single-strain conundrum by estimating the genetic threshold and proposing the most probable cluster of cases for a given outbreak, as determined by its particular epidemiological and microbiological properties. This forward model, applicable to foodborne or environmental-source single point case clusters or outbreaks, is useful for epidemiological surveillance and may inform control measures. Funding European Union Horizon 2020 Research and Innovation Programme.
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- 2023
11. Association between ACTN3 R577X genotype and risk of non-contact injury in trained athletes: A systematic review
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Juan Del Coso, Hassane Zouhal, Guillaume Ravé, Claire Tourny, Abderraouf Ben Abderrahman, Benjamin Barthélémy, Nidhal Jebabli, Cain C T Clark, Anthony C. Hackney, Ayyappan Jayavel, Laboratoire Mouvement Sport Santé (M2S), École normale supérieure - Cachan (ENS Cachan)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Brest (UBO)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Universidad Rey Juan Carlos [Madrid] (URJC), SRM Institute of Science and Technology (SRM), Centre d’études des transformations des activités physiques et sportives (CETAPS), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut de Recherche Interdisciplinaire Homme et Société (IRIHS), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Toulouse Football Club, ISSEP Ksar Saïd, Université de la Manouba [Tunisie] (UMA), Coventry University, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), and Université de Rennes (UR)-École normale supérieure - Rennes (ENS Rennes)-Université de Brest (UBO)-Université de Rennes 2 (UR2)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
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medicine.medical_specialty ,[SDV]Life Sciences [q-bio] ,Physical Therapy, Sports Therapy and Rehabilitation ,Single-nucleotide polymorphism ,Athletic performance ,03 medical and health sciences ,0302 clinical medicine ,Polymorphism (computer science) ,Internal medicine ,Epidemiology ,Genotype ,medicine ,Muscle injury ,Orthopedics and Sports Medicine ,Exercise-related injury ,Association (psychology) ,α-actinin-3 deficiency ,030304 developmental biology ,0303 health sciences ,biology ,business.industry ,Athletes ,030229 sport sciences ,biology.organism_classification ,Single nucleotide polymorphism ,medicine.anatomical_structure ,Ankle ,business ,XX Genotype - Abstract
Background The aim of this study was to review, systematically, evidence concerning the link between the ACTN3 R577X polymorphism and the rates and severity of non-contact injuries and exercise-induced muscle damage in athletes and individuals enrolled in exercise training programs. Methods A computerized literature search was performed in the electronic databases PubMed, Web of Science, and SPORTDiscus, from inception until November 2020. All included studies compared the epidemiological characteristics of non-contact injury between the different genotypes of the ACTN3 R577X polymorphism. Results Our search identified 492 records. After the screening of titles, abstracts, and full texts, 13 studies examining the association between the ACTN3 genotypes and the rate and severity of non-contact injury were included in the analysis. These studies were performed in 6 different countries (Spain, Japan, Brazil, China, Republic of Korea, and Italy) and involved a total participant pool of 1093 participants. Of the studies, 2 studies involved only women, 5 studies involved only men, and 6 studies involved both men and women. All the studies included were classified as high-quality studies (≥6 points in the Physiotherapy Evidence Database (PEDro) scale score). Overall, evidence suggests there is an association between the ACTN3 R577X genotype and non-contact injury in 12 investigations. Six studies observed a significant association between ACTN3 R577X polymorphism and exercise induced muscle damage: two with non-contact ankle injury, three with non-contact muscle injury, and one with overall non-contact injury. Conclusion The present findings support the premise that possessing the ACTN3 XX genotype may predispose athletes to a higher probability of some non-contact injuries, such as muscle injury, ankle sprains, and higher levels of exercise-induced muscle damage.
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- 2023
12. Soins de support nutritionnels dans le parcours des patients atteints de cancers œsogastriques
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de Moura, Alexandre, Turpin, Anthony, Neuzillet, Cindy, Institut Curie [Paris], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CHU Lille, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, 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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Sarcopenia ,Cancer Research ,Oncology ,Physical activity ,[SDV]Life Sciences [q-bio] ,Malnutrition ,Radiology, Nuclear Medicine and imaging ,Esophagogastric neoplasm ,Hematology ,General Medicine ,Prehabilitation ,Nutrition - Abstract
International audience; Supportive care plays a central role in the management of patients with esophagogastric cancers, at all disease stages. Malnutrition has a high prevalence in this population, reaching up to 60 % of the patients. Sarcopenia and cachexia are also common. These complications have negative impact on functional abilities, quality of life and overall survival. They impair anti-tumor treatments effectiveness and increase their toxicity. Early detection and management are needed, before reaching advanced stages, which are refractory to therapeutic interventions. Specific nutritional support is recommended, relying on different nutritional support tools (dietetic counseling, oral supplements, artificial nutrition), depending on the clinical situation. When artificial nutrition is recommended, enteral nutrition (nasogastric tube, gastrostomy or jejunostomy) should be preferred. When enteral nutrition is impossible or insufficient, parenteral nutrition could be necessary. For patients with advanced esophagogastric cancers, digestive prostheses and decompressive radiation therapy may have a symptomatic benefit on dysphagia. Adapted physical activity is also recommended at all stages of cancer care and ongoing clinical trials will help to specify its modalities and to optimize its place in the therapeutic strategy. Finally, psychosocial support could be useful. A combined approach of these different interventions on the nutritional, physical and psychological aspects is beneficial for patients with esophagogastric cancers. This multimodal and multidisciplinary approach applies to both the early stages of the disease, with prehabilitation and/or rehabilitation to reduce perioperative morbidity and mortality and the advanced stages, with a benefit on survival and quality of life, in parallel with anti-tumor treatments.
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- 2023
13. Identification et dosage de la mitragynine dans les cheveux : à propos d’un cas d’un consommateur régulier de substances psychotropes achetées sur le dark web
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Kernalléguen, Angéline, Fabresse, Nicolas, Etting, Isabelle, Larabi, Islam Amine, Alvarez, Jean Claude, Pélissier-Alicot, Anne Laure, Hôpital de la Timone [CHU - APHM] (TIMONE), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Raymond Poincaré [Garches], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Aix Marseille Université (AMU)
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Hair samples ,[SDV]Life Sciences [q-bio] ,Health, Toxicology and Mutagenesis ,Kratom ,Mitragynine ,Toxicology ,Quantitation - Abstract
International audience; Kratom is a preparation obtained from the leaves of a tropical tree native to Southeast Asia, Mitragynia speciosa. Mainly ingested orally, kratom is used recreationally for its opioid and psychostimulant effects. Two of the forty alkaloids identified in the plant are responsible for these effects, the mitragynine and the 7-hydroxymitragynine. Kratom can be used to combat fatigue, improve work performance, treat pain and mood disorders. We report here the case of a 27-year-old young man, regular consumer of kratom (20 grams/day) and who occasionally takes cannabis, opiates, synthetic cannabinoids and “G” (GHB/GBL), purchased on the dark web. The man voluntarily sent his hair cut two months after his last intake of JWH-122 to the laboratory, for analysis. The psychoactive substances were extracted from two 1.5 cm long hair segments by liquid-liquid extraction and then analyzed by ultra-high performance liquid chromatography coupled with mass spectrometry (LC-HRMS). Screening was positive and quantification by LC-MS/MS analytically confirmed the presence of mitragynine at amounts of 2235 pg/mg (proximal segment) and 1717 pg/mg (distal segment) as well as JWH-122. This case supports the limited data available in the literature on the usual concentrations of mitragynine found in the hair.
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- 2023
14. Modifications of the endosomal compartment in fibroblasts from sporadic Alzheimer’s disease patients are associated with cognitive impairment
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Laura Xicota, Julien Lagarde, Fanny Eysert, Benjamin Grenier-Boley, Isabelle Rivals, Alexandra Botté, Sylvie Forlani, Sophie Landron, Clément Gautier, Cecilia Gabriel, Michel Bottlaender, Jean-Charles Lambert, Mounia Chami, Marie Sarazin, Marie-Claude Potier, Institut du Cerveau = Paris Brain Institute (ICM), 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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), GHU Paris Psychiatrie et Neurosciences, Université Paris Cité (UPCité), Université Paris-Saclay, Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Université de Lille, CHU Lille, 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), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Recherches SERVIER (IRS), Service NEUROSPIN (NEUROSPIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Xicota, Laura
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[SDV] Life Sciences [q-bio] ,Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,[SDV]Life Sciences [q-bio] ,Biological Psychiatry - Abstract
Morphological alterations of the endosomal compartment have been widely described in post-mortem brains from Alzheimer’s disease (AD) patients and subjects with Down syndrome (DS) who are at high risk for AD. Immunostaining with antibodies against endosomal markers such as Early Endosome Antigen 1 (EEA1) revealed increased size of EEA1-positive puncta. In DS, peripheral cells such as peripheral blood mononuclear cells (PBMCs) and fibroblasts, share similar phenotype even in the absence of AD. We previously found that PBMCs from AD patients have larger EEA1-positive puncta, correlating with brain amyloid load. Here we analysed the endosomal compartment of fibroblasts from a very well characterised cohort of AD patients (IMABio3) who underwent thorough clinical, imaging and biomarkers assessments. Twenty-one subjects were included (7 AD with mild cognitive impairment (AD-MCI), 7 AD with dementia (AD-D) and 7 controls) who had amyloid-PET at baseline (PiB) and neuropsychological tests at baseline and close to skin biopsy. Fibroblasts isolated from skin biopsies were immunostained with anti-EEA1 antibody and imaged using a spinning disk microscope. Endosomal compartment ultrastructure was also analysed by electron microscopy. All fibroblast lines were genotyped and their AD risk factors identified. Our results show a trend to an increased EEA1-positive puncta volume in fibroblasts from AD-D as compared to controls (p.adj = 0.12) and reveal enhanced endosome area in fibroblasts from AD-MCI and AD-AD versus controls. Larger puncta size correlated with PiB retention in different brain areas and with worse cognitive scores at the time of biopsy as well as faster decline from baseline to the time of biopsy. Finally, we identified three genetic risk factors for AD (ABCA1, COX7C and MYO15A) that were associated with larger EEA1 puncta volume. In conclusion, the endosomal compartment in fibroblasts could be used as cellular peripheral biomarker for both amyloid deposition and cognitive decline in AD patients.
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- 2023
15. Brain endothelial CXCL12 attracts protective natural killer cells during ischemic stroke
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Wang, S, de Fabritus, L, Kumar, PA, Werner, Y, Ma, M, Li, D, Siret, C, Simic, M, Li, B, Kerdiles, YM, Hou, L, Stumm, R, van de Pavert, SA, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Jena University Hospital [Jena], Shanghai Jiao Tong University School of Medicine, Beijing Tongren Hospital, and van de Pavert, Serge
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CXCR4 ,General Neuroscience ,[SDV]Life Sciences [q-bio] ,Immunology ,Cdh5 ,NK cells ,ILC1 ,[SDV] Life Sciences [q-bio] ,Cellular and Molecular Neuroscience ,Beam-walk sensorimotor test ,Neurology ,Photothrombotic stroke ,Whole mount imaging ,Flow cytometry ,CNS ,Blood-brain barrier - Abstract
Background The innate lymphoid cell (ILC) family consists of NK cells, ILC type 1, 2, 3 and lymphoid tissue inducer cells. They have been shown to play important roles in homeostasis and immune responses and are generally considered tissue resident. Not much is known about the presence of ILC members within the central nervous system and whether they are tissue resident in this organ too. Therefore, we studied the presence of all ILC members within the central nervous system and after ischemic brain insult. Methods We used the photothrombotic ischemic lesion method to induce ischemic lesions within the mouse brain. Using whole-mount immunofluorescence imaging, we established that the ILCs were present at the rim of the lesion. We quantified the increase of all ILC members at different time-points after the ischemic lesion induction by flow cytometry. Their migration route via chemokine CXCL12 was studied by using different genetic mouse models, in which we induced deletion of Cxcl12 within the blood–brain barrier endothelium, or its receptor, Cxcr4, in the ILCs. The functional role of the ILCs was subsequently established using the beam-walk sensorimotor test. Results Here, we report that ILCs are not resident within the mouse brain parenchyma during steady-state conditions, but are attracted towards the ischemic stroke. Specifically, we identify NK cells, ILC1s, ILC2s and ILC3s within the lesion, the highest influx being observed for NK cells and ILC1s. We further show that CXCL12 expressed at the blood–brain barrier is essential for NK cells and NKp46+ ILC3s to migrate toward the lesion. Complementary, Cxcr4-deficiency in NK cells prevents NK cells from entering the infarct area. Lack of NK cell migration results in a higher neurological deficit in the beam-walk sensorimotor test. Conclusions This study establishes the lack of ILCs in the mouse central nervous system at steady-state and their migration towards an ischemic brain lesion. Our data show a role for blood–brain barrier-derived CXCL12 in attracting protective NK cells to ischemic brain lesions and identifies a new CXCL12/CXCR4-mediated component of the innate immune response to stroke.
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- 2023
16. Widening the landscape of transcriptional regulation of green algal photoprotection
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Marius Arend, Yizhong Yuan, M. Águila Ruiz-Sola, Nooshin Omranian, Zoran Nikoloski, Dimitris Petroutsos, Bioinformatics Group, Institute of Biochemistry and Biology, University of Potsdam, Systems Biology and Mathematical Modeling Group, Max-Planck-Institute of Molecular Plant Physiology, Dynamique du protéome et biogenèse du chloroplaste (ChloroGenesis), Physiologie cellulaire et végétale (LPCV), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), The Human Frontiers Science Program (project RGP0046/2018), The Prestige Marie-Curie co-financing grant PRESTIGE-2017-1-0028, The International Max Planck Research School ‘Primary Metabolism and Plant Growth at the Max Planck Institute of Molecular Plant Physiology, ANR-18-CE20-0006,MetaboLIGHT,Regulation de la photosynthèse par la Lumière et le métabolisme chez les algues(2018), ANR-15-IDEX-0002,UGA,IDEX UGA(2015), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), and Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular
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MESH: Chlamydomonas reinhardtii ,Multidisciplinary ,[SDV]Life Sciences [q-bio] ,General Physics and Astronomy ,MESH: Carbon ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,General Chemistry ,MESH: Carbon Dioxide ,MESH: Chlamydomonas ,MESH: Gene Expression Regulation ,General Biochemistry, Genetics and Molecular Biology ,MESH: Photosynthesis - Abstract
Availability of light and CO2, substrates of microalgae photosynthesis, is frequently far from optimal. Microalgae activate photoprotection under strong light, to prevent oxidative damage, and the CO2 Concentrating Mechanism (CCM) under low CO2, to raise intracellular CO2 levels. The two processes are interconnected; yet, the underlying transcriptional regulators remain largely unknown. Employing a large transcriptomic data compendium of Chlamydomonas reinhardtii’s responses to different light and carbon supply, we reconstruct a consensus genome-scale gene regulatory network from complementary inference approaches and use it to elucidate transcriptional regulators of photoprotection. We show that the CCM regulator LCR1 also controls photoprotection, and that QER7, a Squamosa Binding Protein, suppresses photoprotection- and CCM-gene expression under the control of the blue light photoreceptor Phototropin. By demonstrating the existence of regulatory hubs that channel light- and CO2-mediated signals into a common response, our study provides an accessible resource to dissect gene expression regulation in this microalga.
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- 2023
17. Core genome sequencing and genotyping of Leptospira interrogans in clinical samples by target capture sequencing
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Linda Grillova, Thomas Cokelaer, Jean-François Mariet, Juliana Pipoli da Fonseca, Mathieu Picardeau, Biologie des Spirochètes / Biology of Spirochetes, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Biomics (plateforme technologique), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, This work was supported by the Institut Pasteur through grant PTR 30-2017 and Santé Publique France to MP. TC and JP (Biomics Platform, C2RT, Institut Pasteur, Paris, France), supported by France Génomique (ANR-10-INBS-09) and IBISA., and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)
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Leptospira ,MESH: Genotype ,Genotyping ,MESH: Leptospira interrogans ,Infectious Diseases ,MESH: Humans ,[SDV]Life Sciences [q-bio] ,Leptospirosis ,MESH: Animals ,Genomics ,MESH: Leptospirosis ,MESH: Zoonoses ,MESH: Leptospira - Abstract
Background The life-threatening pathogen Leptospira interrogans is the most common agent of leptospirosis, an emerging zoonotic disease. However, little is known about the strains that are currently circulating worldwide due to the fastidious nature of the bacteria and the difficulty to isolate cultures. In addition, the paucity of bacteria in blood and other clinical samples has proven to be a considerable challenge for directly genotyping the agent of leptospirosis directly from patient material. Our understanding of the genetic diversity of strains during human infection is therefore limited. Methods Here, we carried out hybridization capture followed by Illumina sequencing of the core genome directly from 20 clinical samples that were PCR positive for pathogenic Leptospira to elucidate the genetic diversity of currently circulating Leptospira strains in mainland France. Results Capture with RNA probes covering the L. interrogans core genome resulted in a 72 to 13,000-fold increase in pathogen reads relative to standard sequencing without capture. Variant analysis of the genomes sequenced from the biological samples using 273 Leptospira reference genomes was then carried out to determine the genotype of the infecting strain. For samples with sufficient coverage (19/20 samples with coverage > 8×), we could unambiguously identify L. interrogans serovars Icterohaemorrhagiae and Copenhageni (14 samples), L. kirschneri serovar Grippotyphosa (4 samples), and L. interrogans serovar Pyrogenes (1 sample) as the infecting strains. Conclusions We obtained high-quality genomic data with suitable coverage for confident core genome genotyping of the agent of leptospirosis for most of our clinical samples. The recovery of the genome of the serovars Icterohaemorrhagiae and Copenhageni directly from multiple clinical samples revealed low adaptive diversification of the core genes during human infection. The ability to generate culture-free genomic data opens new opportunities for better understanding of the epidemiology of this fastidious pathogen and pathogenesis of this neglected disease.
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- 2023
18. Structural basis of Ty1 integrase tethering to RNA polymerase III for targeted retrotransposon integration
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Phong Quoc Nguyen, Sonia Huecas, Amna Asif-Laidin, Adrián Plaza-Pegueroles, Beatrice Capuzzi, Noé Palmic, Christine Conesa, Joël Acker, Juan Reguera, Pascale Lesage, Carlos Fernández-Tornero, Architecture et fonction des macromolécules biologiques (AFMB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centro de Investigaciones Biológicas (CSIC), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), the Spanish Ministry of Science / Agencia Estatal de Investigación (BFU2017-87397-P, RED2018-102467-T and PID2020-116722GB-I00 to C. F.-T., PRE2018-087012 to A. P.-P.), intramural funding from CSIC (2020AEP152 and PIE-202120E047-Conexiones-Life to C. F.-T.), Fondation pour la Recherche Médicale (FRM-EQU202203014635 to P. L., FRM-SPF20170938755 to A. A.-L., FRM-ECO202206015504 to B. C.), and intramural funding from CNRS, Université de Paris and INSERM (to P. L.), ANR-17-CE11-0025,INstruc,Etude structurale du mécanisme d'intégration des rétrotransposons de levure dans les gènes transcrits par l'ARN Polymérase III(2017), Agence Nationale de la Recherche (France), Agencia Estatal de Investigación (España), Consejo Superior de Investigaciones Científicas (España), Fondation pour la Recherche Médicale, Centre National de la Recherche Scientifique (France), Université Paris Cité, Institut National de la Santé et de la Recherche Médicale (France), Nguyen, Phong Quoc, Huecas, Sonia, Asif-Laidin, Amna, Plaza-Pegueroles, Adrián, Capuzzi, Beatrice, Palmic, Noé, Acker, Joël, Reguera, Juan, Lesage, Pascale, and Fernández-Tornero, Carlos
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Multidisciplinary ,Cryoelectron microscopy ,DNA recombination ,[SDV]Life Sciences [q-bio] ,General Physics and Astronomy ,General Chemistry ,Transcription ,General Biochemistry, Genetics and Molecular Biology - Abstract
13 p.-6 fig., The yeast Ty1 retrotransposon integrates upstream of genes transcribed by RNA polymerase III (Pol III). Specificity of integration is mediated by an interaction between the Ty1 integrase (IN1) and Pol III, currently uncharacterized at the atomic level. We report cryo-EM structures of Pol III in complex with IN1, revealing a 16-residue segment at the IN1 C-terminus that contacts Pol III subunits AC40 and AC19, an interaction that we validate by in vivo mutational analysis. Binding to IN1 associates with allosteric changes in Pol III that may affect its transcriptional activity. The C-terminal domain of subunit C11, involved in RNA cleavage, inserts into the Pol III funnel pore, providing evidence for a two-metal mechanism during RNA cleavage. Additionally, ordering next to C11 of an N-terminal portion from subunit C53 may explain the connection between these subunits during termination and reinitiation. Deletion of the C53 N-terminal region leads to reduced chromatin association of Pol III and IN1, and a major fall in Ty1 integration events. Our data support a model in which IN1 binding induces a Pol III configuration that may favor its retention on chromatin, thereby improving the likelihood of Ty1 integration., This work was supported by the Agence Nationale de la Recherche (ANR-17-CE11-0025 to P.L., J.A., J.R. and C.F.-T.), the Spanish Ministry of Science/Agencia Estatal de Investigación (BFU2017-87397-P, RED2018-102467-T and PID2020-116722GB-I00 to C.F.-T.; PRE2018-087012 to A.P.-P.), intramural funding from CSIC (2020AEP152 and PIE-202120E047-Conexiones-Life to C. F.-T.), Fondation pour la Recherche Médicale (FRM-EQU202203014635 to P.L.; FRM-SPF20170938755 to A.A.-L.; FRM-ECO202206015504 to B.C.), and intramural funding from CNRS, Université Paris Cité and INSERM (to P.L.).
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- 2023
19. Rapid protection induced by a single-shot Lassa vaccine in male cynomolgus monkeys
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Mathieu Mateo, Stéphanie Reynard, Natalia Pietrosemoli, Emeline Perthame, Alexandra Journeaux, Kodie Noy, Clara Germain, Xavier Carnec, Caroline Picard, Virginie Borges-Cardoso, Jimmy Hortion, Hélène Lopez-Maestre, Pierrick Regnard, Lyne Fellmann, Audrey Vallve, Stéphane Barron, Ophélie Jourjon, Orianne Lacroix, Aurélie Duthey, Manon Dirheimer, Maïlys Daniau, Catherine Legras-Lachuer, Caroline Carbonnelle, Hervé Raoul, Frédéric Tangy, Sylvain Baize, Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), 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)-Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), 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), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Université de Strasbourg (UNISTRA), Simian Laboratory Europe (SILABE), Laboratoire P4 Jean Mérieux-Inserm [Lyon] (Unité de service 3), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Européen de Recherche en Virologie et Immunologie [Lyon] (Tour Inserm CERVI), Délégation régionale Auvergne Rhône-Alpes [Bron, France], Institut National de la Santé et de la Recherche Médicale (INSERM), ViroScan3D SAS [Trévoux, France], Laboratoire d’innovation : vaccins – Innovation lab : vaccines, This study was funded by a grant from the Coalition for Epidemic Preparedness and Innovations (CEPI-CfP-001) to S. Baize and by a grant from the Agence Nationale de la Recherche (ANR-21-CE18-0004-01) to M. Mateo., and ANR-21-CE18-0004,EXPUNGER,Vaccins post exposition contre les virus emergents(2021)
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Multidisciplinary ,[SDV]Life Sciences [q-bio] ,General Physics and Astronomy ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology - Abstract
Lassa fever hits West African countries annually in the absence of licensed vaccine to limit the burden of this viral hemorrhagic fever. We previously developed MeV-NP, a single-shot vaccine protecting cynomolgus monkeys against divergent strains one month or more than a year before Lassa virus infection. Given the limited dissemination area during outbreaks and the risk of nosocomial transmission, a vaccine inducing rapid protection could be useful to protect exposed people during outbreaks in the absence of preventive vaccination. Here, we test whether the time to protection can be reduced after immunization by challenging measles virus pre-immune male cynomolgus monkeys sixteen or eight days after a single shot of MeV-NP. None of the immunized monkeys develop disease and they rapidly control viral replication. Animals immunized eight days before the challenge are the best controllers, producing a strong CD8 T-cell response against the viral glycoprotein. A group of animals was also vaccinated one hour after the challenge, but was not protected and succumbed to the disease as the control animals. This study demonstrates that MeV-NP can induce a rapid protective immune response against Lassa fever in the presence of MeV pre-existing immunity but can likely not be used as therapeutic vaccine.
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- 2023
20. Transcriptomic responses of bat cells to European bat lyssavirus 1 infection under conditions simulating euthermia and hibernation
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Markéta Harazim, Juliette Perrot, Hugo Varet, Hervé Bourhy, Julien Lannoy, Jiri Pikula, Veronika Seidlová, Laurent Dacheux, Natália Martínková, Institute of Vertebrate Biology of the Czech Academy of Sciences (IVB / CAS), Czech Academy of Sciences [Prague] (CAS), Masaryk University [Brno] (MUNI), Lyssavirus, épidémiologie et neuropathologie - Lyssavirus Epidemiology and Neuropathology, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, University of Veterinary and Pharmaceutical Sciences [Brno] (VFU), and This study was supported by The Czech Science Foundation (17-20286S), Masaryk University grant MUNI/A/1098/2019, RECETOX Research Infrastructure (No. LM2018121) financed by the Ministry of Education, Youth and Sports, and the Operational Programme Research, Development and Education (the CETOCOEN EXCELLENCE project No. CZ.02.1.01/0.0/0.0/17_043/0009632), and Institut Pasteur. MetaCentrum computational resources were supplied by the project 'e-Infrastruktura CZ' (e-INFRA CZ LM2018140) supported by the Ministry of Education, Youth and Sports of the Czech Republic. MH’s stay at Institut Pasteur was supported by the Barrande fellowship program provided by the French Ministry of Foreign Affairs.
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Innate immunity ,In vitro infection model ,Chiroptera ,Hibernation ,[SDV]Life Sciences [q-bio] ,Immunology ,Myotis myotis ,Antiviral state ,Heat shock proteins (HSPs) ,Transcriptome ,Lyssaviruses ,EBLV-1 - Abstract
Background Coevolution between pathogens and their hosts decreases host morbidity and mortality. Bats host and can tolerate viruses which can be lethal to other vertebrate orders, including humans. Bat adaptations to infection include localized immune response, early pathogen sensing, high interferon expression without pathogen stimulation, and regulated inflammatory response. The immune reaction is costly, and bats suppress high-cost metabolism during torpor. In the temperate zone, bats hibernate in winter, utilizing a specific behavioural adaptation to survive detrimental environmental conditions and lack of energy resources. Hibernation torpor involves major physiological changes that pose an additional challenge to bat-pathogen coexistence. Here, we compared bat cellular reaction to viral challenge under conditions simulating hibernation, evaluating the changes between torpor and euthermia. Results We infected the olfactory nerve-derived cell culture of Myotis myotis with an endemic bat pathogen, European bat lyssavirus 1 (EBLV-1). After infection, the bat cells were cultivated at two different temperatures, 37 °C and 5 °C, to examine the cell response during conditions simulating euthermia and torpor, respectively. The mRNA isolated from the cells was sequenced and analysed for differential gene expression attributable to the temperature and/or infection treatment. In conditions simulating euthermia, infected bat cells produce an excess signalling by multitude of pathways involved in apoptosis and immune regulation influencing proliferation of regulatory cell types which can, in synergy with other produced cytokines, contribute to viral tolerance. We found no up- or down-regulated genes expressed in infected cells cultivated at conditions simulating torpor compared to non-infected cells cultivated under the same conditions. When studying the reaction of uninfected cells to the temperature treatment, bat cells show an increased production of heat shock proteins (HSPs) with chaperone activity, improving the bat’s ability to repair molecular structures damaged due to the stress related to the temperature change. Conclusions The lack of bat cell reaction to infection in conditions simulating hibernation may contribute to the virus tolerance or persistence in bats. Together with the cell damage repair mechanisms induced in response to hibernation, the immune regulation may promote bats’ ability to act as reservoirs of zoonotic viruses such as lyssaviruses.
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- 2023
21. Brucella effectors NyxA and NyxB target SENP3 to modulate the subcellular localisation of nucleolar proteins
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Arthur Louche, Amandine Blanco, Thais Lourdes Santos Lacerda, Lison Cancade-Veyre, Claire Lionnet, Célia Bergé, Monica Rolando, Frédérique Lembo, Jean-Paul Borg, Carmen Buchrieser, Masami Nagahama, Francine C. A. Gérard, Jean-Pierre Gorvel, Virginie Gueguen-Chaignon, Laurent Terradot, Suzana P. Salcedo, Microbiologie moléculaire et biochimie structurale / Molecular Microbiology and Structural Biochemistry (MMSB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Reproduction et développement des plantes (RDP), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biologie des Bactéries intracellulaires - Biology of Intracellular Bacteria, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Meiji Pharmaceutical University, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), SFR Biosciences, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CB lab was funded by the Institut Pasteur and ANR-10-LABX-62-IBEID for the Legionella experiments. These effectors were discovered under the ERA-Net Pathogenomics grant and the remaining work funded by ANR-15-CE15-0011-01 attributed to Suzana Salcedo. The work was completed with the ANR SNAPshot ANR-21-CE15-0024 attributed to Suzana Salcedo., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-15-CE15-0011,NucPath,Caractérisation du rôle cellulaire de nouveaux effecteurs bactériens ciblant les noyaux des cellules hôtes(2015), ANR-21-CE15-0024,SNAPshot,Détournement du stress nucléaire par les bactéries pathogènes(2021), Laurent, Terradot, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Caractérisation du rôle cellulaire de nouveaux effecteurs bactériens ciblant les noyaux des cellules hôtes - - NucPath2015 - ANR-15-CE15-0011 - AAPG2015 - VALID, Détournement du stress nucléaire par les bactéries pathogènes - - SNAPshot2021 - ANR-21-CE15-0024 - AAPG2021 - VALID, and École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL)
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[SDV] Life Sciences [q-bio] ,Multidisciplinary ,[SDV]Life Sciences [q-bio] ,General Physics and Astronomy ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology - Abstract
The cell nucleus is a primary target for intracellular bacterial pathogens to counteract immune responses and hijack host signalling pathways to cause disease. Here we identify two Brucella abortus effectors, NyxA and NyxB, that interfere with host protease SENP3, and this facilitates intracellular replication of the pathogen. The translocated Nyx effectors directly interact with SENP3 via a defined acidic patch (identified from the crystal structure of NyxB), preventing nucleolar localisation of SENP3 at late stages of infection. By sequestering SENP3, the effectors promote cytoplasmic accumulation of nucleolar AAA-ATPase NVL and ribosomal protein L5 (RPL5) in effector-enriched structures in the vicinity of replicating bacteria. The shuttling of ribosomal biogenesis-associated nucleolar proteins is inhibited by SENP3 and requires the autophagy-initiation protein Beclin1 and the SUMO-E3 ligase PIAS3. Our results highlight a nucleomodulatory function of two Brucella effectors and reveal that SENP3 is a crucial regulator of the subcellular localisation of nucleolar proteins during Brucella infection, promoting intracellular replication of the pathogen.
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- 2023
22. Vector competence of sterile male Glossina fuscipes fuscipes for Trypanosoma brucei brucei: implications for the implementation of the sterile insect technique in a sleeping sickness focus in Chad
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Mahamat Hissene Mahamat, Adeline Ségard, Jean-Baptiste Rayaisse, Rafael Argiles-Herrero, Andrew Gordon Parker, Philippe Solano, Adly Mohamed Mohamed Abd-Alla, Jérémy Bouyer, Sophie Ravel, Institut de Recherche en Elevage pour le Developpement [N'Djamena, Tchad] (IRED), Interactions hôtes-vecteurs-parasites-environnement dans les maladies tropicales négligées dues aux trypanosomatides (UMR INTERTRYP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université de Bordeaux (UB), Centre international de recherche-développement sur l'élevage en zone sub-humide (CIRDES), Insect Pest Control Laboratory (IPC laboratory), Food and Agriculture Organization of the United Nations [Rome, Italie] (FAO)-International Atomic Energy Agency [Vienna] (IAEA), Animal, Santé, Territoires, Risques et Ecosystèmes (UMR ASTRE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département Systèmes Biologiques (Cirad-BIOS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Joint FAO/IAEA Programme - Nuclear Techniques in Food and Agriculture, This work was funded by IAEA grant EVT 1804311 to Hissene Mahamat and was supported by the project, Research Infrastructures for the control of vector-borne diseases (Infravec2), which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement number 731060., and European Project: 731060,INFRAVEC2(2017)
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Infectious Diseases ,Trypanosoma brucei gambiense ,[SDV]Life Sciences [q-bio] ,Trypanocide ,Isometamidium ,Parasitology ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Tsetse - Abstract
Background Human African trypanosomiasis (HAT) is a neglected tropical disease caused by Trypanosoma brucei gambiense transmitted by tsetse flies in sub-Saharan West Africa. In southern Chad the most active and persistent focus is the Mandoul focus, with 98% of the reported human cases, and where African animal trypanosomosis (AAT) is also present. Recently, a control project to eliminate tsetse flies (Glossina fuscipes fuscipes) in this focus using the sterile insect technique (SIT) was initiated. However, the release of large numbers of sterile males of G. f. fuscipes might result in a potential temporary increase in transmission of trypanosomes since male tsetse flies are also able to transmit the parasite. The objective of this work was therefore to experimentally assess the vector competence of sterile males treated with isometamidium for Trypanosoma brucei brucei. Methods An experimental infection was set up in the laboratory, mimicking field conditions: the same tsetse species that is present in Mandoul was used. A T. b. brucei strain close to T. b. gambiense was used, and the ability of the sterile male tsetse flies fed on blood with and without a trypanocide to acquire and transmit trypanosomes was measured. Results Only 2% of the experimentally infected flies developed an immature infection (midgut) while none of the flies developed a metacyclic infection of T. b. brucei in the salivary glands. We did not observe any effect of the trypanocide used (isometamidium chloride at 100 mg/l) on the development of infection in the flies. Conclusions Our results indicate that sterile males of the tested strain of G. f. fuscipes were unable to cyclically transmit T. b. brucei and might even be refractory to the infection. The data of the research indicate that the risk of cyclical transmission of T. brucei by sterile male G. f. fuscipes of the strain colonized at IAEA for almost 40 years appears to be small. Graphical Abstract
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- 2023
23. Changing epidemiology of Plasmodium vivax malaria in Nouakchott, Mauritania: a six-year (2015–2020) prospective study
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Inejih El Moustapha, Jemila Deida, Mariem Dadina, Abdellahi El Ghassem, Mariem Begnoug, Mariem Hamdinou, Khadijetou Mint Lekweiry, Mohamed Salem Ould Ahmedou Salem, Yacoub Khalef, Amal Semane, Khyarhoum Ould Brahim, Sébastien Briolant, Hervé Bogreau, Leonardo Basco, Ali Ould Mohamed Salem Boukhary, Université de Nouakchott Al-Aasriya (UNA), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), and WorldWide Antimalarial Resistance Network Falciparum Haematology Study Group
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Infectious Diseases ,[SDV]Life Sciences [q-bio] ,Parasitology - Abstract
Background Plasmodium vivax malaria is one of the major infectious diseases of public health concern in Nouakchott, the capital city of Mauritania and the biggest urban setting in the Sahara. The assessment of the current trends in malaria epidemiology is primordial in understanding the dynamics of its transmission and developing an effective control strategy. Methods A 6 year (2015–2020) prospective study was carried out in Nouakchott. Febrile outpatients with a clinical suspicion of malaria presenting spontaneously at Teyarett Health Centre or the paediatric department of Mother and Children Hospital Centre were screened for malaria using a rapid diagnostic test, microscopic examination of Giemsa-stained blood films, and nested polymerase chain reaction. Data were analysed using Microsoft Excel and GraphPad Prism and InStat software. Results Of 1760 febrile patients included in this study, 274 (15.5%) were malaria-positive by rapid diagnostic test, 256 (14.5%) were malaria-positive by microscopy, and 291 (16.5%) were malaria-positive by PCR. Plasmodium vivax accounted for 216 of 291 (74.2%) PCR-positive patients; 47 (16.1%) and 28 (9.6%) had P. falciparum monoinfection or P. vivax–P. falciparum mixed infection, respectively. During the study period, the annual prevalence of malaria declined from 29.2% in 2015 to 13.2% in 2019 and 2.1% in 2020 (P P. vivax infections, but not P. falciparum infections, occurred at low levels during the rest of the year. The most affected subset of patient population was adult male white and black Moors. The decline in malaria prevalence was correlated with decreasing annual rainfall (r = 0.85; P = 0.03) and was also associated with better management of the potable water supply system. A large majority of included patients did not possess or did not use bed nets. Conclusions Control interventions based on prevention, diagnosis, and treatment should be reinforced in Nouakchott, and P. vivax-specific control measures, including chloroquine and 8-aminoquinolines (primaquine, tafenoquine) for treatment, should be considered to further improve the efficacy of interventions and aim for malaria elimination.
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- 2023
24. Migration of surface-associated microbial communities in spaceflight habitats
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Daniele Marra, Thodoris Karapantsios, Sergio Caserta, Eleonora Secchi, Malgorzata Holynska, Simon Labarthe, Bastien Polizzi, Sandra Ortega, Margaritis Kostoglou, Christophe Lasseur, Ioannis Karapanagiotis, Sigolene Lecuyer, Arnaud Bridier, Marie-Françoise Noirot-Gros, Romain Briandet, 'Federico II' University of Naples Medical School, Aristotle University of Thessaloniki, Department of Civil, Environmental and Geomatic Engineering [ETH Zürich] (D-BAUG), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), ESA - ESTEC (Netherlands), Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Mathématiques de Besançon (UMR 6623) (LMB), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Laboratoire Interdisciplinaire de Physique [Saint Martin d’Hères] (LIPhy ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Laboratoire de Fougères - ANSES, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Elsevier
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Space flight ,Biofilm ,Microgravity ,Transcriptomic ,Adaptation ,Evolution ,Control ,[SDV]Life Sciences [q-bio] ,Cell Biology ,Molecular Biology ,Applied Microbiology and Biotechnology ,Microbiology - Abstract
Astronauts are spending longer periods locked up in ships or stations for scientific and exploration spatial missions. The International Space Station (ISS) has been inhabited continuously for more than 20 years and the duration of space stays by crews could lengthen with the objectives of human presence on the moon and Mars. If the environment of these space habitats is designed for the comfort of astronauts, it is also conducive to other forms of life such as embarked microorganisms. The latter, most often associated with surfaces in the form of biofilm, have been implicated in significant degradation of the functionality of pieces of equipment in space habitats. The most recent research suggests that microgravity could increase the persistence, resistance and virulence of pathogenic microorganisms detected in these communities, endangering the health of astronauts and potentially jeopardizing long-duration manned missions. In this review, we describe the mechanisms and dynamics of installation and propagation of these microbial communities associated with surfaces (spatial migration), as well as long-term processes of adaptation and evolution in these extreme environments (phenotypic and genetic migration), with special reference to human health. We also discuss the means of control envisaged to allow a lasting cohabitation between these vibrant microscopic passengers and the astronauts., Biofilm, 5, ISSN:2590-2075
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- 2023
25. Variants in SART3 cause a spliceosomopathy characterised by failure of testis development and neuronal defects
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Ayers, Katie, Eggers, Stefanie, Rollo, Ben, Smith, Katherine, Davidson, Nadia, Siddall, Nicole, Zhao, Liang, Bowles, Josephine, Weiss, Karin, Zanni, Ginevra, Burglen, Lydie, Ben-Shachar, Shay, Rosensaft, Jenny, Raas-Rothschild, Annick, Jørgensen, Anne, Schittenhelm, Ralf, Huang, Cheng, Robevska, Gorjana, van den Bergen, Jocelyn, Casagranda, Franca, Cyza, Justyna, Pachernegg, Svenja, Wright, David, Bahlo, Melanie, Oshlack, Alicia, O'Brien, Terrence, Kwan, Patrick, Koopman, Peter, Hime, Gary, Girard, Nadine, Hoffmann, Chen, Shilon, Yuval, Zung, Amnon, Bertini, Enrico, Milh, Mathieu, Ben Rhouma, Bochra, Belguith, Neila, Bashamboo, Anu, Mcelreavey, Ken, Banne, Ehud, Weintrob, Naomi, Benzeev, Bruria, Sinclair, Andrew, Murdoch Children's Research Institute (MCRI), University of Melbourne, Victorian Clinical Genetics Services, Monash University [Melbourne], The Walter and Eliza Hall Institute of Medical Research (WEHI), University of Queensland [Brisbane], Technion - Israel Institute of Technology [Haifa], Bambino Gesù Children’s Hospital [Rome, Italy], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Génétique des Troubles du Neurodéveloppement = Developmental Brain Disorders Laboratory (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Tel Aviv Sourasky Medical Center [Te Aviv], The Hebrew University Hadassah Medical School, Chaim Sheba Medical Center, Tel Aviv University (TAU), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Monash University [Clayton], Peter Mac Callum Cancer Centre, Service de pédiatrie et neurologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Kaplan Medical Center [Rehovot, Israel], Université de Gabès, Université de Sfax - University of Sfax, Hôpital Charles Nicolle [Tunis], Génétique du Développement humain - Human developmental genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Wolfson Medical Center, This study was supported by a National Health and Medical Research Council (NHMRC) programme grant (1074258) awarded to AS, NHMRC project grant (1156942) (K.A.), a Medical Research Future Fund Stem Cells Mission grant (MRF1201781) (K.A., B.N.R. and P.Kw), an Australian Research Council Future Fellowship (FT100100764) to M.B., A NHMRC Investigator Grant (1174040) to D.W., Agence Nationale de la Recherche funding ANR-10-LABX-73 REVIVE, ANR-17-CE14-0038-01 and ANR 20 CE14 0007 to K.M., ANR-19-CE140022 and ANR-19-CE14-0012 to A.B., G.Z. and E.B. are members of the European Reference Network for Rare Neurological Diseases - Project ID No 739510., ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), ANR-20-CE14-0007,Goldilocks,Analyse intégrée du rôle du facteur de transcription SF-1 / NR5A1 et de ses gènes cibles dépendants du dosage dans la fonction gonadique et les troubles du développement sexuel (DSD)(2020), ANR-19-CE14-0022,SexDiff,Régulation de la détermination du sexe et de la différenciation ovarienne : implications dans les troubles du développement sexuel(2019), and ANR-19-CE14-0012,RNA-SEX,Fonction de l'ARN hélicase dans la détermination du sexe chez les vertébrés et les troubles du développement du sexe chez l'homme (DSD)(2019)
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MESH: Humans ,MESH: RNA-Binding Proteins ,MESH: Testis ,[SDV]Life Sciences [q-bio] ,MESH: Gonadal Dysgenesis ,MESH: Antigens, Neoplasm ,MESH: Induced Pluripotent Stem Cells ,MESH: Male ,MESH: Intellectual Disability - Abstract
International audience; Squamous cell carcinoma antigen recognized by T cells 3 ( SART3 ) is an RNA-binding protein with numerous biological functions including recycling small nuclear RNAs to the spliceosome. Here, we identify recessive variants in SART3 in nine individuals presenting with intellectual disability, global developmental delay and a subset of brain anomalies, together with gonadal dysgenesis in 46,XY individuals. Knockdown of the Drosophila orthologue of SART3 reveals a conserved role in testicular and neuronal development. Human induced pluripotent stem cells carrying patient variants in SART3 show disruption to multiple signalling pathways, upregulation of spliceosome components and demonstrate aberrant gonadal and neuronal differentiation in vitro. Collectively, these findings suggest that bi-allelic SART3 variants underlie a spliceosomopathy which we tentatively propose be termed INDYGON syndrome ( I ntellectual disability, N eurodevelopmental defects and D evelopmental delay with 46,X Y GON adal dysgenesis). Our findings will enable additional diagnoses and improved outcomes for individuals born with this condition.
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- 2023
26. FT-GPI, a highly sensitive and accurate predictor of GPI-anchored proteins, reveals the composition and evolution of the GPI proteome in Plasmodium species
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Lena M. Sauer, Rodrigo Canovas, Daniel Roche, Hosam Shams-Eldin, Patrice Ravel, Jacques Colinge, Ralph T. Schwarz, Choukri Ben Mamoun, Eric Rivals, Emmanuel Cornillot, Institut de Biologie Computationnelle (IBC), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université de Montpellier (UM), Institute for Virology [Marburg], Philipps Universität Marburg = Philipps University of Marburg, Méthodes et Algorithmes pour la Bioinformatique (MAB), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), 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), and Yale School of Medicine [New Haven, Connecticut] (YSM)
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GPI-proteome ,GPI-anchored protein ,Infectious Diseases ,FT-GPI ,[SDV]Life Sciences [q-bio] ,Plasmodium falciparum ,P. vivax ,Parasitology ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology - Abstract
Background Protozoan parasites are known to attach specific and diverse group of proteins to their plasma membrane via a GPI anchor. In malaria parasites, GPI-anchored proteins (GPI-APs) have been shown to play an important role in host–pathogen interactions and a key function in host cell invasion and immune evasion. Because of their immunogenic properties, some of these proteins have been considered as malaria vaccine candidates. However, identification of all possible GPI-APs encoded by these parasites remains challenging due to their sequence diversity and limitations of the tools used for their characterization. Methods The FT-GPI software was developed to detect GPI-APs based on the presence of a hydrophobic helix at both ends of the premature peptide. FT-GPI was implemented in C ++and applied to study the GPI-proteome of 46 isolates of the order Haemosporida. Using the GPI proteome of Plasmodium falciparum strain 3D7 and Plasmodium vivax strain Sal-1, a heuristic method was defined to select the most sensitive and specific FT-GPI software parameters. Results FT-GPI enabled revision of the GPI-proteome of P. falciparum and P. vivax, including the identification of novel GPI-APs. Orthology- and synteny-based analyses showed that 19 of the 37 GPI-APs found in the order Haemosporida are conserved among Plasmodium species. Our analyses suggest that gene duplication and deletion events may have contributed significantly to the evolution of the GPI proteome, and its composition correlates with speciation. Conclusion FT-GPI-based prediction is a useful tool for mining GPI-APs and gaining further insights into their evolution and sequence diversity. This resource may also help identify new protein candidates for the development of vaccines for malaria and other parasitic diseases.
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- 2023
27. Ultraviolet exposure regulates skin metabolome based on the microbiome
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Vijaykumar Patra, Natalie Bordag, Yohann Clement, Harald Köfeler, Jean-Francois Nicolas, Marc Vocanson, Sophie Ayciriex, Peter Wolf, Medical University Graz, 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), Medical University of Graz, CheMod, Institut des Sciences Analytiques (ISA), 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)-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), ANABIO-MS - Analyse biomoléculaire par spectrométrie de masse - Biological Analysis by Mass Spectrometry, BioTechMed-Graz, Graz University of Technology [Graz] (TU Graz)-Karl-Franzens-Universität Graz-Medical University Graz, and Austrian Science Fund (FWF, W1241)
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[STAT]Statistics [stat] ,Multidisciplinary ,[SDV]Life Sciences [q-bio] - Abstract
Skin metabolites (
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- 2023
28. CusProSe: a customizable protein annotation software with an application to the prediction of fungal secondary metabolism genes
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Oliveira, Leonor, Chevrollier, Nicolas, Dallery, Jean-Felix, O’connell, Richard, Lebrun, Marc-Henri, Viaud, Muriel, Lespinet, Olivier, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), BIOlogie et GEstion des Risques en agriculture (BIOGER), Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Herbifun project 16-CE20-0023-01 ANR, ANR-17-EURE-0007,SPS-GSR,Ecole Universitaire de Recherche de Sciences des Plantes de Paris-Saclay(2017), and AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
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Multidisciplinary ,[SDV]Life Sciences [q-bio] ,Annotation ,polyketide synthase ,[SDE]Environmental Sciences ,Software - Abstract
We report here a new application, CustomProteinSearch (CusProSe), whose purpose is to help users to search for proteins of interest based on their domain composition. The application is customizable. It consists of two independent tools, IterHMMBuild and ProSeCDA. IterHMMBuild allows the iterative construction of Hidden Markov Model (HMM) profiles for conserved domains of selected protein sequences, while ProSeCDA scans a proteome of interest against an HMM profile database, and annotates identified proteins using user-defined rules. CusProSe was successfully used to identify, in fungal genomes, genes encoding key enzyme families involved in secondary metabolism, such as polyketide synthases (PKS), non-ribosomal peptide synthetases (NRPS), hybrid PKS-NRPS and dimethylallyl tryptophan synthases (DMATS), as well as to characterize distinct terpene synthases (TS) sub-families. The highly configurable characteristics of this application makes it a generic tool, which allows the user to refine the function of predicted proteins, to extend detection to new enzymes families, and may also be applied to biological systems other than fungi and to other proteins than those involved in secondary metabolism.
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- 2023
29. Interferential therapy for chronic constipation in adults: The CON‐COUR randomizedcontrolled trial
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Veronique Vitton, François Mion, Anne‐Marie Leroi, Charlène Brochard, Benoit Coffin, Frank Zerbib, Henri Damon, Chloé Melchior, Henri Duboc, Michel Queralto, Karine Baumstarck, Assistance Publique - Hôpitaux de Marseille (APHM), Hospices Civils de Lyon (HCL), Application des ultrasons à la thérapie (LabTAU), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU), Service de physiologie digestive, urinaire, respiratoire et de l'exercice [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d'Hépato-Gastroentérologie [CHU Rouen], and Service de Colo-proctologie, Clinique des Cèdres, Cornebarrieu, France
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Oncology ,[SDV]Life Sciences [q-bio] ,Gastroenterology - Published
- 2023
30. Changes in French family medicine residents’ perspectives about patient partners’ participation in teaching: A qualitative study in co-facilitated practice exchange groups
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Juliette Guary, Priscille Hébert, Arnaud Maury, Maud Le Ridant, Pierric Renaut, Sylvie Odent, Laure Fiquet, Emmanuel Allory, Université de Caen Normandie (UNICAEN), Normandie Université (NU), Université de Rennes (UR), France Assos Santé Bretagne, CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de référence Maladies Rares CLAD-Ouest [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire éducations et promotion de la santé (LEPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, and This article is supported by the French network of University Hospitals HUGO (‘Hôpitaux Universitaires du Grand Ouest’)’.
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general practice ,medical student ,[SDV]Life Sciences [q-bio] ,Patient participation ,General Medicine ,medical education ,qualitative research ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Education - Abstract
International audience; PURPOSE: The patient partner in teaching method is progressively developing for clinical training in France. Practice exchange groups (PEG) co-facilitated by patient partners in teaching are used during the training of family medicine (FM) residents. This study explored the FM residents’ perspectives about patient partner in teaching’s participation in co-facilitated PEGs and how they changed over time. STUDENTS AND METHODS: In 2020, qualitative focus groups were carried out with 26 FM residents before and after a 5-month intervention based on monthly PEGs co-facilitated by patient partners in teaching. A reflective thematic analysis of the focus group interviews was performed according to Braun and Clarke’s approach. RESULTS: FM residents supported patient partners in teaching’s facilitation role and had high expectations concerning their contribution to the development of their skills and competencies. They expected patient partners in teaching to bring their individual experience and also a collective knowledge. Some limitations mentioned by FM residents disappeared over time, such as the loss of the medical group feeling among physicians, while others persisted and required pedagogical support targeted to FM residents before PEG initiation. CONCLUSION: This study shows the good acceptance of patient partners in teaching by FM residents in the context of PEGs. Attention should be paid to make FM residents aware of patient partners in teaching’s missions before their introduction.[Box: see text].
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- 2023
31. Loss‐of‐function of gynoecium‐expressed phospholipase pPLAIIγ triggers maternal haploid induction in Arabidopsis
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Jin Hoon Jang, Hae Seong Seo, Thomas Widiez, Ok Ran Lee, Chonnam National University [Gwangju], Reproduction et développement des plantes (RDP), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ANR-19-CE20-0012,NOT-LIKE-DAD,Gynogenèse in vivo chez le maïs : nouvelles connaissances sur la double fécondation chez les plantes(2019), and ANR-21-PRRD-0097,SUNNY-HAPLOID,New in planta haploid induction systems
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haploid ,Haploid inducer line ,Physiology ,[SDV]Life Sciences [q-bio] ,Phospholipase ,Plant Science ,Embryo development - Abstract
International audience; Production of in planta haploid embryos that inherit chromosomes from only one parent can greatly increase breeding efficiency via quickly generating homozygous plants, called doubled haploid. One of the main players of in planta haploid induction is a pollen-specific phospholipase A, which is able, when mutated, to induce in vivo haploid induction in numerous monocots. However, no functional orthologous gene has been identified in dicots plants. Here, we show that loss-of-function of gynoecium-expressed phospholipase AII (pPLAIIγ) triggers maternal haploid plants in Arabidopsis, at an average rate of 1.07%. Reciprocal crosses demonstrate that haploid plants are triggered from the female side and not from the pollen, and the haploid plants carry the maternal genome. Promoter activity of pPLAIIγ shows enriched expression in the funiculus of flower development stages 13 and 18, and pPLAIIγ fused to yellow fluorescent protein reveals a plasma-membrane localization Interestingly, the polar localized PIN1 at the basal plasma membrane of the funiculus was all internalized in pplaIIγ mutants, suggesting that altered PIN1 localization in female organ could play a role in maternal haploid induction.
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- 2023
32. Therapeutic Drug Monitoring and Dosage Adjustments of Immunosuppressive Drugs When Combined With Nirmatrelvir/Ritonavir in Patients With COVID-19
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Lemaitre, F., Budde, K., Gelder, T. van, Bergan, S., Lawson, R., Noceti, O., Venkataramanan, R., Elens, L., Moes, D.J.A.R., Hesselink, D.A., Pawinski, T., Johnson-Davis, K.L., Winter, B.C.M. de, Pattanaik, S., Brunet, M., Masuda, S., Langman, L.J., Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Leiden University Medical Center (LUMC), University of Oslo (UiO), Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), National Center for Liver Transplantation [Montevideo, Uruguay], University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Université Catholique de Louvain = Catholic University of Louvain (UCL), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Medical University of Warsaw - Poland, University of Utah, Post Graduate Institute of Medical Education and Research [Chandigarh, India] (PGIMER), University of Barcelona, Dokkyo Medical University, Mayo Clinic [Rochester], None, Jonchère, Laurent, Universiteit Leiden, and UCL - SSS/LDRI - Louvain Drug Research Institute
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Pharmacology ,Transplantation ,mTOR inhibitors ,[SDV]Life Sciences [q-bio] ,[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences ,Tacrolimus ,[SDV] Life Sciences [q-bio] ,[SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences ,Calcineurin inhibitors ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Drug-drug interactions ,Pharmacology (medical) - Abstract
International audience; Nirmatrelvir/ritonavir (Paxlovid®) consists of a peptidomimetic inhibitor (Nirmatrelvir) of the SARS-CoV-2 main protease and a pharmacokinetic enhancer (Ritonavir). It is approved for the treatment of mild-to-moderate COVID-19. This combination of nirmatrelvir and ritonavir can mediate significant and complex drug-drug interactions (DDIs), primarily due to the ritonavir component. Indeed, ritonavir inhibits the metabolism of nirmatrelvir through cytochrome P450 3A (CYP3A) leading to higher plasma concentrations and a longer half-life of nirmatrelvir. Co-administration of nirmatrelvir/ritonavir with immunosuppressant drugs (ISDs) is particularly challenging given the major involvement of CYP3A in the metabolism of most of these drugs and their narrow therapeutic ranges. Exposure of ISDs will be drastically increased through the potent ritonavir-mediated inhibition of CYP3A, resulting in an increased risk of adverse drug reactions. While a decrease in the dosage of ISDs can prevent toxicity, an inappropriate dosage regimen may also result in insufficient exposure and a risk of rejection. Here we provide some general recommendations for therapeutic drug monitoring (TDM) of ISDs and dosing recommendations when co-administered with nirmatrelvir/ritonavir. Particularly, tacrolimus should be discontinued, or patients should be given a microdose on day-1, while cyclosporine dosage should be reduced to 20% of the initial dosage during the antiviral treatment. Dosages of mammalian target of rapamycin inhibitors (m-TORis) should also be adjusted while dosages of mycophenolic acid and corticosteroids are expected to be less impacted.
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- 2023
33. Management of acute mesenteric ischaemia: Results of a worldwide survey
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Benjamin Hess, Martin Cahenzli, Alastair Forbes, Rosa Burgos, Federico Coccolini, Olivier Corcos, Mette Holst, Øivind Irtun, Stanislaw Klek, Loris Pironi, Henrik Højgaard Rasmussen, Mireille J. Serlie, Ronan Thibault, Simon Gabe, Annika Reintam Blaser, Emrah Akin, Syed Muhammad Ali, Giulio Argenio, Semra Demirli Atici, Goran Augustin, Efstratia Baili, Lovenish Bains, Miklosh Bala, Edoardo Baldini, Oussama Baraket, Mirko Barone, Alan Biloslavo, null Roberto Bini, Cristina Bombardini, Giuseppe Brisinda, Luis Buonomo, Fausto Catena, Marco Ceresoli, Maria Michela Chiarello, Christos Chouliaras, Fabrizio D'Acapito, Dimitrios Damaskos, Belinda De Simone, Daniele Delogu, Zaza Demetrashvili, Isidoro Di Carlo, Mario D'Oria, Virginia María Durán-Muñoz-Cruzado, Patrice Forget, Laura Fortuna, Pietro Fransvea, Christian Frey, Olga Gapejeva, Pierre Garcon, Jörn-Markus Gass, Ricardo Alessandro Teixeira Gonsaga, Ewen Griffiths, Kursat Gundogan, Mohan Gurjar, Hytham K.S. Hamid, Juan Ignacio Silesky Jiménez, Karri Kase, Syed Sajid Hussain Kazmi, Aristotelis Kechagias, Vladimir Khokha, Yoshiro Kobe, Dimitrios P. Korkolis, Andrey Litvin, Eftychios Lostoridis, Hans Alexander Mahendran, Fabio Marino, Andres Martinuzzi, Cristian Mesina, Vincenzo Neri, Marina Panisic, Ciro Paolillo, Nikolaos Pararas, Gennaro Perrone, Antonio Pesce, Biagio Picardi, Charlotte Pither, Mauro Podda, Tomas Poskus, Florian Poullenot, Matras Przemyslaw, Massimo Sartelli, Diego Sasia, Maximilian Scheiterle, Fotios Seretis, Kjetil Søreide, Ruslan Sydorchuk, Kinga Szczepanek, Zsolt Bodnar, Fabienne Tamion, Antonio Tarasconi, Martin Teraa, Matti Tolonen, Tim Vanuytsel, Massimiliano Veroux, Lars Vinter-Jensen, Diego Visconti, Lukas Widmer, Andee Dzulkarnaen Zakaria, Nadezhda Zubareva, null Endorsing International Societies, null ESICM (European Society of Intensive Care Medicine), null WSES (World Society of Emergency Surgery), null WSACS (The Abdominal Compartment Society), null In-principle support, null WFICC (World Federation of Intensive and Critical Care), Endocrinology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Lucerne Cantonal Hospital [Luzern, Switzerland], University of Tartu, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Aalborg University [Denmark] (AAU), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Universiteit van Amsterdam (UvA), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), None, Hess, B, Cahenzli, M, Forbes, A, Burgos, R, Coccolini, F, Corcos, O, Holst, M, Irtun, Ø, Klek, S, Pironi, L, Rasmussen, H, Serlie, M, Thibault, R, Gabe, S, Reintam Blaser, A, Akin, E, Ali, S, Argenio, G, Atici, S, Augustin, G, Baili, E, Bains, L, Bala, M, Baldini, E, Baraket, O, Barone, M, Biloslavo, A, Roberto, B, Bombardini, C, Brisinda, G, Buonomo, L, Catena, F, Ceresoli, M, Chiarello, M, Chouliaras, C, D'Acapito, F, Damaskos, D, De Simone, B, Delogu, D, Demetrashvili, Z, Di Carlo, I, D'Oria, M, Durán-Muñoz-Cruzado, V, Forget, P, Fortuna, L, Fransvea, P, Frey, C, Gapejeva, O, Garcon, P, Gass, J, Teixeira Gonsaga, R, Griffiths, E, Gundogan, K, Gurjar, M, Hamid, H, Silesky Jiménez, J, Kase, K, Hussain Kazmi, S, Kechagias, A, Khokha, V, Kobe, Y, Korkolis, D, Litvin, A, Lostoridis, E, Mahendran, H, Marino, F, Martinuzzi, A, Mesina, C, Neri, V, Panisic, M, Paolillo, C, Pararas, N, Perrone, G, Pesce, A, Picardi, B, Pither, C, Podda, M, Poskus, T, Poullenot, F, Przemyslaw, M, Sartelli, M, Sasia, D, Scheiterle, M, Seretis, F, Søreide, K, Sydorchuk, R, Szczepanek, K, Bodnar, Z, Tamion, F, Tarasconi, A, Teraa, M, Tolonen, M, Vanuytsel, T, Veroux, M, Vinter-Jensen, L, Visconti, D, Widmer, L, Zakaria, A, Zubareva, N, Endorsing International, S, Institut Català de la Salut, [Hess B, Cahenzli M] Department of Intensive Care Medicine, Lucerne Cantonal Hospital, Lucerne, Switzerland. [Forbes A] Department of Anaesthesiology and Intensive Care, University of Tartu, Tartu, Estonia. [Burgos R] Unitat de Suport Nutricional, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Coccolini F] General, Emergency and Trauma Surgery Department, Pisa University Hospital, Pisa, Italy. [Corcos O] Intestinal Vascular Emergencies Structure (SURVI), Beaujon Hospital/Assistance Publique, Hopitaux de Paris, France, and Vall d'Hebron Barcelona Hospital Campus
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Investigative Techniques::Epidemiologic Methods::Data Collection::Surveys and Questionnaires [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Occlusive intestinal ischaemia ,Nutrition and Dietetics ,Acute mesenteric ischaemia ,[SDV]Life Sciences [q-bio] ,Endocrinology, Diabetes and Metabolism ,NOMI (Non-occlusive mesentericandnbsp ,enfermedades del sistema digestivo::enfermedades gastrointestinales::enfermedades intestinales::isquemia mesentérica [ENFERMEDADES] ,Otros calificadores::/diagnóstico [Otros calificadores] ,Isquèmia intestinal - Tractament ,610 Medicine & health ,técnicas de investigación::métodos epidemiológicos::recopilación de datos::encuestas y cuestionarios [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Acute mesenteric infarction ,Intestinal failure ,Enquestes ,Treatment ,Isquèmia intestinal - Diagnòstic ,Other subheadings::/diagnosis [Other subheadings] ,NOMI (Non-occlusive mesenteric ischaemia) ,Survey ,Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Mesenteric Ischemia [DISEASES] ,ischaemia) - Abstract
Background: Acute mesenteric ischaemia (AMI) is a condition with high mortality. This survey assesses current attitudes and practices to manage AMI worldwide.Methods: A questionnaire survey about the practices of diagnosing and managing AMI, endorsed by several specialist societies, was sent to different medical specialists and hospitals worldwide. Data from individual health care professionals and from medical teams were collected.Results: We collected 493 individual forms from 71 countries and 94 team forms from 34 countries. Almost half of respondents were surgeons, and most of the responding teams (70%) were led by surgeons. Most of the respondents indicated that diagnosis of AMI is often delayed but rarely missed. Emergency revascularisation is often considered for patients with AMI but rarely in cases of transmural ischaemia (intestinal infarction). Responses from team hospitals with a dedicated special unit (14 team forms) indicated more aggressive revascularisation. Abdominopelvic CT-scan with intravenous contrast was suggested as the most useful diagnostic test, indicated by approximately 90% of respondents. Medical history and risk factors were thought to be more important in diagnosis of AMI without transmural ischaemia, whereas for intestinal infarction, plasma lactate concentrations and surgical exploration were considered more useful. In elderly patients, a palliative approach is often chosen over extensive bowel resection. There was a large variability in anticoagulant treatment, as well as in timing of surgery to restore bowel continuity.Conclusions: Delayed diagnosis of AMI is common despite wide availability of an adequate imaging modality, i.e. CT-scan. Large variability in treatment approaches exists, indicating the need for updated guidelines. Increased awareness and knowledge of AMI may improve current practice until more robust evidence becomes available. Adherence to the existing guidelines may help in improving differences in treatment and outcomes. Background: Acute mesenteric ischaemia (AMI) is a condition with high mortality. This survey assesses current attitudes and practices to manage AMI worldwide.Methods: A questionnaire survey about the practices of diagnosing and managing AMI, endorsed by several specialist societies, was sent to different medical specialists and hospitals worldwide. Data from individual health care professionals and from medical teams were collected.Results: We collected 493 individual forms from 71 countries and 94 team forms from 34 countries. Almost half of respondents were surgeons, and most of the responding teams (70%) were led by surgeons. Most of the respondents indicated that diagnosis of AMI is often delayed but rarely missed. Emergency revascularisation is often considered for patients with AMI but rarely in cases of transmural ischaemia (intestinal infarction). Responses from team hospitals with a dedicated special unit (14 team forms) indicated more aggressive revascularisation. Abdominopelvic CT-scan with intravenous contrast was suggested as the most useful diagnostic test, indicated by approximately 90% of respondents. Medical history and risk factors were thought to be more important in diagnosis of AMI without transmural ischaemia, whereas for intestinal infarction, plasma lactate concentrations and surgical exploration were considered more useful. In elderly patients, a palliative approach is often chosen over extensive bowel resection. There was a large variability in anticoagulant treatment, as well as in timing of surgery to restore bowel continuity.Conclusions: Delayed diagnosis of AMI is common despite wide availability of an adequate imaging modality, i.e. CT-scan. Large variability in treatment approaches exists, indicating the need for updated guidelines. Increased awareness and knowledge of AMI may improve current practice until more robust evidence becomes available. Adherence to the existing guidelines may help in improving differences in treatment and outcomes.
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- 2023
34. Enzyme synergy for plant cell wall polysaccharide degradation
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Ahmed Khamassi, Claire Dumon, Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)
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[SDV]Life Sciences [q-bio] ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Molecular Biology ,Biochemistry - Abstract
Valorizing plant cell wall, marine and algal polysaccharides is of utmost importance for the development of the circular bioeconomy. This is because polysaccharides are by far the most abundant organic molecules found in nature with complex chemical structures that require a large set of enzymes for their degradation. Microorganisms produce polysaccharide-specific enzymes that act in synergy when performing hydrolysis. Although discovered since decades enzyme synergy is still poorly understood at the molecular level and thus it is difficult to harness and optimize. In the last few years, more attention has been given to improve and characterize enzyme synergy for polysaccharide valorization. In this review, we summarize literature to provide an overview of the different type of synergy involving carbohydrate modifying enzymes and the recent advances in the field exemplified by plant cell-wall degradation.
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- 2023
35. Mistimed origin licensing and activation stabilize common fragile sites under tight DNA-replication checkpoint activation
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Olivier Brison, Stefano Gnan, Dana Azar, Stéphane Koundrioukoff, Rodrigo Melendez-Garcia, Su-Jung Kim, Mélanie Schmidt, Sami El-Hilali, Yan Jaszczyszyn, Anne-Marie Lachages, Claude Thermes, Chun-Long Chen, Michelle Debatisse, Intégrité du génome et cancers (IGC), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Dynamique de l'information génétique : bases fondamentales et cancer (DIG CANCER), Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Institut de Biologie Intégrative de la Cellule (I2BC), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
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Structural Biology ,[SDV]Life Sciences [q-bio] ,Molecular Biology - Abstract
International audience; Genome integrity requires replication to be completed before chromosome segregation. The DNA-replication checkpoint (DRC) contributes to this coordination by inhibiting CDK1, which delays mitotic onset. Under-replication of Common Fragile Sites (CFSs) however escapes surveillance, resulting in mitotic chromosome breaks. Here we asked whether loose DRC activation induced by modest stresses commonly used to destabilize CFSs could explain this leakage. We found that tightening DRC activation or CDK1 inhibition stabilizes CFSs in human cells. Repli-Seq and molecular combing analyses showed a burst of replication initiations implemented in mid S-phase across a subset of late-replicating sequences, including CFSs, while the bulk genome was unaffected. CFS rescue and extra-initiations required CDC6 and CDT1 availability in S-phase, implying that CDK1 inhibition permits mistimed origin licensing and firing. In addition to delaying mitotic onset, tight DRC activation therefore supports replication completion of late origin-poor domains at risk of under-replication, two complementary roles preserving genome stability.
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- 2023
36. Inpatient target discharge weight for early-onset anorexia nervosa: Restoring premorbid BMI percentile to improve height prognosis
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A. Ayrolles, J. Clarke, M. Dechaux, A. Lefebvre, A. Cohen, C. Stordeur, H. Peyre, A. Bargiacchi, N. Godart, H. Watson, R. Delorme, Hôpital Robert Debré Paris, Hôpital Robert Debré, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre de Psychiatrie et Neurosciences (U894), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Fondation Santé des Etudiants de France, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Curtin University [Perth], Planning and Transport Research Centre (PATREC), and The University of Western Australia (UWA)
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Early-onset ,Nutrition and Dietetics ,Height prognosis ,[SDV]Life Sciences [q-bio] ,Endocrinology, Diabetes and Metabolism ,Anorexia nervosa ,Weight suppression - Abstract
International audience; Objective: Early-onset anorexia nervosa (EO-AN) is characterized by restricted food intake leading to low body weight, emerging before 14 years old. Most patients reaching a target body mass index (BMI) around the 25th percentile at hospitalization discharge display an incomplete prospective height catch-up. A better understanding of height prognosis determinants is required. Methods: In 74 children with an EO-AN, we collected height and weight premorbidly, at hospitalization, and at discharge, 6 months, 12 months, and at longer-term follow-up of 36 months. We defined a height prognosis parameter (HPP) as the difference between the height percentile at follow-up times and the premorbid height percentile. We explored the relationship between weight parameters and height catch-up at follow-up with linear regression analyses. Results: A higher weight suppression (WS) - i.e., difference between premorbid and current BMI - at admission and discharge was associated with lower HPP - i.e., a greater loss of height - at 12 months and 36 months follow-up. Similarly, a higher premorbid BMI percentile was associated with a lower HPP at 12 and 36 months. Conclusion: Target discharge weight for EO-AN patients should be tailored and based on premorbid BMI trajectory to improve height prognosis.
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- 2023
37. Yoga and Physical Exercises as Immunogenic Fortifiers for Coronavirus Vaccine Responses
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Govindasamy, Karuppasamy, Zouhal, Hassane, Kaur, Dilpreet, Dhiman, Aakash, Singh, Vikas, Chaware, Utsav, Pandey, Rajesh Kumar, Salian, Prasad, Baro, Mantu, Gogoi, Hemantajit, Borah, Poli, Gogoi, Lakshyajit, Parpa, Koulla, Ben Abderrahman, Abderraouf, SRM Institute of Science and Technology (SRM), Laboratoire Mouvement Sport Santé (M2S), École normale supérieure - Cachan (ENS Cachan)-Université de Rennes (UR)-Université de Brest (UBO)-Université de Rennes 2 (UR2)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Panjab University [Chandigarh], Government College of Engineering, Dibrugarh University, Mahatma Gandhi University [Kerala], University of Cyprus = Université de Chypre, and ISSEP Ksar Saïd
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Coronavirus ,Yoga ,[SDV]Life Sciences [q-bio] ,COVID-19 ,Vaccine ,Physical Exercises - Abstract
International audience; Background and aim: Coronavirus has emerged as a pandemic leading to pneumonia and death in susceptible populations, especially in immunocompromised hosts and the elderly. Though national governance and drug firms work in cohesion to develop vaccines, the fear and anxiety towards misconceptions about vaccine efficacy and adverse effects lead to underutilization of the vaccines. Though known for its immunogenic responses against infections, conservative lifestyle modifications such as Yoga and physical exercise's synergistic effects with coronavirus vaccine's immunogenic response remains unknown. Methods: We administered a systematic search on the contemporary evidence investigating the immune responses of physical activity or Yoga in three databases: PubMed, Embase and Web of Science. In the present review, we reviewed the empirical evidence that explored the role of Yoga and physical exercise as an immunity booster and extrapolated their effects against coronavirus infection. Results: We found sixteen articles emphasizing physical activity to augment immune responses towards Coronavirus. Discussion and Conclusion: Considering the contemporary evidence, complementary therapies such as Yoga or physical activity are speculated to improve the influenza vaccines' immune responses. We recommend that Yoga and physical exercises be affordable, practical and effective strategies that could be advocated along with vaccination doses. We hope the present review may help readers and policymakers explore complementary therapies that could be administered as adjuncts to vaccine-mediated immunity in combating the deadly pandemic. © 2023 by authors, all rights reserved.
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- 2023
38. mScarlet3
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Theodorus W. J. Gadella, Laura van Weeren, Jente Stouthamer, Mark A. Hink, Anouk H. G. Wolters, Ben N. G. Giepmans, Sylvain Aumonier, Jérôme Dupuy, Antoine Royant, Center for Liver, Digestive and Metabolic Diseases (CLDM), Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Swammerdam Institute for Life Sciences, Biomedical Sciences of Cells & Systems, University of Groningen [Groningen], Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), and European Synchrotron Radiation Facility (ESRF)
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MESH: Humans ,MESH: Middle Aged ,MESH: Fluorescence Resonance Energy Transfer ,[SDV]Life Sciences [q-bio] ,Cell Biology ,Biochemistry ,MESH: Male ,MESH: Trichophytin ,MESH: T-Lymphocytes ,MESH: HeLa Cells ,MESH: Luminescent Proteins ,MESH: Female ,Molecular Biology ,Biotechnology - Abstract
We report the evolution of mScarlet3, a cysteine-free monomeric red fluorescent protein with fast and complete maturation, as well as record brightness, quantum yield (75%) and fluorescence lifetime (4.0 ns). The mScarlet3 crystal structure reveals a barrel rigidified at one of its heads by a large hydrophobic patch of internal residues. mScarlet3 behaves well as a fusion tag, displays no apparent cytotoxicity and it surpasses existing red fluorescent proteins as a Förster resonance energy transfer acceptor and as a reporter in transient expression systems.
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- 2023
39. Diversity of greenspace design and management impacts pollinator communities in a densely urbanized landscape: the city of Paris, France
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Vincent ZANINOTTO, Arthur FAUVIAU, Isabelle DAJOZ, Institut d'écologie et des sciences de l'environnement de Paris (iEES Paris ), Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris Cité (UPCité), and This work was partially funded by the City of Paris (CIFRE n°2018/0699), by the Institut de la Transition Environnementale – Sorbonne University ('Yapudsaison' 2019 and 2020), and by the Société Centrale d’Apiculture (« Pollinisateurs sauvages et communautés végétales urbaines », 2019).
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Urban Studies ,Ecology ,[SDV]Life Sciences [q-bio] ,Impervious surfaces ,[SDE]Environmental Sciences ,Community ecology ,Bees ,Spontaneous plants ,Functional traits ,Ornamental plants - Abstract
The response of insect pollinator communities to increasing urbanization is shaped by landscape and local factors. But what about habitats that are already highly artificial? We investigated the drivers of pollinator diversity in a dense urban matrix, the city of Paris. We monitored insect pollinator communities monthly (March-October) for two consecutive years in 12 green spaces that differed in their management practices, focusing on four insect orders (Hymenoptera, Diptera, Lepidoptera, Coleoptera). Pollinator abundance and species richness were both positively tied to green space size and flowering plant species richness, but negatively linked to surrounding impervious surfaces. In addition, environmental features at both the local and landscape scales influenced the composition and functional diversity of wild bee communities. Indeed, small and large bees responded differently, with the occurrence of large-bodied species being impaired by the proportion of impervious surfaces but strongly enhanced by plant species richness. Also, sites with a majority of spontaneous plant species had more functionally diverse bee communities, with oligolectic species more likely to be found.These results, consistent with the literature, can guide the design and management practices of urban green spaces to promote pollinator diversity and pollination function, even in dense urban environments.
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- 2023
40. Impact of Arterial CO2Retention in Patients With Moderate or Severe ARDS
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Maamar, Adel, Delamaire, Flora, Reizine, Florian, Lesouhaitier, Mathieu, Painvin, Benoit, Quelven, Quentin, Coirier, Valentin, Guillot, Pauline, Le Tulzo, Yves, Tadie, Jean Marc, Gacouin, Arnaud, Centre Hospitalier Universitaire [Rennes], Université de Rennes - Faculté de Médecine (UR Médecine), Université de Rennes (UR), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and None
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Pulmonary and Respiratory Medicine ,[SDV]Life Sciences [q-bio] ,cohort study ,ARDS ,hypercapnia ,General Medicine ,Critical Care and Intensive Care Medicine ,mortality ,[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract - Abstract
International audience; BACKGROUND: Lung-protective ventilation (reduced tidal volume and limited plateau pressure) may lead to CO(2) retention. Data about the impact of hypercapnia in patients with ARDS are scarce and conflicting. METHODS: We performed a non-interventional cohort study with subjects with ARDS admitted from 2006 to 2021 and with P(aO(2)) /F(IO(2)) ≤ 150 mm Hg. We examined the association between severe hypercapnia (P(aCO(2)) ≥ 50 mm Hg) on the first 5 days after the diagnosis of ARDS and death in ICU for 930 subjects. All the subjects received lung-protective ventilation. RESULTS: Severe hypercapnia was noted in 552 subjects (59%) on the first day of ARDS (day 1); 323/930 (34.7%) died in the ICU. Severe hypercapnia on day 1 was associated with mortality in the unadjusted (odds ratio 1.54, 95% CI 1.16-1.63; P = .003) and adjusted (odds ratio 1.47, 95% CI 1.08-2.43; P = .004) models. In the Bayesian analysis, the posterior probability that severe hypercapnia was associated with ICU death was > 90% in 4 different priors, including a septic prior for this association. Sustained severe hypercapnia on day 5, defined as severe hypercapnia present from day 1 to day 5, was noted in 93 subjects (12%). After propensity score matching, severe hypercapnia on day 5 remained associated with ICU mortality (odds ratio 1.73, 95% CI 1.02-2.97; P = .047). CONCLUSIONS: Severe hypercapnia was associated with mortality in subjects with ARDS who received lung-protective ventilation. Our results deserve further evaluation of the strategies and treatments that aim to control CO(2) retention.
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- 2023
41. Cyclopeptide mushroom poisoning: A retrospective series of 204 patients
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Jérémy Lecot, Morgane Cellier, Arnaud Courtois, Dominique Vodovar, Gaël Le Roux, Anne Landreau, Magali Labadie, Chloé Bruneau, Alexis Descatha, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Bordeaux [Bordeaux], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA), Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, and Hofstra University [Hempstead]
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mushroom poisoning ,Pharmacology ,cyclopeptide mushroom ,[SDV]Life Sciences [q-bio] ,[SDV.TOX]Life Sciences [q-bio]/Toxicology ,severity factor ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,amatoxins ,acute liver failure ,General Medicine ,Amanita phalloides poisoning ,poison control centres ,Toxicology - Abstract
International audience; Cyclopeptide mushroom poisoning is responsible for 90%-95% of deaths from macrofungi ingestion. The main objectives of this study are to describe cases of cyclopeptide mushroom poisoning and to determine risk factors that may influence the severity/mortality of poisoned patients. We included all cases of amatoxin toxicity reported to two French Poison Centers from 2013 through 2019. We compared the severity with the Poison Severity Score (PSS) and the outcomes of patients using simple logistic regression and multinomial logistic regression. We included 204 cases of amatoxin toxicity. More than three-quarters developed an increase in AST and/or ALT (78.1%), and over half developed a decrease in prothrombin ratio (
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- 2023
42. Discovery of a PDZ Domain Inhibitor Targeting the Syndecan/Syntenin Protein–Protein Interaction: A Semi-Automated 'Hit Identification-to-Optimization' Approach
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Laurent Hoffer, Manon Garcia, Raphael Leblanc, Mikael Feracci, Stéphane Betzi, Khaoula Ben Yaala, Avais M. Daulat, Pascale Zimmermann, Philippe Roche, Karine Barral, Xavier Morelli, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU), ANR-11-IDEX-0001,Amidex,INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE(2011), ANR-18-CE13-0017,SynTEV,Rôle des réseaux tétraspanines-syndécanes-PDZ dans l'hétérogénéité moléculaire et fonctionelle des vésicules extracellulaires(2018), and ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010)
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Inhibitors ,[SDV]Life Sciences [q-bio] ,Organic compounds ,Drug Discovery ,Binding modes ,Reaction products ,Molecular Medicine ,Alkyls - Abstract
International audience; The rapid identification of early hits by fragment-based approaches and subsequent hit-to-lead optimization represents a challenge for drug discovery. To address this challenge, we created a strategy called 'DOTS' that combines molecular dynamic simulations, computer-based library design (chemoDOTS) with encoded medicinal chemistry reactions, constrained docking, and automated compound evaluation. To validate its utility, we applied our DOTS strategy to the challenging target syntenin, a PDZ domain containing protein and oncology target. Herein, we describe the creation of a 'best-in-class' sub-micromolar small molecule inhibitor for the second PDZ domain of syntenin validated in cancer cell assays. Key to the success of our DOTS approach was the integration of protein conformational sampling during hit identification stage and the synthetic feasibility ranking of the designed compounds throughout the optimization process. This approach can be broadly applied to other protein targets with known 3D structures to rapidly identify and optimize compounds as chemical probes and therapeutic candidates.
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- 2023
43. Impact of the gut microbiome on nicotine’s motivational effects and glial cells in the ventral tegmental area in male mice
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Alina Lakosa, Anaïs Rahimian, Flavio Tomasi, Fabio Marti, Lauren M. Reynolds, Léa Tochon, Vincent David, Anne Danckaert, Candice Canonne, Sylvana Tahraoui, Fabrice de Chaumont, Benoît Forget, Uwe Maskos, Morgane Besson, Neurobiologie intégrative des Systèmes cholinergiques / Integrative Neurobiology of Cholinergic Systems (NISC), Institut Pasteur [Paris] (IP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire Plasticité du Cerveau Brain Plasticity (UMR 8249) (PdC), 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), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Plateforme technologique Bioimagerie Photonique - Photonic BioImaging Technologic Platform, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), This work was supported by the Institut Pasteur, Paris (GPF Microbes and Brain, project 'µBIOTADDICT'). UtechS PBI/C2RT is part of the France BioImaging infrastructure supported by the French National Research Agency (ANR-10-INSB-04-01, 'Investments for the future') and is supported by Conseil de la Region Ile-de-France (Domaine d’Intérêt Majeur DIM1HEALTH) and by Fondation Française pour la Recherche Médicale (Programme Grands Equipements)., and ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010)
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Pharmacology ,Psychiatry and Mental health ,[SDV]Life Sciences [q-bio] - Abstract
International audience; A link between gut dysbiosis and the pathogenesis of brain disorders has been identified. A role for gut bacteria in drug reward and addiction has been suggested but very few studies have investigated their impact on brain and behavioral responses to addictive drugs so far. In particular, their influence on nicotine’s addiction-like processes remains unknown. In addition, evidence shows that glial cells shape the neuronal activity of the mesolimbic system but their regulation, within this system, by the gut microbiome is not established. We demonstrate that a lack of gut microbiota in male mice potentiates the nicotine-induced activation of sub-regions of the mesolimbic system. We further show that gut microbiota depletion enhances the response to nicotine of dopaminergic neurons of the posterior ventral tegmental area (pVTA), and alters nicotine’s rewarding and aversive effects in an intra-VTA self-administration procedure. These effects were not associated with gross behavioral alterations and the nicotine withdrawal syndrome was not impacted. We further show that depletion of the gut microbiome modulates the glial cells of the mesolimbic system. Notably, it increases the number of astrocytes selectively in the pVTA, and the expression of postsynaptic density protein 95 in both VTA sub-regions, without altering the density of the astrocytic glutamatergic transporter GLT1. Finally, we identify several sub-populations of microglia in the VTA that differ between its anterior and posterior sub-parts, and show that they are re-organized in conditions of gut microbiota depletion. The present study paves the way for refining our understanding of the pathophysiology of nicotine addiction.
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- 2023
44. Description of supportive care and feasibility of physical exercise program to improve quality of life in advanced melanoma patients
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Boileau, M., Templier, C., Massip, E., Dehoux, C., Dziwniel, V., Fabre, Claudine, Thevenon, André, Mortier, L., Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369 - ULR 4488 (URePSSS), and Université d'Artois (UA)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille
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Cancer Research ,Oncology ,[SDV]Life Sciences [q-bio] ,Dermatology - Abstract
Physical activity is the first-line treatment of cancer-related fatigue. It has shown benefits on patient's quality of life (QoL) when practiced during and after treatment. New treatments have drastically changed the prognosis of melanoma. Still, few data are available about research program of supportive care in advanced melanoma. The primary outcome was to assess the feasibility of setting up a prospective study evaluating the benefits of Adapted Physical Activity (APA) on the QoL of patients with advanced melanoma. Feasibility was defined with a combination of five criteria including completion of questionnaire, recruitment, participant retention, patient adhesion to supportive care, and absence of adverse event. Between September 2019 and March 2021, 271 melanoma patients were questioned. Around 60% of stage IV melanoma patients were interested in support care. Patient retention at 3 months was sufficient. Only one patient could not be evaluated after 3 months of enrolment because of deterioration of the general state. Adhesion to exercise and sessions was good. Supervised APA program appeared to be safe and well tolerated as no adverse events or discontinuations were reported. Setting up a prospective research program evaluating the benefits of physical activity in advanced melanoma patients seems feasible. With melanoma becoming a chronic disease, supportive care may reduce fatigue, improve QoL and help maintain a healthy lifestyle. Data supporting its benefits on this survivor population are needed.
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- 2023
45. Regulatory B Cells Contribute to the Clinical Response After Bone Marrow-Derived Mesenchymal Stromal Cell Infusion in Patients With Systemic Sclerosis
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Séverine Loisel, Pauline Lansiaux, Delphine Rossille, Cédric Ménard, Joëlle Dulong, Céline Monvoisin, Nadège Bescher, Isabelle Bézier, Maëlle Latour, Audrey Cras, Dominique Farge, Karin Tarte, CHU Pontchaillou [Rennes], Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Recherche clinique appliquée à l'hématologie (URP_3518), McGill University = Université McGill [Montréal, Canada], and AOM 11â€'250, National Hospital Clinical Research Program
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immune monitoring ,systemic sclerosis ,[SDV]Life Sciences [q-bio] ,clinical trial ,Breg ,Cell Biology ,General Medicine ,mesenchymal stromal cells ,Developmental Biology - Abstract
Mesenchymal stromal cells (MSCs) have recently emerged as an interesting therapeutic approach for patients with progressive systemic sclerosis (SSc), a rare and life-threatening orphan autoimmune disease. Whereas MSC immunomodulatory potential is considered as a central mechanism for their clinical benefit, very few data are available on the impact of MSCs on immune cell subsets in vivo. In the current extended study of a phase I/II clinical trial exploring the injection of a single dose of allogeneic bone marrow-MSCs (alloBM-MSCs) in patients with severe SSc (NCT02213705), we performed a longitudinal in-depth characterization of circulating immune cells in 19 MSC-treated patients, including 14 responders and 5 non-responders. By a combination of flow cytometry and transcriptomic analyses, we highlighted an increase in circulating CD24hiCD27posCD38lo/neg memory B cells, the main IL-10-producing regulatory B cell (Breg) subset, and an upregulation of IL10 expression in ex-vivo purified B cells, specifically in responder patients, early after the alloBM-MSC infusion. In addition, a deeper alteration of the B-cell compartment before alloBM-MSC treatment, including a higher expression of profibrotic cytokines IL6 and TGFβ by sorted B cells was associated with a non-responder clinical status. Finally, BM-MSCs were able to directly upregulate IL-10 production in activated B cells in vitro. These data suggest that cytokine-producing B cells, in particular Breg, are pivotal effectors of BM-MSC therapeutic activity in SSc. Their quantification as activity biomarkers in MSC potency assays and patient selection criteria may be considered to reach optimal clinical benefit when designing MSC-based clinical trials.
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- 2023
46. Moving the Dial on Airway Inflammation in Response to Trikafta in Adolescents with Cystic Fibrosis
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Agathe, Lepissier, Anne Sophie, Bonnel, Nathalie, Wizla, Laurence, Weiss, Marie, Mittaine, Katia, Bessaci, Eitan, Kerem, Véronique, Houdouin, Philippe, Reix, Christophe, Marguet, Isabelle, Sermet-Gaudelus, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre de Référence Maladies Rares, Mucoviscidose et maladies apparentées (CRMR2MA / CHU Necker - Enfants Malades [AP-HP]), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital de Hautepierre [Strasbourg], Service Pneumologie et allergologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de pédiatrie générale et spécialisée [CHU de Reims - American Memorial Hospital] (SPGS), Centre Hospitalier Universitaire de Reims (CHU Reims)-American Memorial Hospital (Reims), Hadassah Hebrew University Medical Center [Jerusalem], Centre de ressources et de compétences pour la mucoviscidose [Debré], AP-HP Hôpital universitaire Robert-Debré [Paris], Université Paris Cité (UPCité), Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-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), Groupe de Recherche sur le Handicap Ventilatoire (GRHV), CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dynamique Microbienne associée aux Infections Urinaires et Respiratoires (DYNAMICURE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Goethe-University Frankfurt am Main, and dormoy, valerian
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[SDV] Life Sciences [q-bio] ,Pulmonary and Respiratory Medicine ,Cystic Fibrosis ,[SDV]Life Sciences [q-bio] ,Biomarker ,Inflammation ,Critical Care and Intensive Care Medicine ,CFTR modulator - Abstract
International audience; No abstract available
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- 2023
47. Development of Ovaries and Sex Change in Fish: Bringing Potential into Action
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Mateus Contar Adolfi, Alexandra Depincé, Ming Wen, Qiaowei Pan, Amaury Herpin, University of Würzburg = Universität Würzburg, Laboratoire de Physiologie et Génomique des Poissons (LPGP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hunan Normal University (HNU), Université de Lausanne = University of Lausanne (UNIL), and European Project: 871108 ,AQUAEXCEL3.0
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Oocyte ,Embryology ,Fish ,Plasticity ,[SDV]Life Sciences [q-bio] ,Endocrinology, Diabetes and Metabolism ,Ovary ,Germ cells ,Ovarian development ,Gonadal differentiation ,Developmental Biology - Abstract
Background: Encompassing about half of the 60,000 species of vertebrates, fish display the greatest diversity of sex determination mechanisms among metazoans. As such that phylum offers a unique playground to study the impressive variety of gonadal morphogenetic strategies, ranging from gonochorism, with either genetic or environmental sex determination, to unisexuality, with either simultaneous or consecutive hermaphroditism. Summary: From the two main types of gonads, the ovaries embrace the important role to produce the larger and non-motile gametes, which is the basis for the development of a future organism. The production of the egg cells is complex and involves the formation of follicular cells, which are necessary for the maturation of the oocytes and the production of feminine hormones. In this vein, our review focuses on the development of ovaries in fish with special emphasis on the germ cells, including those that transition from one sex to the other as part of their life cycle and those that are capable of transitioning to the opposite sex depending on environmental cues. Key messages: Clearly, establishing an individual as either a female or a male is not accomplished by the sole development of two types of gonads. In most cases, that dichotomy, be it final or transient, is accompanied by coordinated transformations across the entire organism, leading to changes in the physiological sex as a whole. These coordinated transformations require both molecular and neuroendocrine networks, but also anatomical and behavioural adjustments. Remarkably, fish managed to tame the ins and outs of sex reversal mechanisms to take the most advantages of changing sex as adaptive strategies in some situations.
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- 2023
48. Structural and functional insights into the activation of the dual incision activity of UvrC, a key player in bacterial NER
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Anna Seck, Salvatore De Bonis, Meike Stelter, Mats Ökvist, Müge Senarisoy, Mohammad Rida Hayek, Aline Le Roy, Lydie Martin, Christine Saint-Pierre, Célia M Silveira, Didier Gasparutto, Smilja Todorovic, Jean-Luc Ravanat, Joanna Timmins, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), European Synchrotron Radiation Facility (ESRF), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Instituto de Tecnologia Química e Biológica António Xavier (ITQB), and Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)
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MESH: DNA Damage ,MESH: DNA Repair ,MESH: Escherichia coli ,[SDV]Life Sciences [q-bio] ,Genetics ,MESH: DNA Helicases ,MESH: Endodeoxyribonucleases ,MESH: Bacterial Proteins ,MESH: DNA, Bacterial ,MESH: Deinococcus - Abstract
Bacterial nucleotide excision repair (NER), mediated by the UvrA, UvrB and UvrC proteins is a multistep, ATP-dependent process, that is responsible for the removal of a very wide range of chemically and structurally diverse DNA lesions. DNA damage removal is performed by UvrC, an enzyme possessing a dual endonuclease activity, capable of incising the DNA on either side of the damaged site to release a short single-stranded DNA fragment containing the lesion. Using biochemical and biophysical approaches, we have probed the oligomeric state, UvrB- and DNA-binding abilities and incision activities of wild-type and mutant constructs of UvrC from the radiation resistant bacterium, Deinococcus radiodurans. Moreover, by combining the power of new structure prediction algorithms and experimental crystallographic data, we have assembled the first model of a complete UvrC, revealing several unexpected structural motifs and in particular, a central inactive RNase H domain acting as a platform for the surrounding domains. In this configuration, UvrC is maintained in a ‘closed’ inactive state that needs to undergo a major rearrangement to adopt an ‘open’ active state capable of performing the dual incision reaction. Taken together, this study provides important insight into the mechanism of recruitment and activation of UvrC during NER.
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- 2023
49. Serum persistent organic pollutants and diminished ovarian reserve: a single-exposure and mixture exposure approach from a French case–control study
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M Génard-Walton, C Warembourg, S Duros, F Mercier, T Lefebvre, A Guivarc’h-Levêque, M -T Le Martelot, B Le Bot, B Jacquemin, C Chevrier, S Cordier, N Costet, L Multigner, R Garlantézec, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), CHU Pontchaillou [Rennes], Laboratoire d'étude et de recherche en environnement et santé (LERES), Centre hospitalier universitaire de Nantes (CHU Nantes), Clinique mutualiste La Sagesse, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Département des sciences en santé environnementale (DEESSE), Fondation de France [2014-50537, 00110196], and French Biomedicine Agency
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ovarian reserve ,Reproductive Medicine ,polychlorinated biphenyls ,female infertility ,[SDV]Life Sciences [q-bio] ,Rehabilitation ,environmental exposure ,Obstetrics and Gynecology ,persistent organic pollutants ,pesticides - Abstract
STUDY QUESTION Are persistent organic pollutants (POPs) associated with a diminished ovarian reserve (DOR) in women of reproductive age? SUMMARY ANSWER Amongst 17 POPs detected in over 20% of serum samples, only p,p′-DDE was significantly associated with an increased risk of DOR, and β-hexachlorocyclohexane (β-HCH) was significantly associated with a decreased risk of DOR whilst mixture analyses yielded non-significant associations and did not detect any interactions between POPs. WHAT IS KNOWN ALREADY Animal studies have shown that several POPs can alter folliculogenesis and increase follicle depletion. However, only a few studies have been conducted in humans, with small sample sizes and inconsistent results. STUDY DESIGN, SIZE, DURATION Our study included 138 cases and 151 controls from the AROPE case–control study. Study participants were women between 18 and 40 years of age recruited amongst couples consulting for infertility in four fertility centres in western France between 2016 and 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS Cases of DOR were defined as women with anti-Müllerian hormone (AMH) levels ≤1.1 ng/ml and/or antral follicle count (AFC) MAIN RESULTS AND THE ROLE OF CHANCE Of the 43 POPs, 17 were detected in over 20% of the serum samples. In the single-exposure multivariate logistic regressions, p,p′-DDE (median 165.0 IQR 161.0 ng/l in controls) as a continuous exposure was significantly associated with an increased risk of DOR (odds ratio (OR) 1.39, 95% CI 1.10–1.77) and non-significantly associated with an increased risk of DOR for the second and third terciles (OR 1.46, 95% CI 0.74–2.87, and OR 1.72, 95% CI 0.88–3.37, respectively). β-HCH (median 24.2 IQR 21.5 ng/l in controls) was significantly associated with a decreased risk of DOR when β-HCH was treated as a continuous exposure (OR 0.63, 95% CI 0.44–0.89) and for the third tercile of exposure (OR 0.43, 95% CI 0.21–0.84) and non-significantly associated with a decreased risk of DOR for the second tercile (OR 0.77, 95% CI 0.42–1.42). All sensitivity analyses confirmed our results. BKMR showed similar associations for single exposures but found no significant associations for the total mixture effect. In addition, the BKMR results did not suggest any interactions between POPs. LIMITATIONS, REASONS FOR CAUTION Controls were recruited amongst infertile couples and thus may not be representative of all women of reproductive age. However, their POP concentrations were in the same range as in the general French population. WIDER IMPLICATIONS OF THE FINDINGS This study is the first to examine the associations between serum POPs and DOR. The well-recognized anti-androgenic properties of p,p′-DDE and estrogenic properties of β-HCH could explain these associations of opposite direction. If these results are replicated elsewhere, this could have an impact on fertility prevention messages and help in understanding the impact of POPs on the female reproductive system. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the Fondation de France (grant numbers 2014-50537 and 00110196) and the French Biomedicine Agency (2016). None of the authors have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A.
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- 2023
50. Narrow Near-Infrared Emission from InP QDs Synthesized with Indium(I) Halides and Aminophosphine
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Ranjana Yadav, Yongju Kwon, Céline Rivaux, Christine Saint-Pierre, Wai Li Ling, Peter Reiss, SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Institut de biologie structurale (IBS - UMR 5075), and Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG)
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Colloid and Surface Chemistry ,[SDV]Life Sciences [q-bio] ,General Chemistry ,Biochemistry ,Catalysis - Abstract
Nonpyrophoric aminophosphines reacted with indium(III) halides in the presence of zinc chloride have emerged as promising phosphorus precursors in the synthesis of colloidal indium phosphide (InP) quantum dots (QDs). Nonetheless, due to the required P/In ratio of 4:1, it remains challenging to prepare large-sized (>5 nm), near-infrared absorbing/emitting InP QDs using this synthetic scheme. Furthermore, the addition of zinc chloride leads to structural disorder and the formation of shallow trap states inducing spectral broadening. To overcome these limitations, we introduce a synthetic approach relying on the use of indium(I) halide, which acts as both the indium source and reducing agent for aminophosphine. The developed zinc-free, single-injection method gives access to tetrahedral InP QDs with an edge length > 10 nm and narrow size distribution. The first excitonic peak is tunable from 450 to 700 nm by changing the indium halide (InI, InBr, InCl). Kinetic studies using phosphorus NMR reveal the coexistence of two reaction pathways, the reduction of transaminated aminophosphine by In(I) and via redox disproportionation. Etching the surface of the obtained InP QDs at room temperature with in situ-generated hydrofluoric acid (HF) leads to strong photoluminescence (PL) emission with a quantum yield approaching 80%. Alternatively, surface passivation of the InP core QDs was achieved by low-temperature (140 °C) ZnS shelling using the monomolecular precursor zinc diethyldithiocarbamate. The obtained InP/ZnS core/shell QDs that emit in a range of 507-728 nm exhibit a small Stokes shift (110-120 meV) and a narrow PL line width (112 meV at 728 nm).
- Published
- 2023
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