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Deposition of microplastics on the sedimentation active band of rivers
No full textInternational audienc
La rhinopneumonie : doit-on s’inquiéter ?
No full textNational audienceLa prise de température : un geste simple, rapide, peu couteux qui peut limiter l’apparition d’épisodes de rhinopneumonie.Les premiers instants avec les bons gestes sont essentiels pour éviter la dissémination du virus et éviter l’apparition d’une large épidémie.Le typage des variants HVE-1 est important d’un point de vue recherche et contrôle de l’efficacité des outils PCR, mais sur le terrain les mesures de biosécurité à appliquer sont les mêmes quel que soit le variant incriminé
Valproic Acid Improves Antisense-Mediated Exon-Skipping Efficacy in mdx Mice
No full textInternational audienceDuchenne muscular dystrophy (DMD) is a severe genetic disorder characterized by the progressive degeneration of skeletal and cardiac muscles due to the absence of dystrophin. Exon-skipping therapy is among the most promising approaches for treating DMD, with several antisense oligonucleotides (ASO) already approved by the FDA; however, their limited efficacy highlights substantial potential for further improvement. In this study, we evaluate the potential of combining ASO with valproic acid (VPA) to enhance dystrophin expression and improve functional outcomes in a murine model of DMD. Our results indicate that the ASO+VPA treatment significantly increases dystrophin restoration across various muscle tissues, with particularly pronounced effects observed in cardiac muscle, where levels are nearly doubled compared to ASO monotherapy. Additionally, we demonstrate significant improvements in functional outcomes in treated mdx mice. Our findings suggest that the combined ASO+VPA therapy holds promise as an effective therapeutic approach to ameliorate muscle function in DMD, warranting further exploration of its mechanistic pathways and long-term benefits
Analytical modeling of the permeability of filter media exhibiting a bimodal fibre diameter distribution - Beyond empirical models
No full textInternational audienceThe prediction of the permeability of bimodal fibrous media dedicated to air filtration, i.e. highly porous media, is addressed. Two types of models, using similar input parameters (mean porosity and mean fibre diameter), are compared: several analytical models and the empirical models still commonly used by the air filtration community. It is demonstrated than even if every model underpredicts the media permeability, the isotropic versions of the analytical Representative Unit Cell (RUC) model and Tomadakis and Robertson model yield significantly better predictions than the empirical models. The additional improvement in the analytical model predictions, by including the bimodal fibre diameter distribution as a unimodal equivalent diameter, is furthermore outlined. This model comparison is made possible due to new accurate experimental data, obtained from the characterization of the structural properties of a commercial bimodal fibrous medium. The fibre diameter distribution and mean medium porosity are determined from SEM analyzes and mercury porosimetry, respectively. The anisotropic/isotropic and homogeneous/heterogeneous nature of the medium is evaluated based on X-ray micro-tomography data. Finally, to go further than the prediction of one permeability value based on mean media properties, permeability mappings are generated based on the porosity mappings and the adapted RUC permeability model
Bien être (enrichissement) et protection animale (abattage) chez le poisson
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Scalability of spheroid-derived small extracellular vesicles production in stirred systems
No full textInternational audienceIntroduction: Small extracellular vesicle (sEV)-based therapies have gained widespread interest, but challenges persist to ensure standardization and high-scale production. Implementing upstream processes in a chemically defined media in stirred-tank bioreactors (STBr) is mandatory to closely control the cell environment, and to scale-up production, but it remains a significant challenge for anchorage-dependent cells.Methods: We used a human β cell line, grown as monolayer or in suspension as spheroid in stirred systems. We assessed the consequences of culturing these cells in 3D with, or without fetal bovine serum in a chemically defined medium, for cell growth, viability and metabolism. We next explored how different scale-up strategies might influence cell and spheroid formation in spinner flask, with the aim to transfer the process in instrumented Ambr®250 STBr. Lastly, we analyzed and characterized sEV production in monolayer, spinner flask and STBr.Results and discussion: Generation of spheroids in a chemically defined medium allowed the culture of highly viable cells in suspension in stirred systems. Spheroid size depended on the system’s volumetric power input (P/V), and maintaining this parameter constant during scale-up proved to be the optimal strategy for standardizing the process. However, transferring the spinner flask (SpF) process to the Ambr®250 STBr at constant P/V modified spheroid size, due to important geometric differences and impeller design. Compared to a monolayer reference process, sEV yield decreased two-fold in SpF, but increased two-fold in STBr. Additionally, a lower expression of the CD63 tetraspanin was observed in sEV produced in both stirred systems, suggesting a reduced release of exosomes compared to ectosomes. This study addresses the main issues encountered in spheroid culture scale-up in stirred systems, rather conducive for the production of ectosomes
The prion-family protein Doppel exerts a protective role during influenza virus infection
No full textInternational audienceThe cellular form of the prion protein (PrPC), known for its involvement as a misfolded isoform in transmissible spongiform encephalopathies, has recently been identified to exert a protective effect against viral infections. In this study, we explored the role of 2 other prion family members, Shadoo and Doppel, in protection against influenza A virus infection in mice. Lung expression levels of these genes revealed marked differences, with high expression of PrPC, low expression of Doppel, while Shadoo remained undetectable.Mice genetically knocked out for the genes encoding PrPC, Prnp−/− or Doppel, Prnd−/−, showed increased susceptibility to the virus, resulting in elevated morbidity compared with wild-type mice and mice knocked out for Shadoo, Sprn−/−. Unlike previous results observed in Prnp−/− mice, the absence of Doppel does not show enhancing effect on virus replication levels. Histological analysis of lung tissue from Prnd−/− mice revealed no difference in lesion size and severity compared with wild-type mice. However, transcriptomic analysis on day 7 postinfection revealed distinct signatures in Prnd−/− mice, highlighting the role of specific genes associated with polymorphonuclear neutrophil cells. Bronchoalveolar lavages confirmed a substantial neutrophil influx and increased inflammatory markers in the lungs of Prnd−/− mice. Neutrophil depletion experiments demonstrated a direct link between excessive neutrophil influx and increased susceptibility, mitigating pathology and partially restoring a wild-type phenotype in Prnd−/− mice. These findings underscore the complex role of Doppel in modulating the host immune response to influenza virus infection, particularly in regulating neutrophil recruitment and its implications on disease outcomes
Histophilus somni et son implication dans les troubles de la reproduction bovine
No full textInternational audienceHistophilus somni est un habitant obligatoire des muqueuses génitales et respiratoires bovines depuis lesquelles il est fréquemment isolé chez des individus sains. Grâce à plusieurs composantes et ses facteurs de virulence, il peut agir comme pathogène primaire, opportuniste ou commensal, causant des épidémies d'endométrites cliniques et plus rarement des avortements par bactériémie ou des posthites et urétrites chez les taureaux. L'émergence de résistances aux antibiotiques est observée pour H. somni, cependant la guérison est souvent spontanée ou obtenue grâce aux molécules utilisées dans le traitement des BPIE (broncho-pneumonies infectieuses enzootiques). Sa culture difficile et sa dualité commensal/pathogène compliquent son diagnostic, avec probablement de nombreux cas non détectés. Une meilleure compréhension de ses mécanismes d'infection ainsi que le recours à l'antibiogramme apparaissent nécessaires pour optimiser les stratégies de détection, prévention et traitement
Inhibiting EZH2 Alleviates Osteoarthritis and Pain in an Experimental Murine Model Through Modulating Synovial and Macrophage Inflammation, Axon Guidance, and Osteoclastogenesis
No full textEnhancer of zeste homolog 2 (EZH2), a histone methyltransferase, has gained attention as a promising therapeutic target in osteoarthritis (OA) due to its central role in modulating inflammation, catabolism, and hypertrophy within chondrocytes. Previous studies have further demonstrated that EZH2 inhibition can slow OA progression in surgically induced mouse models, highlighting its potential in reducing joint degradation. However, the precise mechanisms by which EZH2 influences other key cell types in OA pathology remain poorly understood. In this study, we aimed to evaluate the effects of EZH2 inhibition in an alternative OA model and investigate its broader impact on cellular and molecular pathways across various tissues involved in OA progression and joint pain.OA was induced in mice via intra-articular injection of monosodium iodoacetate (MIA), with disease progression evaluated by histological and behavioral assessments. In parallel, human synoviocytes and bone marrow-derived cells were isolated from OA patients. Synoviocytes were stimulated with interleukin-1β (IL-1β) in the presence or absence of the EZH2 inhibitor EPZ-6438 (Tazemetostat), and ChIP-Seq and proteomic analyses were conducted to identify genomic and proteomic targets of EZH2. Additionally, the effects of EZH2 inhibition on M1 macrophage polarization and osteoclast differentiation were analyzed.Results revealed that EZH2 inhibition attenuated both OA progression and joint pain in the MIAinduced mouse model. IL-1β stimulation significantly upregulated EZH2 expression in synoviocytes, and treatment with the EZH2 inhibitor reduced the expression of genes linked to inflammation, pain, and catabolism while promoting autophagy. Proteomic analysis highlighted significant alterations in pathways related to IL-1β signaling, matrix metalloproteinase (MMP) activation, and autophagy, as well as changes in proteins associated with metabolic regulation and axon guidance. Importantly, EZH2 inhibition decreased M1 macrophage polarization and osteoclast formation, cellular processes that contribute to OA pain and inflammation.In conclusion, this study underscores the pivotal role of the histone methyltransferase EZH2 in the pathophysiology of osteoarthritis and associated joint pain. Our findings reveal that EZH2 inhibition not only attenuates inflammation in synovial cells and macrophages but also modulates axon guidance and osteoclastogenesis, both critical in OA progression and pain. These insights position EZH2 inhibition as a promising, multi-targeted therapeutic approach for addressing the complex cellular interactions underlying osteoarthritis, offering new hope for effective treatment strategies in this debilitating condition