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GPRASP1 deletion suppresses antinociceptive tolerance during chronic activation of delta opioid receptor in persistent pain
No full textInternational audienceDelta-opioid receptor (DOR) agonists display antinociceptive properties with less adverse effects than morphine derivatives and other opioids targeting mu-opioid receptor. However, a loss of their antinociceptive effect (tolerance) rapidly develops upon repeated treatments and could be due to the fast degradation of DOR. The G Protein-coupled Receptor-Associated Sorting Protein 1 (GPRASP1) has been involved in DOR sorting for degradation in vitro. Here, using a novel mouse line combining a knock-out for GPRASP1 and a knock-in for a fluorescent DOR-eGFP, we show that GPRASP1 is mandatory for the development of antinociceptive tolerance to the DOR agonist SNC80 in models of neuropathic and inflammatory pain. Surprisingly, DOR down-regulation upon repeated activations, phosphorylation kinetics of SNC80-activated DOR and DOR coupling to Gi proteins were unaffected by the loss of GPRASP1. Instead, changes in the dynamics of DOR plasma membrane localization were observed in GPRASP1 knockout neurons. Affinity-Purification of DOR followed by Mass Spectrometry analyses revealed, for the first time in the brain, that SNC80 alters DOR's interactome. In the absence of GPRASP1, the association of activated DOR with newly identified partners, particularly Synapse differentiation-inducing gene protein 1 SYNG1, was reduced. These findings indicate that SNC80-induced antinociceptive tolerance is not driven by DOR down-regulation but rather by GPRASP1-mediated changes in DOR trafficking and downstream signaling
Coarse-grained physics-based modelling for tape casting of fuel-electrode supports in Solid Oxide Cells
No full textInternational audienceOptimising the tape casting process for fabricating NiO/YSZ cermet-based fuel-electrode supports in Solid Oxide Cells remains a resource-intensive challenge. Improving the green tape properties are often reliant on trial-and-error procedures or proprietary knowledge that is inaccessible to the broader scientific community. In this work, we use computational simulations as a powerful tool to link the manufacturing process to the final microstructure of the tape. A novel three-dimensional physics-based model is presented to simulate the slip preparation and the homogeneous drying process of the tape casting producing the fuel electrode support in Solid Oxide Cells. Our model is well-calibrated to experimental data, and we investigate the dried microstructure of the simulated support
Secret des affaires versus droit à la preuve, suite… mais pas fin !
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Caractérisation de la condition préalable du délit de participation frauduleuse à une pratique anticoncurrentielle
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Rehabilitating the benefits of gene tree correction in the presence of incomplete lineage sorting
No full textInternational audienceGene trees play an important role in various areas of phylogenomics. However, their reconstruction often relies on limited-length sequences and may not account for complex evolutionary events, such as gene duplications, losses, or incomplete lineage sorting (ILS), which are not modeled by standard phylogenetic methods. To address these challenges, it is common to first infer gene trees using fast algorithms for conventional models, then refine them through species tree-aware correction methods. Recently, it has been argued that such corrections can lead to overfitting and force gene trees to resemble the species tree, thereby obscuring genuine gene-level variation caused by ILS. In this paper, we challenge and refute this hypothesis, and we demonstrate that, when applied carefully, correction methods can offer significant benefits, even in the presence of ILS
Radio-anatomopathological discrepancies in lymphonodal staging of squamous cell carcinoma of the upper aerodigestive tract
No full textInternational audienceObjectives: The therapeutic strategy for squamous cell carcinomas of the upper aerodigestive tract (SCC-UADT) relies, in part, on the histopathological study of the neck dissection. Currently, several studies aim to limit the use of lymph node neck dissection based on a radioclinical cTNM evaluation. The objective of this study was therefore to assess the accuracy of clinical and radiological examination in nodal analysis of SCC-UADT compared with the histopathological assessment of neck dissection, in order to evaluate the risk of inadequate oncological management in the absence of decision-making based on the histopathological gold standard.Methods: A retrospective single-centre study was carried out between 2010 and 2024, including patients who had undergone excision and neck dissection for a primary SCC-UADT. The primary endpoint was the number of cases in which cN and pN differed during lymph node assessment of SCC-UADT. In addition, the number of lymph node metastases in level IIB in patients classified as cTXN0, as well as the number of metastases bypassing the theoretical first lymphatic drainage level in patients classified as cT1/T2N0, were collected.Results: A total of 1167 patients were identified. 457 patients (164 women and 293 men) with a mean age of 58.3 years were included. 194 patients showed a discrepancy between cN (clinical-radiological CT scan examination) and pN. 41 patients classified as cTxN0 presented a metastasis in level IIB. 16 patients classified as cT1/T2N0 had an occult metastasis bypassing the theoretical first lymph node drainage level.Conclusions: Clinical and radiological examination is not yet sufficiently reliable to serve as the sole basis for an oncological strategy concerning SCC-UADT. It is therefore necessary to pursue further investigations into the safety and reliability of therapeutic de-escalation measures.Contribution to the literature: Although there is currently a desire to place imaging at the centre of oncological strategy, this publication highlights the limitations of such an approach and the importance of histopathological assessment in the management of lymph node metastases in squamous cell carcinomas of the upper aerodigestive tract
Three non-capitalist approaches of peasant economics mobilising the principle of reciprocity
No full textSource Agritrop Cirad (https://agritrop.cirad.fr/616172/)International audienceSeveral socio-economic and socio-anthropological approaches associate peasant agricultures to production and redistribution systems based on other conceptions of value than this of capitalistic market exchange and on other relations than competition for the accumulation of private profit. This article examines three proposals from diverse backgrounds but sharing a common analysis of peasant farming around the notions of ethics, affection, autonomy and resistance. There are the moral economy of Scott (1976), the economy of affection of Hyden (1980) and the peasant principle of Ploeg (2008). These three authors also refer to the principle of reciprocity; thus, I propose first to analyze their contribution regarding the theory of reciprocity in anthropology (Scubla, 1985; Temple, 1997 and 2003, Sabourin, 2012) and, secondly, I will examine how these approaches could dialogue. The article is divided in three parts. The first proposes a reading of the three contributions; the second presents briefly the main points of the theory of reciprocity and the third one discusses commons lessons and perspectives of these approaches
Chapitre 5. Pas de relationalité sans solidarité. La fabrique de la solidarité écologique : affects, relations et assemblages pour la gouvernance des territoires vivants
No full textChapitre 5International audienceCe chapitre interroge l’impasse des gouvernances environnementales fondées sur des savoirs abstraits, incapables de produire des actions transformatrices et de résoudre des conflits qui opposent des mondes vécus. En mobilisant les savoirs situés, l’affect, l’adaptation affective et la « connaissance qui affecte », les auteurs proposent de requalifier la solidarité écologique : d’un principe juridique et cognitif à un affect émergent. Par une approche deleuzo-guattarienne de l’assemblage, la solidarité devient une intensité ressentie de l’interdépendance, produite par l’alignement de perspectives hétérogènes (scientifique, agricole, cynégétique, conservationniste). L’étude des marais de Camargue montre comment des pratiques de co-production (gestion concertée de l’eau, pâturage, suivis partagés) peuvent générer un « monde commun » et ouvrir sur des dispositifs durables (pactes socio-écologiques, arènes délibératives des vivants). Elle plaide pour une gouvernance relationnelle, attentive aux médiations matérielles et sensibles, où faciliter la rencontre compte plus que décider, afin d’instituer la solidarité
Une association inédite entre Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Achromobacter sp. et un isolat environnemental d’amibe libre
No full textInternational audienceObjectif : La colonisation du tractus respiratoire des patients atteints de mucoviscidose (CF) est un processus évolutif et polymicrobien, influencé par l’âge, l’état clinique, l’exposition environnementale et les traitements antibiotiques. Plusieurs bactéries opportunistes CF – comme Mycobacterium avium, Pseudomonas aeruginosa, Stenotrophomonas maltophilia ou Burkholderia cepacia – ont déjà été décrites comme capables de survivre ou de se multiplier dans des amibes libres (FLA). Très présentes dans les réseaux d’eau, ces protozoaires se nourrissent de bactéries par phagocytose mais peuvent également héberger des bactéries capables de résister à la digestion et d’y persister. Bien que les caractéristiques cliniques des pathogènes CF soient bien connues, leurs réservoirs environnementaux et voies d’acquisition respiratoire restent peu étudiés. Si certaines de ces espèces ont déjà été observées individuellement dans des FLA, leur co-hébergement dans une même FLA n’a jamais été documentée.Méthodes : L’ADN d’un isolat environnemental de FLA, incluant celui de ses bactéries associées, a été séquencé par métagénomique. Après assemblage, le génome des microorganismes a été reconstitué par une approche de binning pour caractériser leur taxonomie.Résultats : L’assemblage métagénomique a permis d’obtenir un génome fragmenté de l’amibe hôte appartenant au phylum Heterolobosea, composée de 53 783 contigs (23 949 ≥ 1kb), avec un contenu GC de 41,8 % et un N50 de 3198pb. En parallèle du génome amibien, trois génomes bactériens distincts ont été reconstruits à plus de 92 %. Ils correspondent, de manière surprenante, à trois pathogènes opportunistes majeurs dans la mucoviscidose : P. aeruginosa ST 549, S. maltophilia et Achromobacter sp. Cette co-occurrence tripartite représente, à notre connaissance, la première preuve génomique d’une FLA hébergeant simultanément ces trois pathogènes majeurs de la mucoviscidose.Conclusion : Nos résultats renforcent l’idée que les FLA peuvent servir de réservoirs environnementaux multi-pathogènes CF, favorisant potentiellement leur persistance et leur transmission. Ces observations soulignent la nécessité d'intégrer la surveillance environnementale et le séquençage génomique dans l’étude des dynamiques d’infection et des voies de transmission des pathogènes liés à la mucoviscidose
