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Flagellin nebulization enhances respiratory immune responses in the porcine model
No full textInternational audienceRespiratory delivery of the Toll-like receptor 5 agonist FLAMOD, a recombinant flagellin stimulates the airway epithelium, mobilizing immune cells and effectors in mouse models to combat respiratory infections, especially bacterial pneumonia. This study represents a comprehensive assessment of FLAMOD delivered by nebulization in pigs. A single nebulized dose was well tolerated with no adverse clinical effects. FLAMOD treatment led to immune cell infiltration in the lung tissue and granulocyte recruitment in conducting airways, as shown by histology and flow cytometry. RNA sequencing established immune activation across the respiratory tract, from the nose, trachea, bronchi to the lungs, highlighting innate immunity, bacterial defense, cytokine and chemokine signaling, and granulocyte chemotaxis as key biological pathways. These findings demonstrate that FLAMOD stimulates a robust and common respiratory immunity, as well as compartment-specific response, providing a proof-of-concept for inhalation based therapeutic strategies to combat bacterial pneumonia in the clinical setting
Susceptibility of Conventional and Organic Chicken Breast and Thigh Meat to Lipid and Protein Oxidation During Heating and In Vitro Digestion
No full textInternational audienceIt was hypothesized that differences in production system and muscle type may influence the formation of lipid oxidation products (LOP) as well as protein oxidation (protein carbonyl compounds, PCC) during the in vitro gastrointestinal digestion of chicken meat. To test our hypothesis, we investigated the formation of LOP and PCC after heating and in vitro gastrointestinal digestion of conventional and organic chicken breast and thigh meat and Wooden Breast meat. Prior to the in vitro digestion, thigh and breast meat was minced and heated. Digests of organic thigh meat had significantly higher levels of all LOP measured compared to conventional thigh meat (between +37% and +173%). Lower levels of LOP were found in digests of breast meat regardless of the production system and Wooden Breast phenotype. LOP correlated positively with heme-Fe and polyunsaturated fatty acids, negatively with anserine, and not with carnosine and α-tocopherol. PCC levels were significantly higher in thigh meat than in breast meat after heating (+43%) and digestion (+25%), irrespective of the production system. Overall, organic thigh meat exhibited the highest oxidative sensitivity during digestion. The cut-dependent differences in composition and oxidative susceptibility between organic and conventional chicken highlight the need for further research to assess potential health implications
Des variants faux-sens du gène DPYSL5, associés à des troubles neurodéveloppementaux et à des malformations cérébrales, entraînent une maturation neuronale altérée in vitro.
No full textInternational audienceNeurodevelopmental disorders (NDD) with brain malformations have recently been associated with de novo variants in the DPYSL5 gene, which encodes a member of the dihydropyrimidinase-like proteins family. Here, we aimed to understand its role in NDD by characterizing novel or recurrent de novo variants at the molecular and cellular levels. We collected clinical data on individuals in whom DPYSL5 missense variants were identified through clinical genetic assessment of NDD or following the identification of brain malformations in fetuses. Functional analyses of wild-type and variant DPYSL5 proteins were performed to evaluate their impact on in vitro neuronal development and maturation, using primary neuronal cultures from mouse embryonic brains or hiPSC-derived human neural stem cells. We describe six different missense variants in DPYSL5 in nine individuals (including three fetuses), including the previously identified p.(Glu41Lys) recurrent mutation (in 2 individuals), a novel recurrent missense p.(Glu25Lys) de novo variant (in 3 individuals including 2 fetuses), and 3 novel candidates. Common features were developmental delay, intellectual disability, as well as brain malformations including agenesis of the corpus callosum for the N-terminal variants. Functional assays in differentiating mouse or human neuronal cultures revealed impairments in dendritic arborization, axonal elongation, and synaptic density. We thus expanded the functional characterization of DPYSL5 variants in NDD with brain malformations, including at the fetal stage, highlighting a fundamental role of the DPYSL5 gene in brain formation and functioning.Les troubles neurodéveloppementaux (TND) avec malformations cérébrales ont récemment été associés à des variants de novo du gène DPYSL5, qui code pour une protéine de la famille des dihydropyrimidinases. Dans l'étude que nous rapportons ici, nous avons cherché à comprendre le rôle de ce gène dans les TND en caractérisant une série de variants de novo, nouveaux ou récurrents, aux niveaux moléculaire et cellulaire. Nous avons recueilli des données cliniques d'individus chez lesquels des variants faux-sens de DPYSL5 ont été identifiés lors d'un bilan génétique clinique de TND ou suite à la détection de malformations cérébrales chez le fœtus. Des analyses fonctionnelles des variants protéiques de DPYSL5 ont été réalisées afin d'évaluer leur impact sur le développement et la maturation neuronaux in vitro, à l'aide de cultures neuronales primaires issues de cerveaux d'embryons de souris ou de cellules souches neurales humaines dérivées de cellules hiPSC. Nous décrivons six variants faux-sens du gène DPYSL5 chez neuf individus (dont trois fœtus), incluant la mutation récurrente p.(Glu41Lys) déjà décrite (chez deux individus), un nouveau variant faux-sens récurrent de novo p.(Glu25Lys) (chez trois individus, dont deux fœtus), et trois nouveaux candidats. Les caractéristiques communes observées sont un retard de développement, une déficience intellectuelle, ainsi que des malformations cérébrales, notamment une agénésie du corps calleux pour les variants N-terminaux. Des analyses fonctionnelles sur des cultures neuronales de souris ou humaines en différenciation ont révélé des altérations de l'arborisation dendritique, de l'élongation axonale et de la densité synaptique. Nous avons ainsi élargi la caractérisation fonctionnelle des variants de DPYSL5 dans les troubles neurodéveloppementaux associés à des malformations cérébrales, y compris au stade fœtal, soulignant le rôle fondamental du gène DPYSL5 dans la formation et le fonctionnement du cerveau
Toward a Taxol-producing microbial cell factory
No full textInternational audienceScedosporium species are opportunistic filamentous fungi found in human-impacted areas. Clinically relevant species, such as S. apiospermum, rank as the second most frequent colonizers of the airways of patients with cystic fibrosis (CF), which are characterized by persistent oxidative stress. This raises the question of how Scedosporium species abate conditions imposed in hostile environments. Since the High Osmolarity Glycerol (HOG) pathway plays a central role in fungal adaptation to stress, we aimed to pheno-profile the involvement of the pathway in response to stress in S. apiospermum using Western blot. We show for the first time that a wide range of stress distinctively activates the HOG pathway in S. apiospermum, including oxidants (H2O2, menadione, cumene hydroperoxide, diamide, paraquat, and honokiol), osmotic agents (sorbitol and KCl), cell-wall stress agents (caffeine, calcofluor white, and Congo Red), heavy metals (cadmium and arsenite), fungicides (fludioxonil and iprodione), antifungals (voriconazole and amphotericin B), and acid stress (pH 4). We suggest that the function of the HOG pathway as a general stress regulator is also conserved in S. apiospermum
Further analysis and refinements of the perceived stressors in intensive care units (PS-ICU) scale: a French nation-wide cross-sectional multicentre study
No full textInternational audienceAbstract Background Assessing sources of job stress in intensive care units is a critical issue for preventing many occupational health and care-related issues, such as burnout, voluntary turnover and decrease in quality and safety of care. Accordingly, this French nation-wide multicentre study aims to provide supplementary evidence regarding the validity of a recent tool: the Perceived Stressors in Intensive Care Units (PS-ICU) scale. More precisely, this study has three main objectives: to 1) confirm the metrological properties of the PS-ICU scale on a large sample of professionals; 2) test its measurement invariance between nurses, physicians and residents (initial population targeted by the scale); 3) examine whether the scale would also be suited for use with nursing auxiliaries. In addition, depending on the results (which may suggest the removal of several items), this study offers the possibility to shorten the scale to facilitate its use. Method and results 2241 ICU professionals (1135 nurses, 308 physicians, 179 residents, and 619 nursing auxiliaries; overall participation rate of 58.10%) from 42 ICUs in France, voluntarily completed an online questionnaire collecting socio-demographic data and perceived job stressors (PS-ICU). Exploratory structural equation modelling (ESEM), unidimensional reliability (McDonald’s Omega) and item response theory (IRT) analyses overall confirmed the metrological properties of the scale, while several items were removed and the sixth factor (“lack of support and resources from the organisation”) measured by the scale was revised. Results regarding measurement invariance show that the PS-ICU scale can be used to compare occupational groups, including nursing auxiliaries. Finally, all analyses resulted in a reduction of the scale to a 26-item version. Conclusions The PS-ICU scale, which measures generic and ICU-specific job stress factors, is a valid and reliable scale that can be used to collect data from nurses, physicians and residents, as well as from nursing auxiliaries. With 26 items, it can be used by researchers and managers in ICUs to assess the extent and type of stress factors perceived by healthcare professionals
Catherine Grandjean. Du Péloponnèse et d'ailleurs
No full textInternational audienceCatherine Grandjean is a specialist of the ancient Greek world, acknowledged by her peers and admired by her students. This collection of articles in English, French, German and Italian, brings together their tributes to her as teacher, scholar and friend. The articles deal with the themes that were the common thread running through her academic research: ancient economics, through the treatises attributed to Aristotle; numismatics, through studies of Hellenistic coins and forays into the Roman world and the Western Middle Ages; and the origins of federal states, particularly in central Greece. The contributors also discuss the reception of Antiquity and the representation of female power (Cleopatra, etc.) on stage and screen (Italian peplums). Readers will find extensive bibliographies on the subjects covered in each contribution. An introduction by three of Catherine Grandjean’s students – Pierre-Olivier Hochard, Gerbert-Sylvestre Bouyssou and Franck Wojan – highlights both the importance of her work in the development of French studies of ancient coinage and her integration into an international network of researchers.Catherine Grandjean est une spécialiste du monde grec antique, reconnue par ses pairs et admirée de ses élèves. Ce recueil d’articles rassemble leurs hommages, en anglais, allemand, français ou italien, au professeur, au savant, à l’amie. Les articles y traitent des thématiques qui ont constitué le fil rouge de ses recherches universitaires : l’économie ancienne, à travers les traités attribués à Aristote ; la numismatique, via des études sur des frappes hellénistiques et des incursions dans le monde romain ou le Moyen Âge occidental ; les origines des États fédéraux, en particulier en Grèce centrale. Les contributeurs évoquent aussi la réception de l’Antiquité, notamment la représentation du pouvoir féminin (Cléopâtre…) sur les scènes de théâtre puis dans les péplums du cinéma italien. Le lecteur y trouvera de riches bibliographies sur les sujets abordés dans chaque contribution.Une introduction rédigée par trois élèves de Catherine Grandjean – Pierre-Olivier Hochard, Gerbert-Sylvestre Bouyssou et Franck Wojan – rappelle l’importance de ses travaux dans l’évolution des études françaises sur la monnaie ancienne, ainsi que son intégration à un réseau international de chercheurs
Affiliative behaviours regulate allostasis development and shape biobehavioural trajectories in horse
No full textInternational audienceSocial interactions shape both physiological and behavioural development of offspring and poor care/early caregiver loss are known to promote negative outcomes in adulthood in both animals and humans. How affiliative behaviours impact future development of offspring remains unknown. Here, we used Equus caballus (domestic horse) as a model to investigate this question. By coupling magnetic resonance imaging, longitudinal biobehavioural assessment and advanced multivariate statistical modelling we found that maternal presence during childhood promotes maturation of brain territories involved in both social behaviour (anterior cingulate, retrosplenial cortex) and physiological regulation (hypothalamus, amygdala). Additionally, we found that offsprings benefiting from prolonged maternal presence showed higher default mode network (DMN) connectivity, improved social competences, more efficient feeding behaviours, and metabolic profiles. The present study underscores the salient role of social interactions for the development of allostatic regulation in offspring
Redécouvrir la valeur des maîtres avec María Zambrano
No full texthttps://lepartageculturel.wordpress.com/2025/11/15/redecouvrir-la-valeur-des-maitres-avec-maria-zambrano/Human life, says Zambrano, ‘is a journey of knowledge towards reality’ and, consequently, this search and quest for meaning requires education: it calls for a teacher. A guide, precisely, and not a model. A presence that ‘does not transmit a revelation’, but which, at most, ‘sometimes only indicates’.The teacher is therefore not someone who wants to inspire ‘mimesis’ in the student, but rather someone who wants to awaken them to true self-knowledge. The teacher is a ‘mediator’ between knowledge and ignorance, between reason and the confusion in which every human being initially finds themselves
Vocal Smile Processing In Autism: Intact Representation But No Facial Reactivity
No full textInternational audienceAtypical production of emotional prosody have been reported in autism. However, it remains unclear whether these differences stem from atypical mental representations of vocal emotions or from altered motor resonance. This study aimed to investigate the mental representation and contagion process of vocal smiles in autistic adults. Twenty autistic and twenty neurotypical participants completed an auditory reverse correlation (RevCor) task, allowing extraction of the acoustic features underlying their mental representations and the variability in these representations (internal noise). Additionally, facial electromyographic (fEMG) responses of the Zygomaticus major and Corrugator supercilii were also recorded during a prosody recognition task to assess facial motor resonance. The majority of autistic participants (11/20) based their mental representation of vocal smiles on acoustic features similar to those used by neurotypical individuals, with no group differences in internal noise levels. Cluster analyses revealed that differences in representational typicality were driven by a small subset of autistic participants (5/20) who displayed less typical representations. Importantly, some neurotypical participants were also found to have a different representation of the vocal smile. In terms of facial reactivity, autistic adults showed no significant motor response—neither to emotional perception nor to explicit judgement—despite preserved internal representations. In contrast, neurotypical adults exhibited a dissociation between implicit and explicit motor resonance: Zygomaticus major activity reflected perception (with greater activation for smiling voices), while Corrugator supercilii activity was linked to explicit judgment of emotion. A qualitative analysis of the facial reactivity in each cluster will be provided. Thanks to this integrative approach, it was possible to disentangle atypical motor resonance from atypical mental representation of vocal smile in autism. These findings suggest that while most autistic adults have intact mental representations of vocal smile, reduced motor resonance may contribute to the observed social difficulties. This study highlights the importance of jointly exploring and describing mental representations and motor resonance processes in understanding emotion processing in autism
Formation de Faisceaux Adaptée à une Sonde Bimodale pour la Sonoporation Guidée par Ultrasons
No full textTransducteurs électroacoustiques et MEMS acoustiques; GTEA - Transducteurs et Électroacoustique: GAPSUS - Acoustique Physique, Sous-Marine et Ultra-SonoreNational audienceLa sonoporation est une méthode de thérapie qui combine microbulles et champs ultrasonore basse fréquence (BF), afin d’augmenter la perméabilité des cellules aux agents thérapeutiques. Afin de développer un système complet pour le petit animal, capable à la fois d’émettre la séquence thérapeutique (BF) et d’imager (HF), une sonde mixte bimodale a été conçue (1). Cette sonde associe une matrice de 16x16 élément (1 MHz) et une barrette linéaire HF de 128 éléments (20 MHz). Dans ce travail, nous décrivons la caractérisation de la sonde fabriquée, incluant des mesures électroacoustiques pour les fonctions HF et BF (fréquence centrale, bande passante, sensibilité). Des images sur fantôme filaires ont été réalisées avec la partie HF et comparées à une sonde commerciale. Pour la partie BF, nous avons mesuré la directivité élémentaire de la matrice puis utilisé cette donnée afin de simuler le champ de pression émis pour différentes configurations de formation de faisceaux (Dream (2)). Nous avons identifié 2 stratégies afin de répondre au mieux aux spécifications du protocole de sonoporation (volume et pression). Ces stratégies ont été caractérisées par des mesures du champs de pression avec un hydrophone. Un suivi de la montée en température de la sonde a également été réalisé afin de vérifier que l’échauffement interne de la sonde reste faible. Des expériences de sonoporation in vitro sur des cellules de mélanome ont été menés. Les résultats démontrent des performances similaires à celles obtenues avec un protocole précédemment établi en utilisant un transducteur monoélément, avec taux de 60 % de perméabilisation des cellules. Les prochaines étapes incluent des tests in vivo sur des modèles animaux pour valider l’utilisation de cette sonde en mode sonoporation et imagerie