De l’identification à l’acceptabilité sociale des risques : une approche pluridisciplinaire

International audienc

Traduire les comics Retour vers le Futur: approche transmédiatique

International audienceL’univers médiatique est sans cesse en expansion : un roman se transforme en film qui se décline en série télévisée qui sera elle-même adaptée en jeu vidéo. Les amateurs d’univers fictionnels peuvent profiter de leurs mondes préférés encore et encore sous diverses formes. Ces mondes imaginaires peuvent être un vrai défi à la traduction, détruisant plus ou moins (parfois complétement) nos cadres de références pour les rebâtir et créer un tout nouvel espace fictionnel dans la réalité de l’audience. Néanmoins, la multiplicité des médias permet à ces mondes de s’étendre au-delà des frontières établies par les premiers créateurs et d’ajouter des couches sémantiques, si ce n’est syntaxiques et terminologiques, qui viennent s’autoréférencer les unes les autres plus ou moins explicitement. Ainsi, en plus des contraintes techniques et linguistiques qui sous-tendent chaque média, les professionnels de la traduction doivent prendre en compte ces univers étendus pour offrir aux lecteurs/joueurs/spectateurs cibles l’expérience la plus proche de celles délivrée en langue source. La bande dessinée ne fait pas exception et les adaptations BD d’œuvres littéraires ou cinématographiques s’étalent sur les étagères des librairies (et inversement). Prenant comme point de départ une expérience de traduction professionnelle, nous évoquerons les spécificités liées à la traduction de bande dessinées en français à l’aide d’exemples concrets (contraintes spatiales, oralité de la langue, onomatopée, lien visuel), mais nous nous intéresserons également à la question du transmédia à travers l’adaptation en bande dessinée d’un classique du cinéma de science-fiction : Retour vers le futur (Zemeckis, 1985) qui a connu maintes adaptations en comics, dont Une Longue peine (Barber et Ferreira, 2017), Une Peine purgée (Barber, Ferreira et Fabbio, 2017) et Histoires du train spatio-temporel (Barber et Levens, 2018)

On-farm hatching and contact with adult hen post hatch induce sex-dependent effects on performance, health and robustness in broiler chickens

Preprint version 4 of this article has been peer-reviewed and recommended by Peer Community In Animal Science (https://doi.org/10.24072/pci.animsci.100199; Gondret, 2024)International audienceTo improve the early perinatal conditions of broiler chicks, alternative hatching systems have beendeveloped. On-farm hatching (OFH) with an enriched microbial and stimulating environment by thepresence of an adult hen is a promising solution. Day-old chicks were allotted within five hatchingand rearing conditions: OFH, conventional hatchery (CH), CH and post-hatching treatment withantibiotics (CH + AB), as well as both hatching systems with an adult hen at hatching (OFH + H,CH + H). To challenge the robustness of chickens, they were exposed on D27 to suboptimal rearingconditions by combining for 4 h transport in boxes in a new room at a lower temperature andfasting. On their return to the original room, the chicken density was increased, and birds wereorally vaccinated with the Gumboro vaccine. The impacts of these conditions on hatchability, chickquality score, performance, health and robustness were determined. The OFH chick body weights(BWs) were significantly greater than those of CH chicks at hatching.Whereas there was no effectof hatching conditions, the presence of hens decreased the hatchability rate, the quality score ofOFH chicks and increased mortality at hatching. Treatment of CH chicks with antibiotics (CH + AB)temporarily decreased chicken BW at D19, but the feed conversion ratio (FCR) was not modified.At D19, OFH chicks had the highest BWcompared to the other groups, and the presence of hens athatching harmed chicken BWregardless of the hatching condition and FCR. An interaction betweenthe effect of experimental rearing conditions and chicken sex was observed later for BW. In males,the OFH chickens were the heaviest compared to the other groups at D34 but not at D56. Thepresence of hens negatively impacted CH chicken BW at D56. In females, there was no effect ofhatching condition on the BWs at D34 and D56, and the presence of hens had a positive impact onOFH chicken BW. There was no effect of hatching conditions on health parameters. In conclusion,the OFH system was a hatching system at least equivalent to the CH system. The presence of thehen at hatching and during the chick start-up phase on performance interacted with the hatchingcondition and the sex of the chickens

Barriers and Enablers for Deprescribing Glucose-Lowering Treatment in Older Adults: A Systematic Review

International audienc

GRID1/ GluD1 homozygous variants linked to intellectual disability and spastic paraplegia impair mGlu1/5 receptor signaling and excitatory synapses

International audienceAbstract The ionotropic glutamate delta receptor GluD1, encoded by the GRID1 gene, is involved in synapse formation, function, and plasticity. GluD1 does not bind glutamate, but instead cerebellin and D-serine, which allow the formation of trans-synaptic bridges, and trigger transmembrane signaling. Despite wide expression in the nervous system, pathogenic GRID1 variants have not been characterized in humans so far. We report homozygous missense GRID1 variants in five individuals from two unrelated consanguineous families presenting with intellectual disability and spastic paraplegia, without (p.Thr752Met) or with (p.Arg161His) diagnosis of glaucoma, a threefold phenotypic association whose genetic bases had not been elucidated previously. Molecular modeling indicated that Arg161His and Thr752Met mutations alter the hinge between GluD1 cerebellin and D-serine binding domains and the stiffness of this latter domain, respectively. Expression, trafficking, physical interaction with metabotropic glutamate receptor mGlu1, and cerebellin binding of GluD1 mutants were not conspicuously altered. Conversely, we found that both GluD1 mutants hampered signaling of metabotropic glutamate receptor mGlu1/5 via the ERK pathway in neurons of primary cortical culture. Moreover, both mutants impaired dendrite morphology and excitatory synapse density in neurons of primary hippocampal culture. These results show that the clinical phenotypes are distinct entities segregating in the families as an autosomal recessive trait, and caused by pathophysiological effects of GluD1 mutants involving metabotropic glutamate receptor signaling and neuronal connectivity. Our findings unravel the importance of the GluD1 receptor signaling in sensory, cognitive and motor functions of the human nervous system

A novel Fc-engineered cathepsin D-targeting antibody enhances ADCC, triggers tumor-infiltrating NK cell recruitment, and improves treatment with paclitaxel and enzalutamide in triple-negative breast cancer

International audienceIntroduction: Triple-negative breast cancer (TNBC) prognosis is poor. Immunotherapies to enhance the antibody-induced natural killer (NK) cell antitumor activity are emerging for TNBC that is frequently immunogenic. The aspartic protease cathepsin D (cath-D), a tumor cell-associated extracellular protein with protumor activity and a poor prognosis marker in TNBC, is a prime target for antibody-based therapy to induce NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC). This study investigated whether Fc-engineered anti-cath-D antibodies trigger ADCC, their impact on antitumor efficacy and tumor-infiltrating NK cells, and their relevance for combinatory therapy in TNBC.Methods: Cath-D expression and localization in TNBC samples were evaluated by western blotting, immunofluorescence, and immunohistochemistry. The binding of human anti-cath-D F1M1 and Fc-engineered antibody variants, which enhance (F1M1-Fc + ) or prevent (F1M1-Fc − ) affinity for CD16a, to secreted human and murine cath-D was analyzed by ELISA, and to CD16a by surface plasmon resonance and flow cytometry. NK cell activation was investigated by flow cytometry, and ADCC by lactate dehydrogenase release. The antitumor efficacy of F1M1 Fc-variants was investigated using TNBC cell xenografts in nude mice. NK cell recruitment, activation, and cytotoxic activity were analyzed in MDA-MB-231 cell xenografts by immunophenotyping and RT-qPCR. NK cells were depleted using an anti-asialo GM1 antibody. F1M1-Fc + antitumor effect was assessed in TNBC patient-derived xenografts (PDXs) and TNBC SUM159 cell xenografts, and in combination with paclitaxel or enzalutamide.Results Cath-D expression on the TNBC cell surface could be exploited to induce ADCC. F1M1 Fc-variants recognized human and mouse cath-D. F1M1-Fc + activated NK cells in vitro and induced ADCC against TNBC cells and cancer-associated fibroblasts more efficiently than F1M1. F1M1-Fc − was ineffective. In the MDA-MB-231 cell xenograft model, F1M1-Fc + displayed higher antitumor activity than F1M1, whereas F1M1-Fc − was less effective, reflecting the importance of Fc-dependent mechanisms in vivo. F1M1-Fc + triggered tumor-infiltrating NK cell recruitment, activation and cytotoxic activity in MDA-MB-231 cell xenografts. NK cell depletion impaired F1M1-Fc + antitumor activity, demonstrating their key role. F1M1-Fc + inhibited growth of SUM159 cell xenografts and two TNBC PDXs. In combination therapy, F1M1-Fc + improved paclitaxel and enzalutamide therapeutic efficacy without toxicity.Conclusions F1M1-Fc + is a promising immunotherapy for TNBC that could be combined with conventional regimens, including chemotherapy or antiandrogens

Validation of a serum ELISA test for cyathostomin infection in equines

International audienceCyathostomins are ubiquitous equine nematodes. Infection can result in larval cyathostominosis due to mass larval emergence. Although faecal egg count (FEC) tests provide estimates of egg shedding, these correlate poorly with burden and provide no information on mucosal/luminal larvae. Previous studies describe a serum IgG(T)-based ELISA (CT3) that exhibits utility for detection of mucosal/luminal cyathostomins. Here, this ELISA is optimised/validated for commercial application using sera from horses for which burden data were available. Optimisation included addition of total IgG-based calibrators to provide standard curves for quantification of antigen-specific IgG(T) used to generate a CT3-specific 'serum score' for each horse. Validation dataset results were then used to assess the optimised test's performance and select serum score cutoff values for diagnosis of burdens above 1000, 5000 and 10,000 cyathostomins. The test demonstrated excellent performance (Receiver Operating Characteristic Area Under the Curve values > 0.9) in diagnosing infection, with > 90% sensitivity and > 70% specificity at the selected serum score cutoff values. CT3-specific serum IgG(T) profiles in equines in different settings were assessed to provide information for commercial test use. These studies demonstrated maternal transfer of CT3-specific IgG(T) in colostrum to newborns, levels of which declined before increasing as foals consumed contaminated pasture. Studies in geographically distinct populations demonstrated that the proportion of horses that reported as test positive at a 14.37 CT3 serum score (1000-cyathostomin threshold) was associated with parasite transmission risk. Based on the results, inclusion criteria for commercial use were developed. Logistic regression models were developed to predict probabilities that burdens of individuals are above defined thresholds based on the reported serum score. The models performed at a similar level to the serum score cutoff approach. In conclusion, the CT3 test provides an option for veterinarians to obtain evidence of low cyathostomin burdens that do not require anthelmintic treatment and to support diagnosis of infection

PENALIZATION OF GALTON WATSON TREES WITH MARKED VERTICES

We consider a Galton-Watson tree where each node is marked independently of each others with a probability depending on itsout-degree. Using a penalization method, we exhibit new martingales where the number of marks up to level n − 1 appears. Then, we use these martingales to define new probability measures via a Girsanov transformation and describe the distribution of the random trees under these new probabilities.Nous considérons un arbre de Galton-Watson dont chaque sommet est marqué, indépendemment des autres sommets, avec une probabilité qui dépend de son nombre d'enfants.En utilisant une méthode de pénalisation, nous obtenons de nouvelles martingales qui font intervenir le nombre de marques sur l'arbre jusqu'au niveau n-1. Nous utilisons ensuite ces martingales pour définir de nouvelles mesures de probabilité via une transformation de Girsanov et décrivons la loi de l'arbre sous ces nouvelles mesures

L’article 1192 du Code civil interdisant la dénaturation des clauses claires et précises à l’aune de la jurisprudence

International audienceLa codification de l’interdiction de la dénaturation des actes (C. civ., art. 1192) interroge le juriste quant au sens de la règle, sa force, son domaine et sa portée. Une analyse chiffrée des décisions rendues en 2022 par les chambres civiles de la Cour de cassation révèle que près d’un arrêt de cassation sur vingt l’a été au visa du principe selon lequel le juge du fond a l’obligation de ne pas dénaturer les écrits qui lui sont soumis. Le contrôle de la dénaturation judiciaire a été initié en 1872 ; un principe a été formulé en 1986. L’ensemble des arrêts rendus à son visa est ici analysé sous un angle quantitatif et qualitatif. Loin d’être anecdotique comme il est parfois présenté, le contrôle de dénaturation opéré depuis 150 ans est devenu considérable et symptomatique de l’évolution latente de la Cour suprême de l’ordre judiciaire

Evolution of pH-sensitive transcription termination during adaptation to repeated long-term starvation

Abstract Fluctuating environments that consist of regular cycles of co-occurring stress are a common challenge faced by cellular populations. For a population to thrive in constantly changing conditions, an ability to coordinate a rapid cellular response is essential. Here, we identify a mutation conferring an arginine-to-histidine (Arg to His) substitution in the transcription terminator Rho. The rho R109H mutation frequently arose in E. coli populations experimentally evolved under repeated long-term starvation conditions, during which feast and famine result in drastic environmental pH fluctuations. Metagenomic sequencing revealed that populations containing the rho mutation also possess putative loss-of-function mutations in ydcI , which encodes a recently characterized transcription factor associated with pH homeostasis. Genetic reconstructions of these mutations show that the rho allele confers a plastic alkaline-induced reduction of Rho function that, when found in tandem with a Δ ydcI allele, leads to intracellular alkalinization and genetic assimilation of Rho mutant function. We further identify Arg to His substitutions at analogous sites in rho alleles from species originating from fluctuating alkaline environments. Our results suggest that Arg to His substitutions in global regulators of gene expression can serve to rapidly coordinate complex responses through pH sensing and shed light on how cellular populations across the tree of life use environmental cues to coordinate rapid responses to complex, fluctuating environments