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GM-CSF drives IL-6 production by macrophages in polymyalgia rheumatica
No full textInternational audienceInsight into the immunopathology of polymyalgia rheumatica (PMR) is scarce and mainly derived from peripheral blood studies. The limited data available point towards macrophages as potential key players in PMR. This study aimed to identify the factors driving proinflammatory macrophage development and their functions in the immunopathology of PMR. Methods: Monocyte phenotypes were investigated by flow cytometry in peripheral blood (PMR, n = 22; healthy controls, n = 20) and paired subacromial-subdeltoid (SASD) bursal fluid (PMR, n = 9). Macrophages in SASD bursa were characterised by immunohistochemistry and immunofluorescence (PMR, n = 12; controls undergoing shoulder replacement surgery, n = 10). The</div
OpenArchaeo : Un portail web sémantique appliqué aux données archéologiques
No full textInternational audienceWith the rise of Open Science practices, numerous heterogeneous datasets have beenpublished by researchers to support these initiatives. In Europe, such datasets can now befound on platforms like Nakala in France, e-Archeo in Italy, and ADS in the UnitedKingdom. The aim of Open Science is to make these datasets available to other researchersfor reuse in scientific endeavours, and accessible to the public as findable data reflectingrecent knowledge.While many Open Science platforms publish data in standardised ways, the publisheddatasets can still still vary in terms of structures, formats, and scientific expressions of thedata producer. These involvements still make the data heterogeneous and difficult tocross-referenced. These variations contribute to the heterogeneity of the data, makingcross-referencing and integration difficult. Although mandatory metadata required bypublishers provides some level of cross-referencing, it remains generic and linked to entiredatasets rather than specific data.Based on this observation, the Huma-Num Consortium MASAplus, dedicated to the Frencharcheological community’s data, developed a solution based on semantic web technology,and linked open data elements: the OpenArchaeo portal.Avec l'essor des pratiques de la Science Ouverte, de nombreux jeux de données hétérogènes ont été publiés par des chercheurs pour soutenir ces initiatives. En Europe, de tels jeux de données peuvent désormais être trouvés sur des plateformes comme Nakala en France, e-Archeo en Italie et ADS au Royaume-Uni. L'objectif de la Science Ouverte est de rendre ces jeux de données disponibles pour d'autres chercheurs afin qu'ils puissent les réutiliser dans des entreprises scientifiques, et accessibles au public en tant que données trouvables reflétant les connaissances récentes.Bien que de nombreuses plateformes de Science Ouverte publient des données de manière standardisée, les jeux de données publiés peuvent encore varier en termes de structures, de formats et d'expressions scientifiques du producteur de données. Ces implications rendent toujours les données hétérogènes et difficiles à référencer croisées. Ces variations contribuent à l'hétérogénéité des données, rendant le référencement croisé et l'intégration difficiles. Bien que les métadonnées obligatoires requises par les éditeurs fournissent un certain niveau de référencement croisé, elles restent génériques et liées à des jeux de données entiers plutôt qu'à des données spécifiques.Sur la base de cette observation, le Consortium Huma-Num MASAplus, dédié aux données de la communauté archéologique française, a développé une solution basée sur la technologie du web sémantique et les éléments de données ouvertes liées : le portail OpenArchaeo
Évaluation automatique d’un système de question-réponse RAG alimenté par LLMs sur un corpus français
No full textEvaluation de l'implémentation d'interventions en milieu scolaire visant à améliorer la couverture vaccinale HPV en France : résultats d'une étude mixte au sein de l'essai contrôlé randomisé PrevHPV
No full textInternational audienceBackground and objective(s)Human papillomavirus (HPV) vaccine coverage (VC) remains lower than expected in many countries, particularly France. In 2018, the French authorities launched the PrevHPV research program to codevelop school- and primary care-based interventions with stakeholders and evaluate their effectiveness and implementation. The school-based interventions were ‘education and motivation’ and ‘at-school vaccination’. Analyses, without considering the dose of intervention received, showed that only the ‘at-school vaccination’ intervention significantly increased VC at two months. Implementation weaknesses may negatively impact effectiveness; therefore, it is worth having an in-depth understanding of the intervention implementation. This investigation aimed to evaluate the implementation of the school-based interventions of the PrevHPV program.Material and MethodsWe carried out a mixed-method study embedded in the national cluster randomized controlled trial PrevHPV (July 2021-June 2022). The cluster was the municipality (n=91). The ‘education and motivation’ intervention consisted (i) for parents, of a web conference on HPV infection and vaccination; and, (ii) for 8th–9th grade pupils, of two educational group sessions on those topics during school hours, using participatory learning and e-health tools. The ‘at-school vaccination’ intervention consisted of offering free vaccination to all pupils whose parents agreed on school premises. Quantitative data were collected through standardized activity reports and self-administered questionnaires; the implementation outcomes were fidelity, dose, reach, acceptability and sustainability. Qualitative data were collected through semi-structured group interviews with school staff and analyzed using the Consolidated Framework for Implementation Research.ResultsWe found high rates for: fidelity (e.g., 69% of the targeted classes had two sessions and 89% of schools invited all pupils for at-school vaccination); acceptability (e.g., pupils’ attentiveness and participation satisfying in 90% of the sessions, 96% of vaccinated pupils and 78% of school staff satisfied with the organization of vaccination days); and sustainability (e.g., 91% and 76% of participating schools considered conducting sessions and vaccination days the following year, respectively). However, the withdrawal of 1/3 of schools before the trial started and difficulties in mobilizing parents (e.g., <1% of invited parents participated in a web conference) negatively impacted dose and reach. Facilitators of and barriers to the implementation related to the intervention content and format, the characteristics of both the external and internal environment of the school, the numerous stakeholders and individuals involved, and the implementation strategies used. Facilitators included well-designed provided tools, supportive regulations, motivated leaders, and the presence of an external facilitator; barriers included staff workload, financial and material resources.ConclusionSchools can play a significant role in HPV vaccine promotion but are challenging settings for implementation. This study highlights challenges for involving stakeholders (parents, school staff) and the organizational changes this implies. This study has practical implications for implementing such interventions in real life, which is more valuable since HPV vaccination has been offered at school to all French 7th-grade pupils since 2023
mRNA loaded Lipid Nanocapsule Formulation: a promising therapeutic strategy to treat Pseudoxanthoma elasticum
No full textInternational audiencePseudoxanthoma elasticum (PXE) is a rare genetic disorder characterized by progressive ectopic calcification, which is caused by mutations in the ABCC6 gene. PXE predominantly affects the elastic fibers of the skin, Bruch’s membrane in the retina and the cardiovascular system. Unfortunately, no curative treatment exists. To compensate the deficiency of the protein normally expressed in hepatocytes, the delivery of the corresponding mRNA has emerged as a promising therapeutic strategy. However, this approach requires a nanocarrier to cross the cell membrane, protect the mRNA, and ensure delivery to the targeted tissues.During the Covid-19 pandemic, lipid nanoparticles (LNP) highlighted the huge potential of nanomedicines: they successfully demonstrated their ability to protect and deliver mRNA. Among LNP, lipid nanocapsules (LNC) were designed and patented in 2014 by the MINT laboratory (patent FR 3026009 (A1)) with the goal of protecting genetic material such as DNA, siRNA, and miRNA.The objective of this project is to formulate and characterize mRNA loaded LNC, assessing their in vitro toxicity on the hepatocyte cell lines HepG2 and SNU-387 and to validate the therapeutic strategy in Abcc6−/− mice.As a model to validate the formulation, mRNA encoding Enhanced Green Fluorescent Protein (EGFP) was initially used. In parallel, a total of 948.2 µg of ABCC6 mRNA was produced in Prof. Pichon’s laboratory. Both ABCC6 and EGFP mRNA-loaded LNC were fully characterized. Subsequently, dose-dependent cytotoxicity was assessed using MTT and LDH assays, resulting in the determination of an IC50 that will be utilized in future experiments.Cell internalization studies using flow cytometry revealed an efficient uptake of DiD-labeled EGFP mRNA loaded LNC over time with a 100% internalization after 24 hours. Finally, in vivo studies were conducted in healthy mice by intravenous injection of DiD-labeled LNC. The results showed a significant accumulation of LNC in the liver 24 hours post-injection: ABCC6 being predominantly expressed in the liver, this biodistribution is an important result. Encouragingly, hepatic mRNA expression was also observed 6h post-injection, offering promising prospects for future therapeutic applications in PXE
Displacement memory for flyby
No full textInternational audienceZel’dovich and Polnarev, in their seminal paper (Zel’dovich and Polnarev, 1974) suggested that a gravitational wave generated by flyby would merely displace the particles. We confirm their prediction numerically by fine-tuning the wave profile proposed by Gibbons and Hawking (1971), and then analytically for its approximation by a Pöschl–Teller potential. Higher-order derivative profiles proposed for gravitational collapse, etc (Gibbons and Hawking, 1971) are shortly discussed
The social dimension of equine welfare: how social contact positively influences the emotional state of stalled horses
No full textInternational audienceThe housing conditions of domestic animals influence their welfare; their emotional state can be negatively affected if their needs are not met. This can lead to behavioural changes or disorders that can damage the animal-human relationship. In social species such as horses, Equus caballus, social contact is a fundamental need that is severely restricted by individual housing. Thus, this study aimed to evaluate the impact of socialization on the emotional state of horses in different contexts. We studied 20 adult horses housed in individual stalls. The horses were divided equally into two experimental conditions: horses without social interaction (isolated condition) and horses with the opportunity to interact temporarily with a conspecific (social condition). For 4 months, the horses under the social condition interacted in pairs for 1 h daily in a meeting box. Throughout this period, the behaviour of the entire sample of horses in individual stalls and during grooming sessions with humans was recorded. In addition, a judgement bias test was conducted at the end of the study period. In the individual stall, we collected indicators of poor welfare such as hypervigilance, apathy, aggressiveness towards humans and stereotypies. During grooming, we observed negative and positive behaviours, alertness levels and general attitude. Horses in the social condition exhibited fewer stereotyped behaviours in the individual stall than the isolated ones. During grooming, they expressed fewer negative behaviours, spent less time in a vigilant state and showed a less tense attitude. In the judgement bias test, horses in the social condition showed an optimistic bias compared with the isolated horses. These findings indicate that horses that are allowed to interact socially perceive their environment more positively than their isolated counterparts. Temporary but regular social contacts positively affect the emotional state of horses in various contexts, indicating an overall improved welfare. (c) 2024 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies
Le DELF au défi de la contextualisation : enjeux, réflexions et perspectives
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Evaluation of Antitoxoplasmic Potential of Selected Antimalarial Medicinal Plants from Togo: Artemisia annua L., Jatropha curcas L., Moringa oleifera Lam., and Sarcocephalus latifolius (Smith) Bruce
No full textInternational audienceIntroduction: Toxoplasmosis, a prevalent zoonotic disease, poses significant health challenges, particularly in Togo with high prevalence. Limited public awareness and suboptimal treatments necessitate exploring novel therapeutic avenues. This study investigated Togolese medicinal plants, especially those traditionally used to cure malaria, as potential sources of antitoxoplasmic agents, leveraging ethnobotanical knowledge and scientific validation for accessible drug discovery. Materials and Methods: Phytochemical screening quantified key groups: phenols, tannins, flavonoids, and polysaccharides in ethanolic extracts. In vitro biological activities were evaluated, including antioxidant capacity (AAPH & DPPH assays), cytotoxicity (UptiBlue assay), hemolytic potential, and antitoxoplasmic activity against Toxoplasma gondii in Human Foreskin Fibroblasts using the CPRG method. Cytokine secretion (TNFα, NO) from RAW264.7 macrophages was also assessed. Statistical analysis employed Kruskal‒Wallis and Tukey’s post hoc tests. Results: Phytochemical analysis revealed ethanolic extracts, particularly from Artemisia annua, Moringa oleifera, and Sarcocephalus latifolius, to be rich in phenols and tannins. Jatropha curcas ethanolic extract showed high flavonoid content. In vitro assays demonstrated high antioxidant activity in ethanolic extracts, with Artemisia annua outperforming ascorbic acid in AAPH assay. Ethanolic extracts of Artemisia annua, Jatropha curcas, and Sarcocephalus latifolius exhibited significant antitoxoplasmic activity, Artemisia annua being the most potent. Discussion: This study demonstrated a correlation between phytochemical profiles and biological activities. Ethanolic extracts, abundant in phenols and tannins, displayed enhanced antioxidant and antitoxoplasmic properties, particularly in Artemisia annua. The show in vitro validation of antitoxoplasmic activity in antimalarial plants like Vernonia amygdalina and Sarcocephalus latifolius suggests pharmacological overlap. These findings highlight the synergistic value of ethnobotany and scientific methods in discovering bioactive compounds for parasitic diseases and oxidative stress, reinforcing the importance of traditional medicine and biodiversity. Conclusion: This research successfully reveal the anti-toxoplasmic potential of Togolese medicinal plants, notably, Artemisia annua, Sarcocephalus latifolius, Jatropha curcas. The results support further phytochemical investigations, in vivo validation, and clinical trials to fully realize the therapeutic potential and advocate for integrative healthcare strategies addressing global health challenges like toxoplasmosis
ПРИМЕНЕНИЕ s-ГАРМОНИЧЕСКОГО РАСШИРЕНИЯ К ИЗУЧЕНИЮ ОСОБЕННОСТЕЙ УРАВНЕНИЙ ЭМДЕНА
No full textInternational audienceАннотация. Мы используем расширение Каффарелли-Сильвестра на R+ × R N для изучения изолированных особенностей функций, удовлетворяющих дробно-полулинейному уравнениюМы получаем априорные оценки и анализируем множество самоподобных решений. Мы даем полное описание возможного поведения решений вблизи особенности.Ключевые слова: уравнение Эмдена, дробно-полулинейное уравнение, расширение Каффарелли-Сильвестра, самоподобные решения.Заявление о конфликте интересов. Автор заявляет об отсутствии конфликта интересов.Благодарности и финансирование. Автор заявляет об отсутствии финансовой поддержки.</div