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Anti-inflammatory effects of trans-cinnamic acid through modulation of endothelial ICAM-1 expression and neutrophil recruitment
No full textInternational audienceNatural phenolic acid compounds have been extensively studied for their anti-inflammatory properties, particularly in the context of inflammation-associated diseases. In this study, we investigated the anti-inflammatory effects of trans-cinnamic acid on neutrophil accumulation during inflammatory processes using both in vivo and in vitro approaches. For the in vivo experiments, LPS-induced pleurisy was used in mice pretreated with trans-cinnamic acid. Inflammatory parameters, including plasma leakage, leukocyte infiltration, and proinflammatory cytokine levels (IL-6 and TNF-alpha), were quantified in the pleural exudate. In vitro, the effects of trans-cinnamic acid on neutrophil chemotaxis toward CXCL1 were assessed using the Boyden chamber assay. Additionally, human endothelial EA.hy926 cells were stimulated with TNF-alpha to evaluate neutrophil adhesion and the expression of the adhesion molecule ICAM-1 following trans-cinnamic acid treatment. Pretreatment with trans-cinnamic acid significantly inhibited LPS-induced pleurisy in mice by reducing protein-rich exudate formation, neutrophil infiltration, and local concentrations of TNF-alpha and IL-6. In vitro, trans-cinnamic acid did not alter CXCL1-induced neutrophil chemotaxis, nor the secretion of CXCL8 produced by TNF-alpha-stimulated EA.hy926 cells. However, it markedly reduced neutrophil adhesion to TNF-alpha-activated EA.hy926 cells. This reduction was associated with the downregulation of ICAM-1 expression at both the mRNA and protein levels. Overall, these findings demonstrated that trans-cinnamic acid exerted anti-inflammatory effects by inhibiting vascular permeability and leukocyte recruitment, particularly through the suppression of ICAM-1-mediated neutrophil adhesion to endothelial cells. These results support trans-cinnamic acid as a promising candidate for the development of new therapeutic agents targeting inflammatory diseases
Reassessing the benefits of European integration and the European Union's ability to achieve strategic autonomy
No full textEuropean integration is now faced with the question of strategic autonomy. Against this backdrop, this paper has three objectives. First, it uses disaggregated trade data and established empirical methods to assess the benefits of European integration on trade among the members of the European Union (EU) as well as on trade between EU members and non-member countries, including non-members that are part of the Single Market. Second, it evaluates the costs of EU strategic autonomy -implying not trading with "riskier" partners. Third, it asks whether deeper integration within the EU can alleviate these costs. The paper shows that the gains from European integration are substantial, albeit heterogeneous across Member States, non-members, and sectors, and that the costs of strategic autonomy can be offset by deeper, but comparatively more modest, integration efforts within the European Union
Toxic cocktails in soils -Evidence for synergistic effects of the imidacloprid-epoxiconazole mixture on earthworm life-history traits
No full textSoils are vital reservoirs of biodiversity and providers of ecosystem services, yet they are increasingly threatened by agricultural intensification and pesticide use. Residues often persist as complex mixtures, while environmental risk assessment still largely focuses on single substances, potentially underestimating mixture effects. Earthworms play a key role in soil functioning and are particularly vulnerable to pesticide contamination. We investigated the effects of a binary mixture of epoxiconazole and imidacloprid, two persistent and frequently detected pesticides, on life-history traits of Aporrectodea caliginosa. We estimated each compound relative potency using dose-response experiments on juvenile growth and cocoon production. Next, we assessed the potential for synergy or antagonism in a fixed-ratio ray design including five concentration ratios and seven additive isoboles (36 conditions). Both compounds showed significant toxicity. Imidacloprid showed high potency (juvenile growth NOEC = 0.28 mg/kg; reproduction EC 50 = 0.55 mg/kg), whereas epoxiconazole had moderate effects (juvenile growth NOEC = 9.3 mg/kg; reproduction EC 50 = 126.8 mg/kg). Reproductive endpoints were more sensitive than adult growth, with juvenile growth being the most sensitive overall. Mixture analysis using Jonker's models revealed significant deviation from Independent Action only under the simple interaction model, indicating synergism, consistent with cytochrome P450 interference reported in other taxa. Field-reported imidacloprid concentrations often approach effect thresholds, suggesting potential risks for earthworm populations. Overall, the combined effects of epoxiconazole and imidacloprid may exceed predictions not taking interactions into account. These results highlight the need to incorporate pesticide mixture effects into environmental risk assessment
Reputational Conservatism in Expert Advice
No full textNational audienceWe develop a tractable career–concerns model of expert recommendations with a continuous private signal. In equilibrium, advice obeys a cutoff rule: the expert recommends the risky option if and only if the signal exceeds a threshold. Under a mild relative–diagnosticity condition, the threshold is (weakly) increasing in reputation, yielding reputational conservatism. Signal informativeness and success priors lower the cutoff, while stronger career concerns raise it. A success–contingent bonus implements any target experimentation rate via a one–to–one mapping, providing an implementable design lever
Les hydrogels synthétiques disponibles dans le commerce ne peuvent pas remplacer le Matrigel pour promouvoir la polarisation et la lumenogenèse d’agrégats 3D de cellules souches embryonnaires
No full textPluripotency is defined as the ability of cells to differentiate into all cell types. In vivo, this capacity is gradually acquired by pluripotent cells in the epiblast as they polarize and arrange themselves into a three-dimensional structure known as a 'rosette', which then forms a lumen. Major epigenetic and metabolic changes occur during this crucial period of early development. Embryonic stem cells (ESCs), an in vitro model for early epiblast cells, can self-organise into rosettes when cultured in 3D, making them an ideal model for studying the events that accompany this morphogenesis. While this model is relevant to the 3Rs in terms of reducing the use of embryos, there is a significant drawback: the hydrogel commonly used for 3D cultures, Matrigel, is derived from animals. Furthermore, some rosette formation protocols use a serum-containing medium. The aim of this study was therefore to test alternative, commercially available, synthetic hydrogels and to compare the use of serum-containing and serumfree medium for modelling epiblast morphogenesis. Our results demonstrate that morphogenesis is more efficient in serum-free medium but did not occur in the synthetic hydrogels tested. This underscores the need for further optimisation of these systems.La pluripotence est définie comme la capacité des cellules à se différencier en tous les types cellulaires. In vivo, cette capacité est progressivement acquise par les cellules pluripotentes de l’épiblaste lorsqu’elles se polarisent et s’organisent en une structure tridimensionnelle appelée « rosette », qui forme ensuite une lumière. Des modifications épigénétiques et métaboliques majeures surviennent durant cette période clé du développement précoce. Les cellules souches embryonnaires (CSE), modèle in vitro des cellules de l’épiblaste précoce, peuvent s’auto-organiser en rosettes en culture 3D, constituant ainsi un modèle pertinent pour étudier les événements associés à cette morphogenèse. Bien que ce modèle contribue aux principes des 3R en réduisant l’utilisation d’embryons, il présente une limite importante : l’hydrogel couramment utilisé pour les cultures 3D, le Matrigel, est d’origine animale. De plus, certains protocoles de formation de rosettes utilisent des milieux contenant du sérum. L’objectif de cette étude était donc de tester des hydrogels synthétiques commerciaux alternatifs et de comparer l’utilisation de milieux avec ou sans sérum pour modéliser la morphogenèse de l’épiblaste. Nos résultats montrent que la morphogenèse est plus efficace en milieu sans sérum, mais qu’elle ne se produit pas dans les hydrogels synthétiques testés, soulignant la nécessité d’optimiser davantage ces systèmes
Soil carbon literature review in the humanities and the social sciences
No full textInternational audienceDespite rising interest in the humanities and social sciences, as attested in this book, soil carbon remains scarcely addressed in these fields. This literature review introduces three emerging sets of literature in social and human sciences that started addressing the knowledge, governance and practices related to soil carbon. We do not aim for comprehensiveness: instead, we would like to outline some major inspirations and orientations of recent research into soil carbon. We shall distinguish between: -Social studies of soil carbon sciences – i.e. a strand of research in history and sociology that focuses on the social practices of knowledge production on soil carbon within the scientific communities, and their reconfigurations in the context of the fight against climate change. -Social studies of soil carbon economy – i.e. a strand of research in political ecology and economic sociology that analyses the rising focus on soils as carbon sinks in climate governance and the associated development of soil carbon accounting schemes and metrics. -Social studies of soil regeneration – i.e. a set of writings in environmental humanities that addresses soil organic matter regeneration understandings and practices, such as composting, in a range of rural and urban contexts
Phytochemical and pharmacological elucidation of Jasonia glutinosa (L.) fourr. essential oil: a promising therapeutic source against inflammation and cancer
No full textInternational audienceThe growing demand for natural therapeutics with safer pharmacological profiles has renewed interest in aromatic plants traditionally used in folk medicine. Jasonia glutinosa (L.) Fourr. (Asteraceae), commonly known as "sticky fleabane", is a medicinal and aromatic species widely employed for its digestive and anti-inflammatory benefits. Despite its ethnopharmacological relevance, the bioactive potential of its essential oil remains poorly explored. This study provides a multifaceted investigation of the chemical composition, safety profile, and pharmacological activities of J. glutinosa essential oil (JGEO). Gas chromatography-mass spectrometry (GC-MS) analysis revealed nerolidol (51.29%) as the predominant constituent, accompanied by isoaromadendrene epoxide (17.39%) and cis-α-copaene-8-ol (9.92%). The genotoxicity assessment, conducted using the alkaline comet assay on rat leukocytes, demonstrated no significant DNA damage at concentrations up to 100 µg/mL, confirming the oil's genomic safety within the tested range. Pharmacological evaluation showed that JGEO exerted potent anti-inflammatory effects, significantly reducing nitric oxide (NO) and prostaglandin E₂ (PGE₂) production in LPS-stimulated macrophages - with NO levels decreasing to 18.4% of control values and PGE₂ from 720 µM to 108.2 µM (p < 0.001). Moreover, JGEO exhibited selective cytotoxicity against multiple human cancer cell lines, with IC₅₀ values of 15.43 µg/mL (MCF-7), 24.24 µg/mL (MDA-MB-468), 74.57 µg/mL (HCT-15), and 18.06 µg/mL (HepG2). Remarkably, high selectivity indices for MCF-7 (SI = 63.67) and HepG2 (SI = 54.40) surpassed those of doxorubicin, highlighting its favorable therapeutic window. Collectively, these findings provide a scientific basis for the traditional uses of J. glutinosa, emphasizing its safety, efficacy, and chemical richness. The study positions JGEO as a promising natural source of bioactive terpenoids for the development of anti-inflammatory and anticancer agents, supporting its further exploration in pharmaceutical and nutraceutical formulations
How long-lived trees remember: Epigenetic memory and priming of drought and heat stress in meristems and embryos
No full textInternational audienceAbstractWith climate change accelerating the frequency and intensity of heat and drought events, forestry urgently needs strategies that enhance stress tolerance without relying solely on genetic improvement, which in trees requires decades. Priming, pre-exposing plants to mild stress or biological signals to reinforce future responses, offers a promising approach for long-lived species. Unlike annual model plants, trees experience multi-year stress cycles, making priming particularly relevant for forestry, restoration, and climate-adaptive management. Our research focuses on developmental windows and cell dividing tissues with high potential for epigenetic memory, somatic embryos and meristems, examined under water deficit, thermal stress, biochar amendment, and mycorrhizal symbiosis. Across experiments, we observe persistent molecular signatures lasting weeks to seasons, and in some cases trans-annual memory. In contrast to short-lived species where histone modifications dominate, trees often display stronger involvement of DNA methylation in these persistent states, consistent with our recent findings in maritime pine embryogenesis and poplar cambium (Trontin et al., 2025; Duplan et al., 2025; and ongoing work). More recently, we investigated how biochar and beneficial root symbioses interact with drought priming in poplar. These studies form the basis of long-term research frameworks and national programs, including EPIMYC (ANR-24-CE20-5751) and the PEPR Agroecology & Digital initiative (ANR-24-PEAE-0001). Ultimately, our goal is to integrate omics layers to build predictive models of priming responsiveness and epigenetic plasticity, enabling identification of biomarkers and management-ready diagnostic tools to guide climate-adaptive forestry.References1.Trontin, J.F., Sow, M.D., Delaunay, A., Modesto, I., Teyssier, C., Reymond, I., Canlet, F., Boizot, N., Le Metté, C., Gibert, A., Chaparro, C., Daviaud, C., Tost, J., Miguel, C., Lelu-Walter, M.A., & Maury, S. 2025. Epigenetic memory of temperature sensed during somatic embryo maturation in 2-yr-old maritime pine trees. Plant Physiology, 197(2), kiae600. https://doi.org/10.1093/plphys/kiae6002.Duplan, A., Feng, Y.Q., Laskar, G., Cai, B.D., Segura, V., Delaunay, A., Le Jan, I., Daviaud, C., Toumi, A., Laurans, F., Sow, M.D., Rogier, O., Poursat, P., Duruflé, H., Jorge, V., Sanchez, L., Cochard, H., Allona, I., Tost, J., Fichot, R., & Maury, S. 2025. Drought induced epigenetic memory in the cambium of poplar trees persists and primes future stress responses. bioRxiv 2025.10.14.681991. https://doi.org/10.1101/2025.10.14.68199
Do skewed sex ratios reduce son preference?
No full texthttps://voxdev.org/topic/institutions-political-economy/do-skewed-sex-ratios-reduce-son-preferenc
Selection for function in complex distributed pathological systems
No full textInternational audiencePathological processes are often conceptualized as localized phenomena anchored in a primary tumor, a focal lesion, or a single organ. However, growing evidence indicates that many diseases persist and progress as complex distributed systems, maintained by interactions among multiple sites. Building on the emerging framework of selection for function, which can be applied to understand the evolutionary persistence of both replicating and non‐replicating entities, we propose that metastases, amyloidoses, fibroses, autoimmune syndromes, granulomatous diseases, and multifocal reproductive disorders can all be understood as complex evolving pathological systems within individuals. In these contexts, local units such as metastatic nodules, amyloid plaques, or fibrotic foci act as semi‐autonomous entities, yet achieve collective persistence through systemic flows, feedback loops, and network‐level interactions, where local structuration gives rise to systemic effects. At certain points, lesions that produce mediators can trigger systemic alterations that, in turn, favor the emergence and persistence of additional lesions. This creates a vicious cycle in which local and systemic dynamics reinforce one another, helping these specific pathological networks to overcome host defense mechanisms and persist (i.e., be ‘selected’ via differential persistence). This perspective unifies seemingly disparate conditions under the principle of system persistence, reframing pathology as an emergent organizational property of a pathological system rather than as isolated local breakdowns of organismal components. It also carries important implications for evolutionary medicine, suggesting a taxonomy of diseases that distinguishes localized from distributed functional pathologies. Clinically, it underscores the need to go beyond focal interventions, advocating instead for therapies that disrupt pathological connectivity, destabilize network coherence, and monitor systemic biomarkers of disease persistence. Recognizing the role of selection for function in the emergence and persistence of complex pathological systems opens new avenues for both theoretical integration and therapeutic innovation in evolutionary medicine