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Chronic graft-versus-host disease in long-term survivors of childhood leukemia
No full textInternational audienceHematopoietic stem cell transplantation (HSCT) is a curative treatment for high-risk childhood leukemia but may lead to chronic graft-versus-host disease (cGvHD), a severe long-term complication. This study analyzed data from the LEA cohort, including 446 childhood leukemia survivors treated with allogeneic HSCT. The standardized cGvHD evaluation, using the NIH consensus criteria, was conducted 8.7 ± 0.3 years post-HSCT. Long-term cGvHD was reported in 21% of patients (9% mild, 7% moderate, 5% severe), primarily affecting eyes, skin, lungs, and mouth, with some cases involving multiple organs. Most patients with long-term cGvHD were untreated (84%), while 11% received systemic and 5% local treatments. cGvHD was associated with other long-term complications. Administration of anti-thymocyte globulin was a significant determinant (OR 0.6, 95% CI 0.4-0.99, P = 0.045). Long-term cGvHD showed a marked detrimental effect on the quality of life (QoL), even after adjusting for the other long-term complications. The SF-36 physical and psychological adjusted composite scores in patients with versus without cGvHD were 50 ± 2 versus 55 ± 1 (P = 0.01) and 38 ± 2 versus 43 ± 1 (P = 0.01), respectively. Even mild and moderate forms significantly affected the QoL, especially on psychological dimensions. These findings support standardized cGvHD evaluation and management to improve long-term outcomes of transplanted childhood leukemia survivors
Rapid identification of bacterial spores by Raman and OPTIR infrared spectroscopy using chemometrics and machine learning
No full textInternational audienceCo-localized IR/Raman O-PTIR imaging enables rapid, label-free identification of Bacillus spores, discriminating species (B. cereus, B. subtilis, B. coagulans) and strains within a specie.This approach could be extended to identify additional strains/species (pathogenic B. cereus), other genera (Clostridium) and vegetative bacteria. It will allow to investigate whether spectra can distinguish sporulation conditions or germination stage.The next step in development will be to determine the minimum number of informative wavelengths in order to design simplified, sensor-based measurements
Public Communication in Regime Change games
No full textNational audienceWe study a regime change game in which the state and an opposition leader both observe the regime’s true strength and may engage in costly communication by manipulating the mean of citizens’ private signals. Each citizen then decides whether to attack the regime. From the perspective of both the state and the opposition, the size of the attack is uncertain, as the number of committed partisans—those who always attack regardless of their signal—is not observed in advance. We show that a regime on the brink of collapse optimally refrains from propaganda, while the opposition engages in counter-propaganda. The equilibrium level of counter-propaganda increases with the opposition’s benefit-cost ratio and with the precision of citizens’ private signals, and decreases with the cost of attacking
Recruitment of bifunctional regulator thermospermine to methylated ribosomes directs xylem fate
No full textInternational audiencePolyamines are often associated with ribosomes and are thought to stabilize their integrity. In Arabidopsis , the polyamine thermospermine (tSpm) affects xylem cell fate. tSpm induces translation of SUPPRESSOR-OF-ACAULIS51 (SAC51) and SAC51-LIKEs (SACLs), which inhibit heterodimerization of the xylem development proteins LONESOME-HIGHWAY (LHW) and TARGET-OF-MONOPTEROS5. Here, we report a methyltransferase, OVERACHIEVER, that methylates the peptidyl transferase center of the 25 S ribosomal RNA (rRNA). Residue m 3 U2952 promotes functional tSpm binding to a specific site connecting the P-site transfer RNA (tRNA) with rRNA residues in the peptidyl transferase center. This interaction enhances the translation of SACLs but inhibits that of LHW. Our study uncovers the dependency between a conserved rRNA base methylation and a polyamine in orchestrating cell fate decisions, highlighting a role for the ribosome chemical landscape in translational regulation
Dynamic network formation with farsighted players and limited capacities
No full textInternational audienceWe investigate a T-stage dynamic network formation game with linear-quadratic payoffs. Players interact through network which they create as a result of their actions. We study two versions of the dynamic game and provide the equilibrium analysis. First, we assume that players sequentially propose links to others with whom they want to connect and choose the levels of contribution for their links. The players have limited total contributions or capacities for forming links at every stage which can differ among players and over time. They cannot delete links, but the principle of natural elimination of links with no contribution is adopted. Next, we assume that the players simultaneously and independently propose links to other players and have overall limited capacities for the whole game, and not for each stage. This means that every player can redistribute the capacity not only over links, but also over time. The equilibrium concept for the first version of the dynamic game is subgame perfect equilibrium, while it is the Nash equilibrium in open-loop strategies for the second version. Both models are illustrated with numerical examples
The way forward for assessing the human health safety of cosmetics in the EU: Proceedings of Workshop 2
No full textInternational audienceUnder the European Cosmetic Regulation, safety assessments of cosmetics and their ingredients must be conducted without the use of animals. This regulatory requirement poses a number of challenges, as validated alternative methods are only available for some of the toxicological endpoints that are typically considered in standard human health risk assessments. Despite significant progress since the ban in 2013, particularly in the development of New Approach Methodologies (NAMs) for local and acute toxicity, and for mutagenicity/genotoxicity, there remains an urgent need for non-animal test methods to assess systemic toxicity, which often becomes evident after repeated or long-term exposure. Currently, no validated animal-free alternatives are available for assessing sub-acute, sub-chronic and chronic toxicity, carcinogenicity, developmental/reproductive toxicity, or for a major part of toxicokinetics. In response to these challenges, the Methodology Working Group of the Scientific Committee on Consumer Safety organised a dedicated workshop in December 2024 to discuss advances in the application of Next Generation Risk Assessment (NGRA) as a strategic animal-free approach for the safety assessment of cosmetic ingredients. The workshop focused on a number of important key issues for the practical application of NAMs and NGRA, their regulatory acceptance and identification of possible (partial) solutions to overcome existing limitations
Selection of intra‐forest meadows by red deer increases with winter temperature
No full textInternational audienceSurvival and reproduction drive animals to occupy specific habitats within their home range. Red deer shows a particular preference for forest gaps, whereas the elevated browsing pressure can limit tree regeneration. Nevertheless, intra-forest meadows can attract red deer within forests by providing accessible grass, particularly as warmer winter temperatures, driven by climate change, result in earlier vegetation onset and lower snow cover. Using GPS monitoring of red deer in two populations from France and Belgium, we analysed how their selection of intra-forest meadows varies according to season, seasonal mean temperature and time of day (night-time and daytime). We show that red deer preferentially selects intra-forest meadows at night, irrespective of the season, although the strength of this selection is reduced in winter. However, the strength of night-time selection of meadows increases with winter mean temperature. We proposed that this pattern is explained by seasonal variations of vegetation availability (minimal in winter), which is positively linked to winter temperature. These results suggested that meadows act as critical foraging areas for red deer across all seasons in a climate change context with warmer winters. We also hypothesised that intra-forest meadows modify the spatial distribution of browsing pressure within neighbouring forest areas, a key issue for forest managers
Water in mantle minerals. In the aftermath of more than two decades of research, what have we discovered, what should we believe, and what are the unresolved questions ?
No full textSeminar at the Sapienza University, RomaInternational audienceTo comprehend the dynamic of the lithosphere, it is crucial to determine the extent of its “wetness” and its heterogeneity. Water concentration in the Nominally Anhydrous Minerals (NAMs) in xenoliths has been extensively employed in the past two decades to monitor the water content in the lithospheric mantle. Many experimental, numerical modelling and analytical studies of NAMs have been conducted in this lapse of time. The present state of knowledge on the subject, the major questions that remain unanswered, and the future of the topic will be examined through concrete examples