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Advancing Near-Infrared Optical Imaging Agents for Investigating SKCa Channel Regulation via the cAMP/PKA Pathway in Cancer Cells
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« L’effet mâle » chez les ovins et caprins: une technique qui nous vient du Néolithique?
No full textInternational audienceChez les petits ruminants, la remise en présence d’un mâle sexuellement actif avec des femelles au printemps pendant leur période de repos sexuel saisonnier, entraîne une reprise synchrone des ovulations sous 48 heures. C’est « l’effet mâle1 ». Il est efficace chez les ovins et caprins des zones tempérées et subtropicales qui manifestent une saison de reproduction marquée. Il permet d’obtenir des mise-bas d’automne, à « contre-saison », qui ont un certain nombre d’avantages techniques et économiques. Cette technique est utilisée actuellement par les éleveurs mais ce n’est qu’au début du 20ème siècle qu’elle a été identifiée et ses mécanismes décryptés par le monde scientifique. Dans les textes anciens et dans les analyses archéologiques, il existe des éléments permettant de penser que ces mise-bas d’automne étaient assez fréquentes dans les troupeaux méditerranéens, depuis le Néolithique. Mais était-ce le résultat d’une volonté délibérée de l’éleveur ou bien de la combinaison d’une aptitude au dé-saisonnement des populations ovines et caprines utilisées et d’un cadre bioclimatique favorable ? La nécessité d’une séparation préalable des mâles et de leur réintroduction pour aboutir à une proportion élevée de mise-bas d’automne dans le troupeau suggère que, dans les sites Néolithiques étudiés, ce mode de conduite résulte probablement d’une volonté délibérée de l’éleveur
« L'effet mâle » chez les ovins et caprins : une technique qui nous vient du Néolithique ?
No full textInternational audienceIn small ruminants, the introduction of a sexually active male among females during the spring sexual rest period leads to a resumption of ovulation within 48 hours. This is the "male effect". This technique is currently used by breeders, but it was not until the beginning of the 20th century that it was identified and its mechanisms deciphered. Zooarchaeological analyses suggest that these autumn births were quite frequent in Mediterranean flocks since the Neolithic. But was it the result of a deliberate intention on the part of the farmer or of a combination of an ability of the sheep populations used to reproduce out of season and a favourable bioclimatic framework? The need for prior separation of the males and their reintroduction to achieve a high proportion of autumn lambing in the flock suggests that, in the Neolithic sites studied, this mode of management could be the result of a deliberate will on the part of the breeder.Keywords: reproduction, ewe, she-goat, seasonalityChez les petits ruminants, la remise en présence d'un mâle sexuellement actif avec des femelles pendant le repos sexuel printanier entraîne une reprise des ovulations sous 48 heures. C'est « l'effet mâle ». Cette technique est utilisée actuellement par les éleveurs mais ce n'est qu'au début du 20 ème siècle qu'elle a été identifiée et ses mécanismes décryptés. Les analyses archéozoologiques suggèrent que ces mise-bas d'automne étaient assez fréquentes dans les troupeaux ovins méditerranéens, depuis le Néolithique. Mais était-ce le résultat d'une volonté délibérée de l'éleveur ou bien de la combinaison d'une aptitude au désaisonnement des populations ovines utilisées et d'un cadre bioclimatique favorable ? La nécessité d'une séparation préalable des mâles et de leur réintroduction pour aboutir à une proportion élevée de mise-bas d'automne dans le troupeau suggère que, dans les sites néolithiques étudiés, ce mode de conduite a pu résulter d'une volonté délibérée de l'éleveur
A (poly)Pro tip for preserving native disulfide connectivity during thiol-maleimide bioconjugation of disulfide-rich peptides
No full textGeneration of specific antibodies against peptides by immunization requires their covalent conjugation to protein carriers to override their inherently weak immunogenicity. The vast majority of bioconjugation approaches to achieve peptide-protein constructs rely on thiol-maleimide chemistry and capitalize on a wide array of commercial maleimide-functionalized protein carriers. Disulfide-rich peptides (DRPs) possess a rigid, constrained structure that makes them ideal for designing synthetic mimics of protein regions/domains. For bioconjugation purposes, the introduction of a single spare thiol moiety into a linear peptide antigen is straightforward, while DRPs’ disulfide bonds are prone to intramolecular thiophilic attack by the reactive thiolate. This unintended reactivity competes with the desired Michael addition to the maleimide moiety, ultimately disrupting the native disulfide bridging framework. As a result, DRP’s tertiary structure will be altered, affording an immunogen that is a poor mimic of the native target. Although a few studies have explored the late-stage introduction of thiol-containing cross-linkers onto DRP antigens for their conjugation onto protein carriers, the stability of DRP’s disulfide pattern in the presence of an extra thiol has never been examined. In this study, we systematically evaluated the influence of different spacers in “DRP-spacer-thiol” constructs, under thiol-maleimide reaction condtions. Our results highlight how both linker lenght and flexibility are key to maintain DRP disulfides unaltered, providing a general approach to achieve DRP bioconjugation by thiol-maleimide chemistry. We have applied our approach to a small DRP predicted to closely mimic a surface-accessible epitope of the full LINGO-1 protein, and obtained a very specific antibody response upon immunization; the resulting polyclonal IgG was able to selectively bind the full-length protein in a cellular context, with stringent selectivity across its four homologs
Exploring the landscape of black hole mimickers
No full textInternational audienceWe identify a general class of spacetime metrics that mimic the properties of black holes without possessing a true event horizon. These metrics are constrained by the requirements of being singularity-free and geodesically complete. Specifically, we study metrics that do not possess symmetry and may deviate slightly or significantly from the symmetric case. Focusing on scalar perturbations propagating on such backgrounds, we analyze the resulting effective radial potentials and their dependence on different corners of the mimicker landscape. We further investigate the corresponding quasinormal modes and explore their characteristic features. Finally, we survey the landscape for potential observational signatures, including shadow properties and the possible presence or absence of echo effects
Interactive Dashboard Generation for Analyzing Survival-Changing Patterns and Employee Attrition
No full textInternational audienceEmployee retention is a major issue for companies. In our previous work [1], we proposed an approach that extracts frequent patterns from employee trajectories to identify those associated with improved retention thanks to survival analysis. Those are called survival-changing patterns. However, the large volume and complexity of these patterns limited their interpretability and practical use by Human Resources (HR) teams. In this paper, we introduce an interactive dashboard that combines sequential pattern mining with survival analysis to support HR decision-making. Our approach refines and visualizes survival-changing patterns, enabling a clearer understanding of attrition dynamics. The dashboard provides a global view of retention trends, an identification of at-risk employees, and a simulation of targeted interventions. Our contributions include the definition of HR personas and use cases, a method for selecting representative pattern of a sequence, the design of tailored visualizations for employee trajectories, and a real-world illustration of how the tool works in practice
Recherche d’information : processus cognitifs et apprentissage tout au long de la vie
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Board games in the elementary classroom : teachers’ perspectives
No full textInternational audienceBackgroundRecent research highlights the importance of developing children’s emotional and social competencies alongside academic knowledge and skills. Learning through play is a promising pedagogy that can contribute to children’s holistic development. Through playful pedagogies, children can develop social skills, cognitive abilities, and emotional competencies. Despite a global emphasis on learning through play, playful pedagogies tend to be less common in elementary schools than in pre-schools, and elementary school teachers rarely use them in their classrooms.PurposeAmong the diverse range of playful pedagogies, board games stand out as one particularly engaging activity for fostering pupils’ holistic skills during middle childhood (aged 5 to 11). This study aimed to contribute to a gap in knowledge between the reported benefits of board games for children’s academic learning, emotional, and social competencies, and the actual practices of elementary school teachers. We asked the following research questions: 1) What are teachers’ perceptions of board games?; and 2) What are the key factors shaping their integration into classroom practices?MethodsThe study was conducted in France and gathered qualitative data through four semi-structured focus groups involving 18 elementary school teachers across four elementary schools. Data were analysed thematically.FindingsAuthors identified four overarching themes: 1) teachers’ knowledge about board games, 2) teachers’ role in classroom board games and their academic benefits, 3) board games for emotion regulation and social competencies, and 4) enablers and barriers to the implementation of board games in elementary school.ConclusionWhile elementary school teachers see the potential of board games to enhance academic, social, and emotional competencies, they face several barriers to implementing board game practice in their classrooms. These include official educational recommendations, the decline of play – both at home and in schools, and a lack of resources
Globally defined Carroll symmetry of gravitational waves
No full textInternational audienceThe locally defined Carroll symmetry of a gravitational wave is extended to a globally defined one by switching to Brinkmann coordinates. Translations and Carroll boosts associated with two independent globally defined solutions of a Sturm-Liouville equation allow us to describe the motions. The Displacement Memory Effect arises for particular choices of the parameters which yield trajectories with zero momentum. The relation to the Schwarzian derivative is highlighted. We illustrate our general statements by the Pöschl-Teller profile
PEEP-AKI-COVID ICU: Effect of positive end-expiratory pressure on acute kidney injury development in patients with COVID-19-associated acute respiratory distress syndrome: an ancillary analysis of the COVID-ICU study
No full textInternational audienceBackground: Acute Kidney Injury (AKI) is common in patients admitted to the intensive care unit (ICU) for severe SARS-CoV-2 pneumonia and is associated with a worse prognosis. Mechanical ventilation has been identified as a risk factor for renal damage in COVID-19. However, few studies have examined the specific ventilatory settings involved. We hypothesized that positive end-expiratory pressure (PEEP) may contribute to the onset of AKI. Our primary objective was to assess the relationship between PEEP levels and the development of AKI in critically ill patients with COVID-19-related ARDS.Methods: We conducted an ancillary analysis of the international, prospective, multicenter COVID-ICU study, which included 4244 COVID-19 ICU patients across 149 intensive care units. For our study, only patients who underwent mechanical ventilation for at least 48 h and had normal renal function before intubation were included. The primary outcome was AKI, defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. A multivariable logistic regression model was used to evaluate the association between PEEP levels and the development of AKI (KDIGO score > 1).Results: A total of 1,066 patients were included in the analysis. Among them, 510 (48%) developed AKI within the first 5 days after intubation. After multivariable adjustment, higher daily mean PEEP levels, averaged over the first 3 days of mechanical ventilation and treated as a continuous variable, were independently associated with the development of AKI (odds ratio [OR] 1.10; 95% confidence interval [CI] 1.05-1.16). A PEEP level exceeding 15.2 cmH2O was significantly associated with the occurrence of AKI.Conclusion: In patients with COVID-19-related ARDS patients, higher PEEP levels within the first 5 days after intubation were independently associated with AKI. These findings underscore the importance of ventilatory strategies to balance oxygenation and kidney protection