Scientific Publications of the University of Toulouse II Le Mirail
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AFflecto: A web server to generate conformational ensembles of flexible proteins from AlphaFold models
No full textInternational audienceIntrinsically disordered proteins and regions (IDPs/IDRs) leverage their structural flexibility to fulfill essential cellular functions, with dysfunctions often linked to severe diseases. However, the relationships between their sequences, structural dynamics and functional roles remain poorly understood. Understanding these complex relationships is crucial for therapeutic development, highlighting the need for methods to generate plausible IDP/IDR conformational ensembles. While AlphaFold (AF) excels at modeling structured domains, it fails to accurately represent disordered regions, leaving a significant portion of proteomes inaccurately modeled. We present AFflecto, a user-friendly web server for generating large conformational ensembles of proteins that include both structured domains and IDRs from AF structural models. AFflecto identifies IDRs as tails, linkers or loops by analyzing their structural context. Additionally, it incorporates a method to identify conditionally folded IDRs that AF may incorrectly predict as natively folded elements. The conformational space is globally explored using efficient stochastic sampling algorithms. AFflecto's web interface allows users to customize the modeling, by modifying boundaries between ordered and disordered regions, and selecting among several sampling strategies. The web server is freely available at https://moma.laas.fr/applications/AFflecto/
Far-right movements in the Western world: How media exposure relates to normative beliefs and attitudes toward the far-right
No full textInternational audienceConsidering the rise of far-right groups in Western countries, we examined whether exposure to media coverage on the far-right is associated with attitudes toward it, using surveys in 15 Western democratic countries (total N = 2,576). We hypothesized that greater media exposure to the far-right will be associated with greater perceived prevalence and acceptability of it, which will in turn be associated with divergent attitudes. On the one hand, greater perceived prevalence may be associated with more unfavorable attitudes toward the far-right (a threat response). On the other hand, greater perceived acceptability may be associated with more favorable attitudes toward the far-right (a normalization response). Overall, there was more evidence for a threat response than a normalization response: media exposure was consistently related to greater perceived prevalence (but not acceptability) of the far-right. This research underscores the importance of studying the consequences of the rise of the far-right
What does coexistence mean? Insight from place‐based trajectories of pastoralists and bears encounters in the Pyrenees
No full textInternational audience1. The recovery of large carnivores in Europe raises issues related to sharing landscape with humans. Beyond technical solutions, it is widely recognized that social factors also contribute to shaping coexistence. In this context, scholars increasingly stress the need to adopt place-based approaches by analysing how humans and wildlife interact and co-adapt in specific landscapes. In the burgeoning field of 'more-than-human' geography, both humans and non-humans are considered as co-constitutive of places. According to this tradition, animals should not simply be seen as objects under human control but approached as powerful actors in multi-species landscapes.2. By tracking how brown bear recovery in the French Pyrenees has shaped different places of encounters with pastoralists (i.e. farmers and shepherds in extensive sheep farming in mountain pastures during summer), this paper discusses what coexistence means when viewed through the lens of more-than-human geography. We use an in-depth, retrospective and multi-sources approach to describe the inter-relationships of bears and pastoralists on three mountain pastures since the return of bears at the end of the 1990s. Semi structured interviews, participant observation, administrative and institutional data about bear depredation and genetics, as well as pastoral practices form the basis of an integrated narrative analysis.3. Our study reveals how the return of a large carnivore has produced three different, singular, context-specific coexistence 'patches'. Each of these three pastures represent a distinct landscape dynamically shaped over time by bears, pastoralists and the rest of biotic and abiotic environment
Language attrition and maintenance in multilinguals
No full textInternational audienceThis chapter reflects on the specific implications and challenges that speakers of multiple languages raise for research on language attrition and maintenance. Before turning specifically to multilingualism, current views on language attrition and a summary of some of the most important debates and findings about language attrition in bilinguals are presented. Then the few studies taking into account multilingualism in attrition of both the first and foreign languages are outlined. These suggest that multiple languages are linked through complex relations modulated by factors such as age and order of acquisition, typological overlap, language use and so on. Different models of language management in multilinguals are then discussed in order to see how they can account for these complex links between languages. Finally, the methodological challenges of language attrition studies in multilinguals are discussed with a call for more diverse empirical studies of activation and inhibitory links between multiple languages
Agent-based modelling to improve the antitumoral activity of oncolytic virus
No full textInternational audiencePancreatic adenocarcinoma (PDAC) is an aggressive cancer with limited treatment options and a dismal prognosis. Oncolytic viruses (OVs) are emerging as novel therapeutics for PDAC and other cancers. These viruses selectively infect, replicate within, and destroy cancer cells while sparing normal cells. As cancer cells are lysed by the virus, viral particles are released, enabling further infection of surrounding cancer cells. Despite their potential, OV dosing and optimization remain largely empirical due to the complex, nonlinear interactions between a growing tumor and a replicating virus.Computational modeling has become an invaluable tool in modern oncology, allowing researchers to simulate intricate biological interactions and test hypotheses. We used ISiCell, a user-friendly software designed to simulate cell cycle dynamics and complex cellular behaviors. The software utilizes state-transition diagrams to represent the phenotypical state of cells and activity diagrams to depict cell behaviors, facilitating rapid prototyping and hypothesis testing.We developed a 2D computational model of cell proliferation and viral interactions, integrating experimentally derived parameters like cell cycle duration and migration speed with abstract parameters. Using PIP-FUCCI-expressing PDAC cells, we non-invasively imaged cell cycle transitions in real time, enabling precise measurement of each phase duration. Additionally, we modeled cell migration speed—a key factor influencing viral dissemination—using real-time imaging.The model was calibrated using TPE (Tree-structured Parzen Estimator) sampling to match simulated results with experimental data. Specifically, GFP-tagged PDAC cell counts after OV infection provided critical data aligning with model simulations. The exploration of parameters validated the model’s accuracy and highlighted parameters governing OV activity, offering new insights into OV-host interactions.Our work establishes a robust foundation for understanding OV therapy in PDAC. Future efforts will refine the model, incorporate additional biological data, and expand into 3D systems to better represent the tumor microenvironment. This framework paves the way for more effective OV-based therapies and their translation into clinical success
Le nombre de conflits environnementaux augmente chaque année
No full textPresse écrite "Médiacités" du 13/01/202
Formal Integration of Derived Foliations
No full textFrobenius' theorem in differential geometry asserts that every involutive subbundle of the tangent bundle of a manifold M integrates to a decomposition of M into smooth leaves. We prove an infinitesimal analogue of this result for locally coherent qcqs schemes X over coherent rings. More precisely, we integrate partition Lie algebroids on X to formal moduli stacks X → S, where S is the formal leaf space and the fibres of X → S are the formal leaves. We deduce that deformations of X-families of algebro-geometric objects are controlled by partition Lie algebroids on X. Combining our integration equivalence with a result of Fu, we deduce that Toën–Vezzosi's infinitesimal derived foliations (under suitable finiteness hypotheses) are formally integrable