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Spatial self-organization of cancer stem cell niches revealed by live single-cell imaging
No full textInternational audienceBackground: Phenotypic plasticity is a major factor in tumor heterogeneity and treatment resistance. In particular, cancer stem cells (CSCs) represent a small subpopulation within tumors that possesses self-renewal and tumor-forming capabilities. Understanding reprogramming, maintenance, and lineage properties of CSCs requires dedicated tools to disentangle the respective influences of phenotypic inheritance and cell-cell interactions.Methods: Here, we set up ultra-wide field microscopy to image breast cancer cell lines expressing a stemness fluorescent reporter over several days. The fluorescent reporter distinguishes three phenotypes: CSCs, cancer differentiated cells (CDCs), and intermediate/transiting cancer cells (iCCs).Results: Spatial statistics indicate significant zonation in which CSCs cluster together and are spatially separated from CDCs, forming patterns resembling niches. Surprisingly, single-cell time series reveal spontaneous reprogramming events from CDC to CSC even in unperturbed populations. We identify that such transitions are prone to arise during the cell cycle. Moreover, lineage analysis shows that the phenotype is partially inherited from ancestor cells. However, such heredity is not sufficient to explain the spatial properties of the cell population, which also depend on cell-cell interactions. Indeed, we find that phenotypic transitions of cancer cells are influenced by the phenotypic state of neighboring cells. Reprogramming into CSCs is respectively promoted and inhibited by the presence of CSCs and CDCs in the neighborhood.Conclusions: Altogether, our results disentangle how phenotypic inheritance and intercellular interactions orchestrate the spatio-temporal self-organization of cancer cell heterogeneity, maintaining a subpopulation of CSCs within niches
Estimation des forces musculaires individuelles des ischio-jambiers lors d’entrainement contre résistance : vers une prédiction des adaptations musculaires
No full textResistance training induces major muscular adaptations, yet their magnitude and localization vary widely across muscles, even under identical training protocols. This variability may result from neuromechanical differences between muscle heads, including variations in length or muscle force production. The hamstrings provide a relevant model to explore these mechanisms, given their distinct neuromechanical behavior and their frequent targeting in resistance training. This thesis aimed to estimate individual hamstring muscle forces during resistance exercises to better understand the neuromechanical determinants of structural adaptations. A neuromusculoskeletal modeling approach driven by electromyographic data was applied and compared with experimental measures of muscle damage and hypertrophy. The results show that (i) hamstring muscles experience markedly different neuromechanical conditions even within the same exercise, (ii) the interaction between length and force strongly influences the location of training-induced adaptations, and (iii) model-based neuromechanical estimates accurately predict which hamstring head is most affected by training.L’entraînement contre résistance entraîne des adaptations musculaires majeures, mais leurs amplitudes et localisations varient fortement entre les muscles même pour un protocole identique. Cette variabilité pourrait s’expliquer par des différences neuromécaniques entre les chefs musculaires, notamment en termes de longueur ou de force produite pendant le mouvement. Les ischiojambiers constituent un modèle pertinent pour explorer ces mécanismes, en raison de leurs comportements neuromécaniques distincts et du fait qu’ils sont fréquemment ciblés en entrainement contre résistance. Ce travail de thèse visait donc à estimer les forces musculaires individuelles des ischiojambiers lors d’exercices de renforcement, afin de mieux comprendre les déterminants neuromécaniques des adaptations musculaires. Une approche de modélisation neuromusculosquelettique guidée par électromyographie a été appliquée et confrontée à des mesures expérimentales de dommages et d’hypertrophie musculaires. Les résultats montrent (i) que les ischio-jambiers sont soumis à des contextes neuromécaniques différents, même au sein d’un même exercice, (ii) que l’interaction entre longueur et force musculaire influence fortement la localisation des adaptations, et (iii) que les estimations issues de la modélisation permettent de prédire avec précision le chef musculaire le plus impacté par l’entraînement
Extracting and clustering human visual strategies from video gaze data with hidden markov models for video-QA performance understanding
No full textInternational audienceHuman gaze patterns during tasked viewing of an action offer insights into human attention, intention recognition, and the cognitive state of the viewer. These insights have applications in many domains such as collaborative robotics, user interface design, and medical assessment.In this work, we demonstrate an association between visual strategies employed during task-driven viewing and performance in video question answering (Video-QA). To do so, we leverage eye-tracking data to analyze human visual strategies during action recognition. Specifically, we record participants' gaze as they watch demonstrations of short atomic actions, which form a basis to describe all long form actions, followed by a questionanswering step to assess their comprehension. We model the spatio-temporal dynamics of gaze behavior using Hidden Markov Models (HMMs) and cluster visual strategies for demonstrations of the same task based on visual behavior similarity. We use Binomial Generalized Linear Mixed Model (BGLMM) to investigate how this behavior relates to Video-QA performance. Our results show that participants who exhibit specific visual strategies, as well as participants who are consistent in their visual strategy across different videos, perform better on the question-answering task, while other visual strategies are associated with poor performance and can reveal misunderstandings of the questions. Specifically, more dynamic gaze behavior, with more focused fixations on a relevant object, and more relevant objects considered in the scene are all properties of a better performing visual strategy.By identifying gaze patterns associated with Video-QA performance, using a probabilistic Bayesian method with interpretable learnable parameters, our approach enables clearer insights into human perception, potentially contributing to more robust and efficient action recognition machine learning models.</p
Ethylene sulfite and vinylene carbonate additives in acetonitrile-containing electrolytes for lithium-ion batteries: SEI impedance and XPS investigation
No full textInternational audienceElectrolyte solvents play a crucial role in extending the operating temperature range of Li-ion batteries. This article emphasizes the importance of precise adjustment of the amount of vinylene carbonate (VC) additive when incorporated with ethylene sulfite (ES) into a 20 vol% acetonitrile-containing carbonate electrolyte, with the aim to achieve enhanced LiNi0.5Mn0.3Co0.2O2/graphite pouch cell power performance at −5 °C. After determining the intrinsic characteristics of the electrolyte, including its ionic conductivity, viscosity, and lithium cation solvation shell using Raman spectroscopy analysis, the Li+ cation transport properties within the SEI are meticulously examined through the study of the distribution of relaxation times (DRT) extracted from electrochemical impedance spectroscopy (EIS) spectra and its composition elucidated by infrared (IR) and X-ray photoelectron spectroscopy (XPS). This study reveals significant information about the reduction reaction mechanisms leading to varying amounts of ES, VC, lithium bis(fluorosulfonyl)imide (LiFSI), acetonitrile and carbonate reduction compounds in the SEI, some of which are suspected to be the main compounds responsible for the observed differences in power performance
Cardioprotective effects of the extracellular chaperone clusterin in acute myocardial infarction
No full textInternational audienceBackground Acute myocardial infarction (AMI) remains one of the leading causes of mortality worldwide. Recently, a cardioprotective effect of clusterin (CLU), a ubiquitous extracellular chaperone, has been reported. However, the underlying mechanisms remain unresolved. We hypothesized that CLU exerts its protective effect on AMI by neutralizing cytotoxic and proinflammatory properties of extracellular histones, a new class of damage‐associated molecular patterns (DAMPs), that are released after massive cell injury. Methods and Results In vitro, we showed that exogenous CLU reduces histone‐induced cell death in H9C2 cells after hypoxia−reoxygenation (.78 ± .15 vs. 1.39 ± .20; p = .0059). Moreover, we found increased CLU protein levels in the ischemic zone vs. non‐ischemic zone after AMI in mice ( p < .05). Correspondingly, CLU‐deficient (CLU −/− ) mice presented significantly increased infarct size vs. wild‐type (CLU +/+ ) mice (46.29 ± 5.13% vs. 27.47 ± 1.92%; p = .0176). This cardioprotective effect of CLU is accompanied by an attenuation of the post‐AMI proinflammatory response through a decrease in the expression of proinflammatory cytokines interleukin (IL)‐6 and IL‐1β, a decrease in phosphorylated nuclear factor kappa B (NF‐kB) p65, as well as a decrease in the activation of the nucleotide‐binding oligomerization domain (NOD)‐like receptor pyrin domain containing 3 (NLRP3) inflammasome. Also, we found that in patients with acute ST‐segment elevation myocardial infarction (STEMI), circulating CLU‐histone complexes were significantly increased compared to healthy controls ( p < .001). Conclusions From these results, CLU protects the heart from inflammatory injury in AMI and this cardioprotection is due at least in part to its ability to neutralise extracellular histones released from the damaged tissue
Childhood Humoral Immunity During and After COVID-19 Lockdowns
No full textInternational audienceOur study, including serum from 3678 hospital inpatients and outpatients sampled before, during and after the COVID-19 lockdown periods, showed a significant decrease in overall IgG levels during the periods of sanitary restriction, particularly in children 3–10 years of age. Few months after the lifting of COVID-19 restrictions, immunoglobulin levels normalized. COVID-19 lockdowns may have induced a transient humoral immune gap
Rephrasing Euripides, reshaping the tragic: Euripides’ Trojan Women from Stiblin’s Troades to Garnier’s Troade
No full textInternational audienceIn conclusion to the argument of the Troade, Robert Garnier the most famous French tragedian of the 16th century, acknowledges that “the subject of this play is borrowed partly to Euripides’ Hecuba and Trojan Women, and partly to Seneca’s Troades. Indeed, the phenomenon of contamination with Senecan tragedies has been explored in depth but the relationship between Garnier and Euripides is yet to be deepened. If it is undeniable that the first act of the Troade (1579) follows the Greek tragedy at the point that some lines look like translations, Garnier’s knowledge of Greek remains undecided: could he read the original text or did he benefit from the help of a Hellenist friend1? We will argue that some lexical choices point towards a reading of Euripides mediated by Caspar Stiblin's Latin translation, published alongside the Greek text (1562). This scholar furnishes as well a rich paratext, in particular his own praefationes and argumenta in which he proposes a didactic and moral reading of the tragedies.We intend to investigate the many ways (lexical but also interpretative) in which Stiblin's interpretation may have influenced Garnier's appropriation of Euripides. Thus, we hope to shed light both on his knowledge of Greek and his handling of ancient sources, in order to demonstrate the importance of Latin translations in the reception process. Reworded, rephrased, transfigured: this mode of access to a Greek text will have had an importance on Garnier’s refiguration of the tragic
Evaluation de la SER multistatique d’une cible à partir des courants surfaciques physiques extraits de mesures sectorielles de champs proches
No full textEvaluating the Radar Cross Section (RCS) is a major challenge for electronic warfare risk management, right from the design phase of a military platform. Multistatic radar systems can improve detection and surveillance capabilities in a variety of environments. These radar systems have been attracting renewed interest in recent years, and must therefore be able to detect the field in order to characterise current and future military platforms, in particular with the RCS. It is in this context that the subject of the thesis falls. The aim of the thesis is to propose a method for evaluating the multistatic RCS of a target from the reconstruction of surface currents (equivalent or physical) obtained by backpropagation of a near-field measurement over a limited angular sector. Initially, the work focused on evaluating the RCS of a canonical target in the near and far fields. In a second phase, the research focused on characterizing the surface current of the object and then evaluating the electric field from these currents in the far field. The evaluation of the farfield RCS from a near-field measurement was carried out using an asymptotic and rigorous model.L’évaluation de la Surface Équivalente Radar (SER) constitue un enjeu de taille pour la maîtrise des risques en Guerre électronique dès les phases de conception d’une plateforme militaire. Les systèmes radar multistatiques permettent d’améliorer les capacités de détection et de surveillance au sein de milieux divers. Ces systèmes radar, montrant un regain d’intérêt depuis quelques années, doivent donc être en capacité de détecter le champ pour pouvoir caractériser, notamment avec la SER, les actuelles et futures plateformes militaires. C’est dans ce contexte que le sujet de thèse s’inscrit. L’objectif de la thèse est de proposer une méthode d’évaluation de la SER multistatique d’une cible à partir de la reconstruction de courants surfaciques (équivalents ou physiques) obtenus par rétropropagation d’une mesure en champ proche sur un secteur angulaire limité. Les travaux se sont donc orientés dans un premier temps sur l’évaluation de la SER d’un cible canonique en champ proche et lointain. Dans un deuxième temps, les recherches se sont concentrées sur la caractérisation du courant surfacique de l’objet puis de l’évaluation du champ électrique à partir de ces courants en champ lointain. L’évaluation de la SER en champ lointain à partir d’une mesure en champ proche a été réalisée sur un modèle asymptotique et rigoureux