Membrane Shape Modulates Transmembrane Protein Distribution

SummaryAlthough membrane shape varies greatly throughout the cell, the contribution of membrane curvature to transmembrane protein targeting is unknown because of the numerous sorting mechanisms that take place concurrently in cells. To isolate the effect of membrane shape, we used cell-sized giant unilamellar vesicles (GUVs) containing either the potassium channel KvAP or the water channel AQP0 to form membrane nanotubes with controlled radii. Whereas the AQP0 concentrations in flat and curved membranes were indistinguishable, KvAP was enriched in the tubes, with greater enrichment in more highly curved membranes. Fluorescence recovery after photobleaching measurements showed that both proteins could freely diffuse through the neck between the tube and GUV, and the effect of each protein on membrane shape and stiffness was characterized using a thermodynamic sorting model. This study establishes the importance of membrane shape for targeting transmembrane proteins and provides a method for determining the effective shape and flexibility of membrane proteins

Par3 cooperates with Sanpodo for the assembly of Notch clusters following asymmetric division of Drosophila sensory organ precursor cells

In multiple cell lineages, Delta-Notch signalling regulates cell fate decisions owing to unidirectional signalling between daughter cells. In Drosophila pupal sensory organ lineage, Notch regulates the intra-lineage pIIa/pIIb fate decision at cytokinesis. Notch and Delta that localise apically and basally at the pIIa-pIIb interface are expressed at low levels and their residence time at the plasma membrane is in the order of minutes. How Delta can effectively interact with Notch to trigger signalling from a large plasma membrane area remains poorly understood. Here, we report that the signalling interface possesses a unique apico-basal polarity with Par3/Bazooka localising in the form of nano-clusters at the apical and basal level. Notch is preferentially targeted to the pIIa-pIIb interface, where it co-clusters with Bazooka and its cofactor Sanpodo. Clusters whose assembly relies on Bazooka and Sanpodo activities are also positive for Neuralized, the E3 ligase required for Delta activity. We propose that the nano-clusters act as snap buttons at the new pIIa-pIIb interface to allow efficient intra-lineage signalling

Water-stable isotopes in the LMDZ4 general circulation model: Model evaluation for present-day and past climates and applications to climatic interpretations of tropical isotopic records

International audienceWe present simulations of water-stable isotopes from the LMDZ general circulation model (the LMDZ-iso GCM) and evaluate them at different time scales (synoptic to interannual). LMDZ-iso reproduces reasonably well the spatial and seasonal variations of both delta O-18 and deuterium excess. When nudged with reanalyses, LMDZ-iso is able to capture the synoptic variability of isotopes in winter at a midlatitude station, and the interannual variability in mid and high latitudes is strongly improved. The degree of equilibration between the vapor and the precipitation is strongly sensitive to kinetic effects during rain reevaporation, calling for more synchronous vapor and precipitation measurements. We then evaluate the simulations of two past climates: Last Glacial Maximum (21 ka) and Mid-Holocene (6 ka). A particularity of LMDZ-iso compared to other isotopic GCMs is that it simulates a lower d excess during the LGM over most high-latitude regions, consistent with observations. Finally, we use LMDZ-iso to explore the relationship between precipitation and delta O-18 in the tropics, and we discuss its paleoclimatic implications. We show that the imprint of uniform temperature changes on tropical delta O-18 is weak. Large regional changes in delta O-18 can, however, be associated with dynamical changes of precipitation. Using LMDZ as a test bed for reconstructing past precipitation changes through local delta O-18 records, we show that past tropical precipitation changes can be well reconstructed qualitatively but not quantitatively. Over continents, nonlocal effects make the local reconstruction even less accurate

The LifeCycle Project-EU Child Cohort Network : a federated analysis infrastructure and harmonized data of more than 250,000 children and parents

Early life is an important window of opportunity to improve health across the full lifecycle. An accumulating body of evidence suggests that exposure to adverse stressors during early life leads to developmental adaptations, which subsequently affect disease risk in later life. Also, geographical, socio-economic, and ethnic differences are related to health inequalities from early life onwards. To address these important public health challenges, many European pregnancy and childhood cohorts have been established over the last 30 years. The enormous wealth of data of these cohorts has led to important new biological insights and important impact for health from early life onwards. The impact of these cohorts and their data could be further increased by combining data from different cohorts. Combining data will lead to the possibility of identifying smaller effect estimates, and the opportunity to better identify risk groups and risk factors leading to disease across the lifecycle across countries. Also, it enables research on better causal understanding and modelling of life course health trajectories. The EU Child Cohort Network, established by the Horizon2020-funded LifeCycle Project, brings together nineteen pregnancy and childhood cohorts, together including more than 250,000 children and their parents. A large set of variables has been harmonised and standardized across these cohorts. The harmonized data are kept within each institution and can be accessed by external researchers through a shared federated data analysis platform using the R-based platform DataSHIELD, which takes relevant national and international data regulations into account. The EU Child Cohort Network has an open character. All protocols for data harmonization and setting up the data analysis platform are available online. The EU Child Cohort Network creates great opportunities for researchers to use data from different cohorts, during and beyond the LifeCycle Project duration. It also provides a novel model for collaborative research in large research infrastructures with individual-level data. The LifeCycle Project will translate results from research using the EU Child Cohort Network into recommendations for targeted prevention strategies to improve health trajectories for current and future generations by optimizing their earliest phases of life.Peer reviewe

Effets du confinement sur l auto-organisation du cytosquelette

Le but de cette thèse a été d étudier quantitativement l effet d un confinement physique, mimant les conditions de compartimentations cellulaires, sur des processus auto-organisationnels de fibres du cytosquelette. Nous avons développé une méthode permettant l encapsulation au sein de gouttelettes et de vésicules d un extrait cellulaire de Xénope, formant un aster à partir des interactions entre microtubules et moteurs moléculaires. Nous avons en particulier montré que cette auto-organisation dépendait fortement de la dimension du confinement. Trois structures distinctes de microtubules, chacune associée à une gamme de taille ont été ainsi observées : asters, asters asymétriques et faisceaux corticaux. Les transitions pour lesquelles les brisures de symétries apparaissent, se produisent pour des diamètres bien définis. Ces observations ont été expliquées qualitativement par un modèle physique simple et reproduites par des simulations numériques prenant en compte les propriétés physiques intrinsèques des objets biologiques (élasticité des microtubules, moteurs moléculaires ). Une seconde étape, consistant à encapsuler l extrait cellulaire, au sein de vésicules a permis d observer de nouvelles structures en forme de protrusions, mettant en évidence le rôle de la rigidité du confinement. L utilisation de cette méthode a permis de réaliser des expériences préliminaires sur l organisation d un réseau d actine au sein de gouttelettes et a mis en évidence la présence d un flux directionnel des filaments d actine pouvant aboutir à la formation d un anneau contractile, reproduisant ainsi une des étapes essentielles de la cytokinèse.We studied the effect of a confined physical environment on cytoskeleton self-organized processes. In order to reproduce the cell s confinement, we developed an efficient bottom-up approach to encapsulate a Xenopus cell extract within droplets and vesicles. The qualitative and quantitative studies on a microtubule aster encapsulated within droplets showed three different patterns: asters, asymmetrical asters, and cortical bundles. Monitoring of the morphologies adopted by microtubule arrays showed that symmetry breaking in the organization of microtubules and formation of an aster in a spherical environment is dependent on the size of the droplet. Computer simulations based on physical considerations reproduced the various structures observed, and a simple physical model identified the main physical parameters of the transitions. The use of vesicles with more elastic boundaries resulted in very different morphologies of microtubule structure, such as protrusions, highlighting the importance of the rigidity of the confinement. We also used this system and this approach to study the re-organization of the actin network within droplets. Preliminary results demonstrate the existence of an actin directional flow around a contractile ring, reproducing in vivo processes present during cytokinesis.RENNES1-BU Sciences Philo (352382102) / SudocSudocFranceF

Spatio-Temporal Regulation of Notch Activation in Asymmetrically Dividing Sensory Organ Precursor Cells in Drosophila melanogaster Epithelium

International audienceThe Notch communication pathway, discovered in Drosophila over 100 years ago, regulates a wide range of intra-lineage decisions in metazoans. The division of the Drosophila mechanosensory organ precursor is the archetype of asymmetric cell division in which differential Notch activation takes place at cytokinesis. Here, we review the molecular mechanisms by which epithelial cell polarity, cell cycle and intracellular trafficking participate in controlling the directionality, subcellular localization and temporality of mechanosensitive Notch receptor activation in cytokinesis

Soyez agiles dans les A.L.P.E.S. ! Une pédagogie en mode agile.

National audienceThis article proposes a feedback on the generalization of an educational innovation that aims at the integration of agile approaches of management project in educational context. Named A.L.P.E.S. (which means in French Approches agiLes Pour l’Enseignement Supérieur), this innovation proposes a toolbox based on agile approaches used in the corporate world by adapting them to higher education. Through numerous feedbacks in various contexts, we present the generalization of our approach and the tools chosen by the teachers. A summary is given with the considered improvements.Cet article donne un retour sur la généralisation d’une innovation pédagogique proposant l’intégration des approches agiles de gestion de projets dans des enseignements utilisant la pédagogie par projet. Baptisées les A.L.P.E.S. (Approches agiLes Pour l’Enseignement Supérieur), cette innovation propose une boîte à outils tirés des approches agiles utilisées dans le monde de l’entreprise en les adaptant à la pédagogie dans l’enseignement supérieur. Au travers des retours de nombreuses mises en place des A.L.P.E.S. dans divers contextes, nous présentons la généralisation de notre approche et les outils choisis par les enseignants. Un bilan est donné avec les pistes d’amélioration envisagées

Soyez agiles dans les A.L.P.E.S. ! Une pédagogie en mode agile.

National audienceThis article proposes a feedback on the generalization of an educational innovation that aims at the integration of agile approaches of management project in educational context. Named A.L.P.E.S. (which means in French Approches agiLes Pour l’Enseignement Supérieur), this innovation proposes a toolbox based on agile approaches used in the corporate world by adapting them to higher education. Through numerous feedbacks in various contexts, we present the generalization of our approach and the tools chosen by the teachers. A summary is given with the considered improvements.Cet article donne un retour sur la généralisation d’une innovation pédagogique proposant l’intégration des approches agiles de gestion de projets dans des enseignements utilisant la pédagogie par projet. Baptisées les A.L.P.E.S. (Approches agiLes Pour l’Enseignement Supérieur), cette innovation propose une boîte à outils tirés des approches agiles utilisées dans le monde de l’entreprise en les adaptant à la pédagogie dans l’enseignement supérieur. Au travers des retours de nombreuses mises en place des A.L.P.E.S. dans divers contextes, nous présentons la généralisation de notre approche et les outils choisis par les enseignants. Un bilan est donné avec les pistes d’amélioration envisagées