Topological Control of Life and Death in Non-Proliferative Epithelia

Programmed cell death is one of the most fascinating demonstrations of the plasticity of biological systems. It is classically described to act upstream of and govern major developmental patterning processes (e.g. inter-digitations in vertebrates, ommatidia in Drosophila). We show here the first evidence that massive apoptosis can also be controlled and coordinated by a pre-established pattern of a specific ‘master cell’ population. This new concept is supported by the development and validation of an original model of cell patterning. Ciona intestinalis eggs are surrounded by a three-layered follicular organization composed of 60 elongated floating extensions made of as many outer and inner cells, and indirectly spread through an extracellular matrix over 1200 test cells. Experimental and selective ablation of outer and inner cells results in the abrogation of apoptosis in respective remaining neighbouring test cells. In addition incubation of outer/inner follicular cell-depleted eggs with a soluble extract of apoptotic outer/inner cells partially restores apoptosis to apoptotic-defective test cells. The 60 inner follicular cells were thus identified as ‘apoptotic master’ cells which collectively are induction sites for programmed cell death of the underlying test cells. The position of apoptotic master cells is controlled by topological constraints exhibiting a tetrahedral symmetry, and each cell spreads over and can control the destiny of 20 smaller test cells, which leads to optimized apoptosis signalling

The Canadian Childhood Nephrotic Syndrome (CHILDNEPH) project: Overview of design and methods

Background: Nephrotic syndrome is a commonly acquired kidney disease in children that causes significant morbidity due to recurrent episodes of heavy proteinuria. The management of childhood nephrotic syndrome is known to be highly variable among physicians and care centres. Objectives: The primary objective of the study is to determine centre-, physician-, and patient-level characteristics associated with steroid exposure and length of steroid treatment. We will also determine the association of dose and duration of steroid treatment and time to first relapse as a secondary aim. An embedded qualitative study utilizing focus groups with health care providers will enrich the quantitative results by providing an understanding of the attitudes, beliefs and local contextual factors driving variation in care. Design: Mixed-methods study; prospective observational cohort (quantitative component), with additional semi-structured focus groups of healthcare professionals (qualitative component). Setting: National study, comprised of all 13 Canadian pediatric nephrology clinics. Patients: 400 patients under 18 years of age to be recruited over 2.5 years. Measurements: Steroid doses for all episodes (first presentation, first and subsequent relapses) tracked over course of the study. Physician and centre-level characteristics catalogued, with reasons for treatment preferences documented during focus groups. Methods: All patients tracked prospectively over the course of the study, with data comprising a prospective registry. One focus group at each site to enrich understanding of variation in care. Limitations: Contamination of treatment protocols between physicians may occur as a result of concurrent focus groups. Conclusions: Quantitative and qualitative results will be integrated at end of study and will collectively inform strategies for the development and implementation of standardized evidence-based protocols across centres

Multi-probe analysis of the galaxy cluster CL J1226.9+3332: Hydrostatic mass and hydrostatic-To-lensing bias

The precise estimation of the mass of galaxy clusters is a major issue for cosmology. Large galaxy cluster surveys rely on scaling laws that relate cluster observables to their masses. From the high-resolution observations of ∼45 galaxy clusters with the NIKA2 and XMM-Newton instruments, the NIKA2 Sunyaev-Zela'dovich Large Program should provide an accurate scaling relation between the thermal Sunyaev-Zela'dovich effect and the hydrostatic mass. In this paper we present an exhaustive analysis of the hydrostatic mass of the well-known galaxy cluster CL J1226.9+3332, the highest-redshift cluster in the NIKA2 Sunyaev-Zela'dovich Large Program at z=0.89. We combined the NIKA2 observations with thermal Sunyaev-Zela'dovich data from the NIKA, Bolocam, and MUSTANG instruments and XMM-Newton X-ray observations, and tested the impact of the systematic effects on the mass reconstruction. We conclude that slight differences in the shape of the mass profile can be crucial when defining the integrated mass at R500, which demonstrates the importance of the modelling in the mass determination. We prove the robustness of our hydrostatic mass estimates by showing the agreement with all the results found in the literature. Another key factor for cosmology is the bias of the masses estimated assuming the hydrostatic equilibrium hypothesis. Based on the lensing convergence maps from the Cluster Lensing And Supernova survey with Hubble (CLASH) data, we obtain the lensing mass estimate for CL J1226.9+3332. From this we are able to measure the hydrostatic-To-lensing mass bias for this cluster, which spans from 1-bHSE/lens∼0.7 to 1, presenting the impact of data sets and mass reconstruction models on the bias

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Approximation of single layer distributions by Dirac masses in Finite Element computations

We are interested in the finite element solution of elliptic problems with a right-hand side of the single layer distribution type. Such problems arise when one aims at accounting for a physical hypersurface (or line, for bi-dimensional problem), but also in the context of fictitious domain methods, when one aims at accounting for the presence of an inclusion in a domain (in that case the support of the distribution is the boundary of the inclusion). The most popular way to handle numerically the single layer distribution in the finite element context is to spread it out by a regularization technique. An alternative approach consists in approximating the single layer distribution by a combination of Dirac masses. As the Dirac mass in the right hand side does not make sense at the continuous level, this approach raises particular issues. The object of the present paper is to give a theoretical background to this approach. We present a rigorous numerical analysis of this approximation, and we present two examples of application of the main result of this paper. The first one is a Poisson problem with a single layer distribution as a right-hand side and the second one is another Poisson problem where the single layer distribution is the Lagrange multiplier used to enforce a Dirichlet boundary condition on the boundary of an inclusion in the domain. Theoretical analysis is supplemented by numerical experiments in the last section

Caractérisation de l'apoptose des cellules folliculaires de l'oeuf de "Ciona intestinalis"

MONTPELLIER-BU Sciences (341722106) / SudocSudocFranceF

Détection d'Objets Faibles près de l'Anneau des Géostationnaires

L'existence de nombreux débris spatiaux préoccupe de plus en plus les agences spatiales en raison des risques d'impact. Si l'utilisation de radars s'impose pour les orbites basses, pour les orbites géostationnaires l'observation optique reste le seul moyen de détection pour des petits objets. Nous avons étudié les possibilités de détection sur cette orbite avec le télescope de Schmidt de l'Observatoire de la Côte d'Azur. Nous avons mis en oeuvre une caméra CCD de 2000 x 2000 qui nous a amené à développer un logiciel de détection des candidats, avec mesure de leur position et de leur flux et détermination de leurs paramètres orbitaux. La méthode de traitement des images est basée sur la soustraction des traînées avec un seuillage de l'image tenant compte de l'environnement local. Une campagne d'exploitation du logiciel est en cours

D’Arcy Thompson aurait-il prédit un contrôle topologique de l’apoptose ?

International audienceThe laws that drive morphogenesis remain a major biological question. Today's views emphasize molecular autonomous processes rather than physical and mechanical constraints proposed by d'Arcy Thompson earlier on. In Ciona intestinalis oocyte, follicular cells formed by two distinct sets of geometrically-ordered epithelial monolayers positioned over the egg control apoptosis, implying that physically-predetermined shapes play a role in the control of cell determinism. In follicular cells ideally positioned over the spherical geometry of the egg, a drastic, optimized and polarized inward apoptosis sequence directly results from this positioning, suggesting the existence of some apoptotic master cells which control the destiny of neighboring cells. This concept could shed a new light on the origin of massive apoptosis phases that take place during embryogenesis in vertebrates (e.g., cavitation, inter-digitation). It could also be applied to specific therapeutic strategies to fight cancer.Un des défis majeurs en biologie est de comprendre les lois qui régissent la morphogenèse. L’origine de l’apparition des formes est aujourd’hui généralement considérée comme découlant uniquement de processus moléculaires autonomes plutôt que reposant sur des contraintes physiques et mécaniques comme l’avait suggéré d’Arcy Thompson dès 1917. Dans un organisme modèle, l’œuf de Ciona intestinalis, un processus cellulaire, l’apoptose, est sous le contrôle de cellules géométriquement ordonnées au sein de deux monocouches épithéliales étroitement interconnectées (cellules folliculaires) et recouvrant une sphère (ovocyte). Ces observations suggèrent que des formes préexistantes générées par des contraintes physiques participent au contrôle du déterminisme cellulaire. Ainsi, le positionnement « idéal » des cellules folliculaires est exclusivement lié à la géométrie sphérique de l’ovocyte, et l’optimisation de l’apoptose massive observée dans l’épithélium sous-jacent découle directement de ce positionnement. De ces observations est né le concept d’« organisateur apoptotique » : certaines cellules seraient capables de contrôler le destin d’autres cellules, notamment en coordonnant les processus de mort cellulaire programmée. Ce concept pourrait éclairer d’un jour nouveau l’origine des phases d’apoptose massive et coordonnée nécessaires au bon déroulement de l’embryogenèse (cavitation, interdigitation). Il pourrait également être appliqué à certaines stratégies thérapeutiques anticancéreuses