Otx2 Gene Deletion in Adult Mouse Retina Induces Rapid RPE Dystrophy and Slow Photoreceptor Degeneration

International audienceBACKGROUND: Many developmental genes are still active in specific tissues after development is completed. This is the case for the homeobox gene Otx2, an essential actor of forebrain and head development. In adult mouse, Otx2 is strongly expressed in the retina. Mutations of this gene in humans have been linked to severe ocular malformation and retinal diseases. It is, therefore, important to explore its post-developmental functions. In the mature retina, Otx2 is expressed in three cell types: bipolar and photoreceptor cells that belong to the neural retina and retinal pigment epithelium (RPE), a neighbour structure that forms a tightly interdependent functional unit together with photoreceptor cells. METHODOLOGY/PRINCIPAL FINDINGS: Conditional self-knockout was used to address the late functions of Otx2 gene in adult mice. This strategy is based on the combination of a knock-in CreERT2 allele and a floxed allele at the Otx2 locus. Time-controlled injection of tamoxifen activates the recombinase only in Otx2 expressing cells, resulting in selective ablation of the gene in its entire domain of expression. In the adult retina, loss of Otx2 protein causes slow degeneration of photoreceptor cells. By contrast, dramatic changes of RPE activity rapidly occur, which may represent a primary cause of photoreceptor disease. CONCLUSIONS: Our novel mouse model uncovers new Otx2 functions in adult retina. We show that this transcription factor is necessary for long-term maintenance of photoreceptors, likely through the control of specific activities of the RPE

Conserved genes and pathways in primary human fibroblast strains undergoing replicative and radiation induced senescence

Additional file 3: Figure S3. Regulation of genes of Arrhythmogenic right ventricular cardiomyopathy pathway during senescence induction in HFF strains Genes of the “Arrhythmogenic right ventricular cardiomyopathy” pathway which are significantly up- (green) and down- (red) regulated (log2 fold change >1) during irradiation induced senescence (120 h after 20 Gy irradiation) in HFF strains. Orange color signifies genes which are commonly up-regulated during both, irradiation induced and replicative senescence

Euclid preparation TBD. The effect of baryons on the Halo Mass Function

The Euclid photometric survey of galaxy clusters stands as a powerful cosmological tool, with the capacity to significantly propel our understanding of the Universe. Despite being sub-dominant to dark matter and dark energy, the baryonic component in our Universe holds substantial influence over the structure and mass of galaxy clusters. This paper presents a novel model to precisely quantify the impact of baryons on galaxy cluster virial halo masses, using the baryon fraction within a cluster as proxy for their effect. Constructed on the premise of quasi-adiabaticity, the model includes two parameters calibrated using non-radiative cosmological hydrodynamical simulations and a single large-scale simulation from the Magneticum set, which includes the physical processes driving galaxy formation. As a main result of our analysis, we demonstrate that this model delivers a remarkable one percent relative accuracy in determining the virial dark matter-only equivalent mass of galaxy clusters, starting from the corresponding total cluster mass and baryon fraction measured in hydrodynamical simulations. Furthermore, we demonstrate that this result is robust against changes in cosmological parameters and against varying the numerical implementation of the sub-resolution physical processes included in the simulations. Our work substantiates previous claims about the impact of baryons on cluster cosmology studies. In particular, we show how neglecting these effects would lead to biased cosmological constraints for a Euclid-like cluster abundance analysis. Importantly, we demonstrate that uncertainties associated with our model, arising from baryonic corrections to cluster masses, are sub-dominant when compared to the precision with which mass-observable relations will be calibrated using Euclid, as well as our current understanding of the baryon fraction within galaxy clusters.Comment: 18 pages, 10 figures, 4 tables, 1 appendix, abstract abridged for arXiv submissio

Operating a full tungsten actively cooled tokamak: overview of WEST first phase of operation

WEST is an MA class superconducting, actively cooled, full tungsten (W) tokamak, designed to operate in long pulses up to 1000 s. In support of ITER operation and DEMO conceptual activities, key missions of WEST are: (i) qualification of high heat flux plasma-facing components in integrating both technological and physics aspects in relevant heat and particle exhaust conditions, particularly for the tungsten monoblocks foreseen in ITER divertor; (ii) integrated steady-state operation at high confinement, with a focus on power exhaust issues. During the phase 1 of operation (2017–2020), a set of actively cooled ITER-grade plasma facing unit prototypes was integrated into the inertially cooled W coated startup lower divertor. Up to 8.8 MW of RF power has been coupled to the plasma and divertor heat flux of up to 6 MW m−2 were reached. Long pulse operation was started, using the upper actively cooled divertor, with a discharge of about 1 min achieved. This paper gives an overview of the results achieved in phase 1. Perspectives for phase 2, operating with the full capability of the device with the complete ITER-grade actively cooled lower divertor, are also described

An automated, cost-effective and scalable, flood-and-drain based root phenotyping system for cereals

Background: Genetic studies on the molecular mechanisms of the regulation of root growth require the characterisation of a specific root phenotype to be linked with a certain genotype. Such studies using classical labour-intensive methods are severely hindered due to the technical limitations that are associated with the impeded observation of the root system of a plant during its growth. The aim of the research presented here was to develop a reliable, cost-effective method for the analysis of a plant root phenotype that would enable the precise characterisation of the root system architecture of cereals. Results: The presented method describes a complete system for automatic supplementation and continuous sensing of culture solution supplied to plants that are grown in transparent tubes containing a solid substrate. The presented system comprises the comprehensive pipeline consisting of a modular-based and remotely-controlled plant growth system and customized imaging setup for root and shoot phenotyping. The system enables an easy extension of the experimental capacity in order to form a combined platform that is comprised of parallel modules, each holding up to 48 plants. The conducted experiments focused on the selection of the most suitable conditions for phenotyping studies in barley: an optimal size of the glass beads, diameters of the acrylic tubes, composition of a medium, and a rate of the medium flow. Conclusions: The developed system enables an efficient, accurate and highly repeatable analysis of the morphological features of the root system of cereals. Because a simple and fully-automated control system is used, the experimental conditions can easily be normalised for different species of cereals. The scalability of the module-based system allows its capacity to be adjusted in order to meet the requirements of a particular experiment

From Architectured Materials to Large-Scale Additive Manufacturing

The classical material-by-design approach has been extensively perfected by materials scientists, while engineers have been optimising structures geometrically for centuries. The purpose of architectured materials is to build bridges across themicroscale ofmaterials and themacroscale of engineering structures, to put some geometry in the microstructure. This is a paradigm shift. Materials cannot be considered monolithic anymore. Any set of materials functions, even antagonistic ones, can be envisaged in the future. In this paper, we intend to demonstrate the pertinence of computation for developing architectured materials, and the not-so-incidental outcome which led us to developing large-scale additive manufacturing for architectural applications

Reclaiming the child left behind: the case for corporate cultural responsibility

Although a reasonable understanding of corporate social responsibility (CSR) exists, one dimension remains largely ignored. That is, the cultural impacts of corporations, or the bearing, at various levels of their business models, activities, and outcomes on the value systems and enduring beliefs of affected people. We introduce the notion of corporate cultural responsibility (CCR). The way corporations address CCR concerns can be reflected according to three stances: cultural destructiveness, cultural carelessness, and cultural prowess. Taken sequentially, they reflect a growing comprehension and increasingly active consideration of CCR concerns by corporations. In turn, we explicitly address issues related to the complex question of determining the cultural responsibilities of corporate actors; specify key CCR-related conceptualizations; and lay a foundation for discussions, debates, and research efforts centered on CCR concerns and rationales

In situ study of the sintering of a lead phosphovanadate in an Environmental Scanning Electron Microscope

cited By 3International audienceThe in situ sintering of a powder of Pb3(VO4) 1.6(PO4)0.4 composition was performed in an Environmental Scanning Electron Microscope. The electric current induced by the electron beam was found to reduce the effective temperature of sintering as well as to accelerate the kinetics of shrinkage of a cluster composed of sub-micrometric grains of material. The presence of the residual current flow in the cluster during observation for in situ experiments helps to reduce the apparent sintering temperatures from 50 to 150 °C compared to conventional heating conditions without current. © 2011 Elsevier B.V. All rights reserved