Negative regulation of EB1 turnover at microtubule plus ends by interaction with microtubule-associated protein ATIP3

International audienceThe regulation of microtubule dynamics is critical to ensure essential cell functions. End binding protein 1 (EB1) is a master regulator of microtubule dynamics that autonomously binds an extended GTP/GDP-Pi structure at growing microtubule ends and recruits regulatory proteins at this location. However, negative regulation of EB1 association with growing microtubule ends remains poorly understood. We show here that microtubule-associated tumor suppressor ATIP3 interacts with EB1 through direct binding of a non-canonical proline-rich motif. Results indicate that ATIP3 does not localize at growing microtubule ends and that in situ ATIP3-EB1 molecular complexes are mostly detected in the cytosol. We present evidence that a minimal EB1-interacting sequence of ATIP3 is both necessary and sufficient to prevent EB1 accumulation at growing microtubule ends in living cells and that EB1-interaction is involved in reducing cell polarity. By fluorescence recovery of EB1-GFP after photobleaching, we show that ATIP3 silencing accelerates EB1 turnover at microtubule ends with no modification of EB1 diffusion in the cytosol. We propose a novel mechanism by which ATIP3-EB1 interaction indirectly reduces the kinetics of EB1 exchange on its recognition site, thereby accounting for negative regulation of microtubule dynamic instability. Our findings provide a unique example of decreased EB1 turnover at growing microtubule ends by cytosolic interaction with a tumor suppressor. INTRODUCTION Microtubules (MTs) are polarized structures that continuously switch between periods of polymerization and depolymerization at their growing (plus) ends. This process, termed MT dynamic instability, allows rapid reorganization of the MT cytoskeleton during essential cell functions such as cell polarity and migration, mitosi

Delta-like 4 inhibits choroidal neovascularization despite opposing effects on vascular endothelium and macrophages.: DLL4's opposing effects in choroidal neovascularization

International audienceInflammatory neovascularization, such as choroidal neovascularization (CNV), occur in the presence of Notch expressing macrophages. DLL4s anti-angiogenic effect on endothelial cells (EC) has been widely recognized, but its influence on Notch signaling on macrophages and its overall effect in inflammatory neovascularization is not well understood. We identified macrophages and ECs as the main Notch 1 and Notch 4 expressing cells in CNV. A soluble fraction spanning Ser28-Pro525 of the murine extracellular DLL4 domain (sDLL4/28-525) activated the Notch pathway, as it induces Notch target genes in macrophages and ECs and inhibited EC proliferation and vascular sprouting in aortic rings. In contrast, sDLL4/28-525 increased pro-angiogenic VEGF, and IL-1β expression in macrophages responsible for increased vascular sprouting observed in aortic rings incubated in conditioned media from sDLL4/28-525 stimulated macrophages. In vivo, Dll4(+/-) mice developed significantly more CNV and sDLL4/28-525 injections inhibited CNV in Dll4(+/-) CD1 mice. Similarly, sDLL4/28-525 inhibited CNV in C57Bl6 and its effect was reversed by a γ-secretase inhibitor that blocks Notch signaling. The inhibition occurred despite increased VEGF, IL-1β expression in infiltrating inflammatory macrophages in sDLL4/28-525 treated mice and might be due to direct inhibition of EC proliferation in laser-induced CNV as demonstrated by EdU labelling in vivo. In conclusion, Notch activation on macrophages and ECs leads to opposing effects in inflammatory neovascularization in situations such as CNV

Global phylogeography of marine synechococcus in coastal areas reveals strong community shifts

Marine Synechococcus comprise a numerically and ecologically prominent phytoplankton group, playing a major role in both carbon cycling and trophic networks in all oceanic regions except in the polar oceans. Despite their high abundance in coastal areas, our knowledge of Synechococcus communities in these environments is based on only a few local studies. Here, we use the global metagenome data set of the Ocean Sampling Day (June 21st, 2014) to get a snapshot of the taxonomic composition of coastal Synechococcus communities worldwide, by recruitment on a reference database of 141 picocyanobacterial genomes, representative of the whole Prochlorococcus, Synechococcus, and Cyanobium diversity. This allowed us to unravel drastic community shifts over small to medium scale gradients of environmental factors, in particular along European coasts. The combined analysis of the phylogeography of natural populations and the thermophysiological characterization of eight strains, representative of the four major Synechococcus lineages (clades I to IV), also brought novel insights about the differential niche partitioning of clades I and IV, which most often co-dominate the Synechococcus community in cold and temperate coastal areas. Altogether, this study reveals several important characteristics and specificities of the coastal communities of Synechococcus worldwide

Differential global distribution of marine picocyanobacteria gene clusters reveals distinct niche-related adaptive strategies

The ever-increasing number of available microbial genomes and metagenomes provides new opportunities to investigate the links between niche partitioning and genome evolution in the ocean, especially for the abundant and ubiquitous marine picocyanobacteria Prochlorococcus and Synechococcus. Here, by combining metagenome analyses of the Tara Oceans dataset with comparative genomics, including phyletic patterns and genomic context of individual genes from 256 reference genomes, we show that picocyanobacterial communities thriving in different niches possess distinct gene repertoires. We also identify clusters of adjacent genes that display specific distribution patterns in the field (eCAGs) and are thus potentially involved in the same metabolic pathway and may have a key role in niche adaptation. Several eCAGs are likely involved in the uptake or incorporation of complex organic forms of nutrients, such as guanidine, cyanate, cyanide, pyrimidine, or phosphonates, which might be either directly used by cells, for example for the biosynthesis of proteins or DNA, or degraded to inorganic nitrogen and/or phosphorus forms. We also highlight the enrichment of eCAGs involved in polysaccharide capsule biosynthesis in Synechococcus populations thriving in both nitrogen- and phosphorus-depleted areas vs. low-iron (Fe) regions, suggesting that the complexes they encode may be too energy-consuming for picocyanobacteria thriving in the latter areas. In contrast, Prochlorococcus populations thriving in Fe-depleted areas specifically possess an alternative respiratory terminal oxidase, potentially involved in the reduction of Fe(III) to Fe(II). Altogether, this study provides insights into how phytoplankton communities populate oceanic ecosystems, which is relevant to understanding their capacity to respond to ongoing climate change

Differential global distribution of marine picocyanobacteria gene clusters reveals distinct niche-related adaptive strategies

The ever-increasing number of available microbial genomes and metagenomes provides new opportunities to investigate the links between niche partitioning and genome evolution in the ocean, especially for the abundant and ubiquitous marine picocyanobacteria Prochlorococcus and Synechococcus. Here, by combining metagenome analyses of the Tara Oceans dataset with comparative genomics, including phyletic patterns and genomic context of individual genes from 256 reference genomes, we show that picocyanobacterial communities thriving in different niches possess distinct gene repertoires. We also identify clusters of adjacent genes that display specific distribution patterns in the field (eCAGs) and are thus potentially involved in the same metabolic pathway and may have a key role in niche adaptation. Several eCAGs are likely involved in the uptake or incorporation of complex organic forms of nutrients, such as guanidine, cyanate, cyanide, pyrimidine, or phosphonates, which might be either directly used by cells, for example for the biosynthesis of proteins or DNA, or degraded to inorganic nitrogen and/or phosphorus forms. We also highlight the enrichment of eCAGs involved in polysaccharide capsule biosynthesis in Synechococcus populations thriving in both nitrogen- and phosphorus-depleted areas vs. low-iron (Fe) regions, suggesting that the complexes they encode may be too energy-consuming for picocyanobacteria thriving in the latter areas. In contrast, Prochlorococcus populations thriving in Fe-depleted areas specifically possess an alternative respiratory terminal oxidase, potentially involved in the reduction of Fe(III) to Fe(II). Altogether, this study provides insights into how phytoplankton communities populate oceanic ecosystems, which is relevant to understanding their capacity to respond to ongoing climate change

Association entre anticorps antithyroïdiens et urticaire chronique et évaluation du traitement par thyroxine

CAEN-BU Médecine pharmacie (141182102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

L'automédication et les personnes âgées

Aujourd'hui, 2.1 millions de personnes ont plus de 80 ans. Dans 10 ans, elles seront 3.3 millions. Cette croissance démographique importante, nous amène en tant que futur médecin traitant, à nous interroger sur cette population représentant une part importante de la clientèle du généraliste. A partir d'un questionnaire, nous allons étudier le comportement des personnes agées de plus de 65 ans dans 2 foyers-logements, un citadin et un rural, face à l'automédication. Nous allons rechercher l'importance de cette automédication et surtout les risques de cette conduite à cette âge de la vie. Nous terminerons donc par les risques en terme de iatrogénie.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Behaviour of nanocrystalline silicon carbide under low energy heavy ion irradiation

International audienceSilicon carbide is one of the most studied materials for core components of the next generation of nuclear plants (Gen IV). In order to overcome its brittle properties, materials with nanometric grain size are considered. In spite of the growing interest for nano-structured materials, only few experiments deal with their behaviour under irradiation. To assess and predict their evolution under working conditions, it is important to characterize their microstructure and structure. To this purpose, we have studied microcrystalline and nanocrystalline samples before and after irradiation at room temperature with 4 MeV Au ions. In fact, it is well established that such irradiation conditions lead to amorphisation of the material, which can be restored after annealing at high temperature. We have performed isochronal annealings of both materials to point out the characteristics of the healing process and eventual differences related to the initial microstructure of the samples. To this purpose Grazing Incidence X-Ray Diffraction has been performed to determine the microstructure and structure parameters. We observe the amorphisation of both samples at similar doses but different annealing kinetics are observed. The amorphous nanocrystalline sample recovers its initial crystalline state at higher temperature than the microcrystalline one. This effect is clearly related to the initial microstructures of the materials. Therefore, the grain size appears as a key parameter for the structural stability and mechanical properties of this ceramic material under irradiation

Interaction of Maf Transcription Factors with Pax-6 Results in Synergistic Activation of the Glucagon Promoter

International audienceIn the endocrine pancreas, ␣-cell-specific expression of the glucagon gene is mediated by DNA-binding proteins that interact with the G1 proximal promoter element. Among these proteins, the paired domain transcription factor Pax-6 has been shown to bind to G1 and to transactivate glucagon gene expression. Close to the Pax-6-binding site, we observed the presence of a binding site for a basic leucine zipper transcription factor of the Maf family. In the present study, we demonstrate the presence of Maf family members in the endocrine pancreas that bind to G1 and transactivate glucagon promoter expression. In transient transfection experiments, we found that the transactivating effect on the glucagon promoter was greatly enhanced by the simultaneous expression of Maf transcription factors and Pax-6. This enhancement on glucagon transactivation could be correlated with the ability of these proteins to interact together but does not require binding of Maf proteins to the G1 element. Furthermore, we found that Maf enhanced the Pax-6 DNA binding capacity. Our data indicate that Maf transcription factors may contribute to glucagon gene expression in the pancreas