The Arrestin Fold: Variations on a Theme

Endocytosis of ligand-activated plasma membrane receptors has been shown to contribute to the regulation of their downstream signaling. β-arrestins interact with the phosphorylated tail of activated receptors and act as scaffolds for the recruitment of adaptor proteins and clathrin, that constitute the machinery used for receptor endocytosis. Visual- and β-arrestins have a two-lobe, immunoglobulin-like, β-strand sandwich structure. The recent resolution of the crystal structure of VPS26, one of the retromer subunits, unexpectedly evidences an arrestin fold in this protein, which is otherwise unrelated to arrestins. From a functional point of view, VPS26 is involved in the retrograde transport of the mannose 6-P receptor from the endosomes to the trans-Golgi network. In addition to the group of genuine arrestins and Vps26, mammalian cells harbor a vast repertoire of proteins that are related to arrestins on the basis of their PFAM Nter and Cter arrestin- domains, which are named Arrestin Domain- Containing proteins (ADCs). The biological role of ADC proteins is still poorly understood. The three subfamilies have been merged into an arrestin-related protein clan

The arrestin-domain containing protein AdcA is a response element to stress.

International audienceBACKGROUND: Cell behaviour is tightly determined by sensing and integration of extracellular changes through membrane detectors such as receptors and transporters and activation of downstream signalling cascades. Arrestin proteins act as scaffolds at the plasma membrane and along the endocytic pathway, where they regulate the activity and the fate of some of these detectors. Members of the arrestin clan are widely present from unicellular to metazoa, with roles in signal transduction and metabolism. As a soil amoeba, Dictyostelium is frequently confronted with environmental changes likely to compromise survival. Here, we investigated whether the recently described arrestin-related protein AdcA is part of the cell response to stresses. RESULTS: Our data provide evidence that AdcA responds to a variety of stresses including hyperosmolarity by a transient phosphorylation. Analysis in different mutant backgrounds revealed that AdcA phosphorylation involves pathways other than the DokA and cGMP-dependent osmostress pathways, respectively known to regulate PKA and STATc, key actors in the cellular response to conditions of hyperosmolarity. Interestingly, however, both AdcA and STATc are sensitive to changes in the F-actin polymerization status, suggesting a common primary sensor/trigger and linking the stress-sensitive kinase responsive for AdcA phosphorylation to the actin cytoskeleton. We also show that STATc-dependent transcriptional activity is involved for the timely dephosphorylation of AdcA in cells under stress. CONCLUSION: Under osmotic stress, AdcA undergoes a phosphorylation-dephosphorylation cycle involving a stress-sensitive kinase and the transcription regulator STATc. This transient post-transcriptional modification may allow a regulation of AdcA function possibly to optimize the cellular stress response

Aspect-Oriented Software Development with Java Aspect Components

In the last four years, our research project dealt with separation of concerns for distributed programming environments and applications. This research effort led to the implementation of the Java Aspect Component (JAC) framework for aspect-oriented programming (AOP) in Java. Among the many requirements for distribution, flexibility and adaptability play a stringent role. The high variability of executing conditions (in terms of resources, servers availability, faults, ...) also brings the need for powerful programming paradigms. This led us to develop a dynamic model of AOP which, unlike statically compiled approaches, allows to on-the-fly deploy and undeploy aspects on top of running applications. This model comes with an UML notation and an implementation. An IDE is provided with JAC to support all the development steps of an aspect oriented application, from its design, to its implementation, to its deployment

Moulins-sur-Orne, Argentan – Brûle-Piquet, Les Hogues

Situé dans la continuité de la Plaine de Caen, le paysage autour d’Argentan est marqué par une concentration rare de quatre types de sites : les enceintes à fossé interrompu, les minières à silex, les sites funéraires et les occupations domestiques/habitats. À Moulins-sur-Orne, les observations du xixe s. mentionnent un monument aux dimensions très importantes (jusqu’à 75 m de longueur). La structure mégalithique sous tumulus est compartimentée en plusieurs chambres accueillant les inhumation..

FYVE-Dependent Endosomal Targeting of an Arrestin-Related Protein in Amoeba

International audienceBACKGROUND: Visual and β-arrestins are scaffolding proteins involved in the regulation of receptor-dependent intracellular signaling and their trafficking. The arrestin superfamilly includes several arrestin domain-containing proteins and the structurally related protein Vps26. In Dictyostelium discoideum, the arrestin-domain containing proteins form a family of six members, namely AdcA to -F. In contrast to canonical arrestins, Dictyostelium Adc proteins show a more complex architecture, as they possess, in addition to the arrestin core, other domains, such as C2, FYVE, LIM, MIT and SAM, which potentially mediate selective interactions with either lipids or proteins. METHODOLOGY AND PRINCIPAL FINDINGS: A detailed analysis of AdcA has been performed. AdcA extends on both sides of the arrestin core, in particular by a FYVE domain which mediates selective interactions with PI(3)P, as disclosed by intrinsic fluorescence measurements and lipid overlay assays. Localization studies showed an enrichment of tagged- and endogenous AdcA on the rim of early macropinosomes and phagosomes. This vesicular distribution relies on a functional FYVE domain. Our data also show that the arrestin core binds the ADP-ribosylation factor ArfA, the unique amoebal Arf member, in its GDP-bound conformation. SIGNIFICANCE: This work describes one of the 6 arrestin domain-containing proteins of Dictyostelium, a novel and atypical member of the arrestin clan. It provides the basis for a better understanding of arrestin-related protein involvement in trafficking processes and for further studies on the expanding roles of arrestins in eukaryotes

Antibacterial Resistance, Wayampis Amerindians, French Guyana

Drug resistance in fecal bacteria was high in Wayampis Amerindians who did not take antibacterial agents and were not hospitalized for 1 year. In the Wayampis Amerindians, an isolated traditional community in French Guyana, antibacterial use was 0.64 treatments per person per year. Hospitalization rate was 6.1% per year. Antibacterial drug–resistant bacteria can spread in persons who are not taking antibacterial agents

Multidrug-resistant tuberculosis and migration to Europe.

Multidrug-resistant tuberculosis (MDR-TB) in low-incidence countries in Europe is more prevalent among migrants than the native population. The impact of the recent increase in migration to EU and EEA countries with a low incidence of TB (<20 cases per 100 000) on MDR-TB epidemiology is unclear. This narrative review synthesizes evidence on MDR-TB and migration identified through an expert panel and database search. A significant proportion of MDR-TB cases in migrants result from reactivation of latent infection. Refugees and asylum seekers may have a heightened risk of MDR-TB infection and worse outcomes. Although concerns have been raised around 'health tourists' migrating for MDR-TB treatment, numbers are probably small and data are lacking. Migrants experience significant barriers to testing and treatment for MDR-TB, exacerbated by increasingly restrictive health systems. Screening for latent MDR-TB is highly problematic because current tests cannot distinguish drug-resistant latent infection, and evidence-based guidance for treatment of latent infection in contacts of MDR patients is lacking. Although there is evidence that transmission of TB from migrants to the general population is low-it predominantly occurs within migrant communities-there is a human rights obligation to improve the diagnosis, treatment and prevention of MDR-TB in migrants. Further research is needed into MDR-TB and migration, the impact of screening on detection or prevention, and the potential consequences of failing to treat and prevent MDR-TB among migrants in Europe. An evidence-base is urgently needed to inform guidelines for effective approaches for MDR-TB management in migrant populations in Europe

The PLIN4 Variant rs8887 Modulates Obesity Related Phenotypes in Humans through Creation of a Novel miR-522 Seed Site

PLIN4 is a member of the PAT family of lipid storage droplet (LSD) proteins. Associations between seven single nucleotide polymorphisms (SNPs) at human PLIN4 with obesity related phenotypes were investigated using meta-analysis followed by a determination if these phenotypes are modulated by interactions between PLIN4 SNPs and dietary PUFA. Samples consisted of subjects from two populations of European ancestry. We demonstrated association of rs8887 with anthropometrics. Meta-analysis demonstrated significant interactions between the rs8887 minor allele with PUFA n3 modulating anthropometrics. rs884164 showed interaction with both n3 and n6 PUFA modulating anthropometric and lipid phenotypes. In silico analysis of the PLIN4 3′UTR sequence surrounding the rs8887 minor A allele predicted a seed site for the human microRNA-522 (miR-522), suggesting a functional mechanism. Our data showed that a PLIN4 3′UTR luciferase reporter carrying the A allele of rs8887 was reduced in response to miR-522 mimics compared to the G allele. These results suggest variation at the PLIN4 locus, and its interaction with PUFA as a modulator of obesity related phenotypes, acts in part through creation of a miR-522 regulatory site

Le langage du FN ou l’appel du vide : l’inflexion totalitaire de la langue du Front National

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