Regulation of NKG2D-Dependent NK Cell Functions: The Yin and the Yang of Receptor Endocytosis.

Natural-killer receptor group 2, member D (NKG2D) is a well characterized natural killer (NK) cell activating receptor that recognizes several ligands poorly expressed on healthy cells but up-regulated upon stressing stimuli in the context of cancer or viral infection. Although NKG2D ligands represent danger signals that render target cells more susceptible to NK cell lysis, accumulating evidence demonstrates that persistent exposure to ligand-expressing cells causes the decrease of NKG2D surface expression leading to a functional impairment of NKG2D-dependent NK cell functions. Upon ligand binding, NKG2D is internalized from the plasma membrane and sorted to lysosomes for degradation. However, receptor endocytosis is not only a mechanism of receptor clearance from the cell surface, but is also required for the proper activation of signalling events leading to the functional program of NK cells. This review is aimed at providing a summary of current literature relevant to the molecular mechanisms leading to NKG2D down-modulation with particular emphasis given to the role of NKG2D endocytosis in both receptor degradation and signal propagation. Examples of chronic ligand-induced down-regulation of NK cell activating receptors other than NKG2D, including natural cytotoxicity receptors (NCRs), DNAX accessory molecule-1 (DNAM1) and CD16, will be also discussed

Aerobic Lineage of the Oxidative Stress Response Protein Rubrerythrin Emerged in an Ancient Microaerobic, (Hyper)Thermophilic Environment

Indexación: Web of Science; Scopus.Rubrerythrins (RBRs) are non-heme di-iron proteins belonging to the ferritin-like superfamily. They are involved in oxidative stress defense as peroxide scavengers in a wide range of organisms. The vast majority of RBRs, including classical forms of this protein, contain a C-terminal rubredoxin-like domain involved in electron transport that is used during catalysis in anaerobic conditions. Rubredoxin is an ancient and large protein family of short length (<100 residues) that contains a Fe-S center involved in electron transfer. However, functional forms of the enzyme lacking the rubredoxin-like domain have been reported (e.g., sulerythrin and ferriperoxin). In this study, phylogenomic evidence is presented that suggests that a complete lineage of rubrerythrins, lacking the rubredoxin-like domain, arose in an ancient microaerobic and (hyper)thermophilic environments in the ancestors of the Archaea Thermoproteales and Sulfolobales. This lineage (termed the "aerobic-type" lineage) subsequently evolved to become adapted to environments with progressively lower temperatures and higher oxygen concentrations via the acquisition of two co-localized genes, termed DUF3501 and RFO, encoding a conserved protein of unknown function and a predicted Fe-S oxidoreductase, respectively. Proposed Horizontal Gene Transfer events from these archaeal ancestors to Bacteria expanded the opportunities for further evolution of this RBR including adaption to lower temperatures. The second lineage (termed the cyanobacterial lineage) is proposed to have evolved in cyanobacterial ancestors, maybe in direct response to the production of oxygen via oxygenic photosynthesis during the Great Oxygen Event (GOE). It is hypothesized that both lineages of RBR emerged in a largely anaerobic world with "whiffs" of oxygen and that their subsequent independent evolutionary trajectories allowed microorganisms to transition from this anaerobic world to an aerobic one.http://journal.frontiersin.org/article/10.3389/fmicb.2016.01822/ful

Divergence in Dialogues *

International audienceThis work is part of a project which goal is to understand natural language by taking dialogue as a primitive notion. For this aim, the core of our theoretical framework is a logical theory of interaction, namely Ludics. Ludics is a logical theory developed by J.Y. Girard as an achievement of both proof theoretical and computational theoretical considerations. Above all it is a theory of interaction in the sense that interaction is ontologically the primitive element of Ludics. Ludics being a logical theory, our framework is relevant for grasping logical dimensions of language, especially for studying argumentation but also divergences in dialogue as we show in this paper. In particular complementary aspects of argumentation and divergence in dialogues are modelled in a uniform way: from logics and pragmatics to semantics and syntax. Furthermore we account for several features of dialogues directly at the formal level. Therefore, we may expect a fine-grained representation of various dialogical phenomenas. More precisely we illustrate this last point by describing how different divergences in dialogue may be distinguished in our modelling

Une introduction à la Ludique et à ses applications à la Pragmatique

Ce texte, écrit avec l'aide de spécialistes de la ludique (Marie-Renée Fleury et Myriam Quatrini) introduit à ce difficile sujet. En résumé, la ludique est une nouvelle manière de penser la logique, imaginée par Jean-Yves Girard, qui tente de dépasser le dualisme bien connu entre les preuves (objets syntaxiques) et les modèles (objets sémantiques). En ludique, les preuves s'opposent à des contre-preuves, le tout pouvant être subsumé sous le concept général d'épreuves (appellation proposée par Pierre Livet). On retrouve alors des notions mathématiques générales comme celle d'orthogonalité qui permettent de dessiner l'espace des "disputes". Les figures ainsi obtenues, appelées "dessins", peuvent être interprétées en termes de jeu et sont alors vues aussi comme des "desseins". La logique qu'on espère trouver au terme de cette exploration est celle qui possède les dessins les plus simples et les plus convaincants. Elle peut être la logique linéaire ou une de ses variantes (logique affine?). Le point de vue présenté dans ce papier introductif, qui sert de base à un programme financé par l'ANR (PRELUDE) est qu'on peut trouver dans la ludique un fondement commun à la logique et à la pragmatique des dialogues

Inferences and Dialogues in Ludics

International audience– We propose to use Ludics as a unified framework for the analysis of dialogue and as a reasoning system. Not only Ludics gives a denotational semantics for Linear Logic, but it uses interaction as a primitive notion. We first sketch a model for pragmatical and rhetorical aspects of dialogue after a brief review of the way the interactive aspect of dialogue may be represented in Ludics. Then we show how taking into account inferences that occur during a dialogue, with respect to a ISU-like model of dialogue. Through various examples we give an analysis of deductive inferences as well as processes making facts explicit that take place during knowledge updating

Women with disability across Europe: issues on updated and available data

The collection of comparable estimates of Women with Disability (WwD) is essential for successful policy-making, and can be directly addressed to the reduction of the barriers that WwD have to face so to achieve full participation in all aspects of their lives. In order to minimize and prevent barriers for WwD, a common policy and a research framework is needed within the European countries. Therefore, the aim of this paper is to underline the issues related to availability, type, and comparability of European data about WwD, and to suggest how to overcome some of the open needs. In particular, the International Classification of Functioning, Disability and Health (ICF) issued by the World Health Organization could be the core conceptual model for collecting data and measuring disability, acting as the basis for relevant social policies, since information at all levels on the functioning of WwD is essential for policy purposes

High diversity of methanotrophic bacteria in geothermal soils affected by high methane fluxes

Volcanic and geothermal systems emit endogenous gases by widespread degassing from soils, including CH4, a greenhouse gas 25 times as potent as CO2. Recently, it has been demonstrated that volcanic/geothermal soils act as source, but also as biological filter for methane release to the atmosphere. For long time, volcanic/geothermal soils has been considered inhospitable for methanotrophic microorganisms, but new extremophile methanotrophs belonging to Verrucomicrobia were identified in three different areas (Pozzuoli, Italy; Hell’s Gate, New Zealand; Kamchatka, Russia), explaining anomalous behaviours in methane leakages of several geothermal/volcanic sites. Our aim was to increase the knowledge of the relationship between methane emissions from volcanic/geothermal areas and biological methane oxidation, by investigating a geothermal site of Pantelleria island (Italy). Pantelleria Island hosts a high enthalpy geothermal system characterized by high temperature, high CH4 and very low H2S fluxes. Such characteristics are reflected in potentially great supply of methane for methanotrophs and scarce presence of inhibitors of their activity (H2S and NH3) in the Pantelleria soils. Potential methanotrophic activity within these soils was already evidenced by the CH4/CO2 ratio of the flux measurements which was lower than that of the respective fumarolic manifestations indicating a loss of CH4 during the gas travel towards the earth’s surface. In this study laboratory incubation experiments using soils sampled at Favara Grande, the main hydrothermal area of Pantelleria, showed very high methane consumption rates (up to 9500 ng CH4 h1 g1). Furthermore, microbiological and culture-independent molecular analyses allowed to detect the presence of methanotrophs affiliated to Gamma- and Alpha-Proteobacteria and to the newly discovered acidothermophilic methanotrophs Verrucomicrobia. Culturable methanotrophic Alpha-proteobacteria of the genus Methylocystis were isolated by enrichment cultures. The isolates showed a wide range of tolerance to pH (3.5 – 8) and temperatures (18 – 45 C), and an average methane oxidation rate of 450 ppm/h. A larger diversity of proteobacterial and verrucomicrobial methanotrophs was detected by the amplification of the methane mono-oxygenase gene pmoA. This study demonstrates the coexistence of both the methanotrophic phyla Verrucomicrobia and Proteobacteria in the same geothermal site. The presence of proteobacterial methanotrophs was quite unexpected because they are generally considered not adapted to live in such harsh environments. Their presence at Favara Grande could be explained by not so low soil pH values (> 5) of this specific geothermal site and by the high methane availability. Such species could have found their niches in the shallowest part of the soils, were the temperatures are not so high, thriving on the abundant upraising methane. Understanding the ecology of methanotrophy in geothermal sites will increase our knowledge of their role in methane emissions to the atmosphere

Ubiquitin-dependent endocytosis of NKG2D-DAP10 receptor complexes activates signaling and functions in human NK cells

Cytotoxic lymphocytes share the presence of the activating receptor NK receptor group 2, member D (NKG2D) and the signaling-competent adaptor DNAX-activating protein 10 (DAP10), which together play an important role in antitumor immune surveillance. Ligand stimulation induces the internalization of NKG2D-DAP10 complexes and their delivery to lysosomes for degradation. In experiments with human NK cells and cell lines, we found that the ligand-induced endocytosis of NKG2D-DAP10 depended on the ubiquitylation of DAP10, which was also required for degradation of the internalized complexes. Moreover, through combined biochemical and microscopic analyses, we showed that ubiquitin-dependent receptor endocytosis was required for the activation of extracellular signal-regulated kinase (ERK) and NK cell functions, such as the secretion of cytotoxic granules and the inflammatory cytokine interferon-γ. These results suggest that NKG2D-DAP10 endocytosis represents a means to decrease cell surface receptor abundance, as well as to control signaling outcome in cytotoxic lymphocytes