Stepwise Release of Biologically Active HMGB1 during HSV-2 Infection

BACKGROUND: High mobility group box 1 protein (HMGB1) is a major endogenous danger signal that triggers inflammation and immunity during septic and aseptic stresses. HMGB1 recently emerged as a key soluble factor in the pathogenesis of various infectious diseases, but nothing is known of its behaviour during herpesvirus infection. We therefore investigated the dynamics and biological effects of HMGB1 during HSV-2 infection of epithelial HEC-1 cells. METHODOLOGY/PRINCIPAL FINDINGS: Despite a transcriptional shutdown of HMGB1 gene expression during infection, the intracellular pool of HMGB1 protein remained unaffected, indicating its remarkable stability. However, the dynamics of HMGB1 was deeply modified in infected cells. Whereas viral multiplication was concomitant with apoptosis and HMGB1 retention on chromatin, a subsequent release of HMGB1 was observed in response to HSV-2 mediated necrosis. Importantly, extracellular HMGB1 was biologically active. Indeed, HMGB1-containing supernatants from HSV-2 infected cells induced the migration of fibroblasts from murine or human origin, and reactivated HIV-1 from latently infected T lymphocytes. These effects were specifically linked to HMGB1 since they were blocked by glycyrrhizin or by a neutralizing anti-HMGB1 antibody, and were mediated through TLR2 and the receptor for Advanced Glycation End-products (RAGE). Finally, we show that genital HSV-2 active infections also promote HMGB1 release in vivo, strengthening the clinical relevance of our experimental data. CONCLUSIONS: These observations target HMGB1 as an important actor during HSV-2 genital infection, notably in the setting of HSV-HIV co-infection

A High-Sensitivity Method for Detection and Measurement of HMGB1 Protein Concentration by High-Affinity Binding to DNA Hemicatenanes

BACKGROUND: Protein HMGB1, an abundant nuclear non-histone protein that interacts with DNA and has an architectural function in chromatin, was strikingly shown some years ago to also possess an extracellular function as an alarmin and a mediator of inflammation. This extracellular function has since been actively studied, both from a fundamental point of view and in relation to the involvement of HMGB1 in inflammatory diseases. A prerequisite for such studies is the ability to detect HMGB1 in blood or other biological fluids and to accurately measure its concentration. METHODOLOGY/PRINCIPAL FINDINGS: In addition to classical techniques (western blot, ELISA) that make use of specific anti-HMGB1 antibodies, we present here a new, extremely sensitive technique that is based on the fact that hemicatenated DNA loops (hcDNA) bind HMGB1 with extremely high affinity, higher than the affinity of specific antibodies, similar in that respect to DNA aptamers. DNA-protein complexes formed between HMGB1 and radiolabeled hcDNA are analyzed by electrophoresis on nondenaturing polyacrylamide gels using the band-shift assay method. In addition, using a simple and fast protocol to purify HMGB1 on the basis of its solubility in perchloric acid allowed us to increase the sensitivity by suppressing any nonspecific background. The technique can reliably detect HMGB1 at a concentration of 1 pg per microliter in complex fluids such as serum, and at much lower concentrations in less complex samples. It compares favorably with ELISA in terms of sensitivity and background, and is less prone to interference from masking proteins in serum. CONCLUSION: The new technique, which illustrates the potential of DNA nanoobjects and aptamers to form high-affinity complexes with selected proteins, should provide a valuable tool to further investigate the extracellular functions of HMGB1 and its involvement in inflammatory pathologies

L’ACTION PUBLIQUE EN MATIÈRE D’ALIMENTATION LOCALE. Les compétences accordées par la loi et les règlements aux collectivités locales (régions, départements, communes) dans le domaine de la production, la transformation et la consommation d’aliments locaux.

The aim of this work is to identify the direct or indirect legal competencies of French local authorities (regions, departments, municipalities) in matter of production, processing and consumption of local foods. It is a simplified but complete tool giving an overview of the different legal fields of action for French local authorities, of the overlapping of the competencies or on the contrary their exclusivity (local authorities and State ).This guide has been conceived as an evolving tool according to legal changes and new practices of the actors.The ultimate goal is to develop an online version of this work in order to provides a dynamic interactivity with users.This work was carried out as part of the research project FRUGAL "Urban forms and food governance" (http://projetfrugal.fr/), PSDR 4 (https://www.psdr.fr/).Ce travail a pour objectif d'identifier les compétences légales directes ou indirectes des collectivités territoriales françaises (régions, départements, communes) en matière de production, de transformation et de consommation d’aliments locaux . Il s'agit d'offrir un outil simplifié mais le plus complet possible permettant de saisir rapidement les différents champs d’action légaux à la disposition des collectivités locales et d'observer la superposition des compétences ou au contraire leur exclusivité (collectivités territoriales et Etat).Ce guide a été envisagé de manière à ce qu’il puisse évoluer dans le temps en fonction des modifications du droit et de la confrontation des compétences légales avec les pratiques des acteurs.L'objectif final est de développer une version électronique en ligne de ce livret proposant une forme d’interactivité dynamique avec les utilisateurs.Ce travail a été effectué dans le cadre du projet de recherche FRUGAL « Formes urbaines et gouvernance alimentaire » (http://projetfrugal.fr/), PSDR 4 (https://www.psdr.fr/)

Evolution des versants rocheux alpins en moyenne montagne et changement climatique

International audienc

Evolution des versants rocheux alpins en moyenne montagne et changement climatique

International audienc

Modelling the geochemical cycle of boron: Implications for the long-term d11B evolution of seawater and oceanic crust

International audienceThe boron geochemical cycle has been simulated using a time-dependent geochemical box model that was coupled to a onedimension model of seawater–oceanic crust interactions. Boron elemental and isotopic compositions of oceanic rocks as a function of depth were calculated by mass balance, using the temperature and porosity profiles of the crust as well as the available experimental and empirical distribution coefficients and fractionation factors between mineral and water. Ranges of boron elemental and isotopic variations of seawater were calculated for crust–seawater interactions that take place from the ridge-axis to the off-axis closure of the hydrothermal system. The present-day d11B of seawater (40‰) could represent a steady-state value. However, depending on crustal permeability, lifetime of water–rock interactions, and expansion rate of the oceanic ridge, the d11B of seawater may vary from 30‰ to 50‰ at the 10 million year scale. Some boron isotope compositions of Cretaceous biogenic carbonates and ophiolitic serpentinites from Oman are comparable to modern rock samples, suggesting that the d11B of Cretaceous seawater was close to the present-day value. Low d11B values of some biogenic carbonates cannot be attributed to low pH values of past seawater, but more probably to d11B variations of seawate or diagenetic alteration by crustal aqueous fluids. Boron isotope composition of hydrothermally altered serpentines could be considered as a promising proxy of the seawater composition

Jeux de données issus des recherches sur le gisement de Waziers le Bas-Terroir (opérations 2013-2015) en lien avec les articles des volumes 33-4 (2022) et 34-1 (2023) de la revue Quaternaire.

International audienceThe present dataset comes from rechearch led on the Waziers le Bas-Terroir site since 2013 (Hérisson et al., 2022, for detailsabout the research and fieldwork). The present data paper aims to share with the scientific community the raw or supplementary datato those presented in the papers of the volume 1 and 2 dedicated to Waziers le Bas-Terroir eemian site, corresponding to volumes33-4 (2022) et 34-1 (2023) of Quaternaire. Data (except for data set #5) is stored in the Research Data Warehouse for Human andSocial Sciences called Nakala. Nakala data is stored on servers managed by Huma-Num, at the IN2P3 data centre in France. Alldata in this data paper are grouped in a collection entitled « Waziers le Bas-Terroir tome 1 & 2 Data paper revue Quaternaire » andaccessible through the DOI 10.34847/nkl.de671e05 or through the DOI indicated for each file in the data paper. Data set #5 has beendeposited on the PRIDE platform PRIDE (PRoteomics IDEntifications Database). The files are provided under a licence CreativeCommons Attribution Non Commercial No Derivates 4.0 International (CC-BY-NC-ND-4.0).Les jeux de données présentés ci-après sont issus des recherches menées sur le gisement de Waziers le Bas-Terroir depuis 2013 (Hérisson et al., 2022, pour les détails des recherches et opérations de terrain). Le présent data paper vise donc à mettre à disposition de la communauté scientifique des données brutes ou complémentaires à celles présentées au sein des articles des tomes 1 et 2 consacrés au gisement eemien de Waziers le Bas-Terroir, à savoir les numéros 33-4 (2022) et 34-1 (2023) de la revue Quaternaire. Les données (hormis le set de données n°5) sont stockées au sein de l'entrepôt de données de recherche pour les Sciences Humaines et Sociales Nakala. Les données de Nakala sont stockées sur des serveurs gérés par Huma-Num, au centre de calcul de l'IN2P3 en France. Toutes les données du présent data paper sont regroupées au sein d'une collection intitulée « Waziers le Bas-Terroir tome 1 & 2 Data paper revue Quaternaire » et accessible via le DOI 10.34847/nkl.de671e05 ou via le DOI indiqué pour chaque fichier dans le data paper. Le set de données n°5 a été déposé sur la plateforme PRIDE (PRoteomics IDEntifications Database). Les fichiers sont mis à disposition sous une licence Creative Commons Attribution Non Commercial No Derivates 4.0 International (CC-BY-NC-ND-4.0)

L’ACTION PUBLIQUE EN MATIÈRE D’ALIMENTATION LOCALE. Les compétences accordées par la loi et les règlements aux collectivités locales (régions, départements, communes) dans le domaine de la production, la transformation et la consommation d’aliments locaux.

The aim of this work is to identify the direct or indirect legal competencies of French local authorities (regions, departments, municipalities) in matter of production, processing and consumption of local foods. It is a simplified but complete tool giving an overview of the different legal fields of action for French local authorities, of the overlapping of the competencies or on the contrary their exclusivity (local authorities and State ).This guide has been conceived as an evolving tool according to legal changes and new practices of the actors.The ultimate goal is to develop an online version of this work in order to provides a dynamic interactivity with users.This work was carried out as part of the research project FRUGAL "Urban forms and food governance" (http://projetfrugal.fr/), PSDR 4 (https://www.psdr.fr/).Ce travail a pour objectif d'identifier les compétences légales directes ou indirectes des collectivités territoriales françaises (régions, départements, communes) en matière de production, de transformation et de consommation d’aliments locaux . Il s'agit d'offrir un outil simplifié mais le plus complet possible permettant de saisir rapidement les différents champs d’action légaux à la disposition des collectivités locales et d'observer la superposition des compétences ou au contraire leur exclusivité (collectivités territoriales et Etat).Ce guide a été envisagé de manière à ce qu’il puisse évoluer dans le temps en fonction des modifications du droit et de la confrontation des compétences légales avec les pratiques des acteurs.L'objectif final est de développer une version électronique en ligne de ce livret proposant une forme d’interactivité dynamique avec les utilisateurs.Ce travail a été effectué dans le cadre du projet de recherche FRUGAL « Formes urbaines et gouvernance alimentaire » (http://projetfrugal.fr/), PSDR 4 (https://www.psdr.fr/)

Freins et leviers de l’adaptation au changement climatique : représentations des acteurs de moyenne montagne

International audienceIn the context of climate change, authorities must take actions for adapting to local impacts. However, one can notice that they have difficulties doing so. In this study, we aim at identifying the obstacles to action, or on the contrary, what can be levers for adaptation. We investigated mid altitude mountains at mid latitudes in the French Alps (western Europe), where the impacts of climate change are already clear. A double survey has been realized with authorities over the French region Auvergne Rhône-Alpes, for observing their perception of levers and obstacles for adaptation at local scale. Nuancing literature, the results states that the failure to bring action at local scale is not necessarily due to a weak awareness of climate change impacts, but rather to uncertainties in i) possible futures of climate and territories, ii) knowledge brokering on global changes and their local impacts and iii) relevance of actions undertaken. Interviewees, local actors directly involved into the definition of adaptation strategies, reveal a need of places for dialogue and sharing of experiences on adaptation, but also a need for guidance to initiate major changes toward reducing vulnerabilities of mid altitude mountains.Le fait de prendre en considération l'environnement, et notamment sa protection, est de plus en plus d'actualité. Le présent numéro se concentre plus spécifiquement sur diverses applications en matière d'aménagement territorial en lien avec l'environnement et avec la protection de ce dernier et c'est autour de cette thématique que se déclinent les différentes contributions, à travers diverses échelles et dans des contextes géographiques variés et fort éclairants. Même s'ils sont appliqués à des réalités politiques, culturelles, légales différentes, les articles réunis ici ont pour caractéristique commune d'apporter un éclairage nouveau, pouvant enrichir d'autres contextes