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SUMOylation is a post-translational modification essential to cell homeostasis. A tightly controlled equilibrium between SUMOylation and deSUMOylation processes is also critical to the neuronal function including neurotransmitter release and synaptic transmission and plasticity. Disruption of the SUMOylation homeostasis in neurons is associated with several neurological disorders. The balance between the SUMOylation and deSUMOylation of substrate proteins is maintained by a group of deSUMOylation enzymes called SENPs. We previously showed that the activation of type 5 metabotropic glutamate receptors (mGlu5R) first triggers a rapid increase in synaptic SUMOylation and then upon the sustained activation of these receptors, the deSUMOylase activity of SENP1 allows the increased synaptic SUMOylation to get back to basal levels. Here, we combined the use of pharmacological tools with subcellular fractionation and live-cell imaging of individual hippocampal dendritic spines to demonstrate that the synaptic accumulation of the deSUMOylation enzyme SENP1 is bidirectionally controlled by the activation of type 1 mGlu1 and mGlu5 receptors. Indeed, the pharmacological blockade of mGlu1R activation during type 1 mGluR stimulation leads to a faster and greater accumulation of SENP1 at synapses indicating that mGlu1R acts as a brake to the mGlu5R-dependent deSUMOylation process at the post-synapse. Altogether, our findings reveal that type 1 mGluRs work in opposition to dynamically tune the homeostasis of SUMOylation at the mammalian synapse.

La revue de sante scolaire et universitaire - Sous presse. Epreuves corrigees par l'auteur. Disponible en ligne depuis le jeudi 3 decembre 2020

A new diagnostic tool to study dielectric barrier discharges (DBDs) at atmospheric pressure by local electrical measurements is introduced. The square ground electrode is divided into 64 square segments (3.44 mm side length) so as to measure the discharge currents and gas voltages with spatial resolutions, which allows a 2D mapping. The electrical measurement results are validated by a comparison with short exposure time photographs taken from the top view of the discharge cell. For this purpose, we changed the local discharge behavior by varying locally the gas gap and the barrier capacitance and also by using a gas flow. Then, in both situations, the breakdown voltage depends on the position, and the discharge current and gas voltage are different as well. The measurements performed for a planar DBD in nitrogen with admixed nitrous oxide gas show that even if the discharge operates in a diffuse regime, the discharge does not behave exactly homogeneously on the whole surface area. The resulting electrical parameters allow us to refine the understanding of planar DBDs. The discharge activity changes the gas composition and thus, the level of preionization in the direction of the gas flow. This influences the local breakdown voltage and thus, the discharge morphology and local power density on the surface. The use of this new electrical diagnostic tool will allow us to refine the analysis of the spatial development of the discharge. This work gives some clues to improve the spatial resolution of this tool in the future.

International audience; This collection brings together thirty-three articles by Jean Andreau, all of which have already been published elsewhere, in journals or collective works. The oldest date from the 1970s and the most recent from the 2010s.Some of them deal with the work of the great Russian historian of the ancient economy, Michel I. Rostovtzeff. The others deal with some of the major aspects of the economic and social life of the ancient Roman world: currency and markets; the economic and financial policy of the Empire; the economic interests of the elites; the milieu of the former slaves, the freedmen, who played a major role in manufacturing and trade; and finally, social relations and social mobility.; Ce recueil réunit trente-trois articles de Jean Andreau, tous déjà publiés ailleurs, dans des revues ou des ouvrages collectifs. Les plus anciens datent des années 1970 et les plus récents des années 2010.Quelques-uns traitent de l’œuvre du grand historien russe de l’économie antique, Michel I. Rostovtzeff. Les autres portent sur quelques grands aspects de la vie économique et sociale du monde romain antique : la monnaie et les marchés ; la politique économique et financière de l’Empire ; les intérêts économiques des élites ; le milieu des anciens esclaves, des affranchis, qui jouaient un grand rôle dans la fabrication et le commerce ; enfin, les relations sociales et la mobilité sociale.

Fragile X syndrome (FXS) is the most frequent form of inherited intellectual disability and the best-described monogenic cause of autism. CGG-repeat expansion in the FMR1 gene leads to FMR1 silencing, loss-of-expression of the Fragile X Mental Retardation Protein (FMRP), and is a common cause of FXS. Missense mutations in the FMR1 gene were also identified in FXS patients, including the recurrent FMRP-R138Q mutation. To investigate the mechanisms underlying FXS caused by this mutation, we generated a knock-in mouse model (Fmr1R138Q) expressing the FMRP-R138Q protein. We demonstrate that, in the hippocampus of the Fmr1R138Q mice, neurons show an increased spine density associated with synaptic ultrastructural defects and increased AMPA receptor-surface expression. Combining biochemical assays, high-resolution imaging, electrophysiological recordings, and behavioural testing, we also show that the R138Q mutation results in impaired hippocampal long-term potentiation and socio-cognitive deficits in mice. These findings reveal the functional impact of the FMRP-R138Q mutation in a mouse model of FXS., The R138Q mutation in the Fragile X Mental Retardation 1 (FMR1) gene has been associated with Fragile X syndrome (FXS). Here, the authors present a Fmr1R138Q Knock-In mouse model and show that R138Q mutation results in impaired long-term potentiation and socio-cognitive performance in these mice.

Fragile X syndrome (FXS) is the most frequent form of inherited intellectual disability and the best-described monogenic cause of autism. FXS is usually caused by a CGG-repeat expansion in the FMR1 gene leading to its silencing and the loss-of-expression of the Fragile X Mental Retardation Protein (FMRP). Missense mutations were also identified in FXS patients, including the recurrent FMRP-R138Q mutation. To investigate the mechanisms underlying FXS in these patients, we generated a knock-in mouse model (Fmr1R138Q) expressing the FMRP-R138Q protein. We demonstrate that the Fmr1R138Q hippocampus has an increased spine density associated with postsynaptic ultrastructural defects and increased AMPA receptor surface expression. Combining biochemical assays, high-resolution imaging and electrophysiological recordings, we also show that the mutation impairs the hippocampal long-term potentiation (LTP) and leads to socio-cognitive deficits in Fmr1R138Q mice. These findings reveal that the R138Q mutation impacts the synaptic functions of FMRP and highlight potential mechanisms causing FXS in FMRP-R138Q patients.

An increasing number of offshore structures are being deployed worldwide to meet the growing demand for renewable energy. Besides energy production, these structures can also provide new artificial habitats to a diversity of fish and crustacean species. This study characterises how concrete mattresses that stabilise the submarine power cable of a tidal energy test site can increase habitat capacity for benthic megafauna. A five-year monitoring, which relied on both visual counts and video-based surveys by divers, revealed that these mattresses provide a suitable habitat for 5 taxa of large crustaceans and fish. In particular, two commercially valuable species, i.e. the edible crab Cancer pagurus and the European lobster Homarus gammarus, showed a constant occupancy of these artificial habitats throughout the course of the project. The shape and the number of shelters available below individual mattresses largely determine potential for colonisation by mobile megafauna. Local physical characteristics of the implantation site (e.g. substratum type, topography, exposition to current etc.) significantly impact amount and type of shelters provided by the concrete mattresses. Thus, to characterise habitat potential of artificial structures, it is not only essential to consider (i) the design of the structures, but also to (ii) account for their interactions with local environmental conditions when deployed on the seafloor.

International audience; The Fragile X Mental Retardation Protein (FMRP) is an RNA-binding protein essential to the regulation of local translation at synapses. In the mammalian brain, synapses are constantly formed and eliminated throughout development to achieve functional neuronal networks. At the molecular level, thousands of proteins cooperate to accomplish efficient neuronal communication. Therefore, synaptic protein levels and their functional interactions need to be tightly regulated. FMRP generally acts as a translational repressor of its mRNA targets. FMRP is the target of several post-translational modifications (PTMs) that dynamically regulate its function. Here we provide an overview of the PTMs controlling the FMRP function and discuss how their spatiotemporal interplay contributes to the physiological regulation of FMRP. Importantly, FMRP loss-of-function leads to Fragile X syndrome (FXS), a rare genetic developmental condition causing a range of neurological alterations including intellectual disability (ID), learning and memory impairments, autistic-like features and seizures. Here, we also explore the possibility that recently reported missense mutations in the FMR1 gene disrupt the PTM homoeostasis of FMRP, thus participating in the aetiology of FXS. This suggests that the pharmacological targeting of PTMs may be a promising strategy to develop innovative therapies for patients carrying such missense mutations.

The fragile X mental retardation protein (FMRP) is an RNA-binding protein involved in translational regulation of mRNAs that play key roles in synaptic morphology and plasticity. The functional absence of FMRP causes the fragile X syndrome (FXS), the most common form of inherited intellectual disability and the most common monogenic cause of autism. No effective treatment is available for FXS. We recently identified the Phosphodiesterase 2A (Pde2a) mRNA as a prominent target of FMRP. PDE2A enzymatic activity is increased in the brain of Fmr1-KO mice, a recognized model of FXS, leading to decreased levels of cAMP and cGMP. Here, we pharmacologically inhibited PDE2A in Fmr1-KO mice and observed a rescue both of the maturity of dendritic spines and of the exaggerated hippocampal mGluR-dependent long-term depression. Remarkably, PDE2A blockade rescued the social and communicative deficits of both mouse and rat Fmr1-KO animals. Importantly, chronic inhibition of PDE2A in newborn Fmr1-KO mice followed by a washout interval, resulted in the rescue of the altered social behavior observed in adolescent mice. Altogether, these results reveal the key role of PDE2A in the physiopathology of FXS and suggest that its pharmacological inhibition represents a novel therapeutic approach for FXS.

International audience; This contribution presents a so far overlooked Celtic coin type which mentions an hitherto unkown Gallic Iulius. It offers a catalogue of the five known copies as well as a tentative interpretation. The coins sport the head of Jupiter Ammon on the observe and a sphinx on the reverse; its minting can be placed in the 30s-20s BC, possibly on the Treveran territory.; Cette contribution présente le catalogue des cinq exemplaires répertoriés, ainsi qu’une tentative d’interprétation d’une émission monétaire méconnue, qui présente notamment l’intérêt de nous faire connaître un nouveau Iulius gaulois. Présentant au droit la tête de Jupiter Ammon et au revers un sphinx, divers indices permettent d’en situer l’émission dans les années 30/20 av. J.-C., peut-être sur le territoire trévire.

International audience; This paper stems from the discovery of a coin consciously deposited in a wall in the course of its construction, at the Villa of Diomedes in Pompeii. Other cases have been recorded and various interpretation advanced. The case studied here, with a coin deposited in a wall already partially erected, has prompted us to reexamine the problem of the so-called “foundation offerings”.; Cette contribution fait suite à la découverte récente d’une monnaie volontairement déposé dans un mur en cours de construction, dans la Villa de Diomède à Pompéi. Plusieurs cas ont déjà été recensés et on a proposé diverses interprétations de cette pratique. C’est la situation particulière de l’exemple étudié ici, dans un mur déjà partiellement monté, qui nous incite à revenir sur le problème de ces « offrandes de fondation ».

Review-article of Holger Komnick, Die Fundmunzen der romischen Zeit aus dem Bereich der Colonia Ulpia Traiana (Xantener Berichte, Bd. 29; Verlag Philipp von Zabern; Darmstadt 2015, with further thoughts on how to publish coin-finds, starting from a paper published by Kris Lockyear in 2007 in Britannia.

Glucocorticoid hormones, via activation of their receptors, promote memory consolidation, but the exact underlying mechanisms remain elusive. We examined how corticosterone regulates AMPA receptor (AMPAR) availability in the synapse, which is important for synaptic plasticity and memory formation. Peptides which specifically block the interaction between N-Ethylmaleimide-Sensitive Factor (NSF) and the AMPAR-subunit GluA2 prevented the increase in synaptic transmission and surface expression of AMPARs known to occur after corticosterone application to hippocampal neurons. Combining a live imaging Fluorescence Recovery After Photobleaching (FRAP) approach with the use of the pH-sensitive GFP-AMPAR tagging revealed that this NSF/GluA2 interaction was also essential for the increase of the mobile fraction and reduction of the diffusion of AMPARs after treating hippocampal neurons with corticosterone. We conclude that the interaction between NSF and GluA2 contributes to the effects of corticosterone on AMPAR function. © 2016 Wiley Periodicals, Inc.

International audience; The attached table gives a catalogue of rural granaries studied and mentioned in the various contributions of the following book: Stéphane Martin, ed., Rural Granaries in Northern Gaul (Sixth Century BC – Fourth Century AD). From Archaeology to Economic History, Radboud Studies in Humanities (Leiden / Boston: Brill, forthcoming).Legend to the table as well as literature are to be found in the attached PDF file.; Le tableur fournit un catalogue des greniers ruraux étudiés et cités dans les différents chapitres du livre suivant : Stéphane Martin, éd., Rural Granaries in Northern Gaul (Sixth Century BC – Fourth Century AD). From Archaeology to Economic History, Radboud Studies in Humanities (Leiden / Boston: Brill, à paraître).La grille de lecture du tableau ainsi que la bibliographie sont fournies dans le fichier PDF associé.

Background and Purpose We have described a novel antidepressant peptide, spadin, that acts by blocking the TWIK-related-potassium channel, type 1 (TREK-1). Here, we examined possible mechanisms of action of spadin at both molecular and cellular levels. Experimental Approaches Effects of spadin were measured in primary cultures of neurons or tissues from mice injected i.v. with spadin. Western blots, qPCR, histochemical and electrophysiological techniques were used. Key Results In vitro, spadin increased neuronal membrane potential and activated both the MAPK and PI3K signalling pathways, in a time- and concentration-dependent manner. The latter pathway was involved in the protective effect of spadin against staurosporine-induced apoptosis. Also, spadin enhanced both mRNA expression and protein of two markers of synaptogenesis, the post-synaptic density protein of 95 kDalton (PSD-95) and synapsin. We confirmed these effects on synaptogenesis by the observation that spadin treatment significantly increased the proportion of mature spines in cortical neurons. Finally, in vivo injections of spadin led to a rapid increase in both mRNA expression and protein level of brain-derived neurotrophic factor (BDNF) in the hippocampus, confirming the antidepressant action of the peptide. We argue for a new role of spadin in synaptogenesis as both PSD-95 and synapsin mRNA expression and protein levels were further enhanced in the hippocampus, following treatment in vivo with the peptide. Conclusions and Implications These findings provide new mechanisms of action for the rapidly acting antidepressant peptide spadin by stimulating expression of BDNF and synaptic proteins, both in vitro and in vivo.

International audience

International audience; Dés la reprise des fouilles sur le mont Beuvray, au milieu des années 1980, Katherine Gruel joua un rôle actif dans la construction de ce projet singulier, à la fois scientifique et culturel, qui a progressivement vu le jour sur le site de l’ancienne capitale éduenne. Franchement numismate, mais aussi résolument archéologue, comme elle le revendique elle-même, Katherine a assumé pendant de longues années la responsabilité de l’étude des monnaies de Bibracte. Elle s’est aussi beaucoup investie dans l’organisation du programme de recherche et dans la mise en place de l’offre éducative destinée au jeune public. Il était donc normal qu’à l’heure où elle achève une longue carrière au CNRS, toute entière passée au sein du laboratoire d’archéologie de l’École normale supérieurs de la rue d’Ulm, ses collègues et ses anciens étudiants choisissent la collection Bibracte pour lui offrir un volume d’hommages auquel ont contribué 91 chercheurs. Conformément aux différents intérêts scientifiques de Katherine Gruel, le lecteur trouvera dans ces pages un aperçu de l’actualité de la recherche sur un ensemble de sujets comme la numismatique celtique, l’archéologie de la monnaie, l’économie protohistorique, ou encore les outils de la recherche archéologique.

International audience

International audience; Synthesis on the coins found during the excavations in Oedenburg between 1998 and 2012, especially in the civilian part of the settlement, with special attention payed to their stratigraphical contexts.; Synthèses sur les découvertes numismatiques des fouilles d'Oedenburg menées de 1998 à 2012, en particulier dans la partie civile de l'agglomération, avec une attention spéciale à leurs contextes de découverte statigraphiques.