La situation concurrentielle des principaux secteurs bancaires européens entre 1993 et 2000 : quels enseignements pour la future structure des marchés financiers issue de l'UEM ?

The competition among European bank firms between 1993 and 2000 : what future for the European banking sector structure ? Aiming to estimate the impacts of EMU on the European banking sectors structure, this paper analyses the degree of competition among bank firms of the 4 major European continental banking sectors (Germany, France, Italy and Spain ones) between 1993 and 2000 using two main tools of the new industrial organization theory : the Panzar-Rosse (1987) and Lerner’s indexes. The first model allows to reject the monopolistic competition hypothesis for any of the represented sector for the whole 1993-2000 period. The second assessment, in spite of describing substantial differences between countries, does not globally show an increase of bank margins (or at least a stabilization for German, French and Italian banks) in the same period. On the whole, both kinds of indexes show how the high degree of competition persists within the European Union during the concerned period. JEL classification : F36, G21Ce travail évalue les conséquences de l’UEM sur la structure du système bancaire européen. Ainsi, il analyse le degré de concurrence existant entre les firmes constituant les 4 principaux secteurs bancaires européens continentaux (Allemagne, Espagne, France et Italie) entre 1993 et 2000, à l’aide du test de Panzar et Rosse (1987) et de l’indice de Lerner. Le premier test permet de rejeter l’hypothèse de concurrence monopolistique pour chacun des secteurs représentés sur la période. Dans le même temps, et malgré d’importantes différences entre les pays considérés, la seconde catégorie d’estimations ne montre globalement pas de croissance des marges bancaires. En conclusion, les estimations des deux instruments permettent d’observer le maintien d’une concurrence élevée sur les marchés bancaires européens sur la période étudiée. Classification JEL : F36, G21Boutillier Michel, Gaudin Jimmy, Grandperrin Stéphanie. La situation concurrentielle des principaux secteurs bancaires européens entre 1993 et 2000 : quels enseignements pour la future structure des marchés financiers issue de l'UEM ? . In: Revue d'économie financière, n°81, 2005. Fonctionnement des systèmes bancaires et financiers. pp. 15-42

Influence of the small Rho GTPases on neuronal différentiation

Le neurone est une cellule polarisée, formée d'un corps cellulaire d'où partent deux types de prolongements plus ou moins arborisés: les dendrites et l'axone. La morphologie des neurones joue une rôle primordial dans leur capacité d'intégration. La formation des extensions se fait lors de la différenciation neuronale (au cours de l'étape de maturation) et implique de nombreux changements au niveau du cytosquelette des neurones. En effet, le développement de l'arbre dendritique est un processus dynamique qui implique l'extension et la rétraction partielle de dendrites. Les petites protéines G de la famille Rho (RhoA, Rac1 et Cdc42) régulent le cytosquelette d'actine des cellules. Notre étude, réalisée dans la lignée de neuroblastes NG 108-15 ainsi que dans des cultures primaires de neurones hippocampiques, porte sur l'influence des protéines G dans la différenciation neuronale et plus particulièrement sur leur rôle dans la formation et le maintien des extensions. Nous avons montré que l'activation de Rac1 et Cdc42 permet la formation d'extensions pourvues de branches tandis que celle de RhoA et de sa cascade de signalisation induit leur rétraction. Cependant, sous certaines conditions, nous avons mis en évidence que la stimulation de RhoA pouvait également engendrer la formation de dendrites. De plus, nous avons montré que le maintien des extensions et de leurs branches nécessite l'inhibition de la phosphoinoside 3-kinase. Notre étude met en évidence une étroite collaboration entre les petites protéines G et la phosphoinositide 3-kinase. Cette coopération permet l'élaboration de l'arbre dendritique.Neurons are polarised cells which present two types of extensions: dendrites and axons. For neurons shape is linked to function. Neurite extensions occur during the neuronal differentiation at the maturation state. This process involves important morphological changes, which implicate cytoskeletal reorganization. Indeed, dendritic arbor formation is a dynamic process which involves initiation and partial retraction of the newly formed extensions. Small Rho GTPases (RhoA, Rac1 and Cdc42) are key regulators of the cellular actin cytoskeleton. Our analyses were aimed at identifying the role of Rho proteins in neuronal differentiation and in neurite extension. We used neuroblastoma NG 108-15 cells as well as hippocampal neurons in primary culture. We show that the activation of Rac1 and Cdc42 is necessary for branched neurite formation, whereas RhoA signalling cascade induces retraction of extensions. However, we also showed that under certain conditions, RhoA activation could lead to dendrite formation. We demonstrate that the inhibition of the phosphoinoside 3-kinase is necessary for the maintenance of the branched dendrites. Our study highlights the cooperation between the small Rho GTPases and the phosphoinositide 3-kinase pathways. These interactions between the two signalling cascades play an important role in the dendritic arbor development.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

Altered enhancer transcription underlies Huntington’s disease striatal transcriptional signature

International audienceEpigenetic and transcriptional alterations are both implicated in Huntington’s disease (HD), aprogressive neurodegenerative disease resulting in degeneration of striatal neurons in the brain.However, how impaired epigenetic regulation leads to transcriptional dysregulation in HD is unclear.Here, we investigated enhancer RNAs (eRNAs), a class of long non-coding RNAs transcribed fromactive enhancers. We found that eRNAs are expressed from many enhancers of mouse striatum andshowed that a subset of those eRNAs are deregulated in HD vs control mouse striatum. Enhancerregions producing eRNAs decreased in HD mouse striatum were associated with genes involved instriatal neuron identity. Consistently, they were enriched in striatal super-enhancers. Moreover,decreased eRNA expression in HD mouse striatum correlated with down-regulation of associatedgenes. Additionally, a significant number of RNA Polymerase II (RNAPII) binding sites were lost withinenhancers associated with decreased eRNAs in HD vs control mouse striatum. Together, this indicatesthat loss of RNAPII at HD mouse enhancers contributes to reduced transcription of eRNAs, resultingin down-regulation of target genes. Thus, our data support the view that eRNA dysregulation in HDstriatum is a key mechanism leading to altered transcription of striatal neuron identity genes, throughreduced recruitment of RNAPII at super-enhancer

HP1α guides neuronal fate by timing E2F-targeted genes silencing during terminal differentiation

A critical step of neuronal terminal differentiation is the permanent withdrawal from the cell cycle that requires the silencing of genes that drive mitosis. Here, we describe that the α isoform of the heterochromatin protein 1 (HP1) protein family exerts such silencing on several E2F-targeted genes. Among the different isoforms, HP1α levels progressively increase throughout differentiation and take over HP1γ binding on E2F sites in mature neurons. When overexpressed, only HP1α is able to ensure a timed repression of E2F genes. Specific inhibition of HP1α expression drives neuronal progenitors either towards death or cell cycle progression, yet preventing the expression of the neuronal marker microtubule-associated protein 2. Furthermore, we provide evidence that this mechanism occurs in cerebellar granule neurons in vivo, during the postnatal development of the cerebellum. Finally, our results suggest that E2F-targeted genes are packaged into higher-order chromatin structures in mature neurons relative to neuroblasts, likely reflecting a transition from a ‘repressed' versus ‘silenced' status of these genes. Together, these data present new epigenetic regulations orchestrated by HP1 isoforms, critical for permanent cell cycle exit during neuronal differentiation

Exacerbation of C1q dysregulation, synaptic loss and memory deficits in tau pathology linked to neuronal adenosine A2A receptor

International audienceAccumulating data support the role of tau pathology in cognitive decline in ageing and Alzheimer's disease, but underlying mechanisms remain ill-defined. Interestingly, ageing and Alzheimer's disease have been associated with an abnormal upregulation of adenosine A2A receptor (A2AR), a fine tuner of synaptic plasticity. However, the link between A2AR signalling and tau pathology has remained largely unexplored. In the present study, we report for the first time a significant upregulation of A2AR in patients suffering from frontotemporal lobar degeneration with the MAPT P301L mutation. To model these alterations, we induced neuronal A2AR upregulation in a tauopathy mouse model (THY-Tau22) using a new conditional strain allowing forebrain overexpression of the receptor. We found that neuronal A2AR upregulation increases tau hyperphosphorylation, potentiating the onset of tau-induced memory deficits. This detrimental effect was linked to a singular microglial signature as revealed by RNA sequencing analysis. In particular, we found that A2AR overexpression in THY-Tau22 mice led to the hippocampal upregulation of C1q complement protein-also observed in patients with frontotemporal lobar degeneration-and correlated with the loss of glutamatergic synapses, likely underlying the observed memory deficits. These data reveal a key impact of overactive neuronal A2AR in the onset of synaptic loss in tauopathies, paving the way for new therapeutic approaches

Caffeine intake exerts dual genome-wide effects on hippocampal metabolism and learning-dependent transcription

Caffeine is the most consumed psychoactive substance worldwide. Strikingly, molecular pathways engaged by its regular consumption remain unclear. We herein addressed the mechanisms associated with habitual (chronic) caffeine consumption in the mouse hippocampus using untargeted orthogonal-omics techniques. Our results revealed that chronic caffeine exerts concerted pleiotropic effects in the hippocampus, at the epigenomic, proteomic and metabolomic levels. Caffeine lowers metabolic-related processes in the bulk tissue, while it induces neuronal-specific epigenetic changes at synaptic transmission/plasticity-related genes and increased experience-driven transcriptional activity. Altogether, these findings suggest that regular caffeine intake improves the signal-to-noise ratio during information encoding, in part through a fine-tuning of metabolic genes while boosting the salience of information processing during learning in neuronal circuits.This work was supported by grants from Hauts-de-France (PARTEN-AIRR, COGNADORA; START-AIRR, INS-SPECT) and Programs d’Investissements d’Avenir LabEx (excellence laboratory) DISTALZ (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer’s disease) and EGID (European Genomic Institute for Diabetes ANR-10LABX-46). Our laboratories are also supported by ANR (GRAND to LB, ADORATAU, ADORASTrAU, METABOTAU to DB and BETAPLASTICITY to JSA), COEN (5008), Fondation pour la Recherche Médicale, France Alzheimer/Fondation de France, FHU VasCog research network (Lille, France), Fondation Vaincre Alzheimer (ADOMEMOTAU), European Foundation for the Study of Diabetes (EFSD to JSA), Fondation Plan Alzheimer as well as Inserm, CNRS, Université Lille, Lille Métropole Communauté Urbaine, DN2M. KC hold a doctoral grant from Lille University. VG-M was supported by Fondation pour la Recherche Médicale (SPF20160936000). CM was supported by Région Hauts753 30 754 de-France. ALB is supported by CNRS, Unistra (Strasbourg, France), ANR-16-CE92-0031 755 756 757 758 759 760 761 762 (EPIFUS), ANR-18-CE16-0008-02 (ADORASTrAU), Alsace Alzheimer 67, France Alzheimer (AAP SM 2017 #1664). IP is supported by Fondation pour la Recherche Médicale (SPF201909009162). CEM is grateful for the support by the Alzheimer Forschung Initiative e.V. (AFI, Düsseldorf, Germany). LC was funded by SIF Italian Society of Pharmacology. RAC was supported by LaCaixa Foundation (LCF/PR/HP17/52190001) and FCT (POCI-01-0145-FEDER-03127). Santa Casa da Misericórdia (MB-7-2018) and CEECIND/01497/2017 to LVL