Sleep function: current questions and new approaches.

The mammalian brain oscillates through three distinct global activity states: wakefulness, non-rapid eye movement (NREM) sleep and REM sleep. The regulation and function of these 'vigilance' or 'behavioural' states can be investigated over a broad range of temporal and spatial scales and at different levels of functional organization, i.e. from gene expression to memory, in single neurons, cortical columns or the whole brain and organism. We summarize some basic questions that have arisen from recent approaches in the quest for the functions of sleep. Whereas traditionally sleep was viewed to be regulated through top-down control mechanisms, recent approaches have emphasized that sleep is emerging locally and regulated in a use-dependent (homeostatic) manner. Traditional markers of sleep homeostasis, such as the electroencephalogram slow-wave activity, have been linked to changes in connectivity and plasticity in local neuronal networks. Thus waking experience-induced local network changes may be sensed by the sleep homeostatic process and used to mediate sleep-dependent events, benefiting network stabilization and memory consolidation. Although many questions remain unanswered, the available data suggest that sleep function will best be understood by an analysis which integrates sleep's many functional levels with its local homeostatic regulation.

Proteomic analysis of Intercept-treated platelets.

In the past decades, transfusion medicine has been driven by the quest for increased safety against transfusion-transmitted infections, mainly by better donor selection and by the development of improved serological and nucleic-acid-based screening assays. Recently, pathogen reduction technologies became available and started to be implemented in several countries, with the primary goal to fight against bacterial contamination of blood products, a rare but dramatic event against which there was no definitive measure. Though pathogen reduction technologies represent a quantum leap in transfusion safety, the biomedical efficacy of platelet concentrates (PCs) treated with various pathogen reduction techniques has been recently questioned by clinical studies. Here, a gel-based proteomic analysis of PCs (n=5), Intercept-treated or untreated, from pooled buffy-coat (10 donors per PC) at Days 1, 2 and 8, shows that the Intercept process that is the most widespread pathogen reduction technique to date, has relatively low impact on the proteome of treated platelets: the process induces modifications of DJ-1 protein, glutaredoxin 5, and G(i)alpha 2 protein. As for the impact of storage, chloride intracellular channel protein 4 (CLIC4) and actin increased independently of Intercept treatment during storage. Whereas alteration of the DJ-1 protein and glutaredoxin 5 points out an oxidative stress-associated lesion, modification of G(i)alpha2 directly connects a possible Intercept-associated lesion to haemostatic properties of Intercept-treated platelets. This article is part of a Special Issue entitled: Integrated omics.

Conflits politiques et réseaux sociaux au XVIIIe siècle

Abstract: On Sunday 1745-8-29 a small upheaval occurred in Bagnes, a rather marginal mountain valley in the Swiss Alps, against the abbot of St-Maurice, the local feudal lord. In our perspective, this movement was nothing but one element in a long-term struggle, carried out by a stable and quite well organized political faction. The detailed analysis of the conflicts, of their protagonists as well as an analysis of the mobilization networks allows to highlight crucial aspects of local political life and reveals the active role of working classes. The micro-historical approach leads to some conclusions which challenge classical interpretation of pre-modern rural revolts. The case of Bagnes sheds light on the active and innovative character of popular politics, still underestimated in studies about pre-modern rural societies. The participants in the struggle against the abbot had a political program which was not limited to the quest for local autonomy. They fought for an opening of local corporations and a weakening of the control mechanism, for economic, political and cultural evolution of their valley. Bagnes rebels were decidedly "innovative rebels" Résumé: Le dimanche 29 août 1745, une petite émeute éclate à Bagnes, une vallée marginale des Alpes suisses, contre le seigneur, l'abbé de St-Maurice. Dans notre perspective, cette révolte n'est qu'un élément d'une lutte de longue haleine, pendant laquelle l'opposition au seigneur représente une partie active et bien organisée du conflit. L'analyse détaillée des protagonistes des luttes politiques, ainsi que des réseaux sociaux qui influencent la mobilisation, permet de mieux comprendre les dynamiques d'organisation de la vie politique locale et le rôle actif des couches populaires. Cette perspective autorise quelques conclusions, qui remettent en question les interprétations classiques des révoltes rurales d'Ancien Régime. Dans le cas de Bagnes, le caractère actif et novateur de la « politique populaire » encore négligé dans les études sur la période moderne, apparaît évident. Les protagonistes de la lutte contre l'abbé soutiennent un projet politique qui ne se réduit pas à une autonomie maximale de la région. Au contraire, ils prônent une ouverture des corporations locales, une transformation des structures économiques, politiques et culturelles de la vallée. Les émeutiers du Châble étaient décidément des « rebelles-novateurs ».

Monnaie, citoyenneté et globalisation financière. Les citoyens entre protection sociale et promesses de la capitalisation boursière

La monnaie a été étudiée par des économistes hétérodoxes, des sociologues et des historiens qui ont souligné ses rapports à l'ordre collectif, mais elle n'est que rarement analysée sous l'angle de la citoyenneté. Notre thèse propose une réflexion théorique sur quatre types de fonctions (politique, symbolique, socioéconomique et psychoaffective) qui permettent à la monnaie de jouer un rôle de médiation de la citoyenneté. A partir d'une perspective qui combine les apports de l'économie politique internationale et de l'école de la régulation, nous montrons que cette médiation ne mobilise pas seulement des mécanismes sociopolitiques nationaux, mais aussi des mécanismes internationaux qui rétroagissent sur la sphère domestique des États et affectent leur capacité à définir leur régime de citoyenneté. Cette relation est analysée dans le contexte de l'institutionnalisation du système monétaire international de Bretton Woods (1944) et du développement de la globalisation financière depuis les années 1970. Si la monnaie a été mise au service d'un principe de protection des droits sociaux des citoyens contre les pressions financières extérieures après la Seconde guerre mondiale, elle contribue aujourd'hui à l'ouverture de la sphère domestique des Etats aux flux de capitaux transnationaux et à la création d'un ordre politique et juridique favorable aux droits des investisseurs. Cette dynamique est impulsée par l'essor de nouveaux intermédiaires financiers (notamment les agences de notation et les investisseurs institutionnels) et l'émergence concomitante d'une nouvelle forme d'Etat légitimée à partir d'un discours politique néolibéral insistant sur la quête de compétitivité, la réduction de la protection sociale et la responsabilisation individuelle. Elle se traduit par la privatisation des régimes de retraite et le développement des politiques d'éducation financière qui incitent les citoyens à se comporter en « preneurs de risques » actifs et responsables, assurant eux-mêmes leur sécurité économique à travers le placement de leur épargne retraite sur les marchés financiers. Nous soulignons toutefois les difficultés institutionnelles, cognitives et socioéconomiques qui rendent cette transformation de la citoyenneté contradictoire et problématique. Money has been studied by heterodox economists, sociologists and historians who stressed its relationship to collective order. However, it has hardly been analysed from the viewpoint of its relationship to citizenship. We propose a theoretical account of four types of functions (political, symbolic, socioeconomic and psychoaffective) enabling money to operate as a mediation of citizenship. From a perspective that combines the contributions of international political economy and the regulation school, we show that this mediation mobilises not only national sociopolitical mechanisms, but also international mechanisms which feed back on the domestic sphere of states and affect their capacity to define their regime of citizenship. This relationship is analysed in the context of the institutionalisation of the international monetary system of Bretton Woods (1944) and the development of financial globalization since the 1970s. If money has served to protect the social rights of citizens against external financial pressures after the Second World War, today it contributes to the opening of the domestic sphere of states to transnational capital flows and to the creation of a political and legal order favorable to the rights of investors. This dynamic is driven by the rise of new financial intermediaries (in particular rating agencies and institutional investisors) and the simultaneous emergence of a new form of state legitimized from a neoliberal political discourse emphasizing the quest for competitiveness, reduced social protection and individual responsibilization. It results in the privatization of pension systems and the development of policies of financial education that encourage citizens to behave as active and responsible « risk takers », ensuring their own economic security through the investment of their savings retirement on financial markets. However, we emphasize the institutional, cognitive and socioeconomic difficulties that make this transformation of citizenship contradictory and problematic. - Money has been studied by heterodox economists, sociologists and historians who stressed its relationship to collective order. However, it has hardly been analysed from the viewpoint of its relationship to citizenship. We propose a theoretical account of four types of functions (political, symbolic, socioeconomic and psychoaffective) enabling money to operate as a mediation of citizenship. From a perspective that combines the contributions of international political economy and the regulation school, we show that this mediation mobilises not only national sociopolitical mechanisms, but also international mechanisms which feed back on the domestic sphere of states and affect their capacity to define their regime of citizenship. This relationship is analysed in the context of the institutionalisation of the international monetary system of Bretton Woods (1944) and the development of financial globalization since the 1970s. If money has served to protect the social rights of citizens against external financial pressures after the Second World War, today it contributes to the opening of the domestic sphere of states to transnational capital flows and to the creation of a political and legal order favorable to the rights of investors. This dynamic is driven by the rise of new financial intermediaries (in particular rating agencies and institutional investisors) and the simultaneous emergence of a new form of state legitimized from a neoliberal political discourse emphasizing the quest for competitiveness, reduced social protection and individual responsibilization. It results in the privatization of pension systems and the development of policies of financial education that encourage citizens to behave as active and responsible « risk takers », ensuring their own economic security through the investment of their savings retirement on financial markets. However, we emphasize the institutional, cognitive and socioeconomic difficulties that make this transformation of citizenship problematic.

Problemáticas psicossociais da abordagem da noção de sujeito

O presente artigo trata da importância da questão do sujeito nas representações sociais. Para tanto, repassa alguns modelos da psicologia social e alude às novas perspectivas sobre o sujeito desenvolvidas nas ciências sociais e humanas. Feito um breve panorama do uso da categoria sujeito na história dessa disciplina, com destaque a seu retorno às ciências sociais nos anos 1990 e a noções correlatas, como "ator" e "agente", aponta-se a necessidade de trabalhar com a noção de "subjetivação" em pesquisas que considerem a subjetividade sem perder a dimensão social no estudo das representações, consideradas em dois níveis: o subjetivo e o transubjetivo.

Vascular integrins in tumor angiogenesis: mediators and therapeutic targets.

The notion that tumor angiogenesis may have therapeutic implications in the control of tumor growth was introduced by Dr. Judah Folkman in 1971. The approval of Avastin in 2004 as the first antiangiogenic systemic drug to treat cancer patients came as a validation of this visionary concept and opened new perspectives to the treatment of cancer. In addition, this success boosted the field to the quest for new therapeutic targets and antiangiogenic drugs. Preclinical and clinical evidence indicate that vascular integrins may be valid therapeutic targets. In preclinical studies, pharmacological inhibition of integrin function efficiently suppressed angiogenesis and inhibited tumor progression. alphaVbeta3 and alphaVbeta5 were the first vascular integrins targeted to suppress tumor angiogenesis. Subsequent experiments revealed that at least four additional integrins (i.e., alpha1beta1, alpha2beta1, alpha5beta1, and alpha6beta4) might be potential therapeutic targets. In clinical studies low-molecular-weight integrin inhibitors and anti-integrin function-blocking antibodies demonstrated low toxicity and good tolerability and are now being tested in combination with radiotherapy and chemotherapy for anticancer activity in patients. In this article the authors review the role of integrins in angiogenesis, present recent development in the use of alphaVbeta3 and alpha5beta1 integrin antagonists as potential therapeutics in cancer, and discuss future perspectives.

Astrocytic αVβ3 integrin inhibits neurite outgrowth and promotes retraction of neuronal processes by clustering Thy-1.

Thy-1 is a membrane glycoprotein suggested to stabilize or inhibit growth of neuronal processes. However, its precise function has remained obscure, because its endogenous ligand is unknown. We previously showed that Thy-1 binds directly to α(V)β(3) integrin in trans eliciting responses in astrocytes. Nonetheless, whether α(V)β(3) integrin might also serve as a Thy-1-ligand triggering a neuronal response has not been explored. Thus, utilizing primary neurons and a neuron-derived cell line CAD, Thy-1-mediated effects of α(V)β(3) integrin on growth and retraction of neuronal processes were tested. In astrocyte-neuron co-cultures, endogenous α(V)β(3) integrin restricted neurite outgrowth. Likewise, α(V)β(3)-Fc was sufficient to suppress neurite extension in Thy-1(+), but not in Thy-1(-) CAD cells. In differentiating primary neurons exposed to α(V)β(3)-Fc, fewer and shorter dendrites were detected. This effect was abolished by cleavage of Thy-1 from the neuronal surface using phosphoinositide-specific phospholipase C (PI-PLC). Moreover, α(V)β(3)-Fc also induced retraction of already extended Thy-1(+)-axon-like neurites in differentiated CAD cells as well as of axonal terminals in differentiated primary neurons. Axonal retraction occurred when redistribution and clustering of Thy-1 molecules in the plasma membrane was induced by α(V)β(3) integrin. Binding of α(V)β(3)-Fc was detected in Thy-1 clusters during axon retraction of primary neurons. Moreover, α(V)β(3)-Fc-induced Thy-1 clustering correlated in time and space with redistribution and inactivation of Src kinase. Thus, our data indicates that α(V)β(3) integrin is a ligand for Thy-1 that upon binding not only restricts the growth of neurites, but also induces retraction of already existing processes by inducing Thy-1 clustering. We propose that these events participate in bi-directional astrocyte-neuron communication relevant to axonal repair after neuronal damage.

Incidence of anatomical variations and disease of the maxillary sinuses as identified by cone beam computed tomography: a systematic review.

PURPOSE: To analyze available evidence on the incidence of anatomical variations or disease of the maxillary sinuses as identified by cone beam computed tomography (CBCT) in dentistry. MATERIALS AND METHODS: A focused question was developed to search the electronic databases MEDLINE, EMBASE, the Cochrane Oral Health Group Trials Register, and CENTRAL and identify all relevant papers published between 1980 and January 19, 2013. Unpublished literature at ClinicalTrials.gov, in the National Research Register, and in the Pro-Quest Dissertation Abstracts and Thesis database was also included. Studies were included irrespective of language. These results were supplemented by hand and gray literature searches. RESULTS: Twenty-two studies were identified. Twenty were retrospective cohort studies, one was a prospective cohort study, and one was a case control study. The main indication for CBCT was dental implant treatment planning, and the majority of studies used a small field of view for imaging. The most common anatomical variations included increased thickness of the sinus membrane, the presence of sinus septa, and pneumatization. Reported sinus disease frequency varied widely, ranging from 14.3% to 82%. There was a wide range in the reported prevalence of mucosal thickening related to apical pathology, the degree of lumenal opacification, features of sinusitis, and the presence of retention cysts and polyps. More pathologic findings in the maxillary sinus were reported in men than in women, and the medial wall and sinus floor were most frequently affected. CONCLUSION: CBCT is used primarily to evaluate bony anatomy and to screen for overt pathology of the maxillary sinuses prior to dental implant treatment. Differences in the classification of mucosal findings are problematic in the consistent and valid assessment of health and disease of the maxillary sinus.

En busca de la lengua perfecta: pasado, presente y futuro

Análisis de las lenguas artificiales más importantes que se han creado a lo largo de la historia con el objetivo de encontrar una lengua perfecta común para todos y presentación del Rodinio, una nueva lengua artificial basada en una serie de criterios en busca de esa perfección.

Sharing and Learning= Changing. A real story at the Institute of Public Security of Catalonia

The Institute has professionals with extensive experience in training, specifically with experience in the field of police and emergencies training. Moreover, it also has very talented people. But above all, our institution has public professionals with a desire to serve, who love security and emergency responders and want to provide them with the best knowledge to make them every day better professionals. In the quest for continuous training improvement, its during 2009 when e-learning begins to have a presence at the Institute. Virtual training methodology becomes a facilitator for the training of various professionals, avoiding geographical displacement and easing the class schedule.

Direct Thy-1/alphaVbeta3 integrin interaction mediates neuron to astrocyte communication.

Thy-1 is an abundant neuronal glycoprotein of poorly defined function. We recently provided evidence indicating that Thy-1 clusters a beta3-containing integrin in astrocytes to induce tyrosine phosphorylation, RhoA activation and the formation of focal adhesions and stress fibers. To date, the alpha subunit partner of beta3 integrin in DI TNC1 astrocytes is unknown. Similarly, the ability of neuronal, membrane-bound Thy-1 to trigger astrocyte signaling via integrin engagement remains speculation. Here, evidence that alphav forms an alphavbeta3 heterodimer in DI TNC1 astrocytes was obtained. In neuron-astrocyte association assays, the presence of either anti-alphav or anti-beta3 integrin antibodies reduced cell-cell interaction demonstrating the requirement of both integrin subunits for this association. Moreover, anti-Thy-1 antibodies blocked stimulation of astrocytes by neurons but not the binding of these two cell types. Thus, neuron-astrocyte association involved binding between molecular components in addition to the Thy-1-integrin; however, the signaling events leading to focal adhesion formation in astrocytes depended exclusively on the latter interaction. Additionally, wild-type (RLD) but not mutated (RLE) Thy-1 was shown to directly interact with alphavbeta3 integrin by Surface Plasmon Resonance analysis. This interaction was promoted by divalent cations and was species-independent. Together, these results demonstrate that the alphavbeta3 integrin heterodimer interacts directly with Thy-1 present on neuronal cells to stimulate astrocytes.

Presència de Rousseau a Catalunya: entre el mite i la realitat

En aquest article s’ofereix un perfil del pensament de Rousseau a partir de la seva relació amb la filosofia estoica i la seva dependència respecte de les idees de Montaigne, alhora que es remarca —atenint-se a la Professió de fe del vicari savoià— la dimensió religiosa i espiritual de la seva cosmovisió. Sobre la base d’aquests supòsits es revisa l’impacte de les idees de Rousseau en el Romanticisme del segle xix, sense perdre de vista les crítiques que la seva pedagogia va merèixer dels ideòlegs del Noucentisme (Eugeni d’Ors, Joaquim Xirau). Finalment, es conclou que la presència de la pedagogia de Rousseau en el Moviment de Renovació Pedagògica, viscut durant les primeres dècades del segle xx a Catalunya, constitueix més un horitzó que no pas una realitat bastida sistemàticament i sòlidament.

An efficient algorithm to perform multiple testing in epistasis screening

Background: Research in epistasis or gene-gene interaction detection for human complex traits has grown over the last few years. It has been marked by promising methodological developments, improved translation efforts of statistical epistasis to biological epistasis and attempts to integrate different omics information sources into the epistasis screening to enhance power. The quest for gene-gene interactions poses severe multiple-testing problems. In this context, the maxT algorithm is one technique to control the false-positive rate. However, the memory needed by this algorithm rises linearly with the amount of hypothesis tests. Gene-gene interaction studies will require a memory proportional to the squared number of SNPs. A genome-wide epistasis search would therefore require terabytes of memory. Hence, cache problems are likely to occur, increasing the computation time. In this work we present a new version of maxT, requiring an amount of memory independent from the number of genetic effects to be investigated. This algorithm was implemented in C++ in our epistasis screening software MBMDR-3.0.3. We evaluate the new implementation in terms of memory efficiency and speed using simulated data. The software is illustrated on real-life data for Crohn’s disease. Results: In the case of a binary (affected/unaffected) trait, the parallel workflow of MBMDR-3.0.3 analyzes all gene-gene interactions with a dataset of 100,000 SNPs typed on 1000 individuals within 4 days and 9 hours, using 999 permutations of the trait to assess statistical significance, on a cluster composed of 10 blades, containing each four Quad-Core AMD Opteron(tm) Processor 2352 2.1 GHz. In the case of a continuous trait, a similar run takes 9 days. Our program found 14 SNP-SNP interactions with a multiple-testing corrected p-value of less than 0.05 on real-life Crohn’s disease (CD) data. Conclusions: Our software is the first implementation of the MB-MDR methodology able to solve large-scale SNP-SNP interactions problems within a few days, without using much memory, while adequately controlling the type I error rates. A new implementation to reach genome-wide epistasis screening is under construction. In the context of Crohn’s disease, MBMDR-3.0.3 could identify epistasis involving regions that are well known in the field and could be explained from a biological point of view. This demonstrates the power of our software to find relevant phenotype-genotype higher-order associations.