Storage and uptake of D-serine into astrocytic synaptic-like vesicles specify gliotransmission.

Glial cells are increasingly recognized as active players that profoundly influence neuronal synaptic transmission by specialized signaling pathways. In particular, astrocytes have been shown recently to release small molecules, such as the amino acids l-glutamate and d-serine as "gliotransmitters," which directly control the efficacy of adjacent synapses. However, it is still controversial whether gliotransmitters are released from a cytosolic pool or by Ca(2+)-dependent exocytosis from secretory vesicles, i.e., by a mechanism similar to the release of synaptic vesicles in synapses. Here we report that rat cortical astrocytes contain storage vesicles that display morphological and biochemical features similar to neuronal synaptic vesicles. These vesicles share some, but not all, membrane proteins with synaptic vesicles, including the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) synaptobrevin 2, and contain both l-glutamate and d-serine. Furthermore, they show uptake of l-glutamate and d-serine that is driven by a proton electrochemical gradient. d-Serine uptake is associated with vesicle acidification and is dependent on chloride. Whereas l-serine is not transported, serine racemase, the synthesizing enzyme for d-serine, is anchored to the membrane of the vesicles, allowing local generation of d-serine. Finally, we reveal a previously unexpected mutual vesicular synergy between d-serine and l-glutamate filling in glia vesicles. We conclude that astrocytes contain vesicles capable of storing and releasing d-serine, l-glutamate, and most likely other neuromodulators in an activity-dependent manner.

Comparación entre la videografía y el método Sit and Reach para la valoración de la flexibilidad isquiotibial en deportistas escolares

Existen diferentes test para evaluar la flexibilidad articular. El objetivo de nuestro estudio era el de comparar el test de sit and reach y el de goniometría de la rodilla en extensión, mediante videografía para la valoración de la flexibilidad isquiotibial en una muestra de 139 deportistas escolares, de edades comprendidas entre los 7 y los 16 años. El coeficiente de Kappa muestra una concordancia muy débil entre las dos pruebas (0,022 (I.C. 95% -0,07 – 0,12)). Demostrando que el sit and reach no es un test válido para la evaluación de la flexibilidad isquiotibial.

The role of neutrophils upon leishmania major infection

Les neutrophiles constituent la première ligne de défense contre un grand nombre de pathogènes. Après infection avec Leishmania major, les neutrophiles migrent rapidement et massivement au site d'infection par le parasite. Les neutrophiles sont d'importants acteurs dans l'orchestration de la réponse anti-Leishmania, via la sécrétion de nombreuses cytokines, chimiokines et composés stockés dans leurs granules. De plus, les neutrophiles interagissent avec les cellules présentatrices d'antigènes, telles que les cellules dendritiques et en conséquences contribuent au développement de la réponse adaptative. A ce jour, l'impact des neutrophiles sur 1'activation des cellules dendritiques et les possibles conséquences de l'interaction neutrophiles avec ces dernières sur l'évolution de la maladie suite à l'infection avec L. major reste peu connu. Ainsi, nous avons dans un premier temps investigué l'influence des neutrophiles sur 1'activation des cellules dendritiques in vitro. Suite à cela, nous avons analysé le rôle des neutrophiles sur 1'activation des cellules dendritiques présentes au site d'infection et dans les ganglions drainants in vivo, après inoculation intra-dermale de L. major dans le pavillon auriculaire de souris de souche C57BL/6 et BALB/c, ainsi que les conséquences de la déplétion des neutrophiles sur l'évolution de la maladie. Nous avons pu démontrer que les neutrophiles ont un impact négatif sur l'activation des cellules dendritiques exposées à L. major in vitro, via des mécanismes impliquant la sécrétion de Prostaglandines par les neutrophiles et la séquestration des parasites. La déplétion des neutrophiles dans les souris BALB/c durant les premiers jours après infection avec L. major dans le derme de l'oreille résulte en une augmentation de l'expression de marqueurs d'activation des cellules dendritiques présentes dans les ganglions drainants, mais pas au site d'infection. De plus, les souris BALB/c transitoirement déplétées en neutrophiles développent des lésions significativement plus petites, une réponse de type Th2 diminuée et une charge parasitaire plus faible au site d'infection que les souris non déplétées. La déplétion des neutrophiles dans les souris C57BL/6 n'a pas d'influence détectable sur l'activation des cellules dendritiques que ce soit au niveau des ganglions drainants ou au site d'infection. La progression de la lésion et la charge parasitaire ne sont pas affectées par la déplétion des neutrophiles, malgré le développement d'une réponse Th2 diminuée par rapport aux souris non déplétées. En résumé, dans les premières heures après infection, les neutrophiles ont un effet négatif sur l'activation des cellules dendritiques et sur la réponse anti-Leishmania dans les souris BALB/c tandis que leur rôle paraît moins important dans les souris C57BL/6. Ces résultats peuvent avoir d'importantes implications en terme de développement de nouveaux vaccins contre Leishmania. - Neutrophils constitute the first line of defense against a variety of pathogens. Following Leihmania major infection neutrophils migrate rapidly and massively to the site of parasite inoculation. They are important players in the orchestration of the anti-leishmania response through the release of a plethora of cytokines, chemokines and granular components. In addition, neutrophils interact with antigen-presenting cells such as dendritic cells (DCs) and thereby contribute to the development of the adaptive immune response. However, the impact of neutrophils on the activation of DCs and possible consequences on disease progression following L. major infection are poorly understood. Therefore, we first investigated the influence of neutrophils on DC activation in vitro. Next we analyzed the role of neutrophils on the activation of DCs present at the site of infection and in the draining lymph node (dLN) following inoculation of L. major in the ear pinna of C57BL/6 and BALB/c mice and analyzed the consequences of early neutrophil depletion on disease progression. We could demonstrate that neutrophils had a negative impact on the activation of DCs exposed to L. major in vitro through mechanisms involving neutrophil-derived prostaglandins and sequestration of parasites. In BALB/c mice, depletion of neutrophils during the first days of infection with L. major in the ear dermis increased the expression of activation markers on dLN DCs but not on DCs present at the site of infection. In addition, BALB/c mice transiently depleted of neutrophils developed significantly smaller lesions, a decreased Th2 immune response and harbored fewer parasites at the site of infection compared to non-depleted littermates. In C57BL/6, mice early depletion of neutrophils had no detectable impact on the activation of DCs both at the site of infection and in the dLN following L. major inoculation. Furthermore, depletion of neutrophils had no major effect on lesion evolution and parasite loads despite the development of a decreased Th2 immune response compared to non- depleted littermates. In summary, at the onset of infection, neutrophils are detrimental for DC activation and the anti-leishmania response in BALB/c mice while their role appears to be less important in C57BL/6 mice. These findings could have important implications for the design of new vaccination strategies.

Le ballon ne tourne pas rond en Afrique: les effets pervers d'une "extraversion dépendante"

Les dirigeants du football africain ont abandonné les politiques protectionnistes pour bâtir des sélections nationales performantes. Ils s'orientent vers des stratégies libérales qui favorisent le départ de joueurs à l'étranger et leur rapatriement pour les matches de l'équipe nationale. De plus en plus systématiquement, les footballeurs d'origine africaine ayant grandi en Europe sont « récupérés ». Si le recours à la « diaspora » permet de compenser le gâchis de talents résultant de la faiblesse de la formation locale de footballeurs, cette pratique empêche le football national de se structurer. The managers of African football have abandoned their protectionist policies in order to build up high-performing national teames. They are adopting liberal strategies fostering the departure of players abroad and their repatriation for national team matches. Footballers of African origin who have grown up in Europe are increasingly often being "retrieved". Although this recourse to the "diaspora" offsets the waste of talent brought about by the shortcomings of local training for footballers, this practice puts a brake on the structuring of national football.

Endogenous depth of reasoning

We introduce a model of strategic thinking in games of initial response. Unlike standard level-k models, in this framework the player's `depth of reasoning' is endogenously determined, andit can be disentangled from his beliefs over his opponent's cognitive bound. In our approach,individuals act as if they follow a cost-benefit analysis. The depth of reasoning is a function ofthe player's cognitive abilities and his payoffs. The costs are exogenous and represent the gametheoretical sophistication of the player; the benefit instead is related to the game payoffs. Behavioris in turn determined by the individual's depth of reasoning and his beliefs about the reasoningprocess of the opponent. Thus, in our framework, payoffs not only affect individual choices inthe traditional sense, but they also shape the cognitive process itself. Our model delivers testableimplications on players' chosen actions as incentives and opponents change. We then test themodel's predictions with an experiment. We administer different treatments that vary beliefs overpayoffs and opponents, as well as beliefs over opponents' beliefs. The results of this experiment,which are not accounted for by current models of reasoning in games, strongly support our theory.Our approach therefore serves as a novel, unifying framework of strategic thinking that allows forpredictions across games.

The slow transformation of Swiss federal administrative elites

This article sets out to study the profile of Swiss administrative elites at federal level by showing how their profile has evolved in the light of what has come to be known as the wave of New Public Management (NPM), which has benefited from a very fertile ground in Switzerland. These elites correspond to a specific institutional order, in relation to specific organizational structures and workings, and have specific characteristics in terms of career paths and academic background. However, the administrative reforms that have been rolled out since the 1980s have transformed the institutional order within which executives of the federal administration evolve. This article analyses the extent to which these transformations have had an impact on the characteristics of these elites, through indicators such as academic capital, social capital, and career path within and outside the administration. The results show a slow but significant transformation in the profiles of these elites towards an increasing managerialization, reflecting that of the context in which they evolve.Points for practitioners The relationship between politics and the administration is naturally shaped by individuals but is closely dependent on the profiles of the players. They are currently undergoing a transformation in the wake of administrative reforms, and also of the changing profiles of both the political and administrative players. Gaining an insight into the slow transformation of the profiles of administrative elites therefore sheds light on the political-administrative nexus. The gradual managerialization of the administrative elite highlighted in this article also allows for a better understanding of which professional experiences, qualifications and skills are valued today within the senior civil service in Switzerland.

Small but thick enough-the Arabidopsis hypocotyl as a model to study secondary growth.

The continuous production of vascular tissues through secondary growth results in radial thickening of plant organs and is pivotal for various aspects of plant growth and physiology, such as water transport capacity or resistance to mechanical stress. It is driven by the vascular cambium, which produces inward secondary xylem and outward secondary phloem. In the herbaceous plant Arabidopsis thaliana (Arabidopsis), secondary growth occurs in stems, in roots and in the hypocotyl. In the latter, radial growth is most prominent and not obscured by parallel ongoing elongation growth. Moreover, its progression is reminiscent of the secondary growth mode of tree trunks. Thus, the Arabidopsis hypocotyl is a very good model to study basic molecular mechanisms of secondary growth. Genetic approaches have succeeded in the identification of various factors, including peptides, receptors, transcription factors and hormones, which appear to participate in a complex network that controls radial growth. Many of these players are conserved between herbaceous and woody plants. In this review, we will focus on what is known about molecular mechanisms and regulators of vascular secondary growth in the Arabidopsis hypocotyl.

Axiomatization of the nucl eolus of assignment games

On the domain of general assignment games (with possible reservation prices) the core is axiomatized as the unique solution satisfying two consistency principles: projection consistency and derived consistency. Also, an axiomatic characterization of the nucleolus is given as the unique solution that satisfies derived consistency and equal maximum complaint between groups. As a consequence, we obtain a geometric characterization of the nucleolus. Maschler et al. (1979) provide a geometrical characterization for the intersection of the kernel and the core of a coalitional game, showing that those allocations that lie in both sets are always the midpoint of certain bargaining range between each pair of players. In the case of the assignment game, this means that the kernel can be determined as those core allocations where the maximum amount, that can be transferred without getting outside the core, from one agent to his / her optimally matched partner equals the maximum amount that he / she can receive from this partner, also remaining inside the core. We now prove that the nucleolus of the assignment game can be characterized by requiring this bisection property be satisfied not only for optimally matched pairs but also for optimally matched coalitions. Key words: cooperative games, assignment game, core, nucleolus