Tissue-specificity of antibodies raised against TrkB and p75NTR receptors ; implications for platelets as models of neurodegenerative diseases

Platelets and neurons share many similarities including comparable secretory granule types with homologous calcium-dependent secretory mechanisms as well as internalization, sequestration and secretion of many neurotransmitters. Thus, platelets present a high potential to be used as peripheral biomarkers to reflect neuronal pathologies. The brain-derived neurotrophic factor (BDNF) acts as a neuronal growth factor involved in learning and memory through the binding of two receptors, the tropomyosin receptor kinase B (TrkB) and the 75 kDa pan-neurotrophic receptor (p75NTR). In addition to its expression in the central nervous system, BDNF is found in much greater quantities in blood circulation, where it is largely stored within platelets. Levels 100- to 1,000-fold those of neurons make platelets the most important peripheral reservoir of BDNF. This led us to hypothesize that platelets would express canonical BDNF receptors, i.e., TrkB and p75NTR, and that the receptors on platelets would bear significant resemblance to the ones found in the brain. However, herein we report discrepancies regarding detection of these receptors using antibody-based assays, with antibodies displaying important tissue-specificity. The currently available antibodies raised against TrkB and p75NTR should therefore be used with caution to study platelets as models for neurological disorders. Rigorous characterization of antibodies and bioassays appears critical to understand the interplay between platelet and neuronal biology of BDNF

Platelets selectively regulate the release of BDNF, but not that of its precursor protein, proBDNF

Background: Brain-derived neurotrophic factor (BDNF) plays a role in synaptic plasticity and neuroprotection. BDNF has well-established pro-survival effects, whereas its precursor protein, proBDNF, induces apoptosis. Thus, it has been suggested that the proBDNF/BDNF ratio could be an indicator of neuronal health. Access to neurons is, understandably, limited. Because of their similarities, platelets have been put forward as a non-invasive biomarker of neuronal health; indeed, they store large quantities of BDNF and can release it into circulation upon activation, similarly to neurons. However, whether platelets also express the precursor proBDNF protein remains unknown. We therefore sought to characterize proBDNF levels in human platelets and plasma. Methods: The presence of proBDNF was assessed by immunoblotting, cell fractionation, flow cytometry, and confocal microscopy in washed platelets from 10 healthy volunteers. Platelets from 20 independent healthy volunteers were activated with several classical agonists and the release of BDNF and proBDNF into plasma was quantified by ELISA. Results: Platelets expressed detectable levels of proBDNF (21 ± 13 fmol/250 x 106 platelets). ProBDNF expression was mainly localized in the intracellular compartment. The proBDNF to BDNF molar ratio was ~1:5 in platelets and 10:1 in plasma. In stark contrast to the release of BDNF during platelet activation, intraplatelet and plasma concentrations of proBDNF remained stable following stimulation with classical platelet agonists, consistent with non-granular expression. Conclusions: Platelets express both the mature and the precursor form of BDNF. Whether the intraplatelet proBDNF to BDNF ratio could be used as a non-invasive biomarker of cognitive health warrants further investigation

Unreliable Transport Protocol for Commodity-Based OpenGL Distributed Visualization

International audienceThis paper presents a way to use an unreliable transport protocol to perform distributed OpenGL visualization on a commodity network of computers. We present a performance evaluation of a prototype implementation based on the Chromium environment

Clinical correlates identify ProBDNF and thrombo-inflammatory markers as key predictors of circulating p75NTR extracellular domain levels in older adults

The p75NTR receptor binds all neurotrophins and is mostly known for its role in neuronal survival and apoptosis. Recently, the extracellular domain (ECD) of p75NTR has been reported in plasma, its levels being dysregulated in numerous neurological diseases. However, the factors associated with p75NTR ECD levels remain unknown. We investigated clinical correlates of plasma p75NTR ECD levels in older adults without clinically manifested neurological disorders. Circulating p75NTR levels were measured by enzyme-linked immunosorbent assay in plasma obtained from participants in the BEL-AGE cohort (n = 1,280). Determinants of plasma p75NTR ECD levels were explored using linear and non-linear statistical models. Plasma p75NTR ECD levels were higher in male participants; were positively correlated with circulating concentrations of pro-brain-derived neurotrophic factor, and inflammatory markers interleukin-6 and CD40 Ligand; and were negatively correlated with the platelet activation marker P-selectin. While most individuals had p75NTR levels ranging from 43 to 358 pg/ml, high p75NTR levels reaching up to 9,000 pg/ml were detectable in a subgroup representing 15% of the individuals studied. In this cohort of older adults without clinically manifested neurological disorders, there was no association between plasma p75NTR ECD levels and cognitive performance, as assessed by the Montreal Cognitive Assessment score. The physiological relevance of high p75NTR ECD levels in plasma warrants further investigation. Further research assessing the source of circulating p75NTR is needed for a deeper understanding of the direction of effect, and to investigate whether high p75NTR ECD levels are predictive biomarkers or consequences of neuropathology

Skiroc: A Front-end Chip to Read Out the Imaging Silicon-Tungsten Calorimeter for ILC

Integration and low-power consumption of the read-out ASIC for the International Linear Collider (ILC) 82-millionchannel W-Si calorimeter must reach an unprecedented level as it will be embedded inside the detector. Uniformity and dynamic range performance has to reach the accuracy to achieve calorimetric measurement. A first step towards this goal has been a 10,000-channel physics prototype of 18*18 cm which is currently in test beam in CERN. A new version of a full integrated read out chip (SKIROC) has been designed to equip the technologic prototype to be built for 2009. Based on the running physics prototype ASIC (FLC_PHY3), it embeds most of the required features expected for the final detector. The dynamic range has been improved from 500 to 2000 MIP. An auto-trigger capability has been added allowing built-in zero suppress. The number of channel has been doubled reaching 36 to fit smaller silicon pads and the lownoise charge preamplifier now accepts both AC and DC coupled detectors. After an exhaustive description, the measurement results of that new front-end chip will be presented. The results on the technological R&D concurrently conducted on the ultra-thin PCB hosting both the front-end electronic and the silicon detectors will also be described

Figurer l'espace en sciences sociales

La revue en ligne n'est plus accessible.Les articles du dossier de ce numéro double de Transeo s'inscrivent dans une problématique qui interroge les manières dont les pratiques et les représentations sociales, en déterminant enjeux et les stratégies de par leur relation, conduisent à mettre en formes des espaces. Mais, avant de présenter ces études dans sa dernière partie, notre introduction revient sur le principe selon lequel figurer l'espace consiste à (re)construire une image de la réalité à partir d'un ensemble d'éléments identifiables et de la distance qu'ils entretiennent les uns avec les autres. Cette (re)construction dépendant de la position du chercheurs, des méthodes, outils et épistémologie(s) dont il use, autant que des données qu'il sélectionne et positionne, figurer l'espace nous apparaît moins comme la possibilité de sortir d'un point de vue particulier, comme le souhaiteraient certains courants de la cartographie, que comme le moyen de donner un point de vue spécifique sur un ensemble de points. D'où la nécessite peut-être, afin d'élargir ce point de vue spécifique, de se situer dans une perspective transdisciplinaire, de tenter de faire coïncider ou coordonner un ensemble d'axes paradigmatiques, c'est-à-dire de se situer dans plusieurs (sous)espaces disciplinaires et d'en cumuler les outils de connaissances afin d'affiner toujours davantage cette (re)construction. Ainsi, après être revenu, sans objectif d'exhaustivité, sur diverses études qui ont figuré l'espace en sciences sociales (« Figuration de l'espace et sciences sociales », p.3) en dépassant les grandes oppositions qui structurent cet univers de production culturelle particulier que représente le champ scientifique, notre propos a consisté à chercher une articulation entre trois types d'espaces différents qui y co-existent : l'espace physique, l'espace social et l'espace socio-cognitif. Cette option théorique comme piste de recherche pour rendre compte de l'activité du monde social (« Espaces figurés et articulations des figurations de l'espace », p.7), demandant de passer par l'objectivation de et des positions dans la mesure où ce sont en effet ces positions qui permettent de localiser des points de repère délimitant alors un espace, de (se) le représenter pour tenter d'en saisir les agencements et les configurations qui procèdent de la relation entre ces points. Ensemble de positions dont les relations élident donc des espaces, qu'il s'agisse de lieux, de textes, de groupes de personnes et/ou de représentations, permettant aussi de saisir alors ce qui les lie autant que les espaces qu'elles définissent et qui contribuent à les définir. Dans tous les cas, les dimensions sociales et leurs enjeux (de pouvoir et de domination) se retraduisent, de manière « brouillée » dirait Bourdieu ou « masquée » pour Lacoste, toujours en termes spatiaux, comme les dimensions spatiales sont l'œuvre d'incessantes pratiques (qui peuvent être non moins brouillées et/ou masquées) de qualifications, de classifications, de représentations, de hiérarchisations sociales de personnes, de groupes... Ce que montrent bien chacun des textes qui se situent d'ailleurs tous à l'intersection de plusieurs disciplines pour rendre compte des objets qu'ils se sont donnés d'analyser

HARPS3 for a Roboticized Isaac Newton Telescope

We present a description of a new instrument development, HARPS3, planned to be installed on an upgraded and roboticized Isaac Newton Telescope by end-2018. HARPS3 will be a high resolution (R = 115,000) echelle spectrograph with a wavelength range from 380-690 nm. It is being built as part of the Terra Hunting Experiment - a future 10 year radial velocity measurement programme to discover Earth-like exoplanets. The instrument design is based on the successful HARPS spectrograph on the 3.6m ESO telescope and HARPS-N on the TNG telescope. The main changes to the design in HARPS3 will be: a customised fibre adapter at the Cassegrain focus providing a stabilised beam feed and on-sky fibre diameter ~ 1.4 arcsec, the implementation of a new continuous flow cryostat to keep the CCD temperature very stable, detailed characterisation of the HARPS3 CCD to map the effective pixel positions and thus provide an improved accuracy wavelength solution, an optimised integrated polarimeter and the instrument integrated into a robotic operation. The robotic operation will optimise our programme which requires our target stars to be measured on a nightly basis. We present an overview of the entire project, including a description of our anticipated robotic operation.Comment: 13 pages, 8 figures, SPIE conference proceeding

Soil microbial CNP and respiration responses to organic matter and nutrient additions: evidence from a tropical soil incubation

Soil nutrient availability has a strong influence on the fate of soil carbon (C) during microbial decomposition, contributing to Earth's C balance. While nutrient availability itself can impact microbial physiology and C partitioning between biomass and respiration during soil organic matter decomposition, the availability of labile C inputs may mediate the response of microorganisms to nutrient additions. As soil organic matter is decomposed, microorganisms retain or release C, nitrogen (N) or phosphorus (P) to maintain a stoichiometric balance. Although the concept of a microbial stoichiometric homeostasis has previously been proposed, microbial biomass CNP ratios are not static, and this may have very relevant implications for microbial physiological activities. Here, we tested the hypothesis that N, P and potassium (K) nutrient additions impact C cycling in a tropical soil due to microbial stoichiometric constraints to growth and respiration, and that the availability of energy-rich labile organic matter in the soil (i.e. leaf litter) mediates the response to nutrient addition. We incubated tropical soil from French Guiana with a ¹³C labeled leaf litter addition and with mineral nutrient additions of +K, +N, +NK, +PK and +NPK for 30 days. We found that litter additions led to a ten-fold increase in microbial respiration and a doubling of microbial biomass C, along with greater microbial N and P content. We found some evidence that P additions increased soil CO² fluxes. Additionally, we found microbial biomass CP and NP ratios varied more widely than CN in response to nutrient and organic matter additions, with important implications for the role of microorganisms in C cycling. The addition of litter did not prime soil organic matter decomposition, except in combination with +NK fertilization, indicating possible P-mining of soil organic matter in this P-poor tropical soil. Together, these results point toward an ultimate labile organic substrate limitation of soil microorganisms in this tropical soil, but also indicate a complex interaction between C, N, P and K availability. This highlights the difference between microbial C cycling responses to N, P, or K additions in the tropics and explains why coupled C, N and P cycling modeling efforts cannot rely on strict microbial stoichiometric homeostasis as an underlying assumption