Cannabinoid Receptors Modulate Neuronal Morphology and AnkyrinG Density at the Axon Initial Segment

Peer reviewe

Hsp90 activity is necessary to acquire a proper neuronal polarization

Chaperones are critical for the folding and regulation of a wide array of cellular proteins. Heat Shock Proteins (Hsps) are the most representative group of chaperones. Hsp90 represents up to 1-2% of soluble protein. Although the Hsp90 role is being studied in neurodegenerative diseases, its role in neuronal differentiation remains mostly unknown. Since neuronal polarity mechanisms depend on local stability and degradation, we asked whether Hsp90 could be a regulator of axonal polarity and growth. Thus, we studied the role of Hsp90 activity in a well established model of cultured hippocampal neurons using an Hsp90 specific inhibitor, 17-AAG. Our present data shows that Hsp90 inhibition at different developmental stages disturbs neuronal polarity formation or axonal elongation. Hsp90 inhibition during the first 3. h in culture promotes multiple axon morphology, while this inhibition after 3. h slows down axonal elongation. Hsp90 inhibition was accompanied by decreased Akt and GSK3 expression, as well as, a reduced Akt activity. In parallel, we detected an alteration of kinesin-1 subcellular distribution. Moreover, these effects were seconded by changes in Hsp70/Hsc70 subcellular localization that seem to compensate the lack of Hsp90 activity. In conclusion, our data strongly suggests that Hsp90 activity is necessary to control the expression, activity or location of specific kinases and motor proteins during the axon specification and axon elongation processes. Even more, our data demonstrate the existence of a >time-window> for axon specification in this model of cultured neurons after which the inhibition of Hsp90 only affects axonal elongation mechanisms. © 2013 Elsevier B.V.Peer Reviewe

Hybrid optical CDMA-FSO communications network under spatially correlated gamma-gamma scintillation

\u3cp\u3eIn this paper, we propose a new hybrid network solution based on asynchronous optical code-division multiple-access (OCDMA) and free-space optical (FSO) technologies for last-mile access networks, where fiber deployment is impractical. The architecture of the proposed hybrid OCDMA-FSO network is thoroughly described. The users access the network in a fully asynchronous manner by means of assigned fast frequency hopping (FFH)-based codes. In the FSO receiver, an equal gain-combining technique is employed along with intensity modulation and direct detection. New analytical formalisms for evaluating the average bit error rate (ABER) performance are also proposed. These formalisms, based on the spatially correlated gamma-gamma statistical model, are derived considering three distinct scenarios, namely, uncorrelated, totally correlated, and partially correlated channels. Numerical results show that users can successfully achieve error-free ABER levels for the three scenarios considered as long as forward error correction (FEC) algorithms are employed. Therefore, OCDMA-FSO networks can be a prospective alternative to deliver high-speed communication services to access networks with deficient fiber infrastructure.\u3c/p\u3

Fade statistics of M-turbulent optical links

A new and generalized statistical model, called Málaga or simply ℳ distribution, has been derived recently to characterize the irradiance fluctuations of an unbounded optical wavefront propagating through a turbulent medium under all irradiance fluctuation conditions. The aforementioned model extends and unifies in a simple analytical closed-form expression most of the proposed statistical models for free-space optical (FSO) communications widely employed until now in the scientific literature. Based on that ℳ model, we have studied some important features associated to its fade statistics and expressed in terms of the expected number of fades per second. The derived expressions become relevant for many aspects in a FSO system, especially those ones related to determine the optimum threshold in a receiver based on a direct detection scheme employing a fixed detection threshold

ATP-P2X7 Receptor Modulates Axon Initial Segment Composition and Function in Physiological Conditions and Brain Injury

© 2014 The Author. All rights reserved. Axon properties, including action potential initiation and modulation, depend on both AIS integrity and the regulation of ion channel expression in the AIS. Alteration of the axon initial segment (AIS) has been implicated in neurodegenerative, psychiatric, and brain trauma diseases, thus identification of the physiological mechanisms that regulate the AIS is required to understand and circumvent AIS alterations in pathological conditions. Here, we show that the purinergic P2X7 receptor and its agonist, adenosine triphosphate (ATP), modulate both structural proteins and ion channel density at the AIS in cultured neurons and brain slices. In cultured hippocampal neurons, an increment of extracellular ATP concentration or P2X7-green fluorescent protein (GFP) expression reduced the density of ankyrin G and voltage-gated sodium channels at the AIS. This effect is mediated by P2X7-regulated calcium influx and calpain activation, and impaired by P2X7 inhibition with Brilliant Blue G (BBG), or P2X7 suppression. Electrophysiological studies in brain slices showed that P2X7-GFP transfection decreased both sodium current amplitude and intrinsic neuronal excitability, while P2X7 inhibition had the opposite effect. Finally, inhibition of P2X7 with BBG prevented AIS disruption after ischemia/reperfusion in rats. In conclusion, our study demonstrates an involvement of P2X7 receptors in the regulation of AIS mediated neuronal excitability in physiological and pathological conditions.Plan Nacional I+D+i (Spain), INSERM and Agence National de la Recherche (EXCION, EPISOM)Peer Reviewe

Revisiting the use of Live Attenuated viruses as models to study the pathogenesis and the mechanisms involved in protection against African swine fever

Trabajo presentado en el 8th EPIZONE Annual Meeting "Primed for tomorrow", celebrado en Copenhague (Dinamarca) del 23 al 25 de septiembre de 2014.The meeting is entitled: "Primed for tomorrow" and will address the latest developments aimed at monitoring and understanding the evolution, emergence, transmission and spread of epizootic viruses. The focus will remain on the EPIZONE themes aimed at improved disease control through integration and collaboration of research in diagnosis, intervention strategies, risk assessment, surveillance and epidemiology. A stimulating scientific programme will be provided by invited speakers and selected poster and oral presentations describing recent research on epizootic diseases of cattle, pigs, poultry, sheep, goats, fish and horses. This meeting builds on previous highly successful EPIZONE meetings and will provide extensive opportunities for networking, scientific exchange and fostering collaboration

Polymorphisms within the TNFSF4 and MAPKAPK2 Loci influence the risk of developing invasive aspergillosis: A two-stage case control study in the context of the aspBIOmics consortium

Here, we assessed whether 36 single nucleotide polymorphisms (SNPs) within the TNFSF4 and MAPKAPK2 loci influence the risk of developing invasive aspergillosis (IA). We conducted a two-stage case control study including 911 high-risk patients diagnosed with hematological malignancies that were ascertained through the aspBIOmics consortium. The meta-analysis of the discovery and replication populations revealed that carriers of the TNFSF4rs7526628T/T genotype had a significantly increased risk of developing IA (p = 0.00022). We also found that carriers of the TNFSF4rs7526628T allele showed decreased serum levels of TNFSF14 protein (p = 0.0027), and that their macrophages had a decreased fungicidal activity (p = 0.048). In addition, we observed that each copy of the MAPKAPK2rs12137965G allele increased the risk of IA by 60% (p = 0.0017), whereas each copy of the MAPKAPK2rs17013271T allele was estimated to decrease the risk of developing the disease (p = 0.0029). Mechanistically, we found that carriers of the risk MAPKAPK2rs12137965G allele showed increased numbers of CD38+IgM-IgD- plasmablasts in blood (p = 0.00086), whereas those harboring two copies of the allele had decreased serum concentrations of thymic stromal lymphopoietin (p = 0.00097). Finally, we also found that carriers of the protective MAPKAPK2rs17013271T allele had decreased numbers of CD27-IgM-IgD- B cells (p = 0.00087) and significantly lower numbers of CD14+ and CD14+CD16- cells (p = 0.00018 and 0.00023). Altogether, these results suggest a role of the TNFSF4 and MAPKAPK2 genes in determining IA risk.This study was supported by grants PI20/01845, PI12/02688, and ISCIII-FEDER PI17/02276 from Fondo de Investigaciones Sanitarias (Madrid, Spain), PIM2010EPA-00756 from the ERA-NET PathoGenoMics (0315900A), the Collaborative Research Center/Transregio 124 FungiNet, the Fundacao para a Ciencia e Tecnologia (FCT) (PTDC/SAU-SER/29635/2017, PTDC/MED-GEN/28778/2017, CEECIND/03628/2017, and CEECIND/04058/2018), the European Union's Horizon 2020 research and innovation programme under grant agreement no. 847507, and the "la Caixa" Foundation (ID 100010434) and FCT under the agreement LCF/PR/HP17/52190003)