Endocannabinoid CB1 receptors modulate visual output from the thalamus

[Abstract] Rationale Endocannabinoids have emerged as a modulatory brain system affecting different types of synapses, broadly distributed throughout the CNS, which explain the diverse psychophysical effects observed following activation of the endocannabinoid system. Objectives and methods The present study aimed to characterize the effect of CB1-mediated activity in the visual thalamus. In vivo single-unit extracellular recordings were performed in anaesthetized adult pigmented rats, measuring visual and spontaneous activity, combined with application of CB1 receptor agonists (anandamide, 2-AG, and O2545) and one antagonist, AM251. Results CB1 receptors activation revealed two cellular populations, with excitatory effects on ∼28% of cells and inhibitory in ∼72%, actions which were blocked by the antagonist AM251. The agonist action significantly altered both spontaneous and visual activity, shifting the signal-tonoise ratio (S/N), with accompanying changes in the variability within the visual response. Increased responses by agonist application were accompanied by a decrease in S/N and an increase in variability, while those cells inhibited by the agonist showed an increase in S/N and a decrease in variability. There was no obvious correlation between the two effects and any other response property suggesting a more general role in modulating all information passing from LGN to cortex. Conclusions Our data support a role for CB1 at the level of the thalamus acting as a dynamic modulator of visual information being sent to the cortex, apparently maintaining the salience of the signal within upper and lower boundaries. This may account for some of the behavioral effects of cannabis.Ministerio de Ciencia e Innovación; BFU2009-08169Xunta de Galicia; 2007/000140-

Study of breast cancer incidence in patients of lymphangioleiomyomatosis

Molecular evidence has linked the pathophysiology of lymphangioleiomyomatosis (LAM) to that of metastatic breast cancer. Following on this observation, we assessed the association between LAM and subsequent breast cancer. An epidemiological study was carried out using three LAM country cohorts, from Japan, Spain, and the United Kingdom. The number of incident breast cancer cases observed in these cohorts was compared with the number expected on the basis of the country-specific incidence rates for the period 2000–2014. Immunohistochemical studies and exome sequence analysis were performed in two and one tumors, respectively. All cohorts revealed breast cancer standardized incidence ratios (SIRs) ≥ 2.25. The combined analysis of all cases or restricted to pre-menopausal age groups revealed significantly higher incidence of breast cancer: SIR = 2.81, 95 % confidence interval (CI) = 1.32–5.57, P = 0.009; and SIR = 4.88, 95 % CI = 2.29–9.99, P = 0.0007, respectively. Immunohistochemical analyses showed positivity for known markers of lung metastatic potential. This study suggests the existence of increased breast cancer risk among LAM patients. Prospective studies may be warranted to corroborate this result, which may be particularly relevant for pre-menopausal women with LAM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10549-016-3737-8) contains supplementary material, which is available to authorized users

Breaking the Vehicular Wireless Communications Barriers: Vertical Handover Techniques for Heterogeneous Networks

“© 2014 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.”End users increasingly expect ubiquitous connectivity while on the move. With a variety of wireless access technologies available, we expect to always be connected to the technology that best matches our performance goals and price points. Meanwhile, sophisticated onboard units (OBUs) enable geolocation and complex computation in support of handover. In this paper, we present an overview of vertical handover techniques and propose an algorithm empowered by the IEEE 802.21 standard, which considers the particularities of the vehicular networks (VNs), the surrounding context, the application requirements, the user preferences, and the different available wireless networks [i.e., Wireless Fidelity (Wi-Fi), Worldwide Interoperability for Microwave Access (WiMAX), and Universal Mobile Telecommunications System (UMTS)] to improve users' quality of experience (QoE). Our results demonstrate that our approach, under the considered scenario, is able to meet application requirements while ensuring user preferences are also met.This work was supported in part by the Spanish Ministry of Economy and Competitiveness under Grant TIN2011-27543-C03-01 and Grant BES-2012-052673, by Universitat Politecnica de Valencia through the ABATIS Project (PAID-05-12), and by the Science Foundation Ireland under Grant 10/IN.1/I3007 and Grant 10/CE/I1853. The review of this paper was coordinated by Dr. Y. Ji.Marquez-Barja, JM.; Ahmadi, H.; Tornell, SM.; Tavares De Araujo Cesariny Calafate, CM.; Cano Escribá, JC.; Manzoni, P.; Dasilva, LA. (2015). Breaking the Vehicular Wireless Communications Barriers: Vertical Handover Techniques for Heterogeneous Networks. IEEE Transactions on Vehicular Technology. 64(12):5878-5890. https://doi.org/10.1109/TVT.2014.2386911S58785890641

High-resolution mapping of infraslow cortical brain activity enabled by graphene microtransistors

Recording infraslow brain signals (<0.1 Hz) with microelectrodes is severely hampered by current microelectrode materials, primarily due to limitations resulting from voltage drift and high electrode impedance. Hence, most recording systems include high-pass filters that solve saturation issues but come hand in hand with loss of physiological and pathological information. In this work, we use flexible epicortical and intracortical arrays of graphene solution-gated field-effect transistors (gSGFETs) to map cortical spreading depression in rats and demonstrate that gSGFETs are able to record, with high fidelity, infraslow signals together with signals in the typical local field potential bandwidth. The wide recording bandwidth results from the direct field-effect coupling of the active transistor, in contrast to standard passive electrodes, as well as from the electrochemical inertness of graphene. Taking advantage of such functionality, we envision broad applications of gSGFET technology for monitoring infraslow brain activity both in research and in the clinic.This work was funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 696656 (Graphene Flagship) and no. 732032 (BrainCom). This work has made use of the Spanish ICTS Network MICRONANOFABS partially supported by MINECO and the ICTS ‘NANBIOSIS’, more specifically by the Micro-NanoTechnology Unit of the CIBER in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) at the IMB-CNM. E.M.C. acknowledges that this work has been done in the framework of the PhD in Electrical and Telecommunication Engineering at the Universitat Autònoma de Barcelona. E..C. thanks the Spanish Ministerio de Economía y Competitividad for the Juan de la Cierva postdoctoral grant IJCI-2015–25201. T. Durduran acknowledges support from Fundació CELLEX Barcelona, Ministerio de Economía y Competitividad /FEDER (PHOTODEMENTIA, DPI2015–64358-C2–1-R), the “Severo Ochoa” Programme for Centres of Excellence in R&D (SEV-2015–0522) and the Obra Social “la Caixa” Foundation (LlumMedBcn). M.V.S.V. acknowledges support from MINECO BFU2017-85048-R. ICN2 is supported by the Severo Ochoa programme fromSpanish MINECO (grant no. SEV-2017-0706).Peer reviewe

Altered neocortical dynamics in a mouse model of Williams-Beuren syndrome

Williams-Beuren syndrome (WBS) is a rare neurodevelopmental disorder characterized by moderate intellectual disability and learning difficulties alongside behavioral abnormalities such as hypersociability. Several structural and functional brain alterations are characteristic of this syndrome, as well as disturbed sleep and sleeping patterns. However, the detailed physiological mechanisms underlying WBS are mostly unknown. Here, we characterized the cortical dynamics in a mouse model of WBS previously reported to replicate most of the behavioral alterations described in humans. We recorded the laminar local field potential generated in the frontal cortex during deep anesthesia and characterized the properties of the emergent slow oscillation activity. Moreover, we performed micro-electrocorticogram recordings using multielectrode arrays covering the cortical surface of one hemisphere. We found significant differences between the cortical emergent activity and functional connectivity between wild-type mice and WBS model mice. Slow oscillations displayed Up states with diminished firing rate and lower high-frequency content in the gamma range. Lower firing rates were also recorded in the awake WBS animals while performing a marble burying task and could be associated with the decreased spine density and thus synaptic connectivity in this cortical area. We also found an overall increase in functional connectivity between brain areas, reflected in lower clustering and abnormally high integration, especially in the gamma range. These results expand previous findings in humans, suggesting that the cognitive deficits characterizing WBS might be associated with reduced excitability, plus an imbalance in the capacity to functionally integrate and segregate information.This work was supported by EU H2020 Research and Innovation Programme under Grant Agreement No. 720270 (HBP SGA2), BFU2017-85048-R Spanish Ministry of Science and CERCA Programme/Generalitat de Catalunya to MVSV

Surfing transcriptomic landscapes. A step beyond the annotation of chromosome 16 proteome.

The Spanish team of the Human Proteome Project (SpHPP) marked the annotation of Chr16 and data analysis as one of its priorities. Precise annotation of Chromosome 16 proteins according to C-HPP criteria is presented. Moreover, Human Body Map 2.0 RNA-Seq and Encyclopedia of DNA Elements (ENCODE) data sets were used to obtain further information relative to cell/tissue specific chromosome 16 coding gene expression patterns and to infer the presence of missing proteins. Twenty-four shotgun 2D-LC-MS/MS and gel/LC-MS/MS MIAPE compliant experiments, representing 41% coverage of chromosome 16 proteins, were performed. Furthermore, mapping of large-scale multicenter mass spectrometry data sets from CCD18, MCF7, Jurkat, and Ramos cell lines into RNA-Seq data allowed further insights relative to correlation of chromosome 16 transcripts and proteins. Detection and quantification of chromosome 16 proteins in biological matrices by SRM procedures are also primary goals of the SpHPP. Two strategies were undertaken: one focused on known proteins, taking advantage of MS data already available, and the second, aimed at the detection of the missing proteins, is based on the expression of recombinant proteins to gather MS information and optimize SRM methods that will be used in real biological samples. SRM methods for 49 known proteins and for recombinant forms of 24 missing proteins are reported in this study