Parallel readout of pathway-specific inputs to laminated brain structures

Local field potentials (LFPs) capture the electrical activity produced by principal cells during integration of converging synaptic inputs from multiple neuronal populations. However, since synaptic currents mix in the extracellular volume, LFPs have complex spatiotempo-ral structure, making them hard to exploit. Here we propose a biophysical framework to identify and separate LFP-generators. First we use a computational multineuronal model that scales up single cell electrogenesis driven by several synaptic inputs to realistic aggregate LFPs. This approach relies on the fixed but distinct locations of synaptic inputs from different presynaptic populations targeting a laminated brain structure. Thus the LFPs are contributed by several pathway-specific LFP-generators, whose electrical activity is defined by the spatial distribution of synaptic terminals and the time course of synaptic currents initiated in target cells by the corresponding presynaptic population. Then we explore the efficacy of independent component analysis to blindly separate converging sources and reconstruct pathway-specific LFP-generators. This approach can optimally locate synaptic inputs with subcellular accuracy while the reconstructed time course of pathway-specific LFP-generators is reliable in the millisecond scale. We also describe few cases where the non-linear intracellular interaction of strongly overlapping LFP-generators may lead to a significant cross-contamination and the appearance of derivative generators. We show that the approach reliably disentangle ongoing LFPs in the hippocampus into contribution of several LFP-generators.We were able to readout in parallel the pathway-specific presynap-tic activity of projection cells in the entorhinal cortex and pyramidal cells in the ipsilateral and contralateral CA3. Thus we provide formal mathematical and experimental support for parallel readout of the activity of converging presynaptic populations in working neuronal circuits from common LFPs. © 2011 Makarova, Ibarz, Makarov, Benito and Herreras.This study has been financed by grants FIS2010-20054 and BFU2010-19192 of the Spanish Ministry of Science and Innovation.Peer Reviewe

Population structure of anisakis simplex (nematoda) in harbor porpoises phocoena phocoena off Denmark

The population structure and habitat selection of Anisakis simplex in 35 harbor porpoises off Denmark are described. The nematodes were collected from the stomach and duodenal ampulla and were categorized as third-stage larvae, fourth-stage larvae, subadults, and adults. The porpoises harbored 8,043 specimens of A. simplex. The proportion of adults and subadults increased with infrapopulation size. The number of development stages across infrapopulations covaried significantly (Kendall's test of concordance). Concordance was higher in hosts with the highest intensities than in those with low and medium intensities. All stages occurred mainly in the forestomach, but this trend was stronger for the adults. Adult and subadult sex ratios did not depart significantly from 1:1. Our data suggested that recruitment and duration of each stage were the main factors accounting for infrapopulation structure. The preference of A. simplex for the forestomach conformed with previous studies, but the narrower distribution of adults relative to other stages might indicate a strategy to enhance mating opportunities. Information on sex ratios of A. simplex is scarce and contradictory. We suggest that the discrepancies might partly reflect differences in categorization criteria and statistical methods.Herreras Belled, Maria Victoria, [email protected] ; Balbuena Diaz-Pines, Juan Antonio, [email protected] ; Aznar Avendaño, Francisco Javier, [email protected] ; Raga Esteve, Juan Antonio, [email protected]

EVALUATION OF RETRIEVED AEROSOL EXTINCTION PROFILES USING AS REFERENCE THE AEROSOL OPTICAL DEPTH DIFFERENCES BETWEEN VARIOUS HEIGHTS

Aerosol extinction vertical profiles at Granada (Spain) are calculated with the GRASP (Generalized Retrieval of Aerosol and Surface Properties) code using as input Aerosol Optical Depth (AOD) and sky radiance measurements from AERONET (AEerosol RObotic NETwork) and ceilometer RCS (Range Corrected Signal) profiles, both corresponding to the Granada (Spain) station. This methodology is so called GRASPpac due to the combination of sun/sky photometer and ceilometer on GRASP. In order to evaluate the accuracy of these retrieved extinction profiles at Granada, two more nearby AERONET stations, located at different altitudes, are used. The AOD difference of the three choosen AERONET sun/sky photometers have been used to calculate the Integrated Aerosol Extinction (IAE) at different height layers. These three AERONET sun/sky photometers are used as a reference and compared against the integrated extinction at the same layers from the extinction profiles retrieved by GRASPpac. The differences between AERONET and GRASPpac retrieved IAE values indicate that GRASPpac aerosol extinction profiles are at least within the uncertainty of the sun/sky photometer measurements, but GRASPpac method overestimates the AERONET extinction at low altitudes and underestimates it at high levels. The most accurate and precise retrieved extinction correspond to the intermediate layer with a mean bias error (MBE ± standard deviation) of 0.00 ± 0.01 (0 ± 59%) for 1020 nm, and the worst integrated extinction results were obtained for the upper layers with a MBE of −0.01 ± 0.02 (28 ± 36%) for 1020 nm. In general these MBE values increases for shorter wavelengths. In order to obtain a complete characterization of this bias, the dependence of the obtained differences on the aerosol size and the solar zenith angle, among others, are analysed in detail. Finally, the behaviour of vertically-resolved aerosol extinction at Granada is evaluated using averages of the retrieved profiles from November of 2012 to December of 2017. The highest IAE values are found in Summer with mean values of 0.09 for the lower layers and 0.07 for the upper ones, both at 440 nm wavelength.Andalusia Regional Government (project P12-RNM-2409)“Consejería de Educación” of “Junta de Castilla y León” (project VA100U14)Spanish Ministry of Economy and Competitiveness under the projects, CMT2015-66742-R, CGL2016-81092-R, “Juan de la Cierva-Incorporación” program (FIJCI-2016-30007) and CGL2017-90884-RED

Investigación de los efectos del consumo moderado de vino en la enfermedad de Alzheimer en modelos de ratones con patología Aß y Tau

Resumen La enfermedad de Alzheimer (EA) es la forma más común de demencia y tiene una elevada morbilidad y mortalidad. La EA se caracteriza principalmente por la presencia de dos estructuras aberrantes en el cerebro de los pacientes, placas seniles formadas por péptido-β-amiloide (Aβ) y ovillos neurofibrilares cuyo principal componente es la proteína tau fosforilada. Aunque actualmente no se conoce bien la etiopatogenia, cada vez son más los estudios que demuestran un efecto causal del microbioma intestinal sobre la EA y las funciones cognitivas, a través del "eje microbiota intestino-cerebro". Las evidencias científicas sugieren un posible efecto protector de los polifenoles del vino frente a los trastornos neurodegenerativos aunque se desconocen los mecanismos y, hasta el momento, los estudios para evaluar de forma exhaustiva el efecto del vino sobre la etiopatogenia de la EA son muy escasos. El objetivo principal de la línea de investigación que enmarca este trabajo es entender cómo la dieta, y especialmente los polifenoles presentes en los alimentos vegetales, y otros factores del estilo de vida interactúan con el microbioma oral e intestinal, en relación con la salud digestiva y el deterioro cognitivo. Para ello, se está llevando a cabo una aproximación experimental que tiene como finalidad evaluar el posible efecto protector de los polifenoles del vino, mediante la suplementación de la dieta en dos modelos murinos de la EA (patología Aß y Tau), y, por otro lado, se está profundizando en el estudio de los mecanismos de protección mediante la evaluación de los efectos del ácido protocatéquico sobre la actividad eléctrica del cerebro

Consensus document on allergic conjunctivitis (DECA)

Allergic conjunctivitis (AC) is an inflammatory disease of the conjunctiva caused mainly by an IgE-mediated mechanism. It is the most common type of ocular allergy. Despite being the most benign form of conjunctivitis, AC has a considerable effect on patient quality of life, reduces work productivity, and increases health care costs. No consensus has been reached on its classification, diagnosis, or treatment. Consequently, the literature provides little information on its natural history, epidemiological data are scarce, and it is often difficult to ascertain its true morbidity. The main objective of the Consensus Document on Allergic Conjunctivitis (Documento dE Consenso sobre Conjuntivitis Alérgica [DECA]), which was drafted by an expert panel from the Spanish Society of Allergology and Spanish Society of Ophthalmology, was to reach agreement on basic criteria that could prove useful for both specialists and primary care physicians and facilitate the diagnosis, classification, and treatment of AC. This document is the first of its kind to describe and analyze aspects of AC that could make it possible to control symptoms

Retrieval of aerosol properties from zenith sky radiance measurements

This study explores the potential to retrieve aerosol properties with the GRASP algorithm (Generalized Retrieval of Atmosphere and Surface Properties) using as input measurements of zenith sky radiance (ZSR), which are sky radiance values measured in the zenith direction, recorded at four wavelengths by a ZEN-R52 radiometer. To this end, the ZSR measured at 440, 500, 675 and 870 nm by a ZEN-R52 (ZSRZEN), installed in Valladolid (Spain), is employed. This instrument is calibrated by intercomparing the signal of each channel with coincident ZSR values simulated (ZSRSIM) at the same wavelengths with a radiative transfer model (RTM). These simulations are carried out using the GRASP forward module as RTM and the aerosol information from a co-located CE318 photometer belonging to AERONET (AErosol RObotic NETwork) as input. The dark signal and the signal dependence on temperature are characterized and included in the calibration process. The uncertainties for each channel are quantified by an intercomparison with a co-located CE318 photometer, obtaining lower values for shorter wavelengths; they are between 3 % for 440 nm and 21 % for 870 nm. The proposed inversion strategy for the aerosol retrieval using the ZSRZEN measurements as input, i.e. so-called GRASP-ZEN, assumes the aerosol as an external mixture of five pre-calculated aerosol types. A sensitivity analysis is conducted using synthetic ZSRZEN measurements, pointing out that these measurements are sensitive to aerosol load and type. It also assesses that the retrieved aerosol optical depth (AOD) values in general overestimate the reference ones by 0.03, 0.02, 0.02 and 0.01 for 440, 500, 675 and 870 nm, respectively. The calibrated ZSRZEN measurements, recorded during 2.5 years at Valladolid, are inverted by the GRASP-ZEN strategy to retrieve some aerosol properties like AOD. The retrieved AOD shows a high correlation with respect to independent values obtained from a co-located AERONET CE318 photometer, with determination coefficients (r2) of 0.86, 0.85, 0.79 and 0.72 for 440, 500, 675 and 870 nm, respectively, and finding uncertainties between 0.02 and 0.03 with respect to the AERONET values. Finally, the retrieval of other aerosol properties, like aerosol volume concentration for total, fine and coarse modes (VCT, VCF and VCC, respectively), is also explored. The comparison against independent values from AERONET presents r2 values of 0.57, 0.56 and 0.66 and uncertainties of 0.009, 0.016 and 0.02 µm3 µm−2 for VCT, VCF and VCC, respectively.</p

State recognition for ‘contested languages’: a comparative study of Sardinian and Asturian, 1992–2010

While the idea of a named language as a separate and discrete identity is a political and social construct, in the cases of Sardinian and Asturian doubts over their respective ‘languageness’ have real material consequences, particularly in relation to language policy decisions at the state level. The Asturian example highlights how its lack of official status means that it is either ignored or subjected to repeated challenges to its status as a language variety deserving of recognition and support, reflecting how ‘official language’ in the Spanish context is often understood in practice as synonymous with the theoretically broader category of ‘language’. In contrast, the recent state recognition of Sardinian speakers as a linguistic minority in Italy (Law 482/1999) illustrates how legal recognition served to overcome existing obstacles to the implementation of regional language policy measures. At the same time, the limited subsequent effects of this Law, particularly in the sphere of education, are a reminder of the shortcomings of top-down policies which fail to engage with the local language practices and attitudes of the communities of speakers recognized. The contrastive focus of this article thus acknowledges the continued material consequences of top-down language classification, while highlighting its inadequacies as a language policy mechanism which reinforces artificial distinctions between speech varieties and speakers deserving of recognition

The Effects of NMDA Subunit Composition on Calcium Influx and Spike Timing-Dependent Plasticity in Striatal Medium Spiny Neurons

Calcium through NMDA receptors (NMDARs) is necessary for the long-term potentiation (LTP) of synaptic strength; however, NMDARs differ in several properties that can influence the amount of calcium influx into the spine. These properties, such as sensitivity to magnesium block and conductance decay kinetics, change the receptor's response to spike timing dependent plasticity (STDP) protocols, and thereby shape synaptic integration and information processing. This study investigates the role of GluN2 subunit differences on spine calcium concentration during several STDP protocols in a model of a striatal medium spiny projection neuron (MSPN). The multi-compartment, multi-channel model exhibits firing frequency, spike width, and latency to first spike similar to current clamp data from mouse dorsal striatum MSPN. We find that NMDAR-mediated calcium is dependent on GluN2 subunit type, action potential timing, duration of somatic depolarization, and number of action potentials. Furthermore, the model demonstrates that in MSPNs, GluN2A and GluN2B control which STDP intervals allow for substantial calcium elevation in spines. The model predicts that blocking GluN2B subunits would modulate the range of intervals that cause long term potentiation. We confirmed this prediction experimentally, demonstrating that blocking GluN2B in the striatum, narrows the range of STDP intervals that cause long term potentiation. This ability of the GluN2 subunit to modulate the shape of the STDP curve could underlie the role that GluN2 subunits play in learning and development

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research