Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort

Dyslexia is one of the most common childhood disorders with a prevalence of around 5-10% in school-age children. Although an important genetic component is known to have a role in the aetiology of dyslexia, we are far from understanding the molecular mechanisms leading to the disorder. Several candidate genes have been implicated in dyslexia, including DYX1C1, DCDC2, KIAA0319, and the MRPL19/C2ORF3 locus, each with reports of both positive and no replications. We generated a European cross-linguistic sample of school-age children-the NeuroDys cohort-that includes more than 900 individuals with dyslexia, sampled with homogenous inclusion criteria across eight European countries, and a comparable number of controls. Here, we describe association analysis of the dyslexia candidate genes/locus in the NeuroDys cohort. We performed both case-control and quantitative association analyses of single markers and haplotypes previously reported to be dyslexia-associated. Although we observed association signals in samples from single countries, we did not find any marker or haplotype that was significantly associated with either case-control status or quantitative measurements of word-reading or spelling in the meta-analysis of all eight countries combined. Like in other neurocognitive disorders, our findings underline the need for larger sample sizes to validate possibly weak genetic effects. © 2014 Macmillan Publishers Limited All rights reserved.

Specification and quantitative analysis of probabilistic cloud deployment patterns

Cloud computing is a new technological paradigm offering computing infrastructure, software and platforms as a pay-as-you-go, subscription-based service. Many potential customers of cloud services require essential cost assessments to be undertaken before transitioning to the cloud. Current assessment techniques are imprecise as they rely on simplified specifications of resource requirements that fail to account for probabilistic variations in usage. In this paper, we address these problems and propose a new probabilistic pattern modelling (PPM) approach to cloud costing and resource usage verification. Our approach is based on a concise expression of probabilistic resource usage patterns translated to Markov decision processes (MDPs). Key costing and usage queries are identified and expressed in a probabilistic variant of temporal logic and calculated to a high degree of precision using quantitative verification techniques. The PPM cost assessment approach has been implemented as a Java library and validated with a case study and scalability experiments. © 2012 Springer-Verlag Berlin Heidelberg.

Specific Increase in MDR1 Mediated Drug-Efflux in Human Brain Endothelial Cells following Co-Exposure to HIV-1 and Saquinavir

Persistence of HIV-1 reservoirs within the Central Nervous System (CNS) remains a significant challenge to the efficacy of potent anti-HIV-1 drugs. The primary human Brain Microvascular Endothelial Cells (HBMVEC) constitutes the Blood Brain Barrier (BBB) which interferes with anti-HIV drug delivery into the CNS. The ATP binding cassette (ABC) transporters expressed on HBMVEC can efflux HIV-1 protease inhibitors (HPI), enabling the persistence of HIV-1 in CNS. Constitutive low level expression of several ABC-transporters, such as MDR1 (a.k.a. P-gp) and MRPs are documented in HBMVEC. Although it is recognized that inflammatory cytokines and exposure to xenobiotic drug substrates (e.g HPI) can augment the expression of these transporters, it is not known whether concomitant exposure to virus and anti-retroviral drugs can increase drug-efflux functions in HBMVEC. Our in vitro studies showed that exposure of HBMVEC to HIV-1 significantly up-regulates both MDR1 gene expression and protein levels; however, no significant increases in either MRP-1 or MRP-2 were observed. Furthermore, calcein-AM dye-efflux assays using HBMVEC showed that, compared to virus exposure alone, the MDR1 mediated drug-efflux function was significantly induced following concomitant exposure to both HIV-1 and saquinavir (SQV). This increase in MDR1 mediated drug-efflux was further substantiated via increased intracellular retention of radiolabeled [3H-] SQV. The crucial role of MDR1 in 3H-SQV efflux from HBMVEC was further confirmed by using both a MDR1 specific blocker (PSC-833) and MDR1 specific siRNAs. Therefore, MDR1 specific drug-efflux function increases in HBMVEC following co-exposure to HIV-1 and SQV which can reduce the penetration of HPIs into the infected brain reservoirs of HIV-1. A targeted suppression of MDR1 in the BBB may thus provide a novel strategy to suppress residual viral replication in the CNS, by augmenting the therapeutic efficacy of HAART drugs.

Data compilation on the biological response to ocean acidification: environmental and experimental context of data sets and related literature

The exponential growth of studies on the biological response to ocean acidification over the last few decades has generated a large amount of data. To facilitate data comparison, a data compilation hosted at the data publisher PANGAEA was initiated in 2008 and is updated on a regular basis (doi:10.1594/PANGAEA.149999). By January 2015, a total of 581 data sets (over 4 000 000 data points) from 539 papers had been archived. Here we present the developments of this data compilation five years since its first description by Nisumaa et al. (2010). Most of study sites from which data archived are still in the Northern Hemisphere and the number of archived data from studies from the Southern Hemisphere and polar oceans are still relatively low. Data from 60 studies that investigated the response of a mix of organisms or natural communities were all added after 2010, indicating a welcomed shift from the study of individual organisms to communities and ecosystems. The initial imbalance of considerably more data archived on calcification and primary production than on other processes has improved. There is also a clear tendency towards more data archived from multifactorial studies after 2010. For easier and more effective access to ocean acidification data, the ocean acidification community is strongly encouraged to contribute to the data archiving effort, and help develop standard vocabularies describing the variables and define best practices for archiving ocean acidification data.

Medida de uma codificação de estímulos sonoros por potenciais pós-sinápticos e potenciais de campo local usando teoria da informação

Coding process is a fundamental aspect of cerebral functioning. The sensory stimuli transformation in neurophysiological responses has been a research theme in several areas of Neuroscience. One of the most used ways to measure a neural code e ciency is by the use of Information Theory measures, such as mutual information. Using these tools, recent studies show that in the auditory cortex both local eld potentials (LFPs) and action potential spiking times code information about sound stimuli. However, there are no studies applying Information Theory tools to investigate the e ciency of codes that use postsynaptics potentials (PSPs), alone and associated with LFP analysis. These signals are related in the sense that LFPs are partly created by joint action of several PSPs. The present dissertation reports information measures between PSP and LFP responses obtained in the primary auditory cortex of anaesthetized rats and auditory stimuli of distinct frequencies. Our results show that PSP responses hold information about sound stimuli in comparable levels and even greater than LFP responses. We have also found that PSPs and LFPs code sound information independently, since the joint analysis of these signals did neither show synergy nor redundancy.

The influence of interhemispheric connections on ongoing and evoked orientation preference maps and spiking activity in the cat primary visual cortex

In the primary visual cortex, neurons with similar physiological features are clustered together in columns extending through all six cortical layers. These columns form modular orientation preference maps. Long-range lateral fibers are associated to the structure of orientation maps since they do not connect columns randomly; they rather cluster in regular intervals and interconnect predominantly columns of neurons responding to similar stimulus features. Single orientation preference maps – the joint activation of domains preferring the same orientation - were observed to emerge spontaneously and it was speculated whether this structured ongoing activation could be caused by the underlying patchy lateral connectivity. Since long-range lateral connections share many features, i.e. clustering, orientation selectivity, with visual inter-hemispheric connections (VIC) through the corpus callosum we used the latter as a model for long-range lateral connectivity. In order to address the question of how the lateral connectivity contributes to spontaneously generated maps of one hemisphere we investigated how these maps react to the deactivation of VICs originating from the contralateral hemisphere. To this end, we performed experiments in eight adult cats. We recorded voltage-sensitive dye (VSD) imaging and electrophysiological spiking activity in one brain hemisphere while reversible deactivating the other hemisphere with a cooling technique. In order to compare ongoing activity with evoked activity patterns we first presented oriented gratings as visual stimuli. Gratings had 8 different orientations distributed equally between 0º and 180º. VSD imaged frames obtained during ongoing activity conditions were then compared to the averaged evoked single orientation maps in three different states: baseline, cooling and recovery. Kohonen self-organizing maps were also used as a means of analysis without prior assumption (like the averaged single condition maps) on ongoing activity. We also evaluated if cooling had a differential effect on evoked and ongoing spiking activity of single units. We found that deactivating VICs caused no spatial disruption on the structure of either evoked or ongoing activity maps. The frequency with which a cardinally preferring (0º or 90º) map would emerge, however, decreased significantly for ongoing but not for evoked activity. The same result was found by training self-organizing maps with recorded data as input. Spiking activity of cardinally preferring units also decreased significantly for ongoing when compared to evoked activity. Based on our results we came to the following conclusions: 1) VICs are not a determinant factor of ongoing map structure. Maps continued to be spontaneously generated with the same quality, probably by a combination of ongoing activity from local recurrent connections, thalamocortical loop and feedback connections. 2) VICs account for a cardinal bias in the temporal sequence of ongoing activity patterns, i.e. deactivating VIC decreases the probability of cardinal maps to emerge spontaneously. 3) Inter- and intrahemispheric long-range connections might serve as a grid preparing primary visual cortex for likely junctions in a larger visual environment encompassing the two hemifields.

The influence of interhemispheric connections on ongoing and evoked orientation preference maps and spiking activity in the cat primary visual cortex

In the primary visual cortex, neurons with similar physiological features are clustered together in columns extending through all six cortical layers. These columns form modular orientation preference maps. Long-range lateral fibers are associated to the structure of orientation maps since they do not connect columns randomly; they rather cluster in regular intervals and interconnect predominantly columns of neurons responding to similar stimulus features. Single orientation preference maps – the joint activation of domains preferring the same orientation - were observed to emerge spontaneously and it was speculated whether this structured ongoing activation could be caused by the underlying patchy lateral connectivity. Since long-range lateral connections share many features, i.e. clustering, orientation selectivity, with visual inter-hemispheric connections (VIC) through the corpus callosum we used the latter as a model for long-range lateral connectivity. In order to address the question of how the lateral connectivity contributes to spontaneously generated maps of one hemisphere we investigated how these maps react to the deactivation of VICs originating from the contralateral hemisphere. To this end, we performed experiments in eight adult cats. We recorded voltage-sensitive dye (VSD) imaging and electrophysiological spiking activity in one brain hemisphere while reversible deactivating the other hemisphere with a cooling technique. In order to compare ongoing activity with evoked activity patterns we first presented oriented gratings as visual stimuli. Gratings had 8 different orientations distributed equally between 0º and 180º. VSD imaged frames obtained during ongoing activity conditions were then compared to the averaged evoked single orientation maps in three different states: baseline, cooling and recovery. Kohonen self-organizing maps were also used as a means of analysis without prior assumption (like the averaged single condition maps) on ongoing activity. We also evaluated if cooling had a differential effect on evoked and ongoing spiking activity of single units. We found that deactivating VICs caused no spatial disruption on the structure of either evoked or ongoing activity maps. The frequency with which a cardinally preferring (0º or 90º) map would emerge, however, decreased significantly for ongoing but not for evoked activity. The same result was found by training self-organizing maps with recorded data as input. Spiking activity of cardinally preferring units also decreased significantly for ongoing when compared to evoked activity. Based on our results we came to the following conclusions: 1) VICs are not a determinant factor of ongoing map structure. Maps continued to be spontaneously generated with the same quality, probably by a combination of ongoing activity from local recurrent connections, thalamocortical loop and feedback connections. 2) VICs account for a cardinal bias in the temporal sequence of ongoing activity patterns, i.e. deactivating VIC decreases the probability of cardinal maps to emerge spontaneously. 3) Inter- and intrahemispheric long-range connections might serve as a grid preparing primary visual cortex for likely junctions in a larger visual environment encompassing the two hemifields.

Sediment and pore water chemistry of cores 214 and 755 recovered during Meteor M72/1 and POSEIDON cruise POS317/2, northwestern Black Sea

High-resolution sedimentary records of major and minor elements (Al, Ba, Ca, Sr, Ti), total organic carbon (TOC), and profiles of pore water constituents (SO42-, CH4, Ca2+, Ba2+, Mg2+, alkalinity) were obtained for two gravity cores (core 755, 501 m water depth and core 214, 1686 m water depth) from the northwestern Black Sea. The records were examined in order to gain insight into the cycling of Ba in anoxic marine sediments characterized by a shallow sulfate-methane transition (SMT) as well as the applicability of barite as a primary productivity proxy in such a setting. The Ba records are strongly overprinted by diagenetic barite (BaSO4) precipitation and remobilization; authigenic Ba enrichments were found at both sites at and slightly above the current SMT. Transport reaction modeling was applied to simulate the migration of the SMT during the changing geochemical conditions after the Holocene seawater intrusion into the Black Sea. Based on this, sediment intervals affected by diagenetic Ba redistribution were identified. Results reveal that the intense overprint of Ba and Baxs (Ba excess above detrital average) strongly limits its correlation to primary productivity. These findings have implications for other modern and ancient anoxic basins, such as sections covering the Oceanic Anoxic Events for which Ba is frequently used as a primary productivity indicator. Our study also demonstrates the limitations concerning the use of Baxs as a tracer for downward migrations of the SMT: due to high sedimentation rates at the investigated sites, diagenetic barite fronts are buried below the SMT within a relatively short period. Thus, 'relict' barite fronts would only be preserved for a few thousands of years, if at all.

Sea surface and the sea floor regionalization of the Southern Ocean by multivariate cluster analysis, links to ArcGIS project files

This study subdivides the Weddell Sea, Antarctica, into seafloor regions using multivariate statistical methods. These regions are categories used for comparing, contrasting and quantifying biogeochemical processes and biodiversity between ocean regions geographically but also regions under development within the scope of global change. The division obtained is characterized by the dominating components and interpreted in terms of ruling environmental conditions. The analysis uses 28 environmental variables for the sea surface, 25 variables for the seabed and 9 variables for the analysis between surface and bottom variables. The data were taken during the years 1983-2013. Some data were interpolated. The statistical errors of several interpolation methods (e.g. IDW, Indicator, Ordinary and Co-Kriging) with changing settings have been compared for the identification of the most reasonable method. The multivariate mathematical procedures used are regionalized classification via k means cluster analysis, canonical-correlation analysis and multidimensional scaling. Canonical-correlation analysis identifies the influencing factors in the different parts of the cove. Several methods for the identification of the optimum number of clusters have been tested. For the seabed 8 and 12 clusters were identified as reasonable numbers for clustering the Weddell Sea. For the sea surface the numbers 8 and 13 and for the top/bottom analysis 8 and 3 were identified, respectively. Additionally, the results of 20 clusters are presented for the three alternatives offering the first small scale environmental regionalization of the Weddell Sea. Especially the results of 12 clusters identify marine-influenced regions which can be clearly separated from those determined by the geological catchment area and the ones dominated by river discharge.