29 research outputs found

    Understanding Actions of Others: The Electrodynamics of the Left and Right Hemispheres. A High-Density EEG Neuroimaging Study

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    Background: When we observe an individual performing a motor act (e.g. grasping a cup) we get two types of information on the basis of how the motor act is done and the context: what the agent is doing (i.e. grasping) and the intention underlying it (i.e. grasping for drinking). Here we examined the temporal dynamics of the brain activations that follow the observation of a motor act and underlie the observer’s capacity to understand what the agent is doing and why. Methodology/Principal Findings: Volunteers were presented with two-frame video-clips. The first frame (T0) showed an object with or without context; the second frame (T1) showed a hand interacting with the object. The volunteers were instructed to understand the intention of the observed actions while their brain activity was recorded with a high-density 128-channel EEG system. Visual event-related potentials (VEPs) were recorded time-locked with the frame showing the hand-object interaction (T1). The data were analyzed by using electrical neuroimaging, which combines a cluster analysis performed on the group-averaged VEPs with the localization of the cortical sources that give rise to different spatiotemporal states of the global electrical field. Electrical neuroimaging results revealed four major steps: 1) bilateral posterior cortical activations; 2) a strong activation of the left posterior temporal and inferior parietal cortices with almost a complete disappearance of activations in the right hemisphere; 3) a significant increase of the activations of the right temporo-parieta

    Extreme phenotypic heterogeneity in non-expansion spinocerebellar ataxias

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    Although the best-known spinocerebellar ataxias (SCAs) are triplet repeat diseases, many SCAs are not caused by repeat expansions. The rarity of individual non-expansion SCAs, however, has made it difficult to discern genotype-phenotype correlations. We therefore screened individuals who had been found to bear variants in a non-expansion SCA-associated gene through genetic testing, and after we eliminated genetic groups that had fewer than 30 subjects, there were 756 subjects bearing single-nucleotide variants or deletions in one of seven genes: CACNA1A (239 subjects), PRKCG (175), AFG3L2 (101), ITPR1 (91), STUB1 (77), SPTBN2 (39), or KCNC3 (34). We compared age at onset, disease features, and progression by gene and variant. There were no features that reliably distinguished one of these SCAs from another, and several genes—CACNA1A, ITPR1, SPTBN2, and KCNC3—were associated with both adult-onset and infantile-onset forms of disease, which also differed in presentation. Nevertheless, progression was overall very slow, and STUB1-associated disease was the fastest. Several variants in CACNA1A showed particularly wide ranges in age at onset: one variant produced anything from infantile developmental delay to ataxia onset at 64 years of age within the same family. For CACNA1A, ITPR1, and SPTBN2, the type of variant and charge change on the protein greatly affected the phenotype, defying pathogenicity prediction algorithms. Even with next-generation sequencing, accurate diagnosis requires dialogue between the clinician and the geneticist. Neurological Motor Disorder

    New insights into the genetic etiology of Alzheimer's disease and related dementias

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    Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

    Role of lateral interactions in adsorption kinetics: CO/Rh{100}

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    The coverage-dependent heats of adsorption and sticking probabilities for CO on Rh{100} were measured. The initial heat is 118 +/- 4 kJ mol(-1), with an initial sticking probability of similar to 0.87; the saturation coverage is similar to 0.8 monolayer: By means of a Kisliuk fit to the sticking probability data, the transition between the two main adsorbate phases (c(2 x 2) structure at 0.5 monolayer and p(4 root 2x root 2)R45 degrees structure at 0.75 monolayer) could be detected, allowing the determination of two independent Kisliuk parameters for the first (K = 0.3) and second (K = 1) regime; The differential heat data was successfully reproduced by means of a Monte Carlo simulation. A discrete CO-CO interaction potential was implemented and optimized, giving CO-CO interaction energies of E-nn = 9 +/- 1 kJ mol(-1) (nearest neighbor), E-nnn = 1 +/- 0.5 kJ mol(-1) (next-nearest neighbor) and E-nnnn = -1 +/- 0.5 kJ mol(-1) (next-next-nearest neighbor). These energies agree well with the experimentally determined vm and nnn interaction energies and with a calculated CO-CO interaction potential (DFT) for CO on Pt{111}

    Femtomole adsorption calorimetry on single-crystal surfaces

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