The neural basis of the bilateral distribution advantage

Letters can be matched by their physical identity (i.e., a–a: same/A–a: different) or by their name (both a–a and A–a: same). The latter, more demanding task has in previous experiments led to an advantage of bilateral over within-hemifield matches, which was not observed in the former. We have investigated the neural basis of this bilateral distribution advantage (BDA) in letter name matching with event-related fMRI. Unilateral, compared to bilateral, name matching led to increased activation in the contralateral fusiform and lateral occipital gyri. This increase went along with an ipsilateral increase of activation in homologous areas. Such a hemispheric resource sharing was not observed for letter shape matching. This pattern of activation shows that letter name matching induces hemispheric resource sharing in visual areas, which occurs when task demands in the hemisphere of input reach a critical level. Activation in anterior cingulate complex and posterior cingulate/retrosplenial cortex showed a task × visual field interaction with lower activation for bilateral than unilateral name matches but higher activation for bilateral than unilateral shape matches, which fits the interhemispheric transfer demands in these tasks

Multisensory calibration Is independent of cue reliability

Multisensory calibration is fundamental for proficient interaction within a changing environment. Initial studies suggested a visual-dominant mechanism. More recently, a cue-reliability based model, similar to optimal cue-integration, has been proposed. However, a more general, reliability-independent model of fixed-ratio adaptation (of which visual-dominance is a sub-case) has never been tested. Here, we studied behavior of both humans and monkeys performing a heading-discrimination task. Subjects were presented with either visual (optic-flow), vestibular (motion-platform) or combined (visual/vestibular) stimuli, and required to report whether self-motion was to the right/left of straight ahead. A systematic heading-discrepancy was introduced between the visual and vestibular cues, without external feedback. Cue-calibration was measured by the resulting sensory adaptation. Both visual and vestibular cues significantly adapted in the direction required to reduce cue-conflict. However, unlike multisensory cue-integration, cue-calibration was not reliability-based. Rather, a model of fixed-ratio adaptation best described the data, whereby vestibular adaptation was greater than visual adaptation, irrespective of relative cue-reliability. The average ratio of vestibular to visual adaptation was 1.75 and 2.30 for the human and monkey data, respectively. Furthermore, only through modeling fixed-ratio adaptation (using the ratio extracted from the data), were we were able to account for reliability-based cue-integration during the adaptation process. The finding that cue-calibration does not depend on cue-reliability is consistent with the notion that it follows an underlying estimate of cue-accuracy. Cue-accuracy is generally independent of cue-reliability and its estimate may change with a much slower time-constant. Thus, greater vestibular vs. visual (fixed-ratio) adaptation suggests lower vestibular vs. visual cue-accuracy

Parasagittal Asymmetries of the Corpus Callosum

Significant relationships have been reported between midsagittal areas of the corpus callosum and the degree of interhemispheric transfer, functional lateralization and structural brain asymmetries. No study, however, has examined whether parasagittal callosal asymmetries (i.e. those close to the midline of the brain), which may be of specific functional consequence, are present in the human brain. Thus, we applied magnetic resonance imaging and novel computational surface-based methods to encode hemispheric differences in callosal thickness at a very high resolution. Discrete callosal areas were also compared between the hemispheres. Furthermore, acknowledging the frequently reported sex differences in callosal morphology, parasagittal callosal asymmetries were examined within each gender. Results showed significant rightward asymmetries of callosal thickness predominantly in the anterior body and anterior third of the callosum, suggesting a more diffuse functional organization of callosal projections in the right hemisphere. Asymmetries were increased in men, supporting the assumption of a sexually dimorphic organization of male and female brains that involves hemispheric relations and is reflected in the organization and distribution of callosal fiber

NOACs added to WHO’s essential medicines list: recommendations for future policy actions

The introduction of non-vitamin K antagonists oral anticoagulants, a class of medicines which includes dabigatran, apixaban, edoxaban and rivaroxaban, has resulted in improvements in the safety and efficacy of non valvular atrial fibrillation treatment for stroke prevention, with significant reductions in stroke, intracranial haemorrhage, and mortality. For these reasons, a team of World Heart Federation Emerging Leaders led efforts to add non-vitamin K antagonists oral anticoagulants to the World Health Organization’s Model List of Essential Medicines in 2019. Following the inclusion of this class of medicines in the Essential Medicines List, this editorial proposes several recommendations to improve the accessibility, affordability and acceptability of non-vitamin K oral anticoagulants, especially in low- and middle-income settings, in order to successfully manage non-valvular atrial fibrillation and to lower the risk of stroke

Quantitative Multicolor Compositional Imaging Resolves Molecular Domains in Cell-Matrix Adhesions

Background: Cellular processes occur within dynamic and multi-molecular compartments whose characterization requires analysis at high spatio-temporal resolution. Notable examples for such complexes are cell-matrix adhesion sites, consisting of numerous cytoskeletal and signaling proteins. These adhesions are highly variable in their morphology, dynamics, and apparent function, yet their molecular diversity is poorly defined. Methodology/Principal Findings: We present here a compositional imaging approach for the analysis and display of multicomponent compositions. This methodology is based on microscopy-acquired multicolor data, multi-dimensional clustering of pixels according to their composition similarity and display of the cellular distribution of these composition clusters. We apply this approach for resolving the molecular complexes associated with focal-adhesions, and the time-dependent effects of Rho-kinase inhibition. We show here compositional variations between adhesion sites, as well as ordered variations along the axis of individual focal-adhesions. The multicolor clustering approach also reveals distinct sensitivities of different focaladhesion-associated complexes to Rho-kinase inhibition. Conclusions/Significance: Multicolor compositional imaging resolves ‘‘molecular signatures’ ’ characteristic to focaladhesions and related structures, as well as sub-domains within these adhesion sites. This analysis enhances the spatial information with additional ‘‘contents-resolved’ ’ dimensions. We propose that compositional imaging can serve as

Inclusion in the World Health Organization model list of essential medicines of non-vitamin K anticoagulants for treatment of non-valvular atrial fibrillation: a step towards reducing the burden of cardiovascular morbidity and mortality

Non-vitamin K antagonist oral anticoagulants (NOACs) represent a paradigm shift in the treatment of non-valvular atrial fibrillation (AF) with major practice guidelines around the world recommending NOACs over vitamin K antagonist oral anticoagulants for initial treatment of AF for stroke prevention. Here we describe the evidence collated and the process followed for the successful inclusion of NOACs into the 21st WHO Model List of Essential Medicines (EML). Individual NOACs have been reported to be non-inferior or superior to warfarin in preventing stroke and systemic embolism in eligible AF patients with a reduction in the risk of stroke and systemic embolism and a lower risk of major bleeding in patients with non-valvular AF compared with warfarin in both RCTs and real-world data. The successful inclusion of NOACs in the WHO EML is an important step forward in the global fight against cardiovascular morbidity and mortality, especially in low- and middle-income countries, where the burden of disease is high and limited access to diagnosis and treatment translates into a higher burden of morbidity, mortality, and economic costs

High-Resolution Quantification of Focal Adhesion Spatiotemporal Dynamics in Living Cells

Focal adhesions (FAs) are macromolecular complexes that provide a linkage between the cell and its external environment. In a motile cell, focal adhesions change size and position to govern cell migration, through the dynamic processes of assembly and disassembly. To better understand the dynamic regulation of focal adhesions, we have developed an analysis system for the automated detection, tracking, and data extraction of these structures in living cells. This analysis system was used to quantify the dynamics of fluorescently tagged Paxillin and FAK in NIH 3T3 fibroblasts followed via Total Internal Reflection Fluorescence Microscopy (TIRF). High content time series included the size, shape, intensity, and position of every adhesion present in a living cell. These properties were followed over time, revealing adhesion lifetime and turnover rates, and segregation of properties into distinct zones. As a proof-of-concept, we show how a single point mutation in Paxillin at the Jun-kinase phosphorylation site Serine 178 changes FA size, distribution, and rate of assembly. This study provides a detailed, quantitative picture of FA spatiotemporal dynamics as well as a set of tools and methodologies for advancing our understanding of how focal adhesions are dynamically regulated in living cells. A full, open-source software implementation of this pipeline is provided at http://gomezlab.bme.unc.edu/tools

Quantitative analysis of cortical pyramidal neurons after corpus callosotomy.

This study quantitatively explored the dendritic/spine extent of supragranular pyramidal neurons across several cortical areas in two adult male subjects who had undergone a callosotomy several decades before death. In all cortical areas, there were numerous atypical, supragranular pyramidal neurons with elongated “tap root” basilar dendrites. These atypical cells could be associated with an underlying epileptic condition and/or could represent a compensatory mechanism in response to deafferentation after callosotomy

Endoplasmic spreading requires coalescence of vimentin intermediate filaments at force-bearing adhesions

10.1091/mbc.E12-05-0377Molecular Biology of the Cell24121-30MBCE