Altered structural connectivity in patients with medial temporal lobe epilepsy: A Diffusion Spectrum Imaging and Graph Analysis study

In this study we investigated the effect of medial temporal lobe epilepsy (MTLE) on the global characteristics of brain connectivity estimated by topological measures. We used DSI (Diffusion Spectrum Imaging) to construct a connectivity matrix where the nodes represents the anatomical ROIs and the edges are the connections between any pair of ROIs weighted by the mean GFA/FA values. A significant difference was found between the patient group vs control group in characteristic path length, clustering coefficient and small-worldness. This suggests that the MTLE network is less efficient compared to the network of the control group.

Cross-cultural adaptations of the Oxford-12 HIP score to the French speaking population.

BACKGROUND: An objective measurement of surgical procedures outcomes is inherent to professional practices quality control; this especially applies in orthopaedics to joint replacement outcomes. A self-administered questionnaire offers an attractive alternative to surgeon's judgement but is infrequently used in France for these purposes. The British questionnaire, the 12-item Oxford Hip Score (OHS) was selected for this study because of its ease of use. HYPOTHESIS: The objective of this study was to validate the French translation of the self-assessment 12-item Oxford Hip Score and compare its results with those of the reference functional scores: the Harris Hip Score (HHS) and the Postel-Merle d'Aubigné (PMA) score. MATERIALS AND METHODS: Based on a clinical series of 242 patients who were candidates for total hip arthroplasty, the French translation of this questionnaire was validated. Its coherence was also validated by comparing the preoperative data with the data obtained from the two other reference clinical scores. RESULTS: The translation was validated using the forward-backward translation procedure from French to English, with correction of all differences or mistranslations after systematized comparison with the original questionnaire in English. The mean overall OHS score was 43.8 points (range, 22-60 points) with similarly good distribution of the overall value of the three scores compared. The correlation was excellent between the OHS and the HHS, but an identical correlation between the OHS and the PMA was only obtained for the association of the pain and function parameters, after excluding the mobility criterion, relatively over-represented in the PMA score. DISCUSSION AND CONCLUSION: Subjective questionnaires that contribute a personal appreciation of the results of arthroplasty by the patient can easily be applied on a large scale. This study made a translated and validated version of an internationally recognized, reliable self-assessment score available to French orthopaedic surgeons. The results obtained encourage us to use this questionnaire as a complement to the classical evaluation scores and methods.

O-mannosyl phosphorylation of alpha-dystroglycan is required for laminin binding.

Alpha-dystroglycan (alpha-DG) is a cell-surface glycoprotein that acts as a receptor for both extracellular matrix proteins containing laminin-G domains and certain arenaviruses. Receptor binding is thought to be mediated by a posttranslational modification, and defective binding with laminin underlies a subclass of congenital muscular dystrophy. Using mass spectrometry- and nuclear magnetic resonance (NMR)-based structural analyses, we identified a phosphorylated O-mannosyl glycan on the mucin-like domain of recombinant alpha-DG, which was required for laminin binding. We demonstrated that patients with muscle-eye-brain disease and Fukuyama congenital muscular dystrophy, as well as mice with myodystrophy, commonly have defects in a postphosphoryl modification of this phosphorylated O-linked mannose, and that this modification is mediated by the like-acetylglucosaminyltransferase (LARGE) protein. These findings expand our understanding of the mechanisms that underlie congenital muscular dystrophy.

The relationship between monocarboxylate transporters 1 and 4 expression in skeletal muscle and endurance performance in athletes

The purpose of this study was to examine the relationship between skeletal muscle monocarboxylate transporters 1 and 4 (MCT1 and MCT4) expression, skeletal muscle oxidative capacity and endurance performance in trained cyclists. Ten well-trained cyclists (mean +/- SD; age 24.4 +/- 2.8 years, body mass 73.2 +/- 8.3 kg, VO(2max) 58 +/- 7 ml kg(-1) min(-1)) completed three endurance performance tasks [incremental exercise test to exhaustion, 2 and 10 min time trial (TT)]. In addition, a muscle biopsy sample from the vastus lateralis muscle was analysed for MCT1 and MCT4 expression levels together with the activity of citrate synthase (CS) and 3-hydroxyacyl-CoA dehydrogenase (HAD). There was a tendency for VO(2max) and peak power output obtained in the incremental exercise test to be correlated with MCT1 (r = -0.71 to -0.74; P < 0.06), but not MCT4. The average power output (P (average)) in the 2 min TT was significantly correlated with MCT4 (r = -0.74; P < 0.05) and HAD (r = -0.92; P < 0.01). The P (average) in the 10 min TT was only correlated with CS activity (r = 0.68; P < 0.05). These results indicate the relationship between MCT1 and MCT4 as well as cycle TT performance may be influenced by the length and intensity of the task.

A Structural Analysis of the Health Expenditures and Portfolio Choices of Retired Agents

Richer and healthier agents tend to hold riskier portfolios and spend proportionally less on health expenditures. Potential explanations include health and wealth effects on preferences, expected longevity or disposable total wealth. Using HRS data, we perform a structural estimation of a dynamic model of consumption, portfolio and health expenditure choices with recursive utility, as well as health-dependent income and mortality risk. Our estimates of the deep parameters highlight the importance of health capital, mortality risk control, convex health and mortality adjustment costs and binding liquidity constraints to rationalize the stylized facts. They also provide new perspectives on expected longevity and on the values of life and health.

Repression and Protest Structural Models and Strategic Interactions

The recent wave of upheavals and revolts in Northern Africa and the Middle East goes back to an old question often raised by theories of collective action: does repression act as a negative or positive incentive for further mobilization? Through a review of the vast literature devoted to this question, this article aims to go beyond theoretical and methodological dead-ends. The article moves on to non-Western settings in order to better understand, via a macro-sociological and dynamic approach, the causal effects between mobilizations and repression. It pleads for a meso- and micro-level approach to this issue: an approach that puts analytical emphasis both on protest organizations and on individual activists' careers.

Functional chromatin features are associated with structural mutations in cancer.

BACKGROUND: Structural mutations (SMs) play a major role in cancer development. In some cancers, such as breast and ovarian, DNA double-strand breaks (DSBs) occur more frequently in transcribed regions, while in other cancer types such as prostate, there is a consistent depletion of breakpoints in transcribed regions. Despite such regularity, little is understood about the mechanisms driving these effects. A few works have suggested that protein binding may be relevant, e.g. in studies of androgen receptor binding and active chromatin in specific cell types. We hypothesized that this behavior might be general, i.e. that correlation between protein-DNA binding (and open chromatin) and breakpoint locations is common across divergent cancers. RESULTS: We investigated this hypothesis by comprehensively analyzing the relationship among 457 ENCODE protein binding ChIP-seq experiments, 125 DnaseI and 24 FAIRE experiments, and 14,600 SMs from 8 diverse cancer datasets covering 147 samples. In most cancers, including breast and ovarian, we found enrichment of protein binding and open chromatin in the vicinity of SM breakpoints at distances up to 200 kb. Furthermore, for all cancer types we observed an enhanced enrichment in regions distant from genes when compared to regions proximal to genes, suggesting that the SM-induction mechanism is independent from the bias of DSBs to occur near transcribed regions. We also observed a stronger effect for sites with more than one protein bound. CONCLUSIONS: Protein binding and open chromatin state are associated with nearby SM breakpoints in many cancer datasets. These observations suggest a consistent mechanism underlying SM locations across different cancers.

Coordination pattern variability provides functional adaptations to constraints in swimming performance.

In a biophysical approach to the study of swimming performance (blending biomechanics and bioenergetics), inter-limb coordination is typically considered and analysed to improve propulsion and propelling efficiency. In this approach, 'opposition' or 'continuous' patterns of inter-limb coordination, where continuity between propulsive actions occurs, are promoted in the acquisition of expertise. Indeed a 'continuous' pattern theoretically minimizes intra-cyclic speed variations of the centre of mass. Consequently, it may also minimize the energy cost of locomotion. However, in skilled swimming performance there is a need to strike a delicate balance between inter-limb coordination pattern stability and variability, suggesting the absence of an 'ideal' pattern of coordination toward which all swimmers must converge or seek to imitate. Instead, an ecological dynamics framework advocates that there is an intertwined relationship between the specific intentions, perceptions and actions of individual swimmers, which constrains this relationship between coordination pattern stability and variability. This perspective explains how behaviours emerge from a set of interacting constraints, which each swimmer has to satisfy in order to achieve specific task performance goals and produce particular task outcomes. This overview updates understanding on inter-limb coordination in swimming to analyse the relationship between coordination variability and stability in relation to interacting constraints (related to task, environment and organism) that swimmers may encounter during training and performance.

In-vivo magnetic resonance imaging of the structural core of the Papez circuit in humans.

Papez circuit is one of the major pathways of the limbic system, and it is involved in the control of memory and emotion. Structural and functional alterations have been reported in psychiatric, neurodegenerative, and epileptic diseases. Despite the clinical interest, however, in-vivo imaging of the entire circuit remains a technological challenge. We used magnetic resonance diffusion spectrum imaging to comprehensively picture the Papez circuit in healthy humans: (i) the hippocampus-mammillary body pathway, (ii) the connections between the lateral subiculum and the cingulate cortex, and (iii) the mammillo-thalamic tract. The diagnostic and therapeutic implications of these results are discussed in the context of recent findings reporting the involvement of the Papez circuit in neurological and psychiatric diseases.

Whole genome sequencing in patients with retinitis pigmentosa reveals pathogenic DNA structural changes and NEK2 as a new disease gene.

We performed whole genome sequencing in 16 unrelated patients with autosomal recessive retinitis pigmentosa (ARRP), a disease characterized by progressive retinal degeneration and caused by mutations in over 50 genes, in search of pathogenic DNA variants. Eight patients were from North America, whereas eight were Japanese, a population for which ARRP seems to have different genetic drivers. Using a specific workflow, we assessed both the coding and noncoding regions of the human genome, including the evaluation of highly polymorphic SNPs, structural and copy number variations, as well as 69 control genomes sequenced by the same procedures. We detected homozygous or compound heterozygous mutations in 7 genes associated with ARRP (USH2A, RDH12, CNGB1, EYS, PDE6B, DFNB31, and CERKL) in eight patients, three Japanese and five Americans. Fourteen of the 16 mutant alleles identified were previously unknown. Among these, there was a 2.3-kb deletion in USH2A and an inverted duplication of ∼446 kb in EYS, which would have likely escaped conventional screening techniques or exome sequencing. Moreover, in another Japanese patient, we identified a homozygous frameshift (p.L206fs), absent in more than 2,500 chromosomes from ethnically matched controls, in the ciliary gene NEK2, encoding a serine/threonine-protein kinase. Inactivation of this gene in zebrafish induced retinal photoreceptor defects that were rescued by human NEK2 mRNA. In addition to identifying a previously undescribed ARRP gene, our study highlights the importance of rare structural DNA variations in Mendelian diseases and advocates the need for screening approaches that transcend the analysis of the coding sequences of the human genome.

Mapping the structural core of human cerebral cortex.

Structurally segregated and functionally specialized regions of the human cerebral cortex are interconnected by a dense network of cortico-cortical axonal pathways. By using diffusion spectrum imaging, we noninvasively mapped these pathways within and across cortical hemispheres in individual human participants. An analysis of the resulting large-scale structural brain networks reveals a structural core within posterior medial and parietal cerebral cortex, as well as several distinct temporal and frontal modules. Brain regions within the structural core share high degree, strength, and betweenness centrality, and they constitute connector hubs that link all major structural modules. The structural core contains brain regions that form the posterior components of the human default network. Looking both within and outside of core regions, we observed a substantial correspondence between structural connectivity and resting-state functional connectivity measured in the same participants. The spatial and topological centrality of the core within cortex suggests an important role in functional integration.

Mouse alarm pheromone shares structural similarity with predator scents.

Sensing the chemical warnings present in the environment is essential for species survival. In mammals, this form of danger communication occurs via the release of natural predator scents that can involuntarily warn the prey or by the production of alarm pheromones by the stressed prey alerting its conspecifics. Although we previously identified the olfactory Grueneberg ganglion as the sensory organ through which mammalian alarm pheromones signal a threatening situation, the chemical nature of these cues remains elusive. We here identify, through chemical analysis in combination with a series of physiological and behavioral tests, the chemical structure of a mouse alarm pheromone. To successfully recognize the volatile cues that signal danger, we based our selection on their activation of the mouse olfactory Grueneberg ganglion and the concomitant display of innate fear reactions. Interestingly, we found that the chemical structure of the identified mouse alarm pheromone has similar features as the sulfur-containing volatiles that are released by predating carnivores. Our findings thus not only reveal a chemical Leitmotiv that underlies signaling of fear, but also point to a double role for the olfactory Grueneberg ganglion in intraspecies as well as interspecies communication of danger.