A summary of the beatwave experiments at Ecole Polytechnique

We present a summary of the beatwave particle acceleration program developed at Ecole Polytechnique. In dedicated experiments, plasma formation, plasma wave generation and saturation, and particle acceleration were successively studied and understood in detail. A maximum energy gain of 1.3 MeV was obtained, which is compatible with an accelerating gradient of 0.7 GV/m.Comment: 3 pages, 4 figure

Experimental Study of electron acceleration by plasma beat-waves with Nd lasers

International audienceWe have observed the acceleration of electrons by a beat-wave generated in a deuterium plasma by two Nd-YAG and Nd-YLF laser wavelengths. Electrons injected at an energy of 3.3 MeV are observed to be accelerated up to 4.7 MeV after the plasma. The energy gain is compatible with a peak electric field of the order of 1.2 GV/m. The experiment has been performed with different injection energies, from 2.5 to 3.3 MeV, with different plasma dimensions, and with different laser intensitie

Cloning, annotation and developmental expression of the chicken intestinal MUC2 gene

Intestinal mucin 2 (MUC2) encodes a heavily glycosylated, gel-forming mucin, which creates an important protective mucosal layer along the gastrointestinal tract in humans and other species. This first line of defense guards against attacks from microorganisms and is integral to the innate immune system. As a first step towards characterizing the innate immune response of MUC2 in different species, we report the cloning of a full-length, 11,359 bp chicken MUC2cDNA, and describe the genomic organization and functional annotation of this complex, 74.5 kb locus. MUC2 contains 64 exons and demonstrates distinct spatiotemporal expression profiles throughout development in the gastrointestinal tract; expression increases with gestational age and from anterior to posterior along the gut. The chicken protein has a similar domain organization as the human orthologue, with a signal peptide and several von Willebrand domains in the N-terminus and the characteristic cystine knot at the C-terminus. The PTS domain of the chicken MUC2 protein spans ~1600 amino acids and is interspersed with four CysD motifs. However, the PTS domain in the chicken diverges significantly from the human orthologue; although the chicken domain is shorter, the repetitive unit is 69 amino acids in length, which is three times longer than the human. The amino acid composition shows very little similarity to the human motif, which potentially contributes to differences in the innate immune response between species, as glycosylation across this rapidly evolving domain provides much of the musical barrier. Future studies of the function of MUC2 in the innate immune response system in chicken could provide an important model organism to increase our understanding of the biological significance of MUC2 in host defense and highlight the potential of the chicken for creating new immune-based therapies

BDNF Methylation and Maternal Brain Activity in a Violence-Related Sample

It is known that increased circulating glucocorticoids in the wake of excessive, chronic, repetitive stress increases anxiety and impairs Brain-Derived Neurotrophic Factor (BDNF) signaling. Recent studies of BDNF gene methylation in relation to maternal care have linked high BDNF methylation levels in the blood of adults to lower quality of received maternal care measured via self-report. Yet the specific mechanisms by which these phenomena occur remain to be established. The present study examines the link between methylation of the BDNF gene promoter region and patterns of neural activity that are associated with maternal response to stressful versus non-stressful child stimuli within a sample that includes mothers with interpersonal violence-related PTSD (IPV-PTSD). 46 mothers underwent fMRI. The contrast of neural activity when watching children-including their own-was then correlated to BDNF methylation. Consistent with the existing literature, the present study found that maternal BDNF methylation was associated with higher levels of maternal anxiety and greater childhood exposure to domestic violence. fMRI results showed a positive correlation of BDNF methylation with maternal brain activity in the anterior cingulate (ACC), and ventromedial prefrontal cortex (vmPFC), regions generally credited with a regulatory function toward brain areas that are generating emotions. Furthermore we found a negative correlation of BDNF methylation with the activity of the right hippocampus. Since our stimuli focus on stressful parenting conditions, these data suggest that the correlation between vmPFC/ACC activity and BDNF methylation may be linked to mothers who are at a disadvantage with respect to emotion regulation when facing stressful parenting situations. Overall, this study provides evidence that epigenetic signatures of stress-related genes can be linked to functional brain regions regulating parenting stress, thus advancing our understanding of mothers at risk for stress-related psychopathology

The association of serotonin receptor 3A methylation with maternal violence exposure, neural activity, and child aggression

Background Methylation of the serotonin 3A receptor gene (HTR3A) has been linked to child maltreatment and adult psychopathology. The present study examined whether HTR3A methylation might be associated with mothers' lifetime exposure to interpersonal violence (IPV), IPV-related psychopathology, child disturbance of attachment, and maternal neural activity. Methods Number of maternal lifetime IPV exposures and measures of maternal psychopathology including posttraumatic stress disorder (PTSD), major depression and aggressive behavior (AgB), and a measure of child attachment disturbance known as “secure base distortion” (SBD) were assessed in a sample of 35 mothers and children aged 12–42 months. Brain fMRI activation was assessed in mothers using 30-s silent film excerpts depicting menacing adult male-female interactions versus prosocial and neutral interactions. Group and continuous analyses were performed to test for associations between clinical and fMRI variables with DNA methylation. Results Maternal IPV exposure-frequency was associated with maternal PTSD; and maternal IPV-PTSD was in turn associated with child SBD. Methylation status of several CpG sites in the HTR3A gene was associated with maternal IPV and IPV-PTSD severity, AgB and child SBD, in particular, self-endangering behavior. Methylation status at a specific CpG site (CpG2_III) was associated with decreased medial prefrontal cortical (mPFC) activity in response to film-stimuli of adult male-female interactions evocative of violence as compared to prosocial and neutral interactions. Conclusions Methylation status of the HTR3A gene in mothers is linked to maternal IPV-related psychopathology, trauma-induced brain activation patterns, and child attachment disturbance in the form of SBD during a sensitive period in the development of self-regulation

Phylotranscriptomic insights into the diversification of endothermic Thunnus tunas

Birds, mammals, and certain fishes, including tunas, opahs and lamnid sharks, are endothermic, conserving internally generated, metabolic heat to maintain body or tissue temperatures above that of the environment. Bluefin tunas are commercially important fishes worldwide, and some populations are threatened. They are renowned for their endothermy, maintaining elevated temperatures of the oxidative locomotor muscle, viscera, brain and eyes, and occupying cold, productive high-latitude waters. Less cold-tolerant tunas, such as yellowfin tuna, by contrast, remain in warm-temperate to tropical waters year-round, reproducing more rapidly than most temperate bluefin tuna populations, providing resiliency in the face of large-scale industrial fisheries. Despite the importance of these traits to not only fisheries but also habitat utilization and responses to climate change, little is known of the genetic processes underlying the diversification of tunas. In collecting and analyzing sequence data across 29,556 genes, we found that parallel selection on standing genetic variation is associated with the evolution of endothermy in bluefin tunas. This includes two shared substitutions in genes encoding glycerol-3 phosphate dehydrogenase, an enzyme that contributes to thermogenesis in bumblebees and mammals, as well as four genes involved in the Krebs cycle, oxidative phosphorylation, β-oxidation, and superoxide removal. Using phylogenetic techniques, we further illustrate that the eight Thunnus species are genetically distinct, but found evidence of mitochondrial genome introgression across two species. Phylogeny-based metrics highlight conservation needs for some of these species

Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Abstract: Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10−10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10−10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis