Synaptic processes and immune-related pathways implicated in Tourette syndrome.

Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS

Atmospheric benzenoid emissions from plants rival those from fossil fuels

Despite the known biochemical production of a range of aromatic compounds by plants and the presence of benzenoids in floral scents, the emissions of only a few benzenoid compounds have been reported from the biosphere to the atmosphere. Here, using evidence from measurements at aircraft, ecosystem, tree, branch and leaf scales, with complementary isotopic labeling experiments, we show that vegetation (leaves, flowers, and phytoplankton) emits a wide variety of benzenoid compounds to the atmosphere at substantial rates. Controlled environment experiments show that plants are able to alter their metabolism to produce and release many benzenoids under stress conditions. The functions of these compounds remain unclear but may be related to chemical communication and protection against stress. We estimate the total global secondary organic aerosol potential from biogenic benzenoids to be similar to that from anthropogenic benzenoids (~10 Tg y-1), pointing to the importance of these natural emissions in atmospheric physics and chemistry

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

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

Observation of electroweak production of Wγ with two jets in proton-proton collisions at √s = 13 TeV

A first observation is presented for the electroweak production of a W boson, a photon, and two jets in proton-proton collisions. The W boson decays are selected by requiring one identified electron or muon and an imbalance in transverse momentum. The two jets are required to have a high dijet mass and a large separation in pseudorapidity. The measurement is based on data collected with the CMS detector at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb$^{-1}$. The observed (expected) significance for this process is 4.9 (4.6) standard deviations. After combining with previously reported CMS results at 8 TeV, the observed (expected) significance is 5.3 (4.8) standard deviations. The cross section for the electroweak W$_{γjj}$ production in a restricted fiducial region is measured as 20.4 +/- 4.5 fb and the total cross section for W$_{γ}$ production in association with 2 jets in the same fiducial region is 108 +/- 16 fb. All results are in good agreement with recent theoretical predictions. Constraints are placed on anomalous quartic gauge couplings in terms of dimension-8 effective field theory operators

Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture

The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained

Measurements of production cross sections of polarized same-sign W boson pairs in association with two jets in proton-proton collisions at s=13 TeV

The first measurements of production cross sections of polarized same-sign W±W±boson pairs in proton-proton collisions are reported. The measurements are based on a data sample collected with the CMS detector at the LHC at a center-of-mass energy of 13TeV, corresponding to an integrated luminosity of 137fb−1. Events are selected by requiring exactly two same-sign leptons, electrons or muons, moderate missing transverse momentum, and two jets with a large rapidity separation and a large dijet mass to enhance the contribution of same-sign W±W±scattering events. An observed (expected) 95% confidence level upper limit of 1.17 (0.88)fbis set on the production cross section for longitudinally polarized same-sign W±W±boson pairs. The electroweak production of same-sign W±W±boson pairs with at least one of the Wbosons longitudinally polarized is measured with an observed (expected) significance of 2.3 (3.1) standard deviations.SCOAP