Additions to Philippine slender skinks of the Brachymeles bonitae complex (Reptilia: Squamata: Scincidae) IV: Resurrection and redescription of Brachymeles burksi

The diversity of Philippine amphibians and reptiles has increased over the last few decades, in part due to re-evaluation of species formerly believed to be widespread. Many of these investigations of widespread species have uncovered multiple closely related cryptic lineages comprising species complexes, each restricted to individual Pleistocene Aggregate Island Complexes (PAICs). One group in particular for which widespread cryptic diversity has been common is the clade of Philippine skinks of the genus Brachymeles. Recent phylogenetic studies of the formerly recognized widespread species Brachymeles bonitae have indicated that this species is actually a complex distributed across several major PAICs and smaller island groups in the central and northern Philippines, with numerous species that exhibit an array of digit loss and limb reduction patterns. Despite the recent revisions to the B. bonitae species complex, studies suggest that unique cryptic lineages still exist within this group. In this paper, we resurrect the species Brachymeles burksi Taylor 1917, for a lineage of non-pentadactyl, semi-fossorial skink from Mindoro and Marinduque islands. First described in 1917, B. burksi was synonymized with B. bonitae in 1956, and has rarely been reconsidered since. Evaluation of genetic and morphological data (qualitative traits, meristic counts, and mensural measurements), and comparison of recently-obtained specimens to Taylor’s original description support this species’ recognition, as does its insular distribution on isolated islands in the central portions of the archipelago. Morphologically, B. burksi is differentiated from other members of the genus based on a suite of unique phenotypic characteristics, including a small body size, digitless limbs, a high number of presacral vertebrae, the absence of auricular openings, and discrete (non-overlapping) meristic scale counts. The recognition of this central Philippine species further increases the diversity of non-pentadactyl members of the B. bonitae complex, and reinforces the biogeographic uniqueness of the Mindoro faunal region

Increased GABAA Receptor ε-Subunit Expression on Ventral Respiratory Column Neurons Protects Breathing during Pregnancy

GABAergic signaling is essential for proper respiratory function. Potentiation of this signaling with allosteric modulators such as anesthetics, barbiturates, and neurosteroids can lead to respiratory arrest. Paradoxically, pregnant animals continue to breathe normally despite nearly 100-fold increases in circulating neurosteroids. ε subunit-containing GABAARs are insensitive to positive allosteric modulation, thus we hypothesized that pregnant rats increase ε subunit-containing GABAAR expression on brainstem neurons of the ventral respiratory column (VRC). In vivo, pregnancy rendered respiratory motor output insensitive to otherwise lethal doses of pentobarbital, a barbiturate previously used to categorize the ε subunit. Using electrode array recordings in vitro, we demonstrated that putative respiratory neurons of the preBötzinger Complex (preBötC) were also rendered insensitive to the effects of pentobarbital during pregnancy, but unit activity in the VRC was rapidly inhibited by the GABAAR agonist, muscimol. VRC unit activity from virgin and post-partum females was potently inhibited by both pentobarbital and muscimol. Brainstem ε subunit mRNA and protein levels were increased in pregnant rats, and GABAAR ε subunit expression co-localized with a marker of rhythm generating neurons (neurokinin 1 receptors) in the preBötC. These data support the hypothesis that pregnancy renders respiratory motor output and respiratory neuron activity insensitive to barbiturates, most likely via increased ε subunit-containing GABAAR expression on respiratory rhythm-generating neurons. Increased ε subunit expression may be critical to preserve respiratory function (and life) despite increased neurosteroid levels during pregnancy

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Mouth magnetoencephalography: A unique perspective on the human hippocampus

Traditional magnetoencephalographic (MEG) brain imaging scanners consist of a rigid sensor array surrounding the head; this means that they are maximally sensitive to superficial brain structures. New technology based on optical pumping means that we can now consider more flexible and creative sensor placement. Here we explored the magnetic fields generated by a model of the human hippocampus not only across scalp but also at the roof of the mouth. We found that simulated hippocampal sources gave rise to dipolar field patterns with one scalp surface field extremum at the temporal lobe and a corresponding maximum or minimum at the roof of the mouth. We then constructed a fitted dental mould to accommodate an Optically Pumped Magnetometer (OPM). We collected data using a previously validated hippocampal-dependant task to test the empirical utility of a mouth-based sensor, with an accompanying array of left and right temporal lobe OPMs. We found that the mouth sensor showed the greatest task-related theta power change. We found that this sensor had a mild effect on the reconstructed power in the hippocampus (~10% change) but that coherence images between the mouth sensor and reconstructed source images showed a global maximum in the right hippocampus. We conclude that augmenting a scalp-based MEG array with sensors in the mouth shows unique promise for both basic scientists and clinicians interested in interrogating the hippocampus

Common Genetic Variation And Age at Onset Of Anorexia Nervosa

Background Genetics and biology may influence the age at onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to AN age at onset and to investigate the genetic associations between age at onset of AN and age at menarche. Methods A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed which included 9,335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age at onset, early-onset AN (< 13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses. Results Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (SNP-h2) were 0.01-0.04 for age at onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early- and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age at onset and early-onset AN estimated from independent GWASs significantly predicted age at onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early-onset AN. Conclusions Our results provide evidence consistent with a common variant genetic basis for age at onset and implicate biological pathways regulating menarche and reproduction.Peer reviewe

Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (P-Bonferroni <1.06 x 10(-7)). In additional analyses in 7,278 participants,Peer reviewe

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Measurement of associated Z plus charm production in proton-proton collisions at root s=8TeV

A study of the associated production of a Z boson and a charm quark jet (Z + c), and a comparison to production with a b quark jet (Z + b), in pp collisions at a centre-of-mass energy of 8 TeV are presented. The analysis uses a data sample corresponding to an integrated luminosity of 19.7 fb(-1), collected with the CMS detector at the CERN LHC. The Z boson candidates are identified through their decays into pairs of electrons or muons. Jets originating from heavy flavour quarks are identified using semileptonic decays of c or b flavoured hadrons and hadronic decays of charm hadrons. The measurements are performed in the kinematic region with two leptons with pT(l) > 20 GeV, vertical bar eta(l)vertical bar 25 GeV and vertical bar eta(jet)vertical bar Z + c + X) B(Z -> l(+)l(-)) = 8.8 +/- 0.5 (stat)+/- 0.6 (syst) pb. The ratio of the Z+c and Z+b production cross sections is measured to be sigma(pp -> Z+c+X)/sigma (pp -> Z+b+X) = 2.0 +/- 0.2 (stat)+/- 0.2 (syst). The Z+c production cross section and the cross section ratio are also measured as a function of the transverse momentum of theZ boson and of the heavy flavour jet. The measurements are compared with theoretical predictions.Peer reviewe

Measurement of differential cross sections in the kinematic angular variable phi* for inclusive Z boson production in pp collisions at root s=8 TeV

Measurements of differential cross sections d sigma/d phi* and double-differential cross sections d(2)sigma/ld phi*d/y/ for inclusive Z boson production are presented using the dielectron and dimuon final states. The kinematic observable phi* correlates with the dilepton transverse momentum but has better resolution, and y is the dilepton rapidity. The analysis is based on data collected with the CMS experiment at a centre-of-mass energy of 8 TeV corresponding to an integrated luminosity of 19.7 fb(-1). The normalised cross section (1/sigma) d sigma/d phi*, within the fiducial kinematic region, is measured with a precision of better than 0.5% for phi* <1. The measurements are compared to theoretical predictions and they agree, typically, within few percent.Peer reviewe