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We report the first multi-differential measurements of strange hadrons of K −, φ and − yields as well as the ratios of φ/K − and φ/− in Au+Au collisions at √sNN = 3 GeV with the STAR experiment fixed target configuration at RHIC. The φ mesons and − hyperons are measured through hadronic decay channels, φ → K + K − and Ξ− → Λπ−. Collision centrality and rapidity dependence of the transverse momentum spectra for these strange hadrons are presented. The 4π yields and ratios are compared to thermal model and hadronic transport model predictions. At this collision energy, thermal model with grand canonical ensemble (GCE) under-predicts the φ/K − and φ/− ratios while the result of canonical ensemble (CE) calculations reproduce φ/K −, with the correlation length rc ∼ 2.7 fm, and φ/−, rc ∼ 4.2 fm, for the 0-10% central collisions. Hadronic transport models including high mass resonance decays could also describe the ratios. While thermal calculations with GCE work well for strangeness production in high energy collisions, the change to CE at 3 GeV implies a rather different medium property at high baryon density.
We report on the measurements of directed flow v1 and elliptic flow v2 for hadrons (π±, K ±, K0 S , p, φ, Λ and ) from Au+Au collisions at √sN N = 3 GeV and v2 for (π±, K ±, p and p) at 27 and 54.4 GeV with the STAR experiment. While at the two higher energy midcentral collisions the numberof-constituent-quark (NCQ) scaling holds, at 3 GeV the v2 at midrapidity is negative for all hadrons and the NCQ scaling is absent. In addition, the v1 slopes at midrapidity for almost all observed hadrons are found to be positive, implying dominant repulsive baryonic interactions. The features of negative v2 and positive v1 slope at 3 GeV can be reproduced with a baryonic mean-field in transport model calculations. These results imply that the medium in such collisions is likely characterized by baryonic interactions.
Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at sqrt[sNN] = 130 GeV using the STAR Time Projection Chamber at the Relativistic Heavy Ion Collider. The elliptic flow signal, v2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.
Measurements of the π±, K±, and proton double differential yields emitted from the surface of the 90-cm-long carbon target (T2K replica) were performed for the incoming 31 GeV/c protons with the NA61/SHINE spectrometer at the CERN SPS using data collected during 2010 run. The double differential π± yields were measured with increased precision compared to the previously published NA61/SHINE results, while the K± and proton yields were obtained for the first time. A strategy for dealing with the dependence of the results on the incoming proton beam profile is proposed. The purpose of these measurements is to reduce significantly the (anti)neutrino flux uncertainty in the T2K long-baseline neutrino experiment by constraining the production of (anti)neutrino ancestors coming from the T2K target.
The physics goal of the strong interaction program of the NA61/SHINE experiment at the CERN Super Proton Synchrotron (SPS) is to study the phase diagram of hadronic matter by a scan of particle production in collisions of nuclei with various sizes at a set of energies covering the SPS energy range. This paper presents differential inclusive spectra of transverse momentum, transverse mass and rapidity of π− mesons produced in central 40Ar+45Sc collisions at beam momenta of 13A, 19A, 30A, 40A, 75A and 150A Ge V /c. Energy and system size dependence of parameters of these distributions – mean transverse mass, the inverse slope parameter of transverse mass spectra, width of the rapidity distribution and mean multiplicity – are presented and discussed. Furthermore, the dependence of the ratio of the mean number of produced pions to the mean number of wounded nucleons on the collision energy was derived. The results are compared to predictions of several models.
The most precise measurements to date of the 3ΛH lifetime τ and Λ separation energy BΛ are obtained using the data sample of Pb-Pb collisions at √= 5.02 TeV collected by ALICE at the LHC. The 3ΛH is reconsNN structed via its charged two-body mesonic decay channel (3ΛH→ 3He + π− and the charge-conjugate process). The measured values τ=[253±11 (stat.)±6 (syst.)] ps and BΛ=[102±63 (stat.)±67 (syst.)] keV are compatible with predictions from effective field theories and confirm that the 3ΛH structure is consistent with a weakly-bound system.
The nucleosynthesis of elements beyond iron is dominated by neutron captures in the s and r processes. However, 32 stable, proton-rich isotopes cannot be formed during those processes, because they are shielded from the s-process flow and r-process β-decay chains. These nuclei are attributed to the p and rp process.
For all those processes, current research in nuclear astrophysics addresses the need for more precise reaction data involving radioactive isotopes. Depending on the particular reaction, direct or inverse kinematics, forward or time-reversed direction are investigated to determine or at least to constrain the desired reaction cross sections.
The Facility for Antiproton and Ion Research (FAIR) will offer unique, unprecedented opportunities to investigate many of the important reactions. The high yield of radioactive isotopes, even far away from the valley of stability, allows the investigation of isotopes involved in processes as exotic as the r or rp processes.
A measurement of the transverse momentum spectra of jets in Pb-Pb collisions at sNN−−−√=2.76 TeV is reported. Jets are reconstructed from charged particles using the anti-kT jet algorithm with jet resolution parameters R of 0.2 and 0.3 in pseudo-rapidity |η|<0.5. The transverse momentum pT of charged particles is measured down to 0.15 GeV/c which gives access to the low pT fragments of the jet. Jets found in heavy-ion collisions are corrected event-by-event for average background density and on an inclusive basis (via unfolding) for residual background fluctuations and detector effects. A strong suppression of jet production in central events with respect to peripheral events is observed. The suppression is found to be similar to the suppression of charged hadrons, which suggests that substantial energy is radiated at angles larger than the jet resolution parameter R=0.3 considered in the analysis. The fragmentation bias introduced by selecting jets with a high pT leading particle, which rejects jets with a soft fragmentation pattern, has a similar effect on the jet yield for central and peripheral events. The ratio of jet spectra with R=0.2 and R=0.3 is found to be similar in Pb-Pb and simulated PYTHIA pp events, indicating no strong broadening of the radial jet structure in the reconstructed jets with R<0.3.
Mid-rapidity transverse mass spectra and multiplicity densities of charged and neutral kaons are reported for Au + Au collisions at √sNN = 130 GeV at RHIC. The spectra are exponential in transverse mass, with an inverse slope of about 280 MeV in central collisions. The multiplicity densities for these particles scale with the negative hadron pseudo-rapidity density. The charged kaon to pion ratios are K+/π− = 0.161± 0.002(stat) ± 0.024(syst) and K−/π− = 0.146± 0.002(stat) ± 0.022(syst) for the most central collisions. The K+/π− ratio is lower than the same ratio observed at the SPS while the K−/π− is higher than the SPS result. The ratios are enhanced by about 50% relative to p + p and p¯ + p collision data at similar energies.
Transverse momentum spectra of π±, K± and p(p¯) up to pT = 20 GeV/c at mid-rapidity in pp, peripheral (60–80%) and central (0–5%) Pb–Pb collisions at √sNN = 2.76 TeV have been measured using the ALICE detector at the Large Hadron Collider. The proton-to-pion and the kaon-to-pion ratios both show a distinct peak at pT ≈ 3 GeV/c in central Pb–Pb collisions. Below the peak, pT < 3 GeV/c, both ratios are in good agreement with hydrodynamical calculations, suggesting that the peak itself is dominantly the result of radial flow rather than anomalous hadronization processes. For pT > 10 GeV/c particle ratios in pp and Pb–Pb collisions are in agreement and the nuclear modification factors for π±, K± and p(p¯) indicate that, within the systematic and statistical uncertainties, the suppression is the same. This suggests that the chemical composition of leading particles from jets in the medium is similar to that of vacuum jets.
A newly developed observable for correlations between symmetry planes, which characterize the direction of the anisotropic emission of produced particles, is measured in Pb-Pb collisions at sNN−−−√=2.76 TeV with ALICE. This so-called Gaussian Estimator allows for the first time the study of these quantities without the influence of correlations between different flow amplitudes. The centrality dependence of various correlations between two, three and four symmetry planes is presented. The ordering of magnitude between these symmetry plane correlations is discussed and the results of the Gaussian Estimator are compared with measurements of previously used estimators. The results utilizing the new estimator lead to significantly smaller correlations than reported by studies using the Scalar Product method. Furthermore, the obtained symmetry plane correlations are compared to state-of-the-art hydrodynamic model calculations for the evolution of heavy-ion collisions. While the model predictions provide a qualitative description of the data, quantitative agreement is not always observed, particularly for correlators with significant non-linear response of the medium to initial state anisotropies of the collision system. As these results provide unique and independent information, their usage in future Bayesian analysis can further constrain our knowledge on the properties of the QCD matter produced in ultrarelativistic heavy-ion collisions.
Hadronic resonances are used to probe the hadron gas produced in the late stage of heavy-ion collisions since they decay on the same timescale, of the order of 1 to 10 fm/c, as the decoupling time of the system. In the hadron gas, (pseudo)elastic scatterings among the products of resonances that decayed before the kinetic freeze-out and regeneration processes counteract each other, the net effect depending on the resonance lifetime, the duration of the hadronic phase, and the hadronic cross sections at play. In this context, the Σ(1385)± particle is of particular interest as models predict that regeneration dominates over rescattering despite its relatively short lifetime of about 5.5 fm/c. The first measurement of the Σ(1385)± resonance production at midrapidity in Pb-Pb collisions at sNN−−−√=5.02 TeV with the ALICE detector is presented in this Letter. The resonances are reconstructed via their hadronic decay channel, Λπ, as a function of the transverse momentum (pT) and the collision centrality. The results are discussed in comparison with the measured yield of pions and with expectations from the statistical hadronization model as well as commonly employed event generators, including PYTHIA8/Angantyr and EPOS3 coupled to the UrQMD hadronic cascade afterburner. None of the models can describe the data. For Σ(1385)±, a similar behaviour as K∗(892)0 is observed in data unlike the predictions of EPOS3 with afterburner.
Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
his Erratum replaces incorrect plots shown in Fig. 7 with the corrected ones. In the publication, the NA57 [1] ratios of Ξ− and Ξ¯¯¯¯+ to the number of wounded nucleons at ⟨NW⟩=349 by mistake were plotted at the wrong values. The ratios were calculated and plotted by mistake using ⟨NW⟩=249.
The correct normalization does not change the conclusions of the paper. The correctly normalized results are presented in Fig. 7.
The production of Ξ(1321)− and Ξ¯¯¯¯(1321)+ hyperons in inelastic p+p interactions is studied in a fixed target experiment at a beam momentum of 158 GeV/c. Double differential distributions in rapidity y and transverse momentum pT are obtained from a sample of 33M inelastic events. They allow to extrapolate the spectra to full phase space and to determine the mean multiplicity of both Ξ− and Ξ¯¯¯¯+. The rapidity and transverse momentum spectra are compared to transport model predictions. The Ξ− mean multiplicity in inelastic p+p interactions at 158 GeV/c is used to quantify the strangeness enhancement in A+A collisions at the same centre-of-mass energy per nucleon pair.
A measurement of charged hadron pair correlations in two-dimensional ηφ space is presented. The analysis is based on total 30 million central Be + Be collisions observed in the NA61/SHINE detector at the CERN SPS for incident beam momenta of 19A, 30A, 40A, 75A, and 150A GeV/c. Measurements were carried out for unlike-sign and like-sign charge hadron pairs independently. The C(η, φ) correlation functions were compared with results from a similar analysis on p + p interactions at similar beam momenta per nucleon. General trends of the backto-back correlations are similar in central Be + Be collisions and p + p interactions, but are suppressed in magnitude due to the increased combinatorial background. Predictions from the Epos and UrQMD models are compared to the measurements. Evolution of an enhancement around (η, φ) = (0, 0) with incident energy is observed in central Be + Be collisions. It is not predicted by both models and almost non-existing in proton–proton collisions at the same momentum per nucleon.
We report the first measurement of inclusive antiproton production at midrapidity in Au+Au collisions at sqrt[sNN] = 130 GeV by the STAR experiment at RHIC. The antiproton transverse mass distributions in the measured transverse momentum range of 0.25<pperp<0.95 GeV/c are found to fall less steeply for more central collisions. The extrapolated antiproton rapidity density is found to scale approximately with the negative hadron multiplicity density.
Two-particle angular correlations between unidentified charged trigger and associated particles are measured by the ALICE detector in p–Pb collisions at a nucleon–nucleon centre-of-mass energy of 5.02 TeV. The transverse-momentum range 0.7 < pT,assoc < pT,trig < 5.0 GeV/c is examined, to include correlations induced by jets originating from low momentum-transfer scatterings (minijets). The correlations expressed as associated yield per trigger particle are obtained in the pseudorapidity range |η| < 0.9. The near-side long-range pseudorapidity correlations observed in high-multiplicity p–Pb collisions are subtracted from both near-side short-range and away-side correlations in order to remove the non-jet-like components. The yields in the jet-like peaks are found to be invariant with event multiplicity with the exception of events with low multiplicity. This invariance is consistent with the particles being produced via the incoherent fragmentation of multiple parton–parton scatterings, while the yield related to the previously observed ridge structures is not jet-related. The number of uncorrelated sources of particle production is found to increase linearly with multiplicity, suggesting no saturation of the number of multi-parton interactions even in the highest multiplicity p–Pb collisions. Further, the number scales only in the intermediate multiplicity region with the number of binary nucleon–nucleon collisions estimated with a Glauber Monte-Carlo simulation.
Freeze-out radii extracted from three-pion cumulants in pp, p–Pb and Pb–Pb collisions at the LHC
(2014)
In high-energy collisions, the spatio-temporal size of the particle production region can be measured using the Bose–Einstein correlations of identical bosons at low relative momentum. The source radii are typically extracted using two-pion correlations, and characterize the system at the last stage of interaction, called kinetic freeze-out. In low-multiplicity collisions, unlike in high-multiplicity collisions, two-pion correlations are substantially altered by background correlations, e.g. mini-jets. Such correlations can be suppressed using three-pion cumulant correlations. We present the first measurements of the size of the system at freeze-out extracted from three-pion cumulant correlations in pp, p–Pb and Pb–Pb collisions at the LHC with ALICE. At similar multiplicity, the invariant radii extracted in p–Pb collisions are found to be 5–15% larger than those in pp, while those in Pb–Pb are 35–55% larger than those in p–Pb. Our measurements disfavor models which incorporate substantially stronger collective expansion in p–Pb as compared to pp collisions at similar multiplicity.
We report on the measurement of the inclusive Υ (1S) production in Pb–Pb collisions at √sNN = 2.76 TeV carried out at forward rapidity (2.5 < y < 4) and down to zero transverse momentum using its μ+μ−decay channel with the ALICE detector at the Large Hadron Collider. A strong suppression of the inclusive Υ (1S) yield is observed with respect to pp collisions scaled by the number of independent nucleon–nucleon collisions. The nuclear modification factor, for events in the 0–90% centrality range, amounts to 0.30 ± 0.05(stat) ± 0.04(syst). The observed Υ (1S) suppression tends to increase with the centrality of the collision and seems more pronounced than in corresponding mid-rapidity measurements. Our results are compared with model calculations, which are found to underestimate the measured suppression and fail to reproduce its rapidity dependence.
We present measurements of ρ0, ω and K∗0 spectra in π−+ C production interactions at 158 GeV / c and ρ0 spectra at 350 GeV / c using the NA61/SHINE spectrometer at the CERN SPS. Spectra are presented as a function of the Feynman’s variable xF in the range 0<xF<1 and 0<xF<0.5 for 158 and 350 GeV / c respectively. Furthermore, we show comparisons with previous measurements and predictions of several hadronic interaction models. These measurements are essential for a better understanding of hadronic shower development and for improving the modeling of cosmic ray air showers.
White matter abnormalities across different epilepsy syndromes in adults: an ENIGMA Epilepsy study
(2019)
The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analyzed from 1,069 non-epileptic controls and 1,249 patients: temporal lobe epilepsy with hippocampal sclerosis (N=599), temporal lobe epilepsy with normal MRI (N=275), genetic generalized epilepsy (N=182) and nonlesional extratemporal epilepsy (N=193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fiber tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at p<0.001). Across “all epilepsies” lower fractional anisotropy was observed in most fiber tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. Less robust effects were seen with mean diffusivity. Syndrome-specific fractional anisotropy and mean diffusivity differences were most pronounced in patients with hippocampal sclerosis in the ipsilateral parahippocampal cingulum and external capsule, with smaller effects across most other tracts. Those with temporal lobe epilepsy and normal MRI showed a similar pattern of greater ipsilateral than contralateral abnormalities, but less marked than those in patients with hippocampal sclerosis. Patients with generalized and extratemporal epilepsies had pronounced differences in fractional anisotropy in the corpus callosum, corona radiata and external capsule, and in mean diffusivity of the anterior corona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of microstructural abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibers in a large multicentre study of epilepsy. Overall, epilepsy patients showed white matter abnormalities in the corpus callosum, cingulum and external capsule, with differing severity across epilepsy syndromes. These data further define the spectrum of white matter abnormalities in common epilepsy syndromes, yielding new insights into pathological substrates that may be used to guide future therapeutic and genetic studies.
Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium
(2017)
Two-pion correlation functions in Au+Au collisions at sqrt[sNN] = 130 GeV have been measured by the STAR (solenoidal tracker at RHIC) detector. The source size extracted by fitting the correlations grows with event multiplicity and decreases with transverse momentum. Anomalously large sizes or emission durations, which have been suggested as signals of quark-gluon plasma formation and rehadronization, are not observed. The Hanbury Brown-Twiss parameters display a weak energy dependence over a broad range in sqrt[sNN].
The first measurements of light antinucleus production in Au+Au collisions at the Relativistic Heavy-Ion Collider are reported. The observed production rates for d-bar and 3He-bar are much larger than in lower energy nucleus-nucleus collisions. A coalescence model analysis of the yields indicates that there is little or no increase in the antinucleon freeze-out volume compared to collisions at CERN SPS energy. These analyses also indicate that the 3He-bar freeze-out volume is smaller than the d-bar freeze-out volume.
We present the first measurement of midrapidity vector meson phi production in Au+Au collisions at RHIC (sqrt[sNN]=130 GeV) from the STAR detector. For the 11% highest multiplicity collisions, the slope parameter from an exponential fit to the transverse mass distribution is T=379±50(stat)±45(syst) MeV, the yield dN/dy=5.73±0.37(stat)±0.69(syst) per event, and the ratio N phi /Nh- is found to be 0.021±0.001(stat)±0.004(syst). The measured ratio N phi /Nh- and T for the phi meson at midrapidity do not change for the selected multiplicity bins.
We report first results on elliptic flow of identified particles at midrapidity in Au+Au collisions at sqrt[sNN] = 130 GeV using the STAR TPC at RHIC. The elliptic flow as a function of transverse momentum and centrality differs significantly for particles of different masses. This dependence can be accounted for in hydrodynamic models, indicating that the system created shows a behavior consistent with collective hydrodynamical flow. The fit to the data with a simple model gives information on the temperature and flow velocities at freeze-out.
The minimum-bias multiplicity distribution and the transverse momentum and pseudorapidity distributions for central collisions have been measured for negative hadrons ( h-) in Au+Au interactions at sqrt[sNN] = 130 GeV. The multiplicity density at midrapidity for the 5% most central interactions is dNh-/d eta | eta = 0 = 280±1(stat)±20(syst), an increase per participant of 38% relative to pp-bar collisions at the same energy. The mean transverse momentum is 0.508±0.012 GeV/c and is larger than in central Pb+Pb collisions at lower energies. The scaling of the h- yield per participant is a strong function of pperp. The pseudorapidity distribution is almost constant within | eta |<1.
A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.
We report results on the ratio of midrapidity antiproton-to-proton yields in Au+Au collisions at sqrt[sNN] = 130 GeV per nucleon pair as measured by the STAR experiment at RHIC. Within the rapidity and transverse momentum range of | y|<0.5 and 0.4<pt<1.0 GeV/c, the ratio is essentially independent of either transverse momentum or rapidity, with an average of 0.65±0.01(stat)±0.07(syst) for minimum bias collisions. Within errors, no strong centrality dependence is observed. The results indicate that at this RHIC energy, although the p-p-bar pair production becomes important at midrapidity, a significant excess of baryons over antibaryons is still present.
In particle collider experiments, elementary particle interactions with large momentum transfer produce quarks and gluons (known as partons) whose evolution is governed by the strong force, as described by the theory of quantum chromodynamics (QCD)1. These partons subsequently emit further partons in a process that can be described as a parton shower2, which culminates in the formation of detectable hadrons. Studying the pattern of the parton shower is one of the key experimental tools for testing QCD. This pattern is expected to depend on the mass of the initiating parton, through a phenomenon known as the dead-cone effect, which predicts a suppression of the gluon spectrum emitted by a heavy quark of mass mQ and energy E, within a cone of angular size mQ/E around the emitter3. Previously, a direct observation of the dead-cone effect in QCD had not been possible, owing to the challenge of reconstructing the cascading quarks and gluons from the experimentally accessible hadrons. We report the direct observation of the QCD dead cone by using new iterative declustering techniques4,5 to reconstruct the parton shower of charm quarks. This result confirms a fundamental feature of QCD. Furthermore, the measurement of a dead-cone angle constitutes a direct experimental observation of the non-zero mass of the charm quark, which is a fundamental constant in the standard model of particle physics.
Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.
Principal findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10−6) and 14 (IGHV1-67 p = 7.9×10−8) which indexed novel susceptibility loci.
Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
The ALICE Collaboration at the LHC reports measurement of the inclusive production cross section of electrons from semi-leptonic decays of beauty hadrons with rapidity |y| < 0.8 and transverse momentum 1 < pT < 10 GeV/c, in pp collisions at √s = 2.76 TeV. Electrons not originating from semi-electronic decay of beauty hadrons are suppressed using the impact parameter of the corresponding tracks. The production cross section of beauty decay electrons is compared to the result obtained with an alternative method which uses the distribution of the azimuthal angle between heavy-flavour decay electrons and charged hadrons. Perturbative QCD predictions agree with the measured cross section within the experimental and theoretical uncertainties. The integrated visible cross section, σb→e = 3.47 ± 0.40(stat) +1.12 −1.33(sys) ± 0.07(norm) μb, was extrapolated to full phase space using Fixed Order plus Next-to-Leading Log (FONLL) calculations to obtain the total bb production ¯ cross section, σbb¯ = 130 ± 15.1(stat) +42.1 −49.8(sys) +3.4 −3.1(extr) ± 2.5(norm) ± 4.4(BR) μb.
We report on the production of inclusive Υ (1S) and Υ (2S) in p–Pb collisions at √sNN = 5.02 TeV at the LHC. The measurement is performed with the ALICE detector at backward (−4.46 < ycms < −2.96) and forward (2.03 .< ycms < 3.53) rapidity down to zero transverse momentum. The production cross sections of the Υ (1S) and Υ (2S) are presented, as well as the nuclear modification factor and the ratio of the forward to backward yields of Υ (1S). A suppression of the inclusive Υ (1S) yield in p–Pb collisions with respect to the yield from pp collisions scaled by the number of binary nucleon–nucleon collisions is observed at forward rapidity but not at backward rapidity. The results are compared to theoretical model calculations including nuclear shadowing or partonic energy loss effect.
The interaction between Λ baryons and kaons/antikaons is a crucial ingredient for the strangeness S=0 and S=−2 sector of the meson–baryon interaction at low energies. In particular, the ΛK‾ might help in understanding the origin of states such as the Ξ(1620), whose nature and properties are still under debate. Experimental data on Λ–K and Λ–K‾ systems are scarce, leading to large uncertainties and tension between the available theoretical predictions constrained by such data. In this Letter we present the measurements of Λ–K⊕+Λ‾–K− and Λ–K⊕−Λ‾–K+ correlations obtained in the high-multiplicity triggered data sample in pp collisions at s=13 TeV recorded by ALICE at the LHC. The correlation function for both pairs is modeled using the Lednický–Lyuboshits analytical formula and the corresponding scattering parameters are extracted. The Λ–K⊕−Λ‾–K+ correlations show the presence of several structures at relative momenta k⁎ above 200 MeV/c, compatible with the Ω baryon, the Ξ(1690), and Ξ(1820) resonances decaying into Λ–K− pairs. The low k⁎ region in the Λ–K⊕−Λ‾–K+ also exhibits the presence of the Ξ(1620) state, expected to strongly couple to the measured pair. The presented data allow to access the ΛK+ and ΛK− strong interaction with an unprecedented precision and deliver the first experimental observation of the Ξ(1620) decaying into ΛK−.
The measurement of the production of deuterons, tritons and 3He and their antiparticles in Pb-Pb collisions at √sNN = 5.02 TeV is presented in this article. The measurements are carried out at midrapidity (y|< 0.5) as a function of collision centrality using the ALICE detector. The pT-integrated yields, the coalescence parameters and the ratios to protons and antiprotons are reported and compared with nucleosynthesis models. The comparison of these results in different collision systems at different center-of-mass collision energies reveals a suppression of nucleus production in small systems. In the Statistical Hadronisation Model framework, this can be explained by a small correlation volume where the baryon number is conserved, as already shown in previous fluctuation analyses. However, a different size of the correlation volume is required to describe the proton yields in the same data sets. The coalescence model can describe this suppression by the fact that the wave functions of the nuclei are large and the fireball size starts to become comparable and even much smaller than the actual nucleus at low multiplicities.
It is proposed to install an experimental setup in the fixed-target hall of the Nuclotron with the final goal to perform a research program focused on the production of strange matter in heavyion collisions at beam energies between 2 and 6 A GeV. The basic setup will comprise a large acceptance dipole magnet with inner tracking detector modules based on double-sided Silicon micro-strip sensors and GEMs. The outer tracking will be based on the drift chambers and straw tube detector. Particle identification will be based on the time-of-flight measurements. This setup will be sufficient perform a comprehensive study of strangeness production in heavy-ion collisions, including multi-strange hyperons, multi-strange hypernuclei, and exotic multi-strange heavy objects. These pioneering measurements would provide the first data on the production of these particles in heavy-ion collisions at Nuclotron beam energies, and would open an avenue to explore the third (strangeness) axis of the nuclear chart. The extension of the experimental program is related with the study of in-medium effects for vector mesons decaying in hadronic modes. The studies of the NN and NA reactions for the reference is assumed.
The ALICE Collaboration reports a differential measurement of inclusive jet suppression using pp and Pb−Pb collision data at a center-of-mass energy per nucleon-nucleon collision sNN−−−√=5.02 TeV. Charged-particle jets are reconstructed using the anti-kT algorithm with resolution parameters R= 0.2, 0.3, 0.4, 0.5, and 0.6 in pp collisions and R= 0.2, 0.4, 0.6 in central (0−10%), semi-central (30−50%), and peripheral (60−80%) Pb−Pb collisions. A novel approach based on machine learning is employed to mitigate the influence of jet background. This enables measurements of inclusive jet suppression in new regions of phase space, including down to the lowest jet pT≥40 GeV/c at R=0.6 in central Pb−Pb collisions. This is an important step for discriminating different models of jet quenching in the quark-gluon plasma. The transverse momentum spectra, nuclear modification factors, derived cross section, and nuclear modification factor ratios for different jet resolution parameters of charged-particle jets are presented and compared to model predictions. A mild dependence of the nuclear modification factor ratios on collision centrality and resolution parameter is observed. The results are compared to a variety of jet-quenching models with varying levels of agreement.
The balance function is a new observable based on the principle that charge is locally conserved when particles are pair produced. Balance functions have been measured for charged particle pairs and identified charged pion pairs in Au+Au collisions at sqrt[sNN]=130 GeV at the Relativistic Heavy Ion Collider using STAR. Balance functions for peripheral collisions have widths consistent with model predictions based on a superposition of nucleon-nucleon scattering. Widths in central collisions are smaller, consistent with trends predicted by models incorporating late hadronization.
Azimuthal anisotropy (v2) and two-particle angular correlations of high pT charged hadrons have been measured in Au+Au collisions at sqrt[sNN]=130 GeV for transverse momenta up to 6 GeV/c, where hard processes are expected to contribute significantly. The two-particle angular correlations exhibit elliptic flow and a structure suggestive of fragmentation of high pT partons. The monotonic rise of v2(pT) for pT<2 GeV/c is consistent with collective hydrodynamical flow calculations. At pT>3 GeV/c, a saturation of v2 is observed which persists up to pT=6 GeV/c.
The first measurement of the e+e− pair production at low lepton pair transverse momentum (pT,ee) and low invariant mass (mee) in non-central Pb−Pb collisions at sNN−−−√=5.02 TeV at the LHC is presented. The dielectron production is studied with the ALICE detector at midrapidity (|ηe|<0.8) as a function of invariant mass (0.4≤mee<2.7 GeV/c2) in the 50−70% and 70−90% centrality classes for pT,ee<0.1 GeV/c, and as a function of pT,ee in three mee intervals in the most peripheral Pb−Pb collisions. Below a pT,ee of 0.1 GeV/c, a clear excess of e+e− pairs is found compared to the expectations from known hadronic sources and predictions of thermal radiation from the medium. The mee excess spectra are reproduced, within uncertainties, by different predictions of the photon−photon production of dielectrons, where the photons originate from the extremely strong electromagnetic fields generated by the highly Lorentz-contracted Pb nuclei. Lowest-order quantum electrodynamic (QED) calculations, as well as a model that takes into account the impact-parameter dependence of the average transverse momentum of the photons, also provide a good description of the pT,ee spectra. The measured ⟨p2T,ee⟩−−−−−√ of the excess pT,ee spectrum in peripheral Pb−Pb collisions is found to be comparable to the values observed previously at RHIC in a similar phase-space region.
The first measurement of the e+e− pair production at low lepton pair transverse momentum (pT,ee) and low invariant mass (mee) in non-central Pb−Pb collisions at sNN−−−√=5.02 TeV at the LHC is presented. The dielectron production is studied with the ALICE detector at midrapidity (|ηe|<0.8) as a function of invariant mass (0.4≤mee<2.7 GeV/c2) in the 50−70% and 70−90% centrality classes for pT,ee<0.1 GeV/c, and as a function of pT,ee in three mee intervals in the most peripheral Pb−Pb collisions. Below a pT,ee of 0.1 GeV/c, a clear excess of e+e− pairs is found compared to the expectations from known hadronic sources and predictions of thermal radiation from the medium. The mee excess spectra are reproduced, within uncertainties, by different predictions of the photon−photon production of dielectrons, where the photons originate from the extremely strong electromagnetic fields generated by the highly Lorentz-contracted Pb nuclei. Lowest-order quantum electrodynamic (QED) calculations, as well as a model that takes into account the impact-parameter dependence of the average transverse momentum of the photons, also provide a good description of the pT,ee spectra. The measured ⟨p2T,ee⟩−−−−−√ of the excess pT,ee spectrum in peripheral Pb−Pb collisions is found to be comparable to the values observed previously at RHIC in a similar phase-space region.
Azimuthal anisotropy (v2) and two-particle angular correlations of high pT charged hadrons have been measured in Au+Au collisions at sqrt[sNN]=130 GeV for transverse momenta up to 6 GeV/c, where hard processes are expected to contribute significantly. The two-particle angular correlations exhibit elliptic flow and a structure suggestive of fragmentation of high pT partons. The monotonic rise of v2(pT) for pT<2 GeV/c is consistent with collective hydrodynamical flow calculations. At pT>3 GeV/c, a saturation of v2 is observed which persists up to pT=6 GeV/c.
Elliptic flow holds much promise for studying the early-time thermalization attained in ultrarelativistic nuclear collisions. Flow measurements also provide a means of distinguishing between hydrodynamic models and calculations which approach the low density (dilute gas) limit. Among the effects that can complicate the interpretation of elliptic flow measurements are azimuthal correlations that are unrelated to the reaction plane (nonflow correlations). Using data for Au + Au collisions at sqrt[sNN]=130 GeV from the STAR time projection chamber, it is found that four-particle correlation analyses can reliably separate flow and nonflow correlation signals. The latter account for on average about 15% of the observed second-harmonic azimuthal correlation, with the largest relative contribution for the most peripheral and the most central collisions. The results are also corrected for the effect of flow variations within centrality bins. This effect is negligible for all but the most central bin, where the correction to the elliptic flow is about a factor of 2. A simple new method for two-particle flow analysis based on scalar products is described. An analysis based on the distribution of the magnitude of the flow vector is also described.
We report the first observation of K*(892)0--> pi K in relativistic heavy ion collisions. The transverse momentum spectrum of (K*0+K*0)/2 from central Au+Au collisions at sqrt[sNN]=130 GeV is presented. The ratios of the K*0 yield derived from these data to the yields of negative hadrons, charged kaons, and phi mesons have been measured in central and minimum bias collisions and compared with model predictions and comparable e+e-, pp, and p-barp results. The data indicate no dramatic reduction of K*0 production in relativistic heavy ion collisions despite expected losses due to rescattering effects.
The STAR Collaboration reports the first observation of exclusive rho 0 photoproduction, AuAu-->AuAu rho 0, and rho 0 production accompanied by mutual nuclear Coulomb excitation, AuAu-->Au [star] Au [star] rho 0, in ultraperipheral heavy-ion collisions. The rho 0 have low transverse momenta, consistent with coherent coupling to both nuclei. The cross sections at sqrt[sNN]=130 GeV agree with theoretical predictions treating rho 0 production and Coulomb excitation as independent processes.
We report STAR results on the azimuthal anisotropy parameter v2 for strange particles K0S, Lambda , and Lambda -bar at midrapidity in Au+Au collisions at sqrt[sNN]=130 GeV at the Relativistic Heavy Ion Collider. The value of v2 as a function of transverse momentum, pt, of the produced particle and collision centrality is presented for both particles up to pt~3.0 GeV/c. A strong pt dependence in v2 is observed up to 2.0 GeV/c. The v2 measurement is compared with hydrodynamic model calculations. The physics implications of the pt integrated v2 magnitude as a function of particle mass are also discussed.
Inclusive transverse momentum distributions of charged hadrons within 0.2<pT<6.0 GeV/c have been measured over a broad range of centrality for Au+Au collisions at sqrt[sNN]=130 GeV. Hadron yields are suppressed at high pT in central collisions relative to peripheral collisions and to a nucleon-nucleon reference scaled for collision geometry. Peripheral collisions are not suppressed relative to the nucleon-nucleon reference. The suppression varies continuously at intermediate centralities. The results indicate significant nuclear medium effects on high-pT hadron production in heavy-ion collisions at high energy.
We report the first measurement of strange ( Lambda ) and antistrange ( Lambda -bar) baryon production from sqrt[sNN]=130 GeV Au+Au collisions at the Relativistic Heavy Ion Collider (RHIC). Rapidity density and transverse mass distributions at midrapidity are presented as a function of centrality. The yield of Lambda and Lambda -bar hyperons is found to be approximately proportional to the number of negative hadrons. The production of Lambda -bar hyperons relative to negative hadrons increases very rapidly with transverse momentum. The magnitude of the increase cannot be described by existing hadronic string fragmentation models alone.
DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10−7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3–82%) of the aggression–methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.
This letter reports the first measurement of spin alignment, with respect to the helicity axis, for D⁎+ vector mesons and their charge conjugates from charm-quark hadronisation (prompt) and from beauty-meson decays (non-prompt) in hadron collisions. The measurements were performed at midrapidity (|y|<0.8) as a function of transverse momentum (pT) in proton–proton (pp) collisions collected by ALICE at the centre-of-mass energy √s=13TeV. The diagonal spin density matrix element ρ00 of D⁎+ mesons was measured from the angular distribution of the D⁎+→D0(→K−π+)π+ decay products, in the D⁎+ rest frame, with respect to the D⁎+ momentum direction in the pp centre of mass frame. The ρ00 value for prompt D⁎+ mesons is consistent with 1/3, which implies no spin alignment. However, for non-prompt D⁎+ mesons an evidence of ρ00 larger than 1/3 is found. The measured value of the spin density element is ρ00=0.455±0.022(stat.)±0.035(syst.) in the 5<pT<20GeV/c interval, which is consistent with a Pythia 8 Monte Carlo simulation coupled with the EvtGen package, which implements the helicity conservation in the decay of D⁎+ meson from beauty mesons. In non-central heavy-ion collisions, the spin of the D⁎+ mesons may be globally aligned with the direction of the initial angular momentum and magnetic field. Based on the results for pp collisions reported in this letter it is shown that alignment of non-prompt D⁎+ mesons due to the helicity conservation coupled to the collective anisotropic expansion may mimic the signal of global spin alignment in heavy-ion collisions.
Multiplicity (Nch) distributions and transverse momentum (pT) spectra of inclusive primary charged particles in the kinematic range of |η|<0.8 and 0.15 GeV/c<pT<10 GeV/c are reported for pp, p–Pb, Xe–Xe and Pb–Pb collisions at centre-of-mass energies per nucleon pair ranging from √sNN=2.76 TeV up to 13 TeV. A sequential two-dimensional unfolding procedure is used to extract the correlation between the transverse momentum of primary charged particles and the charged-particle multiplicity of the corresponding collision. This correlation sharply characterises important features of the final state of a collision and, therefore, can be used as a stringent test of theoretical models. The multiplicity distributions as well as the mean and standard deviation derived from the pT spectra are compared to state-of-the-art model predictions. Providing these fundamental observables of bulk particle production consistently across a wide range of collision energies and system sizes can serve as an important input for tuning Monte Carlo event generators.
The measurement of the production of charm jets, identified by the presence of a D0 meson in the jet constituents, is presented in proton–proton collisions at centre-of-mass energies of √s = 5.02 and 13 TeV with the ALICE detector at the CERN LHC. The D0 mesons were reconstructed from their hadronic decay D0 → K−π+ and the respective charge conjugate. Jets were reconstructed from D0-meson candidates and charged particles using the anti-kT algorithm, in the jet transverse momentum range 5 < pT,chjet < 50 GeV/c, pseudorapidity |ηjet| < 0.9 − R, and with the jet resolution parameters R = 0.2, 0.4, 0.6. The distribution of the jet momentum fraction carried by a D0 meson along the jet axis (z ch) was measured in the range 0.4 < z ch < 1.0 in four ranges of the jet transverse momentum. Comparisons of results for different collision energies and jet resolution parameters are also presented. The measurements are compared to predictions from Monte Carlo event generators based on leading-order and next-to-leading-order perturbative quantum chromodynamics calculations. A generally good description of the main features of the data is obtained in spite of a few discrepancies at low pT,chjet. Measurements were also done for R = 0.3 at √s = 5.02 and are shown along with their comparisons to theoretical predictions in an appendix to this paper.
W±-boson production in p–Pb collisions at √sNN = 8.16 TeV and Pb–Pb collisions at √sNN = 5.02 TeV
(2023)
The production of the W± bosons measured in p−Pb collisions at a centre-of-mass energy per nucleon−nucleon collision sNN−−−−√=8.16 TeV and Pb−Pb collisions at √sNN=5.02 TeV with ALICE at the LHC is presented. The W± bosons are measured via their muonic decay channel, with the muon reconstructed in the pseudorapidity region −4<ημlab<−2.5 with transverse momentum pμT>10 GeV/c. While in Pb−Pb collisions the measurements are performed in the forward (2.5<yμcms<4) rapidity region, in p−Pb collisions, where the centre-of-mass frame is boosted with respect to the laboratory frame, the measurements are performed in the backward (−4.46<yμcms<−2.96) and forward (2.03<yμcms<3.53) rapidity regions. The W− and W+ production cross sections, lepton-charge asymmetry, and nuclear modification factors are evaluated as a function of the muon rapidity. In order to study the production as a function of the p−Pb collision centrality, the production cross sections of the W− and W+ bosons are combined and normalised to the average number of binary nucleon−nucleon collision ⟨Ncoll⟩. In Pb−Pb collisions, the same measurements are presented as a function of the collision centrality. Study of the binary scaling of the W±-boson cross sections in p−Pb and Pb−Pb collisions is also reported. The results are compared with perturbative QCD (pQCD) calculations, with and without nuclear modifications of the Parton Distribution Functions (PDFs), as well as with available data at the LHC. Significant deviations from the theory expectations are found in the two collision systems, indicating that the measurements can provide additional constraints for the determination of nuclear PDF (nPDFs) and in particular of the light-quark distributions.
W±-boson production in p–Pb collisions at √sNN = 8.16 TeV and Pb–Pb collisions at √sNN = 5.02 TeV
(2023)
The production of the W± bosons measured in p–Pb collisions at a centreof-mass energy per nucleon–nucleon collision √sNN = 8.16 TeV and Pb–Pb collisions at √sNN = 5.02 TeV with ALICE at the LHC is presented. The W± bosons are measured via their muonic decay channel, with the muon reconstructed in the pseudorapidity region −4 < ηµ lab < −2.5 with transverse momentum p µ T > 10 GeV/c. While in Pb–Pb collisions the measurements are performed in the forward (2.5 < yµ cms < 4) rapidity region, in p–Pb collisions, where the centre-of-mass frame is boosted with respect to the laboratory frame, the measurements are performed in the backward (−4.46 < yµ cms < −2.96) and forward (2.03 < yµ cms < 3.53) rapidity regions. The W− and W+ production cross sections, leptoncharge asymmetry, and nuclear modification factors are evaluated as a function of the muon rapidity. In order to study the production as a function of the p–Pb collision centrality, the production cross sections of the W− and W+ bosons are combined and normalised to the average number of binary nucleon–nucleon collision hNcolli. In Pb–Pb collisions, the same measurements are presented as a function of the collision centrality. Study of the binary scaling of the W±-boson cross sections in p–Pb and Pb–Pb collisions is also reported. The results are compared with perturbative QCD calculations, with and without nuclear modifications of the Parton Distribution Functions (PDFs), as well as with available data at the LHC. Significant deviations from the theory expectations are found in the two collision systems, indicating that the measurements can provide additional constraints for the determination of nuclear PDFs and in particular of the light-quark distributions.
Data from the first physics run at the Relativistic Heavy-Ion Collider at Brookhaven National Laboratory, Au+Au collisions at sqrt[sNN]=130 GeV, have been analyzed by the STAR Collaboration using three-pion correlations with charged pions to study whether pions are emitted independently at freeze-out. We have made a high-statistics measurement of the three-pion correlation function and calculated the normalized three-particle correlator to obtain a quantitative measurement of the degree of chaoticity of the pion source. It is found that the degree of chaoticity seems to increase with increasing particle multiplicity.
Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
Autophagy is a core molecular pathway for the preservation of cellular and organismal homeostasis. Pharmacological and genetic interventions impairing autophagy responses promote or aggravate disease in a plethora of experimental models. Consistently, mutations in autophagy-related processes cause severe human pathologies. Here, we review and discuss preclinical data linking autophagy dysfunction to the pathogenesis of major human disorders including cancer as well as cardiovascular, neurodegenerative, metabolic, pulmonary, renal, infectious, musculoskeletal, and ocular disorders.
National greenhouse gas inventories (GHGIs) are submitted annually to the United Nations Framework Convention on Climate Change (UNFCCC). They are estimated in compliance with Intergovernmental Panel on Climate Change (IPCC) methodological guidance using activity data, emission factors and facility-level measurements. For some sources, the outputs from these calculations are very uncertain. Inverse modelling techniques that use high-quality, long-term measurements of atmospheric gases have been developed to provide independent verification of national GHGIs. This is considered good practice by the IPCC as it helps national inventory compilers to verify reported emissions and to reduce emission uncertainty. Emission estimates from the InTEM (Inversion Technique for Emission Modelling) model are presented for the UK for the hydrofluorocarbons (HFCs) reported to the UNFCCC (HFC-125, HFC-134a, HFC-143a, HFC-152a, HFC-23, HFC-32, HFC-227ea, HFC-245fa, HFC-43-10mee and HFC-365mfc). These HFCs have high global warming potentials (GWPs), and the global background mole fractions of all but two are increasing, thus highlighting their relevance to the climate and a need for increasing the accuracy of emission estimation for regulatory purposes. This study presents evidence that the long-term annual increase in growth of HFC-134a has stopped and is now decreasing. For HFC-32 there is an early indication, its rapid global growth period has ended, and there is evidence that the annual increase in global growth for HFC-125 has slowed from 2018. The inverse modelling results indicate that the UK implementation of European Union regulation of HFC emissions has been successful in initiating a decline in UK emissions from 2018. Comparison of the total InTEM UK HFC emissions in 2020 with the average from 2009–2012 shows a drop of 35 %, indicating progress toward the target of a 79 % decrease in sales by 2030. The total InTEM HFC emission estimates (2008–2018) are on average 73 (62–83) % of, or 4.3 (2.7–5.9) Tg CO2-eq yr−1 lower than, the total HFC emission estimates from the UK GHGI. There are also significant discrepancies between the two estimates for the individual HFCs.
National Greenhouse Gas Inventories (GHGI) are submitted annually to the United Nations Framework Convention on Climate Change (UNFCCC). They are estimated in compliance with Intergovernmental Panel on Climate Change (IPCC) methodological guidance using activity data, emission factors and facility-level measurements. For some sources, the outputs from these calculations are very uncertain. Inverse modelling techniques that use high-quality, long-term measurements of atmospheric gases have been developed to provide independent verification of national GHGI. This is considered good practice by the IPCC as it helps national inventory compilers to verify reported emissions and to reduce emission uncertainty. Emission estimates from the InTEM (Inversion Technique for Emissions Modelling) model are presented for the UK for the hydrofluorocarbons (HFCs) reported to the UNFCCC (HFC-125, HFC-134a, HFC-143a, HFC-152a, HFC-23, HFC-32, HFC-227ea, HFC-245fa, HFC-43-10mee and HFC-365mfc). These HFCs have high Global Warming Potentials (GWPs) and the global background mole fractions of all but two are increasing, thus highlighting their relevance to the climate and a need for increasing the accuracy of emission estimation for regulatory purposes. This study presents evidence that the long-term annual increase in growth of HFC-134a has stopped and is now decreasing. For HFC-32 there is an early indication its rapid global growth period has ended, and there is evidence that the annual increase in global growth for HFC-125 has slowed from 2018. The inverse modelling results indicate that the UK implementation of European Union regulation of HFC emissions has been successful in initiating a decline in UK emissions in the since 2018. Comparison of the total InTEM UK HFC emissions in 2020 with the average from 2009–2012 shows a drop of 35%, indicating progress toward the target of a 79% decrease in sales by 2030. The total InTEM HFC emission estimates (2008–2018) are on average 73 (62–83)% of, or 4.3 (2.7–5.9) Tg CO2-eq yr−1 lower than, the total HFC emission estimates from the UK GHGI inventory. There are also significant discrepancies between the two estimates for the individual HFCs.
Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed.
Angular distributions for elastic and inelastic transitions in 20Ne + 16O scattering have been measured at E(20Ne)=50 MeV. For the 0+, 2+, and 4+ members of the 20Ne ground-state rotational band, the angular distributions exhibit pronounced backward peaking characteristic of an alpha -cluster exchange mechanism. The analysis of the ground-state transition in the first-order elastic transfer model yields no satisfactory fit although microscopic cluster form factors and full recoil corrections are employed. A coupled channels calculation for the 0+, 2+, and 4+ transitions reveals very strong coupling effects, indicating that the coherent superposition of first-order optical model and distorted-wave Born-approximation amplitudes may not be an adequate model for these reactions. NUCLEAR REACTIONS 16O(20Ne, 16O) and 16O(20Ne, 20Ne), elastic and inelastic transfer; E=50MeV; measured sigma (Ef , theta ); optical model + DWBA, and CCBA analyses.
Unequivocal international guidelines regarding the diagnosis and management of patients with acute appendicitis are lacking. The aim of the consensus meeting 2015 of the EAES was to generate a European guideline based on best available evidence and expert opinions of a panel of EAES members. After a systematic review of the literature by an international group of surgical research fellows, an expert panel with extensive clinical experience in the management of appendicitis discussed statements and recommendations. Statements and recommendations with more than 70 % agreement by the experts were selected for a web survey and the consensus meeting of the EAES in Bucharest in June 2015. EAES members and attendees at the EAES meeting in Bucharest could vote on these statements and recommendations. In the case of more than 70 % agreement, the statement or recommendation was defined as supported by the scientific community. Results from both the web survey and the consensus meeting in Bucharest are presented as percentages. In total, 46 statements and recommendations were selected for the web survey and consensus meeting. More than 232 members and attendees voted on them. In 41 of 46 statements and recommendations, more than 70 % agreement was reached. All 46 statements and recommendations are presented in this paper. They comprise topics regarding the diagnostic work-up, treatment indications, procedural aspects and post-operative care. The consensus meeting produced 46 statements and recommendations on the diagnostic work-up and management of appendicitis. The majority of the EAES members supported these statements. These consensus proceedings provide additional guidance to surgeons and surgical residents providing care to patients with appendicitis.
Within the SEASTAR project at RIKEN-RIBF, 66Cr and 70,72Fe have been produced via protonknockout reactions, and their first excited 2+ and 4+ states have been discovered. The combination of the liquid-hydrogen target and TPC system MINOS has been used in combination with the DALI2 detector array for the first time. A 345 MeV/u 238U beam with a mean intensity of about 12 pnA impinged on a Be target. Fission fragments were separated and identified using the BigRIPS spectrograph, and reaction products were analyzed using the ZeroDegree spectrograph. A plateau of excitation energies, with a small change in the systematic trends past N = 44, reveals an extension of the N = 40 region of collectivity toward N = 50. Hence, the isotopes of interest are located within the N = 40 island of inversion. An interpretation of the observed trends is offered through large scale shell model calculations.
Background: Autism spectrum disorder (“autism”) is a highly heterogeneous neurodevelopmental condition with few effective treatments for core and associated features. To make progress we need to both identify and validate neural markers that help to parse heterogeneity to tailor therapies to specific neurobiological profiles. Atypical hemispheric lateralization is a stable feature across studies in autism, but its potential as a neural stratification marker has not been widely examined. Methods: In order to dissect heterogeneity in lateralization in autism, we used the large EU-AIMS (European Autism Interventions—A Multicentre Study for Developing New Medications) Longitudinal European Autism Project dataset comprising 352 individuals with autism and 233 neurotypical control subjects as well as a replication dataset from ABIDE (Autism Brain Imaging Data Exchange) (513 individuals with autism, 691 neurotypical subjects) using a promising approach that moves beyond mean group comparisons. We derived gray matter voxelwise laterality values for each subject and modeled individual deviations from the normative pattern of brain laterality across age using normative modeling. Results: Individuals with autism had highly individualized patterns of both extreme right- and leftward deviations, particularly in language, motor, and visuospatial regions, associated with symptom severity. Language delay explained most variance in extreme rightward patterns, whereas core autism symptom severity explained most variance in extreme leftward patterns. Follow-up analyses showed that a stepwise pattern emerged, with individuals with autism with language delay showing more pronounced rightward deviations than individuals with autism without language delay. Conclusions: Our analyses corroborate the need for novel (dimensional) approaches to delineate the heterogeneous neuroanatomy in autism and indicate that atypical lateralization may constitute a neurophenotype for clinically meaningful stratification in autism.
Background: Autism Spectrum Disorder (henceforth ‘autism’) is a highly heterogeneous neurodevelopmental condition with few effective treatments for core and associated features. To make progress we need to both identify and validate neural markers that help to parse heterogeneity to tailor therapies to specific neurobiological profiles. Atypical hemispheric lateralization is a stable feature across studies in autism, however its potential of lateralization as a neural stratification marker has not been widely examined.
Methods: In order to dissect heterogeneity in lateralization in autism, we used the large EU-AIMS Longitudinal European Autism Project dataset comprising 352 individuals with autism and 233 neurotypical (NT) controls as well as a replication dataset from ABIDE (513 autism, 691 NT) using a promising approach that moves beyond mean-group comparisons. We derived grey matter voxelwise laterality values for each subject and modelled individual deviations from the normative pattern of brain laterality across age using normative modeling.
Results: Results showed that individuals with autism had highly individualized patterns of both extreme right- and leftward deviations, particularly in language-, motor- and visuospatial regions, associated with symptom severity. Language delay (LD) explained most variance in extreme rightward patterns, whereas core autism symptom severity explained most variance in extreme leftward patterns. Follow-up analyses showed that a stepwise pattern emerged with individuals with autism with LD showing more pronounced rightward deviations than autism individuals without LD.
Conclusion: Our analyses corroborate the need for novel (dimensional) approaches to delineate the heterogeneous neuroanatomy in autism, and indicate atypical lateralization may constitute a neurophenotype for clinically meaningful stratification in autism.
While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.
Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
The first evidence of spin alignment of vector mesons (K*0 and ϕ) in heavy-ion collisions at the Large Hadron Collider (LHC) is reported. The spin density matrix element ρ00 is measured at midrapidity (|y|< 0.5) in Pb-Pb collisions at a center-of-mass energy (√sNN) of 2.76 TeV
with the ALICE detector. ρ00 values are found to be less than 1/3 (1/3 implies no spin alignment) at low transverse momentum (pT<2 GeV/c) for K*0 and ϕ at a level of 3σ and 2σ, respectively. No significant spin alignment is observed for the K0S meson (spin = 0) in Pb-Pb collisions and for the vector mesons in pp collisions. The measured spin alignment is unexpectedly large but qualitatively consistent with the expectation from models which attribute it to a polarization of quarks in the presence of angular momentum in heavy-ion collisions and a subsequent hadronization by the process of recombination.
The transverse momentum (pT) differential yields of (anti-)3He and (anti-)3H measured in p-Pb collisions at sNN−−−√ = 5.02 TeV with ALICE at the Large Hadron Collider (LHC) are presented. The ratios of the pT-integrated yields of (anti-)3He and (anti-)3H to the proton yields are reported, as well as the pT dependence of the coalescence parameters B3 for (anti-)3He and (anti-)3H. For (anti-)3He, the results obtained in four classes of the mean charged-particle multiplicity density are also discussed. These results are compared to predictions from a canonical statistical hadronization model and coalescence approaches. An upper limit on the total yield of 4He¯ is determined.
Scattering studies with low-energy kaon-proton femtoscopy in proton-proton collisions at the LHC
(2020)
The study of the strength and behaviour of the antikaon-nucleon (K¯¯¯¯N) interaction constitutes one of the key focuses of the strangeness sector in low-energy Quantum Chromodynamics (QCD). In this letter a unique high-precision measurement of the strong interaction between kaons and protons, close and above the kinematic threshold, is presented. The femtoscopic measurements of the correlation function at low pair-frame relative momentum of (K+ p ⊕ K− p¯¯¯) and (K− p ⊕ K+ p¯¯¯) pairs measured in pp collisions at s√ = 5, 7 and 13 TeV are reported. A structure observed around a relative momentum of 58 MeV/c in the measured correlation function of (K− p ⊕ K+ p¯¯¯) with a significance of 4.4. σ constitutes the first experimental evidence for the opening of the (K¯¯¯¯0n⊕K0n¯¯¯) isospin breaking channel due to the mass difference between charged and neutral kaons. The measured correlation functions have been compared to Jülich and Kyoto models in addition to the Coulomb potential. The high-precision data at low relative momenta presented in this work prove femtoscopy to be a powerful complementary tool to scattering experiments and provide new constraints above the K¯¯¯¯N threshold for low-energy QCD chiral models.
Scattering studies with low-energy kaon-proton femtoscopy in
proton–proton collisions at the LHC
(2019)
The study of the strength and behaviour of the antikaon-nucleon (K¯¯¯¯N) interaction constitutes one of the key focuses of the strangeness sector in low-energy Quantum Chromodynamics (QCD). In this letter a unique high-precision measurement of the strong interaction between kaons and protons, close and above the kinematic threshold, is presented. The femtoscopic measurements of the correlation function at low pair-frame relative momentum of (K+ p ⊕ K− p¯¯¯) and (K− p ⊕ K+ p¯¯¯) pairs measured in pp collisions at s√ = 5, 7 and 13 TeV are reported. A structure observed around a relative momentum of 58 MeV/c in the measured correlation function of (K− p ⊕ K+ p¯¯¯) constitutes the first experimental evidence for the opening of the (K¯¯¯¯0n⊕K0n¯¯¯) isospin breaking channel due to the mass difference between charged and neutral kaons. The measured correlation functions have been compared to several models. The high-precision data at low relative momenta presented in this work prove femtoscopy to be a powerful complementary tool to scattering experiments and provide new constraints above the K¯¯¯¯N threshold for low-energy QCD chiral models.
Scattering studies with low-energy kaon-proton femtoscopy in proton–proton collisions at the LHC
(2020)
The study of the strength and behaviour of the antikaon-nucleon (K¯¯¯¯N) interaction constitutes one of the key focuses of the strangeness sector in low-energy Quantum Chromodynamics (QCD). In this letter a unique high-precision measurement of the strong interaction between kaons and protons, close and above the kinematic threshold, is presented. The femtoscopic measurements of the correlation function at low pair-frame relative momentum of (K+ p ⊕ K− p¯¯¯) and (K− p ⊕ K+ p¯¯¯) pairs measured in pp collisions at s√ = 5, 7 and 13 TeV are reported. A structure observed around a relative momentum of 58 MeV/c in the measured correlation function of (K− p ⊕ K+ p¯¯¯) with a significance of 4.4. σ constitutes the first experimental evidence for the opening of the (K¯¯¯¯0n⊕K0n¯¯¯) isospin breaking channel due to the mass difference between charged and neutral kaons. The measured correlation functions have been compared to Jülich and Kyoto models in addition to the Coulomb potential. The high-precision data at low relative momenta presented in this work prove femtoscopy to be a powerful complementary tool to scattering experiments and provide new constraints above the K¯¯¯¯N threshold for low-energy QCD chiral models.
Investigators in the cognitive neurosciences have turned to Big Data to address persistent replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. While there is tremendous potential to advance science through open data sharing, these efforts unveil a host of new questions about how to integrate data arising from distinct sources and instruments. We focus on the most frequently assessed area of cognition - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated raw data from 53 studies from around the world which measured at least one of three distinct verbal learning tasks, totaling N = 10,505 healthy and brain-injured individuals. A mega analysis was conducted using empirical bayes harmonization to isolate and remove site effects, followed by linear models which adjusted for common covariates. After corrections, a continuous item response theory (IRT) model estimated each individual subject’s latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance by 37% while preserving covariate effects. The effects of age, sex, and education on scores were found to be highly consistent across memory tests. IRT methods for equating scores across AVLTs agreed with held-out data of dually-administered tests, and these tools are made available for free online. This work demonstrates that large-scale data sharing and harmonization initiatives can offer opportunities to address reproducibility and integration challenges across the behavioral sciences.
Study Design: Survey of 100 worldwide spine surgeons.
Objective: To develop a spine injury score for the AOSpine Thoracolumbar Spine Injury Classification System.
Methods: Each respondent was asked to numerically grade the severity of each variable of the AOSpine Thoracolumbar Spine Injury Classification System. Using the results, as well as limited input from the AOSpine Trauma Knowledge Forum, the Thoracolumbar AOSpine Injury Score was developed.
Results: Beginning with 1 point for A1, groups A, B, and C were consecutively awarded an additional point (A1, 1 point; A2, 2 points; A3, 3 points); however, because of a significant increase in the severity between A3 and A4 and because the severity of A4 and B1 was similar, both A4 and B1 were awarded 5 points. An uneven stepwise increase in severity moving from N0 to N4, with a substantial increase in severity between N2 (nerve root injury with radicular symptoms) and N3 (incomplete spinal cord injury) injuries, was identified. Hence, each grade of neurologic injury was progressively given an additional point starting with 0 points for N0, and the substantial difference in severity between N2 and N3 injuries was recognized by elevating N3 to 4 points. Finally, 1 point was awarded to the M1 modifier (indeterminate posterolateral ligamentous complex injury).
Conclusion: The Thoracolumbar AOSpine Injury Score is an easy-to-use, data-driven metric that will allow for the development of a surgical algorithm to accompany the AOSpine Thoracolumbar Spine Injury Classification System.
We report about the properties of the underlying event measured with ALICE at the LHC in pp and p−Pb collisions at sNN−−−√=5.02 TeV. The event activity, quantified by charged-particle number and summed-pT densities, is measured as a function of the leading-particle transverse momentum (ptrigT). These quantities are studied in three azimuthal-angle regions relative to the leading particle in the event: toward, away, and transverse. Results are presented for three different pT thresholds (0.15, 0.5, and 1 GeV/c) at mid-pseudorapidity (|η|<0.8). The event activity in the transverse region, which is the most sensitive to the underlying event, exhibits similar behaviour in both pp and p−Pb collisions, namely, a steep increase with ptrigT for low ptrigT, followed by a saturation at ptrigT≈5 GeV/c. The results from pp collisions are compared with existing measurements at other centre-of-mass energies. The quantities in the toward and away regions are also analyzed after the subtraction of the contribution measured in the transverse region. The remaining jet-like particle densities are consistent in pp and p−Pb collisions for ptrigT>10 GeV/c, whereas for lower ptrigT values the event activity is slightly higher in p−Pb than in pp collisions. The measurements are compared with predictions from the PYTHIA 8 and EPOS LHC Monte Carlo event generators.
We report about the properties of the underlying event measured with ALICE at the LHC in pp and p−Pb collisions at sNN−−−√=5.02 TeV. The event activity, quantified by charged-particle number and summed-pT densities, is measured as a function of the leading-particle transverse momentum (ptrigT). These quantities are studied in three azimuthal-angle regions relative to the leading particle in the event: toward, away, and transverse. Results are presented for three different pT thresholds (0.15, 0.5, and 1 GeV/c) at mid-pseudorapidity (|η|<0.8). The event activity in the transverse region, which is the most sensitive to the underlying event, exhibits similar behaviour in both pp and p−Pb collisions, namely, a steep increase with ptrigT for low ptrigT, followed by a saturation at ptrigT≈5 GeV/c. The results from pp collisions are compared with existing measurements at other centre-of-mass energies. The quantities in the toward and away regions are also analyzed after the subtraction of the contribution measured in the transverse region. The remaining jet-like particle densities are consistent in pp and p−Pb collisions for ptrigT>10 GeV/c, whereas for lower ptrigT values the event activity is slightly higher in p−Pb than in pp collisions. The measurements are compared with predictions from the PYTHIA 8 and EPOS LHC Monte Carlo event generators.
Neuronal nAChRs are a diverse family of pentameric ion channels with wide distribution throughout cells of the nervous and immune systems. However, the role of specific subtypes in normal and pathological states remains poorly understood due to the lack of selective probes. Here, we used a binding assay based on acetylcholine-binding protein (AChBP), a homolog of the nicotinic acetylcholine ligand-binding domain, to discover a novel alpha-conotoxin (alpha-TxIA) in the venom of Conus textile. alpha-TxIA bound with high affinity to AChBPs from different species and selectively targeted the alpha3beta2 nAChR subtype. A co-crystal structure of Ac-AChBP with the enhanced potency analog TxIA(A10L), revealed a 20° backbone tilt compared to other AChBP–conotoxin complexes. This reorientation was coordinated by a key salt bridge formed between Arg5 (TxIA) and Asp195 (Ac-AChBP). Mutagenesis studies, biochemical assays and electrophysiological recordings directly correlated the interactions observed in the co-crystal structure to binding affinity at AChBP and different nAChR subtypes. Together, these results establish a new pharmacophore for the design of novel subtype-selective ligands with therapeutic potential in nAChR-related diseases.
Review of the Natural History of the Handsome Fungus Beetles (Coleoptera: Cucujoidea: Endomychidae)
(2009)
The literature pertaining to natural history of Endomychidae (Coleoptera: Cucujoidea) is reviewed. One hundred fungal host records are provided for 32 endomychid species. Twenty-three records of endomychid yeast endosymbionts are compiled. Summaries are also presented for feeding preferences, interactions with natural enemies, non-lethal symbiotic relationships, and pest activity within the family. Unusual endomychid behaviors and habitats are reviewed, with particular attention to gregariousness and defensive strategies within Endomychidae.
Background: The newly introduced German pediatric screening examination at the end of the third year of life (U7a) incorporates visual function testing in particular; there is no ophthalmic screening during childhood in Germany. The purpose of this study is to investigate the relationship between participation in U7a and visual function at the preschool health examination (PHE) in the sixth year of life. Methods: This study evaluated PHE data from school enrollment years 2009/2010 to 2014/2015 of Rhineland-Palatinate, Germany. Visual acuity (VA) at PHE was assessed with Rodenstock visual acuity test device (tumbling E) wearing glasses if present. The relationship between participation in U7a and VA <0.7 at PHE was calculated for reduced monocular and binocular VA using multiple logistic regression adjusted for potential confounders. Results: Data from 189,704 children (91,041 girls) in 35 out of 36 districts were included. The first children to participate in U7a were enrolled in 2011/2012 school year. In total, 90,339 children (47.6%) had U7a before PHE, while 99,365 (52.4%) had not. VA <0.7 in at least one eye was measured at PHE in 8429 (4.4%) children, and in both eyes in 4345 (2.3%) children. Participation in U7a was not associated with VA <0.7 at PHE (odds ratio 0.99; 95% confidence interval: 0.94–1.04). Conclusions: The proportion of children with VA <0.7 at PHE was high. No beneficial effect of newly introduced German U7a pediatric screening examination was found for reduced VA at PHE.
Labahitha spiders (Arachnida: Araneae: Filistatidae) from islands in the Indian and Pacific Ocean
(2022)
The genus Labahitha has hitherto comprised two species from peninsular Malaysia and Christmas Island (Australia). We here demonstrate that the genus is widespread in islands and territories across the Indian and Pacific Oceans, including the following species that have been previously assigned to other filistatid genera: Labahitha marginata (Kishida, 1936) comb. nov. (= Filistata bakeri Berland, 1938 syn. nov.), Labahitha garciai (Simon, 1892) comb. nov. (= Pritha heikkii Saaristo, 1978 syn. nov., = Pritha sechellana Benoit, 1978 syn. nov.), Labahitha nicobarensis (Tikader, 1977) comb. nov., Labahitha littoralis (Roewer, 1938) comb. nov., Labahitha insularis (Thorell, 1891) comb. nov., Labahitha sundaica (Kulczyński, 1908) comb. nov. (all transferred from Pritha, the latter three provisionally, pending re-examination of the type material); Labahitha fuscata (Nakatsudi, 1943) comb. nov. and Labahitha ryukyuensis (Ono, 2013) comb. nov. (both transferred from Tricalamus). Many of these species have been collected in synanthropic settings and from disparate islands thousands of kilometers apart. This suggests either high dispersal capabilities or, more likely, human-mediated introductions. At least L. marginata has been introduced to continental America. Two new species of Labahitha are described: Labahitha platnicki sp. nov. from New Caledonia and the Bismarck Islands and Labahitha incerta sp. nov. from Queensland, Australia. The male of Labahitha gibsonhilli (Savory, 1943) is reported for the first time. Wandella loloata sp. nov. is described from Papua New Guinea, representing the first record of this genus outside Australia. Pritha hasselti (Simon, 1906) from Indonesia is shown to be a Filistatinae, and thus the species is provisionally transferred back to Filistata.
We document the presence of Larra bicolor Fabricius (Hymenoptera: Crabronidae) in 46 of Florida's 67 counties. The species is represented by two stocks. The first (released in 1981) originated in Pará, Brazil, but was obtained from Puerto Rico, and became established in Broward County in southern Florida. The second (released in 1988) originated in Santa Cruz de la Sierra, Bolivia, and became established in Alachua County in northern Florida. The Bolivian stock, aided by additional satellite releases from Alachua County, is now widely distributed. The species probably occupies all counties in central and northern Florida, but may yet be absent from some southern counties. Introduction was made for classical biological control of invasive mole crickets.
During early G1 phase, Rb is exclusively mono-phosphorylated by cyclin D:Cdk4/6, generating 14 different isoforms with specific binding patterns to E2Fs and other cellular protein targets. While mono-phosphorylated Rb is dispensable for early G1 phase progression, interfering with cyclin D:Cdk4/6 kinase activity prevents G1 phase progression, questioning the role of cyclin D:Cdk4/6 in Rb inactivation. To dissect the molecular functions of cyclin D:Cdk4/6 during cell cycle entry, we generated a single cell reporter for Cdk2 activation, RB inactivation and cell cycle entry by CRISPR/Cas9 tagging endogenous p27 with mCherry. Through single cell tracing of Cdk4i cells, we identified a time-sensitive early G1 phase specific Cdk4/6-dependent phosphorylation gradient that regulates cell cycle entry timing and resides between serum-sensing and cyclin E:Cdk2 activation. To reveal the substrate identity of the Cdk4/6 phosphorylation gradient, we performed whole proteomic and phospho-proteomic mass spectrometry, and identified 147 proteins and 82 phospho-peptides that significantly changed due to Cdk4 inhibition in early G1 phase. In summary, we identified novel (non-Rb) cyclin D:Cdk4/6 substrates that connects early G1 phase functions with cyclin E:Cdk2 activation and Rb inactivation by hyper-phosphorylation.
Under the Kigali Amendment to the Montreal Protocol, new controls are being implemented to reduce emissions of HFC-23 (CHF3), a by-product during the manufacture of HCFC-22 (CHClF2). Starting in 2015, China and India, who dominate global HCFC-22 production (75% in 2017), set out ambitious programs to reduce HFC-23 emissions. Here, we estimate that these measures should have seen global emissions drop by 87% between 2014 and 2017. Instead, atmospheric observations show that emissions have increased and in 2018 were higher than at any point in history (15.9 ± 0.9 Gg yr−1). Given the magnitude of the discrepancy between expected and observation-inferred emissions, it is likely that the reported reductions have not fully materialized or there may be substantial unreported production of HCFC-22, resulting in unaccounted-for HFC-23 by-product emissions. The difference between reported and observation-inferred estimates suggests that an additional ~309 Tg CO2-equivalent emissions were added to the atmosphere between 2015 and 2017.
Background: The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC. Methods: The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 3-year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating. Discussion: If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC. (trial registered at www.clinicaltrials.gov: NCT00355862) (EudraCT Number: 2005-005362-36)
The SARS-CoV-2 genome encodes for approximately 30 proteins. Within the international project COVID19-NMR, we distribute the spectroscopic analysis of the viral proteins and RNA. Here, we report NMR chemical shift assignments for the protein Nsp3b, a domain of Nsp3. The 217-kDa large Nsp3 protein contains multiple structurally independent, yet functionally related domains including the viral papain-like protease and Nsp3b, a macrodomain (MD). In general, the MDs of SARS-CoV and MERS-CoV were suggested to play a key role in viral replication by modulating the immune response of the host. The MDs are structurally conserved. They most likely remove ADP-ribose, a common posttranslational modification, from protein side chains. This de-ADP ribosylating function has potentially evolved to protect the virus from the anti-viral ADP-ribosylation catalyzed by poly-ADP-ribose polymerases (PARPs), which in turn are triggered by pathogen-associated sensing of the host immune system. This renders the SARS-CoV-2 Nsp3b a highly relevant drug target in the viral replication process. We here report the near-complete NMR backbone resonance assignment (1H, 13C, 15N) of the putative Nsp3b MD in its apo form and in complex with ADP-ribose. Furthermore, we derive the secondary structure of Nsp3b in solution. In addition, 15N-relaxation data suggest an ordered, rigid core of the MD structure. These data will provide a basis for NMR investigations targeted at obtaining small-molecule inhibitors interfering with the catalytic activity of Nsp3b.
The International Halocarbons in Air Comparison Experiment (IHALACE) was conducted to document relationships between calibration scales among various laboratories that measure atmospheric greenhouse and ozone depleting gases. Six stainless steel cylinders containing natural and modified natural air samples were circulated among 19 laboratories. Results from this experiment reveal relatively good agreement among commonly used calibration scales for a number of trace gases present in the unpolluted atmosphere at pmol mol−1 (parts per trillion) levels, such as chlorofluorocarbons (CFCs), hydrochlorofluorocarbons (HCFCs), and hydrofluorocarbons (HFCs). Some scale relationships were found to be consistent with those derived from bi-lateral experiments or from analysis of atmospheric data, while others revealed discrepancies. The transfer of calibration scales among laboratories was found to be problematic in many cases, meaning that measurements tied to a common scale may not, in fact, be compatible. These results reveal substantial improvements in calibration over previous comparisons. However there is room for improvement in communication and coordination of calibration activities with respect to the measurement of halogenated and related trace gases.
We report on HCFC-22 data acquired by the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) in the reduced spectral resolution nominal observation mode. The data cover the period from January 2005 to April 2012 and the altitude range from the upper troposphere (above cloud top altitude) to about 50 km. The profile retrieval was performed by constrained nonlinear least squares fitting of modelled spectra to the measured limb spectral radiances. The spectral ν4-band at 816.5 ± 13 cm−1 was used for the retrieval. A Tikhonov-type smoothing constraint was applied to stabilise the retrieval. In the lower stratosphere, we find a global volume mixing ratio of HCFC-22 of about 185 pptv in January 2005. The rate of linear growth in the lower latitudes lower stratosphere was about 6 to 7 pptv year−1 in the period 2005–2012. The profiles obtained were compared with ACE-FTS satellite data v3.5, as well as with MkIV balloon profiles and cryosampler balloon measurements. Between 13 and 22 km, average agreement within −3 to +5 pptv (MIPAS – ACE) with ACE-FTS v3.5 profiles is demonstrated. Agreement with MkIV solar occultation balloon-borne measurements is within 10–20 pptv below 30 km and worse above, while in situ cryosampler balloon measurements are systematically lower over their full altitude range by 15–50 pptv below 24 km and less than 10 pptv above 28 km. MIPAS HCFC-22 time series below 10 km altitude are shown to agree mostly well to corresponding time series of near-surface abundances from the NOAA/ESRL and AGAGE networks, although a more pronounced seasonal cycle is obvious in the satellite data. This is attributed to tropopause altitude fluctuations and subsidence of polar winter stratospheric air into the troposphere. A parametric model consisting of constant, linear, quasi-biennial oscillation (QBO) and several sine and cosine terms with different periods has been fitted to the temporal variation of stratospheric HCFC-22 for all 10°-latitude/1-to-2-km-altitude bins. The relative linear variation was always positive, with relative increases of 40–70 % decade−1 in the tropics and global lower stratosphere, and up to 120 % decade−1 in the upper stratosphere of the northern polar region and the southern extratropical hemisphere. Asian HCFC-22 emissions have become the major source of global upper tropospheric HCFC-22. In the upper troposphere, monsoon air, rich in HCFC-22, is instantaneously mixed into the tropics. In the middle stratosphere, between 20 and 30 km, the observed trend is inconsistent with the trend at the surface (corrected for the age of stratospheric air), hinting at circulation changes. There exists a stronger positive trend in HCFC-22 in the Southern Hemisphere and a more muted positive trend in the Northern Hemisphere, implying a potential change in the stratospheric circulation over the observation period.
We report on HCFC-22 data acquired by the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) in reduced spectral resolution nominal mode in the period from January 2005 to April 2012 from version 5.02 level-1b spectral data and covering an altitude range from the upper troposphere (above cloud top altitude) to about 50 km. The profile retrieval was performed by constrained nonlinear least squares fitting of measured limb spectral radiances to modelled spectra. The spectral v4-band at 816.5 ± 13 cm-1 was used for the retrieval. A Tikhonov-type smoothing constraint was applied to stabilise the retrieval. In the lower stratosphere, we find a global volume mixing ratio of HCFC-22 of about 185 pptv in January 2005. The linear growth rate in the lower latitudes lower stratosphere was about 6 to 7 pptv yr-1 in the period 2005–2012. The obtained profiles were compared with ACE-FTS satellite data v3.5, as well as with MkIV balloon profiles and in situ cryosampler balloon measurements. Between 13 and 22 km, average agreement within -3 to +5 pptv (MIPAS–ACE) with ACE-FTS v3.5 pro files is demonstrated. Agreement with MkIV solar occultation balloon-borne measurements is within 10–20 pptv below 30 km and worse above, while in situ cryosampler balloon measurements are systematically lower over their full altitude range by 15– 50 pptv below 24 km and less than 10 pptv above 28 km. Obtained MIPAS HCFC-22 time series below 10 km altitude are shown to agree mostly well to corresponding time series of near-surface abundances from NOAA/ESRL and AGAGE networks, although a more pronounced seasonal cycle is obvious in the satellite data, probably due to tropopause altitude fluctuations and subsidence of polar winter stratospheric air into the troposphere. A parametric model consisting of constant, linear, quasi-biennial oscillation (QBO) and several sine and cosine terms with different periods has been fitted to the temporal variation of stratospheric HCFC-22 for all 10° latitude/1 to 2 km altitude bins. The relative linear variation was always positive, with relative increases of 40–70%decade-1 in the tropics and global lower stratosphere, and up to 120%decade-1 in the upper stratosphere of the northern polar region and the southern extratropical hemisphere. In the middle stratosphere between 20 and 30 km, the observed trend is not consistent with the age of stratospheric air-corrected trend at ground, but stronger positive at the Southern Hemisphere and less strong increasing in the Northern Hemisphere, hinting towards changes in the stratospheric circulation over the observation period.
A key event in cellular physiology is the decision between membrane biogenesis and fat storage. Phosphatidic acid (PA) is an important intermediate at the branch point of these pathways and is continuously monitored by the transcriptional repressor Opi1 to orchestrate lipid metabolism. In this study, we report on the mechanism of membrane recognition by Opi1 and identify an amphipathic helix (AH) for selective binding of PA over phosphatidylserine (PS). The insertion of the AH into the membrane core renders Opi1 sensitive to the lipid acyl chain composition and provides a means to adjust membrane biogenesis. By rational design of the AH, we tune the membrane-binding properties of Opi1 and control its responsiveness in vivo. Using extensive molecular dynamics simulations, we identify two PA-selective three-finger grips that tightly bind the PA phosphate headgroup while interacting less intimately with PS. This work establishes lipid headgroup selectivity as a new feature in the family of AH-containing membrane property sensors.
Calcium (Ca2+) elevation is an essential secondary messenger in many cellular processes, including disease progression and adaptation to external stimuli, e.g., gravitational load. Therefore, mapping and quantifying Ca2+ signaling with a high spatiotemporal resolution is a key challenge. However, particularly on microgravity platforms, experiment time is limited, allowing only a small number of replicates. Furthermore, experiment hardware is exposed to changes in gravity levels, causing experimental artifacts unless appropriately controlled. We introduce a new experimental setup based on the fluorescent Ca2+ reporter CaMPARI2, onboard LED arrays, and subsequent microscopic analysis on the ground. This setup allows for higher throughput and accuracy due to its retrograde nature. The excellent performance of CaMPARI2 was demonstrated with human chondrocytes during the 75th ESA parabolic flight campaign. CaMPARI2 revealed a strong Ca2+ response triggered by histamine but was not affected by the alternating gravitational load of a parabolic flight.
Background: Misconceptions about ADHD stigmatize affected people, reduce credibility of providers, and prevent/delay treatment. To challenge misconceptions, we curated findings with strong evidence base. Methods: We reviewed studies with more than 2000 participants or meta-analyses from five or more studies or 2000 or more participants. We excluded meta-analyses that did not assess publication bias, except for meta-analyses of prevalence. For network meta-analyses we required comparison adjusted funnel plots. We excluded treatment studies with waiting-list or treatment as usual controls. From this literature, we extracted evidence-based assertions about the disorder. Results: We generated 208 empirically supported statements about ADHD. The status of the included statements as empirically supported is approved by 80 authors from 27 countries and 6 continents. The contents of the manuscript are endorsed by 366 people who have read this document and agree with its contents. Conclusions: Many findings in ADHD are supported by meta-analysis. These allow for firm statements about the nature, course, outcome causes, and treatments for disorders that are useful for reducing misconceptions and stigma.
Background Reward processing has been proposed to underpin atypical social behavior, a core feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social rewards in ASD. Utilizing a large sample, we aimed to assess altered reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD.
Methods Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6-30.5 years) and 181 typically developing (TD) participants (7.6-30.8 years).
Results Across social and monetary reward anticipation, whole-brain analyses (p<0.05, family-wise error-corrected) showed hypoactivation of the right ventral striatum (VS) in ASD. Further, region of interest (ROI) analysis across both reward types yielded hypoactivation in ASD in both the left and right VS. Across delivery of social and monetary reward, hyperactivation of the VS in individuals with ASD did not survive correction for multiple comparisons. Reward type by diagnostic group interactions, and a dimensional analysis of autism trait scores were not significant during anticipation or delivery. Levels of attention-deficit/hyperactivity disorder (ADHD) symptoms did not affect reward processing in ASD.
Conclusions Our results do not support current theories linking atypical social interaction in ASD to specific alterations in processing of social rewards. Instead, they point towards a generalized hypoactivity of VS in ASD during anticipation of both social and monetary rewards. We suggest that this indicates attenuated subjective reward value in ASD independent of social content and ADHD symptoms.
Archaeological evidence indicates that pig domestication had begun by ∼10,500 y before the present (BP) in the Near East, and mitochondrial DNA (mtDNA) suggests that pigs arrived in Europe alongside farmers ∼8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process.
Background: Marked sex differences in autism prevalence accentuate the need to understand the role of biological sex-related factors in autism. Efforts to unravel sex differences in the brain organization of autism have, however, been challenged by the limited availability of female data.
Methods: We addressed this gap by using a large sample of males and females with autism and neurotypical (NT) control individuals (ABIDE; Autism: 362 males, 82 females; NT: 409 males, 166 females; 7-18 years). Discovery analyses examined main effects of diagnosis, sex and their interaction across five resting-state fMRI (R-fMRI) metrics (voxel-level Z > 3.1, cluster-level P < 0.01, gaussian random field corrected). Secondary analyses assessed the robustness of the results to different pre-processing approaches and their replicability in two independent samples: the EU-AIMS Longitudinal European Autism Project (LEAP) and the Gender Explorations of Neurogenetics and Development to Advance Autism Research (GENDAAR).
Results: Discovery analyses in ABIDE revealed significant main effects across the intrinsic functional connectivity (iFC) of the posterior cingulate cortex, regional homogeneity and voxel-mirrored homotopic connectivity (VMHC) in several cortical regions, largely converging in the default network midline. Sex-by-diagnosis interactions were confined to the dorsolateral occipital cortex, with reduced VMHC in females with autism. All findings were robust to different pre-processing steps. Replicability in independent samples varied by R-fMRI measures and effects with the targeted sex-by-diagnosis interaction being replicated in the larger of the two replication samples – EU-AIMS LEAP.
Limitations: Given the lack of a priori harmonization among the discovery and replication datasets available to date, sample-related variation remained and may have affected replicability.
Conclusions: Atypical cross-hemispheric interactions are neurobiologically relevant to autism. They likely result from the combination of sex-dependent and sex-independent factors with a differential effect across functional cortical networks. Systematic assessments of the factors contributing to replicability are needed and necessitate coordinated large-scale data collection across studies.
Competing Interest Statement: ADM receives royalties from the publication of the Italian version of the Social Responsiveness Scale Child Version by Organization Speciali, Italy. JKB has been a consultant to, advisory board member of, and a speaker for Takeda/Shire, Medice, Roche, and Servier. He is not an employee of any of these companies and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, or royalties. CFB is director and shareholder in SBGneuro Ltd. TC has received consultancy from Roche and Servier and received book royalties from Guildford Press and Sage. DM has been a consultant to, and advisory board member, for Roche and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. TB served in an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Shire, and Infectopharm. He received conference support or speakers fee by Lilly, Medice, and Shire. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press; the present work is unrelated to these relationships. JT is a consultant to Roche. The remaining authors declare no competing interests.
A key event in cellular physiology is the decision between membrane biogenesis and fat storage. Phosphatidic acid (PA) is an important lipid intermediate and signaling lipid at the branch point of these pathways and constantly monitored by the transcriptional repressor Opi1 to orchestrate lipid metabolism. Here, we report on the mechanism of membrane recognition by Opi1 and identify an amphipathic helix (AH) for the selective binding to membranes containing PA over phosphatidylserine (PS). The insertion of the AH into the hydrophobic core of the membrane renders Opi1 sensitive to the lipid acyl chain composition as an important factor contributing to the regulation of membrane biogenesis. Based on these findings, we rationally designed the membrane binding properties of Opi1 to control its responsiveness in the physiological context. Using extensive molecular dynamics (MD) simulations, we identified two PA-selective three-finger grips that tightly bind the phosphate headgroup, while interacting less intimately and more transiently with PS. This work establishes lipid headgroup selectivity as a new feature in the family of AH-containing membrane property sensors.