Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

Observation of quantum entanglement with top quarks at the ATLAS detector

Entanglement is a key feature of quantum mechanics with applications in fields such as metrology, cryptography, quantum information and quantum computation. It has been observed in a wide variety of systems and length scales, ranging from the microscopic to the macroscopic. However, entanglement remains largely unexplored at the highest accessible energy scales. Here we report the highest-energy observation of entanglement, in top–antitop quark events produced at the Large Hadron Collider, using a proton–proton collision dataset with a centre-of-mass energy of √s = 13 TeV and an integrated luminosity of 140 inverse femtobarns (fb)−1 recorded with the ATLAS experiment. Spin entanglement is detected from the measurement of a single observable D, inferred from the angle between the charged leptons in their parent top- and antitop-quark rest frames. The observable is measured in a narrow interval around the top–antitop quark production threshold, at which the entanglement detection is expected to be significant. It is reported in a fiducial phase space defined with stable particles to minimize the uncertainties that stem from the limitations of the Monte Carlo event generators and the parton shower model in modelling top-quark pair production. The entanglement marker is measured to be D = −0.537 ± 0.002 (stat.) ± 0.019 (syst.) for 340 GeV < mtt < 380 GeV. The observed result is more than five standard deviations from a scenario without entanglement and hence constitutes the first observation of entanglement in a pair of quarks and the highest-energy observation of entanglement so far

Search for periodic signals in the dielectron and diphoton invariant mass spectra using 139 fb−1 of pp collisions at √s = 13 TeV with the ATLAS detector

A search for physics beyond the Standard Model inducing periodic signals in the dielectron and diphoton invariant mass spectra is presented using 139 fb−1 of √s =13 TeV pp collision data collected by the ATLAS experiment at the LHC. Novel search techniques based on continuous wavelet transforms are used to infer the frequency of periodic signals from the invariant mass spectra and neural network classifiers are used to enhance the sensitivity to periodic resonances. In the absence of a signal, exclusion limits are placed at the 95% confidence level in the two-dimensional parameter space of the clockwork gravity model. Model-independent searches for deviations from the background-only hypothesis are also performed

Body size declines despite positive directional selection on heritable size traits in a barnacle goose population

Analyses of more than 2000 marked barnacle geese (Branta leucopsis) in the largest Baltic colony, Sweden, showed that structurally large females generally produced larger clutches and larger eggs, hatched their broods earlier in the season, and produced more and heavier-young than smaller females. In males, the corresponding relationships between reproductive parameters and structural body size were weaker or nonsignificant. Because structural body size traits have previously been found to be significantly heritable and positively genetically correlated, an increase in mean structural body size of individuals as a response to selection might have been expected. By contrast, we found that the mean adult head length and mean adult tarsus length decreased significantly in the largest colony by approximately 0.7 and 0.5 standard deviations, respectively, in both males and females during the 13-year study period. Environmental factors, such as the amount of rain in different years, were found to affect the availability of high-quality food for growing geese. As a consequence of this temporal variability in the availability of high-quality food, the mean adult structural body size of different cohorts differed by up to 1.3 standard deviations. Comparisons of mean body size of cohorts born in different colonies suggest that the most likely explanation for the body-size decline in the main study colony is that a density-dependent process, which mainly was in effect during the very early phase of colony growth, negatively affected juvenile growth and final size. We conclude that large environmental effects on growth and final structural body size easily can mask microevolutionary responses to selection. Analyses of environmental causes underlying temporal and spatial body size variation should always be considered in the reconstruction and prediction of evolutionary changes in natural populations

Facing the rain after the phase out : Performance evaluation of alternative fluorinated and non-fluorinated durable water repellents for outdoor fabrics

Fluorinated durable water repellent (DWR) agents are used to obtain water and stain repellent textiles. Due to the on-going phase-out of DWRs based on side-chain fluorinated polymers (SFP) with “long” perfluoroalkyl chains, the textile industry lacks suitable alternatives with comparable material characteristics. The constant development and optimization of SFPs for textile applications initiated more than half a century ago has resulted in a robust and very efficient DWR-technology and textiles with exceptional hydro- and oleo-phobic properties. The industry is now in the predicament that the long-chain SFPs with the best technical performance have undesirable toxicological and environmental behaviour. This study provides a comprehensive overview of the technical performance of presently available fluorinated and non-fluorinated DWRs as part of a chemical alternatives assessment (CAA). The results are based on a study with synthetic outdoor fabrics treated with alternative DWRs and tested for repellency using industrial standard and complementary methods. Using this approach, the complex structure-property relationships of DWR-polymers could be explained on a molecular level. Both short-chain SFPs and non-fluorinated DWRs showed excellent water repellency and durability in some cases while short-chain SFPs were the more robust of the alternatives to long-chain SFPs. A strong decline in oil repellency and durability with perfluoroalkyl chain length was shown for SFP DWRs. Non-fluorinated alternatives were unable to repel oil, which might limit their potential for substitution in textile application that require repellency towards non-polar liquids