A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
Context. On March 4, 2013 the Fermi-EAT and AGILE reported a flare from the direction of the Crab nebula in which the high-energy (HE; E > 100 MeV) flux was six times above its quiescent level. Simultaneous observations in other energy bands give us hints about the emission processes during the flare episode and the physics of pulsar wind nebulae in general.
Aims. We search for variability in the emission of the Crab nebula at very-high energies (VHF,; E > 100 GeV), using contemporaneous data taken with the H.E.S.S. array of Cherenkov telescopes.
Methods. Observational data taken with the H.E.S.S. instrument on five consecutive days during the flare were analysed for the flux and spectral shape of the emission from the Crab nebula. Night-wise light curves are presented with energy thresholds of 1 TeV and 5 TeV.
Results. The observations conducted with H.E.S.S. on March 6 to March 10, 2013 show no significant changes in the flux. They limit the variation in the integral flux above 1 TeV to less than 63% and the integral flux above 5 TeV to less than 78% at a 95% confidence level.
The selaginella genome identifies genetic changes associated with the evolution of vascular plants
(2011)
Vascular plants appeared similar to 410 million years ago, then diverged into several lineages of which only two survive: the euphyllophytes (ferns and seed plants) and the lycophytes. We report here the genome sequence of the lycophyte Selaginella moellendorffii (Selaginella), the first nonseed vascular plant genome reported. By comparing gene content in evolutionarily diverse taxa, we found that the transition from a gametophyte- to a sporophyte-dominated life cycle required far fewer new genes than the transition from a nonseed vascular to a flowering plant, whereas secondary metabolic genes expanded extensively and in parallel in the lycophyte and angiosperm lineages. Selaginella differs in posttranscriptional gene regulation, including small RNA regulation of repetitive elements, an absence of the trans-acting small interfering RNA pathway, and extensive RNA editing of organellar genes.
Introducing the CTA concept
(2013)
The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project.
This Letter reports the discovery of a remarkably hard spectrum source, HESS J1641-463, by the High Energy Stereoscopic System (H.E.S.S.) in the very high energy (VHE) domain. HESS J1641-463 remained unnoticed by the usual analysis techniques due to confusion with the bright nearby source HESS J1640-465. It emerged at a significance level of 8.5 standard deviations after restricting the analysis to events with energies above 4 TeV. It shows a moderate flux level of phi(E > 1TeV) = (3.64 +/- 0.44(stat)+/- 0.73(sys)) x 10(-13) cm(-2) s(-1), corresponding to 1.8% of the Crab Nebula flux above the same energy, and a hard spectrum with a photon index of Gamma = 2.07 +/- 0.11(stat)+/- 0.20(sys). It is a point-like source, although an extension up to a Gaussian width of sigma = 3 arcmin cannot be discounted due to uncertainties in the H.E.S.S. point-spread function. The VHE gamma-ray flux of HESS J1641-463 is found to be constant over the observed period when checking time binnings from the year-by-year to the 28 minute exposure timescales. HESS J1641-463 is positionally coincident with the radio supernova remnant SNR G338.5+0.1. No X-ray candidate stands out as a clear association; however, Chandra and XMM-Newton data reveal some potential weak counterparts. Various VHE gamma-ray production scenarios are discussed. If the emission from HESS J1641-463 is produced by cosmic ray protons colliding with the ambient gas, then their spectrum must extend close to 1 PeV. This object may represent a source population contributing significantly to the galactic cosmic ray flux around the knee.
In this paper we report on the analysis of all the available optical and very high-energy gamma-ray (> 200 GeV) data for the BL Lac object PKS 2155-304, collected simultaneously with the ATOM and H.E.S.S. telescopes from 2007 until 2009. This study also includes X-ray (RXTE, Swift) and high-energy gamma-ray (Fermi-LAT) data. During the period analysed, the source was transitioning from its flaring to quiescent optical states, and was characterized by only moderate flux changes at different wavelengths on the timescales of days and months. A flattening of the optical continuum with an increasing optical flux can be noted in the collected dataset, but only occasionally and only at higher flux levels. We did not find any universal relation between the very high-energy gamma-ray and optical flux changes on the timescales from days and weeks up to several years. On the other hand, we noted that at higher flux levels the source can follow two distinct tracks in the optical flux-colour diagrams, which seem to be related to distinct gamma-ray states of the blazar. The obtained results therefore indicate a complex scaling between the optical and gamma-ray emission of PKS 2155 304, with different correlation patterns holding at different epochs, and a gamma-ray flux depending on the combination of an optical flux and colour rather than a flux alone.
G349.7+0.2 is a young Galactic supernova remnant (SNR) located at the distance of 11.5 kpc and observed across the entire electromagnetic spectrum from radio to high energy (HE; 0.1 GeV < E < 100 GeV) gamma-rays. Radio and infrared observations indicate that the remnant is interacting with a molecular cloud. In this paper, the detection of very high energy (VHE, E > 100 GeV) gamma-ray emission coincident with this SNR with the High Energy Stereoscopic System (HESS.) is reported. This makes it one of the farthest Galactic SNR ever detected in this domain. An integral flux F(E > 400 GeV) = (6.5 +/- 1.1(stat) +/- 1.3(syst)) x 10-11 ph cm(-2) s(-1) corresponding to similar to 0.7% of that of the Crab Nebula and to a luminosity of similar to 10(34) erg s(-1) above the same energy threshold, and a steep photon index Gamma(VHE) = 2.8 +/- 0.27(stat) +/- 0.20(syst) are measured. The analysis of more than 5 yr of Fermi-LAT data towards this source shows a power-law like spectrum with a best-fit photon index Gamma(HE) = 2.2 +/- 0.04.2(stat-0.31sys)(+0.13), The combined gamma-ray spectrum of 0349.7+0.2 can be described by either a broken power law (I3PL) or a power law with exponential (or sub exponential) cutoff (PLC). In the former case, the photon break energy is found at E-br,E-gamma = 551(-30)(+70) GeV, slightly higher than what is usually observed in the HE/VHE gamma-ray emitting middle-aged SNRs known to be interacting with molecular clouds. In the latter case. the exponential (respectively sub-exponential) cutoff energy is measured at E-cat,E-gamma = 1.4(-0.55)(+1.6) (respectively 0.35(-0.21)(+0.75)) TeV. A pion decay process resulting from the interaction of the accelerated protons and nuclei with the dense surrounding medium is clearly the preferred scenario to explain the gamma-ray emission. The BPL with a spectral steepening of 0.5-1 and the PLC provide equally good fits to the data. The product or the average gas density and the total energy content of accelerated protons and nuclei amounts to nu W-p similar to 5 x 10(51) erg cm(-3)