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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.
Gamma-ray bursts (GRBs) are brief flashes of gamma-rays and are considered to be the most energetic explosive phenomena in the Universe(1). The emission from GRBs comprises a short (typically tens of seconds) and bright prompt emission, followed by a much longer afterglow phase. During the afterglow phase, the shocked outflow-produced by the interaction between the ejected matter and the circumburst medium-slows down, and a gradual decrease in brightness is observed(2). GRBs typically emit most of their energy via.-rays with energies in the kiloelectronvolt-to-megaelectronvolt range, but a few photons with energies of tens of gigaelectronvolts have been detected by space-based instruments(3). However, the origins of such high-energy (above one gigaelectronvolt) photons and the presence of very-high-energy (more than 100 gigaelectronvolts) emission have remained elusive(4). Here we report observations of very-high-energy emission in the bright GRB 180720B deep in the GRB afterglow-ten hours after the end of the prompt emission phase, when the X-ray flux had already decayed by four orders of magnitude. Two possible explanations exist for the observed radiation: inverse Compton emission and synchrotron emission of ultrarelativistic electrons. Our observations show that the energy fluxes in the X-ray and gamma-ray range and their photon indices remain comparable to each other throughout the afterglow. This discovery places distinct constraints on the GRB environment for both emission mechanisms, with the inverse Compton explanation alleviating the particle energy requirements for the emission observed at late times. The late timing of this detection has consequences for the future observations of GRBs at the highest energies.
On 2015 July 18, near perihelion at a heliocentric distance of 1.28 au, the Visible InfraRed Thermal Imaging Spectrometer (VIRTIS-M) on board the Rosetta spacecraft had the opportunity of observing dust activity in the inner coma with a view of the night side (shadowed side) of comet 67P/Churyumov-Gerasimenko. At the time of the measurements we present here, we observe a dust plume that originates on the far side of the nucleus. We are able to identify the approximate location of its source at the boundary between the Hapi and Anuket regions, and we find that it has been in darkness for some hours before the observation. Assuming that this time span is equal to the conductive time scale, we obtain a thermal inertia in the range 25-36 W K-1 m(-2) s(-1/2). These thermal inertia values can be used to verify with a 3D finite-element method (REM) numerical code whether the surface and subsurface temperatures agree with the values found in the literature. We explored three different configurations: (1) a layer of water ice mixed with dust beneath a dust mantle of 5 mm with thermal inertia of 36 J m(-2) K-1 S-0.5 ; (2) the same structure, but with thermal inertia of 100 J m(-2) K-1 S-0.5; (3) an ice-dust mixture that is directly exposed. Of these three configurations, the first seems to be the most reasonable, both for the low thermal inertia and for the agreement with the surface and subsurface temperatures that have been found for the comet 67P/Churyumov-Gerasimenko. The spectral properties of the plume show that the visible dust color ranged from 16 +/- 4.8%/100 nm to 13 +/- 2.6%/100 nm, indicating that this plume has no detectable color gradient. The morphology of the plume can be classified as a narrow jet that has an estimated total ejected mass of between 6 and 19 tons when we assume size distribution indices between -2.5 and -3.
The flat spectrum radio quasar 3C 279 is known to exhibit pronounced variability in the high-energy (100MeV < E < 100 GeV) gamma-ray band, which is continuously monitored with Fermi-LAT. During two periods of high activity in April 2014 and June 2015 target-of-opportunity observations were undertaken with the High Energy Stereoscopic System (H.E.S.S.) in the very-high-energy (VHE, E > 100 GeV) gamma-ray domain. While the observation in 2014 provides an upper limit, the observation in 2015 results in a signal with 8 : 7 sigma significance above an energy threshold of 66 GeV. No VHE variability was detected during the 2015 observations. The VHE photon spectrum is soft and described by a power-law index of 4.2 +/- 0.3. The H.E.S.S. data along with a detailed and contemporaneous multiwavelength data set provide constraints on the physical parameters of the emission region. The minimum distance of the emission region from the central black hole was estimated using two plausible geometries of the broad-line region and three potential intrinsic spectra. The emission region is confidently placed at r greater than or similar to 1 : 7 X 1017 cm from the black hole, that is beyond the assumed distance of the broad-line region. Time-dependent leptonic and lepto-hadronic one-zone models were used to describe the evolution of the 2015 flare. Neither model can fully reproduce the observations, despite testing various parameter sets. Furthermore, the H.E.S.S. data were used to derive constraints on Lorentz invariance violation given the large redshift of 3C 279.
Context. Pulsar wind nebulae (PWNe) represent the most prominent population of Galactic very-high-energy gamma-ray sources and are thought to be an efficient source of leptonic cosmic rays. Vela X is a nearby middle-aged PWN, which shows bright X-ray and TeV gamma-ray emission towards an elongated structure called the cocoon. Aims. Since TeV emission is likely inverse-Compton emission of electrons, predominantly from interactions with the cosmic microwave background, while X-ray emission is synchrotron radiation of the same electrons, we aim to derive the properties of the relativistic particles and of magnetic fields with minimal modelling. Methods. We used data from the Suzaku XIS to derive the spectra from three compact regions in Vela X covering distances from 0.3 to 4 pc from the pulsar along the cocoon. We obtained gamma-ray spectra of the same regions from H.E.S.S. observations and fitted a radiative model to the multi-wavelength spectra. Results. The TeV electron spectra and magnetic field strengths are consistent within the uncertainties for the three regions, with energy densities of the order 10(-12) erg cm(-3). The data indicate the presence of a cutoff in the electron spectrum at energies of similar to 100 TeV and a magnetic field strength of similar to 6 mu G. Constraints on the presence of turbulent magnetic fields are weak. Conclusions. The pressure of TeV electrons and magnetic fields in the cocoon is dynamically negligible, requiring the presence of another dominant pressure component to balance the pulsar wind at the termination shock. Sub-TeV electrons cannot completely account for the missing pressure, which may be provided either by relativistic ions or from mixing of the ejecta with the pulsar wind. The electron spectra are consistent with expectations from transport scenarios dominated either by advection via the reverse shock or by diffusion, but for the latter the role of radiative losses near the termination shock needs to be further investigated in the light of the measured cutoff energies. Constraints on turbulent magnetic fields and the shape of the electron cutoff can be improved by spectral measurements in the energy range greater than or similar to 10 keV.
PKS 1830-211 is a known macrolensed quasar located at a redshift of z = 2.5. Its highenergy gamma-ray emission has been detected with the Fermi-Large Area Telescope (LAT) instrument and evidence for lensing was obtained by several authors from its high-energy data. Observations of PKS 1830-211 were taken with the High Energy Stereoscopic System (H.E.S.S.) array of Imaging Atmospheric Cherenkov Telescopes in 2014 August, following a flare alert by the Fermi-LAT Collaboration. The H.E.S.S observations were aimed at detecting a gamma-ray flare delayed by 20-27 d from the alert flare, as expected from observations at other wavelengths. More than 12 h of good-quality data were taken with an analysis threshold of similar to 67 GeV. The significance of a potential signal is computed as a function of the date and the average significance over the whole period. Data are compared to simultaneous observations by Fermi-LAT. No photon excess or significant signal is detected. An upper limit on PKS 1830-211 flux above 67 GeV is computed and compared to the extrapolation of the Fermi-LAT flare spectrum.
Low thermal conductivity boulder with high porosity identified on C-type asteroid (162173) Ryugu
(2019)
C-type asteroids are among the most pristine objects in the Solar System, but little is known about their interior structure and surface properties. Telescopic thermal infrared observations have so far been interpreted in terms of a regolith-covered surface with low thermal conductivity and particle sizes in the centimetre range. This includes observations of C-type asteroid (162173) Ryugu1,2,3. However, on arrival of the Hayabusa2 spacecraft at Ryugu, a regolith cover of sand- to pebble-sized particles was found to be absent4,5 (R.J. et al., manuscript in preparation). Rather, the surface is largely covered by cobbles and boulders, seemingly incompatible with the remote-sensing infrared observations. Here we report on in situ thermal infrared observations of a boulder on the C-type asteroid Ryugu. We found that the boulder’s thermal inertia was much lower than anticipated based on laboratory measurements of meteorites, and that a surface covered by such low-conductivity boulders would be consistent with remote-sensing observations. Our results furthermore indicate high boulder porosities as well as a low tensile strength in the few hundred kilopascal range. The predicted low tensile strength confirms the suspected observational bias6 in our meteorite collections, as such asteroidal material would be too frail to survive atmospheric entry7
Low thermal conductivity boulder with high porosity identified on C-type asteroid (162173) Ryugu
(2019)
C-type asteroids are among the most pristine objects in the Solar System, but little is known about their interior structure and surface properties. Telescopic thermal infrared observations have so far been interpreted in terms of a regolith-covered surface with low thermal conductivity and particle sizes in the centimetre range. This includes observations of C-type asteroid (162173) Ryugu1,2,3. However, on arrival of the Hayabusa2 spacecraft at Ryugu, a regolith cover of sand- to pebble-sized particles was found to be absent4,5 (R.J. et al., manuscript in preparation). Rather, the surface is largely covered by cobbles and boulders, seemingly incompatible with the remote-sensing infrared observations. Here we report on in situ thermal infrared observations of a boulder on the C-type asteroid Ryugu. We found that the boulder’s thermal inertia was much lower than anticipated based on laboratory measurements of meteorites, and that a surface covered by such low-conductivity boulders would be consistent with remote-sensing observations. Our results furthermore indicate high boulder porosities as well as a low tensile strength in the few hundred kilopascal range. The predicted low tensile strength confirms the suspected observational bias6 in our meteorite collections, as such asteroidal material would be too frail to survive atmospheric entry7.
Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.
Context. We present a detailed view of the pulsar wind nebula (PWN) HESS J1825-137. We aim to constrain the mechanisms dominating the particle transport within the nebula, accounting for its anomalously large size and spectral characteristics. Aims. The nebula was studied using a deep exposure from over 12 years of H.E.S.S. I operation, together with data from H.E.S.S. II that improve the low-energy sensitivity. Enhanced energy-dependent morphological and spatially resolved spectral analyses probe the very high energy (VHE, E > 0.1 TeV) gamma-ray properties of the nebula. Methods. The nebula emission is revealed to extend out to 1.5 degrees from the pulsar, similar to 1.5 times farther than previously seen, making HESS J1825-137, with an intrinsic diameter of similar to 100 pc, potentially the largest gamma-ray PWN currently known. Characterising the strongly energy-dependent morphology of the nebula enables us to constrain the particle transport mechanisms. A dependence of the nebula extent with energy of R proportional to E alpha with alpha = -0.29 +/- 0.04(stat) +/- 0.05(sys) disfavours a pure diffusion scenario for particle transport within the nebula. The total gamma-ray flux of the nebula above 1 TeV is found to be (1.12 +/- 0.03(stat) +/- 0.25(sys)) +/- 10(-11) cm(-2) s(-1), corresponding to similar to 64% of the flux of the Crab nebula. Results. HESS J1825-137 is a PWN with clearly energy-dependent morphology at VHE gamma-ray energies. This source is used as a laboratory to investigate particle transport within intermediate-age PWNe. Based on deep observations of this highly spatially extended PWN, we produce a spectral map of the region that provides insights into the spectral variation within the nebula.