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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.
The quasar HE 0047-1756, at z = 1.67, is found to be split into two images 1."144 apart by an intervening galaxy acting as a gravitational lens. The flux ratio for the two components is roughly 3.5:1, depending slightly upon wavelength. The lensing galaxy is seen on images obtained in the i (800 nm) and K-s bands (2.1 mum); there is also a nearby faint object which may be responsible for some shear. The spectra of the two quasar images are nearly identical, but the emission line ratio between the two components scale differently from the continuum. Moreover, the fainter component has a bluer continuum slope than the brighter one. We argue that these small differences are probably due to microlensing. There is evidence for a partial Einstein ring emanating from the brighter image toward the fainter one
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.
Piggyback basins on the margins of growing orogens commonly serve as sensitive recorders of the onset of thrust deformation and changes in source areas. The Bieertuokuoyi piggyback basin, located in the hanging wall of the Pamir Frontal Thrust, provides an unambiguous record of the outward growth of the northeast Pamir margin in northwest China from the Miocene through the Quaternary. To reconstruct the deformation along the margin, we synthesized structural mapping, stratigraphy, magnetostratigraphy, and cosmogenic burial dating of basin fill and growth strata. The Bieertuokuoyi basin records the initiation of the Pamir Frontal Thrust and the Takegai Thrust similar to 5-6Ma, as well as clast provenance and paleocurrent changes resulting from the Pliocene-to-Recent uplift and exhumation of the Pamir to the south. Our results show that coeval deformation was accommodated on the major structures on the northeast Pamir margin throughout the Miocene to Recent. Furthermore, our data support a change in the regional kinematics around the Miocene-Pliocene boundary (similar to 5-6Ma). Rapid exhumation of NE Pamir extensional domes, coupled with cessation of the Kashgar-Yecheng Transfer System on the eastern margin of the Pamir, accelerated the outward propagation of the northeastern Pamir margin and the southward propagation of the Kashi-Atushi fold-and-thrust belt in the southern Tian Shan. This coeval deformation signifies the coupling of the Pamir and Tarim blocks and the transfer of shortening north to the Pamir frontal faults and across the quasi-rigid Tarim Basin to the southern Tian Shan Kashi-Atushi fold-and-thrust system.
ISMIP6 Antarctica
(2020)
Ice flow models of the Antarctic ice sheet are commonly used to simulate its future evolution in response to different climate scenarios and assess the mass loss that would contribute to future sea level rise. However, there is currently no consensus on estimates of the future mass balance of the ice sheet, primarily because of differences in the representation of physical processes, forcings employed and initial states of ice sheet models. This study presents results from ice flow model simulations from 13 international groups focusing on the evolution of the Antarctic ice sheet during the period 2015-2100 as part of the Ice Sheet Model Intercomparison for CMIP6 (ISMIP6). They are forced with outputs from a subset of models from the Coupled Model Intercomparison Project Phase 5 (CMIP5), representative of the spread in climate model results. Simulations of the Antarctic ice sheet contribution to sea level rise in response to increased warming during this period varies between 7:8 and 30.0 cm of sea level equivalent (SLE) under Representative Concentration Pathway (RCP) 8.5 scenario forcing. These numbers are relative to a control experiment with constant climate conditions and should therefore be added to the mass loss contribution under climate conditions similar to present-day conditions over the same period. The simulated evolution of the West Antarctic ice sheet varies widely among models, with an overall mass loss, up to 18.0 cm SLE, in response to changes in oceanic conditions. East Antarctica mass change varies between 6 :1 and 8.3 cm SLE in the simulations, with a significant increase in surface mass balance outweighing the increased ice discharge under most RCP 8.5 scenario forcings. The inclusion of ice shelf collapse, here assumed to be caused by large amounts of liquid water ponding at the surface of ice shelves, yields an additional simulated mass loss of 28mm compared to simulations without ice shelf collapse. The largest sources of uncertainty come from the climate forcing, the ocean-induced melt rates, the calibration of these melt rates based on oceanic conditions taken outside of ice shelf cavities and the ice sheet dynamic response to these oceanic changes. Results under RCP 2.6 scenario based on two CMIP5 climate models show an additional mass loss of 0 and 3 cm of SLE on average compared to simulations done under present-day conditions for the two CMIP5 forcings used and display limited mass gain in East Antarctica.
In mammals the composition of milk changes during early lactation, with a rapid decline of fat-soluble vitamins and a continuous increase in total lipids. The mechanisms underlying this phenomenon are not well understood, but might involve selective mechanisms related to mammary uptake or secretion into the milk. Since carotenoids are specifically distributed among the lipoprotein fractions in plasma, the simultaneous determination of carotenoids in plasma, lipoprotein fractions and milk might offer an opportunity to gain insight into this phenomenon. In 21 healthy mothers carotenoids in plasma and lipoprotein fractions were investigated at day 2 and 19 and milk on day 4 and 19 after delivery. Plasma levels of alpha-tocopherol and cholesterol as well as lutein, zeaxanthin and cryptoxanthin were significantly lower later in lactation (day 19) than shortly after birth (P < 0.01). The stage of lactation had no effect on the distribution of carotenoids and -tocopherol among the plasma lipoprotein fractions. In milk, triacylglycerol increased (P < 0.01). In contrast, levels of carotenoids, alpha- tocopherol and vitamin A were highest in colostrum and declined (P < 0.01). Because the magnitude of decrease was not the same in all carotenoids, the carotenoid pattern changed substantially. In colostrum the carotenoid pattern resembled those of plasma and the low- density lipoprotein fraction. In mature milk it was similar to the pattern found in the high density lipoprotein fraction. Based on these observations a selective mechanism might be responsible for the transfer of these components in milk involving different lipoprotein fractions at specific times of lactation
New polymers with high electron mobilities have spurred research in organic solar cells using polymeric rather than fullerene acceptors due to their potential of increased diversity, stability, and scalability. However, all-polymer solar cells have struggled to keep up with the steadily increasing power conversion efficiency of polymer: fullerene cells. The lack of knowledge about the dominant recombination process as well as the missing concluding picture on the role of the semi-crystalline microstructure of conjugated polymers in the free charge carrier generation process impede a systematic optimization of all-polymer solar cells. These issues are examined by combining structural and photo-physical characterization on a series of poly(3-hexylthiophene) (donor) and P(NDI2OD-T2) (acceptor) blend devices. These experiments reveal that geminate recombination is the major loss channel for photo-excited charge carriers. Advanced X-ray and electron-based studies reveal the effect of chloronaphthalene co-solvent in reducing domain size, altering domain purity, and reorienting the acceptor polymer crystals to be coincident with those of the donor. This reorientation correlates well with the increased photocurrent from these devices. Thus, effi cient split-up of geminate pairs at polymer/polymer interfaces may necessitate correlated donor/acceptor crystal orientation, which represents an additional requirement compared to the isotropic fullerene acceptors.
We present the results from a study of the host galaxies of 15 optically selected active galactic nuclei (AGNs) with 0.5<z<1.1 from the Galaxy Evolution from Morphology and SEDs project (GEMS). GEMS is a Hubble Space Telescope imaging survey of a similar to28' x 28' contiguous field centered on the Chandra Deep Field-South in the F606W and F850LP filter bands. It incorporates the spectral energy distributions and redshifts of similar to10,000 objects, obtained by the COMBO-17 project. We have detected the host galaxies of all 15 AGNs in the F850LP band (and 13 of 15 in the F606W band), recovering their fluxes, morphologies, and structural parameters. We find that 80% of the host galaxies have early-type (bulge-dominated) morphologies, while the rest have structures characteristic of late-type (disk-dominated) galaxies. We find that 25% of the early types and 30% of the late types exhibit disturbances consistent with galaxy interactions. The hosts show a wide range of colors, from those of red-sequence galaxies to blue colors consistent with ongoing star formation. Roughly 70% of the morphologically early-type hosts have rest-frame blue colors, a much larger fraction than those typical of nonactive morphologically early-type galaxies in this redshift and luminosity range. Yet, we find that the early-type hosts are structurally similar to red-sequence elliptical galaxies, inasmuch as they follow an absolute magnitude versus half-light size correlation that is consistent with the mean relation for early-type galaxies at similar redshifts
Photogeneration, recombination, and transport of free charge carriers in all-polymer bulk heterojunction solar cells incorporating poly(3-hexylthiophene) (P3HT) as donor and poly([N,N'-bis(2-octyldodecyl)-naphthelene-1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5'-(2,2'-bithiophene)) (P(NDI2OD-T2)) as acceptor polymer have been investigated by the use of time delayed collection field (TDCF) and time-of-flight (TOF) measurements. Depending on the preparation procedure used to dry the active layers, these solar cells comprise high fill factors (FFs) of up to 67%. A strongly reduced bimolecular recombination (BMR), as well as a field-independent free charge carrier generation are observed, features that are common to high performance fullerene-based solar cells. Resonant soft X-ray measurements (R-SoXS) and photoluminescence quenching experiments (PQE) reveal that the BMR is related to domain purity. Our results elucidate the similarities of this polymeric acceptor with the superior recombination properties of fullerene acceptors.
Background/Aims: The renal function, including the excretion of low-molecular-weight proteins, changes during pregnancy and may cause a urinary excretion of retinol-binding protein (RBP). Whether it is accompanied by a substantial loss of vitamin A ( retinol) has not been established yet. We therefore determined the excretion of retinol and RBP in urine of pregnant women. Methods: The study involved analyses of urine samples from 40 healthy pregnant women and 29 women with pregnancy complications during the third trimester. Analyses of plasma and urine of 7 healthy women and 5 women with pregnancy complications were also carried out 6 weeks antepartum, at time of delivery and 1 week postpartum. Results: Urinary retinol was higher in women who suffered from pregnancy disorders with an influence on maternal metabolism ( p < 0.01). RBP was excreted at substantial concentrations in the urine of all 69 women, but there were no differences between the groups. Women with a concomitant excretion of retinol had higher levels of urinary RBP than those without a retinol excretion ( p < 0.05). Differences in plasma retinol and RBP were not significant. Conclusion: The excretion of urinary retinol may increase significantly during pregnancy complications, which needs further clarification to which extent this condition may negatively affect the vitamin A status in such women. Copyright (C) 2004 S. Karger AG, Basel
We report the discovery of extended X-ray emission within the young star cluster NGC 602a in the Wing of the Small Magellanic Cloud (SMC) based on observations obtained with the Chandra X-Ray Observatory. X-ray emission is detected from the cluster core area with the highest stellar density and from a dusty ridge surrounding the H II region. We use a census of massive stars in the cluster to demonstrate that a cluster wind or wind-blown bubble is unlikely to provide a significant contribution to the X-ray emission detected from the central area of the cluster. We therefore suggest that X-ray emission at the cluster core originates from an ensemble of low-and solar-mass pre-main-sequence (PMS) stars, each of which would be too weak in X-rays to be detected individually. We attribute the X-ray emission from the dusty ridge to the embedded tight cluster of the newborn stars known in this area from infrared studies. Assuming that the levels of X-ray activity in young stars in the low-metallicity environment of NGC 602a are comparable to their Galactic counterparts, then the detected spatial distribution, spectral properties, and level of X-ray emission are largely consistent with those expected from low-and solar-mass PMS stars and young stellar objects (YSOs). This is the first discovery of X-ray emission attributable to PMS stars and YSOs in the SMC, which suggests that the accretion and dynamo processes in young, low-mass objects in the SMC resemble those in the Galaxy.
We report on multifrequency observations performed during 2012 December-2013 August of the first narrow-line Seyfert 1 galaxy detected in gamma-rays, PMN J0948+0022 (z = 0.5846). A y -ray flare was observed by the Large Area Telescope on board Fermi during 2012 December-2013 January, reaching a daily peak flux in the 0.1-100 GeV energy range of (155 31) x 10 8 ph cm(-2) S-1 on 2013 January 1, corresponding to an apparent isotropic luminosity of similar to 1.5 x 1048 erg s(-1). The y -ray flaring period triggered Swift and Very Energetic Radiation Imaging Telescope Array System (VERITAS) observations in addition to radio and optical monitoring by Owens Valley Radio Observatory, Monitoring Of Jets in Active galactic nuclei with VLBA Experiments, and Catalina Real-time Transient Survey. A strong flare was observed in optical, UV, and X-rays on 2012 December 30, quasi-simultaneously to the y -ray flare, reaching a record flux for this source from optical to y gamma-rays. VERITAS observations at very high energy (E > 100 GeV) during 2013 January 6-17 resulted in an upper limit of F>0.2 Trev < 4.0 x 10(-12) ph cm(-2) s(-1). We compared the spectral energy distribution (SED) of the flaring state in 2013 January with that of an intermediate state observed in 2011. The two SEDs, modelled as synchrotron emission and an external Compton scattering of seed photons from a dust torus, can be modelled by changing both the electron distribution parameters and the magnetic field.
The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia
(2019)
The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
Dating growth strata and basin fill by combining Al-26/Be-10 burial dating and magnetostratigraphy
(2018)
Cosmogenic burial dating enables dating of coarse-grained, Pliocene-Pleistocene sedimentary units that are typically difficult to date with traditional methods, such as magnetostratigraphy. In the actively deforming western Tarim Basin in NW China, Pliocene-Pleistocene conglomerates were dated at eight sites, integrating Al-26/Be-10 burial dating with previously published magnetostratigraphic sections. These samples were collected from growth strata on the flanks of growing folds and from sedimentary units beneath active faults to place timing constraints on the initiation of deformation of structures within the basin and on shortening rates on active faults. These new basin-fill and growthstrata ages document the late Neogene and Quaternary growth of the Pamir and Tian Shan orogens between >5 and 1 Ma and delineate the eastward propagation of deformation at rates up to 115 km/m.y. and basinward growth of both mountain belts at rates up to 12 km/m.y.
Dating growth strata and basin fill by combining 26Al/10Be burial dating and magnetostratigraphy
(2018)
Cosmogenic burial dating enables dating of coarse-grained, Pliocene-Pleistocene sedimentary units that are typically difficult to date with traditional methods, such as magnetostratigraphy. In the actively deforming western Tarim Basin in NW China, Pliocene-Pleistocene conglomerates were dated at eight sites, integrating Al-26/Be-10 burial dating with previously published magnetostratigraphic sections. These samples were collected from growth strata on the flanks of growing folds and from sedimentary units beneath active faults to place timing constraints on the initiation of deformation of structures within the basin and on shortening rates on active faults. These new basin-fill and growthstrata ages document the late Neogene and Quaternary growth of the Pamir and Tian Shan orogens between >5 and 1 Ma and delineate the eastward propagation of deformation at rates up to 115 km/m.y. and basinward growth of both mountain belts at rates up to 12 km/m.y.
Data integration has become a useful strategy for uncovering new insights into complex biological networks. We studied whether this approach can help to delineate the signal transducer and activator of transcription 6 (STAT6)-mediated transcriptional network driving T helper (Th) 2 cell fate decisions. To this end, we performed an integrative analysis of publicly available RNA-seq data of Stat6-knockout mouse studies together with STAT6 ChIP-seq data and our own gene expression time series data during Th2 cell differentiation. We focused on transcription factors (TFs), cytokines, and cytokine receptors and delineated 59 positively and 41 negatively STAT6-regulated genes, which were used to construct a transcriptional network around STAT6. The network illustrates that important and well-known TFs for Th2 cell differentiation are positively regulated by STAT6 and act either as activators for Th2 cells (e.g., Gata3, Atf3, Satb1, Nfil3, Maf, and Pparg) or as suppressors for other Th cell subpopulations such as Th1 (e.g., Ar), Th17 (e.g., Etv6), or iTreg (e.g., Stat3 and Hifla) cells. Moreover, our approach reveals 11 TFs (e.g., Atf5, Creb3l2, and Asb2) with unknown functions in Th cell differentiation. This fact together with the observed enrichment of asthma risk genes among those regulated by STAT6 underlines the potential value of the data integration strategy used here. Thus, our results clearly support the opinion that data integration is a useful tool to delineate complex physiological processes.
We have performed Hubble Space Telescope imaging of a sample of 23 high-redshift (1.8<z<2.75) active galactic nuclei (AGNs), drawn from the COMBO-17 survey. The sample contains moderately luminous quasars (M(B)similar to-23). The data are part of the Galaxy Evolution from Morphologies and SEDs imaging survey that provides high-resolution optical images obtained with the Advanced Camera for Surveys in two bands (F606W and F850LP), sampling the rest-frame UV flux of the targets. To deblend the AGN images into nuclear and resolved (host galaxy) components, we use a point-spread function subtraction technique that is strictly conservative with respect to the flux of the host galaxy. We resolve the host galaxies in both filter bands in nine of the 23 AGNs, whereas the remaining 14 objects are considered nondetections, with upper limits of less than 5% of the nuclear flux. However, when we co-add the unresolved AGN images into a single high signal-to-noise ratio composite image, we find again an unambiguously resolved host galaxy. The recovered host galaxies have apparent magnitudes of 23.0<F606W<26.0 and 22.5<F850LP<24.5, with rest-frame UV colors in the range -0.2<(F606W-F850LP)(obs)<2.3. The rest-frame absolute magnitudes at 200 nm are -20.0<M-200 nm<-22.2. The photometric properties of the composite host are consistent with the individual resolved host galaxies. We find that the UV colors of all host galaxies are substantially bluer than expected from an old population of stars with formation redshift z<=5, independent of the assumed metallicities. These UV colors and luminosities range up to the values found for Lyman break galaxies (LBGs) at z=3. Our results suggest either a recent starburst of, e. g., a few percent of the total stellar mass at 100 Myr before observation, with mass fraction and age strongly degenerate, or the possibility that the detected UV emission may be due to young stars forming continuously. For the latter case we estimate star formation rates of typically &SIM;6 M&ODOT; yr(-1) (uncorrected for internal dust attenuation), which again lies in the range of rates implied from the UV flux of LBGs. Our results agree with the recent discovery of enhanced blue stellar light in AGN hosts at lower redshifts