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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.
Alpine ecosystems on the Tibetan Plateau are being threatened by ongoing climate warming and intensified human activities. Ecological time-series obtained from sedimentary ancient DNA (sedaDNA) are essential for understanding past ecosystem and biodiversity dynamics on the Tibetan Plateau and their responses to climate change at a high taxonomic resolution. Hitherto only few but promising studies have been published on this topic. The potential and limitations of using sedaDNA on the Tibetan Plateau are not fully understood. Here, we (i) provide updated knowledge of and a brief introduction to the suitable archives, region-specific taphonomy, state-of-the-art methodologies, and research questions of sedaDNA on the Tibetan Plateau; (ii) review published and ongoing sedaDNA studies from the Tibetan Plateau; and (iii) give some recommendations for future sedaDNA study designs. Based on the current knowledge of taphonomy, we infer that deep glacial lakes with freshwater and high clay sediment input, such as those from the southern and southeastern Tibetan Plateau, may have a high potential for sedaDNA studies. Metabarcoding (for microorganisms and plants), metagenomics (for ecosystems), and hybridization capture (for prehistoric humans) are three primary sedaDNA approaches which have been successfully applied on the Tibetan Plateau, but their power is still limited by several technical issues, such as PCR bias and incompleteness of taxonomic reference databases. Setting up high-quality and open-access regional taxonomic reference databases for the Tibetan Plateau should be given priority in the future. To conclude, the archival, taphonomic, and methodological conditions of the Tibetan Plateau are favorable for performing sedaDNA studies. More research should be encouraged to address questions about long-term ecological dynamics at ecosystem scale and to bring the paleoecology of the Tibetan Plateau into a new era.
A second peak in the extreme ultraviolet sometimes appears during the gradual phase of solar flares, which is known as the EUV late phase (ELP). Stereotypically ELP is associated with two separated sets of flaring loops with distinct sizes, and it has been debated whether ELP is caused by additional heating or extended plasma cooling in the longer loop system. Here we carry out a survey of 55 M-and-above GOES-class flares with ELP during 2010-2014. Based on the flare-ribbon morphology, these flares are categorized as circular-ribbon (19 events), two-ribbon (23 events), and complex-ribbon (13 events) flares. Among them, 22 events (40%) are associated with coronal mass ejections, while the rest are confined. An extreme ELP, with the late-phase peak exceeding the main-phase peak, is found in 48% of two-ribbon flares, 37% of circular-ribbon flares, and 31% of complex-ribbon flares, suggesting that additional heating is more likely present during ELP in two-ribbon than in circular-ribbon flares. Overall, cooling may be the dominant factor causing the delay of the ELP peak relative to the main-phase peak, because the loop system responsible for the ELP emission is generally larger than, and well separated from, that responsible for the main-phase emission. All but one of the circular-ribbon flares can be well explained by a composite "dome-plate" quasi-separatrix layer (QSL). Only half of these show a magnetic null point, with its fan and spine embedded in the dome and plate, respectively. The dome-plate QSL, therefore, is a general and robust structure characterizing circular-ribbon flares.
Arctic and alpine aquatic ecosystems are changing rapidly under recent global warming, threatening water resources by diminishing trophic status and changing biotic composition. Macrophytes play a key role in the ecology of freshwaters and we need to improve our understanding of long-term macrophytes diversity and environmental change so far limited by the sporadic presence of macrofossils in sediments.
In our study, we applied metabarcoding using the trnL P6 loop marker to retrieve macrophyte richness and composition from 179 surface-sediment samples from arctic Siberian and alpine Chinese lakes and three representative lake cores.
The surface-sediment dataset suggests that macrophyte richness and composition are mostly affected by temperature and conductivity, with highest richness when mean July temperatures are higher than 12 degrees C and conductivity ranges between 40 and 400 mu S cm(-1). Compositional turnover during the Late Pleistocene/Holocene is minor in Siberian cores and characterized by a less rich, but stable emergent macrophyte community. Richness decreases during the Last Glacial Maximum and rises during wetter and warmer climate in the Late-glacial and Mid-Holocene.
In contrast, we detect a pronounced change from emergent to submerged taxa at 14 ka in the Tibetan alpine core, which can be explained by increasing temperature and conductivity due to glacial runoff and evaporation.
Our study provides evidence for the suitability of the trnL marker to recover modern and past macrophyte diversity and its applicability for the response of macrophyte diversity to lake-hydrochemical and climate variability predicting contrasting macrophyte changes in arctic and alpine lakes under intensified warming and human impact.
Although many high-energy neutrinos detected by the IceCube telescope are believed to have an extraterrestrial origin, their astrophysical sources remain a mystery. Recently, an unprecedented discovery of a high-energy muon neutrino event coincident with a multiwavelength flare from a blazar, TXS 0506 + 056, shed some light on the origin of the neutrinos. It is usually believed that a blazar is produced by a relativistic jet launched from an accreting supermassive black hole (SMBH). Here, we show that the high-energy neutrino event can be interpreted by the inelastic hadronuclear interactions between the accelerated cosmic-ray protons in the relativistic jet and the dense gas clouds in the vicinity of the SMBH. Such a scenario only requires a moderate proton power in the jet, which could be much smaller than that required in the conventional hadronic model which instead calls upon the photomeson process. Meanwhile, the flux of the multiwavelength flare from the optical to gamma-ray band can be well explained by invoking a second radiation zone in the jet at a larger distance to the SMBH. In our model, the neutrino emission lasts a shorter time than the multiwavelength flare, so the neutrino event is not necessarily correlated with the flare, but it is probably accompanied by a spectrum hardening above a few giga-electron-volt (GeV).
We establish methods for quantum state tomography based on compressed sensing. These methods are specialized for quantum states that are fairly pure, and they offer a significant performance improvement on large quantum systems. In particular, they are able to reconstruct an unknown density matrix of dimension d and rank r using O(rdlog(2)d) measurement settings, compared to standard methods that require d(2) settings. Our methods have several features that make them amenable to experimental implementation: they require only simple Pauli measurements, use fast convex optimization, are stable against noise, and can be applied to states that are only approximately low rank. The acquired data can be used to certify that the state is indeed close to pure, so no a priori assumptions are needed.
Magnetic reconnection is a fundamental process of topology change and energy release, taking place in plasmas on the Sun, in space, in astrophysical objects and in the laboratory. However, observational evidence has been relatively rare and typically only partial. Here we present evidence of fast reconnection in a solar filament eruption using high-resolution H-alpha images from the New Vacuum Solar Telescope, supplemented by extreme ultraviolet observations. The reconnection is seen to occur between a set of ambient chromospheric fibrils and the filament itself. This allows for the relaxation of magnetic tension in the filament by an untwisting motion, demonstrating a flux rope structure. The topology change and untwisting are also found through nonlinear force-free field modelling of the active region in combination with magnetohydrodynamic simulation. These results demonstrate a new role for reconnection in solar eruptions: the release of magnetic twist.
Caldera unrest can lead to major volcanic eruptions. Analysis of subtle subsidence or inflation at calderas helps understanding of their subsurface volcanic processes and related hazards. Several subsiding calderas have shown similar patterns of ground deformation composed of broad subsidence affecting the entire volcanic edifice and stronger localized subsidence focused inside the caldera. Physical models of internal deformation sources used to explain these observations typically consist of two magma reservoirs at different depths in an elastic half-space. However, such models ignore important subsurface structures, such as ring faults, that may influence the deformation pattern. Here we use both analog subsidence experiments and boundary element modeling to study the three-dimensional geometry and kinematics of caldera subsidence processes, evolving from an initial downsag to a later collapse stage. We propose that broad subsidence is mainly caused by volume decrease within a single magma reservoir, whereas buried ring-fault activity localizes the deformation within the caldera. Omitting ring faulting in physical models of subsiding calderas and using multiple point/sill-like sources instead can result in erroneous estimates of magma reservoir depths and volume changes. (C) 2019 Elsevier B.V. All rights reserved.
The Hartousov mofette system is a natural CO2 degassing site in the central Cheb Basin (Eger Rift, Central Europe). In early 2016 a 108 m deep core was obtained from this system to investigate the impact of ascending mantle-derived CO2 on indigenous deep microbial communities and their surrounding life habitat. During drilling, a CO2 blow out occurred at a depth of 78.5 meter below surface (mbs) suggesting a CO2 reservoir associated with a deep low-permeable CO2-saturated saline aquifer at the transition from Early Miocene terrestrial to lacustrine sediments. Past microbial communities were investigated by hopanoids and glycerol dialkyl glycerol tetraethers (GDGTs) reflecting the environmental conditions during the time of deposition rather than showing a signal of the current deep biosphere. The composition and distribution of the deep microbial community potentially stimulated by the upward migration of CO2 starting during Mid Pleistocene time was investigated by intact polar lipids (IPLs), quantitative polymerase chain reaction (qPCR), and deoxyribonucleic acid (DNA) analysis. The deep biosphere is characterized by microorganisms that are linked to the distribution and migration of the ascending CO2-saturated groundwater and the availability of organic matter instead of being linked to single lithological units of the investigated rock profile. Our findings revealed high relative abundances of common soil and water bacteria, in particular the facultative, anaerobic and potential iron-oxidizing Acidovorax and other members of the family Comamonadaceae across the whole recovered core. The results also highlighted the frequent detection of the putative sulfate-oxidizing and CO2-fixating genus Sulfuricurvum at certain depths. A set of new IPLs are suggested to be indicative for microorganisms associated to CO2 accumulation in the mofette system.
The Indian Summer Monsoon (ISM) is one of the most important climate systems, whose variability and driving mechanisms are of broad interest for academic and societal communities. Here, we present a well-dated high-resolution pollen analysis from a 4.82-m long sediment core taken from Basomtso, in the southeastern Tibetan Plateau (TP), which depicts the regional climate changes of the past millennium. Our results show that subalpine coniferous forest was dominant around Basomtso from ca. 867 to ca. 750 cal. yr BP, indicating a warm and semi-humid climate. The timberline in the study area significantly decreased from ca. 750 to ca.100 cal. yr BP, and a cold climate, corresponding to the Little Ice Age (LIA) prevailed. Since ca. 100 cal. yr BP, the vegetation type changed to forest-meadow with rising temperatures and moisture. Ordination analysis reveals that the migration of vegetation was dominated by regional temperatures and then by moisture. Further comparisons between the Basomtso pollen record and the regional temperature reconstructions underscore the relevance of the Basomtso record from the southeastern TP for regional and global climatologies. Our pollen based moisture reconstruction demonstrates the strong multicentennial-scale link to ISM variability, providing solid evidence for the increase of monsoonal strengths over the past four centuries. Spectral analysis indicates the potential influence of solar forcing. However, a closer relationship has been observed between multicentennial ISM variations and Indian Ocean sea surface temperature anomalies (SSTs), suggesting that the variations in monsoonal precipitation over the southeastern TP are probably driven by the Indian Ocean Dipole on the multicentennial scale. (C) 2017 Elsevier Ltd. All rights reserved.
Abrupt climate changes and fluctuations over short time scales are superimposed on long-term climate changes. Understanding rapid climate fluctuations at the decadal time scale over the past millennium will enhance our understanding of patterns of climate variability and aid in forecasting climate changes in the future. In this study, climate changes on the southeastern Tibetan Plateau over the past millennium were determined from a 4.82-m-long sediment core from Basomtso Lake. At the centennial time scale, the Medieval Climate Anomaly (MCA), Little Ice Age (LIA) and Current Warm Period (CWP) are distinct in the Basomtso region. Rapid climate fluctuations inferred from five episodes with higher sediment input and likely warmer conditions, as well as seven episodes with lower sediment input and likely colder conditions, were well preserved in our record. These episodes with higher and lower sediment input are characterized by abrupt climate changes and short time durations. Spectral analysis indicates that the climate variations at the centennial scale on the southeastern Tibetan Plateau are influenced by solar activity during the past millennium.