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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.
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 uniquely introduce convex production costs into a cartel model involving spatial price discrimination. We demonstrate that greater convexity improves cartel stability and that for sufficient convexity first best locations will be adopted. We show that allowing locations to vary over the game reduces cartel stability but that greater convexity continues to improve that stability. Moreover, when the degree of convexity does not support the first best collusive locations, other collusive locations exist that require less stability and these may either increase or decrease social welfare relative to competition. Critically, these locations that require less stability are more dispersed in sharp contrast to the known result assuming linear production costs.
GrassPlot is a collaborative vegetation-plot database organised by the Eurasian Dry Grassland Group (EDGG) and listed in the Global Index of Vegetation-Plot Databases (GIVD ID EU-00-003). GrassPlot collects plot records (releves) from grasslands and other open habitats of the Palaearctic biogeographic realm. It focuses on precisely delimited plots of eight standard grain sizes (0.0001; 0.001;... 1,000 m(2)) and on nested-plot series with at least four different grain sizes. The usage of GrassPlot is regulated through Bylaws that intend to balance the interests of data contributors and data users. The current version (v. 1.00) contains data for approximately 170,000 plots of different sizes and 2,800 nested-plot series. The key components are richness data and metadata. However, most included datasets also encompass compositional data. About 14,000 plots have near-complete records of terricolous bryophytes and lichens in addition to vascular plants. At present, GrassPlot contains data from 36 countries throughout the Palaearctic, spread across elevational gradients and major grassland types. GrassPlot with its multi-scale and multi-taxon focus complements the larger international vegetationplot databases, such as the European Vegetation Archive (EVA) and the global database " sPlot". Its main aim is to facilitate studies on the scale-and taxon-dependency of biodiversity patterns and drivers along macroecological gradients. GrassPlot is a dynamic database and will expand through new data collection coordinated by the elected Governing Board. We invite researchers with suitable data to join GrassPlot. Researchers with project ideas addressable with GrassPlot data are welcome to submit proposals to the Governing Board.
Microbial life inhabiting subseafloor sediments plays an important role in Earth’s carbon cycle. However, the impact of geodynamic processes on the distributions and carbon-cycling activities of subseafloor life remains poorly constrained. We explore a submarine mud volcano of the Nankai accretionary complex by drilling down to 200 m below the summit. Stable isotopic compositions of water and carbon compounds, including clumped methane isotopologues, suggest that ~90% of methane is microbially produced at 16° to 30°C and 300 to 900 m below seafloor, corresponding to the basin bottom, where fluids in the accretionary prism are supplied via megasplay faults. Radiotracer experiments showed that relatively small microbial populations in deep mud volcano sediments (10 2 to 10 3 cells cm −3 ) include highly active hydrogenotrophic methanogens and acetogens. Our findings indicate that subduction-associated fluid migration has stimulated microbial activity in the mud reservoir and that mud volcanoes may contribute more substantially to the methane budget than previously estimated.
The origin of the First Bend of the Yangtze River is key to understanding the birth of the modern Yangtze River. Despite considerable efforts, the timing and mechanism of formation of the First Bend remain highly debated. Inverse river-profile modeling of three tributaries (Chongjiang, Lima, and Gudu) of the Jinsha River, integrated with regional tectonic and geomorphic interpretations, allows the onset of incision at the First Bend to be constrained to 28-20 Ma. The spatio-temporal coincidence of initial river incision and activity of Yulong Thrust Belt in southeastern Tibet highlights thrusting to be fundamental in reshaping the pre-existing stream network at the First Bend. These results enable us to reinterpret a change in sedimentary environment from a braided river to a swamp-like lake in the Jianchuan Basin south of the First Bend, recording the destruction of the hypothesized southwards-flowing paleo-Jinsha and Shuiluo Rivers at ~36-35 Ma by magmatism. During the late Oligoceneearly Miocene, the paleo-Shuiluo River was diverted to the north by focused rock uplift due to thrusting along the Yulong Thrust Belt, which also led to exhumation of the Jianchuan Basin. Diversion of the paleo-Shuiluo River can be explained by capture from a downstream river in the footwall of the Yulong Thrust Belt. Subsequent rapid headward erosion, that was caused by thrusting-induced drop of local base level, is recorded by upstream younging ages for the onset of incision and led to the formation of the First Bend. The combination of new ages for the onset of incision at 28-20 Ma at the First Bend and younger ages upstream indicates northwards expansion of the Jinsha River at a rate of 62 +/- 18 mm/yr. Our results suggest that the origin of the First Bend was likely triggered by thrusting at 28-20 Ma, after which the Yangtze River formed.
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.
Extra-tropical circulation systems impede poleward moisture advection by the Indian Summer Monsoon. In this context, the Himalayan range is believed to insulate the south Asian circulation from extra-tropical influences and to delineate the northern extent of the Indian Summer Monsoon in central Asia. Paleoclimatic evidence, however, suggests increased moisture availability in the Early Holocene north of the Himalayan range which is attributed to an intensification of the Indian Summer Monsoon. Nevertheless, mechanisms leading to a surpassing of the Himalayan range and the northern maximum extent of summer monsoonal influence remain unknown. Here we show that the Kunlun barrier on the northern Tibetan Plateau [similar to 36 degrees N] delimits Indian Summer Monsoon precipitation during the Holocene. The presence of the barrier relocates the insulation effect 1,000 km further north, allowing a continental low intensity branch of the Indian Summer Monsoon which is persistent throughout the Holocene. Precipitation intensities at its northern extent seem to be driven by differentiated solar heating of the Northern Hemisphere indicating dependency on energy-gradients rather than absolute radiation intensities. The identified spatial constraints of monsoonal precipitation will facilitate the prediction of future monsoonal precipitation patterns in Central Asia under varying climatic conditions.