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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.
Questions Has plant species richness in semi-natural grasslands changed over recent decades? Do the temporal trends of habitat specialists differ from those of habitat generalists? Has there been a homogenization of the grassland vegetation? Location Different regions in Germany and the UK. Methods We conducted a formal meta-analysis of re-survey vegetation studies of semi-natural grasslands. In total, 23 data sets were compiled, spanning up to 75 years between the surveys, including 13 data sets from wet grasslands, six from dry grasslands and four from other grassland types. Edaphic conditions were assessed using mean Ellenberg indicator values for soil moisture, nitrogen and pH. Changes in species richness and environmental variables were evaluated using response ratios. Results In most wet grasslands, total species richness declined over time, while habitat specialists almost completely vanished. The number of species losses increased with increasing time between the surveys and were associated with a strong decrease in soil moisture and higher soil nutrient contents. Wet grasslands in nature reserves showed no such changes or even opposite trends. In dry grasslands and other grassland types, total species richness did not consistently change, but the number or proportions of habitat specialists declined. There were also considerable changes in species composition, especially in wet grasslands that often have been converted into intensively managed, highly productive meadows or pastures. We did not find a general homogenization of the vegetation in any of the grassland types. Conclusions The results document the widespread deterioration of semi-natural grasslands, especially of those types that can easily be transformed to high production grasslands. The main causes for the loss of grassland specialists are changed management in combination with increased fertilization and nitrogen deposition. Dry grasslands are most resistant to change, but also show a long-term trend towards an increase in more mesotrophic species.
Infrared matrix-assisted desorption and ionization (IR-MALDI) enables the transfer of sub-micron particles (sMP) directly from suspensions into the gas phase and their characterization with differential mobility (DM) analysis. A nanosecond laser pulse at 2940 nm induces a phase explosion of the aqueous phase, dispersing the sample into nano- and microdroplets. The particles are ejected from the aqueous phase and become charged. Using IR-MALDI on sMP of up to 500 nm in diameter made it possible to surpass the 100 nm size barrier often encountered when using nano-electrospray for ionizing supramolecular structures. Thus, the charge distribution produced by IR-MALDI could be characterized systematically in the 50-500 nm size range. Well-resolved signals for up to octuply charged particles were obtained in both polarities for different particle sizes, materials, and surface modifications spanning over four orders of magnitude in concentrations. The physicochemical characterization of the IR-MALDI process was done via a detailed analysis of the charge distribution of the emerging particles, qualitatively as well as quantitatively. The Wiedensohler charge distribution, which describes the evolution of particle charging events in the gas phase, and a Poisson-derived charge distribution, which describes the evolution of charging events in the liquid phase, were compared with one another with respect to how well they describe the experimental data. Although deviations were found in both models, the IR-MALDI charging process seems to resemble a Poisson-like charge distribution mechanism, rather than a bipolar gas phase charging one.
The unusual mix of morphological traits displayed by extinct South American native ungulates (SANUs) confounded both Charles Darwin, who first discovered them, and Richard Owen, who tried to resolve their relationships. Here we report an almost complete mitochondrial genome for the litoptern Macrauchenia. Our dated phylogenetic tree places Macrauchenia as sister to Perissodactyla, but close to the radiation of major lineages within Laurasiatheria. This position is consistent with a divergence estimate of B66Ma (95% credibility interval, 56.64-77.83 Ma) obtained for the split between Macrauchenia and other Panperissodactyla. Combined with their morphological distinctiveness, this evidence supports the positioning of Litopterna (possibly in company with other SANU groups) as a separate order within Laurasiatheria. We also show that, when using strict criteria, extinct taxa marked by deep divergence times and a lack of close living relatives may still be amenable to palaeogenomic analysis through iterative mapping against more distant relatives.
The unusual mix of morphological traits displayed by extinct South American native ungulates (SANUs) confounded both Charles Darwin, who first discovered them, and Richard Owen, who tried to resolve their relationships. Here we report an almost complete mitochondrial genome for the litoptern Macrauchenia. Our dated phylogenetic tree places Macrauchenia as sister to Perissodactyla, but close to the radiation of major lineages within Laurasiatheria. This position is consistent with a divergence estimate of B66Ma (95% credibility interval, 56.64-77.83 Ma) obtained for the split between Macrauchenia and other Panperissodactyla. Combined with their morphological distinctiveness, this evidence supports the positioning of Litopterna (possibly in company with other SANU groups) as a separate order within Laurasiatheria. We also show that, when using strict criteria, extinct taxa marked by deep divergence times and a lack of close living relatives may still be amenable to palaeogenomic analysis through iterative mapping against more distant relatives.
Fjords and old-growth forests store large amounts of organic carbon. Yet the role of episodic disturbances, particularly volcanic eruptions, in mobilizing organic carbon in fjord landscapes covered by temperate rainforests remains poorly quantified. To this end, we estimated how much wood and soils were flushed to nearby fjords following the 2008 eruption of Chaiten volcano in south-central Chile, where pyroclastic sediments covered >12km(2) of pristine temperate rainforest. Field-based surveys of forest biomass, soil organic content, and dead wood transport reveal that the reworking of pyroclastic sediments delivered similar to 66,500+14,600/-14,500tC of large wood to two rivers entering the nearby Patagonian fjords in less than a decade. A similar volume of wood remains in dead tree stands and buried beneath pyroclastic deposits (similar to 79,900+21,100/-16,900tC) or stored in active river channels (5,900-10,600tC). We estimate that bank erosion mobilized similar to 132,300(+21,700)/(-30,600)tC of floodplain forest soil. Eroded and reworked forest soils have been accreting on coastal river deltas at >5mmyr(-1) since the eruption. While much of the large wood is transported out of the fjord by long-shore drift, the finer fraction from eroded forest soils is likely to be buried in the fjords. We conclude that the organic carbon fluxes boosted by rivers adjusting to high pyroclastic sediment loads may remain elevated for up to a decade and that Patagonian temperate rainforests disturbed by excessive loads of pyroclastic debris can be episodic short-lived carbon sources. Plain Language Summary Fjords and old-growth forests are important sinks of organic carbon. However, the role of volcanic eruptions in flushing organic carbon in fjord landscapes remains unexplored. Here we estimated how much forest vegetation and soils were lost to fjords following the 2008 eruption ofunknownChaiten volcano in south-central Chile. Pyroclastic sediments obliterated near-pristine temperateunknownrainforest, and the subsequent reworking of these sediments delivered in less than a decade similar to 66,000 tC of large wood to the mountain rivers, draining into the nearby Patagonian fjords. A similar volume of wood remains in dead tree stands and buried beneath pyroclastic deposits or stored in active riverunknownchannels. We estimate that similar to 130,000 tC of organic carbon-rich soil was lost to erosion, thus adding to the carbon loads. While much of the wood enters the long-shore drift in the fjord heads, the finerunknownfraction from eroded forest soils is likely to be buried in the fjords at rates that exceed regional estimates by an order of magnitude. We anticipate that these eruption-driven fluxes will remain elevated forunknownthe coming years and that Patagonian temperate rainforests episodically switch from carbon sinks to hitherto undocumented carbon sources if disturbed by explosive volcanic eruptions.
Megathrust earthquakes are commonly accompanied by increased upper-plate seismicity and occasionally triggered fault slip. In Chile, crustal faults slipped during and after the 2010 Maule (M8.8) earthquake. We studied the El Yolki fault (EYOF), a transtensional structure midways the Maule rupture not triggered in 2010. We mapped a Holocene coastal plain using light detection and ranging, which did not reveal surface ruptures. However, the inner-edge and shoreline angles along the coastal plain as well as 4.3- to 4.0-ka intertidal sediments are back-tilted on the EYOF footwall block, documenting 10 m of vertical displacement. These deformed markers imply similar to 2-mm/year throw rate, and dislocation models a slip rate of 5.6 mm/year for the EYOF. In a 5-m-deep trench, the Holocene intertidal sediments onlap to five erosive steps, interpreted as staircase wave-cut landforms formed by discrete events of relative sea level drop. We tentatively associated these steps with coseismic uplift during EYOF earthquakes between 4.3 and 4.0 ka. The Maule earthquake rupture may be subdivided into three subsegments based on coseismic slip and gravity anomalies. Coulomb stress transfer models predict neutral stress changes at the EYOF during the Maule earthquake but positive changes for a synthetic slip distribution at the central subsegment. If EYOF earthquakes were triggered by megathrust events, their slip distribution was probably focused in the central subsegment. Our study highlights the millennial variability of crustal faulting and the megathrust earthquake cycle in Chile, with global implications for assessing the hazards posed by hidden but potentially seismogenic coastal faults along subduction zones.
Hydrological response to earthquakes has long been observed, yet the mechanisms responsible still remain unclear and likely vary in space and time. This study explores the base flow response in small upland catchments of the Coastal Range of south-central Chile after the M-W 8.8 Maule earthquake of 27 February 2010. An initial decline in streamflow followed by an increase of up to 400% of the discharge measured immediately before the earthquake occurred, and diurnal streamflow oscillations intensified after the earthquake. Neither response time, nor time to maximum streamflow discharge showed any relationship with catchment topography or size, suggesting non-uniform release of water across the catchments. The fast response, unaffected stream water temperatures and a simple diffusion model point to the sandy saprolite as the source of the excess water. Base flow recession analysis reveals no evidence for substantial enhancement of lateral hydraulic conductivity in the saprolite after the earthquake. Seismic energy density reached similar to 170 J/m(3) for the main shock and similar to 0.9 J/m(3) for the aftershock, exceeding the threshold for liquefaction by undrained consolidation only during the main shock. Although increased hydraulic gradient due to ground acceleration-triggered, undrained consolidation is consistent with empirical magnitude-distance relationships for liquefaction, the lack of independent evidence for liquefaction means that enhanced vertical permeability (probably in combination with co-seismic near-surface dilatancy) cannot be excluded as a potential mechanism. Undrained consolidation may have released additional water from the saturated saprolite into the overlying soil, temporarily reducing water transfer to the creeks but enlarging the cross-section of the saturated zone, which in turn enhanced streamflow after establishment of a new hydraulic equilibrium. The enlarged saturated zone facilitated water uptake by roots and intensified evapotranspiration.
Timber harvesting by clear cutting is known to impose environmental impacts, including severe disturbance of the soil hydraulic properties which intensify the frequency and magnitude of surface runoff and soil erosion. However, it remains unanswered if harvest areas act as sources or sinks for runoff and soil erosion and whether such behavior operates in a steady state or evolves through time. For this purpose, 92 small-scale rainfall simulations of different intensities were carried out under pine plantation conditions and on two clear-cut harvest areas of different age. Nonparametrical Random Forest statistical models were set up to quantify the impact of environmental variables on the hydrological and erosion response. Regardless of the applied rainfall intensity, runoff always initiated first and yielded most under plantation cover. Counter to expectations, infiltration rates increased after logging activities. Once a threshold rainfall intensity of 20mm/h was exceeded, the younger harvest area started to act as a source for both runoff and erosion after connectivity was established, whereas it remained a sink under lower applied rainfall intensities. The results suggest that the impact of microtopography on surface runoff connectivity and water-repellent properties of the topsoil act as first-order controls for the hydrological and erosion processes in such environments. Fast rainfall-runoff response, sediment-discharge-hystereses, and enhanced postlogging groundwater recharge at catchment scale support our interpretation. At the end, we show the need to account for nonstationary hydrological and erosional behavior of harvest areas, a fact previously unappreciated in predictive models.
We report on the formation of wrinkle-patterned surface morphologies in cesium formamidinium-based Cs(x)FA(1-y)Pb(I1-yBry)(3) perovskite compositions with x = 0-0.3 and y = 0-0.3 under various spin-coating conditions. By varying the Cs and Br contents, the perovskite precursor solution concentration and the spin-coating procedure, the occurrence and characteristics of the wrinkle-shaped morphology can be tailored systematically. Cs(0.17)FA(0.83)Pb(I0.83Br0.17)(3) perovskite layers were analyzed regarding their surface roughness, microscopic structure, local and overall composition, and optoelectronic properties. Application of these films in p-i-n perovskite solar cells (PSCs) with indium-doped tin oxide/NiOx/perovskite/C-60/bathocuproine/Cu architecture resulted in up to 15.3 and 17.0% power conversion efficiency for the flat and wrinkled morphology, respectively. Interestingly, we find slightly red-shifted photoluminescence (PL) peaks for wrinkled areas and we are able to directly correlate surface topography with PL peak mapping. This is attributed to differences in the local grain size, whereas there is no indication for compositional demixing in the films. We show that the perovskite composition, crystallization kinetics, and layer thickness strongly influence the formation of wrinkles which is proposed to be related to the release of compressive strain during perovskite crystallization. Our work helps us to better understand film formation and to further improve the efficiency of PSCs with widely used mixed-perovskite compositions.