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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 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.
STRUCTURE, STABILITY, AND EVOLUTION OF MAGNETIC FLUX ROPES FROM THE PERSPECTIVE OF MAGNETIC TWIST
(2016)
We investigate the evolution of NOAA Active Region (AR) 11817 during 2013 August 10–12, when it developed a complex field configuration and produced four confined, followed by two eruptive, flares. These C-and-above flares are all associated with a magnetic flux rope (MFR) located along the major polarity inversion line, where shearing and converging photospheric flows are present. Aided by the nonlinear force-free field modeling, we identify the MFR through mapping magnetic connectivities and computing the twist number ${{ \mathcal T }}_{w}$ for each individual field line. The MFR is moderately twisted ($| {{ \mathcal T }}_{w}| \lt 2$) and has a well-defined boundary of high squashing factor Q. We found that the field line with the extremum $| {{ \mathcal T }}_{w}| $ is a reliable proxy of the rope axis, and that the MFR's peak $| {{ \mathcal T }}_{w}| $ temporarily increases within half an hour before each flare while it decreases after the flare peak for both confined and eruptive flares. This pre-flare increase in $| {{ \mathcal T }}_{w}| $ has little effect on the AR's free magnetic energy or any other parameters derived for the whole region, due to its moderate amount and the MFR's relatively small volume, while its decrease after flares is clearly associated with the stepwise decrease in the whole region's free magnetic energy due to the flare. We suggest that ${{ \mathcal T }}_{w}$ may serve as a useful parameter in forewarning the onset of eruption, and therefore, the consequent space weather effects. The helical kink instability is identified as the prime candidate onset mechanism for the considered flares.
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.
A comprehensive understanding of the regional vegetation responses to long-term climate change will help to forecast Earth system dynamics. Based on a new well-dated pollen data set from Kanas Lake and a review on the published pollen records in and around the Altai Mountains, the regional vegetation dynamics and forcing mechanisms are discussed. In the Altai Mountains, the forest optimum occurred during 10-7ka for the upper forest zone and the tree line decline and/or ecological shifts were caused by climatic cooling from around 7ka. In the lower forest zone, the forest reached an optimum in the middle Holocene, and then increased openness of the forest, possibly caused by both climate cooling and human activities, took place in the late Holocene. In the lower basins or plains around the Altai Mountains, the development of protograssland or forest benefited from increasing humidity in the middle to late Holocene. Plain Language Summary In the Altai Mountains and surrounding area of central Asia, the previous studies of the Holocene paleovegetation and paleoclimate studies did not discuss the different ecological limiting factors for the vegetation in high mountains and low-elevation areas due to limited data. With accumulating fossil pollen data and surface pollen data, it is possible to understand better the geomorphological effect on the vegetation and discrepancies of vegetation/forest responses to large-scale climate forcing, and it is also possible to get reliable quantitative reconstructions of climate. Here our new pollen data and review on the published fossil pollen data will help us to look into the past climate change and vertical evolution of vegetation in this important area of the Northern Hemisphere. Based on our study, it can be concluded that the growth of taiga forest in the wetter areas may be promoted under a future warmer climate, while the forest in the relatively dry areas is liable to decline, and the different vegetation dynamics will contribute to future high-resolution coupled vegetation-climate model for Earth system modelling.
The origins and development of the arid and highly seasonal steppe-desert biome in Central Asia, the largest of its kind in the world, remain largely unconstrained by existing records. It is unclear how Cenozoic climatic, geological, and biological forces, acting at diverse spatial and temporal scales, shaped Central Asian ecosystems through time. Our synthesis shows that the Central Asian steppe-desert has existed since at least Eocene times but experienced no less than two regime shifts, one at the Eocene-Oligocene Transition and one in the mid-Miocene. These shifts separated three successive "stable states," each characterized by unique floral and faunal structures. Past responses to disturbance in the Asian steppe-desert imply that modern ecosystems are unlikely to recover their present structures and diversity if forced into a new regime. This is of concern for Asian steppes today, which are being modified for human use and lost to desertification at unprecedented rates.
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.
Historically, the giant panda was widely distributed from northern China to southwestern Asia [1]. As a result of range contraction and fragmentation, extant individuals are currently restricted to fragmented mountain ranges on the eastern margin of the Qinghai-Tibet plateau, where they are distributed among three major population clusters [2]. However, little is known about the genetic consequences of this dramatic range contraction. For example, were regions where giant pandas previously existed occupied by ancestors of present-day populations, or were these regions occupied by genetically distinct populations that are now extinct? If so, is there any contribution of these extinct populations to the genomes of giant pandas living today? To investigate these questions, we sequenced the nuclear genome of an similar to 5,000-year-old giant panda from Jiangdongshan, Teng-chong County in Yunnan Province, China. We find that this individual represents a genetically distinct population that diverged prior to the diversification of modern giant panda populations. We find evidence of differential admixture with this ancient population among modern individuals originating from different populations as well as within the same population. We also find evidence for directional gene flow, which transferred alleles from the ancient population into the modern giant panda lineages. A variable proportion of the genomes of extant individuals is therefore likely derived from the ancient population represented by our sequenced individual. Although extant giant panda populations retain reasonable genetic diversity, our results suggest that this represents only part of the genetic diversity this species harbored prior to its recent range contractions.