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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.
Pollen records from large lakes have been used for quantitative palaeoclimate reconstruction, but the influences that lake size (as a result of species-specific variations in pollen dispersal patterns that smaller pollen grains are more easily transported to lake centre) and taphonomy have on these climatic signals have not previously been systematically investigated. We introduce the concept of pollen source area to pollen-based climate calibration using the north-eastern Tibetan Plateau as our study area. We present a pollen data set collected from large lakes in the arid to semi-arid region of central Asia. The influences that lake size and the inferred pollen source areas have on pollen compositions have been investigated through comparisons with pollen assemblages in neighbouring lakes of various sizes. Modern pollen samples collected from different parts of Lake Donggi Cona (in the north-eastern part of the Tibetan Plateau) reveal variations in pollen assemblages within this large lake, which are interpreted in terms of the species-specific dispersal and depositional patterns for different types of pollen, and in terms of fluvial input components. We have estimated the pollen source area for each lake individually and used this information to infer modern climate data with which to then develop a modern calibration data set, using both the multivariate regression tree (MRT) and weighted-averaging partial least squares (WA-PLS) approaches. Fossil pollen data from Lake Donggi Cona have been used to reconstruct the climate history of the north-eastern part of the Tibetan Plateau since the Last Glacial Maximum (LGM). The meanannual precipitation was quantitatively reconstructed using WA-PLS: extremely dry conditions are found to have dominated the LGM, with annual precipitation of around 100 mm, which is only 32% of present-day precipitation. A gradually increasing trend in moisture conditions during the Late Glacial is terminated by an abrupt reversion to a dry phase that lasts for about 1000 yr and coincides with "Heinrich event 1" in the North Atlantic region. Subsequent periods corresponding to the Bolling/Allerod interstadial, with annual precipitation (P-ann) of about 350 mm, and the Younger Dryas event (about 270 mm P-ann) are followed by moist conditions in the early Holocene, with annual precipitation of up to 400 mm. A drier trend after 9 cal. ka BP is followed by a second wet phase in the middle Holocene, lasting until 4.5 cal. ka BP. Relatively steady conditions with only slight fluctuations then dominate the late Holocene, resulting in the present climatic conditions. The climate changes since the LGM have been primarily driven by deglaciation and fluctuations in the intensity of the Asian summer monsoon that resulted from changes in the Northern Hemisphere summer solar insolation, as well as from changes in the North Atlantic climate through variations in the circulation patterns and intensity of the westerlies.
Coronal mass ejections (CMEs) erupt and expand in a magnetically structured solar corona. Various indirect observational pieces of evidence have shown that the magnetic field of CMEs reconnects with surrounding magnetic fields, forming, e.g., dimming regions distant from the CME source regions. Analyzing Solar Dynamics Observatory (SDO) observations of the eruption from AR 11226 on 2011 June 7, we present the first direct evidence of coronal magnetic reconnection between the fields of two adjacent active regions during a CME. The observations are presented jointly with a data-constrained numerical simulation, demonstrating the formation/intensification of current sheets along a hyperbolic flux tube at the interface between the CME and the neighboring AR 11227. Reconnection resulted in the formation of new magnetic connections between the erupting magnetic structure from AR 11226 and the neighboring active region AR 11227 about 200 Mm from the eruption site. The onset of reconnection first becomes apparent in the SDO/AIA images when filament plasma, originally contained within the erupting flux rope, is redirected toward remote areas in AR 11227, tracing the change of large-scale magnetic connectivity. The location of the coronal reconnection region becomes bright and directly observable at SDO/AIA wavelengths, owing to the presence of down-flowing cool, dense (1010 cm(-3)) filament plasma in its vicinity. The high-density plasma around the reconnection region is heated to coronal temperatures, presumably by slow-mode shocks and Coulomb collisions. These results provide the first direct observational evidence that CMEs reconnect with surrounding magnetic structures, leading to a large-scale reconfiguration of the coronal magnetic field.
Testing magnetofrictional extrapolation with the Titov-Demoulin model of solar active regions
(2010)
We examine the nonlinear magnetofrictional extrapolation scheme using the solar active region model by Titov and Demoulin as test field. This model consists of an arched, line-tied current channel held in force-free equilibrium by the potential field of a bipolar flux distribution in the bottom boundary. A modified version with a parabolic current density profile is employed here. We find that the equilibrium is reconstructed with very high accuracy in a representative range of parameter space, using only the vector field in the bottom boundary as input. Structural features formed in the interface between the flux rope and the surrounding arcade - "hyperbolic flux tube" and "bald patch separatrix surface" - are reliably reproduced, as are the flux rope twist and the energy and helicity of the configuration. This demonstrates that force-free fields containing these basic structural elements of solar active regions can be obtained by extrapolation. The influence of the chosen initial condition on the accuracy of reconstruction is also addressed, confirming that the initial field that best matches the external potential field of the model quite naturally leads to the best reconstruction. Extrapolating the magnetogram of a Titov-Demoulin equilibrium in the unstable range of parameter space yields a sequence of two opposing evolutionary phases, which clearly indicate the unstable nature of the configuration: a partial buildup of the flux rope with rising free energy is followed by destruction of the rope, losing most of the free energy.
A co-actor's intentionality has been suggested to be a key modulating factor for joint action effects like the joint Simon effect (JSE). However, in previous studies intentionality has often been confounded with agency defined as perceiving the initiator of an action as being the causal source of the action. The aim of the present study was to disentangle the role of agency and intentionality as modulating factors of the JSE. In Experiment 1, participants performed a joint go/nogo Simon task next to a co-actor who either intentionally controlled a response button with own finger movements (agency+/intentionality+) or who passively placed the hand on a response button that moved up and down on its own as triggered by computer signals (agency-/intentionality-). In Experiment 2, we included a condition in which participants believed that the co-actor intentionally controlled the response button with a Brain-Computer Interface (BCI) while placing the response finger clearly besides the response button, so that the causal relationship between agent and action effect was perceptually disrupted (agency-/intentionality+). As a control condition, the response button was computer controlled while the co-actor placed the response finger besides the response button (agency-/intentionality-). Experiment 1 showed that the JSE is present with an intentional co-actor and causality between co-actor and action effect, but absent with an unintentional co-actor and a lack of causality between co-actor and action effect. Experiment 2 showed that the JSE is absent with an intentional co-actor, but no causality between co-actor and action effect. Our findings indicate an important role of the co-actor's agency for the JSE. They also suggest that the attribution of agency has a strong perceptual basis.
Referential Coding Does Not Rely on Location Features: Evidence for a Nonspatial Joint Simon Effect
(2015)
The joint Simon effect (JSE) shows that the presence of another agent can change one's representation of one's task and/or action. According to the spatial response coding approach, this is because another person in one's peri-personal space automatically induces the spatial coding of one's own action, which in turn invites spatial stimulus-response priming. According to the referential coding approach, the presence of another person or event creates response conflict, which the actor is assumed to solve by emphasizing response features that discriminate between one's own response and that of the other. The 2 approaches often make the same predictions, but the spatial response coding approach considers spatial location as the only dimension that can drive response coding, whereas the referential coding approach allows for other dimensions as well. To compare these approaches, the authors ran 2 experiments to see whether a nonspatial JSE can be demonstrated. Participants responded to the geometrical shape of a central colored stimulus by pressing a left or right button, while wearing gloves of the same or different color as the stimuli. Participants performed the task individually, either by responding to either stimulus shapes (Experiment 1) or by responding to only 1 of the 2 shapes (Experiment 2), and in the presence of a coactor. Congruence between stimulus and glove color affected performance in the 2-choice and the joint tasks but not in the individual go/no-go task. This demonstration of a nonspatial JSE is inconsistent with the spatial response coding approach but supports the referential coding approach.
Results of a paleolimnological investigation of a well-dated lake sediment section from Shikotan Island (Southern Kurils) showed that from ca 8.0 to 5.8 cal ka BP a warm and humid period corresponding to middle Holocene optimum took place. Cooling thereafter corresponds to Neoglacial. A reconstructed from ca 0.9 to ca 0.58 cal ka BP warm period can correspond to a Medieval Warm Period. Cooling after 0.58cal ka BP can be correlated with the LIA. Marine regression stages were identified at ca 6.2-5.9, 5.5-5.1 and 1.07-0.36 cal ka BP. The general chronology of major climatic events of Holocene in the island is in accordance with the climate records from the North Pacific region. Revealed spatial differences in timing and magnitude of the Late Holocene climatic episodes (LIA, MWP) in the region needs further investigations.
Slow rise and partial eruption of a double-decker filament. I. observations and interpretation
(2012)
We study an active-region dextral filament that was composed of two branches separated in height by about 13 Mm, as inferred from three-dimensional reconstruction by combining SDO and STEREO-B observations. This "double-decker" configuration sustained for days before the upper branch erupted with a GOES-class M1.0 flare on 2010 August 7. Analyzing this evolution, we obtain the following main results. (1) During the hours before the eruption, filament threads within the lower branch were observed to intermittently brighten up, lift upward, and then merge with the upper branch. The merging process contributed magnetic flux and current to the upper branch, resulting in its quasi-static ascent. (2) This transfer might serve as the key mechanism for the upper branch to lose equilibrium by reaching the limiting flux that can be stably held down by the overlying field or by reaching the threshold of the torus instability. (3) The erupting branch first straightened from a reverse S shape that followed the polarity inversion line and then writhed into a forward S shape. This shows a transfer of left-handed helicity in a sequence of writhe-twist-writhe. The fact that the initial writhe is converted into the twist of the flux rope excludes the helical kink instability as the trigger process of the eruption, but supports the occurrence of the instability in the main phase, which is indeed indicated by the very strong writhing motion. (4) A hard X-ray sigmoid, likely of coronal origin, formed in the gap between the two original filament branches in the impulsive phase of the associated flare. This supports a model of transient sigmoids forming in the vertical flare current sheet. (5) Left-handed magnetic helicity is inferred for both branches of the dextral filament. (6) Two types of force-free magnetic configurations are compatible with the data, a double flux rope equilibrium and a single flux rope situated above a loop arcade.
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.