Genome-wide association studies (GWAS) of psychiatric phenotypes have tended to focus on categorical diagnoses, but to understand the biology of mental illness it may be more useful to study traits ...which cut across traditional boundaries. Here, we report the results of a GWAS of mood instability as a trait in a large population cohort (UK Biobank, n = 363,705). We also assess the clinical and biological relevance of the findings, including whether genetic associations show enrichment for nervous system pathways. Forty six unique loci associated with mood instability were identified with a SNP heritability estimate of 9%. Linkage Disequilibrium Score Regression (LDSR) analyses identified genetic correlations with Major Depressive Disorder (MDD), Bipolar Disorder (BD), Schizophrenia, anxiety, and Post Traumatic Stress Disorder (PTSD). Gene-level and gene set analyses identified 244 significant genes and 6 enriched gene sets. Tissue expression analysis of the SNP-level data found enrichment in multiple brain regions, and eQTL analyses highlighted an inversion on chromosome 17 plus two brain-specific eQTLs. In addition, we used a Phenotype Linkage Network (PLN) analysis and community analysis to assess for enrichment of nervous system gene sets using mouse orthologue databases. The PLN analysis found enrichment in nervous system PLNs for a community containing serotonin and melatonin receptors. In summary, this work has identified novel loci, tissues and gene sets contributing to mood instability. These findings may be relevant for the identification of novel trans-diagnostic drug targets and could help to inform future stratified medicine innovations in mental health.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A correction for streamwise Reynolds stress data acquired with insufficient spatial resolution is proposed for wall-bounded flows. The method is based on the attached eddy hypothesis to account for ...spatial filtering effects at all wall-normal positions. This analysis reveals that outside the near-wall region the spatial filtering effect scales inversely with the distance from the wall, in contrast to the commonly assumed scaling with the viscous length scale. The new formulation is shown to work very well for data taken over a wide range of Reynolds numbers and wire lengths.
The severity of congenital diaphragmatic hernia (CDH) can be estimated prenatally using observed-to-expected lung-head ratios (by ultrasound) and total fetal lung volumes (by magnetic resonance ...imaging), as well as fetal liver position. Infants with CDH require intensive cardiopulmonary support after birth, including immediate endotracheal intubation and "gentle ventilation," as well as judicious fluid and inotropic support. Pulmonary hypertension, as assessed by echocardiography, may require the use of pulmonary vasodilators and other medical adjuncts or, in severe cases, extracorporeal life support, if available. Open surgical repair of the diaphragmatic defect should usually be delayed until physiologic stability has been achieved, but a failure to perform surgery within the first two weeks of life should prompt a team discussion of priorities with the family. Infants with CDH should undergo long-term, multidisciplinary surveillance that includes standardized neurodevelopmental testing, especially if they are considered high risk (i.e., needing pulmonary support at 30 days, needing a patch repair or requiring extracorporeal life support).
Timely perception of adverse environmental changes is critical for survival. Dynamic changes in gases are important cues for plants to sense environmental perturbations, such as submergence. In ...Arabidopsis thaliana, changes in oxygen and nitric oxide (NO) control the stability of ERFVII transcription factors. ERFVII proteolysis is regulated by the N-degron pathway and mediates adaptation to flooding-induced hypoxia. However, how plants detect and transduce early submergence signals remains elusive. Here we show that plants can rapidly detect submergence through passive ethylene entrapment and use this signal to pre-adapt to impending hypoxia. Ethylene can enhance ERFVII stability prior to hypoxia by increasing the NO-scavenger PHYTOGLOBIN1. This ethylene-mediated NO depletion and consequent ERFVII accumulation pre-adapts plants to survive subsequent hypoxia. Our results reveal the biological link between three gaseous signals for the regulation of flooding survival and identifies key regulatory targets for early stress perception that could be pivotal for developing flood-tolerant crops.
OBJECTIVE:Atherosclerosis is the underlying cause of most cardiovascular disease, but mechanisms underlying atherosclerosis are incompletely understood. Ultrasound measurement of the carotid ...intima-media thickness (cIMT) can be used to measure vascular remodeling, which is indicative of atherosclerosis. Genome-wide association studies have identified many genetic loci associated with cIMT, but heterogeneity of measurements collected by many small cohorts have been a major limitation in these efforts. Here, we conducted genome-wide association analyses in UKB (UK Biobank; N=22 179), the largest single study with consistent cIMT measurements.
APPROACH AND RESULTS:We used BOLT-LMM software to run linear regression of cIMT in UKB, adjusted for age, sex, and genotyping chip. In white British participants, we identified 5 novel loci associated with cIMT and replicated most previously reported loci. In the first sex-specific analyses of cIMT, we identified a locus on chromosome 5, associated with cIMT in women only and highlight VCAN as a good candidate gene at this locus. Genetic correlations with body mass index and glucometabolic traits were also observed. Two loci influenced risk of ischemic heart disease.
CONCLUSIONS:These findings replicate previously reported associations, highlight novel biology, and provide new directions for investigating the sex differences observed in cardiovascular disease presentation and progression.
Photosynthetic production of organic matter by microscopic oceanic phytoplankton fuels ocean ecosystems and contributes roughly half of the Earth's net primary production. For 13years, the ...Sea-viewing Wide Field-of-view Sensor (SeaWiFS) mission provided the first consistent, synoptic observations of global ocean ecosystems. Changes in the surface chlorophyll concentration, the primary biological property retrieved from SeaWiFS, have traditionally been used as a metric for phytoplankton abundance and its distribution largely reflects patterns in vertical nutrient transport. On regional to global scales, chlorophyll concentrations covary with sea surface temperature (SST) because SST changes reflect light and nutrient conditions. However, the ocean may be too complex to be well characterized using a single index such as the chlorophyll concentration. A semi-analytical bio-optical algorithm is used to help interpret regional to global SeaWiFS chlorophyll observations from using three independent, well-validated ocean color data products; the chlorophyll a concentration, absorption by CDM and particulate backscattering. First, we show that observed long-term, global-scale trends in standard chlorophyll retrievals are likely compromised by coincident changes in CDM. Second, we partition the chlorophyll signal into a component due to phytoplankton biomass changes and a component caused by physiological adjustments in intracellular chlorophyll concentrations to changes in mixed layer light levels. We show that biomass changes dominate chlorophyll signals for the high latitude seas and where persistent vertical upwelling is known to occur, while physiological processes dominate chlorophyll variability over much of the tropical and subtropical oceans. The SeaWiFS data set demonstrates complexity in the interpretation of changes in regional to global phytoplankton distributions and illustrates limitations for the assessment of phytoplankton dynamics using chlorophyll retrievals alone.
•Evaluation of the SeaWiFS climate data record of chlorophyll concentrations.•Colored dissolved organic matter obfuscates the empirical retrieval of chlorophyll.•Global trends and patterns depend on the choice of bio-optical model used.•Chlorophyll changes reflects both phytoplankton biomass and physiological changes.•The SeaWiFS mission laid out a blueprint for future satellite ocean color missions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Mastcam-Z is a multispectral, stereoscopic imaging investigation on the Mars 2020 mission’s
Perseverance
rover. Mastcam-Z consists of a pair of focusable, 4:1 zoomable cameras that provide broadband ...red/green/blue and narrowband 400-1000 nm color imaging with fields of view from 25.6° × 19.2° (26 mm focal length at 283 μrad/pixel) to 6.2° × 4.6° (110 mm focal length at 67.4 μrad/pixel). The cameras can resolve (≥ 5 pixels) ∼0.7 mm features at 2 m and ∼3.3 cm features at 100 m distance. Mastcam-Z shares significant heritage with the Mastcam instruments on the Mars Science Laboratory
Curiosity
rover. Each Mastcam-Z camera consists of zoom, focus, and filter wheel mechanisms and a 1648 × 1214 pixel charge-coupled device detector and electronics. The two Mastcam-Z cameras are mounted with a 24.4 cm stereo baseline and 2.3° total toe-in on a camera plate ∼2 m above the surface on the rover’s Remote Sensing Mast, which provides azimuth and elevation actuation. A separate digital electronics assembly inside the rover provides power, data processing and storage, and the interface to the rover computer. Primary and secondary Mastcam-Z calibration targets mounted on the rover top deck enable tactical reflectance calibration. Mastcam-Z multispectral, stereo, and panoramic images will be used to provide detailed morphology, topography, and geologic context along the rover’s traverse; constrain mineralogic, photometric, and physical properties of surface materials; monitor and characterize atmospheric and astronomical phenomena; and document the rover’s sample extraction and caching locations. Mastcam-Z images will also provide key engineering information to support sample selection and other rover driving and tool/instrument operations decisions.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The Large Binocular Telescope Interferometer (LBTI) enables nulling interferometric observations across the N band (8 to 13 m) to suppress a star's bright light and probe for faint circumstellar ...emission. We present and statistically analyze the results from the LBTI/Hunt for Observable Signatures of Terrestrial Systems survey for exozodiacal dust. By comparing our measurements to model predictions based on the solar zodiacal dust in the N band, we estimate a 1 median sensitivity of 23 zodis times the solar system dust surface density in its habitable zone (HZ; 23 zodis) for early-type stars and 48 zodis for Sun-like stars, where 1 zodi is the surface density of HZ dust in the solar system. Of the 38 stars observed, 10 show significant excess. A clear correlation of our detections with the presence of cold dust in the systems was found, but none with the stellar spectral type or age. The majority of Sun-like stars have relatively low HZ dust levels (best-fit median: 3 zodis, 1 upper limit: 9 zodis, 95% confidence: 27 zodis based on our N band measurements), while ∼20% are significantly more dusty. The solar system's HZ dust content is consistent with being typical. Our median HZ dust level would not be a major limitation to the direct imaging search for Earth-like exoplanets, but more precise constraints are still required, in particular to evaluate the impact of exozodiacal dust for the spectroscopic characterization of imaged exo-Earth candidates.
Despite the universally recognized importance of fostering trust and avoiding distrust in governance relationships, there remains considerable debate on core questions like the relation between ...(dis)trust and the evaluations of the characteristics that make a governance agent appear (un)worthy of trust. In particular, it remains unclear whether levels of (dis)trust simply follow levels of (dis)trustworthiness-such that building trust is primarily a question of increasing evidence of trustworthiness and avoiding evidence of distrustworthiness, or if their dynamics are more complicated. The current paper adds novel theory for thinking about the management of trust and distrust in the governance context through the application of principles borrowed from resilience theory. Specifically, we argue that trust and distrust exist as distinct, self-reinforcing (i.e., stable) states separated by a threshold. We then theorize as to the nature of the self-reinforcing processes and use qualitative data collected from and inductively coded in collaboration with Flint residents as part of a participatory process to look for evidence of our argument in a well-documented governance failure. We conclude by explaining how this novel perspective allows for clearer insight into the experience of this and other communities and speculate as to how it may help to better position governance actors to respond to future crises.
ABSTRACT The Large Binocular Telescope Interferometer (LBTI) is a versatile instrument designed for high angular resolution and high-contrast infrared imaging (1.5-13 m). In this paper, we focus on ...the mid-infrared (8-13 m) nulling mode and present its theory of operation, data reduction, and on-sky performance as of the end of the commissioning phase in 2015 March. With an interferometric baseline of 14.4 m, the LBTI nuller is specifically tuned to resolve the habitable zone of nearby main-sequence stars, where warm exozodiacal dust emission peaks. Measuring the exozodi luminosity function of nearby main-sequence stars is a key milestone to prepare for future exo-Earth direct imaging instruments. Thanks to recent progress in wavefront control and phase stabilization, as well as in data reduction techniques, the LBTI demonstrated in 2015 February a calibrated null accuracy of 0.05% over a 3 hr long observing sequence on the bright nearby A3V star β Leo. This is equivalent to an exozodiacal disk density of 15-30 zodi for a Sun-like star located at 10 pc, depending on the adopted disk model. This result sets a new record for high-contrast mid-infrared interferometric imaging and opens a new window on the study of planetary systems.
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