| 1. |
- Algaba, Juan-Carlos, et al.
(författare)
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Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign
- 2021
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
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Forskningsöversikt (refereegranskat)abstract
- In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded.
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| 2. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 3. |
- Jonsson, Lina, 1982, et al.
(författare)
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Characterisation of age and polarity at onset in bipolar disorder
- 2021
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Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 219:6, s. 659-669
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Tidskriftsartikel (refereegranskat)abstract
- Background Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools. Aims To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics. Method Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts. Results Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (beta = -0.34 years, s.e. = 0.08), major depression (beta = -0.34 years, s.e. = 0.08), schizophrenia (beta = -0.39 years, s.e. = 0.08), and educational attainment (beta = -0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO. Conclusions AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
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| 4. |
- Dalton, A. S., et al.
(författare)
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An updated radiocarbon-based ice margin chronology for the last deglaciation of the North American Ice Sheet Complex
- 2020
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 234
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Tidskriftsartikel (refereegranskat)abstract
- The North American Ice Sheet Complex (NAISC; consisting of the Laurentide, Cordilleran and Innuitian ice sheets) was the largest ice mass to repeatedly grow and decay in the Northern Hemisphere during the Quaternary. Understanding its pattern of retreat following the Last Glacial Maximum is critical for studying many facets of the Late Quaternary, including ice sheet behaviour, the evolution of Holocene landscapes, sea level, atmospheric circulation, and the peopling of the Americas. Currently, the most up-to-date and authoritative margin chronology for the entire ice sheet complex is featured in two publications (Geological Survey of Canada Open File 1574 [Dyke et al., 2003]; 'Quaternary Glaciations - Extent and Chronology, Part II' [Dyke, 2004]). These often-cited datasets track ice margin recession in 36 time slices spanning 18 ka to 1 ka (all ages in uncalibrated radiocarbon years) using a combination of geomorphology, stratigraphy and radiocarbon dating. However, by virtue of being over 15 years old, the ice margin chronology requires updating to reflect new work and important revisions. This paper updates the aforementioned 36 ice margin maps to reflect new data from regional studies. We also update the original radiocarbon dataset from the 2003/2004 papers with 1541 new ages to reflect work up to and including 2018. A major revision is made to the 18 ka ice margin, where Banks and Eglinton islands (once considered to be glacial refugia) are now shown to be fully glaciated. Our updated 18 ka ice sheet increased in areal extent from 17.81 to 18.37 million km(2), which is an increase of 3.1% in spatial coverage of the NAISC at that time. Elsewhere, we also summarize, region-by-region, significant changes to the deglaciation sequence. This paper integrates new information provided by regional experts and radiocarbon data into the deglaciation sequence while maintaining consistency with the original ice margin positions of Dyke et al. (2003) and Dyke (2004) where new information is lacking; this is a pragmatic solution to satisfy the needs of a Quaternary research community that requires up-to-date knowledge of the pattern of ice margin recession of what was once the world's largest ice mass. The 36 updated isochrones are available in PDF and shapefile format, together with a spreadsheet of the expanded radiocarbon dataset (n = 5195 ages) and estimates of uncertainty for each interval. (C) 2020 Elsevier Ltd. All rights reserved.
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| 5. |
- Mullins, Niamh, et al.
(författare)
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Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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| 6. |
- Docherty, Anna R, et al.
(författare)
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GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
- 2023
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Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
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Tidskriftsartikel (refereegranskat)abstract
- Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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| 7. |
- Windhorst, Rogier A., et al.
(författare)
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JWST PEARLS. Prime extragalactic areas for reionization and lensing science : project overview and first results
- 2023
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Ingår i: Astronomical Journal. - : Institute of Physics (IOP). - 0004-6256 .- 1538-3881. ; 165:1
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Tidskriftsartikel (refereegranskat)abstract
- We give an overview and describe the rationale, methods, and first results from NIRCam images of the JWST “Prime Extragalactic Areas for Reionization and Lensing Science” (PEARLS) project. PEARLS uses up to eight NIRCam filters to survey several prime extragalactic survey areas: two fields at the North Ecliptic Pole (NEP); seven gravitationally lensing clusters; two high redshift protoclusters; and the iconic backlit VV 191 galaxy system to map its dust attenuation. PEARLS also includes NIRISS spectra for one of the NEP fields and NIRSpec spectra of two high-redshift quasars. The main goal of PEARLS is to study the epoch of galaxy assembly, active galactic nucleus (AGN) growth, and First Light. Five fields—the JWST NEP Time-Domain Field (TDF), IRAC Dark Field, and three lensing clusters—will be observed in up to four epochs over a year. The cadence and sensitivity of the imaging data are ideally suited to find faint variable objects such as weak AGN, high-redshift supernovae, and cluster caustic transits. Both NEP fields have sightlines through our Galaxy, providing significant numbers of very faint brown dwarfs whose proper motions can be studied. Observations from the first spoke in the NEP TDF are public. This paper presents our first PEARLS observations, their NIRCam data reduction and analysis, our first object catalogs, the 0.9–4.5 μm galaxy counts and Integrated Galaxy Light. We assess the JWST sky brightness in 13 NIRCam filters, yielding our first constraints to diffuse light at 0.9–4.5 μm. PEARLS is designed to be of lasting benefit to the community.
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| 8. |
- Zaidi, Syed H., et al.
(författare)
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Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival
- 2020
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR=0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR=1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features. Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds.
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| 9. |
- Bruch, Rachel J., et al.
(författare)
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The Prevalence and Influence of Circumstellar Material around Hydrogen-rich Supernova Progenitors
- 2023
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 952:2
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Tidskriftsartikel (refereegranskat)abstract
- Narrow transient emission lines (flash-ionization features) in early supernova (SN) spectra trace the presence of circumstellar material (CSM) around the massive progenitor stars of core-collapse SNe. The lines disappear within days after the SN explosion, suggesting that this material is spatially confined, and originates from enhanced mass loss shortly (months to a few years) prior to the explosion. We performed a systematic survey of H-rich (Type II) SNe discovered within less than 2 days from the explosion during the first phase of the Zwicky Transient Facility survey (2018–2020), finding 30 events for which a first spectrum was obtained within <2 days from the explosion. The measured fraction of events showing flash-ionization features (>36% at the 95% confidence level) confirms that elevated mass loss in massive stars prior to SN explosion is common. We find that SNe II showing flash-ionization features are not significantly brighter, nor bluer, nor more slowly rising than those without. This implies that CSM interaction does not contribute significantly to their early continuum emission, and that the CSM is likely optically thin. We measured the persistence duration of flash-ionization emission and find that most SNe show flash features for ≈5 days. Rarer events, with persistence timescales >10 days, are brighter and rise longer, suggesting these may be intermediate between regular SNe II and strongly interacting SNe IIn.
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| 10. |
- Ho, Anna Y. Q., et al.
(författare)
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A Search for Extragalactic Fast Blue Optical Transients in ZTF and the Rate of AT2018cow-like Transients
- 2023
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 949:2
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Tidskriftsartikel (refereegranskat)abstract
- We present a search for extragalactic fast blue optical transients (FBOTs) during Phase I of the Zwicky Transient Facility (ZTF). We identify 38 candidates with durations above half-maximum light 1 day < t (1/2) < 12 days, of which 28 have blue (g - r less than or similar to -0.2 mag) colors at peak light. Of the 38 transients (28 FBOTs), 19 (13) can be spectroscopically classified as core-collapse supernovae (SNe): 11 (8) H- or He-rich (Type II/IIb/Ib) SNe, 6 (4) interacting (Type IIn/Ibn) SNe, and 2 (1) H&He-poor (Type Ic/Ic-BL) SNe. Two FBOTs (published previously) had predominantly featureless spectra and luminous radio emission: AT2018lug (The Koala) and AT2020xnd (The Camel). Seven (five) did not have a definitive classification: AT 2020bdh showed tentative broad H alpha in emission, and AT 2020bot showed unidentified broad features and was 10 kpc offset from the center of an early-type galaxy. Ten (eight) have no spectroscopic observations or redshift measurements. We present multiwavelength (radio, millimeter, and/or X-ray) observations for five FBOTs (three Type Ibn, one Type IIn/Ibn, one Type IIb). Additionally, we search radio-survey (VLA and ASKAP) data to set limits on the presence of radio emission for 24 of the transients. All X-ray and radio observations resulted in nondetections; we rule out AT2018cow-like X-ray and radio behavior for five FBOTs and more luminous emission (such as that seen in the Camel) for four additional FBOTs. We conclude that exotic transients similar to AT2018cow, the Koala, and the Camel represent a rare subset of FBOTs and use ZTF's SN classification experiments to measure the rate to be at most 0.1% of the local core-collapse SN rate.
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