| 1. |
- Namkoong, H, et al.
(författare)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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| 2. |
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| 3. |
- Wang, QBS, et al.
(författare)
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The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
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Tidskriftsartikel (refereegranskat)abstract
- Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.
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| 4. |
- Noda, C. Quintero, et al.
(författare)
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Chromospheric polarimetry through multiline observations of the 850-nm spectral region - II. A magnetic flux tube scenario
- 2017
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 472:1, s. 727-737
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Tidskriftsartikel (refereegranskat)abstract
- In this publication, we continue the work started in Quintero Noda et al., examining this time a numerical simulation of a magnetic flux tube concentration. Our goal is to study if the physical phenomena that take place in it, in particular, the magnetic pumping, leaves a specific imprint on the examined spectral lines. We find that the profiles from the interior of the flux tube are periodically doppler shifted following an oscillation pattern that is also reflected in the amplitude of the circular polarization signals. In addition, we analyse the properties of the Stokes profiles at the edges of the flux tube discovering the presence of linear polarization signals for the Ca II lines, although they are weak with an amplitude around 0.5 per cent of the continuum intensity. Finally, we compute the response functions to perturbations in the longitudinal field, and we estimate the field strength using the weak-field approximation. Our results indicate that the height of formation of the spectral lines changes during the magnetic pumping process, which makes the interpretation of the inferred magnetic field strength and its evolution more difficult. These results complement those from previous works, demonstrating the capabilities and limitations of the 850-nm spectrum for chromospheric Zeeman polarimetry in a very dynamic and complex atmosphere.
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| 5. |
- Quintero Noda, C., et al.
(författare)
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Chromospheric polarimetry through multiline observations of the 850nm spectral region III : Chromospheric jets driven by twisted magnetic fields
- 2019
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 486:3, s. 4203-4215
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the diagnostic potential of the spectral lines at 850 nm for understanding the magnetism of the lower atmosphere. For that purpose, we use a newly developed 3D simulation of a chromospheric jet to check the sensitivity of the spectral lines to this phenomenon as well as our ability to infer the atmospheric information through spectropolarimetric inversions of noisy synthetic data. We start comparing the benefits of inverting the entire spectrum at 850 nm versus only the Ca II 8542 angstrom spectral line. We found a better match of the input atmosphere for the former case, mainly at lower heights. However, the results at higher layers were not accurate. After several tests, we determined that we need to weight more the chromospheric lines than the photospheric ones in the computation of the goodness of the fit. The new inversion configuration allows us to obtain better fits and consequently more accurate physical parameters. Therefore, to extract the most from multiline inversions, a proper set of weights needs to be estimated. Besides that, we conclude again that the lines at 850 nm, or a similar arrangement with Ca II 8542 angstrom plus Zeeman-sensitive photospheric lines, pose the best-observing configuration for examining the thermal and magnetic properties of the lower solar atmosphere.
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| 6. |
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| 7. |
- Noda, C. Quintero, et al.
(författare)
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Chromospheric polarimetry through multiline observations of the 850-nm spectral region
- 2017
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 464:4, s. 4534-4543
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Tidskriftsartikel (refereegranskat)abstract
- Future solar missions and ground-based telescopes aim to understand the magnetism of the solar chromosphere. We performed a supporting study in Quintero Noda et al. focused on the infrared Ca (II) 8542 angstrom line and we concluded that it is one of the best candidates because it is sensitive to a large range of atmospheric heights, from the photosphere to the middle chromosphere. However, we believe that it is worth trying to improve the results produced by this line observing additional spectral lines. In that regard, we examined the neighbourhood solar spectrum looking for spectral lines which could increase the sensitivity to the atmospheric parameters. Interestingly, we discovered several photospheric lines which greatly improve the photospheric sensitivity to the magnetic field vector. Moreover, they are located close to a second chromospheric line which also belongs to the Ca (II) infrared triplet, i.e. the Ca (II) 8498 angstrom line, and enhances the sensitivity to the atmospheric parameters at chromospheric layers. We conclude that the lines in the vicinity of the Ca (II) 8542 A line not only increase its sensitivity to the atmospheric parameters at all layers, but also they constitute an excellent spectral window for chromospheric polarimetry.
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| 8. |
- Noda, C. Quintero, et al.
(författare)
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Spectropolarimetric capabilities of Ca II 8542 angstrom line
- 2016
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 459:3, s. 3363-3376
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Tidskriftsartikel (refereegranskat)abstract
- The next generation of space-and ground-based solar missions aim to study the magnetic properties of the solar chromosphere using the infrared Ca II lines and the He I 10830 angstrom line. The former seem to be the best candidates to study the stratification of magnetic fields in the solar chromosphere and their relation to the other thermodynamical properties underlying the chromospheric plasma. The purpose of this work is to provide a detailed analysis of the diagnostic capabilities of the Ca II 8542 angstrom line, anticipating forthcoming observational facilities. We study the sensitivity of the Ca II 8542 angstrom line to perturbations applied to the physical parameters of reference semi-empirical 1D model atmospheres using response functions and we make use of 3D magnetohydrodynamics simulations to examine the expected polarization signals for moderate magnetic field strengths. Our results indicate that the Ca II 8542 angstrom line is mostly sensitive to the layers enclosed in the range log tau = [0, -5.5], under the physical conditions that are present in our model atmospheres. In addition, the simulated magnetic flux tube generates strong longitudinal signals in its centre and moderate transversal signals, due to the vertical expansion of magnetic field lines, in its edge. Thus, observing the Ca II 8542 angstrom line we will be able to infer the 3D geometry of moderate magnetic field regions.
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| 9. |
- Hirao, Yuki, et al.
(författare)
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OGLE-2017-BLG-0406 : Spitzer Microlens Parallax Reveals Saturn-mass Planet Orbiting M-dwarf Host in the Inner Galactic Disk
- 2020
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 160:2
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery and analysis of the planetary microlensing event OGLE-2017-BLG-0406, which was observed both from the ground and by the Spitzer satellite in a solar orbit. At high magnification, the anomaly in the light curve was densely observed by ground-based-survey and follow-up groups, and it was found to be explained by a planetary lens with a planet/host mass ratio of q = 7.0 x 10(-4) from the light-curve modeling. The ground-only and Spitzer-only data each provide very strong one-dimensional (1D) constraints on the 2D microlens parallax vector pi(E). When combined, these yield a precise measurement of pi(E) and of the masses of the host M-host = 0.56 +/- 0.07 M-circle dot and planet M-planet = 0.41 +/- 0.05 M-Jup. The system lies at a distance D-L = 5.2 +/- 0.5 kpc from the Sun toward the Galactic bulge, and the host is more likely to be a disk population star according to the kinematics of the lens. The projected separation of the planet from the host is a(perpendicular to) = 3.5 +/- 0.3 au (i.e., just over twice the snow line). The Galactic-disk kinematics are established in part from a precise measurement of the source proper motion based on OGLE-IV data. By contrast, the Gaia proper-motion measurement of the source suffers from a catastrophic 10 sigma error.
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| 10. |
- Rachmeler, L. A., et al.
(författare)
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Quiet Sun Center to Limb Variation of the Linear Polarization Observed by CLASP2 Across the Mg ıı h and k Lines
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 936:1
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Tidskriftsartikel (refereegranskat)abstract
- The CLASP2 (Chromospheric LAyer Spectro-Polarimeter 2) sounding rocket mission was launched on 2019 April 11. CLASP2 measured the four Stokes parameters of the Mg ıı h and k spectral region around 2800 Å along a 200'' slit at three locations on the solar disk, achieving the first spatially and spectrally resolved observations of the solar polarization in this near-ultraviolet region. The focus of the work presented here is the center-to-limb variation of the linear polarization across these resonance lines, which is produced by the scattering of anisotropic radiation in the solar atmosphere. The linear polarization signals of the Mg ıı h and k lines are sensitive to the magnetic field from the low to the upper chromosphere through the Hanle and magneto-optical effects. We compare the observations to theoretical predictions from radiative transfer calculations in unmagnetized semiempirical models, arguing that magnetic fields and horizontal inhomogeneities are needed to explain the observed polarization signals and spatial variations. This comparison is an important step in both validating and refining our understanding of the physical origin of these polarization signatures, and also in paving the way toward future space telescopes for probing the magnetic fields of the solar upper atmosphere via ultraviolet spectropolarimetry.
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