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| 2. |
- 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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| 3. |
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| 4. |
- 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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| 5. |
- Fomalont, E. B., et al.
(författare)
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THE 2014 ALMA LONG BASELINE CAMPAIGN: AN OVERVIEW
- 2015
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 808:1
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Tidskriftsartikel (refereegranskat)abstract
- A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to similar to 15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from 2014 September to late November, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C 138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at similar to 350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy.
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| 6. |
- Yamada, K., et al.
(författare)
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Long-term outcome of targeted therapy for low back pain in elderly degenerative lumbar scoliosis
- 2021
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Ingår i: European Spine Journal. - : Springer Science and Business Media LLC. - 0940-6719 .- 1432-0932. ; 30, s. 2020-2032
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Treatment of low back pain (LBP) associated with elderly degenerative lumbar scoliosis (DLS) remains controversial. We have developed percutaneous intervertebral-vacuum polymethylmethacrylate injection (PIPI) targeting to the intervertebral vacuum as a minimally invasive surgery. The present study compared the long-term clinical outcomes of PIPI to that of nonoperative treatment. Methods Patients with de novo DLS, aged >= 65 years, who had LBP with visual analog scale (VAS) of >= 50 for >= 6 months with intervertebral vacuum on computed tomography and bone marrow edema (BME) on magnetic resonance imaging were included. The clinical outcomes were evaluated using VAS and the Oswestry Disability Index (ODI) at baseline, 1, 6, 12, 24 months, and at the final follow-up. The course of BME was also evaluated. Results One hundred and one patients underwent PIPI and 61 received nonoperative treatment. The mean follow-up duration after PIPI and nonoperative treatment was 63.7 +/- 32.4 and 43.9 +/- 20.9 months, respectively. VAS and ODI after PIPI were significantly improved compared to post-nonoperative treatment. BME decreased substantially in the PIPI group and it was significantly correlated with VAS and ODI improvement. Following PIPI, LBP recurred in 28 patients (35%). LBP recurrence was identified at the same level of PIPI in 10 patients, at the adjacent level of PIPI in 11 patients, and at the non-adjacent level of PIPI in seven patients. Eighteen patients underwent additional PIPIs, and both VAS and ODI were significantly improved after additional PIPIs. Conclusion Bone marrow lesions of the endplate are strongly associated with the presence of LBP. PIPI can be considered as an effective, safe and repeatable treatment for LBP in elderly DLS patients.
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| 7. |
- Yamada, K., et al.
(författare)
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Targeted Therapy for Low Back Pain in Elderly Degenerative Lumbar Scoliosis
- 2016
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Ingår i: Spine. - : Ovid Technologies (Wolters Kluwer Health). - 0362-2436. ; 41:10, s. 872-879
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Tidskriftsartikel (refereegranskat)abstract
- Study Design. Prospective cohort study. Objective. To compare the novel treatment procedure with nonoperative treatment for low back pain (LBP) in elderly patients with degenerative lumbar scoliosis (DLS). Summary of Background Data. Treatment of LBP associated with elderly DLS is controversial. We developed a novel treatment procedure, termed percutaneous intervertebral-vacuum polymethylmethacrylate injection (PIPI). Methods. We included patients with de novo DLS aged >= 65 years who had LBP with a visual analogue scale (VAS) score of >50 for >= 6 months with intervertebral vacuum and vertebral bone marrow edema (BME) defined on fat-saturated T2-weighted or gadolinium-enhanced T1-weighted magnetic resonance imaging. The primary outcomes were evaluated using the VAS score and modified Oswestry Disability Index (ODI). As an objective measurement, we scored BME on magnetic resonance imaging. Results. Between August 2004 and July 2011, 109 patients underwent PIPI and 53 received nonoperative treatment. At 1 month, mean improvements in VAS scores were -55.3 (95% CI, -60.5 to -50.1) and -1.9 (CI, -7.7 to 3.8) and mean improvements in ODI were -22.7 (CI, -27.3 to -18.2) and -0.6 (CI, -6.6 to 5.4) for the PIPI and nonoperative groups, respectively. At 2 years, mean improvements in VAS scores were -52.2 (CI, -59.9 to -44.4) and -4.0 (CI, -10.9 to 3.0) and mean improvements in ODI were -20.7 (CI, -27.3 to -14.5) and -1.0 (CI, -7.7 to 5.7) for the PIPI and nonoperative groups, respectively. BME substantially decreased in the PIPI group compared with the nonoperative group (P < 0.001) and correlated with VAS score and ODI improvements (VAS score: r = 0.502, P < 0.001; ODI: r = 0.372, P< 0.001). Conclusion. PIPI improved treatment for LBP, with a sustained clinical benefit for at least 2 years.
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| 8. |
- Galbany, L., et al.
(författare)
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Evidence for a Chandrasekhar-mass explosion in the Ca-strong 1991bg-like type la supernova 2016hnk
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 630
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Tidskriftsartikel (refereegranskat)abstract
- Aims. We present a comprehensive dataset of optical and near-infrared photometry and spectroscopy of type Ia supernova (SN) 2016hnk, combined with integral field spectroscopy (IFS) of its host galaxy, MCG -01-06-070, and nearby environment. Our goal with this complete dataset is to understand the nature of this peculiar object.Methods. Properties of the SN local environment are characterized by means of single stellar population synthesis applied to IFS observations taken two years after the SN exploded. We performed detailed analyses of SN photometric data by studying its peculiar light and color curves. SN 2016hnk spectra were compared to other 1991bg-like SNe Ia, 2002es-like SNe Ia, and Ca-rich transients. In addition, we used abundance stratification modeling to identify the various spectral features in the early phase spectral sequence and also compared the dataset to a modified non-LTE model previously produced for the sublumnious SN 1999by.Results. SN 2016hnk is consistent with being a subluminous (M-B = -16.7 mag, S-BV =0.43 +/- 0.03), highly reddened object. The IFS of its host galaxy reveals both a significant amount of dust at the SN location, residual star formation, and a high proportion of old stellar populations in the local environment compared to other locations in the galaxy, which favors an old progenitor for SN 2016hnk. Inspection of a nebular spectrum obtained one year after maximum contains two narrow emission lines attributed to the forbidden [Ca II] lambda lambda 7291,7324 doublet with a Doppler shift of 700 km s(-1). Based on various observational diagnostics, we argue that the progenitor of SN 2016hnk was likely a near Chandrasekhar-mass (M-Ch) carbon-oxygen white dwarf that produced 0.108 M-circle dot of Ni-56. Our modeling suggests that the narrow [Ca II] features observed in the nebular spectrum are associated with Ca-48 from electron capture during the explosion, which is expected to occur only in white dwarfs that explode near or at the M-Ch limit.
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| 9. |
- Gkini, Anamaria, et al.
(författare)
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SN2020zbf : A fast-rising hydrogen-poor superluminous supernova with strong carbon lines
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 685
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Tidskriftsartikel (refereegranskat)abstract
- SN 2020zbf is a hydrogen-poor superluminous supernova (SLSN) at z = 0.1947 that shows conspicuous C II features at early times, in contrast to the majority of H-poor SLSNe. Its peak magnitude is Mg = −21.2 mag and its rise time (≲26.4 days from first light) places SN 2020zbf among the fastest rising type I SLSNe. We used spectra taken from ultraviolet (UV) to near-infrared wavelengths to identify spectral features. We paid particular attention to the C II lines as they present distinctive characteristics when compared to other events. We also analyzed UV and optical photometric data and modeled the light curves considering three different powering mechanisms: radioactive decay of 56Ni, magnetar spin-down, and circumstellar medium (CSM) interaction. The spectra of SN 2020zbf match the model spectra of a C-rich low-mass magnetar-powered supernova model well. This is consistent with our light curve modeling, which supports a magnetar-powered event with an ejecta mass Mej = 1.5 M⊙. However, we cannot discard the CSM-interaction model as it may also reproduce the observed features. The interaction with H-poor, carbon-oxygen CSM near peak light could explain the presence of C II emission lines. A short plateau in the light curve around 35–45 days after peak, in combination with the presence of an emission line at 6580 Å, can also be interpreted as being due to a late interaction with an extended H-rich CSM. Both the magnetar and CSM-interaction models of SN 2020zbf indicate that the progenitor mass at the time of explosion is between 2 and 5 M⊙. Modeling the spectral energy distribution of the host galaxy reveals a host mass of 108.7 M⊙, a star formation rate of 0.24−0.12+0.41 M⊙ yr−1, and a metallicity of ∼0.4 Z⊙.
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