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- 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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| 7. |
- Bao, Min, et al.
(författare)
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Physical properties of the southwest outflow streamer in the starburst galaxy NGC 253 with ALCHEMI
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 687
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Tidskriftsartikel (refereegranskat)abstract
- Aims . The physical properties of galactic molecular outflows are important as they could constrain outflow formation mechanisms. In this work, we study the properties of the southwest (SW) outflow streamer including gas kinematics, optical depth, dense gas fraction, and shock strength through molecular emission in the central molecular zone of the starburst galaxy NGC 253. Methods . We imaged the molecular emission in NGC 253 at a spatial resolution of 1.600(∼27 pc at D ∼ 3.5 Mpc) based on data from the ALMA Comprehensive High-resolution Extragalactic Molecular Inventory (ALCHEMI) large program. We traced the velocity and velocity dispersion of molecular gas with the CO(1–0) line and studied the molecular spectra in the region of the SW streamer, the brightest CO streamer in NGC 253. We constrained the optical depth of the CO emission with the CO/13CO(1–0) ratio, the dense gas fraction with the HCN/CO(1–0), H13CN/13CO(1–0) and N2H+/13CO(1–0) ratios, as well as the shock strength with the SiO(2–1)/13CO(1–0) and CH3OH(2k–1k)/13CO(1–0) ratios. Results . The CO/13CO(1–0) integrated intensity ratio is ∼21 in the SW streamer region, which approximates the C/13C isotopic abundance ratio. The higher integrated intensity ratio compared to the disk can be attributed to the optically thinner environment of CO(1–0) emission inside the SW streamer. The HCN/CO(1–0) and SiO(2–1)/13CO(1–0) integrated intensity ratios both approach ∼0.2 in three giant molecular clouds (GMCs) at the base of the outflow streamers, which implies a higher dense gas fraction and strength of fast shocks in those GMCs than in the disk, while the HCN/CO(1–0) integrated intensity ratio is moderate in the SW streamer region. The contours of those two integrated intensity ratios are extended in the directions of outflow streamers, which connect the enhanced dense gas fraction and shock strength with molecular outflow. Moreover, the molecular gas with an enhanced dense gas fraction and shock strength located at the base of the SW streamer shares the same velocity as the outflow. Conclusions . The enhanced dense gas fraction and shock strength at the base of the outflow streamers suggest that star formation inside the GMCs can trigger shocks and further drive the molecular outflow. The increased CO/13CO(1–0) integrated intensity ratio coupled with the moderate HCN/CO(1–0) integrated intensity ratio in the SW streamer region are consistent with the picture that the gas velocity gradient inside the streamer may decrease the optical depth of CO(1–0) emission, as well as the dense gas fraction in the extended streamer region.
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| 8. |
- Butterworth, Joshua, et al.
(författare)
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Molecular isotopologue measurements toward super star clusters and the relation to their ages in NGC 253 with ALCHEMI
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 686
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Tidskriftsartikel (refereegranskat)abstract
- Context. Determining the evolution of the CNO isotopes in the interstellar medium (ISM) of starburst galaxies can yield important constraints on the ages of super star clusters (SSCs), or on other aspects and factors contributing to their evolution, such as the initial mass function (IMF). Due to the time-dependent nature of the abundances of isotopes within the ISM -as they are supplied from processes such as nucleosynthesis or chemical fractionation -, this provides the opportunity to test whether or not isotope ratios trace the ages of highly star-forming regions, such as SSCs. Aims. The goal of this study is to investigate whether the isotopic variations in SSC regions within NGC 253 are correlated with their different ages as derived from stellar population modelling. Methods. We measured abundance ratios of CO, HCN, and HCO+ isotopologues in six regions containing SSCs within NGC 253 using high-spatial-resolution (1.6″, ~28 pc) data from the ALCHEMI (ALma Comprehensive High-resolution Extragalactic Molecular Inventory) ALMA Large program. We then analysed these ratios using RADEX radiative transfer modelling, with the parameter space sampled using the nested sampling Monte Carlo algorithm MLFriends. These abundance ratios were then compared to ages predicted in each region via the fitting of observed star-formation tracers (such as Brγ) to Starburst99 starburst stellar population evolution models. Results. We determined the isotopic column density ratios across multiple regions of SSC activity in NGC 253 using non-LTE radiative transfer modelling. We do not find any significant trend with age for the CO and HCN isotopologue ratios on timescales of the ages of the SSC∗ regions observed. However, HCO+ may show a correlation with age over these timescales in 12C/13C. Conclusions. The driving factors of these ratios within SSCs could be the IMF or fractionation effects. To further probe these effects in SSCs over time, a larger sample of SSCs must be observed spanning a larger age range.
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| 9. |
- Harada, N., et al.
(författare)
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The ALCHEMI Atlas: Principal Component Analysis Reveals Starburst Evolution in NGC 253
- 2024
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Ingår i: Astrophysical Journal, Supplement Series. - 1538-4365 .- 0067-0049. ; 271:2
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Tidskriftsartikel (refereegranskat)abstract
- Molecular lines are powerful diagnostics of the physical and chemical properties of the interstellar medium (ISM). These ISM properties, which affect future star formation, are expected to differ in starburst galaxies from those of more quiescent galaxies. We investigate the ISM properties in the central molecular zone of the nearby starburst galaxy NGC 253 using the ultrawide millimeter spectral scan survey from the Atacama Large Millimeter/submillimeter Array Large Program ALCHEMI. We present an atlas of velocity-integrated images at a 1.″6 resolution of 148 unblended transitions from 44 species, including the first extragalactic detection of HCNH+ and the first interferometric images of C3H+, NO, and HCS+. We conduct a principal component analysis (PCA) on these images to extract correlated chemical species and to identify key groups of diagnostic transitions. To the best of our knowledge, our data set is currently the largest astronomical set of molecular lines to which PCA has been applied. The PCA can categorize transitions coming from different physical components in NGC 253 such as (i) young starburst tracers characterized by high-excitation transitions of HC3N and complex organic molecules versus tracers of on-going star formation (radio recombination lines) and high-excitation transitions of CCH and CN tracing photodissociation regions, (ii) tracers of cloud-collision-induced shocks (low-excitation transitions of CH3OH, HNCO, HOCO+, and OCS) versus shocks from star formation-induced outflows (high-excitation transitions of SiO), as well as (iii) outflows showing emission from HOC+, CCH, H3O+, CO isotopologues, HCN, HCO+, CS, and CN. Our findings show these intensities vary with galactic dynamics, star formation activities, and stellar feedback.
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| 10. |
- Hasegawa, Y., et al.
(författare)
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Role of Mfa5 in Expression of Mfa1 Fimbriae in Porphyromonas gingivalis
- 2016
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Ingår i: Journal of Dental Research. - : International & American Associations for Dental Research. - 0022-0345 .- 1544-0591. ; 95:11, s. 1291-1297
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Tidskriftsartikel (refereegranskat)abstract
- Fimbriae are protein-based filamentous appendages that protrude from the bacterial cell surface and facilitate host adhesion. Two types of fimbriae, FimA and Mfa1, of the periodontal pathogen Porphyromonas gingivalis are responsible for adherence to other bacteria and to host cells in the oral cavity. Both fimbrial forms are composed of 5 proteins, but there is limited information about their polymerization mechanisms. Here, the authors evaluated the function of Mfa5, one of the Mfa1 fimbrial accessory proteins. Using mfa5 gene disruption and complementation studies, the authors revealed that Mfa5 affects the incorporation of other accessory proteins, Mfa3 and Mfa4, into fibers and the expression of fimbriae on the cell surface. Mfa5 is predicted to have a C-terminal domain (CTD) that uses the type IX secretion system (T9SS), which is limited to this organism and related Bacteroidetes species, for translocation across the outer membrane. To determine the relationship between the putative Mfa5 CTD and the T9SS, mutants were constructed with in-frame deletion of the CTD and deletion of porU, a C-terminal signal peptidase linked to T9SS-mediated secretion. The ∆CTD-expressing strain presented a similar phenotype to the mfa5 disruption mutant with reduced expression of fimbriae lacking all accessory proteins. The ∆porU mutants and the ∆CTD-expressing strain showed intracellular accumulation of Mfa5. These results indicate that Mfa5 function requires T9SS-mediated translocation across the outer membrane, which is dependent on the CTD, and subsequent incorporation into fibers. These findings suggest the presence of a novel polymerization mechanism of the P. gingivalis fimbriae.
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