Ammonia mapping observations of the Galactic infrared bubble N49: Three NH3_3 clumps along the molecular filament

We have carried out the NH$_3$ $(J,K)=(1,1),(2,2),$ and $(3,3)$ mapping observations toward the Galactic infrared bubble N49 (G28.83-0.25) using the Nobeyama 45 m telescope. Three NH$_3$ clumps (A, B, and C) were discovered along the molecular filament with the radial velocities of $\sim$ 96, 87, and 89 km s$^{-1}$, respectively. The kinetic temperature derived from the NH$_3$ (2,2)/NH$_3$ (1,1) shows $T_{\rm kin} = 27.0 \pm 0.6$ K enhanced at Clump B in the eastern edge of the bubble, where position coincides with massive young stellar objects (MYSOs) associated with the 6.7 GHz class II methanol maser source. This result shows the dense clump is locally heated by stellar feedback from the embedded MYSOs. The NH$_3$ Clump B also exists at the 88 km s$^{-1}$ and 95 km s$^{-1}$ molecular filament intersection. We therefore suggest that the NH$_3$ dense gas formation in Clump B can be explained by a filament-filament interaction scenario. On the other hand, NH$_3$ Clump A and C at the northern and southern side of the molecular filament might be the sites of spontaneous star formation because these clumps are located $\sim$5$-$10 pc away from the edge of the bubble.Comment: 29 pages, 13 figures, 3 tables, accepted for Publications of the Astronomical Society of Japan (PASJ

ASTE CO(3-2) Mapping toward the Whole Optical Disk of M 83: Properties of Inter-arm GMAs

We present a new on-the-fly (OTF) mapping of CO(J=3-2) line emission with the Atacama Submillimeter Telescope Experiment (ASTE) toward the 8' x 8' (or 10.5 x 10.5 kpc at the distance of 4.5 Mpc) region of the nearby barred spiral galaxy M 83 at an effective resolution of 25''. Due to its very high sensitivity, our CO(J=3-2) map can depict not only spiral arm structures but also spur-like substructures extended in inter-arm regions. This spur-like substructures in CO(J=3-2) emission are well coincident with the distribution of massive star forming regions traced by Halpha luminosity and Spitzer/IRAC 8 um emission. We have identified 54 CO(J=3-2) clumps as Giant Molecular-cloud Associations (GMAs) employing the CLUMPFIND algorithm, and have obtained their sizes, velocity dispersions, virial masses, and CO luminosity masses. We found that the virial parameter alpha, which is defined as the ratio of the virial mass to the CO luminosity mass, is almost unity for GMAs in spiral arms, whereas there exist some GMAs whose alpha are 3 -- 10 in the inter-arm region. We found that GMAs with higher $\alpha$ tend not to be associated with massive star forming regions, while other virialized GMAs are. Since alpha mainly depends on velocity dispersion of the GMA, we suppose the onset of star formation in these unvirialized GMAs with higher alpha are suppressed by an increase in internal velocity dispersions of Giant Molecular Clouds within these GMAs due to shear motion.Comment: 42 pages, 16 figures, ApJ in press, version with high resolution figures is available via http://www.nro.nao.ac.jp/~kmuraoka/m83paper/m83aste-otf.pd

Independent association of HLA-DPB1*02:01 with rheumatoid arthritis in Japanese populations

ObjectiveRheumatoid arthritis (RA) is a chronic autoimmune disease characterized with joint destructions; environmental and genetic factors were thought to be involved in the etiology of RA. The production of anti-citrullinated peptide antibodies (ACPA) is specifically associated with RA. DRB1 is associated with the susceptibility of RA, especially ACPA-positive RA [ACPA(+)RA]. However, a few studies reported on the independent associations of DPB1 alleles with RA susceptibility. Thus, we investigated the independent association of DPB1 alleles with RA in Japanese populations.MethodsAssociation analyses of DPB1 were conducted by logistic regression analysis in 1667 RA patients and 413 controls.ResultsIn unconditioned analysis, DPB1*04:02 was nominally associated with the susceptibility of ACPA(+)RA (P = 0.0021, corrected P (Pc) = 0.0275, odds ratio [OR] 1.52, 95% confidence interval [CI] 1.16–1.99). A significant association of DPB1*02:01 with the susceptibility of ACPA(+)RA was observed, when conditioned on DRB1 (Padjusted = 0.0003, Pcadjusted = 0.0040, ORadjusted 1.47, 95%CI 1.19–1.81). DPB1*05:01 was tended to be associated with the protection against ACPA(+)RA, when conditioned on DRB1 (Padjusted = 0.0091, Pcadjusted = 0.1184, ORadjusted 0.78, 95%CI 0.65–0.94). When conditioned on DRB1, the association of DPB1*04:02 with ACPA(+)RA was disappeared. No association of DPB1 alleles with ACPA-negative RA was detected.ConclusionThe independent association of DPB1*02:01 with Japanese ACPA(+)RA was identified

Association of Human Leukocyte Antigen with Interstitial Lung Disease in Rheumatoid Arthritis: A Protective Role for Shared Epitope

INTRODUCTION: Interstitial Lung Disease (ILD) is frequently associated with Rheumatoid Arthritis (RA) as one of extra-articular manifestations. Many studies for Human Leukocyte Antigen (HLA) allelic association with RA have been reported, but few have been validated in an RA subpopulation with ILD. In this study, we investigated the association of HLA class II alleles with ILD in RA. METHODS: An association study was conducted on HLA-DRB1, DQB1, and DPB1 in 450 Japanese RA patients that were or were not diagnosed with ILD, based on the findings of computed tomography images of the chest. RESULTS: Unexpectedly, HLA-DRB1*04 (corrected P [Pc] = 0.0054, odds ratio [OR] 0.57), shared epitope (SE) (P = 0.0055, OR 0.66) and DQB1*04 (Pc = 0.0036, OR 0.57) were associated with significantly decreased risk of ILD. In contrast, DRB1*16 (Pc = 0.0372, OR 15.21), DR2 serological group (DRB1*15 and *16 alleles) (P = 0.0020, OR 1.75) and DQB1*06 (Pc = 0.0333, OR 1.57, respectively) were significantly associated with risk of ILD. CONCLUSION: HLA-DRB1 SE was associated with reduced, while DR2 serological group (DRB1*15 and *16) with increased, risk for ILD in Japanese patients with RA

Common Variants in a Novel Gene, FONG on Chromosome 2q33.1 Confer Risk of Osteoporosis in Japanese

Osteoporosis is a common disease characterized by low bone mass, decreased bone quality and increased predisposition to fracture. Genetic factors have been implicated in its etiology; however, the specific genes related to susceptibility to osteoporosis are not entirely known. To detect susceptibility genes for osteoporosis, we conducted a genome-wide association study in Japanese using ∼270,000 SNPs in 1,747 subjects (190 cases and 1,557 controls) followed by multiple levels of replication of the association using a total of ∼5,000 subjects (2,092 cases and 3,114 controls). Through these staged association studies followed by resequencing and linkage disequilibrium mapping, we identified a single nucleotide polymorphism (SNP), rs7605378 associated with osteoporosis. (combined P = 1.51×10−8, odds ratio = 1.25). This SNP is in a previously unknown gene on chromosome 2q33.1, FONG. FONG is predicted to encode a 147 amino-acid protein with a formiminotransferase domain in its N-terminal (FTCD_N domain) and is ubiquitously expressed in various tissues including bone. Our findings would give a new insight into osteoporosis etiology and pathogenesis

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. 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