Double-Stranded RNA of Intestinal Commensal but Not Pathogenic Bacteria Triggers Production of Protective Interferon-β

SummaryThe small intestine harbors a substantial number of commensal bacteria and is sporadically invaded by pathogens, but the response to these microorganisms is fundamentally different. We identified a discriminatory sensor by using Toll-like receptor 3 (TLR3). Double-stranded RNA (dsRNA) of one major commensal species, lactic acid bacteria (LAB), triggered interferon-β (IFN-β) production, which protected mice from experimental colitis. The LAB-induced IFN-β response was diminished by dsRNA digestion and treatment with endosomal inhibitors. Pathogenic bacteria contained less dsRNA and induced much less IFN-β than LAB, and dsRNA was not involved in pathogen-induced IFN-β induction. These results identify TLR3 as a sensor to small intestinal commensal bacteria and suggest that dsRNA in commensal bacteria contributes to anti-inflammatory and protective immune responses

Monitoring the Size and Flux Density of Sgr A* during the Active State in 2019 with East Asian VLBI Network

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).In this work, we studied the Galactic Center supermassive black hole (SMBH), Sagittarius A* (Sgr A∗ ), with the KVN and VERA Array (KaVA)/East Asian VLBI Network (EAVN) monitoring observations. Especially in 13 May 2019, Sgr A∗ experienced an unprecedented bright near infra-red (NIR) flare; so, we find a possible counterpart at 43 GHz (7 mm). As a result, a large temporal variation of the flux density at the level ∼15.4%, with the highest flux density of 2.04 Jy, is found on 11 May 2019. Interestingly, the intrinsic sizes are also variable, and the area and major-axis size show marginal correlation with flux density with ≳2 . Thus, we interpret that the emission region at 43 GHz follows the larger-when-brighter relation in 2019. The possible origins are discussed with an emergence of a weak jet/outflow component and the position angle change of the rotation axis of the accretion disk in time. © 2023 by the authors. Licensee MDPI, Basel, Switzerland.The work at the IAA-CSIC is supported in part by the Spanish Ministerio de Economía y Competitividad (grants AYA2016-80889-P and PID2019-108995GB-C21), the Consejería de Economía, Conocimiento, Empresas y Universidad of the Junta de Andalucía (grant P18-FR-1769), the Consejo Superior de Investigaciones Científicas (grant 2019AEP112), and the State Agency for Research of the Spanish MCIU through the “Center of Excellence Severo Ochoa” award to the Instituto de Astrofísica de Andalucía (SEV-2017-0709). This work was also supported by JSPS KAKENHI Grant Numbers JP18K13594, and MEXT as “Program for Promoting Researches on the Supercomputer Fugaku” (Toward a unified view of the universe: from large scale structures to planets, JPMXP1020200109) (T.K). Numerical computations were in part carried out on Cray XC50 at Center for Computational Astrophysics, National Astronomical Observatory of Japan. This work was supported by Brain Pool Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (2019H1D3A1A01102564).With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2021-001131-S).Peer reviewe

A Universal Power-law Prescription for Variability from Synthetic Images of Black Hole Accretion Flows

We present a framework for characterizing the spatiotemporal power spectrum of the variability expected from the horizon-scale emission structure around supermassive black holes, and we apply this framework to a library of general relativistic magnetohydrodynamic (GRMHD) simulations and associated general relativistic ray-traced images relevant for Event Horizon Telescope (EHT) observations of Sgr A*. We find that the variability power spectrum is generically a red-noise process in both the temporal and spatial dimensions, with the peak in power occurring on the longest timescales and largest spatial scales. When both the time-averaged source structure and the spatially integrated light-curve variability are removed, the residual power spectrum exhibits a universal broken power-law behavior. On small spatial frequencies, the residual power spectrum rises as the square of the spatial frequency and is proportional to the variance in the centroid of emission. Beyond some peak in variability power, the residual power spectrum falls as that of the time-averaged source structure, which is similar across simulations; this behavior can be naturally explained if the variability arises from a multiplicative random field that has a steeper high-frequency power-law index than that of the time-averaged source structure. We briefly explore the ability of power spectral variability studies to constrain physical parameters relevant for the GRMHD simulations, which can be scaled to provide predictions for black holes in a range of systems in the optically thin regime. We present specific expectations for the behavior of the M87* and Sgr A* accretion flows as observed by the EHT

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.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

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

Broadband multi-wavelength properties of M87 during the 2017 Event Horizon Telescope campaign

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 × 109Me. 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.http://iopscience.iop.org/2041-8205am2022Physic

Selective Dynamical Imaging of Interferometric Data

Recent developments in very long baseline interferometry (VLBI) have made it possible for the Event Horizon Telescope (EHT) to resolve the innermost accretion flows of the largest supermassive black holes on the sky. The sparse nature of the EHT's (u, v)-coverage presents a challenge when attempting to resolve highly time-variable sources. We demonstrate that the changing (u, v)-coverage of the EHT can contain regions of time over the course of a single observation that facilitate dynamical imaging. These optimal time regions typically have projected baseline distributions that are approximately angularly isotropic and radially homogeneous. We derive a metric of coverage quality based on baseline isotropy and density that is capable of ranking array configurations by their ability to produce accurate dynamical reconstructions. We compare this metric to existing metrics in the literature and investigate their utility by performing dynamical reconstructions on synthetic data from simulated EHT observations of sources with simple orbital variability. We then use these results to make recommendations for imaging the 2017 EHT Sgr A* data set

Polarimetric Properties of Event Horizon Telescope Targets from ALMA

We present the results from a full polarization study carried out with the Atacama Large Millimeter/submillimeter Array (ALMA) during the first Very Long Baseline Interferometry (VLBI) campaign, which was conducted in 2017 April in the λ3 mm and λ1.3 mm bands, in concert with the Global mm-VLBI Array (GMVA) and the Event Horizon Telescope (EHT), respectively. We determine the polarization and Faraday properties of all VLBI targets, including Sgr A*, M87, and a dozen radio-loud active galactic nuclei (AGNs), in the two bands at several epochs in a time window of 10 days. We detect high linear polarization fractions (2%–15%) and large rotation measures (RM > 103.3–105.5 rad m−2), confirming the trends of previous AGN studies at millimeter wavelengths. We find that blazars are more strongly polarized than other AGNs in the sample, while exhibiting (on average) order-of-magnitude lower RM values, consistent with the AGN viewing angle unification scheme. For Sgr A* we report a mean RM of (−4.2 ± 0.3) × 105 rad m−2 at 1.3 mm, consistent with measurements over the past decade and, for the first time, an RM of (–2.1 ± 0.1) × 105 rad m−2 at 3 mm, suggesting that about half of the Faraday rotation at 1.3 mm may occur between the 3 mm photosphere and the 1.3 mm source. We also report the first unambiguous measurement of RM toward the M87 nucleus at millimeter wavelengths, which undergoes significant changes in magnitude and sign reversals on a one year timescale, spanning the range from −1.2 to 0.3 × 105 rad m−2 at 3 mm and −4.1 to 1.5 × 105 rad m−2 at 1.3 mm. Given this time variability, we argue that, unlike the case of Sgr A*, the RM in M87 does not provide an accurate estimate of the mass accretion rate onto the black hole. We put forward a two-component model, comprised of a variable compact region and a static extended region, that can simultaneously explain the polarimetric properties observed by both the EHT (on horizon scales) and ALMA (which observes the combined emission from both components). These measurements provide critical constraints for the calibration, analysis, and interpretation of simultaneously obtained VLBI data with the EHT and GMVA

The polarized image of a synchrotron-emitting ring of gas orbiting a black hole

Synchrotron radiation from hot gas near a black hole results in a polarized image. The image polarization is determined by effects including the orientation of the magnetic field in the emitting region, relativistic motion of the gas, strong gravitational lensing by the black hole, and parallel transport in the curved spacetime. We explore these effects using a simple model of an axisymmetric, equatorial accretion disk around a Schwarzschild black hole. By using an approximate expression for the null geodesics derived by Beloborodov and conservation of the Walker–Penrose constant, we provide analytic estimates for the image polarization. We test this model using currently favored general relativistic magnetohydrodynamic simulations of M87*, using ring parameters given by the simulations. For a subset of these with modest Faraday effects, we show that the ring model broadly reproduces the polarimetric image morphology. Our model also predicts the polarization evolution for compact flaring regions, such as those observed from Sgr A* with GRAVITY. With suitably chosen parameters, our simple model can reproduce the EVPA pattern and relative polarized intensity in Event Horizon Telescope images of M87*. Under the physically motivated assumption that the magnetic field trails the fluid velocity, this comparison is consistent with the clockwise rotation inferred from total intensity images.http://iopscience.iop.org/0004-637Xam2023Physic