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

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

Surface Modification of Bi₂Te₃ Nanoplates Deposited with Tin, Palladium, and Tin/Palladium Using Electroless Deposition

Surface-modified nanoplate-shaped thermoelectric materials can achieve good thermoelectric performance. Herein, single-crystalline Bi2Te3 nanoplates with regular hexagonal shapes were prepared via solvothermal techniques. Surface modification was performed to deposit different metals onto the nanoplates using electroless deposition. Nanoparticle-shaped tin (Sn) and layer-shaped palladium (Pd) formed on the Bi2Te3 nanoplates via electroless deposition. For the sequential deposition of Sn and Pd, the surface morphology was mostly the same as that of the Sn-Bi2Te3 nanoplates. To assess the thermoelectric properties of the nanoplates as closely as possible, they were compressed into thin bulk shapes at 300 K. The Sn-Bi2Te3 and Sn/Pd-Bi2Te3 nanoplates exhibited the lowest lattice thermal conductivity of 1.1 W/(m·K), indicating that nanoparticle-shaped Sn facilitated the scattering of phonons. By contrast, the Pd-Bi2Te3 nanoplates exhibited the highest electrical conductivity. Thus, the highest power factor (15 μW/(m∙K2)) and dimensionless ZT (32 × 10−3) were obtained for the Pd-Bi2Te3 nanoplates. These thermoelectric properties were not as high as those of the sintered Bi2Te3 samples; however, this study revealed the effect of different metal depositions on Bi2Te3 nanoplates for improving thermoelectric performance. These findings offer venues for improving thermoelectric performance by sintering nanoplates deposited with appropriate metals

On Fourier coefficients of some meromorphic modular forms

1. Main theorem 2. Proof 3. Remarks ReferencesWe prove a congruence modulo a prime of Fourier coefficients of several meromorphic modular forms of low weights. We prove the result by establishing a generalization of a theorem of Garthwaite

Energy Expenditure of Disaster Relief Operations Estimated Using a Tri-Axial Accelerometer and a Wearable Heart Rate Monitor

The management of nutrition, food, and health for disaster relief personnel is one of the crucial aspects for carrying out effective rescue activities during large-scale natural disasters, such as a big earthquake, flooding, and landslide following heavy rainfall or man-made disasters, such as widespread fire in industrial areas. Rescue workers, such as fire fighters and rescue teams who work on the disaster relief operations, have to work long, hard, and irregular hours that require energy (both intake and expenditure), with especially altered eating patterns. Reliable estimates of the energy expenditure (TEE) for such disaster relief operations have not been fully established. Here, we propose to clarify the energy expenditure for each type of large-scale disaster activity conducted by fire fighters. Thirty fire fighters (survey participants in this research) who participated in the simulation training of large-scale disaster activities wore tri-axial accelerometers and heart rate monitors during training; and, post-training, 28 fire fighters submitted complete activity record tables. An estimation formula combining tri-axial accelerometer and heart rate monitor data was used. Additionally, energy expenditure per hour (excluding resting energy expenditure: REE) (per average body weight of participants) was calculated for 10 types of large-scale disaster response activities. We propose utilization of these data as a reference value for examining the TEE of firefighting and rescue operations in future large-scale disasters

Suppressive effects of a novel compound on interphotoreceptor retinoid-binding protein-induced experimental autoimmune uveoretinitis in rats

The immunosuppressive effect of ethyl O-(N-(pcarboxyphenyl)-carbamoyl)-mycophenolate(CAM) was examined in interphotoreceptor retinoid-binding protein (IRBP)-induced experimental autoimmune uveoretinitis (EAU) in rats. Lewis rats immunized with bovine IRBP were treated with various oral doses of CAM postimmunization. The degree of inflammation was assessed clinically each day and histologically on day 14 or day 20. Production of various cytokines and IRBP-specific antibody, as well as IRBP-specific proliferation response, was assessed. Complete inhibition of EAU in rats, both by clinical and histologic criteria, was achieved with 50 mg/kg CAM when administered daily for 14 days following IRBP immunization. Partial inhibition was observed at lesser doses of CAM. This CAM-mediated response was accompanied by diminished production of cytokines interleukin-2, interferon-γ and tumor necrosis factor-α, as well as a reduction in IRBP-specific antibody production. Furthermore, administration of CAM either in the induction phase only (days 0–7) or in the effector phase only (days 9 or 11 to day 20) was also capable of suppressing EAU, as assessed histopathologically on day 20. We conclude that CAM is effective in suppressing EAU in rats and its mechanism of action appears to involve modulation of T cell function