{2-[(Dimethyl­amino)­meth­yl]phen­yl}bis­(4-methyl­phen­yl)bis­muthane

The title compound, [Bi(C7H7)2(C9H12N)], was obtained by treating chlorodi(p-tol­yl)bis­muthane with o-lithio-N,N-dimethyl­benzyl­amine. An intra­molecular Bi⋯N nonbonding inter­action is observed in the distorted trigonal triaryl­bis­muth coordination of the title compound

Topological Thermal Hall Effect Induced by Magnetic Skyrmions

Quantized transports of fermions are topological phenomena determined by the sum of the Chern numbers of all the energy bands below the Fermi energy. For bosonic excitations, e.g. phonons and magnons in a crystal, topological transport is dominated by the Chern number of the lowest energy band because the energy distribution of the bosons is limited below the thermal energy. Here, we demonstrate the existence of topological transport by bosonic magnons in a lattice of magnetic skyrmions - topological defects formed by a vortex-like texture of spins. We find a distinct thermal Hall signal when the ferromagnetic spins in an insulating polar magnet GaV4Se8 form magnetic skyrmions. Its origin is identified as the topological thermal Hall effect of magnons in which the trajectories of these magnons are bent by an emergent magnetic field produced by the magnetic skyrmions. Our theoretical simulations confirm that the thermal Hall effect is indeed governed by the Chern number of the lowest energy band of the magnons in a triangular lattice of magnetic skyrmions. Our findings lay a foundation for studying topological phenomena of other bosonic excitations.Comment: 13 pages, 3 figures, and Supplementary Informatio

Feedback Control of the Arachidonate Cascade in Osteoblastic Cells by 15-deoxy-Δ12,14-Prostaglandin J2

15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and an anti-diabetic thiazolidinedione, troglitazone (TRO) are peroxisome proliferator-activated receptor (PPAR)-γ ligands, which regulate immuno-inflammatory reactions as well as adipocyte differentiation. We previously reported that 15d-PGJ2 can suppress interleukin (IL)-1β-induced prostaglandin E2 (PGE2) synthesis in synoviocytes of rheumatoid arthritis (RA). IL-1 also stimulates PGE2 synthesis in osteoblasts by regulation of cyclooxygenase (COX)-2 and regulates osteoclastic bone resorption in various diseases such as RA and osteoporosis. In this study, we investigated the feedback mechanism of the arachidonate cascade in mouse osteoblastic cells, MC3T3-E1 cells, which differentiate into mature osteoblasts. Treatment with 15d-PGJ2 led to a significant increase in IL-1α-induced COX-2 expression and PGE2 production in a dose dependent manner. The effect of 15d-PGJ2 was stronger than that of TRO. However, it did not affect the expression of COX-1. In addition, cell viability of MC3T3-E1 cells was not changed in the condition we established. This means that 15d-PGJ2 exerts a positive feedback regulation of the arachidonate cascade of PGE2 in osteoblastic cells. These results may provide important information about the pathogenesis and treatment of bone resorption in a variety of diseases such as RA and osteoporosis

Nobeyama Millimeter Interferometric HCN(1-0) and HCO+(1-0) Observations of Further Luminous Infrared Galaxies

We report the results of interferometric HCN(1-0) and HCO+(1-0) observations of four luminous infrared galaxies (LIRGs), NGC 2623, Mrk 266, Arp 193, and NGC 1377, as a final sample of our systematic survey using the Nobeyama Millimeter Array. Our survey contains the most systematic interferometric, spatially-resolved, simultaneous HCN(1-0) and HCO+(1-0) observations of LIRGs. Ground-based infrared spectra of these LIRGs are also presented to elucidate the nature of the energy sources at the nuclei. We derive the HCN(1-0)/HCO+(1-0) brightness-temperature ratios of these LIRGs and confirm the previously discovered trend that LIRG nuclei with luminous buried AGN signatures in infrared spectra tend to show high HCN(1-0)/HCO+(1-0) brightness-temperature ratios, as seen in AGNs, while starburst-classified LIRG nuclei in infrared spectra display small ratios, as observed in starburst-dominated galaxies. Our new results further support the argument that the HCN(1-0)/HCO+(1-0) brightness-temperature ratio can be used to observationally separate AGN-important and starburst-dominant galaxy nuclei.Comment: 25 pages (emulateapj.cls), 12 figures, accepted for publication in Astronomical Journal (March 2009 issue). Higher resolution version is available at http://optik2.mtk.nao.ac.jp/~imanishi/Paper/HCN3/HCN3emu.pd

Subaru and Gemini High Spatial Resolution Infrared 18 Micron Imaging Observations of Nearby Luminous Infrared Galaxies

We present the results of a ground-based, high spatial resolution infrared 18 micron imaging study of nearby luminous infrared galaxies (LIRGs), using the Subaru 8.2-m and Gemini South 8.1-m telescopes. The diffraction-limited images routinely achieved with these telescopes in the Q-band (17-23 micron) allow us to investigate the detailed spatial distribution of infrared emission in these LIRGs. We then investigate whether the emission surface brightnesses are modest, as observed in starbursts, or are so high that luminous active galactic nuclei (AGNs; high emission surface brightness energy sources) are indicated. The sample consists of 18 luminous buried AGN candidates and starburst-classified LIRGs identified in earlier infrared spectroscopy. We find that the infrared 18 micron emission from the buried AGN candidates is generally compact, and the estimated emission surface brightnesses are high, sometimes exceeding the maximum value observed in and theoretically predicted for a starburst phenomenon. The starburst-classified LIRGs usually display spatially extended 18 micron emission and the estimated emission surface brightnesses are modest, within the range sustained by a starburst phenomenon. The general agreement between infrared spectroscopic and imaging energy diagnostic methods suggests that both are useful tools for understanding the hidden energy sources of the dusty LIRG population.Comment: 17 pages, 3 figures, accepted for publication in AJ (No. 141, 2011 May issue). Higher resolution version is available at http://optik2.mtk.nao.ac.jp/~imanishi/Paper/20um/20um.pd

SORL1 Is Genetically Associated with Late-Onset Alzheimer’s Disease in Japanese, Koreans and Caucasians

To discover susceptibility genes of late-onset Alzheimer’s disease (LOAD), we conducted a 3-stage genome-wide association study (GWAS) using three populations: Japanese from the Japanese Genetic Consortium for Alzheimer Disease (JGSCAD), Koreans, and Caucasians from the Alzheimer Disease Genetic Consortium (ADGC). In Stage 1, we evaluated data for 5,877,918 genotyped and imputed SNPs in Japanese cases (n = 1,008) and controls (n = 1,016). Genome-wide significance was observed with 12 SNPs in the APOE region. Seven SNPs from other distinct regions with p-values ,261025 were genotyped in a second Japanese sample (885 cases, 985 controls), and evidence of association was confirmed for one SORL1 SNP (rs3781834, P=7.3361027 in the combined sample). Subsequent analysis combining results for several SORL1 SNPs in the Japanese, Korean (339 cases, 1,129 controls) and Caucasians (11,840 AD cases, 10,931 controls) revealed genome wide significance with rs11218343 (P=1.7761029) and rs3781834 (P=1.0461028). SNPs in previously established AD loci in Caucasians showed strong evidence of association in Japanese including rs3851179 near PICALM (P=1.7161025) and rs744373 near BIN1 (P = 1.3961024). The associated allele for each of these SNPs was the same as in Caucasians. These data demonstrate for the first time genome-wide significance of LOAD with SORL1 and confirm the role of other known loci for LOAD in Japanese. Our study highlights the importance of examining associations in multiple ethnic populations

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

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