X-ray spectral variations of Circinus X-1 observed with NICER throughout an entire orbital cycle

Circinus X-1 (Cir X-1) is a neutron star binary with an elliptical orbit of 16.6~days. The source is unique for its extreme youth, providing a key to understanding early binary evolution. However, its X-ray variability is too complex to reach a clear interpretation. We conducted the first high cadence (every 4 hours on average) observations covering one entire orbit using the NICER X-ray telescope. The X-ray flux behavior can be divided into stable, dip, and flaring phases. The X-ray spectra in all phases can be described by a common model consisting of a partially covered disk black body emission and the line features from a highly-ionized photo-ionized plasma. The spectral change over the orbit is attributable to rapid changes of the partial covering medium in the line-of-sight and gradual changes of the disk black body emission. Emission lines of the H-like and He-like Mg, Si, S, and Fe are detected, most prominently in the dip phase. The Fe emission lines change to absorption in the course of the transition from the dip phase to the flaring phase. The estimated ionization degree indicates no significant changes, suggesting that the photo-ionized plasma is stable over the orbit. We propose a simple model in which the disk black body emission is partially blocked by such a local medium in the line-of-sight that has spatial structures depending on the azimuth of the accretion disk. Emission lines upon the continuum emission are from the photo-ionized plasma located outside of the blocking material.Comment: Accepted for publication in ApJ, 16 pages, 7 figure

DNA Methylation Suppresses Leptin Expression in Adipocytes

Leptin is a key regulator of energy intake and expenditure. This peptide hormone is expressed in mouse white adipose tissue, but hardly expressed in 3T3-L1 adipocytes. Using bisulfite sequencing, we found that CpG islands in the leptin promoter are highly methylated in 3T3-L1cells. 5-azacytidine, an inhibitor of DNA methyltransferase, markedly increased leptin expression as pre-adipocytes matured into adipocytes. Remarkably, leptin expression was stimulated by insulin in adipocytes derived from precursor cells exposed to 5-azacytidine, but suppressed by thiazolidinedione and dexamethasone. In contrast, adipocytes derived from untreated precursor cells were unresponsive to both 5-azacytidine and hormonal stimuli, although lipid accumulation was sufficient to boost leptin expression in the absence of demethylation. Taken together, the results suggest that leptin expression in 3T3-L1 cells requires DNA demethylation prior to adipogenesis, transcriptional activation during adipogenesis, and lipid accumulation after adipogenesis

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

Relationship between Oral Health Status and Bone Mineral Density in Community-Dwelling Elderly Individuals: A Cross-Sectional Study

The relationship between oral health status and bone mineral density has been poorly elucidated. We conducted a cross-sectional study to examine the relationship between oral health status and bone mineral density with data from healthy community-dwelling elderly individuals in Ohnan-cho, Shimane Japan who were recruited in 2019 for the Shimane Center for Community-Based Health Research and Education (CoHRE) study. The study included 702 participants (306 men and 396 women). The median age, bone mineral density, and number of remaining teeth were 69.0 years, 86.2%, and 26.0, respectively. The two groups (Low teeth group and High teeth group) showed significant differences in age, hemoglobin A1c (HbA1c) level, and masticatory function in men (p < 0.05). In women, age, number of untreated teeth, and masticatory function were significantly different (p < 0.05). The odds ratio of propensity score analysis for the association between the number of remaining teeth and bone mineral density was 27.7 (95% confidence interval: 1.86–414.9, p < 0.05). The number of remaining teeth could be associated with bone mineral density in the healthy elderly women, and no significant association was observed in men. Number of remaining teeth and bone mineral density may be interrelated, and oral care by dentists/dental hygienists may play an important role in maintaining bone mineral density in elderly women

DNA Methylation Suppresses Leptin Gene in 3T3-L1 Adipocytes

<div><p>Leptin is a key regulator of energy intake and expenditure. This peptide hormone is expressed in mouse white adipose tissue, but hardly expressed in 3T3-L1 adipocytes. Using bisulfite sequencing, we found that CpG islands in the leptin promoter are highly methylated in 3T3-L1cells. 5-azacytidine, an inhibitor of DNA methyltransferase, markedly increased leptin expression as pre-adipocytes matured into adipocytes. Remarkably, leptin expression was stimulated by insulin in adipocytes derived from precursor cells exposed to 5-azacytidine, but suppressed by thiazolidinedione and dexamethasone. In contrast, adipocytes derived from untreated precursor cells were unresponsive to both 5-azacytidine and hormonal stimuli, although lipid accumulation was sufficient to boost leptin expression in the absence of demethylation. Taken together, the results suggest that leptin expression in 3T3-L1 cells requires DNA demethylation prior to adipogenesis, transcriptional activation during adipogenesis, and lipid accumulation after adipogenesis.</p></div

Simulations of systematic effects arising from cosmic rays in the LiteBIRD space telescope, and effects on the measurements of CMB B-modes

International audienceSystematic effects arising from cosmic rays have been shown to be a significant threat to space telescopes using high-sensitivity bolometers. The LiteBIRD space mission aims to measure the polarised Cosmic Microwave Background with unprecedented sensitivity, but its positioning in space will also render it susceptible to cosmic ray effects. We present an end-to-end simulator for evaluating the expected scale of cosmic ray effects on the LiteBIRD space mission, which we demonstrate on a subset of detectors on the 166 GHz band of the Low Frequency Telescope. The simulator couples the expected proton flux at L2 with a model of the thermal response of the LFT focal plane and the electrothermal response of its superconducting detectors, producing time-ordered data which is projected into simulated sky maps and subsequent angular power spectra