Construction of Ribonuclease-Decorated Artificial Virus-like Capsid by Peptide Self-assembly

Artificial virus-like capsids decorated with ribonuclease S (RNase S) on their exterior were constructed by the self-assembly of β-annulus-S-peptide and the interaction between S-peptide moiety and S-protein. The β-annulus-S-peptide was synthesized by native chemical ligation of β-annulus-SBz peptide with Cys-containing S-peptide that self-assembled into artificial virus-like capsids of approximately 47 nm in size. Reconstruction of RNase S on the artificial virus-like capsids afforded spherical assembly attached small spheres on the surface, which retained ribonuclease activity

measurement of the 30 s α system for type i x ray bursts

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Overexpression of Chitinase 3-Like 1/YKL-40 in Lung-Specific IL-18-Transgenic Mice, Smokers and COPD

We analyzed the lung mRNA expression profiles of a murine model of COPD developed using a lung-specific IL-18-transgenic mouse. In this transgenic mouse, the expression of 608 genes was found to vary more than 2-fold in comparison with control WT mice, and was clustered into 4 groups. The expression of 140 genes was constitutively increased at all ages, 215 genes increased gradually with aging, 171 genes decreased gradually with aging, and 82 genes decreased temporarily at 9 weeks of age. Interestingly, the levels of mRNA for the chitinase-related genes chitinase 3-like 1 (Chi3l1), Chi3l3, and acidic mammalian chitinase (AMCase) were significantly higher in the lungs of transgenic mice than in control mice. The level of Chi3l1 protein increased significantly with aging in the lungs and sera of IL-18 transgenic, but not WT mice. Previous studies have suggested Chi3l3 and AMCase are IL-13-driven chitinase-like proteins. However, IL-13 gene deletion did not reduce the level of Chi3l1 protein in the lungs of IL-18 transgenic mice. Based on our murine model gene expression data, we analyzed the protein level of YKL-40, the human homolog of Chi3l1, in sera of smokers and COPD patients. Sixteen COPD patients had undergone high resolution computed tomography (HRCT) examination. Emphysema was assessed by using a density mask with a cutoff of −950 Hounsfield units to calculate the low-attenuation area percentage (LAA%). We observed significantly higher serum levels in samples from 28 smokers and 45 COPD patients compared to 30 non-smokers. In COPD patients, there was a significant negative correlation between serum level of YKL-40 and %FEV1. Moreover, there was a significant positive correlation between the serum levels of YKL-40 and LAA% in COPD patients. Thus our results suggest that chitinase-related genes may play an important role in establishing pulmonary inflammation and emphysematous changes in smokers and COPD patients

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

Tuberculosis in foreign students in Japan, 2010–2014: a comparison with the notification rates in their countries of origin

This study characterizes the foreign students with tuberculosis (TB) registered in Japan from 2010 to 2014 and compares their TB notification rates with those in their countries of origin. The TB notification rates in foreign students were retrieved from the National Epidemiological Surveillance of Infectious Disease system in Japan. National TB notification data from 16 countries and areas were extracted from the World Health Organization’s and the official health websites of the countries and areas. There were 1128 foreign students in Japan who developed TB between 2010 and 2014; nearly half of the cases were from China (n = 530, 46.9%), and 688 (61.0%) were male with a median age of 23 years. The TB notification data for foreign students were highest in students from the Philippines (675/100 000 person years, 95% confidence interval: 372–977). The notification rates in foreign students from seven countries were significantly higher than the average notification rate in their countries of origin (China, Indonesia, Mongolia, Myanmar, Nepal, the Philippines and Viet Nam). The Republic of Korea and Taiwan, China had significantly lower rates in foreign students than in their countries of origin. The notification rates for foreign students in Japan may reflect a more accurate risk of developing TB among the immigrants to Japan than the TB notification rates in their countries of origin. These results may be helpful to identify the immigrants’ countries/areas of origin with the necessity of pre-entry TB screening

Evaluation of Harmonic Signals Derived From Multiple Spatially Separated Samples for Magnetic Particle Imaging

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Isolation of a major genetic interaction associated with an extreme phenotype using assorted F2 populations in rice

Detection of quantitative trait loci (QTLs) is dependent on the materials used in the analysis, as different combinations of parental materials may lead to different outcomes in QTLs for the same trait. On the other hand, an extreme phenotype associated with a given trait implies the potential involvement of a particular allele in various allelic interactions. A genetic factor associated with such an extreme phenotype may frequently be identified from various genetic populations consisting of different parental combinations. In this study, we attempted to uncover the genetic factor associated with extremely early heading date in rice, using various F2 populations. Heading date in rice has been characterized by at least 19 QTLs, from which 12 genes have been identified. A58, a rice strain with an extremely early heading date, is adapted to Hokkaido, the northernmost limit of rice cultivation. Six F2 populations derived from crosses of A58 with six other strains displayed a range of heading dates. Genotyping using 19 QTL markers indicated that the A58 allele of the Ghd7 locus was present in most F2 individuals exhibiting extremely early heading dates. This analysis also demonstrated that when the wild-type Ehd1 allele was present, the Ghd7 allele from A58 accelerated floral induction. The results of this study demonstrate that assorted F2 populations are valuable materials for comprehensive genotyping to explore major genetic factors for extreme phenotypes, and that this methodology is broadly applicable to other unknown traits

Chromatic Numbers of Quadrangulations on Closed Surfaces

It has been shown that every quadrangulation on any non-spherical orientable closed surface with a sufficiently large representativity has chromatic number at most 3. In this paper, we show that a quadrangulation G on a nonorientable closed surface N k has chromatic number at least 4 if G has a cycle of odd length which cuts open N k into an orientable surface. Moreover, we characterize the quadrangulations on the torus and the Klein bottle with chromatic number exactly 3. By our characterization, we prove that every quadrangulation on the torus with representativity at least 9 has chromatic number at most 3, and that a quadrangulation on the Klein bottle with representativity at least 7 has chromatic number at most 3 if a cycle cutting open the Klein bottle into an annulus has even length. As an application of our theory, we prove that every nonorientable closed surface N k admits an eulerian triangulation with chromatic number at least 5 which has arbitrarily large representativity