シクロデキストリンの調製と単離について(農芸化学部門)

Bacillus macerans IFO No. 3490を用いてシクロデキストリンの調製を行なった。個々のシクロデキストリンの生成比は用いる酵素量によって著しく影響されることが明らかになった。又個々のシクロデキストリンの単離法として, 水に対する各シクロデキストリンの溶解度の相違を従来用いられている複合体試薬による分離法に併用するのが有効であることが分った。The cyclodextrins were prepared from potato starch by the action of Bacillus macerans (IFO No. 3490) amylase. It was found that the ratio of the yields of the individual dextrins obtained is governed by the varying amounts of enzyme added. The combined use of the differences in solubility of the individual dextrins in water and selective precipitation with organic molecules greatly simplified the procedure of the isolation of the dextrins hitherto employed so that the dextrins can be more readlily available in both quautity and purity

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

Detection of nuclear tracks comprising gold grains in nuclear emulsion by using gold deposition development method

The gold deposition development method instead of the normal development method was applied to a nuclear track detector by using silver halide photography. Fine tracks formed by spherical gold grains were observed without any filaments. The grain size does not depend on the initial size of the silver halide crystals but only on the deposition period. This implies that the grain size can be adjusted to a size similar to the resolving power of an optical microscope in spite of the use of an ultra-fine crystal emulsion. In addition, the developer used in the gold deposition method does not contain harmful organic reagents, and it contains a lower amount of inorganic salts than normal developers. The solution can be safely handled and the disposing treatment of the solution is easy

Dispersion of Latent Image Specks in Silver-salt Photographic Materials Formed by Exposure to an Electron Beam with Constant Energy

The system used to analyze the process of the formation of latent image specks (LISs) in silver-salt photographic materials due to radiation exposure to obtain the dispersion index, which is the number of LISs in a silver halide grain formed by one impact of high-energy particle, was improved. By using the electron beam from a transmission electron microscope, electrons of uniform energy could be produced for irradiation purposes. The number of electrons impacting a single silver halide grain along with the energy of each electron was controlled by varying the current density and the applied voltage. A new analysis method which included the probability that LIS may not be formed despite an impact of high-energy particle was proposed. The number of LISs was counted by the arrested development method. The probability and the dispersion index were estimated at approximately 0.5 and 1, respectively, for an unsensitized emulsion with cubic grains. This method will be useful in the design of new nuclear emulsion plates

Myocardial beta-Adrenergic Receptor Density Assessed by 11C-CGP12177 PET Predicts Improvement of Cardiac Function After Carvedilol Treatment in Patients with Idiopathic Dilated Cardiomyopathy

We evaluated whether myocardial b-adrenergic receptor (b-AR) density, as determined by 11C-CGP12177 PET, could predict improvement of cardiac function by b-blocker carvedilol treatment in patients with idiopathic dilated cardiomyopathy (IDC). Methods: Ten patients with IDC (left ventricular ejection fraction [LVEF] , 45%) were studied. Myocardial b-AR density was estimated using 11C-CGP12177 PET before treatment with carvedilol. Changes of LVEF in response to dobutamine infusion (DLVEF-dobutamine) were also measured by echocardiography. Changes of LVEF (DLVEF-carvedilol) were evaluated after 20 mo of carvedilol treatment. Results: Baseline myocardial b-AR density significantly correlated with DLVEF-carvedilol (r 5 20.88, P , 0.001). In contrast, DLVEF-dobutamine did not correlate with DLVEF-carvedilol (P50.65).Myocardial b-ARdensitywas the significant multivariate independent predictor of DLVEF-carvedilol (b 5 20.88, P , 0.001) among univariate predictors, including functional class (r 5 0.76, P , 0.05), plasma norepinephrine (r 5 0.85, P,0.01), LVEF (r520.64, P,0.05), and age as confounding factors. Furthermore, myocardial b-AR density was significantly correlated with plasma norepinephrine (r 5 20.79, P , 0.01) and LVEF (r 5 0.70, P , 0.05). Conclusion: Myocardial b-AR density is more tightly related to improvement of LVEFcarvedilol than is cardiac contractile reserve in patients with IDC. Patients with decreased myocardial b-AR have higher resting adrenergic drive, as reflected by plasma norepinephrine, and may receive greater benefit from being treated by antiadrenergic drugs