The Perspective of Symbiosis in Japanese Business in China

「共生(symbiosis)」という言葉が新たに着目されるようになってきた。しかし明確な定義があるわけではない。ただし、現在は社会の中で「共生」という言葉がいろいろなところで用いられる。たとえば、個人と個人との共生、個人と組織(代表的には企業)との共生、組織と組織(企業と企業)との共生、国家と国家との共生、民族と民族との共生などさまざまである。本稿は企業の「共生」問題を中国に進出した日系企業の活動を通して論じる。研究対象は当然、中国に進出した日系企業であり、研究の方法は暫定的に企業の「共生」のフレームワークを仮定し、それに基づいて現時点で中国に進出した日系企業が「共生」活動をどのように考え、そしてどのように実施しているかを明らかにする。「共生」活動のデータはわれわれが2005年10月に実施した中国藩陽市に進出している日系企業に対するインタビュー調査において収集したものである

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

Mass Spectrometry Imaging of Flavonols and Ellagic Acid Glycosides in Ripe Strawberry Fruit

Flavonols and ellagic acid glycosides are major phenolic compounds in strawberry fruit. They have antioxidant activity, show protective functions against abiotic and biotic stress, and provide health benefits. However, their spatial distribution in ripe fruit has not been understood. Therefore, matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry imaging (MSI) was performed to investigate their distribution in fruit tissues. Using strawberry extract, five flavonols, namely, three kaempferols and two quercetins, and two ellagic acid glycosides, were tentatively identified by MALDI-tandem MS. To investigate the tentatively identified compounds, MALDI-MSI and tandem MS imaging (MS/MSI) analyses were performed. Kaempferol and quercetin glycosides showed similar distribution patterns. They were mainly found in the epidermis, while ellagic acid glycosides were mainly found in the achene and in the bottom area of the receptacle. These results suggested that the difference in distribution pattern between flavonols and ellagic acid glycosides depends on the difference between their aglycones. Seemingly, flavonols play a role in protective functions in the epidermis, while ellagic acid glycosides play a role in the achene and in the bottom side of the receptacle, respectively. These results demonstrated that MALDI-MSI is useful for distribution analysis of flavonols and ellagic acid glycosides in strawberry fruit

ラット前立腺におけるエストロゲン結合物質の性状

前立腺腫瘍の治療としてエストロゲン投与がおこなわれるが， その作用機序を明らかにする手始めとして，去勢ラット腹側前立腺の胞体可溶分画および核におけるエストロゲン結合物質の性状について検討を加えた。その結果，次の諸点が明らかとなった. (1)各臓器の胞体可溶分商を得た後，それに対する放射性エストラジオールー17βの結合を炭末吸着法によって検討すると，前立腺において最もよく結合し，続いて肝臓，腎臓，精巣，精嚢の順となり，骨格筋にはわずかしか結合しなかった. (2)前立腺可溶分画を放射性エストラジオールー17βのみ， あるいはそれに非放射性の各種ステロイドを加えてインキュペーションした後，ポリアクリルアミドゲル電気泳動法によって分析を加えると， エストロゲンに特異的に結合するものと，ステロイド特異性のないものの2種の物質が認められた。ともに血清タンパクの混入によるものではない。また炭末吸着法を用いたスキャッチヤード・プロット分析によって，結合部位数および解離定数を求めると，それぞれ9.3x10[-16]モル/mgタンパクKd=2.2 X 10[-11]M と計算された. (3)前立腺組織細片を放射性エストラジオールー17βを含む培養液でインキュベーションした場合でも，核抽出液および胞体可溶分画中に2種の結合物質が認められた. (4)放射性エストラジオールー17βとインキュベーションした組織から得た核と担体可溶分画に対して，薄層クロマトグラフィーによってステロイド分析をおこなうと，胞体可溶分画においては， エストラジオールー17βの多くがエストロンに変換されているが，核においてはその多くがエストラジオールー17βのままで寄在することが明らかになった。これらの結果は，去勢ラットの腹側前立腺に，結合部位数が少なくエストロゲンに親和性の高い高分子物質の存在を強く示唆している。Polyacrylamide gel electrophoresis, dextran-coated charcoal adsorption, Sephadex gel filtration and thin-layer chromatography allowed us to attempt the characterization of estrogen-binding components in the castrated rat prostate. The results are as follows: 1) Among various tissue cytosols examined, the ventral prostate cytosol showed the highest binding of 3H-estradiol-17β, followed by the cytosols of the liver, kidney, testis, seminal vesicle and skeletal muscle. 2) After incubation of the ventral prostate cytosol with [3]H-estradiol-17βin the absence or the presence of various unlabeled steroids, a specific estrogen-binding material was found with low binding capacity and high affinity for this hormone. This binding was found not due to the contamination of blood serum proteins. 3) After incubation of the ventral prostate with [3]H-estradiol-17β, estrogen-binding material was also found both in the cytosol and in the nucleus of the tissue. 4) Using the thin-layer chromatographic technique it was found that estrone and estradiol-1 7βoccupied most of the radioactivity in various subcellular fractions obtained from the ventral prostate incubated with 3H-estradiol-17β, and the ratio of estradiol: estrone was highest in the nucleus, followed by the binding component of the cytosol and the cytosol. These results may suggest that there is a specific low capacity-high affinity estrogenbinding component in the adult rat prostate

Novel Blotting Method for Mass Spectrometry Imaging of Metabolites in Strawberry Fruit by Desorption/Ionization Using Through Hole Alumina Membrane

Mass spectrometry imaging (MSI) using matrix-assisted laser desorption/ionization (MALDI) is a powerful technique for visualizing metabolites in the strawberry fruit. During sample preparation for MALDI-MSI, sectioning of the samples is usually required. In general, MALDI-MSI analysis of strawberry fruits that are larger than a single glass slide is difficult because thin sections cannot be prepared. In this study, we attempted to visualize metabolites in large strawberry fruits by MSI, employing a blotting method that uses desorption ionization using a through-hole alumina membrane (DIUTHAME) chip. Large strawberry fruits were cut and a DIUTHAME chip was set on the cross-section to blot the metabolites. After drying the DIUTHAME chip, the metabolites were measured in positive and negative ion modes using a commercial MALDI-type mass spectrometer. Several peaks were detected in both the ion modes. Various metabolites related to food quality, such as sugars, organic acids, and anthocyanins, were detected and successfully visualized by blotting on a DIUTHAME chip in MSI. These results suggest that blotting using a DIUTHAME chip in MSI is useful for visualizing the metabolites present in the strawberry fruit

Unique Distribution of Diacyl-, Alkylacyl-, and Alkenylacyl-Phosphatidylcholine Species Visualized in Pork Chop Tissues by Matrix-Assisted Laser Desorption/Ionization–Mass Spectrometry Imaging

Phosphatidylcholine (PC) is the major phospholipid in meat and influences meat qualities, such as healthiness. PC is classified into three groups based on the bond at the sn-1 position: Diacyl, alkylacyl, and alkenylacyl. To investigate their composition and distribution in pork tissues, including longissimus thoracis et lumborum (loin) spinalis muscles, intermuscular fat, and transparent tissues, we performed matrix-assisted laser desorption/ionization–mass spectrometry imaging (MALDI–MSI). Eleven diacyl-, seven alkylacyl-, and six alkenylacyl-PCs were identified using liquid chromatography (LC)-tandem MS (MS/MS) analysis. Despite many alkylacyl- and alkenylacyl-PC species sharing identical m/z values, we were able to visualize these PC species using MALDI–MSI. Diacyl- and alkylacyl- and/or alkenylacyl-PC species showed unique distribution patterns in the tissues, suggesting that their distribution patterns were dependent on their fatty acid compositions. PCs are a major dietary source of choline in meat, and the amount was significantly higher in the muscle tissues. Consumption of choline mitigates age-related memory decline and neurodegenerative diseases; therefore, the consumption of pork muscle tissues could help to mitigate these diseases. These results support the use of MALDI–MSI analysis for assessing the association between PC species and the quality parameters of meat