Recognition of acrolein-specific epitopes by B cell receptors triggers an innate immune response

peer reviewedNatural antibodies, predominantly immunoglobulin M (IgM), play an important role in the defense against pathogens and in maintaining homeostasis against oxidized molecules known as oxidation-specific epitopes, such as those contained in oxidized low-density lipoproteins. However, owing to the complexity of the oxidized products, very few individual epitopes have been characterized in detail. In the present study, to identify endogenous sources of oxidation-specific epitopes, we stimulated mouse spleen and peritoneal cavity (PerC) cells in vitro with bovine serum albumin modified with a variety of lipid peroxidation–related carbonyl compounds and identified the acrolein-modified bovine serum albumin as the most efficient trigger studied for the production of IgM in PerC cells. The acrolein-specific epitopes accelerated the differentiation of B-1a cells, a fetal-derived B cell lineage, to plasma cells. In addition, acrolein-modified bovine serum albumin was specifically bound to B-1a cells, suggesting the presence of an acrolein-specific IgM–B cell receptor (BCR). A hybridoma, RE-G25, producing an acrolein-specific IgM, was established from the PerC cells and was indeed identified as a population of B cells expressing a specific IgM–BCR. In addition, we analyzed the BCR repertoire of acrolein-specific B cells and identified the most frequent IgM heavy chain gene segments of the B cells. These data established the presence of innate B cells expressing the acrolein-specific BCR and suggested that in addition to our understanding of acrolein as a toxic aldehyde, it may play a role as a trigger of the innate immune response

Further expansion of distributional range of an introduced spider Badumna insignis in the eastern part of Tottori Prefecture (Results of the surveys in 2017).

2017 年の夏から秋にかけて鳥取県の東部を中心として外来種のクロガケジグモ（クモ目ウシオグモ科）の分布範囲を調査した。これまで本種が未確認の鳥取県西部でも数地点（境港市，米子市，大山町，日南町）調べたが，今回も生息は確認できなかった。鳥取県東部では，既知生息範囲から遠く離れた若桜町内や岩美町内でもそれぞれ1 地点で生息を確認した。離れているこれら2 地点を除いたほぼ連続的と考えられる鳥取市周辺の本種の今回の生息確認範囲は2014 年における生息確認範囲よりも広く，西は国道9 号線沿いの白兎海岸，南は国道53 号沿いに河原町布袋，国道29 号線沿いに八頭町下坂まで伸びていた（西へは約2.5 km，南には約6 km 拡大）。いっぽう，交通量の少ない鳥取市南西側の県道沿いには新規の拡大はみられず，本種の分布域の拡大に人の移動や物流が関係していることを示唆した。本種が生息する地点では在来種のクモの個体数が減少していた。クロガケジグモの個体数の多さが目立つのは，早くから本種の生息域となっている湖山町周辺が含まれる千代川以西・国体道路以北の鳥取市街地であった。 We surveyed distribution of an introduced spider Badumna insignis (Araneae: Desidae) in Tottori Prefecture in 2017. There were no sites where B. insignis was found in the western part of Tottori Prefecture, as reported in the former surveys. On the other hand, we found the species in Iwami-cho and Wakasa-cho, where B. insignis had not been found. Continuous range of distribution of the species in Tottori City expanded ca. 2.5 km toward west along the national route 9, and ca. 6 km toward south, along major national routes (Routes 29 and 53). On the other hand, there was no expansion of the species toward southwestern part of the city where only prefectural roads with a few traffic extend. These facts suggest that human movements and logistics help expansion of the spider. The individual number of native spiders at sites where B. insignis inhabits was much fewer than that at sites without B. insignis

Flame-retardant thermoplastics derived from plant cell wall polymers by single ionic liquid substitution

金沢大学理工研究域生命理工学系Three components of plant cell walls—cellulose, hemicellulose and lignin—were converted into flame-retardant thermoplastics by adducting only a single ionic liquid species via covalent bonds. They showed thermoplasticity and formed thin films by hot pressing. They also showed flame retardancy and self-extinguished the fire during burning. The properties of the samples depend on the cation species of ionic liquids adducted and thus are controllable. In the present study, more than 66% of the hydroxyl groups present on the polymers were maintained after derivatisation; they thus have the potential for further functionalisation for moulding, practical use and so on, in addition to flame retardancy and thermoplasticity.Embargo Period 12 monthsThis paper has supplementary information

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

Bilateral vertebral artery dissection extending to the left posterior cerebral artery: A case report

Intracranial artery dissection accounts for a small percentage (1%-2%) of all ischemic strokes. Vertebral artery dissection sometimes extends to the basilar artery but very rarely to the posterior cerebral artery. We report a case of bilateral vertebral artery dissection extending to the left posterior cerebral artery with the characteristic distribution of intramural hematoma. A 51-year-old woman presented with right hemiparesis and dysarthria 3 days after sudden neck pain. Magnetic resonance imaging on admission revealed infarcts in the left thalamus and temporo-occipital lobe and findings suggestive of bilateral vertebral artery dissection. No infarct was detected in the brainstem. The patient was treated conservatively. Initially, we suspected that infarction in the left posterior cerebral artery territory had been caused by artery-to-artery embolism from the dissected vertebral arteries. However, T1-weighted imaging on day 15 of admission revealed intramural hematoma extending from the left vertebral artery to the left posterior cerebral artery. Therefore, we diagnosed bilateral vertebral artery dissection extending to the basilar artery and the left posterior cerebral artery. The patient's symptoms subsequently improved with conservative treatment, and she was discharged with a modified Rankin Scale score of 1 on day 62 of admission. In this case, intramural hematoma of the basilar artery was found in the anterior vessel wall. Brainstem infarction is less likely when intramural hematoma is located in the anterior vessel wall of the basilar artery in vertebrobasilar artery dissection. T1-weighted imaging is useful for the diagnosis of this rare condition and can predict potentially impaired branches and possible symptoms

Involvement of Galectin-3 with Vascular Cell Adhesion Molecule-1 in Growth Regulation of Mouse BALB/3T3 Cells*

β-Galactose residues on N-glycans have been implicated to be involved in growth regulation of cells. In the present study we compared the galactosylation of cell surface N-glycans of mouse Balb/3T3 cells between 30 and 100% densities and found the β-1,4-galactosylation of N-glycans increases predominantly in a 100-kDa protein band on lectin blot analysis in combination with digestions by diplococcal β-galactosidase and N-glycanase. When cells at 100% density were treated with jack bean β-galactosidase, the incorporation of 5-bromodeoxyuridine into the cells was stimulated in a dose-dependent manner, suggesting the involvement of the galactose residues in growth regulation of cells. A galactose-binding protein was isolated from the plasma membranes of cells at 100% density by affinity chromatography using an asialo-transferrin-Sepharose column and found to be galectin-3 as revealed by mass spectrometric analysis. The addition of recombinant galectin-3 into cells at 50% density inhibited the incorporation of 5-bromodeoxyuridine in a dose-dependent manner, but the inhibition was prevented with haptenic sugar. An immunocytochemical study showed that galectin-3 is present at the surface of cells at 100% density but not at 30% density where it locates inside the cells. Several glycoproteins bind to a galectin-3-immobilized column, a major of which was identified as vascular cell adhesion molecule (VCAM)-1. Immunocytochemical studies showed that some galectin-3 and VCAM-1 co-localize at the surface of cells at 100% density, indicating that the binding of galectin-3 secreted from cells to VCAM-1 is one of the pathways involved in the growth regulation of Balb/3T3 cells