CaCO₃ mineralization in polymer composites with cellulose nanocrystals providing a chiral nematic mesomorphic structure

CaCO₃ mineralization was carried out using cellulose nanocrystal (CNC)/polymer composites wherein a chiral nematic structure of CNC assembly was immobilized in advance via a polymerization process of the precursory aqueous CNC/vinyl monomer lyotropics (7–11 wt% CNC in feed). Two series of polymer composites were prepared: CNC/poly(2-hydroxyethyl methacrylate) (PHEMA) and CNC/poly(2-hydroxyethyl methacrylate-co-acrylic acid) (P(HEMA-co-AA), HEMA:AA = 95:5–70:30 in mol). The mineralization was allowed to proceed solely by soaking the composite films in a salt solution containing Ca²⁺ and HCO₃− under a low-basic condition (pH ≤ 9). Polymorphism of CaCO3 deposited inside the films was examined by X-ray diffractometry as a function of the soaking time (1–5 day) and also of the matrix composition. In the CNC/PHEMA series, the polymorphic form changed from amorphous calcium carbonate (ACC) (1-day soaking) to metastable crystalline vaterite (3-day soaking) and then to a mixture of vaterite and aragonite (5-day soaking). In the mineralization of the CNC/P(HEMA-co-AA) series, the formation of stable calcite was prominent besides minor appearance of vaterite. It was deduced that the mesofiller CNC and the AA unit in the vinyl polymer, both bearing an anionic group (-SO₃− or -COO−), contributed to capturing Ca²⁺ to facilitate the CaCO₃ deposition in the swollen film matrix. The pre-invested chiral nematic organization was kept in any of the mineralized films (dried); however, the helical pitch was appreciably reduced relative to that observed before the mineralization, attributable to the increase of ionic strength in the CNCs' surroundings accompanied by the wet process. Thermogravimetry showed that the mineralization definitely improved the thermal performance (heat/flame resistance) of the mesomorphic order-retaining CNC/polymer composites

Strategies of Impoliteness in Japanese Spontaneous Talks

If, on the one hand, Japanese language, with its richness of marked allomorphs used for honorifics, has been considered one of the most attractive languages to investigate the phenomenon of politeness, on the other hand, a very small number of studies have been devoted to Japanese impoliteness, most of them limited to BBSs’ (Bulletin Board System) chats on Internet. Interestingly, Japanese native speakers declare, in general, that their language has a very limited number of offensive expressions and that ‘impoliteness’ is not a characteristic of their mother tongue. I tried to analyse some samples of spontaneous conversations taken from YouTube and other multimedia repertoires, in order to detect the main strategies used in Japanese real conversations to cause offence or to show a threatening attitude toward the partner’s face. It seems possible to state that, notwithstanding the different ‘cultural’ peculiarities, impoliteness shows, also in Japanese, a set of strategies common to other languages and that impoliteness, in terms of morphology, is not a mirror counterpart of keigo

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

KCNE1の遺伝子多型であるD85NはQT延長症候群の発症に関与する

京都大学0048新制・課程博士博士(医学)甲第15937号医博第3522号新制||医||985(附属図書館)28516京都大学大学院医学研究科医学専攻(主査)教授 松田 文彦, 教授 坂田 隆造, 教授 川村 孝学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Genetic Background of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy: Time to Start Asian Registry!

AbstractArrhythmogenic right venticular dysplasia/cardiomyopathy (ARVD/C) is an inherited cardiomyopathy with a very low penetrance affecting the right ventricle (RV) and presenting palpitation and syncope due to ventricular tachycardia (VT) originating from RV. The VT can degenerate into ventricular fibrillation and sudden cardiac death. The genetic background of ARVD/C has recently been found to be heterogeneous, mainly resulting from cell adhesion abnormalities due to mutations in five different genes encoding members of the desmosome complex. In Asian countries, however, the genetic aspect of the disease has not been fully studied, although the clinical features of Asian ARVD/C patients are different from those in Western countries in the penetrance of phenotypes, relation to Brugada syndrome and link to RV outflow tract ventricular tachycardia. It is of urgent need to have a registry of Asian ARVD/C patients and to conduct a more detailed genetic survey on the candidate genes, including desomosomal ones

The structural differences between α glycoprotein specific F-box protein Fbs1 and its homologous protein FBG3

The Skp1-Cul1-F-box protein (SCF) complex catalyzes protein ubiquitination in diverse cellular processes and is one of the best-characterized ubiquitin ligases. F-box proteins determine the substrate specificities of SCF ubiquitin ligases. Among these, Fbs1/FBG1/FBXO2, Fbs2/FBG2/FBXO6, and Fbs3/FBG5/FBXO27 recognize the N-glycans of glycoproteins, whereas FBG3/FBXO44 has no sugar-binding activity, despite the high sequence homology and conservation of the residues necessary for oligosaccharide binding between Fbs1.3 and FBG3. Here we determined the crystal structure of the Skp1.FBG3 complex at a resolution of 2.6 A. The substrate-binding domain of FBG3 is composed of a 10-stranded antiparallel β-sandwich with three helices. Although the overall structure of FBG3 is similar to that of Fbs1, the residues that form the Fbs1 carbohydrate-binding pocket failed to be superposed with the corresponding residues of FBG3. Structure-based mutational analysis shows that distinct hydrogen bond networks of four FBG3 loops, i.e., β2-β3, β5-β6, β7-β8, and β9-β10, prevent the formation of the carbohydrate-binding pocket shown in Fbs1