Diagnosis of renal AL amyloidosis using DAPI

Amyloidosis is often overlooked because its clinical manifestations can mimic those of more-common diseases. It is important to get a precise diagnosis as early as possible for the prevention of further organ damages. Amyloidosis is a disorder caused by deposition of insoluble abnormal amyloid. The kidney is a frequent site of amyloid deposition. The amyloid fibrils have a characteristic appearance and generate birefringence under polarized light when stained with the Congo red dye. Classification of amyloidosis is based on the precursor protein that forms the amyloid fibrils and the distribution of amyloid deposits as either systemic or localized. Involvement of amyloid fibrils in kidneys mainly occurs as amyloid light-chain (AL) or amyloid A (AA) amyloidosis. The potassium permanganate method with Congo red staining was once used widely to discriminate AL and AA amyloidoses, but thismethod has a problem of false positive results. We found that extracellular and cytoplasmic glomerular 4’,6-diamidino-2-phenylindole (DAPI)-positive areas were clearly consistent with amyloid deposition in AL amyloidosis. In contrast, the overlapping staining was not seen in AA amyloidosis. Therefore, we propose that DAPI staining readily distinguishes AL renal amyloidosis from AA renal amyloidosis as a simple and reproducible histochemical method

Fabp7 Maps to a Quantitative Trait Locus for a Schizophrenia Endophenotype

Deficits in prepulse inhibition (PPI) are a biological marker for schizophrenia. To unravel the mechanisms that control PPI, we performed quantitative trait loci (QTL) analysis on 1,010 F2 mice derived by crossing C57BL/6 (B6) animals that show high PPI with C3H/He (C3) animals that show low PPI. We detected six major loci for PPI, six for the acoustic startle response, and four for latency to response peak, some of which were sex-dependent. A promising candidate on the Chromosome 10-QTL was Fabp7 (fatty acid binding protein 7, brain), a gene with functional links to the N-methyl-D-aspartic acid (NMDA) receptor and expression in astrocytes. Fabp7-deficient mice showed decreased PPI and a shortened startle response latency, typical of the QTL's proposed effects. A quantitative complementation test supported Fabp7 as a potential PPI-QTL gene, particularly in male mice. Disruption of Fabp7 attenuated neurogenesis in vivo. Human FABP7 showed altered expression in schizophrenic brains and genetic association with schizophrenia, which were both evident in males when samples were divided by sex. These results suggest that FABP7 plays a novel and crucial role, linking the NMDA, neurodevelopmental, and glial theories of schizophrenia pathology and the PPI endophenotype, with larger or overt effects in males. We also discuss the results from the perspective of fetal programming

Identification of 45 New Neutron-Rich Isotopes Produced by In-Flight Fission of a 238U Beam at 345 MeV/nucleon

A search for new isotopes using in-flight fission of a 345 MeV/nucleon 238U beam has been carried out at the RI Beam Factory at the RIKEN Nishina Center. Fission fragments were analyzed and identified by using the superconducting in-flight separator BigRIPS. We observed 45 new neutron-rich isotopes: 71Mn, 73,74Fe, 76Co, 79Ni, 81,82Cu, 84,85Zn, 87Ga, 90Ge, 95Se, 98Br, 101Kr, 103Rb, 106,107Sr, 108,109Y, 111,112Zr, 114,115Nb, 115,116,117Mo, 119,120Tc, 121,122,123,124Ru, 123,124,125,126Rh, 127,128Pd, 133Cd, 138Sn, 140Sb, 143Te, 145I, 148Xe, and 152Ba

CLD セイト ノ キョウイク ニ タイスル コウコウ キョウシ ノ ビリーフ ヘンヨウ ニゲンゴ サクブン アセスメント ヲ トオシテ

文化的言語的に多様な生徒（以下、CLD生徒）の教育では、教授言語の発達のみならず、母語・継承語として生徒が持つ言語資源の活用の重要性が指摘されているが、国内の教育現場においてはそうした考え方はいまだに広く浸透するに至らず、理論と実践の統合が課題となっている。本研究では外国人集住地区にある公立高校で二言語作文アセスメントを実施したことをきっかけに、様々な立場でCLD生徒に関わる３人の教員がどのように教師ビリーフを変容させたのか、質的に分析した結果を報告する。分析の結果、二言語作文アセスメントを通じて、異なる立場の３人の教師にそれぞれの気づきを促し、CLD生徒の持つ様々な言語資源を総体としてみることの重要性を認識させるに至ったことが浮き彫りとなった。報告にあたり、このビリーフ変容のきっかけとなった二言語作文アセスメントの実施の詳細とその結果についても、その理論的基盤を含めて詳しく報告する。The importance of not only the development of the language of instruction but also the utilization of the students’ linguistic resources as mother tongue and inherited language has been highlighted in educating culturally and linguistically diverse students (CLD students). Such an idea is, however, not widely accepted in at the levels of practice, and thus bridging between theory and practice is urgently called for. This study reports the results of a qualitative analysis of how three teachers working with CLD students in different positions transformed their teacher beliefs after conducting a bilingual writing assessment in a public high school in an area of high concentration of CLD students. The analysis revealed that the bilingual writing assessment helped the three teachers to develop their own awareness of the importance of looking at the entire linguistic resources that CLD students possess. The details of the implementation of the bilingual writing assessment and its outcomes that led to this change in beliefs, together with its theoretical foundations are included in the report.研究論文Research Paper

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

Isolation and Characterization of Mosquito-Associated Spiroplasma cantharicola from Aedes japonicus Collected in Hokkaido, Japan

Species of the genus Spiroplasma are common within arthropods and plants worldwide. Mosquito-associated Spiroplasma spp. have been reported to show pathogenicity toward mosquitoes, which serve as vectors of several infectious diseases that have detrimental effects on public health. Although Spiroplasma spp. are expected to have potential use as biological vector-control tools, characteristics such as their distribution, host species, and cytopathogenic effects (CPEs) are not well understood. In this study, we isolated a Spiroplasma sp. from a female Aedes japonicus collected in Hokkaido, northern Japan. Phylogenetic analysis based on the 16S rRNA gene sequence indicated our isolate was closely related to S. cantharicola. We screened 103 mosquito pools consisting of 3 genera and 9 species, but only detected S. cantharicola in the first isolation. In an in vitro assay, our isolate grew well at 28 °C, but no propagation was observed at 37 °C. Furthermore, the isolate showed strong CPE on a mosquito-derived cultured cell line (C6/36), and its propagation slightly increased when co-cultured with C6/36 cells. To our knowledge, this is the third report of the isolation of S. cantharicola from mosquitoes and the first case in Asia. Our findings provide epidemiological data on S. cantharicola distribution in the region

Isolation and Characterization of Mosquito-Associated Spiroplasma cantharicola from Aedes japonicus Collected in Hokkaido, Japan

Species of the genus Spiroplasma are common within arthropods and plants worldwide. Mosquito-associated Spiroplasma spp. have been reported to show pathogenicity toward mosquitoes, which serve as vectors of several infectious diseases that have detrimental effects on public health. Although Spiroplasma spp. are expected to have potential use as biological vector-control tools, characteristics such as their distribution, host species, and cytopathogenic effects (CPEs) are not well understood. In this study, we isolated a Spiroplasma sp. from a female Aedes japonicus collected in Hokkaido, northern Japan. Phylogenetic analysis based on the 16S rRNA gene sequence indicated our isolate was closely related to S. cantharicola. We screened 103 mosquito pools consisting of 3 genera and 9 species, but only detected S. cantharicola in the first isolation. In an in vitro assay, our isolate grew well at 28 °C, but no propagation was observed at 37 °C. Furthermore, the isolate showed strong CPE on a mosquito-derived cultured cell line (C6/36), and its propagation slightly increased when co-cultured with C6/36 cells. To our knowledge, this is the third report of the isolation of S. cantharicola from mosquitoes and the first case in Asia. Our findings provide epidemiological data on S. cantharicola distribution in the region