The Development of the Japanese Lesson to Foster Independent Reader

本研究は，グローバル化社会において自立した読書人となるために必要な資質・能力を育てるための小学校国語科における読書カリキュラムの開発を行うことを目的としている。 本年度は，自立した読書人に必要な資質・能力を「読書に関する知識・技能」「読書を通した思考力・判断力・表現力」「主体的・積極的に読書に取り組み，読書を通して情緒を育て，様々な人の中に参入する態度」とし，カリキュラムの内容も同じ３領域で編成した。国語科の指導内容は，系統的・段階的につながるとともに，螺旋的・反復的に学習することで能力の定着を図ることが大切であると考える。そこで，「読書に関する知識・技能」「読書を通した思考力・判断力・表現力」は，それぞれの学年で焦点化したり重点化したりしながら指導していくが，指導対象学年を明確に分けることはしない。「主体的・積極的に読書に取り組み，読書を通して情緒を育て，様々な人の中に参入する態度」は，読書に向かう態度と本によって培う人間性とに分け，２学年ずつで段階的に指導していくこととした。これに基づいて実践を４本行い，その成果と課題からカリキュラムの妥当性を検証した。In this research, we aimed to develop the reading curriculum in elementary school in order to foster independent reader in the global society. We examined and configured the reading curriculum based three competences:（1）reading skills, （2）the competency of thinking, judging and expressing through reading, （3）the positive attitude to reading, the affect through reading and the positive attitude to participate in the community. We think it is important to teach in the gradual and repeated approach. Then, we planned and practiced the four lessons based these three competences, examined the achievement and problems of these lessons and validity checked our reading curriculum

Access to mechanical thrombectomy and ischemic stroke mortality in Japan: a spatial ecological study

BackgroundAdvances in stroke treatment have greatly improved outcomes; however, disparities in access to treatment might increase. Achieving equitable access to stroke treatment is a health policy challenge, as rapid treatment is essential for positive outcomes. This ecological cross-sectional study aimed to determine the relationship between the disparities in spatial accessibility to mechanical thrombectomy (SAMT) and stroke mortality rates in Japan, hypothesizing that disparities in SAMT may increase the differences in stroke mortality between regions.MethodsWe used the average number of ischemic stroke (IS) deaths between 2020 and 2021 as the response variable; and SAMT, medical resources, and socioeconomic characteristics of each municipality as explanatory variables. A conditional autoregressive model was used to examine the association between the risk of stroke mortality and SAMT. The standardized mortality ratio (SMR) was mapped to understand the nationwide disparities in stroke mortality risk.ResultsThe median number of IS deaths was 17.5 persons per year in the municipalities (2020 to 2021). The study also found that municipalities with low SAMT were located in the northern part of Japan. The non-spatial regression model results indicated that poor accessibility, a small proportion of bachelor’s degrees or higher, and a high proportion of workers in secondary industries were related to high IS mortality. Three models were evaluated using spatial analysis; Model 1 with accessibility indicators alone, Model 2 with medical resources added to Model 1, and Model 3 with socioeconomic characteristics added to Model 2. In Models 1 and 2, the population-weighted spatial accessibility index (PWSAI) showed a significant negative relationship with stroke mortality. However, this was not evident in Model 3. Mapping using Model 3 showed that the high-risk areas were predominantly located in northern Japan, excluding Hokkaido.ConclusionAccess to mechanical thrombectomy was estimated, and regional differences were observed. The relationship between accessibility and IS mortality is unknown; however, regardless of accessibility, municipalities with a high proportion of workers in secondary industries and a small proportion with bachelor’s degrees or above are at risk of death from stroke

MMP-10/Stromelysin-2 Promotes Invasion of Head and Neck Cancer

Background: Periostin, IFN-induced transmembrane protein 1 (IFITM1) and Wingless-type MMTV integration site family, member 5B (Wnt-5b) were previously identified as the invasion promoted genes of head and neck squamous cell carcinoma(HNSCC) by comparing the gene expression profiles between parent and a highly invasive clone. We have previously reported that Periostin and IFITM1 promoted the invasion of HNSCC cells. Here we demonstrated that Wnt-5b overexpression promoted the invasion of HNSCC cells. Moreover, stromelysin-2 (matrix metalloproteinase-10; MMP-10) was identified as a common up-regulated gene among Periostin, IFITM1 and Wnt-5b overexpressing HNSCC cells by using microarray data sets. In this study, we investigated the roles of MMP-10 in the invasion of HNSCC. Methods and Findings: We examined the expression of MMP-10 in HNSCC cases by immunohistochemistry. High expression of MMP-10 was frequently observed and was significantly correlated with the invasiveness and metastasis in HNSCC cases. Next, we examined the roles of MMP-10 in the invasion of HNSCC cells in vitro. Ectopic overexpression of MMP-10 promoted the invasion of HNSCC cells, and knockdown of MMP-10 suppressed the invasion of HNSCC cells. Moreover, MMP-10 knockdown suppressed Periostin and Wnt-5b-promoted invasion. Interestingly, MMP-10 overexpression induced the decreased p38 activity and MMP-10 knockdown induced the increased p38 activity. In addition, treatment with a p38 inhibitor SB203580 in HNSCC cells inhibited the invasion. Conclusions: These results suggest that MMP-10 plays an important role in the invasion and metastasis of HNSCC, and that invasion driven by MMP-10 is partially associated with p38 MAPK inhibition. We suggest that MMP-10 can be used as a marker for prediction of metastasis in HNSCC

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

Sequestration and Oxidation of Cr(III) by Fungal Mn Oxides with Mn(II) Oxidizing Activity

Biogenic manganese oxides (BMOs) have gained increasing attention for environmental application because of their sequestration and oxidizing abilities for various elements. Oxidation and sequestration of Cr(III) by BMOs, however, still remain unknown. We prepared BMOs in liquid cultures of Acremonium strictum strain KR21-2, and subsequently conducted single or repeated treatment experiments in Cr(NO3)3 at pH 6.0. Under aerobic conditions, newly formed BMOs exhibited a rapid production of Cr(VI) without a significant release of Mn(II), demonstrating that newly formed BMO mediates a catalytic oxidation of Cr(III) with a self-regeneration step of reduced Mn. In anaerobic solution, newly formed BMOs showed a cessation of Cr(III) oxidation in the early stage of the reaction, and subsequently had a much smaller Cr(VI) production with significant release of reduced Mn(II). Extraordinary sequestration of Cr(III) was observed during the repeated treatments under anaerobic conditions. Anaerobically sequestered Cr(III) was readily converted to Cr(VI) when the conditions became aerobic, which suggests that the surface passivation is responsible for the anaerobic cessation of Cr(III) oxidation. The results presented herein increase our understanding of the roles of BMO in Cr(III) oxidation and sequestration processes in potential application of BMOs towards the remediation of Cr(III)/Cr(VI) in contaminated sites

Analysis of essential pathways for self-renewal in common marmoset embryonic stem cells

Common marmoset (CM) is widely recognized as a useful non-human primate for disease modeling and preclinical studies. Thus, embryonic stem cells (ESCs) derived from CM have potential as an appropriate cell source to test human regenerative medicine using human ESCs. CM ESCs have been established by us and other groups, and can be cultured in vitro. However, the growth factors and downstream pathways for self-renewal of CM ESCs are largely unknown. In this study, we found that basic fibroblast growth factor (bFGF) rather than leukemia inhibitory factor (LIF) promoted CM ESC self-renewal via the activation of phosphatidylinositol-3-kinase (PI3K)-protein kinase B (AKT) pathway on mouse embryonic fibroblast (MEF) feeders. Moreover, bFGF and transforming growth factor β (TGFβ) signaling pathways cooperatively maintained the undifferentiated state of CM ESCs under feeder-free condition. Our findings may improve the culture techniques of CM ESCs and facilitate their use as a preclinical experimental resource for human regenerative medicine