An Analysis and Some Considerations of Empirical Lessons in the Unit "Forest, Atmosphere and Life" in Social Studies Education (2): An Analysis and Some Considerations of Workbooks.

本研究は、開発した単元「森林と大気と生活」の学習書に基づいて実施した実験授業の結果を分析、考察したものである。実験授業の結果、問題集、作文、推せん課題レポート、プリテスト、ポストテスト等のデータを得ることができた。これらのデータ分析・考察することによって、開発した学習書が個別学習用教材として適切であったか、どのような社会認識を形成したか、実験授業によって社会認識がどのように変化したか、その理由は何かなどを明らかにすることを目的としている。本稿は、問題編の問題群への回答の分析と考察を行い、どのよう社会認識が形成されたかを明らかにした

State-of-the-art liver disease research using liver-on-a-chip

To understand disease pathophysiologies, models that recapitulate human functions are necessary. In vitro models that consist of human cells are preferred to ones using animal cells, because organ functions can vary from species to species. However, conventional in vitro models do not recapitulate human organ functions well. Organ-on-a-chip technology provides a reliable in vitro model of the functional units of human organs. Organ-on-a-chip technology uses microfluidic devices and their accessories to impart organ functions to human cells. Using microfluidic devices, we can co-culture multiple cell types that compose human organs. Moreover, we can culture human cells under physiologically relevant stresses, such as mechanical and shear stresses. Current organ-on-a-chip technology can reproduce the functions of several organs including the liver. Because it is difficult to maintain the function of human hepatocytes, which are the gold standard of in vitro liver models, under conventional culture conditions, the application of liver-on-a-chips to liver disease research is expected. This review introduces the current status and future prospects of liver-on-a-chips in liver disease research

An Analysis and Some Considerations of Empirical Lessons in the Unit“ Forest, Atmosphere and Life” in Elementary Social Studies Education (7): An Analysis and Some Considerations of Questionnaire.

本研究は，小学校６年生を対象に開発した単元「森林と大気と生活」の学習書に基づいて実施した実験授業の結果を分析・考察したものである。実験授業の結果，問題集，作文，「推せん課題」レポート，自己評価（反省），アンケートなどのデータを得ることができた。これらのデータを分析・考察することによって，開発した学習書が個別学習用教材として適切であったか，どのような社会認識を形成したか，実験授業によって社会認識がどのように変化したか，その理由は何かなどを明らかにすることを目的としている。本稿では，アンケート調査の結果を分析し，５，６年時に行った「ひとり学習」及び５年時に実施した単元「森林と水と生活」と６年時に実施した単元「森林と大気と生活」の実験授業が児童にとってどのような意味を持っていたかを明らかにした

Prevention and Recovery of COVID-19 Patients With Kampo Medicine: Review of Case Reports and Ongoing Clinical Trials

Coronavirus disease 2019 (COVID-19) spread to Japan in 2020, where the number of infected patients exceeded 250,000 and COVID-related deaths exceeded 3,500 in one year. Basic guidelines for infection control were implemented in Japan, and research and development of effective drugs and vaccines were promoted. This included considering Kampo medicine, which has a long history of treating recurring emerging viral infections. Considering the characteristics of the disease (inflammation of the upper and lower respiratory tract as well as potential neural damage and vasculitis), Kampo medicine could be considered as a treatment strategy due to its antiviral and anti-inflammatory effects induced by multiple active substances that could aid in disease prevention and recovery. In this study, case reports on the management of COVID-19 with Kampo medicine, which were published until March 31, 2021, were reviewed. The search strategy involved the use of Medline and hand-searching. Twenty two patients were treated using Kampo medicines with or without Western medicine, based on individual conditions. On the other hand, the effects of Kampo medicines as a potential preventive treatment (pre-infection), active treatment (especially in the acute and subacute stage), or treatment of sequelae to aid recovery (after infection) in the different stages of COVID-19 are being studied as research projects in the Japan Society for Oriental Medicine (JSOM). JSOM has also organized a pioneering project of clinical trials for COVID-19, some of which are now in progress

Design of a chimeric ACE-2/Fc-silent fusion protein with ultrahigh affinity and neutralizing capacity for SARS-CoV-2 variants

BACKGROUND: As SARS-CoV-2 continues to mutate into Variants of Concern (VOC), there is growing and urgent need to develop effective antivirals to combat COVID-19. Monoclonal antibodies developed earlier are no longer capable of effectively neutralizing currently active VOCs. This report describes the design of variant-agnostic chimeric molecules consisting of an Angiotensin-Converting Enzyme 2 (ACE-2) domain mutated to retain ultrahigh affinity binding to a wide variety of SARS-CoV-2 variants, coupled to an Fc-silent immunoglobulin domain that eliminates antibody-dependent enhancement and extends biological half-life. METHODS: Molecular modeling, Surrogate Viral Neutralization tests (sVNTs) and infection studies of human airway organoid cultures were performed with synthetic chimeras, SARS-CoV-2 spike protein mimics and SARS-CoV-2 Omicron variants B.1.1.214, BA.1, BA.2 and BA.5. RESULTS: ACE-2 mutations L27, V34 and E90 resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 93 pM and 73 pM for binding to the Alpha B1.1.7 and Omicron B.1.1.529 variants, and notably, 78fM, 133fM and 1.81pM affinities to the Omicron BA.2, BA2.75 and BQ.1.1 subvariants, respectively. sVNT assays revealed titers of ≥4.9 ng/ml, for neutralization of recombinant viral proteins corresponding to the Alpha, Delta and Omicron variants. The values above were obtained with LVE-ACE-2/mAB chimeras containing the FcRn-binding Y-T-E sequence which extends biological half-life 3-4-fold. CONCLUSIONS: The ACE-2-mutant/Fc silent fusion proteins described have ultrahigh affinity to a wide variety of SARS-CoV-2 variants including Omicron. It is proposed that these chimeric ACE-2/mABs will constitute variant-agnostic and cost-effective prophylactics against SARS-CoV-2, particularly when administered nasally

Exocyst complex component 2 is a potential host factor for SARS-CoV-2 infection

iPS細胞やオルガノイド技術を用いた新型コロナウイルス感染におけるEXOC2の機能解析. 京都大学プレスリリース. 2022-10-27.An important host factor in SARS-CoV-2 infection, identified using iPS cell and organoid technology. 京都大学プレスリリース. 2022-10-31.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an epidemic and spread rapidly all over the world. Because the analysis of host factors other than receptors and proteases has not been sufficiently performed, we attempted to identify and characterize host factors essential for SARS-CoV-2 infection using iPS cells and airway organoids (AO). Based on previous CRISPR screening and RNA-seq data, we found that exocyst complex component 2 (EXOC2) is one important host factor for SARS-CoV-2 infection. The intracellular SARS-CoV-2 nucleocapsid (N) expression level was decreased to 3.7 % and the virus copy number in cell culture medium was decreased to 1.6 % by EXOC2 knockdown. Consistently, immunostaining results showed that N protein-positive cells were significantly decreased by EXOC2 knockdown. We also found that EXOC2 knockdown downregulates SARS-CoV-2 infection by regulating IFNW1 expression. In conclusion, controlling the EXOC2 expression level may prevent SARS-CoV-2 infection and deserves further study

A Novel Animal Model of Nonalcoholic Steatohepatitis (NASH): Hypoxemia Enhances the Development of NASH

Recent reports described a high incidence of nonalcoholic steatohepatitis (NASH) in patients with obstructive sleep apnea. Accordingly, we hypothesized that recurrent and intermittent hypoxemia plays an important role in the pathogenesis of NASH. Our objective was construction of a practical and accurate experimental model to reproduce the key features of NASH in humans. Chemical hypoxemia through methemoglobinemia was induced by daily intraperitoneal injection of sodium nitrite (40 mg/kg) for 4 weeks in rats with fatty liver. The later was induced by 4-week feeding a choline-deficient high-fat diet (CDHF). Besides, the normal chow diets feeding groups were prepared with in the same manner except for CDHF feeding. The animal experiment was performed in four groups; Normal control, Hypoxemia, CDHF, and CDHF + hypoxemia. Nitrite was given for the later 4 weeks to each rat of Hypoxemia and CDHF + hypoxemia. CDHF + hypoxemia rats were confirmed to develop histological changes that resemble those of patients with NASH, together with biochemical liver dysfunction, while CDHF group was limited in mild steatosis, and Hypoxemia group liver was normal. Present study established a reproducible and useful NASH model resembling the main features of NASH in humans, and showed first that recurrent and intermittent hypoxemia aggravate fatty liver to steatohepatitis and liver fibrosis

Hexagonal distributions of cities in Southern Germany and Eastern USA: Group-theoretic spectrum analysis

Cities in Southern Germany are envisaged to form hexagonal distributions in central place theory; however, rigorous verification of this theory has been lacking over years. To support this theory, we introduce a group-theoretic Fourier spectrum analysis that can detect geometrical patterns of cities based on the statistical population data. In addition to hexagonal patterns in the theory, we propose a core--satellite pattern. Using this analysis, we detected a strong power spectrum for this pattern for population data in Southern Germany. Moreover, a gigantic hexagonal distribution of cities in Eastern USA was found to be an assemblage of the core--satellite and hexagonal patterns. The amazing geometrical regularity of this distribution implies the existence of such patterns in the real world, thereby underpinning the theory