A Report on Overseas Teaching Practicum by Graduate Students in Elementary/Secondary Schools in the United States（Ⅹ）

This short paper reports on the 10th overseas teaching practicum in the United States by 8 graduate students of Hiroshima University， Japan， partly organized by Hiroshima University Global Partnership School Center (GPSC). This year marks the 10-year anniversary of this project since its start. This year’s participants were students of Graduate School of Education and Graduate School for International Development and Cooperation (IDEC). They observed and conducted lessons in English in four local public schools in North Carolina. This project had the following three aims: 1) to self-develop practical instructional competence by teaching pupils with different cultural backgrounds; 2) to enhance the abilities in developing teaching materials through hands-on teaching experiences in English; and 3) to acquire the abilities to design， implement and evaluate programs for promoting global partnership. Like previous years， their teachings were very positively covered by the local newspapers and websites. Later， the project was followed by cross-cultural field study visits to NC State Capitol， Raleigh and the U.S. Capitol， Washington， D.C. It is hoped that this intensive experience will raise the prospective teachers’ global awareness and confidence in teaching

Trapping of CDC42 C-terminal variants in the Golgi drives pyrin inflammasome hyperactivation

CDC42-C末端異常症に於ける炎症病態を解明 --ゴルジ体への異常蓄積がパイリンインフラマソーム形成を過剰促進--. 京都大学プレスリリース. 2022-05-02.Mutations in the C-terminal region of the CDC42 gene cause severe neonatal-onset autoinflammation. Effectiveness of IL-1β–blocking therapy indicates that the pathology involves abnormal inflammasome activation; however, the mechanism underlying autoinflammation remains to be elucidated. Using induced-pluripotent stem cells established from patients carrying CDC42[R186C], we found that patient-derived cells secreted larger amounts of IL-1β in response to pyrin-activating stimuli. Aberrant palmitoylation and localization of CDC42[R186C] protein to the Golgi apparatus promoted pyrin inflammasome assembly downstream of pyrin dephosphorylation. Aberrant subcellular localization was the common pathological feature shared by CDC42 C-terminal variants with inflammatory phenotypes, including CDC42[*192C*24] that also localizes to the Golgi apparatus. Furthermore, the level of pyrin inflammasome overactivation paralleled that of mutant protein accumulation in the Golgi apparatus, but not that of the mutant GTPase activity. These results reveal an unexpected association between CDC42 subcellular localization and pyrin inflammasome activation that could pave the way for elucidating the mechanism of pyrin inflammasome formation

Synthetic biology based construction of biological activity-related library of fungal decalin-containing diterpenoid pyrones

A synthetic biology method based on heterologous biosynthesis coupled with genome mining is a promising approach for increasing the opportunities to rationally access natural product with novel structures and biological activities through total biosynthesis and combinatorial biosynthesis. Here, we demonstrate the advantage of the synthetic biology method to explore biological activity-related chemical space through the comprehensive heterologous biosynthesis of fungal decalin-containing diterpenoid pyrones (DDPs). Genome mining reveals putative DDP biosynthetic gene clusters distributed in five fungal genera. In addition, we design extended DDP pathways by combinatorial biosynthesis. In total, ten DDP pathways, including five native pathways, four extended pathways and one shunt pathway, are heterologously reconstituted in a genetically tractable heterologous host, Aspergillus oryzae, resulting in the production of 22 DDPs, including 15 new analogues. We also demonstrate the advantage of expanding the diversity of DDPs to probe various bioactive molecules through a wide range of biological evaluations

Helical peptides with disordered regions for measles viruses provide new generalized insights into fusion inhibitors

Summary: Despite effective vaccines, measles virus (MeV) outbreaks occur sporadically. Therefore, developing anti-MeV agents remains important for suppressing MeV infections. We previously designed peptide-based MeV fusion inhibitors, M1 and M2, that target MeV class I fusion protein (F protein). Here, we developed a novel fusion inhibitor, MEK35, that exerts potent activity against M1/M2-resistant MeV variants. Comparing MEK35 to M1 derivatives revealed that combining disordered and helical elements was essential for overcoming M1/M2 resistance. Moreover, we propose a three-step antiviral process for peptide-based fusion inhibitors: (i) disordered peptides interact with F protein; (ii) the peptides adopt a partial helical conformation and bind to F protein through hydrophobic interactions; and (iii) subsequent interactions involving the disordered region of the peptides afford a peptide-F protein with a high-affinity peptide-F protein interaction. An M1-resistant substitution blocks the second step. These results should aid the development of novel viral fusion inhibitors targeting class I F protein

Association of physiological factors with grip and leg extension strength: tohoku medical megabank community-based cohort study

Abstract Background Upper and lower extremity muscle strength can be used to predict health outcomes. However, the difference between the relation of upper extremity muscle and of lower extremity muscle with physiological factors is unclear. This study aimed to evaluate the association between physiological data and muscle strength, measured using grip and leg extension strength, among Japanese adults. Methods We conducted a cross-sectional study of 2,861 men and 6,717 women aged ≥ 20 years living in Miyagi Prefecture, Japan. Grip strength was measured using a dynamometer. Leg extension strength was measured using a hydraulic isokinetic leg press machine. Anthropometry and physiological data, including blood pressure, calcaneal ultrasound bone status, pulmonary function, carotid echography, and blood information, were assessed. We used a general linear model adjusted for age, body composition, and smoking status to evaluate the association between muscle strength and physiological factors. Results Grip and leg extension strength were positively associated with bone area ratio, vital capacity, forced vital capacity, forced expiratory volume in one second, and estimated glomerular filtration rate, and negatively associated with waist circumference and percentage body fat mass in both the sexes. Diastolic blood pressure was positively associated with grip strength in both the sexes and leg extension strength in men, but not women. High-density lipoprotein cholesterol and red blood cell counts were positively associated with grip and leg extension strength in women, but not men. In both the sexes, pulse rate, total cholesterol, and uric acid were consistently associated with only leg extension strength, but not grip strength. In women, glycated hemoglobin demonstrated negative and positive associations with grip and leg extension strength, respectively. Conclusions Grip and leg extension strength demonstrated similar associations with anthropometry, pulmonary function, and estimated glomerular filtration rate, but the associations with the other factors were not always consistent

Addressing challenges in children’s mental health in disaster-affected areas in Japan and the Philippines – highlights of the training program by the National Center for Global Health and Medicine

Abstract Background and purpose Natural disasters such as earthquakes, typhoons, floods, and volcanic eruptions frequently occur in Republic of Philippines and mental health care for children affected by these natural disasters is a major public health concern. Aiming to train health professionals on children’s mental health, to conduct a situational analysis to identify the local needs and resources for children’s mental health, and to propose a mental health program for children that can be transferred from Japan to the Philippines, the National Center for Global Health and Medicine (NCGM) conducted a training program for children’s mental health in disaster-affected areas in Japan and the Philippines in June, October, and December, 2017. The training was organized by NCGM for the Program for International Promotion of Japan’s Healthcare Technologies and Services funded by Ministry of Health, Labour, & Welfare, Japan in relation to the Memorandum of Understanding in the Field of Healthcare between NCGM in Japan and University of the Philippines Manila, College of Public Health. Key highlights The training program consisted of classroom trainings, site visits, and round table discussions in Japan and the Philippines. The classroom trainings and site visits focused on two points: the experiences of individuals and families who survived the Great East Japan Earthquake (GEJE) in 2011 and super typhoon Haiyan in 2013 and the program and activities, especially on mental health, of various government and non-government organizations in helping the affected families and communities. The round table discussion, on the other hand, was conducted to identify challenges related to children’s mental health in disaster-affected areas and to develop recommendations to address these challenges. The major recommendations for the Philippines were to give equal emphasis to physical and psychosocial preparedness and to develop a comprehensive program to care for carers. In Japan, public health and mental health should be integrated in the Disaster Medical Service. Experts from both countries should also generate evidence on the effectiveness of interventions in reducing mental health stigma and collaborate with school personnel and communities in order to learn more about psychosocial preparedness. Finally, mental health must be mainstreamed in programs not only in Japan but also in other countries. Implications The training program enabled key stakeholders to describe the current situation of mental health in Japan and the Philippines, to identify mental health challenges common to disaster-affected areas in both countries, and to propose short- and long-term plans and recommendations. The training program is expected to address the mental health needs of children in disaster-affected areas through a responsive community-based support network. The training participants agreed to form a network and build partnerships toward the common goal of mainstreaming community-based support for children’s mental health in disaster-affected areas in Japan and the Philippines

Synthesis of a Vpr-Binding Derivative for Use as a Novel HIV-1 Inhibitor

<div><p>The emergence of multidrug-resistant viruses compromises the efficacy of anti-human immunodeficiency virus type 1 (HIV-1) therapy and limits treatment options. Therefore, new targets that can be used to develop novel antiviral agents need to be identified. We previously identified a potential parent compound, hematoxylin, which suppresses the nuclear import of HIV-1 via the Vpr-importin α interaction and inhibits HIV-1 replication in a Vpr-dependent manner by blocking nuclear import of the pre-integration complex. However, it was unstable. Here, we synthesized a stable derivative of hematoxylin that bound specifically and stably to Vpr and inhibited HIV-1 replication in macrophages. Furthermore, like hematoxylin, the derivative inhibited nuclear import of Vpr in an <i>in vitro</i> nuclear import assay, but had no effect on Vpr-induced G2/M phase cell cycle arrest or caspase activity. Interestingly, this derivative bound strongly to amino acid residues 54–74 within the C-terminal α-helical domain (αH3) of Vpr. These residues are highly conserved among different HIV strains, indicating that this region is a potential target for drug-resistant HIV-1 infection. Thus, we succeeded in developing a stable hematoxylin derivative that bound directly to Vpr, suggesting that specific inhibitors of the interaction between cells and viral accessory proteins may provide a new strategy for the treatment of HIV-1 infection.</p></div