Creating an LMS ePortfolio Building System That Enhances the Quality of College Life from One That Supports Self-Regulated Learning

During the recent coronavirus disease 2019 (COVID-19) pandemic, the ability to be a self-regulated learner has become more important with the introduction of online classes. These changes mean that students are now required to review their learning strategies and self-manage their learning time. We have developed a new “ePortfolio system” with the aim of building a system that fosters self-regulated learners and can visualize students’ learning outcomes. This paper introduces the concepts of our ePortfolio system as a Learning Management System ePortfolio building system that will provide enhanced functions and become a university-wide initiative

Regulation of Mitochondrial Dynamics and Neurodegenerative Diseases

Mitochondria are important cellular organelles in most metabolic processes and have a highly dynamic nature, undergoing frequent fission and fusion. The dynamic balance between fission and fusion plays critical roles in mitochondrial functions. In recent studies, several large GTPases have been identified as key molecular factors in mitochondrial fission and fusion. Moreover, the posttranslational modifications of these large GTPases, including phosphorylation, ubiquitination and SUMOylation, have been shown to be involved in the regulation of mitochondrial dynamics. Neurons are particularly sensitive and vulnerable to any abnormalities in mitochondrial dynamics, due to their large energy demand and long extended processes. Emerging evidences have thus indicated a strong linkage between mitochondria and neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and Huntington's disease. In this review, we will describe the regulation of mitochondrial dynamics and its role in neurodegenerative diseases

Assessment of human stress and depression by DNA microarray analysis

Precise assessment of stress is an imminent issue to deal with stress-related social, medical and psychological problems. Psychological stress is known to stimulate the neuroendocrine, sympathetic nervous, and immune systems. By analyzing mRNA expression levels in leukocytes, which express receptors for hormones, neurotransmitters, growth factors, cytokines, and other stress related signals, levels of stress may be adequately measured. In a series of studies, our group has developed a cDNA microarray specifically designed to measure the mRNA levels of stress-related genes in peripheral blood leukocytes. This microarray enabled us to sensitively detect the response to psychological stress. In addition, our preliminary study suggests that the array could differentiate patients with depression from sex- and age-matched control subjects

胃癌におけるクローディン4標的化によるシスプラチン化学療法感受性の向上

Claudins are major tight-junction proteins that mediate cellular polarity and differentiation. The present study investigated whether the 4D3 antibody to the human CLDN4 extracellular domain (that we previously established) is capable of modulating chemotherapeutic sensitivity in gastric cancer (GC). The results of the present study showed that CLDN4 was overexpressed in 137 of the 192 analyzed GC cases, and that CLDN4 expression was retained in tumors of a lower histological grade (more differentiated), and/or those that were caudal-type homeobox protein 2 (CDX2)-positive, but was reduced in more highly undifferentiated, and CDX2-negative GC cases. The study also compared the synergic effects of combining 4D3 with CDDP treatment and knocking down CLDN4 expression in MKN74 and TMK-1 human GC cells. Co-treatment with 4D3 increased anti-tumor effects of CDDP, whereas CLDN4 knockdown did not. In the TMK-1 cells, non-tight junction CLDN4 associated with integrin β1, increasing stem cell-associated proteins via FAK-c-SRC signals. The anti-tumoral effect of CDDP and 4D3 was examined in a nude mouse subcutaneous tumor model. In the two GC cell lines, concurrent treatment with 4D3 and CDDP synergistically inhibited cell proliferation and increased tumor necrosis and apoptosis to a greater degree than CDDP treatment alone. These findings suggest that 4D3 might increase chemotherapeutic sensitivity by evoking structural disintegration of tight-junction CLDN4 expressed in gastric cancer.博士（医学）・甲第713号・令和元年6月26日Copyright: Nishiguchi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0 https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

A Serine Palmitoyltransferase Inhibitor Blocks Hepatitis C Virus Replication in Human Hepatocytes

Background & AimsHost cell lipid rafts form a scaffold required for replication of hepatitis C virus (HCV). Serine palmitoyltransferases (SPTs) produce sphingolipids, which are essential components of the lipid rafts that associate with HCV nonstructural proteins. Prevention of the de novo synthesis of sphingolipids by an SPT inhibitor disrupts the HCV replication complex and thereby inhibits HCV replication. We investigated the ability of the SPT inhibitor NA808 to prevent HCV replication in cells and mice.MethodsWe tested the ability of NA808 to inhibit SPT’s enzymatic activity in FLR3-1 replicon cells. We used a replicon system to select for HCV variants that became resistant to NA808 at concentrations 4- to 6-fold the 50% inhibitory concentration, after 14 rounds of cell passage. We assessed the ability of NA808 or telaprevir to inhibit replication of HCV genotypes 1a, 1b, 2a, 3a, and 4a in mice with humanized livers (transplanted with human hepatocytes). NA808 was injected intravenously, with or without pegylated interferon alfa-2a and HCV polymerase and/or protease inhibitors.ResultsNA808 prevented HCV replication via noncompetitive inhibition of SPT; no resistance mutations developed. NA808 prevented replication of all HCV genotypes tested in mice with humanized livers. Intravenous NA808 significantly reduced viral load in the mice and had synergistic effects with pegylated interferon alfa-2a and HCV polymerase and protease inhibitors.ConclusionsThe SPT inhibitor NA808 prevents replication of HCV genotypes 1a, 1b, 2a, 3a, and 4a in cultured hepatocytes and in mice with humanized livers. It might be developed for treatment of HCV infection or used in combination with pegylated interferon alfa-2a or HCV polymerase or protease inhibitors

Group 3 sigma factor gene, sigJ, a key regulator of desiccation tolerance, regulates the synthesis of extracellular polysaccharide in cyanobacterium Anabaena sp. strain PCC 7120

The changes in the expression of sigma factor genes during dehydration in terrestrial Nostoc HK-01 and aquatic Anabaena PCC 7120 were determined. The expression of the sigJ gene in terrestrial Nostoc HK-01, which is homologous to sigJ (alr0277) in aquatic Anabaena PCC 7120, was significantly induced in the mid-stage of dehydration. We constructed a higher-expressing transformant of the sigJ gene (HE0277) in Anabaena PCC 7120, and the transformant acquired desiccation tolerance. The results of Anabaena oligonucleotide microarray experiments showed that a comparatively large number of genes relating to polysaccharide biosynthesis were upregulated in the HE0277 cells. The extracellular polysaccharide released into the culture medium of the HE0277 cells was as much as 3.2-fold more than that released by the control cells. This strongly suggests that the group 3 sigma factor gene sigJ is fundamental and conducive to desiccation tolerance in these cyanobacteria

Transmission electron microscopic observations of nanobubbles and their capture of impurities in wastewater

Unique properties of micro- and nanobubbles (MNBs), such as a high adsorption of impurities on their surface, are difficult to verify because MNBs are too small to observe directly. We thus used a transmission electron microscope (TEM) with the freeze-fractured replica method to observe oxygen (O2) MNBs in solutions. MNBs in pure water and in 1% NaCl solutions were spherical or oval. Their size distribution estimated from TEM images close to that of the original solution is measured by light-scattered methods. When we applied this technique to the observation of O2 MNBs formed in the wastewater of a sewage plant, we found the characteristic features of spherical MNBs that adsorbed surrounding impurity particles on their surface