233 research outputs found

    COVID-19 and heat illness in Tokyo, Japan: implications for the summer Olympic and Paralympic Games in 2021

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    The 2020 summer Olympic and Paralympic Games in Tokyo were postponed to July– September 2021 due to the coronavirus disease 2019 (COVID-19) pandemic. While COVID-19 has emerged as a monumental health threat for mass gathering events, heat illness must be acknowl-edged as a potentially large health threat for maintaining health services. We examined the number of COVID-19 admissions and the Tokyo rule for emergency medical care, in Tokyo, from March to September 2020, and investigated the weekly number of emergency transportations due to heat illness and weekly averages of the daily maximum Wet Bulb Globe Temperature (WBGT) in Tokyo in the summer (2016–2020). The peak of emergency transportations due to heat illness overlapped the resurgence of COVID-19 in 2020, and an increase of heat illness patients and WBGT has been observed. Respect for robust science is critical for the decision-making process of mass gathering events during the pandemic, and science-based countermeasures and implementations for COVID-19 will be warranted. Without urgent reconsiderations and sufficient countermeasures, the double burden of COVID-19 and heat-related illnesses in Tokyo will overwhelm the healthcare provision system, and maintaining essential health services will be challenging during the 2021 summer Olympic and Paralympic Games

    CRISPR-Cas9システムを用いた味覚受容体発現調節物質のスクリーニング系の開発

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    Taste recognition mediated by taste receptors is critical for the survival of animals in nature and is an important determinant of nutritional status and quality of life in humans. However, many factors including aging, diabetes, zinc deficiency, infection with influenza or cold viruses, and chemotherapy can trigger dysgeusia, for which a standard treatment has not been established. We here established an engineered strain of medaka (Oryzias latipes) that expresses green fluorescent protein (GFP) from the endogenous taste 1 receptor 3 (T1R3) gene locus with the use of the CRISPR-Cas9 system. This T1R3-GFP knock-in (KI) strain allows direct visualization of expression from this locus by monitoring of GFP fluorescence. The pattern of GFP expression in the T1R3-GFP KI fish thus mimicked that of endogenous T1R3 gene expression. Furthermore, exposure of T1R3-GFP KI medaka to water containing monosodium glutamate or the anticancer agent 5-fluorouracil resulted in an increase or decrease, respectively, in GFP fluorescence intensity, effects that also recapitulated those on T1R3 mRNA abundance. Finally, screening for agents that affect GFP fluorescence intensity in T1R3-GFP KI medaka identified tryptophan as an amino acid that increases T1R3 gene expression. The establishment of this screening system for taste receptor expression in medaka provides a new tool for the development of potential therapeutic agents for dysgeusia

    ソードテールフィッシュXiphophorus helleriの生殖腺の発達と二次性徴

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    Transformation Towards a "new" Public Administration of the Network UtilitiesDuring the 1980s and 1990s privatisation and deregulation movements have been shaken up the European network industries-telecommunication, electricity and railways. These reforms did affect also those parts of the public administrations in charge of managing and controlling the industries. While usually the changes in the relationship 'administration-market' have been the centre of academic attention, this paper attempts to investigate whether the very functions of the public administration themselves have been affected, i.e. altered or even transformed. Goes the emergence of the regulatory state hand in hand with the arrival of a new public administration? Comparing the examples of regulatory reform in the United Kingdom and Germany this paper attempts to provide a first answer

    The SAC51 Family Plays a Central Role in Thermospermine Responses in Arabidopsis

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    The acaulis5 (acl5) mutant of Arabidopsis thaliana is defective in the biosynthesis of thermospermine and shows a dwarf phenotype associated with excess xylem differentiation. SAC51 was identified from a dominant suppressor of acl5, sac51-d, and encodes a basic helix-loop-helix protein. The sac51-d mutant has a premature termination codon in an upstream open reading frame (uORF) that is conserved among all four members of the SAC51 family, SAC51 and SACL1-SACL3 This suggests that thermospermine cancels the inhibitory effect of the uORF in main ORF translation. Another suppressor, sac57-d, has a mutation in the conserved uORF of SACL3 To define further the function of the SAC51 family in the thermospermine response, we analyzed T-DNA insertion mutants of each gene. Although sacl1-1 may not be a null allele, the quadruple mutant showed a semi-dwarf phenotype but with an increased level of thermospermine and decreased sensitivity to exogenous thermospermine that normally represses xylem differentiation. The sac51-1 sacl3-1 double mutant was also insensitive to thermospermine. These results suggest that SAC51 and SACL3 play a key role in thermospermine-dependent negative control of thermospermine biosynthesis and xylem differentiation. Using 5' leader-GUS (β-glucuronidase) fusion constructs, however, we detected a significant enhancement of the GUS activity by thermospermine only in SAC51 and SACL1 constructs. Furthermore, while acl5-1 sac51-1 showed the acl5 dwarf phenotype, acl5-1 sacl3-1 exhibited an extremely tiny-plant phenotype. These results suggest a complex regulatory network for the thermospermine response in which SAC51 and SACL3 function in parallel pathways

    Epithelial-mesenchymal transition-converted tumor cells can induce T-cell apoptosis through upregulation of programmed death ligand 1 expression in esophageal squamous cell carcinoma

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    Esophageal squamous cell carcinoma (ESCC) is an aggressive tumor, and it is urgently needed to develop novel therapeutic strategies including immunotherapy. In this study, we investigated the upregulation of the programmed death ligand 1 (PD-L1) due to epithelial-mesenchymal transition (EMT) in ESCC using an in vitro treatment system with the EMT inducer, glycogen synthase kinase (GSK)-3 inhibitor, and we also analyzed the correlation of EMT and PD-L1 expression in the clinical tumor samples of both tissue microarray (TMA) samples (n = 177) and whole tissue samples (n = 21). As a result, the inhibition of GSK-3β induces EMT phenotype with upregulated vimentin and downregulated E-cadherin as well as increased Snail and Zinc finger E box-binding homeobox (ZEB)-1 gene expression. Simultaneously, we showed that EMT-converted ESCC indicated the upregulation of PD-L1 at both protein (total and surface) and mRNA levels. Of importance, we showed that EMT-converted tumor cells have a capability to induce T-cell apoptosis to a greater extent in comparison to original epithelial type tumor cells. Furthermore, the immunohistochemical stains of ESCC showed that PD-L1 expression on tumor cells was positively correlated with EMT status in TMA samples (P = .0004) and whole tissue samples (P = .0029). In conclusion, our in vitro and in vivo study clearly demonstrated that PD-L1 expression was upregulated in mesenchymal type tumors of ESCC. These findings provide a strong rationale for the clinical use of anti-PD- 1/ anti-PD- L1 monoclonal antibodies for advanced ESCC patients
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