Activation of G-protein coupled fMLP or PAF receptor directly triggers glucose transporter type 1 (GLUT1) translocation in Chinese hamster ovary (CHO) cells stably expressing fMLP or PAF receptor

The chemoattractants, fMLP and PAF, stimulate glucose uptake in phagocytes to obtain an energy source for host defense. Glucose uptake in phagocytes is mainly regulated via glucose transporter type1 (GLUT1). To examine molecular mechanisms of facilitated glucose uptake in response to fMLP or PAF, we established CHO cells stably expressing fMLP or PAF receptor with c-myc epitope tagged GLUT1 which could immunologically detect GLUT1 on the cell surface. In the CHO cells, both fMLP and PAF directly triggered GLUT1 translocation from the intracellular pool to the cell surface, and stimulated glucose uptake. Therefore, in phagocytes, we propose that fMLP and PAF also trigger GLUT1 translocation to stimulate glucose uptake as an energy source for host defense

Symptomatic foramen of Magendie arachnoid cyst in an elderly patient

Background: Arachnoid cysts (ACs) are congenital anomalies of the central nervous system and arise in virtually all locations where the arachnoid membrane exists. Posterior fossa ACs are considered to develop in the posterior aspect of the rhombencephalic roof plate and do not communicate freely with the fourth ventricle or perimedullary subarachnoid space. Although posterior fossa ACs have been reported a number of times, ACs arising from the foramen of Magendie are very rare. Case Description: We report here on a 76-year-old female who presented with progressive gait disturbance. Magnetic resonance imaging of the head showed a large AC in the foramen of Magendie that was compressing the inferior vermis and medial aspects of the cerebellar hemisphere without causing hydrocephalus. Neurological examination revealed cerebellar ataxia without Romberg\u27s sign. A nearly total excision of the cyst was safely performed via a median suboccipital approach. The patient\u27s postoperative course was excellent and her neurological recovery was remarkable. Conclusion: Most cases of ACs located in the foramen of Magendie are reported in children, and it is extremely rare to observe such ACs in the elderly. In fact, to our knowledge, a symptomatic foramen Magendie AC has never been reported previously in an elderly person. Our results indicate that proper surgical intervention can yield highly positive outcomes in such cases

Development of UPS-SMES as a protection from momentary voltage drop

We have been developing the UPS-SMES as a protection from momentary voltage drop and power failure. The superconducting system is suitable as electric power storage for large energy extraction in a short time. The most important feature of superconducting coil system for the UPS-SMES is easy handling and maintenance-free operation. We have selected low temperature superconducting (LTS) coils instead of high temperature superconducting (HTS) coils from the viewpoint of cost and performance. However, it is difficult for the conventional LTS coils to fulfill maintenance-free operation since the cooling methods are either pool boiling with liquid helium or forced flow of supercritical helium. Thus, a conduction cooled LTS pulse coil has been designed as a key component of the UPS-SMES. The development program of 1 MW, 1 sec UPS-SMES is explained

Production and nonclinical evaluation of an autologous iPSC-derived platelet product for the iPLAT1 clinical trial

血小板減少症に対するiPS細胞由来血小板の自己輸血に関する臨床研究」の成果公表（論文発表）について. 京都大学プレスリリース. 2022-09-30.Donor-derived platelets are used to treat or prevent hemorrhage in patients with thrombocytopenia. However, ∼5% or more of these patients are complicated with alloimmune platelet transfusion refractoriness (allo-PTR) due to alloantibodies against HLA-I or human platelet antigens (HPA). In these cases, platelets from compatible donors are necessary, but it is difficult to find such donors for patients with rare HLA-I or HPA. To produce platelet products for patients with aplastic anemia with allo-PTR due to rare HPA-1 mismatch in Japan, we developed an ex vivo good manufacturing process (GMP)–based production system for an induced pluripotent stem cell–derived platelet product (iPSC-PLTs). Immortalized megakaryocyte progenitor cell lines (imMKCLs) were established from patient iPSCs, and a competent imMKCL clone was selected for the master cell bank (MCB) and confirmed for safety, including negativity of pathogens. From this MCB, iPSC-PLTs were produced using turbulent flow bioreactors and new drugs. In extensive nonclinical studies, iPSC-PLTs were confirmed for quality, safety, and efficacy, including hemostasis in a rabbit model. This report presents a complete system for the GMP-based production of iPSC-PLTs and the required nonclinical studies and thus supports the iPLAT1 study, the first-in-human clinical trial of iPSC-PLTs in a patient with allo-PTR and no compatible donor using the autologous product. It also serves as a comprehensive reference for the development of widely applicable allogeneic iPSC-PLTs and other cell products that use iPSC-derived progenitor cells as MCB

Tsunami run-up heights of the 2003 Tokachi-oki earthquake

Tsunami height survey was conducted immediately after the 2003 Tokachi-oki earthquake. Results of the survey show that the largest tsunami height was 4 m to the east of Cape Erimo, around Bansei-onsen, and locally at Mabiro. The results also show that the tsunami height distribution of the 2003 Tokachi-oki earthquake is clearly different from that of the 1952 Tokachi-oki earthquake, suggesting the different source areas of the 1952 and 2003 Tokachioki earthquakes. Numerical simulation of tsunami is carried out using the slip distribution estimated by Yamanaka and Kikuchi (2003). The overall pattern of the observed tsunami height distribution along the coast is explained by the computed ones although the observed tsunami heights are slightly smaller. Large later phase observed at the tide gauge in Urakawa is the edge wave propagating from Cape Erimo along the west coast of the Hidaka area.The 2003 Tokachi-oki earthquak

Reduced mortality during the COVID-19 outbreak in Japan, 2020: a two-stage interrupted time-series design.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to be a major global health burden. This study aims to estimate the all-cause excess mortality occurring in the COVID-19 outbreak in Japan, 2020, by sex and age group. METHODS: Daily time series of mortality for the period January 2015-December 2020 in all 47 prefectures of Japan were obtained from the Ministry of Health, Labour and Welfare, Japan. A two-stage interrupted time-series design was used to calculate excess mortality. In the first stage, we estimated excess mortality by prefecture using quasi-Poisson regression models in combination with distributed lag non-linear models, adjusting for seasonal and long-term variations, weather conditions and influenza activity. In the second stage, we used a random-effects multivariate meta-analysis to synthesize prefecture-specific estimates at the nationwide level. RESULTS: In 2020, we estimated an all-cause excess mortality of -20 982 deaths [95% empirical confidence intervals (eCI): -38 367 to -5472] in Japan, which corresponded to a percentage excess of -1.7% (95% eCI: -3.1 to -0.5) relative to the expected value. Reduced deaths were observed for both sexes and in all age groups except those aged <60 and 70-79 years. CONCLUSIONS: All-cause mortality during the COVID-19 outbreak in Japan in 2020 was decreased compared with a historical baseline. Further evaluation of cause-specific excess mortality is warranted

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

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection