Reactivation from latency displays HIV particle budding at plasma membrane, accompanying CD44 upregulation and recruitment

<p>Abstract</p> <p>Background</p> <p>It has been accepted that HIV buds from the cell surface in T lymphocytes, whereas in macrophages it buds into intracellular endosomes. Recent studies, on the other hand, suggest that HIV preferentially buds from the cell surface even in monocytic cells. However, most studies are based on observations in acutely infected cells and little is known about HIV budding concomitant with reactivation from latency. Such studies would provide a better understanding of a reservoir for HIV.</p> <p>Results</p> <p>We observed HIV budding in latently infected T lymphocytic and monocytic cell lines following TNF-α stimulation and examined the upregulation of host factors that may be involved in particle production. Electron microscopy analysis revealed that reactivation of latently infected J1.1 cells (latently infected Jurkat cells with HIV-1) and U1 cells (latently infected U937 cells with HIV-1) displayed HIV particle budding predominantly at the plasma membrane, a morphology that is similar to particle budding in acutely infected Jurkat and U937 cells. When mRNA expression levels were quantified by qRT-PCR, we found that particle production from reactivated J1.1 and U1 cells was accompanied by CD44 upregulation. This upregulation was similarly observed when Jurkat and U937 cells were acutely infected with HIV-1 but not when just stimulated with TNF-α, suggesting that CD44 upregulation was linked with HIV production but not with cell stimulation. The molecules in endocytic pathways such as CD63 and HRS were also upregulated when U1 cells were reactivated and U937 cells were acutely infected with HIV-1. Confocal microscopy revealed that these upregulated host molecules were recruited to and accumulated at the sites where mature particles were formed at the plasma membrane.</p> <p>Conclusion</p> <p>Our study indicates that HIV particles are budded at the plasma membrane upon reactivation from latency, a morphology that is similar to particle budding in acute infection. Our data also suggest that HIV expression may lead to the upregulation of certain host cell molecules that are recruited to sites of particle assembly, possibly coordinating particle production.</p

Effective Resistance of the HTS Floating Coil of the Mini-RT Project

A magnetically levitated superconducting coil device, Mini-RT, has been constructed using high temperature superconductors for the purpose of examining a new magnetic confinement scheme of high-beta plasmas. The floating coil is wound with Bi-2223/Ag tapes, and it is operated in the temperature range of 20-40 K. The excitation tests of the coil were carried out and persistent current was sustained for magnetic levitation. The decay time constant of the persistent current was measured and the effective resistance of the coil cables was evaluated. The obtained resistance shows a considerable increase than that predicted by the n-value model. This might be caused by some electromagnetic effects such as the loss generation with long-lived shielding currents. This consideration was examined by measuring the magnetization of an HTS sample coil

Engineering research and development of magnetically levitated high-temperature superconducting coil system for mini-RT project

A magnetically levitated superconducting coil system is being developed using high temperature superconductors for examining a new magnetic confinement of high-beta plasmas. A miniature double-pancake coil was fabricated with a Bi-2223 Ag-sheathed tape for the purpose of developing a floating control using laser displacement gauges. The coil was inductively excited with liquid nitrogen cooling and successfully levitated in the air. A persistent current switch is also being developed with a Bi-2223 Ag-0.3wt%Mn-sheathed tape, and a prototype model was successfully tested

Lipid control profile in patients with acute coronary syndrome at Tokushima Prefectural Central Hospital

In Japan atherosclerosis society guideline, it is recommended for secondary prevention of acute coronary syndrome to manage lipid. In particular, hyper-LDLemia is known to develop and promote atherosclerosis, and lowering the LDL-C level leads to suppression of recurrence of atherosclerosis. We investigated the profile of lipid control in patients who succeeded in percutaneous coronary intervention for acute coronary syndrome（ACS）at our hospital, and examined by high risk patients（chronic kidney disease, diabetes, obesity）. The achievement rate of LDL-C <１００ at discharge was６２％ of all cases, and the achievement rate of LDL-C <７０was only１６％. In particular, only１２％ of obese patients achieved LDL-C <７０. In recent years, it has been shown that additional administration of ezetimibe or PCSK９ inhibitor to statins further lowers LDL-C and significantly reduces the risk of developing cardiovascular disease. We should recognize that some ACS patients have not reached their goals and actively treat them for secondary prevention

Pinpoint-fluorinated polycyclic aromatic hydrocarbons (F-PAHs): Syntheses of difluorinated subfamily and their properties

Difluorinated polycyclic aromatic hydrocarbons (PAHs) containing three to five benzene rings were systematically synthesized by the Pd(II)-catalyzed Friedel–Crafts-type cyclization of 1,1,2-trifluoro- and 1,1-difluoro-1-alkenes and the In(III)-catalyzed tandem cyclization of bis(1,1-difluoroallene)s. Using an array of the difluorinated PAHs that were obtained and previously reported monofluorinated PAHs, the physical properties of the pinpoint-fluorinated PAHs were investigated. (i) The 19F NMR signals of the bay-region fluorine atoms were shifted downfield by ca. 8–14 ppm for vic-difluorinated PAHs and ca. 11–19 ppm for non-vic-difluorinated and monofluorinated PAHs. (ii) The introduction of fluorine into PAH molecules increased their solubilities in organic solvents, which was best exemplified by the high solubilities of 6,7-difluoropicene (5.4 wt%) and 6-fluoropicene (5.3 wt%) in THF. (iii) The HOMO–LUMO energy gaps of the pinpoint-fluorinated PAHs were smaller than that of the corresponding fluorine-free PAH (i.e., picene) by 0.02–0.26 eV, and the HOMO and LUMO energy levels were lowered by 0.10–0.22 eV and 0.12–0.41 eV, respectively

Management of esophageal stricture after complete circular endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Endoscopic submucosal dissection (ESD) permits removal of esophageal epithelial neoplasms <it>en bloc</it>, but is associated with esophageal stenosis, particularly when ESD involves the entire circumference of the esophageal lumen. We examined the effectiveness of systemic steroid administration for control of postprocedural esophageal stricture after complete circular ESD.</p> <p>Methods</p> <p>Seven patients who underwent wholly circumferential ESD for superficially extended esophageal squamous cell carcinoma were enrolled in this study. In 3 patients, prophylactic endoscopic balloon dilatation (EBD) was started on the third post-ESD day and was performed twice a week for 8 weeks. In 4 patients, oral prednisolone was started with 30 mg daily on the third post-ESD day, tapered gradually (daily 30, 30, 25, 25, 20, 15, 10, 5 mg for 7 days each), and then discontinued at 8 weeks. EBD was used as needed whenever patients complained of dysphagia.</p> <p>Results</p> <p><it>En bloc </it>ESD with tumor-free margins was safely achieved in all cases. Patients in the prophylactic EBD group required a mean of 32.7 EBD sessions; the postprocedural stricture was dilated up to 18 mm in diameter in these patients. On the other hand, systemic steroid administration substantially reduced or eliminated the need for EBD. Corticosteroid therapy was not associated with any adverse events. Post-ESD esophageal stricture after complete circular ESD was persistent, requiring multiple EBD sessions.</p> <p>Conclusions</p> <p>Use of oral prednisolone administration may be an effective treatment strategy for reducing post-ESD esophageal stricture after complete circular ESD.</p

課外学習を利用した看護シミュレーション教育の場づくり

看護学科は、シミュレーション教育の推進のため看護シミュレータ委員会を設置しその教育に取り組んだ。看護シミュレータ委員会は、平成29年度にシミュレータ教材の活用促進と看護学生の知識及び技術の向上を図るための教育支援として発足した。その中で４年次生は、卒業時OSCEの代用教材である自己学習I.V.トレーニングシステム（バーチャルI.V.）の実施を行い、2年次生、３年次生においては、フィジカルアセスメント“physiko”を活用して看護実践能力の向上を図る場とした。また、本教育プログラムは、看護技術の向上だけでなく学生が主体的に実施・計画を立案し、学年を縦断した学生同士の協働作業により、教え合い学び合うことができるアクティブラーニングの実践の場となった。本プログラムには、対象となる学生の95％以上の学生の参加が認められた。一方で、学生個々の事前学習の在り方やグループ編成に偏りがみられたこと、また教員による学生へのサポート体制の充実などの見直しの必要性が課題となった

CNVs in Three Psychiatric Disorders

BACKGROUND: We aimed to determine the similarities and differences in the roles of genic and regulatory copy number variations (CNVs) in bipolar disorder (BD), schizophrenia (SCZ), and autism spectrum disorder (ASD). METHODS: Based on high-resolution CNV data from 8708 Japanese samples, we performed to our knowledge the largest cross-disorder analysis of genic and regulatory CNVs in BD, SCZ, and ASD. RESULTS: In genic CNVs, we found an increased burden of smaller (500 kb) exonic CNVs in SCZ/ASD. Pathogenic CNVs linked to neurodevelopmental disorders were significantly associated with the risk for each disorder, but BD and SCZ/ASD differed in terms of the effect size (smaller in BD) and subtype distribution of CNVs linked to neurodevelopmental disorders. We identified 3 synaptic genes (DLG2, PCDH15, and ASTN2) as risk factors for BD. Whereas gene set analysis showed that BD-associated pathways were restricted to chromatin biology, SCZ and ASD involved more extensive and similar pathways. Nevertheless, a correlation analysis of gene set results indicated weak but significant pathway similarities between BD and SCZ or ASD (r = 0.25–0.31). In SCZ and ASD, but not BD, CNVs were significantly enriched in enhancers and promoters in brain tissue. CONCLUSIONS: BD and SCZ/ASD differ in terms of CNV burden, characteristics of CNVs linked to neurodevelopmental disorders, and regulatory CNVs. On the other hand, they have shared molecular mechanisms, including chromatin biology. The BD risk genes identified here could provide insight into the pathogenesis of BD

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