65 research outputs found

    Characterization of Clonal Polyp Strains Established from Aurelia sp. Inhabiting the Seto Inland Sea of Japan

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    ミズクラゲ(Aurelia sp.)の生活環の中で,ポリプからストロビラを経てエフィラに形態変化する過程はストロビレーションと呼ばれる。ストロビレーションの分子機構の解明に向けて分子生物学的および生化学的研究を進めるために,瀬戸内海産のミズクラゲからポリプのクローン系統を7株確立した。実験室内でストロビレーションを誘導する条件を検討した結果,これらのクローン系統は,25℃から10℃への低温処理によって32- 42日でストロビレーションを開始し,indomethacin (25μM)の投与によって25℃条件下で4-8日でストロビレーションを開始した。また,短期間だけ低温処理をおこなう飼育実験の結果,ストロビレーションは一旦開始すると低温条件下でなくても正常に進行し完了することが明らかになった。さらに,分子系統解析の結果,今回確立したクローン系統がAurelia sp.1(Dawson et al., 2005)であることが示唆された。In the life cycle of Aurelia sp., the transition from polyp to strobila/ephyra is called“strobilation”. To study the molecular mechanisms of strobilation with molecular biological and biochemical approaches, we established 7 clonal polyp strains from Aurelia sp. inhabiting the Seto Inland Sea of Japan. In laboratory condition, the clonal strains started strobilation in 32 - 42 days by a temperature change from 25˚C to 10˚C, or in 4 - 8 days at 25˚C by administration of indomethacin (25 μM). The experiments of short-term low-temperature treatments revealed that strobilation proceeded to the end independently of temperature after strobilation had been initiated. Further, molecular phylogenetic analysis suggested that the clonal strains could be Aurelia sp. 1 (Dawson et al., 2005).本研究は,平成20年度広島大学後援会・教育研究一般助成および平成20年度広島大学大学院生物圏科学研究科・研究科長裁量経費研究助成の支援のもとで実施されたものである

    Endotoxemia by Porphyromonas gingivalis Injection Aggravates Non-alcoholic Fatty Liver Disease, Disrupts Glucose/Lipid Metabolism, and Alters Gut Microbiota in Mice

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    Many risk factors related to the development of non-alcoholic fatty liver disease (NAFLD) have been proposed, including the most well-known of diabetes and obesity as well as periodontitis. As periodontal pathogenic bacteria produce endotoxins, periodontal treatment can result in endotoxemia. The aim of this study was to investigate the effects of intravenous, sonicated Porphyromonas gingivalis (Pg) injection on glucose/lipid metabolism, liver steatosis, and gut microbiota in mice. Endotoxemia was induced in C57BL/6J mice (8 weeks old) by intravenous injection of sonicated Pg; Pg was deactivated but its endotoxin remained. The mice were fed a high-fat diet and administered sonicated Pg (HFPg) or saline (HFco) injections for 12 weeks. Liver steatosis, glucose metabolism, and gene expression in the liver were evaluated. 16S rRNA gene sequencing with metagenome prediction was performed on the gut microbiota. Compared to HFco mice, HFPg mice exhibited impaired glucose tolerance and insulin resistance along with increased liver steatosis. Liver microarray analysis demonstrated that 1278 genes were differentially expressed between HFco and HFPg mice. Gene set enrichment analysis showed that fatty acid metabolism, hypoxia, and TNFα signaling via NFκB gene sets were enriched in HFPg mice. Although sonicated Pg did not directly reach the gut, it changed the gut microbiota and decreased bacterial diversity in HFPg mice. Metagenome prediction in the gut microbiota showed enriched citrate cycle and carbon fixation pathways in prokaryotes. Overall, intravenous injection of sonicated Pg caused impaired glucose tolerance, insulin resistance, and liver steatosis in mice fed high-fat diets. Thus, blood infusion of Pg contributes to NAFLD and alters the gut microbiota

    保育所幼児の栄養摂取状況と腸内細菌叢との関連

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    【目的】我が国では、幼児期の栄養素等摂取量を定量的に示した研究が少なく、日本人の食事摂取基準(2015年版)では小児の十分な資料が存在しない場合は、成人の値から外挿して栄養素等の基準値が求められている。本研究では、保育所幼児の栄養素等の摂取状況を明らかにし、食生活、生活習慣と関わりのある腸内細菌叢を評価指標として検討した。【方法】調査期間は平成26年12月から平成27年3月である。調査対象者は福岡県上毛町の同意が得られた保育所幼児83名である。調査内容は1)食事の実態調査は秤量記録法で食品名を食事記録ノートに記入および同日の食前食後の料理写真撮影、2)排便調査、3)採便後の腸内細菌叢の分析である。分析は(株)テクノスルガ・ラボに依頼し、Nagashima法によりT-RFLPで解析した。解析はすべて統計解析ソフトSPSS Statistics ver.22を用いた。この研究は中村学園大学の倫理委員会から承諾を得ている。【結果】1日あたりの栄養摂取状況で、男女ともに推定エネルギー必要量、たんぱく質の推奨量、脂質と食塩相当量の目標量は基準値よりも高い数値を示した。食物繊維、炭水化物の目標量、カルシウムと鉄、ビタミンAの推奨量は基準値に対して低い数値を示した。栄養素と腸内細菌叢の関連をみるとカルシウムのBifidobacteriumの割合は低摂取群に比べ高摂取群が有意に高い数値を示した。特に、食物繊維の摂取量では基準値に対して不足している人が38.3%を占め、食物繊維摂取量と腸内細菌叢の関連をみると基準値である中摂取群が低摂取群に比べ、推定される群菌のLactobacillales目の割合が高い数値であった。【考察】幼児の健康増進や生活習慣病予防には腸内環境改善が重要であり、栄養的にバランスのよい食事の摂取が不可欠であると考えられる

    Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 variant

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    SARS-CoV-2オミクロンBA.2.75株(通称ケンタウロス)のウイルス学的性状の解明. 京都大学プレスリリース. 2022-10-12.The SARS-CoV-2 Omicron BA.2.75 variant emerged in May 2022. BA.2.75 is a BA.2 descendant but is phylogenetically distinct from BA.5, the currently predominant BA.2 descendant. Here, we show that BA.2.75 has a greater effective reproduction number and different immunogenicity profile than BA.5. We determined the sensitivity of BA.2.75 to vaccinee and convalescent sera as well as a panel of clinically available antiviral drugs and antibodies. Antiviral drugs largely retained potency but antibody sensitivity varied depending on several key BA.2.75-specific substitutions. The BA.2.75 spike exhibited a profoundly higher affinity for its human receptor, ACE2. Additionally, the fusogenicity, growth efficiency in human alveolar epithelial cells, and intrinsic pathogenicity in hamsters of BA.2.75 were greater than those of BA.2. Our multilevel investigations suggest that BA.2.75 acquired virological properties independent of BA.5, and the potential risk of BA.2.75 to global health is greater than that of BA.5

    Convergent evolution of SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant

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    In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including residues R346, K444, L452, N460, and F486. Here, we characterize the convergent evolution of Omicron subvariants and the properties of one recent lineage of concern, BQ.1.1. Our phylogenetic analysis suggests that these five substitutions are recurrently acquired, particularly in younger Omicron lineages. Epidemic dynamics modelling suggests that the five substitutions increase viral fitness, and a large proportion of the fitness variation within Omicron lineages can be explained by these substitutions. Compared to BA.5, BQ.1.1 evades breakthrough BA.2 and BA.5 infection sera more efficiently, as demonstrated by neutralization assays. The pathogenicity of BQ.1.1 in hamsters is lower than that of BA.5. Our multiscale investigations illuminate the evolutionary rules governing the convergent evolution for known Omicron lineages as of 2022

    Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants

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    In late 2022, SARS-CoV-2 Omicron subvariants have become highly diversified, and XBB is spreading rapidly around the world. Our phylogenetic analyses suggested that XBB emerged through the recombination of two cocirculating BA.2 lineages, BJ.1 and BM.1.1.1 (a progeny of BA.2.75), during the summer of 2022. XBB.1 is the variant most profoundly resistant to BA.2/5 breakthrough infection sera to date and is more fusogenic than BA.2.75. The recombination breakpoint is located in the receptor-binding domain of spike, and each region of the recombinant spike confers immune evasion and increases fusogenicity. We further provide the structural basis for the interaction between XBB.1 spike and human ACE2. Finally, the intrinsic pathogenicity of XBB.1 in male hamsters is comparable to or even lower than that of BA.2.75. Our multiscale investigation provides evidence suggesting that XBB is the first observed SARS-CoV-2 variant to increase its fitness through recombination rather than substitutions

    Compensatory role of the Nrf2-ARE pathway against paraquat toxicity: Relevance of 26S proteasome activity

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    Oxidative stress and the ubiquitin-proteasome system play a key role in the pathogenesis of Parkinson disease. Although the herbicide paraquat is an environmental factor that is involved in the etiology of Parkinson disease, the role of 26S proteasome in paraquat toxicity remains to be determined. Using PC12 cells overexpressing a fluorescent protein fused to the proteasome degradation signal, we report here that paraquat yielded an inhibitory effect on 26S proteasome activity without an obvious decline in 20S proteasome activity. Relative low concentrations of proteasome inhibitors caused the accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2), which is targeted to the ubiquitin-proteasome system, and activated the antioxidant response element (ARE)-dependent transcription. Paraquat also upregulated the protein level of Nrf2 without increased expression of Nrf2 mRNA, and activated the Nrf2-ARE pathway. Consequently, paraquat induced expression of Nrf2-dependent ARE-driven genes, such as γ-glutamylcysteine synthetase, catalase, and hemeoxygenase-1. Knockdown of Nrf2 or inhibition of γ-glutamylcysteine synthetase and catalase exacerbated paraquat-induced toxicity, whereas suppression of hemeoxygenase-1 did not. These data indicate that the compensatory activation of the Nrf2-ARE pathway via inhibition of 26S proteasome serves as part of a cellular defense mechanism to protect against paraquat toxicity

    Enantioselective Total Synthesis of cis

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    One-day psychosocial education program for people with epilepsy: A continuation study of the “Epi-school”

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    Psychosocial education programs for people with epilepsy (PWE) can improve epilepsy knowledge and quality of life (QOL), whereas the availability of these programs is limited in Japan compared to other developed countries. This study evaluated the feasibility and effectiveness of a one-day group psychosocial education program named the “one-day Epi-school” for PWE and their relatives. The previous program (Epi-school) required consistent participation in three sessions, resulting in problems with program continuation rates, with 45.5% of PWE completing the program. Therefore, the “one-day Epi-school” was designed to provide information about epilepsy and address psychosocial issues related to coexisting epilepsy symptoms, such as self-stigma and self-esteem, while allowing participants to accomplish these programs within a single day. The study recruited a sample of 32 PWE and their relatives from a psychiatric clinic. They completed assessments of knowledge, self-stigma, self-esteem, and quality of life before and after the program. The results exhibited a significant increase in epilepsy knowledge after the intervention for PWE and their relatives. However, we could not identify other significant changes. The participation completion rate was 100%. The post-participation questionnaire proved beneficial to interact with other PWE. The study suggests that a single intervention, e.g., the one-day Epi-school, may be insufficient for enhancing other factors, yet it can be an adequate opportunity for learning and interacting. It is also necessary to implement future studies with larger sample sizes, a control group, and prolonged follow-up periods for the program's value and validity
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