Elimination of Hepatitis C Virus from Hepatocytes by a Selective Activation of Therapeutic Molecules

To eliminate hepatitis C virus (HCV) from infected hepatocytes, we generated two therapeutic molecules specifically activated in cells infected with HCV. A dominant active mutant of interferon (IFN) regulatory factor 7 (IRF7) and a negative regulator of HCV replication, VAP-C (Vesicle-associated membrane protein-associated protein subtype C), were fused with the C-terminal region of IPS-1 (IFNβ promoter stimulator-1), which includes an HCV protease cleavage site that was modified to be localized on the ER membrane, and designated cIRF7 and cVAP-C, respectively. In cells expressing the HCV protease, cIRF7 was cleaved and the processed fragment was migrated into the nucleus, where it activated various IFN promoters, including promoters of IFNα6, IFNβ, and IFN stimulated response element. Activation of the IFN promoters and suppression of viral RNA replication were observed in the HCV replicon cells and in cells infected with the JFH1 strain of HCV (HCVcc) by expression of cIRF7. Suppression of viral RNA replication was observed even in the IFN-resistant replicon cells by the expression of cIRF7. Expression of the cVAP-C also resulted in suppression of HCV replication in both the replicon and HCVcc infected cells. These results suggest that delivery of the therapeutic molecules into the liver of hepatitis C patients, followed by selective activation of the molecules in HCV-infected hepatocytes, is a feasible method for eliminating HCV

ドッキョ コウレイシャ エ ノ サイガイ タイサク ノ ジョウホウ テイキョウ ニ オケル ケンキュウ

福岡市の高齢者における地域の災害避難場所の認知について, 実態調査を行い, 独居高齢者への災害支援のありかたについて検討した. 地域包括ケアシステムと介護の啓発を目的とした集会の参加者258 名を分析対象とし, 基本属性, フォーマルな相談窓口の認知と活用の有無, 活用している相談窓口数, 地域の避難場所の認知, 楽しみの有無, 情緒的支援, 自尊感情尺度について調査した. 分析は同居群と独居群の２群の差のカテゴリ変数にはχ2 検定, 連続変数にはMann–Whitney U 検定行い群間差を検定した. その結果, 独居高齢者は同居者がいる高齢者より有意に高齢で, 公の相談窓口を知らず, 相談談窓口数が少なく, 避難場所を知らず, 楽しみを有さず, 情的支援を受けていなかった. 都市部における高齢者への災害支援を充実させるためには, 特に独居高齢者が情的な交流のある生活の中で, 楽しみながら社会活動ができる場づくりを行う必要がある. また, 災害支援の情報提供は，社会活動ができる場で行うことが有益であることが示唆された.The purpose of this study was to countermeasure to living alone elderly when disaster occurs. A total of 258 elderly residents participates. A questionnaire included the following scales and items: Disaster shelter. Recognition a formal consultation. Take advantage of a formal consultation. Take advantage number of adviser. Recognition a countermeasure. In life a pleasure. Emotional support. Self Esteem scale. The more elderly, living alone elderly than living with family elderly. The living alone elderly did not know that Fukuoka-city hall and town office is daily living consultation. The urban area to progress in disaster countermeasures, attention to live-alone elderly, whose are provided emotional support, have in life a pleasure, have a place of social activities.原著論文 = Original articl

クマモト ジシン 6カゲツ ニ オケル シュウロウシャ ノ スイミン ト シュカンテキ ケンコウ ジョウタイ ト ノ カンレン ヨウイン

Objective：This study aimed to clarify the relationship between sleep and subjective health condition by focusing on disaster-affected workers six months after the Kumamoto earthquake.Methods：The study population comprised 676 workers at small and medium-sized companies located in Kamimashikigun, Kumamoto Prefecture, where damage after the Kumamoto earthquake was severe. Participants were sent a questionnaire with items related to basic characteristics （sex, age, and family members）, damage to home after the earthquake, subjective symptoms after the earthquake, injury from the earthquakes, changes in income, subjective wellbeing, changes in workload after the earthquake, Athens Insomnia Scale（AIS）, Impact of Event Scale-Revised（IES-R）, General Health Questionnaire（GHQ 28）, and health related QOL Short-Form Health Survey（SF-8）. Responses were collected from 456 people at 13 companies（68.1% response rate）. Of these, 438 responses（96.1%） were valid. This study was approved by the ethical review committee of Fukuoka University School of Medicine.Results：The participants included 334 males and 104 females with an average age of 43.3 years. Two groups were created based on Abbreviated Injury Scale（AIS）scores：279 participants were in the insomnia group and 159 participants were in the non-insomnia group. Compared with that in the non-insomnia group, the patients in the insomnia group were old, had poor subjective health status, and were more likely to have subjective symptoms and injury after the earthquake. The study found a significant positive correlation with intrusion and hyperarousal symptoms in the IES-R subscales. In the SF-8 responses, there were significant negative correlations with BP（Bodily Pain）, GH（General Health）, VT（Vitality）, SF（Social Functioning）, RE（Role Emotional）, MH（Mental Health）, and MCS（Mental Component Summary）. In a logistic regression analysis of sleeping condition in Athens Insomnia Scale（AIS）, BP［OR： 0.942, CI： 0.907-0.978］and avoidance symptoms［OR：0.881, CI：0.799-0.971］improved sleeping condition, whereas hyperarousal symptoms［OR：1.553, CI：1.324-1.823］, social life function［OR：0.954, CI：0.916-0.994］, and daily role function（mental）［OR：0.916, CI：0.866-0.97］were negatively related with good sleeping condition.Discussion：The Kumamoto earthquake influenced the sleep quality for most disaster-affected workers, with approximately 60% reporting insomnia. Because workers with insomnia may exhibit hidden subjective symptoms or suffer from mental stress, long-term preventive systems should be developed and established by companies to improve worker health. Longitudinal studies are required to further examine factors related to sleep condition and outcomes of support systems.原著論文 = Original articl

Completion of Hepatitis C Virus Replication Cycle in Heterokaryons Excludes Dominant Restrictions in Human Non-liver and Mouse Liver Cell Lines

Hepatitis C virus (HCV) is hepatotropic and only infects humans and chimpanzees. Consequently, an immunocompetent small animal model is lacking. The restricted tropism of HCV likely reflects specific host factor requirements. We investigated if dominant restriction factors expressed in non-liver or non-human cell lines inhibit HCV propagation thus rendering these cells non-permissive. To this end we explored if HCV completes its replication cycle in heterokaryons between human liver cell lines and non-permissive cell lines from human non-liver or mouse liver origin. Despite functional viral pattern recognition pathways and responsiveness to interferon, virus production was observed in all fused cells and was only ablated when cells were treated with exogenous interferon. These results exclude that constitutive or virus-induced expression of dominant restriction factors prevents propagation of HCV in these cell types, which has important implications for HCV tissue and species tropism. In turn, these data strongly advocate transgenic approaches of crucial human HCV cofactors to establish an immunocompetent small animal model

Open data from the third observing run of LIGO, Virgo, KAGRA and GEO

The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in April of 2019 and lasting six months, O3b starting in November of 2019 and lasting five months, and O3GK starting in April of 2020 and lasting 2 weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main dataset, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages.Comment: 27 pages, 3 figure

Open data from the third observing run of LIGO, Virgo, KAGRA, and GEO

The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in 2019 April and lasting six months, O3b starting in 2019 November and lasting five months, and O3GK starting in 2020 April and lasting two weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main data set, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages

Relationships between Cognitive Functions and Mood of Elders in an Institute

This study examined the relationships between the cognitive functions and mood of elders in an institution. Nine elders received the POMS (Profile of Mood Scale: Tense-Anxiety, Depression, Angry, Vigor, Fatigue, Confusion) to measure their mood and the Stroop test and the reverse-Stroop test to measure their cognitive functions. The Stroop interference shows that elders' responses are influenced by word when they name the ink-color of an interfered color-word combination. The reverse-Stroop interference shows that they are interfered by color when they name the word of an incongruent color-word combination. POMS scores were under the cut-off points, and the total correct response score related with Vigor (r=0.62, p=0.04). The Stroop interference score was at the standard level, but the reverse-Stroop interference score was lower than that. The Stroop interference score related with Vigor (r=−0.65, p=0.03); the inverse-Stroop interference score related with Tense-Anxiety (r=−0.70, p=0.02) and Confusion (r=−0.61, p=0.04). These results show that 1) the mood of elders in the institution were at a healthy level and elders with high vigor responded correctly, 2) they could read word with high level, 3)elders with high vigor treated color correctly without interference by word, and 4) elders with high tension and confusion treated with word without inference by color