74 research outputs found

    KSHV Reactivation from Latency Requires Pim-1 and Pim-3 Kinases to Inactivate the Latency-Associated Nuclear Antigen LANA

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    Host signal-transduction pathways are intimately involved in the switch between latency and productive infection of herpes viruses. As with other herpes viruses, infection by Kaposi's sarcoma herpesvirus (KSHV) displays these two phases. During latency only few viral genes are expressed, while in the productive infection the virus is reactivated with initiation of extensive viral DNA replication and gene expression, resulting in production of new viral particles. Viral reactivation is crucial for KSHV pathogenesis and contributes to the progression of KS. We have recently identified Pim-1 as a kinase reactivating KSHV upon over-expression. Here we show that another Pim family kinase, Pim-3, also induces viral reactivation. We demonstrate that expression of both Pim-1 and Pim-3 is induced in response to physiological and chemical reactivation in naturally KSHV-infected cells, and we show that they are required for KSHV reactivation under these conditions. Furthermore, our data indicate that Pim-1 and Pim-3 contribute to viral reactivation by phosphorylating the KSHV latency-associated nuclear antigen (LANA) on serine residues 205 and 206. This counteracts the LANA-mediated repression of the KSHV lytic gene transcription. The identification of Pim family kinases as novel cellular regulators of the gammaherpesvirus life cycle facilitates a deeper understanding of virus-host interactions during reactivation and may represent potential novel targets for therapeutic intervention

    Test-retest reliability of selected items of Health Behaviour in School-aged Children (HBSC) survey questionnaire in Beijing, China

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    <p>Abstract</p> <p>Background</p> <p>Children's health and health behaviour are essential for their development and it is important to obtain abundant and accurate information to understand young people's health and health behaviour. The Health Behaviour in School-aged Children (HBSC) study is among the first large-scale international surveys on adolescent health through self-report questionnaires. So far, more than 40 countries in Europe and North America have been involved in the HBSC study. The purpose of this study is to assess the test-retest reliability of selected items in the Chinese version of the HBSC survey questionnaire in a sample of adolescents in Beijing, China.</p> <p>Methods</p> <p>A sample of 95 male and female students aged 11 or 15 years old participated in a test and retest with a three weeks interval. Student Identity numbers of respondents were utilized to permit matching of test-retest questionnaires. 23 items concerning physical activity, sedentary behaviour, sleep and substance use were evaluated by using the percentage of response shifts and the single measure Intraclass Correlation Coefficients (ICC) with 95% confidence interval (CI) for all respondents and stratified by gender and age. Items on substance use were only evaluated for school children aged 15 years old.</p> <p>Results</p> <p>The percentage of no response shift between test and retest varied from 32% for the item on computer use at weekends to 92% for the three items on smoking. Of all the 23 items evaluated, 6 items (26%) showed a moderate reliability, 12 items (52%) displayed a substantial reliability and 4 items (17%) indicated almost perfect reliability. No gender and age group difference of the test-retest reliability was found except for a few items on sedentary behaviour.</p> <p>Conclusions</p> <p>The overall findings of this study suggest that most selected indicators in the HBSC survey questionnaire have satisfactory test-retest reliability for the students in Beijing. Further test-retest studies in a large and diverse sample, as well as validity studies, should be considered for the future Chinese HBSC study.</p

    KSHV Reactivation from Latency Requires Pim-1 and Pim-3 Kinases to Inactivate the Latency-Associated Nuclear Antigen LANA

    Get PDF
    Host signal-transduction pathways are intimately involved in the switch between latency and productive infection of herpes viruses. As with other herpes viruses, infection by Kaposi's sarcoma herpesvirus (KSHV) displays these two phases. During latency only few viral genes are expressed, while in the productive infection the virus is reactivated with initiation of extensive viral DNA replication and gene expression, resulting in production of new viral particles. Viral reactivation is crucial for KSHV pathogenesis and contributes to the progression of KS. We have recently identified Pim-1 as a kinase reactivating KSHV upon over-expression. Here we show that another Pim family kinase, Pim-3, also induces viral reactivation. We demonstrate that expression of both Pim-1 and Pim-3 is induced in response to physiological and chemical reactivation in naturally KSHV-infected cells, and we show that they are required for KSHV reactivation under these conditions. Furthermore, our data indicate that Pim-1 and Pim-3 contribute to viral reactivation by phosphorylating the KSHV latency-associated nuclear antigen (LANA) on serine residues 205 and 206. This counteracts the LANA–mediated repression of the KSHV lytic gene transcription. The identification of Pim family kinases as novel cellular regulators of the gammaherpesvirus life cycle facilitates a deeper understanding of virus–host interactions during reactivation and may represent potential novel targets for therapeutic intervention

    The Intrinsic Antiviral Defense to Incoming HSV-1 Genomes Includes Specific DNA Repair Proteins and Is Counteracted by the Viral Protein ICP0

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    Cellular restriction factors responding to herpesvirus infection include the ND10 components PML, Sp100 and hDaxx. During the initial stages of HSV-1 infection, novel sub-nuclear structures containing these ND10 proteins form in association with incoming viral genomes. We report that several cellular DNA damage response proteins also relocate to sites associated with incoming viral genomes where they contribute to the cellular front line defense. We show that recruitment of DNA repair proteins to these sites is independent of ND10 components, and instead is coordinated by the cellular ubiquitin ligases RNF8 and RNF168. The viral protein ICP0 targets RNF8 and RNF168 for degradation, thereby preventing the deposition of repressive ubiquitin marks and counteracting this repair protein recruitment. This study highlights important parallels between recognition of cellular DNA damage and recognition of viral genomes, and adds RNF8 and RNF168 to the list of factors contributing to the intrinsic antiviral defense against herpesvirus infection

    The transcriptome of Candida albicans mitochondria and the evolution of organellar transcription units in yeasts

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    Modelling In-Store Consumer Behaviour Using Machine Learning and Digital Signage Audience Measurement Data

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    Audience adaptive digital signage is a new emerging tech- nology, where public broadcasting displays adapt their content to the audience demographic and temporal features. The collected audience measurement data can be used as a unique basis for statistical analysis of viewing patterns, interactive display applications and also for further research and observer modelling. Here, we use machine learning methods on real-world digital signage viewership data to predict consumer behav- iour in a retail environment, especially oriented towards the purchase decision process and the roles in purchasing situations. A case study is performed on data from a small retail shop where demographic and audience data of 1294 store customers were collected, manually verified and analysed. Among all customers, 246 store customers were involved in a buying process that resulted in an actual purchase. Comparison of different machine learning methods shows that by using support vector machines we can predict with 88.6 % classification accuracy whether a customer will actually make a purchase, which outperforms classification accuracy of a baseline (majority) classifier by 7.5%. A similar approach can also be used to predict the roles of an individual in the purchase decision process. We show that by extending the audience measurement dataset with additional heuristic features, the support vector machines classifier on average improves the classification accuracy of a baseline classifier by 15 %
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