Vaccinia protein C16 blocks innate immune sensing of DNA by binding the Ku complex

VACV gene C16L encodes a 37-kDa protein that is highly conserved in orthopoxviruses and functions as an immunomodulator. Intranasal infection of mice with a virus lacking C16L (vΔC16) induced less weight loss, fewer signs of illness and increased infiltration of leukocytes to the lungs compared with wild-type virus. To understand C16’s mechanism of action, tandem affinity purification and mass spectrometry were used to identify C16 binding partners. This revealed that Ku70, Ku80 and PHD2 interact with C16 in cells. Ku70 and Ku80 constitute the Ku heterodimer, a well characterised DNA repair complex. MEFs lacking Ku, or the other component of the DNA-dependent protein kinase (DNA-PK) complex, the catalytic subunit of DNA-PK (DNA-PKcs), were shown to be deficient in the upregulation of IRF-3-dependent genes such as Cxcl10, Il6 and Ifnb in response to transfection of DNA, but not poly (I:C). Furthermore, following infection of MEFs with VACV strain MVA the activation of Cxcl10 or Il6 transcription was dependent on DNA-PK. Therefore, DNA-PK is a DNA sensor capable of detecting poxvirus DNA and activating IRF-3-dependent innate immunity. C16 inhibited the binding of Ku to DNA, and therefore inhibited DNA-mediated induction of Cxcl10 and Il-6 in MEFs. The role of C16 in vivo was also examined: infection with vΔC16 led to increased production of Cxcl10 and Il-6 following intranasal infection of mice compared with wild-type virus. C16 is therefore an inhibitor of DNA-PK-mediated DNA sensing and innate immune activation. C16 was also shown to bind to PHD2, an enzyme involved in regulation of hypoxic signalling. VACV was found to activate the transcription of hypoxia-related genes, and C16 expression in cells was also capable of doing this. The role of hypoxic signalling in VACV infection remains poorly understood

'Learning Styles' and 'Approaches to Studying' in Sports-Related Programmes: Relationships to Academic Achievement and Implications for Successful Learning, Teaching and Assessment: Project Report Summary

There are relatively few recent investigations that have addressed the issues of preferred learning styles and approaches to studying in sports-related disciplines such as: Sports Studies; Sports and Exercise Science; Coaching Science; Sport and Leisure Management and Outdoor Recreation Management. The purpose of this study was therefore to examine student learning across a range of sport-related programmes at a UK University College. It applied tools from two related, but different, educational research paradigms: approaches to learning and learning styles analysis. Thus, these differing means of researching student learning were tested against the same student group. Results were compared to students’ perceptions of their own developing autonomy of learning and achieved grades; insights were generated into the particular learning approaches and styles of sports students; and tentative recommendations are made on the implications of the findings for higher education teachers seeking to promote improvements in the learning of sports subjects

Medical advertising in the Wrexham press, 1855-1906

This is the author's PDF version of a book chapter published by Oak Knoll Press & The British Library© 2005.This book chapter discusses the variety of medical advertisements found in Wrexham newspapers from 1855 to 1906

How to ensure partnerships go wrong

This paper is based upon recent academic research on partnership working in a variety of contexts and personal experience of strategic partnerships in the UK. The paper uses examples to draw out some general lessons about when partnerships are likely to succeed and when they may fail

Gendered Activity and Jesus's Saying Not to Worry

The flowers’ activity in the saying of Jesus about anxiety indicates an interest in cloth production across the socio-economic spectrum. I demonstrate that wool-working is a central feature of the multiform tradition of this saying and that spinning in particular was associated with women. I further note that the activity of gazing at flowers was an activity that was connected with the iconography of the goddess Spes, the Roman personification of Hope. These two cues render the entire saying an exhortation toward the feminine

Heterogeneous mark-ups, growth and endogenous misallocation

The recent work on misallocation argues that aggregate productivity in poor countries is low because various market frictions prevent marginal products from being equalized. By focusing on such allocative inefficiencies, misallocation is construed as a purely static phenomenon. This paper argues that misallocation also has dynamic consequences because it interacts with firms’ innovation and entry decisions, which determine the economy’s growth rate. To study this link between misallocation and growth, I construct a tractable endogenous growth model with heterogeneous firms, where misallocation stems from imperfectly competitive output markets. The model has an analytical solution and hence makes precise predictions about the relationship between growth, misallocation and welfare. It stresses the importance of entry. An increase in entry reduces misallocation by fostering competition. If entry also increases the economy-wide growth rate, static misallocation and growth are negatively correlated. The welfare consequences of misallocation might therefore be much larger once these dynamic considerations are taken into account. Using firm-level panel data from Indonesia, I present reduced form evidence for the importance of imperfect output market and calibrate the structural parameters. A policy, which reduces existing entry barriers, increases growth and reduces misallocation. The dynamic growth effects are more than four times as large as their static counterpart

When outcome expectations become habitual: explaining vs. predicting new media technology use from a social cognitive perspective

This study examined the triadic relationship between expected outcomes, habit strength, and media technology use within the model of media attendance (Larose & Eastin, 2004). Mobile phone users (N = 664) were divided into two groups using a stratified random sampling method. Respondents of group one (n = 334) were surveyed on existing mobile phone use, respondents of group two (n = 310) were surveyed on the intention to use mobile video phone. On the basis of structural equation analysis, the results of this study support the assumption that within the model of media attendance existing media use is more likely to be explained by habit strength, and new media use is more likely to be predicted by outcome expectations