216,730 research outputs found
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
Top Quark Properties at the TeVatron
Discovered in 1995 by CDF and D0 at the Fermilab Tevatron collider, the top
quark remains interesting to test the Standard Model. Having collected more
than 7 fb of integrated luminosity with both experiments until today,
several top quark properties have been measured with increasing precision,
while other properties have been investigated for the first time. In this
article recent measurements of top quark properties from CDF and D0 are
presented, using between 1 fb and 4.8 fb of data. In particular,
the measurement of the top quark mass, the top quark width, the top antitop
mass difference, a check of the electric charge of the top quark, measurements
of the top antitop quark spin correlation and W helicity as well as a search
for charged Higgs bosons are discussed.Comment: 6 pages, Presented at the 2010 Rencontres de Moriond EW, La Thuile,
Aosta Valley, Italy, 06-13 Mar 201
Evaluative Standards In Art Criticism: A Defence
To a superficial consideration, art criticism might appear as a profession of a parasitic nature, nourishing itself on what is produced by others: by artists. In fact, however, the relation between artistic practice and its criticism is more adequately conceived of as a sort of symbiosis. For, while it is true that criticism depends on and presupposes the existence of its objects - that is, works of art - on the other hand nothing would prevent good art from being equated with and contaminated by bad art if critics ceased to draw a distinction between the two
Using the CLA scanning licence to offer 24x7 access to in-demand book chapters and journal articles at the University of Chester
This is the author's PDF version of an article published in Sconul Focus ©2009. It is available online at http://www.sconul.ac.uk/publications/newsletter/47/17.pdfThis article discusses the implementation and operation of the CLA scanning licence at the University of Chester library
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