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

Teleology and mentalizing in the explanation of action

In empirically informed research on action explanation, philosophers and developmental psychologists have recently proposed a teleological account of the way in which we make sense of people’s intentional behavior. It holds that we typically don’t explain an agent’s action by appealing to her mental states but by referring to the objective, publically accessible facts of the world that count in favor of performing the action so as to achieve a certain goal. Advocates of the teleological account claim that this strategy is our main way of understanding people’s actions. I argue that common motivations mentioned to support the teleological account are insufficient to sustain its generalization from children to adults. Moreover, social psychological studies, combined with theoretical considerations, suggest that we do not explain actions mainly by invoking publically accessible, reason-giving facts alone but by ascribing mental states to the agent

Hard Diffractive Results and Prospects at the Tevatron

We review hard diffractive results and prospects at the Tevatron with an emphasis on factorization breaking in diffractive processes. Upper limits on the exclusive di-jet and chi_c^0 production cross sections at CDF and the status of the D0 Forward Proton Detectors are discussed.Comment: 6 pages, 6 figures, presented at the XXXV International Symposium on Multiparticle Dynamics 2005, August 9-15, 2005, Kromeriz, Czech Republi

Demonstration and resolution of the Gibbs paradox of the first kind

The Gibbs paradox of the first kind (GP1) refers to the false increase in entropy which, in statistical mechanics, is calculated from the process of combining two gas systems S1 and S2 consisting of distinguishable particles. Presented in a somewhat modified form, the GP1 manifests as a contradiction to the second law of thermodynamics. Contrary to popular belief, this contradiction affects not only classical but also quantum statistical mechanics. The present paper resolves the GP1 by considering two effects: 1. The uncertainty about which particles are located in S1 and which in S2 contributes to the entropies of S1 and S2. 2. S1 and S2 are correlated by the fact that if a certain particle is located in one system, it cannot be located in the other. As a consequence, the entropy of the total system consisting of S1 and S2 is not the sum of the entropies of S1 and S2.Comment: added section 4 which resolves the GP1 in its original classical for

'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