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

Combinatorially two-orbit convex polytopes

Any convex polytope whose combinatorial automorphism group has two orbits on the flags is isomorphic to one whose group of Euclidean symmetries has two orbits on the flags (equivalently, to one whose automorphism group and symmetry group coincide.) Hence, a combinatorially two-orbit convex polytope is isomorphic to one of a known finite list, all of which are 3-dimensional: the cuboctahedron, icosidodecahedron, rhombic dodecahedron, or rhombic triacontahedron. The same is true of combinatorially two-orbit normal face-to-face tilings by convex polytopes.Comment: 20 page

Searches for Axion-Like Particles with NGC1275: Current and Future Bounds

Galaxy clusters contain large magnetic fields that make them excellent targets to search for ultralight Axion-Like Particles (ALPs). ALP-photon interconversion imprints quasi-sinusoidal oscillations on the X-ray spectra of point sources in or behind the cluster. The absence of substantial oscillations allows us to place bounds on $g_{a \gamma \gamma}$. Here the bounds from the {\it Chandra} X-ray observations of NGC1275 are presented, as well as those predicted for the {\it Athena} X-ray observatory, due to launch in 2028.Comment: Contributed to the 13th Patras Workshop on Axions, WIMPs and WISPs, Thessaloniki, May 15 to 19, 201

Can we motivate student behavior in a first grade classroom? Reward System vs. Conventional Teaching Discipline Plan

What effect does a reward system have on first grade student behavior? Is there any way to have students behave better than they are currently? There is plenty of research conducted on different types of distracting behavior as well as different types of systems and programs that try to influence behavior. Three first grade classes were selected, observed, and data were recorded on any disruptive or unwanted behavior for three consecutive weeks. Post the first three weeks, a reward system was implanted for each class. Each class was given the opportunity to earn a “free day” in physical education class by decreasing their disruptive behavior during class. Only two of the classes were able to earn their free day

A primary investigation of strategic management in further education (FE) in the small island state of Malta : quo vadis?

This paper investigates the presence of a strategic management regime in the further education (FE) sector in Malta using data gathered in 2012. In this way the type of strategic systems followed (if present) and their implementation is delineated. A qualitative approach was used to gain a deeper understanding of strategic management issues in Maltese FE organizations. Data were collected from seven FE organizations via interviews with senior management team (SMT) officials. The use of strategic management is limited, since only one FE organization has a fully-fledged strategic planning system. Important aspects of strategic planning, like mission statement formulation and performance measurement regimes, are also lacking. An interpretative approach makes it possible to uncover particular nuances in specific sectors in small states. The findings indicate that FE organizations in the Maltese FE sector have a low locus of control, meaning that SMTs may have to shift from strategic planning to strategic thinking.peer-reviewe