Role of Rip2 in development of tumor-infiltrating MDSCs and bladder cancer metastasis.

Tumor invasion and metastases represent a complex series of molecular events that portends a poor prognosis. The contribution of inflammatory pathways mediating this process is not well understood. Nod-like receptors (NLRs) of innate immunity function as intracellular sensors of pathogen motifs and danger molecules. We propose a role of NLRs in tumor surveillance and in programming tumor-infiltrating lymphocytes (TILs). In this study, we examined the downstream serine/threonine and tyrosine kinase Rip2 in a murine model of bladder cancer. In Rip2-deficient C57Bl6 mice, larger orthotopic MB49 tumors developed with more numerous and higher incidence of metastases compared to wild-type controls. As such, increased tumor infiltration of CD11b+ Gr1hi myeloid-derived suppressor cells (MDSCs) with concomitant decrease in T cells and NK cells were observed in Rip2-deficient tumor bearing animals using orthotopic and subcutaneous tumor models. Rip2-deficient tumors showed enhanced epithelial-to-mesenchymal transition, with elevated expression of zeb1, zeb2, twist, and snail in the tumor microenvironment. We found that the absence of Rip2 plays an intrinsic role in fostering the development of granulocytic MDSCs by an autocrine and paracrine effect of granulocytic colony stimulating factor (G-CSF) expression. Our findings suggest that NLR pathways may be a novel modality to program TILs and influence tumor metastases

Classification of extremal elliptic K3 surfaces and fundamental groups of open K3 surfaces

We present a complete list of extremal elliptic K3 surfaces. There are altogether 325 of them. The first 112 coincides with Miranda-Persson's list for semi-stable ones. The data include the transcendental lattice which determines uniquely the K3 surface by a result of Shioda and Inose, the singular fibre type and the Mordell Weil group. As an application, we give a sufficient condition for the topological fundamental group of complement to an ADE-configuration of smooth rational curves on a K3 surface to be trivial.Comment: 25 pages, Nagoya Math. J. to appea

Solar surface rotation: N-S asymmetry and recent speed-up

Context. The relation between solar surface rotation and sunspot activity still remains open. Sunspot activity has dramatically reduced in solar cycle 24 and several solar activity indices and flux measurements experienced unprecedentedly low levels during the last solar minimum. Aims. We aim to reveal the momentary variation of solar surface rotation, especially during the recent years of reducing solar activity. Methods. We used a dynamic, differentially rotating reference system to determine the best-fit annual values of the differential rotation parameters of active longitudes of solar X-ray flares and sunspots in 1977-2012. Results. The evolution of rotation of solar active longitudes obtained with X-ray flares and with sunspots is very similar. Both hemispheres speed up since the late 1990s, with the southern hemisphere rotating slightly faster than the north. Earlier, in 1980s, rotation in the northern hemisphere was considerably faster, but experienced a major decrease in the early 1990s. On the other hand, little change was found in the southern rotation during these decades. This led to a positive asymmetry in north-south rotation rate in the early part of the time interval studied. Conclusions. The rotation of both hemispheres has been speeding up at roughly the same rate since late 1990s, with the southern hemisphere rotating slightly faster than the north. This period coincides with the start of dramatic weakening of solar activity, as observed in sunspots and several other solar, interplanetary and geomagnetic parameters.Comment: Astron. Astrophys. Lett. (accepted