B cells are capable of independently eliciting rapid reactivation of encephalitogenic CD4 T cells in a murine model of multiple sclerosis

<div><p>Recent success with B cell depletion therapies has revitalized efforts to understand the pathogenic role of B cells in Multiple Sclerosis (MS). Using the adoptive transfer system of experimental autoimmune encephalomyelitis (EAE), a murine model of MS, we have previously shown that mice in which B cells are the only MHCII-expressing antigen presenting cell (APC) are susceptible to EAE. However, a reproducible delay in the day of onset of disease driven by exclusive B cell antigen presentation suggests that B cells require optimal conditions to function as APCs in EAE. In this study, we utilize an <i>in vivo</i> genetic system to conditionally and temporally regulate expression of MHCII to test the hypothesis that B cell APCs mediate attenuated and delayed neuroinflammatory T cell responses during EAE. Remarkably, induction of MHCII on B cells following the transfer of encephalitogenic CD4 T cells induced a rapid and robust form of EAE, while no change in the time to disease onset occurred for recipient mice in which MHCII is induced on a normal complement of APC subsets. Changes in CD4 T cell activation over time did not account for more rapid onset of EAE symptoms in this new B cell-mediated EAE model. Our system represents a novel model to study how the timing of pathogenic cognate interactions between lymphocytes facilitates the development of autoimmune attacks within the CNS.</p></div

Three-loop QCD corrections and b-quark decays

We present three-loop (NNNLO) corrections to the heavy-to-heavy quark transitions in the limit of equal initial and final quark masses. In analogy with the previously found NNLO corrections, the bulk of the result is due to the beta_0^2 alpha_s^3 corrections. The remaining genuine three-loop effects for the semileptonic b --> c decays are estimated to increase the decay amplitude by 0.2(2)%. The perturbative series for the heavy-heavy axial current converges very well.Comment: 5 page

Quasi-long-range ordering in a finite-size 2D Heisenberg model

We analyse the low-temperature behaviour of the Heisenberg model on a two-dimensional lattice of finite size. Presence of a residual magnetisation in a finite-size system enables us to use the spin wave approximation, which is known to give reliable results for the XY model at low temperatures T. For the system considered, we find that the spin-spin correlation function decays as 1/r^eta(T) for large separations r bringing about presence of a quasi-long-range ordering. We give analytic estimates for the exponent eta(T) in different regimes and support our findings by Monte Carlo simulations of the model on lattices of different sizes at different temperatures.Comment: 9 pages, 3 postscript figs, style files include

Finite size scaling in the 2D XY-model and generalized universality

In recent works (BHP), a generalized universality has been proposed, linking phenomena as dissimilar as 2D magnetism and turbulence. To test these ideas, we performed a MC study of the 2D XY-model. We found that the shape of the probability distribution function for the magnetization M is non Gaussian and independent of the system size --in the range of the lattice sizes studied-- below the Kosterlitz-Thoules temperature. However, the shape of these distributions does depend on the temperature, contrarily to the BHP's claim. This behavior is successfully explained by using an extended finite-size scaling analysis and the existence of bounds for M.Comment: 7 pages, 5 figures. Submitted to Phys. Rev. Lett. Details of changes: 1. We emphasized in the abstract the range of validity of our results. 2. In the last paragraph the temperature dependence of the PDF was slightly re-formulate

Regional astrocyte IFN signaling restricts pathogenesis during neurotropic viral infection

Type I IFNs promote cellular responses to viruses, and IFN receptor (IFNAR) signaling regulates the responses of endothelial cells of the blood-brain barrier (BBB) during neurotropic viral infection. However, the role of astrocytes in innate immune responses of the BBB during viral infection of the CNS remains to be fully elucidated. Here, we have demonstrated that type I IFNAR signaling in astrocytes regulates BBB permeability and protects the cerebellum from infection and immunopathology. Mice with astrocyte-specific loss of IFNAR signaling showed decreased survival after West Nile virus infection. Accelerated mortality was not due to expanded viral tropism or increased replication. Rather, viral entry increased specifically in the hindbrain of IFNAR-deficient mice, suggesting that IFNAR signaling critically regulates BBB permeability in this brain region. Pattern recognition receptors and IFN-stimulated genes had higher basal and IFN-induced expression in human and mouse cerebellar astrocytes than did cerebral cortical astrocytes, suggesting that IFNAR signaling has brain region–specific roles in CNS immune responses. Taken together, our data identify cerebellar astrocytes as key responders to viral infection and highlight the existence of distinct innate immune programs in astrocytes from evolutionarily disparate regions of the CNS

Evaluation of two interaction techniques for visualization of dynamic graphs

Several techniques for visualization of dynamic graphs are based on different spatial arrangements of a temporal sequence of node-link diagrams. Many studies in the literature have investigated the importance of maintaining the user's mental map across this temporal sequence, but usually each layout is considered as a static graph drawing and the effect of user interaction is disregarded. We conducted a task-based controlled experiment to assess the effectiveness of two basic interaction techniques: the adjustment of the layout stability and the highlighting of adjacent nodes and edges. We found that generally both interaction techniques increase accuracy, sometimes at the cost of longer completion times, and that the highlighting outclasses the stability adjustment for many tasks except the most complex ones.Comment: Appears in the Proceedings of the 24th International Symposium on Graph Drawing and Network Visualization (GD 2016