Inhibition of IFN-γ Signaling by an Epstein-Barr Virus Immediate-Early Protein

AbstractViruses have evolved elaborate mechanisms to target many aspects of the host's immune response. The cytokine IFN-γ plays a central role in resistance of the host to infection via direct antiviral effects as well as modulation of the immune response. In this study, we demonstrate that the Epstein-Barr virus (EBV) immediate-early protein, BZLF1, inhibits the IFN-γ signaling pathway. BZLF1 decreases the ability of IFN-γ to activate a variety of important downstream target genes, such as IRF-1, p48, and CIITA, and prevents IFN-γ-induced class II MHC surface expression. Additionally, BZLF1 inhibits IFN-γ-induced STAT1 tyrosine phosphorylation and nuclear translocation. Finally, we demonstrate that BZLF1 decreases expression of the IFN-γ receptor, suggesting a mechanism by which EBV may escape antiviral immune responses during primary infection

The impact of land cover change on surface energy and water balance in Mato Grosso, Brazil

The sensitivity of surface energy and water fluxes to recent land cover changes is simulated for a small region in northern Mato Grosso, Brazil. The Simple Biosphere Model (SiB2) is used, driven by biophysical parameters derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) at 250-m resolution, to compare the effects of different land conversion types. The mechanisms through which changes in vegetation alter surface fluxes of energy, momentum, water, and carbon are analyzed for both wet and dry seasons. It is found that morphological changes contribute to warming and drying of the atmosphere while physiological changes, particularly those associated with a plant’s photosynthetic pathway, counterbalance or exacerbate the warming depending on the type of conversion and the season. Furthermore, this study’s results indicate that initial clearing of evergreen and transition forest to bare ground increases canopy temperature by up to 1.7°C. For subsequent land use such as pasture or cropland, the largest effect is seen for the conversion of evergreen forest to C3 cropland during the wet season, with a 21% decrease of the latent heat flux and 0.4°C increase in canopy temperature. The secondary conversion of pasture to cropland resulted in slight warming and drying during the wet season driven mostly by the change in carbon pathway from C4 to C3. For all conversions types, the daily temperature range is amplified, suggesting that plants replacing forest clearing require more temperature tolerance than the trees they replace. The results illustrate that the effect of deforestation on climate depends not only on the overall extent of clearing but also on the subsequent land use type

Epstein-Barr Virus Immediate-Early Protein BRLF1 Induces the Lytic Form of Viral Replication through a Mechanism Involving Phosphatidylinositol-3 Kinase Activation

Expression of the Epstein-Barr virus (EBV) immediate-early (IE) protein BRLF1 induces the lytic form of viral replication in most EBV-positive cell lines. BRLF1 is a transcriptional activator that binds directly to a GC-rich motif present in some EBV lytic gene promoters. However, BRLF1 activates transcription of the other IE protein, BZLF1, through an indirect mechanism which we previously showed to require activation of the stress mitogen-activated protein kinases. Here we demonstrate that BRLF1 activates phosphatidylinositol-3 (PI3) kinase signaling in host cells. We show that the specific PI3 kinase inhibitor, LY294002, completely abrogates the ability of a BRLF1 adenovirus vector to induce the lytic form of EBV infection, while not affecting lytic infection induced by a BZLF1 adenovirus vector. Furthermore, we demonstrate that the requirement for PI3 kinase activation in BRLF1-induced transcriptional activation is promoter dependent. BRLF1 activation of the SM early promoter (which occurs through a direct binding mechanism) does not require PI3 kinase activation, whereas activation of the IE BZLF1 and early BMRF1 promoters requires PI3 kinase activation. Thus, there are clearly two separate mechanisms by which BRLF1 induces transcriptional activation

Electroweak and finite width corrections to top quark decays into transverse and longitudinal W W -bosons

We calculate the electroweak and finite width corrections to the decay of an unpolarized top quark into a bottom quark and a $W$-gauge boson where the helicities of the $W$ are specified as longitudinal, transverse-plus and transverse-minus. Together with the $O(\alpha_s)$ corrections these corrections may become relevant for the determination of the mass of the top quark through angular decay measurements.Comment: 4 pages, 7 postscript figures adde

Computational micromagnetics with Commics

We present our open-source Python module Commics for the study of the magnetization dynamics in ferromagnetic materials via micromagnetic simulations. It implements state-of-the-art unconditionally convergent finite element methods for the numerical integration of the Landau–Lifshitz–Gilbert equation. The implementation is based on the multiphysics finite element software Netgen/NGSolve. The simulation scripts are written in Python, which leads to very readable code and direct access to extensive post-processing. Together with documentation and example scripts, the code is freely available on GitLab. Program summary: Program title: Commics Program Files doi: http://dx.doi.org/10.17632/29wv9h78h7.1 Licensing provisions: GPLv3 Programming language: Python3 Nature of problem: Numerical integration of the Landau–Lifshitz–Gilbert equation in three space dimensions Solution method: Tangent plane scheme [1]: original first-order version, projection-free version, second-order version, efficient second-order IMEX version; Midpoint scheme [2]: original version, IMEX version; Magnetostatic Maxwell equations are treated by the hybrid FEM–BEM method [3] Additional comments including restrictions and unusual features: An installation of the finite element software Netgen/NGSolve and an installation of the boundary element library BEM++ are required. References [1] F. Alouges. A new finite element scheme for Landau–Lifchitz equations. Discrete Contin. Dyn. Syst. Ser. S, 1(2):187–196, 2008. [2] S. Bartels and A. Prohl. Convergence of an implicit finite element method for the Landau–Lifshitz–Gilbert equation. SIAM J. Numer. Anal., 44(4):1405–1419, 2006. [3] D. R. Fredkin and T. R. Koehler. Hybrid method for computing demagnetization fields. IEEE Trans. Magn., 26(2):415–417, 1990

The Epstein-Barr Virus Protein BRLF1 Activates S Phase Entry through E2F1 Induction

The Epstein-Barr Virus (EBV) immediate-early protein BRLF1 is one of two transactivators which mediate the switch from latent to lytic replication in EBV-infected cells. DNA viruses often modulate the function of critical cell cycle proteins to maximize the efficiency of virus replication. Here we have examined the effect of BRLF1 on cell cycle progression. A replication-deficient adenovirus expressing BRLF1 (AdBRLF1) was used to infect normal human fibroblasts and various epithelial cell lines. BRLF1 expression induced S phase entry in contact-inhibited fibroblasts and in the human osteosarcoma cell line U-2 OS. AdBRLF1 infection produced a dramatic increase in the level of E2F1 but not E2F4. In contrast, the levels of Rb, p107, and p130 were decreased in AdBRLF1-infected cells. Electrophoretic mobility shift assays confirmed an increased level of free E2F1 in the AdBRLF1-infected human fibroblasts. Consistent with the previously described effect of E2F1, AdBRLF1-infected fibroblasts had increased levels of p53 and p21 and died by apoptosis. BRLF1-induced activation of E2F1 may be required for efficient EBV lytic replication, since at least one critical viral replication gene (the viral DNA polymerase) is activated by E2F (C. Liu, N. D. Sista, and J. S. Pagano, J. Virol. 70:2545–2555, 1996)

Many-body physics in two-component Bose-Einstein condensates in a cavity: fragmented superradiance and polarization

We consider laser-pumped one-dimensional two-component bosons in a parabolic trap embedded in a high-finesse optical cavity. Above a threshold pump power, the photons that populate the cavity modify the effective atom trap and mediate a coupling between the two components of the Bose-Einstein condensate. We calculate the ground state of the laser-pumped system and find different stages of self-organization depending on the power of the laser. The modified potential and the laser-mediated coupling between the atomic components give rise to rich many-body physics: an increase of the pump power triggers a self-organization of the atoms while an even larger pump power causes correlations between the self-organized atoms -- the BEC becomes fragmented and the reduced density matrix acquires multiple macroscopic eigenvalues. In this fragmented superradiant state, the atoms can no longer be described as two-level systems and the mapping of the system to the Dicke model breaks down.Comment: 8 pages, 3 figures, software available at http://ultracold.or

Reduced cardiovascular morbidity in patients with hemophilia:results of a 5-year multinational prospective study

Hemophilia is a congenital bleeding disorder caused by low levels of clotting factor VIII or IX. The life expectancy of people with hemophilia (PWH) has increased with the availability of clotting factor concentrates. At the same time, the incidence of cardiovascular disease (CVD) has increased; in retrospective studies, there are conflicting data regarding if, despite this increase, the incidence is still lower than in the general population. We prospectively compared the incidence of CVD in PWH vs the predicted incidence. This prospective, multicenter, observational study included adult PWH (aged &gt;30 years) from The Netherlands and United Kingdom. They were followed up for a 5-year period, and CVD incidence was compared with a predicted event rate based on the QRISK2-2011 CVD risk model. The primary end point was the observed fatal and nonfatal CVD incidence after 5 years compared with the estimated events and in relation to severity of hemophilia. The study included 709 patients, of whom 687 (96.9%) completed 5 years' follow-up or reached an end point. For 108 patients, the QRISK score could not be calculated at inclusion. For the remaining 579, fewer CVD events were observed than predicted: 9 vs 24 (relative risk, 0.38; 95% confidence interval, 0.18-0.80; P 5 .01), corresponding with an absolute risk reduction of 2.4%. Severe hemophilia treated on demand had the highest risk reduction. There was no statistically significant relation between severity of hemophilia and incidence of CVD. In hemophilia, a lower-than-predicted CVD incidence was found, supporting the theory that hemophilia protects against CVD. The study is registered at www.clinicaltrials.gov as #NCT01303900.</p