Strong CP violation and the neutron electric dipole form factor

We calculate the neutron electric dipole form factor induced by the CP violating theta-term of QCD, within a perturbative chiral quark model which includes pion and kaon clouds. On this basis we derive the neutron electric dipole moment and the electron-neutron Schiff moment. From the existing experimental upper limits on the neutron electric dipole moment we extract constraints on the theta-parameter and compare our results with other approaches.Comment: 18 pages, 2 figures, accepted for publication in Phys. Atom. Nuc

Cavity polariton optomechanics: Polariton path to fully resonant dispersive coupling in optomechanical resonators

Resonant photoelastic coupling in semiconductor nanostructures opens new perspectives for strongly enhanced light-sound interaction in optomechanical resonators. One potential problem, however, is the reduction of the cavity Q-factor induced by dissipation when the resonance is approached. We show in this letter that cavity-polariton mediation in the light-matter process overcomes this limitation allowing for a strongly enhanced photon-phonon coupling without significant lifetime reduction in the strongly-coupled regime. Huge optomechanical coupling factors in the PetaHz/nm range are envisaged, three orders of magnitude larger than the backaction produced by the mechanical displacement of the cavity mirrors.Comment: 6 pages, 4 figure

Platelet-Activating Factor-Induced Reduction in Contact Hypersensitivity Responses Is Mediated by Mast Cells via Cyclooxygenase-2-Dependent Mechanisms

Platelet-activating factor (PAF) stimulates numerous cell types via activation of the G protein-coupled PAF receptor (PAFR). PAFR activation not only induces acute proinflammatory responses, but it also induces delayed systemic immunosuppressive effects by modulating host immunity. Although enzymatic synthesis and degradation of PAF are tightly regulated, oxidative stressors, such as UVB, chemotherapy, and cigarette smoke, can generate PAF and PAF-like molecules in an unregulated fashion via the oxidation of membrane phospholipids. Recent studies have demonstrated the relevance of the mast cell (MC) PAFR in PAFR-induced systemic immunosuppression. The current study was designed to determine the exact mechanisms and mediators involved in MC PAFR-mediated systemic immunosuppression. By using a contact hypersensitivity model, the MC PAFR was not only found to be necessary, but also sufficient to mediate the immunosuppressive effects of systemic PAF. Furthermore, activation of the MC PAFR induces MC-derived histamine and PGE2 release. Importantly, PAFR-mediated systemic immunosuppression was defective in mice that lacked MCs, or in MC-deficient mice transplanted with histidine decarboxylase- or cyclooxygenase-2-deficient MCs. Lastly, it was found that PGs could modulate MC migration to draining lymph nodes. These results support the hypothesis that MC PAFR activation promotes the immunosuppressive effects of PAF in part through histamine- and PGE2-dependent mechanisms

Purified plasma membranes inhibit polypeptide growth factor-induced DNA synthesis in subconfluent 3T3 cells.

Plasma membranes derived from NR-6 cells, a variant line of Swiss mouse 3T3 cells that does not have cell surface receptors for epidermal growth factor (EGF), inhibited EGF-induced stimulation of DNA synthesis by 50% in serum-starved, subconfluent 3T3 cells. Membranes derived from SV3T3 cells were much less effective in inhibiting EGF-induced DNA synthesis. This inhibition on DNA synthesis by NR-6 membranes was not a direct effect of membranes on EGF, nor could it be overcome by high concentrations of EGF. NR-6 membranes were most effective when added 3 h before EGF addition and had little effect when added 2 h or more after EGF. NR-6 membranes also reduced the stimulation of DNA synthesis induced by platelet-derived growth factor or fibroblast growth factor in serum-starved 3T3 cells. These findings indicate that membrane-membrane interactions between nontransformed cells may diminish their ability to proliferate in response to serum polypeptide growth factors

The effects of growth factors on multicellular spheroids formed by chick embryonic retinal cells

Retinal cells from chick embryos aged 7.5 days of gestation were cultured for two months in a non-adherent suspension culture dish to study the effects of growth factors and co-culture with retinal pigment epithelial cells on their differentiation. Dissociated retinal cells became cellular aggregates (multicellular spheroids) within a day, and rosettes were formed in the spheroids after 2 days. Ultrastructurally, neurons of the rosettes developed connecting cilia, ellipsoids (accumulation of mitochondria), and external limiting membrane, indicative of their differentiation into photoreceptor cells. Epidermal growth factor enhanced the expression of rhodopsin by rosette-forming neurons, while basic fibroblast growth factor induced the growth of Mueller cells at 4 weeks, and their transdifferentiation into lens-epithelial-like cells at 8 weeks. Co-culture of retinal cells with retinal pigment epithelial cells enhanced the formation of rosettes in spheroids. Multicellular spheroids formed in a dish for suspension culture would provide a convenient in vitro system to examine differentiation and transdifferentiation of the retina.</p

MAPK-activated protein kinase 2-deficiency causes hyperacute tumor necrosis factor-induced inflammatory shock

Background: MAPK-activated protein kinase 2 (MK2) plays a pivotal role in the cell response to (inflammatory) stress. Among others, MK2 is known to be involved in the regulation of cytokine mRNA metabolism and regulation of actin cytoskeleton dynamics. Previously, MK2-deficient mice were shown to be highly resistant to LPS/D-Galactosamine-induced hepatitis. Additionally, research in various disease models has indicated the kinase as an interesting inhibitory drug target for various acute or chronic inflammatory diseases. Results: We show that in striking contrast to the known resistance of MK2-deficient mice to a challenge with LPS/D-Gal, a low dose of tumor necrosis factor (TNF) causes hyperacute mortality via an oxidative stress driven mechanism. We identified in vivo defects in the stress fiber response in endothelial cells, which could have resulted in reduced resistance of the endothelial barrier to deal with exposure to oxidative stress. In addition, MK2-deficient mice were found to be more sensitive to cecal ligation and puncture-induced sepsis. Conclusions: The capacity of the endothelial barrier to deal with inflammatory and oxidative stress is imperative to allow a regulated immune response and maintain endothelial barrier integrity. Our results indicate that, considering the central role of TNF in pro-inflammatory signaling, therapeutic strategies examining pharmacological inhibition of MK2 should take potentially dangerous side effects at the level of endothelial barrier integrity into account

Feedback activation of neurofibromin terminates growth factor-induced Ras activation.

BACKGROUND: Growth factors induce a characteristically short-lived Ras activation in cells emerging from quiescence. Extensive work has shown that transient as opposed to sustained Ras activation is critical for the induction of mitogenic programs. Mitogen-induced accumulation of active Ras-GTP results from increased nucleotide exchange driven by the nucleotide exchange factor Sos. In contrast, the mechanism accounting for signal termination and prompt restoration of basal Ras-GTP levels is unclear, but has been inferred to involve feedback inhibition of Sos. Remarkably, how GTP-hydrolase activating proteins (GAPs) participate in controlling the rise and fall of Ras-GTP levels is unknown. RESULTS: Monitoring nucleotide exchange of Ras in permeabilized cells we find, unexpectedly, that the decline of growth factor-induced Ras-GTP levels proceeds in the presence of unabated high nucleotide exchange, pointing to GAP activation as a major mechanism of signal termination. Experiments with non-hydrolysable GTP analogues and mathematical modeling confirmed and rationalized the presence of high GAP activity as Ras-GTP levels decline in a background of high nucleotide exchange. Using pharmacological and genetic approaches we document a raised activity of the neurofibromatosis type I tumor suppressor Ras-GAP neurofibromin and an involvement of Rsk1 and Rsk2 in the down-regulation of Ras-GTP levels. CONCLUSIONS: Our findings show that, in addition to feedback inhibition of Sos, feedback stimulation of the RasGAP neurofibromin enforces termination of the Ras signal in the context of growth-factor signaling. These findings ascribe a precise role to neurofibromin in growth factor-dependent control of Ras activity and illustrate how, by engaging Ras-GAP activity, mitogen-challenged cells play safe to ensure a timely termination of the Ras signal irrespectively of the reigning rate of nucleotide exchange.We acknowledge funding by the German research council (DFG), grant # RU 860/4-1 (AH), by the Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01EO1002 (I.R., R.M.), by the BBSRC and through the BBSRC Midlands Interdisciplinary BioSciences Training Partnership (MAE-F) (GL - BB/G01227X/1 and BB/M00015X/1) and the National Council on Science and Technology of Mexico (CONACYT) (MAE-F).This is the final published version. It first appeared at http://biosignaling.biomedcentral.com/articles/10.1186/s12964-016-0128-z

A Theory for the Conformal Factor in Quantum R2R^2 Gravity

A new theory for the conformal factor in R$^2$-gravity is developed. The infrared phase of this theory, which follows from the one-loop renormalization group equations for the whole quantum R$^2$-gravity theory is described. The one-loop effective potential for the conformal factor is found explicitly and a mechanism for inducing Einstein gravity at the minimum of the effective potential for the conformal factor is suggested. A comparison with the effective theory of the conformal factor induced by the conformal anomaly, and also aiming to describe quantum gravity at large distances, is done.Comment: 10 pages, LaTeX file, June 1-199