Shear-Velocity Structure and Dynamics Beneath the Sicily Channel and Surrounding Regions of the Central Mediterranean Inferred From Seismic Surface Waves

The evolution of the Sicily Channel Rift Zone (SCRZ) is thought to accommodate the regional tectonic stresses of the Calabrian subduction system. Much of the observations we have today are either limited to the surface or to the upper crust or deeper from regional seismic tomography, missing important details about the lithospheric structure and dynamics. It is unclear whether the rifting is passive from far-field extensional stresses or active from mantle upwelling beneath. We measure Rayleigh-and Love-wave phase velocities from ambient seismic noise and invert for 3-D shear-velocity and radial anisotropic models. Variations in crustal S-velocities coincide with topographic and tectonic features. The Tyrrhenian Sea has a ∼10 km thin crust, followed by the SCRZ (∼20 km). The thickest crust is beneath the Apennine-Maghrebian Mountains (∼55 km). Areas experiencing extension and intraplate volcanism have positive crustal radial anisotropy (VSH > VSV); areas experiencing compression and subduction-related volcanism have negative anisotropy. The crustal anisotropy across the Channel shows the extent of the extension. Beneath the Tyrrhenian Sea, we find very low sub-Moho S-velocities. In contrast, the SCRZ has a thin mantle lithosphere underlain by a low-velocity zone. The lithosphere-asthenosphere boundary rises from 60 km depth beneath Tunisia to ∼33 km beneath the SCRZ. Negative radial anisotropy in the upper mantle beneath the SCRZ is consistent with vertical mantle flow. We hypothesize a more active mantle upwelling beneath the rift than previously thought from an interplay between poloidal and toroidal fluxes related to the Calabrian slab, which in turn produces uplift at the surface and induces volcanism

Early monocyte response following local ablation in hepatocellular carcinoma

Local ablative therapies are established treatment modalities in the treatment of early- and intermediate-stage hepatocellular carcinoma (HCC). Systemic effects of local ablation on circulating immune cells may contribute to patients’ response. Depending on their activation, myeloid cells are able to trigger HCC progression as well as to support anti-tumor immunity. Certain priming of monocytes may already occur while still in the circulation. By using flow cytometry, we analyzed peripheral blood monocyte cell populations from a prospective clinical trial cohort of 21 HCC patients following interstitial brachytherapy (IBT) or radiofrequency ablation (RFA) and investigated alterations in the composition of monocyte subpopulations and monocytic myeloid-derived suppressor cells (mMDSCs) as well as receptors involved in orchestrating monocyte function. We discovered that mMDSC levels increased following both IBT and RFA in virtually all patients. Furthermore, we identified varying alterations in the level of monocyte subpopulations following radiation compared to RFA. (A) Liquid biopsy liquid biopsy of circulating monocytes in the future may provide information on the inflammatory response towards local ablation as part of an orchestrated immune response

Tyrosine 192 within the SH2 domain of the Src-protein tyrosine kinase p56 Lck regulates T-cell activation independently of Lck/CD45 interactions

Funder: DFGFunder: Projekt DEALAbstract: Background: Upon engagement of the T-cell receptor (TCR), the Src-family protein tyrosine kinase p56Lck phosphorylates components of the TCR (e.g. the TCRζ chains), thereby initiating T-cell activation. The enzymatic activity of Lck is primarily regulated via reversible and dynamic phosphorylation of two tyrosine residues, Y394 and Y505. Lck possesses an additional highly conserved tyrosine Y192, located within the SH2 domain, whose role in T-cell activation is not fully understood. Methods: Knock-in mice expressing a phospho-mimetic (Y192E) form of Lck were generated. Cellular and biochemical characterization was performed to elucidate the function of Y192 in primary T cells. HEK 293T and Jurkat T cells were used for in vitro studies. Results: Co-immunoprecipitation studies and biochemical analyses using T cells from LckY192E knock-in mice revealed a diminished binding of LckY192E to CD45 and a concomitant hyperphosphorylation of Y505, thus corroborating previous data obtained in Jurkat T cells. Surprisingly however, in vitro kinase assays showed that LckY192E possesses a normal enzymatic activity in human and murine T cells. FLIM/FRET measurements employing an LckY192E biosensor further indicated that the steady state conformation of the LckY192E mutant is similar to Lckwt. These data suggest that Y192 might regulate Lck functions also independently from the Lck/CD45-association. Indeed, when LckY192E was expressed in CD45−/−/Csk−/− non-T cells (HEK 293T cells), phosphorylation of Y505 was similar to Lckwt, but LckY192E still failed to optimally phosphorylate and activate the Lck downstream substrate ZAP70. Furthermore, LckY19E was recruited less to CD3 after TCR stimulation. Conclusions: Taken together, phosphorylation of Y192 regulates Lck functions in T cells at least twofold, by preventing Lck association to CD45 and by modulating ligand-induced recruitment of Lck to the TCR. Major findings: Our data change the current view on the function of Y192 and suggest that Y192 also regulates Lck activity in a manner independent of Y505 phosphorylation. FN7ZF7ULbDVsMsT6Sckwh1Video Abstrac

Tyrosine 192 within the SH2 domain of the Src-protein tyrosine kinase p56Lck regulates T-cell activation independently of Lck/CD45 interactions.

Funder: DFGFunder: Projekt DEALBACKGROUND: Upon engagement of the T-cell receptor (TCR), the Src-family protein tyrosine kinase p56Lck phosphorylates components of the TCR (e.g. the TCRζ chains), thereby initiating T-cell activation. The enzymatic activity of Lck is primarily regulated via reversible and dynamic phosphorylation of two tyrosine residues, Y394 and Y505. Lck possesses an additional highly conserved tyrosine Y192, located within the SH2 domain, whose role in T-cell activation is not fully understood. METHODS: Knock-in mice expressing a phospho-mimetic (Y192E) form of Lck were generated. Cellular and biochemical characterization was performed to elucidate the function of Y192 in primary T cells. HEK 293T and Jurkat T cells were used for in vitro studies. RESULTS: Co-immunoprecipitation studies and biochemical analyses using T cells from LckY192E knock-in mice revealed a diminished binding of LckY192E to CD45 and a concomitant hyperphosphorylation of Y505, thus corroborating previous data obtained in Jurkat T cells. Surprisingly however, in vitro kinase assays showed that LckY192E possesses a normal enzymatic activity in human and murine T cells. FLIM/FRET measurements employing an LckY192E biosensor further indicated that the steady state conformation of the LckY192E mutant is similar to Lckwt. These data suggest that Y192 might regulate Lck functions also independently from the Lck/CD45-association. Indeed, when LckY192E was expressed in CD45-/-/Csk-/- non-T cells (HEK 293T cells), phosphorylation of Y505 was similar to Lckwt, but LckY192E still failed to optimally phosphorylate and activate the Lck downstream substrate ZAP70. Furthermore, LckY19E was recruited less to CD3 after TCR stimulation. CONCLUSIONS: Taken together, phosphorylation of Y192 regulates Lck functions in T cells at least twofold, by preventing Lck association to CD45 and by modulating ligand-induced recruitment of Lck to the TCR. MAJOR FINDINGS: Our data change the current view on the function of Y192 and suggest that Y192 also regulates Lck activity in a manner independent of Y505 phosphorylation. Video Abstract

Magnetic Properties of FePt Nanoparticles Prepared by a Micellar Method

FePt nanoparticles with average size of 9 nm were synthesized using a diblock polymer micellar method combined with plasma treatment. To prevent from oxidation under ambient conditions, immediately after plasma treatment, the FePt nanoparticle arrays were in situ transferred into the film-growth chamber where they were covered by an SiO2 overlayer. A nearly complete transformation of L10 FePt was achieved for samples annealed at temperatures above 700 °C. The well control on the FePt stoichiometry and avoidance from surface oxidation largely enhanced the coercivity, and a value as high as 10 kOe was obtained in this study. An evaluation of magnetic interactions was made using the so-called isothermal remanence (IRM) and dc-demagnetization (DCD) remanence curves and Kelly–Henkel plots (ΔM measurement). The ΔM measurement reveals that the resultant FePt nanoparticles exhibit a rather weak interparticle dipolar coupling, and the absence of interparticle exchange interaction suggests no significant particle agglomeration occurred during the post-annealing. Additionally, a slight parallel magnetic anisotropy was also observed. The results indicate the micellar method has a high potential in preparing FePt nanoparticle arrays used for ultrahigh density recording media