ADAM15 modulates outside-in signalling in chondrocyte–matrix interactions

ADAM15 belongs to a family of transmembrane multi-domain proteins implicated in proteolysis, cell–cell and cell–matrix interactions in various disease conditions. In osteoarthritis (OA), ADAM15 is up-regulated in the chondrocytes already at early stages of cartilage degeneration where it seems to exert homeostatic effects likely associated with its ability to enhance integrin-mediated chondrocyte adhesion to the surrounding collagen matrix. The aim of our present study was, therefore, to characterize functional domains of ADAM15 involved in collagen II (CII) interaction and to analyse associated outside-in signalling events. Accordingly, ADAM15 and respective deletion mutants were stably transfected into the chondrocyte cell line T/C28a4. Transfected cells were adhered to CII and phosphoproteins analysed by Western blotting. Co-immunoprecipitation served to identify protein binding to ADAM15. Our results elucidate the prodomain as critical for the capacity of ADAM15 to enhance CII adhesion, thereby identifying for the first time a cell-adhesive role of a metalloproteinase prodomain. Moreover, the cytoplasmic tail of ADAM15 confers a modulatory effect on the autophosphorylation site Y397 of the focal adhesion kinase (FAK) during chondrocyte–collagen interaction. In conclusion, the newly uncovered impact of ADAM15 on signalling events that arise from chondrocyte interactions with its collagen matrix might contribute to the elucidation of the mechanism underlying its proposed chondroprotective role in degenerative cartilage disease

Spatially Resolved Spectroscopy of Starburst and Post-Starburst Galaxies in The Rich z~0.55 Cluster CL0016+16

We have used the Low Resolution Imaging Spectrograph (LRIS) on the W.M. Keck I telescope to obtain spatially resolved spectroscopy of a small sample of six post-starburst and three dusty-starburst galaxies in the rich cluster CL0016+16 at z=0.55. We use this to measure radial profiles of the Hdelta and OII3727 lines which are diagnostic probes of the mechanisms that give rise to the abrupt changes in star-formation rates in these galaxies. In the post-starburst sample we are unable to detect any radial gradients in the Hdelta line equivalent width - although one galaxy exhibits a gradient from one side of the galaxy to the other. The absence of Hdelta gradients in these galaxies is consistent with their production via interaction with the intra-cluster medium, however, our limited spatial sampling prevents us from drawing robust conclusions. All members of the sample have early type morphologies, typical of post-starburst galaxies in general, but lack the high incidence of tidal tails and disturbances seen in local field samples. This argues against a merger origin and adds weight to a scenario where truncation by the intra-cluster medium is at work. The post-starburst spectral signature is consistent over the radial extent probed with no evidence of OII3727 emission and strong Hdelta absorption at all radii i.e. the post-starburst classification is not an aperture effect. In contrast the dusty-starburst sample shows a tendency for a central concentration of OII3727 emission. This is most straightforwardly interpreted as the consequence of a central starburst. However, other possibilities exist such as a non-uniform dust distribution (which is expected in such galaxies) and/or a non-uniform starburst age distribution. The sample exhibit late type and irregular morphologies.Comment: accepted for publication in PAS

Effects of F, B2O3 and P2O5 on the solubility of water in haplogranite melts compared to natural silicate melts

The effects of F, B2O3 and P2O5 on the H2O solubility in a haplogranite liquid (36 wt. % SiO2, 39 wt. % NaAlSi3O8, 25 wt. % KAlSi3O8) have been determined at 0.5, 1, 2, and 3 kb and 800, 850, and 900°C. The H2O solubility increases with increasing F and B content of the melt. The H2O solubility increase in more important at high pressure (2 and 3 kb) than at low pressure (0.5 kb). At 2 kb and 800°C, the H2O solubility increases from 5.94 to 8.22 wt. % H2O with increasing F content in the melt from 0 to 4.55 wt. %, corresponding to a linear H2O solubility increase of 0.53 mol H2O/mol F. With addition of 4.35 wt. % B2O3, the H2O solubility increases up to 6.86 wt. % H2O at 2 kb and 800°C, corresponding to a linear increase of 1.05 mol H2O/mol B2O3. The results allow to define the individual effects of fluorine and boron on H2O solubility in haplogranitic melts with compositions close to that of H2O-saturated thermal minima (at 0.5–3 kb). Although P has a dramatic effect on the phase relations in the haplogranite system, its effect on the H2O solubility was found to be negligible in natural melt compositions. The concominant increase in H2O solubility and F can not be interpreted on the basis of the available spectroscopic data (existence of hydrated aluminofluoride complexes or not). In contrast, hydrated borates or more probably boroxol complexes have been demonstrated in B-bearing hydrous melts

Productivity and Economic Growth: the Case of Chile

After a decade and a half of economic growth above 7% per year, the Chilean economy has been growing at rates below 3% during the last five years. In this article we suggest that in order to produce a new surge in economic growth, Chile needs a productivity shock arising from economic policy initiatives aimed at improving economic efficiency and institutions. Although Chile has a good record in both, it is still possible to have an upgrade. We run a cross section regression in which the dependent variable is total factor productivity. We conclude that modest changes in the country’s policies and institutions may increase Chile’s rate of growth in 1.5 percent points.

Surface anchoring on layers of grafted liquid-crystalline chain molecules: A computer simulation

By Monte Carlo simulations of a soft ellipsoid model for liquid crystals, we study whether a layer of grafted liquid-crystalline chain molecules can induce tilt in a nematic fluid. The chains are fairly short (four monomers) and made of the same particles as the solvent. They are attached to a substrate which favors parallel (planar) alignment. At low grafting densities, the substrate dominates and we observe planar alignment. On increasing the grafting density, we find a first order transition from planar to tilted alignment. Beyond the transition, the tilt angle with respect to the surface normal decreases continuously. The range of accessible anchoring angles is quite large.Comment: To appear in J. Chem. Phy

Nonlinear and Quantum Optics with Whispering Gallery Resonators

Optical Whispering Gallery Modes (WGMs) derive their name from a famous acoustic phenomenon of guiding a wave by a curved boundary observed nearly a century ago. This phenomenon has a rather general nature, equally applicable to sound and all other waves. It enables resonators of unique properties attractive both in science and engineering. Very high quality factors of optical WGM resonators persisting in a wide wavelength range spanning from radio frequencies to ultraviolet light, their small mode volume, and tunable in- and out- coupling make them exceptionally efficient for nonlinear optical applications. Nonlinear optics facilitates interaction of photons with each other and with other physical systems, and is of prime importance in quantum optics. In this paper we review numerous applications of WGM resonators in nonlinear and quantum optics. We outline the current areas of interest, summarize progress, highlight difficulties, and discuss possible future development trends in these areas.Comment: This is a review paper with 615 references, submitted to J. Op

Accretion disks around binary black holes of unequal mass: GRMHD simulations near decoupling

We report on simulations in general relativity of magnetized disks onto black hole binaries. We vary the binary mass ratio from 1:1 to 1:10 and evolve the systems when they orbit near the binary-disk decoupling radius. We compare (surface) density profiles, accretion rates (relative to a single, non-spinning black hole), variability, effective $\alpha$-stress levels and luminosities as functions of the mass ratio. We treat the disks in two limiting regimes: rapid radiative cooling and no radiative cooling. The magnetic field lines clearly reveal jets emerging from both black hole horizons and merging into one common jet at large distances. The magnetic fields give rise to much stronger shock heating than the pure hydrodynamic flows, completely alter the disk structure, and boost accretion rates and luminosities. Accretion streams near the horizons are among the densest structures; in fact, the 1:10 no-cooling evolution results in a refilling of the cavity. The typical effective temperature in the bulk of the disk is $\sim 10^5 (M/10^8 M_\odot)^{-1/4} (L/L_{\rm edd})^{1/4} {\rm K}$ yielding characteristic thermal frequencies $\sim 10^{15} (M/10^8 M_\odot)^{-1/4} (L/L_{\rm edd})^{1/4}(1+z)^{-1}{\rm Hz}$. These systems are thus promising targets for many extragalactic optical surveys, such as LSST, WFIRST, and PanSTARRS.Comment: 29 pages, 23 captioned figures, 3 tables, submitted to PR

Identification of low-frequency TRAF3IP2 coding variants in psoriatic arthritis patients and functional characterization

Introduction: In recent genome-wide association studies for psoriatic arthritis (PsA) and psoriasis vulgaris, common coding variants in the TRAF3IP2 gene were identified to contribute to susceptibility to both disease entities. The risk allele of p.Asp10Asn (rs33980500) proved to be most significantly associated and to encode a mutant protein with an almost completely disrupted binding property to TRAF6, supporting its impact as a main disease-causing variant and modulator of IL-17 signaling. Methods: To identify further variants, exons 2-4 encoding both known TNF-receptor-associated factor (TRAF) binding domains were sequenced in 871 PsA patients. Seven missense variants and one three-base-pair insertion were identified in 0.06% to 1.02% of alleles. Five of these variants were also present in 931 control individuals at comparable frequency. Constructs containing full-length wild-type or mutant TRAF3IP2 were generated and used to analyze functionally all variants for TRAF6-binding in a mammalian two-hybrid assay. Results: None of the newly found alleles, though, encoded proteins with different binding properties to TRAF6, or to the cytoplasmic tail of the IL-17-receptor α-chain, suggesting that they do not contribute to susceptibility. Conclusions: Thus, the TRAF3IP2-variant p.Asp10Asn is the only susceptibility allele with functional impact on TRAF6 binding, at least in the German population