Sortilin Is Upregulated in Osteoarthritis-Dependent Cartilage Calcification and Associated with Cellular Senescence.

Osteoarthritis (OA) is a chronic joint disease characterized by articular cartilage calcification, loss of articular cartilage, bone changes, pain, and disability. Cartilage calcification is one hallmark of OA and is predominantly caused by basic calcium crystals formed due to an imbalance of the pyrophosphate pathway. Sortilin is a transmembrane protein that contributes to vascular calcification in atherosclerosis by externalizing alkaline phosphatase (ALP)-containing vesicles. Calcification in atherosclerosis and osteoarthritis has been associated with cellular senescence. The aim of this study was to investigate the potential role of sortilin and senescence in osteoarthritis-dependent cartilage calcification. Osteoarthritic cartilage from human knee joints was collected after joint replacement, and samples were analyzed by immunohistochemistry and quantitative RT-PCR analysis. Human chondrocytes were treated with osteogenic medium for up to 21 days to induce calcification. Western blots for sortilin and ALP, as well as an ALP activity assay, were performed. Human chondrocytes were treated with mitomycin C to induce senescence, and sortilin expression was quantified at the protein and gene levels. Sections of knee joints from a murine model of osteoarthritis were stained for sortilin and p16 and analyzed by immunohistochemistry. Treatment of wild-type chondrocytes using an osteogenic medium similar to human chondrocytes was performed. Osteoarthritic cartilage from mouse and human knee joints showed an increased number of sortilin and p16-positive chondrocytes compared to healthy cartilage. This observation was corroborated by increased gene expression of sortilin and p16 in mild and moderate osteoarthritic cartilage samples. To investigate the mechanism of sortilin regulation, human chondrocytes were treated with osteogenic medium to induce calcification. Sortilin protein levels and expression were increased after 7 days of stimulation, whereas ALP levels and activity were upregulated after 21 days of stimulation. Similar observations were made in a murine osteoarthritis model. Mechanistically, senescent chondrocytes induced by mitomycin C showed an upregulation of sortilin and ALP gene expression compared to non-senescent chondrocytes. Our data indicate that sortilin and ALP are upregulated during cartilage calcification, which is associated with chondrocyte senescence and thus might contribute to the pathogenesis of osteoarthritis. Cellular senescence seems to induce sortilin expression

Visual orbit for the low-mass binary Gliese 22 AC from speckle interferometry

Based on 14 data points obtained with near-infrared speckle interferometry and covering an almost entire revolution, we present a first visual orbit for the low-mass binary system Gliese 22 AC. The quality of the orbit is largely improved with respect to previous astrometric solutions. The dynamical system mass is 0.592 +- 0.065 solar masses, where the largest part of the error is due to the Hipparcos parallax. A comparison of this dynamical mass with mass-luminosity relations on the lower main sequence and theoretical evolutionary models for low-mass objects shows that both probably underestimate the masses of M dwarfs. A mass estimate for the companion Gliese 22 C indicates that this object is a very low-mass star with a mass close to the hydrogen burning mass limit.Comment: Accepted by Astronomy and Astrophysics, 6 pages, 2 figure

Orbital motion in T Tauri binary systems

Using speckle-interferometry we have carried out repeated measurements of relative positions for the components of 34 T Tauri binary systems. The projected separation of these components is low enough that orbital motion is expected to be observable within a few years. In most cases orbital motion has indeed been detected. The observational data is discussed in a manner similar to Ghez et al. (1995). However, we extend their study to a larger number of objects and a much longer timespan. The database presented in this paper is valuable for future visible orbit determinations. It will yield empirical masses for T Tauri stars that now are only poorly known. The available data is however not sufficient to do this at the present time. Instead, we use short series of orbital data and statistical distributions of orbital parameters to derive an average system mass that is independent of theoretical assumptions about the physics of PMS stars. For our sample this mass is 2.0 solar masses and thus in the order of magnitude one expects for the mass sum of two T Tauri stars. It is also comparable to mass estimates obtained for the same systems using theoretical PMS evolutionary models.Comment: Accepted by Astronomy and Astrophysic

A Search for Close Binaries in the Rho Ophiuchus Star-Forming Region

We have carried out a new, near-infrared speckle imaging survey of 19 members of the young stellar population in the nearby (d=140 pc), Rho Ophiuchi cloud core. Results for four binary and one newly discovered triple system are reported. Data for all known multiple systems among the pre-main-sequence population of Rho Oph are tabulated. We define a "restricted binary fraction", Fbr, and a "restricted companion fraction", Fcr, as counting only those systems most detectable in the present and previous high-resolution near-infrared imaging surveys, having separations between 0.1-1.1 arcsec and K-band magnitude differences, Delta K < 3. Analysis of all the available multiplicity data results in updated values of Fbr=Fcr=24%+/-11% for the Ophiuchus pre-main-sequence population. These values are consistent with the values in the Taurus star-forming region, and Fcr is in excess by a factor of 2 relative to the Main Sequence at the 1-sigma level.Comment: 21 pages, 6 figures, 4 table

Infrastructure for Detector Research and Development towards the International Linear Collider

The EUDET-project was launched to create an infrastructure for developing and testing new and advanced detector technologies to be used at a future linear collider. The aim was to make possible experimentation and analysis of data for institutes, which otherwise could not be realized due to lack of resources. The infrastructure comprised an analysis and software network, and instrumentation infrastructures for tracking detectors as well as for calorimetry.Comment: 54 pages, 48 picture

Mass ratios of the components in T Tauri binary systems and implications for multiple star formation

Using near-infrared speckle interferometry we have obtained resolved JHK-photometry for the components of 58 young binary systems. From these measurements, combined with other data taken from literature, we derive masses and particularly mass ratios of the components. We use the J-magnitude as an indicator for the stellar luminosity and assign the optical spectral type of the system to the primary. On the assumption that the components within a binary are coeval we can then place also the secondaries into the HRD and derive masses and mass ratios for both components by comparison with different sets of current theoretical pre-main sequence evolutionary tracks. The resulting distribution of mass ratios is comparatively flat for M(2)/M(1) > 0.2, but depends on assumed evolutionary tracks. The mass ratio is neither correlated with the primary's mass or the components' separation. These findings are in line with the assumption that for most multiple systems in T associations the components' masses are principally determined by fragmentation during formation and not by the following accretion processes. Only very few unusually red objects were newly found among the detected companions. This finding shows that the observed overabundance of binaries in the Taurus-Auriga association compared to nearby main sequence stars should be real and not the outcome of observational biases related to infrared observing.Comment: accepted by Astronomy and Astrophysics, contains extensive tables and figures that will only be published electronically at CDS (in total: 34 pages, 11 figures

Long-term (trophic) purinergic signalling: purinoceptors control cell proliferation, differentiation and death

The purinergic signalling system, which uses purines and pyrimidines as chemical transmitters, and purinoceptors as effectors, is deeply rooted in evolution and development and is a pivotal factor in cell communication. The ATP and its derivatives function as a 'danger signal' in the most primitive forms of life. Purinoceptors are extraordinarily widely distributed in all cell types and tissues and they are involved in the regulation of an even more extraordinary number of biological processes. In addition to fast purinergic signalling in neurotransmission, neuromodulation and secretion, there is long-term (trophic) purinergic signalling involving cell proliferation, differentiation, motility and death in the development and regeneration of most systems of the body. In this article, we focus on the latter in the immune/defence system, in stratified epithelia in visceral organs and skin, embryological development, bone formation and resorption, as well as in cancer. Cell Death and Disease (2010) 1, e9; doi:10.1038/cddis.2009.11; published online 14 January 201

Properties of Graphene: A Theoretical Perspective

In this review, we provide an in-depth description of the physics of monolayer and bilayer graphene from a theorist's perspective. We discuss the physical properties of graphene in an external magnetic field, reflecting the chiral nature of the quasiparticles near the Dirac point with a Landau level at zero energy. We address the unique integer quantum Hall effects, the role of electron correlations, and the recent observation of the fractional quantum Hall effect in the monolayer graphene. The quantum Hall effect in bilayer graphene is fundamentally different from that of a monolayer, reflecting the unique band structure of this system. The theory of transport in the absence of an external magnetic field is discussed in detail, along with the role of disorder studied in various theoretical models. We highlight the differences and similarities between monolayer and bilayer graphene, and focus on thermodynamic properties such as the compressibility, the plasmon spectra, the weak localization correction, quantum Hall effect, and optical properties. Confinement of electrons in graphene is nontrivial due to Klein tunneling. We review various theoretical and experimental studies of quantum confined structures made from graphene. The band structure of graphene nanoribbons and the role of the sublattice symmetry, edge geometry and the size of the nanoribbon on the electronic and magnetic properties are very active areas of research, and a detailed review of these topics is presented. Also, the effects of substrate interactions, adsorbed atoms, lattice defects and doping on the band structure of finite-sized graphene systems are discussed. We also include a brief description of graphane -- gapped material obtained from graphene by attaching hydrogen atoms to each carbon atom in the lattice.Comment: 189 pages. submitted in Advances in Physic