Crystal structure of the heterotrimeric integrin-binding region of laminin-111

Laminins are cell - adhesive glycoproteins that are essential for basement membrane assembly and function. Integrins are important laminin receptors, but their binding site on the heterotrimeric laminin s is poorly defined structurally. We report the crystal structure at 2.13 Å resolution of a minimal integrin - binding fragment of mouse laminin - 111, consisting of ~50 resid ues of α 1 β 1 γ 1 coiled coil and the first three lam inin G - like (LG) domains of the α 1 chain . The LG domains adopt a triangular arrangem ent, with the C - terminus of the coiled coil situated between LG1 and LG2. The critical integrin - binding glutamic acid residue in the γ 1 chain tail is surface - exposed and predicted to bind to the metal ion - dependent adhesion site in the integrin β 1 subunit. Additional contacts to the integrin are likely to be made by the LG1 and LG2 surfaces adjacent to the γ 1 chain tail, which are notably conserved and free of obstructing glycans

Precovery of near-Earth asteroids by a citizen-science project of the Spanish Virtual Observatory

This article describes a citizen-science project conducted by the Spanish Virtual Observatory (SVO) to improve the orbits of near-Earth asteroids (NEAs) using data from astronomical archives. The list of NEAs maintained at the Minor Planet Center (MPC) is checked daily to identify new objects or changes in the orbital parameters of already catalogued objects. Using NEODyS we compute the position and magnitude of these objects at the observing epochs of the 938 046 images comprising the Eigth Data Release of the Sloan Digitised Sky Survey (SDSS). If the object lies within the image boundaries and the magnitude is brighter than the limiting magnitude, then the associated image is visually inspected by the project's collaborators (the citizens) to confirm or discard the presence of the NEA. If confirmed, accurate coordinates and, sometimes, magnitudes are submitted to the MPC. Using this methodology, 3,226 registered users have made during the first fifteen months of the project more than 167,000 measurements which have improved the orbital elements of 551 NEAs (6% of the total number of this type of asteroids). Even more remarkable is the fact that these results have been obtained at zero cost to telescope time as NEAs were serendipitously observed while the survey was being carried out. This demonstrates the enormous scientific potential hidden in astronomical archives. The great reception of the project as well as the results obtained makes it a valuable and reliable tool for improving the orbital parameters of near-Earth asteroids.Comment: 9 pages, 5 figures. Accepted in Astron. Nach

KamLAND and Solar Antineutrino Spectrum

We use the recent KamLAND observations to predict the solar antineutrino spectrum at some confidence limits. We find that a scaling of the antineutrino probability with respect to the magnetic field profile --in the sense that the same probability function can be reproduced by any profile with a suitable peak field value-- can be utilised to obtain a general shape of the solar antineutrino spectrum. This scaling and the upper bound on the solar antineutrino event rate, that can be derived from the data, lead to: 1) an upper bound on the solar antineutrino flux, 2) the prediction of their energy spectrum, as the normalisation of the spectrum can be obtained from the total number of antineutrino events recorded in the experiment. We get $\phi_{\bar\nu}<3.8\times 10^{-3}\phi(^8B)$ or $\phi_{\bar\nu} <5.5\times 10^{-3}\phi(^8B)$ at 95% CL, assuming Gaussian or Poissonian statistics, respectively. And for 90% CL these become $\phi_{\bar\nu}<3.4 \times 10^{-3}\phi(^8B)$ and $\phi_{\bar\nu}<4.9\times 10^{-3}\phi(^8B)$. It shows an improvement by a factor of 3-5 with respect to existing bounds. These limits are quite general and independent of the detailed structure of the magnetic field in the solar interior.Comment: Based on talk given at NANP'03, JINR Dubna, Russia, June 2003. To be published in "Physics of Atomic Nuclie

Distinguishing magnetic moment from oscillation solutions of the solar neutrino problem with Borexino

Assuming that the observed deficit of solar neutrinos is due to the interaction of their transition magnetic moment with the solar magnetic field we derive the predictions for the forthcoming Borexino experiment. Three different model magnetic field profiles which give very good global fits of the currently available solar neutrino data are used. The expected signal at Borexino is significantly lower than those predicted by the LMA, LOW and VO neutrino oscillation solutions of the solar neutrino problem. It is similar to that of the SMA oscillation solution which, however, is strongly disfavoured by the Super-Kamiokande data on day and night spectra and zenith angle distribution of the events. Thus, the neutrino magnetic moment solution of the solar neutrino problem can be unambiguously distinguished from the currently favoured oscillation solutions at Borexino

Effect of the hard magnetic inclusion on the macroscopic anisotropy of nanocrystalline magnetic-materials

It is shown that the presence of highly anisotropic magnetic precipitates in a soft multiphased matrix can produce a remarkable hardening, even when the volume fraction of the precipitates is small. The exchange coupling between the matrix and the precipitates is the relevant parameter. In particular, the simplified analysis we develop in this paper accounts for the magnetic hardening observed in very soft Fe-rich nanocrystals after annealing at higher temperatures

Cholinergic neural activity directs retinal layer-specific angiogenesis and blood retinal barrier formation.

Blood vessels in the central nervous system (CNS) develop unique features, but the contribution of CNS neurons to regulating those features is not fully understood. We report that inhibiting spontaneous cholinergic activity or reducing starburst amacrine cell numbers prevents invasion of endothelial cells into the deep layers of the retina and causes blood-retinal-barrier (BRB) dysfunction in mice. Vascular endothelial growth factor (VEGF), which drives angiogenesis, and Norrin, a Wnt ligand that induces BRB properties, are decreased after activity blockade. Exogenous VEGF restores vessel growth but not BRB function, whereas stabilizing beta-catenin in endothelial cells rescues BRB dysfunction but not vessel formation. We further identify that inhibiting cholinergic activity reduces angiogenesis during oxygen-induced retinopathy. Our findings demonstrate that neural activity lies upstream of VEGF and Norrin, coordinating angiogenesis and BRB formation. Neural activity originating from specific neural circuits may be a general mechanism for driving regional angiogenesis and barrier formation across CNS development

Crystallographic analysis of the laminin β2 short arm reveals how the LF domain is inserted into a regular array of LE domains

Laminins are a major constituent of all basement membranes. The polymerisation of laminins at the cell surface is mediated by the three short arms of the cross-shaped laminin heterotrimer. The short arms contain repeats of laminin-type epidermal growth factor-like (LE) domains, interspersed with globular domains of unknown function. A single LF domain is inserted between LE5 and LE6 of the laminin β1 and β2 chains. We report the crystal structure at 1.85 Å resolution of the laminin β2 LE5-LF-LE6 region. The LF domain consists of a β-sandwich related to bacterial family 35 carbohydrate binding modules, and more distantly to the L4 domains present in the short arms of laminin α and γ chains. An α-helical region mediates the extensive interaction of the LF domain with LE5. The relative arrangement of LE5 and LE6 is very similar to that of consecutive LE domains in uninterrupted LE tandems. Fitting atomic models to a low-resolution structure of the first eight domains of the laminin β1 chain determined by small-angle X-ray scattering suggests a deviation from the regular LE array at the LE4-LE5 junction. These results advance our understanding of laminin structure