Calreticulin is a secreted BMP antagonist, expressed in Hensen's node during neural induction

Hensen's node is the “organizer” of the avian and mammalian early embryo. It has many functions, including neural induction and patterning of the ectoderm and mesoderm. Some of the signals responsible for these activities are known but these do not explain the full complexity of organizer activity. Here we undertake a functional screen to discover new secreted factors expressed by the node at this time of development. Using a Signal Sequence Trap in yeast, we identify several candidates. Here we focus on Calreticulin. We show that in addition to its known functions in intracellular Calcium regulation and protein folding, Calreticulin is secreted, it can bind to BMP4 and act as a BMP antagonist in vivo and in vitro. Calreticulin is not sufficient to account for all organizer functions but may contribute to the complexity of its activity

Two- and three-point functions in two-dimensional Landau-gauge Yang-Mills theory: Continuum results

We investigate the Dyson-Schwinger equations for the gluon and ghost propagators and the ghost-gluon vertex of Landau-gauge gluodynamics in two dimensions. While this simplifies some aspects of the calculations as compared to three and four dimensions, new complications arise due to a mixing of different momentum regimes. As a result, the solutions for the propagators are more sensitive to changes in the three-point functions and the ansaetze used for them at the leading order in a vertex a expansion. Here, we therefore go beyond this common truncation by including the ghost-gluon vertex self-consistently for the first time, while using a model for the three-gluon vertex which reproduces the known infrared asymptotics and the zeros at intermediate momenta as observed on the lattice. A separate computation of the three-gluon vertex from the results is used to confirm the stability of this behavior a posteriori. We also present further arguments for the absence of the decoupling solution in two dimensions. Finally, we show how in general the infrared exponent kappa of the scaling solutions in two, three and four dimensions can be changed by allowing an angle dependence and thus an essential singularity of the ghost-gluon vertex in the infrared.Comment: 24 pages; added references, improved choices of parameters for vertex models; identical to version published in JHE

Genetic and Functional Analyses of SHANK2 Mutations Suggest a Multiple Hit Model of Autism Spectrum Disorders

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23-4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11-q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the "multiple hit model" for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD

Herschel survey of brown dwarf disks in ρ Ophiuchi

International audienceContext. Young brown dwarfs are known to possess circumstellar disks, a characteristic that is fundamental to the understanding of their formation process, and raises the possibility that these objects harbour planets.Aims. We want to characterise the far-IR emission of disks around the young brown dwarf population of the ρ Ophiuchi cluster in LDN 1688.Methods. Recent observations of the ρ Ophiuchi cluster with the Herschel Space Observatory allow us to probe the spectral energy distribution (SED) of the brown dwarf population in the far-IR, where the disk emission peaks. We performed aperture photometry at 70, 100, and 160 μm, and constructed SEDs for all previously known brown dwarfs detected. These were complemented with ancillary photometry at shorter wavelengths. We compared the observed SEDs to a grid of synthetic disks produced with the radiative transfer code MCFOST, and used the relative figure of merit estimated from the Bayesian inference of each disk parameter to analyse the structural properties.Results. We detected 12 Class II brown dwarfs with Herschel, which corresponds to one-third of all currently known brown dwarf members of ρ Ophiuchi. We did not detect any of the known Class III brown dwarfs. Comparison to models reveals that the disks are best described by an inner radius between 0.01 and 0.07 AU, and a flared disk geometry with a flaring index between 1.05 and 1.2. Furthermore, we can exclude values of the disk scale-height lower than 10 AU (measured at a fiducial radius of 100 AU). We combined the Herschel data with recent ALMA observations of the brown dwarf GY92 204 (ISO−Oph 102), and by comparing its SED to the same grid of disk models, we derived an inner disk radius of 0.035 AU, a scale height of 15 AU with a flaring index of β ~ 1.15, an exponent for dust settling of −1.5, and a disk mass of 0.001 M⊙. This corresponds to a disk-to-central object mass ratio of ~1%.Conclusions. The structural parameters constrained by the extended SED coverage (inner radius and flaring index) show a narrow distribution for the young brown dwarfs detected in ρ Ophiuchi, suggesting that these objects share the same disk evolution and, perhaps, formation

Cyclic behaviour of stone and brick masonry under uniaxial compressive loading

An experimental research concerning the uniaxial compressive behaviour of stone and brick specimens, as well as masonry prisms, is presented. Local sandstone and clay brick materials were used in order to obtain results representative with respect to local constructions. Aiming at a comprehensive material description, a set of displacementcontrolled experiments were carried out, both under monotonic and cyclic compressive loading. The procedure adopted for testing is described and the results are discussed, namely material brittleness, intrinsic variability, energy dissipation and stiffness degradation.Dans cet article une recherche expérimentale à propos du comportement en compression uniaxial de spécimens de pierre et de la brique, aussi bien que prismes de maçonnerie, est présenté. Grès et brique de l’argile locale ont été utilisés pour obtenir des résultats représentatifs en ce qui concerne les constructions locales. Avec l’objective de obtenir une description matérielle complète, un ensemble de tests contrôlé par déplacement a été emporté, sous chargement de compression monotonic et cyclique. La procédure adoptée pour tester est décrite et les résultats sont discutés, nommément la fragilité matérielle, variabilité intrinsèque des matériaux, dissipation d’énergie et déchéance de la raideur

On the leading OPE corrections to the ghost-gluon vertex and the Taylor theorem

This brief note is devoted to a study of genuine non-perturbative corrections to the Landau gauge ghost-gluon vertex in terms of the non-vanishing dimension-two gluon condensate. We pay special attention to the kinematical limit which the bare vertex takes for its tree-level expression at any perturbative order, according to the well-known Taylor theorem. Based on our OPE analysis, we also present a simple model for the vertex, in acceptable agreement with lattice data.Comment: Final version published in JHE

Astrobiological Complexity with Probabilistic Cellular Automata

Search for extraterrestrial life and intelligence constitutes one of the major endeavors in science, but has yet been quantitatively modeled only rarely and in a cursory and superficial fashion. We argue that probabilistic cellular automata (PCA) represent the best quantitative framework for modeling astrobiological history of the Milky Way and its Galactic Habitable Zone. The relevant astrobiological parameters are to be modeled as the elements of the input probability matrix for the PCA kernel. With the underlying simplicity of the cellular automata constructs, this approach enables a quick analysis of large and ambiguous input parameters' space. We perform a simple clustering analysis of typical astrobiological histories and discuss the relevant boundary conditions of practical importance for planning and guiding actual empirical astrobiological and SETI projects. In addition to showing how the present framework is adaptable to more complex situations and updated observational databases from current and near-future space missions, we demonstrate how numerical results could offer a cautious rationale for continuation of practical SETI searches.Comment: 37 pages, 11 figures, 2 tables; added journal reference belo

Facile, productive, and cost-effective synthesis of a novel tetrazine-based iron oxide nanoparticle for targeted image contrast agents and nanomedicines

We have developed an operationally simple, time, and cost-effective protocol to produce a novel tetrazine-based iron oxide nanoparticle using commercially available and inexpensive materials. Our protocol proceeds at room temperature and uses hexafluorophosphate azabenzotriazole tetramethyl uronium, a well-known, widely used reagent for the large-scale industrial production of important pharmaceuticals. The nanoparticles obtained have a diameter range between 16 and 21 nm and showed no toxicity against endothelial cell lines. The tetrazine moiety on the nanoparticle surface could potentially allow further attachment of specific targeting vectors by using so-called copper-free click chemistry. We therefore anticipate that our protocol can represent a significant breakthrough in the future development and commercialization of improved, tissue-specific contrast agents and drug delivery for clinical diagnosis, monitoring and therapy of diseases at an asymptomatic stage

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives