7,832 research outputs found

    The C. Elegans ROR receptor tyrosine kinase, CAM-1, non-autonomously inhibits the Wnt pathway

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    Inhibitors of Wnt signaling promote normal development and prevent cancer by restraining when and where the Wnt pathway is activated. ROR proteins, a class of Wnt-binding receptor tyrosine kinases, inhibit Wnt signaling by an unknown mechanism. To clarify how RORs inhibit the Wnt pathway, we examined the relationship between Wnts and the sole C. elegans ROR homolog, cam-1, during C. elegans vulval development, a Wnt-regulated process. We found that loss and overexpression of cam-1 causes reciprocal defects in Wnt-mediated cell-fate specification. Our molecular and genetic analyses revealed that the CAM-1 extracellular domain (ECD) is sufficient to non-autonomously antagonize multiple Wnts, suggesting that the CAM-1/ROR ECD sequesters Wnts. A sequestration model is supported by our findings that the CAM-1 ECD binds to several Wnts in vitro. These results demonstrate how ROR proteins help to refine the spatial pattern of Wnt activity in a complex multicellular environment

    Sensitive and Precise Quantification of Insulin-Like mRNA Expression in Caenorhabditis elegans

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    Insulin-like signaling regulates developmental arrest, stress resistance and lifespan in the nematode Caenorhabditis elegans. However, the genome encodes 40 insulin-like peptides, and the regulation and function of individual peptides is largely uncharacterized. We used the nCounter platform to measure mRNA expression of all 40 insulin-like peptides as well as the insulin-like receptor daf-2, its transcriptional effector daf-16, and the daf-16 target gene sod-3. We validated the platform using 53 RNA samples previously characterized by high density oligonucleotide microarray analysis. For this set of genes and the standard nCounter protocol, sensitivity and precision were comparable between the two platforms. We optimized conditions of the nCounter assay by varying the mass of total RNA used for hybridization, thereby increasing sensitivity up to 50-fold and reducing the median coefficient of variation as much as 4-fold. We used deletion mutants to demonstrate specificity of the assay, and we used optimized conditions to assay insulin-like gene expression throughout the C. elegans life cycle. We detected expression for nearly all insulin-like genes and find that they are expressed in a variety of distinct patterns suggesting complexity of regulation and specificity of function. We identified insulin-like genes that are specifically expressed during developmental arrest, larval development, adulthood and embryogenesis. These results demonstrate that the nCounter platform provides a powerful approach to analyzing insulin-like gene expression dynamics, and they suggest hypotheses about the function of individual insulin-like genes

    Eddington limited starbursts in the central 10pc of AGN, and the Torus in NGC1068

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    We present results from a survey of nearby AGN using the near infrared adaptive optics integral field spectrograph SINFONI. These data enable us to probe the distribution and kinematics of the gas and stars at spatial resolutions as small as 0.085arcsec. We find strong evidence for recent but short lived starbursts residing in very dense nuclear disks. On scales of less than 10pc these would have reached Eddington-limited luminosities when active, perhaps accounting for their short duration. In addition, for NGC1068 at a resolution of 6pc, we present direct observations of molecular gas close around the AGN which we identify with the obscuring torus.Comment: Conference proceedings to appear in "The Central Engine of Active Galactic Nuclei", ed. L. C. Ho and J.-M. Wang (San Francisco: ASP

    Issues in the Design of a Pilot Concept-Based Query Interface for the Neuroinformatics Information Framework

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    This paper describes a pilot query interface that has been constructed to help us explore a "concept-based" approach for searching the Neuroscience Information Framework (NIF). The query interface is concept-based in the sense that the search terms submitted through the interface are selected from a standardized vocabulary of terms (concepts) that are structured in the form of an ontology. The NIF contains three primary resources: the NIF Resource Registry, the NIF Document Archive, and the NIF Database Mediator. These NIF resources are very different in their nature and therefore pose challenges when designing a single interface from which searches can be automatically launched against all three resources simultaneously. The paper first discusses briefly several background issues involving the use of standardized biomedical vocabularies in biomedical information retrieval, and then presents a detailed example that illustrates how the pilot concept-based query interface operates. The paper concludes by discussing certain lessons learned in the development of the current version of the interface

    Local trace formulae and scaling asymptotics in Toeplitz quantization

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    A trace formula for Toeplitz operators was proved by Boutet de Monvel and Guillemin in the setting of general Toeplitz structures. Here we give a local version of this result for a class of Toeplitz operators related to continuous groups of symmetries on quantizable compact symplectic manifolds. The local trace formula involves certain scaling asymptotics along the clean fixed locus of the Hamiltonian flow of the symbol, reminiscent of the scaling asymptotics of the equivariant components of the Szeg\"o kernel along the diagonal
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