Glypican-1 controls brain size through regulation of fibroblast growth factor signaling in early neurogenesis

<p>Abstract</p> <p>Background</p> <p>Cell surface heparan sulfate proteoglycans (HSPGs) act as co-receptors for multiple families of growth factors that regulate animal cell proliferation, differentiation and patterning. Elimination of heparan sulfate during brain development is known to produce severe structural abnormalities. Here we investigate the developmental role played by one particular HSPG, glypican-1 (Gpc1), which is especially abundant on neuronal cell membranes, and is the major HSPG of the adult rodent brain.</p> <p>Results</p> <p>Mice with a null mutation in <it>Gpc1 </it>were generated and found to be viable and fertile. The major phenotype associated with <it>Gpc1 </it>loss is a highly significant reduction in brain size, with only subtle effects on brain patterning (confined to the anterior cerebellum). The brain size difference emerges very early during neurogenesis (between embryonic days 8.5 and 9.5), and remains roughly constant throughout development and adulthood. By examining markers of different signaling pathways, and the differentiation behaviors of cells in the early embryonic brain, we infer that <it>Gpc1</it>^-/-phenotypes most likely result from a transient reduction in fibroblast growth factor (FGF) signaling. Through the analysis of compound mutants, we provide strong evidence that Fgf17 is the FGF family member through which Gpc1 controls brain size.</p> <p>Conclusion</p> <p>These data add to a growing literature that implicates the glypican family of HSPGs in organ size control. They also argue that, among heparan sulfate-dependent signaling molecules, FGFs are disproportionately sensitive to loss of HSPGs. Finally, because heterozygous <it>Gpc1 </it>mutant mice were found to have brain sizes half-way between homozygous and wild type, the data imply that endogenous HSPG levels quantitatively control growth factor signaling, a finding that is both novel and relevant to the general question of how the activities of co-receptors are exploited during development.</p

Small scale statistics of viscoelastic turbulence

The small scale statistics of homogeneous isotropic turbulence of dilute polymer solutions is investigated by means of direct numerical simulations of a simplified viscoelastic fluid model. It is found that polymers only partially suppress the turbulent cascade below the Lumley scale, leaving a remnant energy flux even for large elasticity. As a consequence, fluid acceleration in viscoelastic flows is reduced with respect to Newtonian turbulence, whereas its rescaled probability density is left unchanged. At large scales the velocity field is found to be unaffected by the presence of polymers.Comment: 7 pages, 4 figure

Comment on "A centrosome-independent role for gamma-TuRC proteins in the spindle assembly checkpoint"

Müller et al. (Reports, 27 October 2006, p. 654) showed that inhibition of the γ-tubulin ring complex (γ-TuRC) activates the spindle assembly checkpoint (SAC), which led them to suggest that γ-TuRC proteins play molecular roles in SAC activation. Because γ-TuRC inhibition leads to pleiotropic spindle defects, which are well known to activate kinetochore-derived checkpoint signaling, we believe that this conclusion is premature

Intermittency in two-dimensional Ekman-Navier-Stokes turbulence

We study the statistics of the vorticity field in two-dimensional Navier-Stokes turbulence with a linear Ekman friction. We show that the small-scale vorticity fluctuations are intermittent, as conjectured by Nam et al. [Phys. Rev. Lett. vol.84 (2000) 5134]. The small-scale statistics of vorticity fluctuations coincides with the one of a passive scalar with finite lifetime transported by the velocity field itself.Comment: 4 pages, 7 figure

Evaluation of Mater Bi and Polylactic Acid as materials for biodegradable innovative mini-radiosondes to track small scale fluctuations within clouds

Turbulence plays an important part in determining the chemical and physical processes, on both the micro- and macro-scales, whereby clouds are formed and behave. However, exactly how these are linked together and how turbulence impacts each of these processes is not yet fully understood. This is partly due to a lack of in-situ small scale fluctuation measurements due to a limitation in the available technology. It is in this context that the radiosondes, for which the material characterisation is presented in this paper, are being developed to generate a Lagrangian set of data which can be used to improve the ever-expanding knowledge of atmospheric processes and, in particular, the understanding of the interaction between turbulence and micro-physical phenomenologies inside clouds (www.complete-h2020network.eu). Specifically, the materials developed for the balloons are discussed in further detail within this paper. Mater Bi and polylactic acid are the two common biodegradable thermoplastics that were used initially to make the balloons. To tailor their properties, the balloons were then coated with carnauba wax blended with either pine resin or SiO2 nanoparticles. The properties such as hydrophobicity, toughness, elasticity and helium gas permeability are investigated and improved in order to keep the density of the radiosondes as constant as possible for a couple of hours. This will allow them to float inside and outside clouds on an isopycnic surface, to measure various properties such as velocity, temperature, pressure and humidity by means of solid state sensors and to transmit them to receivers on Earth. Tests have been made under a rigorous metrological approach comparing the 6 new materials with two reference balloon materials, latex and mylar. It was found that Mater Bi with the two carnauba wax coatings is the most suited though its roughness and water vapour permeability should be improved

Individual Taxation Report

Recent developments affecting taxation of individuals, including legislation, regulations, and IRS guidance, are presented in Code section order

STUDIO DELLA STRUTTURA CROSTALE NELLE AREE VULCANICHE DEL VESUVIO E DEI CAMPI FLEGREI

Alla fine degli anni '80 furono effettuate numerose indagini DSS e WARR nell'area campana con l'obiettivo di investigarne la struttura crostale, in particolare quella dell'area vulcanica costiera, impostata nella zona di transizione tra il bacino tirrenico e la catena appenninica. Le geometrie punto di scoppio - punti di registrazione, lineari e a offset costante, furono scelte per ottenere informazioni sulla distribuzione delle velocità sismiche e sulla geometria delle principali discontinuità crostali. In questo lavoro presentiamo i risultati della modellazione dinamica (gaussian-bean dynamic ray-tracing) dei profili PP (Tirreno-Campi Flegrei), PV (Tirreno-Vesuvio), PB (Capri-Penisola Sorrentina) e V3 (Penisola Sorrentina-Vesuvio)e del profilo a offset costante Fan C-B

An integrated care pathway for cancer patients with diabetes: A proposal from the Italian experience

Diabetes and cancer frequently coexist in the same subject, often with relevant clinical effects on the management and prognosis of the comorbid patient. The existing guidelines, however, do not appropriately address many clinical issues in this setting. Although collaboration between diabetologists and oncologists should play an important role in achieving appropriate levels of care, close coordination or agreement between these specialists is seldom offered. There is an urgent need for greater interdisciplinary integration between all specialists involved in this setting, for a shared approach ensuring that organisational silos are overcome. To this end, the Italian Associations of Medical Diabetologists (AMD) and the Italian Association of Medical Oncology (AIOM) recently established a dedicated Working Group on 'Diabetes and Cancer'. The working group outlined a diagnostic and therapeutic clinical pathway dedicated to hospitalised patients with diabetes and cancer. In this article, we describe the Italian proposal including some suggested measures to assess, monitor and improve blood glucose control in the hospital setting, to integrate different specialists from both areas, as well as to ensure discharge planning and continuity of care from the hospital to the territory

CENP-F stabilizes kinetochore-microtubule attachments and limits dynein stripping of corona cargoes

Accurate chromosome segregation demands efficient capture of microtubules by kinetochores and their conversion to stable bioriented attachments that can congress and then segregate chromosomes. An early event is the shedding of the outermost fibrous corona layer of the kinetochore following microtubule attachment. Centromere protein F (CENP-F) is part of the corona, contains two microtubule-binding domains, and physically associates with dynein motor regulators. Here, we have combined CRISPR gene editing and engineered separation-of-function mutants to define how CENP-F contributes to kinetochore function. We show that the two microtubule-binding domains make distinct contributions to attachment stability and force transduction but are dispensable for chromosome congression. We further identify a specialized domain that functions to limit the dynein-mediated stripping of corona cargoes through a direct interaction with Nde1. This antagonistic activity is crucial for maintaining the required corona composition and ensuring efficient kinetochore biorientation