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

Studio pilota per la valutazione di una procedura per la taratura di termometri misuratori della temperatura dell’aria.

This EURAMET project includes two main activities: Perform a pilot study (in the form of an interlaboratory comparison) to explore issues around calibration in air of temperature sensors; Feed into a guidance document the findings from the pilot study. Background and need for the project Air temperature is measured for a multitude of purposes. Atmospheric air temperature is the key variable in indoor climatisation, in meteorological observations and climate studies. It is also critical to precision dimensional and mass measurements. Understanding and fully evaluating measurement uncertainty for air temperature measurements is an open scientific and technical issue now motivating research efforts and discussion both at the CIPM CCT and in WMO expert teams. While calibration of temperature sensors in liquid is well characterised, the calibration of thermometers in air still requires definition of procedures and guidelines. The problem of the lack of a guide for the calibration of thermometers in air was underlined at the EURAMET TC-T meeting of 2017 as a result of a specific scientific workshop on the matter. The analysis of the air temperature measurement procedures and uncertainty evaluation, including the aspects and contributions due to the calibration of sensors is also a task of the CCT Working Group on Environment and is included in the strategy roadmap of CCT

Incorporation of anti-PD1 or anti PD-L1 agents to platinum-based chemotherapy for the primary treatment of advanced or recurrent endometrial cancer. A meta-analysis

Importance: Various randomized trials have explored the efficacy of combining immune checkpoint inhibitors (ICIs) with first-line chemotherapy in advanced endometrial cancer. We aimed to summarize available data and clarify the benefit of adding immunotherapy according to the DNA mismatch repair status (deficient, dMMR or proficient, pMMR) and the specific type of agent used (anti-PD1 or anti-PD-L1). Objective: To assess whether the addition of ICIs to standard platinum-based chemotherapy enhances progression-free survival (PFS) for patients with advanced endometrial cancer both overall and based on DNA mismatch repair status. Data sources: Electronic databases (PubMed, Embase and Cochrane Library) and conference proceedings were searched for first line, randomized and controlled trials integrating ICIs with chemotherapy for the treatment of advanced endometrial cancer published or presented by November 1, 2023. Study selection: Five studies, comprising 2456 patients (1308 received ICIs with chemotherapy and 1148 treated with chemotherapy alone) met the selection criteria and were included in the analysis. Experimental arms included pembrolizumab, dostarlimab (anti-PD1) and durvalumab, atezolizumab and avelumab (anti-PD-L1) combined with standard three-weekly carboplatin-paclitaxel chemotherapy backbone. Endometrial carcinosarcoma were included in 3 out of 5 trials. Data extraction and synthesis: For comparison of PFS outcomes, extrapolation of hazard ratios (HRs), 95% confidence intervals (CI) and PFS events was performed for each included study in the overall population and according to subgroups. Data analysis was conducted using a random-effects model. Results: The addition of ICIs to chemotherapy improved PFS compared to chemotherapy alone in the overall population (pooled HR, 0.63; 95 % CI, 0.52––0.76; P <.001). In the dMMR subgroup the benefit was more pronounced (pooled HR, 0.34; 95 % CI, 0.27––0.44; P <.001) and not affected by drugs used with pooled HRs of 0.39 (95 % CI, 0.28––0.55; P <.001) and 0.34 (95 % CI, 0.27––0.44; P <.001) for PD-L1 and PD1 inhibitors, respectively. For pMMR patients, a statistically significant benefit in terms of PFS was confirmed only when anti-PD1 were used (anti-PD-1: HR 0.64, 95 % CI: 0.46–0.90, P =.010 vs anti-PD-L1: HR 0.87, 95 % CI: 0.73–1.03, P =.104) Conclusions and relevance: This meta-analysis confirmed the advantage in terms of PFS of adding ICIs to standard platinum-based chemotherapy. While dMMR patients benefit from the incorporation of both anti PD-1 or anti PD-L1, this benefit is confined to the association of anti-PD1 agents in pMMR patients. Updated analysis of trials is awaited to clarify the impact of immunotherapy on overall survival