6,103 research outputs found

    Adipogenesis of skeletal muscle fibro/adipogenic progenitors is affected by the WNT5a/GSK3/β-catenin axis

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    Fibro/Adipogenic Progenitors (FAPs) are muscle-interstitial progenitors mediating pro-myogenic signals that are critical for muscle homeostasis and regeneration. In myopathies, the autocrine/paracrine constraints controlling FAP adipogenesis are released causing fat infiltrates. Here, by combining pharmacological screening, high-dimensional mass cytometry and in silico network modeling with the integration of single-cell/bulk RNA sequencing data, we highlighted the canonical WNT/GSK/β-catenin signaling as a crucial pathway modulating FAP adipogenesis triggered by insulin signaling. Consistently, pharmacological blockade of GSK3, by the LY2090314 inhibitor, stabilizes β-catenin and represses PPARγ expression abrogating FAP adipogenesis ex vivo while limiting fatty degeneration in vivo. Furthermore, GSK3 inhibition improves the FAP pro-myogenic role by efficiently stimulating, via follistatin secretion, muscle satellite cell (MuSC) differentiation into mature myotubes. Combining, publicly available single-cell RNAseq datasets, we characterize FAPs as the main source of WNT ligands inferring their potential in mediating autocrine/paracrine responses in the muscle niche. Lastly, we identify WNT5a, whose expression is impaired in dystrophic FAPs, as a crucial WNT ligand able to restrain the detrimental adipogenic differentiation drift of these cells through the positive modulation of the β-catenin signaling

    Cadmium ions and cadmium sulphide particles in γ-titanium dihydrogen phosphate. Synthesis, thermal behaviour and X-ray characterization

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    AbstractLayered compounds with CdS particles supported on the ion-exchanger, γ-titanium dihydrogen phosphate, were prepared by the stepwise reaction of the ion-exchanger and cadmium solution, followed by reaction with H2S gas. The CdS content on the ion-exchanger is dependent on the timeframe of the H2S gas flow. The materials obtained were layered, as shown by the X-ray measurements that exhibit both precursor and CdS diffraction peaks. The thermal treatment of the material obtained gives evidence of its stability (≤ 320°C) before the CdS decomposition, which occurs in a single step

    Inter and intra-tumor heterogeneity of paediatric type diffuse high-grade gliomas revealed by single-cell mass cytometry

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    Paediatric-type diffuse high-grade gliomas (PDHGG) are aggressive tumors affecting children and young adults, with no effective treatment. These highly heterogeneous malignancies arise in different sites of the Central Nervous System (CNS), carrying distinctive molecular alterations and clinical outcomes (inter-tumor heterogeneity). Moreover, deep cellular and molecular profiling studies highlighted the coexistence of genetically and phenotypically different subpopulations within the same tumor mass (intra-tumor heterogeneity). Despite the recent advances made in the field, the marked heterogeneity of PDHGGs still impedes the development of effective targeted therapies and the identification of suitable biomarkers. In order to fill the existing gap, we used mass cytometry to dissect PDHGG inter- and intra-heterogeneity. This is one of the most advanced technologies of the “-omics” era that, using antibodies conjugated to heavy metals, allows the simultaneous measurement of more than 40 markers at single-cell level. To this end, we analyzed eight PDHGG patient-derived cell lines from different locational and molecular subgroups. By using a panel of 15 antibodies, directly conjugated to metals or specifically customized to detect important histone variants, significant differences were highlighted in the expression of the considered antigens. The single-cell multiparametric approach realized has deepened our understanding of PDHGG, confirming a high degree of intra- and inter-tumoral heterogeneity and identifying some antigens that could represent useful biomarkers for the specific PDHGG locational or molecular subgroups

    Probing Ca3Ti2O7Ca_3Ti_2O_7 crystal structure at the atomic level: Insights from 111mCd/111Cd^{111m}Cd/^{111}Cd PAC spectroscopy and ab-initio studies

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    Perturbed angular correlation spectroscopy combined with abinitioab-initio electronic structure calculations is used to unravel the structural phase transition path from the low-temperature polar structure to the high-temperature structural phase in Ca3Ti2O7Ca_3Ti_2O_7, a hybrid improper ferroelectric. This procedure explores the unique features of a local probe environment approach by monitoring the evolution of the electric field gradient tensor at the calcium sites. The local environments, observed above 1057 K, confirm a structural phase transition from the A21amA2_1am symmetry to an orthorhombic AcaaAcaa symmetry in the Ca3Ti2O7Ca_3Ti_2O_7 crystal lattice, disagreeing with the frequently reported avalanche structural transition from the polar A21amA2_1am phase to the aristotype I4/mmmI4/mmm phase. Moreover, the EFG temperature dependency, within the A21amA2_1am temperature stability, is shown to be sensitive to the recently proposed Ca3Ti2O7Ca_3Ti_2O_7 ferroelectric polarization decrease within the 500-800~K temperature range

    Autologous stem cell transplantation for the treatment of pediatric solid tumors in Brazil

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    Hosp Clin, Pediat Oncol Unit, Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, GRAACC, Pediat Oncol Inst, São Paulo, BrazilHosp AC Camargo Fund Antonio Prudente, Dept Pediat, São Paulo, BrazilSanta Casa de São Paulo, Pediat Hematol & Bone Marrow Transplantat Unit, São Paulo, BrazilUniversidade Federal de São Paulo, GRAACC, Pediat Oncol Inst, São Paulo, BrazilWeb of Scienc

    Safety in wine production. A pilot study on the quality evaluation of prosecco wine in the framework of ue regulation

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    In Italy, wine production is considered a sector of excellence, where the wines’ appreciable sensory features are favored by environmental factors, including weather and climate conditions, which benefit territories with a specific vocation. The whole chain involves many economic and agri-food sector operators, and requires an in-depth assessment of specific risks for identifying critical points, keeping the entire production process under control, and ensuring product traceability. This article describes the results of a pilot study conducted in the Prosecco DOCG (Designations of Controlled and Guaranteed Origin) area, concerning the detection of residues of plant protection products in fifty wine bottles. Although considerably below the maximum residue levels, all the samples tested were positive, ranging from two to five active substances detected in each sample. In addition to the provisions of the European Community legislation, this paper critically evaluates some best practices models that are already used by the Wine Federations of Italy, with the aim of identifying advantages of and areas for improvement in production methods, applicable to raw materials reception, rasping, storage, and bottling phases, in order to guarantee product safety and quality

    All-electron magnetic response with pseudopotentials: NMR chemical shifts

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    A theory for the ab initio calculation of all-electron NMR chemical shifts in insulators using pseudopotentials is presented. It is formulated for both finite and infinitely periodic systems and is based on an extension to the Projector Augmented Wave approach of Bloechl [P. E. Bloechl, Phys. Rev. B 50, 17953 (1994)] and the method of Mauri et al [F. Mauri, B.G. Pfrommer, and S.G. Louie, Phys. Rev. Lett. 77, 5300 (1996)]. The theory is successfully validated for molecules by comparison with a selection of quantum chemical results, and in periodic systems by comparison with plane-wave all-electron results for diamond.Comment: 25 pages, 4 tables, submitted to Physical Review

    DMSO removal reduces stem-cell infusion-related toxicity and allows excellent engraftment of cryopreserved unrelated cord blood and autologous stem cells

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    UNIFESP, GRAACC, Pediat Oncol Inst, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilUNIFESP, GRAACC, Pediat Oncol Inst, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc
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