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Sökning: WFRF:(Zucchini Stefano)

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1.
  • Huang-Doran, Isabel, et al. (författare)
  • Insulin resistance uncoupled from dyslipidemia due to C-terminal PIK3R1 mutations.
  • 2016
  • Ingår i: JCI insight. - 2379-3708. ; 1:17
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity-related insulin resistance is associated with fatty liver, dyslipidemia, and low plasma adiponectin. Insulin resistance due to insulin receptor (INSR) dysfunction is associated with none of these, but when due to dysfunction of the downstream kinase AKT2 phenocopies obesity-related insulin resistance. We report 5 patients with SHORT syndrome and C-terminal mutations in PIK3R1, encoding the p85α/p55α/p50α subunits of PI3K, which act between INSR and AKT in insulin signaling. Four of 5 patients had extreme insulin resistance without dyslipidemia or hepatic steatosis. In 3 of these 4, plasma adiponectin was preserved, as in insulin receptor dysfunction. The fourth patient and her healthy mother had low plasma adiponectin associated with a potentially novel mutation, p.Asp231Ala, in adiponectin itself. Cells studied from one patient with the p.Tyr657X PIK3R1 mutation expressed abundant truncated PIK3R1 products and showed severely reduced insulin-stimulated association of mutant but not WT p85α with IRS1, but normal downstream signaling. In 3T3-L1 preadipocytes, mutant p85α overexpression attenuated insulin-induced AKT phosphorylation and adipocyte differentiation. Thus, PIK3R1 C-terminal mutations impair insulin signaling only in some cellular contexts and produce a subphenotype of insulin resistance resembling INSR dysfunction but unlike AKT2 dysfunction, implicating PI3K in the pathogenesis of key components of the metabolic syndrome.
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2.
  • Vomero, Maria, et al. (författare)
  • Conformable polyimide-based μECoGs : Bringing the electrodes closer to the signal source
  • 2020
  • Ingår i: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 255
  • Tidskriftsartikel (refereegranskat)abstract
    • Structural biocompatibility is a fundamental requirement for chronically stable bioelectronic devices. Newest neurotechnologies are increasingly focused on minimizing the foreign body response through the development of devices that match the mechanical properties of the implanted tissue and mimic its surface composition, often compromising on their robustness. In this study, an analytical approach is proposed to determine the threshold of conformability for polyimide-based electrocorticography devices. A finite element model was used to quantify the depression of the cortex following the application of devices mechanically above or below conformability threshold. Findings were validated in vivo on rat animal models. Impedance measurements were performed for 40 days after implantation to monitor the status of the biotic/abiotic interface with both conformable and non-conformable implants. Multi-unit activity was then recorded for 12 weeks after implantation using the most compliant device type. It can therefore be concluded that conformability is an essential prerequisite for steady and reliable implants which does not only depend on the Young's modulus of the device material: it strongly relies on the relation between tissue curvature at the implantation site and corresponding device's thickness and geometry, which eventually define the moment of inertia and the interactions at the material-tissue interface.
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