Project description:The intermediate filament protein Nestin serves as a biomarker for stem cells and has been used to identify subsets of cancer stem-like cells. However, the mechanistic contributions of Nestin to cancer pathogenesis are not understood. Here we report that Nestin binds the hedgehog pathway transcription factor Gli3 to mediate the development of medulloblastomas of the hedgehog subtype. In a mouse model system, Nestin levels increased progressively during medulloblastoma formation resulting in enhanced tumor growth. Conversely, loss of Nestin dramatically inhibited proliferation and promoted differentiation. Mechanistic investigations revealed that the tumor-promoting effects of Nestin were mediated by binding to Gli3, a zinc finger transcription factor that negatively regulates hedgehog signaling. Nestin binding to Gli3 blocked Gli3 phosphorylation and its subsequent proteolytic processing, thereby abrogating its ability to negatively regulate the hedgehog pathway. Our findings show how Nestin drives hedgehog pathway-driven cancers and uncover in Gli3 a therapeutic target to treat these malignancies.
Project description:The intermediate filament protein Nestin serves as a biomarker for stem cells and has been used to identify subsets of cancer stem-like cells. However, the mechanistic contributions of Nestin to cancer pathogenesis are not understood. Here we report that Nestin binds the hedgehog pathway transcription factor Gli3 to mediate the development of medulloblastomas of the hedgehog subtype. In a mouse model system, Nestin levels increased progressively during medulloblastoma formation resulting in enhanced tumor growth. Conversely, loss of Nestin dramatically inhibited proliferation and promoted differentiation. Mechanistic investigations revealed that the tumor-promoting effects of Nestin were mediated by binding to Gli3, a zinc finger transcription factor that negatively regulates hedgehog signaling. Nestin binding to Gli3 blocked Gli3 phosphorylation and its subsequent proteolytic processing, thereby abrogating its ability to negatively regulate the hedgehog pathway. Our findings show how Nestin drives hedgehog pathway-driven cancers and uncover in Gli3 a therapeutic target to treat these malignancies. Nestin+ and Nestin- GNPs (granule neuron precursors) were purified from Nestin-CFP/Math1-Cre/Ptch1-loxp cerebella at postnatal day 4 by FACs, and total RNA from these two cell populations were extracted, and then labeled and hybridized to Affymetrix Mouse Genome 430 2.0 arrays.
Project description:Molecular networking has become a key method to visualize and annotate the chemical space in non-targeted mass spectrometry data. We present feature-based molecular networking (FBMN) as an analysis method in the Global Natural Products Social Molecular Networking (GNPS) infrastructure that builds on chromatographic feature detection and alignment tools. FBMN enables quantitative analysis and resolution of isomers, including from ion mobility spectrometry.
Project description:This paper investigates the utilization of commercial masterbatches of graphene nanoplatelets to improve the properties of neat polymer and wood fiber composites manufactured by conventional processing methods. The effect of aspect ratio of the graphene platelets (represented by the different number of layers in the nanoplatelet) on the properties of high-density polyethylene (HDPE) is discussed. The composites were characterized for their mechanical properties (tensile, flexural, impact) and physical characteristics (morphology, crystallization, and thermal stability). The effect of the addition of nanoplatelets on the thermal conductivity and diffusivity of the reinforced polymer with different contents of reinforcement was also investigated. In general, the mechanical performance of the polymer was enhanced at the presence of either of the reinforcements (graphene or wood fiber). The improvement in mechanical properties of the nanocomposite was notable considering that no compatibilizer was used in the manufacturing. The use of a masterbatch can promote utilization of nano-modified polymer composites on an industrial scale without modification of the currently employed processing methods and facilities.
Project description:Graphene nanoplatelets (GNPs) were prepared using the electrolytic exfoliation method on graphite foil in an ammonium sulfate solution. A series of experiments were conducted in order to optimize the production of the flakes by varying the pH of the solution, applied voltage and current, duration of electrolysis, temperature in the electrolytic system, and type and duration of the ultrasound interaction. The quality of the produced graphene nanoplatelets was analyzed using X-ray diffraction, Raman and IR spectroscopy, and TEM.
Project description:Molecular networking connects mass spectra of molecules based on the similarity of their fragmentation patterns. However, during ionization, molecules commonly form multiple ion species with different fragmentation behavior. As a result, the fragmentation spectra of these ion species often remain unconnected in tandem mass spectrometry-based molecular networks, leading to redundant and disconnected sub-networks of the same compound classes. To overcome this bottleneck, we develop Ion Identity Molecular Networking (IIMN) that integrates chromatographic peak shape correlation analysis into molecular networks to connect and collapse different ion species of the same molecule. The new feature relationships improve network connectivity for structurally related molecules, can be used to reveal unknown ion-ligand complexes, enhance annotation within molecular networks, and facilitate the expansion of spectral reference libraries. IIMN is integrated into various open source feature finding tools and the GNPS environment. Moreover, IIMN-based spectral libraries with a broad coverage of ion species are publicly available.
Project description:Current trends in wound care research focus on creating dressings for diverse wound types, aiming to effectively control the wound healing process. We proposed a wound dressing composed of oxidized hyaluronic acid and amine gelatin with embedded lysine-modified gelatin nanoparticles (HGel-GNPs-lysine). This dressing improves mechanical properties and reduces degradation rates. The storage modulus for HGel-GNPs-lysine was 3,800 Pa, exceeding that of HGel (1,750 Pa). The positively charged surface of GNPs-lysine effectively eliminated Escherichia coli and Staphylococcus aureus. In a diabetic mice model (C57BL/6), HGel-GNPs-lysine immobilized with basic-fibroblast growth factor promoted granulation tissue thickness and collagen density. Gene expression analysis indicated that HGel-GNPs-lysine reduced inflammation and enhanced angiogenesis. This study highlights that HGel-GNPs-lysine could offer alternative treatment strategies for regulating the inflammatory response at the injury site in wound dressing applications.
Project description:Graphene-based powder absorbers have been used to attain excellent microwave absorption. However, it is not clear if inferior microwave absorption by pure graphene materials can be attributed to impedance mismatching or inadequate attenuation capability. In this comparative study, we focus on these aspects. Graphene nanoplatelets (GNPs) multi-component composites (GNPs@NixSy@MoS2) were prepared by hydrothermal reaction with different S and Mo molar ratios. The morphologies, phase crystals, elemental composition, and magnetic properties of the composites were also analyzed. In addition, microwave absorption of the as-prepared samples was investigated and it revealed that the impedance mismatching could be responsible for inferior microwave absorption; higher conductivity can lead to skin effect that inhibits the further incidence of microwaves into the absorbers. Furthermore, the optimum reflection loss (RL) of GNPs@NixSy@MoS2-2 can reach -43.3 dB at a thickness of 2.2 mm and the corresponding bandwidth with effective attenuation (RL < -10 dB) of up to 3.6 GHz (from 7.0 to 10.6 GHz). Compared with the GNPs, the enhanced microwave absorption can be assigned to the synergistic effects of conductive and dielectric losses.