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: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:Mutations in the SFTPC gene associated with interstitial lung disease in human patients result in misfolding, endoplasmic reticulum (ER) retention, and degradation of the encoded surfactant protein C (SP-C) proprotein. To identify candidate genes involved in ER quality control of SP-C, HEK293 cells were transiently transfected with mutant SP-C (SP-CΔexon4 or SP-CL188Q), SP-CWT, or vector cDNAs, and global changes in gene expression were assessed by microarray analyses. Microarray analysis demonstrated that the SPC exon 4 deletion and SPC L188Q mutations invoke very similar transcriptional profiles including the activation of major players mediating ER response and unfolding protein response (UPR) in transient transfection system. In combination with promoter scan (UPRE, ERSE, XBP1 sites) and protein domain analysis (Finding ER Lumen, ER Membrane retention signal, J-Domain and Leucine Zipper domain), we were able to not only verify the known ERAD components (XBP1, Bip, Erdj4&5), but also identify multiple ER components which may play critical roles in the detection and /or degradation of mutant SPC, which in turn will help us to gain better understanding of the entire mammalian ERAD machinery.
Project description:The seminal plasma (SP) modulates the female reproductive immune environment after mating and microRNAs (miRNAs) could participate in the process. Considering the boar ejaculate is built by fractions differing in SP-composition; this study evaluated whether exposure of mucosal explants of the sow internal genital tract (uterus, utero-tubal junction and isthmus) to different SP-fractions changed the profile of explant-secreted miRNAs. Mucosal explants retrieved from oestrus sows (n=3) were in vitro exposed to: Medium 199 (M199, Control) or M199 supplemented (1:40 v/v) with SP from the sperm-rich fraction (SRF), the post-SRF or the entire recomposed ejaculate, for 16 h. After, the explants were cultured in M199 for 24 h to finally collect the media for miRNA analyses using GeneChip miRNA 4.0 Array (Affymetrix). Fifteen differentially expressed (False‐Discovery-Rate < 0.05 and Fold-change ≥ 2) miRNAs (11 down- vs 4 up-regulated) were identified (the most in the media of uterine explants incubated with SP from post-SRF). Bioinformatics analysis identified that predicted target genes of dysregulated miRNAs, mainly miR-34b, miR-205, miR-4776-3p and miR-574-5p, were involved in functions and pathways related to immune response. In conclusion, SP is able to elicit changes in the miRNAs profile secreted by female genital tract, ultimately depending SP-composition.