In the developing mammalian brain neuroepithelial cells interact with blood vessels to regulate angiogenesis, blood-brain barrier (BBB) maturation, and other key neurovascular functions. Genetic studies in mice have shown that sprouting neurovascular development is controlled, in part, by Itgb8 which encodes the neuroepithelial cell-expressed integrin b8 subunit. However, these studies have involved complete loss-of-function Itgb8 mutations, and have not discerned the relative roles for the b8 integrin extracellular matrix (ECM) binding region versus the intracellular signaling tail. Here, Cre/lox strategies have been employed to selectively delete the cytoplasmic domain of Itgb8 without perturbing its transmembrane and extracellular domains. We report that the b8 integrin cytoplasmic domain is essential for inside-out modulation of adhesion, including activation of latent-TGFbs in the ECM. Quantitative sequencing of the brain endothelial cell transcriptome identifies TGFb-regulated genes with putative links to blood vessel morphogenesis, including several genes linked to Wnt/b-catenin signaling. These results reveal that the b8 integrin cytoplasmic domain is essential for the regulation of TGFb-dependent gene expression in endothelial cells and suggest that cross-talk between TGFbs and Wnt pathways is critical for neurovascular development.
Glioblastoma (GBM) is a malignant brain cancer that contains sub-populations of highly invasive tumor cells that drive progression and recurrence after surgery and radiochemotherapy. The exact mechanisms that enable GBM cells to disperse from the main tumor mass and navigate throughout the brain microenvironment remain largely unknown. As a result, there is a lack of effective strategies to block cancer cell invasive growth in primary and recurrent GBM. Here we report that hepatocyte cell adhesion molecule (hepaCAM), which is normally expressed in perivascular astrocytes, plays central roles in controlling the invasive growth features of GBM cells. Genetically targeting HEPACAM induces a transition from GBM cell proliferation/self-renewal to invasion. Increased invasion is due, in part, to an activation of focal adhesion signaling pathways and enhanced GBM cell adhesion to the extracellular matrix (ECM) in the brain microenvironment. Transcriptional profiling of GBM cells reveals various HEPACAM-regulated genes with links to polarity and invasion. Collectively, these data show that hepaCAM balances ECM adhesion and signaling pathways to control cancer cell proliferation versus invasion in the brain parenchyma. Targeting select components of the hepaCAM pathway may be an effective way to block tumor progression and recurrence in patients with GBM.
Vanadium-doped Zinc Silicate (Zn2SiO4) phosphors were synthesized through the sol-gel method. Structural, morphological and optical techniques were used to investigate the effects of vanadium incorporation on their structure, morphology, and optical behaviour. We reported that vanadium incorporation in Zn2SiO4 phosphors significantly modifies their crystallinity, morphology, and photoluminescence properties. When vanadium is added to Zn2SiO4 phosphors, the energy band gap (Eg) changes from 5.29 to 2.34 eV. Vanadium dopants generate imperfections in Zn2SiO4 phosphors, the leading cause of their emissions in visible regions and quantum yield. Quantum yield is estimated at 7.06 % for Zn1-xVxSiO4 (x = 8%) phosphor. The luminescence decay lifetime of the prominent emissions of vanadium-doped Zn2SiO4 was measured using a double exponential fitting technique, and the average lifetime is 11.7 ns.
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