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NRP2 as an Emerging Angiogenic Player; Promoting Endothelial Cell Adhesion and Migration by Regulating Recycling of α5 Integrin.
Angiogenesis relies on the ability of endothelial cells (ECs) to migrate over the extracellular matrix via integrin receptors to respond to an angiogenic stimulus. Of the two neuropilin (NRP) orthologs to be identified, both have been reported to be expressed on normal blood and lymphatic ECs, and to play roles in the formation of blood and lymphatic vascular networks during angiogenesis. Whilst the role of NRP1 and its interactions with integrins during angiogenesis has been widely studied, the role of NRP2 in ECs is poorly understood. Here we demonstrate that NRP2 promotes Rac-1 mediated EC adhesion and migration over fibronectin (FN) matrices in a mechanistically distinct fashion to NRP1, showing no dependence on β3 integrin (ITGB3) expression, or VEGF stimulation. Furthermore, we highlight evidence of a regulatory crosstalk between NRP2 and α5 integrin (ITGA5) in ECs, with NRP2 depletion eliciting an upregulation of ITGA5 expression and disruptions in ITGA5 cellular organization. Finally, we propose a mechanism whereby NRP2 promotes ITGA5 recycling in ECs; NRP2 depleted ECs were found to exhibit reduced levels of total ITGA5 subunit recycling compared to wild-type (WT) ECs. Our findings expose NRP2 as a novel angiogenic player by promoting ITGA5-mediated EC adhesion and migration on FN
Bis(2-aminopyridine-κN 1)silver(I) nitrate
The asymmetric unit of the title compound, [Ag(C5H6N2)2]NO3, consists of one and a half each of both cations and anions, the other halves being generated by crystallographic inversion centres. One of the AgI atoms lies on an inversion center and one of the nitrate ions is disordered across an inversion center. Each AgI atom is bicoordinated in a linear geometry by two N atoms from two 2-aminopyridine ligands. In the crystal structure, the cations and anions are linked into a two-dimensional network parallel to (001) by N—H⋯O and C—H⋯O hydrogen bonds
Bis(2-aminothiazolium) succinate succinic acid
In the title compound, 2C3H5N2S+·C4H4O4
2−·C4H6O4, the thiazolium ring is almost planar, with the maximum deviation from planarity being 0.0056 (8) Å for the C atom carrying the amine substituent. The N atom of the 2-aminothiazole molecule is protonated. Both the anion and the acid lie across inversion centres. The crystal packing is consolidated by intermolecular O—H⋯O, N—H⋯O and C—H⋯O hydrogen bonds. Molecules are stacked down the b axis
Bis(4-aminopyridinium) bis(hydrogen oxalate) monohydrate
In the title compound, 2C5H7N2
+·2C2HO4
−·H2O, the asymmetric unit consists of an aminopyridinium cation, an oxalic actetate anion and a half-molecule of water, which lies on a two-fold rotation axis. The crystal packing is consolidated by intermolecular O—H⋯O, N—H⋯O and C—H⋯O hydrogen bonds. The molecules are linked into an infinite one dimensional chain along [010]
4-Aminopyridinium hydrogen succinate
In the title salt, C5H7N2
+·C4H5O4
−, the asymmetric unit comprises an aminopyridinium cation and a hydrogen succinate anion as protonation of the aromatic N atom of the 4-aminopyridine molecule has occurred. The crystal packing is stabilized by intermolecular O—H⋯O and N—H⋯O hydrogen bonds that lead to a two-dimensional array. Short C—H⋯O contacts are also present
Investigating low-velocity fluid flow in tumours using convection-MRI
Several distinct fluid flow phenemena occur in solid tumours, including intravascular blood flow and interstitial convection. To probe low-velocity flow in tumors resulting from raised interstitial fluid pressure, we have developed a novel magnetic resonance imaging (MRI) technique named convection-MRI. It uses a phase-contrast acquisition with a dual-inversion vascular nulling preparation to separate intra- and extra-vascular flow. Here, we report the results of experiments in flow phantoms, numerical simulations and tumor xenograft models to investigate the technical feasibility of convection-MRI. We report a good correlation between estimates of effective fluid pressure from convection-MRI with gold-standard, invasive measurements of interstitial fluid pressure in mouse models of human colorectal carcinoma and show that convection-MRI can provide insights into the growth and response to vascular-targeting therapy in colorectal cancers
2-Aminopyridinium (2-aminopyridine)trichloridonickelate(II)
In the title compound, (C5H7N2)[NiCl3(C5H6N2)], the NiII atom is four-coordinated by three chloride anions and one N atom of a 2-aminopyridine ligand, forming a distorted tetrahedral coordination. In the crystal structure, cations and complex anions are linked into chains along the a, b and c axes by N—H⋯Cl hydrogen bonds, leading to the formation of a three-dimensional framework
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