Distinct role of PLCβ3 in VEGF-mediated directional migration and vascular sprouting

Endothelial cell proliferation and migration is essential to angiogenesis. Typically, proliferation and chemotaxis of endothelial cells is driven by growth factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). VEGF activates phospholipases (PLCs) – specifically PLCγ1 – that are important for tubulogenesis, differentiation and DNA synthesis. However, we show here that VEGF, specifically through VEGFR2, induces phosphorylation of two serine residues on PLCβ3, and this was confirmed in an ex vivo embryoid body model. Knockdown of PLCβ3 in HUVEC cells affects IP3 production, actin reorganization, migration and proliferation; whereas migration is inhibited, proliferation is enhanced. Our data suggest that enhanced proliferation is precipitated by an accelerated cell cycle, and decreased migration by an inability to activate CDC42. Given that PLCβ3 is typically known as an effector of heterotrimeric G-proteins, our data demonstrate a unique crosstalk between the G-protein and receptor tyrosine kinase (RTK) axes and reveal a novel molecular mechanism of VEGF signaling and, thus, angiogenesis

Original Paper Evaluating Structural Change in a Reference Terminology

Background: Clinical terminologies, like the domains they model, may change over time. Existing methods for identifying and characterizing terminology change, address individual concepts and their interrelationships rather than the overall structure of the terminology. Exposing high level terminology structure may improve developers ’ and users ’ ability to identify changes occurring over time. Objectives: To describe and demonstrate novel structural attributes for terminologies. Methods: We measured novel structural attributes of four successive versions of the National Drug File Reference Terminology Physiologic Effects hierarchy. Attributes included measures for overall size, dimension (ie, width, height, mass, depth), complexity (i.e., node recurrence, leafiness, branchiness) and balance (i.e., skew, variation, smoothness). Results: Among the four versions, the terminology size increased from 711 to 1638 concepts, increased in complexity, but did not improve in terms of symmetry. Conclusions: Visualizing and characterizing the structure of successive terminology versions revealed how the terminology changed at a high level, and where it may have been relatively over specified to meet modeling- or use-based needs

Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial

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