The impact of high density receptor clusters on VEGF signaling

Vascular endothelial growth factor (VEGF) signaling is involved in the process of blood vessel development and maintenance. Signaling is initiated by binding of the bivalent VEGF ligand to the membrane-bound receptors (VEGFR), which in turn stimulates receptor dimerization. Herein, we discuss experimental evidence that VEGF receptors localize in caveloae and other regions of the plasma membrane, and for other receptors, it has been shown that receptor clustering has an impact on dimerization and thus also on signaling. Overall, receptor clustering is part of a complex ecosystem of interactions and how receptor clustering impacts dimerization is not well understood. To address these questions, we have formulated the simplest possible model. We have postulated the existence of a single high affinity region in the cell membrane, which acts as a transient trap for receptors. We have defined an ODE model by introducing high- and low-density receptor variables and introduce the corresponding reactions from a realistic model of VEGF signal initiation. Finally, we use the model to investigate the relation between the degree of VEGFR concentration, ligand availability, and signaling. In conclusion, our simulation results provide a deeper understanding of the role of receptor clustering in cell signaling.Comment: In Proceedings HSB 2013, arXiv:1308.572

High-resolution genome-wide scan of genes, gene-networks and cellular systems impacting the yeast ionome

Peer reviewedPublisher PD

Size-resolved aerosol and cloud condensation nuclei (CCN) properties in the remote marine South China Sea - Part 1: Observations and source classification

Abstract. Ship-based measurements of aerosol and cloud condensation nuclei (CCN) properties are presented for 2 weeks of observations in remote marine regions of the South China Sea/East Sea during the southwestern monsoon (SWM) season. Smoke from extensive biomass burning throughout the Maritime Continent advected into this region during the SWM, where it was mixed with anthropogenic continental pollution and emissions from heavy shipping activities. Eight aerosol types were identified using a k-means cluster analysis with data from a size-resolved CCN characterization system. Interpretation of the clusters was supplemented by additional onboard aerosol and meteorological measurements, satellite, and model products for the region. A typical bimodal marine boundary layer background aerosol population was identified and observed mixing with accumulation mode aerosol from other sources, primarily smoke from fires in Borneo and Sumatra. Hygroscopicity was assessed using the κ parameter and was found to average 0.40 for samples dominated by aged accumulation mode smoke; 0.65 for accumulation mode marine aerosol; 0.60 in an anthropogenic aerosol plume; and 0.22 during a short period that was characterized by elevated levels of volatile organic compounds not associated with biomass burning impacts. As a special subset of the background marine aerosol, clean air masses substantially scrubbed of particles were observed following heavy precipitation or the passage of squall lines, with changes in observed aerosol properties occurring on the order of minutes. Average CN number concentrations, size distributions, and κ values are reported for each population type, along with CCN number concentrations for particles that activated at supersaturations between 0.14 and 0.85 %

Acetylcholine Receptors and Concanavalin A-Binding Sites on Cultured Xenopus Muscle Cells: Electrophoresis, Diffusion, and Aggregation

Using digitally analyzed fluorescence videomicroscopy, we have examined the behavior of acetylcholine receptors and concanavalin A binding sites in response to externally applied electric fields. The distributions of these molecules on cultured Xenopus myoballs were used to test a simple model which assumes that electrophoresis and diffusion are the only important processes involved. The model describes the distribution of concanavalin A sites quite well over a fourfold range of electric field strengths; the results suggest an average diffusion constant of ~2.3 X 10^(-9) cm^2/s. At higher electric field strengths, the asymmetry seen is substantially less than that predicted by the model. Acetylcholine receptors subjected to electric fields show distributions substantially different from those predicted on the basis of simple electrophoresis and diffusion, and evidence a marked tendency to aggregate. Our results suggest that this aggregation is due to lateral migration of surface acetylcholine receptors, and is dependent on surface interactions, rather than the rearrangement of microfilaments or microtubules. The data are consistent with a diffusion-trap mechanism of receptor aggregation, and suggest that the event triggering receptor localization is a local increase in the concentration of acetylcholine receptors, or the electrophoretic concentration of some other molecular species. These observations suggest that, whatever mechanism(s) trigger initial clustering events in vivo, the accumulation of acetylcholine receptors can be substantially enhanced by passive, diffusion-mediated aggregation

Evidence on Competitive Advantage and Superior Stock Market Performance

This article analyzes the value-relevance of industry-based and resource-based competitive advantage in a large sample of firms listed on the Oslo Stock Exchange. We measure competitive advantage by a single variable and perform a new decomposition into its underlying sources. In 1986-2005, the industry-based and the resource-based competitive advantage explain more than 20% of abnormal stock market returns, accumulated over five years. The resource-based advantage is almost four times more important than the industry-based advantage. Differences in both the return and the risk capability of firms’ net assets relative to their industry peers are significant parts of the resource-based advantage, estimated at 60% and 40%, respectively.Competitive advantage; superior performance; value-relevance of performance metrics