Acidosis Activation of the Proton-Sensing GPR4 Receptor Stimulates Vascular Endothelial Cell Inflammatory Responses Revealed by Transcriptome Analysis

Acidic tissue microenvironment commonly exists in inflammatory diseases, tumors, ischemic organs, sickle cell disease, and many other pathological conditions due to hypoxia, glycolytic cell metabolism and deficient blood perfusion. However, the molecular mechanisms by which cells sense and respond to the acidic microenvironment are not well understood. GPR4 is a proton-sensing receptor expressed in endothelial cells and other cell types. The receptor is fully activated by acidic extracellular pH but exhibits lesser activity at the physiological pH 7.4 and minimal activity at more alkaline pH. To delineate the function and signaling pathways of GPR4 activation by acidosis in endothelial cells, we compared the global gene expression of the acidosis response in primary human umbilical vein endothelial cells (HUVEC) with varying level of GPR4. The results demonstrated that acidosis activation of GPR4 in HUVEC substantially increased the expression of a number of inflammatory genes such as chemokines, cytokines, adhesion molecules, NF-κB pathway genes, and prostaglandin-endoperoxidase synthase 2 (PTGS2 or COX-2) and stress response genes such as ATF3 and DDIT3 (CHOP). Similar GPR4-mediated acidosis induction of the inflammatory genes was also noted in other types of endothelial cells including human lung microvascular endothelial cells and pulmonary artery endothelial cells. Further analyses indicated that the NF-κB pathway was important for the acidosis/GPR4-induced inflammatory gene expression. Moreover, acidosis activation of GPR4 increased the adhesion of HUVEC to U937 monocytic cells under a flow condition. Importantly, treatment with a recently identified GPR4 antagonist significantly reduced the acidosis/GPR4-mediated endothelial cell inflammatory response. Taken together, these results show that activation of GPR4 by acidosis stimulates the expression of a wide range of inflammatory genes in endothelial cells. Such inflammatory response can be suppressed by GPR4 small molecule inhibitors and hold potential therapeutic value

The Mediterranean Decision Support System for Marine Safety dedicated to oil slicks predictions

In the Mediterranean sea the risk from oil spill pollution is high due to the heavy traffic of merchant vessels for transporting oil and gas, especially after the recent enlargement of the Suez canal and to the increasing coastal and offshore installations related to the oil industry in general. The basic response to major oil spills includes different measures and equipment. However, in order to strengthen the maritime safety related to oil spill pollution in the Mediterranean and to assist the response agencies, a multi-model oil spill prediction service has been set up, known as MEDESS-4MS (Mediterranean Decision Support System for Marine Safety). The concept behind the MEDESS-4MS service is the integration of the existing national ocean forecasting systems in the region with the Copernicus Marine Environmental Monitoring Service (CMEMS) and their interconnection, through a dedicated network data repository, facilitating access to all these data and to the data from the oil spill monitoring platforms, including the satellite data ones, with the well established oil spill models in the region. The MEDESS-4MS offer a range of service scenarios, multi-model data access and interactive capabilities to suite the needs of REMPEC (Regional Marine Pollution Emergency Response Centre for the Mediterranean Sea) and EMSA-CSN (European Maritime Safety Agency-CleanseaNet)

Elliptic integral solutions of spatial elastica of a thin straight rod bent under concentrated terminal forces

In this article we solve in closed form a system of nonlinear differential equations modelling the elastica in space of a thin, flexible, straight rod, loaded by a constant thrust at its free end. Common linearizations of strength of materials are of course not applicable any way, because we analyze great deformations, even if not so large to go off the linear elasticity range. By passing to cylindrical coordinates ρ, θ, z, we earn a more tractable differential system evaluating ρ as elliptic function of polar anomaly θ and also providing z through elliptic integrals of I and III kind. Deformed rod’s centerline is then completely described under both tensile or compressive load. Finally, the planar case comes out as a degeneracy, where the Bernoulli lemniscatic integral appears