Percolation, Morphogenesis, and Burgers Dynamics in Blood Vessels Formation

Experiments of in vitro formation of blood vessels show that cells randomly spread on a gel matrix autonomously organize to form a connected vascular network. We propose a simple model which reproduces many features of the biological system. We show that both the model and the real system exhibit a fractal behavior at small scales, due to the process of migration and dynamical aggregation, followed at large scale by a random percolation behavior due to the coalescence of aggregates. The results are in good agreement with the analysis performed on the experimental data.Comment: 4 pages, 11 eps figure

Tree effects on urban microclimate: diurnal, seasonal, and climatic temperature differences explained by separating radiation, evapotranspiration, and roughness effects

Increasing urban tree cover is an often proposed mitigation strategy against urban heat as trees are expected to cool cities through evapotranspiration and shade provision. However, trees also modify wind flow and urban aerodynamic roughness, which can potentially limit heat dissipation. Existing studies show a varying cooling potential of urban trees in different climates and times of the day. These differences are so far not systematically explained as partitioning the individual tree effects is challenging and impossible through observations alone. Here, we conduct numerical experiments removing and adding radiation, evapotranspiration, and aerodynamic roughness effects caused by urban trees using a mechanistic urban ecohydrological model. Simulations are presented for four cities in different climates (Phoenix, Singapore, Melbourne, Zurich) considering the seasonal and diurnal cycles of air and surface temperatures. Results show that evapotranspiration of well-watered trees alone can decrease local 2 m air temperature at maximum by 3.1 – 5.8 °C in the four climates during summer. Further cooling is prevented by stomatal closure at peak temperatures as high vapour pressure deficits limit transpiration. While shading reduces surface temperatures, the interaction of a non-transpiring tree with radiation can increase 2 m air temperature by up to 1.6 – 2.1 °C in certain hours of the day at local scale, thus partially counteracting the evapotranspirative cooling effect. Furthermore, in the analysed scenarios, which do not account for tree wind blockage effects, trees lead to a decrease in urban roughness, which inhibits turbulent energy exchange and increases air temperature during daytime. At night, single tree effects are variable likely due to differences in atmospheric stability within the urban canyon. These results explain reported diurnal, seasonal and climatic differences in the cooling effects of urban trees, and can guide future field campaigns, planning strategies, and species selection aimed at improving local microclimate using urban greenery

Absence of Host Plasminogen Activator Inhibitor 1 Prevents Cancer Invasion and Vascularization

Acquisition of invasive/metastatic potential through protease expression is an essential event in tumor progression. High levels of components of the plasminogen activation system, including urokinase, but paradoxically also its inhibitor, plasminogen activator inhibitor 1 (PAI1), have been correlated with a poor prognosis for some cancers. We report here that deficient PAI1 expression in host mice prevented local invasion and tumor vascularization of transplanted malignant keratinocytes. When this PAI1 deficiency was circumvented by intravenous injection of a replication-defective adenoviral vector expressing human PAI1, invasion and associated angiogenesis were restored. This experimental evidence demonstrates that host-produced PAI is essential for cancer cell invasion and angiogenesis

CPT1a-dependent long-chain fatty acid oxidation is essential for maintaining glucagon secretion from pancreatic islets

Glucagon, the principal hyperglycemic hormone, is secreted from pancreatic islet α cells as part of the counter-regulatory response to hypoglycemia. Hence, secretory output from α cells is under high demand in conditions of low glucose supply. Many tissues oxidize fat as an alternate energy substrate. Here, we show that glucagon secretion in low glucose conditions is maintained by fatty acid metabolism in both mouse and human islets, and that inhibiting this metabolic pathway profoundly decreases glucagon output by depolarizing α cell membrane potential and decreasing action potential amplitude. We demonstrate, by using experimental and computational approaches, that this is not mediated by the KATP channel, but instead due to reduced operation of the Na+-K+ pump. These data suggest that counter-regulatory secretion of glucagon is driven by fatty acid metabolism, and that the Na+-K+ pump is an important ATP-dependent regulator of α cell function

Photovoltaic panels as a main component of energy sustainable communities : comparative energy analysis of a village under Swiss and South African climatic loads

Paper presented to the 3rd Southern African Solar Energy Conference, South Africa, 11-13 May, 2015.At the community level, it is difficult to rely on a single centralized energy technology when considering renewable energy and the use of a mix of multiple distributed energy systems (DES) seems advantageous. DES, e.g. photovoltaic panels (PV), are typically integrated at building level and account for a small fraction of required energy. Since energy supply from renewables is highly fluctuating over time and dependent on climatic and local conditions, a reliable integration is a challenging task. In this paper, we use a recently developed concept, that allows to sufficiently improve the energy efficiency of the building stock, to manage energy supply from renewables and to optimize the future energy system using the energy hub approach, while effectively integrating DES. Using the same village characteristics, we found that, due to mismatch of available solar potential and the electricity demand, 18% of available solar potential cannot be utilized in Zernez, while in Johannesburg, this mismatch amounts to 22%.cf201

Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity

The secretome of cancer and stromal cells generates a microenvironment that contributes to tumour cell invasion and angiogenesis. Here we compare the secretome of human mammary normal and cancer-associated fibroblasts (CAFs). We discover that the chloride intracellular channel protein 3 (CLIC3) is an abundant component of the CAF secretome. Secreted CLIC3 promotes invasive behaviour of endothelial cells to drive angiogenesis and increases invasiveness of cancer cells both in vivo and in 3D cell culture models, and this requires active transglutaminase-2 (TGM2). CLIC3 acts as a glutathione-dependent oxidoreductase that reduces TGM2 and regulates TGM2 binding to its cofactors. Finally, CLIC3 is also secreted by cancer cells, is abundant in the stromal and tumour compartments of aggressive ovarian cancers and its levels correlate with poor clinical outcome. This work reveals a previously undescribed invasive mechanism whereby the secretion of a glutathione-dependent oxidoreductase drives angiogenesis and cancer progression by promoting TGM2-dependent invasion

Hypoxia induces dilated cardiomyopathy in the chick embryo: mechanism, intervention, and long-term consequences

Background: Intrauterine growth restriction is associated with an increased future risk for developing cardiovascular diseases. Hypoxia in utero is a common clinical cause of fetal growth restriction. We have previously shown that chronic hypoxia alters cardiovascular development in chick embryos. The aim of this study was to further characterize cardiac disease in hypoxic chick embryos. Methods: Chick embryos were exposed to hypoxia and cardiac structure was examined by histological methods one day prior to hatching (E20) and at adulthood. Cardiac function was assessed in vivo by echocardiography and ex vivo by contractility measurements in isolated heart muscle bundles and isolated cardiomyocytes. Chick embryos were exposed to vascular endothelial growth factor (VEGF) and its scavenger soluble VEGF receptor-1 (sFlt-1) to investigate the potential role of this hypoxia-regulated cytokine. Principal Findings: Growth restricted hypoxic chick embryos showed cardiomyopathy as evidenced by left ventricular (LV) dilatation, reduced ventricular wall mass and increased apoptosis. Hypoxic hearts displayed pump dysfunction with decreased LV ejection fractions, accompanied by signs of diastolic dysfunction. Cardiomyopathy caused by hypoxia persisted into adulthood. Hypoxic embryonic hearts showed increases in VEGF expression. Systemic administration of rhVEGF165 to normoxic chick embryos resulted in LV dilatation and a dose-dependent loss of LV wall mass. Lowering VEGF levels in hypoxic embryonic chick hearts by systemic administration of sFlt-1 yielded an almost complete normalization of the phenotype. Conclusions/Significance: Our data show that hypoxia causes a decreased cardiac performance and cardiomyopathy in chick embryos, involving a significant VEGF-mediated component. This cardiomyopathy persists into adulthood

Contact-inhibited chemotaxis in de novo and sprouting blood-vessel growth

Blood vessels form either when dispersed endothelial cells (the cells lining the inner walls of fully-formed blood vessels) organize into a vessel network (vasculogenesis), or by sprouting or splitting of existing blood vessels (angiogenesis). Although they are closely related biologically, no current model explains both phenomena with a single biophysical mechanism. Most computational models describe sprouting at the level of the blood vessel, ignoring how cell behavior drives branch splitting during sprouting. We present a cell-based, Glazier-Graner-Hogeweg-model simulation of the initial patterning before the vascular cords form lumens, based on plausible behaviors of endothelial cells. The endothelial cells secrete a chemoattractant, which attracts other endothelial cells. As in the classic Keller-Segel model, chemotaxis by itself causes cells to aggregate into isolated clusters. However, including experimentally-observed adhesion-driven contact inhibition of chemotaxis in the simulation causes randomly-distributed cells to organize into networks and cell aggregates to sprout, reproducing aspects of both de novo and sprouting blood-vessel growth. We discuss two branching instabilities responsible for our results. Cells at the surfaces of cell clusters attempting to migrate to the centers of the clusters produce a buckling instability. In a model variant that eliminates the surface-normal force, a dissipative mechanism drives sprouting, with the secreted chemical acting both as a chemoattractant and as an inhibitor of pseudopod extension. The branching instabilities responsible for our results, which result from contact inhibition of chemotaxis, are both generic developmental mechanisms and interesting examples of unusual patterning instabilities.Comment: Thoroughly revised version, now in press in PLoS Computational Biology. 53 pages, 13 figures, 2 supporting figures, 56 supporting movies, source code and parameters files for computer simulations provided. Supporting information: http://www.psb.ugent.be/~romer/ploscompbiol/ Source code: http://sourceforge.net/projects/tst