Vascular endothelial growth factor (VEGF) induces rapid prourokinase (pro-uPA) activation on the surface of endothelial cells

Vascular endothelial growth factor (VEGF) is the pivotal angiogenic growth factor activating endothelial cells to migrate, proliferate, and form capillary tubes. For an ordered endothelial cell migration, tissue invasion, and degradation of the extracellular matrix, proteolytic machinery is indispensable. Such machinery, suitable for localized proteolysis, is provided by the prourokinase-urokinase-plasmin system. Prourokinase (pro-uPA), the initial component of this system, is, however, synthesized in its inactive precursor form and as such bound to its cellular receptor uPAR. Here we identify a mechanism via which VEGF(165) interacting with its receptor VEGFR-2 rapidly induces prourokinase activation that is dependent on a change in integrin affinity, activation of matrix metalloproteinase 2 (MMP-2), and pro-uPA being bound to its surface receptor uPAR. This VEGF-induced pro-uPA activation on endothelial cells is responsible for VEGF-dependent local fibrinolytic activity and might be one of the initial steps in the angiogenic process.     

Baseball implant. A method of secondary insertion of an intraorbital implant

A surgical technique for secondary emplacement of an orbital implant is described in which a spherical implant encased in a scleral homograft is placed in the orbit through a transconjuctival incision and sutured to the superior part of the periosteum.     

Chemo-Enzymatic Fluorescence Labeling Of Genomic DNA For Simultaneous Detection Of Global 5-Methylcytosine And 5-Hydroxymethylcytosine**

5-Methylcytosine and 5-hydroxymethylcytosine are epigenetic modifications involved in gene regulation and cancer. We present a new, simple, and high-throughput platform for multi-color epigenetic analysis. The novelty of our approach is the ability to multiplex methylation and de-methylation signals in the same assay. We utilize an engineered methyltransferase enzyme that recognizes and labels all unmodified CpG sites with a fluorescent cofactor. In combination with the already established labeling of the de-methylation mark 5-hydroxymethylcytosine via enzymatic glycosylation, we obtained a robust platform for simultaneous epigenetic analysis of these marks. We assessed the global epigenetic levels in multiple samples of colorectal cancer and observed a 3.5-fold reduction in 5hmC levels but no change in DNA methylation levels between sick and healthy individuals. We also measured epigenetic modifications in chronic lymphocytic leukemia and observed a decrease in both modification levels (5-hydroxymethylcytosine: whole blood 30 %; peripheral blood mononuclear cells (PBMCs) 40 %. 5-methylcytosine: whole blood 53 %; PBMCs 48 %). Our findings propose using a simple blood test as a viable method for analysis, simplifying sample handling in diagnostics. Importantly, our results highlight the assay‘s potential for epigenetic evaluation of clinical samples, benefiting research and patient management.     

Investigation of the Gas‐Liquid Flow in a Stopper‐Rod Controlled SEN

The behaviour of two‐phase gas‐liquid flows in a stopper‐rod controlled submerged entry nozzle (SEN) is investigated in water model experiments. The observed two‐phase flow patterns can be classified into either bubble coring or bubbly slug. The scaling of the two‐phase flows by means of similarity parameters is discussed. In the experiments, it is found that the liquid flow rates depend strongly on the two‐phase flow patterns. Additionally, the influence of swirl on the flow patterns is investigated in detail. It is shown that swirl has a marked impact on the transition from bubble coring to bubbly slug. Finally, an estimation of the two‐phase argon‐steel flow patterns in industrialscale SEN flows is given.     

The HIV-inactivating protein, cyanovirin-N, does not block gp120-mediated virus-to-cell binding

Concentrations of the potent, HIV(human immunodeficiency virus) inactivating protein, cyanovirin-N (CV-N), which completely inhibit HIV-1 infectivity, do not block the binding of soluble CD4-receptor (sCD4) to HIV-1 lysates nor the attachment of intact HIV-1 virions to several target T-cell lines. Furthermore, in contrast to the known disassociative effects of sCD4 on viral envelope glycoproteins, treatment of HIVRF with high concentrations of CV-N results in complete viral inactivation but without apparent shedding of gp120 or other ultrastructural changes. These results are consistent with the view that the virucidal effects of CV-N result from interference with step(s) in the fusion process subsequent to the initial binding of the virus to target cells.     

Impact on human health of Salmonella spp. on pork in The Netherlands and the anticipated effects of some currently proposed control strategies

Cell-cell and cell-extracellular matrix interactions are fundamental processes involved in cell migration and tissue remodeling. Both the cyclic regeneration of the human endometrium during the menstrual cycle as well as the process of embryo implantation involve such dynamic interactions. It has become quite clear that integrin adhesion molecules expressed on the surface of cells play critical roles in the transmission of signals from the extracellular milieu to the cells. It is these signals that presumably regulate the behavior of these cells during major morphogenetic processes. In recent years, work in human endometrium and trophoblasts has uncovered both the regulated and constitutive expression of integrin subunits and their extracellular matrix ligands in these tissues. In addition, attempts have been made to correlate pathological states related to either infertility or abnormal pregnancy to the aberrant expression of several of these integrins. The purpose of the present review is to describe briefly our present state of knowledge of the expression of integrins in human endometrium and trophoblasts and provide the reader with the necessary background needed to understand, at the cellular and molecular levels, processes in reproduction such as embryo implantation.