Humans Lack iGb3 Due to the Absence of Functional iGb3-Synthase: Implications for NKT Cell Development and Transplantation

The glycosphingolipid isoglobotrihexosylceramide, or isogloboside 3 (iGb3), is believed to be critical for natural killer T (NKT) cell development and self-recognition in mice and humans. Furthermore, iGb3 may represent an important obstacle in xenotransplantation, in which this lipid represents the only other form of the major xenoepitope Galα(1,3)Gal. The role of iGb3 in NKT cell development is controversial, particularly with one study that suggested that NKT cell development is normal in mice that were rendered deficient for the enzyme iGb3 synthase (iGb3S). We demonstrate that spliced iGb3S mRNA was not detected after extensive analysis of human tissues, and furthermore, the iGb3S gene contains several mutations that render this product nonfunctional. We directly tested the potential functional activity of human iGb3S by expressing chimeric molecules containing the catalytic domain of human iGb3S. These hybrid molecules were unable to synthesize iGb3, due to at least one amino acid substitution. We also demonstrate that purified normal human anti-Gal immunoglobulin G can bind iGb3 lipid and mediate complement lysis of transfected human cells expressing iGb3. Collectively, our data suggest that iGb3S is not expressed in humans, and even if it were expressed, this enzyme would be inactive. Consequently, iGb3 is unlikely to represent a primary natural ligand for NKT cells in humans. Furthermore, the absence of iGb3 in humans implies that it is another source of foreign Galα(1,3)Gal xenoantigen, with obvious significance in the field of xenotransplantation

In vitro epithelial-to-mesenchymal transformation in human adult epicardial cells is regulated by TGFβ-signaling and WT1

Adult epicardial cells are required for endogenous cardiac repair. After myocardial injury, they are reactivated, undergo epithelial-to-mesenchymal transformation (EMT) and migrate into the injured myocardium where they generate various cell types, including coronary smooth muscle cells and cardiac interstitial fibroblasts, which contribute to cardiac repair. To understand what drives epicardial EMT, we used an in vitro model for human adult epicardial cells. These cells have an epithelium-like morphology and markedly express the cell surface marker vascular cell adhesion marker (VCAM-1). In culture, epicardial cells spontaneously undergo EMT after which the spindle-shaped cells now express endoglin. Both epicardial cells before and after EMT express the epicardial marker, Wilms tumor 1 (WT1). Adding transforming growth factor beta (TGFβ) induces loss of epithelial character and initiates the onset of mesenchymal differentiation in human adult epicardial cells. In this study, we show that TGFβ-induced EMT is dependent on type-1 TGFβ receptor activity and can be inhibited by soluble VCAM-1. We also show that epicardial-specific knockdown of Wilms tumor-1 (WT1) induces the process of EMT in human adult epicardial cells, through transcriptional regulation of platelet-derived growth factor receptor alpha (Pdgfrα), Snai1 and VCAM-1. These data provide new insights into the process of EMT in human adult epicardial cells, which might provide opportunities to develop new strategies for endogenous cell-based cardiac repair

Report of meeting on measurement of suspended solids in the Meuse

On June 19/20, 2007 a visit was paid to a suspended particulate matter (SPM) sampling and monitoring site in the Ourthe river (Liège region), between the confluence with the Vesdre river and the mouth of the Ourthe in the Meuse river. The next day, a workshop was organised in which backgrounds, methods and procedures for SPM sampling and monitoring were discussed. Results of measuring SPM quantity and quality in the Meuse river basin were presented. The discussions were focused on the implementation of this matrix in WFD instigated monitoring programs. The workshop was very successful, with animated discussions

Propagation of a cadmium spill through an impounded river system

In this paper, the influence of impoundments (sluices, weirs, etc.) and stream components (tributaries, river branches, associated canals) on the metal content in water and suspended particulate matter (SPM) in the Dutch part of the River Meuse is assessed using the decrease in the cadmium content of the particulate and dissolved phase during the transport of a distinct cadmium spill through the river. This anthropogenic spill lasted from July 2005 to June 2006 and is documented by the weekly monitoring results of the Meuse in Eijsden at the Belgian-Dutch border. The monitoring data indicate that cadmium was discharged as a dissolved phase. Redistribution of water towards canals is the cause that during low flow conditions only a limited amount of water with an Eijsden geochemical signature arrives in Keizersveer (near the mouth of the river). During such periods various tributaries and groundwater have significant contributions to the discharge measured in Keizersveer. The monthly variations of cadmium concentrations in total water and SPM, upstream and downstream of the series of impoundments are calculated for the period 1993-2004. Next, the transfer of the cadmium through the impounded part of the river is determined based on the monitoring results obtained in the stations in between and downstream from the impoundments. Finally, possible lag effects of the cadmium spill are quantified using monitoring data obtained in 2006 and 2007. It is concluded that it takes about six months before the cadmium spill is detected in the SPM at the monitoring station of Keizersveer. Leaching of cadmium from the sediment to the surface water may result in high dissolved cadmium concentrations. For a better understanding of the processes in the river system it is essential that the SPM monitoring frequency in river sections downstream of Eijsden is increased, starting with the Keizersveer station. A better system understanding is important in order to define appropriate measures to meet the goals of the Water Framework Directive concerning the chemical status of the Meuse River

Nalevering van stoffen vanuit de waterbodem naar oppervlaktewater

The advent of the Water Framework Directive and the introduction of the Water Act will place the focus of the assessment of aquatic systems on the quality of surface water. This raises the question of the extent to which aquatic sediments act as a source of pollution due to the release of substances. This study examines whether substances are released from aquatic sediments to the water column by means of diffusive transport, and the degree to which this occurs. It also considers what routine or specialist methods are available to measure this subsequent release of substances. Three very different locations (IJmuiden, the Afferdensche and Deestsche Waarden, and the Ghent-Terneuzen Canal) were sampled. A range of measuring techniques were used, and experiments were conducted to quantify emission fluxes of organic compounds (PAHs, PCBs), heavy metals and nutrient