Thrombin responses in human endothelial cells. Contributions from receptors other than PAR1 include the transactivation of PAR2 by thrombin-cleaved PAR1

The recent identification of two new thrombin receptors, PAR3 and PAR4, led us to re-examine the basis for endothelial cell responses to thrombin. Human umbilical vein endothelial cells (HUVEC) are known to express PAR1 and the trypsin/tryptase receptor, PAR2. Northern blots detected both of those receptors and, to a lesser extent, PAR3, but PAR4 message was undetectable and there was no response to PAR4 agonist peptides. To determine whether PAR3 or any other receptor contributes to thrombin signaling in HUVEC, PAR1 cleavage was blocked with two selective antibodies and PAR1 activation was inhibited with the antagonist, BMS200261. The antibodies completely inhibited HUVEC responses to thrombin, but BMS200261 was only partly effective, even though separate studies established that the antagonist completely inhibits PAR1 signaling at the concentrations used. Since peptides mimicking the PAR1 tethered ligand domain can also activate PAR2, we asked whether the remaining thrombin response in the presence of the antagonist could be due in part to the intermolecular transactivation of PAR2 by cleaved PAR1. Evidence that transactivation can occur was obtained in COS-7 cells co-expressing PAR2 and a variant of PAR1 that can be cleaved, but not signal. There was a substantial response to thrombin only in cells expressing both receptors. Conversely, in HUVEC, complete blockade of the thrombin response by the PAR1 antagonist occurred only when signaling through PAR2 was also blocked. From these observations we conclude that 1) PAR1 is the predominant thrombin receptor expressed in HUVEC and cleavage of PAR1 is required for endothelial cell responses to thrombin; 2) although PAR3 may be expressed, there is still no evidence that it mediates thrombin responses; 3) PAR4 is not expressed on HUVEC; and 4) transactivation of PAR2 by cleaved PAR1 can contribute to endothelial cell responses to thrombin, particularly when signaling through PAR1 is blocked. Such transactivation may limit the effectiveness of PAR1 antagonists, which compete with the tethered ligand domain rather than preventing PAR1 cleavage.     

SUMO modification of proteins other than transcription factors

A wide range of eukaryotic proteins has been shown to be sumoylated. Most, but not all of these proteins are nuclear. In all cases documented so far, sumoylation has been shown to occur on lysine residues. In general these are located within the consensus sequence psiKxE, although there are some exceptions to this. The role of sumoylation has been investigated for a number of identified targets. Unlike the situation with ubiquitination, sumoylation does not appear to target proteins for proteasome-mediated degradation. In contrast, the effect of SUMO modification appears to depend on the target protein and includes roles in altering protein activity, protein-protein interactions or protein localisation.     

Predation on Cnidaria by vertebrates other than fishes

Records of predation by reptiles, birds and mammals on Cnidaria are reviewed.     

Commercial application of microalgae other than as biofuels: a brief review

There has been considerable discussion in recent years about the potential of micro-algae for the production of sustainable and renewable biofuels, but there may be other more readily exploitable commercial opportunities for microalgae. This paper briefly reviews the current and potential situation for the commercial application of the growth of microalgae for products other than biofuels.     

Transfusion-transmitted diseases other than AIDS and hepatitis.

Although the major diseases transmitted by transfusion today are AIDS and hepatitis, many others also are known. These include CMV, syphilis, Chagas disease, babesiosis, parvovirus B19, malaria, Epstein-Barr infection, and many others that have been reported only once or twice. Reducing the risk of transfusion-transmitted diseases is a problem for donor centers where donor screening and laboratory testing for possible carriers is undertaken. Physicians should be aware that the potential for disease transmission is always present when transfusions are administered.