Fluidity of bound hydration layers

We have measured the shear forces between solid surfaces sliding past each other across aqueous salt solutions, at pressures and concentrations typical of naturally occurring systems. In such systems the surface-attached hydration layers keep the compressed surfaces apart as a result of strongly repulsive hydration forces. We find, however, that the bound water molecules retain a shear fluidity characteristic of the bulk liquid, even when compressed down to films 1.0 +/- 0.3 nanometer thick. We attribute this to the ready exchange (as opposed to loss) of water molecules within the hydration layers as they rub past each other under strong compression.     

Components of competitiveness

There are various ways of looking at economic competitiveness. Some of the popular conceptions of America's relative position are clarified by examining the concept in terms of wage cost, productivity, profit margins, and exchange rates. A quantitative approach is laid out and examined in relation to similar measures for other countries. Also some relationships between competitiveness and the external deficit on current account for the United States are analyzed.     

Structural basis of glmS ribozyme activation by glucosamine-6-phosphate

The glmS ribozyme is the only natural catalytic RNA known to require a small-molecule activator for catalysis. This catalytic RNA functions as a riboswitch, with activator-dependent RNA cleavage regulating glmS messenger RNA expression. We report crystal structures of the glmS ribozyme in precleavage states that are unliganded or bound to the competitive inhibitor glucose-6-phosphate and in the postcleavage state. All structures superimpose closely, revealing a remarkably rigid RNA that contains a preformed active and coenzyme-binding site. Unlike other riboswitches, the glmS ribozyme binds its activator in an open, solvent-accessible pocket. Our structures suggest that the amine group of the glmS ribozyme-bound coenzyme performs general acid-base and electrostatic catalysis.     

Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome

Aortic aneurysm and dissection are manifestations of Marfan syndrome (MFS), a disorder caused by mutations in the gene that encodes fibrillin-1. Selected manifestations of MFS reflect excessive signaling by the transforming growth factor-beta (TGF-beta) family of cytokines. We show that aortic aneurysm in a mouse model of MFS is associated with increased TGF-beta signaling and can be prevented by TGF-beta antagonists such as TGF-beta-neutralizing antibody or the angiotensin II type 1 receptor (AT1) blocker, losartan. AT1 antagonism also partially reversed noncardiovascular manifestations of MFS, including impaired alveolar septation. These data suggest that losartan, a drug already in clinical use for hypertension, merits investigation as a therapeutic strategy for patients with MFS and has the potential to prevent the major life-threatening manifestation of this disorder.     

Mutation analysis and gene expression profiling of ocular melanomas in cats

Feline ocular melanomas show a high malignant behaviour, but adjunctive therapies are non‐existent. The aim of this pilot study was to determine, whether feline ocular melanomas harbour mutations comparable to mutations in human melanomas and to evaluate the gene expression status of genes known to be involved in initiation and progression of human melanomas. Mutation hotspot regions of several genes of feline ocular melanomas were analysed by DNA sequencing and RNA expression levels of the respective genes and others were evaluated by quantitative real‐time polymerase chain reaction (RT‐qPCR). Common mutations found in human melanomas are not present in feline tumours. Gene expression analysis revealed a significant upregulation of KIT and LTA4H, as well as a downregulation of GNAQ, GNA11, BRAF and RASSF1 in feline ocular melanomas. As KIT seems to harbour a potential as target gene in human uveal melanomas, future studies should further investigate the potential of KIT as target for adjunctive therapy in feline ocular melanomas.     

Spread of viruses through the food chain

Food associated viruses are responsible for a high number of infectious diseases in man, mainly gastroenteritis and hepatitis. The three most important viral agents are noroviruses (NV) (formerly known as Norwalk-like viruses), Rotavirus (RV) and Hepatitis A-Virus (HAV). The numbers of infections in man were in 2002 according to the Robert Koch-Institut for NV and RV 50,000, respectively, and for HAV 1,500, slightly decreasing in 2003. The rate of foodborne infections caused by viruses can only be estimated (appr. 20% of total cases). On the other hand only a very small part of viral gastroenteritis can be diagnosed and notified. Besides the direct infection through contaminated food the human to human infection is the most important source, also responsible for outbreaks. There is at the moment no routine diagnostic tool available for the detection of viruses in food because of the lack of standardized methods. For NV, one of the most important foodborne (live bivalve molluscs) viral pathogens, indicator organisms are in use. There is a scientific evaluation in different member states concerning the value of bacterial indicators vs. bacteriophages. In addition to foodborne viruses (via faecal contamination present in the food chain) there are emerging zoonotic viral agents. Food may be a vector for this agents depending on the production structures (e.g. SARS or influenca).