Comparative proteome analysis of triclabendazole response in the liver fluke, Fasciola hepatica.

Control of Fasciola hepatica infections of livestock in the absence of vaccines depends largely on the chemical triclabendazole (TCBZ) because it is effective against immature and adult parasites. Overdependence on a single drug and improper application is considered a significant factor in increasing global reports of fluke resistant to TCBZ. The mode(s) of action and biological target(s) of TCBZ are not confirmed, delaying detection and the monitoring of early TCBZ resistance. In this study, to further understand liver fluke response to TCBZ, the soluble proteomes of TCBZ-resistant and TCBZ-susceptible isolates of F. hepatica were compared with and without in vitro exposure to the metabolically active form of the parent drug triclabendazole sulphoxide (TCBZ-SO), via two-dimensional gel electrophoresis (2-DE). Gel image analysis revealed proteins displaying altered synthesis patterns and responses both between isolates and under TCBZ-SO exposure. These proteins were identified by mass spectrometry supported by a F. hepatica expressed sequence tag (EST) data set. The TCBZ responding proteins were grouped into three categories; structural proteins, energy metabolism proteins, and “stress” response proteins. This single proteomic investigation supported the reductionist experiments from many laboratories that collectively suggest TCBZ has a range of effects on liver fluke metabolism. Proteomics highlighted differences in the innate proteome profile of different fluke isolates that may influence future therapy and diagnostics design. Two of the TCBZ responding proteins, a glutathione transferase and a fatty acid binding protein, were cloned, produced as recombinants, and both found to bind TCBZ-SO at physiologically relevant concentrations, which may indicate a role in TCBZ metabolism and resistance.

A comparative study of domestic, European and international job-related relocation

This paper explores a number of relocation outcomes for geographically mobile employees in the following three regions: Germany as the home country and destination for domestic assignments (n = 115), Western Europe (n = 116) and other countries (n = 236). The satisfaction with various aspects of the post-relocation environment, the perception of change between the pre- and post-relocation environment and the attachment to the post-relocation environment at various levels were compared between the three groups. For the European and international sub-samples differences in the ideal country and future plans were also investigated. The group that stood out most clearly was the domestic sub-sample. It emerged as the group least satisfied with their job or task characteristics, perceived significantly fewer changes in the environment and was comparatively eager to leave the site they were currently working at and the job they were currently employed in. The sometimes proposed redefinition of intra-European assignments as ‘quasi-domestic’ relocation appears to be inappropriate.

Comparative validation of c-kit exon 11 mutation analysis on cytology samples and corresponding surgical resections of gastrointestinal stromal tumours

Objective: