Base line prevalence and spatial distribution of Echinococcus multilocularis in a newly recognized endemic area in the Netherlands.

The base line prevalence of Echinococcus multilocularis in foxes was determined in the eastern part of the province of Groningen in the Netherlands adjacent to the German border. This region has been identified in a previous study in 1998 as one of the westernmost border areas of E. multilocularis. Base line prevalence data are important for a better insight in the possible spread of the parasite and its changes in time. As fox feces containing E. multilocularis eggs are an important source for human exposure this base line prevalence is also an indicator for the potential risk for public health. The base line prevalence was estimated at 9.4% (95% CI: 5.2-16.5%). These results confirm previous findings of E. multilocularis in the same region. The spatial distribution of the infected foxes has been analyzed as a spatial gradient using a logistic model. The prevalence appeared to change strongest in east-western direction and was highest near the German border, adjacent to a German endemic area. These results suggest that the border areas in the Netherlands are the most margin of E. multilocularis territory.

Arrayed adenoviral expression libraries for functional screening.

With the publication of the sequence of the human genome, we are challenged to identify the functions of an estimated 70,000 human genes and the much larger number of proteins encoded by these genes. Of particular interest is the identification of gene products that play a role in human disease pathways, as these proteins include potential new targets that may lead to improved therapeutic strategies. This requires the direct measurement of gene function on a genomic scale in cell-based, functional assays. We have constructed and validated an individually arrayed, replication-defective adenoviral library harboring human cDNAs, termed PhenoSelect library. The adenoviral vector guarantees efficient transduction of diverse cell types, including primary cells. The arrayed format allows screening of this library in a variety of cellular assays in search for gene(s) that, by overexpression, induce a particular disease-related phenotype. The great majority of phenotypic assays, including morphological assays, can be screened with arrayed libraries. In contrast, pooled-library approaches often rely on phenotype-based isolation or selection of single cells by employing a flow cytometer or screening for cell survival. An arrayed placental PhenoSelect library was screened in cellular assays aimed at identifying regulators of osteogenesis, metastasis, and angiogenesis. This resulted in the identification of known regulators, as well as novel sequences that encode proteins hitherto not known to play a role in these pathways. These results establish the value of the PhenoSelect platform, in combination with cellular screens, for gene function discovery.