Severe malaria is caused by the apicomplexan parasite Plasmodium falciparum. Despite decades of research the unique biology of these parasites has made it challenging to establish high throughput genetic approaches for identification of therapeutic targets. Using transposon mutagenesis of P. falciparum in an approach that exploited its AT-rich genome we generated >38,000 mutants, saturating the genome and defining fitness costs for 95% of genes. Of 5,399 genes we found ~3,000 genes are essential for optimal growth of asexual blood-stages in vitro. Our study defines ∼1000 essential genes, including genes associated with drug resistance, vaccine candidates, and conserved proteins of unknown function. We validated this approach by testing proteasome pathways for individual mutants associated with artemisinin sensitivity.

No abstract

Although it has been suggested that innovation has significant consequences for a firm's economic performance, the past empirical findings are mixed, not always confirming this proposition. Extending previous research, this study demonstrates that the reason for previously conflicting results may be an incomplete understanding of the factors influencing the innovation-performance relationship. We argue that not all firms can reap rewards from innovation. Rather, we suggest that firms need to have a sufficient degree of internationalization, i.e. be active in many markets, to capture successfully the fruits of innovation. Initially, the study offers a theoretical framework that explains how and why a higher degree of internationalization, by affecting both innovative capacity and a number of appropriability factors, influences the effects of innovation. Then, utilizing firm-level data, the study empirically tests this proposition. The results confirm that internationalization enhances a firm's capacity to improve performance through innovation. However, they also show that firms are unable to benefit from innovation if their international activity is below a threshold level.