PTEX is an essential nexus for protein export in malaria parasites

During the blood stages of malaria, several hundred parasite-encoded proteins are exported beyond the double-membrane barrier that separates the parasite from the host cell cytosol. These proteins have a variety of roles that are essential to virulence or parasite growth. There is keen interest in understanding how proteins are exported and whether common machineries are involved in trafficking the different classes of exported proteins. One potential trafficking machine is a protein complex known as the Plasmodium translocon of exported proteins (PTEX). Although PTEX has been linked to the export of one class of exported proteins, there has been no direct evidence for its role and scope in protein translocation. Here we show, through the generation of two parasite lines defective for essential PTEX components (HSP101 or PTEX150), and analysis of a line lacking the non-essential component TRX2 (ref. 12), greatly reduced trafficking of all classes of exported proteins beyond the double membrane barrier enveloping the parasite. This includes proteins containing the PEXEL motif (RxLxE/Q/D) and PEXEL-negative exported proteins (PNEPs). Moreover, the export of proteins destined for expression on the infected erythrocyte surface, including the major virulence factor PfEMP1 in Plasmodium falciparum, was significantly reduced in PTEX knockdown parasites. PTEX function was also essential for blood-stage growth, because even a modest knockdown of PTEX components had a strong effect on the parasite's capacity to complete the erythrocytic cycle both in vitro and in vivo. Hence, as the only known nexus for protein export in Plasmodium parasites, and an essential enzymic machine, PTEX is a prime drug target.

Segregation-of-duties conflicts in the insider threat landscape: an overview and case study

Many insider attacks originate from misuse of privileges granted by organizations to their internal employees, contractors or third-party service providers. A fundamental means of ensuring that conflicts of privilege cannot occur is to segregate role allocations in order to ensure that no individual can perform a task from beginning to end. In this paper, we provide background on insider attacks in connection with conflicts in Segregation of Duties, and present the current strategies for preventing and detecting such conflicts. To illustrate how a conflict can occur and what can result, we present an in-depth case study demonstrating a conflict in Segregation of Dutiesin an organization, along with the consequent fraud, and we discuss how it might have been prevented.

Constitutionalism, good faith and the doctrine of specific performance: rights, duties and equitable discretion

This article will explore the European roots of the doctrine of specific performance and the influence of transformative constitutionalism on these in recent times. The question whether specific performance is available as of right (as in the civil law), or only subject to judicial discretion (as in the common law), will be investigated. The demonstrated impact of constitutional rights on contract law in the mixed system of South Africa will be contrasted with developments in English and Australian contract law, where the common-law rules are more deeply entrenched and the potential scope for human rights-based development of these is arguably smaller, though still important. The article will argue, using comparative rules on specific performance as an example, that the concept of a duty of good faith or contractual fairness is likely to play a greater role in future in all three of the countries under consideration, reducing the common/civil/mixed legal systems divide.