We propose that P. ovale comprises 2 nonrecombining species that are sympatric in Africa and Asia. We speculate on possible scenarios that could have led to this speciation. Furthermore, the relatively high frequency of imported cases of symptomatic P. ovale infection in the United Kingdom suggests that the morbidity caused by ovale malaria has been underestimated.

Graphical abstractResearch highlights► We propose that two related species of malaria parasite cause ovale malaria. ► Discriminatory PCR tests identified both species in African surveys. ► Plasmodium ovale curtisi and Plasmodium ovale wallikeri were found together in time and space. ► Lack of recombination between them is not due to geographic or temporal separation. ► Therefore, the species barrier may be maintained by a biological mechanism(s).

Background: Fixed-dose combination antimalarial drugs have played an increasingly important role in the treatment and chemoprophylaxis of falciparum malaria since the worldwide failure of monotherapy with chloroquine. Atovaquone-proguanil is one such combination drug used both for prophylaxis in travellers, and for treatment of acute malaria cases in European hospitals and clinics.

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Identifying the driving forces and the mechanism of association of huntingtin-exon1, a close marker for the progress of Huntington's disease, is an important prerequisite to finding potential drug targets and, ultimately, a cure. We introduce here a modeling framework based on a key analogy of the physicochemical properties of the exon1 fragment to block copolymers. We use a systematic mesoscale methodology, based on dissipative particle dynamics, which is capable of overcoming kinetic barriers, thus capturing the dynamics of significantly larger systems over longer times than considered before. Our results reveal that the relative hydrophobicity of the poly(glutamine) block as compared with the rest of the (proline-based) exon1 fragment, ignored to date, constitutes a major factor in the initiation of the self-assembly process. We find that the assembly is governed by both the concentration of exon1 and the length of the poly(glutamine) stretch, with a low-length threshold for association, even at the lowest volume fractions we considered. Moreover, this self-association occurs irrespective of whether the glutamine stretch is in random-coil or hairpin configuration, leading to spherical or cylindrical assemblies, respectively. We discuss the implications of these results for reinterpretation of existing research within this context, including that the routes toward aggregation of exon1 may be distinct from those of the widely studied homopolymeric poly(glutamine) peptides. N eurodegenerative disorders are often linked with insoluble protein aggregates of fibrillar morphology, rich in ␤-structure content. In Huntington's disease, aggregates of N-terminal proteolytic fragments (exon1) of the protein huntingtin (1, 2) are found in the nuclei or the perinuclear cytoplasm of neurons (3, 4). Although a major thrust of research (5) is focused on the pathogenic role of huntingtin exon1 association, the underlying driving forces and mechanism of this process, which could ultimately provide a therapeutic approach toward overcoming Huntington's disease, remain to be established (6).The age of onset of Huntington's disease is correlated with the expansion of the CAG trinucleotide repeat sequence that encodes for glutamine, with a pathogenic threshold of 34-41 consecutive glutamines [poly(Q)] (7). Because of this observation, previous research has predominantly focused on the propensity of long homopolymeric poly(Q)s to form hairpin or other ␤-sheet structures as a prerequisite and driving force for the formation of insoluble fibrillar aggregates (8). Perutz's influential proposal (7), that hydrogen bonding between the main chain and side-chain amides could lead to stabilized polar zipper structures only for poly(Q) lengths exceeding the threshold, shares among current models the emphasis on the lengthdependent random coil to ␤-sheet structure transition of the single poly(Q) peptide chain.However, recent experiments have demonstrated instead that poly(Q) in solution is in a stable random-coil conformation irrespective of i...