22 research outputs found
A note on the Painleve analysis of a (2+1) dimensional Camassa-Holm equation
We investigate the Painleve analysis for a (2+1) dimensional Camassa-Holm
equation. Our results show that it admits only weak Painleve expansions. This
then confirms the limitations of the Painleve test as a test for complete
integrability when applied to non-semilinear partial differential equations.Comment: Chaos, Solitons and Fractals (Accepted for publication
Conditional expression of apical membrane antigen 1 in Plasmodium falciparum shows it is required for erythrocyte invasion by merozoites
Malaria is caused by obligate intracellular parasites, of which Plasmodium falciparum is the most lethal species. In humans, P.âfalciparum merozoites (invasive forms of the parasite) employ a host of parasite proteins to rapidly invade erythrocytes. One of these is the P.âfalciparum apical membrane antigen 1 (PfAMA1) which forms a complex with rhoptry neck proteins at the tight junction. Here, we have placed the Pfama1 gene under conditional control using dimerizable Cre recombinase (DiCre) in P.âfalciparum. DiCreâmediated excision of the loxPâflanked Pfama1 gene results in approximately 80% decreased expression of the protein within one intraerythrocytic growth cycle. This reduces growth by 40%, due to decreased invasion efficiency characterized by a postâinvasion defect in sealing of the parasitophorous vacuole. These results show that PfAMA1 is an essential protein for merozoite invasion in P.âfalciparum and either directly or indirectly plays a role in resealing of the red blood cell at the posterior end of the invasion event.Alan Yap, Mauro F. Azevedo, Paul R. Gilson, Greta E. Weiss, Matthew T. OâNeill, Danny W. Wilson, Brendan S. Crabb and Alan F. Cowma
Defining species-specific and conserved interactions of apical membrane protein 1 during erythrocyte invasion in malaria to inform multi-species vaccines
Published online: 27 February 2023Plasmodium falciparum and P. vivax are the major causes of human malaria, and P. knowlesi is an important additional cause in SE Asia. Binding of apical membrane antigen 1 (AMA1) to rhoptry neck protein 2 (RON2) was thought to be essential for merozoite invasion of erythrocytes by Plasmodium spp. Our findings reveal that P. falciparum and P. vivax have diverged and show species-specific binding of AMA1 to RON2, determined by a ÎČ-hairpin loop in RON2 and specific residues in AMA1 Loop1E. In contrast, cross-species binding of AMA1 to RON2 is retained between P. vivax and P. knowlesi. Mutation of specific amino acids in AMA1 Loop1E in P. falciparum or P. vivax ablated RON2 binding without impacting erythrocyte invasion. This indicates that the AMA1âRON2-loop interaction is not essential for invasion and additional AMA1 interactions are involved. Mutations in AMA1 that disrupt RON2 binding also enable escape of invasion inhibitory antibodies. Therefore, vaccines and therapeutics will need to be broader than targeting only the AMA1âRON2 interaction. Antibodies targeting AMA1 domain 3 had greater invasion-inhibitory activity when RON2-loop binding was ablated, suggesting this domain is a promising additional target for vaccine development. Targeting multiple AMA1 interactions involved in invasion may enable vaccines that generate more potent inhibitory antibodies and address the capacity for immune evasion. Findings on specific residues for invasion function and species divergence and conservation can inform novel vaccines and therapeutics against malaria caused by three species, including the potential for cross-species vaccines.Damien R. Drew, Danny W. Wilson, Gretchen E. Weiss, Lee M. Yeoh, Isabelle G. Henshall, Brendan S. Crabb, Sheetij Dutta, Paul R. Gilson, James G. Beeso
Nutritional and energetic value of rice by-products, with or without phytase, for growing pigs
PrevalĂȘncia de neoplasias diagnosticadas em cĂŁes no Hospital VeterinĂĄrio da Universidade Eduardo Mondlane, Moçambique
Evaluation of the effectiveness of an Internet-based continuing education program on pharmacy-based minor ailment management: a randomized controlled clinical trial
Characterisation of PfCZIF1 and PfCZIF2 in Plasmodium falciparum asexual stages
Plasmodium falciparum exerts strong temporal control of gene expression across its lifecycle. Proteins expressed exclusively during late schizogony of blood stages, for example, often have a role in facilitating merozoite invasion of the host red blood cell (RBC), through merozoite development, egress, invasion or early establishment of infection in the RBC. Here, we characterise P. falciparum C3H1 zinc finger 1 (PfCZIF1, Pf3D7_1468400) and P. falciparum C3H1 zinc finger 2 (PfCZIF2, Pf3D7_0818100) which we identified as the only C3H1-type zinc finger proteins with peak expression at schizogony. Previous studies reported that antibodies against PfCZIF1 inhibit merozoite invasion, suggesting this protein may have a potential role during RBC invasion. We show using C-terminal truncations and gene knockouts of each of Pfczif1 and Pfczif2 that neither are essential for blood stage growth. However, they could not both be knocked out simultaneously, suggesting that at least one is needed for parasite growth in vitro. Immunofluorescence localisation of PfCZIF1 and PfCZIF2 indicated that both proteins occur in discrete foci on the periphery of the parasiteâs cytosol and biochemical assays suggest they are peripherally associated to a membrane. Transcriptomic analyses for the C-terminal truncation mutants reveal no significant expression perturbations with PfCZIF1 truncation. However, modification of PfCZIF2 appears to modify the expression for some exported proteins including PfKAHRP. This study does not support a role for PfCZIF1 or PfCZIF2 in merozoite invasion of the RBC and suggests that these proteins may help regulate the expression of proteins exported into the RBC cytosol after merozoite invasion.Juan M. Balbin, Gary K. Heinemann, Lee M. Yeoh, Tim-Wolf Gilberger, Mark Armstrong, Michael F. Duffy, Paul R. Gilson, Danny W. Wilso