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Hemoglobin degradation in intraerythrocytic malaria parasites is a vast process that occurs in an acidic digestive vacuole. Proteases that participate in this catabolic pathway have been defined. Studies of protease biosynthesis have revealed unusual targeting and activation mechanisms. Oxygen radicals and heme are released during proteolysis and must be(More)
All Plasmodium species produce a brown birefringent crystal known as malarial pigment or hemozoin. This work compares the morphology of hemozoin from P. falciparum, P. vivax, P. ovale, P. malariae, P. knowlesi, P. brasilianum, P. yoelii and P. gallinaceum. The human, primate and mouse hemozoins have a regular, flat-faced cuboidal morphology with modest size(More)
Hemozoin (malaria pigment) has been implicated in the modulation of immune responses during malaria infection. This study was designed to evaluate the effect of purified hemozoin on the in vitro activation of myeloid dendritic cells. Our study also revealed that in addition to enhancing the maturation of dendritic cells, hemozoin also greatly promotes(More)
Cerebral malaria is a severe multifactorial condition associated with the interaction of high numbers of infected erythrocytes to human brain endothelium without invasion into the brain. The result is coma and seizures with death in more than 20% of cases. Because the brain endothelium is at the interface of these processes, we investigated the global gene(More)
Malaria caused by Plasmodium falciparum is a disease that is responsible for 880,000 deaths per year worldwide. Vaccine development has proved difficult and resistance has emerged for most antimalarial drugs. To discover new antimalarial chemotypes, we have used a phenotypic forward chemical genetic approach to assay 309,474 chemicals. Here we disclose(More)
Cerebral malaria (CM) is a major complication of Plasmodium falciparum infection in children. The pathogenesis of CM involves vascular inflammation, immune stimulation, and obstruction of cerebral capillaries. Platelets have a prominent role in both immune responses and vascular obstruction. We now demonstrate that the platelet-derived chemokine, platelet(More)
An AccQ*Tag ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry (AccQ*Tag-UPLC-ESI-MS/MS) method for fast, reproducible, and sensitive amino acid quantitation in biological samples, particularly, the malaria parasite Plasmodium falciparum is presented. The Waters Acquity TQD UPLC/MS system equipped with a photodiode(More)
Many parasites digest hemoglobin as an amino acid source, but only a few produce heme polymer pigment instead of catabolizing heme via heme oxygenase. This work compares purified heme polymers produced by Haemoproteus columbae and Schistosoma mansoni to that of Plasmodium falciparum hemozoin and synthetic beta-hematin. Fourier-transform infrared(More)
Haeme metabolism remains a vulnerable problem for the intraerythrocytic Plasmodium which catabolises haemoglobin as a source of amino acids in an acidic, oxygen-rich lysosome-like digestive vacuole. Haeme monomer, capable of generating oxygen radicals, transforms into an inert crystal named malarial pigment or haemozoin by forming unique dimers that then(More)