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Abstract Cerebral malaria involves the expression of a particular var subgroup, termed upsA, in Plasmodium falciparum, which encodes a subset of PfEMP1 variants that avidly bind to human receptors on endothelial cells, resulting in obstruction of microvasculature in the brain and severe pathogenesis. Despite the clinical importance of the upsA var genes, the mechanism of their low-frequency activation in asymptomatic or uncomplicated malaria cases remains poorly understood.
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