Plasmodium falciparum Rosetting Epitopes Converge in the SD3-Loop of PfEMP1-DBL1α

The ability of Plasmodium falciparum parasitized RBC (pRBC) to form rosettes with normal RBC is linked to the virulence of the parasite and RBC polymorphisms that weaken rosetting confer protection against severe malaria. The adhesin PfEMP1 mediates the binding and specific antibodies prevent sequestration in the micro-vasculature, as seen in animal models. Here we demonstrate that epitopes targeted by rosette disrupting antibodies converge in the loop of subdomain 3 (SD3) which connects the h6 and h7 α-helices of PfEMP1-DBL1α. Both monoclonal antibodies and polyclonal IgG, that bound to epitopes in the SD3-loop, stained the surface of pRBC, disrupted rosettes and blocked direct binding of recombinant NTS-DBL1α to RBC. Depletion of polyclonal IgG raised to NTS-DBL1α on a SD3 loop-peptide removed the anti-rosetting activity. Immunizations with recombinant subdomain 1 (SD1), subdomain 2 (SD2) or SD3 all generated antibodies reacting with the pRBC-surface but only the sera of animals immunized with SD3 disrupted rosettes. SD3-sequences were found to segregate phylogenetically into two groups (A/B). Group A included rosetting sequences that were associated with two cysteine-residues present in the SD2-domain while group B included those with three or more cysteines. Our results suggest that the SD3 loop of PfEMP1-DBL1α is an important target of anti-rosetting activity, clarifying the molecular basis of the development of variant-specific rosette disrupting antibodies.

The cultural magazines as spaces of resistence in the lasta argentinian militar dictatorship. From the “El Expreso Imaginario” to “El Porteño”, 1976 – 1983

Although they were a few, there were places during the military dictatorship, which produced innovative cultural goods, in continuity with experiences of the artistic avant-garde in the sixties. Alongside the political and military repression  they could articulate in their environment groups identified with alternative aesthetic  codes, in opposition to the dominant culture in the period. The first one of the aces  we examine in the article, El Expreso Imaginario is a privileged place where we may regard the origins of the traits of that social space. Towards the end of  the dictatorship, another one like El Porteño, marks a new era, even if we can  establish various continuities with the first one. The circulation places of these ideas and practices were often taking place in cellars and other hiding places. Is  that because they take the literal sense of underground in the eighties to groups  who having been part of that story or not, were willing to receive his inspiring legacy. Between both magazines we   fer identifies the transition from one state of the field to another, identifying the evolution of these zone of the culture field.