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.

Los grupos paramilitares en Bogotá y Cundinamarca, 1997-2005

Este artículo considera el período comprendido entre la segunda mitad de los 90, cuando aparecieron “grupos paramilitares” en Cundinamarca y Bogotá, y mediados de la primera década de este siglo, cuando fueron desmanteladas algunas de estas estructuras por parte de las autoridades, hubo entrega de armas por otras y surgieron organizaciones paramilitares “sustitutas” que permanecen activas en el ámbito territorial referido en este estudio. Destaca la actividad “antiinsurgente” desarrollada por los paramilitares en zonas coincidentes con aquellas donde las Fuerzas Militares adelantaron operaciones contrainsurgentes. Además, documenta el proceso de transformación y desintegración que sufrieron en el centro del país algunas estructuras paramilitares que acogieron el proceso de diálogo con el gobierno Uribe como parte de las Autodefensas Unidas de Colombia –AUC–a la vez que enfrentaban una “guerra interna” con otros grupos paramilitares recalcitrantes a participar del acuerdo. Finalmente presenta una apreciación sobre la evolución futura de los “ejércitos privados” que perviven luego de culminado el desarme de las AUC.-----This article surveys the period that covers the second half of the 1990’s, when “paramilitary groups” became visible in Cundinamarca and Bogotá, and the first half of the present decade, when a number of these structures were diminished as a result of law enforcement operations, a few others engaged in disarmament and new “substitute” paramilitary outfits emerged in the area referred by this study. It highlights the “anti-insurgent” activity of the paramilitary in areas that overlap with those where regular military forces carried out counterinsurgent operations. It also references the process of transformation and disintegration of paramilitary units in central Colombia that joined peace talks with the Uribe administration as part of the Autodefensas Unidas de Colombia –AUC–, as they simultaneously engaged in an “internal war” with other paramilitary groups reluctant to the agreement. It concludes with an appreciation about the future evolution of those “private armies” which endure after the AUC disarmament.