Secreted signalling molecules provide cells with positional information that organizes long-range pattern during the development of multicellular animals. Evidence is presented that localized expression of Decapentaplegic instructs cells about their position along the anterior-posterior axis of the Drosophila wing in two distinct ways. One mechanism is based on the local concentration of the secreted protein; the other is based on the ability of the cells to retain an instruction received at an earlier time when their progenitors were in close proximity to the signal. Both mechanisms are involved in axis formation.

Summary Cerebral malaria is a major complication of Plasmodium falciparum infection in children. The pathogenesis of cerebral malaria 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 factor 4 (PF4)/CXCL4, promotes the development of experimental cerebral malaria. Plasmodium infected red blood cells (RBC) activated platelets independent of vascular effects, resulting in increased plasma PF4. PF4 or CXCR3 null mice had less ECM, decreased brain T-cell recruitment, and platelet depletion or aspirin treatment reduced the development of ECM. We conclude that Plasmodium infected RBC can activate platelets and platelet derived PF4 then contributes to immune activation and T-cell trafficking as part of the pathogenesis of ECM.

Drosophila larvae are attracted to a wide variety of chemical stimuli. The olfactory response to ethyl acetate, a powerful attractant, was found to be surprisingly well conserved across a variety of different wild-type strains. Strain differences are documented, however, both in attraction to ethyl acetate and in another chemosensory behavior: avoidance of an aversive stimulus. As a means of analyzing the extent of genetic heterogeneity within strains, one wild-type population, Canton-S, was screened for variant X chromosomes. An enrichment procedure was characterized and used to make the screening more efficient. Lines homozygous for individual X chromosomes were established, and all were found to exhibit a strong olfactory response, although evidence was found for variation among them. The olfactory response was found to be conserved through an extended period of larval development, including the final period during which larvae leave the culture medium in preparation for metamorphosis. The results are discussed in terms of the genetic basis of the response and the use of single-gene mutations as a means of dissecting olfactory system function.

Platelet interactions with dendritic cells, T cells and B cells have been best studied in vasculitis andatherosclerosis, but similar mechanisms may contribute to acute and chronic vascular lesions in transplants. In acute inflammation, platelets adhere to vessels and release mediators that increase endothelial cell activation and leukocyte recruitment. Adherent platelets can also augment antibody and cellular immune responses. Activated platelets recruit T cells and initiate a feedback loop. In this loop, platelets secrete chemokines to recruit T cells, and then activated T cells stimulate platelets through CD40-CD154 interactions to secrete more chemokines thereby recruiting more T cells. The interaction of platelets and T cells is enhanced by P-selectin/PSGL-1 stimulation. Both helper and cytotoxic T cells are stimulated by platelets. Antibody production that is stimulated through increased helper T-cell function can activate complement. This sets up another activation loop because platelets express receptors for antibodies and complement. In addition to inflammation, platelets stimulate repair by releasing growth factors and chemokines to recruit circulating vascular progenitor cells. These repair mechanisms could promote the replacement of donor parenchmal cells with recipient cells and contribute to vascuplopathy. This review discusses the interplay of platelets and the immune system in relation to transplantation.