Host insulin stimulates Echinococcus multilocularis insulin signalling pathways and larval development.

BACKGROUND The metacestode of the tapeworm Echinococcus multilocularis is the causative agent of alveolar echinococcosis, a lethal zoonosis. Infections are initiated through establishment of parasite larvae within the intermediate host's liver, where high concentrations of insulin are present, followed by tumour-like growth of the metacestode in host organs. The molecular mechanisms determining the organ tropism of E. multilocularis or the influences of host hormones on parasite proliferation are poorly understood. RESULTS Using in vitro cultivation systems for parasite larvae we show that physiological concentrations (10 nM) of human insulin significantly stimulate the formation of metacestode larvae from parasite stem cells and promote asexual growth of the metacestode. Addition of human insulin to parasite larvae led to increased glucose uptake and enhanced phosphorylation of Echinococcus insulin signalling components, including an insulin receptor-like kinase, EmIR1, for which we demonstrate predominant expression in the parasite's glycogen storage cells. We also characterized a second insulin receptor family member, EmIR2, and demonstrated interaction of its ligand binding domain with human insulin in the yeast two-hybrid system. Addition of an insulin receptor inhibitor resulted in metacestode killing, prevented metacestode development from parasite stem cells, and impaired the activation of insulin signalling pathways through host insulin. CONCLUSIONS Our data indicate that host insulin acts as a stimulant for parasite development within the host liver and that E. multilocularis senses the host hormone through an evolutionarily conserved insulin signalling pathway. Hormonal host-parasite cross-communication, facilitated by the relatively close phylogenetic relationship between E. multilocularis and its mammalian hosts, thus appears to be important in the pathology of alveolar echinococcosis. This contributes to a closer understanding of organ tropism and parasite persistence in larval cestode infections. Furthermore, our data show that Echinococcus insulin signalling pathways are promising targets for the development of novel drugs.

Cellular and molecular interactions between the apicomplexan parasites Plasmodium and Theileria and their host cells

Apicomplexan parasites of the genera Theileria and Plasmodium have complicated life cycles including infection of a vertebrate intermediate host and an arthropod definitive host. As the Plasmodium parasite progresses through its life cycle, it enters a number of different cell types, both in its mammalian and mosquito hosts. The fate of these cells varies greatly, as do the parasite and host molecules involved in parasite-host interactions. In mammals, Plasmodium parasites infect hepatocytes and erythrocytes whereas Theileria infects ruminant leukocytes and erythrocytes. Survival of Plasmodium-infected hepatocytes and Theileria-infected leukocytes depends on parasite-mediated inhibition of host cell apoptosis but only Theileria-infected cells exhibit a fully transformed phenotype. As the development of both parasites progresses towards the merozoite stage, the parasites no longer promote the survival of the host cell and the infected cell is finally destroyed to release merozoites. In this review we describe similarities and differences of parasite-host cell interactions in Plasmodium-infected hepatocytes and Theileria-infected leukocytes and compare the observed phenotypes to other parasite stages interacting with host cells.

Tropical climate and vegetation simulations during the Heinrich event 1 using an Earth System Model of Intermediate Complexity (EMIC) - the University of Victoria Earth System-Climate Model (UVic ESCM)

Abrupt climate changes from 18 to 15 thousand years before present (kyr BP) associated with Heinrich Event 1 (HE1) had a strong impact on vegetation patterns not only at high latitudes of the Northern Hemisphere, but also in the tropical regions around the Atlantic Ocean. To gain a better understanding of the linkage between high and low latitudes, we used the University of Victoria (UVic) Earth System-Climate Model (ESCM) with dynamical vegetation and land surface components to simulate four scenarios of climate-vegetation interaction: the pre-industrial era, the Last Glacial Maximum (LGM), and a Heinrich-like event with two different climate backgrounds (interglacial and glacial). We calculated mega-biomes from the plant-functional types (PFTs) generated by the model to allow for a direct comparison between model results and palynological vegetation reconstructions. Our calculated mega-biomes for the pre-industrial period and the LGM corresponded well with biome reconstructions of the modern and LGM time slices, respectively, except that our pre-industrial simulation predicted the dominance of grassland in southern Europe and our LGM simulation resulted in more forest cover in tropical and sub-tropical South America. The HE1-like simulation with a glacial climate background produced sea-surface temperature patterns and enhanced inter-hemispheric thermal gradients in accordance with the "bipolar seesaw" hypothesis. We found that the cooling of the Northern Hemisphere caused a southward shift of those PFTs that are indicative of an increased desertification and a retreat of broadleaf forests in West Africa and northern South America. The mega-biomes from our HE1 simulation agreed well with paleovegetation data from tropical Africa and northern South America. Thus, according to our model-data comparison, the reconstructed vegetation changes for the tropical regions around the Atlantic Ocean were physically consistent with the remote effects of a Heinrich event under a glacial climate background.

Collision deformation classification training program: intermediate level - training/reference module.

National Highway Traffic Safety Administration, Washington, D.C.

Intermediate converstional German /

Includes index.

Review of the U.S. Department of Agriculture's change in procedure concerning sales of commodities through the Export Credit Guarantee Program and the Intermediate Export Credit Guarantee Program [microform] : hearing before the Subcommittee on Tobacco and Peanuts of the Committee on Agriculture, House of Representatives, One Hundredth Congress, second session, October 6, 1988.

"Serial no. 100-113."

Human spaceflight : activities for the intermediate student.

"10/85."--P. i (1st group)