The role of proteolytic processing and the stable signal peptide in expression of the Old World arenavirus envelope glycoprotein ectodomain.

Maturation of the arenavirus GP precursor (GPC) involves proteolytic processing by cellular signal peptidase and the proprotein convertase subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P), yielding a tripartite complex comprised of a stable signal peptide (SSP), the receptor-binding GP1, and the fusion-active transmembrane GP2. Here we investigated the roles of SKI-1/S1P processing and SSP in the biosynthesis of the recombinant GP ectodomains of lymphocytic choriomeningitis virus (LCMV) and Lassa virus (LASV). When expressed in mammalian cells, the LCMV and LASV GP ectodomains underwent processing by SKI-1/S1P, followed by dissociation of GP1 from GP2. The GP2 ectodomain spontaneously formed trimers as revealed by chemical cross-linking. The endogenous SSP, known to be crucial for maturation and transport of full-length arenavirus GPC was dispensable for processing and secretion of the soluble GP ectodomain, suggesting a specific role of SSP in the stable prefusion conformation and transport of full-length GPC.

Rabies postexposure prophylaxis in routine practice in view of the new centers for disease control and prevention and world health organization recommendations.

Background. New recommendations for rabies postexposure prophylaxis (PEP) were published by the Centers for Disease Control and Prevention and the World Health Organization in 2010. In view of these new recommendations, we investigated the adequacy of rabies PEP among patients consulting our travel clinic. Methods. A retrospective analysis of the files of all patients who consulted for rabies PEP at the Travel Clinic of the University Hospital in Lausanne, Switzerland, between January 2005 and August 2011 was conducted. Results. A total of 110 patients who received rabies PEP were identified. The median age of the patients was 34 years (range, 2-79 years), and 53% were women. Ninety subjects were potentially exposed to rabies while travelling abroad. Shortcomings in the management of these patients were (1) late initiation of rabies PEP in travelers who waited to seek medical care until returning to Switzerland, (2) administration of human rabies immunoglobulin (HRIG) to only 7 of 50 travelers (14%) who sought care abroad and for whom HRIG was indicated, and (3) antibody levels <0.5 IU/mL in 6 of 90 patients (6.7%) after 4 doses of vaccine. Conclusions. Patients do not always receive optimal rabies PEP under real-life conditions. A significant proportion of patients did not develop adequate antibody levels after 4 doses of vaccine. These data indicate that the measurement of antibody levels on day 21 of the Essen PEP regimen is useful in order to verify an adequate immune response.

The Middle East in the American quest for world order : ideas of power, economics, and social development in United States foreign policy, 1953-1961

Doctoral dissertation, University of Tampere

Temporal and spatial origin of Gesneriaceae in the New World inferred from plastid DNA sequences

Gesneriaceae are represented in the New World (NW) by a major clade (c. 1000 species) currently recognized as subfamily Gesnerioideae. Radiation of this group occurred in all biomes of tropical America and was accompanied by extensive phenotypic and ecological diversification. Here we performed phylogenetic analyses using DNA sequences from three plastid loci to reconstruct the evolutionary history of Gesnerioideae and to investigate its relationship with other lineages of Gesneriaceae and Lamiales. Our molecular data confirm the inclusion of the South Pacific Coronanthereae and the Old World (OW) monotypic genus Titanotrichum in Gesnerioideae and the sister-group relationship of this subfamily to the rest of the OW Gesneriaceae. Calceolariaceae and the NW genera Peltanthera and Sanango appeared successively sister to Gesneriaceae, whereas Cubitanthus, which has been previously assigned to Gesneriaceae, is shown to be related to Linderniaceae. Based on molecular dating and biogeographical reconstruction analyses, we suggest that ancestors of Gesneriaceae originated in South America during the Late Cretaceous. Distribution of Gesneriaceae in the Palaeotropics and Australasia was inferred as resulting from two independent long-distance dispersals during the Eocene and Oligocene, respectively. In a short time span starting at 34 Mya, ancestors of Gesnerioideae colonized several Neotropical regions including the tropical Andes, Brazilian Atlantic forest, cerrado, Central America and the West Indies. Subsequent diversification within these areas occurred largely in situ and was particularly extensive in the mountainous systems of the Andes, Central America and the Brazilian Atlantic forest. Only two radiations account for 90% of the diversity of Gesneriaceae in the Brazilian Atlantic forest, whereas half of the species richness in the northern Andes and Central America originated during the last 10 Myr from a single radiation.