42 research outputs found

    Hostile Takeover by Plasmodium: Reorganization of Parasite and Host Cell Membranes during Liver Stage Egress

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    The protozoan parasite Plasmodium is transmitted by female Anopheles mosquitoes and undergoes obligatory development within a parasitophorous vacuole in hepatocytes before it is released into the bloodstream. The transition to the blood stage was previously shown to involve the packaging of exoerythrocytic merozoites into membrane-surrounded vesicles, called merosomes, which are delivered directly into liver sinusoids. However, it was unclear whether the membrane of these merosomes was derived from the parasite membrane, the parasitophorous vacuole membrane or the host cell membrane. This knowledge is required to determine how phagocytes will be directed against merosomes. Here, we fluorescently label the candidate membranes and use live cell imaging to show that the merosome membrane derives from the host cell membrane. We also demonstrate that proteins in the host cell membrane are lost during merozoite liberation from the parasitophorous vacuole. Immediately after the breakdown of the parasitophorous vacuole membrane, the host cell mitochondria begin to degenerate and protein biosynthesis arrests. The intact host cell plasma membrane surrounding merosomes allows Plasmodium to mask itself from the host immune system and bypass the numerous Kupffer cells on its way into the bloodstream. This represents an effective strategy for evading host defenses before establishing a blood stage infection

    Exoerythrocytic Plasmodium Parasites Secrete a Cysteine Protease Inhibitor Involved in Sporozoite Invasion and Capable of Blocking Cell Death of Host Hepatocytes

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    Plasmodium parasites must control cysteine protease activity that is critical for hepatocyte invasion by sporozoites, liver stage development, host cell survival and merozoite liberation. Here we show that exoerythrocytic P. berghei parasites express a potent cysteine protease inhibitor (PbICP, P. berghei inhibitor of cysteine proteases). We provide evidence that it has an important function in sporozoite invasion and is capable of blocking hepatocyte cell death. Pre-incubation with specific anti-PbICP antiserum significantly decreased the ability of sporozoites to infect hepatocytes and expression of PbICP in mammalian cells protects them against peroxide- and camptothecin-induced cell death. PbICP is secreted by sporozoites prior to and after hepatocyte invasion, localizes to the parasitophorous vacuole as well as to the parasite cytoplasm in the schizont stage and is released into the host cell cytoplasm at the end of the liver stage. Like its homolog falstatin/PfICP in P. falciparum, PbICP consists of a classical N-terminal signal peptide, a long N-terminal extension region and a chagasin-like C-terminal domain. In exoerythrocytic parasites, PbICP is posttranslationally processed, leading to liberation of the C-terminal chagasin-like domain. Biochemical analysis has revealed that both full-length PbICP and the truncated C-terminal domain are very potent inhibitors of cathepsin L-like host and parasite cysteine proteases. The results presented in this study suggest that the inhibitor plays an important role in sporozoite invasion of host cells and in parasite survival during liver stage development by inhibiting host cell proteases involved in programmed cell death

    Value Orientation, Locational Choice and Residential Satisfaction - a Spatial Econometric Analysis

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    An Overview of Population Projections—Methodological Concepts, International Data Availability, and Use Cases

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    Population projections serve various actors at subnational, national, and international levels as a quantitative basis for political and economic decision-making. Usually, the users are no experts in statistics or forecasting and therefore lack the methodological and demographic background to completely understand methods and limitations behind the projections they use to inform further analysis. Our contribution primarily targets that readership. Therefore, we give a brief overview of di erent approaches to population projection and discuss their respective advantages and disadvantages, alongside practical problems in population data and forecasting. Fundamental di erences between deterministic and stochastic approaches are discussed, with special emphasis on the advantages of stochastic approaches. Next to selected projection data available to the public, we show central areas of application of population projections, with an emphasis on German

    Zur Relevanz von Bevölkerungsvorausberechnungen für Arbeitsmarkt-, Bildungs- und Regionalpolitik

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    Die Medien, die Öffentlichkeit und die Politik gehen seit vielen Jahren von einer demografischen Entwicklung aus, die für Deutschland nichts Gutes verheißt. Die Alterung der Bevölkerung bedroht die sozialen Sicherungssysteme, führt zu Fachkräftemangel und zu verdorrten Landschaften - so viele wissenschaftsbasierte Vorhersagen. Kann man diesen Prognosen vertrauen? Der Band zeigt auf, wie wichtig eine differenzierte Betrachtung ist: Ausgewählt wurden Beispiele aus der Arbeitsmarktprognostik, Bildungspolitik und Regionalentwicklung, mit einigen überraschenden Befunden zur Migration, zu Wohnungsbedarfen und zu kommunalen Wachstumsstrategien. Beiträge zum demografischen Wandel in Europa erweitern den Blickwinkel und lassen Rückschlüsse auf künftige Entwicklungen in Deutschland zu
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