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During development in human erythrocytes, the malaria parasite Plasmodium falciparum internalizes a large part of the cellular content of the host cell. The internalized cytosol, consisting largely of hemoglobin, is transported to the parasite’s food vacuole where it is degraded, providing nutrients and space for growth. This host cell cytosol uptake (HCCU) is crucial for parasite survival but the parasite proteins mediating this process remain obscure. Here, we identify P. falciparum VPS45 as an essential factor in HCCU. Conditional inactivation of PfVPS45 led to an accumulation of host cell cytosol-filled vesicles within the parasite and inhibited the delivery of hemoglobin to the parasite's digestive vacuole, resulting in arrested parasite growth. A proportion of these HCCU vesicle intermediates was positive for phosphatidylinositol 3-phosphate, suggesting endosomal characteristics. Thus PfVPS45 provides insight into the elusive machinery of the ingestion pathway in a parasite that contains an endolysosomal system heavily repurposed for protein secretion.
„Wir alle treffen Entscheidungen im Leben, aber letztendlich treffen unsere Entscheidungen uns.“
(2020)
„Wir alle treffen Entscheidungen im Leben, aber letztendlich treffen unsere Entscheidungen uns.“
So erging es den Herausgebern, nachdem sie sich dazu entschlossen hatten, Lehrveranstaltungen an der Universität Potsdam anzubieten, die sich mit dem Medium „Computerspiel“ beschäftigen sollten – und damit auf überraschend große Resonanz stießen. Das Resultat ist vorliegendes Handbuch. Es möchte Eltern, LehrerInnen und MultiplikatorInnen exemplarische Einblicke in die vielschichtigen Welten dieses Phänomens vermitteln. Bei den AutorInnen der Beiträge handelt es sich um EnthusiastInnen aus der Computerspielbranche sowie um videospielbegeisterte SozialarbeiterInnen, KulturwissenschaftlerInnen und LehrerInnen.
Background Athlete's heart as an adaptation to long-time and intensive endurance training can vary considerably between individuals. Genetic polymorphisms in the cardiological relevant insulin-like growth factor 1 (IGF1) signalling pathway seem to have an essential influence on the extent of physiological hypertrophy.
Objective Analysis of polymorphisms in the genes of IGF1, IGF1 receptor (IGF1R) and the negative regulator of the cardiac IGF1 signalling pathway, myostatin (MSTN), and their relation to left ventricular mass (LVM) of endurance athletes.
Methods In 110 elite endurance athletes or athletes with a high amount of endurance training (75 males and 35 females) and 27 male controls, which were examined by echocardiographic imaging methods and ergometric exercise-testing, the genotypes of a cytosine-adenine repeat polymorphism in the promoter region of the IGF1 gene and a G/A substitution at position 3174 in the IGF1R gene were determined. Additionally, a mutation screen of the MSTN gene was performed.
Results The polymorphisms in the IGF1 and the IGF1R gene showed a significant relation to the LVM for male (IGF1: p=0.003; IGF1R: p=0.01), but not for female athletes. The same applies to a previously unnoticed polymorphism in the 1 intron of the MSTN gene, whose deletion allele (AAA -> AA) appears to increase the myostatic effect (p=0.015). Moreover, combinations of the polymorphisms showed significant synergistic effects on the LVM of the male athletes.
Conclusions The authors' results argue for the importance of polymorphisms in the IGF1 signalling pathway in combination with MSTN on the variant degree of physiological hypertrophy of male athletes.