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- Maas, Marc F.P.M., et al.
(författare)
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The mitochondrial plasmid pAL2-1 reduces calorie restriction mediated life span extension in the filamentous fungus Podospora anserina
- 2004
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Ingår i: Fungal Genetics and Biology. ; 41, s. 865-871
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Tidskriftsartikel (refereegranskat)abstract
- Calorie restriction is the only life span extending regimen known that applies to all aging organisms. Although most fungi do not appear to senesce, all natural isolates of the modular filamentous fungus Podospora anserina have a limited life span. In this paper, we show that calorie restriction extends life span also in Podospora anserina. The response to glucose limitation varies significantly among 23 natural isolates from a local population in The Netherlands, ranging from no effect up to a 5-fold life span extension. The isolate dependent effect is largely due to the presence or absence of pAL2-1 homologous plasmids. These mitochondrial plasmids are associated with reduced life span under calorie restricted conditions, suggesting a causal link. This has been substantiated using three combinations of isogenic isolates with and without plasmids. A model is proposed to explain how pAL2-1 homologues influence the response to calorie restriction.
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| 2. |
- Gritli Linde, Amel, 1959, et al.
(författare)
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Shh signaling within the dental epithelium is necessary for cell proliferation, growth and polarization
- 2002
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Ingår i: Development. ; 129:23, s. 5323-5337
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Tidskriftsartikel (refereegranskat)abstract
- Sonic hedgehog (Shh), a member of the mammalian hedgehog (Hh) family, plays a key role during embryogenesis and organogenesis. Tooth development, odontogenesis, is governed by sequential and reciprocal epithelial-mesenchymal interactions. Genetic removal of Shh activity from the dental epithelium, the sole source of Shh during tooth development, alters tooth growth and cytological organization within both the dental epithelium and mesenchyme of the tooth. In this model it is not clear which aspects of the phenotype represent the direct action of Shh on a target tissue or indirect effects due to deficiencies in reciprocal signalings between the epithelial and mesenchymal components. To distinguish between these two alternatives and extend our understanding of Shh’s actions in odontogenesis, we have used the Cre-loxP system to remove Smoothened (Smo) activity in the dental epithelium. Smo, a seven-pass membrane protein is essential for the transduction of all Hh signals. Hence, removal of Smo activity from the dental epithelium should block Shh signaling within dental epithelial derivatives while preserving normal mesenchymal signaling. Here we show that Shh-dependent interactions occur within the dental epithelium itself. The dental mesenchyme develops normally up until birth. In contrast, dental epithelial derivatives show altered proliferation, growth, differentiation and polarization. Our approach uncovers roles for Shh in controlling epithelial cell size, organelle development and polarization. Further, we provide evidence that Shh signaling between ameloblasts and the overlying stratum intermedium may involve subcellular localization of Ptc2 and Gli1 mRNAs, both of which are targets of Shh signaling in these cells.
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| 7. |
- van der Heide, A, et al.
(författare)
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End-of-life decision-making in six European countries: descriptive study
- 2003
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Ingår i: The Lancet. - 1474-547X. ; 362:9381, s. 345-350
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Tidskriftsartikel (refereegranskat)abstract
- Background Empirical data about end-of-life decision-making practices are scarce. We aimed to investigate frequency and characteristics of end-of-life decision-making practices in six European countries: Belgium, Denmark, Italy, the Netherlands, Sweden, and Switzerland. Methods In all participating countries, deaths reported to death registries were stratified for cause (apart from in Switzerland), and samples were drawn from every stratum. Reporting doctors received a mailed questionnaire about the medical decision-making that had preceded the death of the patient. The data-collection procedure precluded identification of any of the doctors or patients. All deaths arose between June, 2001, and February, 2002. We weighted data to correct for stratification and to make results representative for all deaths: results were presented as weighted percentages. Findings The questionnaire response rate was 75% for the Netherlands, 67% for Switzerland, 62% for Denmark, 61% for Sweden, 59% for Belgium, and 44% for Italy. Total number of deaths studied was 20 480. Death happened suddenly and unexpectedly in about a third of cases in all countries. The proportion of deaths that were preceded by any end-of-life decision ranged between 23% (Italy) and 51% (Switzerland). Administration of drugs with the explicit intention of hastening death varied between countries: about 1% or less in Denmark, Italy, Sweden, and Switzerland, 1.82% in Belgium, and 3.40% in the Netherlands. Large variations were recorded in the extent to which decisions were discussed with patients, relatives, and other caregivers. Interpretation Medical end-of-life decisions frequently precede dying in all participating countries. Patients and relatives are generally involved in decision-making in countries in which the frequency of making these decisions is high.
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