Workshop on hastened death as "space for an appreciative discussion": A qualitative study.

AIM: To evaluate the suitability of a drama-based workshop as a method for ethical deliberation. BACKGROUND: Nurses worldwide are inadequately prepared to care for people who desire hastened death, which can lead to ethical and moral dilemmas. To address this problem, we developed a drama-based ethical deliberation workshop to assist nurses in these situations. Senghor and Racine's three moments of ethical deliberation and their quality criteria served as basis for evaluation. DESIGN: Qualitative descriptive study design. METHODS: Non-participant observations and a survey with incomplete sentences to be completed by nursing students were used. Data analysis followed Mayring's deductive content analysis approach. RESULTS: All three moments of ethical deliberation according to Senghor and Racine were identified. Participants recognised hastened death as morally problematic, shared their experiences and gained a deeper understanding of the problem. They reported feeling better prepared for encounters with persons seeking assisted suicide. In terms of its quality, the drama-based workshop achieved good and partial ethical deliberation. CONCLUSIONS: The workshop has demonstrated its suitability as a method for ethical deliberation. The workshop should be complemented by specific modules, such as communication skills and be tailored to other professional groups. A validated instrument is needed to ensure a more comprehensive assessment of the quality.

Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan.

Several pathways modulating longevity and stress resistance converge on translation by targeting ribosomal proteins or initiation factors, but whether this involves modifications of ribosomal RNA is unclear. Here, we show that reduced levels of the conserved RNA methyltransferase NSUN5 increase the lifespan and stress resistance in yeast, worms and flies. Rcm1, the yeast homologue of NSUN5, methylates C2278 within a conserved region of 25S rRNA. Loss of Rcm1 alters the structural conformation of the ribosome in close proximity to C2278, as well as translational fidelity, and favours recruitment of a distinct subset of oxidative stress-responsive mRNAs into polysomes. Thus, rather than merely being a static molecular machine executing translation, the ribosome exhibits functional diversity by modification of just a single rRNA nucleotide, resulting in an alteration of organismal physiological behaviour, and linking rRNA-mediated translational regulation to modulation of lifespan, and differential stress response.

Specialized yeast ribosomes: a customized tool for selective mRNA translation.

Evidence is now accumulating that sub-populations of ribosomes - so-called specialized ribosomes - can favour the translation of subsets of mRNAs. Here we use a large collection of diploid yeast strains, each deficient in one or other copy of the set of ribosomal protein (RP) genes, to generate eukaryotic cells carrying distinct populations of altered 'specialized' ribosomes. We show by comparative protein synthesis assays that different heterologous mRNA reporters based on luciferase are preferentially translated by distinct populations of specialized ribosomes. These mRNAs include reporters carrying premature termination codons (PTC) thus allowing us to identify specialized ribosomes that alter the efficiency of translation termination leading to enhanced synthesis of the wild-type protein. This finding suggests that these strains can be used to identify novel therapeutic targets in the ribosome. To explore this further we examined the translation of the mRNA encoding the extracellular matrix protein laminin ß3 (LAMB3) since a LAMB3-PTC mutant is implicated in the blistering skin disease Epidermolysis bullosa (EB). This screen identified specialized ribosomes with reduced levels of RP L35B as showing enhanced synthesis of full-length LAMB3 in cells expressing the LAMB3-PTC mutant. Importantly, the RP L35B sub-population of specialized ribosomes leave both translation of a reporter luciferase carrying a different PTC and bulk mRNA translation largely unaltered.