Low level genome mistranslations deregulate the transcriptome and translatome and generate proteotoxic stress in yeast

Organisms use highly accurate molecular processes to transcribe their genes and a variety of mRNA quality control and ribosome proofreading mechanisms to maintain intact the fidelity of genetic information flow. Despite this, low level gene translational errors induced by mutations and environmental factors cause neurodegeneration and premature death in mice and mitochondrial disorders in humans. Paradoxically, such errors can generate advantageous phenotypic diversity in fungi and bacteria through poorly understood molecular processes.publishe

A Simple Perspective on the Mass-Area Relationship in Molecular Clouds

Despite over 30 years of study, the mass-area relationship within and among clouds is still poorly understood both observationally and theoretically. Modern extinction datasets should have sufficient resolution and dynamic range to characterize this relationship for nearby molecular clouds, although recent papers using extinction data seem to yield different interpretations regarding the nature and universality of this aspect of cloud structure. In this paper we try to unify these various results and interpretations by accounting for the different ways cloud properties are measured and analyzed. We interpret the mass-area relationship in terms of the column density distribution function and its possible variation within and among clouds. We quantitatively characterize regional variations in the column density PDF. We show that structures both within and among clouds possess the same degree of "universality", in that their PDF means do not systematically scale with structure size. Because of this, mass scales linearly with area.Comment: 10 pages, 8 figures, MNRAS in pres

The Yeast PNC1 Longevity Gene Is Up-Regulated by mRNA Mistranslation

Translation fidelity is critical for protein synthesis and to ensure correct cell functioning. Mutations in the protein synthesis machinery or environmental factors that increase synthesis of mistranslated proteins result in cell death and degeneration and are associated with neurodegenerative diseases, cancer and with an increasing number of mitochondrial disorders. Remarkably, mRNA mistranslation plays critical roles in the evolution of the genetic code, can be beneficial under stress conditions in yeast and in Escherichia coli and is an important source of peptides for MHC class I complex in dendritic cells. Despite this, its biology has been overlooked over the years due to technical difficulties in its detection and quantification. In order to shed new light on the biological relevance of mistranslation we have generated codon misreading in Saccharomyces cerevisiae using drugs and tRNA engineering methodologies. Surprisingly, such mistranslation up-regulated the longevity gene PNC1. Similar results were also obtained in cells grown in the presence of amino acid analogues that promote protein misfolding. The overall data showed that PNC1 is a biomarker of mRNA mistranslation and protein misfolding and that PNC1-GFP fusions can be used to monitor these two important biological phenomena in vivo in an easy manner, thus opening new avenues to understand their biological relevance

Development of the genetic code: insights from a fungal codon reassignment

The high conservation of the genetic code and its fundamental role in genome decoding suggest that its evolution is highly restricted or even frozen. However, various prokaryotic and eukaryotic genetic code alterations, several alternative tRNA-dependent amino acid biosynthesis pathways, regulation of tRNA decoding by diverse nucleoside modifications and recent in vivo incorporation of non-natural amino acids into prokaryotic and eukaryotic proteins, show that the code evolves and is surprisingly flexible. The cellular mechanisms and the proteome buffering capacity that support such evolutionary processes remain unclear. Here we explore the hypothesis that codon misreading and reassignment played fundamental roles in the development of the genetic code and we show how a fungal codon reassignment is enlightening its evolution.publishe

The Project PTDC/CTE-GIX/098968/2008 - High resolution stratigraphy of the Lower Jurassic organic-rich marine series in the Lusitanian Basin (Portugal): Initial expectations and results

Apresenta-se neste trabalho uma caracterização e os principais resultados do Projecto “Estratigrafia de alta resolução das séries marinhas ricas em matéria orgânica do Jurássico Inferior da Bacia Lusitânica”, financiado pela Fundação para a Ciência e Tecnologia (Portugal). Este projecto centrou-se numa análise estratigráfica multidisciplinar baseada num vasto conjunto de parâmetros bióticos e abióticos da sucessão margo-calcária rica em matéria orgânica do Jurássico Inferior da bacia, envolvendo sete objetivos principais: 1. Análise sedimentológica (mineralógica, textural e composicional) e sequencial da sucessão hemipelágica do Jurássico Inferior (Sinemuriano superior–Toarciano); 2. Precisões biostratigráficas a partir do registo de amonóides do intervalo compreendido entre o Sinemuriano superior e o Pliensbaquiano superior; 3. Análise paleontológica e paleoecológica da macrofauna bentónica (fundamentalmente braquiópodes e bivalves); 4. Análise biostratigráfica, taxonómica e paleoecológica da fauna de ostracodos (Sinemuriano–Toarciano); 5. Análise quimiostratigráfica baseada principalmente nos isótopos estáveis de carbono (Sinemuriano–Pliensbaquiano); 6. Análise geoquímica e de petrografia orgânica (carbono orgânico total, pirólise Rock-Eval e biomarcadores) do Sinemuriano–Pliensbaquiano; 7. Análise dos padrões de variação dos raios gama (Sinemuriano–Toarciano.This work presents the main results of the Project ”High resolution stratigraphy of the Lower Jurassic organic-rich marine series in the Lusitanian Basin (Portugal)”, supported by the Portuguese Foundation for Science and Technology. This project was focused on a multidisciplinary stratigraphic analysis based on the study of a range of biotic and abiotic parameters of the Lower Jurassic marl–limestone succession rich in organic matter, embracing seven main objectives: 1. Sedimentological (mineralogical, textural and compositional) and sequential analysis of the whole Lower Jurassic hemipelagic succession (Upper Sinemurian–Toarcian); 2. Ammonite biostratigraphic precisions of the Upper Sinemurian and Upper Pliensbachian; 3. Palaeontological and palaeoecological analysis of the benthic macrofauna (especially brachiopods and bivalves); 4. Biostratigraphical, taxonomic and palaeoecological analysis of the ostracod fauna (Sinemurian–Toarcian); 5. Chemostratigraphic analysis based mainly on carbon stable isotopes (Sinemurian–Pliensbachian); 6. Organic geochemical and petrographic analysis (total organic carbon, palynofacies, Rock-Eval pyrolysis and biomarkers) of the Sinemurian–Pliensbachian; 7. Vertical variation patterns of gamma-ray analysis (Sinemurian–Toarcian). Besides the new results in each specific scientific domain (for example, biostratigraphy, palaeoecology, sedimentology, sequence stratigraphy and cyclicity, chemostratigraphy and organic geochemistry), the integration of all data, in several cases at highresolution level, allows emphasizing the achievement of two main transverse goals: the improvement of the stratigraphy and sedimentary knowledge of the Lower Jurassic series of western Iberia margin, with implications in the palaoenvironmental and palaeoceanographic interpretations of the Tethyan pre-Atlantic basins dynamics and global correlation; taking into consideration the huge number of organic geochemical parameters analyzed, the results of this research contributed significantly to understand the role of the different Sinemurian and Pliensbachian organic-rich intervals as potential hydrocarbon generation sources (quality of organic matter and maturation).Depto. de Geodinámica, Estratigrafía y PaleontologíaFac. de Ciencias GeológicasTRUEFondo Europeo de Desarrollo Regional (COMPETE- FEDER)Fundação para a Ciência e a Tecnologia (FCT)pu

Handbook of Active Ageing and Quality of Life: From Concepts to Applications

La edición de este libro estuvo a cargo de Fermina Rojo-Pérez y Gloria Fernández-Mayoralas.El documento adjunto contiene la cubierta, portada e índice del libro.This handbook presents an overview of studies on the relationship of active ageing and quality of life. It addresses the new challenges of ageing from the paradigm of positive ageing (active, healthy and successful) for a better quality of life. It provides theoretical perspectives and empirical studies, including scientific knowledge as well as practical experiences about the good ageing and the quality of later life around the world, in order to respond to the challenges of an aged population. The handbook is structured in 4 sections covering theoretical and conceptual perspectives, social policy issues and research agenda, methods, measurement instrument-scales and evaluations, and lastly application studies including domains and geographical contexts.Peer reviewe